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PubMed2026

Patient-reported outcomes with tarlatamab in extensive-stage small cell lung cancer after platinum-based chemotherapy: results from the phase 3 DeLLphi-304 trial.

BACKGROUND: Extensive-stage small cell lung cancer (ES-SCLC) is associated with a high symptom burden and impaired health-related quality of life (HRQoL). This prespecified analysis from the phase 3 DeLLphi-304 trial evaluated patient-reported outcomes (PROs) for tarlatamab versus standard-of-care (SoC) chemotherapy following first-line platinum-based therapy. METHODS: DeLLphi-304 is a multicenter, open-label, randomized phase 3 study in adults with ES-SCLC. PROs were assessed using validated instruments, including the EORTC QLQ-C30, EORTC QLQ-LC13, FACT-G GP5, BPI-SF, and the EQ-5D-5L visual analogue scale. Change from baseline, response rates, and time to deterioration in these PROs were analyzed. RESULTS: PRO data from all 509 patients enrolled were evaluated. Compliance with QLQ-C30 and QLQ-LC13 assessments remained above 69% through 19 weeks. A higher proportion of patients receiving tarlatamab achieved symptom or functional improvement at 19 weeks compared with SoC in chest pain (19% vs 10%), cough (35% vs 26%), dyspnea (22% vs 7%), physical functioning (13% vs 8%), and global health status (23% vs 15%), respectively. Tarlatamab also delayed deterioration in symptoms, physical functioning, and pain at worst relative to SoC. FACT-G GP5 results indicated that patients receiving tarlatamab were less bothered by treatment side effects over time. CONCLUSIONS: In addition to its previously reported antitumor activity, tarlatamab demonstrated clinically meaningful improvements in symptoms and HRQoL compared with SoC. These findings support a favorable benefit-risk profile of tarlatamab in patients previously treated for ES-SCLC.

Humans↗

PubMed2026

EffectS of Lifestyle Interventions in Older PEople With Obesity (Effective SLOPE): a Systematic Review With Network Meta-Analyses.

BACKGROUND/AIM: We conducted a systematic review with network meta-analyses (NMA) summarizing the effects and safety of lifestyle interventions containing nutrition (NUT; e.g., calorie restriction), exercise (EX; e.g., aerobic/resistance exercise) and behavior change interventions (BCI; e.g., behavioral therapy) on physical function, body composition, quality of life, psychosocial outcomes, health and adverse events in community-dwelling older adults with obesity. METHODS: We used the methodology proposed by Cochrane and searched six databases and one trial registry for eligible randomized controlled trials (RCTs; intervention duration ≥ 12 weeks) up to May 2022 with a full new search in MEDLINE and a re-assessment of previously identified eligible trial registry entries in October 2025. Random-effects NMA ((standardized) mean difference ((S)MD), 95% confidence intervals) were conducted if possible. RESULTS: We included 72 RCTs (n = 6716) for descriptive summaries and 54 RCTs (n = 4249) for NMA. NUT+EX+BCI improved physical function (performance batteries) compared to control (SMD 3.37 [1.76;4.97]; high certainty of evidence). NUT+EX+BCI may reduce body (MD -8.69 [-13.14;-4.25]) and fat mass (MD -6.58 [-10.44;-2.73]) while not negatively affecting fat-free mass (MD -1.38 [-3.52;0.76]) or bone mineral density (MD -0.01 [-0.05;0.02]) (evidence very uncertain). Other interventions (single/combined) may also be effective; however, effects were often imprecise. For psychosocial outcomes, quality of life, and health events, data were insufficient or too heterogeneous to derive clear results. CONCLUSION: The evidence suggests that NUT+EX+BCI interventions are most suitable for the management of obesity in older adults. Nevertheless, further RCTs-especially in frail populations and on patient-relevant outcomes-are needed.

Humans↗

PubMed2026

Age at menopause and subjective cognitive symptoms predict digital cognitive outcomes at the gynecological Well-Woman visit.

