Comparative efficacy of terlipressin and norepinephrine for treatment of hepatorenal syndrome-acute kidney injury: A systematic review and meta-analysis.

The treatment of choice for hepatorenal syndrome-acute kidney injury (HRS-AKI) is vasoconstrictor therapy in combination with albumin, preferably norepinephrine or terlipressin as recommended by recent guidelines. In the absence of larger head-to-head trials comparing the efficacy of terlipressin and norepinephrine, meta-analysis of smaller studies can provide insights needed to understand the comparative effects of these medications. Additionally, recent changes in the HRS diagnosis and treatment guidelines underscore the need for newer analyses comparing terlipressin and norepinephrine. In this systematic review, we aimed to assess reversal of hepatorenal syndrome (HRS) and 1-month mortality in subjects receiving terlipressin or norepinephrine for the management of HRS-AKI. We searched literature databases, including PubMed, Cochrane, Clinicaltrials.gov, International Clinical Trials Registry Platform, Embase, and ResearchGate, for randomized controlled trials (RCTs) published from January 2007 to June 2023 on June 26, 2023. Only trials comparing norepinephrine and albumin with terlipressin and albumin for the treatment of HRS-AKI in adults were included, and trials without HRS reversal as an endpoint or nonresponders were excluded. Pairwise meta-analyses with the random effects model were conducted to estimate odds ratios (ORs) for HRS reversal and 1-month mortality as primary outcomes. Additional outcomes assessed, included HRS recurrence, predictors of response, and incidence of adverse events (AEs). We used the Cochrane risk of bias assessment tool for quality assessment. We included 7 RCTs with a total of 376 subjects with HRS-AKI or HRS type 1. This meta-analysis showed numerically higher rates of HRS reversal (OR 1.33, 95% confidence interval [CI] [0.80-2.22]; P = 0.22) and short-term survival (OR 1.50, 95% CI [0.64-3.53]; P = 0.26) with terlipressin, though these results did not reach statistical significance. Terlipressin was associated with AEs such as abdominal pain and diarrhea, whereas norepinephrine was associated with cardiovascular AEs such as chest pain and ischemia. Most of the AEs were reversible with a reduction in dose or discontinuation of therapy across both arms. Of the terlipressin-treated subjects, 5.3% discontinued therapy due to serious AEs compared to 2.7% of the norepinephrine-treated subjects. Limitations of this analysis included small sample size and study differences in HRS-AKI diagnostic criteria. As more studies using the new HRS-AKI criteria comparing terlipressin and norepinephrine are completed, a clearer understanding of the comparability of these 2 therapies will emerge.

Vehicle Detection and Attribution from a Multi-Sensor Dataset Using a Rule-Based Approach Combined with Data Fusion.

Vehicle detection using data fusion techniques from overhead platforms (RGB/MSI imagery and LiDAR point clouds) with vector and shape data can be a powerful tool in a variety of fields, including, but not limited to, national security, disaster relief efforts, and traffic monitoring. Knowing the location and number of vehicles in a given area can provide insight into the surrounding activities and patterns of life, as well as support decision-making processes. While researchers have developed many approaches to tackling this problem, few have exploited the multi-data approach with a classical technique. In this paper, a primarily LiDAR-based method supported by RGB/MSI imagery and road network shapefiles has been developed to detect stationary vehicles. The addition of imagery and road networks, when available, offers an improved classification of points from LiDAR data and helps to reduce false positives. Furthermore, detected vehicles can be assigned various 3D, relational, and spectral attributes, as well as height profiles. This method was evaluated on the Houston, TX dataset provided by the IEEE 2018 GRSS Data Fusion Contest, which includes 1476 ground truth vehicles from LiDAR data. On this dataset, the algorithm achieved a 92% precision and 92% recall. It was also evaluated on the Vaihingen, Germany dataset provided by ISPRS, as well as data simulated using an image generation model called DIRSIG. Some known limitations of the algorithm include false positives caused by low vegetation and the inability to detect vehicles (1) in extremely close proximity with high precision and (2) from low-density point clouds.

