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Background: One of the major indications for digoxin use is the treatment of heart failure [HF]. Although clinical application of digoxin in long-term outcomes in patients with HF and reduced ejection fraction [HFrEF] patients is well explained, the association between digoxin therapy and outcomes in patients with HF and preserved ejection fraction [HFpEF] is not very clear. Objectives: The aim of this study was to show the clinical efficacy of digoxin on long-term outcomes in subjects with HFpEF. Methods: PubMed, Embase, Scopus and Web of Science [ISI] electronic databases were searched until May 2021 to obtain relevant studies. The primary outcome was all-cause mortality attributed to treatment with digoxin. The secondary outcomes were “all-cause hospitalization”, “hospitalization because of HF” and “all-cause mortality or hospitalization of HF”. Results: Seven studies with more than 23000 patients with HFpEF, of which more than 4900 were treated with digoxin, fulfilled the eligibility criteria and were included in this meta-analysis. Treatment with digoxin was associated with a neutral effect on all-cause mortality [HR 1.04, 95 % CI 0.91-1.20, I2 = 57.9 %], all-cause hospitalization [HR 0.97, 95 % CI 0.88-1.07, I2 = 0.0 %], HF-hospitalization [HR 0.96, 95 % CI 0.90-1.02, I2 = 41.4 %], and all-cause mortality or HF-hospitalization [HR 1.07, 95 % CI 0.91-1.26, I2 = 81.2 %]. In subgroup meta-analyses based on ejection fraction [EF] , treatment with digoxin did not significantly alter these outcomes in each subset of patients. Conclusion: The results of this meta-analysis suggest that digoxin does not have any significant effect on long-term outcomes of HFpEF patients, including “all-cause mortality”, “all-cause hospitalization”, “hospitalization because of HF” and “all-cause mortality or hospitalization of HF”.

Abstract: Leptomeningeal disease (LMD) is a rare and lethal manifestation that may occur in the advanced stages of solid tumors and hematological malignancies. With advances in diagnostic techniques, the detection and confirmation of the presence of LMD have increased. Although its optimal treatment remains a challenge, the use of the intrathecal route for the delivery of novel therapeutics is now considered a promising drug delivery strategy to complement radiation and systemic-based therapies. Although methotrexate, cytarabine, and thiotepa have a long history in the treatment of LMD, other medications have also been shown to be beneficial. In this article, we have reviewed the effects of novel medications administered via the intrathecal route for the treatment of solid tumors. We have searched PubMed, Scopus, and Google Scholar databases till the end of September 2021 using the following keywords: ''leptomeningeal disease'', ''leptomeningeal carcinomatosis'', ''leptomeningeal metastases'', ''solid tumors'', ''solid cancers'', and ''intrathecal''. Our literature findings have uncovered that most studies on LMD, which occurs secondary to solid cancers, are available as ‘case reports’, and few clinical trials have been conducted to date. Single-drug (monotherapy) or combination drug therapy, administered via the intrathecal route, especially in metastatic breast and lung cancer, has been shown to improve patients' symptoms and overall lifespan, while exhibiting a low and acceptable prevalence of side effects. However, judgments/conclusions about the effectiveness and safety of these drugs still require further clinical evaluation.

Background: The first case of COVID-19 emerged in China in 2019 and spread rapidly worldwide. Therefore, all researchers worldwide sought ways to treat and prevent the disease. Since the production of vaccines and new drugs is time-consuming, a good way is to look at existing drugs to find new effects. Objective: Due to the pathogenic mechanism of COVID-19, most of its symptoms, including anosmia, ageusia, and cytokine storm, are dependent on the release of histamine and its activities. Therefore, one category of drugs that may be effective in treating and improving the symptoms of COVID-19 is antihistamines. This paper reviewed studies that have been done so far on the effects of antihistamines, specially famotidine, in COVID-19. Method: A literature search was performed using scientific databases such as PubMed, Web of Science, Scopus, and Google Scholar from the beginning up to December 2021. The most relevant articles considering the potential impacts of antihistamines against COVID-19 were collected. Results: In addition to the current medications prescribed for the treatment of SARS-CoV-2, H1 and H2 blockers are promising drugs for repurposing in the COVID-19 remedy. Several studies on famotidine were performed using virtual screening to determine whether they are effective. Many studies have shown that famotidine use improved COVID-19 symptoms and reduced the need for intubation and mortality. However, few studies concluded that famotidine is ineffective. Conclusion: Antihistamines, and specifically famotidine, are effective in reducing COVID-19 symptoms. Therefore, they are a good choice for combination therapy with other drugs to treat COVID-19.

