Whole brain radiation therapy resulting in radionecrosis: a possible link with radiosensitising chemoimmunotherapy.

Radionecrosis describes a rare but serious complication of radiation therapy. In clinical practice, stereotactic radiosurgery (SRS) is increasingly used in combination with systemic therapy, including chemotherapy, immune checkpoint inhibitor and targeted therapy, either concurrently or sequentially. There is a paucity of literature regarding radionecrosis in patients receiving whole brain radiation therapy (WBRT) alone (without additional SRS) in combination with immunotherapy or targeted therapies. It is observed that certain combinations increase the overall radiosensitivity of the tumorous lesions. We present a rare case of symptomatic radionecrosis almost 1 year after WBRT in a patient with non-squamous non-small cell lung cancer on third-line chemoimmunotherapy. We discuss available research regarding factors that may lead to radionecrosis in these patients, including molecular and genetic profiles, specific drug therapy combinations and their timing or increased overall survival.

Risk Factors for Postdischarge Major Thromboembolism and Mortality in Hospitalized Patients with COVID-19 with Cardiovascular Comorbidities: Insights from the CORE-19 Registry.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with venous and arterial thromboembolism (VTE and ATE) and all-cause mortality (ACM) in hospitalized patients. High-quality data are needed on postdischarge outcomes in patients with cardiovascular disease. OBJECTIVES: To analyze outcomes and identify risk factors for ATE, VTE, and ACM in a high-risk subgroup of hospitalized COVID-19 patients with baseline cardiovascular disease. METHODS: We investigated postdischarge rates and associated risk factors of ATE, VTE, and ACM in 608 hospitalized COVID-19 patients with coronary artery disease, carotid artery stenosis (CAS), peripheral arterial disease (PAD), or ischemic stroke. RESULTS: Through 90 days postdischarge, outcome rates were: ATE 27.3% (10.2% myocardial infarction, 10.1% ischemic stroke, 13.2% systemic embolism, 12.7% major adverse limb event); VTE 6.9% (4.1% deep vein thrombosis, 3.6% pulmonary embolism); composite of ATE, VTE, or ACM 35.2% (214/608). Multivariate analysis showed significant association between this composite endpoint and age >75 years (odds ratio [OR]: 1.90, 95% confidence interval [CI]: 1.22-2.94, p = 0.004), PAD (OR: 3.23, 95% CI: 1.80-5.81, p ≤ 0.0001), CAS (OR: 1.74, 95% CI: 1.11-2.75, p = 0.017), congestive heart failure (CHF) (OR: 1.84, 95% CI: 1.02-3.35, p = 0.044), previous VTE (OR: 3.08, 95% CI: 1.75-5.42, p < 0.0001), and intensive care unit (ICU) admission (OR: 2.93, 95% CI: 1.81-4.75, p < 0.0001). CONCLUSION: COVID-19 inpatients with cardiovascular disease experience high rates of ATE, VTE, or ACM through 90 days postdischarge. Age >75 years, PAD, CAS, CHF, previous VTE, and ICU admission are independent risk factors.

The abscopal effect: inducing immunogenicity in the treatment of brain metastases secondary to lung cancer and melanoma.

PURPOSE: The phenomenon of radiation therapy (RT) causing regression of targeted lesions as well as lesions outside of the radiation field is known as the abscopal effect and is thought to be mediated by immunologic causes. This phenomena has been described following whole brain radiation (WBRT) and stereotactic radiosurgery (SRS) of brain metastasis (BM) in advanced melanoma and non-small-cell lung cancer (NSCLC). We systematically reviewed the available literature to identify which radiation modality and immunotherapy (IT) combination may elicit the abscopal effect, the optimal timing of RT and IT, and potential adverse effects inherent to the combination of RT and IT. METHODS: Using PRISMA guidelines, a search of PubMed, Medline, and Web of Science was conducted to identify studies demonstrating the abscopal effect during treatment of NSCLC or melanoma with BM. RESULTS: 598 cases of irradiated BM of melanoma or NSCLC in 18 studies met inclusion criteria. The most commonly administered ITs included PD-1 or CTLA-4 immune checkpoint inhibitors (ICI), with RT most commonly administered within 3 months of ICI. Synergy between ICI and RT was described in 16 studies including evidence of higher tumor response within and outside of the irradiated field. In the 12 papers (n = 232 patients) that reported objective response rate (ORR) in patients with BM treated with RT and concurrent systemic IT, the non-weighted mean ORR was 49.4%; in the 5 papers (n = 110 patients) that reported ORR for treatment with RT or IT alone, the non-weighted mean ORR was 27.8%. No studies found evidence of significantly increased toxicity in patients receiving RT and ICI. CONCLUSION: The combination of RT and ICIs may enhance ICI efficacy and induce more durable responses via the abscopal effect in patients with brain metastases of melanoma or NSCLC.

