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Suction-assisted ureteroscopy compared with traditional ureteroscopy for renal stones ≤ 2 cm: a systematic review, Bayesian network meta-analysis and meta-regression.

INTRODUCTION AND OBJECTIVE: Suction-enhanced flexible ureteroscopy (URS) aims to improve stone clearance and reduce complications. We performed a Bayesian network meta-analysis to compare the efficacy and safety of flexible aspiration navigable sheaths (FANS) and direct in-scope suction (DISS) for renal calculi ≤ 2 cm. METHODS: A systematic search of PubMed, MEDLINE, Scopus, Web of Science, and Google Scholar was conducted through June 2026. Comparative studies of FANS, DISS, or conventional access sheaths for renal stones ≤ 2 cm were included. The primary outcome was 30-day stone-free rate (SFR). Secondary outcomes included operative time, fever, sepsis, and complications. A Bayesian random-effects network meta-analysis synthesized direct and indirect evidence. RESULTS: Seventeen studies including 3,657 patients (1,677 FANS, 56 DISS, 1,924 control) were included. FANS showed higher SFR (OR 2.5, 95% CrI 2.0-3.1), while grouped DISS had a similar but less precise effect (OR 3.1, 95% CrI 1.0-8.8). Calyxo V2 had the highest SFR (OR 5.4, 95% CrI 1.0-29.0), whereas PUSEN showed no significant difference (OR 1.6, 95% CrI 0.41-6.3). FANS reduced postoperative fever and complications. FANS also showed lower odds of postoperative sepsis (OR 0.40, 95% CrI 0.12-0.97). CONCLUSIONS: Suction-assisted ureteroscopy improves SFR for renal calculi ≤ 2 cm. FANS was associated with shorter operative time, fever, and complications. DISS systems show promising but limited results, with performance differing by technology configuration. Larger prospective trials are needed.

Humans

Pegcetacoplan Delivers Real-World Therapeutic Benefits and Reduces Disease Burden for Patients With Paroxysmal Nocturnal Haemoglobinuria: A Systematic Literature Review of Pegcetacoplan Real-World Clinical and Patient-Reported Outcomes.

AIMS: Paroxysmal nocturnal haemoglobinuria (PNH) is an ultra-rare, acquired, non-malignant haematological disorder that, if left untreated, can lead to significant morbidity. This systematic literature review (SLR) summarized real-world evidence (RWE) for pegcetacoplan, a complement 3/3b inhibitor (C3i) available since 2021. METHODS: The SLR (PROSPERO-CRD420251043506) followed 2020 PRISMA guidelines and included RW studies of pegcetacoplan (n > 1 pts.; English; to April 2025) in adults (age ≥ 18 years) with PNH. RESULTS: Of 409 identified records, 39 qualified, representing 12 distinct studies. Six studies (n = 4-39) reported median haemoglobin (Hb) with baseline 8.1-9.6 g/dL. Ending median Hb and maximum pegcetacoplan durations were: 12.0 g/dL at 12 months, 11.1-12.1 g/dL at 6 months (3 studies), and 11.1 g/dL at 3 months (1 study). In 4 other studies (n = 48-70), ending mean Hb (maximum pegcetacoplan duration) was: 11.3 g/dL (7.2 months), 11.5 g/dL (6.6 months), 11.5 g/dL (5.9 months), and 11.58 g/dL (3 months). Six studies reported reduced absolute reticulocyte count (ARC; n = 4-39) from baseline median 155-301 × 109/L to median 56-106 × 109/L from 14 days of pegcetacoplan, maintained to maximum pegcetacoplan of 1-12 months. Three studies reported lactate dehydrogenase (LDH; n = 4-62); all showed reductions from baseline median 543.0 to 161.7 U/L after 3 months, and baseline median 299.5-316.0 U/L to 193.5-187.0 U/L after 6 months of pegcetacoplan. In complement 5 inhibitor-naïve, LDH reduced from 977.8 to 358.9 U/L after 8.4 months, and 503.6 to 292.5 U/L in C5i-experienced after 7.2 months. Three studies (n = 4-63) reported reduced LDH from above the upper limit of normal levels. Six studies (n = 23-70) reported reduced red blood cell transfusions (RBCt) after maximum pegcetacoplan durations of up to 12 months, and median durations of 3.0 and 10.2 months. Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale scores in 1 study increased from baseline (mean 28.4) to 38.6 at 3 months, 36.3 at 6 months, and 34.9 at 9 months of pegcetacoplan treatment. Two studies reported FACIT-Fatigue scores of 34.6-40.1 with pegcetacoplan for ≥ 1 month. EQ-5D mean utility scores (0.85-0.94) in 2 studies were comparable to population normative values. On the Short-Form 36 Health Survey, mental and physical component scores were slightly lower than US normative values. CONCLUSIONS: RWE indicates pegcetacoplan is associated with improved haematological outcomes, reduced RBCt dependence and fatigue, and enhanced HRQoL. These findings from real-world studies with diverse cohorts support generalizability and are broadly comparable with clinical trial evidence.

