Prognostic impact of the IASLC grading system of lung adenocarcinoma: a systematic review and meta-analysis.

AIMS: Tumour grading is an essential part of the pathologic assessment that promotes patient management. The International Association for the Study of Lung Cancer (IASLC) proposed a grading system for non-mucinous lung adenocarcinoma in 2020. We aimed to validate the prognostic impact of this novel grading system on overall survival (OS) and recurrence-free survival (RFS) based on literature data. METHODS AND RESULTS: The review protocol was registered in PROSPERO (CRD42023396059). We aimed to identify randomized or non-randomized controlled trials published after 2020 comparing different IASLC grade categories in Medline, Embase, and CENTRAL. Hazard ratios (HRs) with 95% confidence intervals (CIs) of OS and RFS were pooled and the Quality In Prognosis Studies (QUIPS) tool was used to assess the risk of bias in the included studies. Ten articles were eligible for this review. Regarding OS estimates, grade 1 lung adenocarcinomas were better than grade 3 both in univariate and multivariate analyses (HROSuni = 0.19, 95% CI: 0.05-0.66, p = 0.009; HROSmulti = 0.21, 95% CI: 0.12-0.38, p < 0.001). Regarding RFS estimates, grade 3 adenocarcinomas had a worse prognosis than grade 1 in multivariate analysis (HRRFSmulti: 0.22, 95% CI: 0.14-0.35, p < 0.001). CONCLUSION: The literature data and the result of our meta-analysis demonstrate the prognostic relevance of the IASLC grading system. This supports the inclusion of this prognostic parameter in daily routine worldwide.

Addition of epidermal growth factor receptor inhibitors to standard chemotherapy increases survival of advanced head and neck squamous cell carcinoma patients: A systematic review and meta-analysis.

Head and neck squamous cell carcinoma (HNSCC) is among the common tumors associated with high mortality. The aim of our meta-analysis was to determine how additional anti-epidermal growth factor receptor (EGFR) therapy to standard chemotherapy affects the progression-free (PFS) and overall survival (OS) of the patients, besides the most common side effects. We used CENTRAL, MEDLINE, and Embase databases until October 26, 2020, and included 13 eligible randomized controlled trials in our systematic research. The pooled hazard ratios (HR) for the main outcomes from the original data were estimated and for the other dichotomous outcomes, odds ratios (ORs) with their 95% confidence intervals (CI) were calculated. Addition of EGFR inhibitors to conventional chemotherapy significantly decreased the death and disease progression (for PFS HR: 0.68, 95% CI: 0.55-0.81, I2  = 65.5%, p = 0.005) and mortality (for OS HR: 0.83, 95% CI: 0.72-0.94, I2  = 42.3%, p = 0.076). In the EGFR inhibitor group, we revealed an increased chance of the over Grade 3 skin rashes (OR: 4.86; 95% CI: 1.52-15.49, I2  = 2.3%, p = 0.407), and all Grade skin rashes (OR: 18.32, 95% CI: 8.07-41.60, I2  = 56.6%, p = 0.032). Despite their unwanted dermatological side effects, the addition of EGFR inhibitors is recommended to be included in advanced HNSCC therapy.

Network meta-analysis of randomized controlled trials on esophagectomies in esophageal cancer: The superiority of minimally invasive surgery.

BACKGROUND: Previous meta-analyses, with many limitations, have described the beneficial nature of minimal invasive procedures. AIM: To compare all modalities of esophagectomies to each other from the results of randomized controlled trials (RCTs) in a network meta-analysis (NMA). METHODS: We conducted a systematic search of the MEDLINE, EMBASE, Reference Citation Analysis (https://www.referencecitationanalysis.com/) and CENTRAL databases to identify RCTs according to the following population, intervention, control, outcome (commonly known as PICO): P: Patients with resectable esophageal cancer; I/C: Transthoracic, transhiatal, minimally invasive (thoracolaparoscopic), hybrid, and robot-assisted esophagectomy; O: Survival, total adverse events, adverse events in subgroups, length of hospital stay, and blood loss. We used the Bayesian approach and the random effects model. We presented the geometry of the network, results with probabilistic statements, estimated intervention effects and their 95% confidence interval (CI), and the surface under the cumulative ranking curve to rank the interventions. RESULTS: We included 11 studies in our analysis. We found a significant difference in postoperative pulmonary infection, which favored the minimally invasive intervention compared to transthoracic surgery (risk ratio 0.49; 95%CI: 0.23 to 0.99). The operation time was significantly shorter for the transhiatal approach compared to transthoracic surgery (mean difference -85 min; 95%CI: -150 to -29), hybrid intervention (mean difference -98 min; 95%CI: -190 to -9.4), minimally invasive technique (mean difference -130 min; 95%CI: -210 to -50), and robot-assisted esophagectomy (mean difference -150 min; 95%CI: -240 to -53). Other comparisons did not yield significant differences. CONCLUSION: Based on our results, the implication of minimally invasive esophagectomy should be favored.

