Azar, Jehad

Abstract Autoinflammatory syndromes are increasingly recognized as heterogeneous disorders of innate immune dysregulation, often overlapping in clinical and genetic features. Although pulmonary manifestations are uncommon, several autoinflammatory conditions such as VEXAS syndrome, juvenile rheumatoid arthritis, adult-onset Still’s disease, and Familial Mediterranean Fever can produce inflammatory pulmonary nodules that mimic metastatic malignancy. Recognition of these presentations is critical, as they can respond dramatically to immunosuppressive therapy once the correct diagnosis is established. We describe a diagnostically challenging case of a young adult male initially suspected to have metastatic lung cancer, whose evaluation ultimately suggested a previously uncharacterized autoinflammatory process. We present a 26-year-old previously healthy male with progressive dry cough, exertional dyspnea, diffuse myalgias, small joint arthritis involving the fingers, wrists, and ankles, tendonitis, a Gottron-like rash on the hands and lower extremities, low-grade fevers, and occasional bloody stools. Initial external workup revealed a right infrahilar mass, right lower lobe pleural thickening, small pleural effusion, and mediastinal and hilar lymphadenopathy on CT chest, with corresponding PET activity. Initially suspected to have metastatic lung cancer, he was informed his prognosis was poor. However, transbronchial, EBUS, and mediastinal lymph node biopsies showed only active inflammation without malignancy. On presentation to our facility, a broad differential was pursued, with suspicion for an autoinflammatory or autoimmune etiology. Pulmonary function testing was normal. Laboratory evaluation revealed ESR >100, elevated CRP, positive ANA (1:160), negative HLA-B27, normal ferritin, and negative S100 staining. Cytokine analysis showed elevated TNF, IL-6, MCP-1, IL-2, and IL-18. Targeted variant testing identified a UBA1 gene variant, c.123G>T p.(M41L), with low-level mosaicism (0.004%), and a heterozygous MEFV mutation. Although his ethnicity made Familial Mediterranean Fever unlikely, these findings raised the possibility of overlapping somatic and germline contributions to innate immune activation. He was treated empirically with immunosuppression for a presumed multisystem inflammatory disorder, resulting in resolution of symptoms and marked radiologic improvement. This case highlights the expanding spectrum of adult-onset autoinflammatory diseases that may present with pulmonary findings mimicking malignancy. The coexistence of low-level UBA1 mosaicism and MEFV mutation suggests a potential interaction between somatic and inherited variants in triggering inflammation. Similar to the recent discovery of VEXAS syndrome, this case may represent a novel subtype of autoinflammatory disease. Continued genomic and immunologic investigation is warranted, as timely recognition and immunosuppressive therapy can lead to dramatic recovery. This abstract is funded by: None

Abstract Introduction Drug-induced pneumonitis is an important mimic of disseminated infection in immunocompromised hosts. Lenalidomide, an immunomodulatory agent widely used in multiple myeloma, has been associated with organizing and eosinophilic pneumonitis, and occasionally sarcoid-like granulomatous inflammation. The coexistence of acute fibrinous injury and granulomatous inflammation is exceptionally rare. We present a case of lenalidomide-associated acute fibrinous and granulomatous pneumonitis presenting with a miliary pattern following autologous stem cell transplant. Case Presentation A 44-year-old woman with kappa light-chain multiple myeloma, chronic kidney disease stage V, presented with 10 days of fever (to 105 °F), dry cough, hemoptysis, dyspnea and hypoxia requiring high flow oxygen. She had been on maintenance therapy with lenalidomide, daratumumab, and weekly dexamethasone after undergoing an autologous stem cell transplant for multiple myeloma, last administered one week before symptom onset.. CT chest (Figure 1-1) showed innumerable randomly distributed micronodules with ground-glass opacities and septal thickening, suggesting disseminated infection. Laboratory results revealed eosinophilia (950/µL), neutropenia, and profound hypogammaglobulinemia. Empiric piperacillin-tazobactam, doxycycline, and fluconazole were started for possible bacterial and/or fungal infection (history of positive Coccidioides IgM). Two bronchoscopies demonstrated multifocal hypervascular airway lesions. BAL differential showed 15 % eosinophils and > 30 % lymphocytes; cultures, Fungitell, and comprehensive testing for bacterial, fungal, mycobacterial, viral, and parasitic pathogens were negative. Cryobiopsy revealed acute fibrinous and granulomatous pneumonitis with negative GMS and acid-fast stains. Following withdrawal of lenalidomide and daratumumab, the patient’s symptoms and CT findings improved without further antimicrobial therapy within the same hospitalization (Figure 1-2). She received an 8-week prednisone taper with inhaled pentamidine prophylaxis. Follow-up CT showed complete clinical and radiographic resolution (Figure 1-3), confirming a grade 3 drug-induced pneumonitis. A bronchoscopy will be repeated to assess the endobronchial vascular lesions. Discussion Lenalidomide related lung injury typically manifests as organizing or eosinophilic pneumonitis. The presence of both fibrinous and granulomatous inflammation suggests a mixed hypersensitivity and immune-complex reaction possibly potentiated by immune reconstitution after autologous transplant. The miliary pattern and BAL eosinophilia closely mimic disseminated fungal or mycobacterial infection. A Naranjo Adverse Drug Reaction Probability Scale score of 7 supported a highly probable causal relationship. Awareness of this pattern is essential, as prompt drug cessation and corticosteroid therapy are curative and prevent progression to fibrotic lung injury. This abstract is funded by: None

