Superior Efficacy In Terms Research Articles

Machine Learning Analysis of the Impact of Silver Nitrate and Silver Nanoparticles on Wheat (Triticum aestivum L.): Callus Induction, Plant Regeneration, and DNA Methylation.

The objective of this study was to comprehend the efficiency of wheat regeneration, callus induction, and DNA methylation through the application of mathematical frameworks and artificial intelligence (AI)-based models. This research aimed to explore the impact of treatments with AgNO3 and Ag-NPs on various parameters. The study specifically concentrated on analyzing RAPD profiles and modeling regeneration parameters. The treatments and molecular findings served as input variables in the modeling process. It included the use of AgNO3 and Ag-NPs at different concentrations (0, 2, 4, 6, and 8 mg L-1). The in vitro and epigenetic characteristics were analyzed using several machine learning (ML) methods, including support vector machine (SVM), random forest (RF), extreme gradient boosting (XGBoost), k-nearest neighbor classifier (KNN), and Gaussian processes classifier (GP) methods. This study's results revealed that the highest values for callus induction (CI%) and embryogenic callus induction (EC%) occurred at a concentration of 2 mg L-1 of Ag-NPs. Additionally, the regeneration efficiency (RE) parameter reached its peak at a concentration of 8 mg L-1 of AgNO3. Taking an epigenetic approach, AgNO3 at a concentration of 2 mg L-1 demonstrated the highest levels of genomic template stability (GTS), at 79.3%. There was a positive correlation seen between increased levels of AgNO3 and DNA hypermethylation. Conversely, elevated levels of Ag-NPs were associated with DNA hypomethylation. The models were used to estimate the relationships between the input elements, including treatments, concentration, GTS rates, and Msp I and Hpa II polymorphism, and the in vitro output parameters. The findings suggested that the XGBoost model exhibited superior performance scores for callus induction (CI), as evidenced by an R2 score of 51.5%, which explained the variances. Additionally, the RF model explained 71.9% of the total variance and showed superior efficacy in terms of EC%. Furthermore, the GP model, which provided the most robust statistics for RE, yielded an R2 value of 52.5%, signifying its ability to account for a substantial portion of the total variance present in the data. This study exemplifies the application of various machine learning models in the cultivation of mature wheat embryos under the influence of treatments and concentrations involving AgNO3 and Ag-NPs.

INJECTION OF AUTOLOGOUS WHOLE BLOOD VERSUS CORTICOSTEROID FOR LATERAL EPICONDYLITIS: A COMPARATIVE STUDY

Objective: The objective is to compare the efficacy, in terms of pain relief and functional improvement, of autologous whole blood and corticosteroid injection in managing lateral epicondylitis (Tennis elbow). Methods: This was a comparative study conducted in Department of Orthopedics, National Institute of Medical Sciences Jaipur, Rajasthan, India. Eighty patients diagnosed to be having lateral epicondylitis were included in this study on the basis of predefined inclusion and exclusion criteria. The patients were divided into 2 groups on the basis of whether they were given autologous whole blood (Group B) or corticosteroid injection (Group S). Efficacy of both the treatment modality was compared in terms of Pain relief (as assessed by reduction in visual analogue score [VAS] score) and functional improvement (as assessed by improvement in Mayo Elbow performance score). SSPS 22.0 software was used for statistical analysis and p<0.05 was taken as statistically significant. Results: A total of 80 patients were included in this study out of which there were 37 (46.25%) males and 43 (53.75%) females with a M: F ratio of 1:1.16. The mean age of patients in group B and group S was found to be found to be 52.36±9.98 years and 48.46±10.12 years, respectively. The mean age of patients in both the groups was found to be comparable with no statistically significant difference (p=0.0866). At the time of 4 weeks, 8 weeks, and 12 weeks follow–up, the mean VAS score in Group B was less as compared to group S and the difference was found to be statistically highly significant (p<0.0001). At the time of 4 weeks, 8 weeks, and 12 weeks’ follow-up, the mean MEPS in Group B was more as compared to group S, and the difference was found to be statistically significant (p<0.05). Conclusion: For lateral epicondylitis, whole blood injection demonstrated superior efficacy in terms of pain relief and functional improvement as compared to injection of corticosteroid.

Neoadjuvant chemotherapy prior to radical hysterectomy in locally advanced cervical cancer: a systematic review and meta-analysis

ObjectiveThe objective of this systematic review was to evaluate the effect of different types of neoadjuvant chemotherapy regimens, in terms of optimal pathological response and oncological outcomes, in patients with...