INTRODUCTION: Women are at increased risk for Alzheimer's Disease (AD). Growing evidence suggests that the menopausal transition may represent a vulnerable window for development of AD-related pathology. Yet, women are diagnosed with AD later than men. Conducting routine cognitive screenings and integrating information about both cognitive symptoms and age at menopause may help address sex-based disparities in detection and prevention. This study investigated whether subjective cognitive symptoms, in combination with age at menopause, were associated with performance on a digital cognitive task in postmenopausal women. METHODS: 183 postmenopausal women (mean age = 63.8, range = 45-85) were recruited after their Well-Woman visit. Participants completed the Screener for Cognitive Problems in Everyday Life (SCoPE) to assess subjective cognitive symptoms, followed by a sensitive measure of objective cognition: the Linus Health Digital Clock and Recall (DCR™). Information was also collected on age at menopause. We examined associations of subjective cognitive symptoms and age at menopause with digital cognitive performance, adjusting for age, education and depression. Model fit was evaluated using adjusted R2, AIC, and BIC. RESULTS: 48.1% of women reported one or more cognitive symptoms on the SCoPE. On objective testing, 73.2% scored in the normal range, 20.8% in the borderline range, and 6.0% in the impaired range. SCoPE total score was negatively associated with objective cognitive performance in adjusted models (B = -.12, p = .03). Age at menopause showed a significant quadratic association with cognitive performance (B = -0.006, p<.001). SCoPE total was not associated with DCR subtests, while age at menopause predicted both Delayed Recall and Clock Drawing. CONCLUSION: Subjective cognitive symptoms and age at menopause were associated with lower performance on a sensitive, objective cognitive test. Findings support routine cognitive screening and suggest that subjective cognitive symptoms as well as age at menopause are associated with cognitive function.

Humans↗

PubMed2026

Histopathologic, Genomic, and Clinical Characteristics of Primary Cutaneous Melanocytic Tumors With Concomitant NRAS Q61 and IDH1 R132C Mutations.

Cutaneous melanocytic tumors with concomitant NRAS Q61 and IDH1 R132C mutations have been described as intermediate-grade melanocytomas with characteristic biphasic morphology, but the malignant end of this genotype-defined spectrum remains poorly characterized. We assessed histopathologic, immunohistochemical, molecular, and clinical features of 16 primary cutaneous melanocytic tumors harboring both mutations. Following integrated review, 7 tumors were classified as melanocytoma and 9 as melanoma. Melanocytomas showed reproducible biphasic architecture with congenital nevus-like features, a biphasic HMB-45 pattern, low Ki-67, PRAME negativity, retained p16, and minimal copy number variations (CNVs). Melanomas retained partial morphologic overlap in a subset but were distinguished by higher-grade cytology, immunohistochemical features supportive of malignancy, and progression-associated genomic alterations, including TERT promoter mutation (9/9), 9p21/CDKN2A loss (4/7), and higher CNV burden. NRAS and IDH1 variant allele frequencies were strongly concordant (r = 0.83, P < 0.001), supporting their presence in the same dominant clone. Clinically, two patients presented with stage IIIB disease, but no distant metastasis or melanoma-related death occurred during a median melanoma follow-up of 3.9 years (IQR, 2.5-5.1). In exploratory analyses, moderate-to-severe atypia (RR, 6.2; 95% CI, 1.0-38.8; P = .009), Ki-67 ≥10% (RR, 4.4; 95% CI, 1.1-18.4; P = .003), lymphocytic infiltrate (RR, 2.4; 95% CI, 1.1-5.3; P = .03), absence of the typical biphasic pattern (RR, 2.4; 95% CI, 1.1-5.3; P = .03), and complete p16 loss (RR, 2.4; 95% CI, 1.1-5.3; P = .03) were associated with molecular or clinical progression to melanoma, defined as the presence of at least one of the following: TERT promoter mutation, pathogenic CDKN2A mutation, 9p21/CDKN2A loss, ≥3 genome-wide segmental CNVs, or any metastasis. These findings support the existence of NRAS/IDH1 co-mutated melanoma as the malignant counterpart of NRAS/IDH1-mutated melanocytoma within a single genotype-defined spectrum.

IDH1 mutations↗

PubMed2026

All eyes on gas exchange: impact of controlled arterial hypertension on cardiopulmonary function and the effects of high-intensity interval training.

