Citations

Abstract Introduction Rheumatoid arthritis (RA) is a systemic autoimmune rheumatic disease (SARD) primarily associated with articular involvement, but is often associated with lung involvement, sometimes preceding articular symptoms. Common pulmonary manifestations include interstitial lung disease (ILD), airway, and serosal involvement. RA-related pleural disease can mimic empyema due to the pleural fluid's green, pus-like appearance, exudative nature, low pH, markedly low glucose, and elevated lactate dehydrogenase (LDH) levels. Empyema sometimes yields negative cultures which can accentuate the diagnostic challenge in such cases. This report presents a patient with RA-related pleural lung disease who was referred to our hospital with trapped lung presumed to be secondary to empyema in the setting of pleural-based pulmonary abscess. Case Report A 66-year-old female with a 22-year history of RA presented with recurrent right-sided pleural effusions and progressive dyspnea over three years. Her initial presentation in 2022 involved a large right-sided pleural effusion, suspected to result from a ruptured pleural-based pulmonary abscess that led to empyema and subsequently a trapped lung. Pleural fluid analysis showed elevated LDH (1364 U/L), low glucose (45 mg/dL), high cholesterol (121 mg/dL), and low triglycerides (79 mg/dL). Due to refractory exudative effusion and a comprehensive negative infectious evaluation (bacterial, mycobacterial, and fungal cultures), RA-related pleural disease was suspected. The patient underwent video-assisted thoracoscopic surgery (VATS), which revealed pleural-based rheumatoid nodules and pleural thickening. (figure1) Lung and pleural biopsies confirmed RA-associated fibrinous pleuritis, RA-associated follicular bronchiolitis, and usual interstitial pneumonitis. Given the complexity of the infection, a thoracotomy with decortication and pleurectomy was planned and conducted in stages. Immunosuppressive regimen was switched from leflunomide to rituximab. Discussion This case underscores the diagnostic complexity in distinguishing RA-associated pleural effusion from empyema. Features such as pleural nodularity resembling a pulmonary abscess, unilateral exudative effusion, grossly purulent pleural fluid, low pH and glucose, and elevated LDH levels led to an initial misdiagnosis of empyema. Characteristic pleural fluid, along with persistent negative cultures and absence of sepsis pointed towards RA-related pleural disease. VATS and biopsy were instrumental in establishing the final diagnosis through characteristic histopathological findings of RA-associated pleural, parenchymal and airway involvement. Conclusion For RA patients with pleural effusion suggestive of empyema, especially in the context of negative cultures and no signs of sepsis, RA-related pleural disease should be a consideration. Early recognition and timely immunosuppressive therapy escalation can prevent complications such as trapped lungs and reduce the necessity for extensive surgical interventions. Figure1:

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 Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of aggressive inflammation and immune system activation. Its diagnosis is often hindered by its clinical overlap with sepsis, multiorgan failure, and other severe diseases common in the intensive care unit. We present a case of HLH diagnosed in the setting of multiple confounding conditions. Case Presentation: 24-year-old Caucasian male with common variable immunodeficiency presented to local hospital after a week of diffuse swelling and shortness of breath, initially found to be hypoxemic, hypoglycemic, hypovolemic, and febrile to 105°F. He was treated for septic shock, requiring norepinephrine, vasopressin, angiotensin, and stress dose hydrocortisone to maintain perfusion pressures. For work of breathing, he failed noninvasive ventilation and was intubated. Initial labs showed shock liver, acute kidney injury with severe metabolic acidosis, and MSSA bacteremia without endocarditis on transesophageal echocardiogram. He met HLH diagnostic criteria with high fever and ferritin 44,838 ng/mL; other inflammatory markers were not tested. Over two weeks the patient developed significant left lower extremity soft tissue infection concerning for Staphylococcus toxic shock syndrome, cholecystitis