Prothrombin Time Research Articles

Designing 3D-printed concrete structures with scaled fabrication models

This article proposes using scaled fabrication models to assist the design research of 3D-printed discrete concrete structures where full-scale fabrication tests are costly and time-consuming. A scaled fabrication model (SFM) is a scaled model 3D-printed the same way as in actual construction to reflect its fabrication details and acquire alike layer line textures. The components of a 1:10 SFM can be easily produced by consumer-level desktop 3D printers with minimal modification. SFMs assist the design communication and make possible quick tests of distinct fabrication designs that are hard to assess in digital modeling during the conceptual design phase. A case study of a discrete compression-dominant funicular floor derived from graphic statics is presented to illustrate the contribution of SFM to the design research of force-informed toolpathing where the printing direction of a component is aligned to the principal stress line. The design iterations encompass a sequence of component, partial, and full model SFM printing tests to explore and optimize the fabrication schemes where parallel, non-parallel, and creased slicing methods to create toolpaths are compared and chosen to adapt different discrete components.

Predictors of Mortality in Crimean-Congo Hemorrhagic Fever Patients Admitted at a Tertiary Care Hospital in Pakistan over the Last 10 Years: A Case-Control Study.

The objective was to identify predictors of mortality in hospitalized patients with Crimean-Congo hemorrhagic fever (CCHF). A case-control study was conducted on patients hospitalized with CCHF from 2012 to 2022. Risk factors for mortality in CCHF patients were analyzed using logistic regression. A total of 86 patients with a median age of 36 years (interquartile range [IQR], 27-36 years) were included, and the majority were males (78, 90.7%). Thirty-one patients (36%) were cases, whereas 55 (64%) were control patients. Based on univariate logistic regression analysis, patients who were in an age group of ≥40 years (odds ratio [OR]: 4.85; 95% CI: 1.8-12.4) or with presence of gum bleeding (OR: 2.66; 95% CI: 1.0-6.8), unit increase in white blood cell count (WBC) (OR: 1.09; 95% CI: 1.00-1.07), serum glutamate-pyruvate transaminase of ≥500 U/L (OR: 3.68; 95% CI: 1.4-9.3), serum glutamic-oxaloacetic transaminase (SGOT) of ≥1,000 U/L (OR: 8.72; 95% CI: 2.6-28.3), prothrombin time (PT) of ≥120 seconds (OR: 9.85; 95% CI: 3.2-29.8), international normalized ratio of ≥5 (OR: 15.8; 95% CI: 2.0-125.3), or acute respiratory distress syndrome (ARDS) (OR: 28.27; 95% CI: 5.84-136.9) were found to be significantly associated with mortality in CCHF. Factors found to be independently associated with mortality on multivariate analysis included ARDS (adjusted OR [aOR]: 27.7; 95% CI: 4.0-190.5), unit increase in WBC (aOR: 1.02; 95% CI: 1.02-1.26), SGOT of ≥1,000 U/L (aOR: 23.6; 95% CI: 2.32-241.7), and PT of ≥120 seconds (OR: 10.2; 95% CI: 2.00-52.4). CCHF is a rare but fatal disease, and patients with ARDS and increased WBC, high SGOT level, and increased PT indicative of liver injury and coagulopathy at the time of hospitalization are at high risk for mortality.

Risk factors for secondary infection after liver failure and effect of comprehensive nursing intervention.

In patients with liver failure (LF), the high rate of secondary infections, which are associated with poor prognosis, highlights the clinical significance of understanding the underlying risk factors and implementing targeted intervention programs. To investigate risk factors for secondary infections in patients with LF and evaluate the effectiveness of comprehensive nursing interventions. This retrospective study included 64 patients with LF, including 32 with and 32 without secondary infections. A questionnaire was used to collect data on age; laboratory parameters, including total and direct bilirubin, prothrombin time, blood ammonia, and other biochemical parameters; invasive procedures; and complications. Patients with secondary infections received comprehensive nursing intervention in addition to routine nursing care, whereas those without secondary infections received only routine nursing care to compare the effect of nursing intervention on outcomes. The infection rate, which was not associated with age or complications, was significantly associated with biochemical parameters and invasive procedures (P < 0.05). The infection rate was 61.6% in patients who had undergone invasive procedures and 32.1% in those who had not undergone invasive procedures during the hospital stay. The infection rate was also significantly associated with the type of LF (P < 0.05), with the lowest rate observed in patients with acute LF and the highest rate observed in those with subacute LF. The nursing satisfaction rate was 58.3% in the uninfected group and 91.7% in the infected group, indicating significantly higher satisfaction in the infected group (P < 0.05). In patients with LF, the rate of secondary infections was high and associated with biochemical parameters and type of LF. Comprehensive nursing intervention can improve patient satisfaction.

