Requiring Vasopressor Support Research Articles

EP376 - Portal Pyaemia and Fungal Septicaemia Associated with Mesenteric Venous Pneumatosis - Improving Patient Outcomes

Abstract An 82 year old female presented to A&E with a 1 week history of lower abdominal pain, fever, and nausea. She had a known history of sigmoid diverticulosis, however had not had any previous abdominal surgery, and had no other past medical history of note. At presentation she was in septic shock, requiring vasopressor support to maintain her blood pressure. Her abdominal examination revealed left iliac fossa tenderness, however no features of peritonism. Initial investigations revealed a White Cell Count (WCC) 49.3x10^9/L, a C-Reactive Protein (CRP) 191mg/L, and an ALP of 434IU/L. A CT scan of the abdomen and pelvis confirmed acute sigmoid diverticulitis, with radiological features suggesting gas tracking along the inferior mesenteric vein (IMV). An emergency Hartmann’s procedure was performed, and intra-operatively pus was evidence draining directly from the IMV. Pre-operative blood cultures and intra-operative tissue cultures grew Escherichia coli, for which the patient was treated with intravenous meropenem post-operatively. She was transferred to Intensive Care Unit and stepped down to the ward on post-operative day 5. Within the first 48 hours post-operative, the WCC had risen to 64x10^9/L, however within 72 hours of commencing anti-fungals, this dramatically decreased to 16x10^9/L. After this, her recovery was swift, and was discharged shortly after. In the context of acute diverticulitis, any radiological evidence of gas within the portal venous system is likely secondary to portal pyaemia. Urgent operative intervention for source control remains the mainstay of management, with consideration of anti-fungals imperative.

Evaluation of the Sofa Score in Predicating Outcome of Sepsis Patients Admitted to a Tertiary Care Center in Nepal

Background Sepsis is a major health burden with life- threatening conditions, which leads to a high rate of mortality in patients. The Sequential Organ Failure Assessment (SOFA) score, which assesses organ dysfunction across multiple systems, has been considered a reliable indicator of the severity of critical illness. We have carried out this study to evaluate the predictive value of the SOFA score in assessing the mortality of patients with sepsis on admission.  Methods Our study was a cross-sectional, descriptive study carried out in patients with sepsis who were admitted to the medical ICU of Chitwan Medical College from December 15, 2021, to December 14, 2022. Patient sampling was done based on a non-probability convenience sampling technique.  Results In a study of 130 patients, 54.6% were male and 45.4% were female. The mean SOFA score was 7.1, with a median of 7. 38.5% (50 patients) died due to sepsis. The mean SOFA score was higher among deceased patients (9.3) than survivors (5.8). Higher SOFA scores were associated with increased mortality. 46% of patients required inotropes/Vasopressor support for shock. Patients requiring vasopressor support had a significantly higher mortality rate (53.3%) compared to those who did not need support (25.7%). 13.1% of patients required mechanical ventilatory support, and the majority of these patients (70.6%) had mortality.  Conclusion SOFA score is a valuable tool to assess organ dysfunctions and it can predict the outcome of patients admitted with sepsis.

Circumferential correction of spinal deformity and instability secondary to bacterial spondylodiscitis

BackgroundSpinal deformity as a sequela of non-tuberculous spondylodiscitis is a rarely discussed clinical entity. Sagittal plane deformity, segmental instability, and persistently active infection overlap in these patients resulting in severe restriction in activity and quality of life. The presence of multiple medical co-morbidities restricts surgical options but nonoperative care may be ineffective and result in persistent, refractory discitis for years. We describe our experience with vertebrectomy and long-segment fixation for patients with post-infectious thoracic or lumbar deformity. MethodsA retrospective chart review of 23 consecutive patients who underwent vertebrectomy and long-segment fixation for thoracic or lumbar deformity secondary to nontuberculous bacterial spondylodiscitis was performed. Pre-, peri- and postoperative data is compiled and analyzed with a focus on the perioperative management algorithm to safely perform an extensive reconstruction in this very sick patient population. ResultsExtremely low preoperative quality of life was evident with 87% (20/23) of patients bedridden primarily due to pain despite 70% (16/23) of patients being strong enough to ambulate (Frankel D or E). Most patients (87%) already had an identified infection under adequate treatment either through blood cultures, prior biopsy or decompressive surgery. A single-stage posterior-only was the primary surgical approach utilized in the majority (83%) of cases. Complications were present in 100% of patients, most commonly perioperative anemia and hypotension requiring vasopressor support and aggressive blood product replacement. One in-hospital mortality occurred secondarily to pulmonary embolism. Mean preoperative segmental angle was 18±10 degrees of kyphosis which was corrected to 1±9 degrees of lordosis (p=0.001). The mean correction of the segmental angle was 19 degrees (standard deviation 23 degrees). Visual analogue scale scores improved from a pre-operative value of 8.8±0.9 to a post-operative value of 2.5±1.4 (p<0.001), which was obtained at the last outpatient follow-up (mean 631 days after surgery). Full self-care including ambulation was achieved in 18/23 (78%) patients, and the infection was successfully treated in 22/23 (96%) patients after long-term antibiotics. ConclusionsPatients with refractory spondylodiscitis on appropriate care and antibiotics are typically considered extremely poor surgical candidates despite non-operative care often being ineffective. Post-infectious deformity may also be so severe as to preclude a limited surgical treatment strategy. This study suggests that extensive circumferential reconstruction for deformity secondary to bacterial spondylodiscitis can be effective in restoring these extremely sick patients to self-care and ambulatory status.

