Hemorrhagic varices around the pancreatojejunostomy site due to left-sided portal hypertension after pancreaticoduodenectomy: A case report.

Pancreaticoduodenectomy (PD) with combined portal vein resection sometimes causes left-sided portal hypertension, which can be a problem. An appropriate treatment strategy for hemorrhagic ectopic varices due to left-sided portal hypertension after PD has not yet been determined. We report a case of repeated variceal rupture around the pancreatojejunostomy site. A 65-year-old woman with a history of PD for pancreatic head cancer was admitted with a chief complaint of bloody stools. She was diagnosed with pancreatojejunostomy variceal rupture, and an endoscopic cyanoacrylate injection was performed. As rebleeding occurred 2 weeks after the first treatment, endoscopic cyanoacrylate injection was repeated, and hemostasis was achieved. Additionally, she had esophageal, colonic, and gastrojejunostomy varices, and the future risk of these variceal ruptures was considered very high. Hence, a splenectomy was performed to prevent rebleeding or other variceal ruptures. Endoscopic cyanoacrylate injection is a useful treatment for hemorrhagic varices around the pancreatojejunostomy site. It is also necessary to understand portal vein hemodynamics and provide appropriate additional treatment in cases of recurrent variceal rupture due to left-sided portal hypertension after PD.

Pasteurellosis in camels in Southern Mongolia: A case report.

Hemorrhagic septicemia (pasteurellosis) in animals, caused by Pasteurella multocida Trevisan 1887, is a significant but previously undocumented disease in Mongolian camels. Pasteurella multocida, a small Gram-negative coccobacillus, typically exists commensal in the nasopharynx of camels but can cause severe illness under certain environmental stressors. This study reports the first case of cameline hemorrhagic septicemia in Gobi region of Mongolia, specifically in Umnugobi province, where acute septicemia affected 26 camels, resulting in 10 deaths within 24-48 hours. Clinical signs included depression, inappetence, lethargy, increased rectal temperature, and paralysis of the lower lip. Surviving camels responded to treatment with Lactate Ringer solution and antibiotics. Postmortem examinations revealed acute pulmonary congestion and necrotic liver. Molecular diagnostic test, PCR, confirmed the presence of P. multocida with the identification of the KMT1 gene. This case underscores the potential for significant economic losses due to hemorrhagic septicemia in camels and highlights the need for early detection and treatment to mitigate its impact. The initial attempt at implementing a vaccination program effectively controlled the potential further outbreak. This study emphasizes the importance of continuous surveillance and preventive measures in managing hemorrhagic septicemia in livestock.

A septicemia hemorrágica (pasteurelose) em animais, causada por Pasteurella multocida Trevisan 1887, é uma doença significativa, mas anteriormente não documentada, em camelos mongóis. Pasteurella multocida, um pequeno cocobacilo Gram-negativo, normalmente existe como comensal na nasofaringe de camelos, mas pode causar doenças graves sob certos estressores ambientais. Este estudo relata o primeiro caso de septicemia hemorrágica de camelos na região de Gobi, na Mongólia, especificamente na província de Umnugobi, onde a septicemia aguda afetou 26 camelos, resultando em 10 mortes em 24-48 horas. Os sinais clínicos incluíram depressão, inapetência, letargia, aumento da temperatura retal e paralisia do lábio inferior. Os camelos sobreviventes responderam ao tratamento com solução de Lactato Ringer e antibióticos. Os exames post-mortem revelaram congestão pulmonar aguda e fígado necrótico. O teste de diagnóstico molecular, PCR, confirmou a presença de P. multocida com a identificação do gene KMT1. Este caso sublinha o potencial de perdas económicas significativas devido à septicemia hemorrágica em camelos e destaca a necessidade de detecção e tratamento precoces para mitigar o seu impacto. A tentativa inicial de implementar um programa de vacinação controlou eficazmente o potencial novo surto. Este estudo enfatiza a importância da vigilância contínua e de medidas preventivas no manejo da septicemia hemorrágica na pecuária.

Early intervention of 5% albumin shown superior control of vascular integrity and function compared to ringer's lactatein hospitalized adult with grade I & II Dengue hemorrhagic fever: a multicenter randomized controlled trial in Indonesia.

