Acute Eosinophilic Pneumonia Induced by Immune Checkpoint Inhibitor and Anti-TIGIT Therapy.

BACKGROUND Immune checkpoint inhibitors (ICIs) have been linked to various immune-related adverse events, including pneumonitis, necessitating early recognition and potential treatment discontinuation. Acute eosinophilic pneumonia (AEP) induced by ICIs, particularly with no reported cases involving anti-TIGIT therapy, is rare. This report describes a case of AEP following treatment with pembrolizumab and anti-TIGIT therapy. CASE REPORT A 46-year-old woman with lung adenoid cystic carcinoma and chronic hypoxemic respiratory failure on long-term oxygen therapy presented with fever, cough, and shortness of breath. She underwent left pneumonectomy and radiation therapy at diagnosis 9 years earlier. She was participating in a clinical trial using pembrolizumab and anti-TIGIT EOS-448, due to cancer progression. After starting therapy, she developed stable peripheral eosinophilia and a skin rash, suggestive of a drug reaction. On admission, she was in acute-on-chronic hypoxemic respiratory failure, febrile, with an elevated eosinophil count and new multifocal infiltrates in the right lung. Despite broad antibiotics coverage for pneumonia, she developed worsening respiratory symptoms and eosinophilia. She was then empirically started on intravenous methylprednisolone for acute eosinophilic pneumonia without confirmatory bronchoscopy as she was at high risk with her previous pneumonectomy. She subsequently had rapid improvement in her symptoms. CONCLUSIONS AEP should be considered in patients treated with ICIs who develop immune-related adverse effects. Although bronchoscopy findings are part of AEP's diagnostic criteria, this case underscores the importance of clinical judgment in the prompt initiation of steroids, even without confirmatory bronchoscopy, in rapidly progressing cases. The role of anti-TIGIT therapy in this context remains uncertain.

Capecitabine-induced-coronary-vasospasm leading to polymorphic ventricular tachycardia and cardiac arrest.

Capecitabine, a pro-drug of 5-fluorouracil, is commonly used in the treatment of breast and colorectal cancer. Its side effects, including nausea, vomiting, diarrhea, fatigue, loss of appetite, and bone marrow suppression, are well recognized. However, coronary vasospasm represents a less commonly recognized but significant complication of fluoropyrimidine-based therapies such as capecitabine. Proposed mechanisms for this adverse effect complication include direct endothelium-independent vasoconstriction, activation of protein kinase C, and activation of the cyclooxygenase pathway. In this report, we present a case of capecitabine-induced coronary vasospasm leading to progressive, focal ST-elevations, myocardial ischemia, and subsequently polymorphic ventricular tachycardia. These events were captured on telemetry, in a male in his early 40s, diagnosed with stage IIIB sigmoid colon cancer. Notably, the patient had no pre-existing coronary artery disease or other cardiovascular risk factors. Upon diagnosis, the patient was initiated on a calcium channel blocker, verapamil, to mitigate further coronary vasospasm events. After thorough discussions that prioritized the patient's input and values, an implantable cardioverter-defibrillator was placed subcutaneously. Following discharge, the patient restarted capecitabine therapy along with verapamil prophylaxis and did not experience any subsequent shocks from his ICD as assessed during his outpatient follow-up visits. This case emphasizes the need to involve patients in decision-making processes, especially when managing unexpected and serious complications, to ensure treatments align with their quality of life and personal preferences.

Methylprednisolone and 60 Days in Hospital Survival in Coronavirus Disease 2019 Pneumonia.

