Statin Therapy and Lipid Indices in Chronic Kidney Disease: A Systematic Review and Meta-analysis of Randomized Control Trials.

BACKGROUND: Several studies have demonstrated the improvement in serum lipoproteins by statins in patients with Chronic Kidney Diseases (CKDs), including End-Stage Renal Disease (ESRD). However, the results of these studies are inconclusive. AIM: We aimed to systematically investigate the effect of statins on lipid profiles of patients with CKD by performing a meta-analysis of Randomized Controlled Trials (RCTs). METHODS: Major electronic databases (Scopus, MEDLINE/PubMed, and ISI Web of Science) were searched from inception to August, 2023, to find randomized controlled trials (RCTs) evaluating the effect of different statins on serum lipoproteins in CKD patients. Weighted Mean Difference (WMD) with 95% Confidence Intervals (CI) was used to estimate the effect size. Trial Sequential Analysis (TSA) was performed to confirm the robustness of the evidence. RESULTS: A total of 18 publications were identified. It was found that statins reduced serum levels of Low-Density Lipoprotein (LDL)-C (WMD = -27.81 mg/dl, 95% CI = -34.47 to -21.15, P < 0.001) and total cholesterol (WMD = -25.44 mg/dl, 95% CI = -34.71 to -16.18, P < 0.001) in patients with CKD compared to the control group. Nonetheless, the effect of statins on High-Density Lipoprotein (HDL)-C (WMD = 0.57 mg/dl, 95% CI = -0.71 to 1.85, P = 0.38) and Triglyceride (TG) (WMD = -9.08 mg/dl, 95% CI = -22.22 to 2.06, P = 0.11) was not statistically significant. The results of TSA confirmed the robustness of the evidence and were consistent with the pooled effect size. The findings of subgroup analysis and time response analysis were also significant. CONCLUSION: It was found that statin therapy reduced the levels of LDL-C and total cholesterol in patients with CKD.

Atorvastatin versus Placebo in ICU Patients with COVID-19: Ninety-day Results of the INSPIRATION-S Trial.

BACKGROUND: In the INSPIRATION-S trial, atorvastatin versus placebo was associated with a nonsignificant 16% reduction in 30-day composite of venous/arterial thrombosis or death in intensive care unit (ICU) patients with COVID-19. Thrombo-inflammatory response in coronavirus disease 2019 (COVID-19) may last beyond the first 30 days. METHODS: This article reports the effects of atorvastatin 20 mg daily versus placebo on 90-day clinical and functional outcomes from INSPIRATION-S, a double-blind multicenter randomized trial of adult ICU patients with COVID-19. The main outcome for this prespecified study was a composite of adjudicated venous/arterial thrombosis, treatment with extracorporeal membrane oxygenation (ECMO), or all-cause mortality. Functional status was assessed with the Post-COVID-19 Functional Scale. RESULTS: In the primary analysis, 587 patients were included (age: 57 [Q1-Q3: 45-68] years; 44% women). By 90-day follow-up, the main outcome occurred in 96 (33.1%) patients assigned to atorvastatin and 113 (38.0%) assigned to placebo (hazard ratio [HR]: 0.80, 95% confidence interval [CI]: 0.60-1.05, p = 0.11). Atorvastatin in patients who presented within 7 days of symptom onset was associated with reduced 90-day hazard for the main outcome (HR: 0.60, 95% CI: 0.42-0.86, p interaction = 0.02). Atorvastatin use was associated with improved 90-day functional status, although the upper bound CI crossed 1.0 (ORordinal: 0.64, 95% CI: 0.41-1.01, p = 0.05). CONCLUSION: Atorvastatin 20 mg compared with placebo did not significantly reduce the 90-day composite of death, treatment with ECMO, or venous/arterial thrombosis. However, the point estimates do not exclude a potential clinically meaningful treatment effect, especially among patients who presented within 7 days of symptom onset (NCT04486508).

Effect of Statins on the Blood Lipid Profile in Patients with Different Cardiovascular Diseases: A Systematic Review with Meta-analysis of Randomized Clinical Trials.

