Inhibition of Transient Receptor Potential Vanilloid 3 Channels by Antimalarial Hydroxychloroquine (HCQ) Alleviates TRPV3-dependent Dermatitis.

Transient receptor potential vanilloid 3 channel (TRPV3) is closely associated with skin inflammation, but there is a lack of effective and specific inhibitors for clinical use. In this study, we identified antimalarial HCQ as a selective TRPV3 inhibitor following the prediction by network pharmacology data analysis. In whole-cell patch-clamp recordings, HCQ inhibited the current of the TRPV3 channel, with an IC50 of 51.69 ± 4.78 µM. At the single-channel level, HCQ reduced the open probability of TRPV3 and decreased single-channel conductance. Molecular docking and site-directed mutagenesis confirmed that residues in the pore domain were critical for the activity of HCQ. In vivo, HCQ effectively reduced carvacrol-induced epidermal thickening, erythema, and desquamation. Additionally, the serum IgE and inflammatory factors such as TNF-α and IL-6 were markedly decreased in the dorsal skin tissues in the HCQ treatment group, as compared to the model group. Our results suggested the antimalarial HCQ may represent a potential alleviator for treating skin inflammation by inhibiting TRPV3 channels.

The efficacy and safety of anti-EGFR target agents in patients with potentially resectable metastatic colorectal cancer: a meta-analysis of randomized controlled trials.

BACKGROUND: Adding anti-epidermal growth factor receptor (anti-EGFR) target agents to conversion therapy may improve the resection rates and survival of patients with potentially resectable metastatic colorectal cancer (mCRC). This study aims to analyze the efficacy and safety of additional anti-EGFR target agents. METHODS: A systematic search was conducted on PubMed, Web of Science, Embase, and Cochrane Library. And all relevant studies published in English before January 2023 were collected to explore the impact of additional anti-EGFR targeted agent on the efficacy and safety of patients with potentially resectable mCRC (PROSPERO: CRD42022340523, https://www.crd.york.ac.uk/PROSPERO/ ). RESULTS: This study included a total of 8 articles, including 2618 patients. The overall response rate (ORR) and R0 resection rates of the experimental group were higher than those of the control group, while there was no significant difference in progression-free survival (PFS) and overall survival (OS) between the two groups. In RAS/KRAS wild-type patients, the ORR (RR: 1.20, 95% Cl: 1.02-1.41, p = 0.03), R0 resection rate (RR: 1.60, 95% Cl: 1.17-2.20, p = 0.003), PFS (HR: 0.80, 95% Cl: 0.68-0.93, p = 0.003), and OS (HR: 0.87, 95% Cl: 0.76-0.99, p = 0.031) of the experimental group were higher than those of the control group. While in KRAS mutant patients, there was no statistical difference between the two groups in ORR, R0 resection rate, PFS, and OS. CONCLUSION: The addition of anti-EGFR targeted agents can improve the prognosis of RAS/KRAS wild-type patients with potentially resectable mCRC, while KRAS mutant patients may not benefit. In addition, the overall safety factor was controllable.

Systematic Review and Meta-Analysis: Association between Preoperative Ustekinumab and Surgical Complications in Crohn's Disease Patients.

INTRODUCTION: The impact of ustekinumab (UST) therapy on surgical complications in patients with Crohn's disease (CD) remains controversial. The aim of this meta-analysis is to explore the link between these two. METHODS: Databases (PubMed, Web of Science, Cochrane, and Springer Link) were searched until April 2022. Studies of CD patients who received UST and no UST prior to surgery (including no biological therapy, anti-tumor necrosis factor-α [anti-TNF-α] agent, and vedolizumab [VDZ]) were included. Primary outcomes included overall complications, infectious complications, and noninfectious complications. RESULTS: Nine studies totaling 3,225 CD patients were enrolled; 332 patients received UST treatment. There was no evidence of difference in the overall complications (odds ratio [OR] = 0.84, p = 0.37, 95% confidence interval [CI] = [0.57-1.23], I2 = 40%) between CD patients who had UST treatment preoperatively and those who had no UST treatment. There was no evidence of a difference in infectious complications (OR = 1.15, p = 0.35, 95% CI = [0.86-1.53], I2 = 2%). Additionally, there was no significant evidence of difference between these groups in terms of noninfectious complications and death. Specifically, there was no evidence of difference in overall complications, infection complications (including wound complications, sepsis, abscess, and anastomotic leakage), and noninfection complications (ileus, readmission, and return to operation), compared with no biological therapy and anti-TNF-α agents. At the same time, no significant evidence of difference was discovered in the comparison of preoperative UST and VDZ therapy in terms of overall complications, infectious complications (sepsis and abscess), and noninfectious complications (intestinal obstruction, readmission, and recovery surgery). CONCLUSION: In general, compared with other biological agents, preoperative use of UST in the treatment of CD patients is usually safe and does not increase surgical complications.