90Y-ibritumomab Tiuxetan in B-cell Non-Hodgkin Lymphomas: Real-world Data From the United Arab Emirates.

Purpose: B-cell non-Hodgkin lymphomas (NHLs) are significant contributors to cancer-related mortality. In this single-arm, retrospective cohort study, we aimed to examine the outcomes of a radioimmunotherapeutic modality, 90Y-labeled ibritumomab tiuxetan (90YIT) in B-cell NHLs. Methods and Materials: We conducted this study based on data from the United Arab Emirates lymphoma registry. All patients with NHL subjected to 90YIT were eligible for inclusion. The country of research lacked a national autologous stem cell transplantation (ASCT) center, but many ASCT-eligible patients received 90YIT. We investigated overall survival (OS) and event-free survival (EFS), as well as safety outcomes. Results: Between 2004 and 2008, 54 of 111 patients with B-cell NHL received radioimmunotherapy. The therapy was applied as first-line treatment in 18 cases (33.3%) and second- or later-line treatment in 36 cases (66.7%). All patients were evaluable for response. The first-line group consisted mainly of follicular lymphoma cases, and 3 of 18 patients died (16.7%) during the follow-up (range, 22-67 months). Median OS was not reached. No progression occurred after treatment (median EFS, 36.5 months [Q1-Q3 range, 30.5-44 months]). The second- or later-line group consisted mainly of diffuse large B-cell lymphoma cases, and 3 of 36 patients died (8.3%) during the follow-up (range, 4-68 months). Median OS was not reached. One case of progression was registered (median EFS: 33 months [Q1-Q3 range, 30.5-44 months]). 90YIT had acceptable short- and long-term safety profiles. Conclusions: The findings suggest that patients with NHL may benefit from 90YIT as salvage treatment if ASCT is not available; however, this should be validated in randomized studies.

Adjuvant chemotherapy could improve the survival of pulmonary sarcomatoid carcinoma: A systematic review and meta-analysis.

BACKGROUND: Complete surgical removal is currently considered to be the best treatment option for pulmonary sarcomatoid carcinoma (PSC) especially in early stage operable disease; however, the reported recurrence-free survival is low. Benefits of adjuvant chemotherapy in PSC patients are still controversial, and there is no obvious agreement on the optimal treatment modalities of this disease. Therefore, we aimed to investigate the prognosis in terms of overall survival (OS) in patients with PSC who received adjuvant chemotherapy. METHODS: The review protocol was registered in PROSPERO (CRD42022306084). Patients with PSC who underwent surgical therapy with or without adjuvant chemotherapy were included into the meta-analysis. Hazard ratios (HR) with 95% confidence intervals (CIs) for OS were pooled and ROBINS-I tool was used to assess risk of bias of the included studies. RESULTS: We identified four retrospective cohort studies with 6768 records from MEDLINE, Embase, and CENTRAL databases up to 9th September 2021, and altogether 1835 patients were included to the analysis. The present meta-analysis shows that patients receiving adjuvant chemotherapy had a significantly longer OS than patients who underwent surgical treatment alone (HR = 0.5657, 95%CI: 0.4391-0.7290, p < 0.0001). CONCLUSIONS: Despite the limited information on the chemotherapy regimens in the included studies, patients with PSC may benefit from adjuvant chemotherapy. More publications are required to evaluate and compare efficient adjuvant chemotherapy protocols in PSC cases.

Urodynamics in Early Diagnosis of Diabetic Bladder Dysfunction in Women: A Systematic Review and Meta-Analysis.

