Trifluridine-tipiracil plus bevacizumab versus trifluridine-tipiracil monotherapy for chemorefractory metastatic colorectal cancer: a systematic review and meta-analysis.

Colorectal cancer is the leading cause of cancer death worldwide. The first and second lines of treatment for metastatic colorectal cancer (mCRC) include chemotherapy based on 5-fluorouracil. However, treatment following progression on the first and second line is still unclear. We searched PubMed, Scopus, Cochrane, and Web of Science databases for studies investigating the use of trifluridine-tipiracil with bevacizumab versus trifluridine-tipiracil alone for mCRC. We used RStudio version 4.2.3; and we considered p < 0.05 significant. Seven studies and 1,182 patients were included - 602 (51%) received trifluridine-tipiracil plus bevacizumab. Compared with control, the progression-free survival (PFS) (HR 0.52; 95% CI 0.42-0.63; p < 0.001) and overall survival (OS) (HR 0.61; 95% CI 0.52-0.70; p < 0.001) were significantly higher with bevacizumab. The objective response rate (ORR) (RR 3.14; 95% CI 1.51-6.51; p = 0.002) and disease control rate (DCR) (RR 1.66; 95% CI 1.28-2.16; p = 0.0001) favored the intervention. Regarding adverse events, the intervention had a higher rate of neutropenia (RR 1.38; 95% CI 1.19-1.59; p = 0.00001), whereas the monotherapy group had a higher risk of anemia (RR 0.60; 95% CI 0.44-0.82; p = 0.001). Our results support that the addition of bevacizumab is associated with a significant benefit in PFS, OS, ORR and DCR.

The incidence risk of gynecological cancer by antipsychotic use: a meta-analysis of 50,402 patients.

BACKGROUND: Female gynecological cancers represent a serious public health problem, with 1,398,601 new diagnoses and 671,875 deaths per year worldwide. Antipsychotics are often used in psychiatric disorders, including schizophrenia, bipolar disorder, and major depression. It is estimated that the prescription of these drugs is linked to 1,800 deaths a year in the United States, but their association with cancer remains controversial. METHODS: We searched PubMed, Scopus, and Web of Science databases for studies reporting the correlation in the incidence risk of gynecological cancer by antipsychotic use. We used DerSimonian and Laird random-effect models to compute logit transformed odds ratio (OR) for the primary binary endpoint with 95% confidence interval (CI). Heterogeneity was assessed through effect size width along with I-squared and Tau-squared statistics. Review Manager 5.4.1. was used for statistical analyses. A p-value of < 0.05 denoted statistically significant. RESULTS: 50,402 patients were included, of whom 778 (1,54%) took antipsychotic medication for at least 1 year. 1,086 (2,15%) with ovarian cancer and 49,316 (97,85%) with endometrial cancer. Antipsychotic use (OR 1.50; 1.06 to 2.13 95% CI; p-value 0.02), hypertension (OR 1.50; 95% CI 1.06 to 2.13; p-value < 0.01), nulliparity (OR 1.98; 95% CI 1.53 to 2.57; p-value < 0.01) and multiparity (OR 0.53; 95% CI 0.41 to 0.69; p-value < 0.01) showed significantly different distributions between groups of cancer and cancer-free patients. The primary endpoint of incidence risk of gynecological cancer by antipsychotic therapy showed a statistically significant difference (OR 1.67; 95% CI 1.02 to 2.73; p-value < 0.05) against the use of antipsychotic drugs. CONCLUSIONS: Our meta-analysis showed that the use of antipsychotic drugs increases the risk of gynecological cancers, particularly endometrial cancer. This result should be weighed against the potential effects of treatment for a balanced prescribing decision.