292 Predictive Factors for Post-Operative Hypotension Following Carotid Endarterectomy

Abstract Background Post-operative hypotension is a recognised complication following carotid endarterectomy (CEA). This study aimed to examine the incidence of post-operative hypotension requiring vasopressors and to identify variables associated with this phenomenon following CEA. Method A retrospective cohort study of 73 consecutive patients undergoing CEA between June 2022 and June 2023 was conducted. Patient data, including degree of carotid stenosis, and comorbidities such as myocardial infarction, diabetes, hypertension, and chronic kidney disease (CKD), were extracted from medical records. Fisher’s exact test was used to evaluate the difference in prevalence of co-morbidities between groups, and Mann-Whitney U test to assess for difference in degree of carotid stenosis. Results 71 symptomatic and 2 asymptomatic CEAs were performed, with 12.3% (n=9) experiencing post-operative hypotension requiring vasopressors. In the post-CEA hypotension group, 33.3% (n=3) had a history of myocardial infarction, 77.8% (n=7) had hypertension, and none had diabetes or CKD. In comparison, the non-hypotensive group had a prevalence of 17.2% (n=11) for myocardial infarction, 18.8% (n=12) for diabetes, 71.9% (n=46) for hypertension, and 6.3% (n=4) for CKD. There was no significant difference in prevalence of these co-morbidities between the two groups. The degree of carotid stenosis was similar in the post-CEA hypotension and the non-hypotension group, 75% (IQR 60% – 90%), and 70% (IQR 65% - 90%), respectively. Conclusions Approximately 1 in 8 CEA patients require vasopressor support for post-operative hypotension. However, no specific variable emerged as a significant predictor for vasopressor requirement. Consequently, emphasis should be placed on post-operative monitoring to facilitate timely and appropriate intervention.

Inpatient burden and clinical outcomes of cytokine release syndrome in patients with cancer: A National Inpatient Sample study.

11067 Background: Cytokine release syndrome (CRS) is a potentially life-threatening complication commonly seen in patients receiving chimeric antigen receptor (CAR)-T cell therapy, allogeneic stem cell transplant, or immunotherapies. This study aims to evaluate the inpatient burden outcomes of CRS leading to hospitalization in patients diagnosed with cancer. Methods: Hospitalizations for cytokine release syndrome (CRS) were identified using ICD-10 coding from the 2020 National Inpatient Sample (NIS), the largest all-payer inpatient database in the US. Only CRS patients with a co-diagnosis of cancer (identified using the Clinical Classification Software (CCS) coding) were included in this study. The underlying severity of illness index was used to verify CRS grading. Sampling weights were applied to generate nationally representative estimates. Results: In 2020, there were 4,765 hospitalizations coded with CRS. 27.2% of these admissions had a co-diagnosis of cancer (n=1,295) and were included in the final analysis. The top co-diagnoses in the patients with CRS without cancer were COVID-19 infection and sepsis. Hematologic malignancies had the highest incidence amongst cancer types (75.7%), the distribution was as follows: 29.6% with diffuse large B-cell lymphoma, 19.9% with acute lymphoblastic leukemia, 12.8% with multiple myeloma, 12.2% with acute myeloid leukemia, and 7.7% with mantle cell lymphoma. The most common procedures in oncology patients hospitalized with CRS were CAR-T cell therapy (29.3%), chemotherapy (28.6%), stem cell transplant (8.5%), or Blinatumomab bispecific antibody (5.4%). 11.4% of patients with CRS received tocilizumab. Of those that received tocilizumab, 10% were CRS grade 2, 56.7% were grade 3, 33.3% were grade 4. 51.7% of tocilizumab was given in the first 48 hours of admission. A minority of CRS patients required critical care interventions: 12.0% requiring intubation, 5.8% requiring vasopressor support, and 2.7% received dialysis. Overall, 10.4% of all oncology admissions with CRS resulted in death during hospitalization (n=135). Of these deaths, 92.6% were in the extreme severity of illness and 63.0% were CRS grade 4. Those with CRS who died during hospitalization had a significantly longer length of stay (24.6 vs 13.6 days, p&lt;0.001). The overall median hospital charges of a CRS-related admission were $531,692. Conclusions: This study represents the inpatient burden of CRS-related admissions in patients diagnosed with cancer. CRS admissions are commonly seen in patients with hematologic malignancies, those undergoing CAR-T cell or immunotherapies (bispecific antibodies). CRS poses a significant healthcare burden, with average hospital charges being greater than 0.5 million US dollars per admission. About 1 in 10 patients with CRS died during hospitalization with higher mortality likely with severe CRS grades and longer length of stay.

A multicenter clinical study of critically ill patients with sepsis complicated with acute kidney injury in Beijing: incidence, clinical characteristics and outcomes

