Citations

Listing and transplanting patients with acute liver failure (ALF) is challenging, requiring rapid assessment of the likelihood of recovery. The availability of a large number of ALF liver explants, along with their clinical data, afforded an opportunity to retrospectively evaluate liver transplantation (LT) decision-making. We hypothesized that, with the benefit of hindsight, a small number of patients might have recovered without LT. Three hundred liver explants from ALF patients of varying etiologies who had undergone LT over 22 years in the Acute Liver Failure Study Group registry were reviewed for histopathological features and degree of necrosis by a committee of 8 hepatopathologists. A second committee of 8 experienced transplant hepatologists independently reviewed clinical data on these same 300 patients and retrospectively scored the likelihood that each patient required transplantation. Only 3 (1%) of those reviewed by the Clinical Committee were considered to “Definitely” not require liver grafting, while an additional 10 (3.3%) were deemed to “Possibly” not require transplantation (Not Likely Group, N=13). There was no difference in the degree of necrosis in explants in these groups, when compared to the remaining Likely Group, N=287 (95.6%), except in acetaminophen (APAP)-associated ALF, where the degree of necrosis was more uniformly graded as severe, correlating with the need for transplantation. Virtually every patient undergoing LT for ALF retrospectively appeared to need their transplant, based on expert clinical consensus review. Overall, there was poor correlation between clinical severity and apparent degree of necrosis seen in the 300 liver explants, except perhaps for APAP subjects.

Abstract Background: While bipolar disorder is strongly linked to an increased risk of suicide, recent evidence has challenged the assumption that mixed symptoms play a distinct role in suicidal ideation beyond depressive severity. This study examines how depressive, hypo/manic, and mixed features influence suicidal ideation in individuals with bipolar disorder. Data from 903 participants in the Stanley Foundation Bipolar Network (1995–2002) were analyzed to assess associations between mood states, classified by the Inventory of Depressive Symptomatology–Clinician-Rated (IDS-C) and the Young Mania Rating Scale (YMRS), and suicidal ideation, measured using IDS-C item 18, using generalized estimating equations. Results: Depressive symptoms were strongly associated with suicidal ideation (OR = 21.98, 95% CI: 15.31–31.54). Moderate hypo/manic symptoms also conferred risk (OR = 3.11, 95% CI: 1.51–6.49), and milder hypo/mania showed a weaker but significant association (OR = 1.74, 95% CI: 1.05–2.89). The highest suicidal ideation was observed in individuals with hypo/mania featuring mixed symptoms (OR = 29.43), exceeding that of depression or depression with mixed features (OR = 21.98). However, findings diverged based on modeling approach: in continuous predictor models, SI was driven solely by depressive symptom severity, with no significant association observed for hypo/mania or its interaction with depression. In contrast, when mood states were categorized using clinically meaningful thresholds, hypo/mania with mixed features emerged as a distinct contributor to suicidal ideation risk. Conclusion: These findings underscore the need for integrating both dimensional and categorical approaches to mood state classification in research on suicidality in bipolar disorder.

Ebola virus (EBOV) causes severe disease outbreaks in humans with high case fatality rates. EBOV requires adaptation to cause lethal disease in mice by acquiring single mutations in both the nucleoprotein (NP) and VP24 genes. As an attempt to model mouse-adapted EBOV (MA-EBOV), we engineered novel pentacistronic minigenomes (5xMG) containing a reporter gene, VP40, and glycoprotein genes as well as the NP and VP24 genes from either EBOV or MA-EBOV. The 5xMGs were constructed and optimized, and the produced transcription- and replication-competent virus-like particles (trVLPs) were demonstrated to infect several cell lines. Introduction of the mouse-adaptation mutations did not significantly impact the replication and transcription of the 5xMG or the relative infectivity of the trVLPs in vitro. This work demonstrates the development of the 5xMG system as a new versatile tool to study EBOV biology.