Humans

Clinical Trial: Effectiveness and Safety of a Novel Anal Insert Device for Treatment of Faecal Incontinence.

BACKGROUND: Treatment options for medically-refractory faecal incontinence (FI)-including anorectal biofeedback, dextranomer injection, and sacral nerve stimulation-are limited and outcomes are often suboptimal. Anal or vaginal insert devices are infrequently used. AIMS: We evaluated the safety and effectiveness of a new anal insert device (StaySure) in patients with FI. METHODS: Patients with FI for&#x2009;&#x2265;&#x2009;6&#x2009;months and&#x2009;&#x2265;&#x2009;4 moderate or large FI episodes during a 4-week baseline entered a 2-4&#x2009;week fitting/run-in period to individualise device size (10 or 13&#x2009;mm) followed by a 4-week treatment period. Outcomes included effectiveness, safety, and quality of life (QoL). The primary outcome was the proportion achieving a&#x2009;&#x2265;&#x2009;50% reduction in FI frequency. RESULTS: Of 124 enrolled patients, 98, 71, and 61 progressed through the baseline, fitting/run-in, and treatment phases respectively, with few exclusions due to device intolerance. In the intent-to-treat cohort of 59 participants (93% women), mean (SD) number of days with FI declined from 13.2 (7.0) to 6.3 (6.9), and FI weekly episodes declined from 5.4 (6.9) to 2.1 (5.1) (69% reduction; p&#x2009;<&#x2009;0.001) with similar results for both device sizes. The primary endpoint was achieved in 76.3% of participants; 54.2% achieved&#x2009;&#x2265;&#x2009;75% reduction. The FIQoL overall score increased from a mean (SD) of 1.9 (0.6) to 2.3 (0.6) (p&#x2009;<&#x2009;0.001), indicating improved QoL. Improvements in FI frequency, FIQoL exceeded minimal clinically important difference thresholds, confirming clear clinical benefit. No treatment-related serious adverse events were reported. CONCLUSIONS: The StaySure anal insert device is safe, well tolerated, and effective in reducing FI in patients with moderate to severe symptoms refractory to conservative therapies. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03898778.

Adult

A framework for delivering real-time, instrument-relative navigation in transoral robotic surgery.

Transoral robotic surgery (TORS) is a minimally invasive, inside-out technique that, compared with traditional open approaches, provides fewer post-operative complications, shorter hospital stays, and improved survival for early-stage head and neck cancer. However, TORS is limited by its steep learning curve and poor visualization of deep tumor margins. This randomized crossover study evaluated a surgical navigation system's potential to enhance accuracy and user experience with real-time, instrument-relative feedback. Seven Teflon beads (d&#x2009;=&#x2009;2.381&#xa0;mm) were embedded at the tongue base of a porcine pharynx-and-larynx model. Tongue blade compression and retraction were applied to the model to mimic intraoperative tissue deformation, reproducing the anatomical shifts that occur relative to preoperative imaging. Eight participants used the da Vinci Surgical system to localize the beads by placing pins under two conditions: (a) preoperative computed tomography with no navigation; (b) model-based visual navigation with quantitative instrument-to-target metrics. Surgical accuracy was determined by calculating the target localization error (TLE, pin-to-bead Euclidean distance) and the angular error (AE, pin axis trajectory to bead). Accounting for training level and bead depth, surgical navigation reduced TLE by 5.44&#xa0;mm (95% CI, 4.02-6.86&#xa0;mm; p&#x2009;=&#x2009;2.00e-11) and AE by 8.47 degrees (95% CI, 6.21-10.72 degrees; p&#x2009;=&#x2009;5.17e-11). Impressions of the system were generally favorable using a 5-point Likert survey and task duration (p&#x2009;=&#x2009;0.26) or cognitive workload via the NASA-Task Load Index (p&#x2009;=&#x2009;0.22) were not significantly affected. The navigation system demonstrated translational promise, offering improved target localization accuracy and more consistent performance across experience levels, two critical determinants of surgical quality in TORS.

Robotic Surgical Procedures

Effects of exercise on aerobic capacity in people with prehypertension or hypertension: a systematic review and meta-analysis of randomized controlled trials.

This study aimed to quantify the effects of exercise on aerobic capacity in people with prehypertension or hypertension and to identify exercise prescription parameters that optimize improvements. A comprehensive search was conducted in PubMed, Web of Science, Embase, Cochrane Library, and Scopus from inception to 24 October 2025. Data were pooled using standardized mean differences (SMDs) with 95% confidence intervals (CI). Fifteen studies met the inclusion criteria. Exercise significantly improved aerobic capacity in people with prehypertension or hypertension (SMD&#x200a;=&#x200a;0.88; 95% CI: 0.61-1.15; P &#x200a;<&#x200a;0.00001), with multicomponent training demonstrating superior efficacy. Exploratory subgroup analyses suggest that longer programs (&#x2265;12&#x200a;weeks), lower frequency (<3&#x200a;sessions/week), 60-min sessions or longer, total weekly exercise less than 180&#x200a;min, and professional supervision may be associated with better outcomes.

