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Fungi produce a wide range of secondary metabolites. Some of these metabolites are toxic to humans and cause various health disorders, ranging from acute poisoning to chronic diseases. Contrary to this, some fungal metabolites are valuable sources in therapeutics, such as penicillin. Herein, researchers briefly highlight the role played by different fungal metabolites in human health and diseases and give an overview of the most common fungal genera.

The COVID-19 pandemic and its continuing emerging variants emphasize the need to discover appropriate treatment, where vaccines alone have failed to show complete protection against the new variants of the virus. Therefore, treatment of the infected cases is critical. This paper discusses the bio-guided isolation of three indole diketopiperazine alkaloids, neoechinulin A (1), echinulin (2), and eurocristatine (3), from the Red Sea-derived Aspergillus fumigatus MR2012. Neoechinulin A (1) exhibited a potent inhibitory effect against SARS-CoV-2 Mpro with IC50 value of 0.47 μM, which is comparable to the reference standard GC376. Despite the structural similarity between the three compounds, only 1 showed a promising effect. The mechanism of inhibition is discussed in light of a series of extensive molecular docking, classical and steered molecular dynamics simulation experiments. This paper sheds light on indole diketopiperazine alkaloids as a potential structural motif against SARS-CoV-2 Mpro. Additionally, it highlights the potential of different molecular docking and molecular dynamics simulation approaches in the discrimination between active and inactive structurally related Mpro inhibitors.

SARS-CoV-2 virus mutations might increase its virulence, and thus the severity and duration of the ongoing pandemic. Global drug discovery campaigns have successfully developed several vaccines to reduce the number of infections by the virus. However, finding a small molecule pharmaceutical that is effective in inhibiting SARS-CoV-2 remains a challenge. Natural products are the origin of many currently used pharmaceuticals and, for this reason, a library of in-house fungal extracts were screened to assess their potential to inhibit the main viral protease Mpro in vitro. The extract of Penicillium citrinum, TDPEF34, showed potential inhibition and was further analysed to identify potential Mpro inhibitors. Following bio-guided isolation, a series of benzodiazepine alkaloids cyclopenins with good-to-moderate activity against SARS-CoV-2 Mpro were identified. The mode of enzyme inhibition of these compounds was predicted by docking and molecular dynamic simulation. Compounds 1 (isolated as two conformers of S- and R-isomers), 2, and 4 were found to have promising in vitro inhibitory activity towards Mpro, with an IC50 values range of 0.36–0.89 µM comparable to the positive control GC376. The in silico investigation revealed compounds to achieve stable binding with the enzyme active site through multiple H-bonding and hydrophobic interactions. Additionally, the isolated compounds showed very good drug-likeness and ADMET properties. Our findings could be utilized in further in vitro and in vivo investigations to produce anti-SARS-CoV-2 drug candidates. These findings also provide critical structural information that could be used in the future for designing potent Mpro inhibitors.

SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) is a novel coronavirus strain that emerged at the end of 2019, causing millions of deaths so far. Despite enormous efforts being made through various drug discovery campaigns, there is still a desperate need for treatments with high efficacy and selectivity. Recently, marine sulfated polysaccharides (MSPs) have earned significant attention and are widely examined against many viral infections. This article attempted to produce a comprehensive report about MSPs from different marine sources alongside their antiviral effects against various viral species covering the last 25 years of research articles. Additionally, these reported MSPs were subjected to molecular docking and dynamic simulation experiments to ascertain potential interactions with both the receptor-binding domain (RBD) of SARS CoV-2’s spike protein (S-protein) and human angiotensin-converting enzyme-2 (ACE2). The possible binding sites on both S-protein’s RBD and ACE2 were determined based on how they bind to heparin, which has been reported to exhibit significant antiviral activity against SARS CoV-2 through binding to RBD, preventing the virus from affecting ACE2. Moreover, our modeling results illustrate that heparin can also bind to and block ACE2, acting as a competitor and protective agent against SARS CoV-2 infection. Nine of the investigated MSPs candidates exhibited promising results, taking into consideration the newly emerged SARS CoV-2 variants, of which five were not previously reported to exert antiviral activity against SARS CoV-2, including sulfated galactofucan (1), sulfated polymannuroguluronate (SPMG) (2), sulfated mannan (3), sulfated heterorhamnan (8), and chondroitin sulfate E (CS-E) (9). These results shed light on the importance of sulfated polysaccharides as potential SARS-CoV-2 inhibitors.

Coculture is a productive technique to trigger microbes’ biosynthetic capacity by mimicking the natural habitats’ features principally by competition for food and space and interspecies cross-talks. Mixed cultivation of two Red Sea-derived actinobacteria, Actinokineospora spheciospongiae strain EG49 and Rhodococcus sp. UR59, resulted in the induction of several non-traced metabolites in their axenic cultures, which were detected using LC–HRMS metabolomics analysis. Antimalarial guided isolation of the cocultured fermentation led to the isolation of the angucyclines actinosporins E (1), H (2), G (3), tetragulol (5) and the anthraquinone capillasterquinone B (6), which were not reported under axenic conditions. Interestingly, actinosporins were previously induced when the axenic culture of the Actinokineospora spheciospongiae strain EG49 was treated with signalling molecule N-acetyl-d-glucosamine (GluNAc); this finding confirmed the effectiveness of coculture in the discovery of microbial metabolites yet to be discovered in the axenic fermentation with the potential that could be comparable to adding chemical signalling molecules in the fermentation flask. The isolated angucycline and anthraquinone compounds exhibited in vitro antimalarial activity and good biding affinity against lysyl-tRNA synthetase (PfKRS1), highlighting their potential developability as new antimalarial structural motif.

Marine endophytic fungi from under-explored locations are a promising source for the discovery of new bioactivities. Different endophytic fungi were isolated from plants and marine organisms collected from Wadi El-Natrun saline lakes and the Red Sea near Hurghada, Egypt. The isolated strains were grown on three different media, and their ethyl acetate crude extracts were evaluated for their antimicrobial activity against a panel of pathogenic bacteria and fungi as well as their antioxidant properties. Results showed that most of the 32 fungal isolates initially obtained possessed antimicrobial and antioxidant activities. The most potent antimicrobial extracts were applied to three different cellulose containing fabrics to add new multifunctional properties such as ultraviolet protection and antimicrobial functionality. For textile safety, the toxicity profile of the selected fungal extract was evaluated on human fibroblasts. The 21 strains displaying bioactivity were identified on molecular basis and selected for chemical screening and dereplication, which was carried out by analysis of the MS/MS data using the Global Natural Products Social Molecular Networking (GNPS) platform. The obtained molecular network revealed molecular families of compounds commonly produced by fungal strains, and in combination with manual dereplication, further previously reported metabolites were identified as well as potentially new derivatives.

Microbial co-culture or mixed fermentation proved to be an efficient strategy to expand chemical diversity by the induction of cryptic biosynthetic pathways, and in many cases led to the production of new antimicrobial agents. In the current study, we report a rare example of the induction of silent/cryptic bacterial biosynthetic pathway by the co-culture of Durum wheat plant roots-associated bacterium Pantoea aggolomerans and date palm leaves-derived fungus Penicillium citrinum. The initial co-culture indicated a clear fungal growth inhibition which was confirmed by the promising antifungal activity of the co-culture total extract against Pc. LC-HRMS chemical profiling demonstrated a huge suppression in the production of secondary metabolites (SMs) of axenic cultures of both species with the emergence of new metabolites which were dereplicated as a series of siderophores. Large-scale co-culture fermentation led to the isolation of two new pulicatin derivatives together with six known metabolites which were characterised using HRESIMS and NMR analyses. During the in vitro antimicrobial evaluation of the isolated compounds, pulicatin H (2) exhibited the strongest antifungal activity against Pc, followed by aeruginaldehyde (1) and pulicatin F (4), hence explaining the initial growth suppression of Pc in the co-culture environment.