Complement-mediated microvascular injury and thrombosis in the pathogenesis of severe COVID-19: A review.

Coronavirus disease 2019 (COVID-19) causes acute microvascular thrombosis in both venous and arterial structures which is highly associated with increased mortality. The mechanisms leading to thromboembolism are still under investigation. Current evidence suggests that excessive complement activation with severe amplification of the inflammatory response (cytokine storm) hastens disease progression and initiates complement-dependent cytotoxic tissue damage with resultant prothrombotic complications. The concept of thromboinflammation, involving overt inflammation and activation of the coagulation cascade causing thrombotic microangiopathy and end-organ damage, has emerged as one of the core components of COVID-19 pathogenesis. The complement system is a major mediator of the innate immune response and inflammation and thus an appealing treatment target. In this review, we discuss the role of complement in the development of thrombotic microangiopathy and summarize the current data on complement inhibitors as COVID-19 therapeutics.

Use of Anticoagulants in COVID-19: A Review.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with elevated rates of major and fatal thrombotic events, postulated to be the result of a hypercoagulable state mediated through inflammatory and immunomodulatory mechanisms. Early observational studies showed that disease severity and elevated serum D-dimer levels can predict thrombotic risk in patients hospitalized with COVID-19 and reported an alarming phenomenon of breakthrough thrombosis despite standard-of-care prophylaxis, suggesting the need for enhanced thromboprophylactic strategies. AREAS OF UNCERTAINTY: Data on anticoagulant agent selection, dosing, and duration for COVID-19 inpatients are now poised to inform updated professional society guidance. However, there remains limited high-quality data regarding postdischarge and especially ambulatory patients with COVID-19. DATA SOURCES: This review includes published, peer-reviewed, observational, and randomized controlled trial data and major professional society guidance informing thrombosis prevention and treatment in patients with COVID-19. THERAPEUTIC ADVANCES: There remains great variability in the approach to anticoagulation in COVID-19. This article will review pathogenesis of COVID-related thrombosis and the evidence guiding thromboprophylaxis particularly in inpatients, with attention to the INSPIRATION, ACTION, RAPID, HEP-COVID, and multiplatform trials. Emerging thromboprophylaxis data from the postdischarge setting (particularly the recently published MICHELLE trial), and the outpatient setting, will be examined. Finally, thrombosis treatment considerations will briefly be reviewed. CONCLUSIONS: Substantial high-quality data support practice changes to COVID-19 thromboprophylaxis. Risk stratification by setting, disease severity, and biomarkers such as D-dimer is critical in considering choice, dose, and duration of anticoagulants.

External validation of the IMPROVE-DD risk assessment model for venous thromboembolism among inpatients with COVID-19.

There is a need to discriminate which COVID-19 inpatients are at higher risk for venous thromboembolism (VTE) to inform prophylaxis strategies. The IMPROVE-DD VTE risk assessment model (RAM) has previously demonstrated good discrimination in non-COVID populations. We aimed to externally validate the IMPROVE-DD VTE RAM in medical patients hospitalized with COVID-19. This retrospective cohort study evaluated the IMPROVE-DD VTE RAM in adult patients with COVID-19 admitted to one of thirteen Northwell Health hospitals in the New York metropolitan area between March 1, 2020 and April 27, 2020. VTE was defined as new-onset symptomatic deep venous thrombosis or pulmonary embolism. To assess the predictive value of the RAM, the receiver operating characteristic (ROC) curve was plotted and the area under the curve (AUC) was calculated. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Of 9407 patients who met study criteria, 274 patients developed VTE with a prevalence of 2.91%. The VTE rate was 0.41% for IMPROVE-DD score 0-1 (low risk), 1.21% for score 2-3 (moderate risk), and 5.30% for score ≥ 4 (high risk). Approximately 45.7% of patients were classified as high VTE risk, 33.3% moderate risk, and 21.0% low risk. Discrimination of low versus moderate-high VTE risk demonstrated sensitivity 0.971, specificity 0.215, PPV 0.036, and NPV 0.996. ROC AUC was 0.703. In this external validation study, the IMPROVE-DD VTE RAM demonstrated very good discrimination to identify hospitalized COVID-19 patients at low, moderate, and high VTE risk.

