Citations

Abstract INTRODUCTION While cardiac comorbidities or factors predisposing infection are common in patients with ESRD, one less common cause for pleural effusion in peritoneal dialysis (PD) patients is pleuroperitoneal communication. We present herein a case of a PD patient with large, right-sided pleural effusion one year after starting PD. CASE REPORT An 82-year-old female with ESRD managed on home continuous cycling peritoneal dialysis (CCPD) for 1 year presented to the Emergency Department (ED) with new-onset dyspnea. She recently completed a course of vancomycin for bacterial peritonitis secondary to PD catheter infection. She also reported that her home CCPD machine was not draining the fill amount in recent weeks. She was afebrile and hemodynamically stable on arrival. CT at the ED showed a large, right-sided pleural effusion. She underwent thoracentesis with pending fluid analysis, and experienced subsequent improvement in her dyspnea. She was then hospitalized and wished to continue PD over pursuing intermittent hemodialysis (iHD) while workup was pending, despite clinical suspicion for pleuroperitoneal fistula (PPF). She started inpatient CCPD, and drains following each dwell showed less than expected volumes with no additional output on manual drains. She reported worsening dyspnea the next morning, and bedside POCUS confirmed reaccumulation of her pleural effusion. Fluid analysis revealed a transudative pleural fluid profile, with pleural glucose of 583mg/dL and serum glucose of 80mg/dL. Given her recent peritonitis, suspicion was greatest for PPF. The patient was transitioned from PD to iHD to allow time for the suspected fistula to heal, and subsequent imaging obtained during her hospitalization did not show reaccumulation of her unilateral pleural effusion. DISCUSSION Pleuroperitoneal communication may occur due to congenital or acquired diaphagmatic defects, or insults such as the case in our patient with recent peritonitis. In fact, diaphragmatic blebs from age related degeneration and chronic increased intraabdominal pressure have been reported to cause hydrothorax in patients undergoing PD. Diagnosis of PD-associated pleural effusions is based on clinical suspicion, with pleural studies showing high pleural fluid to serum glucose gradient, and imaging commonly showing unilateral right-sided pleural effusions. Recent peritoneal dialysis with low drainage further supports PD as the etiology. Most cases of PD-associated pleural effusions occur soon after PD initiation, but cases occurring years after initiation have been reported. Management involves halting PD and thoracentesis for symptomatic relief. Patients may need transitioning to iHD indefinitely, or may resume PD after a pause if the cause of communication is reversible.

Abstract Food allergy reactions emerging after organ transplantation, particularly following lung transplantation, are uncommon but pose significant clinical challenges. While most documented cases have involved liver transplants and pediatric patients, instances in lung transplant recipients remain rare. Here, we present a case of acute bronchospasm triggered by hummus ingestion, requiring mechanical ventilation in a post-lung transplant patient. This case underscores the need for heightened awareness of potential allergenic reactions in transplant recipients and emphasizes the importance of prompt recognition and management of such reactions in the critical care setting. A 61 year old female experienced an acute respiratory event requiring emergent intubation shortly after ingesting hummus. Initial treatment included duonebs and bronchoscopy, revealing a normal airway architecture but notably stiff lungs. She responded to epinephrine administration. Post-event serum tryptase was within normal limits, suggesting the reaction was primarily respiratory in nature. Despite having a known peanut allergy in her organ donor, her own history was negative for peanut IgE reactivity. Subsequently, she underwent extensive blood IgE testing, confirming negative IgE to peanut, yet yielding positive or equivocal results to chickpea and sesame. Skin testing was positive for “Sabra Snack Hummus,” suggesting reactivity. Prick-to-prick skin testing with chickpea, however, was negative. Additionally, IgE component testing identified Ara h2, a peanut protein with potential cross-reactivity to other legumes, including chickpeas. Managing peanut allergy in post-transplant patients requires careful consideration to prevent severe allergic reactions. Screening is crucial when a donor has a known food allergy, as this can help identify potential allergic responses due to transferred donor immune cells. If a peanut allergy arises post-transplant, strict avoidance of peanuts and cross-reactive allergens, such as certain nuts and legumes, is advised. Transplant recipients with confirmed peanut allergies should carry an epinephrine auto-injector to immediately treat potential anaphylaxis. The pathophysiology of post-transplant food allergies remains under investigation. One theory suggests that donor-derived B lymphocytes producing peanut-specific IgE may enter the recipient's circulation, leading to sensitization. Alternatively, IgE-sensitized mast cells and basophils within the transplanted tissue may react directly in the recipient's lungs or lymph nodes. Another possibility is IgE already attached to mast cells in the bronchial mucosa or lung tissue, heightening allergic reactivity. The safest management includes avoiding all nuts, chickpeas, and sesame seeds, with an epinephrine auto-injector for emergency use. This case underscores the importance of monitoring for food allergies in transplant recipients, especially when the donor has a history of allergies.

