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PubMed2026

In Vitro comparison of herbal and conventional antifungals against Candida strains in Oral candidiasis: A systematic review and meta-analysis.

OBJECTIVE: This study aimed to systematically review and meta-analyze the in vitro antifungal activity of herbal and conventional antifungals against Candida strains. DESIGN: In vitro studies were identified through PubMed, Embase, Scopus, and Web of Science up until May 2026. This review is registered with Prospero (CRD420251128404). Eligibility was determined using the Population, Intervention, Comparison, and Outcome (PICO) framework, with specific inclusion and exclusion criteria focused on in vitro antifungal investigations comparing herbal antifungals with conventional antifungals. The risk of bias was assessed using the modified Quality Assessment Tool for In Vitro Studies (QUIN Tool). A meta-analysis was performed, with the primary outcome measure being the ratio of means (RoM). RESULTS: The systematic review included twenty-five articles. Most studies showed different results in inhibition zones or minimum inhibitory concentrations between herbal and conventional agents. The meta-analysis indicates that certain herbal antifungals are equally effective as or more effective than conventional antifungals against Candida dubliniensis, Candida lusitaniae, and Candida tropicalis. While the efficacy of herbal antifungals for Candida albicans and Candida glabrata was modest, Piper betle L. demonstrated significant inhibitory potential. In contrast, conventional antifungals outperformed herbal antifungals against Candida krusei and Candida parapsilosis. CONCLUSIONS: This systematic review and meta-analysis highlight herbal medicine as a potential antifungal therapy for oral candidiasis, emphasizing the need for new strategies due to resistance to conventional antifungals.

Humans↗

PubMed2026

Impact of a CARE-ORIENT Education Program on Oral Hygiene Among Institutionalized Older Adults: A Double Blinded Cluster Randomized Controlled Study.

BACKGROUND: Older adults residing in long-term care facilities often depend on caregivers for daily oral care. Inadequate caregiver training may contribute to poor plaque control and denture hygiene. METHODS: A six-month parallel-arm cluster randomized controlled study was conducted in selected long-term care facilities in Northern India. Two old age homes were randomly selected, with one allocated to the intervention group and the other to the control group. A total of 150 older adults and 46 caregivers participated. Caregivers in the intervention group received a structured caregiver oriented oral health education. Clinical assessments were performed at baseline, 3 and 6 months. Outcomes included Debris Index, Turesky-Gilmore-Glickman Plaque Index, Denture Plaque Index and Denture Stomatitis Index. Caregiver knowledge and practice were evaluated using a validated questionnaire. RESULTS: Caregiver knowledge and practice scores improved significantly in the intervention group at 3 and 6 months. Significant differences were observed in Debris Index (DI), Plaque Index (PI), and Denture Plaque Index (DPI) in the intervention group over the six-month follow-up (p < 0.001). The Debris Index decreased from 2.76 ± 0.07 at baseline to 1.54 ± 0.05 at 6 months. Plaque Index scores declined from 3.26 ± 0.06 to 1.85 ± 0.08, and Denture Plaque Index scores reduced from 3.22 ± 0.03 to 1.74 ± 0.05. Denture Stomatitis Index improved over time; however, intergroup differences were not statistically significant. CONCLUSION: Structured caregiver-focused oral health education significantly improved oral hygiene among institutionalized older adults over six months, supporting integration of caregiver training within routine long-term care.

Humans↗

PubMed2026

Corrigendum to: "Oral subchronic exposure to the mycotoxin ochratoxin A induces key pathological features of Parkinson's disease in mice six months after the end of the treatment" [Food Chem. Toxicol. (2021) 152 112164].

Explore the source record for details and available documents.

Published Erratum↗

PubMed2026

Reassessment of the effect of oral l-arginine on blood pressure: A systematic review and meta-analysis based on ambulatory blood pressure monitoring.

