Association between neural stem/progenitor cells and biomaterials in spinal cord injury therapies: A systematic review and network meta-analysis.

Spinal cord injury (SCI) is associated with substantial healthcare challenges, frequently resulting in enduring sensory and motor deficits alongside various chronic complications. While advanced regenerative therapies have shown promise in preclinical research, their translation into clinical application has been limited. In response, this study utilized a comprehensive network meta-analysis to evaluate the effectiveness of neural stem/progenitor cell (NSPC) transplantation across animal models of SCI. We analyzed 363 outcomes from 55 distinct studies, categorizing the treatments into NSPCs alone (cell only), NSPCs with scaffolds (cell + scaffold), NSPCs with hydrogels (cell + hydrogel), standalone scaffolds (scaffold), standalone hydrogels (hydrogel), and control groups. Our analysis demonstrated significant enhancements in motor recovery, especially in gait function, within the NSPC treatment groups. Notably, the cell only group showed considerable improvements (standardized mean difference [SMD], 2.05; 95 % credible interval [CrI]: 1.08 to 3.10, p < 0.01), as did the cell + scaffold group (SMD, 3.73; 95 % CrI: 2.26 to 5.22, p < 0.001) and the cell + hydrogel group (SMD, 3.37; 95 % CrI: 1.02 to 5.78, p < 0.05) compared to controls. These therapeutic combinations not only reduced lesion cavity size but also enhanced neuronal regeneration, outperforming the cell only treatments. By integrating NSPCs with supportive biomaterials, our findings pave the way for refining these regenerative strategies to optimize their potential in clinical SCI treatment. Although there is no overall violation of consistency, the comparison of effect sizes between individual treatments should be interpreted in light of the inconsistency. STATEMENT OF SIGNIFICANCE: This study presents a comprehensive network meta-analysis exploring the efficacy of neural stem cell (NSC) transplantation, with and without biomaterials, in animal models of spinal cord injury (SCI). We demonstrate that NSCs, particularly when combined with biomaterials like scaffolds or hydrogels, significantly enhance motor and histological recovery post-SCI. These findings underscore the potential of NSC-based therapies, augmented with biomaterials, to advance SCI treatment, offering new insights into regenerative strategies that could significantly impact clinical practices.

Magnetic Resonance Imaging in Prostate Cancer Screening: A Systematic Review and Meta-Analysis.

Importance: Prostate magnetic resonance imaging (MRI) is increasingly integrated within the prostate cancer (PCa) early detection pathway. Objective: To systematically evaluate the existing evidence regarding screening pathways incorporating MRI with targeted biopsy and assess their diagnostic value compared with prostate-specific antigen (PSA)-based screening with systematic biopsy strategies. Data Sources: PubMed/MEDLINE, Embase, Cochrane/Central, Scopus, and Web of Science (through May 2023). Study Selection: Randomized clinical trials and prospective cohort studies were eligible if they reported data on the diagnostic utility of prostate MRI in the setting of PCa screening. Data Extraction: Number of screened individuals, biopsy indications, biopsies performed, clinically significant PCa (csPCa) defined as International Society of Urological Pathology (ISUP) grade 2 or higher, and insignificant (ISUP1) PCas detected were extracted. Main Outcomes and Measures: The primary outcome was csPCa detection rate. Secondary outcomes included clinical insignificant PCa detection rate, biopsy indication rates, and the positive predictive value for the detection of csPCa. Data Synthesis: The generalized mixed-effect approach with pooled odds ratios (ORs) and random-effect models was used to compare the MRI-based and PSA-only screening strategies. Separate analyses were performed based on the timing of MRI (primary/sequential after a PSA test) and cutoff (Prostate Imaging Reporting and Data System [PI-RADS] score ≥3 or ≥4) for biopsy indication. Results: Data were synthesized from 80 114 men from 12 studies. Compared with standard PSA-based screening, the MRI pathway (sequential screening, PI-RADS score ≥3 cutoff for biopsy) was associated with higher odds of csPCa when tests results were positive (OR, 4.15; 95% CI, 2.93-5.88; P ≤ .001), decreased odds of biopsies (OR, 0.28; 95% CI, 0.22-0.36; P ≤ .001), and insignificant cancers detected (OR, 0.34; 95% CI, 0.23-0.49; P = .002) without significant differences in the detection of csPCa (OR, 1.02; 95% CI, 0.75-1.37; P = .86). Implementing a PI-RADS score of 4 or greater threshold for biopsy selection was associated with a further reduction in the odds of detecting insignificant PCa (OR, 0.23; 95% CI, 0.05-0.97; P = .048) and biopsies performed (OR, 0.19; 95% CI, 0.09-0.38; P = .01) without differences in csPCa detection (OR, 0.85; 95% CI, 0.49-1.45; P = .22). Conclusion and relevance: The results of this systematic review and meta-analysis suggest that integrating MRI in PCa screening pathways is associated with a reduced number of unnecessary biopsies and overdiagnosis of insignificant PCa while maintaining csPCa detection as compared with PSA-only screening.

