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Lancet (London, England) Jul 2021First-line chemotherapy for advanced or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastro-oesophageal junction adenocarcinoma has a... (Comparative Study)
Comparative Study Randomized Controlled Trial
First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial.
BACKGROUND
First-line chemotherapy for advanced or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastro-oesophageal junction adenocarcinoma has a median overall survival (OS) of less than 1 year. We aimed to evaluate first-line programmed cell death (PD)-1 inhibitor-based therapies in gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma. We report the first results for nivolumab plus chemotherapy versus chemotherapy alone.
METHODS
In this multicentre, randomised, open-label, phase 3 trial (CheckMate 649), we enrolled adults (≥18 years) with previously untreated, unresectable, non-HER2-positive gastric, gastro-oesophageal junction, or oesophageal adenocarcinoma, regardless of PD-ligand 1 (PD-L1) expression from 175 hospitals and cancer centres in 29 countries. Patients were randomly assigned (1:1:1 while all three groups were open) via interactive web response technology (block sizes of six) to nivolumab (360 mg every 3 weeks or 240 mg every 2 weeks) plus chemotherapy (capecitabine and oxaliplatin every 3 weeks or leucovorin, fluorouracil, and oxaliplatin every 2 weeks), nivolumab plus ipilimumab, or chemotherapy alone. Primary endpoints for nivolumab plus chemotherapy versus chemotherapy alone were OS or progression-free survival (PFS) by blinded independent central review, in patients whose tumours had a PD-L1 combined positive score (CPS) of five or more. Safety was assessed in all patients who received at least one dose of the assigned treatment. This study is registered with ClinicalTrials.gov, NCT02872116.
FINDINGS
From March 27, 2017, to April 24, 2019, of 2687 patients assessed for eligibility, we concurrently randomly assigned 1581 patients to treatment (nivolumab plus chemotherapy [n=789, 50%] or chemotherapy alone [n=792, 50%]). The median follow-up for OS was 13·1 months (IQR 6·7-19·1) for nivolumab plus chemotherapy and 11·1 months (5·8-16·1) for chemotherapy alone. Nivolumab plus chemotherapy resulted in significant improvements in OS (hazard ratio [HR] 0·71 [98·4% CI 0·59-0·86]; p<0·0001) and PFS (HR 0·68 [98 % CI 0·56-0·81]; p<0·0001) versus chemotherapy alone in patients with a PD-L1 CPS of five or more (minimum follow-up 12·1 months). Additional results showed significant improvement in OS, along with PFS benefit, in patients with a PD-L1 CPS of one or more and all randomly assigned patients. Among all treated patients, 462 (59%) of 782 patients in the nivolumab plus chemotherapy group and 341 (44%) of 767 patients in the chemotherapy alone group had grade 3-4 treatment-related adverse events. The most common any-grade treatment-related adverse events (≥25%) were nausea, diarrhoea, and peripheral neuropathy across both groups. 16 (2%) deaths in the nivolumab plus chemotherapy group and four (1%) deaths in the chemotherapy alone group were considered to be treatment-related. No new safety signals were identified.
INTERPRETATION
Nivolumab is the first PD-1 inhibitor to show superior OS, along with PFS benefit and an acceptable safety profile, in combination with chemotherapy versus chemotherapy alone in previously untreated patients with advanced gastric, gastro-oesophageal junction, or oesophageal adenocarcinoma. Nivolumab plus chemotherapy represents a new standard first-line treatment for these patients.
FUNDING
Bristol Myers Squibb, in collaboration with Ono Pharmaceutical.
Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Therapy, Combination; Esophageal Neoplasms; Esophagogastric Junction; Female; Humans; Immune Checkpoint Inhibitors; Male; Middle Aged; Nivolumab; Progression-Free Survival; Stomach Neoplasms
PubMed: 34102137
DOI: 10.1016/S0140-6736(21)00797-2 -
Molecules (Basel, Switzerland) Jun 2022(L.) Britton, an important pharmaceutical and nutraceutical crop, is widely cultivated in East Asian countries. In this review, we present the latest research findings... (Review)
Review
(L.) Britton, an important pharmaceutical and nutraceutical crop, is widely cultivated in East Asian countries. In this review, we present the latest research findings on the phytochemistry and pharmacological activities of . Different databases, including PubMed, Scopus, CNKI, Agricola, Scifinder, Embase, ScienceDirect, DOAJ, and Web of Science, were searched to present the best review. In this review, we clearly represent the active constituents responsible for each and every pharmacological activity, plausible mechanism of action, and maximum inhibitory concentrations, as well as IC values. Approximately 400 different bioactive compounds, including alkaloids, terpenoids, quinines, phenylpropanoids, polyphenolic compounds, flavonoids, coumarins, anthocyanins, carotenoids, neolignans, fatty acids, polycosanols, tocopherols, and sitosterols, have been reported in the leaves, seeds, roots, and aerial parts of . The bioactive constituents of exhibited different enzyme-inhibition properties, including antihyaluronidase effects and aldose reductase inhibitory, α-glucosidase inhibitory, xanthine oxidase inhibitory, and tyrosinase inhibitory properties. showed strong anti-inflammatory, antidepressant, anti-spasmodic, anticancer, antioxidant, antimicrobial, insecticidal, neuroprotective, and hepatoprotective effects. Hence, the active constituents of used in the treatment of diabetes and diabetic complications (retinopathy, neuropathy, and nephropathy), prevention of hyperuricemia in gout patients, hyper pigmentation, allergic conditions, skin inflammation, skin allergy, atopic dermatitis, periodontosis, androgenic alopecia, gastric inflammation, oesophagitis, carcinogenesis, cardiovascular, Alzheimer's, Parkinson's, and cerebral ischemic disorders. Furthermore, we revealed the most active constituents and possible mechanisms of the pharmacological properties of .
