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A particular epidemiological profile: disparities in access to contraceptive methods in Brazil during the SARS-CoV-2 (COVID-19) pandemic
Marcelino AC, da Cunha Pereira P, Charles CM' and Bahamondes L
Our objective was to study disparities in access to contraception during the COVID-19 pandemic. We performed a cross-sectional study at the University of Campinas, Brazil using a Google questionnaire applied from December 2021 until February 2022, disseminated via snowball technique. The survey asked about sociodemographic characteristics and contraceptive use, as well as the demand for new methods and difficulties in continuing to use contraceptives during the COVID-19 pandemic. We analyzed 1018 completed questionnaires; in total, 742 (72.9%) were women aged between 20 and 39 years, 746 (73.3%) were White and 602 (59.2%) used contraceptives. During the COVID-19 pandemic, about 23% of respondents changed their method and approximately 20% of respondents looked for new methods. Among the latter, 31.3% reported some difficulty with obtaining guidance on new methods while only 5.3% of the respondents reported some difficulty with continuing their contraceptive. The main difficulty in both cases was the difficulty with getting a healthcare provider appointment. Our results point to a particular epidemiological population, of younger black and biracial women, with lower education and lower income, which suffered health disparities during the COVID-19 pandemic and found difficulties with using contraceptives and accessing family planning services.
Consistency analysis of two fingertip capillary blood sampling methods for complete blood count
Hongxiang X, Shiyu L, Yanying Z, Wanju X and Sumei W
This study was performed to analyze fingertip capillary blood sampling in pediatric patients using microcapillary blood collection tubes and microhematocrit tubes and to compare the blood cell analysis results obtained via these two blood collection methods. Finger capillary blood was collected from 110 outpatients using microcapillary blood collection tubes and microhematocrit tubes and complete blood count analysis was performed with a Sysmex XS-900i hematology analyzer and manual microscopy for blood cell morphology. Paired data was evaluated for agreement and bias using the microhematocrit samples as the reference group and the samples from the microcapillary blood collection tubes as the observation group. The two blood collection methods demonstrated good agreement for measuring red blood cell (RBC) parameters (i.e., RBC, Hb, Hct, MCV, MCH and MCHC), wherein the relative bias was > allowable total error (TEa) in 0.91%, 1.82%, 11.82%, 1.82%, 0.91% and 8.18% of the parameter measures, respectively. According to industry requirements, the proportion of samples meeting the acceptable bias level should be > 80%. Additionally, the estimated biases at each medical decision level were within clinically acceptable levels for RBC, Hb, Hct, and MCV. However, the proportion of WBC and PLT counts with relative bias > TEa was 25.45% and 35.45%, respectively. Furthermore, the relative bias of the WBC count at the medical decision level of 0.5 × 10/L and that of the PLT counts at the medical decision levels of 10 × 10/L and 50 × 10/L were clinically significant. Bland-Altman analysis further showed a mean bias of 0.66 × 10/L (95% LoA, - 0.79 to 2.11) for the WBC count and 39 × 10/L (95% LoA, - 46 to 124) for the PLT count from the blood samples collected in the microcapillary blood collection tubes compared with the counts of those collected in the microhematocrit tubes. Neutrophil, monocyte, lymphocyte, eosinophil, and PLT counts increased significantly in the microcapillary blood collection tubes compared with those in the microhematocrit tubes, along with an elevated number of instrument false alarms (P < 0.05). The two capillary blood collection devices exhibit performance differences. Therefore, clinicians should pay attention to the variation in results caused by different blood collection methods.
A pre-operative scoring model to estimate the risk of blood transfusion over an ovarian cancer debulking surgery (BLOODS score): a Memorial Sloan Kettering Cancer Center Team Ovary study
Kahn RM, Boerner T, Kim M, Lam C, Gordhandas S, Yeoshoua E, Zhou QC, Iasonos A, Al-Niaimi A, Gardner GJ, Long Roche K, Sonoda Y, Zivanovic O, Grisham RN, Abu-Rustum NR and Chi DS
To develop a pre-operative tool to estimate the risk of peri-operative packed red blood cell transfusion in primary debulking surgery.
Understanding the genetic complexity of puberty timing across the allele frequency spectrum
Kentistou KA, Kaisinger LR, Stankovic S, Vaudel M, Mendes de Oliveira E, Messina A, Walters RG, Liu X, Busch AS, Helgason H, Thompson DJ, Santoni F, Petricek KM, Zouaghi Y, Huang-Doran I, Gudbjartsson DF, Bratland E, Lin K, Gardner EJ, Zhao Y, Jia RY, Terao C, Riggan MJ, Bolla MK, Yazdanpanah M, Yazdanpanah N, Bradfield JP, Broer L, Campbell A, Chasman DI, Cousminer DL, Franceschini N, Franke LH, Girotto G, He C, Järvelin MR, Joshi PK, Kamatani Y, Karlsson R, Luan J, Lunetta KL, Mägi R, Mangino M, Medland SE, Meisinger C, Noordam R, Nutile T, Concas MP, Polašek O, Porcu E, Ring SM, Sala C, Smith AV, Tanaka T, van der Most PJ, Vitart V, Wang CA, Willemsen G, Zygmunt M, Ahearn TU, Andrulis IL, Anton-Culver H, Antoniou AC, Auer PL, Barnes CLK, Beckmann MW, Berrington de Gonzalez A, Bogdanova NV, Bojesen SE, Brenner H, Buring JE, Canzian F, Chang-Claude J, Couch FJ, Cox A, Crisponi L, Czene K, Daly MB, Demerath EW, Dennis J, Devilee P, De Vivo I, Dörk T, Dunning AM, Dwek M, Eriksson JG, Fasching PA, Fernandez-Rhodes L, Ferreli L, Fletcher O, Gago-Dominguez M, García-Closas M, García-Sáenz JA, González-Neira A, Grallert H, Guénel P, Haiman CA, Hall P, Hamann U, Hakonarson H, Hart RJ, Hickey M, Hooning MJ, Hoppe R, Hopper JL, Hottenga JJ, Hu FB, Huebner H, Hunter DJ, , Jernström H, John EM, Karasik D, Khusnutdinova EK, Kristensen VN, Lacey JV, Lambrechts D, Launer LJ, Lind PA, Lindblom A, Magnusson PKE, Mannermaa A, McCarthy MI, Meitinger T, Menni C, Michailidou K, Millwood IY, Milne RL, Montgomery GW, Nevanlinna H, Nolte IM, Nyholt DR, Obi N, O'Brien KM, Offit K, Oldehinkel AJ, Ostrowski SR, Palotie A, Pedersen OB, Peters A, Pianigiani G, Plaseska-Karanfilska D, Pouta A, Pozarickij A, Radice P, Rennert G, Rosendaal FR, Ruggiero D, Saloustros E, Sandler DP, Schipf S, Schmidt CO, Schmidt MK, Small K, Spedicati B, Stampfer M, Stone J, Tamimi RM, Teras LR, Tikkanen E, Turman C, Vachon CM, Wang Q, Winqvist R, Wolk A, Zemel BS, Zheng W, van Dijk KW, Alizadeh BZ, Bandinelli S, Boerwinkle E, Boomsma DI, Ciullo M, Chenevix-Trench G, Cucca F, Esko T, Gieger C, Grant SFA, Gudnason V, Hayward C, Kolčić I, Kraft P, Lawlor DA, Martin NG, Nøhr EA, Pedersen NL, Pennell CE, Ridker PM, Robino A, Snieder H, Sovio U, Spector TD, Stöckl D, Sudlow C, Timpson NJ, Toniolo D, Uitterlinden A, Ulivi S, Völzke H, Wareham NJ, Widen E, Wilson JF, , , , , , , Pharoah PDP, Li L, Easton DF, Njølstad PR, Sulem P, Murabito JM, Murray A, Manousaki D, Juul A, Erikstrup C, Stefansson K, Horikoshi M, Chen Z, Farooqi IS, Pitteloud N, Johansson S, Day FR, Perry JRB and Ong KK
Pubertal timing varies considerably and is associated with later health outcomes. We performed multi-ancestry genetic analyses on ~800,000 women, identifying 1,080 signals for age at menarche. Collectively, these explained 11% of trait variance in an independent sample. Women at the top and bottom 1% of polygenic risk exhibited ~11 and ~14-fold higher risks of delayed and precocious puberty, respectively. We identified several genes harboring rare loss-of-function variants in ~200,000 women, including variants in ZNF483, which abolished the impact of polygenic risk. Variant-to-gene mapping approaches and mouse gonadotropin-releasing hormone neuron RNA sequencing implicated 665 genes, including an uncharacterized G-protein-coupled receptor, GPR83, which amplified the signaling of MC3R, a key nutritional sensor. Shared signals with menopause timing at genes involved in DNA damage response suggest that the ovarian reserve might signal centrally to trigger puberty. We also highlight body size-dependent and independent mechanisms that potentially link reproductive timing to later life disease.
Virtual resonance: analyzing IPA usage intensity under COVID-19's isolating canopy
Jo H and Baek EM
The widespread adoption of smartphones coupled with advancements in artificial intelligence has significantly propelled the use of intelligent personal assistants (IPAs). These digital assistants have become indispensable for many users, particularly during the COVID-19 pandemic. Employing coviance-based structural equation modeling (CB-SEM) and analyzing data from 260 participants, this study explores the key factors influencing IPA usage intensity. Contrary to expectations, affective risk perception showed no significant impact on either IPA usage or parasocial interaction during the pandemic. In stark contrast, cabin fever syndrome significantly influenced both IPA usage and parasocial interaction, underscoring the role of environmental and psychological stressors in shaping technology use. Furthermore, loneliness was found to significantly enhance parasocial interaction with IPAs, though it did not affect usage intensity. The findings highlight a substantial connection between parasocial interaction and IPA usage intensity, suggesting that users who engage in human-like interactions with IPAs tend to use them more extensively. These insights not only deepen our understanding of how IPAs are utilized during health crises but also point to potential directions for developing IPAs that are more responsive to users' emotional and social needs.
Expression patterns of mismatch repair proteins in cervical cancer uncover independent prognostic value of MSH-2
van den Berg MC, Berg HF, Stokowy T, Hoivik EA, Woie K, Engerud H, Ojesina AI, Haldorsen IS, Trovik J, Bertelsen BI, Krakstad C and Halle MK
Although early-detected cervical cancer is associated with good survival, the prognosis for late-stage disease is poor and treatment options are sparse. Mismatch repair deficiency (MMR-D) has surfaced as a predictor of prognosis and response to immune checkpoint inhibitor(s) in several cancer types, but its value in cervical cancer remains unclear. This study aimed to define the prevalence of MMR-D in cervical cancer and assess the prognostic value of MMR protein expression.
SPEctacle Correction for the TReatment of Amblyopia (SPECTRA): study protocol for a prospective non-randomised interventional trial in adults with anisometropic/mixed mechanism amblyopia
Tan KWS, Park ASY, Cheung BWS, Wong GHT, Thompson B and
Amblyopia is a neurodevelopmental vision disorder typically affecting one eye, resulting in compromised binocular function. While evidence-based treatments exist for children, there are no widely accepted treatments for adults. This trial aims to assess the efficacy of appropriate optical treatment in improving vision and visual functions in adults with amblyopia. This is hypothesised to significantly improve visual acuity of the amblyopic eye and other visual functions.
Hepatitis C risk score as a tool to identify individuals with HCV infection: a demonstration and cross-sectional epidemiological study in Egypt
El-Khoury R, Chemaitelly H, Alaama AS, Hermez JG, Nagelkerke N and Abu-Raddad LJ
Hepatitis C virus (HCV) infection poses a global health challenge. By the end of 2021, the WHO estimated that less than a quarter of global HCV infections had been diagnosed. There is a need for a public health tool that can facilitate the identification of people with HCV infection and link them to testing and treatment, and that can be customised for each country.
Assessing the quality of emergency department data for injury surveillance in Victoria, Australia: a comparative analysis of two Victorian hospital data sources
Rezaei-Darzi E and Berecki-Gisolf J
The emergency department (ED) is pivotal in treating serious injuries, making it a valuable source for population-based injury surveillance. In Victoria, information that is relevant to injury surveillance is collected in the Victorian Emergency Minimum Dataset (VEMD). This study aims to assess the data quality of the VEMD as an injury data source by comparing it with the Victorian Admitted Episodes Dataset (VAED).
Graded Exposure Therapy for Fear Avoidance Behaviour After Concussion (GET FAB): protocol for a multisite Canadian randomised controlled trial
Mikolic A, Klotz T, Brasher P, Yeates K, Vranceanu AM, Kendall KD, Snell DL, Debert CT, Bayley M, Panenka W, Cairncross M, Hunt C, Burke M, Tartaglia MC, Silverberg N and
Persistent symptoms after mild traumatic brain injury (mTBI) negatively affect daily functioning and quality of life. Fear avoidance behaviour, a coping style in which people avoid or escape from activities or situations that they expect will exacerbate their symptoms, maybe a particularly potent and modifiable risk factor for chronic disability after mTBI. This study will evaluate the efficacy of graded exposure therapy (GET) for reducing persistent symptoms following mTBI, with two primary aims: (1) To determine whether GET is more effective than usual care; (2) to identify for whom GET is the most effective treatment option, by evaluating whether baseline fear avoidance moderates differences between GET and an active comparator (prescribed aerobic exercise). Our findings will guide evidence-based care after mTBI and enable better matching of mTBI patients to treatments.
Psychological Distress in the Era of Psychological Safety
Zeglin A, McCarthy M, Nedorost S, Dell M and Logio L
There has been a growing disconnect between learners and educators within medical education. As the landscape of medical education has been altered post-pandemic and cultural shifts favor "safe spaces," we sought to explore the tension that exists between a sense of safety and the discomfort inherent within the learning process. Through separate focus groups conducted with trainees and faculty, a common theme emerged: a sense of vulnerability. Trainees feel a strong sense of vulnerability when receiving feedback, particularly when given in public or when expectations were unclear. Educators feel a sense of vulnerability that their feedback will be interpreted as "retaliatory teaching." This sense of vulnerability was heightened in situations that emphasized the tension between personal well-being vs altruism, safe spaces vs accountability to high standards, and advocacy for system change vs power hierarchy. We must acknowledge this vulnerability and the resulting tensions that can ensue due to the competing commitments of medical training. By cultivating a culture of mutual growth and respect, we can create a learning environment that embodies the highest standards of medicine.