Effect of coenzyme Q10 supplementation on statin-related myopathic pain: a systematic review and meta-analysis of randomized controlled trials

INTRODUCTION: Coenzyme Q10 (CoQ10) has shown promising results as an adjuvant therapy to statins. However, the efficacy of this agent is still unclear. Hypothesis: The use of CoQ10 mitigates statin-related myopathic pain. METHODS: PubMed, Embase, and Cochrane databases were searched for randomized controlled trials (RCTs) comparing CoQ10 supplementation with placebo in patients taking statins. A random-effects model was employed to compute the mean difference (MD) with 95% confidence interval (CI). Statistical analysis was performed using R software 4.3.1. RESULTS: A total of 5 studies and 227 patients were included, of whom 48% were randomized to CoQ10 supplementation. Compared with placebo, CoQ10 had no effects on pain severity score (MD -0.94; 95% CI -3.80 to 1.91; p=0.5), and pain intensity score (MD -1.51; 95% CI -4.09 to 1.06; p = 0.2). Moreover, no association was found with low density lipoprotein cholesterol levels (MD -0.07; 95% CI -0.47 to 0.34; p = 0.7). CONCLUSIONS: In this meta-analysis of 5 RCTs, supplementation with CoQ10 did not yield statistically significant results. These findings suggest that CoQ10 has no impact on statin-related myopathic pain.

Effect of American genomic ancestry on severe toxicities in children with acute lymphoblastic leukemia in the Amazon region.

BACKGROUND: Acute Lymphoblastic Leukemia (ALL) is a neoplasm of the hematopoietic system characterized by a clonal expansion of abnormal lymphocyte precursor cells. ALL is the most common form of cancer in children, but despite advances in treatment, it can still be fatal. Ethnic differences influence survival rates, and genomic ancestry plays an important role, especially in mixed-race populations such as Latin America. This study aims to analyze the influence of genomic ancestry on toxicity in children with ALL in the Amazon region. METHODS: The study included 171 patients (protocol number 119,649/2012-Ethics Committee) with ALL treated at a pediatric treatment center in Belém do Pará, in the Brazilian Amazon. The patients were submitted to the BFM protocol of induction therapy for ALL. Toxicity was assessed based on laboratory tests and adverse events, classified according to the CTC-NCI guide. Genomic ancestry was determined using autosomal informative markers. RESULTS: The majority of children (94.74%) developed some type of toxicity during treatment, 87.04% of which were severe. Infectious toxicity was the most common, present in 84.8% of cases, 77.24% of which were severe. Amerindian ancestry showed an association with the risk of severe general toxicity and severe infectious toxicity, with a contribution of 35.0% demonstrating a significant increase in risk. In addition, post-induction refractoriness and relapse were also associated with an increased risk of death. CONCLUSION: This study highlights the influence of Amerindian genomic ancestry on response to therapy and toxicity in children with ALL in the Amazon region. Understanding these associations can contribute to personalizing treatment and improving clinical outcomes.

Cyclin-Dependent Kinase 4/6 Inhibitors Plus Endocrine Therapy versus Endocrine Therapy Alone for HR-Positive, HER-2-Negative Early Breast Cancer: Meta-Analysis of Phase III Randomized Clinical Trials.

BACKGROUND: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are approved for advanced breast cancer combined with endocrine therapy (ET). The efficacy of CDK4/6 inhibitors plus ET in hormone estrogen-positive, human epidermal growth factor 2-negative (HR+/HER2-) early-stage breast cancer (esBC) is still to be confirmed. METHODS: We performed a systematic review and a meta-analysis to investigate the efficacy of CDK4/6i plus ET in esBC. Main outcomes included invasive disease-free survival (iDFS), distant relapse-free survival (DRFS), and overall survival (OS). We included only phase III randomized controlled trials. We used RStudio version 4.2.3, and we considered p < 0.05 to be statistically significant. RESULTS: Four studies were selected, including 14,168 patients, of which 7089 were treated with CDK4/6i plus ET and 7079 received ET monotherapy. Regarding patient characteristics, 6828 (48.2%) were premenopausal. Compared with ET alone, iDFS rates (HR 0.81; 95% CI: 0.67, 0.98; p = 0.034) were significantly in favor of CDK4/6 inhibitors plus ET. However, there were no significant differences in DRFS (HR 0.79; 95% CI: 0.58, 1.07; p = 0.132) nor OS (HR 0.96; 95% CI: 0.69, 1.35; p = 0.829). CONCLUSIONS: Our results show that the addition of CDK4/6 inhibitors is associated with a significant benefit for HR+/HER2- esBC patients in iDFS. More studies and longer follow-up are needed to assess overall survival benefits.