A Real-World Comparison of Idecabtagene Vicleucel and Ciltacabtagene Autoleucel CAR-T Therapy: A Single Center Experience for Relapsed/ Refractory Multiple Myeloma

Background Chimeric antigen receptor modified T-cell therapy is a promising new treatment for patients with heavily pre-treated multiple myeloma (MM). BCMA (B-cell maturation antigen) directed therapies including idecabtagene vicleucel (Ide-Cel) and ciltacabtagene autoleucel (Cilta-Cel) are currently approved for use in patients with four prior lines of therapy. Both therapies have shown efficacy producing a high overall response rates and durable responses. Both are second-generation designs with identical endodomain (CD3ζ - 4-1BB) to target BCMA on the target cells for patients with relapsed and refractory MM who have been triple-class exposed. The two distinct differences are ectodomain structure and recommended dose. In this single center retrospective study, we report our experience with the use of both CAR-T therapies in patients with heavily pre-treated MM. Methods Following institutional review board approval, we included all patients with MM who were treated with commercially approved BCMA directed CAR-T therapy. Demographic characteristics, molecular studies, treatment and response information were recorded and included in the study. Safety outcomes included the incidence and severity of adverse events (AEs). AEs were graded using National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE 5.0). Cytokine release syndrome (CRS) and immune effector associated neurotoxicity syndrome (ICANS) were graded as per the American Society for Transplantation and Cellular Therapy criteria. Efficacy outcomes included overall response rates (ORR), progression free survival (PFS), overall survival (OS), duration of response (DOR). Survival analysis was performed using the Kaplan-Meier method including PFS and Overall survival (OS). PFS was defined as time from initiation of treatment to progression of disease or death whichever occurred first. OS was defined as time from initiation of treatment to death. The IMW response criteria was utilized for response assessment. Results We identified 56 patients who were treated consecutively at Hackensack University Medical Center between 6/28/2021 and 7/3/2023. 53 patients had data available for evaluable responses and were included in our analysis. 35(66%) patients received Ide-cel, whereas 18(34%) patients received Cilta-Cel. For the entire cohort, 30(56.6%) were male, median age was 69.6 years median time from diagnosis to treatment was 8.1 years. Patients had received a median of 5 prior lines of therapy. 50(94.3%) patients were triple class refractory, all except one patient (98.1%) had a prior autologous stem cell transplant (ASCT). 27(60%) patients had high risk FISH defined as those with t(4;14), t(14;16), 17p(-) or 1q(+), 24(60%) patients were ISS-2 or 3 at diagnosis. Treatment was overall well tolerated, with only one therapy related mortality, 42(79.3%) patients experienced CRS, with only 1(1.9%) having grade 3 or higher CRS. 6(11.3%) patients experienced ICANS, with 2(3.8%) having grade 3 or higher ICANS. Baseline characteristics are summarized in table 1. Overall response rate for the entire cohort was 75.4%, with a median PFS of 11.9 months, median DOR of 13.2 months and mOS was not reached (NR). The median ORR for cilta-cel vs ide-cel was 94.4 % and 65.7% (p=0.01) respectively. The median PFS for cilta- cel vs ide-cel was NR vs 10.9 months (p=0.09) respectively (Figure 1), follow-up being very short for cilta- cel. Baseline characteristics, safety and efficacy data for the cohort and comparison between the two therapies are summarized in table 1. Conclusions In our single center experience, cilta-cel has shown superiority in terms of efficacy compared to ide-cel. Having said that, the authors do strongly recognize that longer manufacturing time for cilta-cel introduces a bias in favor of using ide-cel for patients with more aggressive/rapidly progressing disease, which may therefore result in inferior outcomes. The safety profile for both therapies is very similar and both offer promising results to patients with MM.

Skin Anti-Aging Effect of Oral Vitamin A Supplementation in Combination with Topical Retinoic Acid Treatment in Comparison with Topical Treatment Alone: A Randomized, Prospective, Assessor-Blinded, Parallel Trial