Abstract Introduction: Dyspnea is a common and debilitating symptom in chronic obstructive pulmonary disease (COPD) that significantly impacts quality of life. While often attributed to cardiopulmonary causes, other factors such as neuromuscular, psychogenic, or medication-related issues should also be considered. In older adults, polypharmacy, comorbid conditions, and age-related physiological changes can complicate evaluation. A comprehensive geriatric approach, which includes medication review and functional status assessment, is helpful in evaluating persistent dyspnea. Here, we present a case of an older adult with dyspnea thought to be due to extrapyramidal symptoms (EPS) related to antipsychotic use. Case Description: A 75-year-old male with a history of bipolar disorder, diastolic heart failure, 15-pack-year smoking history, and recently diagnosed with COPD presented with persistent dyspnea on exertion. His symptoms began after initiating lurasidone for bipolar disorder. Along with dyspnea, he developed involuntary movements, including sniffing, facial grimacing, cheek sucking, and tremors. Discontinuation of lurasidone resolved the tremors and cheek sucking, but sniffing and grimacing persisted. Pulmonary workup, including high-resolution chest CT and pulmonary function testing, showed mild emphysematous changes, borderline obstruction with significant bronchodilator response, and normal diffusion capacity. A comprehensive cardiac evaluation, including myocardial perfusion stress testing and echocardiogram, revealed no cardiac cause. Despite pulmonary rehabilitation and inhaler therapy, symptoms persisted. Ultimately, he was evaluated by a neurologist and geriatrician. He reported significant decline in engagement in previously enjoyable activities due to his symptoms. During examination, frequent sniffing tics were observed. His dyspnea was thought to be caused by involuntary respiratory muscle movements resulting from extrapyramidal symptoms (EPS) induced by lurasidone, which can persist even after the medication discontinuation. Tetrabenazine, commonly used to manage EPS in antipsychotic-treated patients, was considered but ruled out due to its potential side effects in older adults, including orthostasis, sedation, and depression. Given the patient's previous adverse medication reactions, he was particularly concerned about avoiding further side effects. Therefore, he was prescribed low-dose guanfacine, a medication used to treat tic disorders with a lower risk of side effects. After one month, he reported improvement in his sensation of dyspnea. Discussion: This case highlights the importance of a geriatric approach when evaluating unexplained dyspnea in older adults. Polypharmacy and medication side effects, such as EPS, can mimic or exacerbate respiratory symptoms. The American Geriatrics Society's “5 M's” framework—mind, mobility, medications, multi-complexity, and matters most—helps guide management in this complex patient population.

