An accurate haplotyping method using multiplex pyrosequencing with AS-PCR to detect ABCB1 haplotypes associated with rivaroxaban-derived hemorrhagic events.

In clinical practice, owing to the comprehensive genetic insights they offer, haplotypes have attracted greater attention than individual single nucleotide polymorphisms (SNPs). Due to the long distances across SNP locations, detecting the haplotype using genomic DNA is challenging. Current haplotyping methods are either expensive and labor-intensive (high-throughput DNA sequencing), or haplotyping a single clinical sample (computational approach) is impossible. Herein, we propose using mRNA as a haplotyping target to minimize the distance among SNPs and employing allele-specific PCR (AS-PCR) to pick up a desired haplotype, followed by multiplex pyrosequencing to type the alleles at the SNP location of interest. AS-PCR was improved by combining an additional 3'-phosphorylated modified probe to achieve the specific separation of two closely similar templates. Only the sample with more than two heterozygotes needs to be haplotyped; therefore, we propose a stratification strategy to screen the samples for further haplotyping. This method was evaluated by associating ABCB1 haplotypes with the rivaroxaban-derived side effect in a cohort of 505 patients with nephrotic syndrome, focusing on the SNPs of ABCB1: rs1236C > T, rs2677G > T/A, and rs3435C > T. We successfully identified five bleeding-related haplotypes: rs1236T-rs2677T-rs3435T, rs1236C-rs2677G-rs3435T, rs1236T-rs2677G-rs3435C, rs1236C-rs2677G-rs3435C, and rs1236T-rs2677T-rs3435C. We compared the results with those from the conventional computational algorithm PHASE and observed that PHASE results dismissed the impact of rs1236C-rs2677G-rs3435C and rs1236C-rs2677G-rs3435T on bleeding risk and erroneously suggested a false positive association of rs1236C-rs2677A-rs3435T with increased bleeding risk.

Assessment of bleeding events in patients receiving DOACs with or without statins to treat venous thromboembolism: insights from the RIETE registry.

OBJECTIVE: To evaluate the impact of coadministering statins with direct oral anticoagulants (DOACs) on the risk of major bleeding events in patients with venous thromboembolism (VTE). DESIGN: Observational cohort analysis based on a multicentre international registry. SETTING: Data were extracted from the Registro Informatizado de Enfermedad TromboEmbolica Registry, which involves 205 centres across 27 countries. PARTICIPANTS: A total of 73 659 patients diagnosed with VTE were classified based on their anticoagulant therapy (DOACs) versus low-molecular-weight heparin (LMWH) or vitamin K antagonists (VKAs) and concurrent use of statins. METHODS: Multivariable Cox proportional hazards models adjusted for confounding variables to assess the risk of major bleeding events stratified by the type of anticoagulant use and statin use. RESULTS: From October 2013 to February 2023, 73 659 patients were recruited: 2573 were statin users on DOACs, 14 090 were statin users on LMWH or VKA therapy, 10 088 were non-statin users on DOACs and 46 908 were non-statin users on LMWH or VKA therapy. Statin users were 10 years older and more likely to have hypertension, diabetes, renal failure or prior artery disease. During anticoagulation (median, 187 days), 1917 patients (2.6%) suffered major bleeding. Rates of major bleeding per 100 patient-years were 2.33 (95% CI 1.72 to 3.09), 3.75 (95% CI 3.43 to 4.10), 1.39 (95% CI 1.13 to 1.69) and 3.10 (95% CI 2.93 to 3.27), respectively. On multivariable analysis, patients treated with DOACs had a significantly lower risk of major bleeding compared with those on LMWH or VKA therapy (adjusted HR 0.59; 95% CI 0.48 to 0.74). The adjusted HR in statin users versus non-users was 1.03 (95% CI 0.92 to 1.14), while in statin users on DOACs versus the rest of patients, it was 1.18 (95% CI 0.79 to 1.76). CONCLUSIONS: In patients with VTE receiving statins, long-term anticoagulation with DOACs was associated with a reduced risk of major bleeding, regardless of the statin use. These findings support the safety profile of DOACs over VKAs or LMWH in the management of VTE in patients requiring statins.