Current updates relating to treatment for interstitial cystitis/bladder pain syndrome: systematic review and network meta-analysis.

BACKGROUND: Despite the publication of several meta-analyses regarding the efficacy of certain therapies in helping individuals with interstitial cystitis (IC) / bladder pain syndrome (BPS), these have not provided a comprehensive review of therapeutic strategies. The study aimed to determine the efficacy of various therapies for IC/BPS and identify potential moderating factors using randomized controlled trials (RCTs). METHODS: We queried the PubMed, Cochrane, and Embase databases to identify prospective RCTs using inclusion criteria: 1) patients diagnosed with IC, 2) interventions included relevant treatments, 3) comparisons were a specified control or placebo, 4) outcomes were mean differences for individual symptoms and structured questionnaires. The pairwise meta-analysis and network meta-analysis (NMA) were performed to compare the treatments used in IC/BPS. Hedges' g standardized mean differences (SMDs) were used for improvement in all outcomes using random-effects models. Efficacy outcomes included individual symptoms such as pain, frequency, urgency, and nocturia, as well as structured questionnaires measuring IC/BPS symptoms. RESULTS: A comprehensive literature search was conducted which identified 70 RCTs with 3,651 patients. The analysis revealed that certain treatments, such as instillation and intravesical injection, showed statistically significant improvements in pain and urgency compared to control or placebo groups in traditional pairwise meta-analysis. However, no specific treatment demonstrated significant improvement in all outcomes measured in the NMA. The results of moderator analyses to explore influential variables indicated that increasing age was associated with increased nocturia, while longer follow-up periods were associated with decreased frequency. CONCLUSION: This systematic review and meta-analysis provide insights into the efficacy of various treatments for IC. Current research suggests that a combination of therapies may have a positive clinical outcome for patients with IC, despite the fact that treatment for this condition is not straightforward. TRIAL REGISTRATION: PROSPERO CRD42022384024.

Increased risk of hearing loss associated with macrolide use: a systematic review and meta-analysis.

The increased risk of hearing loss with macrolides remains controversial. We aimed to systematically review and meta-analyze data on the clinical risk of hearing loss, tinnitus, and ototoxicity following macrolide use. A systematic search was conducted across PubMed, MEDLINE, Cochrane, and Embase databases from database inception to May 2023. Medical Subject Heading (MeSH) terms and text keywords were utilized, without any language restrictions. In addition to the electronic databases, two authors manually and independently searched for relevant studies in the US and European clinical trial registries and Google Scholar. Studies that involved (1) patients who had hearing loss, tinnitus, or ototoxicity after macrolide use, (2) intervention of use of macrolides such as azithromycin, clarithromycin, erythromycin, fidaxomicin, roxithromycin, spiramycin, and/or telithromycin, (3) comparisons with specified placebos or other antibiotics, (4) outcomes measured as odds ratio (OR), relative risk (RR), hazard ratio (HR), and mean difference for ototoxicity symptoms using randomized control trial (RCT)s and observational studies (case-control, cross-section, and cohort studies) were included. Data extraction was performed independently by two extractors, and a crosscheck was performed to identify any errors. ORs along with their corresponding 95% confidence intervals (CIs) were estimated using random-effects models. The Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guidelines for RCTs and Meta-Analysis of Observational Studies in Epidemiology guidelines for observational studies were followed. We assessed the hearing loss risk after macrolide use versus controls (placebos and other antibiotics). Based on data from 13 studies including 1,142,021 patients (n = 267,546 for macrolide and n = 875,089 for controls), the overall pooled OR was 1.25 (95% CI 1.07-1.47). In subgroup analysis by study design, the ORs were 1.37 (95% CI 1.08-1.73) for RCTs and 1.33 (95% CI 1.24-1.43) for case-control studies, indicating that RCT and case-control study designs showed a statistically significant higher risk of hearing loss. The group with underlying diseases such as multiple infectious etiologies (OR, 1.16 [95% CI 0.96-1.41]) had a statistically significant lower risk than the group without (OR, 1.53 [95% CI 1.38-1.70] P = .013). The findings from this systematic review and meta-analysis suggest that macrolide antibiotics increase the risk of hearing loss and that healthcare professionals should carefully consider this factor while prescribing macrolides.

The Efficacy and Safety of Metastasis-directed Therapy in Patients with Prostate Cancer: A Systematic Review and Meta-analysis of Prospective Studies.

