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PubMed2026

Compound muscle action potential amplitudes in newborn screen positive spinal muscular atrophy.

OBJECTIVE: To evaluate the utility of compound muscle action potential (CMAP) amplitudes as biomarkers of disease severity in newborn screening (NBS)-positive infants with spinal muscular atrophy (SMA). METHODS: We conducted a retrospective review of 21 infants identified through SMA NBS (11 with 2 SMN2 copies and 10 with 3 SMN2 copies). Baseline and serial right median, ulnar, and fibular motor nerve CMAP amplitudes (millivolts, mV) were obtained during the study. Functional outcomes were assessed using the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND). RESULTS: At baseline, infants with 2 SMN2 copies demonstrated significantly lower median, ulnar, and fibular CMAP amplitudes compared with infants with 3 SMN2 copies (p < 0.05). In contrast, baseline CHOP-INTEND scores did not differ significantly between the two groups. Prior to genetic confirmation, a right median CMAP amplitude ≥3.2 mV predicted ≥3 SMN2 copies. Following treatment, right median and fibular CMAP amplitudes demonstrated significant improvement over time, including in analyses accounting for SMN2 copies number. CONCLUSION: CMAP amplitudes obtained from multiple upper- and lower-extremity motor nerves provided objective electrophysiological measures that distinguished infants with two versus three SMN2 copies, despite similar baseline CHOP-INTEND scores. Furthermore, CMAP abnormalities were detectable in some cases before confirmatory genetic testing results became available. Serial CMAP measurements demonstrated significant longitudinal changes following treatment, whereas functional assessments approached ceiling values, supporting the potential value of electrophysiological monitoring in the era of disease-modifying therapies. SIGNIFICANCE: CMAP assessment is a useful adjunct in the evaluation of infants identified through SMA NBS.

Humans↗

PubMed2026

Effects of testosterone-augmented multimodal exercise intervention in spinal cord injury: a randomized controlled trial.

CONTEXT: Spinal cord injury (SCI) leads to profound muscle atrophy, aerobic deconditioning, and metabolic dysfunction. Exercise-based interventions alone produce modest benefits. Whether testosterone can augment physiologic responses to exercise in this population remains untested. OBJECTIVE: To evaluate efficacy and safety of home-based intervention combining functional electrical stimulation-assisted leg cycling (FES-LC), arm ergometry (AE), and testosterone compared with FES-LC, AE plus placebo in adults with SCI. METHODS: This randomized, placebo-controlled, double-blind trial enrolled 84 adults (76 males and 8 females) aged 19-70 years with SCI (neurologic levels C4-T12; AIS grades A-D). Participants were randomized to multimodality intervention (home-based FES-LC, AE and intramuscular testosterone undecanoate) (n = 38) or control intervention (FES-LC, AE plus placebo) (n = 46) for 16 weeks. The primary outcome was change in aerobic capacity (peak VO2) during AE cardiopulmonary exercise testing. Secondary outcomes included lean mass, hemoglobin, cardiometabolic markers, and safety. RESULTS: Mean (SD) age was 44 (13) years and time since injury was 13.9 (13) years). Between-group changes in peak VO2 were not statistically significant. Within-group improvements were larger in multimodality (∼19% increase; 0.10 L/min; 95% CI, 0.02-0.18 L/min) compared to controls (∼6% increase; 0.06 L/min; 95% CI, -0.01-0.13). The multimodality group gained significantly more lean mass (whole-body:1.84 kg, 95% CI: 0.52-3.16, P = .007; lower extremity 0.92 kg, 95% CI: 0.38-1.45, P = .001), and anemia was corrected in a greater proportion of participants. Adverse event rates were similar between groups. CONCLUSION: A home-based multimodality intervention combining FES-LC, AE, and testosterone was safe and associated with greater improvements in lean mass and hemoglobin. Although between-group differences in aerobic capacity were not statistically significant, greater within-group increases were observed in the multimodality group. These findings may inform future studies of testosterone-augmented exercise interventions for individuals living with SCI.

Humans↗

PubMed2026

Improving survival in Duchenne muscular dystrophy across eras: a systematic review and cumulative meta-analysis.