Antithrombotic therapy in patients with atrial fibrillation after percutaneous coronary intervention.

INTRODUCTION: Patients who undergo percutaneous coronary intervention (PCI) with stenting usually require a period of dual antiplatelet therapy (DAPT) but, when an indication for long-term oral anticoagulation (OAC) such as atrial fibrillation (AF) coexists, triple antithrombotic therapy (TAT) with DAPT and OAC causes concern for excessive bleeding. Achieving the right balance between bleeding and adequate protection from ischemic events remains an issue of debate and subject to ongoing investigation of various antithrombotic regimens and durations. AREAS COVERED: This review describes the landmark clinical trials comparing TAT to a period of dual antithrombotic therapy (DAT) and subsequent meta-analyses. It also describes the international recommendations that have been derived from this evidence and identifies outstanding issues that could be addressed in upcoming or future trials. EXPERT OPINION: The current recommended default strategy of a short period of TAT with clopidogrel followed by the withdrawal of aspirin faces a challenge from the prospect of more consistent P2Y12 inhibition provided by ticagrelor and prasugrel. Ticagrelor monotherapy has already been trialed in patients after PCI without an indication for OAC. DAT with ticagrelor or prasugrel immediately post-procedure could emerge as a comparably safe and more efficacious regimen than one involving clopidogrel in the right setting.

Life-threatening event in laparoscopic hepatic surgery: Training curriculum on sudden hepatic artery haemorrhage.

BACKGROUND: Exposure of the hepatic artery is a fundamental step in many surgeries, during which iatrogenic hepatic artery injury may occur. Although the incidence of hepatic artery haemorrhage is low, its occurrence can lead to life-threatening haemorrhage. It is difficult and dangerous to accumulate clinical experience in laparoscopic hepatic artery repair in actual patients, and simulation training models for laparoscopic hepatic artery repair are currently lacking. In this study, a 3D printed model was designed to simulate the training curriculum for sudden hepatic artery haemorrhage, but whether training with the 3D printed model could yield superior skill improvement for surgeons remained to be determined. METHODS: A new 3D printed model was designed for this study. Surgeons from the General Surgery Department of Sir Run Run Shaw Hospital participated in this simulation training. The surgical performance of each model was compared, and the authenticity of the model was evaluated and mechanically tested. RESULTS: Experienced surgeons performed better on the 3D printed model. After repeated training, inexperienced surgeons showed significant improvement of their laparoscopic hepatic artery repair skills. The authenticity of the model was generally satisfactory, but shortcomings persisted in the mechanical testing of artery wall tearing, necessitating further improvement. CONCLUSIONS: Few studies have investigated laparoscopic simulation training for sudden hepatic artery haemorrhage. This simulation model distinguishes surgeons with different levels of experience and allows those with less experience to improve their laparoscopic hepatic artery repair skills through training on the model.

Meta-Analysis Comparing Oral Anticoagulant Monotherapy Versus Dual Antithrombotic Therapy in Patients With Atrial Fibrillation and Stable Coronary Artery Disease.

BACKGROUND: Oral anticoagulants (OACs) are routinely used for the management of atrial fibrillation (AF) while antiplatelet agents are used in coronary artery disease (CAD). However, data regarding the comparative clinical outcomes of OAC monotherapy versus dual antithrombotic therapy (anticoagulant plus antiplatelet agent) in patients with AF and stable CAD are limited. METHODS: A comprehensive search of major databases including PubMed/MEDLINE, Cochrane Library, and Embase was performed from inception to September 1, 2024 to identify randomized control trials (RCTs) that compared OAC monotherapy with dual antithrombotic therapy in patients with AF and stable CAD. The risk ratios (RRs) were estimated with corresponding 95% confidence intervals (CIs) for all outcomes. RESULTS: A total of three RCTs reported data for 3945 patients with AF and stable CAD. The mean age of patients was 73.8 (±11.85) years and the mean follow-up was 22 months. OAC monotherapy was associated with a significantly reduced relative risk of major bleeding (RR: 0.55, 95% CI: 0.32-0.95) compared to dual therapy. The risk of all-cause death (RR: 0.85, 95% CI: 0.49-1.48), cardiovascular death (RR: 0.84, 95% CI: 0.50-1.41), any stroke event (RR: 0.74, 95% CI: 0.46-1.18), and myocardial infarction (RR: 1.57, 95% CI: 0.79-3.12) remained comparable across the two groups. CONCLUSION: OAC monotherapy led to a significant relative risk reduction for major bleeding with similar rates of ischemic events and mortality compared to dual antithrombotic therapy in patients with AF and stable CAD.

