High-intensity focused ultrasound alone or combined with transcatheter arterial chemoembolization for the treatment of hepatocellular carcinoma with unsuitable indications for hepatectomy and radiofrequency ablation: a phase II clinical trial.

OBJECTIVES: This study aims to evaluate the efficacy and safety of high-intensity focused ultrasound (HIFU) alone or combined with transcatheter arterial chemoembolization (TACE) for patients with hepatocellular carcinoma (HCC) but were contraindicated for hepatectomy and radiofrequency ablation (RFA). METHODS: Patients between 20 and 80 years of age with 1-3 foci of HCC were selected. Included patients have had primary or recurrent liver lesions with no evidence of extra-hepatic metastasis prior to the study. Patients were treated with ultrasound-guided HIFU alone or HIFU combined with TACE (treated with TACE once within 4 weeks prior to receiving HIFU). RESULTS: Thirty-seven patients were enrolled, for a total of 45 lesions. The 2-year local control (LC) rate was 73.0% and the median LC time was 22 months. The 2-year progression-free survival (PFS) was 29.7% and the median PFS time was 9 months. Finally, the 2-year overall survival (OS) was 70.3%, and the median OS time was 24 months. The most common adverse events (AEs) were elevated liver enzymes, followed by fatigue, and pain, no grade 4 AEs or death occurred. Multivariate analysis showed that age, Child-Pugh class, and the number of tumors were independent prognostic factors for PFS and that the AFP levels and the number of tumors were significantly correlated with the OS. CONCLUSIONS: This study indicates that the HIFU/HIFU combined with TACE treatment is safe, and is capable of achieving both a good LC rate and a considerably good prognosis. The procedure should be considered for patients who were deemed unsuitable for other local treatments.

HIFU for the treatment of difficult colorectal liver metastases with unsuitable indications for resection and radiofrequency ablation: a phase I clinical trial.

BACKGROUND: The goal of this study is to evaluate the safety and efficacy of high intensity focused ultrasound (HIFU) for patients with colorectal liver metastases (CRLM) but were contraindicated for resection and radiofrequency ablation. METHODS: Patients between 20 and 80 years of age with 1-3 liver metastases from colorectal cancer were selected. Included patients have had their primary lesions removed with no evidence of extrahepatic metastasis prior to the study. Ultrasound-guided HIFU was employed and target regions' ablation was achieved with repeated sonications from the deep to shallow regions of the tumors section by section. RESULTS: Thirteen patients were enrolled. The most common adverse events (AEs) were pain (n = 8), followed by fatigue (n = 7), increased aspartate aminotransferase (AST) (n = 7), increased alanine aminotransferase (ALT) (n = 5), and skin edema (n = 4). No grade ≥ 3 AEs occurred and while most patients (76.9%) achieved a complete response, three patients achieved a partial response. The objective response rate was 100% after the first HIFU treatment. Nine patients relapsed but the tumors were mostly isolated to the liver (8/9). The median follow-up period was 25 months. The 2-year progression-free survival (PFS) was 16.7%, and the median PFS was 9 months. Notably, the 2-year overall survival (OS) was 77.8%, and the median OS was 25 months. CONCLUSION: This study indicates that the HIFU treatment is safe, is able to achieve a good tumor response rate and long-term prognosis even when the foci were in high-risk locations, and should be considered for patients who were considered unsuitable for other local treatments.

Efficacy and safety of combination PD-1/PD-L1 checkpoint inhibitors for malignant solid tumours: A systematic review.

Treatment of multiple malignant solid tumours with programmed death (PD)-1/PD ligand (PD-L) 1 inhibitors has been reported. However, the efficacy and immune adverse effects of combination therapies are controversial. This meta-analysis was performed with PubMed, Web of Science, Medline, EMBASE and Cochrane Library from their inception until January 2020. Random-effect model was adopted because of relatively high heterogeneity. We also calculated hazard ratio (HR) of progression-free survival (PFS), overall survival (OS) and risk ratio (RR) of adverse events (AEs), the incidence of grade 3-5 AEs by tumour subgroup, therapeutic schedules and therapy lines. Nineteen articles were selected using the search strategy for meta-analysis. Combined PD-1/PD-L1 inhibitors prolonged OS and PFS (HR 0.72, P < 0.001) and (HR 0.66, P < 0.001). In addition, incidence of all-grade and grade 3-5 AEs was not significant in the two subgroup analyses (HR 1.01, P = 0.31) and (HR 1.10, P = 0.07), respectively. Our meta-analysis indicated that combination therapy with PD-1/PD-L1 inhibitors had greater clinical benefits and adverse events were not increased significantly.