Topical retinoid treatment is considered a standard therapeutic approach for chrono and photo skin aging. Retinol (vitamin A) is the precursor of endogenous retinoids. A prospective, 12-week, randomized, parallel-group trial comparing the combination of vitamins’ oral supplementation (one capsule daily, 50.000 UI vitamin A and 50 mg vitamin E) and a 0.02% retinoic acid topical gel formulation (RG) applied in the evening (Group B) in comparison with the topical RG treatment alone (Group A) was conducted. A total of 60 subjects (men and women, aged >50 years, mean age 60 ± 8 years) with moderate-severe facial skin aging (Glogau score > 2) were enrolled after their written informed consent. Thirty participants were randomly assigned to Group A and 30 to Group B. The primary endpoint was the clinical evaluation of a Skin Aging Global Score (SAGS), at baseline, and after 6 and 12 weeks. A VISIA® (Canfield Scientific, Parsippany, NJ, USA)face sculptor analysis was performed in a subgroup of 20 subjects. Skin tolerability was evaluated in both groups at weeks 6 and 12. In comparison with the baseline, SAGS scores in both groups were reduced by 13% (Group A) and by 14% (Group B) after 6 weeks and by 22% (Group A) and by 27% (Group B) at week 12. At the end of the study, SAGS score absolute reduction in Group B was significantly greater (p < 0.01) in comparison with the absolute reduction in Group A. Both treatment regimens were well tolerated. The combination of medium-high doses of oral retinol supplementation (Vitamin A) and topical retinoic acid gel showed superior efficacy in terms of clinical improvement in comparison with the topical treatment alone in subjects with moderate/severe skin aging.

Investigation of the Influence of Polyamines on Mature Embryo Culture and DNA Methylation of Wheat (Triticum aestivum L.) Using the Machine Learning Algorithm Method.

Numerous factors can impact the efficiency of callus formation and in vitro regeneration in wheat cultures through the introduction of exogenous polyamines (PAs). The present study aimed to investigate in vitro plant regeneration and DNA methylation patterns utilizing the inter-primer binding site (iPBS) retrotransposon and coupled restriction enzyme digestion-iPBS (CRED-iPBS) methods in wheat. This investigation involved the application of distinct types of PAs (Put: putrescine, Spd: spermidine, and Spm: spermine) at varying concentrations (0, 0.5, 1, and 1.5 mM). The subsequent outcomes were subjected to predictive modeling using diverse machine learning (ML) algorithms. Based on the specific polyamine type and concentration utilized, the results indicated that 1 mM Put and Spd were the most favorable PAs for supporting endosperm-associated mature embryos. Employing an epigenetic approach, Put at concentrations of 0.5 and 1.5 mM exhibited the highest levels of genomic template stability (GTS) (73.9%). Elevated Spd levels correlated with DNA hypermethylation while reduced Spm levels were linked to DNA hypomethylation. The in vitro and epigenetic characteristics were predicted using ML techniques such as the support vector machine (SVM), extreme gradient boosting (XGBoost), and random forest (RF) models. These models were employed to establish relationships between input variables (PAs, concentration, GTS rates, Msp I polymorphism, and Hpa II polymorphism) and output parameters (in vitro measurements). This comparative analysis aimed to evaluate the performance of the models and interpret the generated data. The outcomes demonstrated that the XGBoost method exhibited the highest performance scores for callus induction (CI%), regeneration efficiency (RE), and the number of plantlets (NP), with R2 scores explaining 38.3%, 73.8%, and 85.3% of the variances, respectively. Additionally, the RF algorithm explained 41.5% of the total variance and showcased superior efficacy in terms of embryogenic callus induction (ECI%). Furthermore, the SVM model, which provided the most robust statistics for responding embryogenic calluses (RECs%), yielded an R2 value of 84.1%, signifying its ability to account for a substantial portion of the total variance present in the data. In summary, this study exemplifies the application of diverse ML models to the cultivation of mature wheat embryos in the presence of various exogenous PAs and concentrations. Additionally, it explores the impact of polymorphic variations in the CRED-iPBS profile and DNA methylation on epigenetic changes, thereby contributing to a comprehensive understanding of these regulatory mechanisms.

RAS testing of circulating cell-free DNA (cfDNA) from tissue RAS/BRAF wild-type metastatic colorectal carcinoma (mCRC) patients: Preliminary data from the Liquid Biopsy Monoclonal Antibodies in mCRC (LIBImAb) study.

