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Systemic adverse effects and toxicities associated with immunotherapy: A review

Kichloo, Asim; Albosta, Michael; Dahiya, Dushyant; Guidi, Jean Claude; Aljadah, Michael; Singh, Jagmeet; Shaka, Hafeez; Wani, Farah; Kumar, Akshay; Lekkala, Manidhar
Immunotherapy is rapidly evolving secondary to the advent of newer immunotherapeutic agents and increasing approval of the current agents by the United States Food and Drug Administration to treat a wide spectrum of cancers. Immunotherapeutic agents have gained immense popularity due to their tumor-specific action. Immunotherapy is slowly transforming into a separate therapeutic entity, and the fifth pillar of management for cancers alongside surgery, radiotherapy, chemotherapy, and targeted therapy. However, like any therapeutic entity it has its own adverse effects. With the increasing use of immuno-therapeutic agents, it is vital for physicians to acquaint themselves with these adverse effects. The aim of this review is to investigate the common systemic adverse effects and toxicities associated with the use of different classes of immunotherapeutic agents. We provide an overview of potential adverse effects and toxicities associated with different classes of immunotherapeutic agents organized by organ systems, as well as an extensive discussion of the current recommendations for treatment and clinical trial data. As we continue to see increasing usage of these agents in clinical practice, it is vital for physicians to familiarize themselves with these effects.
PMCID:7968107
PMID: 33767971
ISSN: 2218-4333
CID: 5443782

Emerging therapeutics in the management of COVID-19

Kichloo, Asim; Albosta, Michael; Kumar, Akshay; Aljadah, Michael; Mohamed, Mohamed; El-Amir, Zain; Wani, Farah; Jamal, Shakeel; Singh, Jagmeet; Kichloo, Akif
The severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019, COVID-19) pandemic has placed a tremendous burden on healthcare systems globally. Therapeutics for treatment of the virus are extremely inconsistent due to the lack of time evaluating drug efficacy in clinical trials. Currently, there is a deficiency of published literature that comprehensively discusses all therapeutics being considered for the treatment of COVID-19. A review of the literature was performed for articles related to therapeutics and clinical trials in the context of the current COVID-19 pandemic. We used PubMed, Google Scholar, and Clinicaltrials.gov to search for articles relative to the topic of interest. We used the following keywords: "COVID-19", "therapeutics", "clinical trials", "treatment", "FDA", "ICU", "mortality", and "management". In addition, searches through the references of retrieved articles was also performed. In this paper, we have elaborated on the therapeutic strategies that have been hypothesized or trialed to-date, the mechanism of action of each therapeutic, the clinical trials finished or in-process that support the use of each therapeutic, and the adverse effects associated with each therapeutic. Currently, there is no treatment that has been proven to provide significant benefit in reducing morbidity and mortality. There are many clinical trials for numerous different therapeutic agents currently underway. By looking back and measuring successful strategies from previous pandemics in addition to carrying out ongoing research, we provide ourselves with the greatest opportunity to find treatments that are beneficial.
PMCID:7852573
PMID: 33585175
ISSN: 2220-3249
CID: 5443772

Utilization of extracorporeal membrane oxygenation during the COVID-19 pandemic

Kichloo, Asim; Kumar, Akshay; Amir, Rawan; Aljadah, Michael; Farooqi, Najiha; Albosta, Michael; Singh, Jagmeet; Jamal, Shakeel; El-Amir, Zain; Kichloo, Akif; Lone, Nazir
The ongoing outbreak of severe acute respiratory syndrome coronavirus-2 [SARS-CoV-2, or coronavirus disease 2019 (COVID-19)] was declared a pandemic by the World Health Organization on March 11, 2020. Worldwide, more than 65 million people have been infected with this SARS-CoV-2 virus, and over 1.5 million people have died due to the viral illness. Although a tremendous amount of medical progress has been made since its inception, there continues to be ongoing research regarding the pathophysiology, treatments, and vaccines. While a vast majority of those infected develop only mild to moderate symptoms, about 5% of people have severe forms of infection resulting in respiratory failure, myocarditis, septic shock, or multi-organ failure. Despite maximal cardiopulmonary support and invasive mechanical ventilation, mortality remains high. Extracorporeal membrane oxygenation (ECMO) remains a valid treatment option when maximal conventional strategies fail. Utilization of ECMO in the pandemic is challenging from both resource allocation and ethical standpoints. This article reviews the rationale behind its use, current status of utilization, and future considerations for ECMO in critically ill COVID-19 patients.
PMCID:7805254
PMID: 33505868
ISSN: 2220-3141
CID: 5443762