To investigate the epidemiological characteristics and prognosis of critically ill patients with sepsis combined with acute kidney injury (AKI) in intensive care unit (ICU) in Beijing, and to analyze the risk factors associated with in-hospital mortality among these critically ill patients. Data were collected from the Beijing AKI Trial (BAKIT) database, including 9 049 patients consecutively admitted to 30 ICUs in 28 tertiary hospitals in Beijing from March 1 to August 31, 2012. Patients were divided into non-AKI and non-sepsis group, AKI and non-sepsis group, non-AKI and sepsis group, AKI and sepsis group. Clinical data recorded included demographic characteristics, primary reasons for ICU admission, comorbidities, sequential organ failure assessment (SOFA), acute physiology and chronic health evaluation II(APACHE II) within 24 hours of ICU admission, physiological and laboratory indexes, treatment in the ICU, AKI staging based on the Kidney Disease: Improving Global Outcomes (KDIGO), as well as the prognostic indicators including length of stay in ICU, length of stay in hospital, ICU and in-hospital mortality. The primary endpoint was discharge or in-hospital death. Multivariate Logistic regression analysis was used to investigate the risk factors for hospital death in ICU patients. Kaplan-Meier survival curve was drawn to analyze the cumulative survival of ICU patients during hospitalization. A total of 3 107 critically ill patients were ultimately enrolled, including 1 259 cases in the non-AKI and non-sepsis group, 931 cases in the AKI and non-sepsis group, 264 cases in the non-AKI and sepsis groups, and 653 cases in the AKI and sepsis group. Compared with the other three group, patients in the AKI and sepsis group were the oldest, had the lowest mean arterial pressure (MAP), and the highest APACHE II score, SOFA score, blood urea nitrogen (BUN), and serum creatinine (SCr) levels, and they also had the highest proportion of receiving mechanical ventilation, requiring vasopressor support, and undergoing renal replacement therapy (RRT), all P < 0.01. Of these 3 107 patients, 1 584 (51.0%) were diagnosed with AKI, and the incidence of AKI in patients with sepsis was significantly higher than in those without sepsis [71.2% (653/917) vs. 42.5% (931/2 190), P < 0.01]. The highest proportion of KDIGO 0 stage was observed in the non-sepsis group (57.5%), while the highest proportion of KDIGO 3 stage was observed in the sepsis group (32.2%). Within the same KDIGO stage, the mortality of patients with sepsis was significantly higher than that of non-sepsis patients (0 stage: 17.8% vs. 3.1%, 1 stage: 36.3% vs. 7.4%, 2 stage: 42.7% vs. 17.1%, 3 stage: 54.6% vs. 28.6%, AKI: 46.1% vs. 14.2%). The ICU mortality (38.7%) and in-hospital mortality (46.1%) in the AKI and sepsis group were significantly higher than those in the other three groups. Kaplan-Meier survival curves further showed that the cumulative survival rate of patients with AKI and sepsis during hospitalization was significantly lower than that of the other three groups (53.9% vs. 96.9%, 85.8%, 82.2%, Log-Rank: χ 2 = 379.901, P < 0.001). Subgroup analysis showed that among surviving patients, length of ICU stay and total length of hospital stay were significantly longer in the AKI and sepsis group than those in the other three groups (both P < 0.01). Multivariate regression analysis showed that age, APACHE II score and SOFA score within 24 hours of ICU admission, coronary heart disease, AKI, sepsis, and AKI combined with sepsis were independent risk factors for ICU mortality in patients (all P < 0.05). After adjusting for covariates, AKI, sepsis, and sepsis combined with AKI were significantly associated with higher ICU and in-hospital mortality, with the highest ICU mortality [adjusted odds ratio (OR) = 14.82, 95% confidence interval (95%CI) was 8.10-27.12; Hosmer-Lemeshow test: P = 0.816] and in-hospital mortality (adjusted OR = 7.40, 95%CI was 4.94-11.08; Hosmer-Lemeshow test: P = 0.708) observed in patients with sepsis combined with AKI. The incidence of AKI is high in sepsis patients, and those with both AKI and sepsis have a higher disease burden, more abnormalities in physiological and laboratory indicators, and significantly increased ICU and in-hospital mortality. Among surviving patients, the length of ICU stay and total length of hospital stay are also longer in the AKI and sepsis group. Age, APACHE II score and SOFA score within 24 hours of ICU admission, coronary heart disease, AKI, and sepsis are independent risk factors for in-hospital mortality in ICU patients.

Real-world evaluation of imipenem/cilastatin/relebactam across US medical centres

We assessed 160 patients who received imipenem/cilastatin/relebactam for ≥2 days. At treatment initiation, the median Charlson Comorbidity Index was 5, 45% were in the intensive care unit, and 19% required vasopressor support. The in-hospital mortality rate was 24%. These data advance our understanding of real-world indications and outcomes of imipenem/cilastatin/relebactam use.

Dengue induced acute liver failure: A meta summary of case reports.

Dengue fever is the most common cause of viral hemorrhagic fever, with more than 400 million cases being reported annually, worldwide. Even though hepatic involvement is common, acute liver failure (ALF) is a rare complication of dengue fever. To analyze the demographic profile, symptomology, hospital course and outcomes of patients presenting with ALF secondary to dengue infection by reviewing the published case reports. A systematic search was performed from multiple databases including PubMed, Reference Citation Analysis, Science Direct, and Google Scholar. The search terms used were "dengue" OR "severe dengue" OR "dengue shock syndrome" OR "dengue haemorrhagic syndrome" OR "dengue fever" AND "acute liver failure" OR "hepatic failure" OR "liver injury". The inclusion criteria were: (1) Case reports or case series with individual patient details; (2) Reported acute liver failure secondary to dengue infection; and (3) Published in English language and on adult humans. The data were extracted for patient demographics, clinical symptomatology, clinical interventions, hospital and intensive care unit course, need for organ support and clinical outcomes. Data from 19 case reports fulfilling the predefined inclusion criteria were included. The median age of patients was 38 years (inter quartile range: Q3-Q1 26.5 years) with a female preponderance (52.6%). The median days from diagnosis of dengue to development of ALF was 4.5 d. The increase in aspartate aminotransferase was higher than that in alanine aminotransferase (median 4625 U/L vs 3100 U/L). All the patients had one or more organ failure, with neurological failure present in 73.7% cases. 42.1% patients required vasopressor support and hepatic encephalopathy was the most reported complication in 13 (68.4%) cases. Most of the patients were managed conservatively and 2 patients were taken up for liver transplantation. Only 1 death was reported (5.3%). Dengue infection may rarely lead to ALF. These patients may frequently require intensive care and organ support. Even though most of these patients may improve with supportive care, liver transplantation may be a therapeutic option in refractory cases.

Anaesthesia Management for Giant Intraabdominal Tumours: A Case Series Study.