An Investigative Study of Prothrombin Time, Activated Partial Thromboplastin Time and Antithrombin Levels in Patients with Ischaemic Stroke

Background: The haemostatic system maintains a balance between prothrombotic and antithrombotic components in the body. The role of this system in ischaemic stroke is not certain. Objective: Prothrombin time (PT) and Activated Partial Thromboplastin Time(APTT) are widely used screening tests to assess the haemostatic cascade. We sought to evaluate the relevance of these test and antithrombin (AT) levels in patients with ischaemic stroke. Methods: AT, platelet count, PT and APTT tests were carried out for 65 patients with ischaemic stroke and 65 controls with no history of stroke. Results: The mean age of stroke subjects was 60.4 ± 12.3yrs. PT and APTT in the test and control groups were similar and Antithrombin levels did not show significant difference. But there was a significant association between functional AT deficiency and diabetes mellitus in the ischaemic stroke group. A significant negative correlation existed between functional AT activity and prothrombin and between AT Ag levels and APTT Conclusion: There was no difference in the Antithrombin levels, PT and APTT values in patients with ischaemic stroke and those without a history of stroke and carrying out these tests routinely to assess hypercoagulable states in ischaemic stroke patients may not have any diagnostic value in our population.

Analysis of Risk Factors for Severe Postpartum Hemorrhage

Background: The purpose of this study is to outline the probable causes of severe postpartum hemorrhage (sPPH), summarize its risk factors, and present strategies for its prevention and treatment. Methods: This is a retrospective analysis of the medical records of 1824 patients that showed postpartum hemorrhage (PPH) during natural delivery and were admitted to the Fourth Hospital of Shijiazhuang between 1 January, 2014 and 31 December, 2018. The pairing method was used in this study. We collected and analyzed the clinical data after dividing the patients into two groups, a study group (showing sPPH) and a control group (showing non-severe PPH), with each having 912 patients. Risk prevention strategies are also discussed. Results: In the study group, the conditions such as previous history of cesarean section, placental diseases (marginal placenta previa, placenta accreta, central placenta previa and low-lying placenta), IVF-ET pregnancy, antepartum hemorrhage, and prepartum hemoglobin (g/L) were prevalent but rarely reported in the control group. The multivariate logistic regression results showed that BMI before pregnancy, past history of postpartum hemorrhage, prepartum APTT, prepartum fibrinogen (FIB) (g/L), pre-transfusion hemoglobin (g/L), pre-transfusion platelet count (×109), pre-transfusion coagulation function prothrombin time (PT), marginal placenta previa, placenta accreta, central placenta previa, IVF-ET pregnancy and antepartum hemorrhage were all independent risk factors for sPPH. Conclusions: Probable causes of sPPH related and risk factors in order to present prevention and treatment strategies in a retrospective analysis of 1824 patients that showed PPH were outlined. Since occurrence of sPPH has been related to these various factors, constructing a risk prevention strategy against these independent factors can effectively reduce the rate of maternal mortality.

Safety and Effectiveness of Four-Factor Prothrombin Complex Concentrate in Special Populations with INR Below 2: A Post-Marketing Surveillance Study.

We previously conducted a prospective, observational post-marketing surveillance study to assess the safety and effectiveness of four-factor prothrombin complex concentrate (4F-PCC) for rapid vitaminK antagonist (VKA) reversal in Japanese patients. This subgroup analysis compared the safety, especially thromboembolic events (TEEs), and effectiveness of 4F-PCC by stratifying patients into two subgroups according to baseline international normalized ratio (INR) levels with < 2.0 and ≥ 2.0. Of 1271 eligible patients, 215 (17.9%) had INR < 2.0 and 987 (82.1%) had INR ≥ 2.0. Overall baseline characteristics were similar between groups; age (74.0years vs 74.0years), body mass index (22.1kg/m2 vs 21.9kg/m2), ratio of inpatients (90.2% vs 88.7%), manifested atrial fibrillation (46.0% vs 48.8%). Median INRs at baseline were 1.72 (minimum 0.92, maximum 1.99) in the INR < 2.0 group and 2.95 (2.00, 27.11) in the INR ≥ 2.0 group. The most common reason for 4F-PCC administration was intracranial hemorrhage (67.0% vs 59.5%), and lesser gastrointestinal bleeding (0.9% vs 7.5%). After 4F-PCC administration (average doses 24.5IU/kg [INR < 2.0 group] and 29.2IU/kg [INR ≥ 2.0 group]), INRs were significantly reduced to 1.21 (- 28%) and 1.31 (- 68%), respectively, and resulted in hemostasis in a similarly rapid manner. The incidences of adverse drug reactions were 3.7% in each group. TEEs occurred in 4 (1.9%) patients in the INR < 2.0 group and 11 (1.1%) patients in the INR ≥ 2.0 group and were predominantly composed of stroke, while similar rates (67.0% vs 62.9%) of bleeding events post-anticoagulant resumption were observed between groups. This study supports the favorable tolerability and efficacy of 4F-PCC regardless of baseline INR (< 2.0 or ≥ 2.0), with a prompt reduction of INR and substantial hemostatic effectiveness in the real-world setting for patients requiring urgent VKA reversal, although no indicated 4F-PCC dose for VKA reversal exists for INR < 2.0 to date.

