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.

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.

COVID-19 and APOL-1 High-Risk Genotype-Associated Collapsing Glomerulonephritis.

Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily affects the lungs and can lead to acute respiratory distress syndrome (ARDS). The ongoing global pandemic has created healthcare and economic crisis for almost every nation of the world. Though primarily affecting the lungs, it has also affected the kidney in various ways including acute kidney injury (AKI), proteinuria, and hematuria. It has been increasingly shown that African American (AA) individuals affected with COVID-19 and presenting with AKI and nephrotic-range proteinuria are very susceptible to focal segmental glomerulosclerosis (FSGS). The APOL-1 gene, associated with the African American population, has been increasingly recognized as a risk factor for FSGS affected with COVID-19. Our case highlights a similar case of COVID-19 in a 65-year-old AA descendant with biopsy-proven FSGS and genetically confirmed APOL-1 alleles.

A case of neuromyelitis optica spectrum disorder with coexisting systemic lupus erythematosus.

Neuromyelitis Optica or Devic disease is changed to Neuromyelitis Optica spectrum disorder to include more diverse neurological and autoimmune manifestations. This is a severe relapsing autoimmune demyelinating disorder commonly affecting the optic nerve and spinal cord. It has been reported as either the first manifestation of SLE or as a coexisting condition with other autoimmune disorders commonly included but not limited to SLE and SS. We discussed a case of a 49-year-old female patient who was initially presented with a left-sided weakness that rapidly progressed to quadriparesis and bladder dysfunction within a few days. She had positive autoimmune serology tests for SLE posing a diagnostic challenge as SLE is associated with neurological manifestations. Due to a lack of definitive diagnostic criteria for SLE, presence of AQP-4 antibodies in CSF, and evidence of longitudinal extensive transverse myelitis in MRI cervical spine, we conclude that she has Neuromyelitis Optica spectrum disorder with probable SLE. It is possible that she may develop more signs and symptoms of SLE with time and will need close follow up. Timely diagnosis and prompt treatment are vital to decrease morbidity and mortality, as done in our case. The patient was started on high-dose steroids with significant improvement in her symptoms. These patients may need early treatment with plasmapheresis and long-term follow-up with immunotherapy to prevent relapse. There are few case reports in the literature, and more information is needed to understand and better diagnose NMO with coexisting SLE.

Pembrolizumab related Guillain barre syndrome, a rare presentation in a patient with a history of lupus and bladder cancer.

Immune checkpoint inhibitor-related neurotoxicity causing Guillain Barre Syndrome is relatively uncommon. We discussed an 80-year-old patient with known systemic lupus erythematosus who presented with lower extremity weakness, areflexia and then progressed to respiratory muscle and upper extremity weakness after receiving immunotherapy with checkpoint inhibitors for metastatic bladder cancer. With the increasing use of immunotherapy for the management of cancer, awareness of neurological autoimmune side effects is essential. Immune checkpoint inhibitor-mediated GBS can be severe and fatal if not diagnosed promptly. The hospitalists, neurologists, and oncologists should be aware of neurotoxicity related to immune checkpoint inhibitor therapy requiring a multidisciplinary approach to patient care. Prompt initiation of immunosuppressive therapy is required for the management of immune checkpoint inhibitor-related neurotoxicity.

Fat Embolism Syndrome in Sickle Cell ß-Thalassemia Patient With Osteonecrosis: An Uncommon Presentation in a Young Adult.

