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Background: Up to 6% of kidney transplant recipients (KTRs) experience life-threatening complications requiring intensive care unit (ICU) admission, and one of the most common medical complications requiring ICU admission is infection. This study aimed to evaluate the effect of immunosuppressive therapy (IST) modification on prognosis of KTRs with sepsis. Methods: We conducted a multicenter retrospective study in 4 university-affiliated hospitals to evaluate the effect of adjusting the IST in KTRs with sepsis. Only patients who either maintained IST after ICU admission or those who underwent immediate (within 24 h of ICU admission) reduction or withdrawal of IST following ICU admission were included in this study. "Any reduction" was defined as a dosage reduction of any IST or discontinuation of at least 1 IST. "Complete withdrawal of IST" was defined as concomitant discontinuation of all ISTs, except steroids. Results: During the study period, 1596 of the KTRs were admitted to the ICU, and 112 episodes of sepsis or septic shock were identified. The overall in-hospital mortality rate was 35.7%. In-hospital mortality was associated with higher sequential organ failure assessment score, simplified acute physiology score 3, non-identical human leukocyte antigen relation, presence of septic shock, and complete withdrawal of IST. After adjusting for potential confounding factors, complete withdrawal of IST remained significantly associated with in-hospital mortality (adjusted coefficient, 1.029; 95% confidence interval, 0.024-2.035) and graft failure (adjusted coefficient, 2.001; 95% confidence interval, 0.961-3.058). Conclusions: Complete IST withdrawal was common and associated with worse outcomes in critically ill KTRs with sepsis. [ABSTRACT FROM AUTHOR]

Glomerulonephritis (GN) is characterized by podocyte injury or glomerular filtration dysfunction, which results in proteinuria and eventual loss of kidney function. Progress in studying the mechanism of GN, and developing an effective therapy, has been limited by the absence of suitable in vitro models that can closely recapitulate human physiological responses. We developed a microfluidic glomerulus-on-a-chip device that can recapitulate the physiological environment to construct a functional filtration barrier, with which we investigated biological changes in podocytes and dynamic alterations in the permeability of the glomerular filtration barrier (GFB) on a chip. We also evaluated the potential of GN-mimicking devices as a model for predicting responses to human GN. Glomerular endothelial cells and podocytes successfully formed intact monolayers on opposite sides of the membrane in our chip device. Permselectivity analysis confirmed that the chip was constituted by a functional GFB that could accurately perform differential clearance of albumin and dextran. Reduction in cell viability resulting from damage was observed in all serum-induced GN models. The expression of podocyte-specific marker WT1 was also decreased. Albumin permeability was increased in most models of serum-induced IgA nephropathy (IgAN) and membranous nephropathy (MN). However, sera from patients with minimal change disease (MCD) or lupus nephritis (LN) did not induce a loss of permeability. This glomerulus-on-a-chip system may provide a platform of glomerular cell culture for in vitro GFB in formation of a functional three-dimensional glomerular structure. Establishing a disease model of GN on a chip could accelerate our understanding of pathophysiological mechanisms of glomerulopathy. [ABSTRACT FROM AUTHOR]

We developed a 3D glomeruli tissue chip for glomerulonephritis (GN) testing, featuring a gravity-driven glomerular filtration barrier (GFB) with human podocytes and endothelial cells with a bidirectional flow in the bottom channel. Using puromycin-induced GN, we observed decreased cell viability, increased albumin permeability, and reduced WT1 and nephrin compared to the normal GFB. Tacrolimus restored cell viability, reduced albumin permeability, and increased WT1 expression. Using serum from five membranous nephropathy (MN) patients, we created MN models using a GFB-mimicking chip. A notable decline in cell viability was observed in the serum-induced MN1 and MN2 models. However, tacrolimus restored it. Albumin permeability was reduced in the MN1, MN2, and MN5 models by tacrolimus treatment. MN1 displayed the best clinical response to tacrolimus, exhibiting increased expression of WT1 in chip-based evaluations after tacrolimus treatment. We successfully evaluated the efficacy of tacrolimus using puromycin-induced and serum-induced GN models on a chip that mimicked the structure and function of the GFB. The GFB-mimicking chip holds promise as a personalized platform for assessing drug efficacy using patient serum samples. [ABSTRACT FROM AUTHOR]

Colistimethate sodium (CMS) nebulization is associated with reduced systemic toxicity compared to intravenous injection, with potentially enhanced clinical efficacy. This study aimed to assess the pharmacokinetic (PK) properties of colistin during low-dose CMS nebulization in patients with ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii. A nonlinear mixed-effects modeling approach was applied to develop population PK models for colistin in both epithelial lining fluid (ELF) and plasma. Twenty patients participated, and 80 ELF and 100 plasma samples were used for model development. Median colistin concentrations measured in ELF were 614-fold, 408-fold, and 250-fold higher than in plasma at 1, 3, and 5 h, respectively. Time courses in both ELF and plasma were best described by a one-compartment model with a Weibull absorption process. When the final model was simulated, the maximum free concentration and area under the free colistin concentration–time curve at steady state over 24 h in the plasma were approximately 1/90 and 1/50 of the corresponding values in ELF at steady state, respectively. For an A. baumannii MIC of 1 mg/L, inhaling 75 mg of CMS at 6 h intervals was deemed appropriate, with dose adjustments needed for MICs exceeding 2 mg/L. Using a nebulizer for CMS resulted in a notably higher exposure of colistin in the ELF than plasma, indicating the potential of nebulization to reduce systemic toxicity while effectively treating VAP. [ABSTRACT FROM AUTHOR]

