Reduction of RAD23A extends lifespan and mitigates pathology in TDP-43 mice.

Protein misfolding and aggregation are cardinal features of neurodegenerative disease (NDD) and they contribute to pathophysiology by both loss-of-function (LOF) and gain-of-function (GOF) mechanisms. This is well exemplified by TDP-43 which aggregates and mislocalizes in several NDDs. The depletion of nuclear TDP-43 leads to reduction in its normal function in RNA metabolism and the cytoplasmic accumulation of TDP-43 leads to aberrant protein homeostasis. A modifier screen found that loss of rad23 suppressed TDP-43 pathology in invertebrate and tissue culture models. Here we show in a mouse model of TDP-43 pathology that genetic or antisense oligonucleotide (ASO)-mediated reduction in rad23a confers benefits on survival and behavior, histological hallmarks of disease and reduction of mislocalized and aggregated TDP-43. This results in improved function of the ubiquitin-proteasome system (UPS) and correction of transcriptomic alterations evoked by pathologic TDP-43. RAD23A-dependent remodeling of the insoluble proteome appears to be a key event driving pathology in this model. As TDP-43 pathology is prevalent in both familial and sporadic NDD, targeting RAD23A may have therapeutic potential.

Management of hepatorenal syndrome and associated outcomes: a systematic reviews.

BACKGROUND: Hepatorenal syndrome (HRS), a multiorgan condition of acute kidney injury, is seen in advanced liver disease. This study aims to evaluate the current treatment for HRS. METHODS: The authors searched PubMed, Scopus and Google Scholar literature. After quality assessment, 31 studies were included in this review. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology and the population, intervention, comparison and outcome scheme were used. We included human-controlled trials that evaluate the current treatment for HRS. Two authors independently screened articles for inclusion, extracted data and assessed the quality of included studies. RESULTS: This study investigated the studies conducted on the effects of different treatments on follow-up of HRS patients. We gathered 440 articles, so 31 articles remained in our study. Of which 24 articles were conducted on terlipressin versus placebo or other treatments (midodrine/octreotide, norepinephrine, etc) that showed the higher rate of HRS reversal was detected for terlipressin in 17 studies (10 of them were significant), 2 studies achieved an insignificant lower rate of the model for end-stage liver disease score for terlipressin, 15 studies showed a decreased mortality rate in the terlipressin group (4 of them were significant). CONCLUSION: This review showed that terlipressin has a significantly higher reversal rate of HRS than the other treatments. Even the results showed that terlipressin is more efficient than midodrine/octreotide and norepinephrine as a previous medication, in reverse HRS, increasing patient survival.

Frequency and timing of renal biopsy complications.

Background: Percutaneous renal biopsy is the primary diagnostic tool for renal diseases. In this study, we evaluated renal biopsy complications and the timing of complications. Methods: A cross-sectional study was performed on adult patients who underwent renal biopsy. The data gathering sheet collected patient characteristics. Complications were categorized as minor and major which needed an intervention. Data were analyzed using SPSS, and a p-value <0.05 was considered significant. Results: This cross-sectional study was conducted on 215 patients (mean age: 33.1±16.4 and 54.4%: women) who underwent percutaneous renal biopsy in Shiraz Nemazi Hospital for one year. Of the 298 complications that occurred, 90.2% were minors (56.1%of them microscopic hematuria). Moreover, 2 (0.7%) patients developed major complications and received a transfusion. In addition, most of the complications (98.9%, 295 ones) developed within 8 hours post-procedure. Only hemoglobin drop was significantly higher in women (41.0% vs. 21.4%, P=0.003). Conclusion: This study indicates that renal biopsy is a safe procedure; the results revealed that the significant post-biopsy complications were rare and occurred in the first 8 hours.

COVID-19 Associated Acute Kidney Injury: The Incidence and Associated Factors in Different KDIGO Stages Among the Hospitalized Patients.

INTRODUCTION: Acute kidney injury (AKI) is the most common reported renal complication associated with COVID-19. In this study, we evaluated the frequency of AKI, the predisposing factors, and its impact on the patient's outcomes in COVID-19. METHODS: By collecting retrospective data, we conducted a crosssectional study on hospitalized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients in a COVID-19- designated hospital in Shiraz, Iran, from March 2020 to June 2020. Patients' characteristics and laboratory findings were recorded in data gathering sheets. Data were analyzed using SPSS Software Version 16. A P value < .05 was considered significant. RESULTS: This study was conducted on 980 patients with COVID-19 (mean age: 51.2 ± 16.2 years and men: 54.8%), of which 32.6% developed AKI during their hospitalization period, and 1.3% ended up requiring renal replacement therapy. Patients with higher AKI stages experienced more severe/critical COVID-19 (stage 3: 71.0%, stage 2: 44.8%, stage 1: 6.5%; P < .001). The multivariate analysis showed that the proteinuria had the highest relationship with AKI (OR = 6.77 [95% CI: 4.39 to 10.41], P < .001), followed by in-hospital death (OR = 5.14 [95% CI: 1.86 to 14.47], P = .002). In addition, in-hospital death was more observed in higher stages of AKI (OR = 12.69 [95% CI: 3.85 to 42.09], P < .001). CONCLUSIONS: Hospitalized patients with COVID-19 are vulnerable to AKI, especially those who experienced more severe COVID-19 or require mechanical ventilation, which considerably affects the patients' mortality. The high incidence of AKI in our patients demonstrated that it should be considered as one of the common complications of COVID-19, and diagnostic measures, particularly in severe or critical cases, are recommended.  DOI: 10.52547/ijkd.7636.

