Nevin Manimala

Diabetes Obes Metab. 2025 Aug 5. doi: 10.1111/dom.70006. Online ahead of print.

ABSTRACT

AIMS: To assess the glycaemic efficacy and safety of CT-868, a cAMP signal-biased, dual glucagon-like peptide-1/glucose-dependent insulinotropic polypeptide receptor agonist, in participants with type 2 diabetes (T2D).

MATERIALS AND METHODS: This 26-week (W), phase 2, randomized, double-blind placebo-controlled trial enrolled adults with T2D, Body Mass Index ≥27 kg/m², and glycated haemoglobin (HbA1c) 7.0-10.0%. Participants were randomized (1:2:1) to once-daily CT-868 1.75 mg, 4.0 mg, or placebo. Due to COVID-19-related CT-868 supply constraints, some participants randomized to 4.0 mg received 3.25 mg maximum and were analysed as a separate dose arm. The primary endpoint was change from baseline in HbA1c at W26. Secondary endpoints included changes from baseline to W26 in fasting glucose, 7-point self-monitored blood glucose (SMBG), body weight, lipids and the occurrence of adverse events (AEs).

RESULTS: Overall, 103 participants were enrolled (CT-868 1.75 mg, n = 26; 3.25 mg, n = 18; 4.0 mg, n = 32; placebo, n = 27). Clinically meaningful and statistically significant improvements in HbA1c were observed with CT-868 at W26 (-1.61 to -2.24%-points vs. placebo; all p < 0.001). Body weight was modestly reduced with CT-868 4.0 mg at W26 (-2.9% vs. placebo, p < 0.001). CT-868 improved fasting glucose, SMBG, and most lipid parameters vs. placebo. AEs were mostly mild/moderate. No participants experienced hypoglycaemia.

CONCLUSIONS: CT-868 1.75 to 4.0 mg yielded robust, clinically meaningful decreases in HbA1c, supporting potent glycaemic-lowering effects and improved key lipid parameters in participants with overweight/obesity and T2D, despite modest weight loss. CT-868 was well tolerated, supporting future investigation of higher doses to maximize weight loss.

PMID:40762050 | DOI:10.1111/dom.70006

APMIS. 2025 Aug;133(8):e70055. doi: 10.1111/apm.70055.

ABSTRACT

This study is intended to expound the effect of clarithromycin combined with oxymetazoline hydrochloride (OZH) spray in acute exacerbations of chronic rhinosinusitis (AECRS). Patients with AECRS were retrospectively collected and divided into a control group and an observation group. The control group received clarithromycin, and the observation group received OZH spray in addition to clarithromycin. Symptom resolution time, nasal mucociliary transmission velocity, nasal endoscopy score, olfactory function, serum inflammatory factor levels, incidence of adverse reactions, and 6-month recurrence were recorded. After treatment, the observation group showed shorter resolution times for headache, runny nose, nasal congestion, and nasal mucosal edema; higher nasal mucociliary transport rate (MTR) and clearance (MCC); lower Lund-Kennedy score; more Grades I cases; fewer Grades III cases; lower levels of serum IL-6, TNF-α, hs-CRP, IL-8, and IL-1β; and lower recurrence rate than the control group (p < 0.05). The incidence of adverse reactions in the two groups was not statistically significant (p > 0.05). Clarithromycin combined with OZH spray is more effective in patients with AECRS, which can shorten symptom resolution time, increase nasal MTR, improve olfactory function, reduce inflammation and recurrence rates, and have a high degree of safety.

PMID:40762040 | DOI:10.1111/apm.70055

Head Neck. 2025 Aug 5. doi: 10.1002/hed.70003. Online ahead of print.

ABSTRACT

BACKGROUND: Human papilloma virus (HPV) is a DNA virus capable of infecting mucous membranes. In most cases, the infection is cleared by the immune system, but a prolonged exposure to HPV can progress to cancer. 40%-60% of head and neck squamous cell carcinomas (HNSCC) are linked to HPV, which is considered a risk factor especially among young people in industrialized countries. HNSCC are not identified early due to their slow growth and their locations not being easy to see. Despite the prognostic value of HPV, the use of HPV-DNA as a diagnostic marker is not fully developed. HPV-DNA can be detected in saliva specimens of patients with HPV-driven cancers. Considering this, we employed saliva samples to optimize a non-invasive RT-PCR assay for HPV infection and prove the hypothesis that the presence of HPV DNA represents a risk factor for Oral Cavity Squamous Cell Carcinoma (OCSCC). The potential of this work is to highlight how an HPV screening program based on salivary testing can be useful for early cancer detection and patient monitoring.