BACKGROUND: Dengue virus remains a major public health problem with one of the hallmark pathologies is the vascular leakage caused by endothelial dysfunction which can lead to Dengue Hemorrhagic Fever (DHF) manifestation. In the status quo, no specific therapy has been discovered but rather heavily relies on judicious and frequent monitoring of intravenous fluids administration. The current guideline has discussed the roles of fluid therapy during the Dengue Shock Syndrome (DSS) stage, however, administration of early fluid intervention for DHF grade I and II remains uncharted territory. In addition, the choice and timing of colloid administration remains underexplored. As one of the widely available colloids, 5% albumin has known physiological properties that potentially minimize plasma leakage. Therefore, this study aimed to evaluate the benefit of early intervention of 5% albumin in adults with DHF in the hope of preventing the lethal progression to DSS and further, shorten the length of stay (LOS) for patients. METHODS: We conducted a multicenter, open-labeled, randomized controlled trial in Jakarta and Banten to compare the effect of early intervention with 5% albumin in adult patients with DHF compared to Ringer's Lactate (RL). Statistical analyses were conducted using unpaired t-test and Mann-Whitney for normally and abnormally distributed data respectively. RESULTS: Adult patients with a diagnosis of DHF grade I and II that being hospitalized to receive the early intervention of 5% albumin had significantly lower levels of hemoconcentration 4, 12, and 24 h (p = 0.002, 0.001, 0.003, respectively), higher platelet counts 4 h (p = 0.036), higher serum albumin levels 48 h (p = 0.036), lower proteinuria 24 and 48 h post-albumin administration (p < 0.001, < 0.001, respectively), and shorter LOS (p < 0.001) when compared to the RL group. CONCLUSION: Early intervention of 5% albumin showed better control on vascular integrity and function compared to ringer lactate in hospitalized adults with grade I & II DHF, thus halting the progression of DHF into DSS and other related complications which leads to faster recovery and shorter length of stay. TRIAL REGISTRATION: The study was registered to www. CLINICALTRIAL: gov with trial registration number NCT04076254, and registration date October 31st 2016.

Clinical and genetic spectrum of factor XII deficiency in the Han population of East China.

BACKGROUND: Factor XII (FXII or F12) deficiency is a rare inherited disorder, typically lacking haemorrhagic symptoms. There is limited literature exists on FXII deficiency and mutations within the Chinese population. This study aimed to characterize the spectrum of F12 gene mutations in a Chinese cohort and to investigate the relationship between FXII mutations and clinical phenotypes. METHODS: Genetic and clinical data from 51 unrelated probands with FXII deficiency, along with their families, were meticulously collected and analysed. RESULTS: Genetic analysis revealed that 94.1% of probands carried genetic defects, with 29 mutations pinpointed in the F12 gene. Of these, 18 mutations were previously reported for the first time by our research group, including c.303_304delCA, c.1078G > A, c.1285 C > T, among others. Of the mutations, 17 are missense, constituting 58.6% of the total. Additionally, 11 are deletions or insertions, of which 8 result in frameshifts, while the remaining one is a nonsense mutation. These mutations were predominantly concentrated in two crucial regions: the catalytic domain and the kringle domain. The most frequently observed mutations were c.1681G > A, closely followed by c.1561G > A and c.1078G > A, indicating a dominance among these mutations. Additionally, a prevalent polymorphism at position 46 was observed in the majority of probands, with 47.1% having the 46T/T genotype and 13.7% having the 46 C/T genotype, which may potentially impact FXII activity. The broad spectrum of asymptomatic FXII deficiency observed within the Han population of East China. CONCLUSIONS: We speculate on the potential impact of recurrent mutations on the efficacy of new drugs being developed to target FXII for thrombosis prevention and treatment. Furthermore, it is important to explore their influence on FXII-related pathways beyond the activation of the contact pathway in the coagulation cascade.

