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Nevin Manimala Statistics

Postpartum glucose follow-up after gestational diabetes in China: provider and institutional determinants in a multicenter survey across urban public hospitals

Front Endocrinol (Lausanne). 2026 Aug 7;17:1887259. doi: 10.3389/fendo.2026.1887259. eCollection 2026.

ABSTRACT

BACKGROUND: Postpartum glucose follow-up after gestational diabetes mellitus (GDM) represents an important opportunity for early diabetes risk identification and long-term type 2 diabetes prevention. Obstetric healthcare professionals play a key role in initiating postpartum follow-up, yet evidence on provider- and institution-related factors influencing implementation in routine obstetric care remains limited.

METHODS: A multicenter cross-sectional survey was conducted among 638 obstetric healthcare professionals from 128 participating urban public hospitals across 15 provinces in China. A self-developed questionnaire was refined through two rounds of Delphi expert consultation and evaluated using exploratory factor analysis. Data were analysed using descriptive statistics, Pearson’s correlation analysis, Mann-Whitney U tests, Kruskal-Wallis H tests, and robust regression based on a generalised linear model.

RESULTS: Mean scores for knowledge, professional beliefs, and practice were 4.07 ± 0.57, 3.99 ± 0.40, and 3.89 ± 0.73, respectively, indicating that practice lagged behind knowledge and professional beliefs. Knowledge was positively correlated with professional beliefs (r = 0.473, P < 0.001) and practice (r = 0.630, P < 0.001). Participation in specialised GDM training, experience working in a specialist GDM clinic, and self-reported mastery of relevant knowledge were associated with higher scores across domains. Hospital-level differences were observed for practice scores, but these differences did not indicate a simple gradient by hospital level.

CONCLUSION: This study suggests that implementation of postpartum glucose follow-up after GDM in routine obstetric care is associated with both provider- and institution-related factors. Although obstetric healthcare professionals generally demonstrated good knowledge and positive professional beliefs, practice remained comparatively weaker. Specialised training, clinical experience, and institutional context were associated with implementation-related practice. Future efforts to strengthen training, optimise follow-up pathways, and improve institutional support may help reduce missed opportunities for postpartum follow-up and strengthen long-term diabetes prevention after GDM.

PMID:42630220 | PMC:PMC13493272 | DOI:10.3389/fendo.2026.1887259

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Admission direct bilirubin and direct bilirubin-to-lymphocyte ratio as exploratory markers of early severity and in-hospital functional status in acute ischemic stroke

Front Stroke. 2026 Aug 7;5:1800285. doi: 10.3389/fstro.2026.1800285. eCollection 2026.

ABSTRACT

OBJECTIVES: To investigate the correlation between direct bilirubin (DBIL), direct bilirubin-lymphocyte ratio (DBLR), and the severity of acute ischemic stroke (AIS), and to evaluate their potential as auxiliary biomarkers for early severity assessment and short-term in-hospital functional outcome of AIS.

METHODS: A retrospective study was conducted to enroll 234 patients with AIS who presented within 24 h of admission to The First Hospital of Lanzhou University as the AIS Group, and 180 healthy individuals who underwent a health checkup at the same time were randomly selected as the Control Group. The patients’ general information, National Institute of Health Stroke Scale (NIHSS) scores, and laboratory indicators at admission were collected with DBLR calculated as DBIL divided by lymphocyte (LYM) count. The AIS Group was divided into Mild Group (NIHSS ≤ 6, n = 91), Moderate Group (6 < NIHSS < 15, n = 82), and Severe Group (NIHSS ≥ 15, n = 61) according to the NIHSS scores at admission. The AIS Group was further divided into Good early functional outcome Group (mRS < 3, n = 133) and Poor early functional outcome Group (mRS ≥ 3, n = 101) according to the Modified Rankin Scale (mRS) scores at 7 ± 2 days of treatment. The differences in past medical history, general clinical data, and laboratory indicators between the AIS Group and the Control Group were compared, and the differences in laboratory indicators between the different subgroups were analyzed respectively.

