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Frontiers in Immunology 2024Immune checkpoint inhibitors (ICIs) are effective for non-small cell lung cancer (NSCLC) treatment, but the response rate remains low. Programmed cell death ligand 1... (Meta-Analysis)
Meta-Analysis
Prognostic significance of programmed cell death ligand 1 blood markers in non-small cell lung cancer treated with immune checkpoint inhibitors: a systematic review and meta-analysis.
BACKGROUND
Immune checkpoint inhibitors (ICIs) are effective for non-small cell lung cancer (NSCLC) treatment, but the response rate remains low. Programmed cell death ligand 1 (PD-L1) in peripheral blood, including soluble form (sPD-L1), expression on circulating tumor cells (CTCs PD-L1) and exosomes (exoPD-L1), are minimally invasive and promising markers for patient selection and management, but their prognostic significance remains inconclusive. Here, we performed a meta-analysis for the prognostic value of PD-L1 blood markers in NSCLC patients treated with ICIs.
METHODS
Eligible studies were obtained by searching PubMed, EMBAS, Web of Science, and Cochrane Library prior to November 30, 2023. The associations between pre-treatment, post-treatment and dynamic changes of blood PD-L1 levels and progression-free survival (PFS)/over survival (OS) were analyzed by estimating hazard ratio (HR) and 95% confidence interval (CI).
RESULTS
A total of 26 studies comprising 1606 patients were included. High pre- or post-treatment sPD-L1 levels were significantly associated with worse PFS (pre-treatment: HR=1.49, 95%CI 1.13-1.95; post-treatment: HR=2.09, 95%CI 1.40-3.12) and OS (pre-treatment: HR=1.83, 95%CI 1.25-2.67; post-treatment: HR=2.60, 95%CI 1.09-6.20, P=0.032). High pre-treatment exoPD-L1 levels predicted a worse PFS (HR=4.24, 95%CI 2.82-6.38, P<0.001). Pre-treatment PD-L1 CTCs tended to be correlated with prolonged PFS (HR=0.63, 95%CI 0.39-1.02) and OS (HR=0.58, 95%CI 0.36-0.93). Patients with up-regulated exoPD-L1 levels, but not sPD-L1, after ICIs treatment had significantly favorable PFS (HR=0.36, 95%CI 0.23-0.55) and OS (HR=0.24, 95%CI 0.08-0.68).
CONCLUSION
PD-L1 blood markers, including sPD-L1, CTCs PD-L1 and exoPD-L1, can effectively predict prognosis, and may be potentially utilized for patient selection and treatment management for NSCLC patients receiving ICIs.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Immune Checkpoint Inhibitors; Lung Neoplasms; B7-H1 Antigen; Biomarkers, Tumor; Prognosis
PubMed: 38915398
DOI: 10.3389/fimmu.2024.1400262 -
Frontiers in Oncology 2024In the contemporary epoch, cancer stands as the predominant cause of premature global mortality, necessitating a focused exploration of molecular markers and advanced... (Review)
Review
In the contemporary epoch, cancer stands as the predominant cause of premature global mortality, necessitating a focused exploration of molecular markers and advanced therapeutic strategies. N6-methyladenosine (mA), the most prevalent mRNA modification, undergoes dynamic regulation by enzymes referred to as methyltransferases (writers), demethylases (erasers), and effective proteins (readers). Despite lacking methylation activity, RNA-binding motif protein 15 (RBM15), a member of the mA writer family, assumes a crucial role in recruiting the methyltransferase complex (MTC) and binding to mRNA. Although the impact of mA modifications on cancer has garnered widespread attention, RBM15 has been relatively overlooked. This review briefly outlines the structure and operational mechanism, and delineates the unique role of RBM15 in various cancers, shedding light on its molecular basis and providing a groundwork for potential tumor-targeted therapies.
PubMed: 38915367
DOI: 10.3389/fonc.2024.1375942 -
BMC Medicine Jun 2024To combat coronavirus disease 2019 (COVID-19), booster vaccination strategies are important. However, the optimal administration of booster vaccine platforms remains... (Meta-Analysis)
Meta-Analysis
BACKGROUND
To combat coronavirus disease 2019 (COVID-19), booster vaccination strategies are important. However, the optimal administration of booster vaccine platforms remains unclear. Herein, we aimed to assess the benefits and harms of three or four heterologous versus homologous booster regimens.