Due to a lack of randomised controlled trials and guidelines, and only case reports being available in the literature, there is no consensus on how to approach anaesthetic management in patients with giant intraabdominal tumours. This study aimed to evaluate the literature and explore the current status of evidence, by undertaking an observational research design with a descriptive account of characteristics observed in a case series referring to patients with giant intraabdominal tumours who underwent anaesthesia. Twenty patients diagnosed with giant intraabdominal tumours were included in the study, most of them women, with the overall pathology being ovarian-related and sarcomas. Most of the patients were unable to lie supine and assumed a lateral decubitus position. Pulmonary function tests, chest X-rays, and thoracoabdominal CT were the most often performed preoperative evaluation methods, with the overall findings that there was no atelectasis or pleural effusion present, but there was bilateral diaphragm elevation. The removal of the intraabdominal tumour was performed under general anaesthesia in all cases. Awake fiberoptic intubation or awake videolaryngoscopy was performed in five cases, while the rest were performed with general anaesthesia with rapid sequence induction. Only one patient was ventilated with pressure support ventilation while maintaining spontaneous ventilation, while the rest were ventilated with controlled ventilation. Hypoxemia was the most reported respiratory complication during surgery. In more than 50% of cases, there was hypotension present during surgery, especially after the induction of anaesthesia and after tumour removal, which required vasopressor support. Most cases involved blood loss with subsequent transfusion requirements. The removal of the tumor requires prolonged surgical and anaesthesia times. Fluid drainage from cystic tumour ranged from 15.7 L to 107 L, with a fluid extraction rate of 0.5-2.5 L/min, and there was no re-expansion pulmonary oedema reported. Following surgery, all the patients required intensive care unit admission. One patient died during hospitalization. This study contributes to the creation of a certain standard of care when dealing with patients presenting with giant intraabdominal tumour. More research is needed to define the proper way to administer anaesthesia and create practice guidelines.

Predictors of nonpulmonary vein triggers for atrial fibrillation: A clinical risk score

BackgroundTargeting non-pulmonary vein triggers (NPVTs) after pulmonary vein isolation may reduce atrial fibrillation (AF) recurrence. Isoproterenol infusion and cardioversion of spontaneous or induced AF can provoke NPVTs but typically require vasopressor support and increased procedural time. ObjectiveThe purpose of this study was to identify risk factors for the presence of NPVTs and create a risk score to identify higher-risk subgroups. MethodsUsing the AF ablation registry at the Hospital of the University of Pennsylvania, we included consecutive patients who underwent AF ablation between January 2021 and December 2022. We excluded patients who did not receive NPVT provocation testing after failing to demonstrate spontaneous NPVTs. NPVTs were defined as non-pulmonary vein ectopic beats triggering AF or focal atrial tachycardia. We used risk factors associated with NPVTs with P <.1 in multivariable logistic regression model to create a risk score in a randomly split derivation set (80%) and tested its predictive accuracy in the validation set (20%). ResultsIn 1530 AF ablations included, NPVTs were observed in 235 (15.4%). In the derivation set, female sex (odds ratio [OR] 1.40; 95% confidence interval [CI] 0.96–2.03; P = .080), sinus node dysfunction (OR 1.67; 95% CI 0.98–2.87; P = .060), previous AF ablation (OR 2.50; 95% CI 1.70–3.65; P <.001), and left atrial scar (OR 2.90; 95% CI 1.94–4.36; P <.001) were risk factors associated with NPVTs. The risk score created from these risk factors (PRE2SSS2 score; [PRE]vious ablation: 2 points, female [S]ex: 1 point, [S]inus node dysfunction: 1 point, left atrial [S]car: 2 points) had good predictive accuracy in the validation cohort (area under the receiver operating characteristic curve 0.728; 95% CI 0.648–0.807). ConclusionA risk score incorporating predictors for NPVTs may allow provocation of triggers to be performed in patients with greatest expected yield.

Anesthetic Aspects of Cytoreductive Surgery and Hyperthermic Intrathoracic Chemotherapy (HITHOC) in Treatment of Pleural Malignancies - Experiences from IORS

Background: Cytoreductive surgery (CRS) with hyperthermic intrathoracic chemotherapy (HITHOC) is a procedure that includes surgical removal of all visible tumor implants and intrathoracic application of gradually heated cytostatic solution. Numerous changes in hemodynamic, respiratory, core body temperature and metabolic parameters are possible during this complex procedure. The aim of this retrospective study was to analyze pathophysiological changes which occur during CRS + HITHOC procedure, and to suggest efficient strategies for perioperative patient care that might reduce complication rate. Methods: The study included 7 patients who underwent CRS + HITHOC in our cancer center. Enhanced Recovery After Surgery (ERAS) guideline for Thoracic Surgery was applied to all patients. Data on intraoperative hemodynamics (mean arterial pressure, stroke volume, heart rate, cardiac output) and temperature variations were collected from medical records and analyzed in three timelines: during the CRS phase, at the beginning, and the end of cytostatic perfusion. Occurrence of respiratory, renal, and cardiac complications was monitored. Results: All patients were respiratory stable during one-lung ventilation, with adequate gas exchange. Hemodynamic stability was compromised at the beginning of cytostatic perfusion, with significant decrease of mean arterial pressure and stroke volume. Two patients required vasopressor support. Average core body temperature was satisfactory in all patients. Coagulation disorders and acute renal failure were not recorded in postoperative period. One patient developed atrial fibrillation which was successfully pharmacologically restored. Conclusion: Our results indicate that goal directed fluid management following ERAS protocol, with maintaining hemodynamic stability and normothermia, could prevent perioperative complications during HITHOC procedure.

Quality Improvement Curriculum for Intensive Care Unit Upgrades.

Patients admitted to the hospital ward from the emergency department (ED) occasionally decompensate and require transfer to the intensive care unit (ICU). An emergency medicine (EM) curriculum focused on review of these ICU upgrade cases could improve resident knowledge related to patient acuity, critical illness, and appropriate disposition. Furthermore, initial identification of critical pathology in the ED and earlier admission to the ICU could reduce delays in care and improve patient outcomes. We performed a retrospective analysis to determine the effectiveness of a resident quality improvement curriculum evaluating cases where patients require transfer from the inpatient floor to the ICU within 12 hours of admission from the ED. We compared postgraduate year 2 (PGY-2) EM residents who participated in the ICU upgrades curriculum during their first year to PGY-2 EM residents who did not participate in the curriculum. Analysis of the 242 qualifying ICU upgrade cases from July 2019-October 2021 showed post-curriculum residents were responsible for an average of 1.0 upgrades per resident compared to an average of 1.54 upgrades per resident (P = 0.12) for pre-curriculum residents. Although there was no statistically significant difference in ICU upgrades between the groups, there was a trend toward decreased ICU upgrade cases for residents who participated in the curriculum. Common reasons for ICU upgrade included worsening respiratory distress requiring higher level of respiratory support, recurrent hypotension after initial intravenous fluid resuscitation requiring vasopressor support, and declining mental status. This retrospective study showed no significant difference in the number of ICU upgrades for residents who completed the ICU upgrades curriculum compared to residents who were not enrolled in the course. However, the study was likely underpowered to detect a significant difference in the groups, and there was a trend toward reduced ICU upgrades for residents who completed the curriculum. ICU upgrade cases were frequently associated with worsening respiratory status, hypotension, and mental status. These findings highlight the importance of reassessment of vital signs and mental status prior to determining disposition from the ED. Additional, larger studies are needed to better determine the curriculum's impact on resident proficiency in recognizing critical illness and reducing ICU upgrades.