BACKGROUND Urodynamics can detect subtle voiding changes before cystopathy symptoms manifest. The aim of the present study was to assess urodynamic changes in diabetic women. MATERIAL AND METHODS A systematic search was performed on 04 November 2021 to identify studies reporting urodynamic parameters in diabetic women. Data were analyzed in a single-arm meta-analysis due to lack of sufficient studies with direct comparisons to healthy women. For data synthesis, a random-effects model with restricted maximum-likelihood estimation was applied. The calculated effect sizes were visualized in forest plots. Statistical heterogeneity was assessed using the I² measure and the χ² test. The risk of bias was assessed using the QUIPS tool. PROSPERO ID: CRD42021256275. RESULTS Out of 1750 records, 10 studies were used in the analysis (n=2342 diabetic women). Pooled event rates showed that mean voided volume was 288.21 mL [95% confidence interval (CI): 217.35-359.06, I²=98%], mean postvoid residual volume was 93.67 mL [95% CI: 31.35-155.99, I²=100%], mean Qmax was 18.80 mL/sec [95% CI: 15.27-22.33, I²=99%], mean PdetQmax is 30.13 cmH2O [95% CI: 25.53-34.73, I²=90%], mean first sensation of bladder filling was 178.66 mL [95% CI: 150.59-206.72, I²=97%], and mean cystometric capacity was 480.41 mL [95% CI: 409.32-551.50, I²=98%] in diabetic women. CONCLUSIONS Pooled results indicate that diabetic women tend to have a smaller voided volume, slower Qmax and PdetQmax, larger postvoid residual, and higher first sensation of bladder filling and cystometric capacity compared to the general female population.

Frailty and Emergency Surgery: Results of a Systematic Review and Meta-Analysis.

Background: Frailty, a "syndrome of loss of reserves," is a decade old concept. Initially it was used mainly in geriatrics but lately its use has been extended into other specialties including surgery. Our main objective was to examine the association between frailty and mortality, between frailty and length of hospital stay (LOS) and frailty and readmission within 30 days in the emergency surgical population. Methods: Studies reporting on frailty in the emergency surgical population were eligible. MEDLINE (via PubMed), EMBASE, Scopus, CENTRAL, and Web of Science were searched with terms related to acute surgery and frail*. We searched for eligible articles without any restrictions on the 2nd of November 2020. Odds ratios (OR) and weighted mean differences (WMD) were calculated with 95% confidence intervals (CI), using a random effect model. Risk of bias assessment was performed according to the recommendations of the Cochrane Collaboration. As the finally selected studies were either prospective or retrospective cohorts, the "Quality In Prognosis Studies" (QUIPS) tool was used. Results: At the end of the selection process 21 eligible studies with total 562.070 participants from 8 countries were included in the qualitative and the quantitative synthesis. Patients living with frailty have higher chance of dying within 30 days after an emergency surgical admission (OR: 1.99; CI: 1.76-2.21; p < 0.001). We found a tendency of increased LOS with frailty in acute surgical patients (WMD: 4.75 days; CI: 1.79-7.71; p = 0.002). Patients living with frailty have increased chance of 30-day readmission after discharge (OR: 1.36; CI: 1.06-1.75; p = 0.015). Conclusions: Although there is good evidence that living with frailty increases the chance of unfavorable outcomes, further research needs to be done to assess the benefits and costs of frailty screening for emergency surgical patients. Systematic Review Registration: The review protocol was registered on the PROSPERO International Prospective Register of Systematic Reviews (CRD42021224689).

Immune response to influenza and pneumococcal vaccines in adults with inflammatory bowel disease: A systematic review and meta-analysis of 1429 patients.