METHODS
From November 3 2022 to December 21, 2023, we searched five databases for randomised clinical trials (RCT). Reviewers screened, extracted data, and assessed bias risks independently with the Cochrane risk-of-bias 2 tool. We conducted meta-analyses and trial sequential analyses (TSA) on our primary (all-cause mortality; laboratory confirmed symptomatic and severe COVID-19; serious adverse events [SAE]) and secondary outcomes (quality of life [QoL]; adverse events [AE] considered non-serious). We assessed the evidence with the GRADE approach. Subgroup analyses were stratified for trials before and after 2023, three or four boosters, immunocompromised status, follow-up, risk of bias, heterologous booster vaccine platforms, and valency of booster.
RESULTS
We included 29 RCTs with 43 comparisons (12,538 participants). Heterologous booster regimens may not reduce the relative risk (RR) of all-cause mortality (11 trials; RR 0.86; 95% CI 0.33 to 2.26; I 0%; very low certainty evidence); laboratory-confirmed symptomatic COVID-19 (14 trials; RR 0.95; 95% CI 0.72 to 1.25; I 0%; very low certainty); or severe COVID-19 (10 trials; RR 0.51; 95% CI 0.20 to 1.33; I 0%; very low certainty). For safety outcomes, heterologous booster regimens may have no effect on SAE (27 trials; RR 1.15; 95% CI 0.68 to 1.95; I 0%; very low certainty) but may raise AE considered non-serious (20 trials; RR 1.19; 95% CI 1.08 to 1.32; I 64.4%; very low certainty). No data on QoL was available. Our TSAs showed that the cumulative Z curves did not reach futility for any outcome.
CONCLUSIONS
With our current sample sizes, we were not able to infer differences of effects for any outcomes, but heterologous booster regimens seem to cause more non-serious AE. Furthermore, more robust data are instrumental to update this review.
Topics: Humans; COVID-19 Vaccines; Immunization, Secondary; COVID-19; Randomized Controlled Trials as Topic; SARS-CoV-2; Adult; Quality of Life
PubMed: 38915011
DOI: 10.1186/s12916-024-03471-3 -
PloS One 2024Stroke stands as a significant macrovascular complication among individuals with Type 2 diabetes mellitus (T2DM), often resulting in the primary cause of mortality and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Stroke stands as a significant macrovascular complication among individuals with Type 2 diabetes mellitus (T2DM), often resulting in the primary cause of mortality and disability within this patient demographic. Presently, numerous studies have been conducted to investigate the underlying causes of stroke in individuals with T2DM, yet the findings exhibit inconsistencies.
OBJECTIVE
This paper aims to consolidate and summarize the available evidence concerning the influential factors contributing to stroke among patients diagnosed with T2DM.
METHODS
We conducted a comprehensive search across multiple databases, including Cochrane Library, PubMed, Web Of Science, Embase, China Biology Medicine (CBM), China National Knowledge Infrastructure (CNKI), Wanfang and Weipu up to August 2023. Google Scholar was also searched to retrieve gray literature. We calculated odds ratios (OR) and 95% confidence intervals (CI) using Stata software.
RESULTS
Our analysis encompassed 43 observational studies, exploring factors across sociodemographic, biochemical, complications, and hypoglycemic agent categories. The findings identified several risk factors for stroke in patients with T2DM: age, gender, T2DM duration, hypertension, body-mass index (BMI), smoking, Glycated hemoglobin (HbA1c), estimated Glomerular Filtration Rate (eGFR), albuminuria, Triglycerides (TG), Low density lipoprotein cholesterol (LDL-C), Coronary heart disease (CHD), Atrial fibrillation (AF), diabetic retinopathy (DR), Peripheral vascular disease (PVD), and carotid plaque. Conversely, exercise, High density lipoprotein cholesterol (HDL-C), metformin (MET), pioglitazone, and metformin combination therapy emerged as protective factors.
CONCLUSION
This study underscores the multitude of influencing factors contributing to stroke in people with T2DM patients, among which the microvascular complications of T2DM play an most important role. Therefore, we emphasize the importance of screening for microvascular complications in patients with T2DM. However, due to limitations arising from the number of articles reviewed, there remain areas where clarity is lacking. Further research efforts are warranted to expand upon and reinforce our current findings.
