Management of drug-induced neutropenia, thrombocytopenia, and anaemia after solid organ transplantation: A comprehensive review.

WHAT IS KNOWN AND OBJECTIVE: Advances in the development of more effective immunosuppressive drugs have increased graft survival and drug induced adverse effects. Haematological complications including neutropenia, thrombocytopenia, and anaemia are common side effects that affect the grafts' and patients' outcomes. Several studies have stated the important role of various medications in haematological complications after transplantation. They have reported the incidence and different mechanisms of drug induced cytopenia, as well as an overview of possible treatment modalities. However, there is no comprehensive protocol for the management of these complications following transplantation. This narrative review was performed to develop a comprehensive practical approach for management of drug induced haematological complications following solid organ transplantation. METHOD: PubMed, Embase, Cochrane library, Web of Science, and Google scholar databases were searched without time limitations until March, 2021. In addition, some valid drug information data bases (Uptodate and Micromedex) were searched for detailed information until October, 2021. RESULTS AND DISCUSSION: Several immunosuppressive and antimicrobial medications may induce neutropenia, thrombocytopenia or anaemia following transplantation. Most of these agents cause dose-related cytopenia, which resolves with dose reduction or drug withdrawal. However, any change in medications may result in negative consequences such as severe infections, bleeding, cardiovascular complications, acute allograft rejection, and graft or patient loss. Thus, cautious evaluation of the patient's condition and the pharmacological properties of the culprit medication are required. WHAT IS NEW AND CONCLUSION: Three algorithms are presented to guide healthcare providers in the stepwise management of drug-induced neutropenia, thrombocytopenia, and anaemia after solid organ transplantation.

COVID -19: From the Molecular Mechanisms to Treatment.

The 2019 novel coronavirus (SARS-CoV-2) causes severe pneumonia called COVID-19 and leads to severe acute respiratory syndrome with a high mortality rate. The SARS-CoV-2 virus in the human body leads to jumpstarting immune reactions and multi-organ inflammation, which has poorer outcomes in the presence of predisposing conditions, including hypertension, dyslipidemia, dysglycemia, abnormal adiposity, and even endothelial dysfunction via biomolecular mechanisms. In addition, leucopenia, hypoxemia, and high levels of both cytokines and chemokines in the acute phase of this disease, as well as some abnormalities in chest CT images, were reported in most patients. The spike protein in SARS-CoV-2, the primary cell surface protein, helps the virus anchor and enter the human host cells. Additionally, new mutations have mainly happened for spike protein, which has promoted the infection's transmissibility and severity, which may influence manufactured vaccines' efficacy. The exact mechanisms of the pathogenesis, besides molecular aspects of COVID-19 related to the disease stages, are not well known. The altered molecular functions in the case of immune responses, including T CD4+, CD8+, and NK cells, besides the overactivity in other components and outstanding factors in cytokines like interleukin-2, were involved in severe cases of SARS-CoV-2. Accordingly, it is highly needed to identify the SARSCoV-2 biomolecular characteristics to help identify the pathogenesis of COVID-19. This study aimed to investigate the biomolecular aspects of SARSCoV-2 infection, focusing on novel SARS-CoV-2 variants and their effects on vaccine efficacy.

Antibody-Mediated Rejection in Adult Liver Transplant Recipients: A Case Series and Literature Review.