Natural compounds like pterostilbene (PTE) have gained recognition for their various biological activities and potential health benefits. However, challenges related to bioavailability and limited clinical efficacy have prompted efforts to strengthen their therapeutic potential. To meet these challenges, we herein rationally designed and successfully synthesized a pharmaceutical phosphoramidite that allows for the programmable incorporation of PTE into oligonucleotides. The resultant aptamer-PTE conjugate can selectively bind to cancer cells, leading to a specific internalization and drug release. Moreover, compared with free PTE, the conjugate exhibits superior cytotoxicity in cancer cells. Specifically, in a zebrafish xenograft model, the nanomedicine effectively inhibits tumor growth and neovascularization, highlighting its potential for targeted antitumor therapy. This approach presents a promising avenue for harnessing the therapeutic potential of natural compounds via a nanomedicine solution.

Background: Real-world data on atrial fibrillation (AF) ablation outcomes in obese populations have remained scarce, especially the relationship between obesity and in-hospital AF ablation outcome., Hypothesis: Obesity is associated with higher complication rates and higher admission trend for AF ablation., Methods: We drew data from the US National Inpatient Sample to identify patients who underwent AF ablation between 2005 and 2018. Sociodemographic and patients' characteristics data were collected, and the trend, incidence of catheter ablation complications and mortality were analyzed, and further stratified by obesity classification., Results: A total of 153 429 patients who were hospitalized for AF ablation were estimated. Among these, 11 876 obese patients (95% confidence interval [CI]: 11 422-12 330) and 10 635 morbid obese patients (95% CI: 10 200-11 069) were observed. There was a substantial uptrend admission, up to fivefold, for AF ablation in all obese patients from 2005 to 2018 (p < .001). Morbidly obese patients were statistically younger, while coexisting comorbidities were substantially higher than both obese and nonobese patients (p < .01) Both obesity and morbid obesity were significantly associated with an increased risk of total bleeding, and vascular complications (p < .05). Only morbid obesity was significantly associated with an increased risk of ablation-related complications, total infection, and pulmonary complications (p < .01). No difference in-hospital mortality was observed among obese, morbidly obese, and nonobese patients., Conclusion: Our study observed an uptrend in the admission of obese patients undergoing AF ablation from 2005 through 2018. Obesity was associated with higher ablation-related complications, particularly those who were morbidly obese., (© 2022 The Authors. Clinical Cardiology published by Wiley Periodicals, LLC.)

Introduction: Real-world data on atrial fibrillation (AF) ablation among moderate and advanced chronic kidney disease (CKD) patients have so far remained scarce, especially in-hospital AF ablation outcomes., Methods: We drew data from the US National Inpatient Sample to identify hospitalized patients who underwent AF ablation between 2005 and 2018, and further stratified by CKD classification. We assessed the trend of AF ablation, as well as its complications., Results: A total of 152 630 patients who were primarily hospitalized for AF and underwent ablation were estimated. Among these, CKD patients were found in a total of 1509 participants, with 978, 206, and 325 under CKD3, CKD4, and CKD5/ESKD, respectively. There was a significant increment in admission rates for AF ablation in the CKD population across all CKD classifications (p < .001). All CKD patients were statistically older, with higher coexisting comorbidities, while hypertension was found substantially lower than non-CKD patients (p ≤ .001). Importantly, CKD, especially CKD3 and CKD5/ESKD, was significantly associated with an increased risk of total complications, and total bleeding, Neurological complications were found statistically lower in CKD patients (p = .029), and no mortality rates were significantly different (p = .287)., Conclusion: Our study observed an increase in admission trends for AF ablation among moderate and advanced CKD patients from 2005 to 2018. CKD was strongly associated with higher procedure-related complications and bleeding, but neurological safety profiles and mortalities rates were nonsignificantly different., (© 2022 Wiley Periodicals LLC.)

Background: We aimed to determine the optimal range of discharge serum magnesium in hospitalized patients by evaluating one-year mortality risk according to discharge serum magnesium., Methods: This was a single-center cohort study of hospitalized adult patients who survived until hospital discharge. We classified discharge serum magnesium, defined as the last serum magnesium within 48 hours of hospital discharge, into ≤1.6, 1.7-1.8, 1.9-2.0, 2.1-2.2, and ≥2.3 mg/dL. We assessed one-year mortality risk after hospital discharge based on discharge serum magnesium, using discharge magnesium of 2.1-2.2 mg/dL as the reference group., Results: Of 39,193 eligible patients, 8%, 23%, 34%, 23%, and 12% had a serum magnesium of ≤1.6, 1.7-1.8, 1.9-2.0, 2.1-2.2, and ≥2.3 mg/dL, respectively, at hospital discharge. After the adjustment for several confounders, discharge serum magnesium of ≤1.6, 1.7-1.8, and ≥2.3 mg/dL were associated with higher one-year mortality with hazard ratio of 1.35 (95% CI 1.21-1.50), 1.14 (95% CI 1.06-1.24), and 1.17 (95% CI 1.07-1.28), respectively, compared to discharge serum magnesium of 2.1-2.2 mg/dL. There was no significant difference in one-year mortality between patients with discharge serum magnesium of 1.9-2.0 and 2.1-2.2 mg/dL., Conclusion: The optimal range of serum magnesium at discharge was 1.9-2.2 mg/dL. Both hypomagnesemia and hypermagnesemia at discharge were associated with higher one-year mortality.

Background: We aimed to report the incidence of hospital-acquired hypophosphataemia and hyperphosphataemia along with their associated in-hospital mortality., Methods: We included 15 869 adult patients hospitalised at a tertiary medical referral centre from January 2009 to December 2013, who had normal serum phosphate levels at admission and at least two serum phosphate measurements during their hospitalisation. The normal range of serum phosphate was defined as 2.5-4.2 mg/dL. In-hospital serum phosphate levels were categorised based on the occurrence of hospital-acquired hypophosphataemia and hyperphosphataemia. We analysed the association of hospital-acquired hypophosphataemia and hyperphosphataemia with in-hospital mortality using multivariable logistic regression., Results: Fifty-three per cent (n=8464) of the patients developed new serum phosphate derangements during their hospitalisation. The incidence of hospital-acquired hypophosphataemia and hyperphosphataemia was 35% and 27%, respectively. Hospital-acquired hypophosphataemia and hyperphosphataemia were associated with odds ratio (OR) of 1.56 and 2.60 for in-hospital mortality, respectively (p value<0.001 for both). Compared with patients with persistently normal in-hospital phosphate levels, patients with hospital-acquired hypophosphataemia only (OR 1.64), hospital-acquired hyperphosphataemia only (OR 2.74) and both hospital-acquired hypophosphataemia and hyperphosphataemia (ie, phosphate fluctuations; OR 4.00) were significantly associated with increased in-hospital mortality (all p values <0.001)., Conclusion: Hospital-acquired serum phosphate derangements affect approximately half of the hospitalised patients and are associated with increased in-hospital mortality rate., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Acute kidney injury (AKI) is a common and severe complication after left ventricular assist device (LVAD) implantation with an incidence of 37%; 13% of which require kidney replacement therapy (KRT). Severe AKI requiring KRT (AKI-KRT) in LVAD patients is associated with high short and long-term mortality compared with AKI without KRT. While kidney function recovery is associated with better outcomes, its incidence is unclear among LVAD patients with severe AKI requiring KRT., Aim: To identify studies evaluating the recovery rates from severe AKI-KRT after LVAD placement, which is defined by regained kidney function resulting in the discontinuation of KRT. Random-effects and generic inverse variance method of DerSimonian-Laird were used to combine the effect estimates obtained from individual studies., Methods: A total of 268 patients from 14 cohort studies that reported severe AKI-KRT after LVAD were included. Follow-up time ranged anywhere from two weeks of LVAD implantation to 12 mo. Kidney recovery occurred in 78% of enrollees at the time of hospital discharge or within 30 d. Overall, the pooled estimated AKI recovery rate among patients with severe AKI-KRT was 50.5% (95%CI: 34.0%-67.0%) at 12 mo follow up. Majority (85%) of patients used continuous-flow LVAD. While the data on pulsatile-flow LVAD was limited, subgroup analysis of continuous-flow LVAD demonstrated that pooled estimated AKI recovery rate among patients with severe AKI-KRT was 52.1% (95%CI: 36.8%-67.0%). Meta-regression analysis did not show a significant association between study year and AKI recovery rate ( P = 0.08). There was no publication bias as assessed by the funnel plot and Egger's regression asymmetry test in all analyses., Results: A total of 268 patients from 14 cohort studies that reported severe AKI-KRT after LVAD were included. Follow-up time ranged anywhere from two weeks of LVAD implantation to 12 mo. Kidney recovery occurred in 78% of enrollees at the time of hospital discharge or within 30 d. Overall, the pooled estimated AKI recovery rate among patients with severe AKI-KRT was 50.5% (95%CI: 34.0%-67.0%) at 12 mo follow up. Majority (85%) of patients used continuous-flow LVAD. While the data on pulsatile-flow LVAD was limited, subgroup analysis of continuous-flow LVAD demonstrated that pooled estimated AKI recovery rate among patients with severe AKI-KRT was 52.1% (95%CI: 36.8%-67.0%). Meta-regression analysis did not show a significant association between study year and AKI recovery rate ( P = 0.08). There was no publication bias as assessed by the funnel plot and Egger's regression asymmetry test in all analyses., Conclusion: Recovery from severe AKI-KRT after LVAD occurs approximately 50.5%, and it has not significantly changed over the years despite advances in medicine., Competing Interests: Conflict-of-interest statement: The authors declared no potential conflicts of interest., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective : Acute kidney injury (AKI) is associated with higher morbidity and mortality in cardiac arrest (CA). There are limited contemporary data on the incidence and outcomes of AKI in CA. Methods : We comprehensively searched the databases of MEDLINE, EMBASE, PUBMED, and the Cochrane from inception to November 2020. Observational studies that reported the incidence of AKI in CA survivors were included. Data from each study were combined using the random effects to calculate pooled incidence and risk ratios with 95% confidence intervals (CIs). The primary outcome was short-term mortality and secondary outcomes included long-term mortality, incidence of AKI, and use of renal replacement therapy (RRT). Subgroup and meta-regression analyses were performed to explore heterogeneity. Main results : A total of 25 observational studies comprising 8,165 patients were included. The incidence of AKI in CA survivors was 40.3% (range 32.9-47.8%). In stage 3 AKI, one-fourth of patients required RRT. AKI was associated with an increased risk of both short-term (OR 2.27 [95% CI 1.74-2.96]; p < 0.001) and long-term mortality (OR 1.51 [95% CI 1.93-3.25]; p < 0.001). Meta-regression and subgroup analyses did not suggest any effect of hypothermia on incidence of AKI. Conclusion : AKI complicates the care of 40% of CA survivors and is associated with significantly increased short- and long-term mortality.

