Immunotherapy in Bladder Cancer.

BACKGROUND: Bladder cancer is the fifth most common cancer in the United States. Cisplatin-based chemotherapy is the current standard of care in stage IV bladder cancer. It has increased overall survival but rarely results in complete remission, with an overall survival of 14-15 months. The most significant breakthrough in cancer therapy over the last decade was the development of immunotherapy. DATA SOURCES: KEYNOTE-045, IMvigor211, CheckMate275, Javelin Solid Tumor, MEDI4736, and KEYNOTE-0528 clinical trials. AREAS OF UNCERTAINTY: There are ongoing clinical trials using combination of immunotherapy and chemotherapy as first line of therapy in the setting of metastatic urothelial cancer and also to determine the duration of treatment. THERAPEUTIC ADVANCES: Immunotherapy is approved as a second-line treatment for metastatic urothelial cancer. Their use as a first-line agent is only limited to patients who are ineligible for cisplatin-based treatments. Five drugs are approved by Food and Drug Administration for metastatic urothelial cancer including 3 Programmed cell-death protein 1 (PD-1) inhibitors and 2 programmed cell-death ligand 1 (PD-L1) inhibitors in patients who have progressed during or after platinum-based therapy. Pembrolizumab, nivolumab, and atezolizumab are PD-1 inhibitors. Durvalumab and avelumab are PD-L1 inhibitors. However, only 2 drugs were approved based on phase III clinical trials-pembrolizumab and atezolizumab, of which only KEYNOTE study performed with pembrolizumab showed overall survival difference. Atezolizumab and pembrolizumab are the Food and Drug Administration-approved checkpoint inhibitors in cisplatin-ineligible patients. CONCLUSION: This review article summarizes the significance of immunotherapy in treatment of bladder cancer, its side effects, and limitations.

Presenting characteristics, comorbidities, and outcomes of patients coinfected with COVID-19 and Mycoplasma pneumoniae in the USA.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is spreading at a rapid pace, and the World Health Organization declared it as pandemic on 11 March 2020. Mycoplasma pneumoniae is an "atypical" bacterial pathogen commonly known to cause respiratory illness in humans. The coinfection from SARS-CoV-2 and mycoplasma pneumonia is rarely reported in the literature to the best of our knowledge. We present a study in which 6 of 350 patients confirmed with COVID-19 were also diagnosed with M. pneumoniae infection. In this study, we described the clinical characteristics of patients with coinfection. Common symptoms at the onset of illness included fever (six [100%] patients); five (83.3%) patients had a cough, shortness of breath, and fatigue. The other symptoms were myalgia (66.6%), gastrointestinal symptoms (33.3%-50%), and altered mental status (16.7%). The laboratory parameters include lymphopenia, elevated erythrocyte sedimentation rate, C-reactive protein, lactate dehydrogenase, interleukin-6, serum ferritin, and D-dimer in all six (100%) patients. The chest X-ray at presentation showed bilateral infiltrates in all the patients (100%). We also described electrocardiogram findings, complications, and treatment during hospitalization in detail. One patient died during the hospital course.

Immune Checkpoint Inhibitors-Related Cardiotoxicity.

BACKGROUND: Immunotherapy is a significant breakthrough in cancer therapy in the last decade. Immunotherapy is better tolerated compared with chemotherapy. However, it does have side effects, and one of the rare and serious side effects of immunotherapy is cardiotoxicity. Cardiotoxicity has been described with other cancer-related treatments such as chemotherapy and targeted therapy. A high index of suspicion is required, and prompt management with immunosuppression needs to be instituted as soon as possible to prevent fatal outcomes. AREAS OF UNCERTAINTY: Research is still ongoing to identify biomarkers that will help us to choose the patients, who will respond well to immunotherapy. Tumor-infiltrating lymphocytes, tumor PD-L1 expression, and tumor mutational burden explored as potential biomarkers. There are no predictive biomarkers to identify patients who are at higher risk of severe cardiotoxicity. Both cardiologists and oncologists should be aware of cardiac toxicity from immune checkpoint inhibitors. CONCLUSION: All patients who are starting immune checkpoint inhibitors should undergo baseline cardiac risk factor assessment with referral to a cardiologist in a patient with multiple risk factors or previous history of cardiovascular disease. Cardiac immune-related adverse events are higher in patients taking combination therapy with anti-CTLA-4/anti-PD-1 agents compared with monotherapy. Patients with known cardiac comorbidities require a higher level of vigilance to monitor for cardiac toxicity because nonspecific symptoms can lead to rapid clinical deterioration and a higher rate of mortality when treated with checkpoint inhibitors.

