Pancreatic Cancer Risk in Prediabetes: A Systematic Meta-Analysis Approach.

OBJECTIVES: Pancreatic cancer and Prediabetes pose significant public health challenges. Given the lack of strong evidence and inconsistencies, we performed a meta-analysis to assess the risk of pancreatic cancer in prediabetes. METHODS: We performed a thorough search of the major databases over the last 10 years to identify relevant articles. The Pooled odds ratio(OR) and Hazard Ratio(HR) were combined to calculate the effect size(ES). RESULTS: We analyzed 5 studies including 5,425,111 prediabetic individuals and 16,096,467 normoglycemic population across five countries with a median follow-up of 8.5 years. We identified a noteworthy association between prediabetes and pancreatic cancer, reporting an unadjusted effect size (ES) of 1.36 (95% CI 1.05-1.77, P = 0.02) and an adjusted ES of 1.40 (1.23-1.59, P < 0.01). Subgroup analyses by age revealed variations in risk, with studies involving participants aged 60 and above exhibiting a higher effect size (ES 1.83, 95% CI 1.28-2.62, P < 0.01). Geographical differences were also observed, with Japanese studies reporting a higher risk (ES 1.89, 95% CI 1.15-3.10, P < 0.01) compared to those from the USA (ES 1.32, 95% CI 1.13-1.53, P < 0.01). CONCLUSION: We identified 40% higher risk of pancreatic cancer in patients with prediabetes than those with normal blood glucose necessitating urgent attention for further research and policy change.

Long-Term Risk of Colorectal Cancer in Patients With Prediabetes: A Comprehensive Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: Prediabetes is often underdiagnosed and underreported due to its asymptomatic state in over 80% of individuals. Considering its role in promoting cancer incidence and limited evidence linking prediabetes and colorectal cancer (CRC), we conducted a systematic review and meta-analysis to evaluate the incidence of colorectal cancer in people with prediabetes. METHODS: A comprehensive search through PubMed/Medline, Embase, Scopus, and Google Scholar was performed until June 1, 2022, to screen for studies reporting CRC incidence/risk in prediabetics. Binary random-effects models were used to perform meta-analysis and subgroup analyses. Sensitivity analysis was done using leave-one-out method. The quality of the studies was assessed by the Newcastle Ottawa Scale for observational studies. RESULTS: Seven prospective and one retrospective study comprising 15 cohorts and a pooled number of 854,876 cases and 219,0511 controls were included in the analysis (2 Japan, 2 Korea, 1 Sweden, 1 UK, 1 China, and 1 USA). After combining all the studies, the forest plots for adjusted analysis shows a statistically significant increase in odds of having CRC with prediabetes (OR=1.16; 1.08-1.25, p< 0.01; I2=56.06%) and unadjusted analysis also shows a statistically significant increase in odds of having CRC with prediabetes (OR=1.62; 1.35-1.95, p< 0.01; I2=85.72% ). Sensitivity analysis using the Leave-one-out method did confirm equivalent results. Subgroup analysis based on type of study, the odds of developing CRC was higher in prospective studies (OR=1.175; 1.065-1.298) (p=0.001) than retrospective studies (OR=1.162; 1.033- 1.306) (p=0.012). The odds of developing CRC were not significantly higher in ages >60 (OR=1.446; 0.887-2.356) (p=0.139) compared to less than 60 years. The strongest association b/w prediabetes and CRC was found on a median 5-10 years (aOR=1.257; 1.029-1.534) (p=0.025) follow-up compared to < 5 years and 10 years and higher. CONCLUSIONS: This study showed that the odds of developing CRC is 16% higher in patients with prediabetes than those with normal blood glucose. Lifestyle modifications such as weight loss, proper diet, and exercise are essential to control prediabetes. This study further warrants a specific prediabetes screening for patients already at high risk of colorectal cancer with other risk factors.

Systemic oncological therapy in breast cancer patients on dialysis.