Veno-arterial extracorporeal membrane oxygenation uses in trauma: a retrospective analysis of the Japanese nationwide trauma registry.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) can provide temporary circulatory support and vital organ oxygenation and is potentially useful as a bridge therapy in some trauma cases. We aimed to demonstrate the characteristics and outcomes of patients with trauma treated with veno-arterial ECMO (V-A ECMO) using data from a Japanese nationwide trauma registry. METHODS: This retrospective descriptive study analyzed data from the Japan Trauma Data Bank between January 2019 and December 2021. Patients with severe trauma (injury severity score [ISS] ≥ 9) and treated using V-A ECMO were assessed. RESULTS: Among the 72,439 patients with severe trauma, 51 received V-A ECMO. Sixteen patients (31.3%) survived until hospital discharge. On hospital arrival, six (37.5%) survivors and 15 (42.9%) non-survivors experienced cardiac arrest. The median ISS for the survivor and non-survivor group was 25 (range, 25-39) and 25 (range, 17-33), respectively. Thoracic trauma was the most common type of trauma in both groups. In the non-survivor group, open-chest cardiopulmonary resuscitation, aortic cross-clamping, and resuscitative endovascular balloon occlusion of the aorta were performed in 10 (28.6%), 5 (14.3%), and 4 (11.4%) patients, respectively. However, these procedures were not performed in the survivor group. Peripheral oxygen saturation tended to be lower in the survivor group both before and upon arrival at the hospital. CONCLUSIONS: The results of this study suggest the potential benefit of V-A ECMO in some challenging trauma cases. Further studies are warranted to assess the indications for V-A ECMO in patients with trauma.

Hereditary haemorrhagic telangiectasias with recurrent ischemic stroke hinted by manganese deposition in the basal ganglia: a case report and literature review.

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant inherited vascular disorder that can involve multiple organs, thus can be associated with so many clinical departments that proper screening and diagnosis of HHT are needed for providing better management of both patients and their family members. CASE PRESENTATION: We present a 58-year-old female patient with recurrent paradoxical brain embolism due to HHT. She received aspirin therapy and underwent pulmonary arteriovenous malformation embolization, recovering well and discharged 3 days postoperatively. Though ischemic stroke caused by HHT-induced vascular disorders has been reported, our patient presented with both recurrent paradoxical brain embolisms and radiologic findings of bilateral globus pallidus manganese deposition at the same time, a combination rarely reported. We also review the literature on the clinical features and management of HHT for prompt diagnosis of this genetic disease behind paradoxical embolism. CONCLUSIONS: When patients with ischemic stroke, especially recurrent ischemic stroke, have combined arteriovenous malformations (AVMs) in single or multiple organs, or clues for AVMs like manganese deposition in globus pallidus, genetic diseases such as HHT may be the reason for ischemic stroke and shouldn't be missed in the evaluation of embolic sources.

A Rare Intersection: Managing Thrombotic Thrombocytopenic Purpura in the Context of Dengue Fever.

Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening condition that can lead to severe morbidity and mortality if untreated. This case report discusses a 31-year-old male with dengue fever who developed TTP, resulting in fatality despite timely diagnosis and comprehensive treatment. The patient presented with worsening symptoms, including body aches, gastrointestinal bleeding, and neurological issues. Initial treatment focused on managing dengue hemorrhagic fever, but TTP was later suspected, leading to the cessation of platelet transfusions and initiation of plasma exchange, steroids, and rituximab. Despite these efforts, the patient's condition deteriorated. This case underscores the challenges in managing TTP, especially when triggered by infections like dengue. The use of the PLASMIC score can be highly effective in suspecting TTP in these patients, allowing for the initiation of early management. While standard treatments include plasma exchange and immunosuppressive therapy, emerging treatments such as caplacizumab and the potential use of splenectomy may offer hope for better outcomes in the future.

Large right middle cerebral artery stroke with hemorrhagic transformation.

The authors present a case of an acute right middle cerebral artery infarct in a 65-year-old male with a history of diabetes, hypertension, and cardiovascular disease. The timeline of treatment and the evolution of the stroke is described. This case highlights the significant burden of right-sided cerebral artery stroke, even when intervention is swift.

Incidence and risk factors of perioperative suprachoroidal hemorrhage: A systematic review and meta-analysis.