Digital Physical Activity and Exercise Interventions for People Living with Chronic Kidney Disease: A Systematic Review of Health Outcomes and Feasibility
Letton ME, Trần TB, Flower S, Wewege MA, Wang AY, Sandler CX, Sen S and Arnold R
Physical activity is essential to interrupt the cycle of deconditioning associated with chronic kidney disease (CKD). However, access to targeted physical activity interventions remain under-supported due to limited funding and specialised staff. Digital interventions may address some of these factors. This systematic review sought to examine the evidence base of digital interventions focused on promoting physical activity or exercise and their effect on health outcomes for people living with CKD. Electronic databases (PubMed, CINAHL, Embase, Cochrane) were searched from 1 January 2000 to 1 December 2023. Interventions (smartphone applications, activity trackers, websites) for adults with CKD (any stage, including transplant) which promoted physical activity or exercise were included. Study quality was assessed, and a narrative synthesis was conducted. Of the 4057 records identified, eight studies (five randomised controlled trials, three single-arm studies) were included, comprising 550 participants. Duration ranged from 12-weeks to 1-year. The findings indicated acceptability and feasibility were high, with small cohort numbers and high risk of bias. There were inconsistent measures of physical activity levels, self-efficacy, body composition, physical function, and psychological outcomes which resulted in no apparent effects of digital interventions on these domains. Data were insufficient for meta-analysis. The evidence for digital interventions to promote physical activity and exercise for people living with CKD is limited. Despite popularity, there is little evidence that current digital interventions yield the effects expected from traditional face-to-face interventions. However, 14 registered trials were identified which may strengthen the evidence-base.
Cross-sectional study to investigate the seroprevalence and risk factors of among women attending the antenatal clinic in Namwala, Zambia
Daka V, Mukosha M, Zimba SD and Phiri AM
Toxoplasmosis is a zoonotic parasitic disease caused by . It has a wide host range and is capable of vertical transmission in pregnant women, which may lead to undesirable pregnancy outcomes such as congenital malformations, miscarriage, premature birth and stillbirth. This study investigated the seroprevalence of infection among pregnant women attending the antenatal clinic at Namwala District Hospital in Southern Zambia.
Breastfeeding challenges among adolescent mothers: a phenomenological study at the Korle Bu Teaching Hospital in Ghana
Suglo M, Kpekura S and Yiryuo L
The natural and best approach to give newborns the nutrients they need for healthy growth and development is through breast feeding. Breastfeeding rates fall more sharply with time for mothers under the age of 20 years.
Accuracy of a novel method for IOP measurement without applying pressure on the cornea
Biran A, Sayar M, Lazzar M, Mimouni M and Beiran I
To assess the accuracy of a prototype novel instrument for intra ocular pressure (IOP) measurements not involving corneal pressure application.
Trends in antidiabetes medication use among hospitalised patients with type 2 diabetes: a retrospective single-centre cohort study
Meier N, Laager R, Gregoriano C, Schütz P, Mueller B, Struja T and Kutz A
Novel antidiabetes medications with proven cardiovascular or renal benefit, such as sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide 1 receptor agonists (GLP-1 RA), have been introduced to the market. This study explored the 4-year trends of antidiabetes medication use among medical hospitalisations with type 2 diabetes (T2D).
Predictors of hypothyroidism amongst dermatomyositis in-patients and an evaluation of financial and demographic differences based on thyroid status
Desai AD, Prajapati S, Patel AM, Wang Y and Jorizzo JL
The spike of acute angle closure after the epidemic downgrade of COVID-19 management: a hospital-based comparative study from China
Zhang Q, Ye Z, Cheng B, Wang K and Chen M
To analyse and compare the clinical characteristics and treatment outcomes of patients with acute angle closure (AAC) who presented before the COVID-19 pandemic, during the COVID-19 management and after their downgrading.
A qualitative study on the effect of a decision aid on knowledge of cataract surgery in patients in developing countries
Fuseini MN, Gbedemah ZEE, Fordjuor SKEJ, Beecham REM, Baisie-Nkrumah EJ, Ennin CG, Buxton ENA and Amissah-Arthur KN
Despite cataract surgery being a safe procedure with a low incidence of perioperative complications rates, poor knowledge, concerns about the effectiveness of treatment and cost-benefit analysis of the procedure significantly hinder cataract surgery uptake rates in Africa. This study describes the effect of a decision aid on knowledge and decision conflict on cataract patients in Africa.
INfluenza VaccInation To mitigate typE 1 Diabetes (INVITED): a study protocol for a randomised, double-blind, placebo-controlled clinical trial in children and adolescents with recent-onset type 1 diabetes
Pedersen IB, Kjolby M, Hjelholt AJ, Madsen M, Christensen AR, Adolfsen D, Hjelle JS, Kremke B, Støvring H, Jessen N, Vestergaard ET, Kristensen K and Frobert O
Children and adolescents with recent-onset type 1 diabetes (T1D) commonly maintain a certain level of insulin production during the remission phase, which can last months to years. Preserving β-cell function can reduce T1D complications and improve glycaemic control. Influenza vaccination has pleiotropic effects and administration of the vaccine during the early phases of T1D may offer β-cell protection. This study aims to assess the effect of influenza vaccination on preserving β-cell function in children and adolescents with recent-onset T1D.
Infant formula supplemented with milk fat globule membrane compared with standard infant formula for the cognitive development of healthy term-born formula-fed infants: protocol for a randomised controlled trial
Gould JF, Gibson RA, Yelland LN, Colombo J, McPhee AJ, Gallier S, Roberts RM, Shaddy DJ, Bednarz J and Makrides M
Milk fat globule membrane (MFGM) is a complex lipid-protein structure in mammalian milk and human milk that is largely absent from breastmilk substitutes. The objective of this trial is to investigate whether providing infant formula enriched with MFGM versus standard infant formula improves cognitive development at 12 months of age in exclusively formula-fed full-term infants.
Prediction of delayed graft function by early salivary microbiota following kidney transplantation
Xiang X, Peng B, Liu K, Wang T, Ding P, Zhu Y, Cheng K and Ming Y
Delayed graft function (DGF) is a frequently observed complication following kidney transplantation (KT). Our prior research revealed dynamic shifts in salivary microbiota post-KT with immediate graft function (IGF), yet its behavior during DGF remains unexplored. Five recipients with DGF and 35 recipients with IGF were enrolled. Saliva samples were collected during the perioperative period, and 16S rRNA gene sequencing was performed. The salivary microbiota of IGFs changed significantly and gradually stabilized with the recovery of renal function. The salivary microbiota composition of DGFs was significantly different from that of IGFs, although the trend of variation appeared to be similar to that of IGFs. Salivary microbiota that differed significantly between patients with DGF and IGF at 1 day after transplantation were able to accurately distinguish the two groups in the randomForest algorithm (accuracy = 0.8333, sensitivity = 0.7778, specificity = 1, and area under curve = 0.85), with Selenomonas playing an important role. Bacteroidales (Spearman's r =  - 0.4872 and p = 0.0293) and Veillonella (Spearmen's r =  - 0.5474 and p = 0.0125) were significantly associated with the serum creatinine in DGF patients. Moreover, the significant differences in overall salivary microbiota structure between DGF and IGF patients disappeared upon long-term follow-up. This is the first study to investigate the dynamic changes in salivary microbiota in DGFs. Our findings suggested that salivary microbiota was able to predict DGF in the early stages after kidney transplantation, which might help the perioperative clinical management and early-stage intervention of kidney transplant recipients. KEY POINTS: • Salivary microbiota on the first day after KT could predict DGF. • Alterations in salivary taxa after KT are related to recovery of renal function.
Sequential therapy of refractory metastatic pancreatic cancer with 5-FU/LV/irinotecan (FOLFIRI) vs. 5-FU/LV/oxaliplatin (OFF). The PANTHEON trial (AIO PAK 0116)
Modest DP, Heinemann V, Schütt P, Angermeier S, Haberkorn M, Waidmann O, Graeven U, Wille K, Kunzmann V, Henze L, Constantin C, de Wit M, Denzlinger C, Ballhausen A, Kurreck A, Jelas I, Alig AHS, Stahler A, Stintzing S and Oettle H
In patients with metastatic pancreatic cancer, after failure of gemcitabine/nab-paclitaxel, this trial compares the efficacy of second-line therapy with FOLFIRI vs. OFF (1:1 randomisation) with cross-over to the vice-versa regimen as third-line therapy.
Sixty seconds on . . . hologram doctors
Wise J
Impact of tonsillectomy on the efficacy of Alt-RAMEC/PFM treatment protocols in children with class III malocclusion and tonsillar hypertrophy: protocol for a cluster randomised controlled trial
Guo F, Li Q, Ngan P, Guan G, Chen X, Yang X, Lv C, Hua F, Zhao T and He H
Orthodontic treatment using face mask protraction combined with an alternate rapid maxillary expansion and constriction/protraction face mask (Alt-RAMEC/PFM) protocol is effective in the early treatment of patients with class III malocclusion, but the stability of treatment outcomes represents a major concern. Previous studies have suggested that tonsillar hypertrophy can be a risk factor for class III malocclusion and tonsillectomy may prompt the normalisation of dentofacial growth. However, these studies had a low-to-moderate level of evidence. This study was designed to identify the impact of tonsillectomy before orthodontic treatment on the efficacy and stability of Alt-RAMEC/PFM protocols and the sleep quality and oral health in children with anterior crossbite and tonsillar hypertrophy.
[Clinical, imaging, and pathological characteristics of 35 cases of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome]
Xu S, Qu LJ, Chen X, Zhu XL and Niu FN
To summarize the clinical, imaging, and pathological characteristics of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome (MELAS) to improve the diagnosis of this rare disease. A retrospective case series was conducted to collect the clinical data and results of genetic testing, muscle biopsy, and imaging studies including computed tomography (CT), magnetic resonance imaging (MRI), and magnetic resonance spectroscopy (MRS) of 35 patients with MELAS admitted to the Nanjing Drum Tower Hospital from 2012 to 2021. Descriptive statistical analysis including mean, standard deviation, and frequency percentage were carried out. The average age of onset of the patients was 30.2±2.3 years; the prevalence of family history was 20%. The two main initial symptoms were limb weakness and convulsions. The clinical manifestations of the neuromuscular system were proximal muscle weakness and exercise intolerance. The endocrine system is the most affected outside the neuromuscular system, with diabetes being the most common condition. Among the five patients who underwent brain CT, four showed hypodense lesions and two had calcified lesions. Brain MRI in 26 patients showed that the lesions more often affected the parietal lobe, basal ganglia, temporal lobe, occipital lobe, and frontal lobe than the infratentorial areas. Twelve of these individuals exhibited different levels of brain atrophy. Among the 10 patients who underwent H-MRS, nine showed a decrease in N-acetylaspartate (NAA) levels, eight exhibited abnormal lactate elevation (Lac peaks), whereas six had both reduced NAA levels and the presence of Lac peaks. Thirty-one patients underwent genetic testing; among them, 25 were found to have the mt.3243A>G mutation, while the remaining six exhibited rare gene alterations. Muscle biopsies were performed in 21 patients, and 15 showed abnormal mitochondrial proliferation manifested by ragged red fibers and defective oxidative phosphorylation manifested by cytochrome C oxidase (COX) enzyme-deficient muscle fibers. The clinical manifestations of MELAS syndrome are variable and complex, and early atypical symptoms could be missed or misdiagnosed. A detailed clinical history, imaging MRS analysis, muscle biopsy, and genetic testing are necessary to confirm the accurate diagnosis of MELAS.
[Analysis of the correlation between fatty liver index and myocardial remodeling]
Qu JC, Wang AP, Dou JT, Gu WJ, Lyu ZH and Mu YM
To analyze the correlation between fatty liver index (FLI) and myocardial remodeling. For cross-sectional study, cluster sampling was used to conduct a follow-up study of "Risk evaluation of cancers in Chinese diabetic individuals: A longitudinal (REACTION) study" among communities of Gucheng and Pingguoyuan of Beijing from April 2015 to September 2015. According to the inclusion and exclusion criteria, 8 848 participants were selected. Biochemical indicators such as body mass index, waist circumference, triglycerides, and γ-glutamyl transpeptidase were detected to calculate the FLI. The correlation between FLI and myocardial remodeling was analyzed. Interventricular septal thickness (IVS), left atrial diameter (LAD), left ventricular end diastolic diameter (LVEDD), and the presence of diastolic dysfunction were measured by color doppler ultrasound. The participants were divided into Q1 group (FLI<30, 4 529 cases), Q2 group (30≤FLI<60, 2 762 cases), and Q3 group (FLI≥60, 1 557 cases) based on FLI levels. Single factor analysis of variance was used for inter-group comparison, logistic regression analysis was used to analyze the correlation between FLI and myocardial remodeling. A total of 8 848 subjects were selected for the study (3 110 male and 5 738 female, mean age: 59.96 years). The IVS of Q1, Q2, and Q3 groups were (9.35±1.08), (9.73±1.22), and (10.07±1.31) mm, respectively. The LAD were (30.94±3.90), (33.37±4.12), and (34.98±4.47) mm, respectively. The LVEDD were (42.51±5.05), (44.43±5.10), and (46.06±5.52) mm, respectively. All increased with the increase of FLI (all <0.001). FLI was an independent risk factor for IVS thickening, LAD increase, LVEDD increase, and diastolic function decrease. The respective risks for IVS thickening, LAD increase, LVEDD increase, and diastolic function decrease in a population with intermediate and higher FLI levels was 1.62 times (95% 1.39-1.89) and 2.53 times (95% 2.13-3.00); 2.71 times (95% 2.39-3.06) and 5.00 times (95% 4.12-6.08); 2.36 times (95% 1.85-3.00) and 4.33 times (95% 3.33-5.62); and 1.90 times (95% 1.63-2.19) and 1.95 times (95% 1.60-2.37) than those with lower FLI levels. There is a certain relevance between FLI and myocardial remodeling.
