Manjappachar, Nirmala

Purpose: Obesity is a risk factor for sepsis complications in older adults. We assessed the impact of metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUHO) on outcomes in septic shock. Methods: We conducted a retrospective analysis using the National Inpatient Sample (2016-2020) to identify a cohort of 1,737,075 patients aged 65 years and older who were hospitalized with septic shock, as defined by ICD-10 diagnosis codes. Obese patients without hypertension, diabetes, or hyperlipidemia were classified as MHO; those with ≥1 risk factor as MUHO. Baseline demographics and hospital characteristics were compared using χ² and Mann–Whitney U tests. Multivariable logistic regression adjusted for age, sex, race, comorbidity index, and hospital factors estimated odds ratios (ORs) for respiratory failure, mechanical ventilation, in-hospital mortality, and cardiac arrest. Secondary endpoints included length of stay (LOS) and hospitalization cost. Results: Among 268 050 obese patients, 23 915 (1.4%) were classified as MHO and 244 135 (14.1%) as MUHO. Both phenotypes were more prevalent in females and least common among Asian patients. MHO prevalence was highest among Native Americans, while MUHO was most common among Hispanics in 2020. From 2016 to 2019, the prevalence of both phenotypes remained stable, with modest increases observed during the 2020 sepsis surge. Respiratory failure occurred most frequently in the MHO group (∼70%), followed by MUHO (∼65%) and non-obese patients (∼60%). After adjusting for confounders, both MHO and MUHO groups had higher odds of respiratory failure and mechanical ventilation compared to non-obese patients. In-hospital mortality increased across all groups in 2020; however, MUHO patients had lower adjusted mortality risk. Cardiac arrest rates remained unchanged, while length of stay and hospitalization costs were highest among MHO patients. Conclusions: MHO and MUHO both confer higher respiratory failure and ventilation risk; lower mortality in MUHO warrants further study. Clinical Implications Phenotypic obesity classification may improve sepsis risk stratification and inform metabolic-specific management.

Abstract Introduction: Erdheim-Chester disease (ECD) is an exceptionally rare non-Langerhans cell histiocytic malignant disorder but presents a unique diagnostic challenge due to its diverse clinical manifestations from mild symptoms to severe, life-threatening multiorgan disease. Here, we report a case of ECD that presented with pleuro-pulmonary and vascular involvement rather than skeletal lesions. Case description: A 75-year-old man with a history of systemic lupus erythematosus, rheumatoid arthritis, and chronic obstructive pulmonary disease presented with syncope, anorexia, fatigue, and weight loss. He was noted to be in atrial fibrillation. Subsequent imaging studies, including. The CTA of chest and PET-CT scans showed hyperdense wall thickening in multiple arteries and veins, including the pulmonary arteries and veins, aortic arch, thoracic and abdominal aorta, and iliac arteries as well as pulmonary nodules suggestive of a large vessel vasculitis associated with systemic inflammation. The patient underwent a pleural biopsy which only demonstrated nonspecific inflammation. He subsequently underwent surgical wedge biopsy of a superior right lower lobe and multiple pleural biopsies showed atypical histiocytic infiltrate suspicious for a histoplasmic neoplasm with the atypical histiocytes characterized by plump to spindled nuclei with focal emperipolesis. Atypical histiocytes were positive for CD163, factor 13a, cyclin D1 suggestive of ECD. As further testing demonstrated a negative BRAFV600E mutation, the patient was initiated on cobimetinib 40 mg daily. He responded to therapy with subjective and objective improvement. There has been no radiographic evidence of recurrence. Discussion: The diagnosis of ECD relies on clinical presentation, imaging studies, and distinctive pathological findings. Overall, the prognosis depends on the degree of histiocytic damage before initiation of treatment; degree of inflammation; age; digestive tract involvement. A biopsy revealing non-Langerhans cell histiocytosis, supported by immunohistochemistry exams, is essential for confirming the diagnosis. Diagnosing ECD is challenging due to its rarity and multisystem involvement necessitating a multidisciplinary approach. Pulmonary involvement, seen in 43% of cases, often presents with features of interstitial lung disease but does not significantly impact overall prognosis. Recent evidence implicates the BRAFV600E mutation in ECD pathogenesis, suggesting new therapeutic possibilities.

