Comparing the efficacy of dexamethasone implant and anti-VEGF for the treatment of macular edema: A systematic review and meta-analysis.

OBJECTIVES: To evaluate the clinical efficacy of dexamethasone (DEX) implant, for the treatment of macular edema (ME) caused by retinal vein occlusion (RVO) and diabetic retinopathy (DR) through a systematic review and meta-analysis. METHODS: The PubMed, Embase and Cochrane Library databases were comprehensively searched from inception to November 21, 2022, for studies evaluating the clinical efficacy of DEX implant for patients with retinal vein occlusion macular edema (RVO-ME) or diabetic macular edema (DME). Randomized controlled trials (RCTs) published in English were considered eligible. The Cochrane Collaboration tool was applied to assess the risk of bias in each study. Effect estimates with 95% confidence intervals (CIs) were pooled using the random effects model. We also conducted subgroup analyses to explore the sources of heterogeneity and the stability of the results. RESULTS: This meta-analysis included 8 RCTs (RVO-ME [n = 2] and DME [n = 6]) assessing a total of 336 eyes. Compared with anti-VEGF therapy, DEX implant treatment achieved superior outcomes in terms of best corrected visual acuity (BCVA) (mean difference [MD] = -3.68 ([95% CI, -6.11 to -1.25], P = 0.003), and no heterogeneity was observed (P = 0.43, I2 = 0%). DEX implant treatment also significantly reduced central macular thickness (CMT) compared with anti-VEGF treatment (MD = -31.32 [95% CI, -57.92 to -4.72], P = 0.02), and there was a high level of heterogeneity between trials (P = 0.04, I2 = 54%). In terms of severe adverse events, DEX implant treatment had a higher risk of elevated intraocular pressure than anti-VEGF therapy (RR = 6.98; 95% CI: 2.16 to 22.50; P = 0.001), and there was no significant difference in cataract progression between the two groups (RR = 1.83; 95% CI: 0.63 to 5.27, P = 0.31). CONCLUSIONS: Compared with anti-VEGF therapy, DEX implant treatment is more effective in improving BCVA and reducing ME. Additionally, DEX implant treatment has a higher risk of elevated intraocular pressure. Due to the small number of studies and the short follow-up period, the results should be interpreted with caution. The long-term effects of the two treatments need to be further determined. TRIAL REGISTRATION: Prospero Registration Number CRD42021243185.

Impact of hormone replacement therapy on all-cause and cancer-specific mortality in colorectal cancer: A systematic review and dose‒response meta-analysis of observational studies.

OBJECTIVE: The effect of hormone replacement therapy (HRT) on colorectal cancer (CRC) mortality and all-cause mortality remains unclear. We conducted a systematic review and dose-response meta-analysis to determine the effects of HRT on CRC mortality and all-cause mortality. METHODS: We searched the electronic databases of PubMed, Embase, and The Cochrane Library for all relevant studies published until January 2024 to investigate the effects of HRT exposure on survival rates for patients with CRC. Two reviewers independently extracted individual study data and evaluated the risk of bias between the studies using the Newcastle‒Ottawa Scale. We performed a two-stage random-effects dose-response meta-analysis to examine a possible nonlinear relationship between the year of HRT use and CRC mortality. RESULTS: Ten cohort studies with 480,628 individuals were included. HRT was inversely associated with the risk of CRC mortality (hazard ratios (HR) = 0.77, 95% CI (0.68, 0.87), I2 = 69.5%, p < 0.05). The pooled results of seven cohort studies revealed a significant association between HRT and the risk of all-cause mortality (HR = 0.71, 95% CI (0.54, 0.92), I2 = 89.6%, p < 0.05). A linear dose-response analysis (p for nonlinearity = 0.34) showed a 3% decrease in the risk of CRC for each additional year of HRT use; this decrease was significant (HR = 0.97, 95% CI (0.94, 0.99), p < 0.05). An additional linear (p for nonlinearity = 0.88) dose-response analysis showed a nonsignificant decrease in the risk of all-cause mortality for each additional year of HRT use. CONCLUSIONS: This study suggests that the use of HRT is inversely associated with all-cause and colorectal cancer mortality, thus causing a significant decrease in mortality rates over time. More studies are warranted to confirm this association.