Systematic review and meta-analysis: association between obesity/overweight and surgical complications in IBD.

PURPOSE: While the prevalence of obesity in inflammatory bowel disease (IBD) patients is rapidly increasing, it is unclear whether obesity affects surgical outcomes in this population. This meta-analysis aims to assess the impact of obesity/overweight on patients undergoing surgery for IBD. METHODS: Databases (PubMed, Web of Science, Cochrane Library, and Springer) were searched through September 2021. The meta-analysis included patients with surgically treated IBD to investigate the impact of obesity/overweight on this population. Primary outcomes included overall complications, infectious complications, noninfectious complications, and conversion to laparotomy. RESULTS: Fifteen studies totaling 12,622 IBD patients were enrolled. Compared with nonobese (including overweight) patients, obese IBD patients have increased the risk in terms of overall complications (OR = 1.45, p < 0.001), infectious complications (OR = 1.48, p = 0.003) (especially wound complications), as well as conversion to laparotomy (OR = 1.90, p < 0.001). Among the noninfectious complications, only the incidence of visceral injury (OR = 2.36, p = 0.05) had significantly increased. Compared with non-overweight patients, the risk of developing wound complications (OR = 1.65, p = 0.01) and sepsis (OR = 1.73, p = 0.007) were increased in overweight patients, but the rates of overall complications (OR = 1.04, p = 0.81), infectious complications (OR = 1.31, p = 0.07), and conversion to laparotomy (OR = 1.33, p = 0.08) associated with body mass index (BMI) were not significantly different. CONCLUSION: Obesity is a risk factor for surgical complications in IBD patients, mainly reflected in infectious complications. Moreover, obese patients seem to have a more common chance of developing surgical complications than overweight patients.

Assessment of Prophylactic Carbapenem Antibiotics Administration for Severe Acute Pancreatitis: An Updated Systematic Review and Meta-Analysis.

BACKGROUND: The effectiveness of prophylactic antibiotics in severe acute pancreatitis (SAP) remains a debatable issue. This meta-analysis aimed to determine the efficacy of prophylactic carbapenem antibiotics in SAP. METHODS: This meta-analysis of prophylactic carbapenem antibiotics for SAP was conducted in PubMed, EMBASE, Web of Science, MEDLINE, and Cochrane Library up to February 2021. The related bibliographies were manually searched. The primary outcomes involved infected pancreatic or peripancreatic necrosis, mortality, complications, infections, and organ failure. RESULTS: Seven articles comprised 5 randomized controlled trials and 2 retrospective observational studies, including 3,864 SAP participants. Prophylactic carbapenem antibiotics in SAP were associated with a statistically significant reduction in the incidence of infections (odds ratio [OR]: 0.27; p = 0.03) and complications (OR: 0.48; p = 0.009). Nevertheless, no statistically significant difference was demonstrated in the incidence of infected pancreatic or peripancreatic necrosis (OR: 0.74; p = 0.24), mortality (OR: 0.69; p = 0.17), extrapancreatic infection (OR: 0.64, p = 0.54), pulmonary infection (OR: 1.23; p = 0.69), blood infection (OR: 0.60; p = 0.35), urinary tract infection (OR: 0.97; p = 0.97), pancreatic pseudocyst (OR: 0.59; p = 0.28), fluid collection (OR: 0.91; p = 0.76), organ failure (OR: 0.63; p = 0.19), acute respiratory distress syndrome (OR: 0.80; p = 0.61), surgical intervention (OR: 0.97; p = 0.93), dialysis (OR: 2.34; p = 0.57), use of respirator or ventilator (OR: 1.90; p = 0.40), intensive care unit treatment (OR: 2.97; p = 0.18), and additional antibiotics (OR: 0.59; p = 0.28) between the experimental and control groups. CONCLUSIONS: It is not recommended to administer routine prophylactic carbapenem antibiotics in SAP.