Comparison of Quality of Life and Nutritional Status of Between Roux-en-Y and Billroth-I Reconstruction After Distal Gastrectomy: A Systematic Review and Meta-Analysis.

Background: This paper purports to use a meta-analysis to compare the postoperative quality of life (QoL) and nutritional status of between Roux-en-Y (R-Y) and Billroth-I (B-I) reconstruction after distal gastrectomy.Methods: For this study, the following databases were searched for articles published from inception until December 2018: PubMed, Web of Science, EBSCO, and Cochrane library.Results: A total of 13 eligible studies, covering 3645 patients, were selected for a meta-analysis. The analysis showed that compared with B-I group in term of short-term outcomes, patients undergoing R-Y reconstruction did not only have significantly better physiological function (P = 0.02), but had significantly less pain (P = 0.04). In the long-term outcomes, the dyspnea and constipation in the B-I group were worse than that in the R-Y group (P = 0.004; P = 0.04, respectively). Patients in the B-I group had higher cholesterol than those in the R-Y group at 5 years postoperatively (P = 0.003). There were no significant differences in termof other nutritional indicators including total protein, cholesterol, albumin, hemoglobin and weight in short-term outcomes.Conclusions: The final conclusion was that R-Y may be superior to the B-I reconstruction in some aspects of QoL. Besides, R-Y reconstruction could reduce the patient's cholesterol level for a long time. For the short-term outcomes, there were no significant differences in other common nutritional indicators.

Comparison of tenofovir versus entecavir on reducing incidence of hepatocellular carcinoma in chronic hepatitis B patients: A systematic review and meta-analysis.

BACKGROUND AND AIM: Studies had shown that tenofovir (TDF) and entecavir (ETV) are widely used as the first-line therapy to inhibit hepatitis B virus replication, which can reduce the risk of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients, but it was unclear which nucleos(t)ide analogue was most effective. Therefore, we performed a meta-analysis and a systematic review to compare the incidence of HCC in CHB patients who are either on TDF or ETV. METHODS: For this study, the following databases were searched for clinical trials published from its inception until November 2019: PubMed, Web of Science, MEDLINE, Embase, and Cochrane Library. RESULTS: A total of 11 eligible studies were selected, including 70 864 patients. The meta-analysis showed that TDF was superior to ETV with regard to the incidence of HCC, the incidence of death or transplantation, and virologic response. There were no significant differences in terms of biochemical response and loss of seroconversion response among the entire cohort. CONCLUSIONS: The conclusion was that CHB patients treated with TDF had a reduced incidence of HCC compared with patients treated with ETV.

Smokers or non-smokers: who benefits more from immune checkpoint inhibitors in treatment of malignancies? An up-to-date meta-analysis.