BACKGROUND: Patients with inflammatory bowel disease (IBD) have a high risk for infection. Pneumonia related to influenza and pneumococcal infection is one of the most common infection-related complications in IBD. AIMS: To evaluate the immunogenicity of pneumococcal and influenza vaccination in patients with IBD receiving different treatments. METHODS: We searched four databases for studies evaluating seroprotection and seroconversion rates after influenza or pneumococcal vaccination in IBD on 20th October 2020. In the meta-analysis, odds ratios (OR) were calculated with 95% confidence intervals (CI). RESULTS: We included twelve studies (1429 patients with IBD) in this meta-analysis. The seroconversion rate after pneumococcal vaccination and the seroprotection rate after influenza vaccination were not significantly lower in patients receiving conventional immunosuppressive treatment compared to the non-immunosuppressed patients. Meanwhile, the seroconversion rate following pneumococcal vaccine was significantly lower in patients with anti-TNF mono- or combination therapy (OR = 0.28, CI: 0.15-0.53, and OR = 0.27, CI: 0.15-0.49, respectively). In the analysis of patients with IBD on conventional immunosuppressive monotherapy versus anti-TNF therapy, the seroprotection rate after influenza immunization did not differ between patients receiving either anti-TNF mono-or combination therapy (OR = 1.45, CI: 0.62-3.38 and OR = 0.91, CI: 0.37-2.22, respectively). CONCLUSION: Our data suggest that the immunization against Pneumococcus and influenza is safe and immunogenic despite immunosuppression.

Exosomes as prognostic biomarkers in pancreatic ductal adenocarcinoma-a systematic review and meta-analysis.

Extensive research is focused on the role of liquid biopsy in pancreatic cancer since reliable diagnostic and follow-up biomarkers represent an unmet need for this highly lethal malignancy. We performed a systematic review and meta-analysis on the prognostic value of exosomal biomarkers in pancreatic ductal adenocarcinoma (PDAC). MEDLINE, Embase, Scopus, Web of Science, and CENTRAL were systematically searched on the 18th of January, 2021 for studies reporting on the differences in overall (OS) and progression-free survival (PFS) in PDAC patients with positive vs negative exosomal biomarkers isolated from blood. The random-effects model estimated pooled multivariate-adjusted (AHR) and univariate hazard ratios (UHRs) with 95% confidence intervals (CIs). Eleven studies comprising 634 patients were eligible for meta-analysis. Detection of positive exosomal biomarkers indicated increased risk of mortality (UHR = 2.81, CI:1.31-6,00, I2 = 88.7%, P < 0.001), and progression (UHR = 3.33, CI: 2.33-4.77, I2 = 0, P = 0.879) across various disease stages. Positive exosomal biomarkers identified preoperatively revealed a higher risk of mortality in resectable stages (UHR = 5.55, CI: 3.24-9.49, I2 = 0, P = 0.898). The risk of mortality in unresectable stages was not significantly increased with positive exosomal biomarkers (UHR = 2.51, CI: 0.55-11.43, I2 = 90.3%, P < 0.001). Detectable exosomal micro ribonucleic acids were associated with a decreased OS (UHR = 4.08, CI: 2.16-7.69, I2 = 46.9%, P = 0.152) across various stages. Our results reflect the potential of exosomal biomarkers for prognosis evaluation in PDAC. The associated heterogeneity reflects the variability of study methods and need for their uniformization before transition to clinical use.

Prognostic role of cell-free DNA biomarkers in pancreatic adenocarcinoma: A systematic review and meta-analysis.

This systematic review and meta-analysis evaluated the prognostic role of cell-free DNA (cfDNA) in pancreatic ductal adenocarcinoma (PDAC). Eligible studies reported differences in overall (OS) and progression-free survival (PFS) by cfDNA status. The random effect model yielded the pooled hazard ratios (HRs) and 95 % confidence intervals (CI). Detection of circulant-tumor DNA (ctDNA), KRAS mutations and other cfDNA alterations constitute detectable cfDNA biomarkers. Altogether, 38 studies (3,318 patients) were eligible. Progression-free and overall survival were decreased with detectable ctDNA (HR = 1.92, 95 %CI:(1.29,2.86); HR = 2.25, 95 %CI:(1.73,2.92)) and KRAS mutations (HR = 1.88, CI:1.22,2.92,); HR = 1.52, 95 %CI:(1.22,1.90)) respectively, across various stages. In unresectable cases, ctDNA (HR = 2.50, 95 %CI:(1.94,3.23)), but not KRAS mutations (HR = 1.16, 95 %CI:(0.46,2.94)) signaled risk for progression. Detectable cfDNA biomarkers correlated with worse prognosis in resectable cases and if detected during treatment. In conclusion, cfDNA biomarkers indicate accelerated progression and decreased survival in PDAC. Significance of KRAS mutations detection in unresectable cases is to be determined.

Inflammatory Biomarkers Are Inaccurate Indicators of Bacterial Infection on Admission in Patients With Acute Exacerbation of Chronic Obstructive Pulmonary Disease-A Systematic Review and Diagnostic Accuracy Network Meta-Analysis.