Abstract Introduction: Cystic fibrosis (CF) is a genetic disorder characterized by defective chloride ion transport, leading to thick mucus production, chronic respiratory infections, and other multisystem involvement. Although CF is often diagnosed in childhood, the condition can be missed or misdiagnosed in adults. Description of Case: We present the case of a 60-year-old male from India who was diagnosed with CF after a prolonged period of sinopulmonary symptoms. He initially presented in 2014. His medical history was pertinent for asthma, and multiple episodes of clinically and radiographically confirmed pneumonia and polypoid sinusitis requiring IV antibiotics and sinus surgery. He carried a prior diagnosis of allergic bronchopulmonary aspergillosis treated with itraconazole and steroids, as well as elevated IgE levels. His CT chest was notable for extensive bronchiectasis, bronchial wall thickening, and mucus plugging of both lungs. He had no known family history of CF. Sweat chloride testing was in the intermediate range (44, 47 mmol/L; normal <30 mmol/L, intermediate 30 to 59 mmol/L, abnormal >59 mmol/L). Given high suspicion for CF, cystic fibrosis transmembrane conductance regulator (CFTR) full gene analysis was pursued. Sequence analysis and multiplex ligation-dependent probe amplification of the CFTR gene detected heterozygous sequence changes c.1717-2A>T, classified as likely deleterious, and c.1367T>C (p.V456A), variant of uncertain significance. He was thus initially diagnosed as a CF carrier. He re-presented in 2024 with decline in pulmonary function testing and continued sinopulmonary infections. Genetic testing results from 2014 were re-analyzed. Between initial presentation and present, his V456A variant was upgraded to pathogenic. He met diagnostic criteria for CF with two pathogenic CFTR variants, a repeated intermediate sweat chloride (47 mmol/L) suggestive of CFTR protein dysfunction, and disease that could be attributed to CFTR dysfunction. He subsequently started TRIKAFTA® (elexacaftor/tezacaftor/ivacaftor and ivacaftor) and airway clearance therapy. Discussion: The diagnosis of CF in adults can be challenging, particularly in individuals without a known family history, intermediate sweat chloride testing, and with inconclusive genetic testing. Our understanding of CF in Asian populations is limited. CF is suspected to be underreported in patients with Southeast Asian ancestry in part due to genetic heterogeneity. The interpretation of certain genetic variants can evolve over time. A variant of unknown significance may later be reclassified as pathogenic, revealing its true role in disease development. This highlights the critical importance of regularly re-evaluating genetic test results.

Abstract Introduction: Cystic Fibrosis (CF) is traditionally diagnosed through elevated sweat chloride levels followed by genetic testing. However, depending on types of specific CFTR gene mutations, sweat chloride test may not always be conclusive. This case study presents a unique instance of CF in a 50-year-old patient with negative sweat chloride levels who was later found to have CFTR dysfunction during the evaluation for worsening bronchiectasis, highlighting the diagnostic challenges posed by atypical presentations. Description: A 50-year-old female with a long-standing history of bronchiectasis and recurrent exacerbations was evaluated at our clinic. Initial sweat chloride testing yielded negative results (21 and 28 on two separate occasions), which made a CF diagnosis very unlikely. She was subsequently treated with standard airway hygiene measures while alternative diagnoses were explored. However, despite thorough work-up and management, her bronchiectasis continued to worsen, leading to genetic testing to complete the comprehensive evaluation of her condition. The CFTR mutation panel revealed the presence of G551D and D1152H (variants known to be associated with normal sweat chloride test). Despite the negative sweat chloride test, the patient's clinical presentation, including bronchiectasis, recurrent exacerbations, and the identified CFTR mutations, supported a diagnosis of CF. The patient has since responded positively to combination therapy with Elexacaftor, Tezacaftor and Ivacaftor, which is indicated for her genotype. Discussion: This case underscores the limitations of relying solely on sweat chloride testing for diagnosing CF, particularly in patients with atypical CFTR mutations. Variants like D1152H have been reported with normal sweat chloride levels, challenging traditional diagnostic paradigms. Genetic testing plays a crucial role in these cases by identifying mutations that may still lead to significant CFTR dysfunction. The patient's improvement on CFTR modulator therapy further supports the role of genotype-driven treatment strategies in CF care. This case highlights the need for a broader diagnostic approach, including comprehensive genetic testing and clinical correlation, especially for patients presenting with non-classical CF features. It contributes to the growing understanding that CF is a spectrum disorder with varied clinical and biochemical presentations, emphasizing the importance of individualized diagnosis and treatment strategies to optimize patient outcomes.

