Biochemia medicaJia-Min Zou, Tian-Ji Li, Qi Liu, Yong-Gang Hu
The International Normalized Ratio (INR), introduced by the World Health Organization in 1983, is central to vitamin K antagonist (VKA) therapy monitoring. However, thromboplastin standardization alone does not ensure harmonized prothrombin time (PT)/INR results. Residual variability arises throughout the testing continuum. In this narrative review, we examine the principal sources of residual PT/INR non-equivalence across the "vein-to-report" pathway. Particular attention is devoted to clinical settings in which the assumptions underlying INR calibration are only partially satisfied, including advanced liver disease and exposure to direct oral anticoagulants. We further discuss postanalytical factors, such as determination of the mean normal prothrombin time and system-specific verification of the International Sensitivity Index, as well as quality assurance strategies, including the use of commutable external quality assessment materials and patient-based real-time quality control. Prothrombin time/INR harmonization requires integrating preanalytical practices, recognizing reagent-instrument dependencies, and quality strategies reflecting real-world testing conditions.
The Journal of international medical researchShenglan Liu, Shiyun Fu, Shengjie Zhang, Chengyu Zhang
ObjectiveTo assess the association between platelet percent-decrease patterns during the first 168 h after intensive care unit admission and 28-day mortality after a day-7 landmark among intensive care unit patients with a diagnosis of heart failure.MethodsThis retrospective cohort study used Medical Information Mart for Intensive Care IV (MIMIC-IV) version 3.1 records from one US center (2008-2022). The day-7 risk set comprised patients who were not recorded as having died before the landmark. Platelet percent decrease from the first to the last available daily mean during the first 168 h was categorized as stable/increase, percent decrease ≤0%; mild decline, percent decrease >0% and ≤30%; or marked decline, percent decrease >30%. Logistic regression was used to estimate odds ratios for 28-day mortality after the landmark. Supportive analyses examined measurement processes, alternative platelet definitions, narrower heart-failure coding, and an independent 72-h landmark.ResultsAmong 14,762 platelet-classifiable patients in the day-7 risk set, 1736 died within 28 days after the landmark. Observed mortality was 8.66%, 13.14%, and 30.06% in the stable/increase, mild-decline, and marked-decline groups, respectively. Among 14,710 Model 3 complete cases (1729 deaths), adjusted odds ratios were 1.54 (95% confidence interval: 1.37-1.74) for mild decline and 3.51 (95% confidence interval: 2.99-4.12) for marked decline. Adjusted mortality probabilities were 9.08%, 13.07%, and 24.27%, respectively. For marked decline, the odds ratio was 2.69 after adjustment for measurement processes and 2.37 among patients who remained in the intensive care unit on day 7. In the independent 72-h analysis, odds ratios were 1.02 (95% confidence interval: 0.92-1.14) and 1.23 (95% confidence interval: 1.05-1.44).ConclusionsGreater platelet decline was associated with higher mortality after the day-7 landmark. The weaker associations at the 72-h landmark and attenuation after accounting for measurement processes indicate that the magnitude of this association depends on the observation window and may partly reflect prolonged critical illness and monitoring intensity.
Science progressLianzheng Ma, Shu Yang, Wei Liu, Shanchao Hong
ObjectiveTo assess the association of early red blood cell distribution width-to-albumin ratio (RAR) with mortality in mechanically ventilated ICU patients and its value alongside routine clinical assessment.MethodsThis retrospective cohort study used MIMIC-IV and eICU-CRD data. Adults receiving invasive mechanical ventilation within 24 hours of ICU admission who remained in the ICU at 24 hours were included. RAR was calculated from first-day laboratory measurements. Multivariable Cox regression assessed its association with subsequent in-hospital and ICU mortality. Additional analyses examined whether RAR improved prediction beyond its components and established severity scores.ResultsThe study included 3,534 MIMIC-IV patients and 1,929 eICU-CRD patients. Compared with the lowest RAR quartile, the highest quartile was associated with greater in-hospital mortality in both databases (adjusted HR 1.855, 95% CI 1.474-2.335, and HR 1.698, 95% CI 1.231-2.341, respectively). The corresponding ICU mortality association was significant in MIMIC-IV but not in eICU-CRD. Adding RAR to clinical models improved discrimination and reclassification for in-hospital mortality, with performance similar to including RDW and albumin separately. Improvements beyond severity scores varied by outcome and measure.ConclusionsHigher first-day RAR was associated with subsequent in-hospital mortality among mechanically ventilated adults in two ICU databases. RAR may provide supplementary prognostic information, although its role in clinical decisions requires prospective evaluation.
BMJ case reportsAboobacker Mohamed Rafi, Siju V Abraham, Susheela J Innah, Punchalil Chathappan Rajeev
Snakebite-associated coagulopathy is usually attributed to venom-induced consumption of clotting factors, but underlying mechanisms may be heterogeneous and not reliably detected by conventional coagulation tests. A man in his late 40s presented early after Russell's viper envenomation with local signs and a prolonged bedside modified Lee and White clotting time despite normal prothrombin time and activated partial thromboplastin time. Given this discordance, rotational thromboelastometry (ROTEM) was performed at admission. Extrinsically activated thromboelastometry (EXTEM) demonstrated rapid and complete clot lysis, while tranexamic acid-modified antifibrinolytic thromboelastometry (t-APTEM) showed restoration of clot stability with inhibition of fibrinolysis, supporting a hyperfibrinolytic component.The patient was managed with antivenom and supportive care, including plasma transfusion, with subsequent resolution of coagulopathy and an uncomplicated recovery. This report establishes a diagnostic and mechanistic framework for systematic evaluation of fibrinolysis in snakebite-associated coagulopathy and highlights that the role of antifibrinolytic therapy requires further exploration in patients demonstrating evidence of hyperfibrinolysis.
Immunologic researchJosé Roberto Mendes Pegler, Débora Linhares Rodrigues, Renata de Almeida Bordim, Patricia Palmeira, Andréia Rangel-Santos, Isabela de Jesus Silva Avelar, Ana C…
Early thymectomy during congenital heart disease repair may impair thymic output, but long-term effects across age groups remain incompletely defined. We evaluated T-cell receptor excision circles (TRECs) and a comprehensive panel of lymphocyte subsets in 20 adults (mean age, 29.6 years) and 16 children (mean age, 10.7 years) who underwent thymectomy within the first year of life, and in age- and sex-matched controls. TRECs were lower in patients than controls in adults (34 ± 25 vs. 79 ± 45 copies/μL; FDR-adjusted p = 0.001) and children (9 [7-15] vs. 95 [65-160] copies/μL; FDR-adjusted p < 0.0001). Total lymphocyte and T-cell counts were reduced in both age groups, mainly due to lower naïve CD4⁺ and CD8⁺ T cells, including recent thymic emigrants. Most non-naïve subsets did not differ significantly from controls. Regulatory T-cell (Treg) alterations differed by age: children showed broad reductions, whereas adults showed selective naïve Treg reduction. Early thymectomy is associated with persistent thymic output impairment, including in adults approximately three decades after surgery, and with age-specific Treg alterations.
The Journal of international medical researchJian Niu, Yinhua Gong, Juanjuan Cui, Xiaoping Huang, Yiling Zhu
BackgroundSepsis is a significant public health concern associated with high prevalence and mortality rates. This study aimed to evaluate the prognostic value of platelet count, plateletcrit level, mean platelet volume, and platelet distribution width in patients with sepsis.MethodsThe study cohort included 48 patients diagnosed with sepsis, who were allocated to the sepsis group, and 34 patients admitted with infections who did not meet the diagnostic criteria for sepsis, who were allocated to the infection group. Complete blood count was performed for all patients, which included evaluation of platelet count and other parameters (plateletcrit level, mean platelet volume, and platelet distribution width) as well as C-reactive protein levels within 24 h of admission and again on days 3 and 7. Patients in the sepsis group were monitored until discharge or death and categorized into two subgroups based on outcomes: survivors (39 patients) and nonsurvivors (9 patients).ResultsStatistically significant differences were identified in the platelet count, plateletcrit level, mean platelet volume, and platelet distribution width between the sepsis and infection groups (all p < 0.05). Platelet count and plateletcrit level exhibited negative correlations with the Sequential Organ Failure Assessment score (r = -0.657 and -0.638, all p < 0.05), whereas mean platelet volume and platelet distribution width exhibited positive correlations (r = 0.331 and 0.298, all p < 0.05). Additionally, platelet count and plateletcrit level were inversely associated with C-reactive protein levels (r = -0.346 and -0.327, all p < 0.05). Receiver operating characteristic curve analysis revealed that platelet counts had the highest diagnostic value for sepsis, with an area under the curve of 0.864, sensitivity of 94.12%, and specificity of 73.47%. In the dynamic monitoring of platelet parameters, significant differences in platelet count and plateletcrit level were observed in the prognosis group by day 7.ConclusionAdmission platelet count and related parameters serve as specific diagnostic predictors of sepsis. Dynamic monitoring of platelet count and plateletcrit level on day 7 can guide aggressive management strategies to improve outcomes in patients with sepsis.