CONTEXT: Despite the lack of level 1 evidence, metastasis-directed therapy (MDT) is used widely in the management of metastatic prostate cancer (mPCa) patients. Data are continuously emerging from well-designed prospective studies. OBJECTIVE: To summarise and report the evidence on oncological and safety outcomes of MDT in the management of mPCa patients. EVIDENCE ACQUISITION: We searched the PubMed, Scopus, and Web of Science databases for prospective studies assessing progression-free survival (PFS), local control (LC), androgen deprivation therapy (ADT)-free survival (ADT-FS), overall survival (OS), and/or adverse events (AEs) in mPCa patients treated with MDT. A meta-analysis was performed for 1- and 2-yr PFS, LC, ADT-FS, OS, and rate of AEs. Meta-regression and sensitivity analysis were performed to account for heterogeneity and identify moderators. EVIDENCE SYNTHESIS: We identified 22 prospective studies (n = 1137), including two randomised controlled trials (n = 116). Two studies were excluded from the meta-analysis (n = 120). The estimated 2-yr PFS was 46% (95% confidence interval [CI]: 36-56%) or 42% (95% CI: 33-52%) after excluding studies using biochemical or ADT-related endpoints. The estimated 2-yr LC, ADT-FS, and OS were 97% (95% CI: 94-98%), 55% (95% CI: 44-65%), and 97% (95% CI: 95-98%), respectively. Rates of treatment-related grade 2 and ≥3 AEs were 2.4% (95% CI: 0.2-7%) and 0.3% (95% CI: 0-1%), respectively. CONCLUSIONS: MDT is a promising treatment strategy associated with favourable PFS, excellent LC, and a low toxicity profile that allows oligorecurrent hormone-sensitive patients to avoid or defer ADT-related toxicity. Integration of MDT with other therapies offers a promising research direction, in particular, in conjunction with systemic treatments and as a component of definitive care for oligometastatic PCa. However, in the absence of randomised trials, using MDT for treatment intensification remains an experimental approach, and the impact on OS is uncertain. PATIENT SUMMARY: Direct treatment of metastases is a promising option for selected prostate cancer patients. It can delay hormone therapy and is being investigated as a way of intensifying treatment at the expense of manageable toxicity.

Unveiling the Therapeutic Potential and Healthcare Applications of Marine Therapy: A Systematic Review with Meta-Analysis and Meta-Regression.

This study was conducted to estimate the effectiveness of marine-derived resources for treating specific diseases, as well as identify the most effective methods for applying such resources in therapeutic applications. Bibliographic databases (PubMed, Embase, and Cochrane) were searched from their inception until May 2023 using Medical Subject Headings terms and text keywords related to seawater, mineral water, or ocean therapy. Fifteen eligible studies were included, involving 1325 participants aged 42.7-63.0 years. In the subgroup analysis based on treatment type, the mean difference was -1.581 (95% CI: -1.889, -1.274) for seawater with sun exposure and -1.210 (95% CI: -1.417, -1.002) for seawater with sun exposure, mud pack application, and sulfur pool therapy. The pooled standardized mean difference was calculated for different outcomes; the results were -1.110 (95% CI: -3.028, 0.806) for osteoarthritis severity, -0.795 (95% CI: -0.982, -0.607) for arthritis pain, -1.623 (95% CI: -2.036, -1.209) for fibromyalgia pain, and -1.498 (95% CI: -1.888, -1.108) for quality of life. Marine therapy is, therefore, promising for treating chronic skin issues, easing musculoskeletal discomfort, and enhancing the quality of life among patients with musculoskeletal pain.

Diagnostic Accuracy of Liquid Biomarkers for Clinically Significant Prostate Cancer Detection: A Systematic Review and Diagnostic Meta-analysis of Multiple Thresholds.

CONTEXT: Many liquid biomarkers have entered clinical practice with the praise to improve the detection of clinically significant prostate cancer (csPCa), helping avoid unnecessary prostate biopsies. OBJECTIVE: We aimed to assess the diagnostic accuracy of multianalyte biomarkers for csPCa detection using multiple thresholds. EVIDENCE ACQUISITION: A comprehensive literature search was done through PubMed, Web of Science, and Scopus in March 2023 for prospective and retrospective studies reporting the diagnostic performance of liquid biomarkers for detecting csPCa. The outcomes of interest were the diagnostic performance of liquid biomarkers for csPCa detection and identification of optimal thresholds for each biomarker. EVIDENCE SYNTHESIS: Overall, 49 studies were eligible for this meta-analysis. Using each representative threshold based on the Youden Index, the pooled sensitivity and specificity for detecting csPCa were 0.85 and 0.37 for prostate cancer gene 3 (PCA3), 0.85 and 0.52 for prostate health index (PHI), 0.87 and 0.58 for four kallikrein (4K), 0.82 and 0.56 for SelectMDx, 0.85 and 0.54 for ExoDx, and 0.82 and 0.59 for mi prostate score (MPS), respectively. The diagnostic odds ratio was highest for 4K (8.84), followed by MPS (7.0) and PHI (6.28). According to the meta-analysis incorporating multiple thresholds, the corresponding sensitivity was 0.77 for 4K, 0.69 for PHI, and 0.63 for PCA3; specificity was 0.72 for PHI, 0.70 for 4K, and 0.69 for PCA3. CONCLUSIONS: Regarding the detection of csPCa, 4K had the highest diagnostic performance among the commercial liquid biomarkers. Based on the optimal thresholds calculated by the present meta-analysis, 4K had the highest sensitivity and PHI had the highest specificity for detecting csPCa. Nevertheless, clinical decision-making requires combination strategies between liquid and imaging biomarkers. PATIENT SUMMARY: Novel biomarkers for prostate cancer detection were useful for more accurate diagnosis of clinically significant prostate cancer to avoid unnecessary biopsies.