Risk factors of postoperative delirium following spine surgery: A meta-analysis of 50 cohort studies with 1.1 million participants.

Objectives: Postoperative delirium (POD) is considered to be a common complication of spine surgery. Although many studies have reported the risk factors associated with POD, the results remain unclear. Therefore, we performed a meta-analysis to identify risk factors for POD among patients following spinal surgery. Methods: We systematically searched the PubMed, Embase and the Cochrane Library for relevant articles published from 2006 to February 1, 2023 that reported risk factors associated with the incidence of POD among patients undergoing spinal surgery. The Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines were followed, and random effects models were used to estimate pooled odds ratio (OR) estimates with 95 % confidence intervals (CIs) for each factor. The evidence from observational studies was classified according to Egger's P value, total sample size, and heterogeneity between studies. Results: Of 11,329 citations screened, 50 cohort studies involving 1,182,719 participants met the inclusion criteria. High-quality evidence indicated that POD was associated with hypertension, diabetes mellitus, cardiovascular disease, pulmonary disease, older age (>65 years), patients experiencing substance use disorder (take drug ≥1 month), cerebrovascular disease, kidney disease, neurological disorder, parkinsonism, cervical surgery, surgical site infection, postoperative fever, postoperative urinary tract infection, and admission to the intensive care unit (ICU). Moderate-quality evidence indicated that POD was associated with depression, American Society of Anesthesiologists (ASA) fitness grade (>II), blood transfusion, abnormal potassium, electrolyte disorder, length of stay, inability to ambulate and intravenous fluid volume. Conclusions: Conspicuous risk factors for POD were mainly patient- and surgery-related. These findings help clinicians identify high-risk patients with POD following spinal surgery and recognize the importance of early intervention.

Value of ctDNA methylation biomarkers in diagnosis of colorectal tumors.

Tweetable abstract DNA methylation alterations have been identified as promising biological markers for early-stage colorectal cancer detection. Here, the authors highlight some recent advances in DNA methylation and its role in the early diagnosis and overall disease course management of colorectal tumors. New insights into DNA methylation biomarkers for colorectal cancer early diagnosis and management are discussed.

Risk factors of epidural hematoma in patients undergoing spinal surgery: a meta-analysis of 29 cohort studies.

OBJECTIVE: The authors conducted this meta-analysis to identify risk factors for spinal epidural haematoma (SEH) among patients following spinal surgery. METHODS: The authors systematically searched Pub: Med, Embase, and the Cochrane Library for articles that reported risk factors associated with the development of SEH in patients undergoing spinal surgery from inception to 2 July 2022. The pooled odds ratio (OR) was estimated using a random-effects model for each investigated factor. The evidence of observational studies was classified as high quality (Class I), moderate quality (Class II or III) and low quality (Class IV) based on sample size, Egger's P value and between-study heterogeneity. In addition, subgroup analyses stratified by study baseline characteristics and leave-one-out sensitivity analyses were performed to explore the potential sources of heterogeneity and the stability of the results. RESULTS: Of 21 791 articles screened, 29 unique cohort studies comprising 150 252 patients were included in the data synthesis. Studies with high-quality evidence showed that older patients (≥60 years) (OR, 1.35; 95% CI, 1.03-1.77) were at higher risk for SEH. Studies with moderate-quality evidence suggested that patients with a BMI greater than or equal to 25 kg/m² (OR, 1.39; 95% CI, 1.10-1.76), hypertension (OR, 1.67; 95% CI, 1.28-2.17), and diabetes (OR, 1.25; 95% CI, 1.01-1.55) and those undergoing revision surgery (OR, 1.92; 95% CI, 1.15-3.25) and multilevel procedures (OR, 5.20; 95% CI, 2.89-9.37) were at higher risk for SEH. Meta-analysis revealed no association between tobacco use, operative time, anticoagulant use or American Society of Anesthesiologists (ASA) classification and SEH. CONCLUSIONS: Obvious risk factors for SEH include four patient-related risk factors, including older age, obesity, hypertension and diabetes, and two surgery-related risk factors, including revision surgery and multilevel procedures. These findings, however, must be interpreted with caution because most of these risk factors had small effect sizes. Nonetheless, they may help clinicians identify high-risk patients to improve prognosis.