Humans

Identification of elements determining KIR gene demethylation at the CD56-bright stage of NK cell development.

The variegated expression of the KIR family of class I MHC receptors generates specialized natural killer (NK) cells capable of allele-specific HLA recognition. Understanding the mechanism of KIR gene activation will lead to improved methods for the generation of fully functional NK cells. A central RUNX-binding site in the KIR proximal promoter is required for gene activation. RUNX proteins recruit ten-eleven translocation (TET) proteins that generate 5-hydroxymethylcytosine (5hmC) and drive DNA demethylation. Assessment of 5-methylcytosine (5mC) and 5hmC residues at four stages of NK cell development reveals deposition of 5hmC primarily in a CREB site next to the RUNX site at the CD56Bright stage but not the subsequent CD56Dim stage representing fully mature NK cells. KIR promoter demethylation is delayed relative to other lineage-associated genes, indicating a high threshold for KIR gene demethylation in developing NK cells, and a window of opportunity for RUNX/TET-dependent KIR gene activation in CD56Bright NK cells.

6-base sequencing

Associations between multiple essential trace metal concentrations and risk of hyperuricemia: insights from a central Chinese population.

Previous studies have indicated that levels of individual essential trace metals are related to hyperuricemia (HUA), but evidence on their combined effects is limited. To address this gap,&#xa0;the associations of individual and joint levels of 12 essential trace metals (manganese, selenium, nickel, chromium, cobalt, tin, iron, molybdenum, zinc, strontium, vanadium, and copper) with the risk of HUA were investigated in&#xa0;2,021 adults recruited from Hunan Province, China. Inductively coupled plasma mass spectrometry (ICP-MS) was employed to determine urinary metal concentrations. Logistic regression, Bayesian kernel machine regression (BKMR), and quantile g calculation (Qgcomp) were applied to evaluate the associations of single and mixture metal concentrations with HUA. Of the participants,&#xa0;516 (25.53%) were diagnosed with HUA. Inverse associations were found between vanadium, chromium, manganese, iron, cobalt, selenium, strontium, and molybdenum levels and HUA, with ORs ranging from 0.63 to 0.91. Conversely, a positive association was observed between zinc concentration and HUA [OR (95% CI): 1.17 (1.01, 1.37)]. Both BKMR and Qgcomp models showed a negative overall effect of essential trace metals on HUA risk, with strontium (-&#x2009;43.6%) and vanadium (-&#x2009;27.8%) being the main contributors. In addition, formal interaction tests revealed significant effect modification by age for tin and by BMI for zinc.&#xa0;In conclusion, the levels of essential trace metals were linked to a decreased risk of HUA, and these associations were modified by age and BMI only for specific metals.

Humans

Efficacy and safety of JAK inhibitors in Beh&#xe7;et syndrome: systematic literature review.

OBJECTIVES: Given the active role of the JAK signaling pathway and the multifactorial immune mediators observed in Beh&#xe7;et syndrome (BS), JAK inhibitors (JAKi) may be promising agents. In this systematic literature review (SLR), we aim to evaluate the efficacy and safety of JAKi in BS. METHODS: A systematic literature search was conducted in Embase, PubMed, and the Cochrane Library to identify all reports on the efficacy and safety of JAKi in patients with BS. The SLR protocol was registered with the International Prospective Registry of Systematic Reviews (CRD420251000172). We additionally presented our patient with gastrointestinal involvement treated with upadacitinib. RESULTS: Among the 92 patients (48 men, mean (SD) age 38.5 (13.5) years), 46 used tofacitinib, 31 used baricitinib, and 15 used upadacitinib. All but 1 patient had used at least one previous conventional immunosuppressive, and 57.6% were refractory to at least one prior tumor necrosis factor inhibitor. JAKi were used in combination with conventional immunosuppressive and/or glucocorticoids in 90.6% of the patients. The primary indication for JAKi initiation was gastrointestinal involvement in 46 (50%) patients including our patient, vascular involvement in 22 (23.9%), uveitis in 19 (20.6%), and mucocutaneous and/or articular involvement in 5 (5.6%) patients. The remission rates for overall, gastrointestinal, vascular, and eye involvement were 85.9%, 82.6%, 90.9%, and 84.2%. Serious adverse events were observed in 5.4% of the patients. No thrombotic events were reported. CONCLUSION: This SLR showed that JAKi may be effective in refractory BS patients with a favorable safety profile.