Case Report: Efficacy of albumin dialysis for the reversal of bile cast nephropathy-induced acute kidney injury.

Background: Bile cast nephropathy (BCN) is an underdiagnosed renal complication associated with severe hyperbilirubinemia and is seen in patients with liver failure who have cholestatic complications. BCN-induced acute kidney injury (AKI) can require hemodialysis (HD), and the molecular adsorbent recirculating system (MARS) is a potentially useful therapeutic option. Case summary: A 57-year-old male presented with jaundice persisting for 1 month, with laboratory test results indicative of hyperbilirubinemia and AKI. Abdominal imaging and a biopsy confirmed biliary ductal dilation secondary to a pancreatic head mass. The patient had rapidly progressive renal failure and refractory hyperbilirubinemia, despite biliary decompression, and was started on HD. Subsequent therapy with albumin dialysis therapy using MARS was successful in reversing the AKI, the cessation of HD, and the restoration of native renal function. Conclusion: In the setting of BCN-induced AKI, timely initiation of MARS can provide a useful therapeutic strategy to reverse renal dysfunction and facilitate intrinsic renal recovery.

Spatially modulated erbium YAG laser as a treatment for diabetic ulcer.

OBJECTIVE: Diabetic ulcers are a significant healthcare challenge, capable of diminishing quality of life, lengthening hospitalisation stay, and incurring substantial costs for patients and healthcare systems. Erbium-doped yttrium-aluminum-garnet (Er-YAG) laser has been evolving as a prospective intervention for addressing wounds of various aetiologies. Despite this, the literature remains limited in appraising the effectiveness of laser therapy specifically in diabetic wounds. This study investigates the impact of employing a spatially modulated Er-YAG laser as a therapeutic approach for treating diabetic ulcers. METHOD: In a single-arm study conducted from November 2017 to April 2023, patients with hard-to-heal ulcers were treated in a two-step approach of wound debridement using Er-YAG laser for ablation and biostimulation through deep tissue resonance using RecoSMA (Multiline laser system, LINLINE MS, Latvia) laser technology. Ulcers received weekly laser treatment, together with routine care until healing occurred and were then followed up to observe any recurrence. The primary outcome measure was wound closure; the secondary outcome measures were time to closure, and the number of laser treatments required. Data related to sociodemographic details, size and number of diabetic ulcers, and number of sessions related to laser treatment were collected using a predesigned, pretested questionnaire before initiating the treatment. RESULTS: A total of 59 patients attending the clinic during the study period with diabetic ulcers were included in the study. The mean wound surface area at baseline was 25.7cm2 (median: 12cm2). The average number of sessions of laser treatment required was 4.41, ranging from 1-11. The size of the ulcer reduced with each session of laser treatment. The diabetic ulcers healed completely at the end of the treatment, indicating the effectiveness of the Er-YAG/RecoSMA two-step approach. CONCLUSION: Spatially modulated erbium YAG laser is effective as a therapeutic approach for treating diabetic ulcers.

Assessment of Various Multimodal Fusion Approaches Using Synthetic Aperture Radar (SAR) and Electro-Optical (EO) Imagery for Vehicle Classification via Neural Networks.

Multimodal fusion approaches that combine data from dissimilar sensors can better exploit human-like reasoning and strategies for situational awareness. The performance of a six-layer convolutional neural network (CNN) and an 18-layer ResNet architecture are compared for a variety of fusion methods using synthetic aperture radar (SAR) and electro-optical (EO) imagery to classify military targets. The dataset used is the Synthetic and Measured Paired Labeled Experiment (SAMPLE) dataset, using both original measured SAR data and synthetic EO data. We compare the classification performance of both networks using the data modalities individually, feature level fusion, decision level fusion, and using a novel fusion method based on the three RGB-input channels of a residual neural network (ResNet). In the proposed input channel fusion method, the SAR and the EO imagery are separately fed to each of the three input channels, while the third channel is fed a zero vector. It is found that the input channel fusion method using ResNet was able to consistently perform to a higher classification accuracy in every equivalent scenario.

