Immunotherapy-induced autoimmune hypophysitis.

Autoimmune hypophysitis is an immune-related adverse event of immune checkpoint inhibitors. In this article, we present the case of a 58-year-old female patient who presented to the emergency room with gradually worsening nonspecific symptoms of headache, nausea, vomiting and decreased oral intake of one week duration. The patient had been diagnosed with relapsed extensive stage small cell lung cancer. She was being treated with a combination of ipilimumab and nivolumab after progression on chemotherapy. Gadolinium-enhanced magnetic resonance imaging of head revealed pituitary enlargement up to 1.5 cm and pituitary stalk enlargement up to 4 mm consistent with hypophysitis. The patient was treated with corticosteroids resulting in rapid resolution of her symptoms. The objective of our report is to highlight this rare but important adverse event associated with checkpoint inhibitors, and discuss its clinical features, diagnostic work-up and treatment.

A Narrative Review of Existing Options for COVID-19-Specific Treatments.

The new coronavirus disease 2019 (COVID-19) was declared a global pandemic in early 2020. The ongoing COVID-19 pandemic has affected morbidity and mortality tremendously. Even though multiple drugs are being used throughout the world since the advent of COVID-19, only limited treatment options are available for COVID-19. Therefore, drugs targeting various pathologic aspects of the disease are being explored. Multiple studies have been published to demonstrate their clinical efficacy until now. Based on the current evidence to date, we summarized the mechanism, roles, and side effects of all existing treatment options to target this potentially fatal virus.

Predictors of 15-Day Survival for the Intensive Care Unit Patient on Continuous Renal Replacement Therapy: A Retrospective Analysis.

Purpose In the intensive care unit (ICU), acute renal failure is mostly part of multiple organ dysfunction syndromes with mortality ranging from 28%-90%, continuous renal replacement therapy (CRRT) is the predominant mode of RRT used in ICU. The main objective of the study was to evaluate the outcomes in patients with acute kidney injury (AKI) on CRRT in the ICU. Methods A retrospective chart review was conducted for all ICU patients with acute renal failure on CRRT in a tertiary care teaching hospital. A subgroup analysis was conducted between 15 days in hospital survivors and non-survivors to look for predictors of survival for patients on CRRT. Results Two-hundred twenty-six patients underwent CRRT from January 2007 to December 2013. The overall in-hospital mortality was 84.1%. Fifty-six patients (24.77%) survived to the 15-day post-CRRT mark. Acute respiratory failure requiring mechanical ventilation was associated with significantly increased mortality; 89.2% vs. 97.6% (P=0.008), ICU length of stay was significantly longer in the survivor group than the nonsurvivor group. Median±IQR; {20±24 vs 6±7(P: <0.0001)} and so were the ventilator-associated days {16±24 vs 4±6.5 (P: <0.0001)} and duration of CRRT {4.5±5.5 vs 2±2.0(P: <0.0001)}. Patients who survived had a lower incidence of metabolic acidosis {44.6% vs 62.9% (P: 0. 016)} and uremic encephalopathy {12.5% vs 26.5%; (P: 0.031)} but a greater incidence of volume overload {28.6% vs 15.9% (P: 0.031)} as compared to the non-survivor. Acute Physiology And Chronic Health Evaluation II (APACHE II) scores were significantly higher in the non-survivor group (mean SD) 26.9±28.0 vs. 23.9±25.8 (P: 0.0136). Conclusions This observational study in patients undergoing CRRT in an ICU setting revealed that the overall mortality was 84.1%. Fluid overload as an indication of CRRT was associated with improved 15 days' survival whereas higher APACHE II scores and the use of mechanical ventilation were associated with reduced 15 days' survival.

Thirty-day readmissions due to Venous thromboembolism in patients discharged with syncope.

A recent study found that approximately 1 in every 6 patients hospitalized for the 1st episode of syncope had an underlying pulmonary embolism (PE). As current guidelines do not strongly emphasize evaluation for PE in the workup of syncope, we hypothesize that there might be a higher rate of 30-day readmission due to untreated venous thromboembolism (VTE). The objective of this study is to measure the 30-day readmission rate due to VTE and identify predictors of 30-day readmission with VTE among syncope patients. We identified patients admitted with syncope with ICD9 diagnoses code 780.2 in the Nationwide Readmission Database (NRD-2013), Healthcare Cost and Utilization Project (HCUP). The 30-day readmission rate was calculated using methods described by HCUP. Logistic-regression was used to identify predictors of 30-day readmission with VTE. Discharge weights provided by HCUP were used to generate national estimates. In 2013, NRD included 207,339 eligible patients admitted with syncope. The prevalence rates of PE and DVT were 1.1% and 1.4%, respectively. At least one syncope associated condition was present in 60.9% of the patients. Among the patients who were not diagnosed with VTE during index admission for syncope (N = 188,015), 30-day readmission rate with VTE was 0.5% (0.2% with PE and 0.4% with DVT). In conclusion, low prevalence of VTE in patients with syncope and extremely low 30-day readmission rate with VTE argues against missed diagnoses of VTE in index admission for syncope. These results warrant further studies to determine clinical impact of work up for PE in syncope patients without risk factors.