Do proton pump inhibitors affect the effectiveness of cyclin-dependent kinase 4/6 inhibitors in advanced HR positive, HER2 negative breast cancer? A meta-analysis.

Background: The CDK 4/6 inhibitors, including palbociclib and ribociclib, are the standard first-line treatment for hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer. Proton pump inhibitors are one of the most globally prescribed types of medications as part of the treatment for gastroesophageal reflux and heartburn complaints. Medication interactions have been demonstrated, leading to a decrease in the effectiveness of chemotherapy drugs such as capecitabine and pazopanib. However, their role and interaction with targeted therapies such as CDK inhibitors are still poorly understood. Methods: We searched PubMed, Embase and Web of Science databases for studies that investigated the use of PPI with CDK 4/6 inhibitors versus CDK4/6 alone for advanced or metastatic breast cancer. We systematically searched for the currently available CDK inhibitors: palbociclib, ribociclib and abemaciclib. We computed hazard ratios (HRs), with 95% confidence intervals (CIs). We used DerSimonian and Laird random-effect models for all endpoints. Heterogeneity was assessed using I2 statistics. R, version 4.2.3, was used for statistical analyses. Results: A total of 2,737 patients with advanced breast cancer in 9 studies were included, with six studies described the status menopausal as 217 (7.9%) pre-menopause and 1851 (67.6%) post-menopause, for endocrine sensitivity only five studies described1489 (54.4%) patients were endocrine-sensitive and 498 (182%) endocrine-resistent, 910 (33.2%) patients used PPIs. The overall Progression-Free Survival was in favor of the PPI non-users (HR 2.0901; 95% CI 1.410-2.9498; p < 0.001). As well as the subgroup taking palbociclib, revealing statistical relevance for the PPI non-users (HR 2.2539; 95% CI 1.3213-3.8446; p = 0.003) and ribociclib subgroup with a slight decrease in hazard ratio (HR 1.74 95% CI 1.02-2.97; p = 0.04; I2 = 40%). In the multivariate analysis, there was no statistical signifance with ECOG (HR 0.9081; 95% CI 0.4978-16566; p 0.753) and Age (HR 1.2772; 95% CI 0.8790-1.8559; p = 0.199). Either, the univariate analysis did not show statistical significance. Conclusion: Women with HR+ and HER2-advanced metastatic breast undergoing treatment with targeted therapies, specifically CDK 4/6 inhibitors, should be monitored for the use of proton pump inhibitors. Therefore, the use of PPIs should be discussed, weighing the advantages and disadvantages for specific cases. It should be individualized based on the necessity in clinical practice for these cases. Systematic Review Registration: identifier CRD42023484755.

Efficacy and safety of BRAF/MEK inhibitors in BRAFV600E-mutated anaplastic thyroid cancer: a systematic review and meta-analysis.

PURPOSE: Approximately 45% of anaplastic thyroid cancer (ATC) patients harbor a BRAFV600E mutation and are eligible for target therapy (TT) with BRAF and MEK inhibitors (BRAFi/MEKi), nevertheless, few data advocate for this. Hence, we've conducted a systematic review and meta-analysis investigating the effectiveness and safety of BRAFi/MEKi in BRAFV600E ATC patients. METHODS: PubMed, Embase, and the Cochrane Library were systematically searched for BRAFi/MEKi TT in BRAFV600E ATC patients. Outcomes included objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), duration of response (DOR) and adverse events (AEs). RESULTS: Nine studies with 168 patients were included. Median follow-up ranged from 2.0 to 47.9 months. 75% of patients had stage IVc. In a pooled analysis, ORR was 68.15% (95% CI 55.31-80.99, I2 = 47%) and DCR was 85.39% (95% CI 78.10-92.68, I2 = 0), with a median DOR of 14.4 months (95% CI 4.6-14.4) and a median PFS of 6.7 months (95% CI 4.7-34.2). Moreover, 1-year OS rate was 64.97% (95% CI 48.76-81.17, I2 = 84%) and 2-years OS rate was 52.08% (95% CI 35.71-68.45, I2 = 79%). Subgroup analysis showed patients in the neoadjuvant setting had higher rates of 1 and 2-years OS and observational studies tended to report higher rates of ORR than clinical trials. No new or unexpected adverse events were found. CONCLUSIONS: Our study demonstrated BRAFi/MEKi have a decent activity for BRAFV600E ATC patients, especially in the neoadjuvant setting, with a tolerable safety profile. However, further clinical trials are warranted to investigate these findings.