Background Pulmonary hypertension (PH) is a pathophysiological disorder, which involves multiple clinical conditions such as the upregulation of the Rho/ROCK signaling pathway. On the other hand, fasudil as a Rho kinase inhibitor has been investigated in the treatment of PH in some clinical studies. Objectives The present systematic review and meta-analysis aimed to evaluate the human clinical trials regarding the efficacy of fasudil in the management of PH. Methods Databases were searched with pre-defined search terms, up to December 2021. Efficacy measures were such as mean pulmonary arterial pressure (mPAP), systolic PAP (sPAP), pulmonary vascular resistance (PVR), systolic vascular resistance (SVR) and cardiac index (CI). Results A total of 12 studies involving 575 PH patients were included in our research. Eight short-term trials and four mid-term trials were found (no clinical trials on the long-term effects). Short-term trials had a before-after study design and measuring pulmonary hemodynamic parameters’ intervention revealed a statistically significant improvement of mPAP, sPAP, PVR, SVR, and CI in the meta-analysis of five eligible studies. Three mid-term trials also revealed improvement in some pulmonary hemodynamic parameters with fasudil and in another mid-term trial, fasudil significantly decreased rehospitalization and mortality in PH patients. No serious adverse effects with fasudil were reported in these trials. Conclusion Fasudil therapy is efficacious and probably safe in the improvement of some hemodynamics in PH patients along short and mid-term periods. However, long-term randomized controlled trials comparing fasudil with placebo and other treatments are warranted for confirmation of these benefits.

Carbon monoxide (CO) poisoning is a common intoxication and many people die yearly due to CO poisoning and preconditioning agents attenuate brain and cardiac injury caused by intoxication. It is critical to fully understand the efficacy of new methods to directly target the toxic effect of CO, such as conditioning agents, which are currently under development. This study aims to systematically investigate current evidence from animal experiments and the effects of administration preconditions in acute and late phases after CO poisoning on cardiotoxicity and neurotoxicity.Four databases (PubMed, Embase, Scopus, and Web of Science) were systematically searched without language restrictions, and hand searching was conducted until November 2021. We included studies that compare preconditioning agents with the control group after CO poisoning in animals. The SYRCLE RoB tool was used for risk of bias assessments.Thirty-seven studies were included in the study. Erythropoietin, granulocyte colony-stimulating factor (GCSF), hydrogen-rich saline, and N-butylphthalide (NBP) were found to have positive effects on reducing neurotoxicity and cardiotoxicity. As other preconditions have fewer studies, no valuable results can be deduced. Most of the studies were unclear for sources of bias.Administration of the examined preconditioning agents including NBP, hydrogen-rich saline, and GCSF in acute and late phases could attenuate neurotoxicity and cardiotoxicity of CO poisoned animals. For a better understanding of mechanisms and activities, and finding new and effective preconditioning agents, further preclinical and clinical studies should be performed to analyze the effects of preconditioning agents.

Changes in the incidence of bleomycin pulmonary toxicity (BPT) as a result of adding colony-stimulating factors (CSF) to bleomycin regimens has been investigated in numerous studies. We performed a systematic review and meta-analysis to assess the outcomes of these studies.A systematic search was performed using Pubmed, Scopus, Web of Science, and Embase on April 2021. Studies evaluating the incidence of BPT in patients receiving bleomycin with and without CSF were included. In addition, meta-analysis was performed by pooling odds ratios using R.Out of 340 obtained records, our qualitative and quantitative analysis included 3234 and 1956 patients from 22 and 14 studies, respectively. The quantitative synthesis showed that addition of CSF significantly increased the risk of BPT incidence (OR = 1.82, 95 % CI: 1.37-2.40, p 0.0001; I2 = 10.7 %). Subgroup analysis did not show any association between continent, bleomycin dose, cancer type, type of study, and pulmonary function test with BPT incidence.This systematic review and meta-analysis showed that co-administration of CSF with bleomycin increases the incidence of BPT. The physicians need to consider this finding while deciding the best strategy for this cohort of patients.