Abstract 17127: Rapid Progression of Conduction System Disease in Suspected Fulminant Nivolumab Myocarditis

Background: Immune checkpoint inhibitors (ICI) have shown efficacy in treating a wide spectrum of malignancies, but have a known risk of cancer therapy related cardiac toxicity. We present a case that demonstrates how conduction system disease can rapidly progress in a patient with suspected nivolumab (PD1) induced fulminant myocarditis. Case: An 82-year-old male with a history of esophageal carcinoma presented with agonal breathing and altered mental status. He had received his second dose of PD1 therapy three days prior. He was intubated and admitted for hypoxic respiratory failure and elevated troponin. His initial EKG demonstrated new marked 1st degree AV block with right bundle branch block (RBBB) morphology. A stat echocardiogram noted an EF of 60-65% with no wall motion abnormalities. Decision-making: On Day 2, Mobitz Type I block was appreciated on telemetry. The patient met criteria for acute myocarditis with his clinical presentation, new conduction system disease, and high sensitivity troponin of 13,000. Given recent PD1 therapy, lack of infectious prodrome, and lack of prior heart disease, suspicion for ICI induced myocarditis was high. High dose steroid therapy was initiated. On Day 3, the patient was noted to have alternating left bundle branch block and RBBB. On Day 4, he progressed to complete heart block, prompting transvenous pacemaker (PM) placement with subsequent permanent PM placement. A repeat echo showed global hypokinesis with an EF of 40-45% and reduced RV function. He also required vasopressor support meeting criteria for fulminant myocarditis. Due to his hemodynamic instability and low clinical suspicion, he did not receive cardiac catheterization. Cardiac MRI and cardiac biopsy were not readily available in this institution. Conclusion: The clinical findings, lack of infectious prodrome, and worsening arrhythmia requiring pacing and vasopressor support, in patient with recent PD1 treatment suggests nivolumab induced fulminant myocarditis. In institutions without advanced testing infrastructure, rapid recognition of progressive conduction system disease may be used as an early marker for diagnosis, treatment initiation, and referral to tertiary care centers for advanced management of fulminant ICI myocarditis.

High Efficacy and Excellent Safety Profile of Actalycabtagene Autoleucel, a Humanized CD19 CAR-T Product in r/r B-Cell Malignancies: A Phase II Pivotal Trial

Background: Commercially approved CD19 CAR-T cell therapies are effective in r/r B cell malignancies, but are associated with significant albeit manageable toxicities. These toxicities contribute to significant morbidity. We have developed a novel, humanized CD19 CAR-T cell therapy, Actalycabtagene autoleucel (Actaly-cel) and previously reported the safety in Phase I study (Dwivedi et al. Mol Cancer Ther.2021, Karulkar et al. ASH 2022). Here, we present the pooled results from Phase I and a planned interim analysis of the Phase II study evaluating Actaly-cel. Materials and methods: The Phase I study (n=10) was a single-center trial to test the safety of Actaly-cel at a dose of 1x10 7 to 5x10 9 CAR-T cells in patients with r/r DLBCL, tFL and PMBCL (CTRI/2021/04/032727). The Phase II study (n=50) was a single-arm, multi-center study conducted across 3 centers in India (CTRI/2022/12/048211). Patients with r/r B-cell malignancies (including aggressive and indolent B-cell lymphomas and acute lymphoblastic leukemia) aged ≥ 15 years, with normal organ function, ECOG PS 0-2 and measurable disease were eligible. Actaly-cel was manufactured using an integrated semi-automated system. Bridging therapy was allowed at the clinician's discretion. Patients received infusion of Actaly-cel two days after conditioning with fludarabine plus cyclophosphamide. The target dose was ≥5x10 6/kg CAR T-cells (efficacy-evaluable cohort), however doses of ≥0.5x 10 6/kg CAR-T cells were allowed. Patients who received Actaly-cel at any dose were considered in the safety analysis. The primary endpoint was objective response rate, with duration of response, adverse events, PFS and OS as the secondary endpoints. A Simon II-stage design was used to test the hypothesis that the ORR would increase from 25% (historical data) to 40% (⍺- 0.1 and β- 0.2), &amp;gt;15 responses were required out of 50 patients to reject the null hypothesis. The CRS and neurotoxicities (ICANS) were graded and treated as per ASTCT guidelines, other toxicities were graded as per CTCAE v5. Exploratory studies were performed to study the correlation between patient and product related characteristics with response. Results: A total of 59 patients with r/r DLBCL (41), ALL (16) and indolent lymphomas (2) were enrolled (Phase I; 06/2021 till 06/2022 and Phase II; 12/2022 till 07/2023), 56 underwent leukapheresis (ITT set) and 47 received Actaly-cel (safety set). 43 patients received the target dose (Figure 1A). The median age was 43 years (16-71) with 46 (65%) male patients. Patients had a median of 2 prior lines of therapy (1-6), 65% had refractory disease,25% of lymphoma patients had bulky disease, and the median bone marrow blast was 69% (6-98%) in the B-ALL cohort. The median vein-to-vein time was 17(7-132) days. Total 78%(33/43) patients reached the day 28 timepoint at the time of analysis (Figure 1B). The ORR was 70% (23/33), including 58% (19/33) with a CR. In the lymphoma cohort, the ORR was 71%(17/24) and CR was observed in 54%(13/24), while in the leukemia cohort, the CR rate was 66% (6/9, n=5 MRD negative). The median follow-up of evaluable patients was 57 days (21-453). All nine patients and 3 out of 4 patients maintained the response after 3 months and 12 months follow-up, respectively. None of the patients developed ICANS of any grade. CRS developed in 22/33(66%) cases (grade 1/2 in 61%, grade 3/4 in 6%). Of note, no grade &amp;gt;3 CRS was noticed in the lymphoma cohort. Grade 3/4 cytopenias developed in all cases. The median duration of neutropenia was 7 (4-32) days. On Day 28, grade 3/4 neutropenia was observed in 11/33(33%) cases, grade 3/4 thrombocytopenia was observed in 7/33 (21%). Only 1(3%) patient required ICU admission, 2(6%) required vasopressor support, tocilizumab was administered to 18 (55%) patients, median 1 dose (1-4) and steroids were used in 5 (15%) cases. Patients were hospitalized for a median of 8 days (7-19 ). There were no treatment-related deaths. On exploratory analysis, higher CAR-T dose, fewer prior lines of therapy and higher peak CAR-T copies/µg DNA correlated with response. Conclusions: Actaly-cel demonstrated efficacy in r/r B-cell malignancies with a very favorable safety profile. The absence of ICANS, shorter duration of cytopenias and a lower incidence of grade 3/4 CRS makes it one of the safest CD19 CAR-T cell therapy products. Actaly-cel can improve the ease of delivery of CAR T-cell therapy in a wide-range of settings.