OBJECTIVE: This meta-analysis aimed to evaluate the effect of oral l-arginine supplementation on ambulatory blood pressure (ABP). METHODS: A systematic search of PubMed, Cochrane Library, Embase, and Web of Science databases was conducted from their inception through March 1, 2026. Randomized controlled trials (RCTs) assessing the effects of oral l-arginine intervention were included. Outcome measures included 24-h systolic blood pressure (24h SBP), 24-h diastolic blood pressure (24h DBP), daytime systolic blood pressure (dSBP), daytime diastolic blood pressure (dDBP), nighttime systolic blood pressure (nSBP), and nighttime diastolic blood pressure (nDBP). Meta-analysis was performed using Stata 17.0. The weighted mean difference (WMD) was used as the effect size, and the results were pooled with 95% confidence intervals (CIs). RESULTS: A total of 5 RCTs comprising 202 participants were included. Meta-analysis results demonstrated that oral l-arginine significantly reduced 24h SBP (WMD = -4.23 mmHg, 95% CI [-5.87, -2.58]; P < 0.01) and 24h DBP (WMD = -3.04 mmHg, 95% CI [-4.48, -1.59]; P < 0.01). Significant reductions were also observed for dSBP (WMD = -4.16 mmHg, 95% CI [-5.90, -2.41]; P < 0.01) and dDBP (WMD = -4.25 mmHg, 95% CI [-5.85, -2.66]; P < 0.01). Furthermore, oral l-arginine significantly lowered nSBP (WMD = -5.70 mmHg, 95% CI [-7.81, -3.58]; P < 0.01) and nDBP (WMD = -4.18 mmHg, 95% CI [-6.27, -2.09]; P < 0.01). CONCLUSION: Oral l-arginine supplementation significantly reduces ABP. However, the number of included studies was limited, and further validation through additional relevant research is warranted.

Arginine↗

PubMed2026

Socioeconomic differences in the effectiveness of oral health programs for dental caries prevention in Europe: A systematic review and meta-analysis.

AIM: The meta-analysis systematically summarized evidence on how socioeconomic status (SES), access to dental care, and oral health programs (OHP) affect caries prevalence and severity among children and adults in Europe. METHODS: Four electronic databases (PubMed, Scopus, Cochrane Library and Embase) were systematically screened from 1947-2026, supplemented by cross-referencing and manual searches, without language restrictions. Study selection, data extraction and quality assessment were done in duplicate. Methodological quality was assessed using the NHLBI Study Quality Assessment Tools according to study design. Certainty of evidence was graded using GRADE Profiler 3.6. Mean differences (MD) were calculated for changes in DMFT, and odds ratios (OR) for the presence of dental caries in individuals using fixed-or random-effects models. RESULTS: Electronic searching identified 1800 articles; 23 studies were included in the review (>169,000 participants) and 14 in the meta-analyses (>88,000). Nine studies evaluated the effectiveness of OHP stratified by SES, and ten examined OHP in low-SES populations. Among low-SES individuals, participation in OHP was associated with a significantly lower increase in DMFT (MD[95% CI]=-0.63[-0.94;-0.31];very low certainty) and significantly lower odds of having dental caries (OR[95% CI]=0.61[0.52;0.73];very low) compared with non-participation. Among program participants, individuals with low SES showed a significantly greater increase in DMFT than those with high SES (MD[95% CI]=0.79[0.30;1.21];very low) and had significantly higher odds of having dental caries (OR[95% CI]= 2.88[1.97;4.22];very low). CONCLUSION: Participation in OHP may be associated with reducing dental caries in European populations, but benefits are unequally distributed and increase with higher SES. However, this conclusion is based on a limited number of well-conducted trials.

Humans↗

PubMed2026

Evaluating Patient Satisfaction and Oral Health Impact Profile-14 (OHIP-14): A Multicenter Crossover Study Comparing Selective Pressure Impression Conventional Dentures with Mucostatic Digital Dentures.

PURPOSE: To compare patient satisfaction and oral health impact between individuals receiving complete dentures made by digital methods and those using conventional techniques. MATERIALS AND METHODS: In this randomized crossover clinical trial, 23 patients aged 40 years and older with completely edentulous arches were enrolled at three treatment centers. Each participant received two sets of complete dentures: one set created using conventional methods (selective pressure impression) and the other through digital techniques (mucostatic digital impression). The order of denture placement was randomized, with each set used for 4 weeks. A trained specialist administered treatments alongside research tools, including a general information questionnaire, a denture satisfaction survey, and the OHIP-14 interview tool. Statistical analysis was conducted using Mann-Whitney U test. RESULTS: Participants with digital dentures reported significantly higher satisfaction regarding treatment duration, comfort, confidence, chewing ability, esthetics, and overall satisfaction compared to those with conventional dentures. There were no significant differences in satisfaction concerning speech and pronunciation. Overall, the oral health impact on quality of life was similar between denture types, but participants indicated improved quality of life while using dentures compared to being edentulous. CONCLUSIONS: Patients with digital dentures exhibited greater satisfaction across various domains compared to those with conventional dentures, despite similar satisfaction levels in speech and pronunciation. The impact on quality of life was comparable between both types, as measured by the OHIP-14.