The viral infection due to the new coronavirus or coronavirus disease 2019 (COVID-19), which was reported for the first time in December 2019, was named by the World Health Organization (WHO) as Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV2), because of the very similar genome and also its related symptoms to SARS-CoV1. The ongoing COVID-19 pandemic with significant mortality, morbidity, and socioeconomic impact is considered by the WHO as a global public health emergency. Since there is no specific treatment available for SARS-CoV2 infection, and or COVID-19, several clinical and sub-clinical studies are currently undertaken to find a gold-standard therapeutic regimen with high efficacy and low side effect. Based on the published scientific evidence published to date, we summarized herein the effects of different potential therapies and up-to-date clinical trials. The review is intended to help readers aware of potentially effective COVID-19 treatment and provide useful references for future studies. Electronic supplementary material The online version of this article (10.1007/s43440-020-00152-9) contains supplementary material, which is available to authorized users.

Background and Aim. Disseminated intravascular coagulation (DIC) is a critical clinical condition that is expressed by systemic activation of the homeostatic system, leading to elevation of thrombin deposition and result in microvascular thrombi. Heparin makes a good effect on hypercoagulability states through inhibition of thrombin. The present study aimed to summarize and discuss the results of randomized clinical trials and cohort studies regarding the effect of heparin and its preparations on DIC mortality and duration of hospitalization. Methods. The databases of PubMed, Scopus, Embase, and Web of Science were searched systematically up to November 2021. The quality of RCTs was assessed by Cochrane Collaboration’s tool and the risk of bias was assessed for cohort studies through NOS score. Results. Out of 3288 articles, eight studies were eligible to be included in this study. Our review retrieved six RCTs and two retrospective cohort studies consisting of 950 participants diagnosed by DIC. A significant effect of heparin on DIC mortality was identified in four studies. Furthermore, heparin was used as a control group in three studies. Conclusions. We concluded that administration of heparin and its preparations in DIC patients could reduce the mortality rate and duration of hospitalization, especially in the earlier stages of DIC.

In this review, the studies in which potential correlation between the area under the curve/minimum inhibitory concentration ratio of vancomycin (AUC/MIC) and its efficacy and safety had been considered, were assessed. Papers that had defined the potential correlation between vancomycin AUC/MIC and its efficacy, safety, or both as a primary outcome were included. Considering that extent of vancomycin exposure as well as susceptibility of microorganisms were both included, AUC/MIC seemed to be a more accurate index than serum trough concentration for predicting vancomycin efficacy. However, data regarding correlation between this index and vancomycin-induced nephrotoxicity are limited. Different breakpoints have been defined for AUC/MIC. The optimized use of vancomycin can improve its efficacy and defer the occurrence of tolerance. Further studies are needed to define optimum vancomycin AUC/MIC breakpoints and in turn predict its efficacy and safety.

SummaryWhat is known and objective Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare and potentially life-threatening drug reaction. Allopurinol is one of the most frequently reported drugs accounting for DRESS syndrome development. In contrast to allopurinol, DRESS syndrome induced by teicoplanin has not been reported frequently. Case description A 50-year-old woman was admitted to receive FLAG chemotherapy regimen (fludarabine, cytarabine (high-dose Ara-C), granulocyte colony-stimulating factor) for relapsed acute lymphoblastic leukaemia (ALL) treatment. Allopurinol was initiated at a dose of 300 mg per day 48 hours before chemotherapy regimen initiation, for tumour lysis syndrome prophylaxis. Seven days after allopurinol initiation, the patient presented with fever, dyspnoea, shortening of breath, facial oedema, generalized pruritus, erythema and macular rash affecting the face, abdomen, trunk, upper and lower limbs and an elevation in hepatic enzymes. Allopurinol was immediately discontinued and intravenous hydrocortisone was started concomitantly alongside other supportive measures. About 72 hours later, pruritus, erythema and rash were ameliorated and abnormalities in liver tests were improved. Afterwards, teicoplanin administration led to severe deterioration of pruritus, erythema and rash; subsequently, serum alanine aminotransferase increased again and episodes of worsening dyspnea occurred. Signs of hypersensitivity reaction were reduced by discontinuation of teicoplanin and supportive care. What is new and conclusion We report a case of allopurinol-induced DRESS syndrome, which was exacerbated by administration of teicoplanin. It can be suggested that the administration of drugs with high possibility of hypersensitivity reactions should be avoided during the acute phase of DRESS syndrome.