Telemonitoring use for uncontrolled hypertension management: a systematic review and meta-analysis of randomized controlled trials

BACKGROUND: Within the context of uncontrolled blood pressure telemonitoring, the remote tracking of blood pressure and patient data, offers a transformative avenue. We aimed to perform a meta-analysis of the strategic redesign of healthcare services, harnessing information and communication technology (ICT) to enhance hypertension management and blood pressure control in primary care, providing timely interventions, and improving patient outcomes. METHODS: PubMed, Embase, and Cochrane databases were searched for RCTs comparing ICT with usual care in patients with uncontrolled hypertension. A random-effects model was used to calculate the risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs). RESULTS: A total of twenty-eight studies and 13,111 patients were included, of whom 7,312 were randomized to ICT and 5,799 to usual care. Compared with standard care, ICT significantly reduced systolic blood pressure (MD -4.44 mmHg; 95% CI -5.55,-3.33; p<0.01) and diastolic blood pressure (MD -1.08 mmHg; 95% CI -1.71,-0.45; p<0.01). There was no significant difference between groups for adherence (RR 1.16; 95%CI 0.89-1.50; p=0.27). CONCLUSION: In this meta-analysis of RCTs of patients with uncontrolled hypertension, ICT was associated with a reduction in systolic and diastolic blood pressures, compared with usual care.

Efficacy and Safety of Anti-CD38 Monoclonal Antibodies in Patients with Relapsed or Refractory Multiple Myeloma: A Meta-Analysis of Randomized Clinical Trials.

The benefit of associating anti-CD38 monoclonal antibodies to proteasome inhibitor (PI)/immunomodulatory agent (IA) and dexamethasone in the treatment of patients with relapsed or refractory multiple myeloma (MM) remains unclear. PubMed, Embase, and Cochrane Library databases were searched for randomized controlled trials that investigated the addition of anti-CD38 monoclonal antibodies to a therapy composed of PI/IA and dexamethasone versus PI/IA and dexamethasone alone for treating relapsed or refractory MM. Hazard ratios (HRs) or risk ratios (RRs) were computed for binary endpoints, with 95% confidence intervals (CIs). Six studies comprising 2191 patients were included. Anti-CD38 monoclonal antibody significantly improved progression-free survival (HR 0.52; 95% CI 0.43-0.61; p < 0.001) and overall survival (HR 0.72; 95% CI 0.63-0.83; p < 0.001). There was a significant increase in hematological adverse events, such as neutropenia (RR 1.41; 95% CI 1.26-1.58; p < 0.01) and thrombocytopenia (RR 1.14; 95% CI 1.02-1.27; p = 0.02), in the group treated with anti-CD38 monoclonal antibody. Also, there was a significant increase in non-hematological adverse events, such as dyspnea (RR 1.72; 95% CI 1.38-2.13; p < 0.01) and pneumonia (RR 1.34; 95% CI 1.13-1.59; p < 0.01), in the group treated with anti-CD38 monoclonal antibody. In conclusion, the incorporation of an anti-CD38 monoclonal antibody demonstrated a promising prospect for reshaping the established MM treatment paradigms.

Fezolinetant for the treatment of vasomotor symptoms associated with menopause: a meta-analysis.