3046 Background: In mCRC patients RAS/BRAF testing is usually performed on tissue biopsy in order to select patients for treatment with anti-EGFR monoclonal antibodies. Several studies described discordant RAS status between tissue and cfDNA testing from the same patients. In addition, up to 30% of patients with secondary resistance to anti-EGFR therapies become RAS mutant at progression. The LIBImAb study is a phase III, randomized, open-label, comparative, multi-centre trial to assess the superiority in terms of efficacy of bevacizumab versus cetuximab in combination with FOLFIRI chemotherapy in patients with mCRC, RAS/BRAF wild-type on tumor tissue and RAS mutant (RASmut) at liquid biopsy. This study is supported by the Italian Drug Agency (AIFA). We report preliminary data of liquid biopsy testing. Methods: Plasma samples from enrolled patients are analyzed for variants in exons 2, 3 and 4 of KRAS and NRAS genes and for codon 600 BRAF mutations using the fully automated Idylla system (Biocartis). Patients RASmut on liquid biopsy at baseline are randomized to receive FOLFIRI plus Cetuximab or FOLFIRI plus Bevacizumab. Patients RAS wild-type on cfDNA at baseline, are treated with FOLFIRI plus Cetuximab up to 8 cycles and, if not progressed, they are retested for RAS mutations on cfDNA. RASmut patients at re-screening are randomized to continue Cetuximab or to switch to Bevacizumab. Results: Plasma samples from 169 tissue RAS/BRAF wild-type mCRC patients at baseline and 75 patients at 8 cycles of treatment have been tested as of January 31, 2023. Analysis of baseline plasma samples detected 16 RAS mutations in 16/169 patients (9.5%). In particular, 12 KRAS variants (7.1%, 8 in exon 2 and 4 in exon 3) and 4 NRAS variants (2.3%, all in exon 2) were found. The Idylla test also detected 3 BRAFV600 mutations (1.8%) in 3 additional patients. The overall concordance between tissue and cfDNA testing for RAS/BRAF variants was 88.8%. RAS mutations were also detected in 6/75 (8%) plasma samples obtained at 8 cycles of FOLFIRI/cetuximab treatment. The cfDNA test revealed the presence of 5 KRAS (6.7%, 3 in exon 2 and 1 in exon 3) and 1 NRAS mutation (1.3%, exon 2). A BRAFV600 variant was detected in 1 additional patient (1.3%). The rate of RAS/BRAF mutant cases at 8 cycles of treatment was 9.3%. Conclusions: These preliminary data suggest that liquid biopsy might better recapitulate the heterogeneity of mCRC and might be useful in clinical practice to complement tissue testing. The clinical relevance of RAS variants detected in cfDNA will be determined in the LIBImAb trial.

Comparative Efficacy of Various Stents for Palliation in Patients with Malignant Extrahepatic Biliary Obstruction: A Systematic Review and Network Meta-Analysis

Although many studies have investigated the efficacy of stent placement for patients with malignant extrahepatic biliary obstruction, the clinical outcomes and adverse events of biliary stenting have not been comprehensively evaluated. We searched all relevant randomized-controlled trials that evaluated the comparative efficacy of biliary stents, including the plastic stents, uncovered self-expandable metal stents (SEMSs), and covered SEMSs in patients with malignant extrahepatic biliary obstructions. Twenty-one studies with 2326 patients were included. Both uncovered and covered SEMSs had a lower risk of recurrent biliary obstruction (RBO) compared to plastic stents (risk ratio (RR) (95% confidence interval [CI]): uncovered vs. plastic, 0.46 (0.35–0.62); covered vs. plastic, 0.46 (0.34–0.62)). A comparison of the groups using SEMSs revealed that tumor ingrowth was common in the uncovered SEMS group, while stent migration, tumor overgrowth, and occlusion by sludge were common in the covered SEMS group; however, the overall risk of RBO did not differ between these groups (RR (95% CI): uncovered vs. covered: 1.02 (0.80–1.30)). Although the main causes of RBO vary across stents, RBO risk was similar between uncovered and covered SEMS groups. Both SEMSs have superior efficacy in terms of RBO compared to plastic stents.

Suture- or Plug-Based Large-Bore Arteriotomy Closure: A Pilot Randomized Controlled Trial.

This study sought to test the superiority in terms of efficacy and safety of a dedicated plug-based vascular closure device (VCD) during transcatheter aortic valve replacement (TAVR) over a suture-based VCD. Vascular complications after TAVR are relevant and often associated with VCD failure. The MASH (MANTA vs. Suture-based vascular closure after transcatHeter aortic valve replacement) trial is an international, 2-center pilot randomized controlled trial comparing the MANTA VCD (Teleflex, Wayne, Pennsylvania) versus 2 ProGlides (Abbott Vascular, Abbott Park, Illinois). The primary composite endpoint consisted of access site-related major or minor vascular complications at 30-days' follow-up. Secondary endpoints included clinically relevant access site bleeding, time to hemostasis, and modified VCD failure (defined as failure to achieve hemostasis within 5min or requiring additional endovascular maneuvers such as endovascular stenting, surgical techniques, or additional closure devices). Adverse events were adjudicated by an independent clinical events committee according to the VARC-2 definitions. A total of 210 TAVR patients were included between October 2018 and January 2020. Median age was 81 years, 54% were male, and the median STS score was 2.7%. There was no significant difference in the primary endpoint of access site-related vascular complications between MANTA and ProGlide (10% vs. 4%; p=0.16). Clinically significant access site bleedings were similar with both closure techniques (9% vs. 6%; p=0.57). Modified VCD failure occurred less frequently in MANTA versus ProGlide (20% vs. 40%; p<0.01). Suture-based closure required more often additional closure devices, whereas MANTA numerically needed more covered stents and surgical bailouts. Plug-based large-bore arteriotomy closure was not superior to suture-based closure. Plug-based closure required fewer, but a different kind of bailout maneuvers.