[Vertigo and dizziness in child: a clinical analysis in 120 cases]
Gao F and Gong SS
To investigate the disease composition, clinical features, diagnosis, and treatment characteristics of vertigo in children. A total of 120 children with vertigo diagnosed and treated in the Department of Otorhinolaryngology, Children's Hospital, Capital Institute of Pediatrics in Beijing from February 2018 to February 2022 were retrospectively analyzed to explore the clinical characteristics of common peripheral vertigo in children and to summarize the experience of diagnosis and treatment. The etiological composition of 120 cases of vertigo in children are as follows: 63 (52.5%) cases of vestibular migraine of childhood (VMC), 19 (15.8%) of recurrent vertigo of childhood (RVC), 11 (9.2%) of probable vestibular migraine of childhood (PVMC), 10 (8.3%) of secretory otitis media (SOM), 6 (5.0%) of persistent postural-perceptual dizziness (PPPD), 4 (3.3%) of benign paroxysmal positional vertigo (BPPV), 2 (1.7%) of vestibular neuritis (VN), 2 (1.7%) of Meniere's disease (MD), 2 (1.7%) of inner ear malformation (IEM), and 1 (0.8%) of vestibular paroxysmal syndrome (VP).The major cause of vertigo in children of different ages was different. SOM was the most important cause in preschool children, followed by RVC and VMC; VMC was the most important cause in school-age children, followed by RVC; and MD and BPPV were exclusive found in adolescents. The incidence rate of PPPD was higher in adolescents than in preschool and school-age children. Children with vertigo had good prognosis in general. VMC, RVC and SOM are the most common causes in vertigo in children, and their proportion was different in different aged children. Transforming abstract feelings into specific information is the skill required for collecting medical history of children with vertigo. Considering the age and cooperation of children, appropriate hearing and vestibular examination techniques are recommended. We should pay more attention to the mental health of children with vertigo and their parents.
[A case report of ACTH-independent Cushing's syndrome associated with bilateral adrenal adenomas]
Song Y, Shen H, Feng ZP, Du ZP, Yang SM, Li QF and Tian B
[A case report of a MODY 10 family presenting as hypokalemic periodic paralysis]
Li B, Wu T and Gu WJ
[The 507th case: hemolytic anemia, parvovirus B19, and multiple organ dysfunction]
Liu Y, Zhang XH, Cao LQ, Huang XJ and Mo XD
A 19-year-old male patient with high-risk acute B-cell lymphoblastic leukemia received haploidentical stem cell transplantation. He developed anemia repeatedly and parvovirus B19 nucleic acid was positive in blood plasma. The patient was diagnosed with cold agglutinin syndrome and multiple organ dysfunction including respiratory failure and hepatitis. In the conflict between viral infection and the treatment of cold agglutinin syndrome, we provided supportive treatment, complement inhibitors to control hemolysis, and antiviral therapy. After timely glucocorticoid and immunosuppressant therapy, the patient had achieved a good response.
[Erdheim-Chester disease manifesting as diabetes insipidus: a case report]
Huang J, Guo MY, Luo H and Zuo XX
[Analysis of the efficacy and safety of pulsed radiofrequency for the treatment of thoracic postherpetic neuralgia in elderly patients with different pain phenotypes]
Geng SH, Wang R, Zhao DL, Zou YY, Qin MY and Lu LJ
To analyze the efficacy and safety of pulsed radiofrequency (PRF) for the treatment of thoracic postherpetic neuralgia (PHN) in elderly patients with different pain phenotypes. A total of 201 elderly thoracic PHN patients, including 110 males and 91 females aged (72.2±6.9) years who received high-voltage, long-duration PRF at the dorsal root ganglion at Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine from January 2020 to December 2022, were retrospectively included. The neuropathic pain symptom inventory (NPSI) was used to evaluate the five different pain phenotypes, which included superficial spontaneous pain, deep spontaneous pain, paroxysmal pain, evoked pain, and paresthesia/dysesthesia, and to analyze the distribution of the five pain phenotypes. The numerical rating scale (NRS) and NPSI scores of all patients were compared before treatment and three months after treatment to evaluate the efficacy and safety of PRF for different pain phenotypes and pain phenotype combinations. All patients had two or more pain phenotypes, and 50.2% (101/201) of the patients had five pain phenotypes at the same time. Compared with those before treatment, three months after treatment, the NPSI scores for superficial spontaneous pain, deep spontaneous pain, paroxysmal pain, evoked pain and paresthesia/dysesthesia decreased (all <0.05), and the scores decreased by[(,)]3.0 (2.0, 4.0), 1.5 (0.5, 2.5), 3.0 (2.5, 4.0), 2.3 (1.0, 4.0), and 1.0 (0.5, 2.0) points, respectively, the differences were statistically significant (<0.001). The decrease in the NPSI score in patients with paroxysmal pain was greater than that in patients with the other 4 pain phenotypes (all <0.05). After treatment, the NRS score decreased by 4.0 (3.0, 5.0), 4.0 (3.0, 5.0), 4.0 (3.0, 5.0) and 5.0 (4.0, 6.0) points in patients with 2, 3, 4 and 5 pain phenotypes, respectively, and the difference was statistically significant (<0.001). The decrease in the NRS score was greater in patients with a combination of 5 pain phenotypes than that in patients with a combination of 3 and 4 pain phenotypes (all <0.05). No complications, such as pneumothorax, haematoma or infection, occurred in any of the patients during treatment. PRF has different therapeutic effects on PHN patients with different pain phenotypes, it has the best effect on paroxysmal pain, and the treatment is safe.
[Effectiveness and safety of multimodal analgesia in open gastrostomy in patients with end-stage head and neck cancer]
Hu CH, Chen YM, Wu LL, Chen HY, Yuan S and Wang GY
To investigate the effectiveness and safety of multimodal analgesia in patients with end-stage head and neck cancer in open gastrostomy surgery. This was a randomized controlled trial. From June to December 2023, 50 patients with end-stage head and neck cancer who underwent elective open gastrostomy surgery in Beijing Tongren Hospital Affiliated to Capital Medical University were prospectively selected. The patients were divided into multimodal analgesia group and local anesthesia group using the random number table method according to different anesthesia methods, with 25 cases in each group. In multimodal analgesia group, a multimodal analgesia regimen was adopted: ultrasound-guided abdominal wall nerve block (rectus sheath block and transverse abdominis plane block)+intravenous injection of oxycodone+intravenous injection of flurbiprofen axetil and dexamethasone. In local anesthesia group, local infiltration anesthesia with ropivacaine was adopted. The main outcome measure was the incidence of intraoperative pain numeric rating scale (NRS) score>3 points in the two groups. The secondary observation indicators included NRS score and hemodynamic indexes [mean arterial pressure (MAP) and heart rate (HR)] at various time points during surgery [before anesthesia (T0), at the time of incision (T1), 10 minutes after surgery (T2), during gastric body traction (T3), and at the end of surgery (T4)], incidence of adverse reactions, postoperative patient satisfaction score, as well as the NRS scores at rest and activity (coughing) within 24 hours after surgery. The multimodal analgesia group included 21 males and 4 females, aged (61.4±9.9) years. There were 19 males and 6 females in the local anesthesia group, aged (58.6±10.8) years. The incidence of intraoperative NRS score>3 points and the incidence of salvage analgesia in the multimodal analgesia group were both 12.0% (3/25), which were lower than 60.0% (15/25) in the local anesthesia group, and the differences were statistically significant (all <0.001); The NRS score [ (, )] at T3 in the multimodal analgesia group was 2 (2, 3) points, which were lower than 5 (3, 6) points in the local anesthesia group (<0.05). There were smaller variabilities in MAP and HR in the multimodal analgesia group than those in the local anesthesia group (all <0.05). The incidence of intraoperative tachycardia, surgical traction reaction, and nausea in the multimodal analgesia group was lower than that in the local anesthesia group (all <0.05). The postoperative satisfaction score of patients in the multimodal analgesia group was (9.25±0.71) points, which were higher than (7.33±0.87) points in the local anesthesia group (<0.001). NRS score during postoperative activity within 24 hours in the multimodal analgesia group were (2.36±0.75) points, which were lower than (3.03±0.81) points of the local anesthesia group (=0.005). No adverse reactions such as urinary retention, nausea, vomiting and dizziness occurred in both groups. Compared with local anesthesia, the multimodal analgesic strategy could provide better analgesic effect and longer duration, better hemodynamic stability, and fewer intraoperative adverse reactions in patients with end-stage head and neck cancer undergoing open gastrostomy.
[Clinical characteristics of perimenopausal female patients with rheumatoid arthritis]
Ouyang ZM, Pan J, Zou YW, Zheng HW, Ma JD, Yang KM, Lu Y, Jia PW, Wu T and Dai L
To explore the menopause status of patients with rheumatoid arthritis (RA) and clinical characteristics of perimenopausal RA patients. A cross-sectional study. Female RA patients were recruited retrospectively in the Sun Yat-Sen Memorial Hospital from August 2015 to August 2023. Clinical data were collected, including onset age, disease duration, RA disease activity indicators, functional assessment, and radiographic scores. According to menopausal status, the patients were categorized as pre-menopausal, perimenopausal and post-menopausal groups to explore their menopausal and clinical characteristics. A total of 1 151 female patients were enrolled, with a mean age of (50.2±13.0) years. At enrollment, there were 470 (40.8%), 140 (12.2%) and 541 (47.0%) patients in pre-menopause, perimenopause and post-menopause status, respectively. The mean age of menopause was (49.0±4.2) years. Compared with pre-menopausal group, perimenopausal RA patients had higher disease activity indicators [clinical disease activity index (CDAI) 17 (6, 26) vs 10 (3, 19) ], higher levels of inflammation [erythrocyte sedimentation rate (ESR) 35 (21, 65) vs 26 (14, 44) mm/1h, C-reactive protein (CRP) 6.2 (3.2, 16.8) vs 3.3 (3.2, 13.6) mg/L], and a higher proportion of functional limitation [25.0%(35/140) vs 10.4%(49/470)] (all <0.016 7); while there was no significant differences in disease activity[(, )] [CDAI 17 (6, 26) vs 14 (6, 25)], levels of inflammation [ESR 35(21, 65) vs 42 (23, 72) mm/1h, CRP 6.2 (3.2, 16.8) vs 6.2 (3.3, 23.9) mg/L] and functional limitation [25.0%(35/140) vs 28.8%(156/541)] when compared with those in post-menopausal group (all >0.016 7). In RA patients during the perimenopausal period, 49 cases (35.0%) developed RA during this period. Compared with patients with RA onset during reproductive age, patients with RA onset during the perimenopausal period had higher numbers of 28-joint tender joints [7 (2, 10) vs 4 (0, 8)], higher CDAI [20 (12, 29) vs 14 (4, 24)], and higher ESR [45 (25, 72) vs 32 (18, 56) mm/1h] (all <0.05). Perimenopausal patients with RA have severe disease activity and functional limitation.
[Analysis of risk factors for venous thromboembolism in patients with polycythemia vera and establishment of a prediction model]
Ma JY, Zhang YH, Teng GS, Du CX, Zhang HQ, Wang Y, Li YQ, Duan YF, Zhou Y, Shao ZH and Bai J
To investigate the risk factors of venous thrombosis in patients with polycythemia vera (PV) and establish a prediction model for venous thrombosis. PV patients with JAK2 gene mutation positive in the Second Hospital of Tianjin Medical University from September 2017 to November 2023 were retrospectively included. The patients were divided into groups according to whether they had venous thrombosis. After matching age and gender factors with propensity scores, 102 patients were included in the venous thrombosis group [46 males, 56 females, with a median age (, ) of 52 (44, 60) years] and 204 cases were included in the group without venous thrombosis [92 males, 112 females, with a median age of 52 (44, 59) years]. The clinical and laboratory characteristics, disease progression and incidence of gene mutation were compared between the two groups. The follow-up cohort ended on November 20, 2023, with a median follow-up [ (, )] of 11 (1, 53) years. Multivariate Cox risk model was used to analyze the influencing factors of venous thrombosis in PV patients, and establish a scoring system for the venous thrombosis risk factor prediction model of PV patients. Receiver operating characteristic (ROC) curve was used to evaluate the predictive efficiency of the model. Hemoglobin concentration, the ratio of hematopoietic volume≥55%, neutrophil to lymphocyte ratio≥5, hypertension, subcostal spleen≥5 cm and secondary myelofibrosis in venous thrombosis group were higher than those in non-venous thrombosis group (all <0.05). In addition, the proportion of history of thromboembolism, V617F gene mutation load (V617F%)≥50%, diabetes mellitus, ASXL1 mutation and secondary reticular silver staining≥3 in the venous thrombosis group were higher than those in the non-venous thrombosis group (all <0.05). The proportion of PV patients with 3 or more gene mutations was 44.1% (45/102) in venous thrombosis group, which was higher than that of PV patients without venous thrombosis 29.9% (61/204) (=0.014). The proportion of ASXL1 gene mutation in venous thrombosis group was 17.6% (18/102), which was higher than the 4.9% (10/204) in non-venous thrombosis group (<0.001). Multivariate Cox risk model analysis showed that previous thromboembolism history (2.031, 95%: 1.297-3.179, =0.002), V617F%≥50% (2.141 95%: 1.370-3.347, 0.001), ASXL1 mutation (=4.632, 95%: 1.497-14.336, =0.008), spleen subcostal≥5 cm (=1.771, 95% 1.047-2.996, =0.033) are the risk factors of venous thrombosis in PV patients. According to values, a score system for predicting risk of venous thrombosis in PV patients was established: previous history of thromboembolism, V617F%≥50% and spleen subcostoal≥5 cm were assigned 1 point respectively, and ASXL1 mutation was assigned 2 points. Low risk group: score 0, medium risk group: score 1-2, high risk group: score≥3. The ROC curve analysis of the model for predicting venous thrombosis in PV patients showed that the area under the curve (AUC) was 0.807 (95% 0.755-0.860), with the sensitivity of 88.2% and the specificity of 59.8% when the Youden index was 0.48. Previous thromboembolism history, V617F%≥50%, ASXL1 mutation, spleen subcostoal≥5 cm are risk factors of venous thrombosis in PV patients. The established prediction model has good prediction efficiency.
