Category: Statistics

Galen Med J. 2025 Dec 31;14(S Pt 1):e4114. doi: 10.31661/gmj.v14iSP1.4114. eCollection 2025.

ABSTRACT

BACKGROUND: This retrospective study evaluated the success rates of dental implants placed without primary stability in a private practice setting, utilizing three contemporary implant systems (Neodent GM Helix, Biotem AR, MegaGen AnyOne) and stability-oriented protocols.

MATERIALS AND METHODS: Records from 63 patients receiving 97 implants (Neodent GM Helix, n=35; Biotem AR, n=39; MegaGen AnyOne, n=23; 76 in maxilla, 21 in mandible) placed between January 2021 and September 2024 in Qazvin, Iran, were reviewed. Absence of primary stability was defined as insertion torque 10 N·cm and/or intraoperative spinning. Immediate placements (n=23) received grafting; all implants were submerged, uncovered at approximately 3 months, and loaded at approximately 4 months. Success was assessed using modified Albrektsson/Buser criteria. Statistical analysis included Wilson 95% confidence intervals and Fisher’s exact or χ² tests.

RESULTS: Overall success rate was 95.9% (93/97; 95% CI 89.9-98.4%). Success rate by system was 97.1 % (34/35) for Neodent, 94.9% (37/39) for Biotem, 95.7% (22/23) for MegaGen with no significant difference among the systems (P=0.91). Immediate placements achieved a 100% success rate (23 out of 23 implants), compared to 94.6% for delayed placements (70 out of 74 implants), with no significant difference (P=0.58). Success rates were 96.1% in the maxilla (73 out of 76 implants) and 95.2% in the mandible (20 out of 21 implants), with no significant difference (P=1.00). Four early failures occurred (≤4 weeks), all in delayed placements; no late failures were observed. Systemic conditions (diabetes, hypertension, hypothyroidism) did not increase failure rates (P=0.61). All implant failures occurred in posterior regions and delayed timing of placement, while anterior and immediately placed implants achieved 100% success.

CONCLUSION: In carefully selected cases employing atraumatic techniques, socket grafting and sealing for immediate sites, and conservative loading protocols, implants placed without primary stability demonstrated clinically acceptable success rates comparable to private practice benchmarks. Nonetheless, the absence of mechanical primary stability remains a risk factor, particularly in the posterior maxilla or type IV bone; these findings do not advocate replacing primary stability. Prospective, multicenter studies with standardized Implant Stability Quotient (ISQ) monitoring are recommended.

PMID:42500693 | PMC:PMC13109637 | DOI:10.31661/gmj.v14iSP1.4114

Front Immunol. 2026 Jul 10;17:1848431. doi: 10.3389/fimmu.2026.1848431. eCollection 2026.

ABSTRACT

BACKGROUND: Despite the proven efficacy of KRAS G12C inhibitors (KRAS G12Ci) in solid tumors, evidence from direct comparisons with standard of care is scarce, and no analysis has investigated the potential immunological basis for differential responses.

METHODS: PubMed, Embase, Cochrane Library, and ClinicalTrials.gov for randomized controlled trials (RCTs) involving solid tumors patients who had received KRAS G12Ci were retrieved from inception to March 28, 2026. Individual participant data on progression-free survival (PFS) and overall survival (OS) were extracted from the published Kaplan-Meier survival curves. When available, subgroup data by programmed death ligand 1 (PD-L1) expression were extracted to explore immune-related correlates of treatment response.

RESULTS: A total of 4 articles with 3 RCTs and 949 participants were selected. In 1-stage reconstructed individual patient data meta-analyses, PFS was better in the KRAS G12Ci group (HR, 0.62; 95% CI, 0.53-0.74; P < 0.001). However, no statistical difference in OS was observed (HR, 0.93; 95% CI, 0.74-1.16; P = 0.495). The results were confirmed by 2-stage meta-analyses which additionally exhibited an objective response rate (ORR) of 3.60 (95% CI; 2.01-6.46; P < 0.001; I² = 39.7%). Regarding PD-L1 expression, PFS benefits were observed in patients with expression levels <1% (HR, 0.56; 95% CI: 0.38-0.83; P = 0.004) and 1%-49% (HR, 0.58; 95% CI: 0.43-0.78; P < 0.001). KRAS G12Ci demonstrated a better safety profile, apart from diarrhea and rash.

