Background: The contributions of the gut microbiota to obesity and metabolic disease represent a potentially modifiable factor that may explain variation in risk between individuals. This study aimed to explore relationships among microbial composition and imputed functional attributes, a range of soluble metabolic and immune indices, and gene expression markers in males with or without evidence of metabolic dysregulation (MetDys). Methods: This case-control study included healthy males (n=15; 41.9±11.7 years; body mass index [BMI], 22.9±1.2 kg/m2 ) and males with evidence of MetDys (n= 14; 46.6±10.0 years; BMI, 35.1±3.3 kg/m2 ) who provided blood and faecal samples for assessment of a range of metabolic and immune markers and microbial composition using 16S rRNA gene sequencing. Metagenomic functions were imputed from microbial sequence data for analysis. Results: In addition to elevated values in a range of traditional metabolic, adipokine and inflammatory indices in the MetDys group, 23 immunomodulatory genes were significantly altered in the MetDys group. Overall microbial diversity did not differ between groups; however, a trend for a higher relative abundance of the Bacteroidetes (P=0.06) and a lower relative abundance of the Verrucomicrobia (P=0.09) phyla was noted in the MetDys group. Using both family- and genera-level classifications, a partial least square discriminant analysis revealed unique microbial signatures between the groups. Conclusion These findings confirm the need for ongoing investigations in human clinical cohorts to further resolve the relationships between the gut microbiota and metabolic and immune markers and risk for metabolic disease.

Background: The contributions of the gut microbiota to obesity and metabolic disease represent a potentially modifiable factor that may explain variation in risk between individuals. This study aimed to explore relationships among microbial composition and imputed functional attributes, a range of soluble metabolic and immune indices, and gene expression markers in males with or without evidence of metabolic dysregulation (MetDys). Methods: This case-control study included healthy males (n=15; 41.9±11.7 years; body mass index [BMI], 22.9±1.2 kg/m2 ) and males with evidence of MetDys (n= 14; 46.6±10.0 years; BMI, 35.1±3.3 kg/m2 ) who provided blood and faecal samples for assessment of a range of metabolic and immune markers and microbial composition using 16S rRNA gene sequencing. Metagenomic functions were imputed from microbial sequence data for analysis. Results: In addition to elevated values in a range of traditional metabolic, adipokine and inflammatory indices in the MetDys group, 23 immunomodulatory genes were significantly altered in the MetDys group. Overall microbial diversity did not differ between groups; however, a trend for a higher relative abundance of the Bacteroidetes (P=0.06) and a lower relative abundance of the Verrucomicrobia (P=0.09) phyla was noted in the MetDys group. Using both family- and genera-level classifications, a partial least square discriminant analysis revealed unique microbial signatures between the groups. Conclusion These findings confirm the need for ongoing investigations in human clinical cohorts to further resolve the relationships between the gut microbiota and metabolic and immune markers and risk for metabolic disease.

Background: The contributions of the gut microbiota to obesity and metabolic disease represent a potentially modifiable factor that may explain variation in risk between individuals. This study aimed to explore relationships among microbial composition and imputed functional attributes, a range of soluble metabolic and immune indices, and gene expression markers in males with or without evidence of metabolic dysregulation (MetDys). Methods: This case-control study included healthy males (n=15; 41.9±11.7 years; body mass index [BMI], 22.9±1.2 kg/m2 ) and males with evidence of MetDys (n= 14; 46.6±10.0 years; BMI, 35.1±3.3 kg/m2 ) who provided blood and faecal samples for assessment of a range of metabolic and immune markers and microbial composition using 16S rRNA gene sequencing. Metagenomic functions were imputed from microbial sequence data for analysis. Results: In addition to elevated values in a range of traditional metabolic, adipokine and inflammatory indices in the MetDys group, 23 immunomodulatory genes were significantly altered in the MetDys group. Overall microbial diversity did not differ between groups; however, a trend for a higher relative abundance of the Bacteroidetes (P=0.06) and a lower relative abundance of the Verrucomicrobia (P=0.09) phyla was noted in the MetDys group. Using both family- and genera-level classifications, a partial least square discriminant analysis revealed unique microbial signatures between the groups. Conclusion These findings confirm the need for ongoing investigations in human clinical cohorts to further resolve the relationships between the gut microbiota and metabolic and immune markers and risk for metabolic disease.

