Brentuximab-induced pneumonitis and organizing pneumonia: a case report with literiture review.

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.

Kaposi sarcoma-induced immune reconstitution syndrome: a case report.

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.

Efficacy and safety of tranexamic acid in the management of chronic subdural hematoma: a systematic review and meta-analysis.

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.

Bevacizumab-induced pulmonary cystic disease.

The 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.

Folliculin gene-negative Birt-Hogg-Dube syndrome: a case report.

Introduction and importance: Birt-Hogg-Dube (BHD) is a rare genetic disorder that results from a mutation in the folliculin (FLCN) gene. Manifestations include pulmonary cysts, fibrofolliculomas, renal tumors, and pneumothoraces. Genetic testing can be used to confirm the diagnosis when suspected. BHD syndrome is diagnosed in patients with negative FLCN gene results using diagnostic criteria. Case presentation: A male in his 20s presented with recurrent pneumothoraces. A physical examination revealed bumps on his face and upper body. A chest computed tomography scan revealed cystic lesions. Blood tests, ESR, and CRP levels were unremarkable. Punch skin biopsy revealed fibrofolliculomas. Genetic testing for the FLCN mutation returned negative. His history, physical exam, imaging, and histopathology suggested BHD syndrome despite having a negative family history and genetic analysis. Eventually, the patient was diagnosed with FLCN gene-negative BHD syndrome. Clinical discussion: More than a hundred families have been identified to have BHD worldwide. There are a few cases in the literature describing patients phenotypically presenting with BHD despite having a negative genetic analysis. One study in Japan found 16 out of 157 individuals having a clinical presentation of BHD with no mutations. Also, decreased expression of the FLCN mRNA may lead to BHD. Conclusion: BHD syndrome can present with a negative FLCN gene mutation; however, patients must meet the known diagnostic criteria such as criteria made by Menko et al., Gupta et al., and Schmidt et al. in order to have a diagnosis of BHD syndrome. Also, a qualitative decrease of FLCN with the absence of mutations may also lead to BHD.

The Impact of Polypill on Adherence and Cardiovascular Outcomes: A Comprehensive Systematic Review with Meta-Analysis.

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 to -0.44, p<0.01) and DBP (mean difference- 1.10 mmHg, 95% CI: -1.68 to -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.

A Very Uncommon Case of Transudative Chylothorax: A Case Report and Literature Review.

The presence of chyle in the pleural cavity is referred to as chylothorax. Exudative chylothorax is usually related to damage or obstruction of the lymphatic vasculature with subsequent leakage into the pleural space. In contrast, transudative chylothorax is related to increased hydrostatic pressure caused by elevated intra-abdominal pressure, which leads to the translocation of chylous fluid into the pleural space. Cirrhosis is the most common cause of transudative chylothorax, commonly presenting with ascites and portal hypertension. To the best of our knowledge, isolated transudative chylothorax as a consequence of cirrhosis is exceptionally rare and has been scarcely reported in the literature. We herein report a female patient in her fifties who presented to our hospital with isolated unilateral transudative hepatic chylothorax, with no clinical evidence of cirrhosis or any stigmata of portal hypertension at the time of presentation.

Hydroxocobalamin as Rescue Therapy in a Patient With Refractory Amlodipine-Induced Vasoplegia.

Vasoplegic syndrome is a type of distributive shock characterized by mean arterial pressure of less than 65 mmHg, with normal to high cardiac output and often refractory to fluid resuscitation, high doses of intravenous vasopressors, and inotropes. It is usually observed after cardiac and solid organ transplantation surgeries. Here, we report a 56-year-old female patient who presented with a profound vasoplegia manifesting as lethargy and confusion in the setting of amlodipine toxicity. This case of severe vasoplegia was refractory to all conditional lines of medical management reported in the literature. The mainstay treatment modalities for vasoplegia include volume resuscitation, catecholamines, vasopressin, angiotensin II, and possibly methylene blue in unresponsive cases. Our patient was given hydroxocobalamin in favor of methylene blue, given the history of serotonin reuptake inhibitors use, which would have caused a life-threatening serotonin syndrome. Hydroxycobolamine resulted in a dramatic clinical recovery, suggesting its potentially significant role in refractory vasoplegia.

Chronic Cavitary Pulmonary Histoplasmosis in an Immunocompetent Patient.