CONCLUSIONS: A similar OS, but better PFS and ORR with a superior safety profile were observed in patients receiving KRAS G12Ci, suggesting that KRAS G12Ci may be more suitable for later-line therapy. Older patients, those without liver metastases, or those with PD-L1<50% may be the target population. These subgroup observations are hypothesis-generating and require prospective validation.

SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD420251146769.

PMID:42500683 | PMC:PMC13396023 | DOI:10.3389/fimmu.2026.1848431

Front Immunol. 2026 Jul 10;17:1869012. doi: 10.3389/fimmu.2026.1869012. eCollection 2026.

ABSTRACT

INTRODUCTION: Disease-related malnutrition can develop in colorectal cancer (CRC) patients, negatively affecting postoperative clinical outcomes. Nutritional status should be assessed using standardised tools and laboratory parameters to identify malnourished patients and introduce personalised, targeted dietary interventions based on epigenetics, immunologically-related aspects, and gut microbiome. The primary aim of this study is to analyse the immunonutritional status of CRC patients in the preoperative period. The secondary aim is to assess the link between albumin-to-globulin ratio (AGR), prognostic nutritional index (PNI), and TNM staging.

PATIENTS AND METHODS: This study initially included 21 patients with histopathological confirmation of CRC qualified for surgical resection of the tumour. Immunologically-related nutritional status parameters, i.e., AGR and PNI, were calculated for selected 12 patients. The optimal cut-off value of PNI was determined, allowing patients to be divided into two independent groups: PNI-low and PNI-high. The link between AGR, PNI, and TNM was analysed.

RESULTS: TNM classification of the 12 selected participants revealed that most participants classified as T3 (67%), lymph node metastasis was identified in 50% of patients, and there were no distant metastases. Among selected patients, the analysis of mean values of immunological laboratory tests showed that they were within the normal range, except for lymphocyte levels, which were reduced (22.03 ± 7.31%). The optimal cut-off value was set at 51.74 for PNI; thus, patients were accordingly divided into PNI-low and PNI-high groups (<51.74, 34% of cases; ≥51.74, 66%, respectively). PNI-low was initially associated with more advanced cases (based on T assessment) compared to PNI-high (100% versus 75%; respectively); however, it failed to reach statistical significance (p = 0.515; effect size 0.2889; CI 95%, CI = 0.0110-7.5681). Therefore, this finding should be interpreted with caution. Lymph node metastasis was found more often in the PNI-high group than in the PNI-low group.

CONCLUSIONS: Overall concentrations of albumin and total protein were not decreased in CRC patients; however, these parameters allow calculation of AGR and PNI. The link between PNI-low and locally advanced cases of CRC based on T assessment can potentially exist; nevertheless, it should be confirmed with more clinical data. Lymph node metastasis was more often observed in the PNI-high group. This status is also related to higher levels of AGR. A PNI-low value is more related to local than distant pathological processes associated with CRC.

PMID:42500671 | PMC:PMC13395656 | DOI:10.3389/fimmu.2026.1869012

Front Immunol. 2026 Jul 10;17:1855859. doi: 10.3389/fimmu.2026.1855859. eCollection 2026.

ABSTRACT

OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor prognosis. Immune checkpoint inhibitor (ICI) monotherapy has shown limited efficacy in PDAC, whereas the potential clinical value of first-line ICI-based combination regimens remains unclear. Through a systematic review and meta-analysis, this study aimed to evaluate the efficacy and safety of first-line ICI-based combination regimens in advanced PDAC.