Humans↗

PubMed2026

A systematic review and meta-analysis of radiation-induced oral complications in head and neck cancer: Prevalence and clinical outcomes.

BACKGROUND: Radiation-induced oral complications, notably xerostomia and oral mucositis (OM), are common and debilitating in patients with head and neck cancer (HNC), adversely affecting swallowing, nutritional intake, and overall quality of life (QoL). OBJECTIVES: This review aimed to quantify the prevalence of radiation-induced xerostomia and OM and synthesize their impact on dysphagia and nutritional status among HNC patients undergoing radiotherapy (RT). METHODS: A systematic review and meta-analysis were conducted following PRISMA guidelines. Comprehensive searches were performed in MEDLINE, Scopus, SciFinder, Embase, and PubMed for studies published between January 2019 and December 2025. Data from 51 studies were extracted and synthesized. RESULTS: The pooled prevalence was 85% (95% CI: 81.6-87.9%) for xerostomia and 88.3% (95% CI: 73.9-95.3%) for any-grade OM. Severe OM (Grade 3-4) had a prevalence of 39.5% (95% CI: 23.1-58.8%). These complications were strongly interrelated and significantly associated with dysphagia (69.8%; 95% CI: 53.1-83.7%), malnutrition (66.6%; 95% CI: 37.3-95.9%), and poor QoL (pooled mean QoL score: 64.13/100). Studies employing advanced radiation techniques (e.g., IMRT) demonstrated a lower prevalence of xerostomia (OR = 0.58, 95% CI: 0.42-0.80) compared to conventional RT. CONCLUSION: Radiation-induced oral complications (xerostomia & OM) remain prevalent and clinically significant burden in HNC patients, contributing to a cascade of functional impairments and diminished QoL. These findings highlight the need for preventive strategies, symptom management interventions, and the broader adoption of advanced RT techniques. Longitudinal research is warranted to further evaluate long-term outcomes and guide patient-centered care models.

Humans↗

PubMed2026

Comparative Effectiveness of Oral Ivermectin, 1% Permethrin Shampoo, and 4% Dimethicone Liquid Gel in Treatment of Pediculosis Capitis among School Children in Chachoengsao Province, Thailand.

Pediculosis capitis remains a persistent public health issue, especially in developing countries where resistance to standard neurotoxic pediculicides like permethrin is increasingly prevalent. This study aimed to compare the effectiveness of alternative treatment options against the standard care in a resource-limited setting. We conducted a single-blind randomized controlled trial involving three primary schools in Chachoengsao Province, Thailand (ClinicalTrials.gov: NCT06332872). Eighty-five female participants ages 6-13 years with active infestations were enrolled. Schools were randomly assigned to three treatment arms: 1) oral ivermectin (200 µg/kg) on Days 0 and 7; 2) 1% permethrin shampoo on Days 0 and 7, or 3) 4% dimethicone liquid gel as a single dose on Day 0. The primary outcome was the cure rate, defined as the absence of live lice and viable nits upon clinical assessment on Day 9. Of the 66 participants included in the final per-protocol analysis, oral ivermectin achieved a cure rate of 95.5% (21/22), which was significantly higher than that of the 1% permethrin standard of care (37.0%; 10/27) and the 4% dimethicone physical suffocant (29.4%; 5/17) (P <0.001). Although dimethicone achieved high initial parasitic clearance on Day 0 (88.2%), a rapid reinfestation rate of 58.8% was observed by Day 9, indicating that a single-dose protocol may be clinically insufficient. Adverse events were mild and temporary across all groups. Oral ivermectin appears significantly more effective than both 1% permethrin and single-dose 4% dimethicone in this population. These findings suggest that permethrin resistance is clinically prevalent and relevant in this area.

