Friesen, Joelle N.

Abstract Introduction Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy through enhancing T-cell-mediated immune responses but have also been associated with immune-related adverse events. Emerging literature suggests a potential association between ICI therapy and the development or reactivation of tuberculous mycobacterial infections. It is unclear whether ICI therapy is also linked to an increased risk of non-tuberculous mycobacterial (NTM) infections, though case reports are rapidly accumulating. We aim to better elucidate the potential association between ICIs and NTM infections through a case series. Case Series This series includes patients at Mayo Clinic who were diagnosed with active NTM infection during or after ICI use from January 1, 2012 to December 31, 2024. Data including demographics, malignancy details, ICI regimen and duration, timing and site of NTM infection, microbiologic findings, antimycobacterial therapy, and clinical outcomes were evaluated. There were seven patients with positive testing for NTM during or after ICI therapy. Two had one colony of M. gordonae on cultures which were determined by Infectious Disease to be contaminants. One case had a reported culture positive for M. franklinii at an outside hospital without further details available and thus was excluded from analysis. Chart review was performed for the remaining four patients with active NTM infection during or after ICI therapy. Two of the patients had underlying chronic obstructive pulmonary disease with a smoking history; these same two had primary lung malignancy. The other two patients had no known underlying lung disease or malignancy lung involvement (primary or metastatic). ICI therapies included PD-1, PD-L1, and CTLA-4 inhibitors. All four NTM infections predominant had lung involvement and were all different species; two were diagnosed while the patient was actively receiving ICI therapy and two were diagnosed several months after ICI discontinuation. Of the two receiving ICI therapy at the time of diagnosis, the ICI was held for 101 days for one patient and the other continued the ICI without interruption. Three received multi-agent therapy while the fourth declined treatment and died of malignancy complications soon after. The other three were alive at one year after NTM diagnosis and completed approximately one year of antimycobacterial therapy. Conclusions Tuberculous and non-tuberculous mycobacterial infections are increasingly seen after immune checkpoint inhibitor therapy. We present a series of four cases of NTM infections after or during ICI therapy for various types of malignancy with good outcomes after approximately one year of treatment. This abstract is funded by: None

Background While rapid response teams (RRT) are widely implemented to address clinical deterioration in hospitalized patients, their impact on goals of care (GOC) discussions remains underexplored. Aims We aimed to evaluate whether RRT activations were associated with subsequent goals of care discussions, code status changes, and clinical outcomes. Methods We conducted a retrospective single-center review of hospitalized adult patients admitted to medicine services who had RRT activations between January and December 2023. The primary outcome was GOC discussion within 72 h of RRT. GOC discussions were identified through EMR documentation of conversations, code status changes, and ACP notes. Secondary outcomes included code status change, transition to comfort care, and 30- and 90-day mortality. Analyses were adjusted using inverse probability of treatment weighting. Results 1823 RRTs among 1677 patients were analyzed; 47% of patients were female and 88% identified as white. Those transferred to the ICU had higher odds of goals of care discussions (OR 1.52, P < 0.001), code status change (OR 2.43, P < 0.001), and transition to comfort care (OR 1.47, P = 0.026) compared to those who remained on the floor. ICU transfer was also associated with increased 30- (OR 1.39, P = 0.006) and 90-day mortality (OR 1.30, P = 0.014). Conclusions ICU transfer following RRT activation is strongly associated with downstream goals of care discussions, changes in code status, comfort-focused care, and higher mortality. This demonstrates the importance of initiating goals of care discussions early and often, regardless of whether clinical decompensation is anticipated.

Abstract Introduction: Hemolytic uremic syndrome (HUS) is especially uncommon in adults and can manifest as devasting complications including severe acute kidney injury (AKI) and microangiopathic hemolytic anemia (MAHA). Transfusion-related acute lung injury (TRALI) is a rare complication of blood product transfusion that is characterized by the rapid development of noncardiogenic pulmonary edema. We present a rare case of HUS complicated by TRALI requiring mechanical ventilation. Case Description: A 41-year-old female farmer, who occasionally drank raw cow's milk, was admitted with abdominal pain and distension, bloody diarrhea, poor appetite, decreased urine output and fatigue. She was found to have MAHA and stage 3 AKI. Imaging demonstrated pancolitis and workup revealed Shiga toxin-producing E. coli, O157:H7 serotype which was consistent with a diagnosis of HUS. Tests for DIC, TTP and atypical HUS were negative. She was not a candidate for dialysis, plasma exchange or eculizumab. With supportive measures including 3 units of packed red blood cell (pRBC), her symptoms, renal function, and bicytopenia improved and she was discharged. Two days post-discharge, she presented to the ED for unilateral vision changes, left hemiparesis, and lower extremity tremor. After negative neurological evaluation, this was attributed to encephalopathy secondary to HUS. She received 1 unit of pRBCs for a hemoglobin of 6.8. Within 3 hours of transfusion, she developed acute respiratory distress requiring intubation and ICU transfer. CT chest angiogram was negative for pulmonary embolism but demonstrated diffuse bilateral lower lobe dependent consolidations concerning for TRALI (Figure 1). After diuresis, she was able to be extubated within 48 hours with return to her respiratory and neurologic baselines soon after. Discussion: The pathophysiology of TRALI involves neutrophil sequestration and priming in the pulmonary vasculature with subsequent neutrophil activation by donor blood product factors where active infection is a known risk factor. Active HUS likely contributed to neutrophil priming through endothelial damage and systemic inflammation, predisposing this patient to TRALI. There are few reports of similar cases in the literature. TRALI can be subdivided into type I and type II; type I has no risk factors for acute respiratory distress syndrome (ARDS) while type II does. TRALI must also be distinguished from ARDS and transfusion-associated circulatory overload; these distinctions are predominantly made based on timing of respiratory symptom onset. This case highlights the importance of keeping TRALI in the differential for all patients with active or recent infection, including HUS, who develop acute-onset respiratory decompensation after transfusion.