Bir Eğitim ve Araştırma Hastanesinde Yatan Hastalarda Acinetobacter baumannii İnfeksiyonları ve Antibiyotik Direnci: Altı Yıllık Analiz

Introduction: Acinetobacter baumanii causes difficulties in the treatment of nosocomial infections due to increasing resistance worldwide. With an increase in resistant infections, the use of colistin has come to the fore. We aimed to investigate the antimicrobial resistance profile of A. baumanii strains isolated from clinical specimens as hospital-acquired colonizations and infection agents and to evaluate the clinical and microbiologic responses and adverse effects of antibiotic regimens used in patients who were isolated because of having infectious agents. Materials and Methods: A retrospective descriptive study of 326 adult patients with nosocomial A. baumannii colonizations and infections was conducted between January 2012 and December 2017 in Niğde Education and Research Hospital. In addition, a total of 212 adult patients who received at least 72 hours of antimicrobial therapy were evaluated. Standard and automated methods were used to identify isolated strains and antibiotic susceptibility. The antimicrobial susceptibility profile change over the 6-year period was evaluated. Adverse effects, and clinical and microbiologic response were evaluated in patients receiving antimicrobial therapy. Analysis of the variables was performed using SPSS 22.0 (IBM Corporation, Armonk, New York, United States). Results: When antimicrobial resistance rates were examined, it was seen that imipenem (99.7%), ampicillin sulbactam (81.6%), cefoperazone sulbactam (60.3%), netilmicin (89.4%), tobramycin (88.4%), gentamicin (83.1%), amikacin (91.6%) and tigecycline (33.7%) had resistance rates; colistin resistance was not detected in the isolates. Resistance rate to other antibiotic groups was 100%. The resistance rates of ampicillin sulbactam, cefoperazone sulbactam, gentamicin, amikacin, and tigecycline were found to be statistically significant (p&lt; 0.05). There were no significant differences in terms of nephrotoxicity, and clinical and microbiologic response among patients in whom colistin was used in combination with carbapenem, ampicillin/sulbactam, cefoperazone/sulbactam, and tigecycline (p&gt; 0.05). Conclusion: In accordance with the global data, antimicrobial resistance rate in A. baumanii isolates was found to be high in our study. Treatment regimens in which colistin is used with other antimicrobial agents have no superiority in terms of efficacy and adverse effects. There is a clear need for new and effective antimicrobial agents in the treatment of resistant A. baumanii infections.

Ensartinib as Treatment for ALK-Rearranged NSCLC

Ensartinib as Treatment for ALK-Rearranged NSCLC

Efficacy, safety and acceptability of a new chewable formulation versus the solid tablet of mebendazole against hookworm infections in children: An open-label, randomized controlled trial.

BackgroundSoil-transmitted helminths (STHs) infect almost 1·5 billion people worldwide. The control of STH infections is based on preventive chemotherapy using either albendazole or mebendazole. Before being widely used, a sufficient body of evidence on efficacy, safety and acceptability is warranted for the new chewable child-friendly formulation of mebendazole that was recently developed.MethodsWe conducted a randomised controlled superiority trial in four primary schools and kindergartens on Pemba Island, Tanzania. We considered eligible children aged 3 to 12 years with a hookworm infection intensity of at least 50 eggs per gram (EPG) of stool and no chronic diseases. Participants were allocated to treatment arms (ratio 1:1) using a computer generated random sequence. Our primary outcome was geometric mean based egg reduction rate (ERR) against hookworm assessed 14–21 days post-treatment. This trial complete and is registered with ClinicalTrials.gov, number NCT03995680 (June 24, 2019).Findings397 children were eligible and randomised into the solid (198) or chewable (199) tablet arms, of whom 393 were analysed. We found no significant difference between both formulations in terms of ERR (solid 70·8% versus chewable 68·5%, difference in ERRgeometric mean 2·3%-points, 95% CI -7·8 to 12·6, p = 0.65) and CR (11·2 versus 12·7%, 95% CI -4·9 to 7·9, p = 0.65) against hookworm infections. Adverse events were mild in both treatment arms.InterpretationsThough we could not demonstrate superiority in terms of efficacy of the new formulation, the difference between arms was small and therefore, the chewable formulation could be safely used as an alternative to swallowable tablets, in particular in young children who may have swallowing difficulties. This might help increase compliance and, consequently, enhance the effect of preventive chemotherapy.

