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JAMA Network Open Jan 2024The NAPOLI 3 trial showed the superiority of fluorouracil, leucovorin, liposomal irinotecan, and oxaliplatin (NALIRIFOX) over the combination of gemcitabine and... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
The NAPOLI 3 trial showed the superiority of fluorouracil, leucovorin, liposomal irinotecan, and oxaliplatin (NALIRIFOX) over the combination of gemcitabine and nab-paclitaxel (GEM-NABP) as first-line treatment of metastatic pancreatic ductal adenocarcinoma (PDAC). Analyses comparing NALIRIFOX and GEM-NABP with fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) have not yet been reported.
OBJECTIVE
To derive survival, response, and toxic effects data from phase 3 clinical trials and compare NALIRIFOX, FOLFIRINOX, and GEM-NABP.
DATA SOURCES
After a systematic search of PubMed, Scopus, Embase, and American Society of Clinical Oncology and European Society for Medical Oncology meetings' libraries, Kaplan-Meier curves were extracted from phase 3 clinical trials conducted from January 1, 2011, until September 12, 2023.
STUDY SELECTION
Phase 3 clinical trials that tested NALIRIFOX, FOLFIRINOX, or GEM-NABP as first-line treatment of metastatic PDAC and reported overall survival (OS) and progression-free survival (PFS) curves were selected. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses of Individual Participant Data reporting guidelines.
DATA EXTRACTION AND SYNTHESIS
Individual patient OS and PFS data were extracted from Kaplan-Meier plots of original trials via a graphic reconstructive algorithm. Overall response rates (ORRs) and grade 3 or higher toxic effects rates were also collected. A pooled analysis was conducted, and results were validated via a network meta-analysis.
MAIN OUTCOMES AND MEASURES
The primary end point was OS. Secondary outcomes included PFS, ORR, and toxic effects rates.
RESULTS
A total of 7 trials with data on 2581 patients were analyzed, including 383 patients treated with NALIRIFOX, 433 patients treated with FOLFIRINOX, and 1756 patients treated with GEM-NABP. Median PFS was longer in patients treated with NALIRIFOX (7.4 [95% CI, 6.1-7.7] months) or FOLFIRINOX (7.3 [95% CI, 6.5-7.9] months; [HR], 1.21 [95% CI, 0.86-1.70]; P = .28) compared with patients treated with GEM-NABP (5.7 [95% CI, 5.6-6.1] months; HR vs NALIRIFOX, 1.45 [95% CI, 1.22-1.73]; P < .001). Similarly, GEM-NABP was associated with poorer OS (10.4 [95% CI, 9.8-10.8]; months) compared with NALIRIFOX (HR, 1.18 [95% CI, 1.00-1.39]; P = .05], while no difference was observed between FOLFIRINOX (11.7 [95% CI, 10.4-13.0] months) and NALIRIFOX (11.1 [95% CI, 10.1-12.3] months; HR, 1.06 [95% CI, 0.81-1.39]; P = .65). There were no statistically significant differences in ORR among NALIRIFOX (41.8%), FOLFIRINOX (31.6%), and GEM-NABP (35.0%). NALIRIFOX was associated with lower incidence of grade 3 or higher hematological toxic effects (eg, platelet count decreased 1.6% vs 11.8% with FOLFIRINOX and 10.8% with GEM-NABP), but higher rates of severe diarrhea compared with GEM-NABP (20.3% vs 15.7%).
CONCLUSIONS AND RELEVANCE
In this systematic review and meta-analysis, NALIRIFOX and FOLFIRINOX were associated with similar PFS and OS as first-line treatment of advanced PDAC, although NALIRIFOX was associated with a different toxicity profile. Careful patient selection, financial toxic effects consideration, and direct comparison between FOLFIRINOX and NALIRIFOX are warranted.