Humans↗

PubMed2026

Characterization of the Immune Response after Oral Cholera Vaccination (OCV) and Effects of Mycophenolate Mofetil on Priming of this Immune Response-A Randomized, Placebo-Controlled Trial.

Mycophenolate mofetil (MMF) is an immunosuppressive drug widely used by solid organ transplant recipients. Although it is known that MMF suppresses immune responses, its exact effects on specific vaccinations have not been investigated yet. Mucosal vaccinations are increasingly used, such as a cholera vaccination consisting of two oral immunizations (oral cholera vaccination; OCV). This study aimed to investigate the specific immunosuppressive effects of MMF use during the first dose of OCV in a randomized, placebo-controlled trial in healthy volunteers. Moreover, the study aimed to characterize the immune response provoked by OCV in detail. This randomized, placebo-controlled, single-blind trial included 16 healthy volunteers, each receiving two doses of Dukoral® and an intranasal rechallenge. Outcome measures were serum antibody responses (IgA and IgG) and IgA levels in saliva. Additionally, peripheral blood mononuclear cells (PBMCs) of participants were investigated for ex vivo cytokine production and expression of tissue-specific homing markers after OCV. There were considerable serum IgA and IgG responses after vaccination. MMF-treated volunteers still showed a significant cholera antibody response, though data suggest a potential suppression by MMF without reaching statistical significance. There was no substantial IgA response in saliva. Investigation of PBMCs from OCV-treated participants showed a Th2 skewing with increased ex vivo production of TNF, IL-2, IL-5, IL-13, and IL-22 compared to the placebo group. Taken together, this study provides a framework for future clinical pharmacology studies building on OCV as a challenge model and for further investigation of specific effects of MMF on mucosal vaccination responses.

Humans↗

PubMed2026

The identification of growth-promoting lncRNAs in oral cavity squamous cell carcinoma.

Oral Cavity Squamous Cell Carcinoma (OCSCC) is an aggressive tumor that develops within the mouth of patients. Tumor-suppressor gene loss and genomic arrangements fuel tumorigenesis and transcriptional reprogramming. Understanding how these alterations contribute to OCSCC growth and cell survival may identify new therapeutic vulnerabilities or biomarkers. We profiled the role of long non-coding RNAs (lncRNAs) in the growth of three OCSCC cell lines using a CRISPRi-screen and identified 19 lncRNAs that contribute to OCSCC proliferation. By comparing these lncRNAs to other screens, we find that these lncRNAs are uniquely required in OCSCC and not other malignancies. We show that these lncRNAs are abundantly expressed in OCSCC cells and tumors. Independent testing of candidate lncRNAs confirms their role in supporting OCSCC growth. Our results show that a novel subset of lncRNAs are required for the growth of OCSCC cancer cells and that these lncRNAs are cell lineage specific.

CRISPRi↗

PubMed2026

Efficacy of Oral Baicalin in Canine Atopic Dermatitis: A Randomised Placebo Controlled Trial.

BACKGROUND: Baicalin has shown efficacy in various dermatitis models in animals. However, its therapeutic effects on naturally occurring canine atopic dermatitis (cAD) have not been evaluated. OBJECTIVE: To evaluate the efficacy and safety of baicalin in dogs with cAD. ANIMALS: 56 client-owned dogs were enrolled. MATERIALS AND METHODS: All dogs were randomly divided to receive oral baicalin or placebo over a 90day period. All subjects had veterinary evaluations using the Canine Atopic Dermatitis Extent and Severity Index, 4th iteration (CADESI-04) during the trial and owners were requested to evaluate itching using the pruritus Visual Analog Scale (PVAS) and to complete a quality-of-life (QoL) questionnaire at Day (D)0 and D90. Additionally, the transepidermal water loss (TEWL), total serum IgE levels (IgE), complete blood count and serum biochemical results were measured at D0 and D90. RESULTS: The significant decreases in CADESI-04 (p < 0.001), PVAS (p < 0.001), TEWL (p = 0.014), IgE (p < 0.001) and QoL scores (p < 0.001) were observed in the baicalin group D90 compared to baseline. When compared to placebo, the baicalin group had significantly lower scores in CADESI-4 and PVAS (p < 0.001). A significantly higher proportion of subjects in the baicalin group showed a good-to-excellent treatment response (82.1%) compared to those in the placebo group (35.7%). The treatment was well tolerated. CONCLUSIONS AND RELEVANCE: Baicalin had a significant benefit in alleviating pruritus and reducing clinical signs in dogs with mild-to-moderate cAD and was well tolerated.