Early versus Delayed Minimally Invasive Intervention for Acute Necrotizing Pancreatitis: An Updated Systematic Review and Meta-Analysis.

BACKGROUND: Nowadays, minimally invasive intervention (MII) has largely replaced delayed open surgery in acute necrotizing pancreatitis (ANP). However, the timing of MII remains unclear. The present study investigated the effect of early versus delayed MII on complications in ANP. METHODS: Studies evaluating the impact of the timing of MII on complications in ANP patients were thoroughly searched on PubMed, Embase, Cochrane Library, and Web of Science from inception to June 2022. The primary outcome of interest was mortality. Secondary outcomes were the incidence of complications. RESULTS: Nine studies reporting 870 patients undergoing MII for ANP were included. No significant difference was found in mortality between the early and delayed intervention groups. In addition, the timing of MII was not associated with the incidence of new-onset respiratory failure, new-onset cardiovascular failure, new-onset renal failure, new-onset multiple organ failure, gastrointestinal fistula or perforation, pancreatic fistula, stent migration, bleeding, venous thrombosis, and new-onset pancreatic endocrine insufficiency. Notably, in the subgroup analysis of biliary and Asian ANP patients, early intervention was associated with a significantly higher risk of new-onset renal failure than delayed intervention. CONCLUSIONS: Early intervention is safe and recommended only for patients with indications for intervention, such as infection.

The association between caffeine exposure during pregnancy and risk of gestational hypertension/preeclampsia: A meta-analysis and systematical review.

BACKGROUND: The potential effect of caffeine exposure during pregnancy on gestational hypertension (GH)/preeclampsia has attracted attention but remains unclear. METHODS: A systematic literature search of PubMed, Embase, and Cochrane Library databases was performed until March 2022. Observational studies assessing the association between caffeine exposure during pregnancy and the risk of GH/preeclampsia were included. The study protocol was registered in PROSPERO: CRD42022322387. RESULTS: Ten studies involving 114 984 pregnant women (2548 diagnosed with GH and 2473 diagnosed with preeclampsia) were included. Comparing caffeine exposure with noncaffeine exposure, no significant association was found between caffeine exposure during pregnancy and the risk of GH (odds ratio [OR] = 0.99, 95% confidence interval [CI]: 0.90-1.08, p = 0.800) and preeclampsia (OR = 1.13, 95% CI: 0.97-1.31, p = 0.114). Subgroup analyses comparing low to moderate doses with no/lowest doses showed that caffeine exposure during pregnancy was not significant associated with GH (OR = 1.00, p = 0.987) or preeclampsia (OR = 1.03, p = 0.648). Besides, subgroup analyses comparing high doses with no/lowest doses showed that caffeine exposure during pregnancy was not significant associated with GH (OR = 1.06, p = 0.623) or preeclampsia (OR = 1.18, p = 0.192). CONCLUSION: This study found that caffeine exposure during pregnancy was not significantly associated with the risk of GH/preeclampsia.

Association between vedolizumab and postoperative complications in IBD: a systematic review and meta-analysis.