[Role of intercellular adhesion molecule-1 in adhesion and migration of mesenchymal stem cells in ankylosing spondylitis and its mechanisms]
Wang KY, Lu JS, Song CY, Qiao M, Chang MH, Li Y, Li JK, Tang ZL, Bao HD, Qiu Y and Qian BP
To investigate the role and underlying mechanisms of intercellular adhesion molecule-1 (ICAM-1) in the adhesion and migration of mesenchymal stem cells (MSCs) in patients with ankylosing spondylitis (AS). Bone marrow and ligament tissues were collected during surgery from patients with AS and thoracolumbar fractures (as controls, HC) treated from October 2021 to October 2022 at Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital. MSCs were isolated and cultured from the bone marrow using the Ficoll separation method. Cell morphology was observed under high-resolution microscopy, and differences in the cytoskeletal features between AS-and HC-MSCs were analyzed through immunofluorescence staining. The expression of ICAM-1 was quantified in both groups using real-time quantitative polymerase chain reaction (RT-qPCR) and flow cytometry. Transwell migration assays and wound healing experiments were conducted to evaluate the differences in migration rates between the two groups of MSCs. The interspinous ligament and bone marrow was acquired in AS (2 males and 1 female; 33, 37, 32 years old, respectively) and no-AS patients (2 males and 1 female; 35, 32, 38 years old, respectively). AS-MSCs exhibited broader cell morphology compared to HC-MSCs under bright field and fluorescence microscopy. Immunofluorescence staining of the interspinous ligament showed higher expression of ICAM-1 (68.38±3.42 vs 48.31±2.43) and CD105 (37.97±2.16 vs 23.36±2.06) in AS patients (both <0.001). Western blot and RT-qPCR analysis revealed significantly stronger protein expression and transcription levels of ICAM-1 in AS-MSCs when compared to those in HC-MSCs (both <0.001). Flow cytometry confirmed greater mean fluorescence intensity of ICAM-1 in AS-MSCs than in that in HC-MSCs (924.30±54.99 vs 636.47±40.03, =0.002). Regarding cell adhesion efficiency, it showed no significant difference between AS-MSCs and HC-MSCs in the early stage of adhesion (0.5 h: 1 496±213 vs 1 205±163, =0.133), but they were all significantly higher in AS-MSCs in the later stage (1 h: 2 894±172 vs 1 908±155, =0.002; 2 h: 4 540±286 vs 3 334±188, =0.004; 3 h: 5 212±281 vs 4 208±303, =0.014). Finally, cell migration experiments demonstrated a stronger migration capability of AS-MSCs compared to HC-MSCs (5 449±172 vs 4 016±155, <0.001), and the inhibition efficiency of A-205804 on the migration rate of AS-MSCs was stronger than that on HC-MSCs (2 145±239 vs 3 539±316, =0.004). The aberrant expression of ICAM-1 markedly influences the adhesion and migration dynamics of MSCs. Elevated ICAM-1 levels in MSCs derives from patients with AS significantly enhance their migratory capabilities.
ToF-SIMS evaluation of PEG-related mass peaks and applications in PEG detection in cosmetic products
Shen Y, Son J and Yu XY
Polyethylene glycols (PEGs) are used in industrial, medical, health care, and personal care applications. The cycling and disposal of synthetic polymers like PEGs pose significant environmental concerns. Detecting and monitoring PEGs in the real world calls for immediate attention. This study unveils the efficacy of time-of-flight secondary ion mass spectrometry (ToF-SIMS) as a reliable approach for precise analysis and identification of reference PEGs and PEGs used in cosmetic products. By comparing SIMS spectra, we show remarkable sensitivity in pinpointing distinctive ion peaks inherent to various PEG compounds. Moreover, the employment of principal component analysis effectively discriminates compositions among different samples. Notably, the application of SIMS two-dimensional image analysis visually portrays the spatial distribution of various PEGs as reference materials. The same is observed in authentic cosmetic products. The application of ToF-SIMS underscores its potential in distinguishing PEGs within intricate environmental context. ToF-SIMS provides an effective solution to studying emerging environmental challenges, offering straightforward sample preparation and superior detection of synthetic organics in mass spectral analysis. These features show that SIMS can serve as a promising alternative for evaluation and assessment of PEGs in terms of the source, emission, and transport of anthropogenic organics.
Prevalence and 20-year trends in meditation, yoga, guided imagery and progressive relaxation use among US adults from 2002 to 2022
Davies JN, Faschinger A, Galante J and Van Dam NT
Meditation, yoga, guided imagery, and progressive relaxation are promoted as complementary approaches for health and wellbeing in the United States, but their uptake by different sociodemographic groups is unclear. This study assessed the prevalence and 20 year trends in the use of these practices in US adults between 2002-2022. We examined practice use and associations with sociodemographic and health factors in a population-weighted analysis of n = 134,959 participants across 5 cycles of the National Health Interview Survey. The overall use of meditation (18.3%, 60.53 million), yoga (16.8%, 55.78 million) and guided imagery/progressive relaxation (6.7%, 22.22 million) increased significantly from 2002 to 2022. Growth was consistent across most sociodemographic and health strata, however users of 'Other' race (comprising 54% Indigenous Americans, Odds Ratios; ORs = 1.28-1.70) and users with moderate (ORs = 1.19-1.29) psychological distress were overrepresented across all practices, and those with severe psychological distress were overrepresented in meditation (OR = 1.33) and guided imagery/progressive relaxation (OR = 1.42). Meditation use has accelerated over time for 65 + year olds (OR = 4.22), people not accessing mental health care (OR = 1.39), and less educated (OR = 4.02) groups, potentially reflecting unmet health needs. Health professionals should consider the extensive use of complementary practices in service and treatment planning and consider their risks and benefits.
[Analysis of the characteristics of patients with amyotrophic lateral sclerosis with neuromuscular junction dysfunction prior to motor neuron degeneration]
Zhang JH, Chen ZH, Ling L, Cheng HM, Zhang Y, Zhao JR and Huang XS
To investigate the clinical and electrophysiological characteristics of patients with amyotrophic lateral sclerosis (ALS) with positive repetitive nerve stimulation (RNS) test results on the accessory nerve and negative needle electromyography (EMG) test results on the sternocleidomastoid with the goal to enrich the knowledge of disease progression in patients with ALS. The clinical data of 612 patients diagnosed with ALS at the Neurology Department of the First Medical Center, Chinese PLA General Hospital from June 2016 to August 2022 were collected. In total, 267 cases had undergone EMG tests on the sternocleidomastoid following a positive 3 Hz RNS test result on the accessory nerve, who were selected as the study subjects. The differences in clinical indicators were compared between RNS (+)/EMG (-) group and RNS (+)/EMG (+) group. A binomial distribution model with multiple variables was built to quantitatively analyze the major factors and their effects. At the initial visit, 15.8% of patients with ALS were 3 Hz RNS (+) on the accessory nerve and EMG (-) on the ipsilateral sternocleidomastoid, accounting for 36.3% of RNS (+) patients. The decremental range of the 3 Hz RNS test delivered to the accessory nerve in these patients [-14% (-19%, -12%)] was lower than that in patients with RNS (+)/EMG (+) [-17% (-23%, -13%)] (<0.05), while the ratio of upper limb onset (64.9%) and non-definite diagnosis (28.9%) were higher [54.7% and 13.5% for patients with RNS (+)/EMG (+), <0.05]. Furthermore, the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) score [40 (37, 42)], body mass index (BMI) [23.8 (22.0, 25.4) kg/m] and forced vital capacity (FVC) [92.8% (76.6%, 103.8%)] were higher in patients with RNS(+)/EMG(+) (<0.05). The multivariate model suggested that, in patients with RNS (+)/EMG (-), the ratio of upper limb onset to lower limb onset was 1.04, while that of upper limb onset to bulbar onset was 2.02, and that of lower limb onset to bulbar onset was 1.94. The ratio of non-definite ALS to definite ALS was 1.13. The ALSFRS-R score, BMI, and FVC had a protective contribution to the electrophysiological function of the motor neurons. The ratio of the effect size of the ALSFRS-R or BMI to that of FVC was 3.37 and 1.14, respectively. Patients with ALS that were 3 Hz RNS (+) on the accessory nerve and EMG (-) on the ipsilateral sternocleidomastoid had a smaller decremental range of the compound muscle action potential amplitude, and a higher proportion of upper limb onset and non-definite ALS. A higher ALSFRS-R score, BMI, and FVC have a protective effect to the electrophysiological function of motor neurons. The effect size of the ALSFRS-R score is the largest, followed by BMI and FVC.
Collaborative discussions between pharmacists and general practitioners to optimise patient medication: a qualitative study within a clinical trial
Parslow R, Duncan LJ, Caddick B, Chew-Graham CA, Turner K, Payne RA, Mann C, Guthrie B, Blair P and McCahon D
There has been significant investment in pharmacists working in UK general practice to improve the effective and safe use of medicines. However, evidence of how to optimise collaboration between GPs and pharmacists in the context of polypharmacy (multiple medication) is lacking.
Integrating evidence and causal mapping of help-seeking behaviour of migrant women with postpartum depression in Shanghai, China: a scoping review protocol
Lee YJ, Taft A, Kacham R, Wong C, Cai Y, Li H and Darmstadt GL
The estimated prevalence of postpartum depression (PPD) worldwide, in China, and Shanghai is 17.2%, 18.0% and 23.2%, respectively. In 2021, Shanghai housed a population of 3.2 million childbearing-age migrant women, most of whom migrated to the city with their husbands for economic reasons. There is a general lack of help-seeking behaviour for mental disorders in China due to the perceived risk of social stigmatisation. In Shanghai, 70% of women did not seek professional help for perinatal mental health problems. We aim to gather information from multiple perspectives, such as the migrant women with PPD and perinatal depression (PND), their caregivers, health service providers and communities, to understand the help-seeking behaviour of postpartum migrant women with PPD or PND in China.
Are the content and usability of a new direct observation tool adequate for assessing competency in delivering person-centred care: a think-aloud study with patients and healthcare professionals in Sweden
Ekman N, Fors A, Moons P, Boström E and Taft C
To evaluate the content and usability of a new direct observation tool for assessing competency in delivering person-centred care based on the Gothenburg Centre for Person-Centred Care (gPCC) framework.
Cerina: cognitive-behavioural therapy-based mobile application for managing GAD symptoms among Ulster University Students in Northern Ireland - a protocol for a pilot feasibility randomised controlled trial
Eylem-van Bergeijk O, Poulter S, Ashcroft K, Robinson T, Mane P, Islam M, Condell J and Leavey G
University students are one of the most vulnerable populations for anxiety disorders worldwide. In Northern Ireland, anxiety disorders appear to be more common among the university student population due to the population demographics across the region. Despite the need, these students show less inclination to access the widely available on-campus well-being services and other external professional services. Digital cognitive-behavioural therapy (CBT) aims to bridge this gap between the need for psychological help and access to it. However, challenges such as limited reach, low adoption, implementation barriers and poor long-term maintenance are mainstay issues resulting in reduced uptake of digital CBT. As a result, the potential impact of digital CBT is currently restricted. The proposed intervention 'Cerina' is a scalable CBT-based mobile app with an interactive user interface that can be implemented in university settings if found to be feasible and effective.
Acute painful crisis in adults with sickle cell disease
Charles KS, Friday M and Rochford E
Recurrent urinary tract infections and prophylactic antibiotic use in women: cross-sectional study
Sanyaolu L, Best V, Cannings-John R, Wood F, Edwards A, Akbari A, Hayward G and Ahmed H
Despite the considerable morbidity caused by recurrent UTIs (rUTIs), and the wider personal and public health implications from frequent antibiotic use, few studies adequately describe the prevalence and characteristics of women with rUTIs or those who use prophylactic antibiotics.
Acceptability and feasibility of a theatre-based wellness programme to support people living with long COVID: a single-arm feasibility study
Burton A, Bone JK, Lawrence-Lunniss K and Philip KE
To determine acceptability and feasibility of a theatre-based wellness programme to support the health and well-being of people with long COVID.
HPV: Cameroon fights back against one of the world's lowest vaccination rates
Ferguson S
Respiratory support with standard low-flow oxygen therapy, high-flow oxygen therapy or continuous positive airway pressure in adults with acute hypoxaemic respiratory failure in a resource-limited setting: protocol for a randomised, open-label, clinical trial - the Acute Respiratory Intervention StudiEs in Africa (ARISE-AFRICA) study
Kwizera A, Kabatoro D, Owachi D, Kansiime J, Kateregga G, Nanyunja D, Sendagire C, Nyakato D, Olaro C, Audureau E and Mekontso Dessap A
Acute hypoxaemic respiratory failure (AHRF) is associated with high mortality in sub-Saharan Africa. This is at least in part due to critical care-related resource constraints including limited access to invasive mechanical ventilation and/or highly skilled acute care workers. Continuous positive airway pressure (CPAP) and high-flow oxygen by nasal cannula (HFNC) may prove useful to reduce intubation, and therefore, improve survival outcomes among critically ill patients, particularly in resource-limited settings, but data in such settings are lacking. The aim of this study is to determine whether CPAP or HFNC as compared with standard oxygen therapy, could reduce mortality among adults presenting with AHRF in a resource-limited setting.
Canadian Rheumatology Association/Spondyloarthritis Research Consortium of Canada Living Treatment Recommendations for the Management of Axial Spondyloarthritis
Rohekar S, Pardo Pardo J, Mirza R, Aydin SZ, Bessette L, Richard N, Mosher D, Boyd T, Chan J, Eder L, Passalent L, Karam E, Nair B, Hazlewood GS, Tse S, Rumsey D, Zummer M, Haroon N, Inman R and Gladman D
To provide a set of living treatment recommendations that will provide contemporary guidance on the management of patients with axial spondyloarthritis (axSpA) in Canada.
Validation of Different Dementia Code-based Definitions in a Population-based Study of Rheumatoid Arthritis
Vassilaki M, Jose George R, Kumar R, Lovering E, Achenbach SJ, Bielinski SJ, St Sauver J, Davis JM, Crowson CS and Myasoedova E
Rheumatoid arthritis (RA) has been associated with an elevated dementia risk. The study aimed to examine how different diagnostic dementia definitions perform in those with RA compared to individuals without RA.
Coronary-Artery Calcification progression in lupus patients
Ocampo-Torres MC, Hernández-Molina G, Criales-Vera S, Sánchez-Guerrero J, Lara-Reyes P and Romero-Díaz J
To evaluate the progression of coronary-artery calcification (CAC) and risk factors associated in a SLE cohort.