Changing trends, clinicopathological characteristics, surgical treatment patterns, and prognosis of schistosomiasis-associated versus non-schistosomiasis-associated colorectal cancer: a large retrospective cohort study of 31 153 cases in Shanghai, China (2001-2021).

BACKGROUND: With the elimination of schistosomiasis in China, its role in the pathogenesis of colorectal cancer (CRC) has decreased. However, the trends, clinicopathological features, surgical treatment patterns, and prognosis of schistosomiasis-associated CRC (SACRC) versus non-schistosomiasis-associated CRC (NSACRC) in China remain unclear. MATERIALS AND METHODS: The percentage trend of SACRC in CRC patients in China was analyzed using data retrieved from the Pathology Registry of Changhai Hospital (2001-2021). Clinicopathological characteristics, surgical treatment patterns, and prognosis-related parameters were compared between the two groups. Multivariate Cox regression analyses were performed for disease-free survival (DFS) and overall survival (OS). RESULTS: A total of 31 153 CRC cases were included, with 823 (2.6%) cases of SACRC and 30 330 (97.4%) cases of NSACRC. The average percentage of SACRC cases has decreased continuously from 3.8 to 1.7% (from 2001 to 2021). Compared with the NSACRC group, the SACRC group had more men, older age at diagnosis, lower BMI, fewer symptoms; higher rates of rectal cancer, comorbidities, KRAS mutation, multiple primary CRC and concomitant polyps; less lymph node metastasis, distant metastasis, vascular invasion, and tumor budding; less preoperative radiotherapy and preoperative chemotherapy; and more positive resection margins and postoperative targeted therapy. There were no significant differences between the two groups regarding laparoscopic surgery, palliative resection, extended radical resection, or ostomy. Moreover, the SACRC group had adverse DFS and similar OS compared with the NSACRC group. In multivariate analyses, schistosomiasis was not an independent predictor of DFS or OS. CONCLUSION: The percentage of SACRC in CRC (2.6%) in our hospital was very low, and it decreased continuously over the last two decades, indicating that schistosomiasis is no longer an important risk factor for CRC in Shanghai, China. Patients with SACRC have distinct clinicopathological, molecular, and treatment-related features and survival rates similar to those with NSACRC.

Comparison of efficacy and tolerability of adjuvant therapy for resected high-risk stage III-IV cutaneous melanoma: a systemic review and Bayesian network meta-analysis.

Background: Although immune checkpoint inhibitors (ICIs) and targeted therapies have been widely used as adjuvant treatment for resected melanoma, the optimal therapy remains controversial. Therefore, we conducted this updated network meta-analysis (NMA) to assess the efficacy and tolerability of adjuvant therapies for cutaneous melanoma. Methods: PubMed, Embase, Cochrane library, and Web of Science were systematically searched for relevant literatures published in the last 30 years. Disease-free survival (DFS), overall survival (OS), and serious adverse events were considered as the efficacy and tolerability outcomes. Results: In all, 27 randomized controlled trials (RCTs) including 16,709 stage III-IV melanoma patients were enrolled in this NMA. For BRAF wild-type melanoma, our analysis showed that both nivolumab and pembrolizumab demonstrated significantly better DFS and tolerability than ipilimumab (10 mg/kg). Nivolumab, pembrolizumab, ipilimumab (3 mg/kg), and ipilimumab (10 mg/kg) all appeared to be effective in prolonging OS, but no therapy demonstrated significantly better OS than ipilimumab (10 mg/kg). Nivolumab + ipilimumab showed the best DFS, but did not appear to be effective in improving OS and ranked only seventh in tolerability. Vaccines and granulocyte-macrophage colony-stimulating factor therapies were well tolerated, but all failed to improve the DFS or OS in stage III melanoma patients. In terms of BRAF mutation-positive melanoma, ICIs (nivolumab + ipilimumab, nivolumab, pembrolizumab, ipilimumab; 10 mg/kg) exhibited comparable efficacy to dabrafenib + trametinib, and all these therapies showed significantly better DFS than placebo. Conclusion: Considering efficacy and tolerability, nivolumab and pembrolizumab seem to be preferable adjuvant therapies for patients with stage III-IV melanoma. For BRAF mutation-positive patients, more RCTs are still required to determine which is better between ICIs and targeted therapy.

