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Background: Secondary mitral regurgitation (MR) worsens in 10-15 % of heart failure (HF) patients receiving cardiac resynchronization therapy (CRT). Transcatheter edge-to-edge repair (TEER) with Mitra-Clip (Abbot Vascular, Santa Clara, CA, USA) therapy is associated with improved survival and decreased rates of hospitalization for HF in selected patients with secondary MR. Data on TEER outcomes in CRT-non-responders are limited. The purpose of this meta-analysis was to evaluate outcomes of mitral TEER with Mitra-Clip in CRT-non-responders., Methods: Cochrane, Scopus, MEDLINE, and EMBASE were searched for studies discussing outcomes of Mitra-Clip in CRT non-responders. Two reviewers were independently involved in screening studies and extracting relevant data. Individual study incidence rate estimates underwent logit transformation to calculate the weighted summary proportion under the random effect model., Results: A total of eight reports met the inclusion criteria (439 patients). Mitra-Clip improved MR grade to ≤2+ in 83.8 % and 86.8 % of CRT non-responders at six months and one year, respectively. Symptomatic improvement (New York Heart Association class ≤II) was also found in 71 % and 78.1 % of CRT non-responders at six months and one year, respectively. The pooled overall incidence estimates of mortality at 30 days, 6 months, 1 year, and 2 years were 3.6 %, 9.2 %, 17.8 %, and 25.9 %, respectively., Conclusion: TEER with Mitra-Clip in patients with significant secondary MR who do not respond to CRT was associated with MR improvement, alleviation of symptoms, and mortality rates similar to those in the COAPT trial., Competing Interests: Declaration of competing interest None of the authors has any conflict of interest., (Published by Elsevier Ltd.)

Inula viscosa is a widely used plant in traditional Mediterranean and Middle Eastern medicine for various illnesses. I. viscosa has been shown to have anticancer effects against various cancers, but its effects against lung cancer have been under limited investigation. At the same time, I. viscosa is rich in terpenoids whose anti-lung cancer effects have been poorly investigated. This study aimed to examine the potential anticancer properties of methanolic and aqueous extracts of stems and leaves of I. viscosa and its terpenoid-rich fraction against human lung cancer A549 cells. Results showed that the methanolic extracts of I. viscosa had significantly higher polyphenol and flavonoid content and radical scavenging capacity than the aqueous extracts. In addition, leaves methanolic extracts (IVLM) caused the highest reduction in viability of A549 cells among all the extracts. IVLM also reduced the viability of human ovarian SK-OV-3, breast MCF-7, liver HepG2, and colorectal HCT116 cancer cells. A terpenoid-rich I. viscosa fraction (IVL DCM), prepared by liquid-liquid separation of IVLM in dichloromethane (DCM), displayed a substantial reduction in the viability of A549 cells (IC 50 = 27.8 ± 1.5 µg/mL at 48 h) and the panel of tested cancerous cell lines but was not cytotoxic to normal human embryonic fibroblasts (HDFn). The assessment of IVL DCM phytochemical constituents using GC-MS analysis revealed 21 metabolites, highlighting an enrichment in terpenoids, such as lupeol and its derivatives, caryophyllene oxide, betulin, and isopulegol, known to exhibit proapoptotic and antimetastatic functions. IVL DCM also showed robust antioxidant capacity and decent polyphenol and flavonoid contents. Furthermore, Western blotting analysis indicated that IVL DCM reduced proliferation (reduction of proliferation marker Ki67 and induction of proliferation inhibitor proteins P21 and P27), contaminant with P38 MAP kinase activation, and induced the intrinsic apoptotic pathway (P53/BCL2/BAX/Caspase3/PARP) in A549 cells. IVL DCM also reduced the migration of A549 cells, potentially by reducing FAK activation. Future identification of anticancer metabolites of IVL DCM, especially terpenoids, is recommended. These data place I. viscosa as a new resource of herbal anticancer agents.