BACKGROUND: Immune checkpoint inhibitors, which are a milestone in anti-cancer therapy, have been applied in the treatment of multiple malignancies. Real-world data have suggested that smoking status may be associated with the efficacy of anti-PD-1/PD-L1 therapy. Hereby, to evaluate "smoking benefit or not", we included numerous high-quality randomized controlled clinical trials (RCTs) without any restriction on category. METHODS: A systematic search of online database was performed from July 2010 to July 2019. Eligible studies included phase II/III RCTs comparing PD-1/PD-L1 inhibitors with chemotherapy in the treatment of multiple carcinomas and contained subgroup analysis of smoking status. Then, related hazard ratios (HRs) with 95% confidence intervals (CIs) of overall survival (OS) were pooled. RESULTS: In the initial meta-analysis, compared with chemotherapy, the OS of non-smokers (HR, 0.81; 95% CI, 0.67-0.98) and smokers (HR, 0.77; 95% CI, 0.71-0.83) were significantly prolonged with PD-1/PD-L1 inhibitors. Outcomes from subgroup analysis showed that in anti-PD-1/PD-L1 monotherapy groups, non-smokers showed no significant improvement in OS (HR, 0.94; 95% CI, 0.83-1.06), while the OS of smokers was significantly prolonged (HR, 0.79; 95% CI, 0.74-0.85); in groups of PD-1/PD-L1 inhibitors combined with chemotherapy, the OS of non-smokers (HR, 0.45; 95% CI, 0.28-0.71) and smokers (HR, 0.72; 95% CI, 0.61-0.85) were significantly prolonged. Combined ipilimumab and chemotherapy showed no significance in both groups. CONCLUSION: Smokers benefit from either anti-PD-1/PD-L1 monotherapy or the combined regimen compared with chemotherapy. Considering cost-effectiveness, monotherapy was recommended to smokers. For non-smokers, only the combined regimen was feasible in non-small cell lung cancer.

The relationship between the number of examined lymph nodes and the efficacy of chemotherapy for gastric cancer.

BACKGROUND: The purpose of this research was to investigate the relationship between the number of examined lymph nodes (eLNs) and the prognosis. METHODS: A retrospective examination of reports and studies carried out at two institutions was conducted. According to TNM stages, the relationship between the number of eLNs and the prognosis was analyzed. RESULTS: The 5-year disease-specific survival (DSS) of all enrolled patients was 66.3%. A multivariate analysis showed the type of gastrectomy, histologic type, perineural invasion, pT stage, pN stage, chemotherapy and eLNs to be independent prognostic markers. Additionally, with the exception of patients with stage I disease, the 5-year DSS of patients who had < 25 eLNs removed had a higher risk of having a worst prognosis compared to patients who had ≥ 25 eLNs removed. Through this study, a hypothetical TNM staging system was obtained for predicting the prognosis according to the number of eLNs. Chemotherapy was able to improve the prognosis of patients with stage III and < 25 eLNs in stage II. CONCLUSIONS: Extended lymphadenectomy with a new goal of dissecting 25 LNs for the evaluation of stage II-III cancer cases is recommended. Our hypothetical TNM staging system may be able to stratify the risk more accurately compared to the current AJCC 8th system. Chemotherapy can improve the prognosis in advanced gastric cancer, but its benefit may be affected by the surgical quality.

Clinical significance of peripheral blood-derived inflammation markers in advanced gastric cancer after radical resection.

BACKGROUND: The prognostic significance of peripheral blood-derived inflammation markers in patients with gastric cancer (GC) has not been elucidated. This study aimed to investigate the relationship between systemic inflammatory markers and GC prognosis. METHODS: A prospective observational cohort study involving 598 patients was conducted to analyze the prognosis of GC based on systemic inflammatory markers. The following peripheral blood-derived inflammation markers were evaluated: the neutrophil-lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), systemic immune-inflammation index (SII), C-reactive protein/albumin (CRP/Alb) ratio, Glasgow Prognostic Score (GPS), modified Glasgow Prognostic Score (mGPS), prognostic nutrition index (PNI), and prognostic index (PI). The receiver operating characteristics (ROC) curve and the Youden index were used to determine the optimal cutoff values. Univariate and multivariate analysis of prognostic factors was conducted accordingly. RESULTS: The optimal cutoff values of the PNI, fibrinogen, NLR, PLR, SII, and CRP/Alb were 49.5, 397 ng/dl, 2.5, 154, 556, and 0.05, respectively. Multivariate analysis showed that age, PLR, TNM stage, and chemotherapy were the independent prognostic factors for advanced gastric cancer (AGC). Adjuvant chemotherapy improved the long-term prognosis of patients with PLR ≥154, but chemotherapy had no significant effect on the survival of patients with PLR < 154. CONCLUSIONS: Our findings show that higher PLR (≥154) is an independent risk factor for poor prognosis in GC patients. Besides, PLR can predict adjuvant chemotherapy (oxaliplatin/5-fluorouracil combination) response in patients with GC after surgery.

