Venu Madhav Konala

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.

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.

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.

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.

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 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-β-thalassemia–related hemoglobinopathies. It is primarily seen in milder versions of sickle cell disease, including HbSC and sickle cell β-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 β-thalassemia with fat embolic syndrome cases have been reported.

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.

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...

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.

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. 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.’ 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. 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.