Molecular Pro-Apoptotic Activities of Flavanone Derivatives in Cyclodextrin Complexes: New Implications for Anticancer Therapy.

This study evaluates the antiproliferative potential of flavanones, chromanones and their spiro-1-pyrazoline derivatives as well as their inclusion complexes. The main goal was to determine the biological basis of molecular pro-apoptotic activities and the participation of reactive oxygen species (ROS) in shaping the cytotoxic properties of the tested conjugates. For this purpose, changes in mitochondrial potential and the necrotic/apoptotic cell fraction were analyzed. Testing with specific fluorescent probes found that ROS generation had a significant contribution to the biological anticancer activity of complexes of flavanone analogues. TT (thrombin time), PT (prothrombin time) and APTT (activated partial tromboplastin time) were used to evaluate the influence of the compounds on the extrinsic and intrinsic coagulation pathway. Hemolysis assays and microscopy studies were conducted to determine the effect of the compounds on RBCs.

Cigarette smoking and its effect on coagulation profile, hematological parameters, and oxygen saturation in healthy blood donor

Background: Cigarette smoking causes millions of deaths all around the world each year as it is one of the leading causes of cancer and cardiovascular diseases. Aims and Objectives: The study aimed to study the effect of cigarette smoking on coagulation profile, hematological parameters, and oxygen saturation in healthy blood donors. Materials and Methods: A case–control study was carried out at the Department of Pathology, Era’s Lucknow Medical College which is a tertiary care center, and took place between September 2018 and September 2020 (24 months). Results: Cigarette smoking has adverse effects on hematological parameters (red blood cell count, hemoglobin, hematocrit, mean corpuscular hemoglobin, red cell distribution width, and total leukocyte count) and coagulation profile (prothrombin time, activated partial thromboplastin time, and international normalized ratio). In our study, no adverse effects are seen on oxygen saturation though. Conclusion: Our study shows that hematological parameters and coagulation profile were altered in donors who were smokers and thus, it should be considered during blood donation. Although oxygen saturation was not adversely affected, this study strongly recommends the need for further studies to be done on this parameter of donated blood.

Effect of Vascular Senescence on the Efficacy and Safety of Warfarin: Insights from Rat Models and a Prospective Cohort Study.

Warfarin, with its narrow therapeutic range, requires the understanding of various influencing factors for personalized medication. Vascular senescence, marked by vascular stiffening and endothelial dysfunction, has an unclear effect on the efficacy and safety of warfarin. Based on previous studies, we hypothesized that vascular senescence increases the risk of bleeding during warfarin therapy. This study aimed to explore these effects using animal models and clinical cohorts. We established rat models of vascular senescence and calcification using d-galactose, vitamin D, and nicotine. After validating the models, we examined changes in the international normalized ratio (INR) at fixed warfarin doses (0.20 and 0.35 mg/kg). We found that vascular senescence caused significantly elevated INR values and increased bleeding risk. In the prospective clinical cohort study (NCT06428110), hospitalized warfarin patients with standard dose adjustments were divided into vascular senescence and control groups based on ultrasound and computed tomography diagnosis. Using propensity score matching to exclude the influence of confounding factors, we found that the vascular senescence group had lower steady-state warfarin doses and larger dose adjustments, with a higher probability of INR exceeding the therapeutic range. The vascular senescence group tended to experience more bleeding or thromboembolic/ischemic events during 1 year of follow-up, while there was no statistical difference. In conclusion, vascular senescence leads to unstable INR values and increases higher bleeding risk during warfarin therapy, highlighting the importance of considering vascular senescence in future precision warfarin therapies. SIGNIFICANCE STATEMENT: Many factors influence warfarin efficacy; however, the effect of vascular senescence remains unclear. This study aimed to investigate the effects of vascular senescence on the efficacy and safety of warfarin. Through both rat models and clinical cohort studies, our findings indicated that vascular senescence may compromise the stability of warfarin, presenting challenges in maintaining its efficacy and safety.

Predicting septic shock in obstructive pyelonephritis associated with ureteral stones: A retrospective study.