Outcomes of Clostridioides difficile in Patients with Vitamin D Deficiency: A Propensity-Matched National Inpatient Sample Analysis.

OBJECTIVES: We aimed to determine in-hospital outcomes, length of hospital stay, and resource utilization in a contemporary cohort of Clostridioides difficile infection (CDI) and vitamin D deficiency (VDD). METHODS: The National Inpatient Sample database for 2016 and 2017 was used for data analysis using International Classification of Diseases, Tenth Revision, Clinical Modification/Procedure Coding System (ICD-10-CM/PCS) codes to identify the patients with the principal diagnosis of CDI and VDD. We assessed the all-cause in-hospital mortality, morbidity, length of hospital stay (LOS), and total costs between propensity-matched groups of CDI without VDD versus CDI with VDD. RESULTS: We identified 202,234 patients with CDI, 4515 of whom were patients with VDD and 197,719 of whom were without VDD. After propensity matching, there was no difference in the in-hospital mortality between the two groups (odds ratio [OR] 1.5, 95% confidence interval [CI] 0.58-4.3; P = 0.90). CDI with VDD has a higher odds of sepsis (OR 1.6, 95% CI 1.3-1.9; P = 0.0), and peritonitis (OR 1.6, 95% CI 1.4-3.8; P = 0.01). Mean LOS (5.9 ± 1.8 vs 5.4 ± 2, P < 0.01) and mean total charges ($11,500 vs $9971, P < 0.04) were higher in CDI with VDD. The factors affecting the LOS were acute coronary syndrome (P = 0.04), mechanical ventilation (P = 0.03), obesity (P = 0.004), acute kidney injury (P = 0.04), and sepsis (P = 0.05). CONCLUSIONS: In this large cohort in a propensity-matched analysis, VDD does not increase the in-hospital mortality in CDI. VDD increases the odds of complications with a higher LOS and resource utilization. These findings may be clinically relevant to guide clinicians to routinely monitor vitamin D status and supplement in patients at risk of CDI.

Etiology of Syncope in Patients Hospitalized With Syncope and Predictors of Mortality and Readmission for Syncope at 17-Month Follow-Up: A Prospective Study.

We investigated the etiologies of syncope and risk factors for mortality and rehospitalization for syncope at 17-month follow-up in a prospective study of 242 consecutive patients, mean age 69 years, hospitalized for syncope. The etiologies of syncope included the following: vasovagal syncope in 49 patients (20%), volume depletion in 39 patients (16%), orthostatic hypotension in 13 patients (5%), primary cardiac arrhythmias in 25 patients (10.3%), structural cardiac disease in 6 patients (2%), and drug overdose in 5 patients (2%). The etiology of syncope could not be determined in 84 patients (35%). Of the 242 patients, 6 (2%) were rehospitalized for syncope and 12 (5%) died. Stepwise logistic regression analysis showed that the significant independent prognostic factors for rehospitalization for syncope were drug overdose [odds ratio (OR): 11.506; 95% confidence interval (CI): 1.083-22.261]. Stepwise logistic regression analysis showed that significant independent prognostic factors for time to mortality were undetermined etiology of syncope (OR: 4.665; 95% CI: 1.002, 21.727), San Francisco Syncope Score (OR: 3.537; 95% CI: 1.472-8.496), hypertension (OR: 0.099; 95% CI: 0.019-0.504), and glomerular filtration rate (OR: 0.964; 95% CI: 0.937-0.993).

Warfarin use and prevalence of coronary artery calcification assessed by multislice computed tomography.

Warfarin inhibits the synthesis and function of matrix Gla protein, a vitamin K-dependent protein, which is a potent inhibitor of tissue calcification. We had earlier reported the association of warfarin use with valvular calcification in patients with nonvalvular atrial fibrillation. The aim of our present study was to investigate the association of warfarin use with the presence and severity of coronary artery calcification. A total of 233 patients underwent computed tomography scan (CT) at our institution for the assessment of coronary artery calcium score (CACS). Of 233 patients, the mean age was 63 years, 28 patients (12%) were treated with warfarin, and 205 patients (88%) were not on warfarin. Based on their total CACS, the patients were subsequently stratified into 59 with no coronary calcium (CACS = 0), 63 with low CACS (1-100), 49 with moderate CACS (101-400), 33 with severe CACS (410-1000), and 29 with very severe CACS (>1000). The χ test and Student t-test were used for the comparison of categorical and continuous variables, respectively, between warfarin users and nonusers. Using the variables age, gender, race, smoking, hypertension, diabetes, dyslipidemia, glomerular filtration rate, calcium-phosphorus product, alkaline phosphatase, use of aspirin, beta blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and statins, stepwise logistic regression analysis did not show any association of coronary calcification with use of warfarin. In our study, warfarin use was not associated with a higher prevalence or severity of CACS assessed by coronary computed tomography.