Animals↗

PubMed2026

Workforce Representation in Ophthalmology Oral Board Examiners and Examinees.

PURPOSE: To evaluate the characteristics of the American Board of Ophthalmology (ABO) oral board examiners and examinees as well as trends in examiner and examinee gender over time. DESIGN: Retrospective cohort study. SUBJECTS: ABO oral board examiners and examinees. METHODS: We utilized data from the American Board of Ophthalmology (ABO) and Association of American Medical Colleges (AAMC) to assess board examiner and examinee demographic characteristics from 2011 to 2024. Examiner characteristics included gender, years of experience, initial certification year and average examiner score. Examinee characteristics included gender, years since residency graduation and exam outcome (pass/fail). We utilized logistic regression to examine temporal trends in examiner and examinee gender from 2013 to 2024. MAIN OUTCOME MEASURES: Gender distribution of examiners and examinees. RESULTS: Overall, the proportion of women examiners increased over the study period. Notably, the most pronounced increase occurred following the transition from in-person to virtual oral board exam administration in 2020, rising from 31.3% (95% CI: 24.1%-38.4%) in 2019 to 49.1% (95% CI: 43.8%-54.4%) in 2024 (p < .001). The percentage of women examinees remained stable (41.7% [95% CI: 37.6%-45.8%] in 2019; 37.5% [95% CI: 33.0%-42.0%] in 2024, p-value: .019). CONCLUSIONS: The representation of women among the ABO oral board examiners has increased significantly following the transition to virtual exams while the proportion of examinees remained stable. Strategies to increase flexibility in scheduling exams may be beneficial in continuing to improve examiner representation.

Humans↗

PubMed2026

Acute pre-exercise oral intake of cacao polyphenols attenuates central fatigue development during sustained low-intensity ankle dorsiflexion exercise in healthy young male adults.

This double-blind, randomized, crossover study investigated whether acute cacao polyphenol (CP) ingestion attenuates neuromuscular fatigue in 19 healthy young male adults. After consuming CP or placebo, participants performed sustained isometric ankle dorsiflexion at 25% of maximal voluntary isometric contraction (MVIC) torque until task failure. Neuromuscular function (MVIC torque, voluntary activation [VA%], doublet torque) and electromyographic activity were assessed before, immediately after, and during recovery (1 and 5 min). Salivary chromogranin A and α-amylase were measured at baseline and 1 min post-task. Only VA% and chromogranin A showed significant condition × time interactions (p = 0.027-0.039). VA% significantly decreased from before to immediately after the task and 1 min post-task in both conditions (p ≤ 0.002), with significantly higher values in the CP condition than in placebo immediately after and 1 min post-task (p ≤ 0.037). Chromogranin A significantly increased from baseline to 1 min post-task in the placebo condition (p < 0.001) but not in the CP condition (p = 0.083). These findings suggest that acute CP ingestion attenuates the decline in central motor drive and autonomic stress responses following strenuous exercise, without altering performance or peripheral recovery, supporting its potential as a nutritional strategy for modulating central fatigue.

Humans↗

PubMed2026

Opposite metabolic and gut responses to oral glutamine in male and female mice with diet-induced obesity.

Obesity is often associated with sex-dependent metabolic complications, to which altered intestinal barrier function and gut microbiota contribute. Glutamine supplementation has previously shown beneficial effects on gut barrier function and glycemic control. We thus aimed to characterize, in male and female mice, the effects of oral glutamine supplementation during high-fat-diet-induced obesity. Male and female C57BL/6 mice received a standard (SD) or high-fat diet (HFD; 60 % kcal from fat) for 14 weeks (W14). From W12 onward, mice received glutamine in drinking water (2 g/kg/day) or no supplementation. Body composition, glucose tolerance, insulin sensitivity, intestinal permeability, colonic inflammatory response, cecal microbiota and inflammatory/endocrine adipose response were assessed. In both male and female mice, glutamine supplementation failed to improve body weight and body composition. However, glutamine reduced glucose intolerance in HFD-fed males (AUC reduced by 14.57 %) that was associated with a partial restoration of plasma resistin and insulin and a trend toward limiting adipose inflammatory response. In males, glutamine did not affect gut microbiota composition and colonic response. Conversely, in HFD-fed females, glutamine supplementation led to gut microbiota changes (increase in Bacteroidota and Pseudomonadota phyla; increase in Muribaculaceae and Tannerellaceae families), increased colonic inflammatory markers (Il1b, Tlr4, Myd88, Irf3), increased inflammatory response in subcutaneous adipose tissue and increased HOMA-IR. Finally, HFD-fed mice exhibited sex-specific responses to glutamine supplementation with protective effects in males and harmful effects in females that need to be further deeply explored.