Various Combination of Antiviral Treatment of COVID-19 Pneumonia; A Preliminary Observational Study

Background: Coronavirus disease 2019 (COVID-19) has emerged serious medical crisis worldwide. No regimen has been approved as gold standard of treatment. There were no report of other combinations of antiviral cocktail therapy. Methods: We compared time to recovery of COVID-19 pneumonia patients who were treated with various combinations of lopinavir/ritonavir, darunavir /ritonavir, favipiravir, hydroxychloroquine, or no antiviral treatment with lopinavir/ritonavir plus high-dose oseltamivir. Results: Lopinavir/ritonavir plus high-dose oseltamivir had the best efficacy in terms of time to recovery compared to no antiviral treatment (P=0.003) and darunavir/ritonavir plus hydroxychloroquine and favipiravir (P =0.02). Lopinavir/ritonavir plus favipiravir had the borderline efficacy in terms of time to recovery compared to no antiviral treatment (P=0.05).There was no superior efficacy in terms of time to recovery of the combinations of darunavir/ritonavir plus hydroxychloroquine with or without favipiravir compared with no antiviral treatment (P>0.05). Darunavir/ritonavir plus hydroxychloroquine with or without favipiravir had similar efficacy to Lopinavir/ritonavir plus favipiravir (P>0.05). The patients who were treated with hydroxychloroquine 400-1200 mg/day had a significantly increased risk of death (P=0.04). Conclusions: The combination of lopinavir/ritonavir plus high-dose oseltamivir exhibited a trend of superiority compared to the combination of darunavir/ritonavir plus hydroxychloroquine and favipiravir and no antiviral treatment. However, the efficacy of the combinations of antiviral cocktail treatment of COVID-19 pneumonia should be further investigated in a randomized control study registerd as NCT04303299.Trial Registration: NCT04303299.Funding Statement: No support from any organization for the submitted work.Declaration of Interests: No conflicts of interest.Ethics Approval Statement: The electronic case report form and results of this study was acknowledge and approved by the independent ethics committee of the Ministry of Public Health for the NCT04303299 study, which we plan to start in the next phase as an open-label randomized controlled trial.

Comparative efficacy of bariatric endoscopic procedures in the treatment of morbid obesity: a systematic review and network meta-analysis.

The comparative efficacy of bariatric endoscopic procedures has not been completely elucidated. We aimed to comprehensively evaluate the efficacy of bariatric endoscopic procedures. We searched for randomized controlled trials investigating the efficacy of bariatric endoscopic procedures, including the use of an intragastric balloon, duodenal-jejunal bypass liner (DJBL), aspiration therapy, primary obesity surgery endoluminal (POSE) procedure, and botulinum toxin injection to the stomach. Network meta-analyses were performed to determine the percentage of weight loss (%weight loss) and percentage of excess weight loss (%EWL). 22 studies with 2141 patients were included in the meta-analysis. Most endoscopic procedures showed superior efficacy in terms of %weight loss compared with the control (mean difference [MD] [95 % confidence interval (CI)]: aspiration therapy 10.4 % [7.0 % to 13.7 %]; fluid-filled balloon 5.3 % [3.4 % to 7.2 %]; POSE 4.9 % [1.7 % to 8.2 %]; and DJBL 4.5 % [1.4 % to 7.7 %]). In terms of %EWL, aspiration therapy, fluid-filled balloon, POSE, and DJBL were superior to the control (MD [95 %CI]: 27.3 % [15.3 % to 39.3 %]; 22.4 % [15.4 % to 29.4 %]; 15.3 % [2.5 % to 28.0 %]; and 13.0 % [4.9 % to 21.2], respectively). The gas-filled balloon and botulinum toxin injection did not show a significant difference in %weight loss or %EWL compared with the control. For the fluid-filled balloon, the %EWL and %weight loss tended to decrease after balloon removal at 6 months after the procedure. All bariatric endoscopic procedures, except for gas-filled balloon and botulinum toxin injection to the stomach, showed superior short-term efficacy in terms of %weight loss or %EWL compared with lifestyle modification.

Fondaparinux Sodium Compared With Low-Molecular-Weight Heparins for Perioperative Surgical Thromboprophylaxis: A Systematic Review and Meta-analysis.