INTRODUCTION: Arterial hypertension (AH) impairs vascular function which, in turn, may reduce cardiopulmonary function. However, the impact of AH on cardiorespiratory fitness (CRF) and its potential mechanisms remains insufficiently investigated. We compared cardiopulmonary function during exercise testing (CPET) between adults with and without AH (part 1) and evaluated the effects of high-intensity interval training (HIIT) in adults with AH on submaximal cardiopulmonary CPET parameters (part 2). METHODS: Thirty-eight adults with AH and 19 controls without AH partook in the study. Adults with AH were randomized into either HIIT or a control group. CPET assessed CRF and submaximal exercise parameters, including the oxygen uptake efficiency slope (OUES), V̇E/V̇CO 2 slope, PETCO 2 , V̇O 2 /work rate (WR) slope, and O 2 pulse. The HIIT intervention consisted of triweekly sessions over 8 weeks. RESULTS: Adults with AH had a 6.5 ml kg -1  min -1 (95% confidence interval: 1.7-11.3) lower CRF, a steeper V̇E/V̇CO 2 slope (moderate-large effect size), lower PETCO 2 (large effect size), flatter V̇O 2 /WR slope (moderate effect size), and lower O 2 pulse (small-moderate effect size) than adults without AH. HIIT improved CRF and altered certain cardio-circulatory parameters in AH, including OUES (small-large effect size), V̇O 2 /WR slope (small-moderate effect size, low precision) and O 2 pulse (small-moderate effect size). However, effects of HIIT on pulmonary-vascular parameters were inconclusive, with large variability observed in the V̇E/V̇CO 2 slope and PETCO 2 . CONCLUSION: Adults with controlled AH might have lower CRF, indicating limitations in pulmonary-vascular and cardio-circulatory organ systems. A short-term 8-week HIIT enhances CRF and cardio-circulatory function, however, evidence is limited for improvements in pulmonary-vascular function.

Humans↗

PubMed2026

A polygenic risk score for peripheral artery disease and major adverse limb events.

BACKGROUND AND AIMS: Large-scale genome-wide association studies have identified common genetic variants that predict the risk of peripheral artery disease (PAD). This study assessed whether a polygenic risk score (PRS) is associated with PAD and the incidence of major adverse limb events (MALE) independent of clinical risk factors in patients with established cardiometabolic disease. METHODS: A genetic analysis was performed, pooling individual patient-level data from six TIMI trials. The association of a recently validated PAD PRS with prevalent PAD and the incidence of MALE (acute limb ischaemia, chronic limb-threatening ischaemia, major amputation, or peripheral revascularization) was assessed. RESULTS: A total of 68 816 patients were included in this analysis, with a median follow-up of 2.6 years. Of these, 5986 (8.7%) had known PAD at baseline. After adjusting for clinical risk factors, a higher PAD PRS was independently associated with a 15% greater odds of prevalent PAD (adjusted odds ratio per 1-SD: 1.15 [95% confidence interval 1.12-1.18], P < .0001), a magnitude of risk as strong as established clinical risk factors. A total of 577 patients experienced MALE during follow-up. A higher PAD PRS was associated with a 30% increased risk of MALE (adjusted hazard ratio per 1-SD: 1.30 [1.19-1.42], P < .0001). Adding the PAD PRS to clinical risk factors resulted in a statistically significant but modest improvement in discrimination (area under the curve went from 0.651 to 0.662 P < .0001). CONCLUSIONS: In a broad spectrum of patients with cardiometabolic disease, the PAD PRS is associated with an increased risk of PAD and the incidence of MALE beyond clinical risk factors; however, the improvement in discrimination was statistically significant but clinically modest.

Humans↗

PubMed2026

The effect of metformin on the pharmacokinetics of rifampicin, isoniazid, and pyrazinamide in adults with tuberculosis.

Metformin is under investigation as adjunctive host-directed therapy for tuberculosis (TB), which might interact with first-line TB treatment. We used population pharmacokinetic modeling to assess whether metformin alters first-line TB-drug pharmacokinetics in HIV/TB-coinfected adults without diabetes. Rifampicin, isoniazid, and pyrazinamide pharmacokinetics were investigated in participants from a randomized clinical trial of adjunctive metformin (500 mg twice daily to week 12) in adults starting HIV-associated TB treatment. Antiretroviral therapy (ART)-naïve participants initiated dolutegravir-based ART within 8 weeks. Intensive and semi-intensive sampling was conducted at week 5; concentration-time data were analyzed using non-linear mixed-effects modeling. Data from 78 individuals (43 receiving metformin, median weight 60.8 kg, 62.8% male, 79.5% on ART) were analyzed. Rifampicin and pyrazinamide were described by one-compartment models with linear elimination; typical clearances were 15.8 L/h (95% CI: 13.5-18.7) and 3.88 L/h (95% CI: 3.54-4.08), respectively. Isoniazid followed a two-compartment model with a mixture model for acetylator status; clearance was 10.5 L/h (95% CI: 9.44-11.9) in slow acetylators and 28.8 L/h (95% CI: 25.6-31.0) in fast/intermediate acetylators. Metformin reduced isoniazid bioavailability by 15.6% (95% CI: 4.45-26.4%, P < 0.009) and rifampicin bioavailability by 24.0% (95% CI: 7.83-36.3%, P < 0.007), decreasing the area under the curve from 0 to 24 h from 18.2 to 15.6 mg·h/L and from 35.9 to 27.1 mg·h/L, respectively. No significant effect on pyrazinamide was detected. We found that non-diabetic patients on metformin had lower isoniazid and rifampicin bioavailability. Lowered rifampicin exposure might be clinically relevant; simulations suggest that this could be offset by a single 150 mg rifampicin dose.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT04930744.