Background The presence of atrial fibrillation (AF) in patients with heart failure with preserved ejection fraction (HFpEF) dramatically increases higher morbidity and mortality. Recent studies have suggested that early rhythm control may alleviate the burden of poor outcomes. Currently, there remain limited data on whether rhythm or rate control has better efficacy. This study sought to compare both strategies in HFpEF patients with AF. Methods Databases were searched throughout 2020. Studies that reported cardiovascular outcomes amongst HFpEF patients with AF who received either rhythm or rate control were included. Estimates of the effects from the individual studies were extracted and combined using random-effects, a generic inverse variance method of DerSimonian and Laird. Results Five observational studies were included in the analysis, consisting of 16,953 patients, 13.8% of whom were receiving rhythm control. In comparison with rate control, rhythm control was associated with decreased overall mortality rates (pooled RR 0.85, 95% CI 0.75-0.95, with I 2 = 0%, p value = 0.009). Conclusions In HFpEF patients with AF, rhythm control was associated with lower mortality, compared to rate control. Further studies are warranted to validate our observation.

Background: Many studies have demonstrated an association between type 2 diabetes mellitus (T2DM) and atrial fibrillation (AF). However, the potential independent contributions of T2DM and AF to the prevalence of visual impairment have not been evaluated., Aim: To determine whether such an association between T2DM and incident AF with visual impairment exists, and if so, the prevalence and magnitude of this association., Methods: We conducted a nationwide cross-sectional study based on the DM/HT study of the Medical Research Network of the Consortium of Thai Medical Schools. This study had evaluated adult T2DM patients from 831 public hospitals in Thailand in the year 2013. T2DM patients were categorized into two groups: patients without and with incident AF. T2DM patients without AF were selected as the reference group. The association between incident AF and visual impairment among T2DM patients was assessed using multivariate logistic regression., Results: A total of 27281 T2DM patients with available eye examination data were included in this analysis. The mean age was 60.7 ± 10.5 years, and 31.2% were male. The incident AF was 0.2%. The prevalence of severe visual impairment in all T2DM patients, T2DM patients without AF, and T2DM patients with incident AF were 1.4%, 1.4%, and 6.3%, respectively. T2DM patients with incident AF were associated with an increased OR of 3.89 (95%CI: 1.17-13.38) for severe visual impairment compared with T2DM patients without AF., Conclusion: T2DM patients with incident AF were independently associated with increased severe visual impairment. Therefore, early eye screening should be provided for these high-risk individuals., Competing Interests: Conflict-of-interest statement: The authors deny any conflict of interest., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: This study aimed to 1) determine the incidence of acute kidney injury (AKI), 2) identify risk factors for AKI, and 3) evaluate the impact of AKI on in-hospital outcomes in hospitalized patients for methanol intoxication., Methods: We searched the National Inpatient Sample Database for hospitalized patients from 2003 to 2014 with a primary diagnosis of methanol intoxication. We excluded patients with end-stage kidney disease. We identified the AKI using a discharge diagnosis code. We compared clinical characteristics, in-hospital treatment, outcomes, and resource use between AKI and non-AKI patients., Results: A total of 603 hospital admissions for methanol intoxication were analyzed. AKI developed in 135 (22.4%) admissions. Anemia (OR 3.43 p < 0.001), hypertension (OR 1.86; p = 0.02), volume depletion (OR 3.46; p = 0.001), sepsis (OR 6.91; p < 0.001), rhabdomyolysis (OR 6.25; p = 0.003), and acute pancreatitis (OR 5.30; p = 0.004) were independent risk factors for AKI development. AKI was significantly associated with increased risk of in-hospital mortality and organ failure. AKI patients needed more mechanical ventilation, and extracorporeal therapy, had longer length of hospital stay, and higher hospitalization costs., Conclusion: Over one-fifth of methanol intoxication patients developed AKI during hospitalization. AKI was associated with higher morbidity, mortality, and resource utilization.