Introduction: The value of inflammatory biomarkers in the diagnosis of bacterial infection induced acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is currently unclear. Our objective was to investigate the diagnostic accuracy of on-admission inflammatory biomarkers in differentiating bacterial origin in AECOPD. Methods: Systematic literature search was performed to include cross-sectional studies on AECOPD patients with microbiological culture results as gold standard, and at least one on-admission inflammatory biomarker determined from serum: C-reactive protein (CRP), procalcitonin (PCT), neutrophil/lymphocyte ratio, eosinophil percentage, CD64index; or sputum: neutrophil elastase, tumor necrosis factor alfa, interleukin-1-beta (IL-1b), interleukin-8, sputum color, as index tests. We ranked index tests by superiority indices in a network meta-analysis and also calculated pooled sensitivity and specificity. Results: Altogether, 21 eligible articles reported data on 2,608 AECOPD patients (44% bacterial). Out of the 14 index tests, sputum IL-1b showed the highest diagnostic performance with a pooled sensitivity of 74% (CI: 26-97%) and specificity of 65% (CI: 19-93%). Pooled sensitivity for CRP and PCT were: 67% (CI: 54-77%) and 54% (CI: 39-69%); specificity 62% (CI: 52-71%) and 71% (CI: 59-79%), respectively. Conclusion: Admission inflammatory biomarkers are inaccurate indicators of bacterial infection in AECOPD. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/#myprospero, identifier: 42020161301.

Six Autoimmune Disorders Are Associated With Increased Incidence of Gastric Cancer: A Systematic Review and Meta-Analysis of Half a Million Patients.

Background: Gastric cancer is one of the most common cancers worldwide, with a high mortality rate. The potential etiological role of autoimmune (AI) disorders has been described in gastric cancer; however, the literature is controversial. This study aims to provide a comprehensive summary of the association between autoimmune disorders and the incidence of gastric cancer. Methods: This study was registered on PROSPERO under registration number CRD42021262875. The systematic literature search was conducted in four scientific databases up to May 17, 2021. Studies that reported standardized incidence rate (SIR) of gastric cancer in autoimmune disorders were eligible. We calculated pooled SIRs with 95% confidence intervals (CIs) in this meta-analysis. Results: We included 43 articles describing 36 AI disorders with data of 499,427 patients from four continents in our systematic review and meta-analysis. Significantly increased incidence of gastric cancer was observed in dermatomyositis (SIR = 3.71; CI: 2.04, 6.75), pernicious anemia (SIR = 3.28; CI: 2.71, 3.96), inflammatory myopathies (SIR = 2.68; CI:1.40; 5.12), systemic lupus erythematosus (SIR = 1.48; CI: 1.09, 2.01), diabetes mellitus type I (SIR = 1.29; CI:1.14, 1,47), and Graves' disease (SIR = 1.28; CI: 1.16, 1.41). No significant associations could be found regarding other AI disorders. Conclusions: Pernicious anemia, Graves' disease, dermatomyositis, diabetes mellitus type I, inflammatory myopathies, and systemic lupus erythematosus are associated with higher incidence rates of gastric cancer. Therefore, close gastroenterological follow-up or routinely performed gastroscopy and application of other diagnostic measures may be cost-effective and clinically helpful for patients diagnosed with these autoimmune diseases.

Predictive Performance of Serum S100B Versus LDH in Melanoma Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Currently, no consensus on the use of blood tests for monitoring disease recurrence in patients with resected melanoma exists. The only meta-analysis conducted in 2008 found that elevated serum S100B levels were associated with significantly worse survival in melanoma patients. Serum LDH is an established prognostic factor in patients with advanced melanoma. OBJECTIVE: To compare the discriminative and prognostic ability of serum S100B with that of serum LDH in patients with melanoma. METHODS: This systematic review and meta-analysis were reported in accordance with the PRISMA Statement. The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD42019137138). RESULTS: A quantitative analysis of data from 6 eligible studies included 1,033 patients with cutaneous melanoma. The discriminative ability of serum S100B at identifying disease relapse [pooled Area Under the ROC (AUROC) 78.64 (95% CI 70.28; 87.01)] was significantly greater than the discriminative ability of serum LDH [AUROC 64.41 (95% CI 56.05; 7278)] (p=0.013). Ten eligible studies with 1,987 patients were included in the risk of death analysis. The prognostic performance of serum S100B [pooled estimate of adjusted hazard ratio (HR) 1.78 (95% CI 1.38; 2.29)] was independent but not superior to that of serum LDH [HR 1.60 (95% CI 1.36; 2.29)]. LIMITATIONS: A relatively small number of articles were eligible and there was considerable heterogeneity across the included studies. CONCLUSIONS: Serum biomarkers may provide relevant information on melanoma patient status and should be further researched. Serum S100B is a valid marker for diagnosis of melanoma recurrence. SYSTEMATIC REVIEW REGISTRATION: The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD42019137138).