The advancement of renal replacement therapy has significantly enhanced the survival rates of patients with end-stage renal disease (ESRD) over time. However, this prolonged survival has also been associated with a higher likelihood of cancer diagnoses among these patients including breast cancer. Breast cancer treatment typically involves surgery, radiation, and systemic therapies, with approaches tailored to cancer type, stage, and patient preferences. However, renal replacement therapy complicates systemic therapy due to altered drug clearance and the necessity for dialysis sessions. This review emphasizes the need for optimized dosing and administration strategies for systemic breast cancer treatments in dialysis patients, aiming to ensure both efficacy and safety. Additionally, challenges in breast cancer screening and diagnosis in this population, including soft-tissue calcifications, are highlighted.

Association between prediabetes and breast cancer: a comprehensive meta-analysis.

BACKGROUND: Breast cancer accounts for up to 30% of cancer cases in women in the US. Diabetes mellitus has been recognized as a risk factor for breast cancer. Some studies have suggested that prediabetes may also be associated with breast cancer whereas other studies have shown no or an inverse association; thus, we conducted a meta-analysis to assess the risk of breast cancer in prediabetes. METHODS: We searched PubMed/Medline, EMBASE, Google Scholar, and Scopus to identify studies that reported breast cancer risks in patients having prediabetes compared to normoglycemic patients. Binary random-effects model was used to calculate a pooled odds ratio (OR) with 95% confidence intervals. I2 statistics were used to assess heterogeneity. Leave-one-out sensitivity analysis and subgroup analyses were performed. RESULTS: We analyzed 7 studies with 24,586 prediabetic and 224,314 normoglycemic individuals (783 and 5739 breast cancer cases, respectively). Unadjusted odds ratio (OR) for breast cancer was 1.45 (95% CI = 1.14, 1.83); adjusted OR was 1.19 (95% CI = 1.07, 1.34) in prediabetes. Subgroup analysis revealed a higher breast cancer risk in individuals aged less than 60 years (OR = 1.86, 95% CI = 1.39, 2.49) than in those aged 60 years or more (OR = 1.07, 95% CI = 0.97, 1.18). Subgroup analysis by median follow-up length indicated a higher risk of breast cancer for follow-ups of less than or equal to 2 years (OR = 2.34, 95% CI = 1.85, 2.95) than in those of over 10 years (OR = 1.1, 95% CI = 0.99, 1.23) and 6 to 10 years (OR = 1.03, 95% CI = 0.88, 1.21). CONCLUSIONS: In conclusion, individuals with prediabetes have higher risk of developing breast cancer than those with normoglycemia, especially younger prediabetes patients. These individuals may benefit from early identification, monitoring, and interventions to reverse prediabetes.

A Meta-Analysis of Randomized Clinical Trials Assessing the Efficacy of PARP Inhibitors in Metastatic Castration-Resistant Prostate Cancer.

Prostate cancer ranks as the second most common malignancy in males. Prostate cancer progressing on androgen deprivation therapy (ADT) is castration-resistant prostate cancer (CRPC). Poly-ADP ribose polymerase (PARP) inhibitors (PARPis) have been at the forefront of the treatment of CRPC. We aim to better characterize the progression-free survival (PFS) and overall survival (OS) in metastatic CRPC patients treated with PARPis. A systemic review search was conducted using National Clinical Trial (NCT), PubMed, Embase, Scopus, and Central Cochrane Registry. The improvement in overall survival was statistically significant, favoring PARPis (hazard ratio (HR) 0.855; 95% confidence interval (CI) 0.752-0.974; p = 0.018). The improvement in progression-free survival was also statistically significant, with results favoring PARPis (HR 0.626; 95%CI 0.566-0.692; p = 0.000). In a subgroup analysis, similar results were observed where the efficacy of PARPis was evaluated in a subgroup of patients without homologous recombination repair (HRR) gene mutation, which showed improvement in PFS favoring PARPis (HR 0.747; 95%CI 0.0.637-0.877; p = 0.000). Our meta-analysis of seven RCTs showed that PARPis significantly increased PFS and OS when used with or without antihormonal agents like abiraterone or enzalutamide.

Role of innate immunological/inflammatory pathways in myelodysplastic syndromes and AML: a narrative review.