Topics: Humans; Pancreatic Neoplasms; Irinotecan; Antineoplastic Combined Chemotherapy Protocols; Leucovorin; Oxaliplatin; Gemcitabine; Fluorouracil; Adenocarcinoma
PubMed: 38190183
DOI: 10.1001/jamanetworkopen.2023.50756 -
European Journal of Pediatrics Aug 2023Platelet transfusions (PTx) are the principal approach for treating neonatal thrombocytopenia, a common hematological abnormality affecting neonates, particularly... (Meta-Analysis)
Meta-Analysis Review
Platelet transfusions (PTx) are the principal approach for treating neonatal thrombocytopenia, a common hematological abnormality affecting neonates, particularly preterm infants. However, evidence about the outcomes associated with PTx and whether they provide clinical benefit or harm is lacking. The aim of this systematic review and meta-analysis is to assess the association between PTx in preterm infants and mortality, major bleeding, sepsis, and necrotizing enterocolitis (NEC) in comparison to not transfusing or using different platelet count thresholds for transfusion. A broad electronic search in three databases was performed in December 2022. We included randomized controlled trials, and cohort and case control studies of preterm infants with thrombocytopenia that (i) compared treatment with platelet transfusion vs. no platelet transfusion, (ii) assessed the platelet count threshold for PTx, or (iii) compared single to multiple PTx. We conducted a meta-analysis to assess the association between PTx and mortality, intraventricular hemorrhage (IVH), sepsis, and NEC and, in the presence of substantial heterogeneity, leave-one-out sensitivity analysis was performed. We screened 625 abstracts and 50 full texts and identified 18 reports of 13 eligible studies. The qualitative analysis of the included studies revealed controversial results as several studies showed an association between PTx in preterm infants and a higher risk of mortality, major bleeding, sepsis, and NEC, while others did not present a significant relationship. The meta-analysis results suggest a significant association between PTx and mortality (RR 2.4, 95% CI 1.8-3.4; p < 0.0001), as well as sepsis (RR 4.5, 95% CI 3.7-5.6; p < 0.0001), after a leave-one-out sensitivity analysis. There was also found a significant correlation between PTx and NEC (RR 5.2, 95% CI 3.3-8.3; p < 0.0001). As we were not able to reduce heterogeneity in the assessment of the relationship between PTx and IVH, no conclusion could be taken. Conclusion: Platelet transfusions in preterm infants are associated to a higher risk of death, sepsis, and NEC and, possibly, to a higher incidence of IVH. Further studies are needed to confirm these associations, namely between PTx and IVH, and to define the threshold from which PTx should be given with less harm effect. What is Known: • Platelet transfusions are given to preterm infants with thrombocytopenia either to treat bleeding or to prevent hemorrhage. • Lack of consensual criteria for transfusion. What is New: • A significant association between platelet transfusions and mortality, sepsis, and NEC.
Topics: Infant, Newborn; Humans; Infant, Premature; Hemorrhage; Enterocolitis, Necrotizing; Thrombocytopenia; Sepsis
PubMed: 37258776
DOI: 10.1007/s00431-023-05031-y -
Critical Care (London, England) Nov 2023Bacteria are the main pathogens that cause sepsis. The pathogenic mechanisms of sepsis caused by gram-negative and gram-positive bacteria are completely different, and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Bacteria are the main pathogens that cause sepsis. The pathogenic mechanisms of sepsis caused by gram-negative and gram-positive bacteria are completely different, and their prognostic differences in sepsis remain unclear.
