[Endometriosis-related recurrent unilateral hemorrhagic pleural effusion: a case report].

Hemorrhagic pleural effusion (PE) is common in clinical practice. According to the guidelines, the etiological diagnosis of PE should focus on the identification of common diseases. In most cases, the etiology of PE can be determined by clinical history, physical examination, laboratory and imaging examinations, and pleural biopsy or video-assisted thoracic surgery (VAST). We reported a rare case of a 32-year-old woman with recurrent unilateral hemorrhagic pleural effusion (highly correlated with menstrual cycle) and chest pain that was diagnosed as thoracic endometriosis syndrome (TES) by pathological biopsy and immunohistochemistry. Later she underwent surgery combined with hormone therapy. During the follow-up, the right PE decreased, and she had no chest pain. Therefore, women of reproductive age with regular unilateral bloody pleural effusions should be alert to TES.

Assessment of a randomized controlled trial on the safety of pre-placing bronchial balloons in transbronchial lung cryobiopsy for diagnosing interstitial lung disease.

RATIONALE AND OBJECTIVES: Bleeding is a major complication of transbronchial lung cryobiopsy (TBLC), and pre-placing a bronchial balloon is one of the clinical practices used to prevent it, but with very weak evidence, which should be confirmed. This study aimed to conduct whether pre-placing a bronchial balloon in TBLC for diagnosing interstitial lung disease (ILD) is more safety. MATERIALS AND METHODS: In this prospective, single-center, randomized controlled trial, patients with suspected ILD were enrolled and randomly assigned to pre-placed balloon and none-pre-placed balloon groups. The primary outcome was incidence of moderate bleeding in each group. The secondary endpoints were the incidence of severe bleeding, pneumothorax, and other procedural complications. RESULTS: Exactly 250 patients were enrolled between August 2019 and March 2022, with 125 in each group. There were no significant differences in severe bleeding between the none-pre-placed balloon group and pre-placed balloon group (1.6% vs. 0.8%; adjusted p = 0.520), while more moderate bleeding occurred in the none-pre-placed balloon group (26.4% vs. 6.4%, adjusted p = 0.001), as well as more use of hemostatic drug (28.0% vs. 6.4%, adjusted p = 0.001). Three patients in the none-pre-placed balloon group used the bronchial balloon. More samples could be acquired in the pre-placed balloon group than in the none-pre-placed balloon group (3.8 ± 0.9 vs. 3.1 ± 0.9, p < 0.001). There were no significant differences in multidisciplinary discussion (MDD) between the two groups (89.6% vs. 91.2%, adjusted p = 0.182). CONCLUSION: A pre-placed bronchial balloon can reduce the incidence of moderate bleeding and increase the confidence of the bronchoscopists. However, it had no effect on increasing the diagnostic rate of MDD and reducing severe bleeding. REGISTRATION NUMBER: NCT04047667 ( www. CLINICALTRIALS: gov identifier).

Diagnosis and treatment of von Willebrand disease in 2024 and beyond.

MANUSCRIPT BACKGROUND AND AIM: The diagnosis and clinical care of patients with von Willebrand disease (VWD) has continued to evolve since the characterization of the von Willebrand factor (VWF) gene in 1985. This condition is almost certainly the most common inherited bleeding disorder, and the major symptomatic burden of the disease is experienced by females during their reproductive years. Diagnosis relies on the identification of a personal and family history of excessive mucocutaneous bleeding, and laboratory features consistent with quantitative and/or qualitative abnormalities of VWF. This review focuses on three aspects of VWD management, with current updates and a look into the future. MANUSCRIPT THEMES: First, we will address the role of genetics in the diagnosis and possible therapies for VWD. With current technologies, VWD genetic diagnosis is usually confined to the confirmation of type 2 subtypes of the disease and type 3 VWD analysis for family planning. While type 3 VWD is a potential candidate for the application of gene therapy, no treatments are currently close to entering the clinic. Second, the peri-procedural management of patients with VWD remains an important element of care. The choice of product, its dose and schedule all require careful consideration depending upon the type and disruptive nature of the planned procedure. Lastly, in addition to gene therapy, several other novel therapeutic interventions are also being developed for bleeding and prophylaxis in VWD. These include a VWF aptamer interfering with VWF clearance and bioengineered forms of VWF.

