Category: Statistics

Front Immunol. 2026 Aug 7;17:1903694. doi: 10.3389/fimmu.2026.1903694. eCollection 2026.

ABSTRACT

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS), caused by SFTS virus (SFTSV) infection, is an emerging tick-borne infectious disease associated with substantial case fatality and poses a considerable public health burden. Interleukin-10 (IL-10), an important anti-inflammatory and immunoregulatory cytokine, may reflect the magnitude of immune dysregulation in SFTS. This systematic review and meta-analysis primarily aimed to evaluate the association between serum IL-10 levels and mortality in patients with SFTSV infection. As a secondary exploratory objective, we assessed the threshold-based prognostic accuracy of IL-10 for fatal outcomes when sufficient data were available.

METHODS: PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Data, and CQVIP were searched from database inception to October 11, 2025. Prospective and retrospective cohort studies, and case-control studies reporting serum IL-10 levels in survivors and non-survivors with laboratory-confirmed SFTSV infection were eligible. Two reviewers independently screened studies, extracted data, and assessed methodological quality using the Newcastle-Ottawa Scale (NOS) and risk of bias using the Quality In Prognosis Studies (QUIPS) tool for studies on prognostic factors and the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 tool for studies contributing threshold-based prognostic accuracy data. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were pooled using a prespecified random-effects model. Sensitivity analyses, subgroup analyses, meta-regression, funnel plots, and Egger’s test were used to evaluate the robustness of the findings and possible small-study effects.

RESULTS: Twelve studies involving 1,270 patients with SFTSV infection were included, comprising 290 non-survivors and 980 survivors. Serum IL-10 levels were significantly higher in non-survivors than in survivors (pooled SMD = 2.08, 95% CI: 1.40-2.76; P<0.01). Substantial heterogeneity was observed (I ² = 94%, P<0.01), and the 95% prediction interval crossed zero. Sensitivity analyses generally preserved the direction of the association, including an analysis restricted to studies not requiring conversion from medians and quantiles; however, substantial residual heterogeneity and the limited number of directly reported datasets indicated considerable uncertainty regarding the magnitude of the pooled effect. Subgroup analyses according to study design showed a directionally consistent association, whereas exploratory meta-regression found no statistically significant relationship between study-level IL-10 concentration and effect size. Funnel-plot asymmetry and Egger’s regression test indicated possible small-study effects; however, the extreme between-study heterogeneity limited the ability to distinguish selective publication from methodological or clinical variability. Threshold-based prognostic-accuracy analyses suggested potential discriminatory value for mortality prediction, but they were based on only three studies using post hoc, non-validated cut-off values and therefore remained exploratory. The certainty of evidence for the association between IL-10 levels and mortality was rated as very low because of residual confounding, inconsistency, indirectness, and possible small-study effects.

CONCLUSION: Elevated serum IL-10 levels were associated with mortality in SFTS; however, the certainty of evidence was very low. IL-10 should therefore be considered a candidate prognostic biomarker requiring further prospective validation rather than a clinically established stand-alone prognostic tool.

SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier CRD420251149587.

PMID:42630216 | PMC:PMC13493291 | DOI:10.3389/fimmu.2026.1903694

Front Endocrinol (Lausanne). 2026 Aug 7;17:1899934. doi: 10.3389/fendo.2026.1899934. eCollection 2026.

ABSTRACT

OBJECTIVE: To study whether the impact of serum progesterone level on the day of hCG administration on reproductive outcomes varies across age groups and ovarian stimulation protocols in fresh in fresh in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cycles.

METHODS: This single-center, retrospective cohort study was conducted from January 2014 to December 2024 and included 24,868 women undergoing their first fresh embryo transfer following an IVF or ICSI cycle at a university-affiliated fertility center. The exposure was serum progesterone level measured on the day of hCG administration. Primary outcomes were clinical pregnancy rate (CPR), miscarriage rate (MR) and live birth rate (LBR).