METHODS: PubMed, Embase, The Cochrane Library, Scopus, Web of Science, CNKI, Wanfang Data, VIP, and CBM were searched up to April 4, 2026, to identify clinical studies evaluating first-line ICI-based combination therapy for advanced PDAC. Study screening and data extraction were performed in accordance with PRISMA guidelines.

RESULTS: Eight clinical trials involving 379 patients were included. In RCT-only analyses, ICI-based combination regimens showed favorable but statistically non-definitive trends for OS (HR = 0.83, 95% CI: 0.65-1.06) and PFS (HR = 0.75, 95% CI: 0.53-1.05), while ORR was improved (OR = 2.19, 95% CI: 1.32-3.64). Single-arm pooled analysis showed a median PFS of 6.2 months and an ORR of 38.0%. In terms of safety, combination therapy increased the risk of specific Grade 3 or higher adverse events, but the overall incidence was clinically manageable.

CONCLUSION: First-line ICI-based combination regimens showed encouraging antitumor activity in advanced PDAC, particularly for radiological response. However, definitive survival benefits were not established in RCT-only analyses, and further large-scale randomized trials are needed.

SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420261440306, identifier CRD420261440306.

PMID:42500667 | PMC:PMC13396027 | DOI:10.3389/fimmu.2026.1855859

Front Immunol. 2026 Jul 10;17:1839715. doi: 10.3389/fimmu.2026.1839715. eCollection 2026.

ABSTRACT

OBJECTIVE: This study aims to summarize and appraise the credibility of existing epidemiological evidence on the association between periodontal diseases (PDs) and the risk of site-specific cancers.

METHODS: PubMed, Embase, and Cochrane Library were searched from inception to June 2026. Meta-analyses of observational studies investigating PDs and cancer risk were included. Each association was classified into five levels according to a predefined criterion, which included statistical significance, heterogeneity, sample size, and bias assessment. AMSTAR 2 was used to evaluate the quality of studies. Corrected covered area and the author’s own meta-analysis were performed to ensure a rigorous methodology.

RESULTS: In total, 66 associations from 38 meta-analyses investigating 14 cancer types were appraised, including head and neck cancer (HNC), oral, lung, breast, esophageal, gastric, pancreatic, liver, colorectal, bladder, kidney, prostate, melanoma, and hematopoietic and lymphatic cancers. Among 23 main associations, highly suggestive evidence was identified in associations between PDs (odds ratio [OR], 2.42; 95% confidence interval [CI], 1.85-3.17) in HNC, and PDs in oral cancer (OR, 2.94; 95% CI, 2.13-4.07). Another seven associations were recommended as suggestive evidence (class III). Fourteen associations were classified as weak (class IV) or showing no significant evidence (class V).

CONCLUSION: Associations between PDs and site-specific cancers demonstrated varying levels of evidence. This analysis highlighted strong correlations in HNC and oral cancer, while failing to show credible evidence for the remaining 12 cancers. Overall, our study yielded novel insights into oral health interventions, calling for the incorporation of periodontal health into public health policy.

SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD42024585375, identifier CRD42024585375.

PMID:42500648 | PMC:PMC13395657 | DOI:10.3389/fimmu.2026.1839715

Indian J Anaesth. 2026 Jul;70(7):821-828. doi: 10.4103/ija.ija_1635_25. Epub 2026 Jul 21.

ABSTRACT

BACKGROUND AND AIMS: del Nido cardioplegia (DC), initially developed for paediatric cardiac surgery, is increasingly used in adult procedures due to its ability to provide prolonged myocardial protection with a single dose. However, its superiority over blood cardioplegia (BC) remains unclear. This study compared the effects of DC and BC on acid-base balance, potassium levels, and metabolic profiles in adults undergoing elective cardiac surgery with cardiopulmonary bypass (CPB).