with cholecystostomy tube placement, hemorrhagic bullae on all limbs, left thigh hematoma, and new liver lesion that underwent biopsy complicated by significant bleeding requiring interventional radiology embolization. After transfer to our institution, he remained on fluctuating doses of norepinephrine with recurring fevers despite broad spectrum antibiotic and antifungal coverage. Repeat blood cultures were negative, MRI negative for osteomyelitis, pan-CT negative for other occult sources of infection, broad laboratory workup negative for atypical infections or antibodies related to rheumatologic diseases. At this point, he fulfilled HLH criteria given high fever, anemia and thrombocytopenia, splenomegaly, triglyceride 417 mg/dL, ferritin 1,953 ng/mL, and soluble IL-2 receptor >4,000 pg/mL. A multidisciplinary decision was made to start methylprednisone. Patient's fever and hemodynamic instability quickly resolved. He was then transitioned to anakinra with downtrend in his inflammatory markers. Discussion: HLH syndrome is often a delayed diagnosis as clinical manifestations mimic infections, can be triggered by such infections, or mimic other diseases in which a robust inflammatory response occurs. HLH laboratory findings are nonspecific or can have long turnaround time. Even its namesake of “hemophagocytosis” is not pathognomic for the disease. It is only in the case of excessive pathologic immune system activation, i.e. HLH syndrome, that immunosuppression is beneficial. Diagnosing HLH requires a curious clinical mind while treating concomitant urgent conditions, to avoid the “tunnel vision” of the often-cited occam's razor.

Abstract Amiodarone is a commonly used class III antiarrhythmic medication with a rare but well-known adverse effect of pulmonary toxicity. This case illustrates the importance of knowing the risk factors for the development of amiodarone-related lung toxicity, particularly in patients with pre-existing lung disease. Additionally, intensivists must remain mindful of non-infectious causes of ARDS, including acute medication-related lung toxicity. A 73-year-old man was admitted to the Medical Intensive Care Unit (MICU) for worsening hypoxic respiratory failure and progressive pulmonary infiltrates. He has a past medical history of vocal cord malignancy, lung cancer s/p left upper lobe lobectomy and had a left mainstem bronchus stent placed a month prior to presentation. Three weeks before coming to our ICU, the patient was being treated in the outpatient setting for pneumonia post stent placement and was started on rate controlling agents for newly diagnosed atrial fibrillation with rapid ventricular rate. He was ultimately loaded with amiodarone and switched to maintenance for rhythm control. During his stay in the MICU, he underwent a bronchoscopy with bronchoalveolar lavage (BAL), ECHO and repeat CT chest imaging to further investigate his hypoxemia. He was empirically being treated with vancomycin and meropenem. His chest CT compared to one month prior had developed diffuse ground glass opacities and his BAL was limited and unrevealing. He ultimately had progression of disease and was transitioned to comfort care. Amiodarone lung toxicity is a diagnosis of exclusion and presents as interstitial lung disease. A lung biopsy with histopathology is the gold standard for diagnosis and would show foamy laden macrophages. BAL findings include elevated cellular count with 50% of the cases showing eosinophilia. Amiodarone can have an acute, subacute and chronic presentation, with acute being the more aggressive subtype. A double-blind controlled study concluded that the incidence of severe lung fibrosis was 1.2% in doses ranging from 300-800mg compared to < 200mg daily [1] Another retrospective study in Japan found that there is an association with higher incidence of amiodarone induced lung toxicity in age greater than 60. [2] This case highlights a patient presenting with worsening hypoxic respiratory failure, and CT changes, shortly after receiving a second loading dose of amiodarone for atrial fibrillation. He continued to decompensate despite being on appropriate antibiotics and lack of improvement with diuretics. His chest CT was revealing new bilateral ground glass opacities with restrictive physiology on ventilator mechanics, and other causes were ruled out.