Comparison of digital and analog [Ga]Ga-PSMA-11 PET/CT for detecting post-prostatectomy biochemical recurrence in prostate cancer patients: a prospective study
Kim YI, Lee DY, Sung C, Lee SJ, Oh SJ, Oh JS, Yoon S, Lee JL, Lim B, Suh J, Park J, You D, Jeong IG, Hong JH, Ahn H, Kim CS and Ryu JS
Digital positron emission tomography/computed tomography (PET/CT) has shown enhanced sensitivity and spatial resolution compared with analog PET/CT. The present study compared the diagnostic performance of digital and analog PET/CT with [Ga]Ga-PSMA-11 in prostate cancer patients who experienced biochemical recurrence (BCR) after prostatectomy. Forty prostate cancer patients who experienced BCR, defined as serum prostate-specific antigen (PSA) concentrations exceeding 0.2 ng/mL after prostatectomy, were prospectively recruited. These patients were stratified into three groups based on their serum PSA levels. [Ga]Ga-PSMA-11 was injected into each patient, and images were acquired using both analog and digital PET/CT scanners. Analog and digital PET/CT showed comparable lesion detection rate (71.8% vs. 74.4%), sensitivity (85.0% vs. 90.0%), and positive predictive value (PPV, 100.0% vs. 100.0%). However, digital PET/CT detected more lesions (139 vs. 111) and had higher maximum standardized uptake values (SUVmax, 14.3 vs. 10.3) and higher kappa index (0.657 vs. 0.502) than analog PET/CT, regardless of serum PSA levels. On both analog and digital PET/CT, lesion detection rates and interrater agreement increased with increasing serum PSA levels. Compared with analog PET/CT, digital PET/CT detected more lesions with a higher SUVmax and better interrater agreement in prostate cancer patients who experienced BCR after prostatectomy.
Distinct genetic liability profiles define clinically relevant patient strata across common diseases
Trastulla L, Dolgalev G, Moser S, Jiménez-Barrón LT, Andlauer TFM, von Scheidt M, , Budde M, Heilbronner U, Papiol S, Teumer A, Homuth G, Völzke H, Dörr M, Falkai P, Schulze TG, Gagneur J, Iorio F, Müller-Myhsok B, Schunkert H and Ziller MJ
Stratified medicine holds great promise to tailor treatment to the needs of individual patients. While genetics holds great potential to aid patient stratification, it remains a major challenge to operationalize complex genetic risk factor profiles to deconstruct clinical heterogeneity. Contemporary approaches to this problem rely on polygenic risk scores (PRS), which provide only limited clinical utility and lack a clear biological foundation. To overcome these limitations, we develop the CASTom-iGEx approach to stratify individuals based on the aggregated impact of their genetic risk factor profiles on tissue specific gene expression levels. The paradigmatic application of this approach to coronary artery disease or schizophrenia patient cohorts identified diverse strata or biotypes. These biotypes are characterized by distinct endophenotype profiles as well as clinical parameters and are fundamentally distinct from PRS based groupings. In stark contrast to the latter, the CASTom-iGEx strategy discovers biologically meaningful and clinically actionable patient subgroups, where complex genetic liabilities are not randomly distributed across individuals but rather converge onto distinct disease relevant biological processes. These results support the notion of different patient biotypes characterized by partially distinct pathomechanisms. Thus, the universally applicable approach presented here has the potential to constitute an important component of future personalized medicine paradigms.
Prevalence and Risk Factors of Post-Acute Sequela of COVID-19 in Adults with Systemic Autoimmune Rheumatic Diseases
Teles MS, Brundage J, Chiang TP, Alejo JL, Henriquez N, Wallwork R, Christopher Stine L, Massie A, Segev DL, Connolly CM, Paik JJ and Werbel WA
Incidence and manifestations of post-acute sequelae of COVID-19 (PASC) are poorly defined among immunosuppressed populations. We reported, phenotyped, and assessed risk factors for PASC in adults with systemic autoimmune diseases.
Peri-operative, oncological and functional outcomes of robotic versus transanal total mesorectal excision in patients with rectal cancer: A systematic review and meta-analysis
Mohamedahmed AYY, Zaman S, Wuheb AA, Ismail A, Nnaji M, Alyamani AA, Eltyeb HA and Yassin NA
Comparative outcomes of robotic low anterior resection (rTME) and trans-anal total mesorectal excision (TaTME) in patients with low rectal cancer were evaluated.
The Impact of Rheumatoid Arthritis on First Nations and How We Can Work With Communities to Prevent It
El-Gabalawy H
Rheumatoid arthritis (RA) is prevalent in many Indigenous North American First Nations (FN) and tends to be seropositive, familial, and disabling, as well as associated with highly unfavorable outcomes such as early mortality. The risk of developing RA is based on a perfect storm of gene-environment interactions underpinning this risk. The gene-environment interactions include a high frequency of shared epitope encoding HLA alleles, particularly , in the background population, and prevalent predisposing environmental factors such as smoking and periodontal disease. Together, these provide a compelling rationale for an RA prevention agenda in FN communities. Our research team has worked in partnership with several FN communities to prospectively follow the first-degree relatives of FN patients with RA, with the aim of better understanding the preclinical stages of RA in this population. We have focused on specific features of the anticitrullinated protein antibodies (ACPA) and other proteomic biomarkers as predictors of future development of RA. These studies have now led us to consider interventions having a favorable risk-benefit ratio if applied at a stage prior to a hypothetical "point of no return," when the autoimmunity potentially becomes irreversible. Based on a supportive mouse model and available human studies of curcumin, omega-3, and vitamin D supplements, we are undertaking studies where we screen communities using dried blood spot technology adapted for the detection of ACPA, and then enrolling ACPA-positive individuals in studies that use a combination of these supplements. These studies are guided by shared decision-making principles.
Helping ourselves, helping others: the Young Women's Breast Cancer Study (YWS) - a multisite prospective cohort study to advance the understanding of breast cancer diagnosed in women aged 40 years and younger
Rosenberg SM, Zheng Y, Ruddy K, Poorvu PD, Snow C, Kirkner GJ, Meyer ME, Tamimi RM, Schapira L, Peppercorn J, Come S, Borges VF, Warner E, Gelber S, Collins L, Winer EP and Partridge AH
Compared with older women diagnosed with breast cancer, younger women are more likely to die of breast cancer and more likely to suffer psychosocially in both the short-term and long term. The Young Women's Breast Cancer Study (YWS) is a multisite prospective cohort study established to address gaps in our knowledge about this vulnerable and understudied population.
Living with mesothelioma: a systematic review of mental health and well-being impacts and interventions for patients and their informal carers
Sherborne V, Ejegi-Memeh S, Tod AM, Taylor B, Hargreaves S and Gardiner C
Mesothelioma is an aggressive cancer predominantly affecting the lung and abdominal linings. It can have a unique impact on mental health and well-being (MHWB) due to its incurability, poor prognosis and asbestos-exposure causation. This review's aims were to identify/synthesise international evidence on mesothelioma's MHWB impacts; explore MHWB interventions used by patients and carers; and identify evidence of their effectiveness.
Person-centredness in dementia care: an integrative review of theoretical approaches
Serbser-Koal J, Rommerskirch-Manietta M, Purwins D and Roes M
This review identifies and examines theoretical approaches (components and objectives) to person-centred dementia care in order to obtain a better understanding of what is meant by the concept of person-centred dementia care.
Photobiomodulation therapy for chronic knee pain in obese patients in pre-rehabilitation for bariatric surgery: randomised, placebo-controlled, double-blinded, clinical trial protocol
Amorim ACFG, Belchior TCF, Silva Rodarte TND, Rebouças Junior FA, Rodrigues MFSD, Marcos RL, Lino-Dos-Santos-Franco A and Cecatto RB
Obesity has become a worldwide public health problem and is directly linked to loss of quality of life, complications and comorbidities. One of them is chronic pain, especially in the knees, which increases significantly and proportionally with weight gain. In patients with severe obesity, with indication for bariatric surgery, the presence of chronic pain disables and often prevents their participation in a pre-surgical rehabilitation programme. As an analgesic therapy, photobiomodulation (PBM) has been studied with safety, efficacy, well-tolerated used and low costs. Thus, this study aims to evaluate the use of PBM for the treatment of chronic knee pain in obese patients undergoing a pre-surgical rehabilitation programme for bariatric surgery.
Fatigue and physical activity in post-CABG patients: the parallel mediation model of kinesiophobia and self-efficacy : a prospective multicentre and cross-sectional study in China
Li L, Piao JJ and Shang Z
The objective of this study was to investigate how kinesiophobia and self-efficacy explain the relationship between fatigue and physical activity (PA) in post-coronary artery bypass grafting (post-CABG) patients over the age of 45.
Preventing herpes zoster in immunocompromised patients: Current concepts
Calabrese C, Kirchner E, Fernandez J and Calabrese LH
Herpes zoster (HZ) incidence is much higher in immunocompromised individuals than in immunocompetent individuals. HZ also occurs at a younger age and is often more severe in immunocompromised persons. Preventive strategies center around the recombinant zoster vaccine (RZV), which is approved for immunocompromised adults age 19 and older. Identifying those at greatest risk is critical. For those considering vaccination, evidence gaps regarding vaccine efficacy, toxicity, length of protection, and potential effects on underlying conditions may complicate shared and informed decision-making. Recent data have filled some of these gaps, with several societies issuing recommendations regarding vaccination. Remaining gaps are currently addressed by expert opinion.
Economic Burden of Medically Attended Respiratory Syncytial Virus Infections Among Privately Insured Children Under 5 Years of Age in the USA
Tran PT, Nduaguba SO, Wang Y, Diaby V, Finelli L, Choi Y and Winterstein AG
The cost of medically attended RSV LRI (lower respiratory infection) is critical in determining the economic value of new RSV immunoprophylaxes. However, most studies have focused on intermittent RSV encounters, not the episode of care that captures the entirety of RSV illness.
Huge cystic renal cell carcinoma misdiagnosed as ovarian cancer
Dursun P
Assessing the efficacy of a brief universal family skills programme on child behaviour and family functioning in Gilgit-Baltistan, Pakistan: protocol for a feasibility randomised controlled trial of the Strong Families programme
El-Khani A, Asif M, Shahzad S, Bux MS, Maalouf W, Rafiq NUZ, Khoso AB, Chaudhry IB, Van Hout MC, Zadeh Z, Tahir A, Memon R, Chaudhry N and Husain N
The global burden of mental health difficulties among children underscores the importance of early prevention. This study aims to assess the efficacy, feasibility and acceptability of the Strong Families programme in enhancing child behaviour and family functioning in low-resource settings in Gilgit-Baltistan, Pakistan.
First-trimester hemoglobin, haptoglobin genotype, and risk of gestational diabetes mellitus in a retrospective study among Chinese pregnant women
Li Y, Wang F, Huang X, Zong S, Shen Y, Guo L, Cai Q, Sun T, Zhang R, Yu Z, Zhang L, Zang S and Liu J
This study aimed to assess whether the Haptoglobin (Hp) genotype influences the relationship between hemoglobin (Hb) levels and the development of gestational diabetes mellitus (GDM). Additionally, it sought to evaluate the interaction and joint association of Hb levels and Hp genotype with GDM risk.
Use of Mendelian randomization to assess the causal status of modifiable exposures for rheumatic diseases
Zhao SS and Burgess S
The explosion in Mendelian randomization (MR) publications is hard to ignore and shows no signs of slowing. Clinician readers, who may not be familiar with jargon-ridden methods, are expected to discern the good from the many low-quality studies that make overconfident claims of causality or stretch the plausibility of what MR can investigate. We aim to equip readers with foundational concepts, contextualized using examples in rheumatology, to appraise the many MR papers that are or will appear in their journals. We highlight the importance of assessing whether exposures are under plausibly specific genetic influence, whether the hypothesized causal pathways make biological sense, and whether results stand up to replication and use of control outcomes. Quality of research can vary substantially using MR as with any design, and all methods have inherent limitations. MR studies have provided and can still contribute valuable insights in the context of evidence triangulation.
International trends in daily disposable contact lens prescribing (2000-2023): An update
Morgan PB, Efron N, Woods CA, Jones D, Jones L and Nichols JJ
Daily disposable contact lenses offer numerous benefits in terms of ocular health and wearer convenience. The purpose of this work is to update earlier surveys by describing global trends in daily disposable lens fitting between 2000 and 2023.
[Effect of autologous platelet-rich plasma perfusion on cytokines in uterine drainage fluid of patients with intrauterine adhesions following hysteroscopic adhesiolysis]
Shen MH, Guo YS and Duan H
To investigate the effect of autologous platelet-rich plasma (PRP) perfusion on the levels of cytokines in uterine drainage fluid in patients with moderate to severe intrauterine adhesions (IUA) following hysteroscopic adhesiolysis. Thirty patients with moderate to severe IUA who underwent hysteroscopic adhesiolysis at Beijing Obstetrics and Gynecology Hospital, Capital Medical University from November 2020 to March 2021 were randomly divided into two groups: the PRP group (15 patients with placement of intrauterine-suitable balloons and PRP infusion) and the control group (15 patients with placement of intrauterine-suitable balloons only). For all patients, the channel switch was opened 48 hours after the surgery. The drainage fluid of the uterine cavity was collected using syringes through the proximal end of the drainage channel switch at 24 hours after the surgery and through the drainage channel directly at 48, 72, 96, and 120 hours after the surgery, and the levels of related cytokines including platelet-derived growth factor BB (PDGF-BB), vascular endothelial growth factor A (VEGF-A), insulin-like growth factor 1 (IGF-1) and transforming growth factor-β1 (TGF-β1) in the drainage fluid of the uterine cavity were evaluated, respectively. (1) The changes in volumes of uterine cavity drainage fluid: the total drainage fluid volumes of the PRP group and the control group in 120 hours after the surgery were (21.8±2.9) and (22.7±2.7) ml, respectively, and there was no statistically significant difference between the two groups (=-0.847, >0.05). No significant differences were found in the volumes of drainage fluid between the two groups at 72, 96, and 120 hours after the surgery (all >0.05). (2) Variation in cytokine levels in the uterine cavity drainage fluid: ① PDGF-BB: median PDGF-BB levels at 24 and 48 hours after the surgery in the PRP group (6.6 and 9.6 μg/L, respectively) were significantly higher than those in the control group (4.7 and 2.7 μg/L, respectively; all <0.05). There were no significant differences in PDGF-BB levels between the two groups at 72, 96, and 120 hours after the surgery (all >0.05). ② VEGF-A: median VEGF-A levels at 24 and 48 hours after the surgery in the PRP group (3.5 and 2.8 μg/L, respectively) were significantly higher than those in the control group (1.6 and 1.2 μg/L, respectively; all <0.05). There were no significant differences in VEGF-A levels between the two groups at 72, 96, and 120 hours after the surgery (all >0.05). ③ IGF-1: median IGF-1 level at 48 hours after the surgery in the PRP group was significantly higher than that in the control group (39.5 vs 8.6 μg/L, <0.05). No significant differences were found in IGF-1 levels at 24, 72, 96, and 120 hours after the surgery between the two groups (all >0.05). ④ TGF-β1: There were no significant differences in TGF-β1 levles between the two groups at 24, 48, 72, 96, and 120 hours after the surgery (all >0.05). PRP perfusion following hysteroscopic adhesiolysis may increase the levels of PDGF-BB, VEGF-A, and IGF-1 in the uterine cavity drainage fluid, which plays a beneficial role in improving wound microvascular formation, reducing adhesion reformation, and promoting endometrial regeneration and repair.