Fat embolism syndrome is a relatively infrequent presentation in sickle cell thalassemia patients. It most commonly occurs in long bone fractures in the setting of trauma. However, nonorthopedic trauma and nontraumatic cases have been reported to contribute to fat embolism. The fat embolic syndrome is an underdiagnosed, life-threatening, and debilitating complication of sickle-ß-thalassemia-related hemoglobinopathies. It is primarily seen in milder versions of sickle cell disease, including HbSC and sickle cell ß-thalassemia, with the mild prior clinical course without complications; hence, diagnosis can be easily missed. Pathogenesis of fat embolic syndrome is a combination of mechanical obstruction from fat globules released into systemic circulation at the time of bone marrow necrosis and direct tissue toxicity from fatty acids and inflammatory cytokines released from fat globules. Prompt diagnosis and early initiation of treatment can reduce morbidity and mortality and result in better outcomes and prognosis. Red cell exchange transfusion is the mainstay of therapy with mortality benefits. Overall mortality and neurological sequelae continue to be high despite increased red cell exchange transfusion in the last few years. In this article, we discussed a case of a 34-year-old male patient with a history of sickle cell thalassemia and avascular necrosis of the hip, who presented with fever, hypoxia, encephalopathy, and generalized body aches, found to have thrombocytopenia and punctate lesions on magnetic resonance imaging brain, which led to the diagnosis of the fat embolism syndrome. Only a few sickle cell ß-thalassemia with fat embolic syndrome cases have been reported.

Paget-Schroetter Syndrome in a Young Female.

Paget-Schroetter syndrome or effort thrombosis is a relatively rare primary spontaneous thrombosis of upper extremity deep veins secondary to entrapment of axillary subclavian veins from an abnormality of the thoracic outlet. It is commonly seen in young adults who lift heavy weights or strenuous use of the upper extremities during athletic activities. Repetitive microtrauma to the subclavian vein secondary to narrow costoclavicular space and strenuous activities leads to intimal layer inflammation, hypertrophy, fibrosis, and coagulation cascade activation. Management of Paget-Schroetter syndrome differs from the venous thrombosis of the lower extremity as treatment includes anticoagulation, thrombolysis, and surgical decompression. Early recognition and timely management are required to prevent significant disability from post-thrombotic syndrome and long-term morbidity from recurrent thromboembolism and pulmonary embolism. Internists and emergency physicians should be aware of the disease's presentation, treatment options, and early referral to vascular surgeons since prompt initiation of appropriate treatment will have better outcomes than delayed treatment. We discussed a case of a 31-year-old female who lifts heavyweight at work, presented with right arm swelling and pain for 2 weeks, and diagnosed with axillary subclavian vein thrombosis secondary to thoracic outlet obstruction. She received a high-dose heparin drip followed by catheter-directed thrombolysis and underwent surgical decompression of axillary subclavian vein via resection of the first rib, subclavius muscle resection, partial anterior scalenectomy, and venolysis. In our review of the literature, randomized controlled studies lack the efficacy and safety of surgical decompression. However, the results are promising based on accumulated experience from vascular surgery experts and small case series. Extensive studies are needed further to delineate the protocol for the management of Paget-Schroetter syndrome.

Back to basics: review on vitamin D and respiratory viral infections including COVID-19.

IMPORTANCE: As the scientific community is in a marathon in finding out the cure for COVID-19, in this crisis, it is essential for the physicians not to forget about the basics. Due to the pandemic crisis, in many nursing homes and hospitals, there established new policies on decreasing unnecessary medications to minimize cross-contamination. Sometimes these policies are making providers avoid essential drugs such as Vitamins, including Vitamin D. In this paper, we try to emphasize the importance of Vitamin D in COVID-19 and respiratory viral patients. RELEVANCE: Vitamin D helps in decreasing the 'pro-inflammatory cytokines' in the lungs and acts in immunomodulatory function, and 'also it will increase the anti-inflammatory, antiviral responses of the respiratory epithelial cells during infection.' CONCLUSION: Due to the highly contagious nature of COVID-19 and the increased morbidity and mortality with no appropriate therapy and vaccine, one must be cautious and do everything to help COVID-19 patients. In hospitals and other health care settings to decrease cross-contamination, holding other non-essential medications is taking place. Discontinuing Vitamins could increase the mortality and morbidity of those affected, especially in deficient/insufficient individuals. Obtaining serum 25 (OH) D levels in all patients with viral respiratory infections, especially COVID-19, could help in the detection and treatment of Vitamin D deficiency and potentially decrease recovery time and improve outcome. Even though evidence suggests that vitamin D has the anti-inflammatory, antiviral properties, randomized double-blinded controlled trials are needed to verify this further, and to understand Vitamin D and COVID-19 better. ABBREVIATIONS: Vitamin D receptor-VDR; 25(OH)D- 25 hydroxyvitamin D; 1,25 (OH)D-1,25 dihydroxy Vitamin D; 1α,25-dihydroxy Vitamin D-1,25[OH]2 D or calcitriol; IU- International Units; Interferons stimulated genes- ISG; ARI- acute respiratory infection; RSV- respiratory syncytial virus; RTI- Respiratory tract infections; COPD-Chronic obstructive pulmonary disease; BMI-Basal metabolic index; USA-USA.

