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Venous Sinus Stenting for Pulsatile Tinnitus: A Systematic Review and Meta-Analysis.

BACKGROUND: Pulsatile tinnitus (PT) is frequently caused by venous sinus stenosis and may be associated with idiopathic intracranial hypertension (IIH). Venous sinus stenting (VSS) directly addresses venous outflow obstruction and has emerged as a therapeutic option; however, outcome data remain heterogeneous. We performed an updated systematic review and meta-analysis to evaluate the efficacy and durability of VSS for PT and to compare outcomes between IIH-associated and isolated PT. METHODS: MEDLINE, Scopus, and Web of Science were searched from inception through December 2025 following PRISMA guidelines. Clinical studies reporting PT outcomes after VSS were included. Random-effects meta-analyses of proportions were conducted to estimate pooled rates of overall improvement, complete resolution, and recurrence. Prespecified subgroup analyses compared IIH versus isolated PT. RESULTS: Thirty-two studies comprising 850 patients were included (641 with IIH; 209 with isolated PT). Venous sinus stenosis accounted for 90.3% of treated etiologies. The pooled rate of overall PT improvement was 89.8% (95% CI, 85.5-92.9). Complete resolution occurred in 87.1% (95% CI, 82.5-90.6). Recurrence at last follow-up was 10.9% (95% CI, 8.3-14.2). Improvement and complete resolution rates did not differ significantly between IIH and isolated PT. Recurrence was higher in IIH (12.0%) than in isolated PT (5.7%), without reaching statistical significance. CONCLUSIONS: VSS is associated with high rates of PT improvement and complete resolution with low recurrence. Recurrence trends appear higher in IIH, suggesting underlying pathophysiology may influence durability.

Humans

Prevalence of unruptured intracranial aneurysms according to comorbidities, risk factors, country, and time period: a systematic review and meta-analysis.

BACKGROUND: The incidence of aneurysmal subarachnoid haemorrhage declined between 1980 and 2010, which coincided with a decline in smoking and prevalence of hypertension. We aimed to investigate whether the decrease in subarachnoid haemorrhage incidence is paralleled by declines in unruptured intracranial aneurysm (UIA) prevalence. METHODS: For this systematic review and meta-analysis, we searched Embase, PubMed, and Web of Science for articles published in any language from Jan 1, 2011 to Dec 31, 2025, and reassessed 68 articles published before March 1, 2011 from a 2011 systematic review and meta-analysis. Articles were eligible for inclusion if they used a cross-sectional or case-control design and provided the crude number of participants and those with UIA. We only included studies reporting numbers of UIA separately from ruptured aneurysms and with ten or more patients. Summary data were independently extracted by JD with AZ or CB and conflicts were resolved by GJER. The primary outcome was proportion of participants with UIA. Relative to a hypothetical reference population (mean age 50 years, 50% women, and no comorbidities), age and/or sex-adjusted prevalence ratios (PRs) for regions, comorbidities, and risk ratios (RRs) for female sex, smoking, and hypertension were estimated using generalised linear mixed models. A time trend analysis was done by binomial meta regression using the mid-year of data acquisition. We assessed the certainty of evidence using GRADE. The study was registered with PROSPERO, number CRD420261296728. FINDINGS: Our search screened 4708 studies. 67 reassessed and 95 newly identified articles, reporting on 316 131 participants and 11 822 people with UIAs, were included in our meta-analysis. In the reference population, the estimated prevalence of UIAs was 3·9% (95% CI 3·0-5·1). The prevalence of UIAs in individuals with atherosclerosis was 5·5% (4·7-6·4; 2229 of 40970 participants) and the adjusted PR was 1·3 (95% CI 0·8-2·0) compared with the reference population. For positive family history of aneurysmal subarachnoid haemorrhage (aSAH) or UIA, the UIA prevalence was 7·9% (5·6-11·1; 412 of 4252 participants) and the adjusted PR was 2·4 (0·5-11·2). For connective-tissue disorder, the UIA prevalence was 10·3% (6·5-16·0; 94 of 879 participants) and the adjusted PR was 3·9 (2·0-7·6). For autosomal dominant polycystic kidney disease (ADPKD), the UIA prevalence was 12·8% (9·2-17·6; 293 of 1990 participants) and the adjusted PR was 4·4 (1·5-12·6). RRs were for current smoking 1·4 (1·2-1·6; 798 of 27911 participants), for having hypertension 1·6 (1·5-1·7, 4043 of 83053 participants), and for female sex 1·9 (1·8-2·0; 3415 of 65020 women and 2122 of 76130 men). In studies on healthy individuals with MR angiography or CT angiography as imaging modality, the prevalence in 2016-2022 was 6·6% (6·3-6·8; 2904 of 41191 participants). The adjusted PR was 1·8 (1·1-2·8) for 2016-2022 versus 2002-2015. Prevalence of UIAs of 5 mm or larger was 0·7% (0·6-0·8) in 2002-2015 and 1·4% (1·0-1·9) in 2016-2022. The UIA prevalence did not differ between countries. τ2 showed significant heterogeneity between studies. The certainty of the evidence ranged from very low to moderate. INTERPRETATION: Prevalence of UIA is increasing, particularly over the past two decades. This increase is only in part explained by improved detection of small UIAs and an ageing population, and other factors-such as environmental-are likely involved. Alongside patients with ADPKD and a positive family history of aSAH, patients with connective-tissue disorders had a higher prevalence of UIA than the reference population. Our findings warrant further investigation into the potential benefit of personalised screening and management strategies in groups at high risk for having UIAs. FUNDING: None.