Antibody-mediated rejection is a rare complication following liver transplantation, and there is a lack of a comprehensive treatment strategy to provide detailed information about the dose and duration of antibody-mediated rejection treatment. This study describes 8 adult liver transplantation recipients who developed antibody-mediated rejection between 2002 and 2021 in our center, as well as a review of the literature on the reported cases of antibody-mediated rejection in liver transplantation recipients. Our center's medical records were reviewed retrospectively to extract the necessary data on patients' characteristics, management, and outcomes. Then, a comprehensive search using Embase, PubMed, Web of Science, Cochrane Library, and Google Scholar databases was conducted without time limitation until June 2021. Finally, a stepwise protocol was developed for managing acute, chronic, and recurrent antibody-mediated rejection in patients undergoing liver transplantation, based on our own experience, reported cases in the literature, and data from kidney transplantation. By review of the literature, 24 case studies containing 64 patients were identified, and their management strategies and outcomes were evaluated. Although various combinations of corticosteroids, plasma exchange, intravenous immunoglobulin, and biological agents are used in the treatment of acute antibody-mediated rejection in liver transplantation, treatment strategies should be classified according to the type, severity, and the timing of its onset. Given the importance of early treatment, rituximab and/or bortezomib should be started as soon as possible if no improvement in liver enzymes/bilirubin is observed during the initial treatment strategy using corticosteroids, plasma exchange, and intravenous immunoglobulin.

The Role of Hydroxychloroquine in COVID-19: A Systematic Review and Meta-Analysis.

OBJECTIVE: A systematic review and meta-analysis was carried out to examine the role of hydroxychloroquine (HCQ) in the treatment of COVID-19. METHODS: We performed a systematic search in PubMed, Scopus, Embase, CochraneLibrary, Web of Science, Google Scholar, and medRxiv pre-print databases using available MeSH terms for COVID-19 and hydroxychloroquine. Data from all studies that focused on the effectiveness of HCQ with or without the addition of azithromycin (AZM) in confirmed COVID-19 patients, which were published up to 12 September 2020, were collated for analysis using CMA v.2.2.064. RESULTS: Our systematic review retrieved 41 studies. Among these, 37 studies including 45,913 participants fulfilled the criteria for subsequent meta-analysis. The data showed no significant difference in treatment efficacy between the HCQ and control groups (RR: 1.02, 95% CI, 0.81-1.27). Combination of HCQ with AZM also did not lead to improved treatment outcomes (RR: 1.26, 95% CI, 0.91-1.74). Furthermore, the mortality difference was not significant, neither in HCQ treatment group (RR: 0.86, 95% CI, 0.71-1.03) nor in HCQ plus AZM treatment group (RR: 1.28, 95% CI, 0.76-2.14) in comparison to controls. Meta-regression analysis showed that age was the factor that significantly affected mortality (P<0.00001). CONCLUSION: The meta-analysis found that there was no clinical benefit of using either HCQ by itself or in combination with AZM for the treatment of COVID-19 patients. Hence, it may be prudent for clinicians and researchers to focus on other therapeutic options that may show greater promise in this disease.

The Effect of Treating Vitamin D Deficiency or Insufficiency on Serum Adiponectin, Leptin and Insulin Resistance of Type 2 Diabetes Mellitus Patients: A Pilot Study.

Vitamin D deficiency is considered as one of the most prevalent healthcare problems in the world. Vitamin D contributes to insulin synthesis and secretion. Deficiency of vitamin D leads to insulin resistance which is the major cause of type 2 diabetes mellitus. We aim to evaluate the effect of treating vitamin D deficiency or insufficiency on serum adiponectin, leptin, and leptin to adiponectin ratio (LAR) of type 2 diabetes mellitus patients. Forty patients with type 2 diabetes mellitus were included according to the inclusion criteria of the study. Fasting venous blood samples were obtained and evaluated before and after the treatment of vitamin D deficiency or insufficiency. Then, blood levels of leptin, adiponectin, and LAR (an indicator of insulin resistance) were measured. The results of study indicate a significant decline in circulating leptin and adiponectin after vitamin D treatment, but it doesn't cause a noteworthy change in LAR. Furthermore, the study demonstrates that female gender, higher body mass index, and triglyceride levels increase LAR significantly. It was concluded that the treatment of vitamin D deficiency or insufficiency doesn't change insulin resistance in diabetic patients. Moreover, we concluded that LAR is not a reliable method to compare insulin resistance between men and women due to sex-related differences in adipose tissue.