Oral Nutritional Supplements Reduce Body Weight Loss after Gastrectomy in Patients with Gastric Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

This systematic review and meta-analysis aimed to summarize the effects of oral nutritional supplements (ONSs) on body weight loss (BWL) after gastrectomy. A systematic search was conducted across the PubMed, Cochrane, and Embase databases through May 2023. The study inclusion criteria were as follows: (1) studies on interventions including ONSs after gastrectomy in patients with gastric cancer; (2) studies in which comparisons were specified according to standard, regular, or usual postoperative diets; and (3) randomized controlled trial studies including outcomes measured as mean differences in BWL. The data were pooled using the random-effects model and expressed as mean differences with 95% confidence intervals (CI). Based on data from seven studies including 1743 patients (891 for ONSs and 852 for the control), the overall pooled mean difference was 0.848 (95% CI: 0.466 to 1.230) and the Higgins I2 value was 86.0%. This systematic review and meta-analysis is the first study to show that ONSs are significantly associated with reducing BWL, compared with standard diets, after gastrectomy in patients with gastric cancer. Furthermore, we found that ONSs were more effective in patients with lower nutritional kilocalorie intake after gastrectomy.

Impact of performance status on efficacy of systemic therapy for prostate cancer: a meta-analysis.

OBJECTIVE: To evaluate the efficacy of systemic therapies in patients with worse performance status (PS) treated for high-risk non-metastatic prostate cancer (PCa), metastatic hormone-sensitive PCa (mHSPC), and non-metastatic/metastatic castration-resistant PCa (nmCRPC/mCRPC), as there is sparse pooled data showing the effect of PS on oncological outcomes in patients with PCa. METHODS: Three databases were queried in June 2022 for randomised controlled trials (RCTs) analysing patients with PCa treated with systemic therapy (i.e., adding androgen receptor signalling inhibitor [ARSI] or docetaxel [DOC] to androgen-deprivation therapy [ADT]). We analysed the oncological outcomes of patients with PCa with worse PS, defined as Eastern Cooperative Oncology Group PS ≥ 1, treated with combination therapies and compared these to patients with good PS. The main outcomes of interest were overall survival (OS), metastasis-free survival (MFS), and progression-free survival. RESULTS: Overall, 25 and 18 RCTs were included for systematic review and meta-analyses/network meta-analyses, respectively. In all clinical settings, combination systemic therapies significantly improved OS in patients with worse PS as well as in those with good PS, while the MFS benefit from ARSI in the nmCRPC setting was more pronounced in patients with good PS than in those with worse PS (P = 0.002). Analysis of treatment ranking in patients with mHSPC revealed that triplet therapy had the highest likelihood of improved OS irrespective of PS; specifically, adding darolutamide to DOC + ADT had the highest likelihood of improved OS in patients with worse PS. Analyses were limited by the small proportion of patients with a PS ≥ 1 (19%-28%) and that the number of PS 2 was rarely reported. CONCLUSIONS: Among RCTs, novel systemic therapies seem to benefit the OS of patients with PCa irrespective of PS. Our findings suggest that worse PS should not discourage treatment intensification across all disease stages.

Effect of olive oil phenols on oxidative stress biomarkers: A systematic review and dose-response meta-analysis of randomized clinical trials.

The phenolic content of olive oil has a role in cardiovascular protection. Some clinical trial studies demonstrated that phenolic compounds of olive oil have antioxidant activity which can protect macronutrients from oxidative damages. The aim of this study was to summarize the results of clinical trials which assessed the effects of high- versus low-phenol olive oil on oxidative stress biomarkers levels. We searched Scopus, PubMed, Web of Science, Google Scholar, ProQuest, and Embase up to July 2021. Eight clinical trials which evaluated the effect of the phenolic content of olive oil on oxidized-LDL (ox-LDL), malondialdehyde (MDA), or ferric-reducing ability of plasma (FRAP) were included the meta analysis. A significant decrease was observed in ox-LDL level (WMD: -0.29 U/L; 95% CI: -0.51, -0.07) and MDA (WMD: -1.82 µmoL/L; 95% CI: -3.13, -0.50). However, after subgroup analysis for MDA, the result was not significant for not serious limitation (SMD: -0.05, 95% CI: -0.35 to 0.24), but significant for serious limitation (SMD: -3.64, 95% CI: -4.29 to -2.99). Also, no significant change was found in FRAP (WMD: 0.0 mmoL/L; 95% CI: -0.03, 0.04) level. Dose-response analysis indicated a significant linear relationship between the phenolic content of olive oil and ox-LDL. The present study showed some beneficial effects of high-phenol compared with low-phenol olive oil on ox-LDL and MDA levels. According to the meta-regression analysis along with the increasing phenolic content of olive oil, a reduction in oxidative stress biomarkers was observed.