Topics: Diabetes Mellitus, Type 2; Humans; Stroke; Risk Factors; Hypoglycemic Agents; Glycated Hemoglobin
PubMed: 38913694
DOI: 10.1371/journal.pone.0305954 -
International Journal of Colorectal... Jun 2024Locally advanced rectal cancer (LARC) typically involves neoadjuvant chemoradiotherapy (nCRT) followed by surgery (total mesorectal excision, TME). While achieving a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Locally advanced rectal cancer (LARC) typically involves neoadjuvant chemoradiotherapy (nCRT) followed by surgery (total mesorectal excision, TME). While achieving a complete pathological response (pCR) is a strong indicator of a positive prognosis, the specific benefits of adjuvant chemotherapy after pCR remain unclear. To address this knowledge gap, we conducted a systematic review and meta-analysis to assess the potential advantages of adjuvant therapy in patients who achieve pCR.
METHODS
In this study, we searched Medline, Embase, and Web of Science databases for relevant research. We focused on binary outcomes, analyzing them using odds ratios (ORs) with 95% confidence intervals (CIs). To account for potential variability between studies, all endpoints were analyzed with DerSimonian and Laird random-effects models. We assessed heterogeneity using the I statistic and employed the R statistical software (version 4.2.3) for all analyses.
RESULTS
Thirty-four studies, comprising 31,558 patients, were included. The outcomes demonstrated a significant difference favoring the AC group in terms of overall survival (OS) (HR 0.75; 95% CI 0.60-0.94; p = 0.015; I = 0%), and OS in 5 years (OR 1.65; 95% CI 1.21-2.24; p = 0.001; I = 39%). There was no significant difference between the groups for disease-free survival (DFS) (HR 0.94; 95% CI 0.76-1.17; p = 0.61; I = 17%), DFS in 5 years (OR 1.19; 95% CI 0.82-1.74; p = 0.36; I = 43%), recurrence-free survival (RFS) (HR 1.10; 95% CI 0.87-1.40; p = 0.39; I = 0%), and relapse-free survival (OR 1.08; 95% CI 0.78-1.51; p = 0.62; I = 0%).
CONCLUSION
This systematic review and meta-analysis found a significant difference in favor of the ACT group in terms of survival after pCR. Therefore, the administration of this treatment as adjuvant therapy should be encouraged in clinical practice.
Topics: Humans; Rectal Neoplasms; Chemotherapy, Adjuvant; Treatment Outcome; Survival Analysis; Disease-Free Survival; Neoadjuvant Therapy
PubMed: 38913175
DOI: 10.1007/s00384-024-04668-x -
Annals of Surgery Open : Perspectives... Jun 2024This study, examining literature up to December 2023, aims to comprehensively assess surgical care for incarcerated individuals, identifying crucial knowledge gaps for... (Review)
Review
OBJECTIVE
This study, examining literature up to December 2023, aims to comprehensively assess surgical care for incarcerated individuals, identifying crucial knowledge gaps for informing future health services research and interventions.
BACKGROUND
The US prison system detains around 2 million individuals, mainly young, indigent males from ethnic and racial minorities. The constitutional right to healthcare does not protect this population from unique health challenges and disparities. The scarcity of literature on surgical care necessitates a systematic review to stimulate research, improve care quality, and address health issues within this marginalized community.
METHODS
A systematic review, pre-registered with the International Prospective Register of Systematic Reviews (CRD42023454782), involved searches in PubMed, Embase, and Web of Science. Original research on surgical care for incarcerated individuals was included, excluding case reports/series (<10 patients), abstracts, and studies involving prisoners of war, plastic surgeries for recidivism reduction, transplants using organs from incarcerated individuals, and nonconsensual surgical sterilization.
RESULTS
Out of 8209 studies screened, 118 met inclusion criteria, with 17 studies from 16 distinct cohorts reporting on surgical care. Predominantly focusing on orthopedic surgeries, supplemented by studies in emergency general, burns, ophthalmology, and kidney transplantation, the review identified delayed hospital presentations, a high incidence of complex cases, and low postoperative follow-up rates. Notable complications, such as nonfusion and postarthroplasty infections, were more prevalent in incarcerated individuals compared with nonincarcerated individuals. Trauma-related mortality rates were similar, despite lower intraabdominal injuries following penetrating abdominal injuries in incarcerated patients.