Excellent Safety Profile of a Low-Cost Novel Humanized CD19 CAR T-Cell Therapy, Actalycabtagene Autoleucel : Potential Impact on Access and Feasibility

Background: A high incidence of severe toxicities especially grade 3/4 immune effector cell-associated neurotoxicity syndrome (ICANS) and cytokine release syndrome (CRS), need for hospitalization, and the cost of supportive care is an hindrance to the implementation of CAR-T cell therapy for low and middle income countries (LMICs). To address these limitations, we designed a novel humanized CD19 CAR and demonstrated a favorable balance of efficacy to toxicity in the preclinical model and in the first-in-human Phase I study (Dwivedi et al. Mol Cancer Ther. 2021, Karulkar et al. ASH 2022). Here, we quantified the healthcare resource utilization (HCRU) and associated cost of clinical management of Actalycabtagene autoleucel (Actaly-cel) in India from an ongoing Phase I/II study in B-cell malignancies. Methods: This is a retrospective analysis of the HCRU costs of patients with r/r B-cell malignancies treated on Phase I/II study with Actaly-cel at 3 centers in India between June 2021 through July 2023. The key components of HCRUs are defined in Table 1 and were quantified from the electronic records from the time of enrolment till their last follow-up. Once enrolled, bridging therapy was allowed at investigator's discretion. After lymphodepletion (LD) with a fludarabine plus cyclophosphamide (FC) regimen for 3 days, patients received Actaly-cel at a target dose ≥ 5 million CAR-T cells/kg (upper limit; total 2 x10 9). The patients were monitored for toxicities particularly CRS, ICANS and cytopenias, as inpatient (non-HEPA filtered rooms) for at least a week. CRS and ICANS were graded as per ASTCT grading system and cytopenias as per CTCAE v5. Results: Total 59 patients were enrolled in this study and 47 patients received the infusion. Thirty seven patients (r/r lymphoma; n=28, r/r B-ALL; n=9) who completed 28 days post-infusion were evaluable for HCRU analysis. The median age was 37 years (16-71). The median follow-up of the cohort was 60 days (21-644); 19% (7/36) and 11% (4/36) patients completed 6 months and 12 months follow-up respectively. Among all patients (n=37) who received LD therapy, 46% of lymphoma patients received LD in the outpatient setting while 78% of B-ALL patients required hospitalization for LD. The median hospitalization period post Actaly-cel infusion was only 8 days (range: 7-17 days) in the lymphoma cohort, and 13 days (range: 7-19 days) for B-ALL patients. Importantly, none of the lymphoma patients required ICU admission, and only one B-ALL patient required ICU admission for management of adverse events. In the lymphoma cohort, 54% (15/28) of patients developed Grade 1/2 CRS and none had grade &amp;gt;/=3. A single dose of tocilizumab was given to 36% (10/28) of patients and only 4% (1/28) received tocilizumab plus corticosteroids. None of the patients required vasopressor support. Majority of B-ALL patients developed CRS. The incidence and severity of CRS was as follows: G1; 44% , G2; 11% and G3; 22%. There were no grade 4/5 CRS events. While 11% (1/9) of patients received a single dose of tocilizumab, 44% (4/9) received tocilizumab in combination with corticosteroids. Vasopressors were required in 22% of patients. None of the patients developed ICANS of any grade . Most patients (lymphoma and B-ALL) developed hematological toxicities(Table 1). The severity of Grade 3-4 was more prevalent in the B-ALL cohort. IVIG was administered to 25% of lymphoma and 22% of B-ALL patients. The induction and severity of the above toxicities were not dependent on the Actaly-cel dosage (median: 9 x 10 6 ;range: 2 x 10 6-21 x 10 6 CAR-T cells/kg). The projected production cost of Actaly-cel in the regional decentralized manufacturing model at the scale of 300 patients/year is ~15,000 USD per patient. The mean cost of HCRU for clinical management (until last follow-up) per patient was ~ 4,400 USD in an academic centre (lymphoma; ~4,000 USD, B-ALL; ~5,565 USD) and interestingly, only about 14% of these costs were incurred due to inpatient management (Figure 1). Conclusions: Actaly-cel was efficacious, with no incidence of ICANS and manageable CRS across a wide dose range. More importantly, this study reported low HCRUs due to negligible ICU admission and shorter duration of hospitalization, ensuring potential usage of Actaly-cel in outpatient settings, and ultimately improving the access and feasibility of CD19 CAR-T cell therapy in resource constrained settings such as LMICs.