Background: Chronic kidney disease (CKD) is a common medical condition that is increasing in prevalence. Existing published evidence has revealed through regression analyses that several clinical characteristics are associated with mortality in CKD patients. However, the predictive accuracies of these risk factors for mortality have not been clearly demonstrated., Aim: To demonstrate the accuracy of mortality predictive factors in CKD patients by utilizing the area under the receiver operating characteristic (ROC) curve (AUC) analysis., Methods: We searched Ovid MEDLINE, EMBASE, and the Cochrane Library for eligible articles through January 2021. Studies were included based on the following criteria: (1) Study nature was observational or conference abstract; (2) Study populations involved patients with non-transplant CKD at any CKD stage severity; and (3) Predictive factors for mortality were presented with AUC analysis and its associated 95% confidence interval (CI). AUC of 0.70-0.79 is considered acceptable, 0.80-0.89 is considered excellent, and more than 0.90 is considered outstanding., Results: Of 1759 citations, a total of 18 studies ( n = 14579) were included in this systematic review. Eight hundred thirty two patients had non-dialysis CKD, and 13747 patients had dialysis-dependent CKD (2160 patients on hemodialysis, 370 patients on peritoneal dialysis, and 11217 patients on non-differentiated dialysis modality). Of 24 mortality predictive factors, none were deemed outstanding for mortality prediction. A total of seven predictive factors [N-terminal pro-brain natriuretic peptide (NT-proBNP), BNP, soluble urokinase plasminogen activator receptor (suPAR), augmentation index, left atrial reservoir strain, C-reactive protein, and systolic pulmonary artery pressure] were identified as excellent. Seventeen predictive factors were in the acceptable range, which we classified into the following subgroups: predictors for the non-dialysis population, echocardiographic factors, comorbidities, and miscellaneous., Conclusion: Several factors were found to predict mortality in CKD patients. Echocardiography is an important tool for mortality prognostication in CKD patients by evaluating left atrial reservoir strain, systolic pulmonary artery pressure, diastolic function, and left ventricular mass index., Competing Interests: Conflict-of-interest statement: The authors have declared no potential conflicts of interest., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Focal segmental glomerulosclerosis (FSGS) is one of the most common glomerular diseases leading to renal failure. FSGS has a high risk of recurrence after kidney transplantation. Prevention of recurrent FSGS using rituximab and/or plasmapheresis has been evaluated in multiple small studies with conflicting results., Aim: To assess the risk of recurrence of FSGS after transplantation using prophylactic rituximab with or without plasmapheresis, and plasmapheresis alone compared to the standard treatment group without preventive therapy., Methods: This meta-analysis and systematic review were performed by first conducting a literature search of the MEDLINE, EMBASE, and Cochrane databases, from inception through March 2021; search terms included 'FSGS,' 'steroid-resistant nephrotic syndrome', 'rituximab,' and 'plasmapheresis,'. We identified studies that assessed the risk of post-transplant FSGS after use of rituximab with or without plasmapheresis, or plasmapheresis alone. Inclusion criteria were: Original, published, randomized controlled trials or cohort studies (either prospective or retrospective), case-control, or cross-sectional studies; inclusion of odds ratio, relative risk, and standardized incidence ratio with 95% confidence intervals (CI), or sufficient raw data to calculate these ratios; and subjects without interventions (controls) being used as comparators in cohort and cross-sectional studies. Effect estimates from individual studies were extracted and combined using a random effects model., Results: Eleven studies, with a total of 399 kidney transplant recipients with FSGS, evaluated the use of rituximab with or without plasmapheresis; thirteen studies, with a total of 571 kidney transplant recipients with FSGS, evaluated plasmapheresis alone. Post-transplant FSGS recurred relatively early. There was no significant difference in recurrence between the group that received rituximab (with or without plasmapheresis) and the standard treatment group, with a pooled risk ratio of 0.82 (95%CI: 0.47-1.45, I 2 = 65%). Similarly, plasmapheresis alone was not associated with any significant difference in FSGS recurrence when compared with no plasmapheresis; the pooled risk ratio was 0.85 (95%CI: 0.60-1.21, I 2 = 23%). Subgroup analyses in the pediatric and adult groups did not yield a significant difference in recurrence risk. We also reviewed and analyzed post-transplant outcomes including timing of recurrence and graft survival., Conclusion: Overall, the use of rituximab with or without plasmapheresis, or plasmapheresis alone, is not associated with a lower risk of FSGS recurrence after kidney transplantation. Future studies are required to assess the effectiveness of rituximab with or without plasmapheresis among specific patient subgroups with high-risk for FSGS recurrence., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to declare., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Very-low-carbohydrate diets or ketogenic diets are frequently used for weight loss in adults and as a therapy for epilepsy in children. The incidence and characteristics of kidney stones in patients on ketogenic diets are not well studied. Methods: A systematic literature search was performed, using MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews from the databases' inception through April 2020. Observational studies or clinical trials that provide data on the incidence and/or types of kidney stones in patients on ketogenic diets were included. We applied a random-effects model to estimate the incidence of kidney stones. Results: A total of 36 studies with 2795 patients on ketogenic diets were enrolled. The estimated pooled incidence of kidney stones was 5.9% (95% CI, 4.6-7.6%, I2 = 47%) in patients on ketogenic diets at a mean follow-up time of 3.7 +/- 2.9 years. Subgroup analyses demonstrated the estimated pooled incidence of kidney stones of 5.8% (95% CI, 4.4-7.5%, I2 = 49%) in children and 7.9% (95% CI, 2.8-20.1%, I2 = 29%) in adults, respectively. Within reported studies, 48.7% (95% CI, 33.2-64.6%) of kidney stones were uric stones, 36.5% (95% CI, 10.6-73.6%) were calcium-based (CaOx/CaP) stones, and 27.8% (95% CI, 12.1-51.9%) were mixed uric acid and calcium-based stones, respectively. Conclusions: The estimated incidence of kidney stones in patients on ketogenic diets is 5.9%. Its incidence is approximately 5.8% in children and 7.9% in adults. Uric acid stones are the most prevalent kidney stones in patients on ketogenic diets followed by calcium-based stones. These findings may impact the prevention and clinical management of kidney stones in patients on ketogenic diets.

Background: This study aimed to determine the incidence, as well as evaluate risk factors, and impact of gastrointestinal bleeding on outcomes and resource use in patients admitted for salicylate poisoning., Methods: We used the National Inpatient Sample to construct a cohort of patients hospitalized primarily for salicylate poisoning from 2003 to 2014. We compared clinical characteristics, in-hospital treatments, outcomes and resource use between salicylate poisoning patients with and without gastrointestinal bleeding., Results: Of 13 805 hospital admissions for salicylate poisoning, gastrointestinal bleeding occurred in 482 (3.5%) admissions. The risk factors for gastrointestinal bleeding included older age, history of atrial fibrillation and cirrhosis. After adjusting for difference in baseline characteristics, patients with gastrointestinal bleeding required more gastric lavage, gastrointestinal endoscopy, invasive mechanical ventilation and red blood cell transfusion. Gastrointestinal bleeding was significantly associated with increased risk of anemia, circulatory, liver and hematological failure but was not significantly associated with increased in-hospital mortality. The length of hospital stay and hospitalization cost was significantly higher in patients with gastrointestinal bleeding., Conclusion: Gastrointestinal bleeding occurred in about 4% of patients admitted for salicylate poisoning. Gastrointestinal bleeding was associated with higher morbidity and resource use but not mortality., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: This study aimed to determine the rates of inpatient palliative care service use and assess the impact of palliative care service use on in-hospital treatments and resource utilization in hospital admissions for hepatorenal syndrome. Methods: Using the National Inpatient Sample, hospital admissions with a primary diagnosis of hepatorenal syndrome were identified from 2003 through 2014. The primary outcome of interest was the temporal trend and predictors of inpatient palliative care service use. Logistic and linear regression was performed to assess the impact of inpatient palliative care service on in-hospital treatments and resource use. Results: Of 5571 hospital admissions for hepatorenal syndrome, palliative care services were used in 748 (13.4%) admissions. There was an increasing trend in the rate of palliative care service use, from 3.3% in 2003 to 21.1% in 2014 ( p < 0.001). Older age, more recent year of hospitalization, acute liver failure, alcoholic cirrhosis, and hepatocellular carcinoma were predictive of increased palliative care service use, whereas race other than Caucasian, African American, and Hispanic and chronic kidney disease were predictive of decreased palliative care service use. Although hospital admission with palliative care service use had higher mortality, palliative care service was associated with lower use of invasive mechanical ventilation, blood product transfusion, paracentesis, renal replacement, vasopressor but higher DNR status. Palliative care services reduced mean length of hospital stay and hospitalization cost. Conclusion: Although there was a substantial increase in the use of palliative care service in hospitalizations for hepatorenal syndrome, inpatient palliative care service was still underutilized. The use of palliative care service was associated with reduced resource use.

Objective: Cannabis is the most commonly used recreational drug in the United States, and transplant acceptability for cannabis using candidates varies among transplant centers. However, the prevalence and impact of cannabis use on outcomes of kidney transplant recipients remain unclear. This study aimed to summarize the prevalence and impact of cannabis use on outcomes after kidney transplantation., Methods: A literature search was performed using Ovid MEDLINE, EMBASE, and The Cochrane Library Databases from inception until September 2019 to identify studies assessing the prevalence of cannabis use among kidney transplant recipients, and reported adverse outcomes after kidney transplantation. Effect estimates from the individual studies were obtained and combined utilizing random-effects, generic inverse variance method of DerSimonian-Laird., Results: A total of four cohort studies with a total of 55 897 kidney transplant recipients were enrolled. Overall, the pooled estimated prevalence of cannabis use was 3.2% (95% CI 0.4%-20.5%). While the use of cannabis was not significantly associated with all-cause allograft failure (OR = 1.31, 95% CI 0.70-2.46) or mortality (OR = 1.52, 95% CI 0.59-3.92), the use of cannabis among kidney transplant recipients was significantly associated with increased death-censored graft failure with pooled OR of 1.72 (95% CI 1.13-2.60)., Conclusions: The overall estimated prevalence of cannabis use among kidney transplant recipients is 3.2%. The use of cannabis is associated with increased death-censored graft failure, but not mortality after kidney transplantation., (© 2020 Chinese Cochrane Center, West China Hospital of Sichuan University and John Wiley & Sons Australia, Ltd.)

