Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical geneticsYuanyuan Wang, Fang Xie, Chunqiang Liu, Xiaolu Chen, Yusong Guo, Jing Lin, Xiaojun Yang
OBJECTIVE: To conduct blood group identification and genetic analysis on a pregnant woman suspected for having ABO blood group chimerism, and to explore the blood group identification methods and formation mechanisms of her chimerism. METHODS: A pregnant woman with mixed-field (MF) agglutination reactions in ABO forward typing detected at the Department of Transfusion, Zhongshan Hospital, Xiamen University on May 10, 2025 was selected as study subject. Blood grouping was carried out using a microcolumn gel method and saline method. The two populations of red blood cells (RBCs) from the proband, including those agglutinated and non-agglutinated with anti-A reagent, were separated for repeated blood grouping. Flow cytometry was used to quantitatively analyze the proportion of the two RBC populations. ABO genotyping was conducted via direct sequencing and PacBio long-read single-molecule real-time (SMRT) sequencing. Short tandem repeat (STR) analysis was performed on the proband's blood, buccal swabs, hair follicle samples, and the blood samples of her parents. Genetic analysis was carried out using multiplex PCR testing for Y-chromosome microdeletions, chromosomal karyotyping, and fluorescence in situ hybridization (FISH). This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: xmzsyyky 2025-070). RESULTS: The proband's RBCs showed 4+ MF agglutination with anti-A, anti-A1, and anti-AB antibodies. After separation, agglutinated RBCs presented the A1 phenotype and non-agglutinated RBCs presented the O phenotype. Phenotyping for 14 additional RBC antigens showed no MF reaction. Flow cytometry showed that A-phenotype RBCs have accounted for 31.6%, and O-phenotype RBCs have accounted for 69.4%. Direct sequencing of the ABO gene revealed that the proband had an A1.02/O.01.01 genotype. SMRT sequencing results confirmed the presence of three distinct ABO allelic haplotypes: O.01.01 (containing the IVS4+102C>A variant), O.01.01, and A1.02. STR analysis showed that the TH01 and Penta E loci in the proband's multiple tissue samples all exhibited dual paternal and maternal DNA contributions, and a characteristic Y-chromosome peak was detected at the AMEL locus. Multiplex PCR for Y-chromosome microdeletions confirmed that the proband carried the AZFa/b/c, SRY and ZFY genes. G-banded karyotype analysis showed that the proband has a karyotype of 46,XY[1]/46,XX[99]. FISH revealed that the proportion of XY-karyotype cells in cultured peripheral blood was significantly lower than uncultured specimens. CONCLUSION: The proband is an ABO blood group chimera and a tetragametic chimera with a 46,XY/46,XX karyotype distributed throughout the body. This chimerism has originated from the fusion of male and female dizygotic twin embryos during early development.
Journal of medical primatologySarah M Kezar, Sarah J Neal, Gregory K Wilkerson
BACKGROUND: Owl monkeys (Aotus spp.) are a nocturnal nonhuman primate (NHP) native to central and South America that are used as infectious disease research models for human diseases, such as malaria and human immunodeficiency virus. Natural and infectious diseases may cause alterations in the hematology and serum biochemistry values, which necessitate the availability of reliable reference intervals for healthy animals. METHODS: In this study, hematology and serum chemistry reference intervals for Aotus nancymae were calculated from 191 healthy animals (95 female, 96 male) and were generated based on age class (juvenile, adult, geriatric), sex (adults only), and across the entire sample. RESULTS: Significant differences were observed in multiple parameters as a function of sex and age, some of which are inconsistent with existing data from Aotus spp. and other NHPs. CONCLUSIONS: The availability of age and sex specific reference intervals will be a valuable resource for monitoring the clinical health and effects of research interventions in owl monkeys.