Abstract Rational: Talc pleurodesis is an effective intervention for preventing recurrent pleural effusions and pneumothoraces, particularly in non-surgical candidates. Due to its efficacy and safety, it is recommended as the most effective sclerosant for pleurodesis. However, in some cases, the initial pleurodesis fails, necessitating a repeat procedure. The efficacy of repeat talc pleurodesis after an initial failure is an area that requires further exploration. This study explores the safety and efficacy of repeat talc pleurodesis among patients who did not respond to the initial intervention. Methods: This retrospective study analyzed hospitalized patients who underwent 4g talc slurry pleurodesis from 2019 to 2024, focusing on demographics, comorbidities, initial pleurodesis failure, and recurrence rates. Pleurodesis failure was identified by lung sliding, recurrent effusion, or pneumothorax during the same hospitalization. The primary outcome was recurrence post-discharge, assessed by pleural effusion or pneumothorax within 180 days post-repeat pleurodesis. Results: This study included 94 patients (52.1% male, 47.9% female) with a mean age of 67.6. Among them, 79 (84%) received a single 4g dose of talc, while 15 (16%) received multiple 4g talc doses for initial pleurodesis. Recurrence occurred in 20 (25.3%) of the single-dose group and 1 (6.7%) of the multiple-dose group within 180 days, though the difference was not statistically significant (p=0.112). Recurrence-free rates were 93.6% at 30 days, 85.1% at 90 days, and 77.7% at 180 days. Of the 20 patients with recurrence after a single 4g dose of talc, 8 (40%) underwent repeat pleurodesis, with only one recurrence requiring surgical intervention. Additionally, there was no recurrence after repeat talc pleurodesis in the one patient with recurrence after receiving multiple 4g talc doses for initial pleurodesis. No associations were found between recurrence rates and factors like gender (p=0.213) or comorbidities (emphysema, COPD, lung malignancy). Chest pain was a common complaint, but no cases of respiratory distress were reported post-pleurodesis. Conclusion: The efficacy of initial talc pleurodesis (77.7%-93.6%) in this cohort aligns with existing literature. Multiple-dose talc pleurodesis effectively prevented recurrence in 93.3% of patients, with no reported respiratory distress. Additionally, repeat talc pleurodesis was successful in 87.5% of those with recurrence after an initial single 4g dose. These findings support multiple-dose talc pleurodesis and repeat talc pleurodesis as safe and effective options for preventing recurrence post-initial failure and post-repeat talc pleurodesis, respectively. Although no significant recurrence predictors were identified, future research could focus on patient-specific factors to enhance treatment selection and optimize outcomes.

Abstract Introduction: Chronic obstructive pulmonary disease (COPD) represents a significant global health challenge, particularly in its moderate to severe cases, where effective management is crucial to improving patient outcomes. The integration of inhaled corticosteroids with long-acting β2-adrenoceptor agonists and long-acting muscarinic antagonists in fixed-dose combinations has emerged as a cornerstone of therapy. This study evaluates the efficacy of two triple therapy regimens — Glycopyrrolate, Budesonide, and Formoterol Fumarate (GLY/BUD/FOR) and Fluticasone Furoate, Vilanterol, and Umeclidinium (FF/VI/UMEC) —in adults aged 45 and older with diagnosed COPD with FEV1/FVC < 70% to assess the impact of these regimens on the preventing COPD exacerbations and acute hypoxemic respiratory failure. Methods: A retrospective cohort analysis was conducted using the TriNetX database. Patients with moderate to severe COPD and FEV1/FVC < 70% were identified based on ICD codes, and two cohorts were formed based on the prescribed inhaler therapy: GLY/BUD/FOR and FF/VI/UMEC. Patients with comorbid asthma, heart failure, or pneumonia were excluded. A 1:1 propensity-score matching (PSM) analysis was performed to balance covariates such as age, gender, smoking status, and baseline lung function to minimize confounding and bias. Post-matching, both had 16,052 patients. Ultimately, 23,331 patients (FF/VI/UMEC: 11,234, GLY/BUD/FOR: 12,097) with a mean age of 67.4 ± 10.1 years and 55.3% males were included. Results: Among groups, 10.4% of patients on FF/VI/UMEC experienced COPD exacerbations compared to 6.7% on GLY/BUD/FOR (Risk Ratio: 1.55, 95% CI: 1.42-1.69, p < 0.001). Kaplan-Meier analysis showed a lower survival probability in the FF/VI/UMEC group (77.7% vs. 83.9%, p < 0.001). For acute respiratory failure, 3.5% of patients on FF/VI/UMEC experienced this outcome compared to 2.8% on GLY/BUD/FOR (Risk Ratio: 1.28, 95% CI: 1.12-1.45, p = 0.003). Conclusion: Our study suggests that FF/VI/UMEC demonstrated an increased risk of COPD exacerbations and acute hypoxic respiratory failure compared to the group receiving GLY/BUD/FOR. This indicates that GLY/BUD/FOR may provide enhanced protective benefits in patients with moderate to severe COPD, improving disease management and minimizing healthcare resource utilization. Further studies are warranted to explore the long-term benefits and potential mechanisms underlying the observed differences.