A meta-analysis of the medium- and long-term effects of laparoscopic sleeve gastrectomy and laparoscopic Roux-en-Y gastric bypass.

BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic sleeve gastrectomy (LSG) are two representative bariatric surgeries. This study aimed to compare the effects of the LSG and LRYGB based on high-quality analysis and massive amount of data. METHODS: For this study databases of PubMed, Web of Science, EBSCO, Medline, and Cochrane Library were searched for articles published until January 2019 comparing the outcomes of LSG and LRYGB. RESULTS: This study included 28 articles. Overall, 9038 patients (4597, LSG group; 4441, LRYGB group) were included. The remission rate of type 2 diabetes mellitus (T2DM) in the LRYGB group was superior to that in the LSG group at the 3-years follow-up. Five-year follow-up results showed that LRYGB had an advantage over LSG for the percentage of excess weight loss and remission of T2DM, hypertension, dyslipidemia, and abnormally low-density lipoprotein. CONCLUSIONS: In terms of the long-term effects of bariatric surgery, the effect of LRYGB was better than of LSG.

The safety and tolerability of combined immune checkpoint inhibitors (anti-PD-1/PD-L1 plus anti-CTLA-4): a systematic review and meta-analysis.

BACKGROUND: The future of combined immunotherapy (a PD-1/PD-L1 plus a CTLA-4 antagonist) is very bright. However, besides improving efficacy, combined therapy increases treatment-related adverse events (TRAEs). Also, the clinical application is limited in some solid tumors. METHODS: This paper purports to investigate the TRAEs for the combined immunotherapy aiming for a more appropriate utilization of immune checkpoint inhibitors (ICIs) in clinical practice through a meta-analysis. RESULTS: A total of 17 eligible studies covering 2626 patients were selected for a meta-analysis based on specified inclusion and exclusion criteria. The incidence rates of any grade and grade 3 or higher TRAEs were 88% (95%CI, 84-92%) and 41% (95%CI, 35-47%), respectively. The overall incidence of any grade TRAEs leading to discontinuation of treatment was 20% (95%CI, 16-24%). The incidence rate of treatment related deaths was 4.3‰ (95%CI, 1.4‰-8.4‰). Analysis showed that NIVO1 + IPI3 cohort had higher incidences of grade 3 or higher TRAEs (RR = 1.77, 95%CI, 1.34-2.34, p < 0.0001) and any grade TRAEs leading to discontinuation of treatment (RR = 1.81, 95%CI, 1.08-3.04, P = 0.02), compared with NIVO3 + IPI1 regimen. CONCLUSIONS: The combined therapy had high TRAEs. The TRAEs, especially grade 3 or higher, led to discontinuation of the treatment. Furthermore, the incidence of treatment-related deaths was rare. Moreover, the NIVO3 + IPI1 regimen, regardless of efficacy, is more recommended because of better tolerance and lower adverse events.

Clinicopathological and prognostic significance of PD-L1 expression in colorectal cancer: a systematic review and meta-analysis.

OBJECTIVE: To analyze the prognostic value of programmed death factor ligand 1 (PD-L1) in colorectal cancer. METHODS: Electronic databases, such as PubMed, Web of Science, Embase, and Cochrane library, were searched to identify studies evaluating the PD-L1 expression and overall survival (OS) in these patients. Afterwards, the relevant data were extracted to perform the meta-analysis. RESULTS: A total of 3481 patients were included in 10 studies. The combined hazard ratio (HR) was 1.22 (95%CI = 1.01-1.48, P = 0.04), indicating that high expression of PD-L1 was significantly correlated with poor prognosis of colorectal cancer. Apropos of clinicopathological features, the merged odds ratio (OR) exhibited that highly expressed PD-L1 was firmly related to lymphatic invasion (OR = 3.49, 95%CI = 1.54-7.90, P = 0.003) and advanced stage (OR = 1.77, 95%CI = 1.41-2.23, P < 0.00001), but not correlative with patients' gender, microsatellite instability, or tumor location. CONCLUSION: The expression of PD-L1 can be utilized as an independent factor in judging the prognosis of colorectal cancer, and patients with advanced cancer or lymphatic invasion are more likely to express PD-L1. This conclusion may lay a theoretical foundation for the application of PD-1/PD-L1 immunoassay point inhibitors but still needs verifying by sizeable well-designed cohort studies.