Humans

A Phase I Study Assessing the Safety, Tolerability, and Pharmacokinetics of Yinfenidone: A Novel, Potent Drug for Idiopathic Pulmonary Fibrosis Treatment in Healthy Chinese Subjects.

PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease with a median survival of only 2-3 years after diagnosis. Yinfenidone (HEC585) possesses the potential to inhibit the proliferation of pulmonary fibroblasts, making it a promising candidate for the treatment of IPF. This study assessed the safety, tolerability, pharmacokinetics, and metabolic profile of Yinfenidone hydrochloride capsule in healthy Chinese subjects. METHODS: This single-center, randomized, double-blind, placebo-controlled, single ascending-dose trial included seven dose groups(20, 50, 100, 200, 400, 600, and 800 mg). Each group enrolled8 healthy subjects: 6 received Yinfenidone hydrochloride capsules and 2 received matching placebo under fasting conditions. Serial pharmacokinetic (PK) blood samples were collected pre-dose and post-dose, liquid chromatography-tandem mass spectrometry was used to analyze the plasma concentrations of Yinfenidone. Additionally, metabolic biotransformation of Yinfenidone in plasma were conducted in the 100 mg dose group. Safety and tolerability endpoints were monitored via physical examinations, vital signs measurements, clinical laboratory tests, 12-lead electrocardiography (ECG), and adverse events (AEs) documentation throughout the trial. FINDINGS: Yinfenidone was rapidly absorbed, with a median maximum plasma concentration (Tmax) of 1.8-3.0 hours, and had a mean half-life (t1/2) ranging from 31.9 to 62.0 hours. Within the 20-100 mg dose range, systemic drug exposure generally increased with ascending dose, above 100 mg, exposure increased less than proportionally to dose. Metabolite profiling in the 100 mg group revealed that the parentcompound predominated in plasma, with metabolic pathways including mono-oxygenation and N-dealkylation. All reported AEswere mild, classified as Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 grade 1. No serious AEs observed; no subject discontinued the trial due to AEs. Single oral doses of 20-800 mg Yinfenidone hydrochloride capsules administered under fasting conditions demonstrated favorable safety and tolerability profiles in healthy Chinese subjects. IMPLICATIONS: Yinfenidone exhibited rapid absorption (median Tmax, 1.8-3.0 hours) and a long terminal t1/2 ranging from 31.9 to 62.0 hours in this single ascending-dose study, indicating that Yinfenidone can be taken once a day in subsequent clinical studies. Yinfenidone mainly exists in human plasma as the original drug and is metabolized through a variety of metabolic pathways. The AEs observed with Yinfenidone in this study, such as diarrhea, nausea, and dizziness, were similar to those reported with pirfenidone. Overall, Yinfenidone demonstrated a favorable safety and tolerability profile in this cohort of healthy subjects.

Adult

Probiotic supplementation increases fecal TLR4 agonists without improving disease activity in juvenile idiopathic arthritis: a randomized placebo-controlled trial.