Association Between Neurological Status and Outcomes in Cardiac Arrest Patients Undergoing PCI in Contemporary Practice: Insights From BMC2.

BACKGROUND: Coronary artery disease remains the largest contributor to cardiac arrests worldwide; yet, long-term outcomes are often driven by neurological status after resuscitation. We examined the association between pre-percutaneous coronary intervention (PCI) level of consciousness (LOC) and outcomes among patients with cardiac arrest who underwent PCI. METHODS: The study cohort included patients undergoing PCI after cardiac arrest between April 2018 and March 2022 at 48 hospitals in the state of Michigan. Pre-PCI LOC was categorized as mentally alert, partially responsive, unresponsive, and unable to assess. In-hospital outcomes included mortality, bleeding, and acute kidney injury. RESULTS: Among 3021 patients who underwent PCI after cardiac arrest, 1394 (49%) were mentally alert, 132 (5%) were partially responsive, 698 (24%) were unresponsive, and 631 (22%) were unable to assess. The mentally alert cohort had lower mortality (4.59%) compared with the partially responsive (17.42%), unresponsive (50.14%), and unable to assess cohorts (38.03%; P<0.001). After adjusting for baseline differences, compared with mentally alert patients, the odds of mortality were markedly elevated in patients who were partially responsive (adjusted odds ratio, 4.63 [95% CI, 2.67-8.04]; P<0.001), unable to assess (adjusted odds ratio, 13.95 [95% CI, 9.97-19.51]; P<0.001), and unresponsive (adjusted odds ratio, 24.36 [17.34-34.23]; P<0.001). After adjustment, patients with impaired LOC also had higher risks of acute kidney injury and bleeding compared with mentally alert patients. CONCLUSIONS: Pre-PCI LOC is a strong predictor of in-hospital outcomes after PCI among cardiac arrest patients. A patient's pre-PCI LOC should be considered an important factor when weighing treatment options, designing clinical trials, and counseling patients and their families regarding prognosis after PCI.

Randomized Trial of COBRA PzF Stenting to Reduce the Duration of Triple Therapy: The COBRA-REDUCE Trial.

BACKGROUND: Patients with an indication for oral anticoagulation who undergo percutaneous coronary intervention require a combination of oral anticoagulation and antiplatelet therapy. The use of a coronary stent with a thromboresistant and pro-healing coating may allow an abbreviated duration of dual antiplatelet therapy (DAPT) without an increase in the risk of thromboembolic events. METHODS: Patients with an indication for oral anticoagulation undergoing percutaneous coronary intervention were randomized to treatment with the COBRA polyzene F (PzF) stent followed by 14 days of DAPT or a Food and Drug Administration-approved new-generation drug-eluting stent followed by 3 or 6 months of DAPT. The bleeding coprimary end point was Bleeding Academic Research Consortium type ≥2 beyond 14 days (or after hospital discharge) until 6 months. The thromboembolic coprimary end point was the composite of all-cause death, myocardial infarction, definite or probable stent thrombosis, or ischemic stroke at 6 months. The trial hypothesis was that the COBRA PzF stent strategy would be superior with respect to bleeding events and noninferior with respect to thromboembolic events. RESULTS: A total of 996 patients underwent randomization. The bleeding end point occurred in 37 of 475 patients (7.8%) in the COBRA PzF group and 47 of 482 patients (9.8%) in the control group (difference, -2.0 [95% CI, -5.6 to 1.6]; P=0.14). The thromboembolic end point occurred in 37 of 492 patients (7.5%) in the COBRA PzF group and 24 of 490 patients (4.9%) in the control group (difference, 2.6%; prespecified noninferiority margin 5%, upper limit of 1-sided 95% CI of the difference, 5.2%; Pnoninferiority=0.07). CONCLUSIONS: In patients with an indication for oral anticoagulation undergoing percutaneous coronary intervention, treatment with the COBRA PzF stent plus 14 days of DAPT was not superior with respect to bleeding events and was not noninferior with respect to thromboembolic events at 6 months compared with treatment with standard Food and Drug Administration-approved drug-eluting stent plus 3 to 6 months of DAPT. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02594501.