BMJ case reportsLiran Shechtman, Carolyn M Tan, Christophe Langlois, David Nelson Juurlink
A man in his early 60s presented with dyspnoea superimposed on a 2-month to 3-month history of spontaneous mucocutaneous bleeding. Laboratory testing revealed unmeasurably elevated international normalised ratio (INR) and activated partial thromboplastin time. CT of the neck demonstrated supraglottic soft tissue swelling with severe airway narrowing, requiring intubation for airway protection. Further history revealed occupational exposure to rodenticides during pest control work without consistent use of personal protective equipment. Markedly reduced activity of vitamin K-dependent clotting factors (II, VII, IX and X) supported a presumptive diagnosis of superwarfarin toxicity. Treatment with 4-factor prothrombin complex concentrate and vitamin K1 rapidly corrected the coagulopathy, although prolonged high-dose oral vitamin K1 was required because of recurrent INR elevation. He was discharged after 9 days and completed a 3-week vitamin K1 taper. This case highlights a rare presentation of presumed transdermal superwarfarin toxicity causing life-threatening coagulopathy and airway compromise.
INTRODUCTION: We sought to clarify the interference of red blood cell (RBC) and platelet (PLT) parameters on PLT count by impedance method results and establish an intelligent reflex fluorescence PLT count (PLT-F) confirmation model using PLT-F as the reference to quantify the model's clinical efficacy. METHODS: A retrospective analysis was performed on routine blood data from 11 283 patients (June 2023 to February 2024) at our hospital. Patients were stratified into a training set (n = 7898) and verification set (n = 3385) using Laboman AI, version 1.0-312, software (Shanghai Hyson Meikang Medical Electronics Co Ltd). A decision tree algorithm was employed to construct a new model that integrates RBC and PLT parameters for reflex PLT-F confirmation, and the model's effectiveness was evaluated. RESULTS: The combined 3-factor model achieved optimal performance for PLT-F reflex confirmation. Its overall false-negative proportion, release rate, total effective rate, and negative predictive value reached 2.9%, 55.2%, 71.1%, and 94.7%, respectively, in the training set, with matching values of 4.2%, 52.4%, 66.1%, and 91.9%, respectively, in the validation set. DISCUSSION: This study established a novel reflex PLT-F confirmation model based on RBC and PLT parameters. The model achieved a 52.4% sample release rate, with a corresponding overall false-negative proportion of 4.2% in the validation set, presenting a clear trade-off between laboratory operational efficiency and diagnostic safety.
BMJ openXin-Yi Shou, Qing Xiang, Jun Liang, Na Wu, Rui Yang, Yan-Min Wu, Jing Zhang, Yi-Ding Li, Yu-Ding Jiao, Dong-Yang Chen, Xiao-Long He, Jun Yang, Ye Fan
INTRODUCTION: Chronic mountain sickness (CMS) is a clinical syndrome affecting more than 4 million individuals living at high altitudes, primarily characterised by excessive polycythaemia. Current CMS consensus recommends therapies targeting haematocrit (HCT), such as phlebotomy or isovolemic haemodilution. However, the clinical benefit of HCT-reduction strategies in CMS has yet to be established. This trial aims to evaluate whether erythrocytapheresis, regarded as one of the most precise and effective approaches for HCT-reduction, could improve clinical outcomes in patients with CMS. METHODS AND ANALYSIS: Efficacy and safety of erythrocytapheresis in chronic mountain sickness is an investigator-initiated, multicentre, randomised controlled superiority trial with blinded outcome assessment. A total of 112 eligible CMS patients will be consecutively randomised to receive either standard care alone or standard care plus erythrocytapheresis with a 1:1 ratio. The primary efficacy endpoint is the net change in CMS symptom score assessed at 48 hours post-erythrocytapheresis or prior to discharge for controls. The primary safety outcome is treatment-related adverse events before discharge. The primary outcome will be analysed using an analysis of covariance, with a clinical threshold for superiority. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Medical Ethics Committees of the coordinating centre (Xinqiao Hospital, 2020-014-02) and each participating centre. Written informed consent will be acquired prior to enrolment. The trial results will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT04557995.
Journal of Korean medical scienceEunKyung Nam, Jun Yong Choi, Jung Ho Kim, Young Keun Kim, Sang Il Kim, Dae Won Park, Won Suk Choi, Jin-Soo Lee, Joon Young Song, Boyoung Park, Sunghee Hong, Ky…
BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic disrupted healthcare delivery worldwide, raising concerns about continuity of care for people living with HIV (PLWH). However, its long-term effect on HIV treatment outcomes in resource-rich settings with robust public health infrastructure remains unclear. Therefore, this study aims to evaluate the effects of the COVID-19 pandemic on virological outcomes, immunological status, healthcare utilization, medication adherence, and mortality among PLWH enrolled in the Korea HIV/AIDS Cohort. METHODS: A retrospective longitudinal analysis was conducted using the Korea HIV/AIDS Cohort data collected between 2018 and 2023. Outcomes during the pre-pandemic (2018-2019) and pandemic (2020-2023) periods were compared. The primary outcome was virological failure, defined as an HIV RNA level ≥ 200 copies/mL. Secondary outcomes included CD4+ T-cell count, opportunistic infections, visit adherence (≥ 2 clinic visits/year), all-cause mortality, and visual analog scale-assessed self-reported medication adherence. Repeated-measures analyses were performed using generalized estimating equations with an exchangeable correlation structure, adjusted for age and sex. Mortality risk was evaluated using Cox proportional hazards models, with subgroup and sensitivity analyses also performed. RESULTS: Overall, 1,674 patients contributed 9,721 visits. Virological failure decreased from 3.2% pre-pandemic to 1.2% during the pandemic (adjusted odds ratio [OR], 0.37; 95% confidence interval [CI], 0.27-0.50; P < 0.001). CD4+ T-cell counts were higher during the pandemic (β = +33.2 cells/mm³; 95% CI, 23.3-43.1; P < 0.001). Medication adherence improved from 85.3% to 90.2% (adjusted OR, 1.58; P < 0.001), despite reduced visit adherence (81.6% to 60.5%; adjusted OR, 0.49; 95% CI, 0.45-0.54; P < 0.001). All-cause mortality did not differ between periods (hazard ratio, 0.32; 95% CI, 0.07-1.51; P = 0.151), with consistent findings across subgroup and sensitivity analyses. CONCLUSION: Despite reduced clinic utilization during the COVID-19 pandemic, PLWH in Korea maintained or improved virological and immunological outcomes. These observational findings support the feasibility of less intensive monitoring for selected virologically stable individuals. However, given the potential for survivorship bias and unmeasured confounding, prospective studies are required before changes to monitoring practice can be recommended.
Severe Factor V deficiency (parahaemophilia) is a rare autosomal recessive coagulation disorder with a highly variable clinical phenotype. We report the incidental detection of isolated severe Factor V deficiency (<1% activity) in a completely asymptomatic primigravida during routine preoperative evaluation prior to an elective caesarean section. Despite marked prolongation of prothrombin time and activated partial thromboplastin time, the patient had no prior bleeding history. Mixing studies and a normal thrombin time localised the defect to the common pathway, which was confirmed by factor assay. Management involved multidisciplinary planning, peri-operative fresh frozen plasma transfusion and avoidance of neuraxial anaesthesia. The patient underwent caesarean section under general anaesthesia and delivered a healthy neonate without maternal or neonatal complications. This case highlights the poor correlation between plasma Factor V levels and bleeding phenotype and underscores the diagnostic value of thrombin time in evaluating common pathway coagulation defects.