Comparative efficacies of 13 surgical interventions for primary congenital glaucoma in children: a network meta-analysis of randomized clinical trials.

BACKGROUND: Timely and proper intraocular pressure (IOP) management is vital to the prevention of visual impairment in children with primary congenital glaucoma (PCG). Although various surgical interventions have been proposed, no well-founded evidence exists on their comparative efficacies. We aimed to compare the efficacies of surgical interventions for PCG. METHODS: We searched relevant sources up to 4 April 2022. Randomized controlled trials (RCTs) entailing surgical interventions for PCG in children were identified. A network meta-analysis (NMA) was performed, comparing 13 surgical interventions: Conventional partial trabeculotomy ([CPT] control), 240-degree trabeculotomy, Illuminated microcatheter-assisted circumferential trabeculotomy (IMCT), Viscocanalostomy, Visco-circumferential-suture-trabeculotomy, Goniotomy, Laser goniotomy, Kahook dual blade ab-interno trabeculectomy, Trabeculectomy with mitomycin C, Trabeculectomy with modified scleral bed, Deep sclerectomy, Combined trabeculectomy-trabeculotomy with mitomycin C, and Baerveldt implant. The main outcomes were mean IOP reduction and surgical success rate at postoperative 6 months. The mean differences (MDs) or odds ratios (ORs) were analyzed by a random-effects model, and the efficacies were ranked by P -score. We appraised the RCTs using the Cochrane risk-of-bias (ROB) tool (PROSPERO: CRD42022313954). RESULTS: Sixteen RCTs were eligible for NMA, including 710 eyes of 485 participants and 13 surgical interventions, which formed a network of 14 nodes comprising both single interventions and intervention combinations. IMCT was superior to CPT in both IOP reduction [MD (95% CI): -3.10 (-5.50 to -0.69)] and surgical success rate [OR (95% CI): 4.38 (1.61-11.96)]. The MD and OR comparing the other surgical interventions and intervention combinations with CPT were not statistically significant. The P -scores ranked IMCT as the most efficacious surgical intervention in terms of success rate ( P -score =0.777). Overall, the trials had a low-to-moderate ROB. CONCLUSION: This NMA indicated that IMCT is more effective than CPT and might be the most efficacious of the 13 surgical interventions for management of PCG.

Efficacy of surgical treatment for post-prostatectomy urinary incontinence: a systematic review and network meta-analysis.

OBJECTIVES: Post-prostatectomy urinary incontinence (PPUI) is a major complication that reduces the quality of life in patients undergoing prostatectomy for benign prostatic hyperplasia and prostate cancer. However, there are currently limited guidelines on which surgical techniques are preferred after conservative treatment for PPUI. In this study, a systematic review and network meta-analysis (NMA) that can help determine the priority for the selection of surgical methods were performed. MATERIALS AND METHODS: We retrieved data from electronic literature searches of PubMed and the Cochrane Library through August 2021. We searched for randomized controlled trials studies on the surgical treatment of PPUI after surgery for benign prostatic hyperplasia or prostate cancer and included the terms artificial urethral sphincter (AUS), adjustable sling, nonadjustable sling, and injection of the bulking agent.The NMA pooled the odds ratios and 95% credible intervals (CrIs) using the number of patients achieving urinary continence, weight of pads used per day, number of pads used per day, and the International Consultation on Incontinence Questionnaire score. The therapeutic effect of each intervention on PPUI was compared and ranked using the surface under the cumulative ranking curve. RESULTS: A final 11 studies, including 1116 participants, were included in our NMA. The pooled overall odds ratios of patients achieving urinary continence compared with no treatment was 3.31 (95% CrI: 0.749, 15.710) in AUS, 2.97 (95% CrI: 0.412, 16.000) in adjustable sling, 2.33 (95% CrI: 0.559, 8.290) in nonadjustable sling, and 0.26 (95% CrI: 0.025, 2.500) in injection of bulking agent. In addition, this study shows the surface under the cumulative ranking curve values of ranking probabilities for each treatment performance, which indicated that AUS ranked first in terms of continence rate, International Consultation on Incontinence Questionnaire, pad weight, and pad use count. CONCLUSION: The results of this study suggested that only AUS had a statistically significant effect compared to the nontreatment group and the highest PPUI treatment effect ranking among other surgical treatments.

Meta-analysis of diagnostic test accuracy studies with multiple thresholds for data integration.