Prevalence and Prognostic Significance of Hyponatremia in Patients With Lung Cancer: Systematic Review and Meta-Analysis.

Background: The prevalence of hyponatremia is highly variable among patients with lung cancer. However, its prevalence and prognostic significance in subgroups of patients with lung cancer have not yet been evaluated in a meta-analysis. Methods: We have registered our meta-analysis and review protocol to the PROSPERO International Prospective Register of Systematic Reviews, with the following registration number: CRD42020167013. A systematic search was done in the following sources: MEDLINE, Embase, CENTRAL, Web of Science, ClinicalTrials.gov, a WHO Global Health Library. Results: We identified a total of 8,962 potentially eligible studies, and we included 31 articles in our evaluation. The prevalence of hyponatremia in patients with lung cancer varied between 3 and 94.8% with an average of 25% without any significant differences between the following subgroups: histotype, gender, age, Eastern Cooperative Oncology Group (ECOG) state, and the extent of disease. The overall survival (OS) was significantly lower in hyponatremic compared to normonatremic patients at 10 months [RR.59 (95% CI.47-0.74), p < 0.001] and at 20 months [RR.44 (95% CI.33-0.59), p < 0.001], with worse survival rates in non-small cell lung cancer (NSCLC) [RR.27 (95% CI.12-0.44), p < 0.001] than in small cell lung cancer (SCLC) [RR.42 (95% CI.27-0.57), p < 0.001]. If hyponatremia was corrected, OS at 10 months was significantly higher than in the uncorrected hyponatremia group [RR 1.83 (95% CI 1.37-2.44), p < 0.001], but, at 20 months, no statistically significant difference could be found between these subgroups [RR 2.65 (95% CI.94-7.50), p = 0.067]. Conclusions: Patients with lung cancer diagnosed with hyponatremia, especially patients with NSCLC, seem to have significantly lower survival rates than normonatremic patients. If hyponatremia remains uncorrected, the mortality rates might be even higher.

Addition of daratumumab to multiple myeloma backbone regimens significantly improves clinical outcomes: a systematic review and meta-analysis of randomised controlled trials.

Daratumumab has shown clinical benefit in multiple myeloma. We aimed to evaluate the safety and efficacy of adding daratumumab to backbone anti-myeloma treatments. Systematic search was performed up to August 2021 to identify randomised controlled trials comparing the outcomes of backbone therapy with and without daratumumab in relapsed/refractory and newly diagnosed myeloma (RRMM and NDMM, respectively). Odds ratios (ORs) and hazard ratios (HRs) were calculated with 95% confidence intervals (CIs). Primary outcomes were death or disease progression, minimal residual disease (MRD) negativity, and stringent complete response (sCR). Secondary outcomes were complete response or better and safety endpoints prespecified in the study protocol: PROSPERO (CRD42020222904). In NDMM, MRD negativity [OR = 3.61 (CI 2.33-5.61)] and sCR [OR = 2.29 (CI 1.49-3.51)] were more likely and death or disease progression [HR = 0.47 (CI 0.39-0.57)] was less likely to occur with daratumumab compared to control. Regarding RRMM, MRD negativity [OR = 5.43 (CI 2.76-10.66)] and sCR [OR = 3.08 (CI 2.00-4.76)] were more likely and death or disease progression was less likely [HR = 0.50 (CI 0.37-0.67)] with daratumumab compared to control. The addition of daratumumab has shown high clinical efficacy and acceptable toxicity profile for the treatment of NDMM and RRMM regarding the endpoints examined.