Topics: Anthocyanins; Humans; Inflammation; Perilla frutescens; Plant Leaves; Xanthine Oxidase
PubMed: 35684514
DOI: 10.3390/molecules27113578 -
Annals of Palliative Medicine Mar 2020Breathing exercises can improve the symptoms of patients with gastroesophageal reflux disease (GERD), but their specific effect and function are disputed. To evaluate... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Breathing exercises can improve the symptoms of patients with gastroesophageal reflux disease (GERD), but their specific effect and function are disputed. To evaluate and conduct a meta-analysis on the effect of breathing exercises on patients with GERD.
METHODS
A literature search for randomized controlled trials (RCTs) and prospective studies on the effects of employing breathing exercises on patients with GERD was conducted of all major online English databases (PubMed, Embase, the Cochrane library, CENTRAL, Web of Science, AMED, and CINAHL). After the systematic review of all the studies according to inclusion and exclusion criteria, we analyzed the extracted data through meta-analysis by using RevMan 5.3 software.
RESULTS
This thesis analyzes 7 studies (including three RCTs), which together involved 194 patients and 16 healthy volunteers. The primary outcomes of these studies included GERD symptoms, esophageal manometry, esophageal pH monitoring, laryngoscopic findings, and acid suppression usage. The results of meta-analysis indicate that breathing exercises can improve pressure generated by the lower oesophageal sphincter (LES), and a statistically significant difference was observed. The possible mechanism behind this is the enhancement of the anti-regurgitation barrier [especially crural diaphragm (CD) tension].
CONCLUSIONS
To some extent, breathing exercises can relieve the symptoms of patients with GERD.
Topics: Breathing Exercises; Exercise Therapy; Female; Gastroesophageal Reflux; Humans; Male; Prospective Studies; Quality of Life; Randomized Controlled Trials as Topic; Respiratory Function Tests
PubMed: 32233626
DOI: 10.21037/apm.2020.02.35 -
Asian Pacific Journal of Cancer... Nov 2019A systematic literature review and meta-analysis was conducted on the association between firefighting and cancer. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
A systematic literature review and meta-analysis was conducted on the association between firefighting and cancer.
METHODS
A comprehensive literature search of databases including Medline, EMBASE, Biosis, NIOSHTIC2, Web of Science, Cancerlit, and HealthStar, for the period between 1966 to January 2007, was conducted. We also retrieved additional studies by manual searching.
RESULTS
A total of 49 studies were included in the meta-analysis. We found statistically significant associations between firefighting and cancers of bladder, brain and CNS, and colorectal cancers, consistent with several previous risk estimates. We also found statistically significant associations of firefighting with non-Hodgkin's lymphoma, skin melanoma, prostate, and testicular cancer. For kidney, Hodgkin's lymphoma, leukemia, lymphosarcoma and reticulosarcoma, multiple myeloma, and pancreatic cancer, we found some statistically significant but less consistent results. For all other cancers evaluated (esophageal, laryngeal, oral and pharyngeal, liver and gallbladder, lung, lymphatic and hematopoietic, non-melanoma skin cancer, stomach, and urinary cancer) we did not find any statistically significant associations.
CONCLUSIONS
Although our meta-analysis showed statistically significant increased risks of either cancer incidence or mortality of certain cancers in association with firefighting, a number of important limitations of the underlying studies exist, which, precluded our ability to arrive at definitive conclusions regarding causation.
