Sen, Ayan

Pneumocystis jirovecii pneumonia (PCP) is a life-threatening opportunistic infection increasingly recognized among non-HIV immunocompromised patients. In severe cases progressing to acute respiratory distress syndrome, venovenous extracorporeal membrane oxygenation (VV-ECMO) may serve as a rescue therapy. We conducted a retrospective multicenter review of 10 adult patients with proven or probable PCP who received VV-ECMO between 2017 and 2024. Seven of 10 patients survived to discharge, including all three HIV-positive patients and 4 of 7 non-HIV immunocompromised patients. The mean Respiratory ECMO Survival Prediction Score was –1.5, corresponding to a predicted survival of 33–57%. Multiorgan dysfunction was common, including renal failure requiring dialysis in 6 of 10 patients, need for neuromuscular blockade in 8 of 10, and pulmonary vasodilator use in 8 of 10. Despite high acuity and prolonged ECMO support, outcomes were favorable. These findings suggest that VV-ECMO may be a viable salvage therapy for select patients with severe PCP, including those without HIV.

Abstract Background Pneumocystis jirovecii pneumonia (PCP) is increasingly seen in patients who are non-HIV immunocompromised hosts, yet modern risk factors and outcomes are poorly recognized and defined. Methods A retrospective review was conducted of adult patients who met criteria for proven or probable PCP from 2017 to 2024 across a large academic multicenter health system. The primary outcome was mortality among cohorts, defined by etiology of immunosuppression through univariate and age-adjusted logistic regression. Secondary analyses included trends in annual diagnoses and testing patterns. Results A total of 701 patients met criteria for inclusion, representing one of the largest clinically characterized cohorts of PCP to date. The median age was 65 years (IQR, 54–73) and 62% were male. The most common risk groups were hematologic malignancy (32.2%), solid tumor cancers receiving chemotherapy (22.4%), and autoimmune disease with immunosuppression (17.7%). Annual PCP diagnoses increased at a rate of 15.8% (95% CI, 8.9%–23.2%) in parallel with increased testing. Only 5.4% of patients were receiving prophylaxis at the time of diagnosis. Overall mortality was 20% (95% CI, 17%–23%) and highest in cirrhosis (adjusted odds ratio, 6.24; 95% CI, 2.84–13.69; P < .001). Conclusions PCP in the current era affects a broad range of patients who are immunocompromised, with high associated mortality and low rates of prophylaxis. Patients with solid tumors and those with cirrhosis are at particularly high risk of mortality. These findings highlight the need to reassess and redefine PCP prophylaxis guidelines in specific populations and our understanding of who is at risk.

Abstract Hemophagocytic lymphohistiocytosis (HLH) is a rare but critical hyperinflammatory condition that affects around 1.5% of liver transplant patients, with mortality rates reaching up to 33%. This syndrome is characterized by intense, dysregulated activation of macrophages and T-cells, sparking a cytokine surge that leads to severe systemic inflammation and rapid organ failure. Prompt identification and early management are crucial to improve outcomes. Case Presentation: A 61-year-old man with Hepatitis C-induced end-stage liver disease (MELD score 20) underwent a deceased-donor liver transplant. Postoperative complications included atrial fibrillation, stress cardiomyopathy, and a right-sided pleural effusion treated with thoracentesis and extended course of antibiotics. Two weeks later, he presented with fever, hypotension, and nausea, prompting the initiation of IV Zosyn, Vancomycin and Posaconazole. Despite fluid resuscitation, he became hemodynamically unstable, necessitating ICU transfer for vasopressor support. While in the ICU, his condition worsened, with increased fever, tachycardia, anuria and hypoxic respiratory failure that required intubation and continuous renal replacement therapy. Marked hyperferritinemia (ferritin 62,000 µg/L) and hypofibrinogenemia (91 mg/dL) raised suspicion for HLH, with an H score of 244. Comprehensive infectious workup ruled out CMV, EBV, HSV, and other pathogens. Bone marrow biopsy confirmed hemophagocytosis (Figure 1), and flow cytometry ruled out malignant infiltration. Given the strong suspicion for HLH and no identifiable infectious trigger, he was initiated on Dexamethasone, Etoposide, and Ruxolitinib, which lowered ferritin levels and improved vasopressor requirements. However, mentation declined, and imaging revealed a right frontal subarachnoid hemorrhage, likely from disseminated intravascular coagulation, precluding surgical intervention. Despite transient improvement, he developed ventilator associated pneumonia secondary to Stenotrophomonas infections and vancomycin-sensitive Enterococcus bacteremia, leading to refractory hypoxemia. After family and multi-disciplinary team discussions, care was withdrawn. Discussion: HLH remains an exceedingly rare, rapidly fatal syndrome in liver transplant recipients, with only 11 cases documented. Early recognition of HLH can be challenging, as its features, such as fever, cytopenias, and organ dysfunction, overlap with common post-transplant complications, which can delay diagnosis. HLH can be differentiated into primary (genetic) and secondary (acquired) forms, with the latter more common among adults, often triggered by infection, malignancies and autoimmune disorders. Immunosuppressants may inadvertently modulate HLH risk by tempering macrophage and T-cell activation, yet, paradoxically, also predisposing patients to secondary triggers. Clinicians should maintain vigilance for HLH in post-transplant patients with unexplained systemic inflammation, as early intervention is critical, often with Etoposide based regimens to modulate hypercytokinemia, though prognosis remains guarded due to multiorgan failure.