RESULTS: In women aged <35 years, progesterone was inversely associated with CPR (fully adjusted aOR=0.868, 95% CI 0.812-0.927, P<0.001) but positively associated with LBR after adjustment (aOR=1.090, 95% CI 1.019-1.167, P = 0.013). No significant effects were observed in patients aged ≥35 years. The progesterone-outcome relationship was significantly modified by protocol, with a nonlinear inverted U-shaped curve in GnRH-agonist protocols (interaction P<0.001 for CPR, P = 0.005 for LBR). In protocol-stratified analyses, progesterone was independently associated with reduced CPR in ultra-long GnRH-agonist (aOR=0.814, 95% CI 0.718-0.922, P = 0.001) and GnRH-antagonist protocols (aOR=0.849, 95% CI 0.771-0.936, P = 0.001), but not in the long GnRH-agonist protocol. The effect on LBR was positive in the long GnRH-agonist protocol (aOR=1.105, 95% CI 1.013-1.205, P = 0.024) and negative in the GnRH-antagonist protocol (aOR=0.884, 95% CI 0.788-0.991, P = 0.035). Sensitivity analyses confirmed the superiority of GnRH-agonist protocols across all progesterone levels (all adjusted P<0.01).

CONCLUSION: The association between late follicular progesterone elevation and reproductive outcomes differs across ovarian stimulation protocols, demonstrating a nonlinear relationship with both clinical pregnancy and live birth. These results suggest that late follicular progesterone elevation should be interpreted with protocol-specific considerations.

PMID:42630209 | PMC:PMC13493308 | DOI:10.3389/fendo.2026.1899934

Front Neurol. 2026 Aug 7;17:1810736. doi: 10.3389/fneur.2026.1810736. eCollection 2026.

ABSTRACT

OBJECTIVES: To develop a composite imaging phenotype framework for brain abscess (BA) based on conventional imaging features, enabling systematic assessment of imaging heterogeneity, and to explore the distribution of these phenotypes across different age groups and their association with short-term clinical outcomes.

METHODS: This retrospective study consecutively enrolled patients with surgically confirmed BA admitted to two hospitals between January 2019 and December 2025. Patients were stratified into pediatric and adult groups based on age. All patients underwent surgical treatment and standard anti-infective therapy. Based on preoperative conventional imaging, three-dimensional composite phenotypes were defined: structural complexity, spatial complexity, and aggressive features. These were integrated into an “imaging phenotypic burden” score. Analyses examined age-related differences in phenotype distribution, associations with pathogen profiles, and the relationship between phenotypic burden and in-hospital adverse outcomes.

RESULTS: Significant differences were observed in imaging phenotype distribution between children and adults. Structural complexity was more common in the pediatric group (40.0% vs. 9.8%, p = 0.008), while spatial complexity was higher in adults (58.5% vs. 15.0%, p < 0.001). Microbiological analysis indicated a predominance of Streptococcus infections in children (p = 0.002); however, no stable statistical association was found between pathogen category and any specific imaging phenotype. A significant dose-response relationship existed between phenotypic burden and adverse outcome rates (p = 0.004, trend test). The high-burden group (≥2 phenotypes) had a significantly higher adverse outcome rate compared to the low-burden group (30.0% vs. 6.5%, p = 0.017). Deep-seated lesions were the primary anatomical factor driving high phenotypic burden and spatial complexity.

CONCLUSION: The developed composite imaging phenotype framework effectively integrates information from conventional imaging to systematically assess BA heterogeneity. The imaging phenotypic burden is independently associated with short-term adverse outcomes. It serves as an intuitive, quantitative tool for early risk stratification, informing surgical timing decisions, and guiding intensive care resource allocation, demonstrating potential for clinical translation.

PMID:42630207 | PMC:PMC13493290 | DOI:10.3389/fneur.2026.1810736

Front Endocrinol (Lausanne). 2026 Aug 7;17:1870557. doi: 10.3389/fendo.2026.1870557. eCollection 2026.

ABSTRACT

BACKGROUND: Gestational diabetes mellitus (GDM) women often have abnormal lipid levels during pregnancy. Moreover, lipid metabolism and body mass index (BMI) may influence the occurrence of GDM, and the potential relationship between them remains unclear.

OBJECTIVE: To explore the potential association between blood lipid levels, BMI and GDM in early pregnancy.

METHODS: Multivariate logistic regression analysis was employed, and the odds ratio (OR) and its 95% confidence interval (CI) were used to evaluate the associations between early pregnancy lipid levels, such as triglyceride (TG), total cholesterol (TC) as well as BMI and the risk of GDM. Based on the identified significant associated factors, a clinical prediction model was attempted to be constructed. Further use bidirectional Mendelian randomization (MR) analysis to evaluate the potential relationship between screened risk associated blood lipids and GDM.