METHODS: A retrospective observational study was conducted at a tertiary care centre over a period of 6 months. Forty-seven patients were divided into Group BC (received blood cardioplegia) and Group DC (received del Nido cardioplegia). Arterial blood gases were recorded at four intraoperative time points. The four time points were T1, baseline before CPB; T2, immediately after cardioplegia administration; T3, post-rewarming just before separation from CPB; and T4, before transfer to the intensive care unit. Statistical analyses were performed using independent t-tests and Chi-square tests, or their equivalent non-parametric alternatives when appropriate.

RESULTS: Group DC exhibited a significantly higher potential of hydrogen (pH) (7.49 vs 7.43, P = 0.003) and base excess (0.15 vs – 1.80 mmol/L, P = 0.014) at post-rewarming (T3). Potassium was lower in group DC at baseline (T1). Blood glucose was significantly higher in group BC at T3 (275 vs 207 mg/dL, P < 0.001) and T4 (258 vs 217 mg/dL, P = 0.033). Five patients in the DC group required blood transfusion during CPB.

CONCLUSION: DC and BC showed largely comparable intraoperative metabolic and physiological profiles, with most observed differences remaining within acceptable physiological ranges and of limited clinical significance. DC may be a practical alternative to BC; however, larger prospective studies evaluating direct myocardial injury markers and postoperative outcomes are needed.

PMID:42500639 | PMC:PMC13399266 | DOI:10.4103/ija.ija_1635_25

Crit Care. 2026 Jul 24;30(1):385. doi: 10.1186/s13054-026-06099-2.

ABSTRACT

BACKGROUND: Cardiac surgery-associated acute kidney injury (CSA-AKI) following cardiopulmonary bypass (CPB) remains a high-risk complication with limited effective management. Hemoadsorption is increasingly used as an adjunctive therapy due to its potent cytokines clearance in experimental settings, yet its clinical efficacy is debated. This study aimed to evaluate the effect of hemoadsorption versus standard care on CSA-AKI and other major outcomes in adult cardiac surgery patients.

METHODS: An updated systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted following PRISMA guidelines. PubMed, Medline, Embase, Web of Science, and the Cochrane Library were systematically searched from inception to 8 February 2025. Eligible RCTs enrolled adult patients undergoing cardiac surgery and compared intraoperative hemoadsorption with standard care, with reported outcomes including CSA-AKI and other major endpoints. Pooled estimates were synthesized using inverse-variance random-effects models, with heterogeneity quantified by I² statistics. Subgroup, sensitivity and trial sequential analyses (TSA) were further performed.

RESULTS: Fifteen RCTs were included, of which nine reported CSA-AKI (947 patients). Hemoadsorption was not associated with a statistically significant reduction in CSA-AKI (RR 0.80, 95% CI 0.63-1.03, P = 0.08, I² = 40%, GRADE: very low). The finding was sensitive to model choice and the inclusion of two studies (Diab 2022 and Abou-Arab 2025). Subgroup analyses revealed no significant interaction by device type. TSA indicated that the required information size was not reached. No significant differences were observed for CSA-AKI Stage 1 (RR 0.72, 95% CI 0.49-1.05, P = 0.09, I² = 16%), Stage 2 (RR 0.66, 95% CI 0.30-1.43, P = 0.29, I² = 11%), Stage 3 (RR 0.43, 95% CI 0.17-1.05, P = 0.06, I² = 0%), or renal replacement therapy (RR 0.52, 95% CI 0.22-1.25, P = 0.15, I² = 0%). Mortality and other clinical endpoints were comparable between groups. Among exploratory outcomes, only an overall reduction in IL-8 was noted (MD -18.23, 95% CI -31.90 to -4.56, P = 0.009, I² = 40%).

CONCLUSIONS: Intraoperative hemoadsorption did not significantly reduce CSA-AKI or improve clinical outcomes in adult cardiac surgery. Although trends favored severe AKI, very low certainty evidence and insufficient information preclude definitive conclusions, warranting further large-scale RCTs.