Heat therapy shows benefit in patients with type 2 diabetes mellitus: a systematic review and meta-analysis.

AIMS: Type-2 diabetes mellitus (T2DM) is a common health condition which prevalence increases with age. Besides lifestyle modifications, passive heating could be a promising intervention to improve glycemic control. This study aimed to assess the efficacy of passive heat therapy on glycemic and cardiovascular parameters, and body weight among patients with T2DM. METHODS: A systematic review and meta-analysis were reported according to PRISMA Statement. We conducted a systematic search in three databases (MEDLINE, Embase, CENTRAL) from inception to 19 August 2021. We included interventional studies reporting on T2DM patients treated with heat therapy. The main outcomes were the changes in pre-and post-treatment cardiometabolic parameters (fasting plasma glucose, glycated plasma hemoglobin, and triglyceride). For these continuous variables, weighted mean differences (WMD) with 95% confidence intervals (CIs) were calculated. Study protocol number: CRD42020221500. RESULTS: Five studies were included in the qualitative and quantitative synthesis, respectively. The results showed a not significant difference in the hemoglobin A1c [WMD -0.549%, 95% CI (-1.262, 0.164), p = 0.131], fasting glucose [WMD -0.290 mmol/l, 95% CI (-0.903, 0.324), p = 0.355]. Triglyceride [WMD 0.035 mmol/l, 95% CI (-0.130, 0.200), p = 0.677] levels were comparable regarding the pre-, and post intervention values. CONCLUSION: Passive heating can be beneficial for patients with T2DM since the slight improvement in certain cardiometabolic parameters support that. However, further randomized controlled trials with longer intervention and follow-up periods are needed to confirm the beneficial effect of passive heat therapy.

Prophylactic transcatheter arterial embolization reduces rebleeding in non-variceal upper gastrointestinal bleeding: A meta-analysis.

BACKGROUND: Despite the improvement in the endoscopic hemostasis of non-variceal upper gastrointestinal bleeding (NVUGIB), rebleeding remains a major concern. AIM: To assess the role of prophylactic transcatheter arterial embolization (PTAE) added to successful hemostatic treatment among NVUGIB patients. METHODS: We searched three databases from inception through October 19th, 2020. Randomized controlled trials (RCTs) and observational cohort studies were eligible. Studies compared patients with NVUGIB receiving PTAE to those who did not get PTAE. Investigated outcomes were rebleeding, mortality, reintervention, need for surgery and transfusion, length of hospital (LOH), and intensive care unit (ICU) stay. In the quantitative synthesis, odds ratios (ORs) and weighted mean differences (WMDs) were calculated with the random-effects model and interpreted with 95% confidence intervals (CIs). RESULTS: We included a total of 3 RCTs and 9 observational studies with a total of 1329 patients, with 486 in the intervention group. PTAE was associated with lower odds of rebleeding (OR = 0.48, 95%CI: 0.29-0.78). There was no difference in the 30-d mortality rates (OR = 0.82, 95%CI: 0.39-1.72) between the PTAE and control groups. Patients who underwent PTAE treatment had a lower chance for reintervention (OR = 0.48, 95%CI: 0.31-0.76) or rescue surgery (OR = 0.35, 95%CI: 0.14-0.92). The LOH and ICU stay was shorter in the PTAE group, but the difference was non-significant [WMD = -3.77, 95%CI: (-8.00)-0.45; WMD = -1.33, 95%CI: (-2.84)-0.18, respectively]. CONCLUSION: PTAE is associated with lower odds of rebleeding and any reintervention in NVUGIB. However, further RCTs are needed to have a higher level of evidence.

Endoscopic ultrasound-guided ethanol and radiofrequency ablation of pancreatic insulinomas: a systematic literature review.