Humans↗

PubMed2026

Pilot randomized trial of intermittent theta-burst stimulation versus H-Coil transcranial magnetic stimulation for treatment-resistant depression.

BACKGROUND: Intermittent theta burst stimulation (figure-8-coil iTBS) and H7-coil repetitive transcranial magnetic stimulation (rTMS) are FDA-cleared treatments for major depression; yet their comparative effectiveness in treatment-resistant depression (TRD) has not been evaluated in randomized trials. This pilot randomized trial was designed to obtain preliminary comparative estimates and to explore whether baseline cognitive functioning relates to early remission. METHODS: Twenty-eight adults with TRD were randomized to six weeks of figure-8-coil iTBS delivered to the dorsolateral prefrontal cortex (DLPFC) (n = 15) or H7-coil rTMS delivered to the dorsomedial prefrontal cortex (DMPFC) (n = 13). The primary outcome was change in 17-item Hamilton Depression Rating Scale (HRSD-17) score from baseline to week 6, analyzed with ANCOVA. Additional outcomes included response, remission, and symptom trajectories through week 18. Exploratory analyses examined the association between baseline cognitive functioning, such as executive functions and memory, and remission. RESULTS: Twenty-five participants completed all 30 sessions. Adjusted week-6 HRSD-17 scores did not differ between groups (mean difference -0.40, 95% CI -5.23 to 4.43; p=.865). Response rates were 40.0% for figure-8-coil iTBS and 50.0% for H7-coil rTMS (p>.60), and remission rates were identical across groups (20.0%). Remitters showed higher baseline executive functioning than non-remitters in exploratory analyses, although these associations were not confirmed in adjusted models. CONCLUSION: In this pilot trial, figure-8-coil iTBS and H7-coil rTMS showed symptom improvement, with no clear between-group differences. Exploratory findings suggest a potential signal involving executive functioning that warrants further investigation. These results inform the feasibility and design of larger comparative trials. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05902312).

Adult↗

PubMed2026

Prevalence and pattern of psychological symptoms in form of dental fear and anxiety in children and adolescents with traumatic dental injuries: a systematic review.

BACKGROUND/AIMS: This systematic review aimed to evaluate the level and pattern of dental fear and anxiety (DFA) amongst children and adolescents with traumatic dental injuries (TDI) and, where available, to compare these outcomes with non-traumatised controls. METHODS: An a priori protocol was developed and registered in PROSPERO (CRD420261329946). A comprehensive literature search was conducted in PubMed, EMBASE, Web of Science, and Scopus on 3 March 2026, with additional grey literature, citation, and reference searching. No language or time restrictions were applied. Observational clinical studies assessing DFA in individuals with TDI using validated tools were included. Two reviewers independently screened studies, extracted data, and assessed risk of bias using the Joanna Briggs Institute checklist. Certainty of evidence was evaluated using the GRADE approach. RESULTS: A total of 2885 records were identified, of which 4 cross-sectional studies met the inclusion criteria after screening. Studies were conducted in Croatia and Kosovo and included paediatric populations. Sample sizes ranged from 147 to 505 participants. Different validated scales (CFSS-DS, CDAS, S-DAI) were used to assess DFA. Overall, children with TDI demonstrated predominantly low levels of dental fear and anxiety across assessment tools. However, findings were inconsistent, with some studies reporting lower or similar anxiety levels in TDI patients compared to controls. Risk of bias was moderate or high in three of the four studies, and the overall certainty of evidence was rated as low to very low due to methodological limitations, heterogeneity, and imprecision. CONCLUSION: The limited available evidence suggests that children and adolescents with TDI do not consistently present with higher levels of dental fear and anxiety than non-traumatised controls. These findings indicate that TDI does not inherently cause DFA, underscoring the critical role of empathetic behaviour support in mitigating post-traumatic dental fear. However, the evidence is based on a small number of regionally concentrated cross-sectional studies with low to very low certainty. Future prospective studies using standardised TDI classifications, validated DFA instruments, and clearly defined assessment time points are needed.