This systematic review and meta-analysis investigated the efficacy and safety of fezolinetant for the treatment of moderate-to-severe vasomotor symptoms (VMS) associated with menopause. PubMed, Cochrane Library, Embase and Web of Science were searched for randomized controlled trials (RCTs) published from inception to June 2023, comparing fezolinetant to placebo in postmenopausal women suffering from moderate-to-severe VMS. The mean difference and risk ratio were calculated for continuous and binary outcomes, respectively. R software was used for the statistical analysis, and RoB-2 (Cochrane) to assess the risk of bias. We performed subgroup analysis based on different dosing regimens. Five RCTs comprising 3302 patients were included. Compared with placebo, at 12-week follow-up, fezolinetant significantly reduced the daily frequency of moderate-to-severe VMS (weighted mean difference [WMD] - 2.36; 95% confidence interval [CI] - 2.92, -1.81) and daily severity of moderate-to-severe VMS (WMD -0.22; 95% CI -0.31, -0.13). Also, fezolinetant significantly improved the quality of life (WMD -0.42; 95% CI -0.58, -0.26) and sleep disturbance (WMD -1.10; 95% CI -1.96, -0.24). There were no significant differences between groups in adverse events. These findings support the efficacy and safety of fezolinetant for the treatment of VMS related to menopause.

Efficacy and safety of anti-CD38 monoclonal antibodies in patients with relapsed or refractory multiple myeloma: a meta-analysis of randomized clinical trials

The benefit of associating anti-CD38 monoclonal antibodies to proteasome inhibitor (PI)/immunomodulatory agent (IA) and dexamethasone in the treatment of patients with relapsed or refractory multiple myeloma (MM) remains unclear. PubMed, Embase, and Cochrane Library databases were searched for randomized controlled trials that investigated the addition of anti-CD38 monoclonal antibodies to a therapy composed of PI/IA and dexamethasone versus PI/IA and dexamethasone alone for treating relapsed or refractory MM. Hazard ratios (HRs) or risk ratios (RRs) were computed for binary endpoints, with 95% confidence intervals (CIs). Six studies comprising 2191 patients were included. Anti-CD38 monoclonal antibody significantly improved progressionfree survival (HR 0.52; 95% CI 0.43­0.61; p < 0.001) and overall survival (HR 0.72; 95% CI 0.63­0.83; p < 0.001). There was a significant increase in hematological adverse events, such as neutropenia (RR 1.41; 95% CI 1.26­1.58; p < 0.01) and thrombocytopenia (RR 1.14; 95% CI 1.02­1.27; p = 0.02), in the group treated with anti-CD38 monoclonal antibody. Also, there was a significant increase in non-hematological adverse events, such as dyspnea (RR 1.72; 95% CI 1.38­2.13; p < 0.01) and pneumonia (RR 1.34; 95% CI 1.13­1.59; p < 0.01), in the group treated with anti-CD38 monoclonal antibody. In conclusion, the incorporation of an anti-CD38 monoclonal antibody demonstrated a promising prospect for reshaping the established MM treatment paradigms.

Molecular Profile of Variants Potentially Associated with Severe Forms of COVID-19 in Amazonian Indigenous Populations.

Coronavirus disease 2019 (COVID-19) is an infection caused by SARS-CoV-2. Genome-wide association studies (GWASs) have suggested a strong association of genetic factors with the severity of the disease. However, many of these studies have been completed in European populations, and little is known about the genetic variability of indigenous peoples' underlying infection by SARS-CoV-2. The objective of the study is to investigate genetic variants present in the genes AQP3, ARHGAP27, ELF5L, IFNAR2, LIMD1, OAS1 and UPK1A, selected due to their association with the severity of COVID-19, in a sample of indigenous people from the Brazilian Amazon in order to describe potential new and already studied variants. We performed the complete sequencing of the exome of 64 healthy indigenous people from the Brazilian Amazon. The allele frequency data of the population were compared with data from other continental populations. A total of 66 variants present in the seven genes studied were identified, including a variant with a high impact on the ARHGAP27 gene (rs201721078) and three new variants located in the Amazon Indigenous populations (INDG) present in the AQP3, IFNAR2 and LIMD1 genes, with low, moderate and modifier impact, respectively.

Nile Tilapia Skin Xenograft Versus Silver-Based Dressings in the Management of Partial-Thickness Burn Wounds: A Systematic Review and Meta-Analysis.

