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BMJ Open Jul 2024Laparoscopic proximal gastrectomy with double flap technique (LPG-DFT) reconstruction has been used for proximal early gastric cancer in recent years. However, its... (Comparative Study)
Comparative Study
Comparing the antireflux effect of laparoscopic proximal gastrectomy with double-flap technique reconstruction versus laparoscopic total gastrectomy with Roux-en-Y reconstruction for proximal early gastric cancer: study protocol for a multicentre, prospective, open-label, randomised controlled...
INTRODUCTION
Laparoscopic proximal gastrectomy with double flap technique (LPG-DFT) reconstruction has been used for proximal early gastric cancer in recent years. However, its feasibility and safety remain uncertain, as only a few retrospective studies have contained postoperative complications and long-term survival data. LPG-DFT for proximal early gastric cancer is still in the early stages of research. Large-scale, prospective randomised controlled trials (RCTs) are necessary to assess the value of LPG-DFT for proximal early gastric cancer.
METHODS AND ANALYSIS
This study is a multicentre, prospective, open-label, RCT that investigates the antireflux effect of LPG-DFT compared with laparoscopic total gastrectomy with Roux-en-Y (LTG-RY) reconstruction for proximal early gastric cancer. A total of 216 eligible patients will be randomly assigned to the LPG-DFT group or the LTG-RY group at a 1:1 ratio using a central, dynamic and stratified block randomisation method, if inclusion criteria are met. General and clinical data will be collected when the patient is enrolled in the study and keep pace with the patient at each stage of his medical and follow-up pathway. The primary endpoint is the proportion of patients with reflux esophagitis (Los Angeles Grade B or more) within 12 months postoperatively. The secondary endpoints included intraoperative outcomes, postoperative recovery, postoperative pain assessment, pathological outcomes, postoperative quality of life, postoperative nutrition status, morbidity and mortality rate, and oncological outcomes (3-year overall survival (OS), 3-year disease-free survival (DFS), 5-year DFS and 5-year OS).
ETHICS AND DISSEMINATION
The protocol is approved by the Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University ethics committee (registration number: SYSKY-2022-276-02) on 28 September 2022.We will report the positive as well as negative findings in international peer-reviewed journals.
TRIAL REGISTRATION NUMBER
NCT05890339.
Topics: Humans; Stomach Neoplasms; Gastrectomy; Laparoscopy; Prospective Studies; Multicenter Studies as Topic; Surgical Flaps; Postoperative Complications; Randomized Controlled Trials as Topic; Anastomosis, Roux-en-Y; Gastroesophageal Reflux; Quality of Life; Male; Adult; Female
PubMed: 38964794
DOI: 10.1136/bmjopen-2023-079940 -
BMJ Open Jul 2024No consensus exists about the best COVID-19 vaccination strategy to be adopted by low-income and middle-income countries. Brazil adopted an age-based calendar strategy...
OBJECTIVES
No consensus exists about the best COVID-19 vaccination strategy to be adopted by low-income and middle-income countries. Brazil adopted an age-based calendar strategy to reduce mortality and the burden on the healthcare system. This study evaluates the impact of the vaccination campaign in Brazil on the progression of the reported COVID-19 deaths.
METHODS
This ecological study analyses the dynamic of vaccination coverage and COVID-19 deaths in hospitalised adults (≥20 years) during the first year of the COVID-19 vaccination roll-out (January to December 2021) using nationwide data (DATASUS). We stratified the adult population into 20-49, 50-59, 60-69 and 70+ years. The dynamic effect of the vaccination campaign on mortality rates was estimated by applying a negative binomial regression. The prevented and possible preventable deaths (observed deaths higher than expected) and potential years of life lost (PYLL) for each age group were obtained in a counterfactual analysis.
RESULTS
During the first year of COVID-19 vaccination, 266 153 517 doses were administered, achieving 91% first-dose coverage. A total of 380 594 deaths were reported, 154 091 (40%) in 70+ years and 136 804 (36%) from 50-59 or 20-49 years. The mortality rates of 70+ decreased by 52% (rate ratio [95% CI]: 0.48 [0.43-0.53]) in 6 months, whereas rates for 20-49 were still increasing due to low coverage (52%). The vaccination roll-out strategy prevented 59 618 deaths, 53 088 (89%) from those aged 70+ years. However, the strategy did not prevent 54 797 deaths, 85% from those under 60 years, being 26 344 (45%) only in 20-49, corresponding to 1 589 271 PYLL, being 1 080 104 PYLL (68%) from those aged 20-49 years.