Abstract Introduction: Differentiation syndrome (DS) is a life-threatening adverse drug reaction caused by differentiating agents, including all-trans retinoic acid, arsenic trioxide, inhibitors of mutant isocitrate dehydrogenase (e.g., enasidenib), and the FLT3 inhibitor gilteritinib. The proliferation of differentiated leukemic cells can alter cytokine balance, leading to tissue inflammation, but the pathogenesis remains incompletely understood. We present a case of severe DS in a patient with AML and multi-organ failure. Case: An 80-year-old female with a history of polycythemia vera and newly diagnosed AML, on decitabine, venetoclax, and enasidenib. She was admitted after her first treatment cycle with weakness, altered mental status, and neutropenic fever. Enasidenib was discontinued due to suspected DS, and she was treated with dexamethasone for five days. Three days after discontinuing steroids, her respiratory and mental status deteriorated, leading to a rapid response call and transfer to the ICU for acute hypoxemic respiratory failure. Point of care ultrasound revealed underfilled ventricles and collapsible IVC on inhalation. She became hypotensive and unresponsive, requiring intubation. Initial P/F was 72. PV tool with recruitment showed no low inflexion point but recruitable lung. Laboratory results revealed a WBC of 68.7 x 10⁹/L with 89% blasts which was increased from prior days and acute liver injury with hyperbilirubinemia. A CT scan revealed bilateral consolidations and pleural effusions with interlobular septal thickening. Despite initial oxygenation improvement with prone positioning, she remained hypotensive requiring norepinephrine, vasopressin, angiotensin II, and hydrocortisone. Methylene blue was administered with a favorable response. Leukocytosis worsened, and decitabine and hydroxyurea were initiated due to concern for uncontrolled acute leukemia. She was started on continuous renal replacement therapy (CRRT) for oliguric renal failure. After the fourth dose of decitabine, her shock resolved, urinary output improved, and leukocytosis decreased. However, in the following days, her oxygen requirements escalated, WBC again increased to 120 x 10⁹/L with 80% blasts, and she became hypotensive with signs of myocardial ischemia. She was ultimately transitioned to comfort care. Discussion: This case highlights severe DS following enasidenib administration, which progressed to multi-organ failure. Prompt initiation of systemic glucocorticoids is critical in the management of DS, and this condition should be considered in patients receiving active treatment for acute leukemia who require ICU-level care. Risk factors for DS development and the role of prophylaxis remain areas requiring further research in the context of acute leukemia treatment.