Dysregulation of the innate immune system and inflammatory-related pathways has been implicated in hematopoietic defects in the bone marrow microenvironment and associated with aging, clonal hematopoiesis, myelodysplastic syndromes (MDS), and acute myeloid leukemia (AML). As the innate immune system and its pathway regulators have been implicated in the pathogenesis of MDS/AML, novel approaches targeting these pathways have shown promising results. Variability in expression of Toll like receptors (TLRs), abnormal levels of MyD88 and subsequent activation of NF-κß, dysregulated IL1-receptor associated kinases (IRAK), alterations in TGF-ß and SMAD signaling, high levels of S100A8/A9 have all been implicated in pathogenesis of MDS/AML. In this review we not only discuss the interplay of various innate immune pathways in MDS pathogenesis but also focus on potential therapeutic targets from recent clinical trials including the use of monoclonal antibodies and small molecule inhibitors against these pathways.

Efficacy of antiviral therapies for COVID-19: a systematic review of randomized controlled trials.

BACKGROUND: Coronavirus disease 2019 (COVID-19) continues to pose a significant threat to public health worldwide. The purpose of this study was to review current evidence obtained from randomized clinical trials on the efficacy of antivirals for COVID-19 treatment. METHODS: A systematic literature search was performed using PubMed to identify randomized controlled trials published up to September 4, 2021 that examined the efficacy of antivirals for COVID-19 treatment. Studies that were not randomized controlled trials or that did not include treatment of COVID-19 with approved antivirals were excluded. Risk of bias was assessed using the Scottish Intercollegiate Guidelines Network (SIGN) method. Due to study heterogeneity, inferential statistics were not performed and data were expressed as descriptive statistics. RESULTS: Of the 2,284 articles retrieved, 31 (12,440 patients) articles were included. Overall, antivirals were more effective when administered early in the disease course. No antiviral treatment demonstrated efficacy at reducing COVID-19 mortality. Sofosbuvir/daclatasvir results suggested clinical improvement, although statistical power was low. Remdesivir exhibited efficacy in reducing time to recovery, but results were inconsistent across trials. CONCLUSIONS: Although select antivirals have exhibited efficacy to improve clinical outcomes in COVID-19 patients, none demonstrated efficacy in reducing mortality. Larger RCTs are needed to conclusively establish efficacy.

Primary Treatment of Small to Medium (<3 cm) Sporadic Vestibular Schwannomas: A Systematic Review and Meta-Analysis on Hearing Preservation and Tumor Control Rates for Microsurgery versus Radiosurgery.

BACKGROUND: A meta-analysis of patients with sporadic vestibular schwannoma (VS) primarily treated with stereotactic radiosurgery (SRS) or microsurgery (MS) was performed, and hearing preservation outcome (HPO), tumor control (TC), and facial nerve dysfunction (FND) were analyzed. METHODS: A systematic review was conducted (Medline and Scopus database) for the period January 2010-June 2020 with appropriate MeSH. English language articles for small to medium sporadic VS (<3 cm) using SRS or MS as primary treatment modality, with minimum follow-up of 3 years, were included. Studies had to report an acceptable standardized hearing metric. RESULTS: Thirty-two studies met the inclusion criteria: 10 MS; 23 radiosurgery, and 1 comparative study included in both. HPO, at approximately 65 months follow-up, were comparable between MS group (10 studies; 809 patients) and SRS group (23 studies; 1234 patients) (56% vs. 59%; P = 0.1527). TC, at approximately 70 months follow-up, was significantly better in the MS group (9 studies; 1635 patients) versus the SRS group (19 studies; 2260 patients) (98% vs. 92%; P < 0.0001). FND, at approximately 12 months follow-up, was significantly higher in the MS group (8 studies; 1101 patients) versus the SRS group (17 studies; 2285 patients) (10% vs. 2%; P < 0.0001). CONCLUSIONS: MS and SRS are comparable primary treatments for small (<3 cm) sporadic VS with respect to HPO at 5-year follow-up in patients with serviceable hearing at presentation; approximately 50% of patients for both modalities likely lose serviceable hearing by that time point. High TC rates (>90%) were seen with both modalities; MS 98% versus SRS 92%. The posttreatment FND was significantly less with the SRS group (2%) versus the MS group (10%).