Preoperative BMI and Hb levels are important predictors of massive bleeding in liver transplant patients.

OBJECTIVE: This study aims to compare intraoperative bleeding during liver transplant procedures and analyze the predictive role of preoperative laboratory indicators in significant intraoperative bleeding. PATIENTS AND METHODS: A retrospective analysis was conducted on 271 cases of allogeneic liver transplant patients from January 2018 to June 2023. Patients were categorized into the massive bleeding (MB) group and the non-massive bleeding (non-MB) group based on the occurrence of significant intraoperative bleeding. Preoperative laboratory parameters between the MB and non-MB groups were compared, and univariate and multivariate regression analyses were performed. ROC curves were performed to analyze the value of these parameters in distinguishing the MB and non-MB groups. RESULTS: In the MB group, body mass index (BMI), hemoglobin (Hb), platelet count (PLT), fibrinogen (Fib), and total protein (TP) levels were significantly lower than those in the non-MB group (p < 0.05). Conversely, prothrombin time (PT), international normalized ratio (INR), total bilirubin (TBIL), creatinine (CRE), blood urea nitrogen (BUN), the model for end-stage liver disease (MELD) score, length of stay, and hospital stay were significantly higher in the MB group compared to the non-MB group (p < 0.05). Univariate and multivariate logistic regression analyses revealed that preoperative BMI and Hb were independent risk factors for massive bleeding during liver transplantation. ROC curve analysis for predicting massive intraoperative bleeding showed that the area under the curve (AUC) of Hb was considerable (AUC: 0.83). CONCLUSIONS: Preoperative BMI and Hb levels are critical predictors of massive bleeding during liver transplantation, emphasizing the importance of proactive management based on these indicators for improved patient outcomes.

Adrenal Hemorrhage: A Comprehensive Analysis of a Heterogeneous Entity-Etiology, Presentation, Management, and Outcomes.

OBJECTIVE: To investigate the etiology, presentation, management, and outcomes of patients with adrenal hemorrhage (AH). PATIENTS AND METHODS: Longitudinal study of consecutive adult patients with radiologically confirmed AH (January 1, 2017, through December 31, 2021). RESULTS: Of the 363 patients with AH (median age, 62 years [interquartile range (IQR, 52-70 years]; 128 women [35%]), 338 (93%) had unilateral AH and 25 (7%) had bilateral AH. It was discovered incidentally in 152 patients (42%) and during the evaluation of trauma in 103 (28%), abdominal/back pain in 90 (25%), critical illness in 13 (4%), and symptoms of adrenal insufficiency in 5 (1%). Etiologies included postoperative complications in 150 patients (41%), trauma in 107 (30%), coagulopathy in 22 (6%), anticoagulant/antiplatelet therapy in 39 (11%), adrenal neoplasm in 22 (6%), and sepsis in 11, (3%). Overall, 165 patients (46%) were hospitalized, and no deaths occurred due to AH. Median (IQR) baseline AH size was 34 mm (24-40 mm) on the right and 29 mm (22-37 mm) on the left. Among 246 patients with follow-up imaging, AH resolution was complete in 155 (63%) and incomplete in 74 (30%) at a median of 15 months (IQR, 6-31 months). Patients with bilateral AH were more likely to have underlying coagulopathy (44% vs 3%) and to develop primary adrenal insufficiency (72% vs 0%) than those with unilateral AH (P<.001). CONCLUSION: Often, AH presents as an incidental unilateral lesion with normal adrenal function, commonly attributed to postoperative complications or trauma. In contrast, bilateral AH is rare and typically linked to underlying coagulopathy, with primary adrenal insufficiency developing in most patients.