Background: Burns are a serious public health problem worldwide, causing high morbidity and mortality. This study aimed to compare two forms of treatment for partial skin burns and to determine whether one is superior to the other in terms of efficacy and benefits through a meta-analysis of randomized controlled trials. This article highlights the efficacy of tilapia skin in the treatment of burns. We performed a meta-analysis of 199 patients and highlighted the promising results that indicate the clinical relevance of this resource when we compared the cost of dressings with the daily need for dressing changes, healing potential, and reduction in pain level according to the VAS scale and reduced frequency of dressing changes. Methods: A search of PubMed, Cochrane Central, and LILACS was performed to identify randomized controlled trials comparing tilapia skin and silver-based dressings for treating burns. Studies involving overlapping populations and animals were excluded. The outcomes of interest were complete re-epithelialization, decreased pain level, and dressing change. Results: Summarize the article's main findings. Conclusions: Four randomized trials were included with a total of 199 patients with partial-thickness burns between the ages of 2 and 70 years. A total of 99 (49.74%) patients were treated with tilapia skin, and conventional treatment was used on 100 (50.25%) of the patients. Differences were found between the tilapia and silver-based treatments concerning re-epithelialization (MD -0.48; CI 95% -0.71 to -0.24; p < 0.01; I2 = 0%), decreased pain level (MD -0.79; CI 95% -1.10 to -0.47; p < 0.01; I2 = 0%), and dressing change outcome (MD -3.54; 95% CI -5.81 to -1.26; p = 0.02; I2 = 97%).

Genomic Variants and Worldwide Epidemiology of Breast Cancer: A Genome-Wide Association Studies Correlation Analysis.

Breast cancer (BCa) is the most common cancer and leading cause of cancer death among women globally. This can be explained by the genetic factor of this disease. This article aims to correlate the epidemiological data, worldwide incidence, and mortality of BCa with the Single-Nucleotide Polymorphisms (SNPs) associated with the susceptibility and severity in different populations. Two hundred and forty genetic variants associated with BCa susceptibility/severity were selected from the literature through Genome-Wide Association Studies (GWAS). The allele frequencies were obtained from the 1000 Genomes Project, and the epidemiological data were obtained from the World Health Organization (WHO). The BCa incidence, mortality rates, and allele frequencies of the variants were evaluated using Pearson's correlation. Our study demonstrated that 11 SNPs (rs3817578, rs4843437, rs3754934, rs61764370, rs780092, rs2290203, rs10411161, rs6001930, rs16886165, rs8051542 and rs4973768) were significantly correlated with the epidemiological data in different ethnic groups. Seven polymorphisms (rs3817578, rs3754934, rs780092, rs2290203, rs10411161, rs6001930 and rs16886165) were inversely correlated with the incidence rate and four polymorphisms (rs4843437, rs61764370, rs8051542 and rs4973768) were directly correlated with the incidence rate. African and South-East Asian populations have a lower risk of developing BCa when evaluated in terms of genetic factors since they possess variants characterized as protective, as their higher incidence is associated with a lower frequency of BCa cases. The genetic variants investigated here are likely to predispose individuals to BCa. The genetic study described here is promising for implementing personalized strategies to screen for breast cancer in diverse populations.

Efficacy and safety of Zolbetuximab plus chemotherapy for advanced CLDN18.2-positive gastric or gastro-oesophageal adenocarcinoma: a meta-analysis of randomized clinical trials.

BACKGROUND: The benefit of adding Zolbetuximab to the treatment in patients with Claudin-18 isoform 2 (CLDN18.2)-positive, human epidermal growth factor receptor 2-negative, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GC/GEJ) is not yet fully elucidated. METHODS: We searched PubMed, Embase and Cochrane databases for randomized controlled trials (RCTs) that investigated Zolbetuximab plus chemotherapy versus chemotherapy alone for GC or GEJ adenocarcinoma. We computed hazard-ratios (HRs) or odds-ratios (ORs) for binary endpoints, with 95% confidence intervals (CIs). RESULTS: Three studies and 1,233 patients were included. Comparing with Zolbetuximab plus chemotherapy versus chemotherapy alone, progression-free survival (PFS) rate (HR 0.64; 95% CI 0.49-0.84; p < 0.01) and overall survival (OS) rate (HR 0.72; 95% CI 0.62-0.83; p < 0.01) were significant in favor of the Zolbetuximab group. Regarding effectiveness, the Objective Response Rate (ORR) was (OR 1.15; 95% CI 0.87-1.53; p = 0.34). CONCLUSIONS: In this comprehensive systematic review and meta-analysis of RCTs, the incorporation of Zolbetuximab alongside chemotherapy offers a promising prospect for reshaping the established treatment paradigms for patients diagnosed with advanced CLDN18.2-positive GC/GEJ cancer.