CONCLUSION
While some evidence suggests inferior surgical care in incarcerated patients, the limited quality of available studies underscores the urgency of addressing knowledge gaps through future research. This is crucial for patients, clinicians, and policymakers aiming to enhance care quality for a population at risk of surgical complications during incarceration and postrelease.
PubMed: 38911628
DOI: 10.1097/AS9.0000000000000434 -
Annals of Surgery Open : Perspectives... Jun 2024To assess the added value of 3-dimensional (3D) vision, including high definition (HD) technology, in laparoscopic surgery in terms of surgeon preference and clinical...
OBJECTIVE
To assess the added value of 3-dimensional (3D) vision, including high definition (HD) technology, in laparoscopic surgery in terms of surgeon preference and clinical outcome.
BACKGROUND
The use of 3D vision in laparoscopic surgery has been suggested to improve surgical performance. However, the added value of 3D vision remains unclear as a systematic review of randomized controlled trials (RCTs) comparing 3D vision including HD technology in laparoscopic surgery is currently lacking.
METHODS
A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines with a literature search up to May 2023 using PubMed and Embase (PROSPERO, CRD42021290426). We included RCTs comparing 3D versus 2-dimensional (2D) vision in laparoscopic surgery. The primary outcome was operative time. Meta-analyses were performed using the random effects model to estimate the pooled effect size expressed in standard mean difference (SMD) with corresponding 95% confidence intervals (CIs). The level of evidence and quality was assessed according to the Cochrane risk of bias tool.
RESULTS
Overall, 25 RCTs with 3003 patients were included. Operative time was reduced by 3D vision (-8.0%; SMD, -0.22; 95% CI, -0.37 to -0.06; = 0.007; n = 3003; 24 studies; = 75%) compared to 2D vision. This benefit was mostly seen in bariatric surgery (-16.3%; 95% CI, -1.28 to -0.21; = 0.006; 2 studies; n = 58; = 0%) and general surgery (-6.7%; 95% CI, -0.34 to -0.01; = 0.036; 9 studies; n = 1056; = 41%). Blood loss was nonsignificantly reduced by 3D vision (SMD, -0.33; 95% CI, -0.68 to 0.017; = 0.060; n = 1830; = 92%). No differences in the rates of morbidity (14.9% vs 13.5%, = 0.644), mortality (0% vs 0%), conversion (0.8% vs 0.9%, = 0.898), and hospital stay (9.6 vs 10.5 days, = 0.078) were found between 3D and 2D vision. In 15 RCTs that reported on surgeon preference, 13 (87%) reported that the majority of surgeons favored 3D vision.
CONCLUSIONS
Across 25 RCTs, this systematic review and meta-analysis demonstrated shorter operative time with 3D vision in laparoscopic surgery, without differences in other outcomes. The majority of surgeons participating in the RCTs reported in favor of 3D vision.
PubMed: 38911624
DOI: 10.1097/AS9.0000000000000415 -
Frontiers in Pediatrics 2024In 2019, 80% of the 7.4 million global child deaths occurred in low- and middle-income countries (LMICs). Global and regional estimates of cause of hospital death and...
In 2019, 80% of the 7.4 million global child deaths occurred in low- and middle-income countries (LMICs). Global and regional estimates of cause of hospital death and admission in LMIC children are needed to guide global and local priority setting and resource allocation but are currently lacking. The study objective was to estimate global and regional prevalence for common causes of pediatric hospital mortality and admission in LMICs. We performed a systematic review and meta-analysis to identify LMIC observational studies published January 1, 2005-February 26, 2021. Eligible studies included: a general pediatric admission population, a cause of admission or death, and total admissions. We excluded studies with data before 2,000 or without a full text. Two authors independently screened and extracted data. We performed methodological assessment using domains adapted from the Quality in Prognosis Studies tool. Data were pooled using random-effects models where possible. We reported prevalence as a proportion of cause of death or admission per 1,000 admissions with 95% confidence intervals (95% CI). Our search identified 29,637 texts. After duplicate removal and screening, we analyzed 253 studies representing 21.8 million pediatric hospitalizations in 59 LMICs. All-cause pediatric hospital mortality was 4.1% [95% CI 3.4%-4.7%]. The most common causes of mortality (deaths/1,000 admissions) were infectious [12 (95% CI 9-14)]; respiratory [9 (95% CI 5-13)]; and gastrointestinal [9 (95% CI 6-11)]. Common causes of admission (cases/1,000 admissions) were respiratory [255 (95% CI 231-280)]; infectious [214 (95% CI 193-234)]; and gastrointestinal [166 (95% CI 143-190)]. We observed regional variation in estimates. Pediatric hospital mortality remains high in LMICs. Global child health efforts must include measures to reduce hospital mortality including basic emergency and critical care services tailored to the local disease burden. Resources are urgently needed to promote equity in child health research, support researchers, and collect high-quality data in LMICs to further guide priority setting and resource allocation.