RESULTS: Compared to the Control Group; the AIS Group exhibited significantly higher direct bilirubin (DBIL) levels and a lower lymphocyte (LYM) count (P < 0.05). Both the Moderate and Severe Groups presented elevated direct bilirubin (DBIL) levels (P < 0.001), indirect bilirubin (IBIL) levels (P = 0.021), and direct bilirubin ratio (DBLR) (P < 0.001). Notably, DBIL (r = 0.269, P < 0.001) and DBLR (r = 0.321, P < 0.001) were positively correlated with the extent of neurological deficit, while LYM count (r = -0.274, P < 0.001) exhibited a negative correlation with neurological deficit severity. At the time of admission, DBIL and DBLR were identified as risk factors for neurological deficits. This study performed receiver operating characteristic (ROC) curve analysis on DBLR and DBIL among patients with severe strokes. The area under the curve (AUC) for DBLR was 0.612, with an optimal diagnostic threshold of 2.82, yielding a sensitivity of 47.2% and a specificity of 79.4% (P = 0.005, 95% CI: 0.537-0.686). For DBIL, the AUC was 0.596, the optimal diagnostic threshold was 2.85, with a sensitivity of 72.7% and a specificity of 43.5% (P = 0.017, 95% CI: 0.521-0.671), and the difference was statistically significant (P < 0.05). In comparison to the Good early functional outcome Group, the Poor early functional outcome Group showed higher DBIL and DBLR levels, along with a lower LYM count. Moreover, DBIL and DBLR were positively correlated with the Modified Rankin Scale (mRS) scores at 7 ± 2 days. The AUC for DBLR was 0.650, with an optimal diagnostic threshold of 2.86, a sensitivity of 69.8%, and a specificity of 58.5% (P < 0.001, 95% CI: 0.581-0.719). The AUC for DBIL was 0.582, with an optimal diagnostic threshold of 2.55, a sensitivity of 80.8%, and a specificity of 36.6% (P = 0.031, 95% CI: 0.509-0.654), with a statistically significant difference (P < 0.05). Additionally, elevated continuous DBLR was independently associated with poor early functional outcome, and the exploratory cutoff of DBLR > 2.86 indicated a higher risk of poor short-term functional status.

CONCLUSIONS: Admission levels of DBIL and DBLR are significantly correlated with the degree of neurological impairment and short-term (7 ± 2 days) in-hospital functional status in AIS patients, where higher values indicate more severe acute neurological deficits and poorer early outcomes. Elevated DBLR is independently associated with poor short-term functional status, and the exploratory cutoff of DBLR > 2.86 (OR = 5.169, 95% CI: 1.623-16.461, P = 0.005) may assist in early risk stratification. However, their independent predictive ability is limited (all AUCs < 0.7). Therefore, these biomarkers should only be used as auxiliary tools in combination with clinical scores such as the NIHSS, and their clinical value should not be overinterpreted.

PMID:42630218 | PMC:PMC13493299 | DOI:10.3389/fstro.2026.1800285

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Serum interleukin-10 levels and mortality in severe fever with thrombocytopenia syndrome: a systematic review and meta-analysis

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

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Late follicular phase progesterone levels and in vitro fertilization and intracytoplasmic sperm injection outcomes

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

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Conventional imaging-derived phenotypes of brain abscess and short-term clinical outcomes: a comparative study in children and adults

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

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Association between blood lipids, BMI and gestational diabetes mellitus in early pregnancy: a clinical study and Mendelian randomization

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

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Early-pregnancy fasting blood glucose and subsequent GDM define four distinct risk groups for adverse pregnancy outcomes: a cohort study of 15,245 women

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

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Clinical and genetic evidence from East Asian cohorts linking family history burden and menarche timing to curve severity in adolescent idiopathic scoliosis

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

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Association of postoperative delayed bowel function recovery with weight and muscle loss at 6 months in colorectal cancer patients

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

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Whole-genome and pan-genome analyses reveal genomic differences among nontypeable Haemophilus influenzae isolates from bronchiectasis, community-acquired pneumonia, and chronic obstructive pulmonary disease

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