Background : Antidepressants are one of the most prescribed medications, particularly for patients with mental disorders. Nevertheless, there are still limited data regarding the risk of ventricular arrhythmia (VA) and sudden cardiac death (SCD) associated with these medications. Thus, we performed systemic review and meta-analysis to characterize the risks of VA and SCD among patients who used common antidepressants. Methods: A literature search for studies that reported risk of ventricular arrhythmias and sudden cardiac death in antidepressant use from MEDLINE, EMBASE, and Cochrane Database from inception through September 2020. A random-effects model network meta-analysis model was used to analyze the relation between antidepressants and VA/SCD. Surface Under Cumulative Ranking Curve (SUCRA) was used to rank the treatment for each outcome. Results: The mean study sample size was 355,158 subjects. Tricyclic antidepressant (TCA) patients were the least likely to develop ventricular arrhythmia events/sudden cardiac deaths at OR 0.24, 0.028-1.2, OR 0.32 (95% CI 0.038-1.6) for serotonin and norepinephrine reuptake inhibitors (SNRI), and OR 0.36 (95% CI 0.043, 1.8) for selective serotonin reuptake inhibitors (SSRI), respectively. According to SUCRA analysis, TCA was on a higher rank compared to SNRI and SSRI considering the risk of VA/SCD. Conclusion: Our network meta-analysis demonstrated the low risk of VA/SCD among patients using antidepressants for SNRI, SSRI and especially, TCA. Despite the relatively lowest VA/SCD in TCA, drug efficacy and other adverse effects should be taken into account in patients with mental disorders.

Background: This study aimed to assess inpatient prevalence, characteristics, outcomes, and resource utilisation of hospitalisation for heatstroke in the United States. Additionally, this study aimed to explore factors associated with in-hospital mortalities of heatstroke., Methods: The 2003-2014 National Inpatient Sample database was used to identify hospitalised patients with a principal diagnosis of heatstroke. The inpatient prevalence, clinical characteristics, in-hospital treatments, outcomes, length of hospital stay, and hospitalisation cost were studied. Multivariable logistic regression was performed to identify independent factors associated with in-hospital mortality., Results: A total of 3372 patients were primarily admitted for heatstroke, accounting for an overall inpatient prevalence of heatstroke amongst hospitalised patients of 36.3 cases per 1 000 000 admissions in the United States with an increasing trend during the study period (P < .001). Age 40-59 was the most prevalent age group. During the hospital stay, 20% required mechanical ventilation, and 2% received renal replacement therapy. Rhabdomyolysis was the most common complication. Renal failure was the most common end-organ failure, followed by neurological, respiratory, metabolic, hematologic, circulatory, and liver systems. The in-hospital mortality rate of heatstroke hospitalisation was 5% with a decreasing trend during the study period (P < .001). The presence of end-organ failure was associated with increased in-hospital mortality, whereas more recent years of hospitalisation was associated with decreased in-hospital mortality. The median length of hospital stay was 2 days. The median hospitalisation cost was $17 372., Conclusion: The inpatient prevalence of heatstroke in the United States increased, while the in-hospital mortality of heatstroke decreased., (© 2020 John Wiley & Sons Ltd.)

Introduction: As percutaneous coronary intervention (PCI) technologies have been far improved, we hence conducted an updated systemic review and meta-analysis to determine the comparability between coronary artery bypass graft (CABG) and PCI with drug-eluting stent (DES) in ESRD patients., Methods: We comprehensively searched the databases of MEDLINE, EMBASE, PUBMED and the Cochrane from inception to January 2020. Included studies were published observational studies that compared the risk of cardiovascular outcomes among dialysis patients with CABG and DES. Data from each study were combined using the random-effects, generic inverse variance method of DerSimonian and Laird to calculate risk ratios and 95% confidence intervals. Subgroup analyses and meta-regression were performed to explore heterogeneity., Results: Thirteen studies were included in this analysis, involving total 56 422 (CABG 21 740 and PCI 34 682). Compared with DES, our study demonstrated CABG had higher 30-day mortality [odds ratio (OR) 3.85, P = 0.009] but lower cardiac mortality (OR 0.78, P < 0.001), myocardial infarction (OR 0.5, P < 0.001) and repeat revascularization (OR 0.35, P < 0.001). No statistical differences were found between CABG and DES for long-term mortality (OR 0.92, P = 0.055), composite outcomes (OR 0.88, P = 0.112) and stroke (OR 1.49, P = 0.457). Meta-regression suggested diabetes and the presence of left main coronary artery disease as an effect modifier of long-term mortality., Conclusion: PCI with DES shared similar long-term mortality, composite outcomes and stroke outcomes to CABG among dialysis patients but still was associated with an improved 30-day survival. However, CABG had better rates of myocardial infarction, repeat revascularization and cardiac mortality., (Copyright © 2021 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Introduction: This study aimed to assess the risk factors and impact of rhabdomyolysis on treatments, outcomes, and resource utilization in hospitalized patients for salicylate intoxication in the United States., Materials and Methods: The National Inpatient Sample was utilized to identify hospitalized patients with a primary diagnosis of salicylate intoxication from 2003-2014. Rhabdomyolysis was identified using hospital diagnosis code. We compared the clinical characteristics, in-hospital treatment, outcomes, and resource utilization between patients with and without rhabdomyolysis., Results: A total of 13,805 hospital admissions for salicylate intoxication were studied. Of these, rhabdomyolysis developed in 258 (1.9%) admissions. The risk factors for rhabdomyolysis were age>20 years, male sex, volume depletion, hypokalemia, sepsis, and seizure. After adjustment for baseline clinical characteristics, salicylate intoxication patients with rhabdomyolysis required more invasive mechanical ventilation, and renal replacement therapy. Rhabdomyolysis was significantly associated with higher risk of failure of any organ systems, and in-hospital mortality. Length of hospital stay and hospitalization cost were higher when rhabdomyolysis occurred during hospital stay., Conclusions: Rhabdomyolysis was not common in hospitalized patients for salicylate intoxication but it was associated with increased morbidity, mortality, and resource utilization., Competing Interests: The authors have declared that no competing interests exist.

Background: This study aimed to evaluate the risk factors and the association of acute kidney injury (AKI) with outcomes, and resource utilisation in patients hospitalised because of salicylate intoxication in the United States., Methods: Hospitalised patients with a primary diagnosis of salicylate intoxication from 2003 to 2014 were identified in the National Inpatient Sample (NIS) database. End-stage kidney disease patients were excluded. The occurrence of AKI was identified using hospital diagnosis code. Clinical characteristics, in-hospital treatment, outcomes and resource utilisation were compared between patients with and without AKI., Results: A total of 13 787 eligible hospital admissions were included in the analysis. AKI occurred in 1279 (9.3%) admissions. Older age, male sex, more recent year of hospitalisation, anaemia, hypertension, congestive heart failure, chronic kidney disease, volume depletion, sepsis and ventricular arrhythmia/cardiac arrest were significantly associated with increased risk of AKI, whereas Hispanic race was associated with decreased risk. AKI was significantly associated with increased risk of organ failure, and in-hospital mortality. In addition, the need for ventilation support, blood component transfusion, renal replacement therapy, length of hospital stay and hospitalisation cost were higher in AKI patients., Conclusion: Approximately one tenth of salicylate intoxication patients developed AKI during hospitalisation. AKI was associated with higher morbidity, mortality and resource utilisations., (© 2020 John Wiley & Sons Ltd.)

Background: Goodpasture's syndrome is a rare and life-threatening autoimmune disease. While Goodpasture's syndrome is well described in Caucasian and Asian populations, its prevalence and outcomes among African American and Hispanic populations are unclear. We conducted this study to assess the impacts of race on hospital outcomes among patients with Goodpasture's syndrome., Methods: The National Inpatient Sample database was used to identify hospitalized patients with a principal diagnosis of Goodpasture's syndrome from 2003 to 2014. Goodpasture's syndrome patients were grouped based on their race. The differences in-hospital supportive care for organ failure and outcomes between Caucasian, African American, and Hispanic Goodpasture's syndrome patients were assessed using logistic regression analysis., Results: Nine hundred and sixty-four patients were hospitalized with a primary diagnosis of Goodpasture's syndrome. Of these, 786 were included in the analysis: 622 (79%) were Caucasian, 73 (9%) were African American, and 91 (12%) were Hispanic. Hispanics had significantly lower use of plasmapheresis. The use for mechanical ventilation, noninvasive ventilation support, and renal replacement therapy in African Americans and Hispanics were comparable to Caucasians. There was no significant difference in organ failure, sepsis, and in-hospital mortality between African Americans and Caucasians. In contrast, Hispanics had higher in-hospital mortality than Caucasians but similar risk of organ failure and sepsis., Conclusion: African American and Hispanic populations account for 9% and 12% of hospitalizations for Goodpasture's syndrome, respectively. While there is no significant difference in in-hospital mortality between African Americans and Caucasians, Hispanics with Goodpasture's syndrome carry a higher in-hospital mortality compared to Caucasians.