Dental anxiety↗

PubMed2026

Randomized Trial of Intensive Nurse-Led Follow‑Up Versus Standard Care in Inflammatory Bowel Disease.

BACKGROUND:  Nurses play a key role in inflammatory bowel disease (IBD) management. This randomized controlled trial evaluated intensive nurse-led program in patients with IBD starting advanced therapy. METHODS:  Patients were randomized (1:1) to intensive nurse follow‑up (Arm A) or standard care (Arm B). Both arms received baseline nurse education; Arm A additionally had scheduled nurse calls and visits. Primary outcome was reduction in IBD‑Disk score in W12. Secondary outcomes were W52 reduction, robust response (> 20-point improvement), and IBD-Disk remission (score < 40). RESULTS: Overall, 98 patients were randomized (Arm A: n = 50; Arm B: n = 48) with similar baseline characteristics. Mean baseline IBD‑Disk scores were 49.2 ± 20.7 in Arm A and 42.0 ± 19.8 in Arm B (p = 0.07). At W12, both groups improved, with greater IBD-Disk reductions in Arm A (16.1 ± 22.9 vs. 10.1 ± 20.1, p = 0.09). At W52, improvement was greater in Arm A (18.4 ± 20.7 vs 9.4 ± 17.8; p = 0.08). More patients achieved robust response in Arm A (49% vs 21%, p = 0.013) at W12. By W52, IBD-Disk remission was achieved by 22/25 (88%) patients in Arm A vs 18/28 (64%) in Arm B (p = 0.045). CONCLUSIONS:  In this pilot randomized trial, intensive nurse-led follow-up did not significantly improve IBD-Disk at week 12, yet favorable trends of functional outcomes were observed. Intensive nurse‑led follow‑up program may improve quality of life in patients with IBD. These findings support the integration of specialist IBD nurses to improve patient‑centered outcomes.

Humans↗

PubMed2026

Comparing the Effects of Push and Hold Isometric Training on Strength and Musculotendinous Adaptations: A Within-Subject Randomized Controlled Trial.

Lum, D, Oranchuk, DJ, Chen, SE, and Kong, PW. Comparing the effects of push and hold isometric training on strength and musculotendinous adaptations: A within-subject randomized controlled trial. J Strength Cond Res 40(9): 1050-1058, 2026-Despite recent interest in delineating pushing (PIMA) and holding (HIMA) isometric muscle actions, training-induced adaptations have not been examined. As such, we compared the strength and morphological adaptations between PIMA and HIMA training. Twenty limbs across 10 adults (5 men, 5 women, age: 31.4 ± 6.5 years) were randomly assigned to PIMA or HIMA conditions and underwent 12 training sessions over 6 weeks. PIMA required subjects to exert force against a fixed lever while the HIMA limb maintained a set joint angle while resisting an isotonic lever. During each contraction, subjects had to exert force at 70% of maximal voluntary contraction for 20 seconds at an 80° knee angle, for 4-6 repetitions. Subjects completed isometric, concentric, and eccentric knee extension assessments for both limbs before and after the intervention. Pre- and postintervention ultrasound scans were performed to determine quadriceps muscle architecture and patellar tendon thickness. Increased isometric torque was found following both conditions (p < 0.05, g = 0.30-0.36), while concentric (p < 0.05, g = 0.31) and eccentric (p < 0.01, g = 0.50) torque only increased following PIMA. Both conditions increased muscle thickness (p < 0.05, g = 0.27-0.88) and vastus lateralis fascicle length (p < 0.05, g = 0.20-0.31). Only HIMA increased patellar tendon thickness (p < 0.05, g = 0.12). The increase in total quadriceps (p < 0.05, g = 0.46) and especially rectus femoris (p < 0.05, g = 1.44) thickness was greater in HIMA. The results suggest that PIMA may be more effective at improving strength, while HIMA may be superior for inducing morphological adaptations. Larger sample sizes and more ecologically valid training programs are warranted to further elucidate potential differences between different isometric types.

Humans↗

PubMed2026

Effect of flavored on!® nicotine pouch products on smoking behaviors: A sequential, multiple assignment, randomized controlled trial.