Direct Mechanical Thrombectomy Versus Prior Bridging Intravenous Thrombolysis in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

BACKGROUND: The current guideline recommends using an intravenous tissue-type plasminogen activator (IV tPA) prior to mechanical thrombectomy (MT) in eligible acute ischemic stroke (AIS) with emergent large vessel occlusion (ELVO). Some recent studies found no significant differences in the long-term functional outcomes between bridging therapy (BT, i.e., IV tPA prior to MT) and direct MT (dMT). METHODS: We conducted a systematic review and meta-analysis to compare the safety and functional outcomes between BT and dMT in AIS patients with ELVO who were eligible for IV tPA administration. Based on the ELVO location, patients were categorized as the anterior group (occlusion of the anterior circulation), or the combined group (occlusion of the anterior and/or posterior circulation). A subgroup analysis was performed based on the study type, i.e., RCT and non-RCT. RESULTS: Thirteen studies (3985 patients) matched the eligibility criteria. Comparing the BT and dMT groups, no significant differences in terms of mortality and good functional outcome were observed at 90 days. Symptomatic intracranial hemorrhagic (sICH) events were more frequent in BT patients in the combined group (OR = 0.73, p = 0.02); this result remained significant only in the non-RCT subgroup (OR = 0.67, p = 0.03). The RCT subgroup had a significantly higher rate of successful revascularization in BT patients (OR = 0.73, p = 0.02). CONCLUSIONS: Our meta-analysis uncovered no significant differences in functional outcome and mortality rate at 90 days between dMT and BT in patients with AIS who had ELVO. Although BT performed better in terms of successful recanalization rate, there is a risk of increased sICH rate in this group.

Impulse control disorders in hyperprolactinemic patients on dopamine agonist therapy.

Dopamine agonists (DAs) represent a mainstay of therapy for hyperprolactinemia and prolactinomas. The widespread use of DAs, including bromocriptine, cabergoline and (in some countries) quinagolide, has led to the emergence and recognition of impulse control disorders (ICDs) that may occur in association with DA therapy.Such ICDs include pathological gambling, compulsive shopping, hypersexuality and punding (the performance of repetitive tasks), among others. These manifestations can lead to substantial harms to patients and their families, if left undiagnosed and untreated. Several risk factors that may increase the risk of ICDs have been proposed, including younger age, male gender, smoking and alcohol use and history of depression.The diagnosis of ICDs in hyperprolactinemic patients treated with DAs requires a high index of suspicion and a systematic approach, using available screening questionnaires. However, it should be noted that available test instruments, including questionnaires and computerized tasks, have not been validated specifically in hyperprolactinemic patients. Hyperprolactinemic patients who develop ICDs should be withdrawn from DA therapy or, at a minimum, undergo a DA dose reduction, and considered for psychiatric consultation and cognitive behavioral therapy. However, the role of psychopharmacotherapy in hyperprolactinemic patients with ICDs remains incompletely characterized.Patient counseling regarding the risk of ICDs occurring in association with DA therapy, early detection and prompt intervention may mitigate potential harms associated with ICDs. Additional studies are needed to fully characterize risk factors, underlying mechanisms and identify effective therapies for ICDs in patients with hyperprolactinemia receiving DAs.

Efficacy and Safety of Turmeric Dietary Supplementation on Proteinuria in CKD: A Systematic Review and Meta-analysis of RCT.

The beneficial effects of oral turmeric extract on proteinuria levels have been investigated in several human and animal studies. We conducted a systematic review and meta-analysis to evaluate the significance of this new treatment in CKD patients for the first time. We searched ISI Web of Science, PubMed/Medline, Google Scholar, Scopus, SID, and Magiran until March 2021 to identify human-controlled trials that evaluated the effect of turmeric on proteinuria in chronic kidney disease patients. A total of six trials met the selection criteria and were reviewed in our study and four of them were included in the meta-analysis. In these studies, the results showed not only a significant decrease in the level of proteinuria of the trial groups, who had received curcumin but also a significant change in the level of proteinuria between the trial and control groups (SMD = -0.72, 95% CI: -1.10 to 0.35). The results of this meta-analysis demonstrates that turmeric/curcumin oral supplementation significantly improves urinary protein excretion in patients who suffer from chronic kidney diseases with proteinuria; thus, it can be considered as a potential treatment modality in this population.  DOI: 10.52547/ijkd.6772.