Background: This study aimed to evaluate the risk factors for circulatory shock and its impact on outcomes in patients hospitalized for salicylate intoxication., Methods: We used the National Inpatient Sample to identify patients hospitalized primarily for salicylate intoxication from 2003-2014. Circulatory shock was identified based on hospital diagnosis code for any type of shock or hypotension. We compared clinical characteristics, in-hospital treatments, outcomes, and resource use between patients with and without circulatory shock associated with salicylate intoxication., Results: Of 13,805 hospital admissions for salicylate intoxication, circulatory shock developed in 484 (4%) admissions. Risk factors for development of circulatory shock included older age, female sex, concurrent psychotropic medication overdose, anemia, congestive heart failure, volume depletion, rhabdomyolysis, seizure, gastrointestinal bleeding, and sepsis. Circulatory shock was significantly associated with increased odds of any organ failure and in-hospital mortality. Length of hospital stay and hospitalization cost was significantly higher in patients with circulatory shock., Conclusion: Approximately 4% of patients admitted for salicylate intoxication developed circulatory shock. Circulatory shock was associated with worse clinical outcomes and increased resource use.

Background: This study aimed to assess inpatient prevalence, characteristics, outcomes, and resource utilization of hospitalization for methanol intoxication in the United States., Materials and Methods: A total of 603 hospitalized patients with a primary diagnosis of methanol intoxication from 2003 to 2014 were identified in the National Inpatient Sample database. The inpatient prevalence, clinical characteristics, treatments, outcomes, resource utilization, were investigated. Multivariable logistic regression was performed to identify factors independently associated with in-hospital mortality., Results: The overall inpatient prevalence of methanol intoxication among hospitalized patients was 6.4 cases per 1,000,000 admissions in the United States. The mean age was 38±18 (range 0-86) years. 44% used methanol for suicidal attempts. 20% of admissions required mechanical ventilation, and 40% required renal replacement therapy. The three most common complications were metabolic acidosis (44%), hypokalemia (18%), and visual impairment or optic neuritis (8%). The three most common end-organ failures were renal failure (22%), respiratory failure (21%), and neurological failure (17%). 6.5% died in the hospital. Factors associated with increased in-hospital mortality included alcohol drinking, hypernatremia, renal failure, respiratory failure, circulatory failure, and neurological failure. The mean length of hospital stay was 4.0 days. The mean hospitalization cost per patient was $43,222 CONCLUSION: The inpatient prevalence of methanol intoxication in the United States was 6.4 cases per 1,000,000 admissions. The risk of in-hospital mortality mainly depended on the number of end-organ failures., Competing Interests: Declaration of Competing Interest The author has no financial or other conflicts of interest to disclose., (Copyright © 2020 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Background: Recently, smart devices have been used for medical purposes, particularly to screen for atrial fibrillation. However, current data on the diagnostic performance of these devices are scarce., Aims: We performed a systemic review and meta-analysis to assess the accuracy of atrial fibrillation diagnosis by smart gadgets/wearable devices., Methods: We comprehensively searched the MEDLINE, EMBASE and Cochrane databases for all works since the inception of each database until January 2020. Included in this review were published observational studies of the diagnostic accuracy of smartphones or smartwatches in detecting atrial fibrillation. We calculated the area under the summary receiver operating characteristic curves and pooled sensitivities and specificities., Results: Participants in our study were from the general population or were patients with underlying atrial fibrillation. In the overall analyses, the areas under the summary receiver operating characteristic curves were 0.96 and 0.94 for smartphones and smartwatches, respectively. Smartphones had a sensitivity of 94% and a specificity of 96%, and smartwatches showed similar diagnostic accuracy, with a specificity of 94% and a sensitivity of 93%. In subgroup analyses, we found no difference in diagnostic accuracy between photoplethysmography and single-lead electrocardiography., Conclusions: This study suggests that smart devices have similar diagnostic accuracies. Regarding atrial fibrillation detection methods, there was also no difference between photoplethysmography and single-lead electrocardiography. However, further studies are warranted to determine their clinical implications in atrial fibrillation management., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Background: Renal angiomyolipoma (AML) is the most frequent mesenchymal tumor of the kidney. Although there is a rare possibility of malignant transformation of AML, this risk has not been studied in immunosuppressed patients. The safety of donors with AML and their kidney transplant recipients has not been well established., Methods: A literature search was conducted utilizing MEDLINE, EMBASE, and Cochrane databases from inception through May 15, 2018 (updated on October 2019). We included studies that reported the outcomes of kidney donors with AML or recipients of donor with AML. The protocol for this meta-analysis is registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42018095157)., Results: Fourteen studies with a total of 16 donors with AML were identified. None of the donors had a diagnosis of tuberous sclerosis complex (TSC), pulmonary lymphangioleiomyomatosis (LAM), or epithelioid variant of AML. Donor age ranged from 35 to 77 years, and recipient age ranged from 27 to 62 years. Ninety-two percent of the donors were female. Only 8% were deceased donor renal transplant. The majority underwent ex vivo resection (65%) before transplantation, followed by no resection (18%), and the remaining had in vivo resection. Tumor size varied from 0.4 cm to 7 cm, and the majority (87%) were localized in the right kidney. Follow-up time ranged from 1 to 107 months. Donor creatinine prenephrectomy ranged 0.89-1.1 mg/dL and postnephrectomy creatinine 1.0-1.17 mg/dL. In those who did not have resection of the AML, tumor size remained stable. None of the donors with AML had end-stage renal disease or died at last follow-up. None of the recipients had malignant transformation of AML., Conclusion: These findings are reassuring for the safety of donors with AML (without TSC or LAM) as well as their recipients without evidence of malignant transformation of AML. As such, this can also positively impact the donor pool by increasing the number of available kidneys., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Urology Annals.)

Patients with the recovery of kidney function after an episode of acute kidney injury (AKI) have better outcomes compared to those without recovery. The current systematic review is conducted to assess the rates of kidney function recovery among patients with AKI or severe AKI requiring kidney replacement therapy (KRT) within 100 days after hematopoietic stem cell transplant (HSCT). Methods The Ovid MEDLINE, EMBASE, and Cochrane databases were systemically searched from database inceptions through August 2019 to identify studies reporting the rates of recovery from AKI after HSCT. The random-effects and generic inverse variance methods of DerSimonian-Laird were used to combine the effect estimates obtained from individual studies. Results A total of 458 patients from eight cohort studies with AKI after HSCT were identified. Overall, the pooled estimated rates of AKI recovery among patients with AKI and severe AKI requiring KRT within 100 days were 58% (95%CI: 37%-78%) and 10% (95%CI: 2%-4%), respectively. Among patients with AKI recovery, the pooled estimated rates of complete and partial AKI recovery were 60% (95%CI: 39%-78%) and 29% (95%CI: 10%-61%), respectively. There was no clear correlation between study year and the rate of AKI recovery (p=0.26). Conclusion The rate of recovery from AKI after HSCT depends on the severity of AKI. While recovery is common, complete recovery is reported in about two-thirds of all AKI patients. The rate of recovery among those with AKI requiring renal replacement therapy (RRT) is substantially lower., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Kanduri et al.)