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.

Role of Anti-PD-1 Antibodies in Advanced Melanoma: The Era of Immunotherapy.

Advanced melanoma is an aggressive skin cancer characterized by poor survival rates and response to cytotoxic chemotherapy. Immune checkpoint inhibitors are novel agents capable of utilizing one's own immune system to bring about the tumor destruction. Nivolumab and pembrolizumab are fully humanized anti-PD-1 monoclonal antibodies that have shown significant anti-tumor activity in a variety of cancers including melanoma and have significantly improved the survival outcomes in patients with advanced melanoma. In this updated review article, we will discuss the outcomes of various clinical trials evaluating the efficacy and safety of these agents. We will also briefly discuss their mechanism of action and adverse effects.

Emerging role of immunotherapy in precursor B-cell acute lymphoblastic leukemia.

INTRODUCTION: Acute lymphoblastic leukemia (ALL) is an aggressive type of leukemia that carries poor prognosis in adults especially in the setting of high risk cytogenetics and relapsed/refractory (R/R) disease. Advancements in immunotherapy have led to the development of several monoclonal antibodies (MoAbs) and chimeric antigen receptor (CAR) T cells that are capable of targeting certain surface antigens on leukemic cells, resulting in their destruction. Areas covered: This article reviews the mechanism of action, outcomes of various trials, and adverse effects of MoAbs and CAR-T cells used in the treatment of precursor B-cell ALL. Expert commentary: Some of the immunotherapeutic agents that have been approved for the treatment of R/R precursor B-cell ALL have shown superior efficacy and safety profile compared to chemotherapy in advanced disease. Several trials are now being conducted to evaluate the role of certain MoAbs in combination with chemotherapy in the treatment of B-cell ALL. Additionally, their use in the frontline setting with more favorable host characteristics may also result in superior outcomes compared to the current standard of care.

Anti-PD-1/PD-L1 antibodies in non-small cell lung cancer: the era of immunotherapy.

INTRODUCTION: Advanced non-small cell lung cancer (NSCLC) has been conventionally treated with cytotoxic chemotherapy with short-lived responses and significant toxicities. Monoclonal antibodies to programmed death-1 receptor (PD-1) and programmed death ligand 1 (PD-L1) have shown tremendous promise in the treatment of advanced NSCLC in various clinical trials. Areas covered: In this article, we will review the outcomes of various trials of anti-PD-1/anti-PD-L1 antibodies in the treatment of NSCLC. We will also discuss their mechanism of action and toxicities. Expert commentary: Anti-PD-1/PD-L1 antibodies offer several advantages including significant antitumor activity, induction of long lasting responses, and favorable safety profile. Several trials are now being conducted to evaluate their efficacy as first line agents as well as in combination with other agents. More research is also needed to identify other biomarkers, in addition to PD-L1 expression, that could more reliably predict response to these drugs, and aid in better patient selection.

Correlation of Antiglobulin Reactivity and Severity of Pancytopenia in a Patient with Hemophagocytic Lymphohistiocytosis: A Case Report and Review of Literature.

A 46­year­old obese male with a medical history of thalassemia minor presented to the emergency room with complaints of severe fatigue and jaundice worsening over two weeks. On further evaluation, the patient was found to have significant hyperbilirubinemia and transaminitis. The hospital course was further complicated by pancytopenia requiring multiple transfusions, worsening hyperbilirubinemia, severe hyperferritinemia, hypofibrinogenemia, and hypertriglyceridemia. He was also found to have splenomegaly and evidence of hemophagocytosis on bone marrow biopsy. On further testing, the patient was also found to have evidence of hemolysis along with a positive direct Coomb's test consistent with autoimmune hemolytic anemia (AIHA), and elevated soluble IL-2 receptor level. The patient was subsequently diagnosed with hemophagocytic lymphohistiocytosis (HLH). He was treated with HLH-94 protocol along with rituximab for AIHA which resulted in improvement of patient's condition. We present a case of HLH with no prior history of autoimmune disease, associated with Coomb's positive AIHA that resolved after therapy for HLH. Our case also delineates how the intensity of antiglobulin reactivity, if present, may correlate with severity of the disease, its progression, and response to treatment.

Primary Intimal Sarcoma of the Left Atrium: An Incidental Finding on Routine Echocardiography.

Cardiac sarcomas are extremely rare primary malignant tumors of the heart. In this article, we present the case of a 70-year-old female, who was found to have a left atrial mass during a routine outpatient transthoracic echocardiography. Further investigation with cardiac magnetic resonance imaging confirmed the presence of a bilobulated mass with heterogeneous enhancement. Left atrial myxoma was the first diagnostic consideration, followed by other primary cardiac tumors, and thrombus. The patient subsequently underwent resection of the mass, utilizing cardiopulmonary bypass. Upon pathological examination, the mass was found to be an intimal sarcoma. The objective of this report is to describe a case of this rare disease entity, and to discuss its presentation, pathological findings and management.

An Exceptionally Favorable Response to Etoposide and Cisplatin.