Abstract Rationale: The Deterioration Index (DTI) may serve as a crucial tool for predicting adverse patient outcomes; however, there is a paucity of literature attempting to externally validate this tool in specific clinical scenarios. In this study, we analyzed the relationship between DTI scores during rapid response team (RRT) activations and subsequent ICU transfer, initiation of goals of care (GOC) conversations, and 90-day mortality. Methods: This was a retrospective single-center review of adult patients who had an RRT activation while hospitalized between January 1, 2023 and December 31, 2023. This study was approved by our hospital institutional review board. Deterioration scores (0-100) were recorded every 15 minutes during the RRT event, and the highest score of each encounter was selected for analysis. The primary outcome was transfer to the ICU as a direct result of the RRT activation. Secondary outcomes included GOC discussions following RRT activation and 90-day mortality. GOC discussions, defined as physician-led conversations that specifically addressed code status, treatment priorities, or broader goals of care, met criteria only if initiated within 72 hours of the analyzed RRT activation. Logistic regression was used to assess the relationship between DTI scores during RRT activations and the aforementioned variables. Results: A total of 1643 patients were included in the analysis. For every 1-point increase in the deterioration score, the odds of ICU transfer increased by 2.7% (OR: 1.027, CI: 1.021-1.034, p&lt;0.0001), the odds of a goals of care discussion within 72 hours increased by 3.3% (OR: 1.033, CI: 1.025-1.040, p&lt;0.0001), and the likelihood of mortality within 90 days increased by 2.6% (OR: 1.026, CI: 1.019-1.033, p&lt;0.0001). Conclusion: Our findings contribute to external validation of DTI predictive value during RRT events. DTI scores were associated with key clinical outcomes, including ICU transfer and 90-day mortality. There was also an association between DTI scores and the likelihood of physician-led GOC discussions, suggesting that DTI may demonstrate predictive value not only of patient outcomes, but also the likelihood of specific non-medical physician actions. Further validation of these scores in prospective studies, specifically in the context of acute decompensation events, could help facilitate the integration of DTI-based RRT interventions into routine hospital practice.

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.

Background Cirrhosis is associated with significant healthcare utilization, yet data about in-hospital decompensations remain sparse. Additionally, the impact of liver transplant candidacy status on resuscitation and outcomes is largely unknown. Aims We aimed to evaluate the characteristics of resuscitation events for patients with cirrhosis with acute decompensation, analyzing liver transplant candidacy and intensive care unit (ICU) transfer parameters. Methods Retrospective single-center review of adult patients with liver cirrhosis who had a rapid response team (RRT) activation during hospitalization and no prior liver transplantation. Results Patients with cirrhosis who were liver transplant candidates were more likely to be younger ( p = .003), have a higher serum total bilirubin ( p = .015), higher INR ( p < .001), and higher MELD 3.0 ( p = .006). There was no significant difference in ICU transfer ( p = .170) after RRT activation. Liver transplant candidates had a lower 30- and 60-day mortality ( p = .008, p = .014) and were less likely to have a code status discussion after decompensation ( p = .001). Lower serum albumin was associated with ICU transfer ( p = .001). Patients who transferred to the ICU were more likely to have a code status discussion within 24 h after RRT ( p = .011) without significant difference in 30- or 60-day mortality ( p = .059, p = .277). Conclusions Liver transplant candidacy in patients with cirrhosis with acute decompensation is not clearly correlated with ICU transfer. Liver transplant candidates are more likely to be younger, have higher MELD 3.0 scores, less likely to have code status discussed after RRT, and have lower 30- and 60-day mortality rates. Patients who transfer to the ICU are more likely to have a code status discussion without any significant difference in 30- or 60-day mortality.

Diverticular disease is a major cause of hospitalizations, especially in the elderly. Although diverticulosis and its complications predominately affect the colon, the formation of diverticula in the small intestine, most commonly in the duodenum, is well characterized in the literature. Although small bowel diverticula are typically asymptomatic, and diagnosed incidentally, a complication of periampullary duodenal diverticulum is Lemmel syndrome. Lemmel syndrome is an extremely rare condition whereby periampullary duodenal diverticula, most commonly without diverticulitis, leads to obstruction of the common bile duct due to mass effect and associated complications including acute cholangitis and pancreatitis. Here, we present the first case, to our knowledge, of periampullary duodenal diverticulitis complicated by Lemmel syndrome with concomitant colonic diverticulitis with colovesical fistula. Our case and literature review emphasizes that Lemmel syndrome can present with or without suggestions of obstructive jaundice and can most often be managed conservatively if caught early, except in the setting of emergent complications.