BACKGROUND: Statins are the main lipid-lowering drugs and are used in the prevention of cardiovascular diseases (CVDs). Since the results have been, to some extent, inconsistent in the clinical trials concerning different types of CVDs, a systematic review and meta-analysis was performed to prove the effect of statins on decreasing elevated levels of total cholesterol, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in patients with CVDs. METHODS: Literature search was performed on major electronic databases (MEDLINE/ PubMed, Scopus, and ISI Web of Science) from inception up to July 2021 to find randomized controlled trials (RCTs) evaluating the effect of different statins on different types of CVDs. The effect size was determined using weighted mean difference (WMD) and corresponding 95% confidence interval (CI). RESULTS: Statin therapy significantly decreased levels of total cholesterol (WMD = -33.37 mg/dl, 95% CI: -45.98 to -20.76, P<0.001), LDL-C (WMD = -29.42 mg/dl, 95% CI: -36.81 to -22.03, P<0.001), and TG (WMD = -15.19 mg/dl, 95% CI = -26.41 to -3.97, P<0.001), and increased levels of HDL-C (WMD = 1.55 mg/dl, 95% CI: 0.20, to 2.90, P=0.02) in patients with different CVDs. CONCLUSION: Statin therapy was found effective in lowering levels of total cholesterol, LDL-C, and TG, and increasing levels of HDL-C in patients with different CVDs.

Recent progress in the application of plant-based colloidal drug delivery systems in the pharmaceutical sciences.

The potential for utilizing plant-derived components, such as plant proteins, polysaccharides, lipids, and phospholipids, to create targeted drug delivery systems has been demonstrated in recent years. These colloidal delivery systems can encapsulate, protect, and release pharmaceuticals, vitamins, and nutraceuticals, thereby improving their bioavailability and efficacy. Moreover, they have the potential to reduce the side effects associated with some conventional drug formulations, while still achieving controlled or targeted delivery of pharmaceutical agents by various administration routes, including oral, nasal, dermal and inhalation. The pharmacokinetic and pharmacodynamic profiles of drugs can be modulated by altering the composition, dimensions, and structure of drug formulations created using plant-based colloidal delivery systems. The utilization of plant-derived ingredients may also reduce the environmental impact and improve the sustainability of drug formulations. Initially, we provide an overview of the general characteristics and requirements of drug delivery systems. The opportunities and challenges of using plant-derived components to fabricate colloidal particles for drug delivery applications is then discussed. Finally, potential clinical applications of plant-based delivery drug systems are reviewed.

Datura poisoning in a family: Case series and literature review.

Datura spp. is a potentially poisonous plant that is widely spread and is simply accessible, which can yield poisoning with a central and peripheral anticholinergic effect. We reported cases of family poisoning caused by the herbal tea with refreshing effects that were identified as Datura spp.

Nano-enabled plant-based colloidal delivery systems for bioactive agents in foods: Design, formulation, and application.

Consumers are becoming increasingly aware of the impact of their dietary choices on the environment, animal welfare, and health, which is causing many of them to adopt more plant-based diets. For this reason, many sectors of the food industry are reformulating their products to contain more plant-based ingredients. This article describes recent research on the formation and application of nano-enabled colloidal delivery systems formulated from plant-based ingredients, such as polysaccharides, proteins, lipids, and phospholipids. These delivery systems include nanoemulsions, solid lipid nanoparticles, nanoliposomes, nanophytosomes, and biopolymer nanoparticles. The composition, size, structure, and charge of the particles in these delivery systems can be manipulated to create novel or improved functionalities, such as improved robustness, higher optical clarity, controlled release, and increased bioavailability. There have been major advances in the design, assembly, and application of plant-based edible nanoparticles within the food industry over the past decade or so. As a result, there are now a wide range of different options available for creating delivery systems for specific applications. In the future, it will be important to establish whether these formulations can be produced using economically viable methods and provide the desired functionality in real-life applications.