A rare presentation of acute myocarditis as a manifestation of adult-onset Still’s disease: a case report

Abstract Background Adult-onset Still’s disease (AOSD) is a rare systemic autoinflammatory condition characterized by a classical triad of symptoms that include prolonged fever, polyarthritis, and a characteristic salmon-pink skin rash. It can affect a variety of organ systems resulting in many different clinical presentations and is usually a diagnosis of exclusion. Myocarditis complicated by cardiogenic shock is a rare and life-threatening manifestation of AOSD, typically affecting younger patients. There is a limited experience and evidence in how best to manage this challenging patient cohort. Case summary A previously fit and well 22-year-old male presented with fever, arthralgia, and general malaise. On clinical examination, he was pyrexial and hypotensive, requiring vasopressor support for presumed septic shock. Subsequent transthoracic echocardiography and cardiac MRI findings were in keeping with fulminant myocarditis. Further septic and auto-immune screens were negative although he responded well to high-dose intravenous corticosteroids. Attempts to wean immunosuppression were unsuccessful, and his ferritin was markedly elevated (20 233 μg/L). A diagnosis of AOSD was suspected after exclusion of other possible causes. The successful addition of tocilizumab (an interleukin-6 receptor antagonist) therapy allowed for gradual de-escalation of steroid therapy and disease remission, with on-going remission at 18 months on maintenance therapy. Discussion This case highlights the importance of considering AOSD as a rare cause for myocarditis, especially when fever is present, or disease is severe. Failure to improve with first-line therapy involving high-dose corticosteroids, or inability to wean that therapy, should prompt consideration for escalation of therapy, with tocilizumab seemingly an effective treatment option.

Echocardiography Does not Reduce Mortality in Sepsis: A Re-Evaluation Using the Medical Information Mart for Intensive Care IV Dataset.

Echocardiography is commonly used for hemodynamic assessment in sepsis, but data regarding its association with outcome are conflicting. The aim of this study was to evaluate the association between echocardiography and outcomes in patients with septic shock using the Medical Information Mart for Intensive Care IV database. Retrospective cohort study comparing patients who did or did not undergo transthoracic echocardiography within the first 5 days of admission for the primary outcome of 28-day mortality. Admissions to the Beth Israel Deaconess Medical Center intensive care from 2008 to 2019. Adults 16 years old or older with septic shock requiring vasopressor support within 48 hours of admission. Readmissions and patients admitted to the coronary care unit or cardiovascular intensive care were excluded, as well as patients with ST-elevation myocardial infarction or cardiac arrest. None. Echocardiography was performed in 1,515 (27%) of 5,697 eligible admissions. The primary outcome was analyzed using a marginal structural model and rolling entry matching to adjust for baseline and time-varying confounders. Patients who underwent echocardiography showed no significant difference in 28-day mortality (adjusted hazard ratio 1.09; 95% CI, 0.95-1.25; p = 0.24). This was consistent across multiple sensitivity analyses. Secondary outcomes were changes in management instituted within 4 hours of imaging. Treatment changes occurred in 493 patients (33%) compared with 431 matched controls (29%), with the most common intervention being the administration of a fluid bolus. Echocardiography in sepsis was not associated with a reduction in 28-day mortality based on observational data. These findings do not negate the utility of echo in cases of diagnostic uncertainty or inadequate response to initial treatment.

FRI235 Primary Adrenal Insufficiency As Presenting Symptom Of Disseminated Histoplasmosis And Cryptococcus Co-Infection In Immunocompetent Patient

Abstract Disclosure: A. Thompson: None. Background: Autoimmune adrenalitis remains the most common cause of primary adrenal insufficiency in the United States. Infectious etiologies from fungal sources are much less commonly seen. Below we discuss a case of disseminated histoplasmosis and cryptococcus that initially presented with primary adrenal insufficiency. Case: A 74 y/o F with history of Type 2 DM presented to the hospital with 3 months of fatigue and weight loss. She was initially found to be in DKA and shock requiring vasopressor support. Following the resolution of DKA, she remained hypotensive without obvious cause. A random cortisol was found to be 8.2 [6-25 ug/dL]. She then underwent an ACTH stimulation test and her cortisol level at 30 minutes was 5.9 ug/dL and at 60 minutes was 4.2 ug/dL. An ACTH level was obtained and found to be elevated at 69 [7.2-63 pg/mL]. She was subsequently started on Hydrocortisone and her shock resolved. CT adrenal glands were notable for bilateral adrenal masses measuring 4.5 cm on the right and 4.6 cm on the left with HU of 27. No other suspicious lesions were noted on imaging. An infectious work up was initiated, which was notable for fungal serologies positive of Histoplasmosis with titer of 1:8 (&amp;lt;1:8). Histoplasmosis urine antigen was positive as well. She was tested for Cryptococcus, which was positive with a titer of 1:8 (&amp;lt;1:8). She started treatment with Amphotericin B for 4 weeks followed by Itraconazole for maintenance therapy. Discussion: Primary adrenal insufficiency from invasive fungal infection remains uncommon and is found in less than 10% of cases. Disseminated fungal infections are identified as causes like histoplasmosis and paracoccidiomycosis. Disseminated cryptococcus is an exceedingly rare cause of adrenal insufficiency. These invasive infections can lead to bilateral enlargement of the adrenal glands and calcifications are seen on radiographic imaging. Such cases can also lead to perivasculitis and cause thrombosis and subsequent infarction of the adrenal glands. Disseminated fungal infections are more commonly seen in patients with underlying immunodeficiency such as HIV or those receiving immunosuppressant therapy. This case highlights that these infections can still be seen in those without a compromised immune system. Diagnosis can be challenging given the vague symptoms of adrenal insufficiency but should be considered in patients with electrolyte disturbances, hypoglycemia, and hypotension. There is potential for adrenal recovery following treatment with antifungal therapy. Conclusion: Although autoimmune adrenalitis is the most common cause of primary adrenal insufficiency in the US, this case highlights the importance of evaluating for other potential causes such as infectious sources, which can be treated and potentially have adrenal recovery. Presentation: Friday, June 16, 2023