Volume regulation in adhered cells: Roles of surface tension and cell swelling.

The volume of adhered cells has been shown experimentally to decrease during spreading. This effect can be understood from the pump-leak model, which we have extended to include mechano-sensitive ion transporters. We identify a novel effect that has important consequences on cellular volume loss: cells that are swollen due to a modulation of ion transport rates are more susceptible to volume loss in response to a tension increase. This effect explains in a plausible manner the discrepancies between three recent, independent experiments on adhered cells, between which both the magnitude of the volume change and its dynamics varied substantially. We suggest that starved and synchronized cells in two of the experiments were in a swollen state and, consequently, exhibited a large volume loss at steady state. Nonswollen cells, for which there is a very small steady-state volume decrease, are still predicted to transiently lose volume during spreading due to a relaxing viscoelastic tension that is large compared with the steady-state tension. We elucidate the roles of cell swelling and surface tension in cellular volume regulation and discuss their possible microscopic origins.

Admission Serum Metabolites and Thyroxine Predict Advanced Hepatic Encephalopathy in a Multicenter Inpatient Cirrhosis Cohort.

BACKGROUND & AIMS: Grades 3 to 4 hepatic encephalopathy (advanced HE), also termed brain failure, is an organ failure that defines acute-on-chronic liver failure. It is associated with poor outcomes in cirrhosis but cannot be predicted accurately. We aimed to determine the admission metabolomic biomarkers able to predict the development of advanced HE with subsequent validation. METHODS: Prospective inpatient cirrhosis cohorts (multicenter and 2-center validation) without brain failure underwent admission serum collection and inpatient follow-up evaluation. Serum metabolomics were analyzed to predict brain failure on random forest analysis and logistic regression. A separate validation cohort also was recruited. RESULTS: The multicenter cohort included 602 patients, of whom 144 developed brain failure (105 only brain failure) 3 days after admission. Unadjusted random forest analysis showed that higher admission microbially derived metabolites and lower isoleucine, thyroxine, and lysophospholipids were associated with brain failure development (area under the curve, 0.87 all; 0.90 brain failure only). Logistic regression area under the curve with only clinical variables significantly improved with metabolites (95% CI 0.65-0.75; P = .005). Four metabolites that significantly added to brain failure prediction were low thyroxine and maltose and high methyl-4-hydroxybenzoate sulfate and 3-4 dihydroxy butyrate. Thyroxine alone also significantly added to the model (P = .05). The validation cohort including 81 prospectively enrolled patients, of whom 11 developed brain failure. Admission hospital laboratory thyroxine levels predicted brain failure development despite controlling for clinical variables with high specificity. CONCLUSIONS: In a multicenter inpatient cohort, admission serum metabolites, including thyroxine, predicted advanced HE development independent of clinical factors. Admission low local laboratory thyroxine levels were validated as a predictor of advanced HE development in a separate cohort.

The COVID-19 pandemic and the future of telecommuting in the United States.

This study focuses on an important transport-related long-term effect of the COVID-19 pandemic in the United States: an increase in telecommuting. Analyzing a nationally representative panel survey of adults, we find that 40-50% of workers expect to telecommute at least a few times per month post-pandemic, up from 24% pre-COVID. If given the option, 90-95% of those who first telecommuted during the pandemic plan to continue the practice regularly. We also find that new telecommuters are demographically similar to pre-COVID telecommuters. Both pre- and post-COVID, higher educational attainment and income, together with certain job categories, largely determine whether workers have the option to telecommute. Despite growth in telecommuting, approximately half of workers expect to remain unable to telecommute and between 2/3 and 3/4 of workers expect their post-pandemic telecommuting patterns to be unchanged from their pre-COVID patterns. This limits the contribution telecommuting can make to reducing peak hour transport demand.