CONCLUSION
The adopted aged-based calendar vaccination strategy initially reduced mortality in the oldest but did not prevent the deaths of the youngest as effectively as compared with the older age group. Countries with a high burden, limited vaccine supply and young populations should consider other factors beyond the age to prioritise who should be vaccinated first.
Topics: Humans; Brazil; COVID-19; Middle Aged; Aged; COVID-19 Vaccines; Adult; Male; Female; Young Adult; SARS-CoV-2; Vaccination Coverage; Immunization Programs; Vaccination
PubMed: 38964793
DOI: 10.1136/bmjopen-2023-072314 -
Journal For Immunotherapy of Cancer Jul 2024We aimed to investigate the distinct immunological characteristics of the tumor immune microenvironment in epithelial ovarian cancer (EOC) according to mutations status...
BACKGROUND
We aimed to investigate the distinct immunological characteristics of the tumor immune microenvironment in epithelial ovarian cancer (EOC) according to mutations status and differential PD-1 expression levels.
METHODS
Tumor-infiltrating lymphocytes (TILs) were collected from patients with newly diagnosed advanced-stage EOC (YUHS cohort, n=117). This YUHS cohort was compared with The Cancer Genome Atlas (TCGA) data for ovarian serous cystadenocarcinoma (n=482), in terms of survival outcomes and immune-related gene profiles according to status. We used multicolor flow cytometry to characterize the immune phenotypes and heterogeneity of TILs with or without mutations. functional assays were conducted to evaluate the reinvigorating ability of CD8 TILs on anti-PD-1 treatment.
RESULTS
We found that EOC patients with mutations (mt) exhibited better survival outcomes and significantly higher tumor mutation burden (TMB), compared with non-mutated (wt) patients. Furthermore, CD8 TILs within mt tumors displayed characteristics indicating more severe T-cell exhaustion than their wt counterparts. Notably, the capacity for anti-PD-1-mediated reinvigoration of CD8 TILs was significantly greater in wt tumors compared with mt tumors. Additionally, within the wt group, the frequency of PD-1CD8 TILs was positively correlated with the reinvigoration capacity of CD8 TILs after anti-PD-1 treatment.
CONCLUSION
Our results highlight unique immune features of CD8 TILs in EOC and a differential response to anti-PD-1 treatment, contingent on mutation status. These findings suggest that immune checkpoint blockade may be a promising frontline therapeutic option for selected wt EOC patients.
Topics: Humans; Female; Carcinoma, Ovarian Epithelial; Lymphocytes, Tumor-Infiltrating; Mutation; CD8-Positive T-Lymphocytes; BRCA1 Protein; Middle Aged; BRCA2 Protein; Programmed Cell Death 1 Receptor; Ovarian Neoplasms; Immune Checkpoint Inhibitors; Adult; Tumor Microenvironment; Aged
PubMed: 38964784
DOI: 10.1136/jitc-2024-009058 -
International Journal of Hyperthermia :... 2024This study aimed to investigate the efficacy and safety of ultrasound-guided percutaneous radiofrequency ablation (RFA) for the treatment of synovial hyperplasia in the...
PURPOSE
This study aimed to investigate the efficacy and safety of ultrasound-guided percutaneous radiofrequency ablation (RFA) for the treatment of synovial hyperplasia in the knee joints of antigen-induced arthritis (AIA) model rabbits.
METHODS
Forty Japanese large-eared white rabbits were divided into AIA and control groups. After successful induction of the AIA model, the knee joints were randomly assigned to RFA and non-RFA groups. The RFA group underwent ultrasound-guided RFA to treat synovial hyperplasia in the knee joint. Dynamic observation of various detection indices was conducted to evaluate the safety and effectiveness of the RFA procedure.
RESULTS
Successful synovial ablation was achieved in the RFA group, with no intraoperative or perioperative mortality. Postoperative the circumference of the knee joint reached a peak before decreasing in the third week after surgery. The incidence and diameter of postoperative skin ulcers were not significantly different compared to the non-RFA group ( > .05). Anatomical examination revealed an intact intermuscular fascia around the ablated area in the RFA group. The ablated synovial tissue initially presented as a white mass, which subsequently liquefied into a milky white viscous fluid. Gross articular cartilage was observed, along with liquefied necrosis of the synovium on pathological histology and infiltration of inflammatory cells in the surrounding soft tissue.