Surgical laser therapy for cryptoglandular anal fistula: Protocol of a systematic review and meta-analysis.

INTRODUCTION: Anal fistula is the natural evolution of perianal abscess and one of the most common perianal diseases for adults. For complex fistula, it is still very challenging for anorectal surgeons to manage. With the introduction of laser technique in surgery, it is becoming more and more widely used for the treatment of cryptoglandular anal fistula. During the past decade, numerous studies have reported the clinical effectiveness and postoperative outcomes of different forms of laser treatment for anal fistula. However, as these studies were varied in terms of baseline characteristics, the evidence for the true clinical effectiveness of laser treatment for anal fistula need further critical appraisal. Therefore, the purpose of this study is to evaluate the outcomes of surgical laser therapy for cryptoglandular anal fistula stratified by laser type and Parks' classification through a synthesis of quantitative and qualitative evidence. METHODS AND ANALYSIS: This study will be carried out with adherence to the Cochrane Handbook. We will search PubMed, Cochrane Library, and Embase until June, 2022 to identify all relevant interventional and observational studies examining the effects of laser therapy on the clinical outcomes for cryptoglandular anal fistula. Data extraction from eligible studies will be performed independently by two unblinded authors using standardized extraction forms. Risk of bias assessment for each study will be conducted using Cochrane tool for randomized controlled trials (RCTs) and the Newcastle-Ottawa scale (NOS) tool for observational studies. The DerSimonian-Laird random-effects model will be used to calculate the pooled estimates. Heterogeneity will be examined by subgroup analysis stratified by laser type and Parks' classification and other study characteristics. Potential publication bias will be assessed by funnel plot symmetrical and Egger's regression tests. CONCLUSIONS: The synthesis of quantitative and qualitative evidence of this systemic review will yield updated and comprehensive evidence of laser treatment on specific outcomes, which can provide anorectal surgeons with high level evidence-based recommendations to improve patient care and clinical outcomes. OSF registration number: DOI 10.17605/OSF.IO/36ADW.

Effect of Anterograde Lavage via Temporary Loop Ileostoma on the Recovery of Bowel Function in Patients Receiving Stoma Closure: A Retrospective Cohort Study.