Disulfiram Is Effective against Drug-Resistant Mycobacterium abscessus in a Zebrafish Embryo Infection Model.

Mycobacterium abscessus is an emerging nontuberculous mycobacterium (NTM) pathogen infecting susceptible people with cystic fibrosis (CF) and non-CF bronchiectasis. Here, we demonstrated the activity of an FDA-approved drug, disulfiram, against drug-susceptible and drug-resistant M. abscessus strains utilizing in vitro and intracellular macrophage assays and a zebrafish embryo infection model. These data demonstrate effective antimicrobial activity of disulfiram against M. abscessus infection in vivo and strongly support further study of disulfiram in human NTM infections.

The Efficacy of Albumin Dialysis in the Treatment of Severe Cholestatic Drug-Induced Liver Injury.

Drug-induced liver injury (DILI) is a significant cause of acute liver injury and can present as cholestatic injury with or without associated hepatitis. Although most patients with DILI recover with supportive care, some can develop severe refractory cholestasis that impairs recovery of hepatic function, with subsequent progression to acute or chronic liver failure. Current pharmacotherapy and extracorporeal therapies such as hemodialysis have limited benefit. Albumin dialysis is an emerging strategy in the extracorporeal treatment of intoxications caused by protein bound drugs and can be used for the removal of albumin bound bilirubin and bile acids. CASES SERIES: We describe the efficacy of albumin dialysis with the molecular adsorbent recirculating system (MARS) in the successful treatment of five patients with severe cholestatic DILI that was refractory to standard medical therapy. All patients had a sustained improvement in serum bilirubin levels after completing MARS therapy, with a complete resolution of their liver injury. DISCUSSION: Our case series demonstrates that albumin dialysis could provide an important treatment strategy in the setting of severe refractory cholestatic DILI and be considered as a novel therapeutic option in specific cases of drug hepatotoxicity in which the causative agent has high protein binding characteristics.

Association of serum metabolites and gut microbiota at hospital admission with nosocomial infection development in patients with cirrhosis.

Cirrhosis is complicated by a high rate of nosocomial infections (NIs), which result in poor outcomes and are challenging to predict using clinical variables alone. Our aim was to determine predictors of NI using admission serum metabolomics and gut microbiota in inpatients with cirrhosis. In this multicenter inpatient cirrhosis study, serum was collected on admission for liquid chromatography-mass spectrometry metabolomics, and a subset provided stool for 16SrRNA analysis. Hospital course, including NI development and death, were analyzed. Metabolomic analysis using analysis of covariance (ANCOVA) (demographics, Model for End-Stage Liver Disease [MELD] admission score, white blood count [WBC], rifaximin, and infection status adjusted) and random forest analyses for NI development were performed. Additional values of serum metabolites over clinical variables toward NI were evaluated using logistic regression. Stool microbiota and metabolomic correlations were compared in patients with and without NI development. A total of 602 patients (231 infection admissions) were included; 101 (17%) developed NIs, which resulted in worse inpatient outcomes, including intensive care unit transfer, organ failure, and death. A total of 127 patients also gave stool samples, and 20 of these patients developed NIs. The most common NIs were spontaneous bacterial peritonitis followed by urinary tract infection, Clostridioides difficile, and pneumonia. A total of 247 metabolites were significantly altered on ANCOVA. Higher MELD scores (odds ratio, 1.05; p < 0.0001), admission infection (odds ratio, 3.54; p < 0.0001), and admission WBC (odds ratio, 1.05; p = 0.04) predicted NI (area under the curve, 0.74), which increased to 0.77 (p = 0.05) with lower 1-linolenoyl-glycerolphosphocholine (GPC) and 1-stearoyl-GPC and higher N-acetyltryptophan and N-acetyl isoputreanine. Commensal microbiota were lower and pathobionts were higher in those who developed NIs. Microbial-metabolite correlation networks were complex and dense in patients with NIs, especially sub-networks centered on Ruminococcaceae and Pseudomonadaceae. NIs are common and associated with poor outcomes in cirrhosis. Admission gut microbiota in patients with NIs showed higher pathobionts and lower commensal microbiota. Microbial-metabolomic correlations were more complex, dense, and homogeneous among those who developed NIs, indicating greater linkage strength. Serum metabolites and gut microbiota on admission are associated with NI development in cirrhosis.