REGISTRATION: PROSPERO identifier CRD420250651941.

PMID:42498964 | DOI:10.1186/s13054-026-06099-2

Cardiovasc Diabetol. 2026 Jul 24;25(1):210. doi: 10.1186/s12933-026-03292-z.

ABSTRACT

BACKGROUND: Inhibitors of the sodium-glucose cotransporter 2 (SGLT2) provide cardiovascular and renal protection in both diabetic and non-diabetic patients at least in part independently of glycaemic control. Some underlying mechanisms for these clinically beneficial effects were suggested, but the picture is far from complete. In this study we aimed to apply untargeted metabolomics in order to identify new mechanistic leads.

METHODS: Plasma and 24-hour urine samples of 48 diabetic patients taken before and after 6 weeks of treatment from two prospective, randomized, double-blind, placebo-controlled, cross-over trials with dapagliflozin or empagliflozin were used. Additionally, plasma and urine samples of 24 diabetic patients from a prospective, randomized, controlled, parallel-arm, interventional, open-label, single centre study with either empagliflozin and linagliptin or metformin and insulin glargine for 12 weeks were used for confirmation. Changes of metabolite patterns in plasma and urine were determined by untargeted high-resolution mass spectrometry. Moreover, parameters of arterial stiffness and retinal vascular remodelling were correlated with treatment effects of the SGLT2 inhibitors on the modified nucleoside N4-acetylcytidine (ac4C), a potential biomarker for the activity of the enzyme N-acetyltransferase 10 (NAT10).

RESULTS: In accordance with previously reported results treatment with SGLT2 inhibitors led to a reduction of glucose (log₂fc: – 0.23, adj. p < 0.01) and uric acid (log₂fc: – 0.23, adj. p < 0.001), while 3-hydroxybutyric acid (log₂fc: 0.84, adj. p < 0.001) and 3-hydroxybutyrylcarnitine (log₂fc: 0.57, adj. p < 0.001) were increased in plasma. As a new finding, plasma concentrations of ac4C were reduced (log₂fc: – 0.32, adj. p < 0.001) by SGLT2 inhibitors but not by the non-SGLT2 inhibiting glucose lowering treatment. Reduction of urinary concentrations of ac4C corresponded to its reduction in plasma in groups treated with the SGLT2 inhibitors. Wall thickness of retinal arterioles and central systolic blood pressure were significantly correlated to ac4C in plasma.

CONCLUSIONS: Treatment with dapagliflozin and empagliflozin reduced plasma concentrations of ac4C, which was correlated with parameters for vascular health. These exploratory findings may indicate inhibition of NAT10 activity as a potential contributor to the beneficial effects on cardiovascular and renal health by SGLT2 inhibitors.

TRIAL REGISTRATIONS: http://www.

CLINICALTRIALS: gov : NCT02383238, NCT02471963, NCT02752113.

PMID:42498959 | DOI:10.1186/s12933-026-03292-z

BMC Psychiatry. 2026 Jul 23;26(1):564. doi: 10.1186/s12888-026-08423-0.

ABSTRACT

BACKGROUND: The Generalized Anxiety Disorder 7-item scale (GAD-7) could provide currently lacking data on anxiety levels among adolescents and young adults in Sweden. However, psychometric assessments of the scale are scarce in this population. Additionally, the structural validity of the scale needs to be examined further, given conflicting findings in other populations. The aim of this study was to psychometrically evaluate the GAD-7 among 15-29-year-olds using Rasch analysis and confirmatory factor analysis in a Swedish, general population sample. In addition, an iterative process explored if revised versions of the scale could be identified that fit the Rasch model in this sample.