[Acquired hemophilia - quick diagnosis and treatment can significantly reduce the risk of mortality]. / Förvärvad hemofili ­ tidig diagnos och behandling är avgörande.

This case report of a 73-year-old male with bleedings provides insights into the clinical characteristics, diagnosis och treatment of acquired hemophilia A. It's a dangerous non-hereditary bleeding disorder caused by autoantibodies against coagulation factor VIII, often linked with other autoimmune diseases or malignancies, but it is also often idiopathic. The diagnosis remains a challenge due to its rarity and non-specific symtoms, but should be considered in unexplained bleeding cases with prolonged activated partial thromboplastin time (APTT). Quick  diagnosis and treatment can significantly reduce the risk of serious complications and mortality. The long-term prognosis usually depends on the presence of any underlying disease.

A Dynamic, D-dimer-based Thromboprophylaxis Strategy in Patients with COVID-19.

Background: COVID-19 pandemics increases venous thromboembolism (VTE) risk during hospitalization, despite prophylactic anticoagulation. Limited radiological diagnosis in pandemic requires a guided protocol for anticoagulant adjustment. Methods: This retrospective cohort study was conducted at a single center as part of a quality improvement program evaluating the efficacy and safety of anticoagulation protocols. The study focused on implementing a guideline for anticoagulant dosing protocol based on dynamic changes in D-dimer levels in COVID-19 hospitalized patients. The dosing guideline allowed for dose escalation from standard prophylactic levels to escalated prophylactic or therapeutic levels, depending on the patient's risk profile for VTE. The primary endpoints included in-hospital survival comparing between fix and dynamic adjustment treatment groups. Secondary endpoints encompassed major and clinically relevant non-major bleeding (CRNMB) events, incidence of breakthrough thrombosis, length of hospitalization and ICU stay, days of mechanical ventilator use, and survival duration. Findings: Among the 260 COVID-19-infected patients hospitalized between March 15th and June 15th, 2020. The patients received fixed anticoagulant dosage in 188, 72.3%) patients, while 72 (27.7%) were up-titrated according to the protocol. In-hospital survival at 30 days demonstrated superiority among patients whose anticoagulation was up-titrated to either escalated prophylactic or therapeutic (80.2%) compared to receiving fixed anticoagulant dosage (51.3%) (p=0.01). Bleeding events were significantly higher in up-titrate group (12.5%) compared to fixed anticoagulant dosage group (2.13%). Most of them are CRNMB. Conclusion: A dynamic, D-dimer-based dose escalation of anticoagulation for hospitalized patients with COVID-19 holds promise in improving in-hospital mortality rates without a significant increase in fatal bleeding events.

Clinical analysis of bleeding and thrombotic events in haematological-oncology patients with severe thrombocytopenia and a high risk of thrombosis.