Abstract Obstructive shock is rare, occurring in 2% of patients admitted to the intensive care unit (ICU) with shock. Understanding the unique pathophysiology of obstructive shock can aid in resuscitation efforts and significantly impact patient outcomes. Our goal is to expand the current understanding of possible shock etiologies and the treatment of obstructive shock. We present a case of an 88-year-old woman presenting to the ICU following an out-of-hospital cardiac arrest. Family found her unresponsive, called EMS, and started CPR. Upon EMS arrival, she had a pulse; the rhythm was identified as atrial fibrillation. She was cardioverted and transferred to the emergency room. Upon admission, she was intubated and sedated but hemodynamically stable. Shortly after arrival, she developed refractory shock requiring volume resuscitation and rapid titration of three vasoactive medications. She intermittently responded to volume but quickly developed recurrent shock following infusion completion. Bedside ultrasound showed collapse of the right atrium with a pericardial effusion and hyperechoic mobile mass within the pericardial space. Cardiology was called to the bedside for further evaluation of possible cardiac tamponade. There was lack of consensus regarding need for pericardiocentesis. Therefore, further chest imaging was ordered. CTA chest was negative for pulmonary emboli but showed a large hematoma in the anterior mediastinum with active bleeding. Formal echocardiogram confirmed a large extracardiac mass with extrinsic compression of the right atrium as well as a small-moderate circumferential pericardial effusion without obvious features of tamponade. She underwent an urgent IR angiogram with embolization of the internal mammary artery and placement of a 14F locking loop pigtail catheter into the anterior mediastinal hematoma felt to be contained within a known 3.5 cm benign cystic lesion. She experienced significant hemodynamic improvement following embolization and drain placement. The etiology of her presumed PEA arrest remained unclear, though it was concluded that the obstructive shock was due to the anterior mediastinal hematoma, a consequence of CPR. In this case we highlight the risk of arterial hemorrhage following resuscitation for cardiac arrest and the role it can play in the development of obstructive shock. There have been some documented cases of pericardial bleeding and the development of cardiac tamponade but limited case reports regarding arterial hemorrhage following CPR. Quickly identifying extracardiac compression allowed for appropriate and rapid IR embolization which led to clinical improvement in our patient.

Abstract RATIONALE Propofol is the first-line sedative for critically-ill, mechanically-ventilated patients, but it can increase serum triglyceride levels. Machine-learning (ML) offers a promising approach for individualized risk stratification of propofol-associated hypertriglyceridemia, enabling proactive triglyceride monitoring and sedation optimization. This study aims to develop and validate ML models to predict hypertriglyceridemia risks in critically-ill patients receiving propofol. METHODS We analyzed retrospective data from adult ICU patients on mechanical ventilation receiving continuous propofol infusion for ≥24 hours across four Mayo Clinic sites from May 2018 to June 2023. The primary outcome was hypertriglyceridemia, defined as serum triglycerides >400 mg/dL within 10 days of starting propofol. Ten-fold cross-validation and leave-one-site-out nested cross-validation (LOSO-CV) were used for model tuning and external validation of our modeling process, respectively. Feature selection was conducted through a union of Boruta and least absolute shrinkage and selection operator (LASSO). While COVID status was a strong predictor of hypertriglyceridemia, we concurrently developed non-COVID models to ensure future relevance in non-pandemic settings. Six ML algorithms (logistic regression, support vector machines, random forests, LightGBM, XGBoost, and multilayer perceptrons) were tuned using Bayesian optimization to minimize cross-entropy loss. Classification thresholds were set to target sensitivity ≥80%. Model performance was evaluated using AUC-ROC, Brier score, sensitivity, and specificity. Models with the highest Youden's Index were designated the best-performing model. Model explainability was assessed using permutation importance and SHapley Additive exPlanations (SHAP). RESULTS We included 3922 eligible patients with triglyceride measurements. Of these, 3042 patients were COVID-negative and used for non-COVID modeling. The best-performing non-COVID models achieved an average AUC-ROC of 0.69 (95% confidence interval [CI] 0.68-0.70), Brier score of 0.12 (95% CI 0.09-0.14), sensitivity of 0.79 (95% CI 0.75-0.83), and specificity of 0.48 (95% CI 0.44-0.52) during LOSO-CV. The best-performing models that included COVID status achieved an average AUC-ROC of 0.71 (95% CI 0.70-0.72), Brier score of 0.13 (95% CI 0.10-0.16), sensitivity of 0.78 (95% CI 0.71-0.84), and specificity of 0.51 (95% CI 0.45 to 0.56) during LOSO-CV. The permutation importance results of the final non-COVID model are shown in the figure. CONCLUSION We have developed sensitive ML models for predicting hypertriglyceridemia risks in critically-ill patients receiving propofol. Although developed during the COVID-19 pandemic, the non-COVID models are more likely to have future relevance, and they have similar performance as models including COVID status. These models will be integrated into a web-based clinical calculator and undergo further validation in prospective studies.