METHODS: In this retrospective study, 127 patients and 93 control samples were tested for the presence of HPV in self-collected saliva specimens. Viral DNA was extracted from saliva using an automated instrument. A multiplex RT-PCR was employed for the detection of the (28 most frequent HPV Types). Patients’ demographics were collected in a clinical database. Statistics were performed by STATA16, and significance was set at p < 0.05.

RESULTS: Most patients had a diagnosis of OCSCC (49.1%), 38%-9% of which involved the tongue. 9.6% resulted positive for HPV DNA in saliva, specifically for high-risk subtypes (42.9% type 58; 28.6% types 45, 59, 39 and 9.6% type 16, 18). HPV+patients were compared to those who were found negative. HPV infection was related to the TNM stage, especially with pT2N1 (p ≤ 0.002) and with primary vs. relapsed tumors (p = 0.004). Independent of site, the assay reached a sensitivity of 91.7%, a specificity of 100%, and an agreement of 98.5%, compared to the oropharyngeal swab (Cohen’s Kappa = 0.947; n = 65). Test PPV was 100% (95% CI 71.5-100), while NPV was 98.1% (95% CI 90.1-100).

CONCLUSIONS: Our findings indicate that salivary HPV testing is a non-invasive and convenient test that could become part of routine clinical management for HPV infection of the oral cavity. This test represents an ideal mode of screening of asymptomatic individuals and a long-term monitoring tool for HPV-driven cancer patients.

PMID:40762035 | DOI:10.1002/hed.70003

Orthop Surg. 2025 Aug 5. doi: 10.1111/os.70142. Online ahead of print.

ABSTRACT

OBJECTIVE: Hinge fracture is a known complication of lateral open wedge distal femoral osteotomy (LOWDFO). However, few studies have differentiated between intraoperative hinge fractures (IHF) and postoperative hinge fractures (PHF). This study aims to investigate the causes of these two types of fractures to help reduce complication rates and improve surgical outcomes.

METHODS: We retrospectively analyzed data from 100 patients with genu valgum deformity and lateral unicompartmental osteoarthritis who underwent distal femoral osteotomy at our hospital between January 1st, 2022, and January 1st, 2024, in our hospital. Clinical parameters, radiological data, and the associated factors influencing IHF and PHF were analyzed. Radiological data such as mechanical axis deviation (MAD) and mechanical lateral distal femur angle (mLDFA) were collected. Clinical outcomes such as osteoarthritis index and time of healing were evaluated. Based on fracture morphology, IHF and PHF were further classified into Type 1 (extension), Type 2 (distal) and Type 3 (proximal) for detailed analysis. Statistical analyses included t-tests, Chi-square tests, and regression models to identify factors associated with IHF and PHF.

RESULTS: A total of 87 patients were included in this study. The mean healing time of patients with all kinds of hinge fractures (3.4 ± 1.2 months) was longer than that of patients with no hinge fractures (2.8 ± 0.7 months), which was significant, p = 0.013. The MAD correction, mLDFA correction, and mLDFA correction ratio were related to hinge fractures (p = 0.010, 0.002, and 0.002 respectively). The body weight was higher in all types of hinge fractures group (IHF and PHF together) than the no hinge fractures group. The IHF group had a longer time of healing than the no IHF group. In the IHF group, the mLDFA correction (p = 0.005), mLDFA correction ratio (p = 0.005), and BMI (p = 0.031) were higher than the no IHF group. The PHF was related to hinge position. The group of hinge localized proximal to the adductor tubercle (AT) had a higher rate of PHF than the group of hinge localized in the adductor tubercle (p = 0.001). The healing time in the IHF group (3.9 ± 1.4 months) was significantly longer than the healing time in the PHF group (2.7 ± 0.4 months) (p = 0.002).