Journal of clinical apheresisAbbas Ghazi Naqvi, Akshaya Tomar, Neerja Kushwaha, Anis Maaheraa L
Acquired von Willebrand disease (AvWD) in myeloproliferative neoplasms with extreme thrombocytosis causes paradoxical bleeding due to the mechanism of adsorption and ADAMTS13-mediated proteolysis of high-molecular-weight von Willebrand factor (vWF) multimers. When first-line cytoreductive therapy fails due to intolerance or nonadherence, rapid alternatives are limited. We describe a 74-year-old woman with JAK2V617F-mutated myeloproliferative neoplasm and hydroxyurea intolerance who presented with active mucosal bleeding and a platelet count of 952 000/μL. vWF antigen (vWF:Ag) was 0.37 IU/mL (reference range: 0.50-2.00 IU/mL), and vWF Ristocetin Cofactor activity (vWF:RCo) was 0.21 IU/mL (activity/antigen ratio 0.57; reference range 0.7-1.3), consistent with AvWD. A single thrombocytapheresis session on the Fresenius COM.TEC platform reduced the platelet count to 277 000/μL, with prompt cessation of bleeding. Repeat testing at 24 h showed improvement in vWF:RCo to 0.48 IU/mL (ratio 0.68), which likely reflects restoration of functional high-molecular-weight multimers. In this single case, thrombocytapheresis provided rapid and effective platelet reduction for AvWD secondary to myeloproliferative neoplasms when pharmacological cytoreduction is inadequate.
Liver international : official journal of the International Association for the Study of the LiverAndrea Boccatonda, Elena Campello, Angela Napolitano, Antonella Bray, Chiara Simion, Carla Serra, Fabio Piscaglia, Luca Spiezia, Paolo Simioni
BACKGROUND AND AIMS: Bleeding risk in cirrhotic patients undergoing invasive procedures is traditionally assessed using conventional coagulation tests, which poorly reflect the rebalanced haemostatic state of cirrhosis and often lead to unnecessary transfusions. Viscoelastic testing (VET) provides a global assessment of coagulation and may enable more rational transfusion strategies. We performed a systematic review and meta-analysis of randomised controlled trials (RCTs) to evaluate the efficacy and safety of VET-guided transfusion strategies in this setting. METHODS: We systematically searched PubMed, Embase and Scopus from inception to 10 April 2026. RCTs comparing VET-guided versus standard-of-care transfusion strategies in cirrhotic patients undergoing invasive procedures were included. Primary outcome was procedure-related bleeding; secondary outcomes included transfusion requirements. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using the Mantel-Haenszel method. RESULTS: Six RCTs including 296 patients were analysed. Procedure-related bleeding was rare and did not differ between groups (RR 0.74, 95% CI 0.24-2.31; I2 = 0%). In contrast, VET-guided strategies significantly reduced transfusion requirements, including any blood product transfusion (RR 0.33, 95% CI 0.26-0.44; I2 = 56%), platelet transfusion (RR 0.20, 95% CI 0.13-0.32; I2 = 40%), any fresh frozen plasma (FFP) exposure (RR 0.40, 95% CI 0.28-0.57; I2 = 63%) and FFP-only transfusion (RR 0.22, 95% CI 0.10-0.46; I2 = 81%). CONCLUSIONS: VET-guided transfusion strategies significantly reduce blood product utilisation without increasing bleeding risk in cirrhotic patients undergoing invasive procedures. These findings support a shift towards a physiology-based approach to haemostasis, with potential benefits for patient safety and resource optimisation. TRIAL REGISTRATION: ClinicalTrials.gov identifier: CRD420261382437.
Tropical animal health and productionAnil Chitra, S S Dhaka, Y C Bangar, Narender Kumar, C S Patil, Ankit Magotra
The present study was conducted to compare the hematological responses of Sahiwal and Hardhenu calves to different levels of thermal stress, expressed as Temperature-Humidity Index (THI), during the first 90 days of life. Blood samples were collected monthly in the morning (09:00-10:00 h) from 102 female calves, comprising a crossbred strain (Hardhenu, n = 54) and an indigenous breed (Sahiwal, n = 48), maintained at the Cattle Breeding Farm, LUVAS, Hisar, India, from July 2020 to June 2021. Calves were categorized into neonatal (≤ 30 days) and post-neonatal (31-90 days) groups. THI was classified as < 55, 55-75 and ≥ 75. Data were analyzed using a linear mixed model, with breed and THI as fixed effects and animal as a random effect. Estimated marginal means (± SE) were used to evaluate differences among groups. The results indicated that both breed and THI influenced several hematological parameters, with variations observed across age groups. Indigenous Sahiwal calves showed relatively higher erythrocytic indices (RBC, Hct and MCV) and neutrophil (NEU) percentages, suggesting better adaptability to thermal stress. In contrast, crossbred Hardhenu calves exhibited higher leukocyte (WBC) and lymphocyte (LYM) responses, indicating greater sensitivity to environmental conditions.Moderate THI (55-75) was generally associated with more stable hematological profiles, whereas higher THI (≥ 75) was linked with increased variability and changes in several parameters, reflecting heat stress effects. The study revealed significant effects of breed and THI on several hematological traits in calves, indicating breed-related differences in hematological responses under varying thermal environments. These findings may help in developing management strategies for dairy calves under tropical conditions. However, further studies with larger datasets and direct indicators of heat stress are required to validate their application in selection and management programmes under changing climatic conditions.