Abstract Objective Rare large B-cell lymphomas (LBCLs) present with concurrent or subsequent lymphomatous effusion (solid-effusion LBCL, SE-LBCL), which may have an inferior prognosis compared with their noneffusion counterpart. In addition, the relationship between SE-LBCL and human herpesvirus 8–negative effusion-based LBCL (EB-LBCL) remains unclear. Methods We collected 141 cases of SE-LBCL and a control cohort of 101 cases of stage IV solid-only LBCL. The clinicopathologic features were analyzed and compared between SE-LBCL and solid-only LBCL. Results Patients with SE-LBCL had a median age of 67 years with a male-to-female ratio of 1.3:1. Eighty-six patients had concurrent solid lymphoma and lymphomatous effusion, whereas 55 developed lymphomatous effusion subsequently. Most cases involved the pleural cavities (79%, 112/141), followed by the peritoneal (21%, 29/141) and pericardial (11%, 16/141) cavities. BCL6, CD10, and MUM1 were expressed in 77% (90/117), 46% (60/130), and 61% (58/95) of cases, respectively, and 58% (71/123) were subclassified into the germinal center B-cell (GCB) subtype. Rearrangements of BCL2, BCL6, and MYC were detected in 42% (31/73), 35% (22/63), and 40% (35/88), respectively, and 22% (19/87) had both MYC and BCL2 rearrangements. The patients with SE-LBCL had a dismal prognosis, with a median survival of 5.7 months, which was significantly worse than solid-only LBCL (147.5 months; P < .0001). Conclusions The pathologic features of SE-LBCL were similar to those of solid-only LBCL but distinct from those of EB-LBCL; in particular, lymphomatous effusion was an independently adverse prognostic factor in LBCL. Our study underscores the need for surveillance of lymphomatous effusion during LBCL staging and development of effective therapeutic regimens for SE-LBCL.

ObjectiveA dysregulated immune response is involved in the pathogenesis of polymyalgia rheumatica (PMR) and giant cell arteritis (GCA). These diseases have been reported as immune‐related adverse events in patients with cancer treated with immune checkpoints inhibitors. In this cross‐sectional study, the relationship between soluble immune checkpoint molecules (sICMs) and clinical/imaging features of PMR and GCA was investigated.MethodsConsecutive patients with PMR diagnosed according to the criteria by Bird et al were compared with age‐ and sex‐matched healthy controls. Patients with PMR and overlapping GCA had to also satisfy the 1990 ACR classification criteria for GCA. All patients underwent standardized clinical, laboratory examination, and 18F‐fluorodeoxyglucose positron emission tomography/computed tomography scans. The sICM anticytotoxic T Ly‐4, the programmed cell death protein 1 (PD‐1), and PD‐1 ligands PD‐L1 and PD‐L2 were measured by enzyme‐linked immunosorbent assay.ResultsForty patients (80% women, mean age 76 years, and mean disease duration 88 days) were assessed. Of these, 30 had isolated PMR and 10 had PMR with GCA. Patients showed significantly higher concentrations of all sICMs compared with controls (P < 0.001). Conditional logistic regression revealed the strong discriminative capacity of these molecules between patients and healthy controls, with PD‐1 showing complete separation among groups (effect size = 0.78) and PD‐L1 (odds ratio [OR] 134.33, P < 0.001) and PD‐L2 (OR 63.00, P < 0.001) demonstrating the strongest ability to distinguish patients from controls. Correlations between sICM levels and clinical features were generally weak or absent, with no significant differences based on disease phenotype or glucocorticoid exposure. Results were similar in glucocorticoid‐naive patients.ConclusionsICMs are significantly elevated in PMR and GCA and strongly differentiate patients from healthy controls. Although they do not correlate with clinical or imaging features, their consistent elevation in active disease might suggest a complex interplay between innate and adaptive immunity.image

Background Secondary aortoenteric fistulas (SAEF) following endovascular aortic repair (EVAR) is an extremely rare event but life threatening. Our review offers comprehensive knowledge on pathophysiology, clinical presentation, diagnosis, and treatment options. Aim To summarize the current literature regarding pathophysiology, clinical, diagnostic and therapeutic approach of aortoenteric fistulas secondary to EVAR. Methods We performed a literature search in Pubmed/MEDLINE to identify the literature published about SAEF after EVAR. Cases were summarized in a table and prevalences. Other relevant literature was included in the results sections. Results A total of 35 reports (single cases and small series) with 45 patients were included. SAEF after EVAR can result from infection, inflammation, or mechanical factors. Clinical presentation is often non-specific, ranging from a gastrointestinal herald bleed to hemorrhagic shock, or malaise and general infection-related symptoms. Cross-sectional imaging plays a critical role in diagnosing SAEF. The treatment approach involves a multidisciplinary team approach and requires broad-spectrum intravenous antibiotics, endovascular intervention for urgent hemorrhage control, and open surgical intervention for definitive repair. Long-term antimicrobial therapy is essential to avoid reinfection. Conclusions SAEF following EVAR represents a complex, life-threatening condition with limited evidence-based management strategies. Given the growing prevalence of endovascular procedures, comprehensive knowledge of SAEF is crucial for all health care providers to improve early diagnosis and outcomes.