To identify the best combination of potential predictors of septic shock in patients with obstructive acute pyelonephritis associated with ureteral stones (OAPN-US) according to Sepsis-3 criteria. Patients who underwent percutaneous nephrostomy (PCN) with OAPN-US were retrospectively evaluated. Recursive feature elimination (RFE) was applied to patients with and without septic shock to identify factors associated with the prediction of progression to septic shock. We compared combinations of the selected features based on area under the receiver operating curve (AUROC) to determine which combination was most effective. This study included 81 patients who were treated with PCN due to OAPN-US. A comparison was made between 37 patients with septic shock (SS) and 44 patients without septic shock (NSS). SS group had a higher age, poorer Eastern Cooperative Oncology Group status, and significantly higher levels of positivity in urine cultures and blood cultures. There were also differences in laboratory tests between the 2 groups. Procalcitonin (PCT), international normalized ratio (INR), and absolute lymphocyte count (ALC) were selected based on RFE. We compared the predictive power for SS when each marker was used alone, when 2 markers were combined, and when all 3 markers were combined. Among these combinations, using all 3 variables together yielded the highest AUROC of 0.942. Of the 3 variables, PCT had the highest Gini importance score, indicating that it was the most influential factor. Clinical characteristics were different between the SS and the NSS groups. In patients with OAPN-US, the combination of PCT, ALC, and INR was an excellent predictor of septic shock.

Severe acquired hemophilia A associated with COVID-19 vaccination: A case report and literature review.

Acquired hemophilia A (AHA) is a rare autoimmune disease caused by an antibody that inhibits coagulation factor VIII activity. More than half of patients with AHA cannot identify underlying disorders. The remaining patients are associated with malignancies, autoimmune diseases, skin diseases, infections, and medications. Here, we present a case of 56-year-old Korean man with underlying hypertension, dyslipidemia, and diabetes mellitus who developed AHA following the second dose of BNT162b2 COVID-19 vaccination. He presented with a large 20 × 30 cm-sized hematoma along the psoas muscle and intracranial hemorrhage, necessitating intensive care with mechanical ventilation and continuous renal replacement therapy. Laboratory testing demonstrated that activated partial thromboplastin time and prothrombin times were 74.7 seconds (normal range 29-43 seconds) and 17.2 seconds (normal range 12.5-14.7 seconds), respectively. Laboratory tests confirmed AHA with undetectable factor VIII activity (<1.5%) and a positive factor VIII antibody with a titer of 8.49 Bethesda units/mL. Recombinant factor VIIa (NovoSeven®) was administered every 2 hours to control the bleeding, alongside immunosuppression with methylprednisolone 1 mg/kg daily and cyclophosphamide 2 mg/kg daily to eliminate the autoantibody. Despite the treatments, the patient developed sepsis and succumbed 14 weeks after admission. This rare case underscores the importance of monitoring for AHA following COVID-19 vaccination. Although the benefits outweigh the risks of vaccination, AHA should be considered in the differential diagnosis of unusual bleeding following the vaccinations. Early diagnosis and management before severe bleeding are critical for successfully controlling life-threatening bleeding.

Lactate as an early prognostic indicator in yellow phosphorus rodenticide-induced acute hepatic failure: a retrospective observational study in a tertiary care hospital

Introduction Acute hepatic failure due to yellow phosphorus rodenticide ingestion is often lethal. This study aimed to analyze demographic characteristics and prognostic indicators, focusing on hyperlactataemia as a potential early indicator of mortality in patients poisoned with yellow phosphorus rodenticide. Materials and methods This was a retrospective study of 96 patients poisoned with a yellow phosphorus-containing rodenticide (Ratol paste, which contains 3% yellow phosphorus). We examined demographic details, clinical symptoms, and biochemical markers to identify prognostic indicators. Results Demographics were similar among survivors and non-survivors. Mortality (36.5%) correlated with a higher ingested dose and treatment delays, with a mean (±SD) of 5.26 ± 2.2 survival days among those who died. Symptoms, including gastrointestinal and neurological features, typically appeared 48 h after ingestion. Non-survivors developed increased aminotransferase activities (74.3%), prolonged prothrombin time (65.7%), and hyperbilirubinaemia (65.7%) during hospitalization, significantly more commonly compared to survivors (P < 0.0001). Hyperlactataemia (lactate concentration >2 mmol/L) was present in 97.1% of non-survivors, with increased serial lactate concentrations observed in 88.6%. The median (interquartile range) admission lactate concentration among non-survivors was 4.6 mmol/L (3.36–7.53 mmol/L), and their peak median (interquartile range) lactate concentration was 6.1 mmol/L (8.74–10.6 mmol/L). In non-survivors, an increased lactate concentration preceded increased aminotransferase activities and prolonged prothrombin time. Logistic regression and receiver operating characteristic curve analysis confirmed that a 24 h lactate concentration ≥2.67 mmol/L predicted death with 94.3% sensitivity and 91.8% specificity. Discussion The majority of patients who ingest yellow phosphorus remain asymptomatic initially and typically present to hospital following the onset of gastrointestinal symptoms, usually a day later. As progression to death occurs within a week of yellow phosphorus ingestion in most cases, determining prognosis as early as possible enables swift referral to a liver transplant centre. Based on our study, a 24 h lactate concentration ≥2.67 mmol/L appears to be an early prognostic indicator of death. In another study, a lactate concentration >5.8 mmol/L was found to be a poor prognostic indicator. Conclusions Hyperlactataemia on admission and increased serial lactate concentrations appear to be early poor prognostic signs in patients with yellow phosphorus-induced liver failure.