A Case of Laryngeal Tuberculosis, Endobronchial Tuberculosis and Pulmonary Tuberculosis Coexistent in an Immunocompetent Host.

Historically associated with poor prognosis seen in advanced disease, laryngeal tuberculosis (LTB) now represents only 1% of all cases of tuberculosis (TB). The incidence of LTB has decreased drastically with the introduction of anti-tubercular drugs. LTB can be primary or secondary to pulmonary tuberculosis. LTB can mimic laryngeal cancer. We present a case of primary laryngeal TB with descending tracheobronchial spread in an immunocompetent 71-year-old female who developed progressive dysphonia over several months with unintentional weight loss and non-productive cough. Non-contrast enhanced computed tomography (CT) revealed clustering of subcentimeter stellate nodules in the right upper lung field with an enlarging ground-glass opacity in the right lower lung but did not show structural abnormalities within the neck. Positron emission tomography (PET) showed pathologic fluorodeoxyglucose (FDG) uptake within the larynx and trachea with extension into the left mainstream bronchus as well as the proximal left upper and lower lobe bronchi. Diffuse standardized uptake value (SUV) was greatest in the larynx (20.5). Polymerase chain reaction (PCR) on bronchoscope sputum specimen confirmed Mycobacterium tuberculosis. Findings were consistent with primary laryngeal TB with endobronchial extension. She was started on a four-drug regimen comprising of isoniazid, rifampin, ethambutol, and pyrazinamide with a good response. Her close contacts were treated as well. This case highlights the unusual spread of primary laryngeal TB in an immunocompetent host. Early diagnosis can limit adverse complications and unnecessary exposure to healthcare workers. To our knowledge, this is the first case of primary LTB with proximal spread to the tracheobronchial and pulmonary tuberculosis.

Bevacizumab-Induced Pneumonitis in a Patient With Metastatic Colon Cancer: A Case Report.

Bevacizumab is a vascular endothelial growth factor-directed humanized monoclonal antibody used to treat many types of cancer and some eye diseases. Due to inhibition of angiogenesis, many adverse reactions such as bowel necrosis, nasal septal perforation, and renal thrombotic microangiopathy have been described. However, its association with interstitial pneumonitis is scarcely reported in the literature. We report a case of a 79-year-old woman with metastatic colon cancer who presented with cough and dyspnea on exertion the day after initiation of bevacizumab. She was found to have bilateral airspace opacities on imaging. Infectious and cardiogenic etiologies of dyspnea were ruled out. Due to the temporal relationship with the initiation of chemotherapy, she was suspected to have developed bevacizumab-induced interstitial pneumonitis. She improved rapidly with high-dose steroids. Follow-up imaging showed resolution of infiltrates. This is the first reported case in the literature that directly links bevacizumab to interstitial pneumonitis.

Endobronchial aspergilloma-a comprehensive literature review with focus on diagnosis and treatment modalities.

Endobronchial aspergilloma (EBA) is a rare manifestation of pulmonary infection with Aspergillus spp. Comprised of hyphae, mucus, and cellular debris, the massive fungus overgrowth can lead to obstructive pneumonitis in large airways, manifesting as cough, dyspnea, hemoptysis, or weight loss. The aim of this paper is to review the literature on endobronchial aspergilloma to further elucidate this disease entity and to classify it as a non-invasive form of pulmonary aspergillosis. A descriptive analysis was performed on articles on PubMed database that contained the key word "endobronchial aspergilloma." A total of 28 cases were obtained. Four articles were excluded as they were not available in the English format. Although EBA is extremely rare, it should be considered in the differential diagnosis of endobronchial masses in immunocompromised patients. There is a potential for the disease entity to progress to tracheobronchitis and fulminant respiratory failure. As such, early detection with bronchoscopy, biopsy, and culture is required to confirm pulmonary aspergillosis. Current treatment regimens remain to be optimized, though piecemeal resection of the mycetoma with bronchoscopic techniques with the addition of systemic antifungals and their combinations has been reported as efficacious.