Suprachoroidal hemorrhage (SCH) is a potentially visually devastating complication of intraocular surgery, but estimates of perioperative SCH incidence vary. We performed a systematic review and meta-analysis of perioperative SCH incidence among population-based studies published between 1990 and 2023. Thirty-five studies collectively reported 1,657 cases of perioperative SCH from a population of 3,028,911 surgeries. The estimated incidence of SCH was 0.12% (95% CI, 0.10-0.14%), or about one in every 800 surgeries. The estimated incidence of perioperative massive SCH was 0.06% (95% CI, 0.04-0.08%). In multivariable meta-regression, greater SCH incidence was significantly associated with smaller study population size, comparative study design, multicenter study setting, and intraoperative or delayed SCH timing (vs intraoperative alone), while lower SCH incidence was significantly associated with vitreoretinal or mixed surgery type (vs. cataract) (all P < 0.05). Study year was not a significant predictor of SCH incidence, suggesting that the incidence of SCH has not decreased over the past 3 decades despite improvements in surgical technologies and techniques. Given the rarity of SCH, and the strong effect of study population size on reported SCH incidence rates, future studies of SCH incidence should include a minimum population size of at least 1000 surgeries to obtain an accurate estimate of SCH incidence.

A case of hypertensive crisis following administration of nonionic low molecular weight contrast in hemorrhagic stroke patient: a case report.

Introduction: Radiocontrast agents can be iodinated or noniodinated. Iodinated agents are further divided into low and high molecular weights. In recent decades, LOCM has largely replaced the use of HOCM due to safety concerns, but an increasing number of severe side effects cases have been reported. Case presentation: A 62-year-old woman presented with acute right hemiparesis. A CT scan revealed ICH with IVH. A contrasted CTA was ordered, during which Iohexol was administered. Shortly after the injection, she developed a hypertensive crisis. She was transferred to the ICU, intubated, and given labetalol. Repeated CT scan showed increased IVH with posterior edema. Her family declined surgical intervention. Unfortunately, she died. Discussion: This represents a unique adverse effect of a low molecular weight contrast agent that has been rarely reported before, particularly in pheochromocytoma patients. Nevertheless, our patient had subtle hypertension that was revealed during hospital admission but without pheochromcytoma. Conclusion: This case represents an unusual instance of a severe adverse. It suggests that the malignant rise in blood pressure may not be catecholamine-induced.

A Comprehensive Study of Risk Factors, Etiology, and Infarction Patterns in Cerebrovascular Accidents at a Tertiary Care Hospital in India.

Background Stroke is a debilitating cerebrovascular condition characterized by sudden neurological deficits. The incidence of stroke is rising in India, posing significant public health concerns. This study aims to examine the risk factors and etiology of stroke using the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification and analyze infarct areas in cerebrovascular accidents (CVA) at a tertiary care hospital. Methodology This cross-sectional, hospital-based observational study was conducted at Dr. D. Y. Patil Medical College, Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth (Deemed to Be University), Pune, India, from January 2023 to January 2024. The study included 100 adult patients diagnosed with CVA based on clinical and radiological criteria. Patients aged 18 years and older were eligible, while those with a history of head trauma or those below 18 years were excluded. The investigation protocol included routine biochemical assessments and radiological investigations, such as computed tomography (CT), magnetic resonance imaging (MRI) with angiography or venography, and Doppler ultrasound of bilateral carotid arteries. Results The study population consisted of 100 patients, with 84 males (84%) and 16 females (16%). Age distribution showed 44% were over 60 years old, 23% aged 51-60 years, 15% aged 31-40 years, 14% aged 41-50 years, and 4% aged 21-30 years. Hypertension was the most prevalent risk factor, affecting 75% of patients, with a higher occurrence in males (62%), compared to females (13%). Smoking was observed in 51% of patients, and alcohol consumption was seen in 50%. Other significant risk factors included dyslipidemia (39%), diabetes mellitus (33%), chronic kidney disease (11%), ischemic heart disease (10%), atrial fibrillation (4%), valvular heart disease (4%), and pregnancy or postpartum conditions (2%). Ischemic stroke was predominant, occurring in 80% of patients, while hemorrhagic stroke occurred in 20%. High occurrences of ischemic strokes were noted in the frontal lobe (41%), parietal lobe (37%), occipital lobe (27%), and temporal lobe (26%), with the internal capsule region also showing significant numbers (27%). According to the TOAST classification, the most prevalent cause of stroke in this study was undetermined etiology with two or more causes, accounting for 32% of cases, followed by large artery atherosclerosis, which accounted for 30%. Cardioembolic stroke was identified in 11% of the patients, with 4% due to atrial fibrillation, 3% due to acute myocardial infarction, 3% due to rheumatic valvular heart disease, and 1% due to infective endocarditis. Conclusion This study highlights the significant prevalence of hypertension, smoking, alcohol consumption, and hyperhomocysteinemia as major risk factors for stroke. Ischemic strokes were predominant, with high occurrences in the cerebral lobes and gangliocapsular region. These findings emphasize the need for targeted prevention strategies, including managing hypertension and lifestyle modifications such as smoking cessation and reducing alcohol consumption, to mitigate the risk of stroke. Effective management of blood pressure, lipid levels, and blood glucose is crucial for stroke prevention. Recognizing gender-specific differences and addressing comorbidities through an integrated approach can enhance patient outcomes and reduce the burden of stroke.