OBJECTIVES: The objective of this study is to introduce methods to use all of the information without omission when individual studies provide multiple effect sizes according to multiple cut-off values (thresholds) during diagnostic test accuracy (DTA) for data integration. For diagnostic test meta-analysis, a general performance method for synthesizing data according to one cut value in one study and a performance method for synthesizing data according to two or more cut values in one study were compared and analyzed. METHODS: As sample data for meta-analysis of DTA studies, 13 DTA studies on prostate cancer (34 effect sizes including total cut-offs) were collected. The summary statistics were calculated and the summary line was analyzed using the "meta", "mada", and "diagmeta" packagesof the R software. RESULTS: The summary statistics of the random effect model univariate analysis of the "meta" package with a single cut-off corresponding to the highest Youden index in a single study and those of the bivariate analysis of the "mada" package were highly similar. However, in the bivariate analysis of the "diagmeta" package including all cut-off values, the sensitivity decreased and the specificity increased as the amount of data increased. CONCLUSIONS: Considering the heterogeneity of the summary receiver op erating characteristic curve and the use of all given cut-offs, the use of the bivariate analysis model of the "diagmeta" package is recommended. This study focused on practical methods of DTA rather than theoretical concepts for use by researchers whose fields of study are non-statistics related. By performing this study, we hope that many researchers will use R software to determine the DTA more easily, and that there will be greater interest in related research.

Prognostic nutritional index as a prognostic factor for renal cell carcinoma: A systematic review and meta-analysis.

BACKGROUND: Prognostic nutritional index (PNI) is a simple parameter which reflects patient's nutritional and inflammatory status and reported as a prognostic factor for renal cell carcinoma (RCC). Studies were included from database inception until February 2, 2022. The aim of this study is to evaluate prognostic value of PNI by meta-analysis of the diagnostic test accuracy in RCC. METHODS AND FINDINGS: Studies were retrieved from PubMed, Cochrane, and EMBASE databases and assessed sensitivity, specificity, summary receiver operating characteristic curve (SROC) and area under curve (AUC). Totally, we identified 11 studies with a total of 7,296 patients were included to evaluate the prognostic value of PNI in RCC finally. They indicated a pooled sensitivity of 0.733 (95% CI, 0.651-0.802), specificity of 0.615 (95% CI, 0.528-0.695), diagnostic odds ratio (DOR) of 4.382 (95% CI, 3.148-6.101) and AUC of 0.72 (95% CI, 0.68-0.76). Heterogeneity was significant and univariate meta-regression revealed that metastasis and cut-off value of PNI might be the potential source of heterogeneity. Multivariate meta-regression analysis also demonstrated that metastasis might be the source of heterogeneity. CONCLUSIONS: PNI demonstrated a good diagnostic accuracy as a prognostic factor for RCC and especially in case of metastatic RCC.

Androgen Receptor Signaling Inhibitors in Addition to Docetaxel with Androgen Deprivation Therapy for Metastatic Hormone-sensitive Prostate Cancer: A Systematic Review and Meta-analysis.

CONTEXT: Recent randomized controlled trials (RCTs) examined the role of adding androgen receptor signaling inhibitors (ARSIs), including abiraterone acetate (ABI), apalutamide, darolutamide (DAR), and enzalutamide (ENZ), to docetaxel (DOC) and androgen deprivation therapy (ADT) in patients with metastatic hormone-sensitive prostate cancer (mHSPC). OBJECTIVE: To analyze the oncologic benefit of triplet combination therapies using ARSI + DOC + ADT, and comparing them with available treatment regimens in patients with mHSPC. EVIDENCE ACQUISITION: Three databases and meetings abstracts were queried in April 2022 for RCTs analyzing patients treated with first-line combination systemic therapy for mHSPC. The primary interests of measure were overall survival (OS) and progression-free survival (PFS). Subgroup analyses were conducted to assess the differential outcomes in patients with low- and high-volume disease as well as de novo and metachronous metastasis. EVIDENCE SYNTHESIS: Overall, 11 RCTs were included for meta-analyses and network meta-analyses (NMAs). We found that the triplet combinations outperformed DOC + ADT in terms of OS (pooled hazard ratio [HR]: 0.74, 95% confidence interval [CI]: 0.65-0.84) and PFS (pooled HR: 0.49, 95% CI: 0.42-0.58). There was no statistically significant difference between patients with low- and high-volume disease in terms of an OS benefit from adding an ARSI to DOC +ADT (both HR: 0.79; p = 1). Based on NMAs, triplet therapy also outperformed ARSI + ADT in terms of OS (DAR + DOC + ADT: pooled HR: 0.74, 95% CI: 0.55-0.99) and PFS (ABI + DOC + ADT: HR: 0.68, 95% CI: 0.51-0.91, and ENZ + DOC + ADT: HR: 0.70, 95% CI: 0.53-0.93). An analysis of treatment ranking among de novo mHSPC patients showed that triplet therapy had the highest likelihood of improved OS in patients with high-volume disease; however, doublet therapy using ARSI + ADT had the highest likelihood of improved OS in patients with low-volume disease. CONCLUSIONS: We found that the triplet combination therapy improves survival endpoints in mHSPC patients compared with currently available doublet treatment regimens. Our findings need to be confirmed in further head-to-head trials with longer follow-up and among various patient populations. PATIENT SUMMARY: Our study suggests that triplet therapy with androgen receptor signaling inhibitor, docetaxel, androgen deprivation therapy prolongs survival in patients with metastatic hormone-sensitive prostate cancer compared with the current standard doublet therapy.