BACKGROUND: Duchenne muscular dystrophy (DMD) was historically associated with death in the late teens or early twenties, mainly from respiratory failure. Survival has improved substantially with home mechanical ventilation (HMV) and multidisciplinary care, although variability remains. This study evaluated temporal trends in survival in DMD and the impact of HMV. METHODS: A study-level cumulative meta-analysis (PROSPERO CRD420251163011) of studies reporting survival outcomes in patients with DMD was conducted (PubMed 1977 to 13 October 2025). Pooled estimates of median survival were calculated, and random-effects meta-analyses with predefined subgroups (HMV and study period) were performed, alongside meta-regressions. Risk of bias was assessed using the Newcastle-Ottawa Scale. RESULTS: 53 studies (median follow-up 8 years), comprising more than 13,000 patients, of whom 60% received HMV, were included. Median survival differed substantially between ventilated (29 years, 95%CI 27 to 31) and non-ventilated (19 years, 95%CI 18 to 20) patients. Survival improved progressively over time in both groups. Glucocorticoid therapy was not associated with improved survival (p=0.45), whereas treatment with heart failure medications, including renin-angiotensin system inhibitors (p=0.002) and β-blockers (p=0.02), was associated with longer survival. The predominance of mortality shifted from respiratory to cardiac causes, while enhanced cardiac management was associated with a growing contribution of other causes of death. CONCLUSION: Survival in DMD has increased substantially over time, with median survival now approaching the third decade of life among ventilated patients. The growing contribution of cardiac and other non-respiratory causes of death highlights the importance of long-term multidisciplinary and early cardioprotective intervention. STUDY REGISTRATION: The meta-analysis and systematic review have been registered on PROSPERO (CRD420251163011).

Humans↗

PubMed2026

Muscular fiber properties and multi-omics investigation of larval and adult locomotor muscle in Microhyla fissipes.

During metamorphosis, Microhyla fissipes undergoes a critical transition from an aquatic to a terrestrial lifestyle, accompanied by significant remodeling of skeletal muscle. Notably, larval tail muscle degenerates, while adult hindlimb muscle develops. However, the molecular mechanisms that orchestrate these muscle type-specific adaptations to the changing environment remain unclear. In this study, histological observation, transcriptomics, and metabolomics were integrated to compare locomotor muscles from two stages: larval muscle from tail versus adult muscle from hindlimb. Our results revealed that adult muscle fibers exhibited reduced diameter and shorter sarcomere length compared to those of tadpoles. Transcriptomic analysis identified 4103 differentially expressed genes (DEGs), including 2182 up-regulated and 1921 down-regulated genes. Up-regulated genes were mainly involved in energy metabolism and cellular homeostasis pathways, including PPAR signaling and oxidative phosphorylation, whereas down-regulated genes were associated with carbohydrate metabolism and cell proliferation pathways, such as glycolysis/gluconeogenesis and PI3K-Akt signaling. Metabolic profiling indicated a metabolic shift from anaerobic to aerobic energy production, with 57 differential metabolites identified, mainly involved in protein metabolism and insulin-related pathways. Integrated multi-omics analysis further highlighted the AMPK and FoxO signaling pathways play key roles in this process. In conclusion, our findings demonstrate that the metabolic and structural differences between larval and adult skeletal muscles are mediated by AMPK- and FoxO-dependent signaling pathways, providing novel insights into the molecular mechanisms underlying adaptive development and locomotor transition in anuran amphibians.

Animals↗

PubMed2026

Associations Between Antiparietal Cell Antibody Values and Atrophy in a South and Southeast Asian General Population.

GOALS: To investigate the association between atrophy severity and antiparietal cell antibody (APCA) levels in South and Southeast Asia. BACKGROUND: APCA is an autoantibody that damages gastric parietal cells; autoimmune gastritis (AIG) is a chronic gastric inflammatory disease related to APCA and severe predominant corpus atrophy. Although a positive APCA result is a key clinical diagnostic tool for AIG, its rates vary widely among ethnic groups, and its exact relationship with AIG and predominant corpus atrophy remains unclear. STUDY: Associations between histopathology-assessed and endoscopy-assessed atrophy, APCA positivity rates, Helicobacter pylori status, and pepsinogen levels were investigated in 1982 symptomatic patients from Vietnam, Thailand, Myanmar, Bangladesh, and Nepal. RESULTS: Overall, 38.5% of participants were negative for Helicobacter pylori infection, while 57.6% had a current infection. A positive APCA result, defined as a titer >10, was present in 44.0% of participants (95% confidence interval: 41.8%-46.3%, 873/1982). Pathologic atrophy, corpus atrophy, and predominant corpus atrophy were found in 8.7% (169/1982), 5.1% (101/1982), and 4.1% (81/1982) of participants, respectively. Positive APCA rates significantly differed among countries (10.6% to 63.8%, P <0.001). No significant correlation was found between APCA results and the presence or severity of atrophy. CONCLUSIONS: Although APCA positivity was high among symptomatic patients from South and Southeast Asian countries, few had severe predominant corpus atrophy or positive pepsinogen tests, which suggests a low rate of AIG in this population. Long-term surveillance of APCA-positive individuals is necessary to determine the clinical significance of a positive APCA result without AIG.