Author Response: Outcome Predictors of an Intracerebral Hemorrhage also Depend on the Causes of the Bleeding.

How to cite this article: Hazra D. Author Response: Outcome Predictors of an Intracerebral Hemorrhage also Depend on the Causes of the Bleeding. Indian J Crit Care Med 2024;28(9):892-893.

Management of PFO in paradoxical embolic stroke with hemorrhagic conversion: a case report.

A paradoxical embolism is defined as a venous thrombus that crosses through a heart defect, into the systemic circulation, usually through a patent foramen ovale. Treatment varies between closure of patent foramen ovale vs. medical management based on a variety of individual risk factors and the cardiac defect's characteristics. We describe a case of paradoxical stroke complicated by hemorrhagic conversion, ultimately requiring an IVC filter.

Update on Retinal Drug Safety: Proceedings of the ASRS ReST Committee Webinar Part 1.

Purpose: To review the first Research and Safety in Therapeutics (ReST) Committee webinar and summarize the most current recommendations regarding diagnosis and management. Methods: The ReST Committee is comprised of members of the American Society of Retina Surgeons (ASRS). At regular internal meetings, safety issue reports from the website are reviewed. A webinar series was started in 2021 to update members on multiple relevant potential safety events. Results: Topics reviewed in the webinar included pentosan polysulfate sodium (Elmiron) maculopathy, intraocular pressure elevation reported with the aflibercept prefilled syringe (PFS), and brolucizumab-associated inflammation with occlusive retinal vasculitis. Retinal toxicity related to intraoperative medications was reviewed, including hemorrhagic occlusive retinal vasculitis after intraocular vancomycin, dilution errors with intravitreal aminoglycosides, inadvertent overdoses of cefuroxime after cataract surgery, and toxic posterior segment syndrome after dropless cataract surgery using compounded triamcinolone-moxifloxacin. Indocyanine green toxicity has been reported after its use as an adjuvant during macular hole surgery. Conclusions: The past decade has seen advances in retinal pharmaceuticals and drug-delivery devices. The ASRS ReST Committee collects data from its website reporting system to inform members about up-to-date pharmaceutical and device safety concerns. Recently, a webinar was used to inform members of pigmentary maculopathy associated with pentosan polysulfate sodium, safety regarding the aflibercept PFS, intraocular inflammation and occlusive retinal vasculitis secondary to brolucizumab, and retinal toxicity from intraoperative ocular medications.

Case reports of immune-related cystitis and the antibody combination hypothesis.

Immune-related cystitis is a rare condition, and its diagnostic criteria and pathogenesis are not yet fully understood. Here, we report two cases of immune-related cystitis. Both patients were previously diagnosed with lung squamous cell carcinoma and received combined treatment with immune checkpoint inhibitors and chemotherapy, leading to hemorrhagic cystitis. We reviewed the cystoscopic images and pathological features of previous cases and found that autoantibodies against hemidesmosomes may be the cause of immune-related cystitis, proposing the "antibody combination" hypothesis to explain the tissue specificity of the condition.