Animals↗

PubMed2025

Oral semaglutide for weight loss and liver fibrosis in overweight and obesity: A randomized controlled trial.

BACKGROUND AND OBJECTIVES: Obesity is a leading risk factor for fatty liver disease and weight loss has been shown to improve liver parameters. This study evaluates the efficacy of oral semaglutide for weight loss in individuals with overweight or obesity, excluding those with diabetes mellitus. METHODS: A randomized, open-label, controlled trial was conducted at the Asian Institute of Gastroenterology, Hyderabad, from June 2022 to December 2023. Adults (≥ 18 years) with a body mass index (BMI) ≥ 30 or ≥ 27 with comorbidities (pre-diabetes, hypertension, dyslipidemia, obstructive sleep apnea or cardiovascular disease) were randomized into two groups. Both groups received counselling on a reduced-calorie diet and increased physical activity. Group 1 also received oral semaglutide, starting at 3 mg/day and titrated to 14 mg/day over two to four weeks. The objectives were to assess the effects of semaglutide on weight loss, non-invasive markers of liver fibrosis and cardiometabolic parameters. (ClinicalTrials.gov ID: NCT05442450). RESULTS: Total 116 participants (58 per group) completed the study. At 28 weeks, the mean percentage weight reduction was -10.47% (SD 5.3) in the Semaglutide group vs. -2.4% (SD 4.5) in the control group (p < 0.001). Semaglutide treatment significantly improved alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase [SGPT]) levels, along with reductions in the aspartate aminotransferase to platelet ratio index (APRI) score, liver fat content and liver stiffness. However, NFS (NAFLD fibrosis score) and FIB-4 (fibrosis-4 index) did not show significant reductions. Improvements in BMI, waist circumference, HbA1c, fasting insulin and C-reactive protein (CRP) were significantly greater with semaglutide (p < 0.001). Total fat mass decreased by 7.3 kg vs. 1.74 kg (p < 0.0001) in controls, while visceral fat ratings dropped by 3.67 vs. 0.6 (p < 0.0001). CONCLUSIONS: In adults with overweight or obesity without diabetes, oral semaglutide, combined with dietary and lifestyle modifications, led to significant and clinically meaningful weight loss and metabolic improvements compared to lifestyle modifications alone.

Adult↗

PubMed2026

MicroRNAs in Oral Bio-Fluids as Predictive Biomarkers of Orthodontic Tooth Movement: A Systematic Review.

This systematic review was designed to assess scientific evidence of the association of microRNA expression during orthodontic tooth movement through various time points. A systematic review was performed in accordance with the PRISMA checklist. A search strategy was developed in electronic databases including Med Line, Scopus, EBSCO Host and ProQuest Dissertations & Theses Global until June 2025. Eligibility criteria included studies that investigated microRNA expression in saliva/GCF during orthodontic treatment. The risk of bias of the included studies was analysed using the QUADAS-2 and RoB-2 tools. The search retrieved 2800 records, of which nine studies were selected. Minor variations in GCF collection were noted, while stimulated saliva was collected in one study. RT-PCR and the Fluro meter accounted for the majority of miRNA estimation. Thirteen miRNAs were identified as target biomarkers for OTM regulation. Despite the high risk of bias, the evidence from the current systematic review indicates that microRNAs can be considered as potential biomarkers of orthodontic tooth movement in oral biofluids. Trial Registration: Prospero ID-CRD420251153064.