Annals of medicineRuichao Feng, Yang Shao, Yuxin Zhao, Xiangfei Cui, Congcong Jiao, Hua Zhou
BACKGROUND: Given the established association between chronic kidney disease (CKD) and systemic inflammation, this study examined the relationships between complete blood count (CBC)-derived inflammatory markers and prevalent CKD. METHODS: Two data sets (Chinese clinical data, n = 4,518; NHANES 2017-2020, n = 7,724) are analyzed. Seven CBC‑derived inflammatory indices were calculated: SII, SIRI, NLR, dNLR, NMLR, MLR, and PLR. Each index was categorized into quartiles (Q1-Q4). Weighted logistic regression (for NHANES) and unweighted logistic regression (for the Chinese clinical data) were applied to estimate associations with CKD, with sequential adjustment for demographics, body mass index, and comorbidities. To control for multiple comparisons, false discovery rate (FDR) correction was applied. Furthermore, subgroup analysis, restricted cubic spline analysis and sensitivity analysis were also performed in this study. RESULTS: In the two fully adjusted models, the highest quartile (Q4) of SIRI, NLR, and NMLR was significantly associated with higher odds of prevalent CKD compared with Q1. After FDR correction, these associations remained significant in both cohorts: in the Chinese cohort, all padj < 0.001; in NHANES, padj = 0.028 for SIRI, 0.040 for NLR, and 0.041 for NMLR. Sensitivity analyses consistently supported the primary findings: excluding outliers, log2 transformation, and the alternative CKD definition yielded similar effect directions and significance levels. Heterogeneity was observed across subgroups, and restricted cubic splines revealed nonlinear dose‑response relationships (p for nonlinearity <0.05). CONCLUSIONS: Elevated SIRI, NLR, and NMLR are associated with prevalent CKD, suggesting systemic inflammation may play a role, yet prospective studies are required to establish temporality and causality.
BACKGROUND: Eosinophils are involved in the pathogenesis of atopic dermatitis (AD). OBJECTIVE: This post-hoc analysis evaluated the effect of stapokibart on blood eosinophil counts in moderate-to-severe AD patients. METHODS: The phase II AD002 trial (n = 120) randomly assigned patients to stapokibart 300 mg every 2 weeks (Q2W), 150 mg Q2W, or placebo for 16 weeks. The phase III AD005 trial (n = 500) randomly assigned patients to stapokibart 300 mg Q2W or placebo for 16 weeks, followed by open-label stapokibart 300 mg Q2W for 36 weeks. Efficacy and safety were analyzed in subgroups stratified by baseline blood eosinophil counts (≥500 or <500 cells/µL). RESULTS: Stapokibart treatment resulted in sustained reductions in blood eosinophil counts versus placebo (baseline vs. Week 16: high-dose 420 vs. 235 cells/μL, low-dose 530 vs. 315 cells/μL in AD002; 370 vs. 210 cells/μL in AD005). Furthermore, stapokibart demonstrated superior efficacy over placebo in achieving higher Eczema Area and Severity Index (EASI)-75 response rates at Week 16 in both eosinophil subgroups. The incidence of adverse events was similar across eosinophil subgroups, with most events being mild or moderate. CONCLUSION: Stapokibart reduced blood eosinophil counts in AD patients and demonstrated favorable efficacy and safety regardless of baseline blood eosinophil counts.