Pancreaticoduodenectomy versus limited resection for duodenal gastrointestinal stromal tumors: a systematic review and meta-analysis.

BACKGROUND: By comparing the long-term prognostic outcomes after pancreaticoduodenectomy (PD) and limited resection (LR), this study aimed to investigate the optimal surgical modality for duodenal gastrointestinal stromal tumors (GISTs). METHODS: Two authors independently searched PubMed, Web of Science, Embase, and the Cochrane Library for published articles comparing the long-term prognostic and clinicopathological factors of duodenal GIST patients undergoing PD versus LR. Relevant information was extracted and analyzed. RESULTS: After screening, 10 items comprising 623 cases were eventually included. This meta-analysis explicitly indicated that PD treatment was associated with worse long-term prognosis (hazard ratio = 1.93; 95% confidence interval [CI], 1.39-2.69; p < 0.001; I2 = 0) and more complications (odds ratio [OR] = 2.90; 95% CI, 1.90-4.42; p < 0.001; I2 = 10%) than LR treatment. Nevertheless, for duodenal GISTs, PD was related to the following clinicopathological features: invasion of the second part of the duodenum (OR = 3.39; 95% CI, 1.69-6.79; p < 0.001; I2 = 50%), high-degree tumor mitosis (> 5/50 high-power fields; OR = 2.24; 95% CI, 1.42-3.52; p < 0.001; I2 = 0), and high-risk classification (OR = 3.17; 95% CI; 2.13-4.71; p < 0.001; I2 = 0). CONCLUSIONS: Since PD is associated with worse long-term prognosis and more complications, its safety and efficacy should be ascertained. Our findings recommend the use of LR to obtain negative incision margins when conditions permit it.

A meta-analysis of comparison of proximal gastrectomy with double-tract reconstruction and total gastrectomy for proximal early gastric cancer.

BACKGROUND: In theory, proximal gastrectomy with double-tract reconstruction (PG-DT) was superior to total gastrectomy (TG) in hematologic and nutritional outcomes. However, its clinical effects in proximal early gastric cancer (EGC) have been controversial. METHODS: The purpose of this study was to investigate the outcomes of laparoscopic proximal gastrectomy with double-tract reconstruction (LPG-DT) for proximal EGC. For this systematic review and meta-analysis, we searched for articles published before December of 2018 in the following databases: PubMed, Web of Science, EBSCO, Medline, and Cochrane Library. RESULTS: The results showed no significant difference in the anastomotic stenosis (OR = 0.91, 95%CI = 0.33-2.50, p = 0.85) and reflux esophagitis (OR = 1.87, 95%CI = 0.62-5.65, p = 0.27) between LPG-DT and laparoscopic total gastrectomy (LTG). The vitamin B12 supplementation rate in the LPG-DT group was lower than the LTG group (OR = 0.06, 95%Cl = 0.01-0.59, p = 0.02). CONCLUSIONS: Due to comparable clinical effect, PG-DT is comparable to TG for patients with proximal EGC. In addition, LPG-DT not only appears superior to TG in terms of preventing vitamin B12 deficiency, but also does not increase the risk of anastomotic stricture and reflux esophagitis.

Mesh-reinforced pancreaticojejunostomy versus conventional pancreaticojejunostomy after pancreaticoduodenectomy: a retrospective study of 126 patients.