BACKGROUND: The effect of anterograde lavage in patients with rectal cancer who underwent anterior resection and plan to receive stoma closure is unclear. OBJECTIVE: This study aimed to investigate the effect of anterograde lavage on postoperative bowel function recovery in patients who underwent temporary loop ileostomy and stoma closure. DESIGN: This was a hospital-based retrospective cohort study. SETTINGS: This study was conducted at a tertiary referral center. PATIENTS: All consecutive patients who underwent anterior resection for rectal cancer and were planning to receive stoma closure from March through December 2019 were included. INTERVENTIONS: The enrolled patients were divided into 2 groups according to whether they received anterograde lavage before stoma closure. MAIN OUTCOME MEASURES: Short-term functional outcomes, including time to first passing of flatus, first defecation time, and recovery time to first meal, were compared between the groups. Secondary outcomes included length of hospital stay, total cost of hospitalization, and postoperative complications. RESULTS: A total of 222 eligible participants were included in the analysis, including 114 in the lavage group and 108 in the nonlavage group. No statistically significant differences were found in age, sex ratio, or distance between the anastomotic line and dentate line. In the lavage group, patients' time to first passing of flatus (38 vs 42 h; p = 0.006), first defecation time (42 vs 48 h; p < 0.001), recovery time to first meal (48 vs 55.5 h; p < 0.001), and length of hospital stay (5 vs 7 d; p < 0.001) were significantly shorter than those in the nonlavage group, and the total cost of hospitalization was significantly lower than that of the nonlavage group (25,000 vs 28,000 RMB; p < 0.001). No significant difference was found in the incidence of postoperative complications between the 2 groups (p = 0.067). LIMITATIONS: This study is limited by its relatively small sample size and retrospective design with single-center participants. CONCLUSIONS: Anterograde lavage before stoma closure is safe and noninvasive. For patients receiving anterior resection and planning to have stoma closure, this procedure can potentially help recover bowel function more rapidly. See Video Abstract at http://links.lww.com/DCR/C51. EFECTO DEL LAVADO ANTERGRADO MEDIANTE ILEOSTOMA TEMPORAL EN ASA SOBRE LA RECUPERACIN DE LA FUNCIN INTESTINAL EN PACIENTES QUE RECIBEN CIERRE DE ESTOMA UN ESTUDIO DE COHORTE RETROSPECTIVO: ANTECEDENTES:No está claro el efecto del lavado anterógrado en pacientes con cáncer de recto con resección anterior que planean recibir el cierre del estoma.OBJETIVO:Investigar el efecto del lavado anterógrado en la recuperación de la función intestinal posoperatoria en pacientes que se sometieron a ileostomía en asa temporal y cierre de estoma.DISEÑO:Estudio de cohorte retrospectivo basado en el hospital.AJUSTES:Centro de referencia terciario.PACIENTES:Todos los pacientes que se sometieron a una resección anterior por cáncer de recto y que planeaban recibir el cierre del estoma desde marzo hasta diciembre de 2019.INTERVENCIONES:Los pacientes inscritos se dividieron en dos grupos según si recibieron lavado anterógrado antes del cierre del estoma.PRINCIPALES MEDIDAS DE RESULTADO:Los resultados funcionales a corto plazo, incluido el tiempo de la primera evacuación de flatos, tiempo de la primera defecación y tiempo de recuperación hasta la primera comida, se compararon entre los grupos. Resultados secundarios incluyeron duración de la estancia hospitalaria, costo total de la hospitalización y complicaciones posoperatorias.RESULTADOS:Se incluyeron en el análisis un total de 222 participantes elegibles, incluidos 114 en el grupo de lavado y 108 en el grupo de no lavado. No hubo diferencias estadísticamente significativas en la edad, la proporción de sexos o la distancia entre la línea de anastomosis y la línea dentada. En el grupo de lavado, el tiempo de la primera evacuación de flatos de los pacientes (38 vs 42 h; p = 0,006), el tiempo de la primera defecación (42 vs 48 h; p < 0,001), el tiempo de recuperación hasta la primera comida (48 vs 55,5 h; p < 0,001) y la duración de la estancia hospitalaria (5 vs 7 días; p < 0,001) fueron significativamente más cortos que los del grupo de no lavado, y el costo total de la hospitalización fue significativamente menor que el del grupo de no lavado (25000 vs 28000 RMB; p < 0,001). No hubo diferencia significativa en la incidencia de complicaciones postoperatorias entre los dos grupos (p = 0,067).LIMITACIONES:Este estudio está limitado por su tamaño de muestra relativamente pequeño y su diseño retrospectivo con participantes de un solo centro.CONCLUSIONES:El lavado anterógrado antes del cierre del estoma es seguro y no invasivo. Para los pacientes que se someten a una resección anterior y planean cerrar el estoma, este procedimiento puede ayudar potencialmente a recuperar la función intestinal más rápidamente. Consulte Video Resumen en http://links.lww.com/DCR/C51. (Traducción-Dr. Francisco M. Abarca-Rendon).

Scalp Nerve Block, Local Anesthetic Infiltration, and Postoperative Pain After Craniotomy: A Systematic Review and Network Meta-analysis of Randomized Trials.