Humans

Long-term microbiome and clinical effects of a microbiome-guided personalized diet versus low-FODMAP diet in irritable bowel syndrome: A 12-month follow-up randomized controlled trial.

Dietary therapy is central to irritable bowel syndrome (IBS) management, yet the long-term durability of the low-FODMAP diet (LFD), and of microbiome-guided personalization, remains unclear. We assessed the long-term clinical and gut-microbiome effects of a microbiome-guided personalized diet (PD) compared with a standard LFD in adults meeting Rome IV criteria for IBS. In this multicenter, open-label randomized controlled trial with blinded outcome assessment, participants who completed a 6-week dietary intervention (PD or LFD) were followed at 6 and 12 months without further dietary intervention. Outcomes included the IBS Severity Scoring System (IBS-SSS), IBS Quality of Life (IBS-QOL), and the Hospital Anxiety and Depression Scale (HADS); gut microbiota were profiled by 16S rRNA sequencing. Longitudinal changes were evaluated using linear mixed-effects models, responder analyses, PERMANOVA, and PERMDISP. Both diets reduced IBS-SSS at 6 weeks. PD maintained symptom improvement at 6 and 12 months (-82.0 and -78.3 points from baseline), whereas LFD benefits regressed by 12 months (+29.3 points; between-group p&#x2009;=&#x2009;0.001). At 12 months, IBS-SSS responder rates were higher with PD than LFD (62.5% vs 34.5%; absolute risk difference&#x2009;+28.0%, 95% CI 4.2-47.7; Fisher p&#x2009;=&#x2009;0.029), and IBS-QOL, HADS-anxiety, and HADS-depression showed more favourable trajectories with PD. PD was associated with sustained Shannon alpha-diversity gains (+0.488 at 6 weeks;&#x2009;+0.205 at 12 months; both p&#x2009;<&#x2009;0.01). A modest between-group beta-diversity difference at 6 months (R2&#x2009;=&#x2009;0.035; p&#x2009;=&#x2009;0.011) was not significant at 12 months. This hypothesis-generating follow-up suggests more durable benefit with PD; larger trials powered for long-term clinical and microbiome outcomes are warranted.

Humans

Addressing lignin composition and content via Arabidopsis arogenate dehydratase knockout and over-expression genotypes.

Following the down-selection of 14 Arabidopsis thaliana arogenate dehydratase (ADT) knockout and over-expression (OE) genotypes, the most highly contrasting quadruple knockout adt3/4/5/6 and ADT OE genotypes were subjected to proteomics, metabolomics, and scanning electron microscopy (SEM) analyses as needed, with results compared to Columbia wild-type (WT). The basal adt3/4/5/6 stem cross-sections, &#x223c;70% lignin content reduced, exhibited buckled vessel cell walls and partially detached xylary fibers, in contrast to WT and ADT4m/5&#x202f;m OE genotypes that did not. Anatomical defects primarily resulted from guaiacyl lignin level reductions in vessels with concomitant increased stem syringyl:guaiacyl (S/G) ratios. Phenylpropanoid and various upstream shikimate-chorismate pathway enzyme abundances, as well as specific monolignol oxidases (laccases/peroxidases), generally increased in adt3/4/5/6&#x202f;at different stem and rosette leaf growth/development stages, relative to WT. Opposite effects were largely observed with the ADT5m OE genotype. By contrast, flavonoid and glucosinolate pathway enzyme amounts varied. Such enzyme abundance increases were overall unproductive as adt3/4/5/6 was unable to restore WT, ADT4 OE, ADT5 OE, ADT5m OE, and ADT4m/5&#x202f;m OE secondary metabolite (lignin, phenylpropanoid, lignan, flavonoid, phenolic acid, and glucosinolate) levels. Conversely, ADT OE genotypes did not significantly increase programmed lignin levels or alter S/G compositions. In sum, proteomics analyses of adt3/4/5/6 and adt5 'perceived' that lignin and low molecular weight secondary metabolite amounts were not at 'programmed' levels as for WT and ADT OE genotypes but observed increases in relevant pathway protein abundances were futile. Notably though, proteomics analyses did not lead to predicting that lignin and associated biochemical pathways would have reduced metabolite levels, relative to WT and ADT OE genotypes. Genotype adt3/4/5/6, possibly the highest lignin level reduced genotype reported, did not utilize other phenolics to compensate. By contrast, the differential temporal and spatial deposition of cell wall oxidases again indicate the exquisite control over lignin deposition, and our lack of knowledge of precise lignin structure and assembly in subcellular regions of the lignified cell walls.

Lignin

Long-term safety of oral orforglipron in Japanese participants with type 2 diabetes (ACHIEVE-J): a multicentre, randomised, open-label, parallel-group phase 3 trial.