Developmental and comparative immunologyJosé Ricardo de Oliveira-Santos, Geraldo Jorge Barbosa de Moura, Regina Célia Bressan Queiroz de Figueiredo
Amphibians are among the most threatened vertebrates globally, but the physiological mechanisms underlying their vulnerability remain poorly understood, particularly in Neotropical species. This study investigated the associations among body morphometry, Hepatozoon spp. infection, and leukocyte profile of Leptodactylus vastus from the Brazilian Atlantic Forest. Sixty individuals were analyzed for hematologic and parasitic parameters. Hepatozoon spp. prevalence was 100%, and the leukocyte profile was atypical, characterized by a predominance of eosinophils over lymphocytes. Total gamont abundance correlated positively with total leukocyte count. Individuals with high total gamont abundance exhibited leukocytosis, neutrophilia, and lymphopenia, as well as an increased neutrophil-to-lymphocyte ratio. Snout-vent length was a positive independent predictor of total gamont abundance, total leukocyte count, and neutrophils. This study provides the first hematologic and leukocyte characterization of Leptodactylus vastus, revealing an unusual eosinophilic profile and an inflammatory response associated with increasing total gamont abundance, with emphasis on neutrophil-to-lymphocyte ratio and lymphopenia as potential biomarkers of infection-associated physiological stress. These findings contribute to the ecoimmunological knowledge of Neotropical anurans and provide a foundation for future investigations into the effects of parasitism and anthropogenic stressors on amphibian health.
HIV research & clinical practiceHamzah M Alghzawi, Syed Zohad Shah, Zain Ul Abideen, Muhammad Farhan Ashraf
BACKGROUND: The combination of doravirine and islatravir (DOR/ISL) is a novel two-drug regimen for HIV-1. Early development faced challenges due to dose-dependent immunological signals. We aimed to synthesize the evidence on the efficacy and safety of DOR/ISL across all treatment-experience categories, specifically evaluating the impact of islatravir dosage (0.25 mg vs 0.75 mg) on clinical and immunological outcomes. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) following PRISMA guidelines. We searched PubMed, Embase, Cochrane Library, and Google Scholar from inception through April 2026. Primary outcomes were virological suppression (<50 copies/mL) and mean change in CD4+ T-cell count at week 48. Data were pooled using random-effects models. Islatravir dose was evaluated as a pre-specified moderator. Quality was assessed using Cochrane RoB 2.0 and certainty of evidence was graded using the GRADE approach. RESULTS: Seven RCTs (n = 3,600 participants) were included. At Week 48, DOR/ISL showed non-inferior suppression rates (RR 1.01 [95% CI 0.99-1.02]; p = 0.516; moderate-certainty evidence) and a statistically significant reduction in virological failure risk (RR 0.55 [0.33-0.92]; p = 0.022) compared to active control. Overall CD4+ gain was lower with DOR/ISL (MD -34.55 cells/μL; low-certainty evidence); however, a profound moderator effect of dose was observed (p < 0.0001). The 0.75 mg dose was associated with significant CD4+ and lymphocyte declines, whereas the approved 0.25 mg dose was immunologically neutral. DOR/ISL was weight-neutral compared to bictegravir/emtricitabine/tenofovir alafenamide (MD -0.25 kg [-0.66 to 0.16]; low-certainty evidence). CONCLUSION: DOR/ISL 100/0.25 mg once daily achieved virological suppression comparable to standard-of-care ART regimens and was associated with lower rates of virological failure compared with active comparators. The immunological safety concerns observed in early trials were successfully resolved by dose optimization. These findings support the use of DOR/ISL (IDVYNSO) as a potential treatment option for both treatment-naïve and virologically suppressed adults while emphasizing long-term safety surveillance.