The most efficacious methods for controlling postoperative pain in craniotomy remain unknown. A systematic review and network meta-analysis were performed to compare the efficacies of different strategies of scalp nerve block (SNB), scalp infiltration (SI), and control in patients undergoing craniotomy. MEDLINE, Embase, and CENTRAL databases were searched for randomized controlled trials. The primary outcome was postoperative 24-hour pain score, and the secondary outcome was opioid consumption within the first 24 hour after surgery. The effect was estimated using the between-group mean difference and ranked using the surface under the cumulative ranking curve (SUCRA) score. Twenty-four randomized trials were identified for inclusion. SNB using ropivacaine reduced postoperative 24-hour pain score when compared with control (mean difference [95% credible interval], -2.04 [-3.13, -0.94]; low quality), and when compared with SI using ropivacaine (-1.77 [-3.04, -0.51]; low quality) or bupivacaine (-1.96 [-3.65, -0.22]; low quality). SNB using ropivacaine was likely the most efficacious method for pain control (SUCRA, 91%), and also reduced opioid consumption within the first postoperative 24 hours as compared with control (mean difference [95% credible interval], -11.91 [-22.42, -1.4]; low quality). SNB using bupivacaine, lidocaine, and epinephrine combined, and SNB using ropivacaine, were likely the most efficacious methods for opioid consumption reduction (SUCRA, 88% and 80%, respectively). In summary, different methods of SNB / SI seem to have different efficacies after craniotomy. SNB using ropivacaine may be superior to other methods for postcraniotomy pain control; however, the overall quality of evidence was low.

Immune checkpoint inhibitors for patients with microsatellite instability-high colorectal cancer: protocol of a pooled analysis of clinical trials.

Introduction: Colorectal cancer (CRC) is the third most common cause of cancer and the second leading cause of cancer-related deaths worldwide. Microsatellite instability-high (MSI-H) is a distinct molecular subtype of CRC that occurs in approximately 15% of all cases. Recently, immune checkpoint inhibitors (ICIs) have emerged as a promising therapeutic approach for patients with MSI-H colorectal cancer, exhibiting higher response rates than standard chemotherapies. To assess the effectiveness and safety of ICIs for the treatment of patients with MSI-H CRC, we propose a comprehensive pooled analysis of clinical trial data. Methods and analysis: A systematic search of multiple electronic databases, including PubMed, EMBASE, Cochrane Library, and Clinicaltrials.gov, will be conducted from their inception until September, 2023 to identify eligible randomized controlled trials (RCTs) and non-randomized studies. Inclusion criteria comprise studies of adult patients with histologically confirmed MSI-H CRC treated with immune checkpoint inhibitors, with a comparison to a control group receiving conventional therapies. Outcomes of interest will be overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and incidence of treatment-related adverse events (AEs). The Cochrane Risk of Bias tool and the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) tool will be employed to evaluate the methodological quality of included studies. A random-effects model using the DerSimonian and Laird method will be applied for pooling the effect estimates, calculating hazard ratios (HRs) or risk ratios (RRs) with their corresponding 95% confidence intervals (CIs). Heterogeneity will be assessed using I² statistics, and subgroup analysis and meta-regression will be performed to explore potential effect modifiers in case of substantial heterogeneity. Publication bias will be evaluated with funnel plots and Egger's test. Sensitivity analysis will be conducted to assess the robustness of the results. Discussion: This meta-analysis will synthesize available evidence from clinical trials on immune checkpoint inhibitors in treating MSI-H colorectal cancer. The findings will offer valuable information about the effectiveness and safety of ICIs in this patient population, contributing to the refinement of clinical guidelines and enhancing the decision-making process for healthcare providers, policy-makers, and patients. The comprehensive analysis of subgroups and sensitivity allows for an in-depth understanding of potential effect modification, providing essential directions for future research. Ethics and dissemination: This study will involve the use of published data; hence, ethical approval is not required. The results of the study will be disseminated through publications in peer-reviewed journals and presentations at relevant conferences. The findings will potentially impact clinical decision-making and contribute to the development of evidence-based treatment recommendations for patients with MSI-H colorectal cancer. Clinical trial registration: Open Science Framework identifier, 10.17605/OSF.IO/ZHJ85.