CONCLUSION
The experimental results demonstrated that ultrasound-guided RFA of the knee in the treatment of synovial hyperplasia in AIA model animals was both effective and safe.
Topics: Animals; Rabbits; Radiofrequency Ablation; Hyperplasia; Synovial Membrane; Ultrasonography; Male; Ultrasonography, Interventional
PubMed: 38964750
DOI: 10.1080/02656736.2024.2328113 -
Clinical and Molecular Hepatology Jul 2024
PubMed: 38964740
DOI: 10.3350/cmh.2024.0280 -
Clinical and Molecular Hepatology Jul 2024
Metabolic-associated fatty liver disease is less effective in predicting mortality than non-alcoholic fatty liver disease and metabolic dysfunction-associated steatotic liver disease.
PubMed: 38964739
DOI: 10.3350/cmh.2024.0417 -
Cancer Letters Jul 2024Head and neck squamous cell carcinoma (HNSCC) constitutes a significant global cancer burden, given its high prevalence and associated mortality. Despite substantial... (Review)
Review
Head and neck squamous cell carcinoma (HNSCC) constitutes a significant global cancer burden, given its high prevalence and associated mortality. Despite substantial progress in survival rates due to the enhanced multidisciplinary approach to treatment, these methods often lead to severe tissue damage, compromised function, and potential toxicity. Thus, there is an imperative need for novel, effective, and minimally damaging treatment modalities. Neoadjuvant treatment, an emerging therapeutic strategy, is designed to reduce tumor size and curtail distant metastasis prior to definitive intervention. Currently, neoadjuvant chemotherapy (NACT) has fine-tuned the treatment approach for a subset of HNSCC patients, yet it has not produced a noticeable enhancement in overall survival (OS). In the contemporary cancer therapeutics landscape, immunotherapy is gaining traction at an accelerated pace. Notably, neoadjuvant immunotherapy (NAIT) has shown promising radiological and pathological responses, coupled with an encouraging efficacy in several clinical trials. This potentially paves the way for a myriad of possibilities in treatment de-escalation of HNSCC, which warrants further exploration. This paper reviews the existing strategies and efficacy of neoadjuvant immune checkpoint inhibitors (ICIs), along with potential de-escalation strategy. Furthermore, the challenges encountered in the context of the de-escalation strategies of NAIT are explored. The aim is to inform future research directions that strive to improve the quality of life (QoL) for patients battling HNSCC.
PubMed: 38964728
DOI: 10.1016/j.canlet.2024.217095 -
International Journal of Infectious... Jul 2024Background Scrub typhus is underdiagnosed and underreported but emerging as a global public health problem. We aimed to provide the first comprehensive review on the...
Background Scrub typhus is underdiagnosed and underreported but emerging as a global public health problem. We aimed to provide the first comprehensive review on the seroprevalence, incidence, mortality of and risk factors for scrub typhus. Methods We searched PubMed, Scopus, Web of Science, China National Knowledge Infrastructure and other databases. Trended incidence and median mortality were calculated and pooled seroprevalence and risk factors for scrub typhus were evaluated using the random-effects meta-analysis. Findings We included 663 articles from 29 countries/regions. The pooled seroprevalence was 10·73% (95%CI 9·47%-12·13%) among healthy individuals and 22·58% (95%CI: 20·55%-24·76%) among febrile patients. Mainland China reported the highest number of cases and South Korea and Thailand had the highest incidence rates. Median mortalities were 5·00% (range: 0·00%-56·00%) among hospital inpatients, 6·70% (range: 0·00%∼33·33%) among patients without specified admission status and 2·17% (range: 0·00%-22·22%) among outpatients. The significant risk factors included agricultural work, specific vegetation exposure, other outdoor activities, risky personal health habits, and proximity to rodents, livestock, or poultry. Conclusions Our comprehensive review elucidates the significant yet variable burden of scrub typhus across different regions, underscoring its emergence as a critical public health concern globally.