Topics: Firefighters; Humans; Incidence; Neoplasms; Prognosis; Survival Rate; United States
PubMed: 31759344
DOI: 10.31557/APJCP.2019.20.11.3221 -
Nutrients Apr 2023The dipeptide carnosine is a physiologically important molecule in the human body, commonly found in skeletal muscle and brain tissue. Beta-alanine is a limiting... (Review)
Review
The dipeptide carnosine is a physiologically important molecule in the human body, commonly found in skeletal muscle and brain tissue. Beta-alanine is a limiting precursor of carnosine and is among the most used sports supplements for improving athletic performance. However, carnosine, its metabolite -acetylcarnosine, and the synthetic derivative zinc-L-carnosine have recently been gaining popularity as supplements in human medicine. These molecules have a wide range of effects-principally with anti-inflammatory, antioxidant, antiglycation, anticarbonylation, calcium-regulatory, immunomodulatory and chelating properties. This review discusses results from recent studies focusing on the impact of this supplementation in several areas of human medicine. We queried PubMed, Web of Science, the National Library of Medicine and the Cochrane Library, employing a search strategy using database-specific keywords. Evidence showed that the supplementation had a beneficial impact in the prevention of sarcopenia, the preservation of cognitive abilities and the improvement of neurodegenerative disorders. Furthermore, the improvement of diabetes mellitus parameters and symptoms of oral mucositis was seen, as well as the regression of esophagitis and taste disorders after chemotherapy, the protection of the gastrointestinal mucosa and the support of eradication treatment. However, in the areas of senile cataracts, cardiovascular disease, schizophrenia and autistic disorders, the results are inconclusive.
Topics: Humans; Carnosine; Antioxidants; Dietary Supplements; Dipeptides; Muscle, Skeletal; beta-Alanine
PubMed: 37049610
DOI: 10.3390/nu15071770 -
Journal of Cachexia, Sarcopenia and... Feb 2023The loss of skeletal muscle mass and function is defined as sarcopenia, which might develop in elderly patients with cancers. It has been indicated as a potential... (Meta-Analysis)
Meta-Analysis Review
The loss of skeletal muscle mass and function is defined as sarcopenia, which might develop in elderly patients with cancers. It has been indicated as a potential negative factor in the survival of patients with malignant tumours. The aim of this systematic review and meta-analysis was to evaluate the associations between sarcopenia and survival outcomes or postoperative complications in patients with oesophageal cancer (EC). Web of Science, Embase, Medline, and Cochrane Library databases were searched until 10 May 2022, using keywords: sarcopenia, oesophageal cancer, and prognosis. Studies investigating the prognostic value of sarcopenia on EC survival were included. Forest plots and summary effect models were used to show the result of this meta-analysis. The quality of included studies was evaluated with the Newcastle-Ottawa Scale (NOS). A total of 1436 studies were identified from the initial search of four databases, and 41 studies were included for the final quantitative analysis. This meta-analysis revealed a significant association between sarcopenia and overall survival (OS) [hazard ratios (HR):1.68, 95% confidence interval (CI):1.54-1.83, P = 0.004, I = 41.7%] or disease-free survival (DFS) 1.97 (HR: 1.97, 95% CI: 1.44-2.69, P = 0.007, I = 61.9%) of EC patients. Subgroup analysis showed that sarcopenia remained a consistent negative predictor of survival when stratified by different treatment methods, populations, or sarcopenia measurements. Sarcopenia was also a risk factor for postoperative complications with a pooled odds ratio of 1.47 (95% CI: 1.21-1.77, P = 0.094, I = 32.7%). The NOS scores of all included studies were ≥6, and the quality of the evidence was relatively high. The results from the study suggested that sarcopenia was significantly associated with both survival outcomes and postoperative complications in EC patients. Sarcopenia should be appropriately diagnosed and treated for improving short-term and long-term outcomes of patients with EC.
Topics: Humans; Aged; Prognosis; Sarcopenia; Esophageal Neoplasms; Proportional Hazards Models; Postoperative Complications
PubMed: 36415154
DOI: 10.1002/jcsm.13126 -
Seminars in Pediatric Surgery Dec 2022Anomalies in tracheo-esophageal development result in a spectrum of congenital malformations ranging from, most commonly, esophageal atresia with or without...
Anomalies in tracheo-esophageal development result in a spectrum of congenital malformations ranging from, most commonly, esophageal atresia with or without trachea-esophageal fistula (EA+/-TEF) to esophageal web, duplication, stricture, tracheomalacia and tracheal agenesis. Despite the relative frequency of EA, however, the underlying etiology remains unknown and is likely due to a combination of genetic, epigenetic and environmental factors. In recent years, animal models have dramatically increased our understanding of the molecular and morphological processes involved in normal esophageal development during the key stages of anterior-posterior regionalization, dorsal-ventral patterning and morphogenic separation. Moreover, the use of animal models in conjunction with increasingly advanced techniques such as genomic sequencing, sophisticated live imaging studies and organoid models have more recently cast light on potential mechanisms involved in EA pathogenesis. This article aims to unravel some of the mysteries behind the anatomy and embryology of EA whilst providing insights into future directions for research.