The Use of Honey for Cicatrization and Pain Control of Obstetric Wounds: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: Several studies point to antibacterial properties and beneficial effects of honey on scar tissue formation, which is a low-cost and easy-to-use option. This study aimed to compare honey versus a placebo for cicatrization and pain control of obstetric wounds, and determine if one is superior to the other, in terms of efficacy, through a meta-analysis. METHODS: We searched PubMed, Scopus, Cochrane Central Register of Controlled Trials, and Web of Science. Two independent investigators identified randomized controlled trials (RCTs) comparing honey and a placebo for obstetric wounds. The primary outcomes were wound healing and pain control. RESULTS: Five randomized controlled trials and 353 patients were included, of whom, 177 (50.1%) were treated with honey. Differences were not found in the final wound healing between the honey and placebo groups (MD -0.34; 95% CI -1.13, 0.44; p = 0.39); however, there was a decrease in pain levels in the middle of the treatment (SMD -0.54; 95% CI 0.83 to 0.25, p = 0.03), reduction in the use of pain medication (ORR 0.26; 95% CI 0.08, 0.86; p = 0.03), increase in personal satisfaction in women who underwent the intervention (ORR 0.81; 95% CI 0.65, 0.98), and reduction in complications. CONCLUSION: According to the study results, honey treatments showed greater efficiency and provided benefits to the patients by accelerating wound healing and decreasing reported pain.

Modeling the larvae dispersion of sun coral in the Brazil current off Cape Frio: A cyclonic eddy scenario.

The study aims to understand the dispersal patterns of non-indigenous Tubastraea spp. (Sun Coral) larvae in the Brazil Current (BC), specifically in the Cape Frio recurrent cyclonic eddy (CFE) scenario. For this, the Regional Ocean Model System was used to simulate the hydrodynamic fields in a high-resolution nested grid, where a model of lagrangian floats, in a good approximation of the larvae properties and considering massive planulation events, was coupled with surface larval release from the Campos Basin area. The simulation was representative of mesoscale features compared to similar studies, ARGO vertical profiles and a py-eddy-track algorithm was used to obtain eddy variables, such as radius, rotational and translational velocities. These parameters are fundamental to access when an eddy tends to trap or not the water, heat and plankton in its interior. CFE turned out to be highly nonlinear, with a strong tendency to trap larvae in its core, acting as a dispersal constrictor when compared with the organisms in the axis of the higher speed of BC. A strong negative correlation (-0.75) was found between the days that larvae were inside the eddy and their distance from the origin. None of the 48,000 larvae released during simulated experiment a 16-day spawning event reached the coast. There are two different patterns for the dispersal, one along the shelf break and another, with higher larval density, off from the 1000 m isobath. The CFE's presence allows larvae to remain in the same region for longer periods, although in offshore areas. Therefore, as there is considerable availability of fixed substrates on oil rig structures, larvae could settle on them resulting in a possible inter-platforms connectivity between populations of Tubastraea spp. Also, regions in the CFE that present downward vertical velocities (downwelling), may move young larvae to depths of about 60 m suggesting that subsurface colonizations are possible due to specific dynamics of propagating cyclonic eddies. So, identifying the main factors that affect the dispersion of propagules is essential to subsidize management policies for controlling bioinvasion associated with exploitation of hydrocarbon resources in offshore areas.

Mesenchymal-Epithelial Transition Kinase Inhibitor Therapy in Patients with Advanced Papillary Renal-Cell Carcinoma: A Systematic Review and Meta-Analysis.