PURPOSE: To evaluate whether flavored versus unflavored nicotine pouch (NP) access affects cigarette reduction and smoke exposure among adults who smoke daily, and whether delayed flavor introduction affects these outcomes. METHODS: Adults who smoked ≥ 5 cigarettes/day (CPD) with interest in replacing cigarettes with NPs were enrolled in a remote, six-week, sequential multiple assignment randomized trial (n = 402 randomized; n = 400 analyzed). Participants were randomized to immediate access to seven NP flavors (Flavor), unflavored-only access for six weeks (Original), or unflavored-only for three weeks followed by flavor access (Delayed Flavor). Primary outcomes were ≥ 50% reduction in weekly mean expired-air carbon monoxide (CO) from baseline and mean CO at Week 6. Secondary outcomes included ≥ 50% CPD reduction, mean CPD, CO-verified 7-day abstinence, and incident smoke-free days. RESULTS: At Week 6, Flavor and Original did not differ in ≥ 50% CO reduction (14.3% vs 14.2%; IRR=1.0, 95% CI=0.6-1.8) or mean CO (18.3 vs 16.5 ppm; β=1.9, 95% CI=-1.3-5.0). CPD decreased across groups by Week 6, with no differences between Flavor and Original in ≥ 50% CPD reduction (50.3% vs 51.6%; IRR=1.0, 95% CI=0.8-1.2) or CO-verified abstinence (9.3% vs 8.9%; IRR=1.0, 95% CI=0.5-2.2). Flavor increased smoke-free days early, with attenuation over time. Among Week 3 non-responders, delayed flavor access increased ≥ 50% CPD reduction at Week 6 (33.3% vs 18.6%; IRR=1.8, 95% CI=1.0-3.2). CONCLUSIONS: NP access supported cigarette reduction regardless of flavor availability, but flavors may accelerate smoke-free days and improve response among individuals who do not reduce cigarette consumption with unflavored products alone.

Humans↗

PubMed2026

Responsiveness of muscle mass gain to different load intensities of resistance training in older women: A randomized crossover study.

BACKGROUND: Aging is associated with progressive declines in skeletal muscle mass (SMM) and substantial interindividual variability in adaptations to resistance training (RT). However, whether training load intensity influences hypertrophic responsiveness in older adults remains unclear. OBJECTIVE: To investigate the effects of two commonly prescribed RT loading schemes (15RM and 10RM) on estimated SMM adaptations and responsiveness in older women. METHODS: Twenty-seven older women (67.7 ± 4.9 years; 65.7 ± 10.6 kg; 154.5 ± 5.8 cm) completed two 8-week RT interventions performed at 15RM and 10RM in a randomized crossover design, separated by a 12-week detraining period. Estimated SMM was assessed using dual-energy X-ray absorptiometry. Responsiveness was operationally defined using the standard error of measurement, and participants were classified as responders (RP) or non-responders (N-RP) according to changes in estimated SMM. RESULTS: Both loading schemes promoted significant and comparable increases in estimated SMM (15RM: +0.62 ± 0.4 kg vs. 10RM: +0.43 ± 0.3 kg). Overall, 61.1% of participants were classified as responders in at least one condition, whereas 38.9% were classified as non-responders. Responsiveness status was consistent across conditions for most participants, with 48.1% classified as responders under both loading schemes and 25.9% as non-responders under both conditions. Only seven participants (25.9%) changed responsiveness status between interventions. No clear pattern indicated a greater likelihood of responsiveness with either loading scheme. CONCLUSIONS: Results suggest that both the 10RM and 15RM RT protocols significantly increase estimated SMM in older women, with no significant differences between training conditions. Although substantial interindividual variability in adaptive responses exists, training load intensity does not appear to meaningfully influence responsiveness status in most individuals. These findings suggest that both loading schemes can be effectively prescribed to promote SMM gains in older women.

Aged↗

PubMed2026

Effects of essential amino acid supplementation on musculotendinous recovery following eccentric plantar flexor exercise: a randomized controlled trial.

BACKGROUND: Exercise-induced muscle damage (EIMD) resulting from eccentric contractions leads to transient impairments in muscle function. Essential amino acids (EAAs) stimulate muscle protein synthesis and may support recovery following damaging exercise. However, limited research has examined the effects of EAAs on muscle function following eccentric plantar flexor exercise. The purpose of this study was to examine the effects of EAA supplementation on indirect markers of muscle and musculotendinous recovery following EIMD. METHODS: Thirty-six recreationally active males (age: 21.2 ± 2.7 years) were randomly assigned to an EAA group (10 g of EAAs), placebo (10 g of maltodextrin), or control (no supplementation). Supplements were consumed 30 minutes before and immediately after an eccentric plantar flexor protocol (4 × 50 repetitions followed by one set to failure) and during the 72 hours recovery period. Indirect markers of muscle damage were assessed pre-exercise, immediately post-exercise, and 24, 48, and 72 hours post-exercise, consisting of perceived soreness (NPRS), pain pressure threshold (PPT), calf muscle thickness and Achilles tendon thickness (ultrasound), and calf circumference. RESULTS: The eccentric protocol elicited responses consistent with EIMD, including increased soreness (p < 0.001), increased calf muscle thickness and circumference (p < 0.001), and reduced PPT (p = 0.018). EAA supplementation attenuated soreness at 24 hours compared with placebo. Calf muscle thickness increased following exercise in both groups; however, swelling returned to baseline by 72 hours in the EAA group but remained elevated in placebo (Condition × Time, p < 0.001). Achilles tendon thickness decreased immediately post-exercise (p = 0.005) but was not influenced by supplementation. CONCLUSIONS: EAA supplementation modestly reduced soreness and was associated with faster recovery of muscle swelling but did not influence tendon morphology within 72 hours.