RESULTS: In the case-control study, multivariate logistic regression analysis showed that BMI (OR = 1.12, 95% CI = 1.07-1.16, P < 0.05), TG (OR = 1.27, 95%CI=1.13-1.42, P < 0.05), TC (OR = 1.12, 95%CI=1.01-1.25, P < 0.05), LDL-c (OR = 1.13, 95%CI=1.01-1.27, P < 0.05) and HbA1c (OR = 5.94, 95%CI=4.28-8.25, P < 0.05) were significantly associated with the risk of GDM after adjusting for age. Based on TG, TC, LDL-c and BMI, the nomogram demonstrated AUCs of 0.772 in the training set, 0.754 in internal validation and 0.759 in external validation, indicating good and stable predictive performance. In the forward MR analysis, genetic evidence supported potential associations between TG (OR = 1.24, 95%CI=1.10-1.40, P < 0.05), BMI (OR = 1.75, 95%CI=1.51-2.03, P < 0.05) and GDM; while the reverse MR analysis indicated that GDM may have an association effect on TG (OR = 1.03, 95%CI=1.02-1.04, P < 0.05). Leave-one-out sensitivity analyses confirmed the robustness and reliability of the primary findings.

CONCLUSION: This study provides suggestive evidence that TG and BMI may be associated with GDM risk, supported by clinical and genetic evidence. A nomogram demonstrated good and stable predictive performance. and MR analysis provided suggestive evidence of a potential bidirectional relationship between GDM and elevated TG. Further validation is needed.

PMID:42630205 | PMC:PMC13493276 | DOI:10.3389/fendo.2026.1870557

Front Endocrinol (Lausanne). 2026 Aug 7;17:1936170. doi: 10.3389/fendo.2026.1936170. eCollection 2026.

ABSTRACT

OBJECTIVE: To investigate the associations between a four-group classification based on early-pregnancy FBG and subsequent GDM status and maternal and neonatal outcomes, and to characterize the FBG-HDP dose-response relationship.

METHODS: This retrospective cohort study included 15,245 women with singleton pregnancies. Participants were categorized into four groups based on early-pregnancy FBG (< 5.1 vs ≥ 5.1 mmol/L) and subsequent GDM status: Normoglycemia (normal FBG without GDM), GDM-Regression (elevated FBG without GDM), Late-onset GDM (normal FBG with GDM), and GDM-Maintained (elevated FBG with GDM). Multivariable logistic regression was used to estimate adjusted odds ratios (aOR) for outcomes. Restricted cubic spline regression was used to examine the dose-response relationship between FBG and HDP.

RESULTS: The incidence of HDP increased progressively across groups: Normoglycemia 4.6%, GDM-Regression 6.9%, Late-onset GDM 8.1%, and GDM-Maintained 11.0% (P for trend <0.001). Compared with Normoglycemia, the aOR for HDP was 1.32 (95% CI: 1.03-1.68) for GDM-Regression, 1.53 (95% CI: 1.28-1.83) for Late-onset GDM, and 1.65 (95% CI: 1.23-2.18) for GDM-Maintained. GDM-Regression was associated with reduced SGA risk (aOR: 0.69, 95% CI: 0.53-0.87) but elevated LGA (aOR: 1.45, 95% CI: 1.21-1.74) and macrosomia (aOR: 1.62, 95% CI: 1.19-2.17) risks. GDM-Maintained showed the highest risks for LGA (aOR: 1.68), macrosomia (aOR: 1.81), preterm birth (aOR: 1.78), and neonatal asphyxia (aOR: 2.15). Restricted cubic spline analysis revealed a nonlinear relationship between FBG and HDP (overall P < 0.001; P for nonlinearity=0.036), with a statistical inflection point at 4.52 mmol/L. Stratified analyses showed consistent associations across age, BMI, ethnicity, and parity subgroups (all P for interaction >0.05). Sensitivity analyses using alternative FBG cutoffs (≥5.3 and ≥5.6 mmol/L) confirmed the robustness of these findings.

CONCLUSIONS: The four-group classification based on early-pregnancy FBG and subsequent GDM status may be useful for stratifying the risk of adverse pregnancy outcomes. The observed inflection point warrants further investigation. These findings support the potential value of early-pregnancy glycemic assessment in refining risk characterization for pregnant women.