BACKGROUND: Pancreatic fistula is a major cause of morbidity and mortality after pancreaticoduodenectomy. The aim of this study is to compare the safety and efficacy of a newly developed technique, namely mesh-reinforced pancreaticojejunostomy, in comparison with the conventional use of pancreaticojejunostomy after undergoing a pancreaticoduodenectomy. METHODS: Data was collected from regarding 126 consecutive patients, who underwent the mesh-reinforced pancreaticojejunostomy or conventional pancreaticojejunostomy, after standard pancreaticoduodenectomy by one group of surgeons, between the time period of 2005 and 2016. This data was collected retrospectively. Surgical parameters and perioperative outcomes were compared between these two groups. RESULTS: A total of 65 patients received mesh-reinforced pancreaticojejunostomy and 61 underwent conventional pancreaticojejunostomy. There were no substantial differences in surgical parameters, mortality, biliary leakage, delayed gastric emptying, gastrojejunostomy leakage, intra-abdominal fluid collection, postpancreatectomy hemorrhage, reoperation, and the total hospital costs between the two groups. Pancreatic fistula rate (15 versus 34%; p = 0.013), overall surgical morbidity (25 versus 43%; p = 0.032), and length of hospital stay (18 ± 9 versus 23 ± 12 days; p = 0.016) were significantly reduced after mesh-reinforced pancreaticojejunostomy. Multivariate analysis of the postoperative pancreatic fistula revealed that the independent factors that were highly associated with pancreatic fistula were a soft pancreatic texture and the type of conventional pancreaticojejunostomy. CONCLUSIONS: This retrospective single-center study showed that mesh-reinforced pancreaticojejunostomy appears to be a safe technique for pancreaticojejunostomy. It may reduce pancreatic fistula rate and surgical complications after pancreaticoduodenectomy. TRIAL REGISTRATION: This research is waivered from trial registration because it is a retrospective analysis of medical records.

Comparison of clinical outcomes between mesh-reinforced pancreatojejunostomy and pancreatogastrostomy following pancreaticoduodenectomy: a cohort study.

BACKGROUND: Postoperative complications, especially postoperative pancreatic fistulas, remain the major concern following pancreaticoduodenectomy (PD). Mesh-reinforced pancreatic anastomoses, including pancreatojejunostomy (PJ) and pancreatogastrostomy (PG), are a new effective technique in PD. This study was conducted to analyze the safety and efficacy of this new technique and to compare the results of mesh-reinforced PJ vs PG. METHODS: A total of 110 patients who underwent PD between August 2005 and January 2016 were eligible in this study. Perioperative and postoperative data of patients with a mesh-reinforced technique were analyzed. Data were also grouped according to the procedure performed: mesh-reinforced PJ and mesh-reinforced PG. RESULTS: Among patients undergoing PD with the mesh-reinforced technique, 42 had postoperative complications, and the comprehensive complication index (CCI) was 32.7 ± 2.5. Only 10% of patients had pancreatic fistula; three were grade A, six were grade B, and two were grade C. Biliary fistula occurred in only 8.2% of patients. Patients undergoing mesh-reinforced PG showed a significantly lower rate of CCI than did mesh-reinforced PJ patients (27.0 ± 2.1 vs 37.0 ± 3.9, p < 0.05). The mesh-reinforced PG was also favored over mesh-reinforced PJ because of significant differences in intra-abdominal fluid collection (5.9% vs 18.6%, p < 0.05) and delayed gastric emptying (3.9% vs 15.3%, p < 0.05). CONCLUSIONS: PD with the mesh-reinforced technique was a safe and effective method of decreasing postoperative pancreatic fistula. Compared with mesh-reinforced PJ, mesh-reinforced PG did not show significant differences in the rates of pancreatic fistula or biliary fistula. However, CCI, intra-abdominal fluid collection, and delayed gastric emptying were significantly reduced in patients with mesh-reinforced PG.

Efficacy of Glucagon-like Peptide-1 Receptor Agonists in Overweight/Obese and/or T2DM Adolescents: A Meta-analysis Based on Randomized Controlled Trials.