BACKGROUND: The effect of preoperative vedolizumab (VDZ) therapy on postoperative complications in inflammatory bowel disease (IBD) patients is still controversial. This meta-analysis aims to review postoperative complications of IBD patients who preoperatively received VDZ. METHODS: A meta-analysis of the available literature was performed. Studies of IBD patients who received VDZ and non-VDZ therapy (including anti-TNF-α agents, non-biological therapy, other biological agents, ustekinumab, and placebo) before surgery were included. Primary outcomes included overall complications, infectious complications, and non-infectious complications. RESULTS: Twelve studies with 1925 IBD patients were enrolled, among which 709 patients received VDZ treatment. The results show that, compared with non-VDZ treatment, there is no significant difference in the incidence of overall complications (OR = 1.25, p = 0.43) for adult IBD patients treated with VDZ preoperatively, the incidence of infectious complications (OR = 0.49, p = 0.001) decreases, but the risks of all surgical site infection (SSI) (Crohn's disease (CD): OR = 2.97, p < 0.001), superficial surgical site infection (sSSI) (OR = 2.24, p = 0.02), and ileus (OR = 2.16, p < 0.001) increase. The risk of mucocutaneous separation (MCS) (OR = 4.69, p = 0.03) with VDZ is also higher than non-VDZ. Two studies involved pediatric patients and showed no difference in ileus (OR = 0.55, p = 0.55). CONCLUSIONS: Overall, compared with non-VDZ treatment, preoperative use of VDZ is relatively safer in adult IBD patients, which does not increase the risk of overall postoperative complications and reduces the occurrence of infectious complications. But, it increases the risk of all SSI and sSSI in infectious complications and the incidence of ileus and MCS in non-infectious complications. Due to lack of sufficient data, the safety of VDZ in pediatric patients is uncertain and requires further study.

Role of neurogenic inflammation in the pathogenesis of alopecia areata.

Alopecia areata refers to an autoimmune illness indicated by persistent inflammation. The key requirement for alopecia areata occurrence is the disruption of immune-privileged regions within the hair follicles. Recent research has indicated that neuropeptides play a role in the damage to hair follicles by triggering neurogenic inflammation, stimulating mast cells ambient the follicles, and promoting apoptotic processes in keratinocytes. However, the exact pathogenesis of alopecia areata requires further investigation. Recently, there has been an increasing focus on understanding the mechanisms of immune diseases resulting from the interplay between the nervous and the immune system. Neurogenic inflammation due to neuroimmune disorders of the skin system may disrupt the inflammatory microenvironment of the hair follicle, which plays a crucial part in the progression of alopecia areata.

Effect of Neoadjuvant Therapy on the Functional Outcome of Patients With Rectal Cancer: A Systematic Review and Meta-Analysis.

AIMS: The impact of neoadjuvant therapy on the functional outcome of patients with resectable rectal cancer is still controversial. The aim of the present study was to explore the effects of neoadjuvant therapy on anorectal function (ARF), urinary function and sexual function in relevant patients. MATERIALS AND METHODS: PubMed, Embase, Web of Science and the Cochrane Library were searched systematically. All English-language studies, published from January 2000 to July 2021, that explored the (postoperative) effects of neoadjuvant therapy versus upfront surgery on ARF, urinary function and sexual function of patients were included (PROSPERO 2021: CRD42021281617). RESULTS: The data in this study were derived from 37 articles based on 33 studies; in total, 17 917 patients were enrolled. The meta-analysis revealed that the incidence of anorectal dysfunction in the neoadjuvant therapy group was significantly higher than that in the group of upfront surgery, which was manifested by a higher incidence of major low anterior resection syndrome (odds ratio = 3.09, 95% confidence interval = 2.48, 3.84; P < 0.001), reduction of mean squeeze pressure and mean resting pressure, and other manifestations, including clustering of stools, incontinence, urgency and use of pads. With the extension of follow-up time, the adverse effects of neoadjuvant therapy on major low anterior resection syndrome existed. Compared with patients undergoing upfront surgery, neoadjuvant therapy increased the risk of urinary incontinence (odds ratio = 1.31, 95% confidence interval = 1.00, 1.72; P = 0.05) and erectile dysfunction (odds ratio = 1.77, 95% confidence interval = 1.27, 2.45; P < 0.001). CONCLUSION: Compared with upfront surgery, neoadjuvant therapy is not only associated with impairment of ARF, but also with increased incidence of urinary incontinence and male erectile dysfunction. However, the influence of confounding factors (e.g. surgical method, tumour stage) needs to be considered.

Relationship Between SGLT-2i and Ocular Diseases in Patients With Type 2 Diabetes Mellitus: A Meta-Analysis of Randomized Controlled Trials.