Journal of Korean medical scienceYoung Rong Kim, Ji Hyun Park, Eun Jin Kim, Hakjun Hyun, Young Hwa Choi, Jung Yeon Heo
BACKGROUND: The widespread use of antiretroviral therapy (ART) has shifted a change in hospitalization patterns among people with HIV. However, long term trends and causes of hospitalization among people with HIV (PWH) in Korea remain underexplored. This study aimed to investigate 20-year trends in hospitalization rates and causes among PWH. METHODS: We retrospectively analyzed hospitalization data from 803 PWH aged ≥ 18 years who received care at the university-affiliated hospital from 2001 to 2020. Hospitalization data were examined across five 4-year intervals. Hospitalization rates per 100 person-years (PY) were estimated using generalized estimating equation models with a Poisson distribution, adjusting first for sex and age and then baseline CD4 T cell count and HIV viral load. Cox regression identified predictors of first hospitalization. RESULTS: Over 3,998 PY, 593 hospitalizations occurred among 322 patients. Unadjusted all-cause hospitalization rates declined from 92.3 to 8.6 per 100 PY, driven by significant reductions in AIDS-defining illnesses (-79.0% per period; 95% confidence interval [CI], -94.8 to -63.1) and non-AIDS infections (-48.4% per period; 95% CI, -63.3 to -33.5). Maternal conditions increased from 0 to 0.67 per 100 PY, with a mean change of 91.3.% per period (95% CI, 41.3-141.2), whereas most of the other chronic conditions and trauma/injury remained stable. Fully adjusted models demonstrated similar trends in most of the categories. Anal condyloma emerged as a leading causes of hospitalization in the later periods. Multivariate analysis revealed that age ≥ 50 years (adjusted hazard ratio [aHR], 1.42; 95% CI, 1.05-1.92), CD4 counts < 100 cells/mm³ (aHR, 2.48; 95% CI, 1.74-3.53), and HIV RNA > 100,000 copies/mL (aHR, 1.61; 95% CI, 1.13-2.30) at enrollment were associated with a higher hospitalization risk. CONCLUSION: Hospitalization rates among Korean PWH have declined substantially over two decades, primarily driven by a decline in opportunistic infections, attributable to earlier diagnosis and expanded ART access. However, persistent AIDS-related illnesses and the high proportion of non-AIDS-defining cancers diagnosed at advanced stage highlight the ongoing need for earlier HIV detection and a stigma-free healthcare environment that promotes care engagement for PWH.
BACKGROUND: Insulin resistance (IR) is a key mechanism underlying type 2 diabetes mellitus and cardiometabolic disease. Although obesity-related inflammation is a major contributor to IR, increasing evidence indicates that IR may also develop in non-obese individuals. However, readily available inflammatory markers applicable to this population remain limited. We evaluated the association between inflammatory markers and insulin resistance in non-obese adults and assessed their predictive performance across body mass index (BMI) strata. METHODS: This retrospective cross-sectional study included 149 non-obese adults (BMI < 30 kg/m2) evaluated in an internal medicine outpatient clinic between January and December 2025. Insulin resistance was defined as a homeostasis model assessment of insulin resistance (HOMA-IR) ≥ 2.5. Inflammatory markers and composite indices, including the C-reactive protein to high-density lipoprotein cholesterol (CRP/HDL) ratio, were calculated. Multivariable logistic regression, BMI-stratified analyses, and receiver operating characteristic (ROC) curve analyses were performed. RESULTS: Insulin resistance was identified in 54 participants (36.2%). Individuals with IR had higher white blood cell (WBC) counts, CRP levels, and CRP/HDL ratios (all p < 0.05). In multivariable analysis, WBC count was independently associated with IR (OR = 1.407, 95% CI [1.090-1.815]; p = 0.009). BMI-stratified analyses showed that WBC count independently predicted IR in normal-weight individuals (OR = 1.789, 95% CI [1.218-2.627]; p = 0.003), whereas in overweight participants (BMI 25-30 kg/m2), the CRP/HDL ratio was independently associated with IR (OR = 7.793, 95% CI [1.056-57.499]; p = 0.044). ROC analyses demonstrated higher discriminative performance of WBC count in normal-weight individuals (AUC = 0.720) and greater predictive ability of the CRP/HDL ratio in overweight individuals (AUC = 0.695). CONCLUSIONS: Low-grade systemic inflammation is independently associated with insulin resistance in non-obese adults, with distinct inflammatory predictors across BMI categories. WBC count may reflect early immune activation in normal-weight individuals, whereas the CRP/HDL ratio appears more informative among overweight subjects.
Veterinary research communicationsMelissa Harumi Sumiyoshi, Eva Munyque da Cruz, Morgana Maira Hennig, Marcela Natacha Aparecida Rocha, Kayana Mota Caribé de Figueiredo, Nathália Soares Lima Ra…
Increasing and unplanned urbanization can intensify wildlife contact with humans and domestic animals, raising concerns about the spillover of zoonotic pathogens. Bats play a relevant ecological role due to their great niche diversity and wide distribution, and may act as reservoirs for various pathogens. Despite their importance, hematological values for non-hematophagous bats remain limited, hindering the assessment of their health and physiological responses. This study characterized hematological parameters and blood cell morphology in Artibeus planirostris captured in urban green areas of Cuiabá, Brazil, and evaluated agreement between automated and manual hematological methods. Blood samples from 24 bats were analyzed using an automated hematology analyzer, microhematocrit, cyanmethemoglobin assay and blood smear microscopy for differential leukocyte counts, platelet estimation and morphological assessment. Erythrogram values were consistent with patterns previously reported in bats and may reflect physiological adaptations to flight metabolism. More than half of the individuals showed neutrophil predominance over lymphocytes; however, the influence of capture-related stress, infection and anesthetic effects could not be excluded. Bland-Altman and correlation analyses revealed variable agreement between automated and manual methodologies. Although some parameters showed good correlation, systematic biases and high variability indicated limited interchangeability between methods. These findings highlight the need for cautious interpretation of automated hematological analyses in bats and support the combined use of automated and manual approaches. Further studies with larger sample sizes are needed to improve method standardization and establish representative hematological reference data for bats in anthropized environments.
While the association between serum albumin and eosinophils has been investigated in adult asthma, its role in any pediatric atopic triad - asthma, allergic rhinitis, or atopic dermatitis - remains unclear. We assessed the association between serum albumin and blood eosinophil counts in adolescents presenting with any atopic triad, using data from a 2-year National Health and Nutrition Examination Survey (NHANES) cycle. We analyzed data from 658 participants aged 12-18 years with any atopic triad condition from the 2005-2006 NHANES cycle. Multivariate linear regression models were employed to assess the potential association between serum albumin levels and blood eosinophil counts (BEOC). Trend tests, smooth curve fitting, and threshold effect models were applied to confirm this relationship, and stratified analyses were conducted to assess its consistency across subgroups. A significant negative association was observed between serum albumin and BEOC in the fully adjusted model (β = -0.08 × 103 cells/µL, 95% CI: -0.15, -0.01, P = .018). Moreover, curve fitting and threshold effect analyses confirmed a nonlinear relationship between serum albumin and BEOC, with an inflection point for threshold and saturation effects of 4.4 g/dL, beyond which the association attenuated. Stratified analyses confirmed robustness across key subpopulations. Our study identified a nonlinear association between serum albumin levels and BEOC in adolescents with any atopic triad, exhibiting an L-shaped relationship. These findings highlight albumin as a potential biomarker for nutritional-immunological interplay in allergic inflammation and support targeted nutritional strategies in at-risk pediatric populations.
PulmonologyWang Chun Kwok, Kelvin Kai Wang To, Frankie Chi Fat Ko, Herbert Pang, Isaac Sze Him Leung, Wai On Tam, Chi Hung Chau, Anthony Shing Yiu Yu, Hon Cheung Fan, Cha…
BACKGROUND: Roflumilast demonstrated anti-inflammatory activity in COPD. While bronchiectasis is also characterised by neutrophilic inflammation, there is a lack of evidence on the use of roflumilast in bronchiectasis. METHODS: An open‑label observation study with an exploratory nature was conducted in Hong Kong. The primary outcome measure was 24-hour sputum volume. The extent of airway inflammation was indicated by sputum leucocyte density, pro-inflammatory cytokines and neutrophil elastase. All eligible patients were treated with roflumilast, starting at 250 µg daily with possible escalation to 500 µg daily if tolerated. RESULTS: A total of 39 patients were started on roflumilast with 24 (61.5%) completed 12 weeks of treatment and 9 of them escalated to 500 µg daily. There were no significant changes in mean daily sputum volume. The median sputum leucocyte density and TNF-α significantly decreased from the recruitment visit to 12 weeks. In extrapolatory analyses, patients with a baseline daily sputum volume ≥ 20 mL might be more likely to respond with a reduction in sputum volume. CONCLUSION: Roflumilast treatment in non-CF bronchiectasis could provide anti-inflammatory effects with a significant reduction in sputum leucocyte density and TNF-α level over 12 weeks of treatment. Extrapolatory analyses suggested potential benefits in sputum volume reduction among the subgroup with baseline daily sputum volume ≥ 20 mL.