Incidental detection of operational tolerance in a deceased donor kidney transplant recipient lost to follow-up for more than 10 years: A case report and literature review.

Graft tolerance is a clinical state of absence of an immune response in the recipient toward a donor allograft without any exogenous immunosuppression. Although more prevalent in liver transplantation recipients, it has rarely been reported in renal transplant recipients. We present a 62-year-old deceased donor kidney transplant recipient who exhibited operational tolerance as they stopped immunosuppressant medications for more than 10 years and yet demonstrated stable graft function. Although various hypotheses, such as deletion, anergy, immunoregulation, and clonal exhaustion, have been experimentally validated, clinical "operational tolerance" of a renal allograft on a prolonged basis has been infrequently reported in the medical literature. This review intends to highlight possible etiologies and make clinicians aware of this possible rare condition to which more research is needed.

An Uncommon Presentation of Vasopressin-Induced Purpura Fulminans.

Purpura fulminans (PF) is a rarely encountered rapidly evolving dermatological manifestation of ischemia, particularly in critically ill patients. Considered one of the very few dermatological emergencies, it has high mortality rate where patients often succumb to the illness. It can manifest in three forms: neonatal, idiopathic, and the more commonly infectious variety, which can be secondary to mostly bacterial and rarely viral etiology. It is also reported to be highly associated with disseminated intravascular coagulation (DIC), heparin-induced thrombocytopenia (HIT), and acute hepatic failure (AHF). Hereditary or acquired deficiency of protein C and dysregulation of the coagulation cascade, mainly protein C-thrombomodulin, has been implicated in the pathogenesis. We present a 55-year-old male admitted to the intensive care unit for diabetic ketoacidosis (DKA) and septic shock. Along with initiating management protocol for DKA and broad-spectrum antibiotics, he was initially started on norepinephrine for septic shock. Because of persistent refractory septic shock, he was subsequently initiated on phenylephrine and vasopressin to maintain adequate perfusion. The following day, he was found to have sharply demarcated blackish non-blanching discoloration on bilateral knees, lower limbs, and scrotum, sparing the acral regions. This cutaneous manifestation persisted throughout his hospital course, although it improved after discontinuation of vasopressin while continuing with other pressors. Vasopressin has been implicated in a few instances of skin necrosis; however, PF has rarely been documented and never within 1 day like ours. This case demonstrates a unique development of PF likely from vasopressin after ruling out the diagnoses of DIC, HIT, thrombotic thrombocytopenic purpura, and AHF.

Megadose Vitamin C Prescription Through Alternative Medicine Leading to End-Stage Renal Disease: Case Study and Literature Review.

Modern medicine has made tremendous advancements and succeeded in increasing longevity through adequate screening and diagnosis and various new therapeutic approaches. However, alternative medicine is a branch of health care practicing different traditional and unconventional, potentially hazardous therapies to treat commonly known ailments. Standard low-dose vitamin C, ie, 500-1000 mg, is approved in medical conditions like methemoglobinemia, scurvy, burns and also helps iron absorption in anemia. However, toxic doses carry high nephrotoxicity potential like in our case. We present a 74-year-old Caucasian female falling victim to one such alternative therapy leading to acute kidney injury requiring lifelong hemodialysis. She had endometrial cancer and received 100 gm of intravenous vitamin C weekly through a provider for the last 6 weeks as part of this alternate approach to cure her cancer. Upon admission, the serum creatinine level was elevated at 8.2 mg/dl, which subsequently did not improve with conservative management. Renal biopsy revealed diffuse acute tubular injury with polarized microscopy demonstrating calcium oxalate crystals. While her blood vitamin C levels were high, the serum oxalate level was normal. She ended up requiring renal replacement therapy permanently. Alternative medicine continues to be a significant health care hazard with the potential to cause unwanted irreversible nephrotoxicity. Public attention is necessary at various social levels to counter the detrimental outcomes of alternative medicine.

Clinical Characteristics and Predictors of Mortality in Obese African-Americans with COVID-19: a Single-Center Retrospective Study.