PMID:42630200 | PMC:PMC13493287 | DOI:10.3389/fendo.2026.1936170

Front Endocrinol (Lausanne). 2026 Aug 7;17:1876849. doi: 10.3389/fendo.2026.1876849. eCollection 2026.

ABSTRACT

INTRODUCTION: Adolescent idiopathic scoliosis (AIS) affects 2% to 3% of adolescents and progresses rapidly during puberty. Previous studies suggest that a positive family history of AIS and a later age at menarche (AAM) are risk factors for curve severity in AIS, but their quantitative evidence and the causal contribution of AAM remain to be elucidated.

METHODS: We analyzed 5,891 patients with AIS to evaluate the associations of family history and AAM with curve severity. Genetic correlation, Mendelian randomization, harmonized variant-level analyses, and variance component analyses were also performed.

RESULTS: Family history was associated with curve severity (β = 1.26, P = 0.024), and this association showed a dose-dependent relationship (β = 1.31, P = 0.006). Later AAM was linearly associated with greater curve severity (β = 1.95, P = 3.7 × 10^-23). AAM showed genetic correlation with Cobb angle (r_g = 0.25, P = 0.04), but not with susceptibility to AIS (r_g = 0.04, P = 0.33), suggesting distinct contributions of AAM to AIS susceptibility and curve severity. Mendelian randomization provided suggestive evidence for an effect of later AAM on curve severity, with no evidence of horizontal pleiotropy. Harmonized variant-level analyses showed that AIS susceptibility alleles tended to have concordant positive effects on curve severity. A variance component analysis demonstrated that AAM and family history explained 2.7% and 0.2% of the variance in Cobb angle, respectively.

DISCUSSION: This study provides quantitative genetic evidence linking family history of AIS and later AAM to curve severity. These findings support the use of family history and AAM in clinical settings to stratify patients according to the risk of greater curve severity.

PMID:42630198 | PMC:PMC13493220 | DOI:10.3389/fendo.2026.1876849

Front Nutr. 2026 Aug 7;13:1827831. doi: 10.3389/fnut.2026.1827831. eCollection 2026.

ABSTRACT

BACKGROUND: Delayed bowel function recovery (DBFR) is a common postoperative complication after colorectal cancer (CRC) resection. This study aimed to investigate the association between postoperative DBFR and 6-month weight and muscle mass loss in patients with CRC, to inform optimized postoperative prognostic management.

METHODS: A total of 618 patients with CRC were prospectively enrolled. Body weight and five anthropometric parameters (including mid-upper arm circumference) were measured within 3 days before surgery. Skeletal muscle cross-sectional area at the L3 vertebral level was quantified using preoperative abdominal CT scans, with the skeletal muscle index (SMI) subsequently calculated. DBFR was defined as the absence of first flatus and defecation within 72 postoperative hours. All participants completed a 6-month follow-up, and body weight, SMI and the five anthropometric measurements were reassessed at the follow-up endpoint. Multivariate linear regression models were applied for statistical analyses.

RESULTS: Postoperative DBFR was nominally or significantly correlated with lower final body weight, reduced SMI, decreased mid-upper arm circumference, calf circumference and hip circumference, as well as reduced triceps skinfold thickness at 6-month follow-up. Notably, DBFR was significantly associated with larger declines from baseline to follow-up in body weight, SMI, mid-upper arm circumference, calf circumference, waist circumference, hip circumference and triceps skinfold thickness.

CONCLUSION: Postoperative DBFR correlates with medium-term weight and skeletal muscle loss in patients undergoing CRC surgery. Upon further external validation, DBFR may act as a predictive risk factor for these unfavorable nutritional outcomes.

PMID:42630189 | PMC:PMC13493217 | DOI:10.3389/fnut.2026.1827831

Front Cell Infect Microbiol. 2026 Aug 7;16:1827485. doi: 10.3389/fcimb.2026.1827485. eCollection 2026.

ABSTRACT

BACKGROUND: Nontypeable Haemophilus influenzae (NTHi) is a major bacterial pathogen in both acute and chronic respiratory diseases, yet the genomic basis underlying its association with different clinical phenotypes remains incompletely understood.