Histoplasma capsulatum is a fungal organism that causes systemic histoplasmosis. It is commonly asymptomatic in healthy immunocompetent individuals. The clinical symptoms of chronic cavitary histoplasmosis are typically seen in the immunodeficient population, particularly in smokers with pre-existing structural lung disease. We report a case of chronic cavitary histoplasmosis in an immunocompetent patient from an endemic area without pre-existing structural lung pathology. She presented complaining of right hypochondrial pain and had no history of respiratory symptoms nor history suggestive of immunosuppression, tuberculosis, or recent travel. CT scan revealed a cavitary lung lesion and a hilar mediastinal mass. Biopsies obtained by bronchoscopy revealed signs of necrosis, granulomas, and the presence of fungal organisms consistent with histoplasmosis. Histoplasma antibodies by complement fixation for yeast antibodies test were positive establishing the diagnosis of chronic cavitary pulmonary histoplasmosis (CCPH). She was then started on itraconazole with good tolerance. On follow-up three months later, a chest CT done along with measurement of inflammatory markers and liver enzymes demonstrated complete clinical recovery. This case emphasizes the importance of expanding our current understanding of the clinical presentation and manifestations of histoplasmosis beyond the conventional assumption that severe disease only affects immunocompromised individuals.

Scurvy-induced pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a progressive disease of the pulmonary vasculature that results in precapillary pulmonary hypertension. PAH is caused by a group of clinical conditions involving multiple organ systems. Several cases have been reported in the literature demonstrating an association between vitamin C deficiency and PAH. Low endothelial nitric oxide levels in the pulmonary vasculature, combined with the inappropriate activation of hypoxia-inducible transcription factors, seen in patients with ascorbic acid deficiency, are believed to be the main contributors to the pathogenesis of pulmonary vasculopathy and the exaggerated pulmonary vasoconstrictive response seen in patients with scurvy-induced PAH. Vitamin C supplementation is considered the definitive treatment.

Rituximab-Induced Immune Dysregulation Leading to Organizing Pneumonia, Bronchiectasis, and Pulmonary Fibrosis.

We present a case of rituximab-induced organizing pneumonia (OP) along with bronchiectasis and pulmonary fibrosis, in a patient with a history of granulomatosis with polyangiitis (GPA), on long-term maintenance therapy with rituximab. T-cell dysregulation and B-cell depletion associated with the chronic use of rituximab often lead to a profound immunosuppressed state with hypogammaglobulinemia and unbalanced T-cell response. This acquired immunodeficient state with severe immune dysregulation predisposed this patient to recurrent pulmonary infection and ultimately led to bronchiectasis and pulmonary fibrosis.

Parkinsonism-Hyperpyrexia Syndrome: A Case Series and Literature Review.

Parkinsonism-hyperpyrexia syndrome (PHS) is a rare, potentially fatal neurological emergency, that is seen in Parkinson's Disease (PD) patients and mimics neuroleptic malignant syndrome. The most common trigger for PHS is sudden withdrawal of anti-parkinsonian medications, specifically levodopa. However, it can also be due to Deep Brain Stimulation (DBS) device malfunction. In this work, we describe three cases of PHS; the first of which is related to DBS battery depletion, and the remaining two to dopaminergic withdrawal. Additionally, we will include the results of a literature review on PHS, its etiologies, presentation, and management.

Malignant deep brain stimulator withdrawal syndrome.

Parkinsonism-hyperpyrexia syndrome (PHS) is a neurologic potentially fatal emergency that mimics neuroleptic malignant syndrome. It commonly presents as systemic inflammatory response syndrome, acute onset worsening of muscular rigidity, autonomic instability, hyperpyrexia, confusion, diaphoresis and high creatine phosphokinase. The most common trigger for PHS is reduction or withdrawal of anti-Parkinson's medications, especially levodopa. It was also reported in a few cases following deep brain stimulation of the subthalamic nucleus surgery shortly after anti-Parkinson's medications were discontinued. Rare causes of PHS include deep brain stimulator (DBS) malfunction due to battery depletion. To the best of our knowledge, PHS following DBS battery depletion was reported only in three occasions. Here, we report a case of PHS due to DBS battery depletion presented as sepsis and was successfully treated with the administration of dopamine agonists, intravenous fluids and changing the DBS battery.