METHODS
The PubMed, Web of Science, Cochrane Library, and Embase databases were searched for Chinese and English studies (January 2003 to September 2023). Observational studies involving gram-negative (G (-))/gram-positive (G (+)) bacterial infection and the prognosis of sepsis were included. The stability of the results was evaluated by sensitivity analysis. Funnel plots and Egger tests were used to check whether there was publication bias. A meta-regression analysis was conducted on the results with high heterogeneity to identify the source of heterogeneity. A total of 6949 articles were retrieved from the database, and 45 studies involving 5586 subjects were included after screening according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Twenty-seven high-quality studies and 18 moderate-quality studies were identified according to the Newcastle‒Ottawa Scale score. There was no significant difference in the survival rate of sepsis caused by G (-) bacteria and G (+) bacteria (OR 0.95, 95% CI 0.70-1.28). Subgroup analysis according to survival follow-up time showed no significant difference. The serum concentrations of C-reactive protein (CRP) (SMD = 0.39, 95% CI 0.02-0.76), procalcitonin (SMD = 1.95, 95% CI 1.32-2.59) and tumor necrosis factor-alpha (TNF-α) (MD = 0.31, 95% CI 0.25-0.38) in the G (-) bacterial infection group were significantly higher than those in the G (+) bacterial infection group, but there was no significant difference in IL-6 (SMD = 1.33, 95% CI - 0.18-2.84) and WBC count (MD = - 0.15, 95% CI - 0.96-00.66). There were no significant differences between G (-) and G (+) bacteria in D dimer level, activated partial thromboplastin time, thrombin time, international normalized ratio, platelet count, length of stay or length of ICU stay. Sensitivity analysis of the above results indicated that the results were stable.
CONCLUSION
The incidence of severe sepsis and the concentrations of inflammatory factors (CRP, PCT, TNF-α) in sepsis caused by G (-) bacteria were higher than those caused by G (+) bacteria. The two groups had no significant difference in survival rate, coagulation function, or hospital stay. The study was registered with PROSPERO (registration number: CRD42023465051).
Topics: Humans; Prognosis; Tumor Necrosis Factor-alpha; Sepsis; Bacterial Infections; Gram-Negative Bacteria; C-Reactive Protein; Bacteria; Gram-Positive Bacteria
PubMed: 38037118
DOI: 10.1186/s13054-023-04750-w -
The Journal of Maternal-fetal &... Dec 2023Using straightforward and accessible haematological parameters platelet/lymphocyte ratio (PLR) to diagnose preeclampsia (PE) early and precisely remains a challenge.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Using straightforward and accessible haematological parameters platelet/lymphocyte ratio (PLR) to diagnose preeclampsia (PE) early and precisely remains a challenge. Although several clinical studies suggested that PLR is able to diagnose PE, there has been no systematic evaluation of the diagnostic utility.
OBJECTIVES
To examine the diagnostic accuracy and potential applicability of PLR in the detection of PE.
STUDY DESIGN
Seven databases were searched using a combination of PLR and PE terms, and all potentially pertinent studies were systematically searched up to March 2023. All potentially relevant studies both prospective and retrospective were reviewed. To assess the diagnostic value of PLR for PE, pooled sensitivity (Sen), specificity (Spe), diagnostic odds ratio (DOR) and area under the summary receiver operating characteristic curve (SROC-AUC) were calculated.
RESULTS
Thirteen studies were enrolled in the meta-analysis. In the second and third trimesters, the PLR suggested a diagnostic value for PE with a pooled Sen of 54.7% [95% confidence interval (CI) (51.7, 57.6)], Spe of 77.8% [95% CI (75.5, 80.0)], + LR of 2.457 [95% CI (1.897, 3.182)], -LR of 0.584 [95% CI (0.491, 0.695)], DOR of 4.434 [95% CI (3.071, 6.402)], the SROC-AUC of 0.7296 and the standard error (SE) of 0.0370.
CONCLUSION
For the diagnosis of PE, PLR has a limited sensitivity but an acceptable specificity, and showed moderate accuracy. Further using complete blood count (CBC) indicators such as PLR alone or in combination to diagnose and predict PE could reduce healthcare costs and improve maternal and child prognosis.
Topics: Child; Female; Humans; Pregnancy; Lymphocytes; Pre-Eclampsia; Prospective Studies; Retrospective Studies; ROC Curve; Sensitivity and Specificity
PubMed: 37455131
DOI: 10.1080/14767058.2023.2234540 -
Asian Pacific Journal of Cancer... Dec 2023Allogeneic hematopoietic cell transplantation (allo-HCT) serves as a potentially curative intervention for various hematologic disorders. However, its utility can be...