Background:Antipsychotic (AP) medications are the cornerstone treatment for schizophrenia and some other psychiatric diseases. However, some observational studies suggest that these medications might increase the risk of venous thromboembolism (VTE) and pulmonary embolism (PE).Objectives:The aim of this study was to assess whether AP medications are associated with the development of VTE or PE, and to assess the risk based on any type of AP drugs, quality of studies and after adjustment of risk factors.Data sources:To identify relevant studies, we searched PubMed and EMBASE databases up to February 2019. We also searched the reference lists of relevant articles for related studies.Study Selection:Twenty studies fulfilled the eligibility criteria and were included in our meta-analysis after screening relevant observational cohort and case-control studies.Primary Outcome:The primary outcome of our meta-analysis was the occurrence of all VTE or PE only attributed to exposure to AP medications compared with non-exposure to AP medications.Results:Exposure to AP drugs was associated with a significant increase in the risk of VTE (RR 1.53, 95% CI 1.30-1.80, I2 = 85%) and PE (RR 3.69, 95% CI 1.23-11.07, I2 = 90%). In the subgroup metaanalysis, the use of low-potency AP drugs was associated with a higher risk of VTE, (RR 1.90, 95% CI 1.04-3.47, I2 = 78%).Conclusion:AP exposure was associated with a 1.5-fold increase in the risk of VTE and a 3.7-fold increase in the risk of PE. Low-potency AP drugs were associated with a higher risk of VTE. However, high heterogeneity among studies limits the generalizability of the results.

Background: Vancomycin is a glycopeptide antibiotic that was extensively used for treatment of gram positive infections. Therapeutic drug monitoring (TDM) is recommended to optimize efficacy and safety of vancomycin. Data regarding TDM of vancomycin are scant in septic patients especially during augmented renal clearance (ARC) phase. Methods: In this observational study, 39 patients with diagnosis of sepsis that were in ARC phase were evaluated. The breakpoint for serum trough level of vancomycin was considered as 15 mg/l. The patients were stratified in two groups based on the measured serum trough levels (< 15 mg/l versus ≥15 mg/l). Results: Clinical response and microbiological clearance were compared between the groups. In terms of clinical response, there was no significant difference between the groups (P = 0.677). Also, the microbiological clearance was not different between the groups (P= 1.00). Conclusion: Septic patients during ARC phase had comparable clinical and microbial responses regardless of serum trough levels of vancomycin.

Glucosamine (GlcN) is an important precursor in the biochemical synthesis of glycosylated proteins and lipids in human body. It gains importance because of its contribution to human health and its multiple biological and therapeutic effects. In this study, the in vitro oxidative hemolysis of rat erythrocyte was used as a model to study the potential protective effect of glucosamine hydrochloride against free radical-induced damage of biological membranes. Glucosamine hydrochloride exhibited dose-dependent DPPH antioxidant activity. Oxidative hemolysis and lipid/protein peroxidation of erythrocytes induced by a water-soluble free radical initiator 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH) were significantly suppressed by GlcN in a time and dose dependent manner. GlcN also prevented the depletion of cytosolic antioxidant glutathione (GSH) in erythrocytes. These results indicated that glucosamine hydrochloride efficiently protected erythrocytes against free radicals and it could be recommended as a pharmaceutical supplement to alleviate oxidative stress.