BACKGROUND: Haematological patients with severe thrombocytopenia and high thrombotic risk face challenges related to balancing bleeding and thrombosis risks. This study investigated factors associated with bleeding and thrombosis in high-risk haematological oncology patients with severe thrombocytopenia not receiving anticoagulant therapy and characterized their clinical features when both events occurred. METHODS: A total of 446 haematological oncology patients with Caprini scores ≥ 5 were included from July 2022 to June 2023 at Mianyang City Central Hospital. Those not receiving prophylactic anticoagulants due to an admission platelet count < 50 × 109/L were studied. Patients were categorized into bleeding/nonbleeding and thrombotic/nonthrombotic groups on the basis of hospital course. Relevant clinical data were collected, and univariate/multivariate logistic regression was used to analyse the influencing factors. The platelet count at admission was assessed via ROC curves for thrombosis prediction. RESULTS: In the bleeding group, higher proportions of patients with leukaemia, myeloid tumours, lung infections, and a central venous catheter (CVC) with two lumens were observed, along with shorter catheter durations, lower initial and minimum platelet counts during hospitalization, and prolonged plasminogen times (all P < 0.05). The thrombotic group had a greater thrombosis history, initial platelet count, use of two venous catheter lumens, parenteral nutrition, sedation, and autologous haematopoietic stem cell transplantation (Auto-HSCT), with a lower leukaemia proportion (P < 0.05). Logistic regression identified lymphoma type and minimum platelet count as bleeding protective factors and the Charlson Comorbidity Index (CCI) score as an independent risk factor. Thrombosis history, two venous catheter lumens, and sedation were risk factors for thrombosis. The median platelet count was lower at bleeding and thrombosis than at admission (P = 0.007). The platelet count at admission had predictive value for thrombosis, especially severe thrombocytopenia, with an AUC of 0.735 (95% CI 0.613-0.858, P = 0.003) and a cut-off value of 42.5 × 109/L. CONCLUSIONS: For haematological neoplasm patients with a high risk of venous thromboembolism (VTE), severe thrombocytopenia and high CCI scores, risk prevention and control of bleeding take precedence over thrombosis prophylaxis. Prophylactic anticoagulation is still recommended for patients with lymphoma assessed at high risk for VTE and with platelet counts of at least 42.5 × 109/L.

Dengue Envelope Protein as a Cytotoxic Factor Inducing Hemorrhage and Endothelial Cell Death in Mice.

Dengue virus (DENV) infection, prevalent in tropical and subtropical regions, can progress to dengue hemorrhagic fever (DHF), which increases mortality during secondary infections. DHF is characterized by endothelial damage and vascular leakage. Despite its severity, no specific antiviral treatments exist, and the viral factors responsible for endothelial damage remain unclear. This study examines the role of the DENV envelope protein domain III (EIII) in inducing endothelial apoptosis using a mouse model. Additionally, we aim to explore whether cell death-inducing pathways could serve as drug targets to ameliorate EIII-induced endothelial injury and hemorrhage. In vitro experiments using human endothelial HMEC-1 cells demonstrated that both recombinant EIII (rEIII) and DENV markedly induced caspase-3-mediated endothelial cell death, an effect that was attenuated by co-treatment with chondroitin sulfate B (CSB), N-acetyl cysteine (NAC), and the caspase-3 inhibitor z-DEVD-FMK. In vivo, sequential injections of rEIII and anti-platelet immunoglobulin in mice, designed to mimic the clinical phase of DHF with peak viremia followed by an increase in DENV-induced Ig, including autoantibodies, revealed that these dual treatments markedly triggered caspase-3-dependent apoptosis in vascular endothelial cells at hemorrhage sites. Treatments with z-DEVD-FMK effectively reduced DHF-like symptoms such as thrombocytopenia, hemorrhage, inflammation, hypercoagulation, and endothelial damage. Additionally, CSB and NAC alleviated hemorrhagic symptoms in the mice. These results suggest that targeting EIII, reactive oxygen species, and caspase-3-mediated apoptosis could offer potential therapeutic strategies for addressing EIII-induced hemorrhagic pathogenesis.

Challenging anticoagulation decisions in atrial fibrillation: a narrative review.

Atrial fibrillation (AF) is common and warrants consideration of oral anticoagulant (OAC) medication. Usually, the decision is straightforward, following the pathway outlined in the European Society of Cardiology's guideline; however, certain situations fall outside of this evidence base - such as a diagnosis of subclinical AF made via implanted devices or wearable electrocardiogram monitors, or alternatively diagnosis of 'secondary AF' following a major stressor. Subclinical AF is associated with stroke, though not to the extent of clinical AF, and the benefits of anticoagulation appear to be lower. Longer episodes are more clinically meaningful, and recent randomised controlled trials have demonstrated that some patients derive benefit from OAC. Similarly, when AF is triggered by sepsis or non-cardiac surgery, specific evidence supporting OAC initiation is lacking and clinician behaviour is variable. Observational data demonstrate poorer outcomes in these patients, implying that the perception of a transient, reversible phenomenon may not be correct. Contrastingly, cardiac surgery very frequently induces AF, and the benefits of anticoagulation rarely outweigh the risks of bleeding. Following ischaemic stroke, recent evidence suggests that early (re-)initiation of OAC should be considered as this does not increase the risk of haemorrhagic transformation as previously hypothesised. This narrative review summarises the available literature and outlines, where possible, practical advice for clinicians facing these common clinical dilemmas.