Bacteremia Secondary to Uncommon Gram-Negative Bacilli Transmitted From the Canine in a Patient With Multiple Myeloma.

Sphingobacterium multivorum is a gram-negative rod found in the environment and rarely associated with human infections. Sphingobacterium is the causative agent of infections in an immunocompromised host in most cases. We report a rare case of cellulitis in an immunocompromised host by Sphingobacterium multivorum.

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.

Potential Zoonotic Origins of SARS-CoV-2 and Insights for Preventing Future Pandemics Through One Health Approach.

Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that has resulted in a global pandemic and is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Zoonotic diseases are infections that are transmitted from animals to humans. COVID-19 caused by SARS-CoV-2 most likely originated in bats and transmitted to humans through a possible intermediate host. Based on published research so far, pangolins are considered the most likely intermediate hosts. Further studies are needed on different wild animal species, including pangolins that are sold at the same wet market or similar wet markets before concluding pangolins as definitive intermediate hosts. SARS-CoV-2 is capable of reverse zoonosis as well. Additional research is needed to understand the pathogenicity of the virus, especially in companion animals, modes of transmission, incubation period, contagious period, and zoonotic potential. Interdisciplinary one health approach handles these mosaic issues of emerging threats by integrating professionals from multiple disciplines like human medicine, veterinary medicine, environmental health, and social sciences. Given that the future outbreak of zoonotic diseases is inevitable, importance must be given for swift identification of the pathogen, source, and transmission methods. Countries should invest in identifying the hot spots for the origin of zoonotic diseases, enhance diagnostic capabilities, and rapid containment measures at local, regional, and national levels. The threat posed by emerging infectious diseases in modern-days also needs combined efforts internationally where a single discipline or nation cannot handle the burden alone.

Cannabis Vaping-Induced Acute Pulmonary Toxicity: Case Series and Review of Literature.

The use of cannabis for recreational as well as medicinal use is on the rise recently with more states legalizing it. We conducted a review analysis of the literature published on acute respiratory failure from vaping cannabis oil. We have also summarized the clinical details (age, length of stay, mode of ventilation, common clinical findings, and steroid use) along with common laboratory abnormalities. This article aims to educate health care providers on the clinical manifestations and management strategies for vaping-induced acute respiratory failure. We also discussed the different available formulations of cannabis oil and key ingredients responsible for the vaping-associated lung injury.

COVID-19 in Renal Transplant Patient Presenting With Active Typical Symptoms and Resolved Atypical Symptoms.

The novel coronavirus disease has brought the world to standstill with high infectivity and rapid transmission. The disease caused by novel coronavirus is termed as coronavirus disease 2019 (COVID-19). We present the case of a renal transplant patient who was infected with COVID-19 through community spread and presented with fever and gastrointestinal symptoms. Transplant recipients are particularly vulnerable because of the immunosuppressed state. These patients can shed a virus for a prolonged period and can have a higher load of the virus. There have been no COVID-19 cases transmitted through organ donation. Preinfection immunological impairment can aggravate the severity of the infection. The transplant team plays a crucial role in donor and recipient evaluation and guiding the timing of the transplant. Although specific published data are lacking with regard to transplant recipients, they should follow the same precautions as the general population, like avoiding nonessential travel and practice social distancing.