Diagnostic Test Accuracy of 18 F-FDG PET or PET/CT in Merkel Cell Carcinoma.

OBJECTIVE: The purpose of the current study was to evaluate the diagnostic accuracies of 18 F-FDG PET or PET/CT for diagnosis of Merkel cell carcinoma (MCC) through a systematic review and meta-analysis. METHODS: The PubMed, Cochrane database, and EMBASE database, from January 1990 to January 31, 2022, were searched for studies evaluating diagnostic performance of 18 F-FDG PET or PET/CT for MCC. We determined the sensitivities and specificities across studies, calculated positive and negative likelihood ratios (LR+ and LR-), and constructed summary receiver operating characteristic curves. RESULTS: Across 9 studies (259 patients), the pooled sensitivity of 18 F-FDG PET or PET/CT was 0.91 (95% confidence interval [CI], 0.85-0.95) and a pooled specificity of 0.93 (95% CI, 0.86-0.97). Likelihood ratio syntheses gave an overall LR+ of 14.0 (95% CI, 6.6-29.6) and LR- of 0.09 (95% CI, 0.05-0.17). The pooled diagnostic odds ratio was 153 (95% CI, 57-416). CONCLUSION: 18 F-FDG PET/CT showed an excellent performance for diagnosis of MCC. The likelihood ratio scattergram indicated that 18 F-FDG PET or PET/CT is useful for exclusion and confirmation of MCC. Further large multicenter studies would be necessary to substantiate the diagnostic accuracy of 18 F-FDG PET or PET/CT for MCC patients.

Natural Language Processing for Information Extraction of Gastric Diseases and Its Application in Large-Scale Clinical Research.

Background and Aims: The utility of clinical information from esophagogastroduodenoscopy (EGD) reports has been limited because of its unstructured narrative format. We developed a natural language processing (NLP) pipeline that automatically extracts information about gastric diseases from unstructured EGD reports and demonstrated its applicability in clinical research. Methods: An NLP pipeline was developed using 2000 EGD and associated pathology reports that were retrieved from a single healthcare center. The pipeline extracted clinical information, including the presence, location, and size, for 10 gastric diseases from the EGD reports. It was validated with 1000 EGD reports by evaluating sensitivity, positive predictive value (PPV), accuracy, and F1 score. The pipeline was applied to 248,966 EGD reports from 2010-2019 to identify patient demographics and clinical information for 10 gastric diseases. Results: For gastritis information extraction, we achieved an overall sensitivity, PPV, accuracy, and F1 score of 0.966, 0.972, 0.996, and 0.967, respectively. Other gastric diseases, such as ulcers, and neoplastic diseases achieved an overall sensitivity, PPV, accuracy, and F1 score of 0.975, 0.982, 0.999, and 0.978, respectively. The study of EGD data of over 10 years revealed the demographics of patients with gastric diseases by sex and age. In addition, the study identified the extent and locations of gastritis and other gastric diseases, respectively. Conclusions: We demonstrated the feasibility of the NLP pipeline providing an automated extraction of gastric disease information from EGD reports. Incorporating the pipeline can facilitate large-scale clinical research to better understand gastric diseases.

Comparison of Preoperative Imaging Modalities for the Assessment of Malignant Potential of Pancreatic Cystic Lesions: A Network Meta-analysis.

PURPOSE: The aims of this study are to compare the performance of various preoperative imaging modalities for assessing the malignant potential of pancreatic cystic lesions (PCLs) through a network meta-analysis (NMA) and to clarify the role of 18 F-FDG PET in the management of patients with PCL. METHODS: PubMed, EMBASE, and Cochrane Library were searched for the studies evaluating the performance of preoperative imaging modalities for identifying malignant PCLs. The NMA was performed for 4 representative categories of various imaging modalities in terms of diagnostic performance for differentiating malignant from benign PCL and intraductal papillary mucinous neoplasms only as a subgroup analysis. To calculate the probability of each imaging modality being the most effective diagnostic method, the surface under the cumulative ranking curve values were obtained. RESULTS: A total of 1018 patients from 17 direct comparison studies using 2 or more preoperative imaging modalities were included for differentiating malignant from benign PCL. The positive predictive value (PPV) and accuracy of 18 F-FDG PET were significantly higher than that of CT (PPV: odds ratio [OR], 2.66; 95% credible interval [CrI], 1.21-6.17; accuracy: OR, 2.63; 95% CrI, 1.41-5.38) or MRI (PPV: OR, 2.50; 95% CrI, 1.09-6.26; accuracy: OR, 2.50; 95% CrI, 1.28-5.47) in all PCLs, as well as in the subgroup analysis for intraductal papillary mucinous neoplasm only. 18 F-FDG PET showed the highest surface under the cumulative ranking curve values in all diagnostic performance areas of sensitivity, specificity, PPV, negative predictive value, and accuracy, followed by MRI or CT. CONCLUSIONS: The results from this NMA suggest that 18 F-FDG PET is the best preoperative imaging modality for differentiating malignant from benign PCLs and that it can be used for the preoperative evaluation of PCLs.