BACKGROUND: Orforglipron, an oral GLP-1 receptor agonist, requires further evaluation in east Asian populations with type 2 diabetes, given this group's distinct pathophysiological characteristics. This study aimed to assess orforglipron as add-on treatment to diet and exercise alone or to oral antihyperglycaemic medications in Japanese participants with type 2 diabetes. METHODS: This multicentre, randomised, open-label phase 3 study was conducted in 40 medical research centres and hospitals in Japan. Adults with type 2 diabetes and elevated glucose levels managing their condition with diet and exercise alone or with one or two oral antihyperglycaemic medications were assigned (1:1:1) via computer-generated random sequence to receive once-daily oral orforglipron (3 mg, 12 mg, or 36 mg). Randomisation was stratified by background therapy, baseline HbA1c (&#x2264;8&#xb7;5% or >8&#xb7;5%), and metformin use (yes vs no; applied only to &#x3b1;-glucosidase inhibitors, thiazolidinedione, and glinides). Investigators, participants, and site staff were not masked to treatment. The primary endpoint was safety for 52 weeks, assessed in all randomly assigned participants who received at least one dose of orforglipron. This study is registered with ClinicalTrials.gov, NCT06010004 (ACHIEVE-J). FINDINGS: Between Sept 28, 2023, and June 5, 2025, 450 participants were screened and 401 were randomly assigned to three groups (3 mg, n=132; 12 mg, n=135; and 36 mg, n=134). 352 (88%) completed study treatment. 339 participants (85%, 95% CI 80&#xb7;7-87&#xb7;8) had at least one treatment-emergent adverse event (TEAE), more frequently in the 36-mg group (118 [88%, 95% CI 81&#xb7;5-92&#xb7;5]) than in the 3-mg (107 [81%, 73&#xb7;5-86&#xb7;8]) and 12-mg (114 [84%, 77&#xb7;4-89&#xb7;6]) groups. Most TEAEs were of mild (267 [67%, 61&#xb7;8-71&#xb7;0]) or moderate (63 [16%, 12&#xb7;5-19&#xb7;6]) severity. Discontinuations due to an adverse event occurred in 19 of 134 participants (14%, 95% CI 9&#xb7;3-21&#xb7;1) in the 36-mg group compared with seven of 132 (5%, 2&#xb7;6-10&#xb7;5) in the 3-mg group and 11 of 135 (8%, 4&#xb7;6-14&#xb7;0) in the 12-mg group. Across treatment groups, gastrointestinal symptoms were the most common TEAEs leading to study treatment discontinuation (3 mg: 5 [3&#xb7;8%, 1&#xb7;6-8&#xb7;6]; 12 mg: 8 [5&#xb7;9%, 3&#xb7;0-11&#xb7;3]; and 36 mg: 11 [8&#xb7;2%, 4&#xb7;7-14&#xb7;1]). Level 2 (blood glucose <54 mg/dL) hypoglycaemia events occurred in three of 135 participants in the 12-mg group (2%, 0&#xb7;8-6&#xb7;3) and in three of 134 in the 36-mg group (2%, 0&#xb7;8-6&#xb7;4) groups. No level 3 (severe) hypoglycaemia events occurred. Outcomes were generally similar across background therapies. INTERPRETATION: Treatment with orforglipron in combination with diet and exercise alone or one or two oral antihyperglycaemic medications for 52 weeks demonstrated an acceptable safety profile in Japanese adults with type 2 diabetes. FUNDING: Eli Lilly. TRANSLATION: For the Japanese translation of the abstract see Supplementary Materials section.

Aged

The Effect of Breastfeeding on Cervical Dysplasias.

OBJECTIVE: This study aimed to investigate the relationship between breastfeeding and precancerous cervical lesions. MATERIALS AND METHODS: A case control study was conducted at a tertiary training and research hospital between September 1 and November 1, 2023. A total of 168 patients who attended the gynecology outpatient clinic and reported their breastfeeding experiences were included. Patients with abnormal cervical cytology formed the study group (n = 37), while patients with normal cytology formed the control group (n = 131). Breastfeeding duration and patterns were compared between groups. RESULTS: The control group had normal smear results. In the study group, 15 patients had high-grade squamous intraepithelial lesions, and 22 patients had low-grade squamous intraepithelial lesions. Human papillomavirus (HPV) was positive in 54.1% of the study group versus 9.2% of the control group. The mean breastfeeding duration was shorter in the study group (9.18 &#xb1; 3.43 months) than the control group (23.6 &#xb1; 3.35 months; p < 0.05). Most control group patients breastfed for 13-36 months (35.1%), while most study group patients breastfed for <6 months (48.6%; p < 0.05). Shorter breastfeeding (<6 months) and HPV positivity were the strongest predictors of abnormal cytology. Breastfeeding <6 months increased the risk 9.883-fold compared with >36 months, while HPV positivity increased the risk 27.612-fold. CONCLUSION: Breastfeeding and longer breastfeeding duration appear to be associated with a lower risk of cervical intraepithelial neoplasia. Given its multiple health benefits, including prevention of gynecological cancers, promoting breastfeeding through public health policies is strongly recommended. Early recognition and prevention of precancerous lesions remain essential to reducing the risk of cervical cancer.