Physiological reportsEdgar Cristancho-Mejía, Andrea Catalina Trompetero-Gonzalez, William Fernando Benavides-Pinzón, Walter Franz-Joachim Schmidt
Life at altitude is characterized by increased erythropoietic activity and hemoglobin concentration ([Hb]). The first aim of the project was to identify the altitudes at which significant increases in hemoglobin mass (Hbmass) and decreases in plasma volume (PV) occur among residents living at different altitudes. The second aim was to evaluate the extent to which Hbmass and PV contribute to changes in [Hb] at moderate altitudes. The study included 133 young men and 148 women from six Andean regions at altitudes ranging from 970 to 2600 m. Hbmass was determined using carbon monoxide rebreathing. PV was calculated using Hbmass, [Hb], and hematocrit. Hbmass increased up to 2600 m by 35.9 ± 11.6 g, while PV decreased by 208 ± 53 mL (both p < 0.01). The first significant increase in Hbmass occurred at 2180 m and the first significant decrease in PV occurred at 1730 m. At 2600 m, Hbmass and PV contributed equally to the 1.2 g/dL increase in [Hb], that is, 0.56 and 0.61 g/dL, respectively. The threshold for a decrease in PV in Andeans is ~450 m lower than the threshold for an increase in Hbmass. The contribution of hemoconcentration to the increase in [Hb] at moderate altitudes is equal to the contribution of erythropoiesis.
Liver international : official journal of the International Association for the Study of the LiverNiccolò Bitto, Giulia Tosetti, Armando Tripodi, Anna Lecchi, Silvia La Marca, Lidia Padovan, Erica Scalambrino, Marigrazia Clerici, Camilla Caputo, Martina Luc…
BACKGROUND & AIMS: Conventional laboratory tests do not capture platelet-vessel wall interactions (primary haemostasis) occurring in vivo, limiting guidance before invasive procedures. This is relevant in patients with thrombocytopenia, hallmark of advanced cirrhosis. Microfluidic assays may overcome these limitations. The Total Thrombus Analysis System (T-TAS) is a flow chamber that can be adapted for thrombocytopenic samples when equipped with the HD-CHIP. The CirTAS study aimed to assess T-TAS reproducibility and the ability to identify a disease-severity gradient in patients with cirrhosis and thrombocytopenia. METHODS: Eighty-one patients with cirrhosis and thrombocytopenia were enrolled (20 Child-Pugh A, 41 B/C and 20 B/C with bacterial infection). T-TAS measurements were performed using the HD-CHIP. Reproducibility was assessed by intraclass correlation coefficients. Thromboelastometry (ROTEM) parameters were analysed in parallel. Multivariable and piecewise regression analyses were performed to test factors influencing T-TAS parameters. RESULTS: T-TAS showed high reproducibility, with intraclass correlation coefficients ≈0.90 for all parameters (p < 0.001), even in platelet counts < 50 × 109/L. Thrombus formation under flow declined with worsening clinical status and presence of bacterial infection (p < 0.05). Alongside, ROTEM showed a trend towards hypocoagulability with increasing disease severity and correlated with T-TAS parameters. Platelet count and factor VIII (FVIII) were independent determinants of the most representative T-TAS parameters. Exploratory analyses detected a trend towards a stronger platelet count-T-TAS association at 30-50 × 109/L. CONCLUSIONS: T-TAS is reproducible in thrombocytopenic cirrhosis and is associated with reduced thrombus formation alongside disease progression and bacterial infection. Platelet count and FVIII are the main determinants of thrombus formation assessed by T-TAS.
Liver international : official journal of the International Association for the Study of the LiverNicola Pugliese, Davide Polverini, Arianna Bertazzoni, Federica Cerini, Grazia Pennisi, Rosa Lombardi, Valerio Gullace, Stella De Nicola, Chiara Masetti, Andre…
BACKGROUND AND AIMS: Non-invasive tests (NITs) are increasingly used to guide patient selection for pharmacological treatment of metabolic dysfunction-associated steatohepatitis (MASH). We aimed to quantify and compare real-world treatment eligibility according to the AASLD and expert panel-derived criteria and to evaluate classification of patients with available liver histology. METHODS: We retrospectively included 897 adults with MASLD from four Italian referral centres. Eligibility was assessed using AASLD criteria, defined by liver stiffness measurement (LSM) 8-15 kPa without cirrhosis, and expert panel-derived criteria, defined by LSM 10-19.9 kPa, platelet count ≥ 140 × 109/L, and no cirrhosis. A subgroup of 175 patients underwent liver biopsy within ±3 months of first referral. RESULTS: Median age was 62 years, 57.1% were men, 48.4% had obesity, and 36.0% had Type 2 diabetes. Overall, 202 patients (22.5%) met AASLD criteria and 114 (12.7%) met expert panel-derived criteria. Eighty-six patients were eligible according to both criteria, whereas 144 were classified differently. Type 2 diabetes and obesity were independently associated with eligibility under both criteria. In the biopsy subgroup, 73 patients had histological F2-F3 fibrosis; 35 (47.9%) did not meet AASLD criteria and 49 (67.1%) did not meet expert panel-derived criteria. CONCLUSIONS: The AASLD and expert panel-derived criteria identified different real-world populations potentially suitable for MASH pharmacotherapy. In the biopsy subgroup, NIT-based eligibility classification only partly aligned with histological F2-F3 fibrosis.
Ulusal travma ve acil cerrahi dergisi = Turkish journal of trauma & emergency surgery : TJTESBahattin Bayar, Ugurcan Bulut, Bilal Aydın, Abdulkadir Aktepe, Ahmet Alperen Yigitbasi, Sevinç Çetin, Feyza Savaş, Caganay Soysal, Rıfat Peksoz
BACKGROUND: Physiological and hematological changes during pregnancy may complicate the interpretation of conventional inflammatory markers in patients with suspected acute cholecystitis (AC). This study aimed to evaluate the association between mean platelet volume (MPV), derived from routine complete blood count analysis, and AC in pregnant patients and to investigate whether this association remained consistent across pregnancy trimesters. METHODS: This retrospective multicenter exploratory cohort study included 112 pregnant patients presenting with right upper quadrant pain between 2022 and 2025. According to retrospective classification based on the Tokyo Guidelines 2018 criteria, 89 patients were classified as AC and 23 as non-cholecystitis (NC). MPV and other hematological parameters were compared between the groups. Logistic regression analysis adjusted for pregnancy trimester was performed to evaluate the association between MPV and AC. Receiver operating characteristic (ROC) curve analysis with confidence intervals (CIs) was performed to assess the exploratory discriminative performance of MPV. RESULTS: MPV levels were significantly higher in the AC group than in the NC group (10.6 fL vs. 10.3 fL, p=0.034). In univariable logistic regression analysis, MPV was significantly associated with AC (odds ratio [OR]: 1.734, 95% CI: 1.203-2.500, p=0.003), and this association remained significant after adjustment for pregnancy trimester (OR: 1.870, 95% CI: 1.251-2.794, p=0.002). No significant associations were observed for white blood cell, neutrophil-to-lymphocyte ratio, platelet count, or platelet-to-lymphocyte ratio. ROC analysis demonstrated limited discriminative performance for MPV (area under the curve: 0.655). At the identified cut-off value of 8.70 fL, sensitivity was 95.2% and specificity was 36.4%. CONCLUSION: MPV was significantly associated with AC in pregnant patients; however, its limited discriminative performance and low specificity suggest that it should not be used as an independent diagnostic marker. MPV may provide supportive diagnostic value when interpreted together with clinical and ultrasonographic findings. Larger prospective studies including standardized MPV measurements and pregnancy-specific diagnostic frameworks are needed to better define the diagnostic role of MPV in pregnant patients with suspected AC.