Background: Robotic cholecystectomy is being increasingly used for patients with acute gallbladder disease who present to the emergency department, but clinical evidence is limited. We aimed to compare the outcomes of emergent laparoscopic and robotic cholecystectomies in a large real-world database., Methods: Patients who received emergent laparoscopic or robotic cholecystectomies from 2020 to 2022 were identified from the Intuitive Custom Hospital Analytics database, based on deidentified extraction of electronic health record data from US hospitals. Conversion to open or subtotal cholecystectomy and complications were defined using ICD10 and/or CPT codes. Multivariate logistic regression with inverse probability treatment weighting (IPTW) was performed to compare clinical outcomes of laparoscopic versus robotic approach after balancing covariates. Cost analysis was performed with activity-based costing and adjustment for inflation., Results: Of 26,786 laparoscopic and 3,151 robotic emergent cholecystectomy patients being included, 64% were female, 60% were ≥45 years, and 24% were obese. Approximately 5.5% patients presented with pancreatitis, and 4% each presenting with sepsis and biliary obstruction. After IPTW, distributions of all baseline covariates were balanced. Robotic cholecystectomy decreased odds of conversion to open (odds ratio, 0.68; 95% confidence interval, 0.49-0.93; p = 0.035), but increased odds of subtotal cholecystectomy (odds ratio, 1.64; 95% confidence interval, 1.03-2.60; p = 0.037). Surgical site infection, readmission, length of stay, hospital acquired conditions, bile duct injury or leak, and hospital mortality were similar in both groups. There was no significant difference in hospital cost., Conclusion: Robotic cholecystectomy has reduced odds of conversion to open and comparable complications, but increased odds of subtotal cholecystectomy compared with laparoscopic cholecystectomy for acute gallbladder diseases. Further work is required to assess the long-term implications of these differences., Level of Evidence: Therapeutic/Care Management; Level IV., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background & Aims: Cholemic nephropathy (CN) is a severe complication of cholestatic liver diseases for which there is no specific treatment. We revisited its pathophysiology with the aim of identifying novel therapeutic strategies., Methods: Cholestasis was induced by bile duct ligation (BDL) in mice. Bile flux in kidneys and livers was visualized by intravital imaging, supported by MALDI mass spectrometry imaging and liquid chromatography-tandem mass spectrometry. The effect of AS0369, a systemically bioavailable apical sodium-dependent bile acid transporter (ASBT) inhibitor, was evaluated by intravital imaging, RNA-sequencing, histological, blood, and urine analyses. Translational relevance was assessed in kidney biopsies from patients with CN, mice with a humanized bile acid (BA) spectrum, and via analysis of serum BAs and KIM-1 (kidney injury molecule 1) in patients with liver disease and hyperbilirubinemia., Results: Proximal tubular epithelial cells (TECs) reabsorbed and enriched BAs, leading to oxidative stress and death of proximal TECs, casts in distal tubules and collecting ducts, peritubular capillary leakiness, and glomerular cysts. Renal ASBT inhibition by AS0369 blocked BA uptake into TECs and prevented kidney injury up to 6 weeks after BDL. Similar results were obtained in mice with humanized BA composition. In patients with advanced liver disease, serum BAs were the main determinant of KIM-1 levels. ASBT expression in TECs was preserved in biopsies from patients with CN, further highlighting the translational potential of targeting ASBT to treat CN., Conclusions: BA enrichment in proximal TECs followed by oxidative stress and cell death is a key early event in CN. Inhibiting renal ASBT and consequently BA enrichment in TECs prevents CN and systemically decreases BA concentrations., Impact and Implications: Cholemic nephropathy (CN) is a severe complication of cholestasis and an unmet clinical need. We demonstrate that CN is triggered by the renal accumulation of bile acids (BAs) that are considerably increased in the systemic blood. Specifically, the proximal tubular epithelial cells of the kidney take up BAs via the apical sodium-dependent bile acid transporter (ASBT). We developed a therapeutic compound that blocks ASBT in the kidneys, prevents BA overload in tubular epithelial cells, and almost completely abolished all disease hallmarks in a CN mouse model. Renal ASBT inhibition represents a potential therapeutic strategy for patients with CN., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

The development of biobased polymeric materials for wastewater purification has become a demand due to the growing need for water free of hazardous metal ions for safe purposes. The organic components of the OLLW including carbohydrates, phenolics, aromatic acids and others are cost-effective and sustainable choices for this application. This work focuses on a method for turning the organic components of liquid waste from the olive industry (OILW) into a foam-based value-added polymer that has several metal ion binding sites. The process of making the target polymers involved reacting the components of the OILW with hexamethylene diisocyante and 1,4-phnyelene diisocynate to create the polymeric materials LHMIDIC and LPDIC that are in foam forms with urethane linkages, respectively. The adsorption competence of the polymeric foams toward Pb(II) was evaluated as a function of various parameters including adsorbent dose, pH, temperature, initial ion concentration and time. The optimum parameters values that led to a quantitative removal of Pb(II) were identified. The obtained thermodynamic parameters showed that the adsorption by the two foams was spontaneous at room temperature. The isothermal and kinetic values showed that the adsorption by synthesized foams follows a second order kinetic and obeys the Langmuir isothermal model. The foams showed a high tendency for removing multi metal ions present in a real sample of wastewater. The original nature of the starting material used in making the foam, cost and the obtained results showed the potential of using the foam in a large-scale plants of wastewater purification., (© 2023. The Author(s).)