CONCLUSION: In patients with genu valgum undergoing LOWDFO, IHF and PHF represent distinct clinical entities. IHF is associated with greater mLDFA correction, higher mLDFA correction ratios, and increased body weight. In contrast, PHF is primarily associated with hinge position, with a higher incidence observed when the hinge is located proximal to the adductor tubercle. Among the two, IHF has a more pronounced impact on delayed bone healing.

LEVEL OF EVIDENCE: Retrospective study Level IV.

PMID:40762034 | DOI:10.1111/os.70142

J Environ Health Sci Eng. 2025 Aug 2;23(2):26. doi: 10.1007/s40201-025-00951-3. eCollection 2025 Dec.

ABSTRACT

BACKGROUND: Phthalates are one of the most common environmental contaminants and endocrine disruptors. Environmental exposure to phthalates may increase the risk for allergic diseases. However, the existing literature presents conflicting findings regarding the long-term impact of early-life exposure to these substances.

METHODS: We searched the Web of Science, PubMed and Google Scholar, Medline and Embase databases for all related publications from 1974 to September 1st, 2024. Ultimately, 22 studies with a total of 16,161 participants were selected. The relative risks (RRs) with 95% confidence intervals (95% CIs) were used to evaluate whether prenatal phthalate exposure is associated with allergic endpoints. To assess statistical heterogeneity across studies, both the Q-test and I ² statistic were adopted. Publication bias of the included studies was evaluated using Begg’s and Egger’s tests. Stratified analysis was conducted based on the gender of children, molecular weight of phthalates, disease type, phthalate species, parental exposure period and region. The systematic literature search protocol was formally registered in PROSPERO.

RESULTS: Childhood wheeze (RR 1.10, 95% CI: 1.00-1.21), eczema (RR 1.09, 95% CI: 1.01-1.17), and rhinitis (RR 1.05, 95% CI: 1.02-1.09) are potentially associated with prenatal exposure to phthalates, particularly butyl-benzyl phthalate (RR 1.15, 95% CI: 1.06-1.24), di-ethyl-hexyl phthalate (RR 1.08, 95% CI: 1.02-1.15) and di-iso-nonyl phthalate (RR 1.12, 95% CI: 1.02-1.23).

CONCLUSION: Maternal phthalate exposure during pregnancy exhibits a significant association with elevated risks of childhood respiratory and allergic manifestations, including wheezing episodes, eczematous dermatitis, and rhinitis symptoms.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40201-025-00951-3.

PMID:40762014 | PMC:PMC12317961 | DOI:10.1007/s40201-025-00951-3

Front Dent Med. 2025 Jul 21;6:1593218. doi: 10.3389/fdmed.2025.1593218. eCollection 2025.

ABSTRACT

BACKGROUND: Dickkopf-1 is a glycoprotein that inhibits Wingless-related integration site signaling, impairing osteoblast and osteoclast functions, leading to bone loss and systemic inflammation linked to periodontitis and rheumatoid arthritis. Porphyromonas gingivalis exacerbates rheumatoid arthritis through citrullination and inflammation, highlighting their bidirectional relationship. To date no meta-analysis has examined the role of Dickkopf-1 in periodontitis, rheumatoid arthritis, and their comorbidity. Therefore, we conducted this meta-analysis to investigate the association and role of Dickkopf-1 in these comorbid conditions.

METHODS: The present study was conducted in accordance with the guidelines of Transparent Reporting of Systematic Reviews and Meta-Analyses PRISMA statement (registered at PROSPERO under the number CRD42025643227). A total of 15 studies (14 case-control and 1 cross-sectional) were selected out of 386 using databases like PubMed and Google Scholar (by BM, JM, and DP). A random-effects model evaluated Dickkopf-1 levels in serum/gingival crevicular fluid in periodontitis and rheumatoid arthritis via standardized mean difference (SMD) and 95% confidence intervals (CI). Heterogeneity and publication bias were assessed using statistical metrics, forest plots, funnel plots, Begg’s test, and Egger’s regression.

RESULTS: A total of 386 studies were retrieved and 15 were included in the meta-analysis, encompassing 4,438 participants (2,190 cases and 2,248 controls). The pooled SMD of 2.694 (p = 0.02; 95% CI: 1.170-6.203) indicated a significant association of Dickkopf-1 with periodontitis and/or rheumatoid arthritis compared to healthy controls. However, Egger’s test revealed a t-value of 3.05 (p = 0.009), indicating significant publication bias.