Effect of Statins on Serum level of hs-CRP and CRP in Patients with Cardiovascular Diseases: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Several studies have reported that statins have anti-inflammatory effects. Nevertheless, results of clinical trials concerning the effect of statins on the levels of C-reactive protein (CRP) and high-sensitivity CRP (hs-CRP) have been inconsistent. Therefore, we performed a systematic review and meta-analysis of randomized clinical trials (RCTs) evaluating the effect of statins on CRP and hs-CRP levels in patients with cardiovascular diseases (CVDs). METHODS: Literature search of the major databases was performed to find eligible RCTs assessing the effect of statins on serum levels of CRP and hs-CRP from the inception until the last week of April 2021. The effect sizes were determined for weighted mean difference (WMD) and 95% confidence intervals (CI). RESULTS: 26 studies were identified (3010 patients and 2968 controls) for hs-CRP and 20 studies (3026 patients and 2968 controls) for CRP. Statins reduced the serum levels of hs-CRP (WMD = -0.97 mg/L; 95% CI: -1.26 to -0.68 mg/L; P < 0.001) and CRP (WMD = -3.05 mg/L; 95% CI: -4.86 to -1.25 mg/L; P < 0.001) in patients with CVDs. Statins decreased the serum levels of hs-CRP in patients receiving both high-intensity and moderate/low-intensity treatments with these drugs. In addition, the duration of treatment longer than 10 weeks decreased hs-CRP levels. Only high-intensity statin treatment could marginally decrease serum levels of CRP in CVDs patients. CONCLUSIONS: This meta-analysis showed the efficacy of statins to reduce the concentrations of CRP and hs-CRP in patients with different types of CVDs.

Efficacy and Safety of the Fixed-Dose Versus Variable-Dose of 4-PCC for Vitamin K Antagonist Reversal: A Comprehensive Systematic Review and Meta-Analysis.

BACKGROUND: The optimal dosing strategy of four-factor prothrombin complex concentrate (4F-PCC) for vitamin K antagonists (VKAs) reversal is unknown. METHODS: We conducted systematic search on the PubMed, SCOPUS, and Embase databases from inception to December 2020 for clinical studies that compared the fixed-dose versus variable-dose of 4-PCC for VKAs reversal with at least one reported clinical outcome. The treatment effects were expressed as relative ratios (RR) with 95% confidence intervals (CIs) and pooled by a random-effects model. RESULTS: Ten studies, including 988 patients, were included. Fixed-dose 4-PCC was associated with lower rate of mortality (RR= 0.65, 95% CI 0.47 to 0.9, p= 0.009), comparable rate of thromboembolic event (TEE) (RR= 1.10, 95%CI 0.44 to 2.80, p= 0.826), and lower goal INR reached (RR= 0.87, 95%CI 0.78 to 0.96, p= 0.007). Less 4-PCC cumulative dose, shorter duration of order-to-needle time, similar hospital length of stay, the comparable time required for INR reversal, higher post-4-PCC INR, and a higher need for additional dose were observed in fixed-dose. CONCLUSIONS: The use of a fixed-dose of 4-PCC may be considered an effective and safe dosing strategy for VKAs reversal in various clinical situations. However, further well-designed, controlled studies should be conducted focusing on clinical outcomes to determine the optimal dose of 4-PCC for VKAs reversal.

Intermediate-Dose versus Standard-Dose Prophylactic Anticoagulation in Patients with COVID-19 Admitted to the Intensive Care Unit: 90-Day Results from the INSPIRATION Randomized Trial.