OBJECTIVES: To investigate the association between peripheral platelet indices and motoric cognitive risk syndrome (MCR). DESIGN: A cross-sectional analysis using baseline data from the West China Health and Aging Trend (WCHAT) study. SETTING: Community settings across several ethnically diverse regions of western China. PARTICIPANTS: From an initial pool of 7536 community-dwelling adults in the WCHAT study, 4080 participants were included in the final analysis after applying exclusion criteria. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was MCR, defined by the concurrent presence of subjective cognitive complaints and slow gait speed (≥1 SD below sex- and age-stratified mean) in the absence of dementia or mobility disability. The exposures were platelet indices, including platelet count (PLT), mean platelet volume, platelet distribution width (PDW), platelet-large cell ratio (P-LCR) and platelet crit (PCT). Multivariable logistic regression was used to examine the associations between platelet indices and MCR. Restricted cubic spline analysis was performed to explore non-linear associations. RESULTS: Among the 4080 participants, 320 (7.84%) met the diagnostic criteria for MCR. After adjustment for potential confounders, higher PLT (OR=1.17, 95% CI 1.04 to 1.32, p=0.007) and PCT (OR=1.13, 95% CI 1.01 to 1.26, p=0.046) were associated with greater odds of MCR. Conversely, higher PDW (OR=0.85, 95% CI 0.75 to 0.97, p=0.014) and P-LCR (OR=0.87, 95% CI 0.77 to 0.98, p=0.026) were associated with lower odds of MCR. Furthermore, a nonlinear relationship was identified for PDW and MCR (p<0.05), with a threshold at 13.40%. CONCLUSIONS: Specific platelet indices are significantly associated with MCR. Further prospective studies are warranted to confirm these associations and explore the underlying mechanisms. TRIAL REGISTRATION NUMBER: China Clinical Trial Center (ChiCTR1800018895).
Anticancer researchHiroo Suto, Hibiki Sakai, A N Fujita, Marin Muramatsu, Ryosuke Wakamatsu, Ayaka Wakamatsu, Miki Katsuragawa, Mitsugu Tanaya, Kazuya Hiura
BACKGROUND/AIM: Neoadjuvant chemotherapy with gemcitabine plus S-1 (NAC-GS) is used for resectable pancreatic cancer, but adverse events prevent some patients from completing planned therapy. This study examined associations of pretreatment absolute neutrophil count (ANC) and prognostic nutritional index (PNI) with NAC-GS completion and the perioperative treatment course. PATIENTS AND METHODS: This single-center retrospective observational study included 93 patients with resectable pancreatic cancer who received NAC-GS from November 2019 to February 2025. NAC completion was defined as completing the two planned NAC-GS cycles, with or without dose reduction. Baseline hematologic, inflammatory, and nutritional parameters were assessed at NAC initiation. Multivariable logistic regression was used to examine factors associated with NAC discontinuation; receiver operating characteristic curve analysis determined ANC and PNI cutoff values. RESULTS: Of 93 patients, 39 completed NAC-GS and 54 discontinued before completion, with all discontinuations attributed to adverse events. ANC and PNI were independently associated with NAC discontinuation in multivariable analysis. Their cutoff values were 2.6×103/μl and 43, respectively. NAC completion rates were significantly higher with ANC ≥2.6×103/μl than with ANC <2.6×103/μl (52.0% vs. 30.2%, p=0.03) and with PNI ≥43 than with PNI <43 (52.6% vs. 25.0%, p<0.01). Combined ANC/PNI stratification showed stepwise decreases in NAC completion, overall R0 resection rate, and R0 resection rate among patients who underwent pancreatectomy. CONCLUSION: Pretreatment ANC and PNI were independently associated with NAC-GS completion. Combined ANC/PNI stratification may offer a simple pretreatment method for estimating NAC-GS completion and the perioperative treatment course.
BACKGROUND: Combination therapy comprising immune checkpoint inhibitors (ICIs) and chemotherapy is standard treatment for many cancer types. However, the management of adverse events (AEs) induced by combination therapy is more complicated than that of AEs induced by ICI monotherapy. Although immune-related AEs (irAEs) induced by ICIs and AEs induced by chemotherapy require distinct therapeutic approaches, distinguishing between them can be challenging. Therefore, in this exploratory study, we aimed to investigate whether lymphocyte proportion could serve as a candidate biomarker associated with the occurrence of irAEs in patients receiving ICI plus chemotherapy combination therapy. PATIENTS AND METHODS: We categorized 122 patients into the irAE group (those who experienced irAEs), chemo-AE group (those with chemotherapy-induced AEs), and non-AE group (those without AEs) and analyzed their lymphocyte proportions before one course (baseline sample) and two courses (two-course sample) of treatment. RESULTS: Lymphocyte proportions of the baseline samples did not differ between the non-AE, chemo-AE, and irAE groups. The lymphocyte proportion of the two-course sample of the irAE group was significantly higher than that of the non-AE group (25.8% vs. 21.9%; p < 0.05). The lymphocyte proportion of the two-course sample of the irAE group was significantly higher than that of the chemo-AE group (25.8% vs. 19.6%; p < 0.05). The multivariate logistic regression analysis showed that a lymphocyte proportion ≥ 23.9% in the two-course sample significantly increased the risk of irAEs (odds ratio = 3.04; p < 0.05). CONCLUSIONS: An increased lymphocyte proportion before the two courses of treatment was associated with the occurrence of irAEs and may serve as a candidate biomarker.
Journal of clinical apheresisHatice Gizem Gunhan, Onur Direk, Ismail Mustafa Avci, Fatma Arikan, Tayfur Toptas, Isik Atagunduz, Ayse Tulin Tuglular
Efficient peripheral blood stem cell (PBSC) collection from healthy donors is essential for transplantation success and donor safety. While hemoglobin is routinely used in donor evaluation, the contribution of iron-related biomarkers and red cell indices to predicting collection outcomes remains incompletely defined. In this retrospective cohort study, 143 healthy PBSC donors undergoing granulocyte colony-stimulating factor-mediated mobilization and apheresis were evaluated. Baseline hematologic parameters and iron-related biomarkers were analyzed in relation to weight-adjusted total CD34+ cell yield using correlation, threshold-based analyses, and multivariable modeling. The median donor age was 32 years, and 70.6% were male. The overall median CD34+ yield was 5.41 × 106/kg. Ferritin negatively correlated with CD34+ yield in male donors (r = -0.22, p = 0.027). In female donors, folate levels and red cell distribution width showed positive correlations with collection outcomes (r = 0.342, p = 0.027; r = 0.322, p = 0.037). The Mentzer index demonstrated an inverse association with CD34+ yield across both sexes. Transferrin saturation ≥ 18% in females was associated with higher target achievement rates (95.2% vs. 66.7%, p = 0.020). In males, ferritin ≥ 73 μg/L or hemoglobin > 15.3 g/dL was associated with lower collection success. Readily available red cell indices and iron parameters are associated with clinically relevant PBSC collection outcomes and may serve as practical biomarkers for predicting PBSC collection performance and improving donor assessment. Incorporation of these markers into donor assessment may improve collection planning and procedural efficiency.
BMJ case reportsDennis Wegner, Moritz Scholtes, Matthias Moos, Alexander Dullenkopf
The management of a snakebite is often challenging due to limited experience, limited access to intensive care, delays in presentation and high variability in venom composition and specific antivenom availability. Classified within the genus Eristicophis, the MacMahon viper is a venomous snake species for which only two detailed case reports exist. Its venom has predominantly haemotoxic properties while neurotoxic and cytotoxic effects are less pronounced. This case illustrates the effects of Eristicophis macmahonii venom on both haemostasis and cardiovascular stability, in addition to a significant local envenomation reaction that required intervention. Laboratory analysis revealed a rapid onset of thrombocytopenia and impaired haemostatic function expressed in rotational thromboelastometry (ROTEM) analysis. The first 6 hours represented an acute phase with significant hypotension and associated syncope. In the absence of clinical signs of bleeding, transfusion of blood products or administration of coagulation factors was not initiated. Thrombocytopenia resolved spontaneously within 8 days.