Journal of infection and chemotherapy : official journal of the Japan Society of ChemotherapyEiki Ogawa, Yuto Fukuda, Eiji Hisamatsu, Kenta Ito
INTRODUCTION: Urinalysis is commonly used to diagnose urinary tract infections (UTIs), but its accuracy is reduced in children undergoing clean intermittent catheterization (CIC) because of asymptomatic pyuria. This study aimed to determine the optimal urinary leukocyte cutoff value for diagnosing UTIs using a hemocytometer. METHODS: This retrospective observational study included children (<16 years) on CIC at a tertiary children's hospital between April 2020 and March 2025. Quantitative urinalysis was performed using a UF-1500 hemocytometer. UTI was defined as bacteriuria ≥104 CFU/mL accompanied by antimicrobial treatment. Receiver operating characteristic (ROC) curve analysis was used to identify the optimal cutoff for urinary white blood cell (WBC) count. RESULTS: Among 134 patients (2871 specimens), 101 specimens were classified as infection cases (3.5%). Median urinary WBC counts were markedly higher during infection (1514.6/mm3) than during non-infectious periods (21.2/mm3; p < 0.001). ROC analysis yielded an area under the curve of 0.950 (95% CI, 0.935-0.964). The optimal cutoff value was 220.8/mm3, corresponding to 94.1% sensitivity, 84.7% specificity, and 99.7% negative predictive value. WBC counts did not significantly differ among infections caused by different uropathogens. CONCLUSIONS: Hemocytometer-based quantification of pyuria provided high diagnostic accuracy and may be particularly useful as a rule-out test for UTIs in children undergoing CIC.
Journal of infection and public healthKurnia Ardiansyah Akbar, Kraiwuth Kallawicha, Pallop Siewchaisakul, Yu-Liang Leon Guo
BACKGROUND: Black lung disease remains a major occupational health problem among coal miners and is frequently diagnosed at an advanced stage, limiting opportunities for prevention. This study aimed to develop a concise and accessible early detection model using routine complete blood count (CBC) parameters. METHODS: A retrospective longitudinal analysis was conducted using annual health examination data from 807 Indonesian coal miners collected between 2013 and 2021. An artificial neural network (ANN) model was developed and internally validated, with further validation using Cox proportional hazard regression. RESULTS: The cumulative incidence of black lung disease was 13.9%. Eosinophil and monocyte levels consistently emerged as the most influential predictors in both models, with adjusted hazard ratios of 1.286 (95% CI: 1.254-1.319) and 1.136 (95% CI: 1.034-1.247), respectively. The ANN demonstrated high internal predictive performance. CONCLUSION: These findings indicate that routinely collected CBC parameters, particularly eosinophils and monocytes, may serve as practical biomarkers for early identification of black lung disease in high-risk occupational populations. Integrating CBC-based screening into occupational health surveillance could strengthen early detection and prevention strategies.
Annals of medicineJingyue Li, Xiaojuan Li, Tiewei Li, Zhuo Qian, Yiming Peng, Yixin Xu, Pengfei Xuan, Zhipeng Jin
OBJECTIVE: Neutrophils and albumin are established inflammatory biomarkers closely linked to the risk of sepsis. Previous research has indicated that an elevated neutrophil percentage-to-albumin ratio (NPAR) is correlated with an increased risk of all-cause mortality in critically ill patients with severe sepsis or septic shock. However, its application in infants remains underexplored. Therefore, this study aims to investigate the association between NPAR and infant sepsis. METHODS: In this study, 320 infants with suspected sepsis were enrolled. Of these, 215 were ultimately diagnosed with sepsis and categorized into the sepsis group, while the remaining 105 infants were placed in the control group. Clinical and laboratory data were comprehensively collected from electronic health records. A multivariate logistic regression analysis was employed to identify potential independent risk factors for sepsis in infants. Statistical analyses were performed using SPSS version 26.0. RESULTS: Compared to the control group, infants in the sepsis group exhibited higher NPAR levels (p < 0.05). The infants were then divided into three groups based on NPAR tertiles. The analysis demonstrated that the overall incidence of sepsis increased from 57.5% in the first group (NPAR < 1.30) to 76.2% in the third group (NPAR > 1.81). Furthermore, correlation analysis revealed a positive association between NPAR and markers of infection and inflammation, such as C-reactive protein and procalcitonin. Multivariate logistic regression analysis identified NPAR as an independent risk factor for sepsis in infants, with an odds ratio of 1.554 (95% CI: 1.058-2.283, p < 0.05). CONCLUSION: NPAR is positively and independently associated with the presence of infant sepsis.