BACKGROUND: Insulinoma is the most common neuroendocrine neoplasm of the pancreas, characterised by hypoglycaemic symptoms. Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) and ethanol ablation (EUS-EA) are novel methods for treating insulinoma.We aimed to perform a systematic review to assess the efficacy and safety of EUS-guided ablation techniques for pancreatic insulinomas. METHODS: We systematically searched for articles detailing EUS-guided ablations of insulinomas. We performed a qualitative analysis and summarised data on the efficacy and safety of EUS-RFA and EUS-EA techniques. RESULTS: In total, we identified 35 case reports and case series describing 75 patients with insulinomas treatment with EUS-guided ablation. Twenty-seven patients were treated with EUS-RFA, 47 patients with EUS-EA, and 1 patient received EUS-EA and EUS-RFA in the same session. In total, 84 insulinomas were ablated (EUS-RFA: 31, EUS-EA: 53). Most insulinomas were in the head of the pancreas (40%). The clinical success rate for EUS-guided ablation techniques was 98.5%. The median glucose level was 1.95 (Q1-Q3: 1.69-2.13) mmol/L before ablation compared to 6.20 (Q1-Q3: 5.30-7.05) mmol/L after treatment. The median insulin and C-peptide levels before and after RFA/EA were 230 (Q1-Q2: 120-257) pmol/L and 41 (Q1-Q2 35-42) pmol/L; 2077 (Q1-Q2 1644-2459) pmol/L and 819 (Q1-Q2 696-1072) pmol/L, respectively. There were eleven adverse events: seven abdominal pain, two mild acute pancreatitis, one necrotising acute pancreatitis and one local hematoma. All patients recovered, and there were no periprocedural deaths. CONCLUSIONS: EUS-guided ablation of insulinoma seems to be a safe and effective treatment and is an alternative to surgical resection in selected cases.

Diabetes Mellitus Increases the Risk of Hepatocellular Carcinoma After Direct-Acting Antiviral Therapy: Systematic Review and Meta-Analysis.

Background: Hepatitis C virus (HCV)-infected patients treated with direct-acting antivirals (DAAs) are still at risk of developing hepatocellular carcinoma (HCC) after sustained virologic response (SVR). This study aimed to investigate the role of diabetes mellitus (DM) as a potential predictive risk factor in developing de novo HCC in HCV-infected patients after DAA treatment. Methods: This study was registered on PROSPERO under registration number CRD42021230457. We performed a systematic search in four medical databases from inception through November 3rd, 2020. Studies were eligible if they reported on HCV-infected patients treated with DAAs and compared the frequency of de novo HCC in patients with and without DM. We calculated pooled odds ratios, unadjusted (UHR), and adjusted hazard ratios (AHR) with 95% confidence intervals (CIs) in meta-analysis. Results: We included 30 articles in our systematic review and meta-analysis. DM proved to be a significant risk factor of HCC in DAA-treated HCV patients in unadjusted (UHR = 1.44, CI: 1.15-1.79) and adjusted analyses (AHR = 1.31, CI: 1.06-1.62). In the group of patients achieving SVR after DAA therapy, DM increased the risk of HCC in unadjusted (UHR = 1.3, CI: 1.09-1.51) analysis; however, in adjusted results, the risk was non-significant (AHR = 1.07, CI: 0.89-1.28). In patients with advanced liver fibrosis, DM was a risk factor for HCC in adjusted (AHR = 1.36, CI: 1.03-1.8), but not in unadjusted analysis (UHR = 1.11, CI: 0.8-1.42). Conclusions: DM is an independent risk factor of de novo HCC after DAA treatment in HCV-infected patients. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=230457, identifier: CRD42021230457.

Efficacy of first-line treatment options in transplant-ineligible multiple myeloma: A network meta-analysis.

BACKGROUND: Despite major therapeutic advances, the rational choice of the most appropriate first-line regimen in newly diagnosed transplant-ineligible multiple myeloma (TIE-MM) is currently undefined. AIM: We aimed to identify the most effective first-line treatment for TIE-MM patients. METHODS: A total of 37 articles, including 34 treatments and 16,681 patients, were included in this Bayesian network meta-analysis. The outcomes of interest were risk ratios (RR) for progression-free survival (PFS) and overall survival (OS). RESULTS: Based on surface under cumulative ranking curve values, daratumumab-bortezomib-melphalan-prednisone (Dara-VMP) and daratumumab-lenalidomide-dexamethasone (Dara-Rd28) showed superiority compared to other combinations regarding 12-, 24-, 36-, and 48-month PFS. Dara-VMP also ranked first for 12-, 24-, 36-, and 48-month OS. CONCLUSION: Our finding supports the incorporation of daratumumab into first-line regimens. Additionally, these results highlight the relative benefit of incorporating novel agents like monoclonal antibodies, immunomodulatory derivatives, and proteasome inhibitors in combination with the currently existing treatment options.