[Analysis of adverse late-term pregnancy outcomes after cervical cold knife conization]
Wu YZ, Ren Y, Zhong YF, Tang PP and Song YN
To investigate the effects of cervical cold knife conization (CKC) on preterm delivery, other pregnancy complications and neonatal outcomes, and explore the relationship between preterm delivery risk and the depth and volume of conization. The clinical data and pregnancy outcomes of 272 women who underwent CKC in Peking Union Medical College Hospital from January 2002 to March 2018 (conization group) and 1 647 pregnant women who gave birth in Peking Union Medical College Hospital during January to December 2019 (control group) were collected. The preterm delivery, premature rupture of membranes, other pregnancy complications and neonatal outcomes of the two groups were compared, and the relationship between the depth and volume of conization and the risk of preterm delivery in postoperative singleton pregnancy was analyzed. (1) There were no significant differences between the two groups in delivery age, parity, proportion of singleton pregnancy, proportion of assisted reproductive technology (all >0.05). (2) The rate of preterm delivery in the conization group was significantly higher than that in the control group [14.8% (39/264) vs 5.7% (91/1 589); =28.397, <0.001]. There were still significant differences in preterm delivery rates between the two groups at <34 weeks and 34-37 weeks (all <0.01). There was no significant difference in the incidence of premature rupture of membrane between the two groups [23.5% (62/264) vs 23.4% (372/1 589); =0.001, =0.979], but the incidence of preterm premature rupture of membrane in the conization group was significantly higher than that in the control group [11.4% (30/264) vs 2.2% (35/1 589); =56.132, <0.001]. (3) The rate of cesarean section in the conization group was higher than that in the control group [59.6% (162/272) vs 38.8% (639/1 647); =41.377, <0.001]. The birth weight of preterm infants in the conization group was significantly higher than that in the control group [(2 409±680) vs (2 150±684) g; =2.184, =0.030]. However, there were no statistically significant differences in the incidence of gestational diabetes mellitus, hypertensive disorders in pregnancy, the birth weight of full-term infants, incidence of small for gestational age infant and neonatal intensive care unit admission rate between the two groups (all >0.05). (4) The preterm delivery rates of coning depth >15 mm, cone size ≥2 cm and cone size <2 cm were higher than that in the control group (all <0.05). When the coning depth ≤15 mm, the preterm delivery rate in the conization group was higher than that in the control group, but there was no significant difference (=0.620). The rate of preterm delivery of pregnant women with coning depth >15 mm was significantly higher than those with coning depth ≤15 mm (=3.084, 95%: 1.474-6.453; =0.001). There was no significant difference in the preterm delivery rate between pregnant women with cone size >2 cm and those with cone size ≥2 cm (=1.700, 95%: 0.935-3.092; =0.077). The risk of preterm delivery and preterm premature rupture of membranes in subsequent pregnancies are increased after cervical CKC, and the risk of preterm delivery is positively correlated with the depth of cervical coning.
Re-examining the factor structure of the Insomnia Severity Index (ISI) and defining the meaningful within-individual change (MWIC) for subjects with insomnia disorder in two phase III clinical trials of the efficacy of lemborexant
Lenderking WR, Savva Y, Atkinson MJ, Campbell R, Chabot I, Moline M, Meier G and Morin CM
The Insomnia Severity Index (ISI) is a widely used measure of insomnia severity. Various ISI research findings suggest different factor solutions and meaningful within-individual change (MWIC) to detect treatment response in patients with insomnia. This study examined an ISI factor solution and psychometric indices to define MWIC in a robust patient sample from clinical trial settings.
Performance of ChatGPT in classifying periodontitis according to the 2018 classification of periodontal diseases
Tastan Eroglu Z, Babayigit O, Ozkan Sen D and Ucan Yarkac F
This study assessed the ability of ChatGPT, an artificial intelligence(AI) language model, to determine the stage, grade, and extent of periodontitis based on the 2018 classification.
Prognostic relevance of high expression of kynurenine pathway markers in glioblastoma
Jacquerie A, Hoeben A, Eekers DBP, Postma AA, Vanmechelen M, de Smet F, Ackermans L, Anten M, Severens K, Zur Hausen A, Broen MPG and Beckervordersandforth J
Glioblastoma (GBM) continues to exhibit a discouraging survival rate despite extensive research into new treatments. One factor contributing to its poor prognosis is the tumor's immunosuppressive microenvironment, in which the kynurenine pathway (KP) plays a significant role. This study aimed to explore how KP impacts the survival of newly diagnosed GBM patients. We examined tissue samples from 108 GBM patients to assess the expression levels of key KP markers-tryptophan 2,3-dioxygenase (TDO2), indoleamine 2,3-dioxygenase (IDO1/2), and the aryl hydrocarbon receptor (AhR). Using immunohistochemistry and QuPath software, three tumor cores were analyzed per patient to evaluate KP marker expression. Kaplan-Meier survival analysis and stepwise multivariate Cox regression were used to determine the effect of these markers on patient survival. Results showed that patients with high expression of TDO2, IDO1/2, and AhR had significantly shorter survival times. This finding held true even when controlling for other known prognostic variables, with a hazard ratio of 3.393 for IDO1, 2.775 for IDO2, 1.891 for TDO2, and 1.902 for AhR. We suggest that KP markers could serve as useful tools for patient stratification, potentially guiding future immunomodulating trials and personalized treatment approaches for GBM patients.
The effect of cyclosporine a in pterygium surgery using fibrin glue
Arici C and Usta G
To evaluate the effect of topical cyclosporine A (CsA) 0.05% in patients with pterygium surgery using fibrin glue (FG).
Effectiveness of mHealth intervention for trismus exercise in patients with head and neck cancer undergoing proton and heavy ion therapy: a randomized control trial
Dai YM, Virtanen H, Zhu Y and Wan H
This study aimed to compare the effects of a mobile health intervention based on social cognitive theory with standard care on maximal mouth opening, exercise compliance, and self-efficacy in patients receiving proton and heavy ion therapy for head and neck cancer.
[Expert consensus on issues related to abnormal uterine bleeding in adolescents]
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Increased risk of allergic contact dermatitis in patients with cutaneous lichen planus and lichen planopilaris, but not cutaneous lupus erythematosus: An all of us database analysis
Chen LC and Chung HJ
Whole-exome sequencing of individuals from an isolated population under extreme conditions implicates rare risk variants of schizophrenia
Chen L, Du Y, Hu Y, Li XS, Chen Y and Cheng Y
Schizophrenia (SCZ), which affects approximately 1% of the world's population, is a global public health concern. It is generally considered that the interplay between genes and the environment is important in the onset and/or development of SCZ. Although several whole-exome sequencing studies have revealed rare risk variants of SCZ, no rare coding variants have been strongly replicated. Assessing isolated populations under extreme conditions might lead to the discovery of variants with a recent origin, which are more likely to have a higher frequency than chance to reflect gene-environment interactions. Following this approach, we examined a unique cohort of Tibetans living at an average altitude above 4500 meters. Whole-exome sequencing of 47 SCZ cases and 53 controls revealed 275 potential novel risk variants and two known variants (12:46244485: A/G and 22:18905934: A/G) associated with SCZ that were found in existing databases. Only one gene (C5orf42) in the gene-based statistics surpassed the exome-wide significance in the cohort. Metascape enrichment analysis suggested that novel risk genes were strongly enriched in pathways relevant to hypoxia, neurodevelopment, and neurotransmission. Additionally, 47 new risk genes were followed up in Han sample of 279 patients with SCZ and 95 controls, only BAI2 variant appearing in one case. Our findings suggest that SCZ patients living at high altitudes may have a unique risk gene signature, which may provide additional information on the underlying biology of SCZ, which can be exploited to identify individuals at greater risk of exposure to hypoxia.
Immune checkpoint inhibitors-related endocrinopathies exhibit increased severity in breast cancer patients: a real-world study
Gao R, Li C, Zhang S, Liao N and Guan H
This study aims to systematically evaluate the incidence of immune checkpoint inhibitors (ICIs)-related endocrinopathies and their onset time in patients with breast cancer (BC) in a real-world setting.
[Relationship between maternal and fetal ERAP-1 gene polymorphism and pre-eclampsia]
Ma C, Liu XW, Zheng YY and Zhang WY
To investigate the relationship between the polymorphism of endoplasmic reticulum aminopeptidase 1 (ERAP-1) gene and the occurrence of pre-eclampsia (PE). A case-control study was conducted in Beijing Obstetrics and Gynecology Hospital from October 2018 to October 2021. A total of 51 PE pregnant women with onset gestational age<34 weeks were selected as the PE group, and 48 normal pregnant women during the same period were selected as the control group. Venous blood samples were collected from the pregnant women before delivery and umbilical cord within 5 minutes after delivery. Single nucleotide polymorphisms (SNP) of ERAP-1 gene in the pregnant women and their fetus were detected by next-generation sequencing. Univariate analysis and multivariate logistic regression analysis were used to analyze all the SNP loci and alleles detected in the two groups, and the significant SNP were screened. (1) A total of 13 target SNP loci of maternal ERAP-1 gene were selected by univariate analysis. Among them, the frequency distribution of genotypes at 96096828, 96121524, 96121715, 96122260 and 96122281 showed statistically significant differences between PE group and control group (all <0.05). Multivariate logistic regression analysis showed that the risk of PE in pregnant women with TC genotype at locus 96121524 was 2.002 times higher than those with TT genotype (95%: 0.687-5.831, =0.020). (2) A total of 4 target SNP loci of ERAP-1 gene in fetal were selected by univariate analysis, and there was no statistical significance in gene polymorphism of the 4 loci between PE group and control group (all 0.05). Multivariate logistic regression analysis showed that the risk of PE in fetus with genotype AA at locus 96121406 was 0.236 times that of fetus with genotype GG (95%: 0.055-1.025, =0.016). ERAP-1 gene with TC genotype at 96121524 in the mother and GG genotype at 96121406 in the fetus might be related to the incidence of PE.
Temperature-related neonatal deaths attributable to climate change in 29 low- and middle-income countries
Dimitrova A, Dimitrova A, Mengel M, Gasparrini A, Lotze-Campen H and Gabrysch S
Exposure to high and low ambient temperatures increases the risk of neonatal mortality, but the contribution of climate change to temperature-related neonatal deaths is unknown. We use Demographic and Health Survey (DHS) data (n = 40,073) from 29 low- and middle-income countries to estimate the temperature-related burden of neonatal deaths between 2001 and 2019 that is attributable to climate change. We find that across all countries, 4.3% of neonatal deaths were associated with non-optimal temperatures. Climate change was responsible for 32% (range: 19-79%) of heat-related neonatal deaths, while reducing the respective cold-related burden by 30% (range: 10-63%). Climate change has impacted temperature-related neonatal deaths in all study countries, with most pronounced climate-induced losses from increased heat and gains from decreased cold observed in countries in sub-Saharan Africa. Future increases in global mean temperatures are expected to exacerbate the heat-related burden, which calls for ambitious mitigation and adaptation measures to safeguard the health of newborns.
[Ultrasonic convex array probe applied to increase success rate of external cephalic version without anesthesia]
Liu LN, Yang Q, Liu LP, Jiang HF, Zhang SX, Gao C and Jin B
To explore the feasibility of using ultrasonic convex array probe compressing abdominal wall to increase success rate of external cephalic version (ECV) without anesthesia in full-term and near-term pregnancy. Totally 190 singleton and non-cephalic presentation pregnant women in 36-39 weeks of gestation performed ECV from April 2019 to August 2023 in the First Affiliated Hospital of Nanjing Medical University were analyzed. According to whether use the ultrasound probe compressing fetal breech or not, the pregnant women were divided into two groups: 81 cases in the probe-compressing group (including primipara 61 cases and multipara 20 cases) and 109 cases in the non-probe-compressing group(including primipara 72 cases and multipara 37 cases). Clinical data, ECV related factors and complications were analyzed and compared between the two groups. (1) The overall success rate of ECV was 64.2% (122/190). There was no significant difference in the success rate of ECV between probe-compressing group and non-probe-compressing group [69.1% (56/81) vs 60.6% (66/109), =1.490, =0.222]. The total vaginal delivery rate after successful ECV was 81.1% (99/122), while 71.1% (54/76) in primipara and 97.8% (45/46) in multipara, respectively. (2) Compare to the non-probe-compressing group, the success rate of ECV in primipara was significantly higher in the probe-compressing group [45.8% (33/72) vs 70.5% (43/61)], but the gestational age was shorter and the height was higher in the probe-compressing group (all <0.05). The success rate of ECV of multipara in the probe-compressing group (65.0%, 13/20) was lower than that in the non-probe-compressing group (89.2%, 33/37), but there was no significant difference between the two groups (>0.05). (3) Multivariate logistic regression analysis showed that abdominal wall compressed by ultrasound probe (=2.601, 95%: 1.113-6.075; =0.027) and amniotic fluid index (AFI; =1.010, 95%: 1.001-1.020; =0.028) were positive factors for the successful rate of ECV in primipara pregnant women. (4) The main complication of ECV was transient fetal heart rate reduction (8.9%,17/190), the incidence in the probe-compressing group was significantly higher than that in the non-probe-compressing group [14.8% (12/81) vs 4.6% (5/109); =5.967, =0.015]. No statistical differences were found in rates of complications between the ECV successful and unsuccessful pregnant women, and between probe-compressing and non-probe-compressing groups (all >0.05). No adverse maternal and neonatal outcomes related to ECV were observed. The ultrasonic convex array probe compressing could significantly improve the success rate of ECV in primipara without increasing the incidence of adverse maternal and fetal outcomes. The success rate of ECV in primipara is influenced by AFI and operation mode.