Development and Validation of Machine Learning Algorithms to Predict 1-Year Ischemic Stroke and Bleeding Events in Patients with Atrial Fibrillation and Cancer.

In this study, we leveraged machine learning (ML) approach to develop and validate new assessment tools for predicting stroke and bleeding among patients with atrial fibrillation (AFib) and cancer. We conducted a retrospective cohort study including patients who were newly diagnosed with AFib with a record of cancer from the 2012-2018 Surveillance, Epidemiology, and End Results (SEER)-Medicare database. The ML algorithms were developed and validated separately for each outcome by fitting elastic net, random forest (RF), extreme gradient boosting (XGBoost), support vector machine (SVM), and neural network models with tenfold cross-validation (train:test = 7:3). We obtained area under the curve (AUC), sensitivity, specificity, and F2 score as performance metrics. Model calibration was assessed using Brier score. In sensitivity analysis, we resampled data using Synthetic Minority Oversampling Technique (SMOTE). Among 18,388 patients with AFib and cancer, 523 (2.84%) had ischemic stroke and 221 (1.20%) had major bleeding within one year after AFib diagnosis. In prediction of ischemic stroke, RF significantly outperformed other ML models [AUC (0.916, 95% CI 0.887-0.945), sensitivity 0.868, specificity 0.801, F2 score 0.375, Brier score = 0.035]. However, the performance of ML algorithms in prediction of major bleeding was low with highest AUC achieved by RF (0.623, 95% CI 0.554-0.692). RF models performed better than CHA2DS2-VASc and HAS-BLED scores. SMOTE did not improve the performance of the ML algorithms. Our study demonstrated a promising application of ML in stroke prediction among patients with AFib and cancer. This tool may be leveraged in assisting clinicians to identify patients at high risk of stroke and optimize treatment decisions.

Rare bleeding disorders: Real-world data from a Spanish tertiary hospital.

INTRODUCTION: Due to their low prevalence, rare bleeding disorders (RBDs) remain poorly characterized. AIM: To gain insight of RBDs through our clinical practice. METHODS: Retrospective study of the medical records of RBD patients followed up at the Central University Hospital of Asturias between January 2019 and December 2022. RESULTS: A total of 149 patients were included. Factor (F) VII (44 %) and FXI (40 %) deficiencies were the most common diagnosed coagulopathies. Most of the patients were asymptomatic (60.4 %) and the most frequent type of bleeding were mucocutaneous and after surgery. All replacement treatments were administered on demand and no patient was on a prophylaxis regimen. Currently available products were safe; allergic reactions after administration of plasma were the most frequent complication. Genetic analysis, carried out on 55 patients (37 %), showed that the most frequent mutations in RBDs are of missense type (71.9 %). We identified 11 different novel genetic alterations in affected genes. The c.802C > T (p.Arg268Cys) variant, previously described, was identified in 71 % (15 of 21) of the patients with FXI deficiency genotyped and none were related (probable founder effect). CONCLUSION: Our study on an unusual large single center cohort of RBD patients portrays location-dependent distinct genetic drives and clinical practice particularities.

Stop the Bleed in the Era of Virtual Learning: A Novel Strategy for Remote Teaching and Evaluation.

INTRODUCTION: Traumatic hemorrhage is a leading cause of preventable mortality worldwide. The Stop the Bleed (STB) course was developed to equip layperson bystanders with basic bleeding control knowledge and skills. However, large in-person courses have been disrupted due to COVID-19. The aim of this study was to determine the feasibility of teaching and evaluating STB skills through remote video-based instruction. METHODS: After undergoing COVID-19 screening, groups of up to eight STB-naive adults were seated in a socially distanced manner and given individual practice kits. A remote STB-certified instructor provided the standard STB lecture and led a 10-min skills practice session via videoconferencing. Participants' skills were evaluated on a 10-point rubric by one in-person evaluator and three remote evaluators. Participants completed a postcourse survey assessing their perceptions of the course. RESULTS: Thirty-five participants completed the course, all scoring ≥8/10 after examination by the in-person evaluator. Remote instructors' average scores (9.8 ± 0.45) did not significantly differ from scores of the in-person evaluator (9.9 ± 0.37) (P = 0.252). Thirty-three participants (94%) completed the postcourse survey. All respondents reported being willing and prepared to intervene in scenarios of life-threatening hemorrhage, and 97% reported confidence in using all STB skills. CONCLUSIONS: STB skills can be effectively taught and evaluated through a live video-based course. All participants scored highly when evaluated both in-person and remotely, and nearly all reported confidence in skills and knowledge following the course. Remote instruction is a valuable strategy to disseminate STB training to students without access to in-person courses, especially during pandemic restrictions.