Abstract Background The emergence of immune checkpoint inhibitors (ICI) has changed the landscape of cancer treatment; however, they can cause a variety of side effects. One serious complication is Triple M syndrome, which is a triad of ICI toxicities including myositis, myocarditis, and myasthenia gravis. Little literature regarding pathophysiology and guideline directed treatment exists, but case reports estimate a significant mortality rate of 60%. ICIs that have been recognized are pembrolizumab, nivolumab, and avelumab and ICI use in combination increases the risk of the syndrome. Current treatment regimens consist of steroids, immune modulators, and pyridostigmine. Ultimately, the syndrome requires rapid recognition and treatment to reduce mortality outcomes. Patient Case A 62 y.o. male with metastatic hepatocellular on atezolizumab/bevacizumab presented with a couple day history of progressive proximal upper and lower extremity weakness, mild dysarthria and dysphonia and shortness of breath. His head imaging was negative for acute stroke, but work-up revealed an AST of 1600, ALT of 500, total bilirubin of 9.1 and a CK of 9000. Troponin was also elevated at 273. There was immediate concern for Triple M syndrome given clinical and laboratory evidence of myositis and myocarditis. Therefore, the patient was transferred to the ICU and started on high-dose steroids. Myositis was confirmed via EMG and MRI of the left thigh showing intramuscular inflammation. EMG didn't show evidence of neuromuscular junction abnormalities and myasthenia antibodies were negative. Regarding myocarditis, with troponin elevation, TTE showed a hyperdynamic left ventricle and cardiac MRI displayed focal enhancement of the inferior septum consistent with mild myocarditis. Given worsening liver function and clinical status, IVIG was initiated. Unfortunately, the patient continued to decline and ultimately passed away after transitioning to comfort care.Discussion While this case did not clearly present a diagnosis of Triple M syndrome, two of the three triad were present, and the patient also had evidence of hepatitis, which has been seen with the syndrome. As seen in this case, there is a significant mortality rate, which emphasizes the importance to increase the awareness of Triple M syndrome in patients on ICIs. It also highlights our gap in knowledge regarding pathophysiology, standard diagnostic criteria and targeted treatments. Further research to understand which diagnostic markers are most sensitive and specific would help with early recognition but also inform treatment options. Mortality in Triple M remains high but with further understanding we may be able to counter this severe ICI toxicity.

Abstract Background Intracranial hypertension from cerebral edema is a feared complication in patients with acute liver failure. Diagnosing cerebral edema in critically ill patients can be challenging as it may be insidious in onset. We present a case of fulminant hyperammonemia-induced cerebral edema in a patient with newly diagnosed alpha-1-antitrypsin deficiency (A1AD) in the setting of intestinal ileus and ineffective lactulose therapy. Case A 48-year-old male with newly diagnosed A1AD-related cirrhosis, alcohol use, and obesity (BMI 48.9) presented at an outside facility with altered mental status. Physical exam showed waxing and waning mentation, and serum ammonia was 245 mcmol/L. Upon transfer to our facility, hemoglobin was 10.3 g/dL, creatinine 1.77 mg/dL, total bilirubin 1.5 mg/dL, INR 1.2, ALT 60 U/L, AST 107 U/L, ALP 173 U/L, and serum ammonia 138 mcmol/L. Serum alpha-1-antitrypsin returned at 41 mg/dL with SZ phenotype. Abdominal ultrasound showed cirrhosis with moderate ascites. Paracentesis demonstrated no acute peritonitis. After initiation of lactulose and rifaximin, his mental status improved initially. However, he experienced 2 episodes of coffee-ground emesis with hemoglobin dropping to 7.0 g/dL requiring blood transfusions. Urgent esophagogastroduodenoscopy, limited by large residual contents, found no active bleed. A nasogastric tube was placed. CT abdomen pelvis showed diffuse colonic and small bowel dilation consistent with adynamic ileus impairing lactulose administration. His mental status worsened, necessitating ICU transfer and intubation for airway protection. Serum ammonia peaked at 397 mcmol/L. Neostigmine did not restore any effective bowel movement, and continuous renal replacement therapy was initiated to control the hyperammonemia. A convulsive episode prompted imaging. Head CT showed diffuse cerebral edema, later confirmed on MRI (Figure 1). Continuous electroencephalogram showed diffuse slowing without epileptiform discharges. His protracted hospital course was marked by minimal neurological recovery requiring tracheostomy and ongoing supportive measures per family wishes. Discussion Cerebral edema is one of the leading causes of morbidity and mortality in patients with severe hyperammonemia, which can result in irreversible cortical and deep grey matter injury that typically spares perirolandic and medial occipital regions. Although the exact mechanism continues to be researched elevated serum ammonia plays a critical role in disrupting the innate cerebral autoregulation. Prompt diagnosis and early intracranial pressure control (head of the bed elevation, hyperventilation, mannitol, hypertonic saline) are paramount. Typical hyperammonemia treatment includes lactulose, rifaximin, or polyethylene glycol, and correction of any precipitating factors. Dialysis should be considered early to prevent cerebral toxicity in hyperammonemia refractory to conventional treatments.