Topics: Animals; Humans; Tracheoesophageal Fistula; Esophageal Atresia; Trachea; Tracheomalacia
PubMed: 36459913
DOI: 10.1016/j.sempedsurg.2022.151231 -
Orphanet Journal of Rare Diseases Sep 2006Plummer-Vinson or Paterson-Kelly syndrome presents as a classical triad of dysphagia, iron-deficiency anemia and esophageal webs. Exact data about epidemiology of the... (Review)
Review
Plummer-Vinson or Paterson-Kelly syndrome presents as a classical triad of dysphagia, iron-deficiency anemia and esophageal webs. Exact data about epidemiology of the syndrome are not available; the syndrome is extremely rare. Most of the patients are white middle-aged women, in the fourth to seventh decade of life but the syndrome has also been described in children and adolescents. The dysphagia is usually painless and intermittent or progressive over years, limited to solids and sometimes associated with weight loss. Symptoms resulting from anemia (weakness, pallor, fatigue, tachycardia) may dominate the clinical picture. Additional features are glossitis, angular cheilitis and koilonychia. Enlargement of the spleen and thyroid may also be observed. One of the most important clinical aspects of Plummer-Vinson syndrome is the association with upper alimentary tract cancers. Etiopathogenesis of Plummer-Vinson syndrome is unknown. The most important possible etiological factor is iron deficiency. Other possible factors include malnutrition, genetic predisposition or autoimmune processes. Plummer-Vinson syndrome can be treated effectively with iron supplementation and mechanical dilation. In case of significant obstruction of the esophageal lumen by esophageal web and persistent dysphagia despite iron supplementation, rupture and dilation of the web are necessary. Since Plummer-Vinson syndrome is associated with an increased risk of squamous cell carcinoma of the pharynx and the esophagus, the patients should be followed closely.
Topics: Adolescent; Adult; Age Distribution; Aged; Aged, 80 and over; Deglutition Disorders; Diagnosis, Differential; Female; Global Health; Humans; Iron; Male; Middle Aged; Plummer-Vinson Syndrome; Prevalence; Prognosis; Rare Diseases; Sex Distribution; Young Adult
PubMed: 16978405
DOI: 10.1186/1750-1172-1-36 -
Clinical Gastroenterology and... Aug 2023Eosinophilic esophagitis (EoE) can be treated by proton pump inhibitors, topical corticosteroids, or dietary measures. This study systematically assessed the efficacy of... (Meta-Analysis)
Meta-Analysis
BACKGROUND & AIMS
Eosinophilic esophagitis (EoE) can be treated by proton pump inhibitors, topical corticosteroids, or dietary measures. This study systematically assessed the efficacy of 4 major dietary treatment regimens in EoE, updating the evidence presented in a meta-analysis from 2014.
METHODS
Electronic databases such as PubMed, Scopus, and Web of Science, and other sources were searched up to September 2022 to identify studies on dietary treatment of EoE. Based on histologic remission criteria, the efficacy of these treatments was pooled and analyzed with respect to the type of dietary regimen: 6-food elimination diet (SFED), 4-food elimination diet (FFED), 1-food elimination diet (OFED), and a targeted elimination diet (TED). Clinical response rates, food sensitization, and efficacies for a pediatric subpopulation were calculated. Influencing variables on efficacies were estimated via meta-regression analyses.
RESULTS
Thirty-four studies with 1762 patients met the inclusion criteria. The overall rate of histologic remission was 53.8% (95% CI, 48.0%-59.6%), and in the individual dietary groups was 61.3% (95% CI, 53.0%-69.3%) for SFED, 49.4% (95% CI, 32.5%-66.3%) for FFED, 51.4% (95% CI, 42.6%-60.1%) for OFED, and 45.7% (95% CI, 32.0%-59.7%) for TED. Dietary regimen and patient age did not significantly affect rates of histologic remission. The overall rate of clinical response was 80.8% (95% CI, 72.3%-88.2%), with response rates of 92.8% (95% CI, 81.2%-99.6%) for SFED, 74.1% (95% CI, 49.8%-92.6%) for FFED, 87.1% (95% CI, 58.4%-99.9%) for OFED, and 69.0% (95% CI, 50.2%85.3%) for TED.
CONCLUSIONS
Dietary therapy is an effective treatment for EoE patients of any age. The current results could support a trend toward less-restrictive dietary regimens as a primary treatment option.
Topics: Child; Humans; Allergens; Diet; Elimination Diets; Eosinophilic Esophagitis; Food; Treatment Outcome
PubMed: 36731591
DOI: 10.1016/j.cgh.2023.01.019