ABSTRACT Patients with chronic thromboembolic pulmonary disease (CTEPD) without resting pulmonary hypertension (PH) frequently experience dyspnea which is not explained by stationary assessment and therefore requires cardiopulmonary exercise testing for further diagnostic insight. Ventilatory inefficiency in CTEPD is commonly identified; however, consensus definitions are lacking. Upright iCPET and careful definition of ventilatory inefficiency (i.e., lack of reduction in VD/VT with exercise) may allow optimal characterization of patients with chronic thromboembolic disease and specifically helps correctly identify patients with preload insufficiency who may otherwise be misclassified or undiagnosed.

ABSTRACTHepatopulmonary syndrome (HPS) poses a significant challenge in liver transplant recipients, mostly resulting in persistent hypoxaemia postoperatively. We present the case of a 59‐year‐old male with decompensated metabolic dysfunction associated with steatohepatitis (MASH) cirrhosis, who had liver transplantation due to end‐stage liver disease complicated by HPS‐related hypoxaemia. Despite successful transplantation, the patient continued to experience severe hypoxaemia, requiring high supplemental oxygen despite maximal conservative treatment per guidelines. Potential causes for hypoxaemia post‐liver transplant have been excluded; HPS as the sole cause of hypoxaemia was proved with a repeat shunt study, which estimated the shunt at 59%. Treatment with inhaled Treprostinil led to a remarkable improvement in oxygenation, facilitating the successful weaning of oxygen supplementation. The patient's hypoxaemia improved to full recovery upon discharge. This case highlights the persistence of hypoxaemia post‐liver transplantation in HPS patients and underscores the potential role of inhaled Treprostinil as a novel therapeutic approach to address this complication.

OBJECTIVE Chronic subdural hematoma (CSDH) is a prevalent neurosurgical condition, particularly among the elderly. Various treatment options exist, but recurrence rates remain high. This systematic review and meta-analysis aims to assess the efficacy and safety of tranexamic acid (TXA) in the management of CSDH. METHODS The authors conducted a comprehensive literature search adhering to the 2020 PRISMA guidelines, involving three primary databases (Scopus, PubMed, and Web of Science) that were searched for articles compiled from inception until October 20, 2023. The primary outcome was recurrence of CSDH, and secondary outcomes included complications and SDH volume following TXA treatment. The mean difference and odds ratios with 95% confidence intervals were calculated using the random-effects model. RESULTS A total of 5 studies, involving 643 patients in the TXA group and 736 patients in the non-TXA group, met the inclusion criteria. The meta-analysis revealed that TXA use led to a significantly lower CSDH recurrence (OR 0.35, 95% CI 0.23–0.53; p < 0.01) without increasing complications (OR 1.84, 95% CI 0.43–7.95; p = 0.42). Additionally, TXA users had a significantly lower CSDH volume compared to the non-TXA group at 3-month follow-up (mean difference −4.56, 95% CI −8.76 to −0.36; p = 0.03). CONCLUSIONS The findings suggest that TXA might be a promising agent for reducing the risk of CSDH recurrence without elevating the risk of complications. However, these results should be interpreted cautiously due to the limited number of studies included and the methodological heterogeneity. Further large-scale randomized controlled trials are needed to confirm these findings.

AbstractThe use of Bevacizumab has significantly advanced the treatment of various malignancies. Bevacizumab's inhibition of angiogenesis is a known mechanism that impedes tumour growth and facilitates chemotherapy delivery; however, its association with the development of cystic lung disease is not fully understood. We report a unique case of a 73‐year‐old woman with a past medical history of metastatic endometrial adenocarcinoma status post‐chemotherapy with bevacizumab that presented with worsening respiratory symptoms. A follow‐up chest CT scan post chemotherapy showed the transformation of the metastatic lesions into cystic formations. After further extensive evaluation, she was diagnosed with pulmonary cystic disease secondary to bevacizumab. This case illustrates a rare presentation of secondary pulmonary cystic disease following Bevacizumab therapy in a patient with metastatic endometrial adenocarcinoma. It highlights the importance of recognizing uncommon side effects of targeted immunotherapy and underscores the need for ongoing research to understand the underlying mechanisms and manage such complications effectively.