Background: This study aimed to evaluate thrombotic microangiopathy's (TMA) incidence, risk factors, and impact on outcomes and resource use in hospitalized patients with systemic lupus erythematosus (SLE)., Methods: We used the National Inpatient Sample to construct a cohort of hospitalized patients with SLE from 2003-2014. We compared clinical characteristics, in-hospital treatments, outcomes, and resource use between SLE patients with and without TMA., Results: Of 35,745 hospital admissions for SLE, TMA concurrently presented or developed in 188 (0.5%) admissions. Multivariable analysis showed that age ≥ 40 years and Hispanics were significantly associated with decreased risk of TMA, whereas Asian/Pacific Islanders and history of chronic kidney disease were significantly associated with increased risk of TMA. TMA patients required more kidney biopsy, plasmapheresis, mechanical ventilation, and renal replacement therapy. TMA was significantly associated with increased risk of in-hospital mortality and acute conditions including hemoptysis, glomerulonephritis, encephalitis/myelitis/encephalopathy, hemolytic anemia, pneumonia, urinary tract infection, sepsis, ischemic stroke, seizure, and acute kidney injury. The length of hospital stays and hospitalization cost was also significantly higher in SLE with TMA patients., Conclusion: TMA infrequently occurred in less than 1% of patients admitted for SLE, but it was significantly associated with higher morbidity, mortality, and resource use.

Background: Fabry disease (FD) is a rare X-linked lysosomal storage disorder with progressive systemic deposition of globotriaosylceramide, leading to life-threatening cardiac, central nervous system, and kidney disease. Current therapy involves symptomatic medical management, enzyme replacement therapy (ERT), dialysis, kidney transplantation, and, more recently, gene therapy. The aim of this systematic review was to assess outcomes of kidney transplantation among patients with FD., Methods: A comprehensive literature review was conducted utilizing MEDLINE, EMBASE, and Cochrane Database, from inception through to 28 February 2020, to identify studies that evaluate outcomes of kidney transplantation including patient and allograft survival among kidney transplant patients with FD. Effect estimates from each study were extracted and combined using the random-effects generic inverse variance method of DerSimonian and Laird., Results: In total, 11 studies, including 424 kidney transplant recipients with FD, were enrolled. The post-transplant median follow-up time ranged from 3 to 11.5 years. Overall, the pooled estimated rates of all-cause graft failure, graft failure before death, and allograft rejection were 32.5% (95%CI: 23.9%-42.5%), 14.5% (95%CI: 8.4%-23.7%), and 20.2% (95%CI: 15.4%-25.9%), respectively. In the sensitivity analysis, limited only to the recent studies (year 2001 or newer when ERT became available), the pooled estimated rates of all-cause graft failure, graft failure before death, and allograft rejection were 28.1% (95%CI: 20.5%-37.3%), 11.7% (95%CI: 8.4%-16.0%), and 20.2% (95%CI: 15.5%-26.0%), respectively. The pooled estimated rate of biopsy proven FD recurrence was 11.1% (95%CI: 3.6%-29.4%), respectively. There are no significant differences in the risks of all-cause graft failure ( p = 0.10) or mortality (0.48) among recipients with vs. without FD., Conclusions: Despite possible FD recurrence after transplantation of 11.1%, allograft and patient survival are comparable among kidney transplant recipients with vs. without FD.

Currently, the data on independent risk factors for the progression of kidney disease in type 2 diabetes mellitus (T2DM) patients with CKD are limited. This study aimed to investigate CKD progression in T2DM patients who have reduced kidney function with baseline estimated glomerular filtration rate (eGFRs) between 15 and 59 mL/min/1.73 m 2 . This study was composed of a nationwide retrospective cohort of adult T2DM patients from 831 public hospitals in Thailand during the year 2015. T2DM patients with CKD stages 3 and 4 were followed up, until development of CKD stage 5, requirement of chronic dialysis, loss to follow-up, death, or 31 May 2018, whichever came first. Cox proportional hazard regression was utilized for analysis. A total of 8464 participants were included; 30.4% were male. The mean age was 69 ± 10 years. The mean eGFR was 45 ± 11 mL/min/1.73 m 2 . The incidence of CKD stage 5 or the need for chronic dialysis was 16.4 per 1000 person-years. The annual rate of eGFR decline during a mean follow-up of 29 months was -2.3 mL/min/1.73 m 2 ; 14.4% had a rapid decline in eGFR. The risk factors associated with progression to CKD stage 5 or the need for chronic dialysis were diabetes duration, systolic blood pressure, serum uric acid, albuminuria, and baseline eGFR. Conversely, older age and the use of renin-angiotensin aldosterone system blockade were associated with decreased risks for rapid CKD progression and incidence CKD stage 5 or dialysis. This study identifies multiple predictive risk factors that support a multifaceted approach to prevent progression of advanced CKD., (© 2020 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

Background: The objective of this study was to evaluate the predictors and associated outcomes of rhabdomyolysis in admitted patients for heat stroke in the United States., Methods: The National Inpatient Sample was utilized to identify hospitalized patients with a primary diagnosis of heat stroke from the years 2003-2014. Rhabdomyolysis was identified using hospital diagnosis code. We compared the clinical characteristics, in-hospital treatment, complications, outcomes, and resource utilization between patients with and without rhabdomyolysis., Results: A total of 3,372 hospital admissions for heat stroke were studied. Of these, rhabdomyolysis occurred in 1049 (31%) admissions. The risk factors for rhabdomyolysis were age 20-39 years, male sex, African American race, history of alcohol drinking, whereas age ≥60 years, smoking, history of diabetes mellitus, and hypertension were associated with lower risk of rhabdomyolysis. Patients with rhabdomyolysis had greater requirements for mechanical ventilation, blood component transfusion, and renal replacement therapy. Rhabdomyolysis was significantly associated with increased risk of hyponatremia, hypernatremia, hyperkalemia, hypocalcemia, serum phosphorus and magnesium derangement, metabolic acidosis, sepsis, ventricular arrhythmia or cardiac arrest, renal failure, respiratory failure, liver failure, neurological failure, hematologic failure, and in-hospital mortality. Length of hospital stay and hospitalization cost were higher when rhabdomyolysis occurred during hospital stay., Conclusion: Rhabdomyolysis occurred in about one-third of hospitalized patients for heat stroke and was associated with increased morbidity, mortality, and resource utilization.

Background : The objective of this study was to report the incidence of in-hospital serum ionized calcium derangement and its impact on mortality. Methods: We included 12,599 non-dialytic adult patients hospitalized at a tertiary medical center from January 2009 to December 2013 with normal serum ionized calcium at admission and at least 2 in-hospital serum ionized calcium values. Using serum ionized calcium of 4.60-5.40 mg/dL as the normal reference range, in-hospital serum ionized calcium levels were categorized based on the presence of hypocalcemia and hypercalcemia in hospital. We performed logistic regression to assess the relationship of in-hospital serum ionized calcium derangement with mortality. Results: Fifty-four percent of patients developed new serum ionized calcium derangements: 42% had in-hospital hypocalcemia only, 4% had in-hospital hypercalcemia only, and 8% had both in-hospital hypocalcemia and hypercalcemia. In-hospital hypocalcemia only (OR 1.28; 95% CI 1.01-1.64), in-hospital hypercalcemia only (OR 1.64; 95% CI 1.02-2.68), and both in-hospital hypocalcemia and hypercalcemia (OR 1.73; 95% CI 1.14-2.62) were all significantly associated with increased in-hospital mortality, compared with persistently normal serum ionized calcium levels. Conclusions: In-hospital serum ionized calcium derangements affect more than half of hospitalized patients and are associated with increased in-hospital mortality.

Background: The objective of this systematic review was to evaluate the efficacy and safety profiles of sodium-glucose co-transporter 2 (SGLT-2) inhibitors for treatment of diabetes mellitus (DM) among kidney transplant patients., Methods: We conducted electronic searches in Medline, Embase, Scopus, and Cochrane databases from inception through April 2020 to identify studies that investigated the efficacy and safety of SGLT-2 inhibitors in kidney transplant patients with DM. Study results were pooled and analyzed utilizing random-effects model., Results: Eight studies with 132 patients (baseline estimated glomerular filtration rate (eGFR) of 64.5 ± 19.9 mL/min/1.73m 2 ) treated with SGLT-2 inhibitors were included in our meta-analysis. SGLT-2 inhibitors demonstrated significantly lower hemoglobin A1c (HbA1c) (WMD = -0.56% [95%CI: -0.97, -0.16]; p = 0.007) and body weight (WMD = -2.16 kg [95%CI: -3.08, -1.24]; p < 0.001) at end of study compared to baseline level. There were no significant changes in eGFR, serum creatinine, urine protein creatinine ratio, and blood pressure. By subgroup analysis, empagliflozin demonstrated a significant reduction in body mass index (BMI) and body weight. Canagliflozin revealed a significant decrease in HbA1C and systolic blood pressure. In terms of safety profiles, fourteen patients had urinary tract infection. Only one had genital mycosis, one had acute kidney injury, and one had cellulitis. There were no reported cases of euglycemic ketoacidosis or acute rejection during the treatment., Conclusion: Among kidney transplant patients with excellent kidney function, SGLT-2 inhibitors for treatment of DM are effective in lowering HbA1C, reducing body weight, and preserving kidney function without reporting of serious adverse events, including euglycemic ketoacidosis and acute rejection.