METHODS: We performed whole-genome sequencing and comparative genomic analysis of 27 NTHi isolates, including strains derived from patients with bronchiectasis (n = 10), community-acquired pneumonia (CAP; n = 6), and chronic obstructive pulmonary disease (COPD; n = 11). Among these, three isolates (one from each disease group) were newly sequenced using a hybrid Oxford Nanopore-Illumina approach, while the remaining 24 genomes were retrieved from public databases. Pan-genome analysis, multilocus sequence typing (MLST), core genome phylogenetic analysis, accessory genome based discriminant analysis, and pan-genome-wide association analysis (pan-GWAS) were performed to characterize genomic diversity and variation in gene content across isolates.

RESULTS: MLST and core genome phylogenetic analyses revealed substantial genetic diversity, with isolates from bronchiectasis, CAP, and COPD distributed across multiple lineages without clear disease-specific clustering. Accessory genome-based analyses indicated heterogeneous differences in gene content among isolates from different clinical backgrounds, although overlap between groups remained evident. Pan-genome-wide association analysis did not identify any accessory genes that remained statistically significant after Benjamini-Hochberg false discovery rate (FDR) correction. Under a relaxed exploratory threshold (empirical P-value < 0.35 and odds ratio > 1), a subset of accessory genes showing differential distribution patterns among disease groups was identified and reported as exploratory candidates. Comparatively greater accessory genome divergence was observed between bronchiectasis and COPD isolates. Functional annotation indicated that these candidate genes spanned multiple categories, including recombination, membrane-associated processes, transport, and nutrient utilization.

CONCLUSIONS: Clinical heterogeneity among NTHi isolates was not reflected in core genome phylogeny. Differences in accessory gene content were observed across isolates from different clinical sources; however, these patterns were not supported by statistically robust associations after multiple testing correction. The identified candidate genes should therefore be regarded as exploratory, and the findings interpreted as descriptive of genomic diversity rather than evidence of disease-associated functional differentiation.

PMID:42630188 | PMC:PMC13493278 | DOI:10.3389/fcimb.2026.1827485

Front Oncol. 2026 Aug 7;16:1848585. doi: 10.3389/fonc.2026.1848585. eCollection 2026.

ABSTRACT

OBJECTIVE: This study aims to compare the expression of p53, PTEN, and p16 among three groups: endometrial polyps of breast cancer patients receiving endocrine therapy, common sporadic endometrial polyps, and endometrial carcinoma (type I). This study also analyzes the correlation between the immunohistochemical expression of these markers and the clinical characteristics of breast cancer patients receiving endocrine therapy.

METHODS: From 1 December 2022, to 31 December 2023, we retrospectively enrolled 93 breast cancer patients receiving endocrine therapy with endometrial polyps, 60 patients with common sporadic endometrial polyps, and 48 patients with endometrial carcinoma (type I) (all cases were retrieved from our hospital). The expression of p53, PTEN, and p16 was detected using immunohistochemistry. Spearman’s correlation analysis was conducted to explore factors associated with p16 and PTEN expression in the endocrine therapy cohort.

RESULTS: No statistically significant difference in the p53 expression distribution was observed among the tamoxifen (TAM), toremifene (TOR), endometrial polyps (EP), and endometrial carcinoma (EC) groups regardless of menopausal status. In premenopausal patients, the semi-quantitative immunohistochemical (IHC) scores of p16 and PTEN in the TAM and TOR groups were intermediate between those of EP and EC groups (Holm-adjusted P < 0.05). This specific pattern was not observed in the postmenopausal group. In the endocrine therapy-treated cohort, Spearman’s correlation analysis revealed that the semi-quantitative IHC score of p16 was positively correlated with age, blood lipids, and BMI; negatively correlated with abnormal uterine bleeding and endometrial thickness (P < 0.05); the semi-quantitative IHC score of PTEN was negatively correlated with menopausal status and diabetes mellitus (P < 0.05).

CONCLUSIONS: In this retrospective immunohistochemical analysis of premenopausal women, p16 and PTEN expression in the TAM/TOR group was intermediate between those of EP and EC groups. This pattern may suggest a hyperproliferative polyp phenotype, but remains speculative without confirmatory proliferation biomarkers and molecular validation. Long-term surveillance may be considered for this population, though prospective cohort data are needed to confirm its clinical utility. p16 was positively associated with age, blood lipids, and BMI, and negatively associated with abnormal uterine bleeding and endometrial thickness; PTEN was negatively associated with menopausal status and diabetes mellitus. These preliminary associations provide exploratory clues for endometrial follow-up biomarker research.