BACKGROUND: Thrombotic complications are considered among the main extrapulmonary manifestations of coronavirus disease 2019 (COVID-19). The optimal type and duration of prophylactic antithrombotic therapy in these patients remain unknown. METHODS: This article reports the final (90-day) results of the Intermediate versus Standard-dose Prophylactic anticoagulation In cRitically-ill pATIents with COVID-19: An opeN label randomized controlled trial (INSPIRATION) study. Patients with COVID-19 admitted to intensive care were randomized to intermediate-dose versus standard-dose prophylactic anticoagulation for 30 days, irrespective of hospital discharge status. The primary efficacy outcome was a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation (ECMO), or all-cause death. The main safety outcome was major bleeding. RESULTS: Of 600 randomized patients, 562 entered the modified intention-to-treat analysis (median age [Q1, Q3]: 62 [50, 71] years; 237 [42.2%] women), of whom 336 (59.8%) survived to hospital discharge. The primary outcome occurred in 132 (47.8%) of patients assigned to intermediate dose and 130 (45.4%) patients assigned to standard-dose prophylactic anticoagulation (hazard ratio [HR]: 1.21, 95% confidence interval [CI]: 0.95-1.55, p = 0.11). Findings were similar for other efficacy outcomes, and in the landmark analysis from days 31 to 90 (HR: 1.59, 95% CI: 0.45-5.06). There were 7 (2.5%) major bleeding events in the intermediate-dose group (including 3 fatal events) and 4 (1.4%) major bleeding events in the standard-dose group (none fatal) (HR: 1.82, 95% CI: 0.53-6.24). CONCLUSION: Intermediate-dose compared with standard-dose prophylactic anticoagulation did not reduce a composite of death, treatment with ECMO, or venous or arterial thrombosis at 90-day follow-up.

A systematic review and meta-analysis of the impacts of glyphosate on the reproductive hormones.

Worldwide use of glyphosate is constantly increasing and its residues are detected in drinking water, agriculture, and food products. There are controversial data regarding the potential reproductive adverse effects of glyphosate herbicide. Therefore, we conducted a systematic review and meta-analysis on the studies in which the alteration of at least one sexual hormone including testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol was reported as a measured outcome in rats. In November 2020, 284 articles were screened, of which eight were eligible for the meta-analysis. An overall considerable effect of glyphosate exposure was found on decreasing of testosterone (7 studies, WMD = - 1.48 ng/mL; 95% CI, - 2.34 to - 0.61; P = 0.001), LH (3 studies, WMD = - 2.03 mIu/mL; 95% CI, - 3.34 to - 0.71; P = 0.003), and FSH (3 studies, WMD = - 2.28 mIu/mL; 95% CI, - 5.12 to 0.55; P = 0.115). According to our results, glyphosate intake could have major effects on the health of reproductive system. Consequently, strict monitoring of the residual glyphosate content in the drinking water, agricultural crops, and food products is necessary.

Comparing safety of proton-pump inhibitors versus H2-receptor antagonists in kidney transplant recipients: A systematic review and meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: Multiple studies have been conducted to compare the safety of proton-pump inhibitors (PPIs) and H2-receptor antagonists (H2RAs) as acid-suppressive treatment in kidney transplant recipients with conflicting results. This systematic review and meta-analysis aimed to evaluate the risk of adverse effects in kidney transplant patients receiving PPIs compared to those treated with H2RAs. METHODS: A systematic search was performed on the databases from inception to June 2021. The treatment effects were expressed as odds ratio (OR), weighted mean differences (WMD) and their 95% confidence intervals (CI) and pooled by a random-effects model. RESULTS AND DISCUSSIONS: Eight studies, consisting 4,844 patients, were included. Patients were followed for a mean duration of 23.57 months after transplantation. Compared with H2RAs, PPIs exposure was associated with similar rate of biopsy-proven acute rejection (BPAR) (OR = 1.05, 95% CI 0.83-1.34, p = 0.67), mortality (OR = 1.31, 95% CI 0.56-3.07, p = 0.533), graft loss (OR = 1.06, 95% CI 0.59-1.93, p = 0.842), Clostridioides difficile infection (OR = 1.37, 95% CI 0.49-3.85, p = 0.545) and pneumonia (OR = 1.83, 95% CI 0.95-3.52, p = 0.072). The estimated glomerular filtration rate (eGFR) at 12 months was lower in patients who received PPIs than those treated with H2RAs (WMD = -1.01, 95% CI -1.89 to -0.12 ml/min/1.73m2 , p = 0.02). The PPI-treated kidney transplant patients experienced higher rate of antibody-mediated rejection (AMR) (OR = 1.87, 95% CI 1.03-3.04, p = 0.039) and hypomagnesemia (OR = 2.16, 95% CI 1.46-3.20, p Ë‚ 0.001). WHAT IS NEW AND CONCLUSIONS: Compared with H2RAs, PPIs were not associated with higher risks of BPAR, mortality, graft loss or infection-related outcomes. However, taking PPIs was associated with higher rates of AMR and hypomagnesemia, and lower eGFR at one year after transplantation. Further well-controlled studies are needed to assess the impact of acid-suppressive strategy on long-term outcomes in KTRs.