Lung squamous cell carcinoma can produce certain proteins called autoantigens. Some patients treated with immune checkpoint inhibitors might develop antibodies against these autoantigens. A specific combination of these antibodies may cause the bladder lining to slough, leading to immune-related cystitis. Symptoms of this condition include frequent urination, urgent need to urinate, painful urination and blood in the urine. These patients typically require treatment with steroids.

MicroRNAs Regulate the Expression of Genes Related to the Innate Immune and Inflammatory Response in Rabbits Infected with Lagovirus europaeus GI.1 and GI.2 Genotypes.

MicroRNAs (miR) are a group of small, non-coding RNAs of 17-25 nucleotides that regulate gene expression at the post-transcriptional level. Dysregulation of miRNA expression or function may contribute to abnormal gene expression and signaling pathways, leading to disease pathology. Lagovirus europaeus (L. europaeus) causes severe disease in rabbits called rabbit hemorrhagic disease (RHD). The symptoms of liver, lung, kidney, and spleen degeneration observed during RHD are similar to those of acute liver failure (ALF) and multi-organ failure (MOF) in humans. In this study, we assessed the expression of miRs and their target genes involved in the innate immune and inflammatory response. Also, we assessed their potential impact on pathways in L. europaeus infection-two genotypes (GI.1 and GI.2)-in the liver, lungs, kidneys, and spleen. The expression of miRs and target genes was determined using quantitative real-time PCR (qPCR). We assessed the expression of miR-155 (MyD88, TAB2, p65, NLRP3), miR-146a (IRAK1, TRAF6), miR-223 (TLR4, IKKα, NLRP3), and miR-125b (MyD88). We also examined biomarkers of inflammation: IL-1ß, IL-6, TNF-α, and IL-18 in four tissues at the mRNA level. Our study shows that the main regulators of the innate immune and inflammatory response in L. europaeus/GI.1 and GI.2 infection, as well as RHD, are miR-155, miR-223, and miR-146a. During infection with L. europaeus/RHD, miR-155 has both pro- and anti-inflammatory effects in the liver and anti-inflammatory effects in the kidneys and spleen; miR-146a has anti-inflammatory effects in the liver, lungs and kidneys; miR-223 has anti-inflammatory effects in all tissues; however, miR-125b has anti-inflammatory effects only in the liver. In each case, such an effect may be a determinant of the pathogenesis of RHD. Our research shows that miRs may regulate three innate immune and inflammatory response pathways in L. europaeus infection. However, the result of this regulation may be influenced by the tissue microenvironment. Our research shows that infection of rabbits with L. europaeus/GI.1 and GI.2 genotypes causes an overexpression of two critical acute phase cytokines: IL-6 in all examined tissues and TNF-α (in the liver, lungs, and spleen). IL-1ß was highly expressed only in the lungs after L. europaeus infection. These facts indicate a strong and rapid involvement of the local innate immune and inflammatory response in L. europaeus infection-two genotypes (GI.1 and GI.2)-and in the pathogenesis of RHD. Profile of biomarkers of inflammation in rabbits infected with L. europaeus/GI.1 and GI.2 genotypes are similar regarding the nature of changes but are different for individual tissues. Therefore, we propose three inflammation profiles for L. europaeus infection for both GI.1 and GI.2 genotypes (pulmonary, renal, liver, and spleen).

Tense blisters and hemorrhagic bullae as the first manifestation of eosinophilic granulomatosis with polyangiitis.

Eosinophilic granulomatosis with polyangiitis (EGPA) poses a significant diagnostic challenge due to its varied clinical presentation. Here, we present a case of a 59-year-old female with a history of asthma and sinusitis, who manifested with an extremely rare presentation of drastic tense blisters and hemorrhagic bullae alongside purpuric lesions and peripheral neuropathy. Examinations revealed eosinophilia, positive anti-neutrophil cytoplasmic antibody, and characteristic pathological findings with small vessel vasculitis in the purpura. Treatment with glucocorticoids and cyclophosphamide led to rapid improvement in peripheral eosinophilia, skin manifestations and motor neuron deficits. Although rare, our case underscores that bullous skin lesions should be recognized as a potential cutaneous hallmark of EGPA to aid timely diagnosis, since prompt treatment initiation is crucial given the potential irreversible organ damage and poor prognosis of EGPA.