Vitamin K Antagonist Reversal for Urgent Surgery Using 4-Factor Prothrombin Complex Concentrates

Millions of people take vitamin K antagonists (VKAs). Some people who need urgent surgical procedures require rapid VKA reversal to prevent excessive intraoperative bleeding. To evaluate the hemostatic noninferiority of an investigational 4-factor prothrombin complex concentrate (4F-PCC) to a control 4F-PCC for rapid VKA reversal before urgent surgery. This phase 3, double-blind, noninferiority randomized clinical trial (LEX-209) was conducted in 24 hospitals in the US, Russia, Georgia, Belarus, Ukraine, and Romania from June 7, 2017, through November 8, 2021; the study was stopped in February 2022. Participants were adult patients taking VKA who had an international normalized ratio (INR) of 2 or higher and needed urgent surgery with a substantial bleeding risk (≥50 mL). Patients were randomized 1:1 to a single infusion of either the investigational 4F-PCC or the control 4F-PCC. Data analysis followed intention-to-treat and per-protocol approaches. Single intravenous infusion was dosed by body weight and baseline INR. A dose of 25, 35, or 50 IU/kg of investigational 4F-PCC or control 4F-PCC was administered for baseline INR of 2 to less than 4, 4 to 6, or over 6, respectively. The primary end point was hemostatic efficacy at surgery end. An independent adjudication board, blinded to the 4F-PCC treatment allocation, assessed hemostatic efficacy using an objective 4-point scale. A total of 208 patients (median [range] age, 67.5 [31-92] years; 118 males [56.7%]) received the investigational (n = 105) or the control (n = 103) 4F-PCC. The median (range) dose was 25 (16-50) IU/kg in the investigational group and 25 (15-50) IU/kg in the control group, with a median (range) infusion time of 12 (8-50) minutes and 13 (7-30) minutes and a median (range) time from infusion to surgery start of 1.42 (0.25-15.25) hours and 1.50 (0.42-18.50) hours, respectively. Baseline median (range) INR was 3.05 (1.97-21.10) in the investigational group and 3.00 (2.00-11.30) in the control group. In the intention-to-treat analysis, the investigational 4F-PCC was noninferior to the control 4F-PCC, resulting in effective hemostasis in 94.3% of patients vs 94.2% of patients (proportion difference, 0.001; 95% CI, -0.080 to 0.082; P < .001), meeting the prespecified noninferiority margin of 0.15. An INR of 1.5 or lower at 30 minutes after infusion occurred in 78.1% of patients in the investigational group vs 71.8% of patients in the control group (proportion difference, 0.063; 95% CI, -0.056 to 0.181). Thrombotic events (2.9% vs 0%, respectively) and mortality (4.8% vs 1.0%, respectively) were no different than expected for 4F-PCC use. One patient in each treatment group discontinued due to adverse events (cardiac disorders unrelated to 4F-PCC). This randomized clinical trial found that the investigational 4F-PCC was hemostatically noninferior to the control 4F-PCC for rapid VKA reversal in patients needing urgent surgery with considerable bleeding risk; the safety profile of these two 4F-PCCs was similar. These results support the investigational 4F-PCC as a therapeutic option for surgical patients requiring rapid VKA reversal. ClinicalTrials.gov Identifier: NCT02740335.