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal ObstetriciansGilmar de Souza Osmundo, Rosa Maria de Souza Aveiro Ruocco, Stela Verzinhasse Peres, Rossana Pulcineli Vieira Francisco
OBJECTIVES: To evaluate clinical and immunological characteristics associated with adverse perinatal outcomes among pregnant people living with HIV (PPLH). METHODS: This retrospective cohort study included singleton pregnancies of PPLH followed between 2006 and 2019 at a Brazilian tertiary referral center for high-risk pregnancies. Clinical and HIV-related data, including viral load (VL), CD4+ cell count, lymphopenia, and opportunistic infections (OI), were obtained from medical records. The primary endpoint was a composite adverse perinatal outcome defined as preterm birth (PTB) and/or low birth weight (LBW). Multivariable logistic regression was performed to identify factors independently associated with adverse outcomes. RESULTS: A total of 167 pregnancies were analyzed. The prevalence of the composite adverse perinatal outcome was 28.1%. Adverse outcomes were associated with previous opportunistic infection (p = 0.049), gestational opportunistic infection (p = 0.019), higher baseline viral load (p = 0.049), baseline lymphopenia (p = 0.002), lower body mass index (p = 0.044), lower CD4 cell count at 34 weeks (p = 0.014), and lack of viral suppression at 34 weeks (p = 0.008). In multivariable analysis, baseline VL (adjusted OR = 1.73, 95% CI = 1.10-2.99) and baseline lymphopenia (adjusted OR = 7.67, 95% CI = 1.37-42.8) remained independently associated with adverse perinatal outcomes. CONCLUSIONS: Adverse perinatal outcomes remain frequent among PPLH. Baseline viral load and lymphopenia were independently associated with PTB and/or LBW, highlighting the importance of early viral suppression and immune stabilization during pregnancy.
European journal of gastroenterology & hepatologyJiejie Xie, Xiong Pei, Longyan Wang, Xiaopu Ma, Yan Xie
BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is characterized by acute decompensation and high short-term mortality. We investigated whether the albumin-bilirubin (ALBI) score, model for end-stage liver disease (MELD) score, and platelet-albumin-bilirubin (PALBI) score independently predict major ACLF complications. METHODS: This retrospective cross-sectional study enrolled 2104 ACLF patients (2017-2024) fulfilling Asian Pacific Association for the Study of the Liver 2019 criteria. ALBI, MELD, and PALBI were calculated within 48 h of admission. Multivariable logistic regression, restricted cubic spline, and receiver operating characteristic (ROC) analyses assessed associations with ascites, hepatic encephalopathy, hepatorenal syndrome (HRS), coagulopathy, splenomegaly, and spontaneous bacterial peritonitis. RESULTS: All three scores increased significantly with worsening Child-Pugh class (P < 0.001). Per SD increase, ALBI predicted all six complications with adjusted odds ratios (ORs) ranging from 1.98 to 8.73. MELD showed similar predictive ability (ORs: 2.58-7.26). PALBI quartiles 2 and 3 remained significantly associated with HRS (P = 0.007 and P = 0.011, respectively). Restricted cubic spline revealed nonlinear dose-response relationships (P-nonlinearity < 0.005). ROC area under the curve values were consistently higher for MELD than ALBI and PALBI. Subgroup analyses confirmed stability across age, sex, BMI, smoking, and alcohol use. CONCLUSION: ALBI, MELD, and PALBI scores simply and reliably identify ACLF complications, helping clinicians intensify monitoring and tailor therapy for high-risk patients.