Humans↗

PubMed2026

Patient expectations assessed before randomisation and after the first treatment session, and their associations with pain outcome at 3 months in patients with tennis elbow: a secondary analysis of a randomised controlled feasibility trial in Norwegian secondary care.

OBJECTIVE: To evaluate patients' expectations of pain improvement before randomisation (T1) and after the first treatment (T2), and to examine how expectations at these two time points were associated with pain outcome measured at 3 months (T3). DESIGN: Exploratory secondary analyses of a three-arm, randomised controlled feasibility trial in patients with tennis elbow comparing heavy slow resistance training, shock wave therapy and advice (1:1:1). SETTING: Outpatient clinic at Oslo University Hospital. PARTICIPANTS: Adults with lateral epicondylalgia, commonly known as tennis elbow. MAIN OUTCOME MEASURES: Expected pain was rated on a Numeric Rating Scale (NRS, 0-10) at T1 and T2. Present pain (NRS, 0-10) was reported at 3 months (T3). Changes in expectations from T1 to T2 were summarised descriptively. Univariable linear regressions assessed associations between T3 pain and expectations at T1 and T2, treatment group and baseline factors. Explained variance was quantified by R2. Multivariable models including demographics and baseline pain were evaluated via adjusted R2. RESULTS: Fifty-four participants were included. In the shock wave group, nine (47%) came to expect greater improvement from T1 to T2; by contrast, in the advice group, seven (41%) expected less improvement. Expectations at T1 were not associated with T3 pain, whereas expectations at T2 were positively associated with T3 pain (b=0.61, 95% CI 0.33 to 0.89, p<0.01, R2=0.27), suggesting that higher expected pain at T2 was associated with higher reported pain at T3. Adding education and baseline pain increased explained variance modestly (R2 from 0.27 to 0.32). CONCLUSION: In this study, expectations measured after randomisation and one treatment session were associated with pain at 3 months for patients with tennis elbow. Larger, prospectively designed studies should investigate how postrandomisation expectations relate to clinical outcomes in non-blinded musculoskeletal trials. TRIAL REGISTRATION NUMBER: NCT04803825.

Humans↗

PubMed2026

Nutrikinetics and bioavailability of Promunel®, a standardized poplar-type propolis phenolic extract: a double-blinded, placebo-controlled, cross-over, randomized trial.

Brown poplar-type propolis has been recognized and used for centuries to help prevent upper respiratory tract infections (URTIs). However, the scarce, incomplete information in humans on the nutrikinetics and bioavailability of its phenolic constituents, combined with a lack of standardization in its phenolic content and profile pose major challenges to develop bioactive ingredients. Thus, the aim of this study was to establish the nutrikinetics and total bioavailability (NKBA) parameters of brown poplar-type propolis phenolics in humans using the Standardized Propolis Extract (SPE) Promunel®. To achieve this, a 48 h NBKA study was conducted following a double blinded, randomized, placebo-controlled, cross-over design in healthy humans (n = 10) with two doses of SPE (1X = 400 mg or 4X = 1600 mg). Phenolic compounds were detected, identified and quantified in the extract, plasma and urine through different LC-MS/UV technologies. The SPE used is a rich (304.44 ± 15.61 µmol mg-1) and diverse source of phenolic compounds (5 sub-families). A total of 63 and 85 phenolic metabolites were identified and quantified in plasma and urine, mostly in the form of glucuronides and sulfates. In plasma, phenolic metabolites reached Cmax (1.22 ± 0.20 for 1X and 4.80 ± 0.48 µM for 4X) after 1 h of SPE intake, while urinary excretion occurred mostly during the first 3 h after. The total net bioavailability of SPE phenolic compounds at 48 h was 57.16 ± 5.71% for 1X and 43.82 ± 6.77% for 4X. Generally, the data between SPE 1X and 4X were proportional, indicating that a higher dose does not substantially modulate total net bioavailability. Overall, our data shows that brown poplar-type SPE phenolic compounds are highly bioavailable in the form of cinnamic acid and flavonoid conjugates, and that these compounds are rapidly absorbed and eliminated through the urine. Our results suggest that, for a sustained presence in circulation, brown poplar-type propolis supplements should be consumed more than once a day.