Diagnosis and Treatment of Latent Tuberculosis Infection in Kidney and Liver Transplant Recipients in Iranian Candidates for Transplant.

OBJECTIVES: The rates of tuberculosis and its mortality are higher in solid-organ transplant recipients than in the general population. In this study, we compared the rate of active tuberculosis disease conversion in solid organ transplant recipients based on pretransplant tuberculin skin test results and also its association with treatment. MATERIALS AND METHODS: This cross-sectional study included kidney/liver transplant recipients who had pretransplant tuberculin skin test indurations of ≥5 mm and who were seen from March 2009 to March 2019 at the Shiraz Nemazi Hospital Transplant Center (Shiraz, Iran). Data were analyzed using SPSS software, and P < .05 was considered significant. RESULTS: Of 6289 solid-organ transplant recipients seen at our center over the 10-year period, 334 recipients (mean age of 46.0 ± 13.8 years; 67.6% men) had tuberculin skin test indurations of ≥5 mm. Of these 334 recipients, 76.3% had kidney transplant, and the remainder had liver transplant. Of patients who received complete treatment for latent tuberculosis, the rate of conversion to active tuberculosis was lower than in those who did not adhere to medication (8.6% vs 43.7%; P < .001). In addition, the rate of active tuberculosis development was higher in patients who had pretransplant tuberculin skin tests results of ≥10 mm compared with those who had results of 5 to 9 mm (15.8% vs 3.4%; P < .001). CONCLUSIONS: Latent tuberculosis diagnosis and treatment before solid-organ transplant can reduce active tuberculosis conversion and its associated morbidity and mortality. We recommend modifying the cutoff point considered for tuberculin skin test positivity for solid-organ transplant candidates in Iran to ≥10 mm, although further evaluations are needed.

Non-medial infectious orbital cellulitis: etiology, causative organisms, radiologic findings, management and complications.

BACKGROUND: Orbital cellulitis is an ophthalmic emergency, which is associated with vision-threatening adverse effects. The purpose of this study is investigating etiology, radiologic findings, management and complications of patients with non-medial orbital cellulitis. METHOD: A retrospective medical record and radiologic file review of patients with infectious orbital cellulitis was performed to detect all patients with non-medial orbital cellulitis who referred to Khalili hospital from 2016 to 2019. Age, sex, origin of infection, size of collection or abscess, medical or surgical management, microbiology, first and final best-corrected visual acuity, duration of admission, and complications was recorded. Patients divided into two groups; medical management and surgical management groups and all of data compared between in this groups. RESULTS: Of ninety-six patients with infectious orbital cellulitis, 23 cases (14 male, 9 female) were included. Five patients (21.7%) were managed medically and 18 patients (78.3%) were managed surgically. Patients' age range was 5-70 years old. Most common location for non-medial cellulitis was superior space (66.7% in surgical and 40% in medical group; p = 0.511). In 13 cases of surgical group (72.3%) were detected microorganisms. The mean ± SD of collection volume in medical group were 476.5 ± 290.93 mm3 and 2572.94 ± 1075.75 mm3 in surgical group (p < 0.001). Ten patients in surgical group had compressive optic neuropathy. The mean ± SD of collection volume was 3204.97 ± 879.88 mm3 in patient with compressive optic neuropathy and 1280.43 ± 880.68 mm3 in patient without compressive optic neuropathy (P < 0.001). One case complicated by subdural empyema and another case progressed to necrotizing fasciitis. CONCLUSION: Non-medial orbital cellulitis is an uncommon but sight-threatening and life-threatening condition. Timely diagnosis and accurate management reduce morbidity and mortality. Combined surgery for patients with superior or supra-temporal and large non-medial abscess is recommended.

Why African Americans Are a Potential Target for COVID-19 Infection in the United States.

Since the World Health Organization declared the coronavirus disease (COVID-19) outbreak a pandemic, significant changes have occurred in the United States as the infection spread reached and passed its exponential phase. A stringent analysis of COVID-19 epidemiologic data requires time and would generally be expected to happen with significant delay after the exponential phase of the disease is over and when the focus of the health care system is diverted away from crisis management. Although much has been said about high-risk groups and the vulnerability of the elderly and patients with underlying comorbidities, the impact of race on the susceptibility of ethnic minorities living in indigent communities has not been discussed in detail worldwide and specifically in the United States. There are currently some data on disparities between African American and Caucasian populations for COVID-19 infection and mortality. While health care authorities are reorganizing resources and infrastructure to provide care for symptomatic COVID-19 patients, they should not shy away from protecting the general public as a whole and specifically the most vulnerable members of society, such as the elderly, ethnic minorities, and people with underlying comorbidities.