Apolipoprotein E deficiency exacerbates blood-brain barrier disruption and hyperglycemia-associated hemorrhagic transformation after ischemic stroke.

BACKGROUND: The polymorphism of the apolipoprotein E (ApoE) gene has been implicated in both the susceptibility to neurodegenerative disease and the prognosis of traumatic brain injury (TBI). However, the influence of ApoE on the risk of hemorrhagic transformation (HT) after acute ischemic stroke remains inconclusive. The present study aimed to investigate the potential impact of ApoE deficiency on the risk of hyperglycemia-associated HT and to elucidate the underlying mechanisms. METHODS: Wild-type (WT) and ApoE knockout (ApoE-/-) mice were injected with 50 % glucose to induce hyperglycemia and subsequently subjected to 90 min of intraluminal middle cerebral artery occlusion (MCAO). The mortality, neurological function, HT incidence and HT grading-score were evaluated at 24 hours after reperfusion. To evaluate the integrity of blood-brain barrier (BBB), the immunoglobulin G (IgG) leakage and the protein expressions of tight junctions (TJs) were detected using immunofluorescent staining and western blotting. Finally, the levels of matrix metalloproteinases (MMP)-2/9, microglial activation and proinflammatory mediators were investigated using immunofluorescent staining and western blotting. RESULTS: ApoE-/- mice exhibited increased mortality and exacerbated neurological impairment, concomitant with more severe hyperglycemia-associated HT 24 hours post-reperfusion. Meanwhile, ApoE deficiency exacerbated the disruption of BBB, characterized by increased leakage of IgG, aggravated degradation of TJs and microvascular basement membranes. Furthermore, ApoE deficiency further aggravated the upregulation of MMP-2/9 and microglia-triggered neuroinflammation. CONCLUSIONS: Our findings demonstrate that the absence of ApoE exacerbates neurological impairment and hyperglycemia-associated HT in ischemic stroke mice, which is closely associated with MMP-2/9 signaling and neuroinflammation-mediated disruption of BBB.

Need for Transparency and Clinical Interpretability in Hemorrhagic Stroke Artificial Intelligence Research: Promoting Effective Clinical Application.

PURPOSE: This study aimed to evaluate the quality of artificial intelligence (AI)/machine learning (ML) studies on hemorrhagic stroke using the Minimum Information for Medical AI Reporting (MINIMAR) and Minimum Information About Clinical Artificial Intelligence Modeling (MI-CLAIM) frameworks to promote clinical application. MATERIALS AND METHODS: PubMed, MEDLINE, and Embase were searched for AI/ML studies on hemorrhagic stroke. Out of the 531 articles found, 29 relevant original research articles were included. MINIMAR and MI-CLAIM scores were assigned by two experienced radiologists to assess the quality of the studies. RESULTS: We analyzed 29 investigations that utilized AI/ML in the field of hemorrhagic stroke, involving a median of 224.5 patients. The majority of studies focused on diagnostic outcomes using computed tomography scans (89.7%) and were published in computer science journals (48.3%). The overall adherence rates to reporting guidelines, as assessed through the MINIMAR and MI-CLAIM frameworks, were 47.6% and 46.0%, respectively. In MINIMAR, none of the studies reported the socioeconomic status of the patients or how missing values had been addressed. In MI-CLAIM, only two studies applied model-examination techniques to improve model interpretability. Transparency and reproducibility were limited, as only 10.3% of the studies had publicly shared their code. Cohen's kappa between the two radiologists was 0.811 and 0.779 for MINIMAR and MI-CLAIM, respectively. CONCLUSION: The overall reporting quality of published AI/ML studies on hemorrhagic stroke is suboptimal. It is necessary to incorporate model examination techniques for interpretability and promote code openness to enhance transparency and increase the clinical applicability of AI/ML studies.