Long-Term Clinical Outcomes Following the WATCHMAN Device Use in Medicare Beneficiaries.

BACKGROUND: Long-term outcomes following left atrial appendage occlusion outside clinical trials and small registries are largely unknown. Collecting these data was a condition of US market authorization of the WATCHMAN device. The aim of this analysis was to evaluate the rates of stroke, bleeding, and death among Medicare beneficiaries following left atrial appendage occlusion implantation during initial commercial availability of the WATCHMAN left atrial appendage occlusion device overall and in important subgroups. METHODS: All Medicare fee-for-service beneficiaries ≥65 years of age who underwent left atrial appendage occlusion from April 1, 2016, to August 31, 2020, were included based on the International Classification of Diseases, Tenth Revision, and Current Procedural Terminology codes. Over a 5-year follow-up period, the cumulative incidence over time of mortality, ischemic stroke, and major bleeding were calculated using the International Classification of Diseases, Tenth Revision, diagnosis codes for the full study cohort and within important prespecified subgroups. RESULTS: WATCHMAN recipients (n=48 763) were a median of 77 (interquartile range, 72-82) years of age, 42% female, and mostly White (93%). The median CHA2DS2VASc score was 4 (interquartile range, 3-5) with prior major bleeding in 42% and prior stroke in 12%. At 5 years, death occurred in 44%, bleeding in 15% (with higher risk early following implantation), and ischemic stroke in 7%. Each of these end points was more common with greater baseline age. Male patients had greater 5-year mortality than female patients (46.9% versus 40.6%), but there was no difference between sexes in the rates of ischemic stroke (6.6% versus 7.5%) or major bleeding (14.9% for both). WATCHMAN recipients with prior ischemic stroke or a major bleeding event were older and frailer; these groups had higher rates of ischemic stroke, major bleeding, and death. CONCLUSIONS: Compared with patients enrolled in the pivotal clinical trials, Medicare beneficiaries undergoing WATCHMAN implantation were older, more female, and had more comorbid conditions. Substantial long-term mortality and major bleeding following WATCHMAN reflect the high-risk nature of the patient population, while the ischemic stroke rate was relatively low (<1.5% per year).

Validation of the HAS-BLED scale for the assessment of bleeding risk in patients on anticoagulation therapy with a diagnosis of venous thromboembolic disease.

Background: Several models have been developed to assess bleeding risk in patients with venous thromboembolism, such as HAS-BLED, but their external validity has not been adequately assessed. Objective: The objective of the study was to evaluate the discriminative ability and calibration of the HAS-BLED scale for predicting 1-month bleeding risk in patient's anticoagulated for venous thromboembolism. Materials and Methods: External validation study of a prediction model based on a retrospective cohort of patients with venous thromboembolism treated between November 2019 and January 2022. Calibration of the HAS-BLED scale was evaluated using the Hosmer-Lemeshow test and the ratio of observed to expect events within each risk category. Discriminatory ability was assessed using the area under the curve (AUC) of a receiver operating characteristic curve. Results: We included 735 patients (median age 64 years, female sex 55.2%), pulmonary embolism was diagnosed in most patients (60.7%), and 4.9% presented bleeding events. Regarding calibration, the HAS-BLED scale systematically underestimates the risk both in the general population (ROE 3.76, p < 0.001) and in cancer patients (ROE 4.16). The Hosmer-Lemeshow test rejected the hypothesis of adequate calibration (p < 0.001). Discriminatory ability was limited both in the general population (AUC = 0.57, 95% confidence interval [CI]: 0.48-0.66) and in the subgroup with active cancer (AUC = 0.53, 95% CI: 0.36-0.69). Conclusion: The HAS-BLED scale in patients with venous thromboembolism underestimates the risk of bleeding at 1 month and has a low ability to discriminate high-risk patients. Cautious interpretation of the scale is recommended until additional evidence is available.