Objective: This meta-analysis aimed to investigate the effect of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on blood glucose and weight in overweight/obese and/or type 2 diabetes mellitus (T2DM) adolescents aged <18 years. Methods: Herein, we searched PubMed, Embase, Web of Science, and Cochrane Library for all randomized controlled trials (RCTs) comparing GLP-1RAs with placebo in overweight/obese and/or T2DM adolescents and extracted relevant data up to August 2023 for meta-analysis. Results: Fourteen RCTs were included in the meta-analysis with a total of 1262 participants. Results revealed that the GLP-1RAs group had a more significant reduction in glycosylated hemoglobin A1c (HbA1c; risk difference (RD)=-0.34%, P<0.001) than the control group. However, there was no difference in fasting blood glucose (FPG; RD=-2.07mg/dL, P=0.065) between the two groups. Nonetheless, the experimental group that administered exenatide showed a no significant reduction in HbA1c (P=0.253) and FPG (P=0.611) between the two groups. The GLP-1RAs group had a more significant decline in body weight (RD=-4.28kg, P=0.002) and BMI (RD=-1.63kg/m2, P=0.002) compared to the control group. The experimental group was adopted with liraglutide (RD=-2.31kg, P=0.038) or exenatide (RD=-2.70kg, P<0.001). Compared to the control group, the experimental group had a more significant drop in body weight than the control group. But for the experimental group that received liraglutide, the BMI had a no significant reduction between the two groups (RD=-0.81kg/m2, P=0.260). For the experimental group that was adopted with exenatide, BMI revealed a more significant decline in the intervention group than in the control group (RD=-1.14kg/m2, P<0.001). Conclusion: This study showed that GLP-1RAs reduced HbA1c, FPG, and weight loss in overweight/obese and/or T2DM adolescents. Liraglutide is better than exenatide in terms of glucose reduction. Nevertheless, in terms of weight control, exenatide is better than liraglutide.

Transjugular intrahepatic portosystemic shunt for pyrrolidine alkaloids-induced hepatic sinusoidal obstruction syndrome: a retrospective cohort study.

BACKGROUND: This study aimed to investigate the efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) in the treatment of patients with pyrrolidine alkaloids-induced hepatic sinusoidal obstruction syndrome (PA-HSOS). METHODS: Patients diagnosed with PA-HSOS and treated in Ningbo No.2 Hospital between November 2017 and October 2022 were enlisted in this retrospective cohort study. RESULTS: This cohort comprised a total of 22 patients with PA-HSOS, of which 12 patients received TIPS treatment and 10 patients experienced conservative treatment. The median follow-up duration was 10.5 months. Baseline characteristics existed with no significant difference between the two groups. No operation failures or any TIPS-associated intraoperative complications were observed after TIPS. In the TIPS group, the portal venous pressure was substantially decreased from 25.3 ±â€…6.3 mmHg to 14.4 ±â€…3.5 mmHg after TIPS ( P  = 0.002). Compared with preoperative, the ascites after TIPS were significantly subsided ( P  = 0.001) and there existed a considerable decrease in Child-Pugh score. At the end of follow-up, 5 patients died, involving 1 in the TIPS group and 4 in the conservative treatment group. The median survival time was 13 (3-28) months in the TIPS group and 6.5 (1-49) months in the conservative treatment group, respectively. The survival analysis demonstrated that the total survival time of TIPS group was longer than that of the conservative treatment group, no statistical significance was observed ( P  = 0.08). CONCLUSION: TIPS may be a secure and effective therapeutic strategy for PA-HSOS patients who do not respond to conservative treatment.

Association between statins' exposure with incidence and prognosis of gastric cancer: an updated meta-analysis.

BACKGROUND AND AIMS: Previous research has revealed the role of statins in cancer prevention and treatment. This study aimed to determine the relationship between statins' exposure and the incidence and prognosis of gastric cancer (GC). METHODS: Relevant articles until January 2022 were systematically searched in PubMed, EBSCO, Web of Science, and Cochrane Library databases for comparison in GC with or without statins' exposure. The primary referred outcomes were the occurrence of GC and the survival rate. A total of 19 articles were included in this meta-analysis. RESULTS: The analysis showed that statins were associated with reduced GC incidence and increased GC survival rate. Subgroup analysis suggested a decreased incidence of GC in both Eastern and Western countries exposed to statins. Furthermore, the risk of GC was reduced in those exposed to lipophilic statins, yet not in those exposed to hydrophilic statins. CONCLUSIONS: Statins were found to help lower the incidence and improve the survival rate of GC. Furthermore, the incidence of GC was influenced by the population's origin region and the type of statins used.