CONCLUSION: Elevated Dickkopf-1 levels in rheumatoid arthritis and periodontitis patients suggest its critical role in the pathogenesis of both conditions. Hence, Dickkopf-1 holds therapeutic potential for managing interconnected inflammatory and bone disorders and may serve as a biomarker for diagnosing these diseases.

SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/search, PROSPERO CRD42025643227.

PMID:40762009 | PMC:PMC12318980 | DOI:10.3389/fdmed.2025.1593218

Aesthet Surg J Open Forum. 2025 Jun 24;7:ojaf070. doi: 10.1093/asjof/ojaf070. eCollection 2025.

ABSTRACT

BACKGROUND: Body dysmorphic disorder (BDD) is a mental health condition characterized by an obsessive focus on perceived physical flaws, causing significant psychological distress. Aesthetic practitioners often interact with appearance-focused patients, increasing their potential exposure to BDD and its psychological effects. Understanding BDD prevalence and awareness among practitioners is crucial for their professional and personal well-being.

OBJECTIVES: The authors of this study aim to assess the prevalence of BDD among aesthetic practitioners (physicians and surgeons) and evaluate their awareness of the disorder.

METHODS: A cross-sectional study was conducted with 199 participants, including 98 aesthetic practitioners and 101 lawyers (control group). Participants completed the Depression, Anxiety, and Stress Scale (DASS-10) and the Cosmetic Procedure Screening (COPS) questionnaires, along with questions assessing BDD knowledge. Statistical analyses included Pearson’s correlations, χ ² tests, analysis of covariance, and logistic regression.

RESULTS: Possible BDD was identified in 8.2% of aesthetic practitioners vs 2% of controls (P = .056). Aesthetic practitioners showed a significant association with self-reported physical-aesthetic disorders (χ ²(2) = 11.25, P = .004). Total COPS scores correlated significantly with distress, anxiety, and depression levels (all P < .001). Regression analysis revealed that aesthetic practitioners were 7 times more likely to exhibit BDD symptoms compared with controls (b = 2.03, P = .03, odds ratio = 7.59), even after controlling for anxiety and depression.

CONCLUSIONS: In this study, the authors underscore the need for enhanced BDD awareness and mental health training among aesthetic practitioners. Addressing mental health within the aesthetic field is essential to improve professional practices and safeguard psychological well-being.

PMID:40762003 | PMC:PMC12318658 | DOI:10.1093/asjof/ojaf070

Cureus. 2025 Jul 5;17(7):e87339. doi: 10.7759/cureus.87339. eCollection 2025 Jul.

ABSTRACT

OBJECTIVE: This study aimed to analyze cancer incidence and mortality patterns based on population-based cancer registry data for a defined region in Punjab, India, covering the period from January 2012 to December 2016.

MATERIALS AND METHODS: Active hospital and laboratory surveillance and community health worker monitoring identified cases, which were validated using CanReg5 for accuracy. We determined age-adjusted incidence rates (AARs) together with crude rates (CRs) and mortality-to-incidence ratios (M/I %).

RESULTS: A total of 11,471 new cancer cases were recorded, comprising 5,394 (47.0%) men and 6,077 (53.0%) women. The AARs were 108.2 per 100,000 in men and 124.6 per 100,000 in women. The overall CR was 92.7 per 100,000, and the M/I % was 26.9%. The most common cancer sites were the esophagus (987; 18.3%) in men and breast (1,489; 24.5%) in women. Rural residents had higher M/I % (28.5%) than urban residents (24.3%; p = 0.003), indicating later-stage diagnosis and care barriers. The Indian registries recorded the highest incidence of childhood lymphoma among girls.

CONCLUSION: The findings demonstrate the immediate requirement for specific awareness programs and early detection initiatives that should focus on rural regions to decrease Punjab’s cancer statistics.

PMID:40761994 | PMC:PMC12320960 | DOI:10.7759/cureus.87339

Cureus. 2025 Jul 5;17(7):e87322. doi: 10.7759/cureus.87322. eCollection 2025 Jul.