BACKGROUND: Perforated necrotizing enterocolitis (PNEC) is a lethal complication in preterm infants with high mortality, but timely identification and prognostic stratification remain clinically challenging. METHODS: This retrospective cohort study analyzed 110 preterm infants with surgical NEC admitted between 2023-2025, stratified into non-intestinal perforation (NIP group, n = 55) and PNEC (n = 55) subgroups. Correlation, multivariate logistic regression, mediation, and receiver operating characteristic (ROC) curve analyses were performed. RESULTS: Compared with the NIP group, the PNEC group had significantly higher lactate (6.0 vs. 3.9 mmol/L), mean platelet volume (MPV, 12.20 vs. 10.79 fL), neonatal Sequential Organ Failure Assessment (nSOFA, 5.0 vs. 2.0), and mortality (27.3% vs. 10.9%) (all p < 0.05). Multivariate regression identified lactate (OR = 1.218) and MPV (OR = 1.725) as independent risk factors for PNEC. Mediation analysis showed lactate exerted 32.53% indirect effect on PNEC via MPV, and nSOFA mediated 23.95% of lactate's effect on mortality. The combination of lactate + MPV + nSOFA outperformed single markers in predicting PNEC (AUC = 0.800) and mortality (AUC = 0.949). CONCLUSIONS: The combination of lactate, MPV, and nSOFA exhibits synergistic predictive value for PNEC and its associated mortality. Lactate and MPV identify early perforation risk, while nSOFA stratifies mortality risk. This combination provides clinical utility for the early intervention of high-risk neonates with NEC.
Microbial pathogenesisDayat Hidayat, Ilham Saiful Fauzi, Nuning Nuraini
The immune response plays a crucial role in eliminating dengue virus infection from the human body. Both humoral and cellular immune responses are naturally involved in combating the virus. This study presents a mathematical model that captures the dynamics of humoral and cellular immune responses to dengue virus infection, incorporating key interactions between B cells, T cells, and viral particles. Additionally, the model considers hematocrit level as an indicator of disease severity, which is influenced by the interaction between the virus and immune responses. The basic reproduction number is derived, and the existence of equilibrium points are analyzed. Numerical simulations show that hematocrit levels can increase by up to 30% from the normal level and peak approximately two days after the peak of viremia. The results also indicate that although humoral and cellular responses activate together, the humoral response acts earlier as the first line of defense. The insights from this research enhance understanding of immune dynamics in dengue infection and support the development of targeted clinical interventions.
Coagulation factor VII (FVII) is a vitamin K-dependent glycoprotein and serves as a key initiator of the extrinsic coagulation pathway. Hereditary FVII deficiency is an autosomal recessive genetic disorder with a highly heterogeneous bleeding phenotype. It is the most prevalent among rare hereditary bleeding disorders. Among the various genotypes, complex heterozygous variants are of particular importance in hereditary coagulation factor deficiency. This study reports a case of a patient with hereditary FVII deficiency. The patient presented for planned surgery for renal cysts. Preoperative evaluation revealed abnormal coagulation indicators; therefore, the surgery was temporarily postponed. Further investigations to clarify the cause revealed markedly prolonged prothrombin time (PT), significantly reduced FVII activity (FVII:C), and mildly decreased FVII antigen (FVII:Ag). Complex heterozygous variants (p.Ile303Thr and p.Cys389Gly) were identified, confirming the diagnosis of hereditary FVII deficiency. Thrombin generation assay (TGA) and thromboelastography (TEG) suggested that the patient's global coagulation capacity was not substantially impaired. No specific treatment was administered, and regular follow-up was conducted. In this compound heterozygous patient with markedly reduced FVII:C without bleeding, TGA and TEG may offer a better assessment of bleeding risk than FVII:C alone, and family screening facilitates identification and management of at-risk individuals.
Journal of the neurological sciencesMeltem Karadeniz, Robb Wesselingh, Padmakrishnan C Jayakrishnan, Richard P Sequeira, Marie Estupin, Foong Yi Chao, Michael Zhong, Wei Yeh, Tomas Kalincik, Anne…
Multiple sclerosis (MS) relapse diagnosis is impeded by 'pseudo-relapses' whilst relapse treatment lacks specificity. Before we can improve clinical care, we must first improve our understanding of relapse pathogenesis. Currently, the circulatory immune mechanisms underpinning relapse are poorly understood. We aimed to determine changes in circulatory cell counts from people with MS during relapse versus remission and their association with clinical outcomes. Data was collected retrospectively by screening 2316 patient files through which we identified 78 episodes of MS relapse and remission. From these participants full blood examination data, we calculated immune cell counts and ratios. In participants with contrast enhancing lesions on magnetic resonance imaging (MRI, n = 38), total neutrophil count (p = 0.04) and neutrophils/total white cell count (N%) was higher (p = 0.04) in relapse versus remission. Similarly, in participants with a new lesion on MRI (n = 51), total neutrophil count (p = 0.01) was significantly higher during relapse versus remission. Univariable regression analyses demonstrated that lymphocytes, the neutrophil to lymphocyte ratio, monocytes/total white cell count (M%) and N% were all associated with changes in disability scores whilst multivariable regression analyses demonstrated that M% was associated with the presence of contrast enhancing lesions. This study determined that neutrophils are elevated in the circulation of people with MS during relapse compared to remission. Additionally, neutrophils, monocytes and lymphocytes were found to be associated with clinical outcomes of relapse. These findings support the notion that alterations in circulating immune cells may play a role in MS relapse pathogenesis and may inform future biomarker studies.