Effect of Blood Product Transfusion on Perioperative Outcomes After Heart Transplantation

Subramaniam, Kathirvel; Kumar, Akshay; Hernandez, Sergio; Nouraie, Seyed Mehdi
OBJECTIVE(S)/OBJECTIVE:The objective of this study was to identify transfusion-related in-hospital outcomes in orthotopic heart transplantation (OHT) recipients. DESIGN/METHODS:Retrospective chart review. SETTING/METHODS:Tertiary care hospital. PARTICIPANTS/METHODS:Adult OHT recipients undergoing transplantation between January 2010 and December 2016. INTERVENTIONS/METHODS:None. MEASUREMENTS AND MAIN RESULTS/RESULTS:The primary composite outcome was occurrence of any of the following events during admission for OHT: (1) graft dysfunction requiring mechanical circulatory support (MCS); (2) respiratory failure requiring tracheostomy; (3) renal failure requiring hemodialysis; (4) 30-day mortality; (5) complication requiring readmission to intensive care unit; (6) sepsis; and (7) stroke. The authors evaluated these outcomes in relation to all blood component transfusions received intraoperatively and in the first 24 hours postoperatively. The study included 197 patients and the primary composite outcome was present in 72 (36.6%). After adjusting for propensity score, red blood cell (RBC) transfusion was associated with composite outcomes (odds ratio [OR] 1.17, 95% confidence interval [CI] 1.05-1.31, p = 0.004), postoperative MCS use (OR 1.36, 95% CI 1.18-1.58, p < 0.001), acute renal failure requiring hemodialysis (OR 1.21, 5% CI 1.06-1.38, p = 0.004), and 30-day mortality (OR 1.29, 95% CI 1.05-1.59, p = 0.02). Fresh frozen plasma was associated with composite outcome (OR 1.07, 95% CI [1.003-1.15], p = 0.042) and renal failure (OR 1.08, 95% CI 1.08 [1.002-1.17], p = 0.04). CONCLUSIONS:Intra- and postoperative transfusions (first 24 hours) of RBC and FFP were associated with adverse postoperative composite outcomes in patients undergoing OHT.
PMID: 33168431
ISSN: 1532-8422
CID: 5339172

Sudden cardiac death: epidemiology, pathogenesis and management

Kumar, Akshay; Avishay, Dor Mordehay; Jones, Calvin Richard; Shaikh, Juber Dastagir; Kaur, Roopvir; Aljadah, Michael; Kichloo, Asim; Shiwalkar, Nimisha; Keshavamurthy, Suresh
Sudden cardiac death (SCD) is an unexpected sudden death due to a heart condition, that occurs within one hour of symptoms onset. SCD is a leading cause of death in western countries, and is responsible for the majority of deaths from cardiovascular disease. Moreover, SCD accounts for mortality in approximately half of all coronary heart disease patients. Nevertheless, the recent advancements made in screening, prevention, treatment, and management of the underlying causes has decreased this number. In this article, we sought to review established and new modes of screening patients at risk for SCD, treatment and prevention of SCD, and the role of new technologies in the field. Further, we delineate the current epidemiologic trends and pathogenesis. In particular, we describe the advancement in molecular autopsy and genetic testing, the role of target temperature management, extracorporeal membrane oxygenation (ECMO), cardiopulmonary resuscitation (CPR), and transvenous and subcutaneous implantable cardioverter devices (ICDs).
PMID: 33792256
ISSN: 1530-6550
CID: 5339182

Retrograde Intussusception after Roux-en-Y Gastric Bypass [Case Report]

Kumar, Akshay; Ogbonda, Stephanie; Persaud, Purnadeo; Shiwalkar, Nimisha
Retrograde intussusception (RI), although relatively uncommon, has been increasingly seen in adults post Roux-en-Y gastric bypass (RYGB) surgery. The exact mechanism for its occurrence remains unknown but several theories have attributed it to bowel persialtic dysmotility. The increase in bariatric surgery over the last decade has resulted in a proportionate increase in the number of cases of intussusception seen globally. We report a case of RI seven years following RYGB done for morbid obesity.
PMCID:7320641
PMID: 32607307
ISSN: 2168-8184
CID: 5443732