Primary plasma cell leukemia: A case report and review of the literature.

Due to the rarity and fulminant nature of the condition, there are limited data driving dialogue for optimal treatment strategies for plasma cell leukemia (PCL). Additionally, the current diagnostic definition of PCL has not been prospectively studied which may result in delays to initiating early aggressive treatment due to underdiagnosis.

Rhinovirus-induced Rapidly Progressing Acute Respiratory Distress Syndrome in an Immunocompetent Host.

A previously healthy, 59-year-old female presented with respiratory distress and dry cough for one week. Outpatient radiographic findings were suspicious for basilar pneumonia. Empiric broad-spectrum antibiotics were started; however, she continued to deteriorate rapidly over the next 48 hours, with chest X-ray showing diffuse bilateral multifocal airspace opacities consistent with acute respiratory distress syndrome. The ratio of partial pressure arterial oxygen to fraction of inspired oxygen was 225. She required a high-flow nasal cannula with a subsequent upgrade to the intensive care unit (ICU) for increasing respiratory compromise. Polymerase chain reaction (PCR) of the nasopharyngeal aspirate confirmed human rhinovirus (hRV). High-dose intravenous steroids were started as adjuvant therapy due to the rapid decline, presumably due to a dysregulated host immune response. After 10 days in the ICU, she was discharged with tiotropium and steroid taper. Historically thought to be limited to pandemic viruses, improved detection of hRV has led to its implication in serious respiratory disorders extending beyond the oropharynx in immunocompetent hosts. We report a rare case of hRV-induced severe acute respiratory distress syndrome (ARDS) in an immunocompetent host. This case highlights the need for the early identification of viral culprits, which can minimize the use of invasive diagnostic testing and antibiotic usage.

Placental transmogrification of the lung associated with unilateral pleural effusion: A case report with a comprehensive review of the literature.

Placental transmogrification of the lung (PTL) is a rare benign pulmonary lesion resembling chorionic villi. With fewer than 40 cases reported in literature, associations have thus far been made with bullous emphysema, pulmonary fibrochondromatous hamartomas and adenocarcinoma of the lung. Typically presenting as unilateral solitary cystic or bullous lesion, we report the first case of PTL presenting with unilateral pleural effusion. A 70-year-old male presented with recurrent unilateral pleural effusion that failed to resolve with multiple thoracenteses. He underwent thoracoscopic excision and biopsy of a cystic mass identified on computed tomography (CT) scan which revealed characteristic villous and papillary changes. We describe the case and review the literature on this benign but rare pulmonary disease entity.

Venous Thrombosis Secondary to Acute Cytomegalovirus Infection in an Immunocompetent Host: Consideration for New Screening Guidelines.

Serious thrombotic complications associated with an acute cytomegalovirus (CMV) infection in immunocompromised and immunocompetent patients are becoming increasingly recognized. While typically asymptomatic and self-limiting, an acute CMV infection appears to demonstrate a rare propensity for a vascular thrombosis, such as deep vein thrombosis (DVT), thrombophlebitis, and pulmonary embolism (PE). It remains unclear whether other predisposing factors play a role in its pathogenesis. We report the case of a young, immunocompetent male with extensive lower extremity DVT who was coincidentally found to be CMV-immunoglobulin M (IgM) seropositive. In light of the increasing prevalence of CMV-associated thrombotic events, we reviewed the current literature on its incidence, pathophysiology, clinical features, and thrombophilia screening to consider the possibility of CMV seropositivity as an independent risk factor for vascular events. This may have repercussions for screening guidelines and preventive strategies in those with active CMV infection.

Left-sided Catamenial Pneumothorax: A Rare Clinical Entity.

Catamenial pneumothorax (CP) is an extremely rare pulmonary pathology seen in women of reproductive age, typically occurring within 72 hours from the onset of menstrual bleeding. Multiple theories have been proposed to explain the etiopathogenesis of CP; however, the exact underlying mechanism remains elusive. More than 90% of reported cases in the literature describe a right-sided presentation of pneumothorax. In this case report, we describe a rare left-sided presentation of CP and discuss the current literature on underlying etiopathogenesis, diagnostics, and available therapeutic modalities for managing this rare clinical entity.