FRI207 Challenges Of Pheochromocytoma Management In A Heart Failure Patient

Abstract Disclosure: M. Novitskaya: None. M. Sonbol: None. S. Jafri: None. J. Monye: None. E. Japp: None. Introduction: Successful management of pheochromocytoma in patients with heart failure requires a careful balance between blood pressure control and appropriate perioperative volume resuscitation. Clinical Case: A 38-year-old male with heart failure with reduced ejection fraction (EF 15-20%), HTN, and polysubstance use disorder presented with dyspnea and subsequent in-house PEA arrest. Whole body CT showed an incidental 7.3 cm left adrenal mass. Laboratory work-up was notable for elevated plasma free metanephrines 47.30 nmol/L (n&amp;lt;0.89) and normetanephrines 39.8 nmol/L (n&amp;lt;0.49). Medical management of presumed pheochromocytoma was initiated with doxazosin. Left and right heart catheterization showed elevated intracardiac filling pressures (mmHg): RA 10, RV 66/5 (12), PA 55/29 (43), PCWP 35. Subsequent coronary angiogram was aborted due to hypertensive emergency and flash pulmonary edema for which he required IV hydralazine 20 mg, furosemide 80 mg, labetalol 30 mg, verapamil 5 mg, nitroglycerin 800 mg bolus then gtt at 100 mcg/min to achieve hemodynamic stability. He reached the preoperative BP goal after up titration of doxazosin to 12 mg daily and carvedilol to 25 mg twice daily. He subsequently underwent left adrenalectomy. Intraoperatively, the patient’s abdomen was insufflated to 13 mmHg given his reduced EF, and he received 2 L crystalloid prior to adrenal vein division. After a left adrenalectomy, he developed hypotension despite receiving an additional 3 L crystalloid, and was started on norepinephrine, epinephrine, and vasopressin gtt. Postoperatively, he remained intubated for two days due to distributive shock. With continued diuresis, mean arterial pressure recovered to &amp;gt;65 mmHg and he was extubated. He was successfully discharged on metoprolol succinate 25 mg, spironolactone 25 mg and losartan 25 mg daily. Clinical Lessons: Preoperative management of pheochromocytoma involves alpha-adrenergic blockade followed by beta-adrenergic blockade to target a BP of &amp;lt;130/80. A high sodium diet is recommended after adequate alpha-adrenergic blockade, and volume resuscitation is started preoperatively due to vasodilation after adrenalectomy. Successful management of patients with pheochromocytoma and heart failure requires extra attention to BP and volume status. Our patient’s case was complicated by severe HTN during cardiac catheterization resulting in flash pulmonary edema, and postoperative hypotension requiring vasopressor support due to loss of circulating catecholamines. His estimated risk of morbidity/mortality from adrenalectomy was &amp;gt;25% due to these factors. Multidisciplinary collaboration among endocrinologists, cardiologists, anesthesiologists, surgeons, and perfusionists is crucial to optimize patient outcomes. This patient case adds to the literature in presenting a positive adrenalectomy outcome in a patient with heart failure. Presentation: Friday, June 16, 2023

FRI215 Rifampin Induced Adrenal Insufficiency

Abstract Disclosure: S.R. Campbell: None. R.M. Tierney: None. J. Lim: None. Introduction: Rifampin is a main component of antimycobacterial therapy in active tuberculosis disease. Although adrenal insufficiency can be caused by infiltration of the pituitary or adrenal glands by Mycobacterium tuberculosis, rifampin has also been suggested as a potential causative agent. This case shows a rare example of rifampin-induced adrenal insufficiency in the setting of active tuberculosis disease. Case Presentation: A 42-year-old man with a history of gout and anemia presented with fevers, chills, unintentional weight loss, and productive cough for two weeks. He immigrated from Guatemala 20 years prior and was treated for tuberculosis disease as a child. Upon presentation, he was borderline hypertensive with chest CT showing bilateral nodular opacities in a pattern suggestive of atypical pneumonia. Acid fast bacilli stains were positive and cultures grew Mycobacterium tuberculosis. The patient was started on rifampin, isoniazid, pyrazinamide, and ethambutol (RIPE) therapy. Serum cortisol levels on day 4 of RIPE therapy were appropriate in the setting of acute illness (&amp;gt;20 mcg/dl). On day 6 of RIPE therapy, the patient became hypotensive requiring vasopressor support. Labs at that time showed hyponatremia, hypokalemia, and inappropriately low cortisol levels (&amp;lt;20 mcg/dl). ACTH stimulation testing was performed and was blunted with values of 14.50 mcg/dL at 30 minutes and 16.32 mcg/dl at 60 minutes. CT abdomen was also performed and showed no evidence of infiltration. He was started on IV hydrocortisone 50 mg every 6 hours with plans to taper after shock resolved. Following steroid taper, the patient again became hypotensive requiring vasopressors. IV hydrocortisone was resumed, and RIPE therapy was held. He was restarted on PO hydrocortisone 40 mg every 12 hours. Isoniazid, ethambutol, pyrazinamide, and rifampin were sequentially resumed. Pyrazinamide was replaced with moxifloxacin due to recurrent gout flares. The reintroduction of rifampin and rifabutin both resulted in fevers leading to the stoppage of rifamycin therapy. The patient was discharged with stable vital signs on isoniazid 300 mg daily, ethambutol 800 mg daily, moxifloxacin 400 mg daily, and hydrocortisone 30 mg every 12 hours with plans to follow-up with the State Department of Health, internal medicine, and endocrinology. Conclusion: Many drugs are known to cause adrenal insufficiency. There are a few examples in which rifampin has been suggested as a potential cause of adrenal insufficiency. Classically, adrenal insufficiency has been associated with infiltration of the adrenal glands or pituitary gland with Mycobacterium tuberculosis. This case, however, shows further clinical evidence of adrenal insufficiency caused by rifampin therapy and highlights the need for further research to be done to study this adverse effect. Presentation: Friday, June 16, 2023