Humans↗

PubMed2026

Minimally invasive versus open abdominoperineal resection and the risk of postoperative perineal hernia: a systematic review and meta-analysis.

BACKGROUND: The impact of minimally invasive surgery on the risk of postoperative perineal hernia after abdominoperineal resection (APR) or extralevator abdominoperineal excision (ELAPE) remains uncertain. This study compares perineal hernia rates and perioperative outcomes between minimally invasive and open approaches. METHODS: PubMed, Scopus, Web of Science, and Cochrane Library were searched through June 2026. Pooled odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs) were calculated using random-effects models. A Bayesian meta-analysis was additionally performed for the primary outcome. RESULTS: Four comparative observational studies involving 763 patients were included; 249 underwent minimally invasive APR/ELAPE, and 514 underwent open APR/ELAPE. Postoperative perineal hernia was significantly more frequent following minimally invasive surgery (OR 4.13; 95% CI 2.24-7.61; p < 0.001). Intraoperative blood loss was significantly lower in the minimally invasive group (MD - 156.5 mL; 95% CI - 298.4 to - 14.5; p = 0.03), as was operative time (MD - 41.7 min; 95% CI - 60.8 to - 22.5; p < 0.01). No significant differences were observed in hospital stay (MD - 2.5 days; 95% CI - 5.4 to 0.4; p = 0.09) or 30-day readmission rates (OR 1.41; 95% CI 0.82-2.42; p = 0.209). Bayesian analysis yielded a posterior mean OR of 4.04 (95% CrI 1.96-8.36), corresponding to a 99.9% posterior probability that minimally invasive surgery increases the risk of postoperative perineal hernia. CONCLUSION: Minimally invasive APR/ELAPE was associated with an increased risk of postoperative perineal hernia compared with the open approach. Strategies to reduce this complication while preserving the benefits of minimally invasive surgery warrant further investigation.

Humans↗

PubMed2026

Clinical performance of monolithic and veneered zirconia three-unit posterior FDPs: A five-year multicenter randomized controlled trial.

AIM: This randomized controlled clinical study compared monolithic, partially veneered, and fully veneered zirconia FDPs over a 5-year period with respect to survival, technical and biological complications, and patient-reported outcome measures (PROMs). MATERIALS AND METHODS: Sixty-four patients requiring three-unit posterior FDPs were randomly allocated to monolithic (MONO-FDP), partially veneered (PV-FDP), or fully veneered (FV-FDP) groups. All FDPs were fabricated from 4 mol% Y₂O₃ partially stabilized zirconia (4Y-TZP). Follow-up examinations were conducted at baseline, 1, 3, and 5 years. Technical parameters were evaluated using modified USPHS criteria. Periodontal measurements (PPD, BOP, PI) and patient satisfaction were assessed at all time points. RESULTS: A total of 63 FDPs were evaluated at baseline, 57 at 3 years, and 54 at 5 years. Survival at 5 years was 94.7% for MONO-FDPs, 100% for FV-FDPs and 100% for PV-FDPs. Technical complications occurred exclusively in PV-FDP (33%) and FV-FDP (38%) groups and consisted of minor, polishable chipping; no chipping or fractures were recorded in MONO-FDPs (0%) with statistically significant difference between MONO-FDP and the other two groups (p ≤ 0.014). Biological parameters remained stable across all groups, with no significant differences in PPD, BOP, or PI. PV-FDPs and FV-FDPs tended to receive more favorable professional color ratings, whereas PROMs were similar among the groups. CONCLUSIONS: All three FDP designs-monolithic, partially veneered, and fully veneered-fabricated from 4Y-TZP zirconia demonstrated excellent 5-year clinical performance. Technical complications were limited to PV- and FV-FDPs and consisted of minor chipping. Biological outcomes and patient satisfaction were similar across groups. CLINICAL SIGNIFICANCE: The five-year outcomes suggest that veneered, partially veneered, and monolithic FDPs can be used with high clinical reliability; however, restorations incorporating veneering ceramic may present an elevated risk of ceramic chipping.

Humans↗