Efficacy of Adjunctives in Periodontal Surgeries: An Evidenced-Based Summary.

Periodontal surgery is required to access the root surfaces in order to debride them of dental plaque and calculus, promote pocket reduction, create healthy bone architecture, and provide patients greater access to out-of-reach areas to maintain oral hygiene. The use of adjunctive agents and materials-enamel matrix derivatives, low-laser treatment, ozone, locally administered minocycline HCL, doxycycline gels, tetracycline fibers, chlorhexidine chips, granular beta-tricalcium phosphate, and hyaluronic acid, and the like-have been reported to improve pocket depth reduction, periodontal ligament healing, bone defect filling, and mechanical debridement during guided tissue regeneration/flap surgeries. However, the efficacy and benefits of these adjuvants compared to periodontal surgery alone is still widely debated. This evidence-based review critically evaluates and summarizes the efficacy of adjuvants used in periodontal surgery that have been reported in the literature.

Respiratory events with terlipressin and albumin in hepatorenal syndrome: A review and clinical guidance.

Hepatorenal syndrome-acute kidney injury (HRS-AKI) is a serious complication of severe liver disease with a clinically poor prognosis. Supportive care using vasoconstrictors and intravenous albumin are the current mainstays of therapy. Terlipressin is an efficacious vasoconstrictor that has been used for 2 decades as the first-line treatment for HRS-AKI in Europe and has demonstrated greater efficacy in improving renal function compared to placebo and other vasoconstrictors. One of the challenges associated with terlipressin use is monitoring and mitigating serious adverse events, specifically adverse respiratory events, which were noted in a subset of patients in the recently published CONFIRM trial, the largest randomized trial examining terlipressin use for HRS-AKI. In this article, we review terlipressin's pharmacology, hypothesize how its mechanism contributes to the risk of respiratory compromise and propose strategies that will decrease the frequency of these events by rationally selecting patients at lower risk for these events.

Conductivity of Concentrated Electrolytes.

The conductivity of ionic solutions is arguably their most important trait, being widely used in electrochemical, biochemical, and environmental applications. The Debye-Hückel-Onsager theory successfully predicts the conductivity at very low ionic concentrations of up to a few millimolars, but there is no well-established theory applicable at higher concentrations. We study the conductivity of ionic solutions using a stochastic density functional theory, paired with a modified Coulomb interaction that accounts for the hard-core repulsion between the ions. The modified potential suppresses unphysical, short-range electrostatic interactions, which are present in the Debye-Hückel-Onsager theory. Our results for the conductivity show very good agreement with experimental data up to 3 molars, without any fit parameters. We provide a compact expression for the conductivity, accompanied by a simple analytical approximation.

Disease Progression and Mutation Pattern in a Large Cohort of LGMD R1/LGMD 2A Patients from India.