Intensification of Systemic Therapy in Addition to Definitive Local Treatment in Nonmetastatic Unfavourable Prostate Cancer: A Systematic Review and Meta-analysis.

CONTEXT: Several recent randomised trials have evaluated the role of combination systemic treatment using androgen deprivation therapy (ADT) plus chemotherapy or an androgen receptor signaling inhibitor (ARSI) in patients with high-risk and/or unfavourable nonmetastatic prostate cancer (nmPC). OBJECTIVE: To assess the outcomes associated with adding combination systemic treatment to primary definitive local therapy in patients with high-risk and/or unfavourable nmPC. EVIDENCE ACQUISITION: We queried the PubMed, Web of Science, and Scopus databases and conference abstracts to identify prospective randomised trials examining the value of adding chemotherapy or an ARSI to ADT and primary local therapy with curative intent for nmPC. The primary endpoints were overall survival (OS), cancer-specific survival (CSS), metastasis-free survival (MFS), and failure-free survival (FFS). Secondary endpoints included adverse events (AEs) and pathologic outcomes. EVIDENCE SYNTHESIS: We identified 15 randomised studies, of which nine evaluated chemohormonal and six investigated ARSI-based treatment strategies. In both radical prostatectomy (RP) and radiation therapy (RT) settings, addition of docetaxel to ADT was associated with significantly better CSS (pooled hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.49-0.95; p = 0.025), MFS (pooled HR 0.82, 95% CI 0.71-0.95; p = 0.008), and FFS (pooled HR 0.70, 95% CI 0.62-0.79; p < 0.001); the difference did not meet the conventional level of statistical significance for OS (pooled HR 0.86, 95% CI 0.73-1.01; p = 0.072). For patients treated with RT alone, docetaxel-based combination treatment did not meet the significance threshold set for OS (p = 0.3), CSS (p = 0.072), or MFS (p = 0.079), but the difference for FFS was statistically significant (pooled HR 0.72, 95% CI 0.63-0.84; p < 0.001). On network meta-analyses including RT studies, ARSI + ADT outperformed docetaxel + ADT for survival endpoints and had a more favourable AE profile. CONCLUSIONS: Intensification of systemic therapy with docetaxel or an ARSI in addition to ADT improves oncologic endpoints in high-risk and/or unfavourable nmPC treated with local definitive therapy. The highest efficacy was achieved with ARSI + ADT, specifically in patients treated with RT. PATIENT SUMMARY: Our findings highlight that selected patients with high-risk nonmetastatic prostate cancer benefit from intensification of systemic therapy beyond hormonal treatment.

Albumin-to-Alkaline Phosphatase Ratio as a Novel Prognostic Factor in Patients Undergoing Nephrectomy for Non-Metastatic Renal Cell Carcinoma: Propensity Score Matching Analysis.

INTRODUCTION: To evaluate the prognostic value of albumin-to-alkaline phosphatase ratio (AAPR) on recurrence and survival in patients with non-metastatic renal cell carcinoma (RCC) treated with radical or partial nephrectomy. PATIENTS AND METHODS: Between June 1994 and December 2018, 491 patients with RCC who underwent radical or partial nephrectomy at 2 institutions were enrolled in this study. Recurrence-free survival (RFS) and cancer-specific survival (CSS) analyses were performed to distinguish the differences in postoperative recurrence and survival between patients stratified by an optimal cut-off value of AAPR. Multivariable Cox proportional hazards regression models were established to determine the independent prognostic factors after propensity score weighting. RESULTS: Of the total 491 patients, 51 patients (10.4%) developed local recurrence or distant metastasis and 26 patients (5.3%) died of disease during the follow-up period. Patients with AAPR<0.41 had significantly lower rates of RFS and CSS than those of patients with AAPR≥0.41 in multivariate analysis (P < .001 and P = .027, respectively). After propensity scroe matching analyses, this difference was still remained for RFS (P < .001). However, AAPR was not an independent prognostic factor for CSS but the value was almost pregnant (HR = 2.674; 95%CI = 0.872-8.203; P = .086). CONCLUSION: AAPR can serve as a novel and useful tool to refine prognosis in patients with non-metastatic RCC treated with partial or radical nephrectomy. These findings suggest that AAPR could be a promising prognostic factor for prediction of recurrence and survival in patients with non-metastatic RCC who undergo nephrectomy.