Rapid diagnosis of coagulopathies from vitamin K deficiency in a consecutive case cohort evaluated by comparative assessment of factor II by 1-stage assays with prothrombin time vs Ecarin reagents

BackgroundVitamin K (VK) deficiency (VKD) impairs γ-carboxylation of VK-dependent factors (VKDFs), resulting in higher factor (F)II levels measured by Ecarin (FIIE) reagents (that convert des-γ-carboxylated FII to meizothrombin) than by prothrombin time (FII) reagents. ObjectivesTo evaluate FII/FIIE abnormalities among patients assessed for coagulopathies and identify findings predictive of coagulopathy improvement after VK. MethodsWe retrospectively assessed consecutive cases from 2002 to 2021 with FII/FIIE tests and the sensitivity and specificity of FII/FIIE ratios and FIIE-FII differences for VKD defined as international normalized ratio correction/improvement of ≥0.5 after VK. ResultsTwo hundred ninety-two patients (males, 58.2%; adults, 85.6%; median age, 73 years) were evaluated (84.2% hospitalized, 48.3% in intensive care, 71.6% with active liver disease, and 28% deceased at discharge) and 25% to 38% had FII/FIIE findings suggestive of VKD. Among 170 patients assessed for response to VK, FII/FIIE ratios of ≤0.84 to 0.91 and FIIE-FII differences of >0.04 U/mL had similar modest sensitivity (47.7%-69.3%) and modest to good specificity (67.1%-91.5%) for VKD. FII/FIIE ratios of <0.86, suggestive of VKD (sensitivity, 47.7%; specificity, 90.2%), were more common in patients deficient in only VKDF (P = .0001), but were detected in 16% with non-VKDF deficiencies. Low FIIE was commonly associated with active liver disease (P = .0002). Patients with and without probable VKD (based on FII/FIIE ratios of <0.86) had similar mortality, bleeding, and rates of prothrombin complex concentrate and red cell transfusions (P ≥ .78), but fewer with probable VKD received plasma and fibrinogen replacement (P ≤ .024). ConclusionFII/FIIE comparison aids the diagnosis of VKD and predicts clinical responses to VK treatment among patients with coagulopathies.

Effect of oral tranexamic acid on postoperative bleeding in spinal surgery: a randomized controlled trial.

This study aimed to investigate the effect of oral administration of tranexamic acid (TXA) on reducing intraoperative bleeding during spinal surgeries. The study was a single-center, double-blind, randomized, placebo-controlled clinical trial. Participants were individuals over 20 years old who underwent spinal surgery. Patients received 1.5g of TXA orally, 2 h before surgery. Intraoperative bleeding volume, blood volume in the drain after surgery, length of hospital stays after surgery, incidence of nausea or vomiting, decrease in hemoglobin (Hb) level, and postoperative coagulation test results were evaluated in each group. In this study, patients were assigned to each study group based on inclusion and exclusion criteria. The mean age of patients was 69.6±6.47 years, and 65% were male. There was no significant difference in age, sex, pre and postoperative Hb levels, prothrombin time (PT), or international normalized ratio (INR) between the study groups. Intraoperative bleeding volume and blood volume in the drain after surgery were significantly lower in the TXA group. Additionally, the length of hospital stay after surgery was significantly shorter in the TXA group. The incidence of nausea or vomiting was significantly higher in the TXA group. Furthermore, postoperative partial thromboplastin time (PTT) was significantly higher in the TXA group compared to the placebo group. Oral administration of TXA before spinal surgery leads to a significant reduction in intraoperative and postoperative bleeding without significant adverse effects and also reduces the length of hospital stay.

Non-selective beta-blocker is associated with reduced mortality in critically ill patients with cirrhosis: A real-world study.

Apart from direct portal pressure reduction, non-selective beta-blockers (NSBB) modulate inflammatory response, which could be beneficial in patients with acute decompensation (AD). We therefore aimed to evaluate the effect of NSBB on 28-day mortality and markers of systemic inflammation in a propensity score-matched (PSM) cohort of AD patients requiring intensive care unit (ICU) admission. Patients were recruited from registry of AD patients requiring ICU admission. Out of total 445 patients, 108 patients on NSBB before admission (NSBB use group) were PSM for age, gender, pre-admission Child-Turcotte-Pugh score and history of previous decompensation to 108 patients not on NSBB (non-NSBB use group) which served as the control group. ICU parameters, markers of systemic inflammation and 28-day mortality were compared by standard statistical tests. After PSM, no difference was observed in aetiology of cirrhosis, or precipitating event for AD between the groups. Pre-admission creatinine, bilirubin, international normalised ratio and haemoglobin were similar between the groups, whereas pre-admission white cell count (WCC) and neutrophil to lymphocyte ratio (NLR) was lower in NSBB-group. On admission to ICU, NSBB group had lower heart rate (p = 0.006), platelets (p = 0.012), WCC (p = 0.006), NLR (p = 0.039) and C-reactive protein (p = 0.007). Significantly more community acquired bacterial infections (p = 0.006), renal failure (p = 0.033) and higher grades of acute-on-chronic liver failure (ACLF; p = 0.012) were observed in non-NSBB group. Significantly lower 28-day (p = 0.001) and 90-day (p = 0.002) mortality was seen in NSBB group. Univariate and multivariable analysis for 28-day mortality showed that while ACLF at presentation and community acquired bacterial infection were independent negative predictors, prior NSBB use was positive predictors of survival. Prior use of NSBB is associated with improved 28- and 90-day mortality in critically ill cirrhosis patients with AD which is mediated probably by blunting of the inflammatory response.