A 66-year-old female with multiple medical co-morbidities was diagnosed with limited-stage small cell lung carcinoma (SCLC) about 11 years ago, back in 2004. The patient was treated with concomitant chemotherapy and radiotherapy, along with prophylactic whole brain radiation. She received a total of four cycles of etoposide and cisplatin. The patient showed a complete response to the above-mentioned treatment and had no evidence of tumor recurrence on any of the scans until 2015. Her last computed tomography (CT) scan of the chest in October 2015 showed bilateral hilar and mediastinal lymphadenopathy. Fine needle aspiration (FNA) of the left hilar node revealed the presence of malignant cells consistent with SCLC. Median survival for limited stage SCLC ranges from 16-24 months, and the reported five-year survival is 14%. In this report, we present the case of a 66-year-old female who showed an exceptionally favorable response to cisplatin and etoposide chemotherapy characterized by a disease-free survival of 11 years.

Bronchial myeloid sarcoma with concurrent Aspergillus fumigatus infection in a patient presenting with hemoptysis.

Myeloid sarcoma (MS) is an extramedullary myeloid neoplasm characterized by proliferation of myeloblasts which can occur in any organ or site. Bronchial and pulmonary involvement, however, is uncommon. We describe a case of bronchial MS in an 81-year-old female with a history of high-grade myelodysplastic syndrome; she was started on treatment few months before, and she presented with fever, cough and profuse hemoptysis. She was found to be pancytopenic with bilateral airspace consolidations, most notably in the right upper and lower lobes, on imaging studies. She was treated with broad-spectrum antibiotics and antifungals without much improvement in her clinical or radiological status. Ultimately, biopsy of the lung lesions showed myeloid sarcoma with concurrent Aspergillus fumigatus infection. Bronchial/pulmonary MS should be considered in the list of differential diagnoses in a patient with a history of myeloid neoplasm and presenting with respiratory related symptoms, as early administration of chemotherapy may help to improve survival rates.

Pauci-Immune Crescentic Glomerulonephritis: An ANCA-Associated Vasculitis.

Rapidly progressive glomerulonephritis (RPGN) is a syndrome signified by a precipitous loss of renal function, with features of glomerulonephritis including dysmorphic erythrocyturia and glomerular proteinuria. RPGN is associated with extensive crescent formation, and, thus, the clinical term RPGN is often used interchangeably with the pathologic term crescentic glomerulonephritis (CGN). From an immunopathologic standpoint, primary RPGN is divided into pauci-immune GN (PICG), anti-GBM GN, and immune complex GN. PICG, the most common etiology of primary RPGN, refers to a necrotizing glomerulonephritis with few or no immune deposits by immunofluorescence (IF) or electron microscopy (EM). In most patients, pauci-immune CGN is a component of a systemic small vessel vasculitis such as granulomatosis with polyangiitis (GPA). Approximately 90% of patients with PICG have circulating ANCA antibodies, leading to the nomenclature ANCA-associated vasculitis (AAV). Recent research has identified several other antibodies associated with PICG, which is now understood to be a complex spectrum of disease with considerable overlap in terms of clinical phenotype and outcomes. In addition, several genetic and environmental factors have recently been implicated in the pathogenesis of this disorder. With new prognostic classifications, enhanced understanding of immunopathologic mechanisms, and novel treatment paradigms, clinical and experimental interest in PICG remains high.

Hyperglycemia enhances kidney cell injury in HIVAN through down-regulation of vitamin D receptors.

In the present study, we evaluated the effect of short term hyperglycemia on renal lesions in a mouse model (Tg26) of HIV-associated nephropathy (HIVAN). Control and Tg26 mice in groups (n=6) were administered either normal saline (FVBN or Tg) or streptozotocin (FVBN+STZ or Tg26+STZ). After two weeks, biomarkers were collected and kidneys were harvested. FVBN+ STZ and Tg26+STZ displayed elevated serum glucose levels when compared to FVBN and Tg26 respectively. Tg26+STZ displayed elevated (P<0.05) blood urea nitrogen (BUN) levels (P<0.05) and enhanced (P<0.01) proteinuria when compared to Tg26. Tg26+STZ displayed enhanced (P<0.001) number of sclerotic glomeruli and microcysts vs. Tg26. Renal tissues of Tg26 displayed down regulation of vitamin D receptor (VDR) expression and enhanced Ang II production when compared to FVBN mice. Hyperglycemia exacerbated down regulation of VDR and production of Ang II in FVBN and Tg mice. Hyperglycemia increased kidney cell reactive oxygen species (ROS) production and oxidative DNA damage in both FVBN and Tg26 mice. In in vitro studies, HIV down regulated podocyte VDR expression and also enhanced renin angiotensin system activation. In addition, both glucose and HIV stimulated kidney cell ROS generation and DNA damage and compromised DNA repair; however, tempol (superoxide dismutase mimetic), losartan (Ang II blocker) and EB1089 (VDR agonist) provided protection against DNA damaging effects of glucose and HIV. These findings indicated that glucose activated the RAS and inflicted oxidative stress-mediated DNA damage via down regulation of kidney cell VDR expression in HIV milieu both in vivo and in vitro.