Background: This meta-analysis was conducted to explore the association between sodium-glucose cotransporter 2 inhibitors (SGLT-2is) and ocular diseases in type 2 diabetes mellitus (T2DM) patients. Methods: PubMed, Cochrane Central Registry of Controlled Trials, Web of Science and Springer were searched for articles on randomized controlled trials (RCTs) involving T2DM patients treated with SGLT-2i versus placebo or other hypoglycemic agents published prior to August 2021. The primary outcome of this meta-analysis was incidence of ocular diseases, which was assessed using risk ratios (RR) and 95% confidence intervals (CI). We reviewed 47 papers and compared the effect of SGLT-2i with the effect of the control groups (placebo and other hypoglycemic drugs) on the incidence of ocular diseases. Results: Compared with controls, overall SGLT-2i use in T2DM patients was not associated with incidences of cataract, glaucoma, retinal disease and vitreous disease. Ertugliflozin (RR=0.47, P=0.01) reduced the risk for retinal disease, while empagliflozin (RR=0.44, P=0.05) reduced the risk for diabetic retinopathy (DR) compared with controls. SGLT-2i (RR=0.50, P=0.02), perhaps empagliflozin (RR=0.47, P=0.06), reduced the risk of retinal disease compared with active hypoglycemic agents. Canagliflozin (RR=4.50, P=0.03) increased the risk for vitreous disease compared with placebo. Conclusions: There was no significant correlation between overall SGLT-2i and ocular diseases (cataract, glaucoma, retinal disease, vitreous disease, corneal disease, conjunctival disease, uveal disease, eye haemorrhage and vision problems) in T2DM patients. Ertugliflozin and empagliflozin may protect against ocular diseases, but canagliflozin may promote ocular diseases.

Efficacy of Neoadjuvant Therapy in Improving Long-Term Survival of Patients with Resectable Rectal Cancer: A Meta-Analysis.

BACKGROUND: The impact of neoadjuvant therapy on long-term prognosis of patients with resectable rectal cancer is currently unknown. OBJECTIVE: This study aimed to explore the long-term prognosis of patients with resectable rectal cancer following treatment with neoadjuvant therapy. METHODS: Four major databases (PubMed, Web of Science, Embase, Cochrane library) were searched to identify relevant articles published between January 2000 and July 2020. The main outcome indicators were the 5-year Overall Survival (OS) and Disease-Free Survival (DFS). RESULTS: The meta-analysis revealed that 5-year OS (HR: 0.88, 95% Cl: 0.83-0.93) and DFS (HR: 0.95, 95% Cl: 0.91- 0.98) were higher in patients with resectable rectal cancer after receiving neoadjuvant therapy than those treated with upfront surgery. Subgroup analysis demonstrated that the long-term survival of patients in Asia and Europe could benefit from neoadjuvant therapy. The neoadjuvant short-course radiotherapy (SCRT) and neoadjuvant chemoradiotherapy (CRT) improved the 5-year OS and DFS of patients with stage II-III rectal cancer and mid/low rectal cancer. Further research found that patients with stage II only had an increase in OS, while patients with stage Ⅲ have improved 5-year OS and DFS. CONCLUSION: Neoadjuvant therapy improved the long-term survival of patients with mid/low rectal cancer in stage Ⅱ-Ⅲ (especially stage Ⅲ). Additionally, patients in Asia and Europe seemed to be more likely to benefit from neoadjuvant therapy. For the treatment, we recommend neoadjuvant SCRT and neoadjuvant CRT for resectable rectal cancer.

Efficacy and safety of SGLT-2i in overweight/obese, non-diabetic individuals: a meta-analysis of randomized controlled trials.