Application of Nanotechnology to Improve the Performance of Biodegradable Biopolymer-Based Packaging Materials.

There is great interest in developing biodegradable biopolymer-based packaging materials whose functional performance is enhanced by incorporating active compounds into them, such as light blockers, plasticizers, crosslinkers, diffusion blockers, antimicrobials, antioxidants, and sensors. However, many of these compounds are volatile, chemically unstable, water-insoluble, matrix incompatible, or have adverse effects on film properties, which makes them difficult to directly incorporate into the packaging materials. These challenges can often be overcome by encapsulating the active compounds within food-grade nanoparticles, which are then introduced into the packaging materials. The presence of these nanoencapsulated active compounds in biopolymer-based coatings or films can greatly improve their functional performance. For example, anthocyanins can be used as light-blockers to retard oxidation reactions, or they can be used as pH/gas/temperature sensors to produce smart indicators to monitor the freshness of packaged foods. Encapsulated botanical extracts (like essential oils) can be used to increase the shelf life of foods due to their antimicrobial and antioxidant activities. The resistance of packaging materials to external factors can be improved by incorporating plasticizers (glycerol, sorbitol), crosslinkers (glutaraldehyde, tannic acid), and fillers (nanoparticles or nanofibers). Nanoenabled delivery systems can also be designed to control the release of active ingredients (such as antimicrobials or antioxidants) into the packaged food over time, which may extend their efficacy. This article reviews the different kinds of nanocarriers available for loading active compounds into these types of packaging materials and then discusses their impact on the optical, mechanical, thermal, barrier, antioxidant, and antimicrobial properties of the packaging materials. Furthermore, it highlights the different kinds of bioactive compounds that can be incorporated into biopolymer-based packaging.

A systematic review and meta-analysis of the impact of cornelian cherry consumption on blood lipid profiles.

Polyphenolic and flavonoid compounds are claimed to improve blood lipid profiles and to provide protective effects against cardiovascular disease. For this reason, we conducted a systematic review and meta-analysis of studies that comprehensively investigated the effects of cornelian cherry supplementation on lipid profiles in rat models. Up to December 2020, 855 articles were screened, and finally, seven articles were selected as eligible for the meta-analysis. This meta-analysis revealed that cornelian cherry supplementation significantly decreased low-density lipoprotein (LDL) (WMD = -6.38 mg/dl; 95% CI, -9.93 to-2.84; p < .001), triglyceride (TG) (WMD = -52.36 mg/dl; 95% CI, -80.50 to -24.22; p < .005), and cholesterol level (WMD = -37.16 mg/dl; 95% CI, -51.19 to -23.13; p < .005) in treated rats compared with control groups. A nonsignificant increase in high-density lipoprotein (HDL) level was observed (WMD = 4.21 mg/dl; 95% CI, -3.25 to 11.66; p = .268). These results suggest that cherry supplementation may have health effects by modifying lipid profiles. However, there is a need for more well-controlled human clinical trials to make more definitive conclusions about the potential health benefits of cherry supplementation.

Association between cumulative rATG induction doses and kidney graft outcomes and adverse effects in kidney transplant patients: a systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis were performed to explore the association between rabbit thymoglobulin (rATG) doses and transplant-related efficacy and safety outcomes. METHODS: We searched PubMed and Scopus databases from inception up to June 2020. The primary efficacy and safety endpoints in kidney transplant recipients were evaluated. RESULTS: Data of 23 cohort studies (3457 patients) and three RCTs (154 patients) were extracted and analyzed. rATG doses of ≤4.5 m/kg was associated with lower rates of biopsy proven acute rejection, cytomegalovirus infection, BK virus infection, and malignancy with a comparable rate of delayed graft function, patients' mortality, and death-censored graft loss compared to rATG total doses of 4.5-6 mg/kg or more than 6 mg/kg. The rATG doses of 3-4.5 mg/kg was associated with better outcomes in dose-response analysis. EXPERT OPINION: Cumulative rATG induction doses as much as 3-4.5 mg/kg is as effective as higher doses regarding to allograft and patient outcomes while minimizing potential adverse effects in kidney transplant recipients.