BACKGROUND: Sarcopenia, driven by inflammation and lipid dysregulation, lacks inexpensive screening tools. The white blood cell to HDL-C ratio (WHR) integrates these pathways, but its utility for sarcopenia screening remains unvalidated. OBJECTIVE: This study evaluated the WHR-sarcopenia association in dual cohorts, validated it using machine learning, and explored potential effect modification of hepatitis B virus (HBV) status. METHODS: We analyzed 10 131 NHANES (2011-2018) and 7872 KNHANES (2010-2011) adults. Sarcopenia was defined via DXA using FNIH/AWGS criteria. Weighted logistic regression, restricted cubic splines, and machine learning (LASSO, XGBoost) were applied. RESULTS: Higher ln(WHR) was independently associated with sarcopenia in NHANES (adjusted OR = 2.50; 95% CI: 2.01-3.10) and consistently validated in KNHANES (OR = 1.85; 95% CI: 1.49-2.29). WHR ranked among the top predictive features across machine learning models. Exploratory stratified analysis suggests that the association between ln(WHR) and sarcopenia appears to be stronger in the HBV-exposed subgroup. However, although the formal interaction test was not significant (p = 0.270), these findings are hypothesis-generating results. CONCLUSION: WHR, a cost-free routine metric, is robustly linked to sarcopenia. Integrating it into geriatric assessments could facilitate early high-risk identification for timely interventions, while exploratory findings suggesting a possible modifying role of HBV history require prospective validation.
BACKGROUND: Evaluating bone marrow is an invasive and expensive procedure that frequently necessitates sedation or anesthesia in dogs and cats. The immature platelet fraction (IPF(and related immature or reticulated platelet parameters, has been suggested as a non-invasive alternative for assessing megakaryocytic activity. However, a comprehensive assessment of the depth and balance of evidence across the two most prevalent companion animal species has not been conducted previously. OBJECTIVE: Aim of this scoping review was: (1) to map and classify primary studies that report on IPF or reticulated platelets in the context of thrombopoietic activity or bone-marrow activity in dogs and/or cats, (2) to classify the subjects, assays, reference criteria, clinical information, findings etc; and (3) to highlight principal evidence gaps and identify if the evidence generated is adequate and comparable for the systematic review or for a future meta-analysis. METHODS: Following the Population-Concept-Context (PCC) framework and the PRISMA Extension for Scoping Reviews (PRISMA-ScR guidelines, an exhaustive search was conducted in PubMed/MEDLINE, Web of Science, Scopus, and CAB Abstracts. The parameters of immature and reticulated platelets have been examined in relation to bone marrow and platelet status. Records were reviewed to ensure eligibility, and a standard data sheet was used to extract data. RESULTS: Of 35 records identified, 10 met the eligibility criteria. Nine of the ten included studies reported data only in dogs; a single retrospective study reported data in both dogs and cats, and no study addressed cats exclusively. Only one study used a direct bone-marrow reference standard (megakaryocyte cytology); the remainder relied on indirect or clinical classification. CONCLUSIONS: Evidence for IPF/reticulated platelets as a bone-marrow marker is considerably more developed in dogs than in cats. Feline data are essentially limited to a single retrospective analyzer study. Given the small number of studies and marked methodological heterogeneity, a full systematic review with meta-analysis is not currently feasible; a scoping review is the appropriate and informative synthesis at this stage.
This paper develops a theoretical model to examine the role of vasomotion and its effect on mass transfer processes. Vasomotion, consisting of periodic wave-like oscillations of blood vessel walls, is frequently observed in microcirculation and demonstrates distinct features in arterioles. The advection-diffusion equation governs the mass transport. This analysis can be used to model pathological conditions of blood flow, such as the formation of fatty cholesterol plaques and artery-clogging blood clots within the vessel lumen. These obstructions are modeled as a fictitious porous medium with permeability K. The fluid flow is described using the Darcy-Brinkman equation to quantify the effect of vasomotion. The novelty of the proposed framework is that it integrates the understanding of coupled vasomotion-driven flow and mass transfer in clogged arterioles using a lumped-parameter resistance approach. The developed model combines both blood flow and mass transfer resistances under pathological conditions and establishes their interaction via the Chilton-Colburn J-factor analogy. The present study employs the Frobenius method to solve the governing flow equations and obtain an expression for the velocity field. Furthermore, in the limiting case (absence of hematocrit and vasomotion), an approximate resistance formula for blood flow through a porous medium is derived and validated against previously obtained results. The mass transport equation is solved using the method of separation of variables, within the framework of a Sturm-Liouville problem. The governing equations are analyzed in a wave frame of reference moving in the positive axial direction with wave speed c to capture the effects of vasomotion. The influence of hematocrit level, Darcy number, Schmidt number, and power-law index is illustrated through three-dimensional surface plots and corresponding contour plots. The simulation results show that resistance increases with higher hematocrit levels and diffusivity effects, and decreases with increasing Darcy number. Compared with healthy conditions, fatty mass particles significantly increase resistance by altering viscosity and permeability.
BMJ case reportsMiriyala Gaayathri, Amrithanand Vt, Manjupriya G, Manu Ayyan
A woman in her 30s presented with severe haemotoxic snake envenoming complicated by venom-induced consumptive coagulopathy (VICC) and early multiorgan involvement. Despite receiving adequate polyvalent anti-snake venom and initial transfusions at a referral facility, the patient's coagulopathy persisted. On arrival at our emergency department, conventional coagulation tests (prothrombin time and international normalised ratio) were only mildly abnormal, in contrast to her significant clinical severity. Rotational thromboelastometry (ROTEM) revealed severe hypocoagulability with markedly impaired clot formation and strength. Additional targeted transfusions guided by viscoelastic findings successfully corrected major coagulation defects and resulted in clinical improvement. This case highlights the limitations of conventional coagulation tests in assessing the true functional severity of VICC and demonstrates the practical value of ROTEM in guiding targeted therapy for acute haemotoxic snakebites.
BMC cardiovascular disordersMohammed Ahmed Elgazzar, Basma Mohamed Hani, Abdelhamid Fathi Ali, Mahmoud Ahmed Elshafie, Ashraf Moustafa Elnahas
BACKGROUND: Coronary artery bypass grafting (CABG) carries a risk for serious adverse events. The Prognostic Nutritional Index (PNI) and Neutrophil-to-Lymphocyte Ratio (NLR), are simple measures of nutritional and inflammatory statuses, have been proposed as a potential predictor of postoperative outcomes. This study aimed to assess the predictive performance of preoperative PNI and NLR and their dynamic changes for post-CABG outcomes. METHODS AND MATERIALS: The study investigated the medical records of 327 patients who underwent CABG between February 20, 2020, and February 19, 2025. RESULTS: The overall complication and mortality rates were 15%, and 3.36% respectively. The preoperative PNI decreased significantly (P1 < 0.001) at 24-h postoperative and at the time of discharge. At the time of discharge, the mean PNI value increased significantly (P2 < 0.001) compared to that determined at 24-h postoperative. The magnitude of ∆PNI at discharge was significantly smaller than that at 24-h postoperatively (P3 < 0.001). Multivariate binary logistic regression identified preoperative PNI as an independent predictor of 1-month mortality, while ΔPNI at 24 h was independently associated with 1-month mortality. CONCLUSION AND RECOMMENDATIONS: PNI is a simple and inexpensive marker that may serve as a potential predictor of short-term outcomes after CABG. Lower preoperative PNI and greater early postoperative PNI decline were associated with adverse short-term outcomes after CABG, whereas preoperative NLR did not retain independent significance after multivariable adjustment; however, further prospective multicenter studies are required to confirm these findings.
Irish medical journalN M Smyth, H Yadav, A M McDonough, D McGee, K Balogun, C Loh, J E Low, J Byrne, V Tewatia, A Begley, P Kiernan, D Beddy, D Kearney
AIM: Appendicectomy is one of the most common emergency surgeries and is typically associated with minimal blood loss. Despite this, many institutions require routine preoperative type and screening (T&S) prior to appendicectomy. This study aimed to determine the rate of transfusion in appendicectomy. METHODS: Audit approval was obtained (250907). Data was collected retrospectively from health records of all patients who underwent appendicectomy at Connolly Hospital, Ireland, between January 2023 and December 2024. RESULTS: In total, 340 patients were included. The median age was 35.0 years [IQR; 22.3, range: 16 - 84], with 46% female (157). The majority of cases were emergency (330, 97%) and laparoscopic (339, 99%). A preoperative T&S was sent in 320 patients (94%) and 10 patients (3%) were crossmatched. The rate of intraoperative transfusion was 0% and only 1 patient (0.3%) required a postoperative blood transfusion. Haemoglobin was significantly lower in the crossmatched group (mean haemoglobin 12.5 g/dL [SD: 0.83], p = 0.007). The estimated cost per T&S was €54.52, equating to a total of approximately €17,446.40 for the study period. DISCUSSION: The incidence of perioperative transfusion during appendicectomy is extremely low. A selective, risk-based approach - targeting patients with complicated appendicitis or pre-existing anaemia - may safely reduce costs without compromising patient care.