PubMed: 38910960
DOI: 10.3389/fped.2024.1397232 -
Proceedings (Baylor University. Medical... 2024Colorectal cancer (CRC) presents significant mortality risks, underscoring the urgency of timely diagnosis and intervention. Advanced stages of CRC are managed through...
Colorectal cancer (CRC) presents significant mortality risks, underscoring the urgency of timely diagnosis and intervention. Advanced stages of CRC are managed through chemotherapy, targeted therapy, immunotherapy, radiotherapy, and surgery. Immunotherapy, while effective in bolstering the immune system against cancer cells, often carries toxic side effects, including colitis. This study aimed to evaluate the incidence of colitis in patients with metastatic CRC (mCRC) undergoing various immunotherapy treatments. Through a systematic search of Google Scholar and PubMed databases from inception until November 2023, nine relevant studies were identified. Subgroup analyses revealed a higher incidence of colitis, particularly in patients treated with anti-cytotoxic T-lymphocyte-associated molecule-4 (anti-CTLA-4) and combination therapies compared to monotherapy with programmed cell death receptor-1 (PD-1) or programmed cell death ligand receptor-1 (PDL-1) inhibitors. Notably, naive-treated metastatic CRC patients exhibited elevated colitis incidences compared to those previously treated. In conclusion, anti-CTLA-4 and combination therapies, such as nivolumab plus ipilimumab, were associated with increased colitis occurrences in metastatic CRC patients, highlighting the need for vigilant monitoring and management strategies, especially in immunotherapy-naive individuals.
PubMed: 38910824
DOI: 10.1080/08998280.2024.2342723 -
Cureus May 2024Sepsis is a life-threatening condition that occurs when the body's immune response to infection becomes unregulated, causing organ dysfunction and a heightened risk of... (Review)
Review
Sepsis is a life-threatening condition that occurs when the body's immune response to infection becomes unregulated, causing organ dysfunction and a heightened risk of mortality. Despite increased awareness campaigns, its prevalence escalates, annually afflicting over 1.7 million adults in the United States. This research explores the potential of therapeutic plasma exchange (TPE) in septic shock management, aiming to highlight its capacity to improve patient outcomes and reduce mortality. Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, our comprehensive search across 51,534 studies, using keywords such as plasmapheresis, plasma exchange therapy, therapeutic plasma exchange, septic shock, and reduction in mortality integrated with medical subject headings terms, led to the meticulous selection of six pivotal studies. Through rigorous evaluation with tools such as the revised Cochrane Risk-of-Bias tool, Newcastle-Ottawa Scale, and Assessment of Methodological Quality of Systematic Reviews, we extracted strong evidence supporting TPE's significant impact on decreasing mortality in septic shock patients compared to standard care, as demonstrated in three randomized controlled trials and one cohort study, with an odds ratio (OR) of 0.43 (95% confidence interval (CI) = 0.26-0.72). Additionally, two meta-analyses further validate TPE's effectiveness, showing a mortality reduction with an OR of 0.30 (95% CI = 0.20-0.46). This advantage also extends to critically ill COVID-19 patients, underscoring TPE's crucial role in modulating the coagulation cascade, decreasing sepsis-related complications, and reducing the risk of bleeding and organ failure. Nevertheless, the benefits of TPE must be carefully balanced against potential risks such as hypocalcemia, hypotension, and citrate toxicity, especially in patients with underlying renal or liver issues, emphasizing the importance of shared decision-making. While TPE emerges as a promising therapy, its formal integration into standard care protocols awaits further confirmation, highlighting the critical need for more in-depth research to conclusively determine its efficacy and safety in septic shock management.
PubMed: 38910774
DOI: 10.7759/cureus.60947