Humans↗

PubMed2026

A novel neoadjuvant immunotherapy confers improved overall survival in oral cancer patients with low tumor PD-L1 expression The IT-MATTERS Clinical trial - Prognostic role of tumor PD-L1 expression.

OBJECTIVE: Five-year overall survival (OS) remains < 50% for patients with resectable, locally advanced (LA) primary oral squamous cell carcinoma (OSCC) and soft palate, receiving current standard of care (SOC). The aim of our study was to examine neoadjuvant Leukocyte Interleukin Injection (LI) with CIZ (intravenous low dose cyclophosphamide, indomethacin and zinc multivitamins) effect on OS, in low-risk (LR) OSCC patients. PATIENTS AND METHODS: In a randomized, controlled Phase 3 trial, treatment-naïve locally advanced patients, with stage III/IVa OSCC and soft-palate cancer, had surgical tumor samples assessed for pre-defined thresholds of PD-L1 tumor proportion score (TPS). OS was analyzed using proportional hazard models for LI + CIZ + SOC vs SOC, in the intention-to-treat (ITT) population. RESULTS: OS was superior in low risk (LR) patients receiving LI + CIZ + SOC compared to SOC; OS advantage hazard ratio (HR) 0.64, p = 0.0569 (without selecting for N0, PD-L1 TPS < 10%), and the Kaplan-Meier (K-M) lifetable achieved significance (log rank p = 0.0340) favoring LI + CIZ + SOC vs SOC. Applying the selection criteria (cN0 and TPS < 10%) to ITT, OS reached HR 0.34p = 0.0012, Kaplan-Meier log rank p = 0.0015. The ITT LR cohort (cN0 and TPS < 10%) achieved a HR 0.26 (p = 0.0023), Kaplan-Meier log rank p = 0.0013, supported by progression free survival (PFS) HR 0.43, p = 0.0178, Kaplan-Meier log rank p = 0.0431, with 32% absolute survival advantage over control at 60 months. CONCLUSIONS: Significant OS prolongation was observed in ITT population for LI + CIZ + SOC vs SOC, in LR and in ITT LR cN0, PD-L1TPS < 10% cohort having locally advanced squamous cell carcinoma tumors in oral cavity/soft-palate. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT01265849; EudraCT (Identifier: 2010-019952-35).

Humans↗

PubMed2026

Safety and Tolerability of Single and Multiple Daily Oral Doses of Dried Kratom Leaf Powder in a Randomized Trial in Healthy Volunteers.

BACKGROUND: Kratom use is rising, increasing the need for safety and tolerability studies of high-quality and well-characterized kratom products in humans. Kratom's risk-benefit ratio, recommended dose, treatment-emergent adverse events (TEAEs), abuse potential, and withdrawal require evaluation. Thus, the safety and tolerability of 4 escalating single and 15 daily dried kratom leaf powder doses in human volunteers were evaluated over 47 days in the largest controlled kratom-administration study to date. METHODS: A randomized, between-subject, double-blind, placebo-controlled, dose-escalation study of MitraLeaf kratom powder after single doses (SD), during 15 daily doses (multiple doses; MD), and a 23-day follow-up was conducted in 116 volunteers (49 MitraLeaf and 67 placebo). Twelve participants each received a SD of either 6.65, 13.3, 26.6, or 53.2 mg (n = 13) mitragynine in 500, 1000, 2000, or 4000 mg of MitraLeaf, respectively, with a 10-day follow-up. The same participants received 15 daily doses at the same concentration of SD mitragynine received, with a 27-day follow-up period. Inclusion criteria were nonsmoking healthy males and females who never used kratom or had not used kratom for ≥12 months, 18-55 years old, and BMI ≥18.5 and ≤29.9 kg/m 2 . Participants were excluded if they had known CYP3A4, CYP2D6, or CYP1A2 genetic polymorphisms. RESULTS: No serious adverse events or deaths were reported. TEAEs after SD or MD generally increased as the dose increased. Dizziness, nausea, and feeling of relaxation were the most commonly reported TEAEs after SD, and headache, feeling hot, increased alanine aminotransferase level, and nausea were most common after MD. CONCLUSIONS: This SD and first MD controlled study shows that Mitragyna speciosa -derived MitraLeaf kratom powder was safe and well tolerated at the dose ranges tested, with no evidence of meaningful abuse potential or withdrawal.

Humans↗