Abstract Rationale: Medical trainees are often involved in the care of hospitalized patients, yet there are minimal data about correlation of trainee involvement with outcomes for patients with rapid response team (RRT) activations. Methods: This was a retrospective single-center review of adult patients on a primary medicine service who had an RRT activation between January 1, 2023 and December 31, 2023. This study was approved by our hospital institutional review board. Patients were included if they were at least 18 years old and had a hospitalization with an RRT activation. Outcomes analyzed included transfer to the ICU, 90-day mortality, and goals of care discussions. A subset analysis was performed of patients who remained on the floor after RRT. Statistical analysis was performed with Pearson's chi-square and Kruskal-Wallis tests. Results: We analyzed 1686 adult patients who had an RRT activation within the study timeframe. Mean age was 67.3 years (SD 16.8), 792 (47.0%) were female, and 1489 (88.3%) identified as white. Trainees were involved with 1016 (60.3%) patients; 935 of these were on an internal medicine team and 81 were on a family medicine team. Patients were more likely to transfer to the ICU if they were on a primary floor team with trainee involvement (p = 0.006). There was no difference in goals of care discussion occurrence prior to RRT (p = 0.257) or 90-day mortality (p = 0.877). Subset analysis of patients who remained on the floor after RRT was performed. There was no difference in occurrence of goals of care discussions after RRT (p = 0.169), code status change (p = 0.237), or transition to comfort care (p = 0.381) for patients on teams with trainee involvement and those without. Of the 925 patients who remained on the floor after RRT, goals of care discussion occurred after RRT in 210 (22.7%). Conclusions: In this study, we demonstrate that trainee involvement does not correlate with occurrence of goals of care discussions either before or after RRT activations. Trainee involvement also does not correlate with 90-day mortality for patients with decompensation events. However, patients on teams with trainee involvement are more likely to transfer to the ICU as the result of an RRT activation. It is possible that this reflects the increased complexity of patients who are admitted to teaching services; however, further investigation is needed.

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: Ongoing healthcare staffing shortages have prompted new care paradigms that incorporate remote care delivery to support timely detection of patient physiological deterioration through mechanisms other than clinician bedside evaluations. In partnership with institutional Information Technology, our team has developed a unique clinical informatics environment, known as the Advanced Medical Practice (AMP) platform, that incorporates data from multiple sources and platforms and supports remote observation of patients from the electronic intensive care unit(eICU). AMP takes advantage of technologies outside of vendor-supported EHRs, and its advanced user-interface design reduces information overload while incorporating real-time data from novel devices and sensors. We partnered with the hospital practice to co-develop a score within the AMP platform(Clinical Events Detection and Response[CEDAR]) that incorporates heart rate, blood pressure, respiratory rate, and SpO2 to stratify patient risk and generate deterioration alerts for the electronic ICU(eICU) team. This formative evaluation employed an implementation science approach to refine CEDAR and ensure it is acceptable to users and can be feasibly implemented in practice. Methods: The study team conducted this pilot work in the eICU at Mayo Clinic (Rochester, MN). We observed the eICU workflow and documented feedback from eICU staff in fieldnotes. eICU staff were asked to log issues in a tracking file during shifts. Issues were reviewed daily and discussed at multidisciplinary team meetings weekly. Observation and tracking data were coded to constructs in the Consolidated Framework for Implementation Research(CFIR 2.0) framework and mapped to Expert Recommendations for Implementation Change(ERIC) strategies that targeted key determinants. Results: Between 9/23/24 and 10/25/24 we completed 25 days of observations. Most identified issues related to technical/design issues like unclear vital trigger alerts (CFIR: Innovation trialability and design); staff knowledge of CEDAR functionality and attitudes about functionality, complexity, or relative advantage compared to current systems (CFIR: Inner setting access to knowledge and information and relative advantage); and difficulties incorporating CEDAR into workflow(CFIR: Inner setting/compatibility). Implementation strategies mapped to CFIR determinants included promoting adaptability of customized interface features; staging implementation scale-up with iterative improvements; providing local technical assistance; assessing for readiness and identifying facilitators and barriers; and conducting educational outreach visits. Conclusions: Formative evaluation during pilot studies are a critical step in the process of intervention development and testing. User engagement and frameworks from implementation science can identify issues of feasibility and inform strategies to ensure acceptability prior to intervention scale-up in clinical practice and readiness for conducting larger implementation studies.