ABSTRACT

Background Helicobacter pyloriis a widespread bacterial infection that is often linked to significant health and economic burdens in affected populations. The rise of antibiotic resistance has reduced the effectiveness of standard triple therapy (TT), highlighting the need for alternative treatment strategies, especially in resource-constrained countries like Pakistan, where comparative research on different H. pylori treatment regimens remains limited. This study aims to compare the efficacy of concomitant therapy (CT) versus TT in the eradication of H. pylori infection. Methods This retrospective study was conducted over a 12-month period (July 2021 to July 2022) in the medicine and gastroenterology departments of Jinnah Hospital, Lahore, Pakistan. A total of 296 patients diagnosed with H. pylori infection via the urea breath test were enrolled using consecutive sampling, following predefined inclusion and exclusion criteria. Patients were divided into two groups of 148 each: Group A received CT (esomeprazole, amoxicillin, clarithromycin, and metronidazole), and Group B received standard TT (esomeprazole, amoxicillin, and clarithromycin). Data were analyzed using IBM SPSS Statistics for Windows, Version 25.0 (Released 2017; IBM Corp., Armonk, NY, USA), applying independent samples t-tests, chi-square tests, and logistic regression analysis. A p-value of less than 0.05 was considered statistically significant. Results Among the 296 patients, the overall H. pylori eradication rate was 82.09%. The eradication rate was significantly higher in the CT group (91.90%) compared to the TT group (72.29%) (p = 0.008). In the CT group, age (OR: 1.57; 95% CI: 1.25-1.98; p = 0.03) and duration of symptoms (OR: 1.42; 95% CI: 1.10-1.77; p = 0.02) were significant predictors of successful eradication, while gender (OR: 1.10; 95% CI: 1.01-1.32; p = 0.06) was not. In the TT group, age (OR: 1.22; 95% CI: 1.05-1.51; p = 0.06), gender (OR: 1.01; 95% CI: 0.71-1.47; p = 0.07), and duration of symptoms (OR: 1.26; 95% CI: 1.17-1.60; p = 0.09) were not significant predictors of eradication. Conclusions This study suggests that CT is more effective than TT in eradicating H. pylori infection. In the CT group, being younger than 45 years and having symptoms for less than six months were significant predictors of treatment success. These findings provide valuable insights into optimal treatment strategies for H. pylori in resource-limited settings and emphasize the need for further research to establish effective eradication protocols.

PMID:40761984 | PMC:PMC12320471 | DOI:10.7759/cureus.87322

Cureus. 2025 Jul 5;17(7):e87350. doi: 10.7759/cureus.87350. eCollection 2025 Jul.

ABSTRACT

BACKGROUND: Metformin is a drug primarily used for the treatment of diabetes mellitus (DM), but it also offers clinical benefits that extend beyond glycemic control. Existing literature provides an unclear conclusion as to whether metformin’s benefits extend to preventing neurodegeneration, such as in Alzheimer’s disease (AD).

METHODS: A retrospective database study was conducted to evaluate the likelihood of developing AD in DM patients taking metformin compared to those taking glucagon-like peptide (GLP-1) analogs, sulfonylureas, and short-acting insulin variants. An analysis was also run to assess whether metformin has a protective benefit for AD and mortality when used in those with DM compared to those without DM.

RESULTS: In analyses totaling greater than 2.5 million patients, those on metformin had lower A1C percentages and a decreased mortality risk when compared to sulfonylureas (HR = 0.519, (CI: (0.493,0.546)), and short-acting insulins (HR = 0.372, (CI: (0.364,0.380)). Metformin use for DM was associated with a statistically significant increased likelihood of AD diagnosis compared to GLP-1 use (HR = 2.228, CI: (1.036,4.794)) but an insignificant difference compared to both sulfonylureas and insulins. Those with DM were at a significantly higher risk of being diagnosed with Alzheimer’s compared to those without DM (HR = 1.826, (CI: 1.579, 2.111)).

CONCLUSIONS: Metformin, previously thought to have significant benefits in preventing neurodegeneration, may not be the optimal pharmacologic agent of choice, particularly in patients with DM, if neurodegeneration is a primary concern in treatment decision-making based on other risk factors.

PMID:40761983 | PMC:PMC12321270 | DOI:10.7759/cureus.87350