Gut dysbiosis has been implicated in the pathogenesis of juvenile idiopathic arthritis (JIA), suggesting that microbiota-targeted interventions may influence immune signalling during early immune development. We conducted the PERMAJI multicentre randomized, double-blind, placebo-controlled trial to evaluate the effects of probiotic supplementation (VSL#3) on host-microbiota immune interactions and disease activity in children with oligoarticular or RF-negative polyarticular JIA. Participants were randomly assigned (1:1) to receive VSL#3 or placebo for 3 months in addition to standard therapy. Stool and serum samples collected at baseline and month 3 were used to assess gut microbiota composition, fecal innate immune agonists, intestinal permeability, and systemic cytokines. The primary clinical endpoint was the proportion achieving an ACR Pedi 30 response at 3 months. Forty-four children were enrolled between September 2017 and July 2022. Clinical responses did not differ between groups (ACR Pedi 30: 47% with VSL#3 vs 63% with placebo; p = 0.33), and conservative worst-case assumptions for missing data suggested lower response rates with VSL#3 (36% vs 68%; p = 0.03). Probiotic supplementation significantly increased fecal Toll-like receptor 4 (TLR4) agonist activity, whereas gut microbiota diversity, intestinal permeability, and systemic cytokine levels remained unchanged. These findings indicate that probiotic supplementation can modify microbial innate immune signalling without detectable changes in microbial community diversity and may increase exposure to pro-inflammatory microbial stimuli in early-life autoimmune disease. The results highlight the complexity of host-microbiota immune interactions and underscore the need for careful evaluation of microbiome-targeted therapies in paediatric autoimmune disorders.

Humans

TWIST2-dependent transcriptional activation of TPI1 mediates TGF-β1-driven fibroblast activation in pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease characterized by aberrant profibrotic signaling and excessive extracellular matrix deposition, accompanied by fibroblast-to-myofibroblast transition. Despite extensive investigation, the molecular mechanisms underlying IPF pathogenesis remain incompletely understood. Here, we investigated the role of triosephosphate isomerase 1 (TPI1) in IPF progression and its regulation by transforming growth factor-β (TGF-β) signaling. Loss-of-function analyses identified TPI1 as a downstream effector of TGF-β1, as its knockdown markedly suppressed fibrotic marker expression, fibroblast proliferation, and migration. Mechanistically, TWIST2 was shown to function as a direct transcriptional regulator of TPI1, binding to its promoter and promoting transcriptional activation. Rescue experiments further confirmed that the TWIST2-TPI1 axis is central to the progression of pulmonary fibrosis. Notably, knockdown of either TPI1 or TWIST2 effectively attenuated TGF-β1-induced fibrotic phenotypes. Collectively, these findings define the TGF-β1/TWIST2/TPI1 signaling axis as an important regulator of pathogenic fibroblast behavior and pro-fibrotic responses through transcriptional control of TPI1, highlighting its potential as a therapeutic target for IPF.

Twist-Related Protein 1

Associations Between Routine Vaccinations and the Risk of New-Onset Idiopathic Uveitis.

OBJECTIVE: To evaluate the association between vaccination and the risk of new-onset idiopathic uveitis (NIU). DESIGN: Retrospective cohort study of aggregated electronic health records from multiple health systems across the United States. SUBJECTS: Subjects who received the coronavirus disease 2019 (COVID-19), human papillomavirus (HPV), varicella, recombinant herpes zoster, or live herpes zoster vaccinations from 2006 to 2025 and propensity-score matched controls. INTERVENTION: Vaccines against COVID-19, HPV, varicella, recombinant herpes zoster, or live herpes zoster. MAIN OUTCOMES AND MEASURES: The main outcome was the incidence of NIU at 3, 6, and 12 months following vaccination. Vaccinated patients were compared with matched controls who did not receive the respective vaccines. Analyses were repeated, excluding patients with previous diagnosis of the respective viral infection. Risk ratios (RR) with 95% confidence intervals (CIs) were calculated for overall NIU and constituent subtypes (anterior, intermediate, posterior, and panuveitis). RESULTS: All tested vaccinations were associated with reduced risk of NIU through 12 months compared with matched controls. Relative risk reductions were 65% for COVID-19 (RR, 0.35; CI, 0.33-0.37), 56% for HPV (RR, 0.44; CI, 0.35-0.54), 71% for varicella (RR, 0.29; CI, 0.25-0.33), 68% for live zoster (RR, 0.32; CI, 0.23-0.43), and 69% for recombinant zoster vaccination (RR, 0.31; CI, 0.26-0.37). Similar reductions were observed after excluding patients with prior diagnoses of the respective viral infections. CONCLUSIONS: Vaccination was associated with a lower risk of idiopathic uveitis, representing the complex interplay between immune modulation and the development of NIU.