INTRODUCTION
Allogeneic hematopoietic cell transplantation (allo-HCT) serves as a potentially curative intervention for various hematologic disorders. However, its utility can be limited by the emergence of chronic graft-versus-host disease (cGVHD). The clinical manifestations of cGVHD result from a complex immune response characterized by the involvement of both B and T cells. Ibrutinib, a pharmacological agent, acts as an inhibitor of Bruton's tyrosine kinase (BTK) pathway, which becomes activated through the B-cell receptor and regulates B-cell survival. By exerting inhibitory effects on both BTK and inhibitor of interleukin-2 inducible T-cell kinase (ITK), ibrutinib exhibits promise as a therapeutic approach for managing cGVHD. Ibrutinib may be considered as a viable treatment option for active cGVHD in cases where patients exhibit an inadequate response to corticosteroid-based therapies. This systematic review seeks to assess the efficacy and safety of ibrutinib in the context of cGVHD patient management.
METHOD
We incorporated search engines from PubMed, Embase, Cochrane Library, Scopus, Web of Science, and ClinicalTrials.gov. The study was performed following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 and Assessing The Methodological Quality of Systematic Review (AMSTAR). We used Risk of Bias- 2 (RoB-2) tool for assess the risk of bias in randomized controlled studies (RCTs) and Newcastle Ottawa Scale (NOS) for observational and open-label studies.
RESULTS
A total of 7 studies were included in this study consisted of four open-label studies, two retrospective cohort studies, and one RCT study. These studies compared Ibrutinitib with standard therapies. Two studies investigated the pediatric population, and five studies investigated the adult population. Overall, these studies reported the overall response rate (ORR) of ibrutinib for cGVHD were 54%-78%. The results showed that in pediatric patients, the ORR were 54-78%. The results also showed that in adult patients, the ORR were 67%-76%. The most common adverse effects observed across the seven studies included pyrexia, diarrhea, abdominal pain, cough, nausea, stomatitis, vomiting, headache, bleeding and bruising, infection, muscle aches, fatigue, oral bleeding, elevated transaminases, lower gastrointestinal bleeding, persistent dizziness, sepsis, pneumonia, reduced platelet count, exhaustion, sleeplessness, peripheral edema, and fatigue.
CONCLUSION
The majority of studies have indicated that ibrutinib exhibits a high ORR and provides long-lasting responses, while also having manageable side effects.
Topics: Adult; Humans; Child; Bronchiolitis Obliterans Syndrome; Graft vs Host Disease; B-Lymphocytes; Fatigue
PubMed: 38156834
DOI: 10.31557/APJCP.2023.24.12.4025 -
Le Infezioni in Medicina 2023Leptospirosis is a zoonotic bacterial infection with significant mortality and morbidity, especially in resource-limited settings. This systematic review aimed to study... (Review)
Review
INTRODUCTION
Leptospirosis is a zoonotic bacterial infection with significant mortality and morbidity, especially in resource-limited settings. This systematic review aimed to study the clinical profile and outcome of patients with leptospirosis in India.
METHODOLOGY
All articles up to 02.08.2022 were searched using the two databases, PubMed and Scopus. A total of 542 articles were found using the search terms related to 'leptospirosis' and 'India'. After two rounds of screening, 55 articles were included. The data were collected on epidemiology, clinical features, laboratory features and treatment of patients with leptospirosis.
RESULTS
Most cases of leptospirosis were reported from the coastal belt. A large percentage of patients were identified as farmers, and exposure to rainfall was identified as an important risk factor. Fever was present in 97%, and conjunctival suffusion was present in 35% of cases. Haemoptysis, gastrointestinal bleeding, and haematuria were present in 5%, 5% and 12% of patients, respectively. Liver and kidney were involved in 34% and 35% of the patients, respectively. The average haemoglobin, leucocyte count and platelet count across various studies ranged from 9.6-12.5 grams/dl, 8.8-11.3 thousand/μl and 20-130 thousand/μl, respectively. Treatment details were sparsely available in some studies, with penicillin, ceftriaxone, and doxycycline used commonly. The pooled mortality across various studies was calculated as 11% [95% CI-8-15%, I=93%, P<0.001].