Abstract Background: Bronchiectasis is a recognized pulmonary manifestation of ANCA-associated vasculitides (AAV). Although positive AAV workup has been observed in patients with isolated airway diseases, without other systemic involvement, AAV workup is not routinely obtained in patients presenting with bronchiectasis. Patients with bronchiectasis and positive AAV workup may represent a distinct subgroup with unique characteristics and outcomes. Objectives: To establish a cohort of patients with bronchiectasis who also have a positive AAV workup (i.e., presence of ANCA by indirect immunofluorescence AND elevated antibodies to PR3 or MPO) and to describe their characteristics. METHODS: There were 944 patients across Mayo clinic sites with bronchiectasis (J47.9, J47.0 and J 47.1) who underwent AAV workup. Of these 315 (33.36%) had evidence of ANCA on immunofluorescence and an abnormal level of antibodies to PR3 or MPO. Chest CT scans were reviewed, and 118 patients were excluded because their pulmonary disease was mostly interstitial or had no clear bronchiectasis. Co-morbidities were evaluated using respective ICD-10 codes and respiratory cultures were collected. RESULTS: A total of 197 patients were identified with Bronchiectasis (76% female; mean age 66 years, BMI 25 kg/m2), 112 (56.8%) were diagnosed before antibody detection and 85 (43.1%) after. MPO (positive [>0.9] or equivocal [0.4-0.9]) was detected in 177 (89.8%) patients; PR3 (positive [>0.9] or equivocal [0.4-0.9]) in 34 (17.2%). P-ANCA and c-ANCA patterns occurred in 185 (94%) and 15 (4%) patients, respectively. The most common antigen-target/ANCA combinations were MPO/p-ANCA (177, 89.8%), PR3/p-ANCA (22, 11.2%), and PR3/c-ANCA (14, 7.1%). Comorbidities included asthma (66, 33.5%), COPD (58, 29.4%), GERD (64, 32.5%), hypothyroidism (56, 28.4%), and autoimmune/inflammatory conditions (e.g., rheumatoid arthritis [23, 11.7%], IBD [25, 12.7%]). Neurologic (42, 23.9%) and renal (25, 14.7%) manifestations occurred. Respiratory cultures (n=122) isolated yeast (57, 46.7%), Aspergillus (34, 27.9%), and Pseudomonas (30, 24.6%); Mycobacteria and other molds (e.g., Penicillium) each appeared in 23-24 patients (∼19%). Conclusion: This work identifies a cohort of patients with bronchiectasis who also have a positive AAV workup, mostly MPO/p-ANCA. While AAV workup is not routine for patients presenting for bronchiectasis evaluation, some patients in this cohort had primarily airway disease with an abnormal AAV workup, in the absence of other common manifestations of AAV. Further research on this cohort will be conducted to determine whether these patients represent a distinct group with unique characteristics, treatment patterns, and outcomes.