Treatment of toxoplasmic encephalitis with the combination of clindamycin plus azithromycin in an HIV-infected patient: A case report.

The existence of alternative oral therapies could help clinicians to treat toxoplasmic encephalitis (TE) in the HIV patients. The combination of azithromycin and clindamycin may serve as an effective treatment for TE in HIV-infected patients.

Recent Advances in the Development of Smart and Active Biodegradable Packaging Materials.

Interest in the development of smart and active biodegradable packaging materials is increasing as food manufacturers try to improve the sustainability and environmental impact of their products, while still maintaining their quality and safety. Active packaging materials contain components that enhance their functionality, such as antimicrobials, antioxidants, light blockers, or oxygen barriers. Smart packaging materials contain sensing components that provide an indication of changes in food attributes, such as alterations in their quality, maturity, or safety. For instance, a smart sensor may give a measurable color change in response to a deterioration in food quality. This article reviews recent advances in the development of active and smart biodegradable packaging materials in the food industry. Moreover, studies on the application of these packaging materials to monitor the freshness and safety of food products are reviewed, including dairy, meat, fish, fruit and vegetable products. Finally, the potential challenges associated with the application of these eco-friendly packaging materials in the food industry are discussed, as well as potential future directions.

Effect of Intermediate-Dose vs Standard-Dose Prophylactic Anticoagulation on Thrombotic Events, Extracorporeal Membrane Oxygenation Treatment, or Mortality Among Patients With COVID-19 Admitted to the Intensive Care Unit: The INSPIRATION Randomized Clinical Trial.

Importance: Thrombotic events are commonly reported in critically ill patients with COVID-19. Limited data exist to guide the intensity of antithrombotic prophylaxis. Objective: To evaluate the effects of intermediate-dose vs standard-dose prophylactic anticoagulation among patients with COVID-19 admitted to the intensive care unit (ICU). Design, Setting, and Participants: Multicenter randomized trial with a 2 × 2 factorial design performed in 10 academic centers in Iran comparing intermediate-dose vs standard-dose prophylactic anticoagulation (first hypothesis) and statin therapy vs matching placebo (second hypothesis; not reported in this article) among adult patients admitted to the ICU with COVID-19. Patients were recruited between July 29, 2020, and November 19, 2020. The final follow-up date for the 30-day primary outcome was December 19, 2020. Interventions: Intermediate-dose (enoxaparin, 1 mg/kg daily) (n = 276) vs standard prophylactic anticoagulation (enoxaparin, 40 mg daily) (n = 286), with modification according to body weight and creatinine clearance. The assigned treatments were planned to be continued until completion of 30-day follow-up. Main Outcomes and Measures: The primary efficacy outcome was a composite of venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days, assessed in randomized patients who met the eligibility criteria and received at least 1 dose of the assigned treatment. Prespecified safety outcomes included major bleeding according to the Bleeding Academic Research Consortium (type 3 or 5 definition), powered for noninferiority (a noninferiority margin of 1.8 based on odds ratio), and severe thrombocytopenia (platelet count <20 ×103/µL). All outcomes were blindly adjudicated. Results: Among 600 randomized patients, 562 (93.7%) were included in the primary analysis (median [interquartile range] age, 62 [50-71] years; 237 [42.2%] women). The primary efficacy outcome occurred in 126 patients (45.7%) in the intermediate-dose group and 126 patients (44.1%) in the standard-dose prophylaxis group (absolute risk difference, 1.5% [95% CI, -6.6% to 9.8%]; odds ratio, 1.06 [95% CI, 0.76-1.48]; P = .70). Major bleeding occurred in 7 patients (2.5%) in the intermediate-dose group and 4 patients (1.4%) in the standard-dose prophylaxis group (risk difference, 1.1% [1-sided 97.5% CI, -∞ to 3.4%]; odds ratio, 1.83 [1-sided 97.5% CI, 0.00-5.93]), not meeting the noninferiority criteria (P for noninferiority >.99). Severe thrombocytopenia occurred only in patients assigned to the intermediate-dose group (6 vs 0 patients; risk difference, 2.2% [95% CI, 0.4%-3.8%]; P = .01). Conclusions and Relevance: Among patients admitted to the ICU with COVID-19, intermediate-dose prophylactic anticoagulation, compared with standard-dose prophylactic anticoagulation, did not result in a significant difference in the primary outcome of a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days. These results do not support the routine empirical use of intermediate-dose prophylactic anticoagulation in unselected patients admitted to the ICU with COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04486508.