Guidelines in trauma-related bleeding and coagulopathy: an update.

PURPOSE OF REVIEW: The diagnosis and treatment of patients with severe traumatic bleeding and subsequent trauma-induced coagulopathy (TIC) is still inconsistent, although the implementation of standardized algorithms/treatment pathways was repeatedly linked to improved outcome. Various evidence-based guidelines for these patients now exist, three of which have recently been updated. RECENT FINDINGS: A synopsis of the three recently updated guidelines for diagnosis and treatment of seriously bleeding trauma patients with TIC is presented: (i) AWMF S3 guideline 'Polytrauma/Seriously Injured Patient Treatment' under the auspices of the German Society for Trauma Surgery; (ii) guideline of the European Society of Anesthesiology and Intensive Care (ESAIC) on the management of perioperative bleeding; and (iii) European guideline on the management of major bleeding and coagulopathy after trauma in its 6th edition (EU-Trauma). SUMMARY: Treatment of trauma-related bleeding begins at the scene with local compression, use of tourniquets and pelvic binders and rapid transport to a certified trauma centre. After arrival at the hospital, measures to record, monitor and support coagulation function should be initiated immediately. Surgical bleeding control is carried out according to 'damage control' principles. Modern coagulation management includes individualized treatment based on target values derived from point-of-care viscoelastic test procedures.

Massive transfusion in trauma.

PURPOSE OF REVIEW: The purpose of this review is to provide an overview of currently recommended treatment approaches for traumatic hemorrhage shock, with a special focus on massive transfusion. RECENT FINDINGS: Severe trauma patients require massive transfusion, but consensual international definitions for traumatic hemorrhage shock and massive transfusion are missing. Current literature defines a massive transfusion as transfusion of a minimum of 3-4 packed red blood cells within 1 h. Using standard laboratory and/or viscoelastic tests, earliest diagnosis and treatment should focus on trauma-induced coagulopathy and substitution of substantiated deficiencies. SUMMARY: To initiate therapy immediately massive transfusion protocols are helpful focusing on early hemorrhage control using hemostatic dressing and tourniquets, correction of metabolic derangements to decrease coagulopathy and substitution according to viscoelastic assays and blood gases analysis with tranexamic acid, fibrinogen concentrate, red blood cells, plasma and platelets are recommended. Alternatively, the use of whole blood is possible. If needed, further support using prothrombin complex, factor XIII or desmopressin is suggested.

Cytological diagnosis of exercise-induced pulmonary haemorrhage: Comparison of tracheal wash and bronchoalveolar lavage in standardbred racehorses.

BACKGROUND: Cytology of airway samples is sensitive for diagnosis of exercise-induced pulmonary haemorrhage (EIPH), but the association between tracheal wash (TW) and bronchoalveolar lavage fluid (BALF) is unknown. The objective of this study was to determine whether diagnosis of EIPH, using haemosiderophages/macrophages (H/M) ratio, differs when based on TW or BALF. METHODS: A prospective cross-sectional study was conducted on 102 standardbred horses in training. TW and BALF were collected concomitantly from all horses at rest (at least 24 hours after their last training or race), and their H/M ratios were calculated. Spearman's correlation, Cohen's kappa and Gwet's coefficient tests were performed to evaluate the association between TW and BALF samples. RESULTS: With BALF, 21 horses met the cytological inclusion criteria for an EIPH diagnosis from individual and/or pooled samples. With TW, 20 horses had occasional (H/M < 10%) haemosiderophages, and nine, one and three horses had small (10%-25%), moderate (25%-50%) and large (>50%) proportions, respectively. Poor correlations and inconsistent concordances between TW and BALF were found for H/M ratio. LIMITATIONS: Limitations include the use of a single staining method and the absence of a total haemosiderin score. CONCLUSION: No association between TW and BALF was found for the cytological diagnosis of EIPH. Based on H/M ratio, BALF remains the sample type of choice for cytological diagnosis of EIPH.