Abstract Effective communication during handoffs and transitions of care is crucial, as over 50% of sentinel patient events are due to communication gaps, according to the Joint Commission. In our open multi-specialty Intensive Care Unit (ICU) at a tertiary care center, we noticed variability in handoff practices leading to provider dissatisfaction, delays in care and increased potential for errors. To address this, we developed and implemented a standardized handoff procedure. METHODS: A multi-disciplinary team comprised of fellow physicians, nursing and advanced practice provider (APP) leadership conducted an online anonymized baseline survey (B) in December 2023 in our open mixed ICU assessing multidisciplinary provider satisfaction in the process of transitioning patients out of the ICU. Based on this, we identified areas for improvement in the ICU transfer-out process, focusing on communication methods and handoff standardization. Between February and June 2024, we designed and posted signage near provider work areas to clearly designate the primary team based on the level of care and co-managing specialties. We also developed electronic record-based template dot phrases based on the I-PASS format to help standardize information provided during handoff, and ICU team members were educated on the use of the same. Post-implementation (PI) surveys were anonymously conducted in June 2024 to assess the impact of changes, with data analysis comparing pre- and post-implementation metrics, and regular feedback meetings facilitated iterative improvements. RESULTS: We received 40 survey responses (B =20 and PI=20). In the baseline survey, 65% identified room for improvement, particularly with the timing of provider handoffs, inconsistencies in transfer documentation, and clarity on the responsible medical team. Post-implementation survey results showed a 15% improvement with 80% reported no problems during the process, and 85% rated the clarity of the process as “very clear” and “clear,” with 15% neutral. Regarding staff communication, 90% rated it as “good” to “very good,” with 5% neutral. Dot phrase utilization was deemed “very helpful” to “helpful” by 54%, while 46% were neutral. The majority (95%) reported no challenges during the transfer-out process, and 80% were satisfied with the initiative's implementation. CONCLUSION: Our study highlights the impact of a multimodal approach in improving the process of ICU transitioning patients. We were able to improve the primary team identification with posted signage in the ICU.Using computer template-based dot phrases, we were also able to successfully improve satisfaction with the sign out process at time of transition out of the ICU level of care.

Abstract Rationale: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer. They are also associated with life-threatening immune-related adverse events (irAEs), including the rare, poorly understood, and potentially fatal triad of myasthenia gravis, myocarditis, and myositis(triple M syndrome). We aimed to describe the management, intensive care unit (ICU)utilization, and outcomes of patients with irAEs with a specific focus on triple M syndrome. Methods: We conducted a retrospective chart review of patients with irAEs admitted to three quaternary care hospitals between December 2018 and 2023. We aimed to collect data on demographics, cancer type, treatment, ICU resource utilization, and outcomes including mortality. Results: Over this 5-year period, 140 patients were admitted for irAEs. Forty-nine percent were male, median age was 73 (IQR 64-80) years, 7% were of African American or Asian descent, and 32%required ICU admission. Median ICU and hospital length of stay (LOS) were 1.5 (IQR 0.7-2.9)and 7.2 (IQR 4.1-13.4) days, respectively. Among ICU patients, 14/140 (10%) had myositis,22/140 (16%) myocarditis, and 9/140 (6.4%) myasthenia gravis. Triple-M syndrome was diagnosed in 7/140 (5%) patients, including 3 with metastatic melanoma, 2 with genitourinary malignancies, 1 with metastatic lung and 1 with colon cancer. Four had received pembrolizumab and 3 nivolumab. Median ICU and hospital LOS were 3 (IQR 1-6) and 10 (IQR 8-21) days in this group. Three patients required mechanical ventilation, one required tracheostomy, and one required vasopressor support. Triple-M management included corticosteroids, IVIG, pyridostigmine, mycophenolate mofetil, and rituximab. Patients with triple-M syndrome were significantly older than other patients with ICI toxicity (P <0.009) and had higher mortality (57%vs 25%, p = 0.07). Patients discharged from the ICU had a median survival of 67 (IQR 26-201)days. Conclusions: Patients with irAEs frequently require ICU level of support with significant morbidity and mortality, especially with triple M syndrome. Clinicians should always consider the possibility of triple-M syndrome in patients with multiple irAEs as symptoms can be subtle and easily overlooked. Corticosteroids remain the primary treatment of irAEs and can be combined with other immunosuppressive agents such as infliximab, anti-thymocyte globulin, or pyridostigmine. Unfortunately, mortality due to triple-M syndrome remains high underscoring the importance of early recognition and prompt multidisciplinary management of these toxicities.