Sleep medicineFabio Poersch Pavia, Dalva Poyares, Monica Levy Andersen, Sergio Tufik, Daniela Santoro Rosa, Ana Flavia Popi
Sleep disruption and psychological stress influence immune dynamics, but the cross-sectional immune correlates of this interaction in healthy adults remain unclear. We investigated whether sleep disturbance and stress were associated with variation in lymphocyte counts in the absence of overt inflammation. The study was performed using data from the São Paulo Epidemiological Sleep Study (EPISONO). All participants included had undergone full-night polysomnography and completed validated sleep and fatigue questionnaires. Lymphocyte counts, bedtime salivary cortisol, plasma interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor alpha (TNF-α) were quantified. Lymphocyte counts were examined continuously and across physiologically defined strata. Lower sleep efficiency, longer sleep latency, and greater insomnia severity were each associated with higher lymphocyte counts. N1 was the sleep-stage parameter most consistently associated with lymphocyte variation. Elevated bedtime salivary cortisol concentrations were associated with lower sleep efficiency but not with lymphocyte counts, whereas IL-6, IL-10, and TNF-α did not show a consistent association with lymphocyte variation. Fatigue ratings showed a weaker pattern, with participants reporting general fatigue exhibiting the highest lymphocyte counts. These findings suggest that subtle reductions in sleep continuity are associated with mild, non-inflammatory increases in lymphocyte counts, supporting a physiological association between sleep-stress physiology and circulating lymphocyte variation in otherwise healthy adults.
Journal of infection and public healthWenjun Kang, Yueming Shao, Zhenyan Wang, Tangkai Qi, Jianjun Sun, Junyang Yang, Shuibao Xu, Wei Song, Youming Chen, Yang Tang, Li Liu, Renfang Zhang, Jun Chen
BACKGROUND: Tuberculosis (TB) remains the leading cause of death among people living with HIV (PLWH). While tuberculosis preventive treatment (TPT) is universally recommended for PLWH with latent TB infection (LTBI), its necessity for interferon-gamma release assay (IGRA)-negative individuals initiating antiretroviral therapy (ART) is controversial. Therefore, this study aimed to investigate whether TPT is necessary in this specific population. METHODS: We conducted a retrospective cohort study of ART-naïve PLWH with a negative IGRA without prior anti-tuberculosis drug use or active TB at Shanghai Public Health Clinical Center from 2020 to 2024. Demographic characteristics, laboratory results, and TB occurrence during follow-up were recorded. Kaplan-Meier analysis, Cox proportional hazards models, and restricted cubic splines were used to identify risk factors and model the dose-response relationship between CD4 + T-cell count and TB risk. RESULTS: Among 686 participants (89.4% male, median age 41), the median CD4 + T-cell count was 35.52 cells/µL. During a 26-month median follow-up, 22 patients developed TB (incidence: 13.41/1000 person-years). All TB cases occurred in the 583 patients with CD4 + T-cell count < 200 cells/µL (incidence: 15.61/1000 person-years), while no events occurred in those with CD4 + T-cell count ≥ 200 cells/µL. Lower CD4 + T-cell count and residence in high-risk areas (adjusted Hazard Ratio [aHR] = 3.65, 95% CI: 1.35-9.89) were independent risk factors for active TB. A continuous log-linear inverse relationship between CD4 + T-cell count and TB risk was identified, with progressively higher risk at lower CD4 levels. CONCLUSION: IGRA-negative PLWH with CD4 + T-cell count < 200 cells/µL and high-risk area residence may be considered as priority candidates for TPT. This risk-stratification framework warrants prospective validation.