Developing a machine learning model for bleeding prediction in patients with cancer-associated thrombosis receiving anticoagulation therapy.

BACKGROUND: Only 1 conventional score is available for assessing bleeding risk in patients with cancer-associated thrombosis (CAT): the CAT-BLEED score. OBJECTIVES: Our aim was to develop a machine learning-based risk assessment model for predicting bleeding in CAT and to evaluate its predictive performance in comparison to that of the CAT-BLEED score. METHODS: We collected 488 attributes (clinical data, biochemistry, and International Classification of Diseases, 10th Revision, diagnosis) in 1080 unique patients with CAT. We compared CAT-BLEED score, Ridge and Lasso logistic regression, random forest, and Extreme Gradient Boosting (XGBoost) algorithms for predicting major bleeding or clinically relevant nonmajor bleeding occurring 1 to 90 days, 1 to 365 days, and 90 to 455 days after venous thromboembolism (VTE). RESULTS: The predictive performances of Lasso logistic regression, random forest, and XGBoost were higher than that of the CAT-BLEED score in the prediction of bleeding occurring 1 to 90 days and 1 to 365 days after VTE. For predicting major bleeding or clinically relevant nonmajor bleeding 1 to 90 days after VTE, the CAT-BLEED score achieved a mean area under the receiver operating characteristic curve (AUROC) of 0.48 ± 0.13, while Lasso logistic regression and XGBoost both achieved AUROCs of 0.64 ± 0.12. For predicting bleeding 1 to 365 days after VTE, the CAT-BLEED score achieved a mean AUROC of 0.47 ± 0.08, while Lasso logistic regression and XGBoost achieved AUROCs of 0.64 ± 0.08 and 0.59 ± 0.08, respectively. CONCLUSION: This is the first machine learning-based risk model for bleeding prediction in patients with CAT receiving anticoagulation therapy. Its predictive performance was higher than that of the conventional CAT-BLEED score. With further development, this novel algorithm might enable clinicians to perform personalized anticoagulation strategies with improved clinical outcomes.

Diagnostic value of clot formation parameters determined by rotational thromboelastometry in 63 patients with congenital dysfibrinogenemia.

Rotational thromboelastometry (ROTEM) is a global hemostasis assay. The diagnosis added value of ROTEM in congenital dysfibrinogenemia remains to be established. The aim of this study was to analyze clot formation by ROTEM in a cohort of dysfibrinogenemic patients and to establish correlations with genotype, clinical features, and coagulation parameters. The study included genetically confirmed congenital dysfibrinogenemia cases (n = 63) and healthy controls ( n  = 50). EXTEM, INTEM, FIBTEM tests were used to measure ROTEM parameters, that is, clotting time (CT), clot formation time (CFT), maximal clot firmness (MCF) and amplitude 10 min after CT (A10). The ISTH bleeding assessment tool was used to determine bleeding episodes. CT (INTEM) was statistically significantly shorter in congenital dysfibrinogenemia patients compared to controls while CFT (EXTEM) was prolonged. Patients's MCF in EXTEM, INTEM, and FIBTEM were similar to controls while A10 (FIBTEM) was statistically significantly lower. Fibrinogen activity was positively correlated with fibrinogen antigen, A10 and MCF in all three assays. Bleeding phenotypes were observed in 23 (36.5%) patients. Only CFT in EXTEM and CT in INTEM were statistically different in patients with bleeding phenotype versus controls. Carriers of the FGA mutation p.Arg35His had a CT (EXTEM) slightly prolonged and a reduced A10 (FIBTEM) compared to controls. Some ROTEM parameters were able to distinguish congenital dysfibrinogenemia patients from controls, and patients with a bleeding phenotype. Prolonged CFT in EXTEM were associated with congenital dysfibrinogenemia and bleeding phenotype. Bleeding episodes in most patients were generally mild and prevalence of thrombosis was very low.