Background: The COVID-19 (coronavirus disease 2019) pandemic has presented a serious challenge to nephrologists, since it can lead to severe kidney injury in the form of acute tubular necrosis, with many patients requiring renal replacement therapy. This is predominantly seen in people who develop severe respiratory manifestations like ARDS (acute respiratory distress syndrome) from the viral infection, a cytokine storm or septic shock with unstable hemodynamics. It also presents with various glomerular injuries, mainly collapsing glomerulopathy in high-risk APOL1 (Apolipoprotein L1) genotype patients, thrombotic microangiopathy-related renal failure due to hyper coagulopathy and occasionally pauci-immune glomerulonephritis due to immune dysregulation. All the glomerular disorders that are caused by COVID-19 infection have been described under the designation COVAN (COVID-19-associated nephropathy). Proteinuria is a predominant presentation in glomerular disorders. Gross hematuria and AKI without any respiratory symptoms from COVID-19 infection have not been described so far in the literature. We are presenting one such rare case here. Methods: We have encountered a rare case of gross hematuria and severe acute renal failure. His serological work up was negative for all autoimmune etiologies that can cause Glomerulonephritis. He was found to have infection-related crescentic glomerulonephritis due to active COVID-19 infections discovered via kidney biopsy. He tested positive for SARS-CoV-2 but didn’t have any clinical respiratory symptoms. He has responded well to treatment with a steroid taper and antiviral medication (Remdesivir). This is a very rare renal manifestation of COVID-19 infection. Results: COVID-19 infection can result in crescentic glomerulonephritis. This can be diagnosed by kidney biopsy which shows extensive c3 deposits, tubuloreticular inclusion bodies along with crescentic lesions. This responds to treatment with steroids and Antiviral agents. Conclusions: Crescentic Glomerulonephritis should be considered as a possible etiology for severe acute kidney injury with hematuria in patients with active covid-19 infection without any respiratory symptoms. Kidney biopsy helps in diagnosing it and responds to treatment with steroids and antivirals.

Background: Delirium in hospitalized patients has been consistently associated with worse clinical outcomes, including increased mortality and prolonged hospital stays. COPD exacerbation is a common reason for hospitalization, and understanding the impact of delirium on this population is crucial for improving patient care and outcomes. Methods: We conducted a retrospective cohort study using the National In-Patient Sample dataset to assess the impact of delirium on patients hospitalized with COPD exacerbation. Subjects were identified using International Classification of Diseases, 10th Revision, codes for COPD exacerbation and delirium. Baseline characteristics and outcomes, including in-patient mortality and the use of invasive mechanical ventilation, were compared between subjects with and without delirium using chi-square analysis. Multivariate regression analysis was used to adjust for potential confounders. Results: A total of 8,062,333 subjects hospitalized with COPD exacerbation were included, of whom 574,005 (7.2%) had a diagnosis of delirium. Most subjects in both groups were white, covered by Medicare, and treated in large urban teaching hospitals. Subjects with delirium had higher rates of dementia, malnutrition, and chronic kidney disease. The rates of in-patient mortality (13.85% vs 4.29%, P < .01) and use of invasive mechanical ventilation (26.7% vs 7.79%, P < .01) were significantly higher in the delirium group. Delirium was associated with higher odds of mortality (adjusted odds ratio [aOR] 2.48, P < .01) and use of mechanical ventilation (aOR 3.92, P < .01). Subjects with delirium had longer and more costly hospital stays. Conclusions: Delirium was associated with worse outcomes in subjects hospitalized with COPD exacerbation.