CONCLUSIONS
Leptospirosis is associated with significant mortality in Indian settings. There is a need for studies focussing on treatment modalities.
PubMed: 37701390
DOI: 10.53854/liim-3103-4 -
Public Health Nov 2023The study aimed to identify, appraise and update evidence on the association between cold temperatures (i.e. <18°C) within homes (i.e. dwellings) and health and... (Review)
Review
OBJECTIVE
The study aimed to identify, appraise and update evidence on the association between cold temperatures (i.e. <18°C) within homes (i.e. dwellings) and health and well-being outcomes.
STUDY DESIGN
This study was a systematic review.
METHODS
Seven databases (MEDLINE, Embase, Cochrane Database of Systematic Reviews, CINAHL, APA PsycInfo, Applied Social Sciences Index and Abstracts, Coronavirus Research Database) were searched for studies published between 2014 and 2022, which explored the association between cold indoor temperatures and health and well-being outcomes. Studies were limited to those conducted in temperate and colder climates due to the increased risk of morbidity and mortality during winter in those climatic zones. Studies were independently quality assessed using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies.
RESULTS
Of 1209 studies, 20 were included for review. Study outcomes included cardiovascular (blood pressure, electrocardiogram abnormalities, blood platelet count), respiratory (chronic obstructive pulmonary disease symptoms, respiratory viral infection), sleep, physical performance and general health. Seventeen studies found exposure to cold indoor temperatures was associated with negative effects on health outcomes studied. Older individuals and those with chronic health problems were found to be more vulnerable to negative health outcomes.
CONCLUSION
Evidence suggests that indoor temperatures <18°C are associated with negative health effects. However, the evidence is insufficient to allow clear conclusions regarding outcomes from specific temperature thresholds for different population groups. Significant gaps in the current evidence base are identified, including research on the impacts of cold indoor temperatures on mental health and well-being, studies involving young children, and the long-term health effects of cold indoor temperatures.
Topics: Humans; Cold Temperature; Housing; Health Status
PubMed: 37820536
DOI: 10.1016/j.puhe.2023.09.006 -
Ecancermedicalscience 2024Gallbladder cancer is a rare malignancy characterised by poor survival with lack of durable response to treatment. Thus, novel biomarkers are needed to prognosticate... (Review)
Review
BACKGROUND
Gallbladder cancer is a rare malignancy characterised by poor survival with lack of durable response to treatment. Thus, novel biomarkers are needed to prognosticate patients. This systematic review and meta-analysis sought to examine the role of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, platelet count (PC) and serum immune inflammation index in predicting the survival of patients with gallbladder cancer.
MATERIALS AND METHODS
A systematic search was done using PubMed, Cochrane, ClinicalTrials.gov and Google Scholar for articles published from inception until 8 February 2022. Hazard ratios (HR) with 95% confidence intervals (CI) were pooled and subgroup analyses were conducted according to treatment, region and cut-offs. The primary outcome of interest was overall survival (OS). Data were summarised using RevMan version 5.4.
RESULTS
Twenty studies comprising 5,183 patients were included in the analysis. High neutrophil-lymphocyte ratio (HR 1.72, 95% CI 1.47-2.02), platelet-lymphocyte ratio (HR 1.51, 95% CI 1.33-1.72), monocyte-lymphocyte ratio (HR 1.96, 95% CI 1.46-1.64), PC (HR 1.20, 95% CI 1.02-1.40) and serum inflammation index (HR 1.73, 95% CI 1.36-2.18) were all associated with worse survival. The association was consistent across most subgroups on race and cut-offs with a trend towards poor survival for PC above 252.5.
CONCLUSION
High neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, monocyte-lymphocyte ratio, PC and SII are associated with worse OS in gallbladder cancer and are potential biomarkers for prognostication. Prospective studies are recommended to further evaluate their use.