Effects of Intermittent Fasting in Human Compared to a Non-intervention Diet and Caloric Restriction: A Meta-Analysis of Randomized Controlled Trials.

Background: The popularity of applying intermittent fasting (IF) has increased as more and more people are trying to avoid or alleviate obesity and metabolic disease. This study aimed to systematically explore the effects of various IF in humans. Methods: The randomized controlled trials (RCTs) related to IF vs. non-intervention diet or caloric restriction (CR) were retrieved in PubMed, Web of Science, Cochrane Library database, and Embase. Extraction outcomes included, but were not limited to, weight, body mass index (BMI), waist circumference (WC), fasting glucose, and triglyceride (TG). Results: This study includes 43 RCTs with 2,483 participants. The intervention time was at least 1 month, and the median intervention time was 3 months. Contrasting results between IF and non-intervention diet showed that participants had lower weight (weighted mean difference (WMD) = 1.10, 95% CI: 0.09-2.12, p = 0.03) and BMI after IF (WMD = 0.38, 95% CI: 0.08-0.68, p = 0.01). The WC of participants after IF decreased significantly compared with the non-intervention diet (WMD = 1.02, 95% CI: 0.06-1.99, p = 0.04). IF regulated fat mass (FM) more effectively than non-intervention diet (WMD = 0.74, 95% CI: 0.17-1.31, p = 0.01). The fat-free mass of people after IF was higher (WMD = -0.73, 95% CI: (-1.45)-(-0.02), p = 0.05). There was no difference in fasting blood glucose concentrations between participants in the after IF and non-intervention diet groups. The results of insulin concentrations and HOMA-IR, though, indicated that IF was significantly more beneficial than non-intervention diet (standard mean difference (SMD) = -0.21, 95% CI: 0.02-0.40, p = 0.03, and WMD = 0.35, 95% CI: 0.04-0.65, p = 0.03, respectively). Cholesterol and TG concentrations in participants after IF were also lower than that after a nonintervention diet (SMD = 0.22, 95% CI: 0.09-0.35, p = 0.001 and SMD = 0.13, 95% CI: 0.00-0.26, p = 0.05, respectively). IF outcomes did not differ from CR except for reduced WC. Conclusion: Intermittent fasting was more beneficial in reducing body weight, WC, and FM without affecting lean mass compared to the non-intervention diet. IF also effectively improved insulin resistance and blood lipid conditions compared with non-intervention diets. However, IF showed less benefit over CR.

Suppression of the transforming growth factor-ß signaling pathway produces a synergistic effect of combination therapy with programmed death receptor 1 blockade and radiofrequency ablation against hepatic carcinoma in mice.

Primary liver cancer (PLC) significantly affects the health of patients globally owing to its high morbidity and low survival rate. Radiofrequency ablation (RFA) has recently been introduced for the clinical treatment of PLC. However, significant immunosuppressive effects are induced by RFA, which limits its application. This study aimed to explore the potential of combination therapy with RFA by investigating the effects of siRNAs against programmed death receptor 1 (PD-1) and transforming growth factor-ß (TGF-ß) on the antitumor effect induced by RFA. We observed that compared with si-NC, cell viability was reduced, apoptosis rate was elevated, release of inflammatory factors and percentage of CD3+CD8+ cells were increased, and the PI3K/AKT/mTOR pathway was repressed in the co-culture of RFA-treated H22 cells and CD8+ T cells by transfection with si-PD-1 and si-TGF-ß; these effects were further enhanced by co-transfection with si-PD-1 and si-TGF-ß. Additionally, in H22 cell xenograft-bearing mice treated with RFA, compared with the si-NC group, repressed tumor growth, prolonged survival, increased production of inflammatory factors and expression of CD3 and CD8 in tumor tissues, and downregulation of the PI3K/AKT/mTOR pathway were observed in the si-PD-1 and si-TGF-ß groups; these effects were further enhanced in the si-PD-1 + si-TGF-ß group. Taken together, our data revealed that suppression of the TGF-ß signaling pathway produced a synergistic antitumor effect of combination therapy with PD-1 blockade and RFA against PLC. [Figure: see text].