Humans

Vestibular schwannoma associated normal pressure hydrocephalus: clinical features and shunt responsiveness compared with idiopathic NPH.

BACKGROUND: Vestibular schwannoma (VS) is commonly associated with obstructive hydrocephalus due to mass effect; however, a rarer communicating form resembling normal pressure hydrocephalus (NPH) has also been described, possibly related to impaired CSF absorption from elevated CSF protein. We aimed to characterize the clinical and imaging features of VS-associated NPH (VS-NPH) and compare them with those of an idiopathic NPH (iNPH) cohort. METHODS: We retrospectively analyzed 18 patients with VS-NPH identified between 2008 and 2024. For comparison, 41 iNPH patients were drawn from a prospective longitudinal study at our center. Variables included demographics, tumor size, VS treatment modality, CSF parameters, Radscale imaging features, and shunt responsiveness. RESULTS: VS-NPH patients had markedly higher CSF protein levels than patients with iNPH (median 100 vs. 51&#xa0;mg/dL, p&#xa0;<&#xa0;0.001). Radiological features largely overlapped; however, parasagittal sulcal narrowing was more frequent in VS-NPH (61&#xa0;% vs.13&#xa0;%, p&#xa0;=&#xa0;0.002). These differences remained significant in the sensitivity analysis excluding the two patients without gait impairment. VS-NPH patients were younger in the primary analysis (66.8 vs. 72.0&#xa0;years, p&#xa0;=&#xa0;0.03), while exploratory associations between larger tumor size and both earlier NPH symptom onset (r&#xa0;=&#xa0;-0.48, p&#xa0;=&#xa0;0.049) and smaller callosal angle (r&#xa0;=&#xa0;-0.49, p&#xa0;=&#xa0;0.048) attenuated to non-significant trends in the sensitivity analysis. Tumor size was&#xa0;<&#xa0;30&#xa0;mm in 89&#xa0;% of patients. Ventriculoperitoneal shunt (VPS) resulted in clinical improvement in both groups, although response rates were numerically lower in VS-NPH than in iNPH (63&#xa0;% vs.75&#xa0;%). CTT was positive in 9 of 11 VS-NPH patients who underwent testing, although improvement after shunting also occurred in patients with negative CTT results or without prior CTT. CONCLUSIONS: VS-NPH may represent a secondary subtype of NPH with distinct biochemical and subtle imaging features. Elevated CSF protein may contribute to altered CSF dynamics. These findings are exploratory and require confirmation in larger prospective studies.

Humans

Blood pressure management after endovascular thrombectomy in acute ischemic stroke: association with symptomatic intracranial hemorrhage and functional outcome at 3&#xa0;months.

BACKGROUND: No clear consensus exists on ideal systolic blood pressure (SBP) targets after endovascular thrombectomy (EVT) following an acute ischemic stroke (AIS). This study investigated the association between SBP parameters within the first 24&#xa0;h after EVT and 3-month functional outcomes and the risk of symptomatic intracranial hemorrhage (sICH). METHODS: We retrospectively collected and prospectively followed clinical, and radiological data for patients undergoing EVT for AIS from 2016 to 2024, including 2-hourly BP measurements during the first 24&#xa0;h and SBP variability assessed by standard deviation (SD) and coefficient of variation (CV). Outcomes included 3-month functional status and sICH, and their associations with post-EVT BP metrics were analyzed. RESULTS: A total of 268 post EVT patients were included with a median age of 61&#xa0;years (IQR, 51-69). Mean SBP was 129.67&#xa0;&#xb1;&#xa0;17.17&#xa0;mm Hg, with SBP variability (SD 12.6&#xa0;&#xb1;&#xa0;5.4&#xa0;mm Hg; CV 9.6&#xa0;&#xb1;&#xa0;3.8&#xa0;%), while good functional outcome and sICH occurred in 39.7&#xa0;% and 4.9&#xa0;% of patients, respectively. Multivariate regression showed that higher admission NIHSS&#xa0;(>15) [0.90 (95&#xa0;%CI, [0.86, 0.95], p&#xa0;=&#xa0;0.000)], recanalization status [1.88 (95&#xa0;%CI, [1.43, 2.48], p&#xa0;=&#xa0;0.00)], and SBP-CV&#xa0;&#x2265;&#xa0;10 [0.44 (95&#xa0;%CI, [0.2, 0.94], p&#xa0;=&#xa0;0.036)] was independently associated with poor 3-month functional outcome, while higher admission NIHSS (>15) [0.87 (95&#xa0;%CI, [0.77,0.98], p&#xa0;=&#xa0;0.02)] and diabetes [0.12 (95&#xa0;%CI, [0.03, 0.54], p&#xa0;=&#xa0;0.006)] predicted increased risk of sICH. CONCLUSIONS: The study showed that reduced BP variability during the first 24&#xa0;h post-EVT was associated with better 3-month functional outcomes. A clear association between SBP and sICH risk was not demonstrated.