PubMed: 38964725
DOI: 10.1016/j.ijid.2024.107151 -
Neurochemistry International Jul 2024Hepatic encephalopathy (HE) is a neurological complication arising from acute liver failure with poor prognosis and high mortality; the underlying cellular mechanisms...
Hepatic encephalopathy (HE) is a neurological complication arising from acute liver failure with poor prognosis and high mortality; the underlying cellular mechanisms are still wanting. We previously found that neuronal death caused by mitochondrial dysfunction in rostral ventrolateral medulla (RVLM), which leads to baroreflex dysregulation, is related to high fatality in an animal model of HE. Lipocalin-2 (Lcn2) is a secreted glycoprotein mainly released by astrocytes in the brain. We noted the presence of Lcn2 receptor (Lcn2R) in RVLM neurons and a parallel increase of Lcn2 gene in astrocytes purified from RVLM during experimental HE. Therefore, our guiding hypothesis is that Lcn2 secreted by reactive astrocytes in RVLM may underpin high fatality during HE by eliciting bioenergetic failure-induced neuronal death in this neural substrate. In this study, we first established the role of astrocyte-secreted Lcn2 in a liver toxin model of HE induced by azoxymethane (100 μg/g, ip) in C57BL/6 mice, followed by mechanistic studies in primary astrocyte and neuron cultures prepared from postnatal day 1 mouse pups. In animal study, immunoneutralization of Lcn2 reduced apoptotic cell death in RVLM, reversed defunct baroreflex-mediated vasomotor tone and prolonged survival during experimental HE. In our primary cell culture experiments, Lcn2 produced by cultured astrocytes and released into the astrocyte-conditioned medium significantly reduced cell viability of cultured neurons. Recombinant Lcn2 protein reduced cell viability, mitochondrial ATP (mitoATP) production, and pyruvate dehydrogenase (PDH) activity but enhanced the expression of pyruvate dehydrogenase kinase (PDK) 1, PDK3 and phospho-PDHA1 (inactive PDH) through MAPK/ERK pathway in cultured neurons, with all cellular actions reversed by Lcn2R knockdown. Our results suggest that astrocyte-secreted Lcn2 upregulates PDKs through MAPK/ERK pathway, which leads to reduced PDH activity and mitoATP production; the reinforced neuronal death in RVLM is causally related to baroreflex dysregulation that underlies high fatality associated with HE.
PubMed: 38964718
DOI: 10.1016/j.neuint.2024.105800 -
The Annals of Thoracic Surgery Jul 2024The impact of sex-differences on the release of cardiac biomarkers after coronary artery bypass grafting (CABG) remains unknown. The aim of our study was to (a)...
BACKGROUND
The impact of sex-differences on the release of cardiac biomarkers after coronary artery bypass grafting (CABG) remains unknown. The aim of our study was to (a) investigate the impact of sex-differences in cardiac biomarker release after CABG and (b) determine sex-specific thresholds for high-sensitivity troponin (hs-cTn) and creatine kinase-MB (CK-MB) associated with 30-day major adverse cardiovascular event (MACE) and mortality.
METHODS
A consecutive cohort of 3687 patients (female: n= 643 (17.4%); male: 3044 (82.6%) undergoing CABG from 2008-2021 in two tertiary university centers with serial postoperative cTn and CK-MB measurement was analyzed. The composite primary outcome was MACE at 30 days. Secondary endpoints were 30-day mortality and five-year mortality and MACE. Sex-specific thresholds for cTn and CK-MB were determined.
RESULTS
Lower levels of cTn were found in women after CABG (69.18 vs. 77.57 xURL; p<0.001). Optimal threshold value for cTn was calculated at 94.36 times the URL for female and 206.07 times the URL for male patients to predict 30-day MACE. Female patients missed by a general threshold had increased risk for MACE or death within 30 days (cTn: MACE: OR 3.78 CI: 1.03-13.08; p=0.035; death: OR 4.98; CI: 1.20.-20.61; p=0.027; CK-MB: MACE: OR 10.04; CI: 2.07-48.75; p<0.001; death: OR 13.59; CI: 2.66-69.47; p=0.002).
CONCLUSIONS
We provide evidence for sex-specific differences in the outcome and biomarker release after CABG. Sex-specific cut-offs are necessary for the diagnosis of perioperative myocardial injury to improve outcomes of women after CABG.
PubMed: 38964702
DOI: 10.1016/j.athoracsur.2024.06.019