Utility of Three Serum Biomarkers for Early Detection of Systemic Envenoming Following Viper Bites in Sri Lanka

BackgroundEarly detection of systemic envenoming is critical for early antivenom therapy to minimise morbidity and mortality from snakebite. We assessed the diagnostic utility of three serum biomarkers in the early detection of systemic envenoming in viper bites in rural Sri Lanka. MethodsAll confirmed snakebite patients admitted to Teaching Hospital Anuradhapura from July 2020 to June 2021 were included. On admission, blood was collected for venom concentrations, prothrombin time (PT)/international normalised ratio (INR), fibrinogen, serum creatinine (sCr), and three serum biomarkers - secretory phospholipase A2 (sPLA2), neutrophil gelatinase-associated lipocalin (sNGAL) and clusterin (sClu). Systemic envenoming was defined by the presence of venom-induced consumption coagulopathy, neurotoxicity, acute kidney injury or the presence of non-specific clinical effects. ResultsA total of 237 confirmed snakebite patients (Russell’s viper,72; Hump-nosed viper,80; non-venomous snakes,31; and unidentified bites,54) with sufficient pre-antivenom serum samples were recruited [median age: 42y (interquartile range: 29-53y); males: 173 (73%)]. Systemic envenoming occurred in 68 (94%) Russell’s viper bites, 48 (60%) hump-nosed viper bites and 45 (83%) unidentified bites. The median sPLA2 activity was 72nmol/ml/min (IQR: 30–164) for Russell’s viper envenoming, 12nmol/ml/min (IQR:9–16) for hump-nosed viper envenoming and 11nmol/ml/min (IQR:9-14) for non-venomous bites. There was no difference in sNGAL and sCLu between the three groups. The median sPLA2 activity of patients with systemic envenoming was 16nmol/min/mL (IQR:11–59nmol/min/mL) compared to 11 nmol/min/mL(IQR:9–14nmol/min/mL) in patients without systemic envenoming; difference between medians of 5nmol/min/mL (95% CI:4–12nmol/min/mL). The AUC-ROC of admission sPLA2 was the best predictor of systemic envenoming in all snakebites (AUC-ROC 0.72, 95% CI: 0.66 to 0.79), whereas sNGAL and sClu were poor predictors. sPLA2 was a better predictor of systemic envenoming in Russell’s viper bites (AUC-ROC 0.90, 95% CI:0.76-1.00) and in those presenting within 2h of bite. A sPLA2 activity >23.5nmol/min/ml had a sensitivity of 97% (95% CI:91-99.5%), but a low specificity of 41% (95% CI:34%-49%) in predicting systemic envenoming. A sPLA2 concentration of >46 nmol/min/ml on admission had a sensitivity of 100% (95% CI:51%-100%) and a specificity of 67% (95% CI:55%-77%) in predicting systemic envenoming in Russell’s viper bites. ConclusionsPLA2 is an early predictor of systemic envenoming following snakebite, particularly in Russell’s viper bites and in those who present early.

Clinical Characteristics Analysis of EBV-associated Hemophagocytic Lymphohistiocytosis Patients with Acute Kidney Injury

To analyze the clinical characteristics of patients with Epstein-Barr virus(EBV)-associated hemophagocytic lymphohistiocytosis(HLH) with acute kidney injury(AKI). EBV-HLH patients who were hospitalized in our hospital from January 2014 to December 2020 were collected, and their clinical characteristics, treatment, concurrent acute kidney injury and prognosis were retrospectively analyzed. In this study, the incidence of AKI complicated by EBV-HLH was 65.5%, and the 28-day mortality rate was 15.3%. Compared with non-AKI group, patients in the AKI group had higher levels of bilirubin, lactate dehydrogenase, creatinine, urea nitrogen, and β2-microglobulin（β2-MG）, poorer coagulation, and lower soluble IL-2 receptor （sCD25）. Patients in the AKI group had a higher proportion of chemotherapy, transplantation, mechanical ventilation, and the application of vasoactive medications, and were hospitalized for longer periods of time, with higher in-hospital mortality rates and 28-day mortality rates. Patients in the AKI group were analyzed in subgroups according to the Kidney Disease Improving Global Outcomes （KDIGO）classification, and the levels of leukocytes, bilirubin, albumin, creatinine, urea nitrogen, β2-MG, activated partial thromboplastin time （APTT）, and prothrombin time activity （PTA）were more responsive to the severity of the patient's condition. KDIGO grade 2 and 3 had higher proportions of receiving transplants, diuretics, organ support (mechanical ventilation, application of vasoactive medications, and renal replacement therapy), and admissions to the intensive care unit （ICU）, and with higher in-hospital mortality rates and 28-day mortality rates. Regression analysis found that creatinine, β2-MG, APTT, transplantation, and chemotherapy were independent risk factors for the development of AKI; the application of vasoactive drugs was both an independent risk factor for the development of AKI and for death at 28 days; and chemotherapy, length of hospitalization, and HGB and fibrinogen levels were protective factors for death at 28 days. AKI in EBV-HLH has high incidence and high rate of progression to severe disease and death, early attention should be given and strengthened in order to carry out early treatment and improve the prognosis of patients.