A horospherical variety is a normal G-variety such that a connected reductive algebraic group G acts with an open orbit isomorphic to a torus bundle over a rational homogeneous manifold. The projective horospherical manifolds of Picard number one are classified by Pasquier, and it turned out that the automorphism groups of all nonhomogeneous ones are non-reductive, which implies that they admit no Kähler–Einstein metrics. As a numerical measure of the extent to which a Fano manifold is close to be Kähler–Einstein, we compute the greatest Ricci lower bounds of projective horospherical manifolds of Picard number one using the barycenter of each moment polytope with respect to the Duistermaat–Heckman measure based on a recent work of Delcroix and Hultgren. In particular, the greatest Ricci lower bound of the odd symplectic Grassmannian SGr (n , 2 n + 1) can be arbitrarily close to zero as n grows. [ABSTRACT FROM AUTHOR]

Background: Ultrasound-guided percutaneous dilatational tracheostomy (US-PDT) has been adapted for use in intensive care units (ICU). US-PDT is comparable to bronchoscopy-assisted tracheostomy. However, compared to surgical tracheostomy (ST), its safety and effectiveness have not been well studied.Objectives: To determine the efficacy and safety of US-PDT compared to ST.Materials and Methods: A total of 90 patients who underwent US-PDT (n = 36) or ST (n = 54) between July 2019 and September 2020 were enrolled. US-PDT was performed in the ICU without a surgical assistant or bronchoscope. Data were collected retrospectively and analyzed regarding clinical characteristics, procedure times and details, complications, and mortality rate.Results: The success rate of US-PDT was 97.4% and the procedure time was shorter than ST (5.2 ± 3.1 vs. 10.5 ± 5.0 min). There were no significant differences in clinical characteristics and procedure details. There was no procedure-related mortality in either of the groups.Conclusions: US-PDT is time-efficient and as safe as ST. Based on our results, US-PDT may be considered a potential alternative to ST in high-risk patients and in those who cannot be transported. [ABSTRACT FROM AUTHOR]

Sudden sensorineural hearing loss (SSNHL) has several aetiologies and may be a presenting symptom of vestibular schwannoma (VS). The aim of this study was to investigate the recovery rate after steroid treatment and the prognostic factors of SSNHL with VS. This was a retrospective observational study wherein 32 patients with VS who presented with SSNHL were analysed at a tertiary referral centre. Hearing gain and prognostic factors were the main outcome measures for steroid treatment intervention. Among the 1698 patients presenting with SSNHL, VS was found in 43 (2.5%) patients. Eleven cases (34.3%) showed good recovery, with significant improvements in the pure-tone audiometry values. Even though age was a significant factor, there were no associations between steroid response and initial hearing level, presence of vertigo, tumour size, and tumour extension. Our study showed that hearing recovery of SSNHL does not exclude a VS diagnosis. We suggest that steroid treatment be considered in patients with VS presenting SSNHL. [ABSTRACT FROM AUTHOR]

Background: Smoking or weight loss is a risk of tuberculosis (TB) development. However, the impact of weight change after smoking cessation on the occurrence of TB remains elusive. We aimed to determine the relationship between weight change after smoking cessation and the risk of TB development. Methods: We conducted a population-based cohort study using the national database in Republic of Korea. Of the 10,490,491 subjects who underwent health check-up in 2009, we enrolled 9,953,124 subjects without a previous TB history and followed them until 2017. We divided all study participants into the following three groups: never, former, and current smokers. The primary endpoint was newly developed TB. Results: Among 9,953,124 subjects analyzed, 5,922,845 (59.5%) were never smokers, 1,428,209 (14.4%) were former smokers, and 2,602,080 (26.1%) were current smokers. The risk of TB development was significantly higher in current smokers than in never smokers (adjusted hazard ratio (aHR) 1.158; 95% confidence interval [CI] 1.131–1.186). Among current smokers, individuals who stopped smoking and maintained weight after baseline evaluation had a significantly lower risk of TB development compared with those who continued to smoke (aHR 0.771; 95% CI 0.741–0.892). However, even after smoking cessation, individuals who lost weight were at a significantly higher risk of TB development compared with those who continued to smoke (aHR 1.327; 95% CI 1.119–1.715). Conclusions: Our findings suggest that smoking is a risk factor for TB and weight maintenance (neither gaining or losing) after quitting smoking might reduce the risk of TB development. [ABSTRACT FROM AUTHOR]