Abstract IntroductionPatients with interstitial lung disease (ILD) who are admitted to the intensive care unit (ICU) face significant challenges, with high rates of morbidity and mortality. Despite the severity of outcomes in this population, the potential impact of gender disparities on ICU outcomes in ILD has not been well studied.MethodsWe analyzed data from the NIS spanning 2016 to 2018, focusing on adults (≥18 years) hospitalized with ILD (J84), and defined ICU stays using ICD codes for central line placement and mechanical ventilation. The NIS, part of the Healthcare Cost and Utilization Project, provides a weighted, nationally representative sample of U.S. hospitalizations. Demographic, clinical, and hospital characteristics were collected, with race/ethnicity categorized per NIS classifications. Multivariable logistic and linear regression models adjusted for potential confounders to evaluate gender differences in outcomes.ResultsOur study identified 810,295 adult hospitalizations with ILD, of which 42,080 required ICU-level care. Of these, 46.7% were female. Female ICU patients were younger (mean age 66.9 ± 13.8 vs. 69.1 ± 12.7, p<0.001), more likely to be African American (17.0% vs. 10.9%, p<0.001), and less likely to be Caucasian (63.7% vs. 69.2%, p<0.001). Females were more often from lower-income ZIP codes (33.2% vs. 38.3%, p<0.001) and had lower rates of tobacco use disorder (35.0% vs. 43.9%, p<0.001). Mortality was significantly lower in females (40.5% vs. 48.1%, p<0.001). After adjusting for confounders, female gender was independently associated with reduced mortality risk (adjusted odds ratio 0.77, 95% CI 0.70-0.84, p<0.001) and a shorter length of hospital stay (adjusted difference 1.15 days, 95% CI 0.54-1.77).ConclusionOur study highlights notable gender differences in outcomes for patients with ILD admitted to the ICU. Female patients had a significantly lower risk of mortality and shorter hospital stays than male patients, even after adjusting for key clinical and socioeconomic confounders. These findings are consistent with emerging evidence that biological sex and gender-related factors play a critical role in disease expression and outcomes in ILD.Several mechanisms may explain these gender disparities. Sex hormones, such as estrogen, have been shown to exert protective effects in pulmonary fibrosis models, potentially influencing the disease course in women. Incorporating these considerations into clinical practice and future research will be vital for advancing individualized, patient-centered medicine in ILD.

Abstract Introduction:Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory syndrome characterized by excessive immune activation and cytokine release, leading to multi-organ failure and mortality. Despite guideline management to include chemotherapy and transplantation, the characteristics and predictors of critical outcomes in post-transplant-associated hemophagocytic lymphohistiocytosis (PT-HLH) remain poorly understood. Methods:This study is a retrospective cohort analysis of patients admitted to acute care hospitals in the U.S. with HLH between 2016 and 2018. We utilized the National Inpatient Sample, identifying HLH patients using International Classification of Diseases, Tenth Revision-Clinical Modification (ICD-10-CM) codes D76.1, D76.2, and D76.3. Patient demographics, such as age, gender, race, ethnicity, zip code, and insurance status, were obtained from the NIS, while hospital-level characteristics, location and teaching vs. non-teaching status, were considered in the study amongst others. We examined the baseline epidemiology of transplant status, including ICU-related outcomes and resource utilization in patients with and without transplants. Data were analyzed using STATA weighted function, with logistic regression for categorical outcomes. Results:Out of 8,330 adult HLH hospitalizations, 520 (6.2%) were transplant recipients. Among these, 350 (67%) had bone marrow transplants, 90 (17%) had kidney transplants, and 30 (5.8%) had liver transplants. The mean age of HLH patients was 50 ± 19 years; transplant patients were younger (mean age 46 ± 17 years) compared to non-transplant patients (50 ± 18 years), p<0.05. Transplant patients were more likely to be male (72.1% vs. 50.1%, p<0.05), have CMV infection (14.4% vs. 4.1%, p<0.05), be Hispanic (20.8% vs. 14.7%, p<0.05), come from higher median household income areas (38.8% vs. 24.5%, p<0.05), and be treated in teaching hospitals (96.1% vs. 85.8%, p<0.05). Among HLH patients who died in the hospital, 130 (25%) were transplant recipients, compared to 1,180 (15.1%) non-transplant recipients, p<0.05. After adjusting for potential confounders, transplant status was associated with a higher risk of mortality (adjusted odds ratio 1.77, 95% CI 1.11-2.83) and sepsis (adjusted odds ratio o1.78, 95% CI 1.08-2.92). Discussion:In examining a national cohort of PT-HLH cases, our findings review potential risk factors for critical care-related outcomes in post-transplant associated HLH care. PT-HLH patients in our cohort presented with distinct characteristics compared to non-transplant HLH cases. ICU-related outcomes showed statistically significant differences between transplant and non-transplant HLH patients. Specifically, transplant status remained independently associated with a higher risk of mortality and sepsis. Our findings underscore the importance of tailoring treatment plans to each patient's specific risk profile.

Takayasu arteritis is a chronic, large vessel vasculitis that typically affects the aorta and its main branches. We present a case of a 33-year-old male patient who was diagnosed with Takayasu arteritis after being admitted for acute cardiogenic shock requiring inotropes. Initial transthoracic echocardiography demonstrated severe biventricular dysfunction. Computed tomography imaging of his chest showed pulmonary infarcts. Patient subsequently developed sudden lower extremity weakness and bowel incontinence, and urgent magnetic resonance imaging of his spine demonstrated thoracolumbar vascular myelopathy. Transesophageal echocardiography revealed diffuse symmetrical thickening of the walls of the aorta; findings suggestive of aortitis. Patient was initiated on intravenous corticosteroid and systemic anticoagulation. Subsequent computed tomography angiography demonstrated irregular luminal contour of the aortic arch, and complete occlusion of the left subclavian artery, abdominal aorta, superior mesenteric artery, and left renal artery. He underwent an emergent aortoiliac thrombectomy. He was transitioned to oral prednisone, tocilizumab, and azathioprine with excellent recovery.