Calpainopathy is caused by mutations in the CAPN3 . There is only one clinical and genetic study of CAPN3 from India and none from South India. A total of 72 (male[M]:female [F] = 34:38) genetically confirmed probands from 72 independent families are included in this study. Consanguinity was present in 54.2%. The mean age of onset and duration of symptoms are 13.5 ± 6.4 and 6.3 ± 4.7 years, respectively. Positive family history occurred in 23.3%. The predominant initial symptoms were proximal lower limb weakness (52.1%) and toe walking (20.5%). At presentation, 97.2% had hip girdle weakness, 69.4% had scapular winging, and 58.3% had contractures. Follow-up was available in 76.4%, and 92.7% were ambulant at a mean age of 23.7 ± 7.6 years and duration of 4.5 years, remaining 7.3% became wheelchair-bound at 25.5 ± 5.7 years of age (mean duration = 13.5 ± 4.6), 4.1% were aged more than 40 years (duration range = 5-20). The majority remained ambulant 10 years after disease onset. Next-generation sequencing (NGS) detected 47 unique CAPN3 variants in 72 patients, out of which 19 are novel. Missense variants were most common occurring in 59.7% (homozygous = 29; Compound heterozygous = 14). In the remaining 29 patients (40.3%), at least one suspected loss of function variant was present. Common recurrent variants were c.2051-1G > T and c.2338G > C in 9.7%, c.1343G > A, c.802-9G > A, and c.1319G > A in 6.9% and c.1963delC in 5.5% of population. Large deletions were observed in 4.2%. Exon 10 mutations accounted for 12 patients (16.7%). Our study highlights the efficiency of NGS technology in screening and molecular diagnosis of limb-girdle muscular dystrophy with recessive form (LGMDR1) patients in India.

Use of the Molecular Adsorbent Recirculating System in Acute Liver Failure: Results of a Multicenter Propensity Score-Matched Study.

OBJECTIVES: The molecular adsorbent recirculating system removes water-soluble and albumin-bound toxins and may be beneficial for acute liver failure patients. We compared the rates of 21-day transplant-free survival in acute liver failure patients receiving molecular adsorbent recirculating system therapy and patients receiving standard medical therapy. DESIGN: Propensity score-matched retrospective cohort analysis. SETTING: Tertiary North American liver transplant centers. PATIENTS: Acute liver failure patients receiving molecular adsorbent recirculating system at three transplantation centers (n = 104; January 2009-2019) and controls from the U.S. Acute Liver Failure Study Group registry. INTERVENTIONS: Molecular adsorbent recirculating system treatment versus standard medical therapy (control). MEASUREMENTS AND MAIN RESULTS: One-hundred four molecular adsorbent recirculating system patients were propensity score-matched (4:1) to 416 controls. Using multivariable conditional logistic regression adjusting for acute liver failure etiology (acetaminophen: n = 248; vs nonacetaminophen: n = 272), age, vasopressor support, international normalized ratio, King's College Criteria, and propensity score (main model), molecular adsorbent recirculating system was significantly associated with increased 21-day transplant-free survival (odds ratio, 1.90; 95% CI, 1.07-3.39; p = 0.030). This association remained significant in several sensitivity analyses, including adjustment for acute liver failure etiology and propensity score alone ("model 2"; molecular adsorbent recirculating system odds ratio, 1.86; 95% CI, 1.05-3.31; p = 0.033), and further adjustment of the "main model" for mechanical ventilation, and grade 3/4 hepatic encephalopathy ("model 3"; molecular adsorbent recirculating system odds ratio, 1.91; 95% CI, 1.07-3.41; p = 0.029). In acetaminophen-acute liver failure (n = 51), molecular adsorbent recirculating system was associated with significant improvements (post vs pre) in mean arterial pressure (92.0 vs 78.0 mm Hg), creatinine (77.0 vs 128.2 µmol/L), lactate (2.3 vs 4.3 mmol/L), and ammonia (98.0 vs 136.0 µmol/L; p ≤ 0.002 for all). In nonacetaminophen acute liver failure (n = 53), molecular adsorbent recirculating system was associated with significant improvements in bilirubin (205.2 vs 251.4 µmol/L), creatinine (83.1 vs 133.5 µmol/L), and ammonia (111.5 vs 140.0 µmol/L; p ≤ 0.022 for all). CONCLUSIONS: Treatment with molecular adsorbent recirculating system is associated with increased 21-day transplant-free survival in acute liver failure and improves biochemical variables and hemodynamics, particularly in acetaminophen-acute liver failure.