Papillary subtypes of renal-cell carcinoma (pRCC) represent 10-15% of the cases and commonly have MET alterations. This systematic review and single-arm meta-analysis evaluated MET inhibitor therapy (METi) efficacy and safety in adults with confirmed advanced pRCC. The search strategy included PubMed, Web-of-science, Cochrane, and Scopus. We used the DerSimonian/Laird random effect model for all analyses; p-value < 5% was considered significant, and heterogeneity was assessed with I2. Three clinical trials and six cohort studies were included with 504 patients; 31% were MET-driven. Our pooled analysis demonstrated an objective response rate (ORR) in MET-driven, MET-independent, and overall patients of: 36% (95%CI: 10-62), 0% (95%CI: 0-3), and 21% (95%CI: 1-41), respectively. One-year disease control and progression-free survival rates were, respectively, 70% (95%CI: 52-88) and 15% (95%CI: 10-20). Twelve- and twenty-four-month survival rates were, respectively, 43% (95%CI: 23-64) and 10% (95%CI: 0-30). The prevalence of adverse events of any grade and grades 3-5 were 96% (95%CI: 91-100) and 44% (95%CI: 37-50), respectively. We suggest METi has anti-tumor activity and is tolerable in patients with advanced pRCC.

PD-1/PD-L1 Inhibitors plus Chemotherapy Versus Chemotherapy Alone for Resectable Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: The benefit of adding programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors to the treatment of early-stage non-small cell lung cancer (NSCLC), both neoadjuvant therapy (NAT) and adjuvant therapy (AT), is not yet fully elucidated. Methods: We searched PubMed, Embase, and Cochrane databases for randomized controlled trials (RCT) that investigated PD-1/PD-L1 inhibitors plus chemotherapy for resectable stage NSCLC. We computed hazard ratios (HRs) or odds ratios (ORs) for binary endpoints, with 95% confidence intervals (CIs). Results: A total of seven RCTs comprising 3915 patients with resectable stage NSCLC were randomized to chemotherapy with or without PD-1/PD-L1 inhibitors as NAT or AT. As NAT, the PD-1/PD-L1 inhibitors plus chemotherapy group demonstrated significantly improved overall survival (HR 0.66; 95% CI 0.51-0.86) and event-free survival (HR 0.53; 95% CI 0.43-0.67) compared with the chemotherapy alone group. There was a significant increase in favor of the PD-1/PD-L1 inhibitors plus chemotherapy group for major pathological response (OR 6.40; 95% CI 3.86-10.61) and pathological complete response (OR 8.82; 95% CI 4.51-17.26). Meanwhile, as AT, disease-free survival was significant in favor of the PD-1/PD-L1 inhibitors plus chemotherapy group (HR 0.78; 95% CI 0.69-0.90). Conclusions: In this comprehensive systematic review and meta-analysis of RCTs, the incorporation of PD-1/PD-L1 inhibitors alongside chemotherapy offers a promising prospect for reshaping the established treatment paradigms for patients diagnosed with resectable stages of NSCLC. Moreover, our analyses support that neoadjuvant administration with these agents should be encouraged, in light of the fact that it was associated with an increased survival and pathological response, at the expense of a manageable safety profile.

Malignant Neoplasms Arising in the Cardiac Pacemaker Cavity: A Systematic Review.

Cancer is the abnormal proliferation of physiologically inadequate cells. Studies have identified the cardiac pacemaker pocket as a site of rare neoplasms. To evaluate the clinical outcomes, treatment, prognosis, and individualized management of tumors originating in the cardiac pacemaker pocket, a systematic review was conducted using case reports and case series available in the PubMed/Medline, Science Direct, Cochrane Central, LILACS, and Scientific Electronic Library Online (Scielo) databases. Pacemaker pocket tumors affected patients with a mean age of 72.9 years, with a higher incidence in males (76.9%, n = 10). The average time for neoplasm development was 4.4 years (54.07 months). The most prevalent model was Medtronic (38.4%, n = 5), with titanium (83.3%) being the most common metal composition. Chemotherapy was the most performed procedure among patients (38.4%), followed by radiation therapy (38.4%) and surgical tumor resection (30.7%). Six analyzed cases (46.1%) resulted in death, and four patients (30.7%) achieved a cure. Patients with pacemakers should be routinely evaluated for the occurrence of malignant tumors at the site of device implantation.