BACKGROUND: This study aims to add to the body of evidence linking obesity as an established risk factor for COVID-19 infection and also look at predictors of mortality for COVID-19 in the African-Americans (AA) population. METHODS: A retrospective cohort study of patients with confirmed COVID-19 infection was done in a community hospital in New York City. The cohort was divided into two groups, with the non-obese group having a BMI < 30 kg/m2 and the obese group with a BMI ≥ 30 kg/m2. Clinical predictors of mortality were assessed using multivariate regression analysis. RESULTS: Among the 469 (AA) patients included in the study, 56.3% (n = 264) had a BMI < 30 kg/m2 and 43.7% (n = 205) had a BMI ≥ 30 kg/m2. Most common comorbidities were hypertension (n = 304, 64.8%), diabetes (n = 200, 42.6%), and dyslipidemia (n = 74, 15.8%). Cough, fever/chills, and shortness of breath had a higher percentage of occurring in the obese group (67.8 vs. 55.7%, p = 0.008; 58.0 vs. 46.2%, p = 0.011; 72.2 vs. 59.8%, p = 0.005, respectively). In-hospital mortality (41.5 vs. 25.4%, p < 0.001) and mechanical ventilation rates (34.6 vs. 22.7%, p = 0.004) were also greater for the obese group. Advanced age (p = 0.034), elevated sodium levels (p = 0.04), and elevated levels of AST (0.012) were associated with an increase in likelihood of in-hospital mortality in obese group. CONCLUSIONS: Our results show that having a BMI that is ≥ 30 kg/m2 is a significant risk factor in COVID-19 morbidity and mortality. These results highlight the need for caution when managing obese individuals.

Seronegative Atypical Anti-Glomerular Basement Membrane Glomerulonephritis Associated With Thrombotic Microangiopathy: Case Report and Literature Analysis.

Anti-glomerular basement membrane (GBM) antibody nephritis is defined by linear immunofluorescence staining of GBM by immunoglobulin G (IgG), typically associated with GBM rupture, fibrinoid necrosis, and crescent formation. Clinically, the patients present with rapidly worsening renal function, often with hematuria. Typical renal pathologic findings include necrotizing and crescentic glomerulonephritis. In contrast, thrombotic microangiopathy (TMA) is characterized by microvascular thrombosis, which can also lead to acute kidney injury. Thrombotic microangiopathy is associated with some systemic diseases and has characteristic clinical features of microangiopathic hemolytic anemia, platelet consumption, and multiple organ failure. Anti-GBM nephritis associated with TMA has rarely been reported. We describe an unusual case of atypical anti-GBM disease without crescent formation or necrosis but with light microscopic and ultrastructural features consistent with endothelial cell injury and glomerular-limited TMA.

Hepatitis B-Associated Lupus-Like Glomerulonephritis Successfully Treated With Antiretroviral Drugs and Prednisone: A Case Report and Literature Review.

Kidney involvement with hepatitis B virus is varied and mostly limited to nephrotic syndrome with membranous nephropathy and nephritic syndrome with membranous proliferative glomerulonephritis. Lupus nephritis is associated with nephritic or nephrotic range proteinuria with most common finding of sub-endothelial electron-dense deposits and immunological stain demonstrating full-house picture with all immunological marker staining. Our case discusses a young male patient presenting with rapidly worsening renal function along with proteinuria, found to be positive for both hepatitis B core antibody along with hepatitis B surface antibody plus positive anti-neutrophilic antibody but negative anti-double-stranded DNA. Kidney biopsy demonstrated hepatitis B-associated lupus-like glomerulonephritis. He responded successfully with antiretroviral therapy and high-dose prednisone. Patient did not need lupus-specific treatment and recovered with antiretroviral therapy only. Hepatitis B-associated lupus-like glomerulonephritis has rarely been reported and possess a diagnostic and therapeutic challenge to all nephrologists.

Brevibacterium casei Induced Peritonitis in a Patient Undergoing Continuous Cycler Peritoneal Dialysis: Case Report and Literature Review.

Brevibacterium casei is an extremely rare organism that can lead to peritonitis in End-stage renal disease patients of peritoneal dialysis. Out of only five overall Brevibacterium species peritonitis reported worldwide, only two of them had B. casei subspecies peritonitis detected, with both needing peritoneal dialysis catheter removal and change in dialysis modality to hemodialysis. Our patient, an elderly 63-year-old Hispanic male, was on peritoneal dialysis at home and presented with features suggestive of peritonitis. He was diagnosed subsequently with B. casei and started on broad spectrum intraperitoneal antibiotics. However, he did not need dialysis modality change and recovered fully after 3 weeks of appropriate intraperitoneal antibiotics therapy. Longer antibiotics therapy and frequent clinical follow-up plus better clinician awareness are needed to prevent this rare infection.