OBJECTIVES: To determine methylprednisolone's dose, duration, and administration from onset of symptoms and association with 60 days in hospital survival of coronavirus disease 2019 pneumonia. DESIGN: Cohort study. SETTING: Thirteen hospitals in New Jersey, United States during March to June 2020. PATIENTS: Seven-hundred fifty-nine hospitalized coronavirus disease 2019 patients. INTERVENTIONS: We performed a propensity matched cohort study between patients who received methylprednisolone and no methylprednisolone. Patients in the methylprednisolone group were further differentiated into dose (high dose and low dose), duration, and administration from onset of symptoms. MEASUREMENTS AND MAIN RESULTS: In the propensity matched sample, 99 out of 380 (26%) in no methylprednisolone, 69 out of 215 (31.9%) in low-dose methylprednisolone, and 74 out of 164 (55.2%) high-dose methylprednisolone expired. Overall median survival for no methylprednisolone (25.0 d), low-dose methylprednisolone (39.0 d), high-dose methylprednisolone (20.0 d), less than or equal to 7 days duration (19.0 d), 7-14 days duration (30.0 d), greater than 14 days duration (44.0 d), onset of symptoms less than or equal to 7 days (20.0 d), and onset of symptoms 7-14 days (27.0 d) were statistically significant (log-rank p ≤ 0.001). Multivariate Cox regression showed nursing home residents, coronary artery disease, and invasive mechanical ventilation were independently associated with mortality. Methylprednisolone was associated with reduced mortality compared with no methylprednisolone (hazard ratio, 0.40; 95% CI, 0.27-0.59; p < 0.001) but no added benefit with high dose. Low-dose methylprednisolone for 7-14 days was associated with reduced mortality compared with less than or equal to 7 days (hazard ratio, 0.45; 95% CI, 0.22-0.91; p = 0.0273), and no additional benefit if greater than 14 days (hazard ratio, 1.27; 95% CI, 0.60-2.69; p = 0.5434). Combination therapy with tocilizumab was associated with reduced mortality over monotherapy (p < 0.0116). CONCLUSIONS: Low-dose methylprednisolone was associated with reduced mortality if given greater than 7 days from onset of symptoms, and no additional benefit greater than 14 days. High dose was associated with higher mortality.

Clinical and laboratory evaluation of patients with SARS-CoV-2 pneumonia treated with high-titer convalescent plasma.

Here, we report on a phase IIa study to determine the intubation rate, survival, viral clearance, and development of endogenous Abs in patients with COVID-19 pneumonia treated with convalescent plasma (CCP) containing high levels of neutralizing anti-SARS-CoV-2 Abs. Radiographic and laboratory evaluation confirmed all 51 treated patients had COVID-19 pneumonia. Fresh or frozen CCP from donors with high titers of neutralizing Abs was administered. The nonmechanically ventilated patients (n = 36) had an intubation rate of 13.9% and a 30-day survival rate of 88.9%, and the overall survival rate for a comparative group based on network data was 72.5% (1625/2241). Patients had negative nasopharyngeal swab rates of 43.8% and 73.0% on days 10 and 30, respectively. Patients mechanically ventilated had a day-30 mortality rate of 46.7%; the mortality rate for a comparative group based on network data was 71.0% (369/520). All evaluable patients were found to have neutralizing Abs on day 3 (n = 47), and all but 1 patient had Abs on days 30 and 60. The only adverse event was a mild rash. In this study on patients with COVID-19 disease, we show therapeutic use of CCP was safe and conferred transfer of Abs, while preserving endogenous immune response.

Use of Anti-Interleukin-6 Receptor Monoclonal Antibody in Drug-Induced Acute Respiratory Distress Syndrome.

Acute respiratory distress syndrome (ARDS) is a disorder that involves the activation of alveolar macrophages triggering the innate immune system. The parenchymal lung injury seen in ARDS is a result of many proinflammatory elevations including interleukin-6. There remains no effective standard of care of ARDS, and current treatments at this time currently do not target the immunological mechanisms or pathways involved. Treatments involving this pathway should be further investigated as targeted treatment. We discuss a case of a patient with multiple myeloma who was hospitalized with drug-induced ARDS who had a rapid response to an anti-interleukin-6 monoclonal antibody.

Bronchial-oesophageal fistula: a rare initial presentation of squamous cell carcinoma of the lung.

A 61-year-old Caucasian man with hypertension and hepatitis C presented to the emergency department with 7 days of productive cough and low-grade fevers despite outpatient therapy with oral azithromycin. On initial evaluation, he was lethargic with peripheral cyanosis and oxygen saturation in the low 70 s on room air, necessitating endotracheal intubation. Chest imaging revealed diffuse bilateral infiltrates compatible with the diagnosis of acute respiratory distress syndrome. Patient subsequently developed profound hypoxaemia and on day 2 of admission, veno-veno extracorporeal membrane oxygenation (ECMO) was initiated. Bronchoscopy revealed a necrotic ulcer on the posterior wall of the left mainstem bronchus, compatible with a bronchial-oesophageal fistula, which was later confirmed by endoscopy, and stented. Histology revealed poorly differentiated squamous cell carcinoma of the lung. Despite stenting of the fistula and ECMO support, the patient expired 5 days after admission.