BackgroundFondaparinux sodium has been compared with low‐molecular‐weight heparins (LMWH) in randomized controlled trials for perioperative surgical thromboprophylaxis. However, the results from these studies are inconsistent in terms of efficacy and safety to reach a clinical decision. The objective of this study was to systematically review the randomized controlled trials comparing the efficacy and safety of fondaparinux and LMWH for perioperative surgical thromboprophylaxis.Methods and ResultsSystematic search in various databases was done to identify randomized controlled trials comparing fondaparinux and LMWH published during the years 2000 to 2017. Outcomes of interest in this study included venous thromboembolism up to day 15, all‐cause mortality up to day 90, major bleeding, and minor bleeding during the treatment period. Analyses were performed with the relative odds based on a random‐effects model using Mantel‐Haenszel statistics. Results were presented as odds ratios with their 95% CIs. The assessment of study quality was performed as per Cochrane collaboration. After screening 10 644 articles, 12 randomized controlled trials including 14 906 patients were included in the final analyses. Pooled analyses showed the odds of venous thromboembolism in the fondaparinux group were 0.49 times the odds in LMWH group (OR=0.49 [0.38–0.64]). However, the odds of major bleeding in the fondaparinux group were 1.48 times the odds in the LMWH group (OR=1.48 [1.15–1.90]).ConclusionsFondaparinux was associated with a superior efficacy in terms of reduction of venous thromboembolism in this meta‐analysis. However, it was also associated with increased odds of major bleeding.

Strategies to overcome acquired resistance to EGFR TKI in the treatment of non-small cell lung cancer.

Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) represents a paradigm shift in the treatment of non-small cell lung cancer (NSCLC) patients and has been the first-line therapy in clinical practice. While erlotinib, gefitinib and afatinib have achieved superior efficacy in terms of progression-free survival and overall survival compared with conventional chemotherapy in NSCLC patients, most people inevitably develop acquired resistance to them, which presents another challenge in the treatment of NSCLC. The mechanisms of acquired resistance can be classified as three types: target gene mutation, bypass signaling pathway activation and histological transformation. And the most common mechanism is T790M which accounts for approximately 50% of all subtypes. Many strategies have been explored to overcome the acquired resistance to EGFR TKI. Continuation of EGFR TKI beyond progressive disease is confined to patients in asymptomatic stage when the EGFR addiction is still preserved in some subclones. While the combination of EGFR TKI and chemotherapy or other targeted agents has improved the survival benefit in EGFR TKI resistant patients, there are controversies within them. The next-generation EGFR TKI and immunotherapy represent two novel directions for overcoming acquired resistance and have achieved promising efficacy. Liquid biopsy provides surveillance of the EGFR mutation by disclosing the entire genetic landscape but tissue biopsy is still indispensable because of the considerable rate of false-negative plasma.

Economic evaluation of the use of non-vitamin K oral anticoagulants in patients with atrial fibrillation on antiplatelet therapy: a modelling analysis using the healthcare system in the Netherlands.

Non-vitamin K oral anticoagulants (NOACs) have consistently demonstrated superior efficacy in terms of stroke prevention and safety in terms of bleeding over vitamin K antagonist (VKA) in patients with non-valvular atrial fibrillation (AF). The potential use of NOACs in AF patients requiring antiplatelet therapy (APT) has only been assessed in small meta-analyses reporting consistent benefits of NOACs over VKAs. However, the prescription costs of NOACs are higher than those of VKAs. The aim of his study was to estimate the cost-effectiveness (CE) of NOACs compared to VKAs in patients with non-valvular AF also requiring APT with the Dutch healthcare system used as a surrogate of many European healthcare systems. A decision tree was constructed to analyse the CE of NOACs compared to VKAs in patients with non-valvular AF with an indication for APT over a horizon of 1 year. Beside the base-case analysis, univariate probabilistic sensitivity and two sensitivity analyses were performed: first, we assessed the impact of VKA home monitoring; second, we varied the NOACs price assuming patent expiration. Use of NOACs instead of VKA is associated with a health gain of 0.0171 quality-adjusted life years (QALYs) and with an incremental cost of €357, resulting in an incremental cost-effectiveness ratio of €20919, which is almost equal to the generally accepted CE threshold of €20000 used in the Netherlands. The probability that NOACs are cost-effective at a conservative willingness-to-pay threshold of €20000 per QALY was 50%. Introducing home monitoring increased VKAs costs so much that NOACs became the dominant option (less costly and more effective). Price drops associated to patent expiration of NOACs increased its CE. This analysis suggests that the use of NOACs is a cost-effective alternative of VKAs in patients with AF needing APT. Our findings in the Netherlands healthcare system are probably consistent with other European populations.

Systematic review with meta-analysis: the efficacy of vonoprazan-based triple therapy on Helicobacter pylori eradication.