Humans

Air Pollution and Heat Impacts on Respiratory Morbidity and Mortality Outcomes in Africa: A Systematic Review Towards a Meta-analysis.

PURPOSE OF THE REVIEW: This review synthesised evidence on associations between air pollution and respiratory morbidity in Africa. Following PRISMA guidelines, we systematically searched PubMed, ScienceDirect and Elicit for case-control studies published between 2015 and 2025. RECENT FINDINGS: Thirteen studies from ten African countries reported pollutant levels far exceeding WHO guidelines. Indoor PM&#x2082;.&#x2085; in biomass-using homes ranged from 96 to 177&#xa0;&#xb5;g/m&#xb3;, and ambient PM&#x2082;.&#x2085; reached 259&#xa0;&#xb5;g/m&#xb3;. Nitrogen oxides were consistently associated with reduced lung function in children, while household air pollution increased risks of under-five mortality and low birthweight. Associations with acute respiratory infections varied across settings. Vulnerability was greatest among young children, those with airway hyperresponsiveness, and households with poor ventilation. Only three studies included temperature, and none examined heat-respiratory interactions. Across African case-control studies, particulate matter and household air pollution remain consistently linked to adverse respiratory outcomes, highlighting urgent needs for cleaner fuels, improved ventilation, and stronger evidence on combined pollution and heat exposures.

Humans

Effect of a digitally augmented general health promotion intervention on abstinence from health-risk behaviors among emergency department discharge patients: A randomized controlled trial.

BACKGROUND: Noncommunicable diseases (NCDs) are the leading global cause of death and are driven by modifiable behaviors, such as tobacco use, harmful alcohol consumption, unhealthy diet, and physical inactivity. Recognizing that emergency department (ED) visits represent a unique opportunity to promote behavior change, this trial evaluated a digitally augmented, theory based general health promotion approach, combining a brief telephone-based intervention with mobile instant messaging support, to help discharged ED patients abstain from health risk behaviors. METHODS AND FINDINGS: This assessor-blinded randomized controlled trial was conducted in a major public hospital ED in Hong Kong. Adults (18-65 years) triaged as semi-urgent or non-urgent and with &#x2265;1 health-risk behavior and smartphone access were randomized to receive a digitally augmented, theory&#x2011;based general health&#x2011;promotion intervention consisting of a brief telephone&#x2011;based AWARD&#x2011;model intervention (Ask, Warn, Advise, Refer, and Do-it-again) followed by weekly WhatsApp or WeChat messages for 6 months, or to a control group receiving brief telephone advice only. The primary outcome was self-report abstinence from &#x2265;1 health-risk behavior at 6 months; secondary outcomes included the proportion of participants who achieved self-reported abstinence from &#x2265;1 health-risk behavior at 12 months and reduction in the number of behaviors at 6 and 12 months. Of the 2,134 screened patients, 572 were enrolled (286 per group). At 6 months, 30.1% of the intervention participants versus 19.9% of the controls achieved self-reported abstinence (RR&#x2009;=&#x2009;1.51; 95% CI, 1.13-2.02; P&#x2009;=&#x2009;0.006). The intervention also significantly increased the likelihood of fewer risky behaviors at 6 (RR&#x2009;=&#x2009;1.54; P&#x2009;=&#x2009;0.01) and 12 (RR&#x2009;=&#x2009;1.48; P&#x2009;=&#x2009;0.02) months. Physical inactivity showed the greatest improvement at 6 months (31.7% versus 16.2%; P&#x2009;<&#x2009;0.001). The effects attenuated after cessation of booster messaging. Limitations include reliance on self-reported outcomes, the single-center study design, and loss to follow-up, which may have affected the generalizability of the results. CONCLUSIONS: A digitally augmented, theory-based general health promotion strategy delivered at ED discharge through brief telephone intervention and mobile instant messaging support demonstrated short-term benefits in promoting self-reported abstinence and reducing health-risk behaviors at 6 months. However, the absence of a sustained effect at 12 months suggests that extended support or maintenance strategies may be required to maintain these improvements over time. Multicenter trials with longer follow-up are warranted to evaluate long-term effectiveness. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (Registration No: NCT06077565).

Humans

Efficacy and safety of once-weekly semaglutide 2&#xb7;4 mg in Chinese adults with overweight or obesity (STEP 12): a randomised, double-blind, placebo-controlled, multicentre, phase 3b trial.