Background: Chronic kidney disease and hypoglycemia are common complications in individuals with diabetes. Currently, the association of renal function with hypoglycemic complications in type 2 diabetes mellitus (T2DM) is inconclusive. This study aims to assess the associations between estimated glomerular filtration rate (eGFR) and cumulative incidence of hypoglycemia, hypoglycemia-related hospitalizations, and incidence of outpatient hypoglycemia among T2DM patients in Thailand using a nationwide patient sample., Methods: We conducted a nationwide retrospective cohort study based on the DM/HT study of the Medical Research Network of the Consortium of Thai Medical Schools. This study assessed adult T2DM patients from 831 public hospitals in Thailand in the year 2012-2013. eGFR was categorized into ≥90, 60-89, 30-59, 15-29, and <15 mL/min/1.73 m 2 . The associations between eGFR and hypoglycemia, hypoglycemia-related hospitalizations, and incidence of outpatient hypoglycemia were assessed using multivariate logistic regression and Poisson regression., Results: A total of 25,056 T2DM patients with available eGFR were included in the analysis. The mean age was 60.9 ± 10.5 years. The cumulative incidence of hypoglycemia and hypoglycemia-related hospitalizations was 3.6% and 1.7%, respectively. Incidence of outpatient hypoglycemia, mild hypoglycemia, and severe hypoglycemia was 2.99 (2.59-3.43), 2.47 (2.11-2.88), and 0.52 (0.36-0.72) per 100 patient-years, respectively. Patients with eGFR of 30-59, 15-29, and <15 mL/min/1.73 m 2 were significantly associated with an increased risk of hypoglycemia, hypoglycemia-related hospitalizations, and incidence of outpatient hypoglycemia when compared to patients with eGFR of ≥90 mL/min/1.73 m 2 ., Conclusion: Reduced eGFR was independently associated with increased hypoglycemia, hypoglycemia-related hospitalizations, and risk of outpatient hypoglycemia. Increasing awareness of the heightened risk of hypoglycemia with declining renal function may prompt changes to diabetic management for at-risk individuals.

Background: We aimed to evaluate the acute kidney injury (AKI) incidence and its associated risk of mortality in patients with implantable left ventricular assist devices (LVAD). Methods: A systematic literature search in Ovid MEDLINE, EMBASE, and Cochrane Databases was conducted through January 2020 to identify studies that provided data on the AKI incidence and AKI-associated mortality risk in adult patients with implantable LVADs. Pooled effect estimates were examined using random-effects, generic inverse variance method of DerSimonian-Laird. Results: Fifty-six cohort studies with 63,663 LVAD patients were enrolled in this meta-analysis. The pooled incidence of reported AKI was 24.9% (95%CI: 20.1%-30.4%) but rose to 36.9% (95%CI: 31.1%-43.1%) when applying the standard definition of AKI per RIFLE, AKIN, and KDIGO criteria. The pooled incidence of severe AKI requiring renal replacement therapy (RRT) was 12.6% (95%CI: 10.5%-15.0%). AKI incidence did not differ significantly between types of LVAD ( p  = .35) or indication for LVAD use ( p  = .62). While meta-regression analysis did not demonstrate a significant association between study year and overall AKI incidence ( p  = .55), the study year was negatively correlated with the incidence of severe AKI requiring RRT (slope = -0.068, p  < .001). The pooled odds ratios (ORs) of mortality at 30 days and one year in AKI patients were 3.66 (95% CI, 2.00-6.70) and 2.22 (95% CI, 1.62-3.04), respectively. The pooled ORs of mortality at 30 days and one year in severe AKI patients requiring RRT were 7.52 (95% CI, 4.58-12.33) and 5.41 (95% CI, 3.63-8.06), respectively. Conclusion: We found that more than one-third of LVAD patients develop AKI based on standard definitions, and 13% develop severe AKI requiring RRT. There has been a potential improvement in the incidence of severe AKI requiring RRT for LVAD patients. AKI in LVAD patients was associated with increased 30-day and 1 year mortality.

Introduction: The incidence of acute myocardial injury (AMI) among Coronavirus Disease 19 (COVID-19)-infected patients remain unclear. We aimed to conduct a systematic review and meta-analysis to further explore the incidence AMI in these patients. Methods: We comprehensively searched the MEDLINE, EMBASE and Cochrane databases from their inception to August 2020. The included studies were prospective or retrospective cohort studies that reported the event rate of AMI in COVID-19 patients. Data from each study were combined using random-effects to calculate the pooled incidence with 95% confidence intervals. Results: We identified twenty-seven studies consisting of 8971 hospitalized COVID-19-infected patients. The study demonstrated that 20.0% (95% CI 16.1-23.8% with substantial heterogeneity (I 2 = 94.9%)) of hospitalized COVID-19 patients had AMI. In addition, our meta-regression suggested that older age, male and comorbidities were associated with a higher risk of AMI. Conclusion: The incidence of COVID-19-related myocardial injury ranges from 16.1-23.8%. Further larger studies are anticipated, as the pandemic is still ongoing.

Background: C3 glomerulopathy (C3G), a rare glomerular disease mediated by alternative complement pathway dysregulation, is associated with a high rate of recurrence and graft loss after kidney transplantation (KTx). We aimed to assess the efficacy of different treatments for C3G recurrence after KTx., Methods: Databases (MEDLINE, EMBASE, and Cochrane Database) were searched from inception through 3 May, 2019. Studies were included that reported outcomes of adult KTx recipients with C3G. Effect estimates from individual studies were combined using the random-effects, generic inverse variance method of DerSimonian and Laird., The protocol for this meta-analysis is registered with PROSPERO (no. CRD42019125718)., Results: Twelve studies (7 cohort studies and 5 case series) consisting of 122 KTx patients with C3G (73 C3 glomerulonephritis (C3GN) and 49 dense deposit disease (DDD)) were included. The pooled estimated rates of allograft loss among KTx patients with C3G were 33% (95% CI: 12-57%) after eculizumab, 42% (95% CI: 2-89%) after therapeutic plasma exchange (TPE), and 81% (95% CI: 50-100%) after rituximab. Subgroup analysis based on type of C3G was performed. Pooled estimated rates of allograft loss in C3GN KTx patients were 22% (95% CI: 5-46%) after eculizumab, 56% (95% CI: 6-100%) after TPE, and 70% (95% CI: 24-100%) after rituximab. Pooled estimated rates of allograft loss in DDD KTx patients were 53% (95% CI: 0-100%) after eculizumab. Data on allograft loss in DDD after TPE (1 case series, 0/2 (0%) allograft loss at 6 months) and rituximab (1 cohort, 3/3 (100%) allograft loss) were limited. Among 66 patients (38 C3GN, 28 DDD) who received no treatment (due to stable allograft function at presentation and/or clinical judgment of physicians), pooled estimated rates of allograft loss were 32% (95% CI: 7-64%) and 53% (95% CI: 28-77%) for C3GN and DDD, respectively. Among treated C3G patients, data on soluble membrane attack complex of complement (sMAC) were limited to patients treated with eculizumab (N = 7). 80% of patients with elevated sMAC before eculizumab responded to treatment. In addition, all patients who responded to eculizumab had normal sMAC levels after post-eculizumab., Conclusions: Our study suggests that the lowest incidence of allograft loss (33%) among KTX patients with C3G are those treated with eculizumab. Among those who received no treatment for C3G due to stable allograft function, there is a high incidence of allograft loss of 32% in C3GN and 53% in DDD. sMAC level may help to select good responders to eculizumab.