METHODS: A random, age- and sex-stratified sample of 15-29-year-olds from the Swedish population register was drawn, from which stratified groups were randomly invited to participate. Data (n = 590) were collected through a study-specific app. Rasch analyses included investigation of item fit, local independence, principal components analysis of standardized Rasch model residuals, response category functioning, measurement invariance, scale-to-sample targeting, and reliability. In addition, confirmatory factor analyses (CFA) were conducted and interpreted using dynamic, data-adaptive cutoffs. An exploratory, iterative process was undertaken aiming at scale refinement based on results for the GAD-7.

RESULTS: No Rasch analyses provided support for the unidimensionality of the GAD-7, which also displayed issues with disordered response categories and measurement invariance. The CFA found substantial misfit for the one-factor model. The exploratory scale refinement resulted in two abbreviated scales warranting further investigation: Items 1-3 fit the Rasch model as a unidimensional scale and demonstrated acceptable to good reliability. Items 5-7 had good fit after merging the two highest response categories, although demonstrated poor reliability.

CONCLUSIONS: No analyses provided support for the unidimensionality of the GAD-7 among 15-29-year-olds in Sweden. While these findings do not support the use of a single sum score, they require confirmation in independent samples. Future research should evaluate whether the abbreviated, candidate scale comprising items 1-3 could be useful to assess anxiety in this population, including examination of criterion validity and the potential benefits of adding a response category to enhance both reliability and scale-to-sample targeting.

PMID:42498940 | DOI:10.1186/s12888-026-08423-0

BMC Oral Health. 2026 Jul 23;26(1):1348. doi: 10.1186/s12903-026-09303-5.

ABSTRACT

BACKGROUND: Conventional plate osteosynthesis is the corner stone for management of displaced parasymphyseal mandibular fractures that necessitate open reduction and internal fixation (ORIF). Yet, the conventional workflow is labor-intensive, time consuming and limited by variable reduction accuracy as it relies solely on surgeon experience. Recently, various novel computer-guided techniques have been introduced for mandibular fracture repair, hiring surgical guides of diverse designs and strategies. These techniques served as a substitute for the conventional treatment modalities, offering improved precision, speed and reproducibility. Therefore, this randomized controlled trial (RCT) compares the overall precision of this distinct complete computer-guided virtual surgical planning (VSP) protocol as a whole, employing screw-holes locator and custom-made plates versus the conventional workflow for parasymphyseal mandibular fracture repair.

METHODS: Twenty-six cases presented with uncomminuted parasymphyseal mandibular fracture were enrolled and randomized into two groups. The interventional group underwent ORIF utilizing a screw-hole locator and custom-made plates, while the control group utilized ready-made mini-plates for ORIF. In both groups, virtual surgical planning of the fractured mandible was accomplished, creating a virtual reduced model by Mimics software aided by preoperative computer tomography (CT) scan. Then, three-dimensional model derived from the postoperative CT scan was superimposed onto the VSP reduced model. Linear deviations between predefined dental and bony landmarks to established anatomical planes were measured and underwent statistical analysis.

RESULTS: The actual postoperative mandibular model in the computer-guided group demonstrated negligible deviation from the VSP model. While the conventional group revealed considerably greater deviation. The average deviation of the bony landmarks was 0.044 ± 0.14 mm for the intervention group versus 0.69 ± 0.5 mm for the control group (p < 0.001). The average deviation of the dental landmarks was 0.04 ± 0.13 mm for the intervention group versus 0.47 ± 0.33 mm for the control group (p < 0.001). The average surgical time of the intervention group was 1.46 ± 0.18 h versus 1.80 ± 0.34 h for the control group (p = 0.004), with the intergroup difference being statistically significant.

CONCLUSIONS: The integration of screw-holes locator and patient-specific implants (PSI) have improved anatomical reduction precision, facilitated reestablishment of the patient’s native occlusion and ensured more standardized reproducible outcomes, especially beneficial for less experienced surgeons.

TRIAL REGISTRATION: The study is a randomized control trial, registered at ClinicalTrials.gov Protocol Registration and Results System Receipt, NCT05647460, Data: 2022-12-05.

PMID:42498926 | DOI:10.1186/s12903-026-09303-5