Deploying an asthma dashboard to support quality improvement across a nationally representative sentinel network of 7.6 million people in England
Mukherjee M, Okusi C, Jamie G, Byford R, Ferreira F, Fletcher M, de Lusignan S and Sheikh A
Every year, there are ~100,000 hospital admissions for asthma in the UK, many of which are potentially preventable. Evidence suggests that carefully conceptualised and implemented audit and feedback (A&F) cycles have the potential to improve clinical outcomes for those with chronic conditions. We wanted to investigate the technical feasibility of developing a near-real time asthma dashboard to support A&F interventions for asthma management in primary care. We extracted cross-sectional data on asthma from 756 participating GP practices in the Oxford-Royal College of General Practitioners Research and Surveillance Centre (RCGP RSC) database in England comprising 7.6 million registered people. Summary indicators for a GP practice were compared to all participating RCGP RSC practices using practice-level data, for the week 6-12th-Mar-2023. A weekly, automated asthma dashboard with features that can support electronic-A&F cycles that compared key asthma indicators for a GP practice to RCGP RSC could be created ( https://tinyurl.com/3ydtrt85 ): 12-weeks-incidence 0.4% vs 0.4%, annual prevalence 6.1% vs 6.7%, inhaled relievers to preventer 1.2 vs 1.1, self-management plan given 83.4% vs 60.8%, annual reviews 36.8% vs 57.3%, prednisolone prescriptions 2.0% vs 3.2%, influenza vaccination 56.6% vs 55.5%, pneumococcal vaccination ever (aged ≥65 years) 90.2% vs 84.1% and current smokers 14.9% vs 14.8%. Across the RCGP RSC, the rate of hospitalisations was 0.024%; comparative data had to be suppressed for the study practice because of small numbers. We have successfully created an automated near real-time asthma dashboard that can be used to support A&F initiatives to improve asthma care and outcomes in primary care.
Serum levels of leptin, ghrelin putative peptide YY-3 in patients with fetal alcohol spectrum disorders
Podgórski R, Galiniak S, Mazur A, Domin A and Podgórska D
Fetal alcohol spectrum disorders (FASD) are a severe developmental condition resulting from exposure to alcohol during pregnancy. The aim of this study was to examine the concentrations of hormones involved in appetite regulation-ghrelin, leptin, and putative peptide YY-3 (PYY)-in the serum of individuals with FASD. Additionally, we investigated the relationship between these hormone levels and clinical indicators. We conducted an enzyme-linked immunosorbent assay on samples collected from 62 FASD patients and 23 individuals without the condition. Our results revealed a significant decrease in leptin levels among FASD patients compared to the control group (5.124 vs. 6.838 ng/mL, p = 0.002). We revealed no statistically significant differences in the levels of other hormones studied (ghrelin and PYY). Comparisons of hormone levels were also conducted in three subgroups: FAS, neurobehavioral disorders associated with prenatal alcohol exposure and FASD risk, as well as by sex. Assignment to FASD subgroups indicated changes only for leptin. Sex had no effect on the levels of hormones. Moreover, the levels of leptin showed a negative correlation with cortisol levels and a positive correlation with BMI and proopiomelanocortin. Alterations in appetite regulation can contribute to the improper development of children with FASD, which might be another factor that should be taken into consideration in the proper treatment of patients.
[Analysis of therapeutic effects of allogeneic hematopoietic stem cell transplantation in 12 patients with DEK-NUP214 fusion gene positive acute myeloid leukemia]
Shen YY, Yang DL, He Y, Pang AM, Chen X, Ma QL, Zhang RL, Wei JL, Zhai WH, Han MZ, Jiang EL and Feng SZ
Twelve DEK-NUP214 fusion gene-positive patients with acute myeloid leukemia and on allo-HSCT treatment at the Hematology Hospital of the Chinese Academy of Medical Sciences from November 2016 to August 2022 were included in the study, and their clinical data were retrospectively analyzed. The patients comprised five men and seven women with a median age of 34 (16-52) years. At the time of diagnosis, all the patients were positive for the DEK-NUP214 fusion gene. Chromosome karyotyping analysis showed t (6;9) (p23;q34) translocation in 10 patients (two patients did not undergo chromosome karyotyping analysis), FLT3-ITD mutation was detected in 11 patients, and high expression of WT1 was observed in 11 patients. Nine patients had their primary disease in the first complete remission state before transplantation, one patient had no disease remission, and two patients were in a recurrent state. All patients received myeloablative pretreatment, five patients received sibling allogeneic hematopoietic stem cell transplantation, and seven patients received haploid hematopoietic stem cell transplantation. The median number of mononuclear cells in the transplant was 10.87 (7.09-17.89) ×10(8)/kg, and the number of CD34(+) cells was 3.29 (2.53-6.10) ×10(6)/kg. All patients achieved blood reconstruction, with a median time of 14 (10-20) days for neutrophil implantation and 15 (9-27) days for platelet implantation. The 1 year transplant-related mortality rate after transplantation was 21.2%. The cumulative recurrence rates 1 and 3 years after transplantation were 25.0% and 50.0%, respectively. The leukemia free survival rates were (65.6±14.0) % and (65.6±14.0) %, respectively. The overall survival rates were (72.2±13.8) % and (72.2±13.8) %, respectively.
[Allogeneic hematopoietic stem cell transplantation in a patient with MonoMAC syndrome and hematopoietic dysplasia which was induced by GATA2 deficiency: a case report and literature review]
Zhao YF, Shi JM, Fu HR, Zhao YQ, Zhou H and Zhao YM
A retrospective analysis was conducted on a MonoMAC syndrome case admitted in October 2022 to the First Affiliated Hospital of Zhejiang University School of Medicine. The patient, a 16-year-old female with a history of persistent monocytopenia and mild anemia for several years, experienced recurrent symptoms of cough, expectoration, and fever, leading to multiple visits to the hospital. The diagnosis of MonoMAC syndrome was confirmed through comprehensive assessments including routine blood tests, pathogen metagenomic sequencing, lung and bone marrow biopsies, and next-generation sequencing of peripheral blood. The patient underwent haploidentical hematopoietic stem cell transplantation, with a smooth course of transplantation, achieving neutrophil engraftment on + 16 d and platelet engraftment on + 17 d, eventually restoring normal monocyte and NK cell counts. MonoMAC syndrome patients often initially present with infectious symptoms, and the diagnosis can be established based on significant monocytopenia in routine blood tests, history of non-tuberculous mycobacterial infections, and GATA2 germline mutations. Allogeneic hematopoietic stem cell transplantation may be required for some patients to improve their prognosis.
[PICALM-MLLT10 fusion gene positive with multiple gene mutations in a child with T-lymphoblastic lymphoma/leukemia: a case report]
Sun Y, Jiang J, Sun LR, Yan FY and Wang LZ
[Pedigree Analysis and Molecular Mechanism Study of Hereditary Glanzmann Thrombasthenia Caused by Compound Heterozygous Mutation of the ITGA2B Gene]
Lu XM, Fu DY, Zhang YF, Zhao LD, Wang L, Yang J, Liu J, Zheng JW, Yang LH and Wang G
The phenotype and genotype of a pedigree with Glanzmann thrombasthenia caused by compound heterozygous mutation in the ITGA2B gene and its molecular pathogenesis were explored. The platelet aggregation rate of the proband and his family was detected by using a platelet aggregation test with adenosine diphosphate, collagen, epinephrine, arachidonic acid, and ristocetin. The expression levels of CD41 (αⅡb), CD61 (β3), and CD42b (GPⅠb) on the platelet surface was detected by flow cytometry. Gene sequencing technology was used for the genetic identification of the family. RT-PCR was used in the detection of mRNA splicing, and qRT-PCR was used in detecting the relative mRNA level of the ITGA2B gene. Bioinformatics analysis was used to evaluate the pathogenicity of mutation sites and their effects on protein structure and function. The expressions of total αⅡb and β3 in platelets were analyzed by Western blot. Except ristocetin, the other four inducers could not induce platelet aggregation in the proband. Flow cytometry showed that the expression levels of αⅡb and β3 were only 0.25% and 9.76%, respectively, on the platelet surface of the proband, whereas GPⅠb expression was relatively normal. The expression levels of glycoproteins in the other family members were almost normal. c.480C>G and c.2929C>T mutations were detected in the proband through gene sequencing. The c.480C>G mutation was inherited from his mother, and the c.2929C>T mutation was inherited from his father. The RT-PCR and sequencing results showed that the c.480C>G mutation caused mRNA splicing in the proband and his mother, resulting in the deletion of 99 bases in c.476G-574A (p.S160-S192). qRT-PCR showed that the c.2929C>T variant reduced the mRNA level of the ITGA2B gene in the proband and his father. Bioinformatics analysis suggested that the c.480C>G mutation might form a binding sequence with hnRNP A1 protein and generate the 5'SS splice site. The three-dimensional structural model of the αⅡb subunit showed that the β-propeller domain of the p.S160-S192 deletion lost two β-strands and one α-helix in blade 2. The c.2929C>T nonsense mutation caused premature translation termination and produced a truncated protein with the deletion of p.R977-E1039, including the cytoplasmic domain, transmembrane domain, and a β chain of the extracellular Calf-2 domain. The total αⅡb expression of the proband was absent, and the relative expression of β3 was 11.36% of the normal level. The compound heterozygous mutation c.480C>G in exon 4 and c.2929C>T in exon 28 of the ITGA2B gene probably underlies Glanzmann thrombasthenia in this pedigree.
[Clinical characteristics of myeloid tumors combined with the proliferation of large granular lymphocytes]
Du CX, Xiang GP, Peng L, Xiao XY, Teng GS, Zhang YH, Wang Y, Duan YF, Shao ZH and Bai J
Myeloid neoplasms (MNs) belong to a group of hematological malignancies characterized by the abnormal biological functions of hematopoietic stem progenitor cells. The abnormal immune and hematopoietic microenvironment of patients with MN interact with malignant clonal hematopoietic stem cells, promoting the occurrence and development of their diseases. MN large granular lymphocyte proliferation (MN-LGLP) is a special and rare clinical phenomenon in this type of disease. Currently, research on this disease in domestic and international cohorts is limited. This study analyzes the clinical and laboratory characteristics of this type of patient and explores the impact of LGLP on the clinical characteristics and survival of patients with MN. Patients with MN-LGLP are prone to neutropenia and splenomegaly. The presence of LGLP is not a risk factor affecting the survival of patients with MN-LGLP. STAG, ASXL1, and TET2 are the most common accompanying gene mutations in MN-LGLP, and patients with MN-LGLP and STAG2 mutations have poor prognoses.
[Efficacy and safety of gilteritinib-based combination therapy bridging allo-HSCT in relapsed or refractory acute myeloid leukemia patients with positive FLT3-ITD mutation]
Xu Y, Zhang J, Xue SL, Miao M, Wang Y, Chen SN, Qiu HY and Wu DP
This study aims to evaluate the safety and effectiveness of gilteritinib (Gilt) -based combination therapy bridging allo-HSCT for FLT3-ITD(+) R/R AML. Additionally, it aims to assess the impact of Gilt maintenance therapy on the prognosis of patients after allo-HSCT. The clinical data of 26 patients with FLT3-ITD(+) R/R AML treated at the First Affiliated Hospital of Soochow University from August 2019 to January 2023 were retrospectively analyzed. The analysis included an assessment of the composite complete remission rate (CRc), overall survival (OS) time, disease-free survival (DFS) time, and adverse events experienced by all enrolled patients. A total of 26 patients with FLT3-ITD(+) R/R AML were enrolled, including 14 men and 12 women with a median age of 38 (18-65) years. A total of 18 cases were refractory, and eight cases were relapsed. The curative effect evaluation conducted between 14 and 21 days showed that the complete remission (CR) rate was 26.9% (7/26), the CR with hematology incomplete recovery was 57.7% (15/26), and the partial response (PR) rate was 7.7% (2/26). The CRc was 84.6% (22/26), and the minimal residual disease (MRD) negativity rate was 65.4%. The 12 month cumulative OS rate for all patients was 79.0%, and the 24 month cumulative OS rate was 72.0%. The median OS time was not determined. The median follow-up time was 16.0 months. Among the patients who responded to treatment, the 12 month cumulative DFS rate was 78.0%, and the 24 month cumulative DFS rate was 71.0%. The median DFS time was not determined. Patients who received allo-HSCT had a median OS time that was significantly longer than those who did not receive allo-HSCT (3.3 months, 95% 2.2-4.3 months, =0.005). The median OS time of patients with or without Gilt maintenance therapy after allo-HSCT was not determined, but the OS time of patients with Gilt maintenance therapy after allo-HSCT treatment was longer than that of patients without Gilt maintenance therapy after allo-HSCT treatment (=0.019). The FLT3-ITD mutation clearance rate in this study was 38.5%, and the median OS time of patients with FLT3-ITD mutation clearance was not determined but was significantly longer than the median OS of patients without FLT3-ITD mutation clearance (15.0 months; =0.018). The most common grade 3 and above hematological adverse events of Gilt-based combination therapy included leukopenia (76.9%), neutropenia (76.9%), febrile neutropenia (61.5%), thrombocytopenia (69.2%), and anemia (57.7%). One patient developed differentiation syndrome during oral Gilt maintenance therapy after allo-HSCT treatment, but his condition improved after treatment. The Gilt-based combination therapy is highly effective in treating FLT3-ITD(+) R/R AML. It demonstrates a high CRc, MRD negativity rate, and rapid onset, leading to a significant improvement in patients' survival. Furthermore, the clearance rate of FLT3-ITD mutation is notably high. Additionally, implementing bridging allo-HSCT and Gilt maintenance therapy after allo-HSCT treatment has considerably enhances patients' survival. Closely monitoring and managing any adverse event that may occur during treatment are crucial.