EndocrineYuanlin Luo, Xiayue Fan, Qianqian Yang, Hui Liu, Yufeng Liu, Yanan Wang, Hui Guo, Bingyin Shi, Bao Zhang, Yayi He
BACKGROUND: Antithyroid drug-induced agranulocytosis (TIA) is a serious adverse effect in Graves' disease treatment. This study aims to analyze neutrophil recovery patterns in TIA patients. METHODS: We conducted a 12-year retrospective study of patients with Graves' disease diagnosed with TIA. Primary objective was to characterize the recovery patterns of absolute neutrophil count (ANC) after severe agranulocytosis. Secondary objective was to identify factors associated with leukocytosis during granulocyte colony-stimulating factor (G-CSF) treatment using univariate and multivariate logistic regression. RESULTS: 48 TIA patients were included; 43 (89.6%) had a nadir ANC ≤ 0.1 × 10⁹/L (the severe agranulocytosis). Among 36 patients with detailed records, 77.8% had ANC ≤ 0.1 × 10⁹/L persisting 3-8 days. In the slow recovery group (> 3 days, n = 41), 62.5% exhibited rapid increase, with ANC surging from (0.1-0.5) × 10⁹/L to ≥ 0.5 × 10⁹/L within one day. 18 patients developed leukocytosis during G-CSF treatment. Univariate analysis showed that severe agranulocytosis lasting > 3 days significantly associated with leukocytosis (OR = 4.47, 95% CI: 1.05-18.94, P = 0.042). This association remained significant after adjusting for total G-CSF dose (OR = 7.72, 95% CI: 1.37-43.38, P = 0.020), and after further adjusting for sex, age, and total G-CSF dose (OR = 9.66, 95% CI: 1.52-61.36, P = 0.016). CONCLUSIONS: In most severe TIA patients, neutrophil recovery exhibited a biphasic pattern, with ANC recovering rapidly after prolonged severe agranulocytosis. Close monitoring is essential to avoid G-CSF overstimulation, particularly in patients with prolonged severe agranulocytosis.
BMJ openMarina Blanco-Aparicio, Teresa Carrillo-Diaz, Eva Martinez-Moragon, David Bañas-Conejero, M-Guadalupe Sánchez-Herrero, Christian Domingo-Ribas, REDES study gro…
OBJECTIVE: To identify predictors of treatment response to help target mepolizumab to patients with severe asthma with type 2 inflammation (SA-T2) who are most likely to respond to therapy. DESIGN AND SETTING: The REal-worlD Effectiveness and Safety of mepolizumab (REDES), a multicentre, observational cohort study, investigated the effectiveness and safety of mepolizumab in Spanish patients with SA-T2. PARTICIPANTS: We conducted a post hoc analysis of data from REDES to examine relationships between patient characteristics and response to mepolizumab to identify predictive markers of response. Outcomes included annualised clinically significant exacerbations (primary), lung function (forced expiratory volume in 1 s), maintenance oral corticosteroid (OCS) dose and Asthma Control Test (ACT) score. Outcomes after 12 months' treatment with mepolizumab were assessed and stratified by demographic and clinical characteristics. Analyses were descriptive; changes from baseline were summarised as mean (SD) and prespecified two-tailed unpaired t-tests were applied for comparisons (p<0.05). PRIMARY AND SECONDARY OUTCOME MEASURES: These were stratified by various demographic and clinical characteristics collected during the study. RESULTS: In total, 318 patients with SA-T2 were included in the analysis. Mepolizumab was effective in patients with a diverse range of demographic and clinical characteristics. Baseline blood eosinophil count ≥150 or ≥300 cells/µL or fraction of exhaled nitric oxide (FeNO) ≥25 or ≥50 ppb resulted in a 77%-88% reduction in exacerbations compared with 51%-55% in patients with lower baseline levels of these biomarkers (descriptive). Baseline factors of sex, body mass index, smoking status, atopic sensitisation and forced expiratory volume in 1 s had no appreciable effects on exacerbations, maintenance OCS use, lung function or asthma symptoms. CONCLUSIONS: This post hoc analysis indicates mepolizumab is likely to provide clinical benefit in patients with SA-T2 across a broad range of patient characteristics. Patients with baseline blood eosinophils of ≥150 cells/µL and/or FeNO ≥25 ppb are likely to derive more benefit. TRIAL REGISTRATION NUMBER: 213172.
To investigate the clinical, psychological, and functional determinants of kinesiophobia and to examine their interrelationships in patients with systemic lupus erythematosus (SLE). This cross-sectional study included 60 patients with SLE. Demographic characteristics, disease-related variables, laboratory parameters [e.g., C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)] and disease activity were recorded. Kinesiophobia was assessed with the Tampa Scale for Kinesiophobia (TSK). Central sensitization, personality, mental health, quality of life, and sleep were evaluated by the Central Sensitization Inventory (CSI), Type D Scale-14 (DS14), Hospital Anxiety and Depression Scale (HADS), Short Form-12 (SF-12), and Jenkins Sleep Evaluation Scale (JSS), respectively. Serial multiple mediation analysis were performed to examine factors associated with kinesiophobia. A mean age of patients with SLE was 39.7 ± 13.8 years. Kinesiophobia was present in 70% of the study population. Patients with kinesiophobia had significantly higher ESR and CRP, DS14 total and negative affectivity scores, and greater psychological distress across all HADS subscales (p < 0.05, for all). TSK scores correlated positively with CRP, ESR, pain, CSI, DS14, and HADS subscales (correlation coefficients ranged between 307 and 522) and negatively with SF-12 Physical Component Summary score (correlation coefficient=-0.414). Serial mediation analysis explained 40% of TSK score variance (R²=0.40). CRP had a significant direct effect on kinesiophobia (B = 0.87, p = 0.002), independent of age and sex. Neither DS14 nor CSI significantly mediated this association. Kinesiophobia is highly prevalent in patients with SLE and associated with inflammatory, psychological, and functional parameters. Systemic inflammation, reflected by CRP, appears to be independently associated with fear of movement in SLE. These findings underscore the importance of monitoring inflammatory markers in SLE management and integrating personality and central sensitization assessments into a comprehensive biopsychosocial approach.
The American journal of case reportsSwati Gobhil, Arjun Khunger, Prajeesh Kandoth Karerat
BACKGROUND Acquired hemophilia A (AHA) is a rare but potentially life-threatening condition caused by autoantibodies against factor VIII. It often presents in older adults and its presentation can range from isolated lab abnormality of prolonged activated partial thromboplastin time (aPTT) without bleeding to mild bleeding or spontaneous vs disproportionate life-threatening bleeding. Delayed diagnosis is frequent due to the rarity of the condition and propensity to attribute bleeding to other common causes, such as falls. CASE REPORT A 92-year-old woman with recurrent ground-level falls presented with severe right lower extremity pain of several weeks' duration. She was not on any anticoagulant or anti-platelet agent. Computed tomography angiography demonstrated bilateral lower extremity intramuscular hematomas. She had 2 prior admissions for falls within 6 months, including a fall leading to intramuscular hematoma, which was conservatively managed without evaluation of coagulopathy. During current admission, prolonged aPTT prompted further workup, revealing low factor VIII activity of 5% and a high factor VIII inhibitor titer of 15.6 Bethesda Units, establishing the diagnosis of acquired hemophilia A. Bleeding control required sequential bypassing agents, corticosteroids, rituximab, cyclophosphamide, and eventually emicizumab. CONCLUSIONS This case highlights how recurrent or disproportionate intramuscular hematomas following even minor trauma, such as a ground-level fall, in the absence of risk factors such as anticoagulant use, may prompt evaluation for underlying coagulopathy such as AHA. Basic coagulation testing including prothrombin time and aPTT can help screen patients who warrant additional coagulopathy evaluation. Timely diagnosis is critical to avoid life-threatening bleeding complications.