Humans

Cerebrovascular involvement in Erdheim-Chester disease: a case report and systematic literature review.

BACKGROUND: Intracranial perivascular/vascular infiltrations and stenoses related to Erdheim-Chester disease (ECD), often associated with ischemic events, are rarely documented. This study aims to characterize intracranial perivascular/vascular infiltrations and stenoses. METHODS: We first report a new case of strokes revealing ECD with intracranial arterial involvement. We then searched all English- and French-language publications from database inception to November 2025 across 12 different search interfaces, including grey literature sources. Vascular involvement was defined by the presence of intracranial perivascular/vascular infiltrations and stenosis on imaging and/or histopathological evidence of small-vessel involvement. Cases with intracranial nodules or masses abutting vessels but without clear longitudinal perivascular infiltration were excluded. RESULTS: We present a case of recurrent strokes with intracranial vertebral and basilar artery wall stenosis, and aortitis. Initially diagnosed as giant cell arteritis, the patient was treated with corticosteroids, cyclophosphamide followed by methotrexate, but relapsed. The identification of tibial osteosclerosis led to the diagnosis of ECD, with a favorable response to anakinra. Twelve relevant articles were retrieved, in addition to our own case. Most patients exhibited focal cerebrovascular signs (11/13) and associated parenchymal involvement (11/13). Intracranial perivascular/vascular infiltrations and stenoses involved the carotid arteries (7/13), the vertebrobasilar arteries (1/13), or both territories (4/13). Aorta was involved in 8/12 cases. Among the nine patients with available follow-up data, five had poor overall or neurovascular outcomes. CONCLUSIONS: Intracranial perivascular/vascular infiltrations and stenoses, which leads to recurrent focal ischemic events, represents a likely underdiagnosed CNS pattern in ECD, referred to as "cerebrovascular ECD", which worsens overall prognosis. Vascular imaging should be included in brain MRI protocols for patients with ECD, given the overlap with parenchymal involvement.

Humans

Theta-range SEEG stimulation for intracranial mapping: extending conventional 1-Hz and 50-Hz protocols.

OBJECTIVE: Electrical brain stimulations (EBS) are central to epileptic network identification and functional mapping during stereo-electroencephalography, yet stimulation frequencies remain empirical, and standardized across patients and brain regions, producing false negatives and false positives, and potentially compromising surgical outcome. We prospectively investigated theta-range EBS (7&#xa0;Hz) in the temporal lobe, a prominent physiological frequency band in this region, and compared it with conventional 1-Hz and 50-Hz protocols. METHODS: We analyzed 1,408 temporal EBS in 25 drug-resistant epileptic patients. Epileptic responses (afterdischarges, seizures) and clinical signs were assessed across the epileptic network and temporal structures (amygdala, hippocampus, neocortex, parahippocampal gyrus, white matter), and confronted to stimulation parameters (frequency, intensity, duration, total charge). RESULTS: At matched intensity and duration, 7-Hz EBS were associated with a higher occurrence of afterdischarges and clinical signs than 1-Hz EBS in several temporal structures. Effects on usual seizure induction were less consistent. Comparisons with 50&#xa0;Hz showed no systematic significant differences, with responses observed at one or both frequencies depending on structure and outcome. When controlling for total charge, frequency-related differences were attenuated. Some effects were sporadically observed at both intermediate frequency and charge quantity. CONCLUSIONS: EBS responses emerge from the interaction between all electrical parameters and anatomical location and local excitability, and can hardly be disentangled. However, 7-Hz EBS can provide complementary clinical information during temporal-lobe mapping, with a targeted approach. SIGNIFICANCE: These findings support targeted evaluation of broader stimulation parameter spaces, including intermediate frequencies, rather than routine reliance on fixed low- and high-frequency protocols alone.