Risk of fracture following gastric surgery for benign and malignant conditions: A study level pooled analysis of population-based cohort studies.

Background: Metabolic changes may occur following gastric surgery, which has been reported to contribute to bone loss, osteoporosis and even bone fracture. However, the evidence regarding the relationship between gastric surgery for benign and malignant conditions and risk of fracture is controversial. This study was conducted with the aim to evaluate whether gastric surgery is associated with a high risk of fracture. Methods: Major electronic databases were searched from inception through October 2021 for population-based cohort studies investigating the associations between gastric surgery (including bariatric gastric surgeries and surgeries for gastric benign and malignant gastric tumors) and risk of fracture compared with controls. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were derived using the random-effects Mantel-Haenszel model. Multiple subgroup analyses and sensitivity analyses were carried out to test sources of heterogeneity stratified by various study characteristics and the robustness of the results. Results: A total of 14 studies comprising 693134 individuals were identified for analysis. The RR for the risk of fracture in people undergoing gastric surgery was 1.45 [95% confidence interval (CI) 1.23 - 1.72; I2 = 95.8%; P < 0.001] compared with that in control populations, among which the fracture sites of upper limb, spine, lower limb, pelvis and hip showed consistent significant results (all P < 0.05), whereas nonsignificant associations was noted for other fracture sites. Significant associations were also observed for patients having total or subtotal gastrectomy (RR 2.22, 95% CI 1.66 to 3.00), gastric bypass (RR 1.48, 95% CI 1.26 to 1.74), and a similar trend was observed for preserved passage procedures (including sleeve gastrectomy, gastric banding, vertical banded gastroplasty and other procedures that preserved the passage through the duodenum and proximal small bowel, in contrast to gastric bypass), though the difference did not reach statistically significant (RR 1.10, 95% CI 0.95 to 1.26). An evident increased risk in the age range from 40-59 years was observed (40-49 years: RR 1.36, 95% CI 1.19-1.55; 50-59 years: RR 2.48, 95% CI 1.58-3.90). Conclusion: From this large pooled analysis of population-based cohort studies, evidence supports that fracture risk is increased in gastric surgery survivors compared with the control population. Early prevention and effective intervention strategies of bone fracture should be taken from clinicians and health policy makers. Clinical Trial Registration: PROSPERO (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=291394), identifier CRD42021291394.

Obstetric and perinatal outcomes in female survivors of childhood or adolescent cancer: Protocol of a meta-analysis of population-based cohort studies.

INTRODUCTION: Approximately 80% of children, adolescents and young adults (CAYA) cancer patients are expected to fully recover and survive for five years or more. The reproductive health is a particular area of their concern. Evidence demonstrates that previous therapeutic treatments for cancer and comorbidities may have harmful effects on female fertility and delivery outcomes, which will significantly affect patient quality of life. However, these reports are heterogeneous. Therefore, the purpose of this study is to provide the up-to-date evidence on the risk of adverse obstetric and perinatal outcomes in female survivors of childhood or adolescent cancer. METHODS AND ANALYSIS: This meta-analysis will be carried out and reported with adherence to the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines and the Cochrane Handbook. We will search online databases including PubMed, Cochrane Library, and Embase from inception to August, 2022 to identify all relevant cohort studies examining the relationship between cancer and subsequent obstetric and perinatal outcomes. Data extraction from eligible studies will be conducted and crosschecked separately by two investigators using pre-tested standardized data extraction forms. Discrepancies will be resolved via a third investigator. Methodological quality assessment for each study will be conducted using the Newcastle-Ottawa scale (NOS) tool. We will apply the DerSimonian-Laird random-effects model to calculate the pooled estimates. Further sources of heterogeneity will be explored by performing subgroup analysis based on multiple study characteristics. Potential publication bias will be assessed by inspection of a funnel plot, Begg's and Egger's regression tests of funnel plot asymmetry. ETHICS AND DISSEMINATION: Ethical approval will not be required as all data used for this pooled analysis will be obtained from published cohort studies. The results of this study will be disseminated in a peer-reviewed journal and conference presentation. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/K6QBG.