External validation of the PE-SARD risk score for predicting early bleeding in acute pulmonary embolism in the RIETE Registry.

INTRODUCTION: The PE-SARD score (syncope, anemia, renal dysfunction) was developed to predict the risk of major bleeding in the acute phase of pulmonary embolism (PE). METHODS: We analyzed data from 50,686 patients with acute PE included in the RIETE registry to externally validate the PE-SARD score. We calculated the overall reliability of the PE-SARD score, as well as discrimination and calibration for predicting the risk of major bleeding at 30 days. The performance of PE-SARD was compared to the BACS and PE-CH models. RESULTS: During the first 30 days, 640 patients (1.3 %) had a major bleeding event. The incidence of major bleeding within 30 days was 0.6 % in the PE-SARD-defined low-risk group, 1.5 % in the intermediate-risk group, and 2.5 % in the high-risk group, for an OR of 2.22 (95 % CI, 2.02-2.43) for the intermediate-risk group (vs low-risk group), and 3.94 for the high-risk group (vs low-risk group). The corresponding sensitivity was 81.1 % (intermediate/high vs low risk), and specificity was 85.9 % (95 % CI, 85.8-86.1) (low/intermediate vs high risk). The applicability of PE-SARD was consistent across clinically relevant patient subgroups and over shorter time periods of follow-up (i.e., 3 and 7 days). The C-index was 0.654 and calibration was excellent. The PE-SARD bleeding score improved the major bleeding risk prediction compared with the BACS and PE-CH scores. CONCLUSIONS: The PE-SARD score identifies PE patients with a higher risk of bleeding, which could assist providers for potentially adjusting PE management, in a framework of shared decision-making with individual patients.

A comprehensive guide on the optimal timing of PCI in the setting of acute coronary syndrome: An updated meta-analysis.

BACKGROUND: Invasive revascularization is recommended for cohorts of patients with ST-elevation myocardial infarction (STEMI) and non-ST-elevation acute coronary syndrome (NSTE-ACS). However, the optimal timing of invasive revascularization is still controversial and no defined consensus is established. We aim to give a comprehensive appraisal on the optimal timing of invasive strategy in the heterogenous population of ACS. METHODS: Relevant studies were assessed through PubMed, Scopus, Web of science, and Cochrane Library from inception until April 2023. Major adverse cardiovascular events (MACE) and all-cause mortality were our primary outcomes of interest, other secondary outcomes were cardiac death, TVR, MI, repeat revascularization, recurrent ischemia, and major bleeding. The data was pooled as odds ratio (OR) with its 95% confidence interval (CI) in a random effect model using STATA 17 MP. RESULTS: A total of 26 studies comprising 21,443 patients were included in the analysis. Early intervention was favor to decrease all-cause mortality (OR = 0.79, 95% CI: 0.64 to 0.98, p = 0.03), when compared to delayed intervention. Subgroup analysis showed that early intervention was significantly associated with all-cause mortality reduction in only NSTE-ACS (OR = 0.83, 95% CI [0.7 to 0.99], p = 0.04). However, there was no significant difference between early and delayed intervention in terms of MACE, cardiac death, TVR, MI, repeat revascularization, recurrent ischemia, and major bleeding. CONCLUSION: An early intervention was associated with lower mortality rates compared to delayed intervention in NSTE-ACS with no significant difference in other clinical outcomes. PROSPERO registration: CRD42023415574.