Humans

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

Longitudinal functional trajectory and surgical outcomes after intracranial meningioma resection: implications for surgical decision-making in older patients.

OBJECTIVE: As the population ages, meningiomas are increasingly encountered in older patients, yet longitudinal functional outcomes following surgery across age groups remain incompletely characterized. This study evaluated age-related differences in clinical and tumor characteristics, functional trajectory, and surgical outcomes. METHODS: This was a retrospective cohort study of 396 consecutive patients who underwent surgery for intracranial meningiomas at a single academic center between January 2023 and September 2025. Patients were stratified into 5 age groups (< 65, 65-69, 70-74, 75-79, and &#x2265; 80 years). Neurological deficits and Karnofsky Performance Status (KPS) were assessed preoperatively, at discharge, and at last follow-up. Logistic regression analyses identified predictors of prolonged length of stay (LOS) (> 5 days) and poor functional outcome at discharge (KPS < 80). RESULTS: Older patients presented with greater comorbidity burden, larger tumors, and lower preoperative KPS (all p < 0.05), while gross-total resection was achieved at comparable rates across all age groups (p = 0.504). A clinically meaningful inflection point was observed around age 75 years, with KPS < 80 at discharge rising from 7.4% and 9.7% in the < 65-year and 70- to 74-year subgroups and to 36.2% and 57.1% in the 75- to 79-year and &#x2265; 80-year subgroups (p < 0.001), and median LOS increased from 4 days in the younger groups to 9 and 7 days in the 75- to 79-year and &#x2265; 80-year groups (p < 0.001). However, recovery rates among patients who experienced functional decline at discharge were comparable across age strata. On multivariable analysis, independent predictors of prolonged LOS were age &#x2265; 75 years (OR 2.31, p = 0.019), diabetes mellitus (OR 2.85, p = 0.004), posterior fossa location (OR 2.1, p = 0.008), tumor diameter (OR 1.33, p < 0.001), postoperative edema (OR 2.58, p = 0.015), and neurosurgical complications (OR 3.18, p = 0.002). Independent predictors of poor functional outcome at discharge were age &#x2265; 75 years (OR 5.84, p < 0.001), lower preoperative KPS (OR 2.8, p < 0.001), posterior fossa location (OR 3.72, p = 0.003), neurosurgical complications (OR 3.56, p = 0.008), and recurrent meningioma (OR 2.89, p = 0.025). Among 70 endoscopic endonasal approach patients, higher preoperative deficit burden and subtotal resection rates were observed compared to open craniotomy, though overall functional outcomes were comparable. CONCLUSIONS: Surgical risk in meningioma resection increases from age 75 years onwards, yet recovery capacity following initial functional decline remains similar across all age groups. Preoperative functional status, tumor location, comorbidity burden, and recurrence history should guide surgical decision-making rather than age alone.

Humans

Left ventricular hypertrophy in hypertension: a systematic review and meta-analysis of echocardiographic studies published from 2011 to 2025.

AIM: An updated meta-analysis targeting the prevalence of left ventricular hypertrophy (LVH), a cardinal marker of hypertensive heart disease (HHD), over the last 15&#x200a;years is lacking. Thus, we analyzed the literature in order to provide a comprehensive information on LVH prevalence, as assessed by echocardiography, in the hypertensive setting. METHODS: The PubMed, OVID-MEDLINE, and Cochrane Library databases were analyzed to search English-language articles published from 1 January 2011 up to 31 December 2025. Studies were identified by using MeSH terms and crossing the following search items: 'left ventricular hypertrophy', 'left ventricular mass', 'hypertensive heart disease', 'echocardiography', 'hypertension', and 'subclinical cardiac damage'. RESULTS: A total of 51 studies including 74&#x200a;632 hypertensive patients were considered. Overall, the prevalence of LVH in the pooled cohort, defined according to criteria recommended by echocardiographic guidelines, was 36.6% (95% CI: 33.4-40%). Data provided by 18 studies ( n &#x200a;=&#x200a;40&#x200a;108 patients) showed that the probability of having LVH was lower in men than in women (OR&#x200a;=&#x200a;0.62, CI: 0.48-0.80, P &#x200a;<&#x200a;0.0001). Among patients with LVH (17 studies), the risk of concentric LVH was almost twice as high as eccentric (OR&#x200a;=&#x200a;1.94, CI: 1.52-2.49, P &#x200a;<&#x200a;0.0001). CONCLUSION: Our meta-analysis suggests that the high contemporary prevalence of LVH reflects the failure of therapeutic strategies worldwide in the prevention and treatment of HHD. From a clinical perspective, these data imply the need for a more aggressive treatment of hypertension and related cardiovascular risk factors leading to LVH, especially in women.