Association of liver dysfunction with outcomes after percutaneous coronary intervention - a systematic review and meta-analysis.

BACKGROUND: Liver dysfunction is a known risk factor in the cardiovascular field. It specifically increases perioperative risk in patients undergoing coronary bypass surgery. Since percutaneous coronary intervention (PCI) is the much less invasive procedure for the treatment of coronary artery disease, we aimed to assess the relationship of liver dysfunction with outcomes in patients undergoing PCI. METHODS: Three libraries were searched (MEDLINE, Web of Science and The Cochrane Library). We performed a meta-analysis of all studies in patients who underwent PCI that provided information on the presence or absence of liver dysfunction. Primary outcome was short-term mortality. Secondary outcomes were major adverse cardio- and cerebrovascular events (MACCE), bleeding and acute kidney injury. Random-effects model was applied. RESULTS: Five studies were selected and the data from 10,710,317 patients were included in the final analysis. In comparison with the absence of liver dysfunction, patients with liver dysfunction were associated with higher short-term mortality (OR 2.97, 95%CI 1.23-7.18, p = 0.02), higher MACCE (OR 1.42, 95%CI 1.08-1.87, p = 0.01), and higher bleeding (OR 2.23, 95%CI 1.65-3.00, p < 0.01). There was no significant difference regarding acute kidney injury (OR 1.20, 95%CI 0.50-2.87, p = 0.69). CONCLUSIONS: The analysis suggests that liver dysfunction in patients undergoing PCI is independently associated with higher risk of short-term mortality and increased occurrence of MACCE and bleeding. However, there appears to be no association to acute kidney injury.

Hyperbaric oxygen therapy in the treatment of late-onset hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation.

INTRODUCTION: Hemorrhagic cystitis (HC) is a common complication after allogeneic hematopoietic stem cell transplantation (HSCT), characterized by inflammation and bleeding of the bladder. Hyperbaric oxygen therapy (HBOT) has been shown to be effective in the treatment of radiation-induced HC. However, the optimal treatment for HC after allogeneic HSCT has not yet been established. Furthermore, limited research has been conducted on the use of HBOT in this setting. This study aimed to evaluate the effectiveness and safety of HBOT in patients with late-onset HC after allogeneic HSCT. METHODS: Twenty-five-year (1998-2022) retrospective analysis performed in all consecutive patients with confirmed late-onset HC after allogeneic HSCT treated with HBOT at two centers in Portugal. Medical records were reviewed for clinical and laboratory features, primary indications for allogeneic HSCT, conditioning regimen, and treatment strategies for HC. Patients received 100% oxygen at 2.1-2.5 atmosphere absolute pressure (ATA) for 70-90-minute periods, once daily, five times per week. Complete clinical response was defined as the absence of macroscopic hematuria sustained for at least 2 weeks, and partial response was described as a downgrading in the severity of HC. Statistical significance was considered for values of p < 0.05. RESULTS: The sample included 61 patients with a mean age of 28.0 (SD 14.2) years, 33 males. Complete response was achieved in 72.1% (n = 44) of patients and partial response in 14.8% (n = 9). Concerning patients with a complete response, the median number of HBOT sessions was 15.5 sessions (IQR 10.0-26.8). Patients treated with 10 or more sessions of HBOT had a higher rate of complete or partial response (OR 12.5, 95%CI 1.9-83.2, p-value < 0.05). There was no response in 8 (13.1%) patients, and 6 interrupted the treatments early. Only 2 patients suspended the HBOT due to a lack of clinical benefit. CONCLUSION: Our study supports using of HBOT as an adjunctive treatment for late-onset HC after allogeneic HSCT. Furthermore, 10 or more HBOT sessions delivered seem to impact the rate of HC resolution. Prospective, randomized, and well-controlled trials are needed to establish HBOT's definitive efficacy and safety.