Pharmacotherapeutic considerations in solid organ transplant patients with COVID-19.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) has spread rapidly worldwide. While there are presently a few case reports/series on COVID-19 amongst solid organ transplant (SOT) patients, there is no official guideline for the management of SOT patients. AREAS COVERED: The authors discuss the pharmacotherapeutic management of SOT patients during the COVID-19 outbreak and provide their expert perspectives. EXPERT OPINION: Prophylactic reduction of immunosuppression because of fear of COVID-19 is not suggested in SOT patients. With maintenance immunosuppressive regimens, corticosteroids can be continued during COVID-19. Continuing other immunosuppressive drugs with lowest effective dose/blood concentration is suggested for patients with mild to moderate COVID-19. Discontinuation of antimetabolites and perhaps inhibitors of mammalian target of rapamycin (mTOR) is suggested in moderate to severe COVID-19. Calcineurin inhibitors (CNIs) may be continued or substituted for mTOR inhibitors with lowest therapeutic concentrations in moderate to severe COVID-19. If continued in patients with COVID-19, therapeutic drug monitoring of CNIs/mTOR inhibitors and appropriate dose reduction is recommended in co-administration with protease inhibitors, hydroxychloroquine/chloroquine, or interleukin (IL)-1/IL-6 receptor antagonists. Complete blood count monitoring is recommended in patients who continue taking antimetabolites or mTOR inhibitors. Dose modification/avoidance should be considered for chloroquine, atazanavir, oseltamivir, ribavirin, anakinra, and Janus associated kinase inhibitors in patients with organ function impairment.

Effects of pre-transplant L-carnitine supplementation on primary graft dysfunction in liver transplant recipients: a pilot, randomized, placebo-controlled clinical trial.

Primary graft dysfunction (PGD) and non-function (PNF) happen in 8.7-24.7% and 0.9-7.2% of liver transplant recipients, respectively. These phenomena increase treatment cost and patients' death. This study assessed the effect of L-carnitine supplementation on the incidences of PNF/PGD in liver transplant recipients. This randomized, placebo-controlled, clinical trial was performed on adult liver transplant recipients. Patients took L-carnitine syrup 500 mg three times daily or placebo from the time of including in transplant waiting list until the day of transplant surgery (median 14 days, 1-192 days). Thirty-three patients in L-carnitine and 39 patients in placebo group completed the study. Although not statistically significant, PNF and PGD happened less frequently among recipients in L-carnitine compared with placebo group (3% vs. 12.8% for PNF; 15.2% vs. 30.8% for PGD). Alanine aminotransferase (ALT) and aspartate aminotransferase were lower in L-carnitine group at day 3 after transplantation. ALT declined more significantly within 48 h after transplantation in L-carnitine arm (median 120.50 vs. 79 IU/L; P = 0.03). One-month patients' survival was significantly higher in L-carnitine versus placebo group (97% vs. 74.4%; P = 0.008). The rates of PNF and PGD in L-carnitine group were approximately one-fourth and one-half of placebo group respectively. One-month patients' survival was higher in L-carnitine group.