Humans

Maternal vaccination with RSVpreF and risk of hypertensive disorders of pregnancy: a systematic review and meta-analysis.

BACKGROUND: A bivalent respiratory syncytial virus (RSV) prefusion F protein-based vaccine (RSVpreF) was approved in the United States in August 2023 for use during pregnancy to prevent infant RSV-associated lower respiratory tract disease. The pivotal phase 3 trial identified a numerical imbalance in hypertensive disorders of pregnancy (HDP) that did not reach statistical significance; postmarketing observational studies have since reported inconsistent findings. We conducted a systematic review and meta-analysis to assess this association. METHODS: We searched MEDLINE, Embase, CENTRAL, Scopus, ClinicalTrials.gov, and WHO ICTRP from inception to Jan 26, 2026, for randomized controlled trials (RCTs) and observational studies comparing HDP outcomes in RSVpreF-vaccinated versus unvaccinated or placebo-receiving pregnant individuals. Unadjusted risk ratios (RRs) were pooled using a random-effects model; adjusted estimates from observational studies were pooled separately by inverse variance methods. This study is registered with PROSPERO (CRD420251026835). RESULTS: Nine studies were included (3 RCTs, 6 retrospective cohort studies; n&#xa0;=&#xa0;148,267). RSVpreF vaccination was associated with a small but statistically significant increase in overall HDP risk (RR 1&#xb7;08, 95% CI 1&#xb7;02-1&#xb7;13; p&#xa0;=&#xa0;0&#xb7;004; I2&#xa0;=&#xa0;44%), driven by the observational studies group (1&#xb7;08, 1&#xb7;02-1&#xb7;14; I2&#xa0;=&#xa0;61%); RCTs showed a directionally consistent but non-significant RR (1&#xb7;12, 0&#xb7;87-1&#xb7;43; I2&#xa0;=&#xa0;0%). The association was attributable to gestational hypertension, with no significant association for preeclampsia/eclampsia. CONCLUSION: Maternal RSVpreF vaccination was associated with a small increase in HDP attributable to gestational hypertension and driven primarily by observational studies, in which residual confounding remains possible. The benefits of infant RSV prevention remain substantial, and these findings support continued postmarketing surveillance and informed shared decision-making.

Humans

Nebivolol treatment improves hypertension-induced endothelial cell dysfunction by reducing TGF-&#x3b2;1-dependent senescence and normalizing mitochondrial indices.

OBJECTIVES: Serum from patients with hypertension (HT) causes endothelial cell (EC) damage, leading to senescence and dysfunctional phenotype. This study investigated whether serum from patients treated with the antihypertensive drugs could normalize EC activity. METHODS: This study involved 71 patients with newly diagnosed HT, who were randomly assigned to one of three groups based on the antihypertensive treatment: amlodipine, nebivolol, or perindopril. Serum samples collected before and 6&#x200a;weeks after treatment were applied to ECs in vitro to assess their angiogenic activity, cellular senescence, mitochondrial metabolism, and oxidative stress. RESULTS: Results showed that exposure of ECs to serum from patients treated for 6&#x200a;weeks significantly altered EC function, with varying effects among the drugs. Serum from nebivolol-treated patients produced the most consistent benefits, reducing EC proliferation and HIF-1&#x3b1; expression, likely due to lower levels of angiogenic factors such as angiopoietin-1, basic fibroblast growth factor (bFGF), insulin-like growth factor 1 (IGF-1), and vascular endothelial growth factor (VEGF). Additionally, this serum contained reduced levels of pro-inflammatory cytokines (E-selectin, P-selectin, monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor &#x3b1; (TNF&#x3b1;)) and lower TGF-&#x3b2;1, which are linked to HT-related EC senescence. Nebivolol treatment decreased senescence biomarkers such as SA-&#x3b2;-Gal, 53BP1, and p16, with SA-&#x3b2;-Gal reduction comparable to that of TGF-&#x3b2;1 neutralizing antibodies. Oxidative stress was reduced, indicated by lower oxidized DNA product levels. CONCLUSIONS: Nebivolol was the most effective at reducing the factors, associated with HT induced cellular senescence of endothelium, through reducing TGF-&#x3b2;1.