Introduction and importance: Kaposi sarcoma (KS) is an angioproliferative disease, that mostly affects HIV-infected patients with a high viral load and a low CD4 count. In rare cases, the paradoxical worsening of a pre-existing or previously unrecognized opportunistic infection occurs in a phenomenon known as immune reconstitution inflammatory response (IRIS). Case presentation: The authors presented a male patient in his 30s with HIV, who developed a series of complications caused by KS following the initiation of antiretroviral therapy. Despite ongoing antiretroviral therapy (ART), chemotherapy, and supportive measures, the patient developed KS-related IRIS, characterized by rapid clinical deterioration, multiorgan failure, and ultimately succumbed to the disease. Clinical discussion: To the best of our knowledge, very rare cases have been reported with KS-IRIS after the initiation of ART. Many predictors of KS-IRIS development have been identified. Patients must meet the known diagnostic criteria to be diagnosed with IRIS. The treatment of KS-IRIS depends on the stage of KS. ART alone is usually adequate in mild cutaneous KS. Chemotherapy and ART are recommended for patients with severe cutaneous and visceral KS. Conclusion: HIV patients with KS undergoing ART initiation or modification should be closely monitored, particularly during the early stages and in those with extensive disease. Treating opportunistic infections before ART initiation may reduce the risk of KS-IRIS. The increasing prevalence of KS in ART-treated patients with HIV warrants further attention and highlights the need for better management strategies in this population.

Introduction and importance: Brentuximab vedotin (BV) is an anti-CD30 antibody approved for various cancers, including refractory Hodgkin lymphoma (HL), anaplastic large-cell lymphoma (ALCL) among others. In general, BV has been found to be well-tolerated, with the most frequently reported side effects being peripheral neuropathy and neutropenia. BV-induced pneumonitis is extremely rare. To the best of our knowledge, this is the sixth reported instance of BV-induced lung toxicity. Case presentation: This case presents a female patient in her forties diagnosed with cutaneous T-cell lymphoma undergoing BV treatment. She developed acute hypoxic respiratory failure, ultimately, underwent a diagnostic evaluation including a computed tomography (CT) scan, which showed bilateral airspace consolidations and ground-glass opacities, suggestive of organizing pneumonia and diffuse alveolar damage. Bronchoscopy with bronchoalveolar lavage and transbronchial biopsy ruled out infection, and pulmonary lymphoma and confirmed the diagnosis of BV-induced pneumonitis. The patient had significant clinical improvement after stopping the offending agent, and starting steroids, with optimal clinical recovery at 8 weeks follow-up. Clinical discussion: Drug-related pneumonitis poses a significant concern in the management of cancer patients. Numerous chemotherapeutic agents, such as bleomycin, cyclophosphamide, methotrexate, thalidomide, and others, have been associated with pulmonary-related toxicities. These adverse effects primarily stem from direct toxicity or immunosuppression-related infections. Less commonly, immune-mediated injury may occur. Conclusion: Physicians must have a high index of suspicion for BV-induced pneumonitis, hence, early recognition with subsequent holding of the causative agent, initiation of immunosuppression with steroids, and occasionally steroid-sparing medications, prevent an otherwise fatal outcome.

Background: Cardiovascular disease (CVD) remains a leading cause of morbidity and mortality worldwide. Polypills, containing various combinations of medications for primary and secondary CVD prevention, have been developed to enhance medication adherence and reduce the healthcare burden of CVD. However, their effectiveness compared to usual care remains uncertain. Objective: This meta-analysis aimed to evaluate the effects of polypills on cardiovascular risk factors, major adverse cardiovascular events (MACE), and medication adherence. Methods: We conducted a comprehensive search for large-scale randomized controlled trials and observational studies comparing the effects of polypills versus usual care on CVD risk factors and events. Outcomes included changes in systolic and diastolic blood pressure (SBP, DBP), lipid profiles, occurrence of MACE, and medication adherence. Results: The use of polypills led to a statistically significant yet clinically modest reduction in SBP (mean difference -1.47 mmHg, 95% CI: -2.50 - -0.44, p<0.01) and DBP (mean difference1.10 mmHg, 95% CI: -1.68 - -0.51, p< 0.01) compared to usual care. Polypills also showed a significant reduction in the risk of MACE (RR: 0.86, 95% CI: 0.77 -0.95, p<0.01). There was a non-significant reduction in LDL and HDL levels. Adherence to medication improved by up to 17% in polypill users compared to those on usual care (p < 0.01). A multivariable metaregression analysis suggested that adherence may be the underlying factor responsible for the observed effect of the polypills on blood pressure. Conclusion: Polypills were found to significantly reduce SBP, DBP and MACE. An improvement in medication adherence was also observed among polypill users, which might be responsible for the significant reduction in SBP observed users. Future research might benefit from exploring a more personalized approach to the composition of polypills, which could reveal a more clinically significant impact of increased adherence on CVD outcomes.