INTRODUCTION: Sodium-glucose cotransporter 2 inhibitor (SGLT-2i) has been shown to decrease blood glucose levels in type 2 diabetes mellitus (T2DM) patients and potentially yield additional benefits in weight loss. This meta-analysis aimed to investigate the efficacy and safety of giving SGLT-2i to overweight/obese, non-diabetic individuals. MATERIAL AND METHODS: The search was underpinned by PubMed, Cochrane Central Register of Controlled Trials, Web of Science, and Springer to identify English-language papers on randomized controlled trials (RCTs) on the use of SGLT-2i in overweight/obese, nondiabetic individuals published in and before March 2021, to study its effectiveness and safety. Results were evaluated by weighted mean difference (WMD), standardized mean difference (SMD), risk ratio (RR), and 95% confidence interval (CI). RESULTS: We reviewed 13 papers and compared the SGLT-2i group with the control group (other drugs and placebo) and found that SGLT-2i reduced weight (WMD = -1.33, p = 0.002) and waist circumference (WMD = -1.94, p = 0.03) in overweight/obese, non-diabetic individuals. The use of SGLT-2i is more effective than other interventions in terms of weight loss ≥ 5% (RR = 2.04, p < 0.001), but not in terms of weight loss ≥ 10% (RR = 1.83, p = 0.22). In addition, there were no significant changes in other metabolic parameters, like fasting plasma glucose (FPG), lipids, blood pressure, etc. SGLT-2i increased the risk of infections in urinary tract (RR = 1.91, p = 0.009) and reproductive system (RR = 4.09, p < 0.001). CONCLUSIONS: SGLT-2i is a promising candidate to reduce weight and waist circumference to a limited extent in overweight/obese, nondiabetic individuals. Generally, it is safe and effective. However, it potentially increased the risk of urogenital infections, which cannot be ignored.

Comparing Hypofractionated With Conventional Fractionated Radiotherapy After Breast-Conserving Surgery for Early Breast Cancer: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The purpose of this meta-analysis was to compare the safety and efficacy between hypofractionated and conventional fractionation radiotherapy in patients with early-stage breast cancer after breast-conserving surgery. METHODS: We conducted a comprehensive search of PubMed, Embase, Web of Science, and the Cochrane Library to identify relevant randomized controlled trials (RCTs) published before February 2021. At the same time, the hazard ratio (HR), risk ratio (RR), and 95% confidence interval (CI) were calculated to evaluate local recurrence (LR), relapse-free survival (RFS), overall survival (OS), adverse events, and cosmetic outcomes. RESULTS: A total of 14 articles were included in this meta-analysis. Four thousand eight hundred and sixty-nine patients were randomly assigned to the control group to receive conventional radiotherapy (CFRT); 6,072 patients were randomly assigned to the experimental group and treated with hypofractionated radiotherapy (HFRT). The results showed that there was no statistical difference between HFRT and CFRT in LR (HR = 0.99, 95%CI = 0.97-1.02, p = 0.476), RFS (HR = 0.99, 95%CI = 0.97-1.02, p = 0.485), OS (HR = 1.00, 95%CI = 0.97-1.03, p = 0.879), and cosmetic outcomes (RR = 1.03, 95%CI = 0.95-1.12, p = 0.53). In addition, HFRT showed fewer severe adverse reactions such as acute skin toxicity, induration, breast atrophy, and pain. CONCLUSION: Our results suggest that there is no statistical difference between HFRT and CFRT in terms of LR, RFS, OS, and cosmetic outcomes. HFRT reduces the risk of developing toxicity reactions compared to CFRT. HFRT may be a better option for patients with early breast cancer after breast-conserving surgery.

Comparison of Minimally Invasive Versus Abdominal Radical Hysterectomy for Early-Stage Cervical Cancer: An Updated Meta-Analysis.

BACKGROUND: Although minimally invasive surgery (MIS) was commonly used to treat patients with early-stage cervical cancer, its efficacy remained controversial. METHODS: We systematically searched PubMed, Web of Science, and Cochrane Library databases until March 2021 to compare the prognosis of early-stage cervical cancer patients who underwent MIS (laparoscopic or robot-assisted radical hysterectomy) or ARH. The primary outcomes included rates of 3- and 5-year disease-free survival (DFS) and overall survival (OS). The study protocol was registered in PROSPERO: CRD42021258116. RESULTS: This meta-analysis included 48 studies involving 23346 patients (11220, MIS group; 12126, ARH group). The MIS group had a poorer medium-term (3-year) DFS (HR=1.08, 95% CI: 1.01-1.16, p=0.031) than the ARH group, without significant difference in medium-term OS as well as long-term (5-year) DFS and OS. Subgroup analysis of 3-year prognosis revealed that although patients in Western countries who underwent MIS had shorter DFS than those who underwent ARH (HR=1.10, p=0.024), no difference was observed in DFS among those in Asian countries. Moreover, MIS was linked to poorer 3-year DFS in patients with stage I cervical cancer (HR=1.07, p=0.020). Notably, subgroup analysis of 5-year prognosis revealed that patients with tumor size ≥2 cm undergoing MIS exhibited a shorter DFS than those who underwent ARH (HR=1.65, p=0.041). CONCLUSION: Patients with early-stage cervical cancer undergoing MIS may have a poorer prognosis than those undergoing ARH. Therefore, applying MIS in early-stage cervical cancer patients should be conducted with caution. SYSTEMATIC REVIEW REGISTRATION: The study protocol was registered in PROSPERO: CRD42021258116.