Humans

Ultra-high-field 7T MRI reveals neural abnormalities of attention networks in relation to cognitive impairment in hypertension.

Hypertension is a significant risk factor for cognitive impairment (CI), yet the corresponding neural network abnormalities remain underexplored. In this study, we examined the associations among global and domain-specific cognitive dysfunction, neuroimaging measures, and blood pressure in a subgroup of hypertensive patients with CI (N&#xa0;=&#xa0;41) from a randomized controlled trial who underwent ultra-high-field 7&#xa0;T MRI. Structural atrophy related to CI was localized to regions overlapping the attention networks. Both whole-brain and within-network dysfunction of the attention networks were associated with worse global cognitive performance. Notably, hyperconnectivity within key attention network hubs, including the right anterior insula and posterior intraparietal sulcus, was associated with declined processing speed in hypertensive patients, mediating the association between pulse pressure and processing speed. These findings provide new insights into the neural pathophysiology of hypertension-related CI and suggest potential network-based targets for intervention.

Magnetic Resonance Imaging

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), V&#x307;E/V&#x307;CO 2 slope, PETCO 2 , V&#x307;O 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&#x200a;ml&#x200a;kg -1 &#x200a;min -1 (95% confidence interval: 1.7-11.3) lower CRF, a steeper V&#x307;E/V&#x307;CO 2 slope (moderate-large effect size), lower PETCO 2 (large effect size), flatter V&#x307;O 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), V&#x307;O 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 V&#x307;E/V&#x307;CO 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

Transpulmonary proteomic gradient analysis in women with pulmonary arterial hypertension associated with systemic sclerosis.

This study investigated proteomic alterations in the pulmonary circulation of patients with pulmonary arterial hypertension associated with systemic sclerosis (PAH-SSc) by analyzing the transpulmonary protein gradient and comparing the proteomic profiles with systemic sclerosis (SSc) without PAH. Twenty women were included (10 PAH-SSc, 64.6&#xa0;&#xb1;&#xa0;10.8&#xa0;years; 10 SSc, 62.8&#xa0;&#xb1;&#xa0;11.5&#xa0;years). The transpulmonary gradient was defined as the difference in biomarker concentrations between wedge-position and pulmonary artery blood samples. Peptides were analysed using liquid chromatography-mass spectrometry, and differentially abundant proteins were identified with Proteome Discoverer. Protein-protein interaction networks were generated with STRING and visualized in Cytoscape. A total of 270 proteins were detected, with no significant transpulmonary gradient alterations. However, patients with PAH-SSc showed distinct proteomic profiles compared to SSc. Multivariate analysis identified 48 differentially abundant proteins in pulmonary artery plasma, with 15 overrepresented and 33 downregulated in PAH-SSc. Among these, the downregulation of transforming growth factor-beta-induced protein ig-h3 (TGF&#x3b2;I/ig-h3) points to a potential involvement of the TGF-&#x3b2;-related extracellular matrix remodelling pathway in PAH-SSc. However, further validation in larger and independent cohorts is required before its relevance as a biomarker or therapeutic target can be established. In conclusion, while no transpulmonary proteomic gradient was observed, the proteomic profiles of PAH-SSc and SSc were different. The profile in PAH-SSc was characterized by differences in immune response, lipid metabolism, and hemostatic proteins. SIGNIFICANCE: This study offers the first proteomic characterization of the transpulmonary gradient in PAH-SSc and SSc. Although no differences in the gradient were found, the pulmonary artery plasma proteome of PAH-SSc patients showed a distinct pattern compared to SSc. Several proteins associated with immune function, haemostasis, and cellular processes were altered, which may indicate specific pathophysiological features of PAH-SSc or suggest how lung dysfunction develops in SSc. Targeting dysregulated proteins like TGF&#x3b2;I/ig-h3 or addressing immune-coagulation imbalances may support future research studies. Overall, these findings refine the molecular profile of PAH-SSc and provide a basis for future large-scale studies aimed at clarifying disease mechanisms and identifying clinically relevant molecular signatures.

Humans