Corticosteroid therapy for COVID-19: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Corticosteroid treatment is an effective and common therapeutic strategy for various inflammatory lung pathologies and may be an effective treatment for coronavirus disease 2019 (COVID-19). The purpose of this systematic review and meta-analysis of current literature was to investigate the clinical outcomes associated with corticosteroid treatment of COVID-19. METHODS: We systematically searched PubMed, medRxiv, Web of Science, and Scopus databases through March 10, 2021 to identify randomized controlled trials (RCTs) that evaluated the effects of corticosteroid therapies for COVID-19 treatment. Outcomes of interest were mortality, need for mechanical ventilation, serious adverse events (SAEs), and superinfection. RESULTS: A total of 7737 patients from 8 RCTs were included in the quantitative meta-analysis, of which 2795 (36.1%) patients received corticosteroids plus standard of care (SOC) while 4942 (63.9%) patients received placebo and/or SOC alone. The odds of mortality were significantly lower in patients that received corticosteroids as compared to SOC (odds ratio [OR] = 0.85 [95% CI: 0.76; 0.95], P = .003). Corticosteroid treatment reduced the odds of a need for mechanical ventilation as compared to SOC (OR = 0.76 [95% CI: 0.59; 0.97], P = .030). There was no significant difference between the corticosteroid and SOC groups with regards to SAEs and superinfections. CONCLUSION: Corticosteroid treatment can reduce the odds for mortality and the need for mechanical ventilation in severe COVID-19 patients.

Outcomes of acute respiratory distress syndrome in COVID-19 patients compared to the general population: a systematic review and meta-analysis.

INTRODUCTION: Acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19) often leads to mortality. Outcomes of patients with COVID-19-related ARDS compared to ARDS unrelated to COVID-19 is not well characterized. AREAS COVERED: We performed a systematic review of PubMed, Scopus, and MedRxiv 11/1/2019 to 3/1/2021, including studies comparing outcomes in COVID-19-related ARDS (COVID-19 group) and ARDS unrelated to COVID-19 (ARDS group). Outcomes investigated were duration of mechanical ventilation-free days, intensive care unit (ICU) length-of-stay (LOS), hospital LOS, and mortality. Random effects models were fit for each outcome measure. Effect sizes were reported as pooled median differences of medians (MDMs), mean differences (MDs), or odds ratios (ORs). EXPERT OPINION: Ten studies with 2,281 patients met inclusion criteria (COVID-19: 861 [37.7%], ARDS: 1420 [62.3%]). There were no significant differences between the COVID-19 and ARDS groups for median number of mechanical ventilator-free days (MDM: -7.0 [95% CI: -14.8; 0.7], p = 0.075), ICU LOS (MD: 3.1 [95% CI: -5.9; 12.1], p = 0.501), hospital LOS (MD: 2.5 [95% CI: -5.6; 10.7], p = 0.542), or all-cause mortality (OR: 1.25 [95% CI: 0.78; 1.99], p = 0.361). Compared to the general ARDS population, results did not suggest worse outcomes in COVID-19-related ARDS.

Efficacy and safety of lopinavir/ritonavir in the treatment of COVID-19: A systematic review.

Objectives: To systematically review the clinical literature reporting the use of Lopinavir/ritonavir (LPV/r) for the treatment of patients with Cornonavirus disease 19 (COVID-19) to assess the efficacy of LPV/r for the treatment of COVID-19.Methods: The authors systematically searched PubMed and MedRxiv databases for studies describing treatment of COVID-19 patients using LPV/r compared to other therapies. Articles were excluded if they were case reports, opinion editorials, preclinical studies, single-armed studies, not written in English, not relevant to the topic, or published before May 2020. The included outcomes were viral clearance as measured by reverse-transcription polymerase chain reaction (RT-PCR) negativity and/or improvement on chest computed tomography (CT), mortality, and adverse events.Results: Among 858 total studies, 16 studies met the inclusion criteria and were included in the qualitative review. These studies consisted of 3 randomized control trials, 3 open-label trials, and 10 observational studies. Most of these studies did not report positive clinical outcomes with LPV/r treatment.Conclusion: The systematic review revealed insufficient evidence of effectiveness and clinical benefit of LPV/r in the treatment of COVID-19 patients. Specifically, LPV/r does not appear to improve clinical outcome, mortality, time to RT-PCR negativity, or chest CT clearance in patients with COVID-19.