In order to increase eradication rates, vonoprazan, a novel potassium-competitive acid blocker, has been used in Helicobacter pylori eradication therapy. To summarise the results of the efficacy of vonoprazan-based triple therapy, helping clinicians to better understand the benefit of vonoprazan in the treatment of H. pylori infection. We conducted a systematic literature search on MEDLINE, EMBASE, and the Cochrane Library using the primary keywords "vonoprazan," "takecab", "TAK-438," "potassium," "competitive," "potassium-competitive," "Helicobacter," and "pylori." Studies were included if they evaluated the eradication rate between the vonoprazan-based and proton pump inhibitor (PPI)-based triple therapies. Ten studies and 10644 patients were evaluated. The crude H. pylori eradication rate determined by intention-to-treat analysis was 87.9% and 72.8% in the vonoprazan-based triple therapy and PPI-based triple therapy respectively. The eradication rate of the vonoprazan-based triple therapy was superior to that of the PPI-based triple therapy (pooled risk ratio [RR] [95% confidence interval (CI)]=1.19 [1.15-1.24]) In addition, there was no significant difference in dropout rate due to adverse event between the regimens (pooled RR of the vonoprazan-based triple therapy [95% CI]=0.69 [0.23-2.03]). The incidence of any adverse events also did not differ between the regimens (pooled RR [95% CI]=1.02 [0.78-1.34]). The vonoprazan-based triple therapy showed superior efficacy in terms of H. pylori eradication as compared to the PPI-based triple therapy. In addition, the vonoprazan-based triple therapy showed comparable tolerability and incidence of adverse events.

Total fistulectomy, sphincteroplasty and closure of the residual cavity for trans-sphincteric perianal fistula in the elderly patient.

Perianal fistula is a complex and frequent disease. At present, no treatment nor technique has shown an absolute superiority in terms of efficacy and recurrence rate. The technique has to be chosen considering the balance between faecal continence preservation and disease eradication. Rarely concomitant perianal abscess and fistula are treated at the same time, and often time to complete recovery is long. The aim of this study was to evaluate the possibility of treating the abscess and the fistula tract in one procedure with total fistulectomy, sphincteroplasty and an almost complete closure of the residual cavity, thus reducing the healing time in older patients. A non-randomized single-centre series of 86 patients from 2007 to 2012 with low-medium trans-sphincteric perianal fistula (< 30% of external sphincter involvement) with or without synchronous perianal abscess were treated with total fistulectomy, sphincteroplasty and closure of the residual cavity technique. Success rate was 97.7% with a healing time of 4weeks; overall morbidity was 16.2%; recurrence rate was 2.3%; no major alterations of continence were observed. Fistulectomy, sphincteroplasty and closure of the residual cavity are associated with a low rate of recurrence and good faecal continence preservation in older patients. This technique can be safely used even with a concomitant perianal abscess, with reduction in healing time and in the number of surgical procedures needed. Total fistulectomy with sphincteroplasty and partial closure of the residual cavity, as described, is a safe procedure but has to be performed by dedicated colorectal surgeons.

Pulmonary vein isolation in the treatment of atrial fibrillation

Pulmonary vein isolation in the treatment of atrial fibrillation Saurabh Kumar, Gregory F Michaud Cardiac Arrhythmia Service, Cardiovascular Division, Brigham and Women&#39;s Hospital, Boston, MA, USA Abstract: Atrial fibrillation (AF) is the commonest arrhythmia in humans and is associated with marked reduction in quality of life and an elevated thromboembolic risk. Paroxysmal, persistent, and permanent forms of AF have been recognized. Whilst antiarrhythmic drugs are considered as first-line therapy, the role of catheter ablation is increasing due to its superior efficacy in terms of quality of life and reduction in AF burden. The central paradigm for catheter ablation of AF is that triggers for AF are located near and within the pulmonary veins (PVs), and electrical isolation of the PVs from the left atrium forms the cornerstone of most catheter ablation strategies. Whilst paroxysmal form is generally trigger dependent, persistent and permanent forms are associated with variable interaction between triggers and &quot;substrate&quot; comprised of atrial and PV electrical and structural remodeling. Nevertheless, isolation of the PVs still forms a critical component of catheter ablation strategies, regardless of AF type. Procedural efficacy, however, is limited by PV conduction recovery. This is likely due to deficiencies in ablation tools or limitations of intraprocedural assessment of lesion efficacy. Careful attention to surrogates of tissue heating, such as impedance decrease and electrogram morphology changes, along with advances in catheter technology like contact force catheters may improve rates of durable PV isolation and single-procedural success. This review discusses the mechanism of paroxysmal AF with particular focus on the role of the PVs in AF initiation and PV isolation in the management of AF. Keywords: contact force, lesion transmurality, radiofrequency catheter ablation, paroxysmal atrial fibrillation, electrophysiology, AF