BACKGROUND: Semaglutide 2&#xb7;4 mg is a GLP-1 receptor agonist that reduces bodyweight, and provides other cardiometabolic benefits, among people with a BMI at least 30 kg/m2 or at least 27 kg/m2 and with weight-related comorbidities. This trial aimed to evaluate the efficacy, tolerability, and safety of semaglutide 2&#xb7;4 mg in adults from mainland China and Taiwan with overweight or obesity according to locally defined, BMI thresholds. METHODS: This completed randomised, double-blind, placebo-controlled, multicentre, two-armed, parallel-group, phase 3b trial (STEP 12) was conducted at 19 sites across mainland China and Taiwan. Adults with a BMI of 24-<28 kg/m2 and at least one weight-related comorbidity, or a BMI of 28-<30 kg/m2, with or without type 2 diabetes, were randomly assigned (2:1) to once-weekly subcutaneous semaglutide 2&#xb7;4 mg or placebo, plus lifestyle intervention, for 44 weeks. Randomisation was performed by the study sponsor using the Randomisation Trial Supplies Management System. Coprimary endpoints were percentage change in bodyweight and the proportion of participants achieving at least 5% bodyweight reduction. Safety was analysed descriptively in all participants who received the trial intervention. Missing data at week 44 were imputed with washout multiple imputation. This study is registered with ClinicalTrials.gov, NCT06041217, and is completed. FINDINGS: Between Sept 15, 2023, and May 7, 2025, of 254 screened participants, 161 (66&#xb7;5%) of 242 participants were randomly assigned to semaglutide 2&#xb7;4 mg and 81 (33&#xb7;5%) to placebo; 121 (50&#xb7;0%) participants were female, and 47 (19&#xb7;4%) participants had type 2 diabetes. Bodyweight reduction was greater with semaglutide versus placebo (-12&#xb7;1% [SE 0&#xb7;6] vs -2&#xb7;2% [0&#xb7;8]; estimated treatment difference -9&#xb7;9 percentage points [95% CI -11&#xb7;8 to -8&#xb7;0]; p<0&#xb7;0001), with a greater proportion of participants achieving at least 5% bodyweight reduction (80&#xb7;5% vs 24&#xb7;4%; odds ratio [OR] 14&#xb7;8 [95% CI 7&#xb7;4 to 29&#xb7;6]; p<0&#xb7;0001). Adverse events were reported in 141 (87&#xb7;6%) of 161 participants in the semaglutide 2&#xb7;4 mg group and 61 (75&#xb7;3%) of 81 participants in the placebo group, with gastrointestinal disorders being the most common. INTERPRETATION: Semaglutide 2&#xb7;4 mg provided a superior reduction in bodyweight versus placebo in Chinese adults with overweight or obesity. The safety profile was consistent with the known profile of semaglutide. FUNDING: Novo Nordisk A/S. TRANSLATION: For the Mandarin translation of the abstract see Supplementary Materials section.

Adult

Paramedian supracerebellar transtentorial approach for Ya&#x15f;argil T2 tentorial incisura meningiomas.

OBJECTIVE: Tentorial incisura meningiomas, particularly those arising from the middle incisural region (Ya&#x15f;argil T2), are surgically challenging because of their deep location and compression of critical neurovascular structures. These lesions typically have supratentorial or infratentorial extension but can also extend across both compartments. Although approach selection is often guided by the dominant compartment of tumor extension, for lesions with supratentorial-dominant extension, the optimal approach remains controversial, and a standardized strategy has not been established. Authors of this study evaluated the feasibility and outcomes of the paramedian supracerebellar transtentorial (PST) approach for Ya&#x15f;argil T2 tentorial incisura meningiomas with a supratentorial-dominant or combined extension. METHODS: The authors retrospectively reviewed data from consecutive patients with radiographic and intraoperative findings consistent with a Ya&#x15f;argil T2 tentorial incisura lesion treated via the PST approach from September 2005 through December 2025. Patients were placed in a semisitting position whenever feasible and in a semilateral position when semisitting was contraindicated. Collected data included demographics, tumor extension patterns, extent of resection on postoperative MRI, neurological outcomes, histopathology, rate of recurrence, and follow-up. RESULTS: Six patients, 1 male and 5 female, with an overall mean age of 43 years, underwent resection via the PST approach. Four lesions had predominantly supratentorial extension, and 2 had combined supra- and infratentorial growth, with no cases of isolated infratentorial extension. Five patients had been placed in the semisitting position and 1 in a semilateral position because of a cardiac contraindication to the semisitting position. No new permanent neurological deficits were observed. Postoperative MRI showed Simpson grade I resection in all 6 patients. The mean follow-up was 8.6 years. Histopathological analysis revealed 3 WHO grade 1 meningiomas, 1 WHO grade 2 meningioma (clear cell), and 2 solitary fibrous tumors (meningioma mimics). These diagnoses were evaluated according to the 2021 WHO classification. CONCLUSIONS: In this consecutive series, the PST approach was a viable single-corridor strategy for Ya&#x15f;argil T2 tentorial incisura lesions, including supratentorial-dominant tumors, achieving Simpson grade I resection with no permanent neurological deficits. By providing early devascularization at the tentorial attachment and a gravity-assisted, retractorless working corridor with favorable deep venous visualization, the PST approach challenges compartment dominance as the primary determinant of approach selection.