[Clinical efficacy of allogeneic hematopoietic stem cell transplantation for myelodysplastic syndrome-evolved acute myeloid leukemia]
Chen SL, Shi YY, Zhang LN, Gong M, Zhang XY, Zhao XL, Hao MZ, Wei JL, He Y, Feng SZ, Han MZ and Jiang EL
The outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for myelodysplastic syndromes-evolved acute myeloid leukemia (MDS-AML) were explored. A retrospective review was conducted for 54 patients with MDS-AML treated with allo-HSCT in the Institute of Hematology and Blood Disease Hospital from January 2018 to August 2022. The clinical effects after transplantation were observed, and the related risk factors influencing prognosis were explored. Of the total 54 patients, 26 males, 28 females, and 53 patients achieved hematopoietic reconstruction. After a median follow-up of 597 (15-1 934) days, the 1 year overall survival (OS) rate, disease-free survival (DFS) rate, relapse rate (CIR) and non-relapse mortality (NRM) rate were 75.8%±5.8%, 72.1%±6.1%, 12.7%±4.9%, and 17.1%±5.2%, respectively. The 3 year estimated OS, DFS, CIR, and NRM rates were 57.8%±7.5%, 58.1%±7.2%, 23.2%±6.6%, and 23.7%±6.6%, respectively. The cumulative incidence of acute graft-versus-host disease (aGVHD) was 57.5%±6.9%, and the cumulative incidence of chronic graft-versus-host disease (cGVHD) was 48.4%±7.7%. Hematopoietic cell transplantation comorbidity index (HCT-CI) before transplantation was ≥2, minimal residual disease (MRD) was positive on the day of reconstitution, grade Ⅲ/Ⅳ aGVHD, bacterial or fungal infection and no cGVHD after transplantation were adverse prognostic factors for OS (<0.05). COX regression model for multivariate analysis showed that HCT-CI score before transplantation, bone marrow MRD on the day of response, grade Ⅲ or Ⅳ aGVHD, and cGVHD after transplantation were the independent adverse factors for OS (=0.001, =6.981, 95% 2.186-22.300; =0.010, =6.719, 95% 1.572-28.711; =0.026, =3.386, 95% 1.158-9.901; =0.006, =0.151, 95% 0.039-0.581) . For patients with MDS-AML and high risk of relapse, allogeneic transplantation must be considered as soon as possible. The enhanced management of post-transplantation complications and maintenance treatment should be provided whenever possible after transplantation.
[Comparison of etoposide combined with G-CSF and cyclophosphamide combined with G-CSF in the mobilization of autologous peripheral blood stem cells in patients with multiple myeloma]
Wang GR, Yang GZ, Geng CY, Leng Y, Wu Y, Liu AJ and Chen WM
The effect and safety of etoposide combined with G-CSF were compared with those of cyclophosphamide combined with G-CSF in autologous peripheral blood mobilization in patients with multiple myeloma (MM) . Patients with MM who received autologous peripheral blood stem cell mobilization and collection in the Department of Hematology, Beijing Chaoyang Hospital Affiliated to Capital Medical University from January 1, 2020 to July 31, 2023 were included. A total of 134 patients were screened by propensity score matching technology according to a 1∶1 ratio. A total of 67 cases were each treated with ETO combined with G-CSF mobilization scheme (ETO group) and CTX combined with G-CSF mobilization scheme (CTX group). Their clinical data were retrospectively analyzed. ①Collection results: the ETO and CTX groups [2 (1-3) d 2 (1-5) d; <0.001] and CD34(+) cells [7.62×10(6) (2.26×10(6)-37.20×10(6)) /kg 2.73×10(6) (0.53×10(6)-9.85×10(6)) /kg; <0.001] were collected. The success rate of collection was 100.0% (67/67) versus 76.1% (51/67) (<0.001). Excellent rate of collection was 82.1% (55/67) versus 20.9% (14/67; <0.001). Two patients in the ETO group switched protocols after 1 day of collection, and 11 patients in the CTX group switched protocols after 1-2 days of collection. ②Adverse reactions: granular deficiency with fever (21.5%[14/65] 10.7%[6/56]; =0.110), requiring platelet transfusion [10.7% (7/65) 1.8% (1/56) ; =0.047]. ③Until the end of follow-up, 63 cases in the ETO group and 54 cases in the CTX group have undergone autologous transplantation. The median number of CD34(+) cells infused in the two groups was 4.62×10(6) (2.14×10(6)-19.89×10(6)) /kg versus 2.62×10(6) (1.12×10(6)-5.31×10(6)) /kg (<0.001), neutrophil implantation time was 11 (9-14) d versus 11 (10-14) d (=0.049), and platelet implantation time was 11 (0-19) d 12 (0-34) d (=0.035). One case in the CTX group experienced delayed platelet implantation. The mobilization scheme of etoposide combined with G-CSF requires relatively platelet transfusion, but the collection days are shortened. The collection success rate, excellent rate, and the number of CD34(+) cells obtained are high, and the neutrophil and platelet engraftment is accelerated after transplantation.
[Analysis of the efficacy and safety of bone disease treatment in patients with newly diagnosed multiple myeloma treated with denosumab or zoledronic acid]
Ma Y, Xiao XB, Liu YS, Chen XL, Yuan SZ, Zhao SH, Lu Y, Yin H, Chen JL, Wang YQ, Cheng NN, Feng P and Huang WR
This study investigated the efficacy and safety of denosumab (DENOS) versus zoledronic acid (ZOL) in the bone disease treatment of newly diagnosed multiple myeloma. The clinical data of 80 patients with myeloma bone disease (MBD) at the Fifth Medical Center of PLA General Hospital between March 1, 2021 and June 30, 2023 were retrospectively reviewed. Eighteen patients with severe renal impairment (SRI, endogenous creatinine clearance rate<30 ml/min) were treated with DENOS, and 62 non-SRI patients were divided into DENOS (30 patients) and ZOL group (32 patients) . Hypocalcemia was observed in 26 (33%) patients, and 22 patients developed hypocalcemia during the first treatment course. The incidence of hypocalcemia in the non-SRI patients of DENOS group was higher than that in the ZOL group [20% (6/30) 13% (4/32), =0.028]. The incidence of hypocalcemia in SRI was 89% (16/18). Multivariate logistic regression analysis revealed that endogenous creatinine clearance rate<30 ml/min was significantly associated with hypocalcemia after DENOS administration (<0.001). After 1 month of antiresorptive (AR) drug application, the decrease in the serum β-C-terminal cross-linked carboxy-telopeptide of collagen type I concentrations of SRI and non-SRI patients in the DENOS group were significantly higher than that in the ZOL group (68% 59% 27%, <0.001). The increase in serum procollagen type Ⅰ N-terminal propeptide concentrations of patients with or without SRI in the DENOS group were significantly higher than that in the ZOL group (34% 20% 11%, <0.05). The level of intact parathyroid hormone in each group increased after AR drug treatment. None of the patients developed osteonecrosis of the jaw and renal adverse events, and no statistically significant differences in the overall response rate, complete remission and stringent complete remission rates were found among the groups (>0.05), and the median PFS and OS time were not reached (>0.05) . In the treatment of MBD, DENOS minimizes nephrotoxicity and has strong AR effect. Hypocalcemia is a common adverse event but is usually mild or moderate and manageable.
[Clinical efficacy and safety of blinatumomab bridging CAR-T cell therapy in the treatment of patients with adult acute B-cell lymphoblastic leukemia]
Pu Y, Zhou XY, Liu Y, Kong X, Han JJ, Zhang J, Lin ZH, Chen J, Qiu HY and Wu DP
Exploring the efficacy and safety of bridging blinatumomab (BiTE) in combination with chimeric antigen receptor T (CAR-T) cell therapy for the treatment of adult patients with acute B-cell lymphoblastic leukemia (B-ALL) . Clinical data from 36 adult B-ALL patients treated at the First Affiliated Hospital of Suzhou University from August 2018 to May 2023 were retrospectively analyzed. A total of 36 cases were included: 18 men and 18 women. The median age was 43.5 years (21-72 years). Moreover, 21 cases of Philadelphia chromosome-positive acute lymphoblastic leukemia were reported, and 16 of these cases were relapsed or refractory. Eighteen patients underwent blinatumomab bridging followed by CAR-T cell therapy, and 18 patients received CAR-T cell therapy. This study analyzed the efficacy and safety of treatment in two groups of patients. In the BiTE bridge-to-CAR-T group, 16 patients achieved complete remission (CR) after BiTE immunotherapy, with a CR rate of 88.9%. One month after bridging CAR-T therapy, bone marrow examination showed a CR rate of 100.0%, and the minimal residual disease (MRD) negativity rate was higher than the nonbridging therapy group (94.4% . 61.1%, Fisher, =0.041). The incidence of cytokine release syndrome and other adverse reactions in the BiTE bridge-to-CAR-T group was lower than that in the nonbridging therapy group (11.1% . 50.0%, Fisher, =0.027). The follow-up reveals that 13 patients continued to maintain MRD negativity, and five patients experienced relapse 8.40 months (2.57-10.20 months) after treatment. Two of five patients with relapse achieved CR after receiving the second CAR-T cell therapy. In the nonbridging therapy group, 10 patients maintained continuous MRD negativity, 7 experienced relapse, and 6 died. The 1 year overall survival rate in the BiTE bridge-to-CAR-T group was higher than that in the nonbridging therapy group, with a statistically significant difference at the 0.1 level (88.9%±10.5% . 66.7%±10.9%, =0.091) . BiTE bridging CAR-T cell therapy demonstrates excellent efficacy in adult B-ALL treatment, with a low recent recurrence rate and ongoing assessment of long-term efficacy during follow-up.
[Chinese expert consensus on the diagnosis and management of elderly patients with diffuse large B-cell lymphoma (2024)]
and
The general population in China is aging, and thus the number of older patients with diffuse large B-cell lymphoma (DLBCL) will continue to increase. Individualized treatment is required to maximize therapeutic potential while minimizing the risk of toxicity. To improve the diagnosis and treatment of DLBCL in older people in China, the Lymphocyte Disease Group of the Hematology Division of the Chinese Medical Association and Lymphoma Expert Commitee of Chinese Society of Clinical Oncology (CSCO) have organized relevant experts to formulate this consensus.
[Chinese expert consensus on the application of flow cytometry for the detectin of circulating plasma cells in plasma cell disorders (2024)]
and
Flow cytometry plays an important role in the diagnosis and treatment of plasma cell diseases, particularly in the detection of circulating plasma cells (CPCs) in the peripheral blood. A consensus about the normalized use of flow cytometry in detection of CPCs in peripheral blood in clinical practice has been achieved. This consensus is founded on evidence-based principles, which elucidates the timing and value of flow cytometry for the detection of CPCs in the monoclonal gammopathy of undetermined significance, smoldering myeloma, multiple myeloma, and plasma cell leukemia and standardizes flow cytometry in the detection of CPCs in plasma cell diseases.
[Venetoclax combined with dose-reduced HAD as induction treatment for patients with de-novo acute myeloid leukemia]
Yan ZS, Li Y, Zhang B, He JS, Li JS, Wei SN, Wang Q, Li QL, Liu KQ and Mi YC
The efficacy and safety of venetoclax combined with reduced dose HAD regimen in the treatment of newly diagnosed acute myeloid leukemia (AML) was investigated. From May 2022 to January 2023, a total of 25 patients with newly diagnosed AML were treated with venetoclax combined with reduced-dose HAD regimen as induction therapy. Accoding to the 2017 ELN recommendations, 13 (52.0%) in favoable, 3 (12.0%) in intemediate, and 9 (36.0%) in adverse. The ORR (CR rate+PR rate) was 88.0%, and the CR rate was 84.0%. By May 30, 2023, with a median follow-up of 9 months, 1 year overall survival, event-free survival, and relapse-free survival were 100%, 94.7%, and 94.7%, respectively. All patients received 1-5 cycles of consolidation therapy and two median cycles. Treatment with venetoclax and reduced dose of HAD regimen in the treatment of patients with newly diagnosed AML was high effective and safe.
[Clinical analysis of the correlation between the expression of soluble B cell maturation antigen and the efficacy of chimeric antigen receptor T cell targeting B cell maturation antigen in patients with multiple myeloma]
Gao SQ, Mu J, Li X, Wang J, Cui R, Li JY, Sui T and Deng Q
The effect of bone marrow soluble B cell maturation antigen (sBCMA) expression on the efficacy and side effects of chimeric antigen receptor (CAR) -modified T-cell-targeting B cell maturation antigen (BCMA) in patients with multiple myeloma (MM) . This study involved 29 patients with relapsed or refractory MM (RRMM) who received humanized anti-BCMA CAR-T cell clinical trials from January 2018 to December 2021. The expression of sBCMA in bone marrow before and after anti-BCMA CAR-T cell treatment was detected by flow cytometry and compared. ①Two months after BCMA CAR-T cell treatment, 20 patients (68.97%) achieved an overall response (OR), whereas nine patients had stable disease (SD) or miner emission (MR). ②The expression of sBCMA in the bone marrow of 20 patients with OR was higher before treatment than after [26 926 (18 215, 32 488) ng/L 9 968 (6 634, 11 459) ng/L; <0.001]; no significant difference was observed in patients with MR and SD [41 187 (33 816, 47 046) ng/L 33 954 (31 569, 36 256) ng/L; =0.145]; sBCMA expression in patients with OR before CAR-T cell treatment was lower than in patients with MR and SD (=0.005). ③No significant linear correlation was found between the peak value of CAR-T cells and sBCMA expression in the bone marrow of all 29 patients with RRMM ((2)=0.035, =0.330). ④No significant difference in sBCMA expression was found between grades 0-1 CRS group (13 patients) and grades 2-4 CRS group [16 patients; 32 045 (18 742, 40 801) ng/L 29 102 (24 679, 38 776) ng/L, =0.879], nor between grade 0 ICANS group (22 patients) and grade 1-3 ICANS group [seven patients; 30 073 (19 375, 40 065) ng/L 33 816 (22 933, 43 459) ng/L, =0.763]. sBCMA expression in the bone marrow is related to the efficacy of BCMA CAR-T cell therapy in patients with RRMM, but is not significantly correlated with the severity of adverse events. It may serve as a predictive biomarker for the efficacy of BCMA CAR-T cell therapy in these patients.
Reflections of an outgoing SCCT President - It's still all about the SCCT family, the people, and their relationships
Nicol E
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