Geriatric Population During the COVID-19 Pandemic: Problems, Considerations, Exigencies, and Beyond

Dhama, Kuldeep; Patel, Shailesh Kumar; Kumar, Rakesh; Rana, Jigyasa; Yatoo, Mohd Iqbal; Kumar, Akshay; Tiwari, Ruchi; Dhama, Jaideep; Natesan, Senthilkumar; Singh, Rajendra; Harapan, Harapan
The coronavirus disease 2019 (COVID-19) pandemic wreaked havoc worldwide, with more than 20 million confirmed cases and nearly 0. 75 million deaths as of 10th August 2020. Various factors determine the severity and symptoms of this infection. Older age and underlying diseases are the challenges being faced in controlling and treating COVID-19. In 2019, 703 million of the global population was older than 65 years of age. The estimated mortality due to COVID-19 in people older than 76 years of age is reportedly 18%. Frequent infections in older people, higher disease severity, and increased mortality are major challenges in the implementation of appropriate preventive measures and future strategies to protect against this disease in geriatric population. Poor health status, weak immune function, lowered organ function, increased probability of multiple underlying diseases, and poor attention to personal health can increase the susceptibility to various diseases in the geriatric population. Concerning inadequate immunity, the decrease expression of receptors and exaggerated pathophysiologic responses can be debilitating. However, future studies will reveal the hidden facets in these aspects in this COVID-19 catastrophe. In this article, we reviewed the main concerns of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the geriatric population, including the risk of acquiring severe COVID-19 resulting in mortality, variation in clinical manifestations, and other pandemic-related concerns. We also discussed the need for increasing attention toward the elderly, taking appropriate prevention and control measures, and considering geriatric-related adjustments in vaccine design and development.
PMCID:7536316
PMID: 33072713
ISSN: 2296-2565
CID: 5443622

Ex Vivo Lung Perfusion: A Review of Research and Clinical Practices

Chan, Patrick G; Kumar, Akshay; Subramaniam, Kathirvel; Sanchez, Pablo G
End-stage lung disease is ultimately treated with lung transplantation. However, there is a paucity of organs with an increasing number of patients being diagnosed with end-stage lung disease. Ex vivo lung perfusion has emerged as a potential tool to assess the quality and to recondition marginal donor lungs prior to transplantation with the goal of increasing the donor pool. This technology has shown promise with similar results compared with the conventional technique of cold static preservation in terms of primary graft dysfunction and overall outcomes. This review provides an update on the results and uses of this technology. The review will also summarize clinical studies and techniques in reconditioning and assessing lungs on ex vivo lung perfusion. Last, we discuss how this technology can be applied to fields outside of transplantation such as thoracic oncology and bioengineering.
PMID: 32036756
ISSN: 1940-5596
CID: 5443602

Is Sexual Route a Matter of Concern for the SARS-CoV-2/COVID-19?

Patel, Shailesh Kumar; Pathak, Mamta; Sah, Ranjit; Kumar, Akshay; Malik, Yashpal Singh; Rodríguez-Morales, Alfonso J; Dhama, Kuldeep
PMCID:7290188
PMID: 32586655
ISSN: 1873-5487
CID: 5443632

Epstein-Barr Virus Versus Novel Coronavirus-Induced Hemophagocytic Lymphohistocytosis: The Uncharted Waters [Case Report]

Amir, Rawan; Kichloo, Asim; Singh, Jagmeet; Bhanot, Ravinder; Aljadah, Michael; Kumar, Akshay; Albosta, Michael Stanley; Solanki, Shantanu
Hemophagocytic lymphohistocytosis (HLH) is a hyperinflammatory syndrome characterized by fever, hepatosplenomegaly, and pancytopenia. It may be associated with genetic mutations or viral/bacterial infections, most commonly Epstein-Barr virus (EBV) and cytomegalovirus. As for the novel coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), also known as COVID-19 (coronavirus disease-2019), the cytokine storm it triggers can theoretically lead to syndromes similar to HLH. In this article, we report a case of a 28-year-old female who presented with high-grade fevers, found to have both SARS-CoV-2 and EBV infections, and eventually began to show signs of early HLH. To our knowledge, this is the first case reported in literature that raises the possibility of SARS-CoV-2-related HLH development.
PMCID:7427003
PMID: 32787459
ISSN: 2324-7096
CID: 5443612