This study evaluates the performance of a simple age-albumin-red cell distribution width (AAR) score for stratifying 28-day in-hospital mortality risk in an operational cohort of adult emergency department (ED) patients with suspected sepsis and in a later-period subgroup. This single-center retrospective cohort study analyzed an operational ED suspected-sepsis cohort of 852 adults defined by a modified early warning score of 5 or higher plus an infection-related ED discharge diagnosis from 2022 to 2025. The AAR score assigned one point each for age ≥ 75 years, albumin < 3.0 g/dL, and red cell distribution width ≥ 14.5%; scores ≥ 2 indicated high risk. Performance was assessed using the area under the receiver operating characteristic curve (AUROC), classification metrics, calibration, and exploratory clinical net benefit overall and across chronological study periods. Overall, 98 patients (11.5%) died within 28 days. The AAR AUROC was 0.787 (95% confidence interval [CI]: 0.740-0.833) overall and 0.778 (95% CI: 0.703-0.852) in 2024 to 2025; paired comparison did not demonstrate greater discrimination than continuous albumin alone (difference, 0.013; 95% CI: -0.074-0.100; P = .770). However, mortality increased stepwise across AAR categories (2.2%, 7.4%, 21.7%, and 49.2%), and this gradient was preserved in the later-period cohort (1.4%, 6.6%, 15.9%, and 41.4%). The earlier-period equation overpredicted absolute mortality risk in the later period. The AAR score combined 3 routinely available variables into 4 ordinal groups with a consistent mortality gradient across study periods. Its simple 0 to 3-point structure supports further external evaluation as an adjunct to early ED risk stratification. Patient-level probability estimation and decision-support use require additional validation and recalibration.
Observational studies have suggested an association between white blood cell (WBC) count and systemic lupus erythematosus (SLE). However, the causal relationship remains uncertain because of potential confounding factors. This Mendelian randomization (MR) study aimed to investigate the causal effect of WBC count on SLE risk by using genetic instruments. Genetically predicted higher WBC counts were associated with a reduced risk of SLE (inverse-variance weighted [IVW]: odds ratio = 0.384, 95% confidence interval = 0.160-0.920, P = .031; weighted median: odds ratio = 0.326, 95% confidence interval = 0.124-0.859, P = .023). MR-Egger regression revealed no evidence of horizontal pleiotropy (intercept, P = .705), and MR polygenic residual sum and outlier (MR-PRESSO) detected 4 outliers. After outlier removal, heterogeneity decreased, and the IVW and weighted median estimates remained significant (beta = -0.96, P = .03; beta = -1.12, P = .023, respectively). We conducted a 2-sample MR analysis using summary statistics from genome-wide association studies (GWAS) of European ancestry: WBC count (GWAS ID: ieu-b-30, N = 563,946) and SLE (GWAS ID: ieu-a-815, 14,267 cases, and 43,047 controls). Sixty-five independent single-nucleotide polymorphisms (P < 5 × 10-8, clumped at r2 < 0.001) were selected as instrumental variables, with a mean F statistic of 28.6, indicating strong instrument strength. Analyses were performed using R statistical software (R Foundation for Statistical Computing) with the TwoSampleMR and MR-PRESSO packages. The primary analytical methods included IVW, weighted median, and MR-Egger regression. Sensitivity analyses included Cochran Q test for heterogeneity, MR-PRESSO outlier correction, and leave-one-out validation to ensure robustness. This MR analysis supports an independent causal protective effect of genetically predicted higher WBC counts on SLE risk. These findings should not be extrapolated as evidence for therapeutic leukocyte elevation, nor do they alter the clinical management of leukopenia observed in active SLE or during immunosuppressive therapy. The genetic signal likely reflects broader immune homeostatic regulation rather than lineage-specific effects, the mechanistic basis of which warrants dedicated functional investigation.
Journal of global healthZekai Chen, Zhen He, Shasha Zhou, Guanlin Chen, Hong Zheng, Yuxian Wang, Weiqiang Wu, Shouling Wu, Youren Chen
BACKGROUND: Routine platelet indices have been linked to blood pressure and vascular risk. However, longitudinal evidence on the association between platelet count (PLT), mean platelet volume (MPV), plateletcrit (PCT), and platelet distribution width (PDW) and incident hypertension remains limited, and it is unclear whether these associations differ according to adiposity. We aimed to examine associations of PLT, MPV, PCT, and PDW with incident hypertension and assess whether these associations vary by body mass index (BMI). METHODS: We analysed 51,191 hypertension-free adults aged ≥18 years from the 2006 baseline examination of the Kailuan Study, with follow-up through 31 December 2023. We measured PLT, MPV, PCT, and PDW from routine full blood counts. We used weighted Cox regression to estimate overall hazard ratios (HRs) and by Chinese BMI categories, adjusting for age, sex, fasting blood glucose, physical activity, and smoking. Restricted cubic splines assessed dose-response relationships. RESULTS: During a median follow-up of 8.2 years, 29,491 participants developed hypertension (incidence rate = 70.67 per 1000 person-years). Higher PLT (HR = 1.07; 95% confidence interval (CI) = 1.05-1.09) and PDW (HR = 1.03; 95% CI = 1.01-1.04) were associated with greater hypertension risk, whereas MPV showed a modest inverse association (HR = 0.98; 95% CI = 0.96-1.00) and PCT was not significantly associated (HR = 0.99; 95% CI = 0.98-1.01). Absolute incidence rates increased across Chinese BMI categories from 33.59 to 105.13 per 1000 person-years. BMI-stratified analyses suggested heterogeneous patterns, particularly for MPV and PDW. Splines indicated approximately linear positive associations for PLT and PDW, a mild inverse/flat pattern for MPV, and nonlinear associations for PCT. CONCLUSIONS: Routine platelet indices showed modest associations with incident hypertension, with heterogeneous patterns across BMI categories. These findings suggest that platelet-related haematological traits may reflect BMI-dependent differences in hypertension risk, but external validation and formal prediction analyses are needed before clinical use.
Mycoplasma pneumoniae is an important cause of community-acquired pneumonia in children, and severe M pneumoniae pneumonia (SMPP) is frequently complicated by pleural effusion, yet specific risk factors for effusion in this population remain incompletely defined. In this retrospective observational study, 121 hospitalized children with SMPP admitted between January 2022 and June 2023 were enrolled and classified into a pleural effusion group (n = 32) and a non-pleural effusion group (n = 89) based on chest radiography. Demographic data, past medical history, clinical manifestations, laboratory indices, and radiologic findings were extracted from electronic records. Group comparisons were performed using independent-samples t tests and χ2 tests, and factors associated with pleural effusion were evaluated by univariate and multivariate logistic regression. Children with pleural effusion exhibited longer fever duration, higher peak temperature, faster respiratory rate, more frequent chest indrawing, and more extensive radiologic involvement than those without effusion. They also had higher white blood cell counts, neutrophil predominance, lower lymphocyte percentages, and significantly elevated C-reactive protein, procalcitonin, erythrocyte sedimentation rate, lactate dehydrogenase, and D-dimer, together with slightly lower serum albumin. Multivariate analysis identified prolonged fever duration, increased respiratory rate, and elevated C-reactive protein as independently associated with pleural effusion in children with SMPP. These readily available clinical indicators may help clinicians identify patients at higher risk of pleural effusion and facilitate closer monitoring and timely imaging evaluation.
MedicineSezgin Zontul, Zeynep Kaya, Mesude Seda Aydoğdu, Elif İnanç, Merve Çetin, Servet Yolbaş, Ahmet Kadir Arslan, Cihat Uçar
Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease associated with increased cardiometabolic risk. Adipokines are implicated in inflammation and metabolic dysregulation in RA; however, clinical data on serum asprosin, a novel glucogenic adipokine, remain limited. This study aimed to evaluate serum asprosin levels in patients with RA and to assess their relationship with disease activity. In this single-center, cross-sectional observational study conducted between June and August 2025, 42 patients with RA and 40 control participants were included. Serum asprosin levels were measured using enzyme-linked immunosorbent assay (ELISA). Disease activity was assessed using the Disease Activity Score in 28 joints, based on the erythrocyte sedimentation rate (DAS28-ESR). Associations between asprosin levels and clinical, laboratory, and serological parameters were analyzed. Serum asprosin levels differed significantly between patients with RA and control participants, with median (interquartile range) values of 12.43 (9.98) and 9.96 (3.47) ng/mL, respectively (P = .025); however, this association was no longer statistically significant after adjustment for age, sex, BMI, smoking status, and comorbidity in a multivariable regression model (adjusted P = .986). No significant correlations were observed between asprosin and DAS28-ESR, CRP, ESR, RF, or anti-CCP. ROC analysis demonstrated limited discriminatory performance (AUC = 0.643; 95% CI: 0.52-0.767; P = .02). Serum asprosin levels differed between patients with RA and control participants in unadjusted analysis; however, this difference was not retained after adjustment for potential confounders, and no significant association with disease activity or inflammatory markers was identified. These findings suggest that serum asprosin may have limited clinical utility as a standalone biomarker in RA. Further prospective studies with larger sample sizes are needed to clarify the potential role of asprosin in RA pathophysiology.