Acute Kidney Injury in a Case Series of Patients with Confirmed COVID-19 (Coronavirus Disease 2019): Role of Angiotensin-Converting Enzyme 2 and Renin-Angiotensin System Blockade.

The renin-angiotensin system plays a very critical role in hypertension, diabetes, and kidney and heart diseases. The blockade of the renin-angiotensin system results in the prevention of progression of renal and cardiac damage. There have been controversial hypotheses raised regarding the safety of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in COVID-19 (coronavirus disease 2019). We present the case series of four patients (2 men and 2 women; 1 Caucasian and 3 African Americans; two survived and two died) with confirmed COVID-19, presenting with respiratory symptoms and acute kidney injury, who have been on angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Membrane-bound angiotensin-converting enzyme 2 (ACE2) has been implicated as the gateway for viral entry into the human cell in causing the infection. The factors contributing to acute kidney injury are diuretics, iodinated contrast administration, hemodynamic instability apart from ACE inhibitors, and angiotensin receptor blockers. The ACE inhibitors and ARBs were stopped in these patients due to acute kidney injury. We also discussed the role of ACE2 and the renin-angiotensin system (RAS) blockade in patients with COVID-19 infection along with pathogenesis.

Use of Immunotherapy in Extensive-Stage Small Cell Lung Cancer.

Lung cancer is a leading cause of cancer death in the United States and around the world. Approximately 13% of lung cancers are small cell lung cancer (SCLC). SCLC is generally classified as a limited-stage and extensive-stage disease depending on the extent of involvement. For patients with the extensive-stage disease, until recently, chemotherapy alone has been the recommended treatment, although radiotherapy could be used in select patients for palliation of symptoms. The standard of care for extensive-stage SCLC is platinum doublet chemotherapy with either cisplatin or carboplatin in combination with etoposide. Even though first-line therapy has an initial response rate of 60-80%, the prognosis is poor, with overall survival of 10-12 months. The only FDA-approved second line of therapy is topotecan, approved both as an intravenous formulation as well as an oral formulation, with response rates of 6-12% in chemorefractory disease and 15-37% in chemosensitive disease. Immunotherapy has recently been approved as a first-line agent in metastatic SCLC in combination with chemotherapy. It is also approved as a third-line agent in metastatic SCLC after the failure of two chemotherapy regimens. The FDA approved four drugs, two of them being PD-1 inhibitors (pembrolizumab, nivolumab), and two of them being PD-L1 inhibitors (atezolizumab and durvalumab) in SCLC. This review article summarizes the significance of immunotherapy in the treatment of extensive-stage SCLC, its side effects, and limitations.

Cocaine and Alcohol Co-Ingestion-Induced Severe Rhabdomyolysis With Acute Kidney Injury Culminating in Hemodialysis-Dependent End-Stage Renal Disease: A Case Report and Literature Review.

Cocaine toxicity is associated with several organ dysfunctions, including acute kidney injury (AKI). Rhabdomyolysis is the most likely mechanism that mediates AKI, and associated alcohol co-ingestion can amplify the situation. AKI, if severe, can result in end-stage renal disease (ESRD) requiring renal replacement therapy (RRT). All patients with cocaine intoxication should be screened for rhabdomyolysis and AKI along with testing for other drug toxicity, including alcohol. Aggressive measures should be taken to treat the underlying cause that contributes to AKI, and the patients need to be educated about this severe condition. Our patient is a unique case where cocaine and alcohol co-ingestion led to severe rhabdomyolysis, AKI, and subsequently developed ESRD requiring ongoing hemodialysis (HD). He was on daily cocaine and alcohol co-ingestion for seven days and subsequently developed AKI with oliguria from rhabdomyolysis. His creatine kinase (CK) was significantly elevated to 141974 IU/L, and his serum creatinine was 11 mg/dl. Despite aggressive intravenous hydration, his kidney function did not improve, and he ended up needing HD for more than one year despite abstaining from cocaine.