Objective: To investigate the safety and efficacy of laparoscopic surgery in locally advanced gastric cancer patients with neoadjuvant SOX chemotherapy combined with PD-1 inhibitor immunotherapy. Methods: Between November 2020 and April 2021, patients with locally advanced gastric cancer who were admitted to the Union Hospital of Tongji Medical College of Huazhong University of Science and Technology were prospectively enrolled in this study. Inclusion criteria were: (1) patients who signed the informed consent form voluntarily before participating in the study; (2) age ranging from 18 to 75 years; (3) patients staged preoperatively as cT3-4N+M0 by the TNM staging system; (4) Eastern Collaborative Oncology Group score of 0-1; (5) estimated survival of more than 6 months, with the possibility of performing R0 resection for curative purposes; (6) sufficient organ and bone marrow function within 7 days before enrollment; and (7) complete gastric D2 radical surgery. Exclusion criteria were: (1) history of anti-PD-1 or PD-L1 antibody therapy and chemotherapy; (2) treatment with corticosteroids or other immunosuppre- ssants within 14 days before enrollment; (3) active period of autoimmune disease or interstitial pneumonia; (4) history of other malignant tumors; (5) surgery performed within 28 days before enrollment; and (6) allergy to the drug ingredients of the study. Follow-up was conducted by outpatient and telephone methods. During preoperative SOX chemotherapy combined with PD-1 inhibitor immunotherapy, follow-up was conducted every 3 weeks to understand the occurrence of adverse reactions of the patients; follow-up was conducted once after 1 month of surgical treatment to understand the adverse reactions and survival of patients. Observation indicators were: (1) condition of enrolled patients; (2) reassessment after preoperative therapy and operation received (3) postoperative conditions and pathological results. Evaluation criteria were: (1) tumor staged according to the 8th edition of the American Joint Committee on Cancer (AJCC) TNM staging system; (2) tumor regression grading (TRG) of pathological results were evaluated with reference to AJCC standards; (3) treatment-related adverse reactions were evaluated according to version 5.0 of the Common Terminology Criteria for Adverse Events; (4) tumor response was evaluated by CT before and after treatment with RECIST V1.1 criteria; and (5) Clavien-Dindo complication grading system was used for postoperative complications assessment. Results: A total of 30 eligible patients were included. There were 25 males and 5 females with a median age of 60.5 (35-74) years. The primary tumor was located in the gastroesophageal junction in 12 cases, in the upper stomach in 8, in the middle stomach in 7, and in the lower stomach in 3. The preoperative clinical stage of 30 cases was III. Twenty-one patients experienced adverse reactions during neoadjuvant chemotherapy combined with immunotherapy, including four cases of CTCAE grade 3-4 adverse reactions resulting in bone marrow suppression and thoracic aortic thrombosis. All cases of adverse reactions were alleviated or disappeared after active symptomatic treatment. Among the 30 patients who underwent surgery, the time from chemotherapy combined with immunotherapy to surgery was 28 (23-49) days. All 30 patients underwent laparoscopic radical gastrectomy, of which 20 patients underwent laparoscopic-assisted radical gastric cancer resection; 10 patients underwent total gastrectomy for gastric cancer, combined with splenectomy in 1 case and cholecystectomy in 1 case. The surgery time was (239.9±67.0) min, intraoperative blood loss was 84 (10-400) ml, and the length of the incision was 7 (3-12) cm. The degree of adenocarcinoma was poorly differentiated in 18 cases, moderately differentiated in 12 cases, nerve invasion in 11 cases, and vascular invasion in 6 cases. The number lymph nodes that underwent dissection was 30 (17-58). The first of gas passage, the first postoperative defecation time, the postoperative liquid diet time, and the postoperative hospitalization time of 30 patients was 3 (2-6) d, 3 (2-13) d, 5 (3-12) d, and 10 (7-27) d, respectively. Postoperative complications occurred in 23 of 30 patients, including 7 cases of complications of Clavien-Dindo grade IIIa or above. Six patients improved after treatment and were discharged from hospital, while 1 patient died 27 days after surgery due to granulocyte deficiency, anemia, bilateral lung infection, and respiratory distress syndrome. The remaining 29 patients had no surgery-related morbidity or mortality within 30 days of discharge. Postoperative pathological examination showed TRG grades 0, 1, 2, and 3 in 8, 9, 4, and 9 cases, respectively, and the number of postoperative pathological TNM stages 0, I, II, and III was 8, 7, 8, and 7 cases, respectively. The pCR rate was 25.0% (8/32). Conclusion: Laparoscopic surgery after neoadjuvant SOX chemotherapy combined with PD-1 inhibitor immunotherapy for locally advanced gastric cancer is safe and feasible, with satisfactory short-term efficacy. Early detection and timely treatment of related complications are important.
Male ; Female ; Humans ; Middle Aged ; Aged ; Adolescent ; Young Adult ; Adult ; Stomach Neoplasms/pathology* ; Neoadjuvant Therapy ; Immune Checkpoint Inhibitors ; Gastrectomy/methods* ; Esophagogastric Junction/pathology* ; Laparoscopy ; Immunotherapy ; Postoperative Complications ; Retrospective Studies ; Treatment Outcome

Humans ; Carcinoma, Mucoepidermoid/pathology* ; Thyroid Neoplasms/pathology* ; Eosinophilia/pathology*