Near-fatal pheochromocytoma crisis after beta-blocker and tumour haemorrhage.

Pheochromocytomas are rare neuroendocrine tumors characterised by the secretion of catecholamines and their metabolites. While some patients may be asymptomatic, they can also present with various symptoms including hypertensive crisis, headaches, palpitations, diaphoresis or other signs of catecholamine toxicity. Adrenal haemorrhage, though rare, is a potentially fatal complication that is often diagnosed during autopsy. In all patients with suspected pheochromocytoma, regardless of whether haemorrhagic conversion has occurred, prompt diagnosis is imperative. Early identification allows for the timely initiation of treatment, preventing potentially life-threatening complications. This case report details the haemorrhagic conversion of an undiagnosed pheochromocytoma in a female patient in her 30s.

Super-selective renal artery embolization (SRAE) for iatrogenic and traumatic renal hemorrhage.

PURPOSE: To present the radiological and clinical outcomes of super-selective transcatheter renal artery embolization in patients with renal injury hemorrhage, and share our experience. METHODS: 43 patients with renal injury hemorrhage who underwent 46 SRAEs were enrolled in this retrospective review study. Records, images, and outcomes were reviewed. The individual embolic method and its observed effects were investigated. RESULTS: Angiography showed free extravasation in 25 angiograms, pseudoaneurysm in 15 angiograms, and arteriovenous fistulas in 1 angiogram. Most patients achieved initial clinical success (38/43, 88.4%), and 41 patients achieved final clinical success (41/43, 95.3%). 9/11 patients who adopted empirical embolization achieved initial clinical success (81.8%). In our study, the combination of PVA particles and micro-coils has emerged as the most commonly utilized material combination (24/46, 52.2%). Significant differences in hemoglobin levels were observed before and after the embolization procedure (p = 0.026, 95%CI: 1.03-15.54). Post-embolization clinical follow-up showed no evidence of recurrent hematuria, progression of hematoma, hypertension, and no reflux of the embolic agent. CONCLUSION: Though SRAE showed satisfactory results across a broad range of renal injury hemorrhage, there are still some aspects that need attention: (1) Surgical procedure should be understood, including the surgical site, access routes, and placement of implants, such as double-J stents. (2) In cases where identifying the bleeding point proves challenging, consider the possibility of an accessory renal artery. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2400085050, Registration Date: 30 May 2024, retrospectively, non-randomized.

Haemophilia care in Iraq; a multi-centre study.

OBJECTIVE: To evaluate the level of care available for haemophilia patients. METHODS: The descriptive, retrospective analytical study was conducted from December 15, 2020, to March 1, 2021, after approval from the Mustansiriyah University, Baghdad, Iraq, and comprised data from 3 haemophilia treating centres in Iraq participating in the World Bleeding Disorders Registry. The data collected related to patients with haemophilia A and B enrolled in the registry since March 2018, and included age at diagnosis, type of haemophilia, disease severity, age at first bleed and at first joint bleed, type of replacement therapy and outcome. Data was analysed using statistical package of social sciences (SPSS) version 20. RESULTS: Of the 638 patients with mean age 16.2±4.3 (range: 9-29 years), 581(91%) had haemophilia A, 57(8.9%) had haemophilia B, 385(60.5%) had severe haemophilia, 126(19.8%) moderate and 125(19.7%) mild. Further, 259(41%) patients had been diagnosed for <1 year. There were 1354 bleeding events, and haemarthrosis accounted for 959(70.8%) of them. The mean annualised bleeding rate for severe patients was 2 ± 0.6(range 0-4), while the mean annualised joint bleeding rate was 4 ± 1.3(range :2-8). There were 256(32.3%) patients who were tested for inhibitors, and 62(24.3%) were positive. Among 426(73.3%) haemophilia A patients with a treatment history, 248(58%) were on prophylactic therapy, and the corresponding value among 37(65%) haemophilia B patients was 17(46%). CONCLUSIONS: Access to treatment was found to be limited, and patients were found to be suffering from high bleeding rates and joint damage.