SGLT-2i and Risk of Malignancy in Type 2 Diabetes: A Meta-Analysis of Randomized Controlled Trials.

Background: Currently, the association between sodium-glucose cotransporter 2 inhibitor (SGLT-2i) and malignancy risk has yet to be fully elucidated. This meta-analysis aimed to determine the relationship between SGLT-2i and malignancy risk in type 2 diabetes (T2D) patients. Methods: We searched PubMed, ScienceDirect, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science to identify randomized controlled trials (RCTs) published up to August 2020 related to T2D patients treated with SGLT-2i vs. placebo or other hypoglycemic agents. The meta-analysis's primary outcome was malignancies' incidence, and the results were evaluated using risk ratio (RR) and 95% confidence interval (CI). Results: We reviewed 76 articles (77 RCTs), comprising 45,162 and 43,811 patients in SGLT-2i and control groups, respectively. Compared with the control group, SGLT-2i had no significant association with augmented overall malignancy risk in T2D patients (RR = 1.05, 95% CI = 0.97-1.14, P = 0.20), but ertugliflozin may upsurge the risk (RR = 1.80, 95% CI = 1.02-3.17, P = 0.04). Compared with active hypoglycemic agents, dapagliflozin may increase (RR = 2.71, 95% CI = 1.46-6.43, P = 0.02) and empagliflozin may decrease (RR = 0.67, 95% CI = 0.45-0.98, P = 0.04) the malignancy risk. Compared with placebo, empagliflozin may exhibit risk increase (RR = 1.25, 95% CI = 1.05-1.49, P = 0.01), primarily in digestive system (RR = 1.48, 95% CI = 0.99-2.21, P = 0.05). Conclusions: Our results proposed that in diverse comparisons, ertugliflozin and dapagliflozin seemed to increase the malignancy risk in T2D patients. Empagliflozin may cause malignancy risk reduction compared with active hypoglycemic agents but increase overall risk primarily in the digestive system compared with placebo. In short, the relationship between SGLT-2i and malignancy in T2D patients remains unclear.

Neoadjuvant chemotherapy increases the 5-year overall survival of patients with resectable cervical cancer: A systematic review and meta-analysis.

Cervical cancer is a global health challenge in women. Neoadjuvant chemotherapy (NACT) is a recent prospect for alternative cervical cancer treatments. This study investigated the efficacy of NACT against resectable cervical cancer based on the medium and long-term survival of patients with the disease. We searched through PubMed, Web of Science, EBSCO and Cochrane Library for relevant reports published by June 2020. The primary outcomes were 3-year and 5-year progression-free survival (PFS) and overall survival (OS) of patients with resectable cervical cancer. Overall, 22 publications encompassing 5627 patients fulfilled the inclusion criteria. We found NACT not to affect both 3-year PFS and OS as well as 5-year PFS of patients with resectable cervical cancer. However, NACT significantly improves the 5-year OS of patients with resectable cervical cancer (HR = 0.83, 95% CI: 0.73-0.94, p = 0.013). Subgroup analysis (RCTs, non-RCTs, NACT + surgery + AT vs. surgery + AT, NACT + surgery + AT vs. CCRT/RT/CRT) further revealed NACT had no significant effect on 5-year PFS of patients with resectable cervical cancer, converse to the 5-year OS subgroup analysis, which validated the beneficial effect of NACT in patients with resectable cervical cancer. In addition, the effect of NACT was most significant in the non-RCTs subgroup (p = 0.012). NACT may improve the long-term prognosis of patients with resectable cervical cancer. However, further large-scale multicenter studies are needed to validate this finding.