Humans ; Sarcoma ; NFATC Transcription Factors ; RNA-Binding Protein EWS

Humans ; Thyroid Neoplasms/surgery* ; Thyroid Cancer, Papillary

OBJECTIVES: The aim of this study was to provide an overview of published mathematical estimation approaches to quantify the duration of the preclinical detectable phase (PCDP) using data from cancer screening programs. METHODS: A systematic search of PubMed and Embase was conducted for original studies presenting mathematical approaches using screening data. The studies were categorized by mathematical approach, data source, and assumptions made. Furthermore, estimates of the duration of the PCDP of breast and colorectal cancer were reported per study population. RESULTS: From 689 publications, 34 estimation methods were included. Five distinct types of mathematical estimation approaches were identified: prevalence-to-incidence ratio (n=8), maximum likelihood estimation (n=16), expectation-maximization algorithm (n=1), regression of observed on expected (n=6) and Bayesian Markov-chain Monte Carlo estimation (n=5). Fourteen studies used data from both screened and unscreened populations, whereas 19 studies included only information from a screened population. Estimates of the duration of the PCDP varied between 2 years and 7 years for breast cancer in the Health Insurance Plan study (annual mammography and clinical breast examinations in women aged 40-64 years) and 2 years and 5 years for colorectal cancer in the Calvados study (a guaiac fecal occult blood test in men and women aged 45-74 years). CONCLUSIONS Different types of mathematical approaches lead to different estimates of the PCDP duration. We advise researchers to use the method that matches the data available, and to use multiple methods for estimation when possible, since no method is perfect.

Background: Continuous peripheral nerve blocks (CPNBs) have been investigated to control pain for abdominal surgery via midline laparotomy while avoiding the adverse events of opioid or epidural analgesia. The review compiles the evidence comparing CPNBs to multimodal and epidural analgesia. Methods: We conducted a systematic review using broad search terms in MEDLINE, EMBASE, Cochrane. Primary outcomes were pain scores and cumulative opioid consumption at 48 hours. Secondary outcomes were length of stay and postoperative nausea and vomiting (PONV). We rated the quality of the evidence using Cochrane and GRADE recommendations. The results were synthesized by meta-analysis using Revman. Results: Our final selection included 26 studies (1,646 patients). There was no statistically significant difference in pain control comparing CPNBs to either multimodal or epidural analgesia (low quality evidence). Less opioids were consumed when receiving epidural analgesia than CPNBs (mean difference [MD]: –16.13, 95% CI [–32.36, 0.10]), low quality evidence) and less when receiving CPNBs than multimodal analgesia (MD: –31.52, 95% CI [–42.81, –20.22], low quality evidence). The length of hospital stay was shorter when receiving epidural analgesia than CPNBs (MD: -0.78 days, 95% CI [-1.29, -0.27], low quality evidence) and shorter when receiving CPNBs than multimodal analgesia (MD: -1.41 days, 95% CI [-2.45, -0.36], low quality evidence). There was no statistically significant difference in PONV comparing CPNBs to multimodal (high quality evidence) or epidural analgesia (moderate quality evidence). Conclusion CPNBs should be considered a viable alternative to epidural analgesia when contraindications to epidural placement exist for patients undergoing midline laparotomies.

Background: Continuous peripheral nerve blocks (CPNBs) have been investigated to control pain for abdominal surgery via midline laparotomy while avoiding the adverse events of opioid or epidural analgesia. The review compiles the evidence comparing CPNBs to multimodal and epidural analgesia. Methods: We conducted a systematic review using broad search terms in MEDLINE, EMBASE, Cochrane. Primary outcomes were pain scores and cumulative opioid consumption at 48 hours. Secondary outcomes were length of stay and postoperative nausea and vomiting (PONV). We rated the quality of the evidence using Cochrane and GRADE recommendations. The results were synthesized by meta-analysis using Revman. Results: Our final selection included 26 studies (1,646 patients). There was no statistically significant difference in pain control comparing CPNBs to either multimodal or epidural analgesia (low quality evidence). Less opioids were consumed when receiving epidural analgesia than CPNBs (mean difference [MD]: –16.13, 95% CI [–32.36, 0.10]), low quality evidence) and less when receiving CPNBs than multimodal analgesia (MD: –31.52, 95% CI [–42.81, –20.22], low quality evidence). The length of hospital stay was shorter when receiving epidural analgesia than CPNBs (MD: -0.78 days, 95% CI [-1.29, -0.27], low quality evidence) and shorter when receiving CPNBs than multimodal analgesia (MD: -1.41 days, 95% CI [-2.45, -0.36], low quality evidence). There was no statistically significant difference in PONV comparing CPNBs to multimodal (high quality evidence) or epidural analgesia (moderate quality evidence). Conclusion CPNBs should be considered a viable alternative to epidural analgesia when contraindications to epidural placement exist for patients undergoing midline laparotomies.