PMID:42630187 | PMC:PMC13493233 | DOI:10.3389/fonc.2026.1848585

Front Oncol. 2026 Aug 7;16:1866026. doi: 10.3389/fonc.2026.1866026. eCollection 2026.

ABSTRACT

BACKGROUND: Neoadjuvant therapy combined with immunotherapy has emerged as a promising strategy for rectal cancer (RC), but its efficacy in anal sphincter preservation, clinical outcomes, and safety profile remains to be systematically validated. This meta-analysis aims to comprehensively evaluate the anal sphincter preservation rate, clinical efficacy, and safety of neoadjuvant therapy combined with immunotherapy in rectal cancer patients, providing evidence-based support for clinical decision-making.

OBJECTIVE: To assess the anal sphincter preservation rate, key clinical efficacy indicators (including pathological complete response rate, R0 resection rate, and tumor regression grade), and safety indicators (adverse events and postoperative complications) of neoadjuvant therapy combined with immunotherapy in rectal cancer patients. We systematically synthesize the absolute sphincter-preservation, pathological-response, and safety proportions of neoadjuvant immunotherapy in rectal cancer patients, with any comparison to historical data of conventional regimens presented as indirect and exploratory only.

METHODS: This study was prospectively registered in PROSPERO (registration number: CRD420251159170) and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The methodological quality of this systematic review was evaluated using the AMSTAR 2 tool. A comprehensive electronic search was performed across eight databases (PubMed, Embase, Cochrane Library, Web of Science, Sinomed, CNKI, WanFang, and VIP) up to February 2, 2026. Eligible studies included randomized controlled trials (RCTs), single-arm trials, and observational studies (cohort studies, case-control studies) investigating neoadjuvant therapy combined with immunotherapy for rectal cancer. Data extraction was independently performed by two authors, and risk of bias was assessed using the ROBINS-I tool (for non-randomized studies) and the Cochrane Collaboration risk of bias tool (for RCTs). The GRADE approach was used to evaluate the certainty of evidence. Statistical analysis was conducted with R Studio 4.3.2 software, employing random-effects or fixed-effects models based on heterogeneity (assessed by I² statistic and chi-squared test). This meta-analysis does not include controlled comparative trials and that all analyses are single-arm proportion pooling without direct between-group comparisons.

RESULTS: A total of 16 studies involving 540 rectal cancer patients were included. The pooled anal sphincter preservation rate was 0.90 (95% CI: 0.87-0.93) with moderate heterogeneity (I²=37.4%, P = 0.0716). The R0 resection rate was 0.98 (95% CI: 0.96-1.00) (I²=51.4%, P = 0.0361), and the pathological complete response (pCR) rate was 0.34 (95% CI: 0.29-0.38) (I²=71.8%, P < 0.0001). The overall complete response (CR) rate was 0.49 (95% CI: 0.44-0.54) (I²=66.0%, P = 0.0007), and the tumor regression grade (TRG) 0-1 rate was 0.55 (95% CI: 0.49-0.62) (I²=78.6%, P < 0.0001). Regarding safety, the incidence of grade 1-2 adverse events was 0.80 (95% CI: 0.71-0.89) (I²=0.0%, P = 0.8159), grade ≥3 adverse events was 0.17 (95% CI: 0.13-0.21) (I²=97.4%, P < 0.0001), and postoperative complications rate was 0.24 (95% CI: 0.18-0.30) (I²=92.4%, P<0.0001). Pooled estimates within clinically defined subgroups were generally consistent and are reported descriptively only.

CONCLUSIONS: Neoadjuvant therapy combined with immunotherapy was associated with favorable pooled proportions of sphincter preservation and R0 resection in the included studies, although these estimates are derived predominantly from single-arm studies. This regimen warrants further investigation for organ preservation strategies, but confirmatory evidence from high-quality RCTs is needed. Given that the current evidence is predominantly of low-to-moderate certainty, high-quality, large-scale RCTs with long-term follow-up are needed to further validate these findings and optimize treatment regimens.

SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=CRD420251159170, identifier CRD420251159170.

PMID:42630182 | PMC:PMC13493273 | DOI:10.3389/fonc.2026.1866026