A novel genomic instability-derived lncRNA signature to predict prognosis and immune characteristics of pancreatic ductal adenocarcinoma.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignant tumor of the digestive system. Its grim prognosis is mainly attributed to the lack of means for early diagnosis and poor response to treatments. Genomic instability is shown to be an important cancer feature and prognostic factor, and its pattern and extent may be associated with poor treatment outcomes in PDAC. Recently, it has been reported that long non-coding RNAs (lncRNAs) play a key role in maintaining genomic instability. However, the identification and clinical significance of genomic instability-related lncRNAs in PDAC have not been fully elucidated. Methods: Genomic instability-derived lncRNA signature (GILncSig) was constructed based on the results of multiple regression analysis combined with genomic instability-associated lncRNAs and its predictive power was verified by the Kaplan-Meier method. And real-time quantitative polymerase chain reaction (qRT-PCR) was used for simple validation in human cancers and their adjacent non-cancerous tissues. In addition, the correlation between GILncSig and tumor microenvironment (TME) and epithelial-mesenchymal transition (EMT) was investigated by Pearson correlation analysis. Results: The computational framework identified 206 lncRNAs associated with genomic instability in PDAC and was subsequently used to construct a genome instability-derived five lncRNA-based gene signature. Afterwards, we successfully validated its prognostic capacity in The Cancer Genome Atlas (TCGA) cohort. In addition, via careful examination of the transcriptome expression profile of PDAC patients, we discovered that GILncSig is associated with EMT and an adaptive immunity deficient immune profile within TME. Conclusions: Our study established a genomic instability-associated lncRNAs-derived model (GILncSig) for prognosis prediction in patients with PDAC, and revealed the potential functional regulatory role of GILncSig.

Efficacy and safety of taxanes combined with chemotherapy drugs in advanced triple negative breast cancer: A meta-analysis of 26 randomized controlled trials.

Background: Researchers have demonstrated that the combined use of taxanes and chemotherapy drugs, especially paclitaxel-based treatment, appeared to clinically benefit on advanced triple negative breast cancer (TNBC). This meta-analysis aims to obtain the existent evidence on efficacy and safety for taxanes-based combination therapy to treat advanced TNBC. Methods: From 1991 to June 2022, seven databases (PubMed, Web of Science, Cochrane Library, Embase VIP, Wanfang, and CNKI databases) were comprehensively searched with no restricted language and region. The included randomized controlled trials (RCTs) compared taxanes-based combination therapy versus taxanes or other chemotherapy drugs. Statistical analysis was conducted using random-effect model, and the quality of RCTs was assessed using the tool of Cochrane Collaboration risk of bias. Results: Twenty-six RCTs with a total of 8,236 advanced TNBC patients were included. Compared with taxanes monotherapy, taxanes-based combination therapy significantly prolonged progression-free survival (HR=0.79, 95%CI=0.74-0.83, I2= 0.0%, p=0.000) and overall survival (HR=0.88, 95%CI=0.82-0.94, I2= 9.3%, p=0.000) and increased the risk of vomiting (RR=1.26, 95%CI=1.07-1.48) and diarrhea (RR=1.82, 95%CI=1.22-2.70, I2= 90.3%, p=0.003). No statistical differences were observed in complete response rate (CRR), objective response rate (ORR), disease control rate (DCR), and progressive disease (PD) indexes (CRR: RR=1.38, 95%CI=0.96-1.99; ORR: RR=1.20, 95%CI=0.73-1.98; DCR: RR=1.09, 95%CI=1.00-1.19; PD: RR=0.70, 95%CI=0.47-1.04). Compared with other chemotherapy drugs, taxanes plus other chemotherapy drugs significantly reduced the incidence of vomiting (RR=0.60, 95%CI=0.44-0.84, I2= 12.3%, p=0.002) and neutropenia (RR=0.58, 95%CI=0.35-0.96, I2= 73.0%, p=0.036) during the treatment period. Conclusions: Taxanes-based combination therapy is evidently effective and well-tolerated in advanced TNBC, indicating that it might be a recommended option for treating advanced TNBC patients to some extent. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022337802.