Comparative efficacy of double plasma molecular adsorption system combined with plasma exchange versus plasma exchange in treating acute-on-chronic liver failure due to hepatitis B: A meta-analysis.

This meta-analysis aims to evaluate the effectiveness of the double plasma molecular adsorption system (DPMAS) in combination with plasma exchange (PE) compared to plasma exchange alone in the treatment of Acute-on-Chronic liver failure (LF) caused by hepatitis B. Until August 31, 2023, a comprehensive search of databases including Embase, Chinese Medical Journal Full-text Database, China Biomedical Literature Database, Wan Fang Medical Network, PubMed, and the Cochrane Library was carried out using keywords like "liver failure," "acute-on-chronic liver failure," "PE," "DPMAS," and related terms. The quality of the included studies was evaluated using QUADS (quality assessment of diagnostic accuracy studies). Software Revman 5.3 was used to examine the data, while Stata 15.1 was used to run Egger's test. Following thorough screening, 452 patients who received PE alone and 429 patients who received DPMAS in addition to PE were included. Every study that was included was of a high caliber. When comparing the DPMAS plus PE group to the PE alone group, the total bilirubin reduction was considerably higher (mean difference [MD] = -49.09, 95% confidence interval [CI]: -54.84 to -43.35, p < .00001). Prothrombin activity (PTA; MD = -1.53, 95% CI: -3.29 to -0.22, p = .09), albumin (ALB; MD = -0.58, 95% CI: -1.57 to 0.41, p = .25), prothrombin time (PT; MD = -0.07, 95% CI: -1.47 to 1.34, p = .92), and platelet count (PLT; MD = -0.08, 95% CI: -1.33 to 1.66, p = .90) did not differ significantly. The improvement in international standardized ratio (INR) was significantly greater in the PE group (MD = 0.07, 95% CI (0.03, 0.10), p = .0001). When combined with DPMAS, PE has been shown to be more effective in lowering total bilirubin levels. PE can also lower INR in individuals who have hepatitis B-related ACLF. This therapeutic strategy also lessens the need for plasma transfusions.

Selective red blood cell depletion by apheresis in sheep causes severe normovolemic anemia

Background: The setting of normovolemic anemia is required for a variety of research applications, such as testing of novel medication for anemia treatment. Unfortunately, large animal models using full blood draw and replenishment with balanced electrolyte solution (BES) lead to bleeding complications, as coagulation factors and platelets are also drawn. We therefore aimed to establish a model of selective red blood cell (RBC) depletion to the main endpoint of hemoglobin (Hgb) levels of 4–6 g dL−1 using apheresis in sheep. Methods: In vitro experiments were performed first to establish the apheresis protocol. In vivo, anesthetized ewes underwent a sham protocol without apheresis (n = 5) or apheresis (n = 4). Both groups were observed for the following six hours at a defined starting point (BE0) to compare Hgb, hematocrit (Hct), coagulation and clinical parameters. For statistical analysis, unpaired t-test with Welch`s correction was used. Results: Hgb levels were effectively decreased by 51 % to mean Hgb of 4.4 g dL−1 in the apheresis group compared to 9.1 g dL−1 in sham (*p < 0.0001). Hct (11.2% vs 25.1 %, *p = 0.01) and RBCs (3.7 vs 8.2 × 106/µl, *p = 0.003) also decreased. The relative number of platelets compared to baseline was different (55.6 ± 10.6% vs. 100 ± 0 %, *p = 0.004), but no hemorrhage was observed. White blood cells (WBCs), lactate, prothrombin ratio and activated partial thromboplastin time (aPTT) remained within similar ranges. Conclusions: Critical normovolemic anemia without bleeding complications was successfully reached by selective RBC depletion in sheep. Investigations of physiological adaptations to severe anemia and pharmaceutical testing can be performed in large animals with depleted RBCs.