Humans

Endoscopic submucosal dissection for locally recurrent gastric neoplasia following endoscopic resection: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) for locally recurrent gastric neoplasia following endoscopic resection (ER) is technically challenging because of scar-related submucosal fibrosis. We performed a systematic review and meta-analysis to evaluate the efficacy and safety of salvage ESD in this setting. METHODS: Multiple databases were searched through December 2025 for studies reporting ESD outcomes for locally recurrent gastric lesions at or contiguous with a prior ER scar. Primary outcome was curative resection and need for surgery. Secondary outcomes were en bloc and R0 resection, local recurrence, delayed bleeding, and perforation. Meta-analyses were performed using a random effects model. Heterogeneity was assessed using I2. RESULTS: Seven studies (259 patients; 265 ESDs) were included. Across 5 studies and 243 ESDs, pooled curative resection rate was 69.7% (95% CI, 60.6-78.1; I2 = 38%), while 8.2% (95% CI, 3.3-14.6; I2 = 38.4%) required surgery. En bloc resection rate was 92.3% (95% CI, 79.1-99.7; I2 = 83.7%) across 6 studies, and pooled R0 resection rate was 87.5% (95% CI, 82.1-92.2; I2 = 0%) across 4 studies. Over a mean follow-up of 42 months, pooled local recurrence was 2.0% (95% CI, 0.0-9.7; I2 = 54.1%) across 6 studies. Delayed bleeding was 4.1% (95% CI, 0.8-9.0; I2 = 40.8%) and perforation was 4.1% (95% CI, 1.6-7.3; I2 = 0%). CONCLUSIONS: ESD for locally recurrent gastric neoplasia after ER achieves acceptable curative resection, high en bloc/R0 resection, and low local recurrence and morbidity. It is a viable organ-preserving option for appropriately selected patients, ideally performed at expert centers with close surveillance.

Humans

Surgical management of jugular foramen meningiomas: a function-prioritized perioperative workflow.

OBJECTIVE: Jugular foramen meningiomas are challenging because of their deep, neurovascularly crowded location and multicompartment extension; hyperostosis and rigid dural attachment further narrow the corridor and increase the risk of lower cranial nerve morbidity, causing dysphagia and airway complications that may rarely require tracheostomy. This study aimed to describe a contemporary function-first workflow integrating compartment-based anatomy, venous sinus status, preoperative embolization, and continuous vagus nerve monitoring and its relation to clinically actionable recovery endpoints. METHODS: The authors retrospectively reviewed 26 consecutive patients who underwent primary surgery for jugular foramen meningiomas (2014-2025). Tumors were classified as intradural + intrajugular (IJ) or intradural + intrajugular + extracranial extension (IJE). Retrosigmoid, suprajugular, or transjugular approaches were selected by tumor extension and sigmoid-jugular venous status. Selective embolization and continuous vagus nerve monitoring were used when feasible. Outcomes included extubation timing, time to oral intake, 1-year swallowing/voice severity, extent of resection, and salvage stereotactic radiosurgery (SRS) for progression/regrowth. RESULTS: Twenty tumors were IJ and 6 were IJE. Selective embolization was performed in 16 patients (62%) without complications. Continuous vagus nerve monitoring was implemented in 16 patients (62%); lower preservation rates showed an exploratory association with worse 1-year swallowing. All patients were extubated immediately after surgery. Oral intake began by postoperative day &#x2264; 7 in 20 patients (77%); only 1 required > 14 days before resuming oral intake. At 1 year, swallowing and hoarseness remained worse in 54% and 46% of patients, respectively, but almost all cases were mild; the same patient had moderate dysphagia/hoarseness, and none required tracheostomy, gastrostomy, long-term tube feeding, or phonosurgery. Simpson grade IV comprised 69% of cases but predominantly reflected intrajugular/extracranial residual rather than persistent intradural disease. No patient without preoperative facial nerve palsy developed new palsy; serviceable hearing was preserved in 70%, and 38% with preoperative nonserviceable hearing improved to serviceable hearing. During a median 55.6-month follow-up, 3 patients (12%) underwent salvage SRS for regrowth; none required reoperation. CONCLUSIONS: A function-first workflow guided by anatomical compartment extension and intraoperative monitoring can support rapid recovery and durable functional independence in jugular foramen meningiomas. The IJE phenotype identifies a higher-risk subgroup for delayed oral intake and postoperative subjective dysphagia/hoarseness, while continuous vagus nerve monitoring may provide actionable insights to calibrate surgical aggressiveness and support function-prioritized acceptance of intrajugular/extracranial residual with close surveillance and salvage SRS when needed.

Humans