Rhizobium radiobacter-Induced Peritonitis: A Case Report and Literature Analysis.

Rhizobium radiobacter (R. radiobacter) is a gram-negative bacterium, primarily a soil contaminant and rarely pathogenic to humans. Only a few cases of peritonitis secondary to R. radiobacter have been reported worldwide. A 66-year-old male with end-stage renal disease who was on peritoneal dialysis (PD) developed R. radiobacter-induced peritonitis. We have treated the infection successfully with intraperitoneal antibiotics and managed to keep his PD catheter intact without interruption in PD treatment. More prolonged antibiotic therapy and frequent clinical follow-up is required to treat this infection. Better clinician awareness is needed to prevent this rare infection.

Diabetic Ketoacidosis and COVID-19: A Case Series From an Inner-City Community Teaching Hospital in New York.

INTRODUCTION: Throughout the coronavirus disease 2019 (COVID-19) pandemic, studies have repeatedly shown that COVID-19 outcomes are more severe in the elderly and those with comorbidities, with diabetes being a significant risk factor associated with more severe infection. Here, we present the clinical characteristics of 25 patients with pre-existing type 2 diabetes mellitus who presented with diabetic ketoacidosis (DKA) and COVID-19 in a community hospital in Brooklyn, New York, and identify possible predictors of mortality. METHODS: This retrospective case series recruited patients from March 1st to April 9th, 2020, with lab-confirmed COVID-19 and met DKA criteria on admission (based on American Diabetes Association diagnostic criteria for DKA). RESULTS: Of the 25 patients who met the inclusion criteria, 22 were African American and three were Hispanic. Common comorbidities in addition to diabetes were hypertension, obesity, coronary artery disease, and dyslipidemia. Fever, cough, myalgias, and shortness of breath were common presenting symptoms. Most patients had elevated inflammatory markers erythrocyte sedimentation rate, C-reactive protein, D-dimer, and ferritin, but higher values increased the odds of mortality. The overall survival was 64%, with those recovering having more extended hospital stays but requiring less time in the intensive care unit. At the same time, those who died were more likely to require mechanical ventilation, have an acute cardiac injury, and/or be obese. Despite numerous studies on COVID and diabetes, only a few studies described DKA. CONCLUSION: This observational retrospective study illustrated that patients with diabetes are at risk of developing DKA with COVID-19 and identified some predictors of mortality. However, further studies with larger sample sizes and a control group are necessary to understand better the effects of COVID-19 on DKA and their clinical outcomes.

Acute Interstitial Nephritis Induced by Clozapine.

Acute interstitial nephritis (AIN) classically presents as acute kidney injury most often induced by offending drugs. Less frequently it is secondary to infections, autoimmune disorders, or idiopathic conditions. Development of drug-related AIN is not dose dependent and a recurrence can occur with re-exposure to the drug. We present a 50-year-old male with treatment resistant schizoaffective disorder who developed clozapine-induced AIN, confirmed with kidney biopsy within 2 months of taking this medication. His kidney function improved with removal of the drug and treatment with steroids. However, his kidney function was again significantly impaired when rechallenged with even a lower dose of clozapine a year later. Kidney function returned to baseline after stopping clozapine. Monitoring of kidney function during clozapine therapy is essential to therapy. Prompt diagnosis is imperative as discontinuation of offending agent can prevent acute kidney injury.

COVID-19 and Aortic Thrombosis: A Case Report.

Coronavirus disease 2019 (COVID-19) is an infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is known to cause a myriad of symptoms ranging from mild respiratory illness to severe pneumonia and acute respiratory distress. Since its discovery in late 2019 in Wuhan, China, the virus has caused a devastating worldwide pandemic. Although COVID-19 most commonly causes respiratory symptoms, complications such as hypercoagulability are now known to occur in some patients. In this case report, we present a COVID-19 patient that suffered a stroke and was found to have an aortic thrombus. In this case report, we discussed hypercoagulability, venous and arterial thrombosis in COVID-19 patients. We hope to highlight the importance of monitoring laboratory markers of hypercoagulability and thromboembolism symptoms in COVID-19 patients and encourage appropriate prophylaxis and treatment with anticoagulants when necessary. It is unclear whether or not a causal relationship exists given the nature of the syndrome. However, given the growing number of reported cases physicians should maintain awareness of this possible complication when evaluating COVID-19 patients.