PubMed: 38425767
DOI: 10.3332/ecancer.2024.1660 -
Oncology (Williston Park, N.Y.) Dec 2023Purpose To study the potential utility of danazol for treating patients with myelodysplastic syndromes, with a focus on efficacy and adverse effects (AEs). Methods... (Review)
Review
Purpose To study the potential utility of danazol for treating patients with myelodysplastic syndromes, with a focus on efficacy and adverse effects (AEs). Methods MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus were searched for relevant publications from inception June 1, 1950, until June 28, 2022. The studies were screened by title and abstract, followed by full-text screening. The quality of the included studies was assessed via a prespecified set of questionnaires. Data on the efficacy measures and adverse outcomes were extracted and included in a descriptive summary. Results Nine studies consisting of 246 participants were included in our review. The overall quality of the included studies was fair. The age of the participants ranged from 61 to 78 years. In all 9 studies, more male patients had been enrolled than female patients. Overall, a proportion of patients in all the studies reported a desired major response to a danazol dose of 400 to 800 mg/day. Few studies did not observe any improvement in the platelet count. Elevated liver enzyme levels, weight gain, headache, dermatitis, and weakness were the most common AEs observed. One study reported a fatal intracerebral hemorrhage in 1 participant. Conclusions Danazol has been effective in increasing platelet count and hemoglobin level. Despite a few AEs, danazol is a safe drug for the treatment of patients with myelodysplastic syndromes.
Topics: Aged; Female; Humans; Male; Middle Aged; Danazol; Myelodysplastic Syndromes
PubMed: 38133562
DOI: 10.46883/2023.25921009 -
Frontiers in Endocrinology 2023To evaluate the effects of ovarian injection of autologous platelet rich plasma (aPRP) on patients with poor ovarian responder (POR) based on the existing clinical... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the effects of ovarian injection of autologous platelet rich plasma (aPRP) on patients with poor ovarian responder (POR) based on the existing clinical evidence.
METHODS
According to systematic review and meta-analysis, we comprehensively searched nine databases established as of September 6, 2023, and evaluated the impact of ovarian PRP infusion on poor ovarian responder. The research results include serum follicle-stimulating hormone(FSH) and anti-Mullerian hormone(AMH) levels, antral Follicle Count(AFC), oocyte number, and embryo number. The Newcastle Ottawa Scale (NOS) was used to evaluate the quality of inclusion in trials.
RESULTS
Add up to 10 studies consisting of 793 participants were included in the meta-analysis. A review of existing evidence showed that intraovarian injection of PRP has significant therapeutic effects in increasing levels of anti-Müllerian hormone (AMH) (SMD=0.44,95% CI [0.07,0.81], p=0.02), antral follicle count (AFC) (MD=1.15,95% CI [0.4,1.90], p=0.003), oocyte count (MD=0.91, 95% CI [0.40, 1.41], p=0.0004), and embryo number (MD=0.78, 95% CI [0.5,1.07], p<0.0001). We compared the relevant data of patients before and after treatment after 2 months of intervention. It can be seen that ovarian injection of PRP treatment for 2 months has better effects in reducing FSH levels, increasing AMH levels, increasing antral follicle count, and increasing the number of oocytes and embryos (p<0.05). When the dose of PRP injected into each ovary was ≥ 4ml, there was also a significant correlation (p<0.05) with improving the number of AFC, oocytes and embryos. Significant heterogeneity existed among the studies.
CONCLUSION
The pooled results suggest that intra-ovarian injection of PRP can promote ovarian regeneration and improve the reproductive outcomes of patients with ovarian dysfunction. This therapy may have significant clinical potential in improving sex hormone levels, increasing AFC, oocyte count, and embryo count. However, this findings still requires more rigorous and extensive trials worldwide to determine the value of intra-ovarian injection of PRP in POR patients.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk, Identifier CRD42023451232.
Topics: Female; Humans; Ovary; Fertilization in Vitro; Anti-Mullerian Hormone; Ovulation Induction; Follicle Stimulating Hormone; Follicle Stimulating Hormone, Human; Platelet-Rich Plasma
PubMed: 38155954
DOI: 10.3389/fendo.2023.1292168