Humans↗

PubMed2026

A case report of Xp21 contiguous gene deletion syndrome with adrenal crisis and sensorineural hearing loss: clinical highlights and management pitfalls.

OBJECTIVES: To report a rare association of Xp21 contiguous gene deletion syndrome (CGDS) featuring sensorineural hearing loss (SNHL), and to discuss the diagnostic and therapeutic challenges. CASE PRESENTATION: A male infant presented with a salt-wasting adrenal crisis consistent with X-linked adrenal hypoplasia congenita. His follow-up clinical course during childhood revealed global developmental delay and SNHL, the latter of which has been under-reported in the literature for this condition. At five years of age, the development of progressive proximal muscle weakness and markedly elevated creatine phosphokinase levels led to a diagnosis of Duchenne muscular dystrophy (DMD). The patient also exhibited pseudohypertriglyceridemia and elevated urinary glycerol, consistent with glycerol kinase deficiency. While initial exome sequencing failed to detect the genetic abnormality, subsequent chromosomal microarray analysis identified an Xp21 CGDS involving NR0B1, IL1RAPL1, DMD, and GK. Treatment of adrenal insufficiency with fludrocortisone and hydrocortisone was complicated by the higher steroid doses required for the management of DMD, resulting in exogenous Cushing syndrome and associated complications. CONCLUSIONS: This case highlights the necessity of evaluating for Xp21 CGDS in patients presenting with adrenal crisis and emphasizes the importance of multidisciplinary management to optimize outcomes in this complex pediatric endocrine disorder.

Humans↗

PubMed2026

Longitudinal Prediction of Retinal Sensitivity Based on Disease Progression Quantified From Optical Coherence Tomography in Geographic Atrophy.

PURPOSE: The purpose of this study was to analyze the association between disease progression of geographic atrophy (GA) from optical coherence tomography (OCT) with retinal sensitivity (RS) in microperimetry (MP) over a 2-year follow-up period. METHODS: This is a longitudinal analysis of the OAKS Phase-III clinical trial. Both study and fellow eyes with GA that underwent imaging with the Spectralis OCT and consecutive MP examination were eligible. Pointwise quantification of ellipsoid zone (EZ) thickness, EZ and retinal pigment epithelium (RPE) loss from OCT volumes was correlated with localized RS. A longitudinal predictive model using a Markov Chain framework was implemented to predict RS change over time based on OCT biomarkers. The modeling of morphological and functional progression was based on the fellow-eye cohort. RESULTS: A total of 39,681 MP points from 406 patients were analyzed. In the fellow eye cohort, baseline (BSL) EZ thickness was positively associated with RS (0.3 decibel [dB]/µm, P < 0.001). Decrease in EZ thickness between visits during follow-up was significantly associated with decrease in RS (0.1 dB / 1 µm change). RS was significantly lower in MP points within EZ loss during follow-up compared with MP points within the retina with measurable EZ (P < 0.001). The largest functional decline was observed within RPE loss, also associated with the highest probability of absolute scotoma (P < 0.001). Morphological progression to EZ and RPE loss was influenced by EZ thickness and the morphology of adjacent MP points (P < 0.001). CONCLUSIONS: Two exploratory endpoints were developed, namely quantification of EZ thickness and loss, and localized RS within high-risk OCT areas. RS decline during follow-up is associated with automatically quantified disease progression in OCT.

Humans↗

PubMed2026

Effects of an internet-based combined exercise and cognitive-behavioral therapy intervention on endocannabinoid system biomarkers and physical fitness in adults with mild-to-moderate depression: a SONRIE randomized controlled trial.

BACKGROUND: This SONRIE randomized controlled trial (NCT05849792) examined the effects of a 12-week combined physical exercise and internet-based cognitive-behavioral therapy (iCBT) intervention on endocannabinoid system (ES) biomarkers and physical fitness in adults with mild-to-moderate depression. METHODS: Eighty adults were randomly assigned 1:1 to an intervention (IG) or control (CG) group. Outcomes included nine ES biomarkers (2-arachidonoylglycerol, 2-AG; anandamide, AEA; seven analogues) and physical fitness, including cardiorespiratory fitness (CRF; 6-minute walking test) and muscular strength. Measurements were taken at baseline, post-intervention and 8-week follow-up. Primary analysis performed 2 × 3 repeated-measures ANOVA on completers; mixed-effects intention-to-treat model as sensitivity analysis. RESULTS: No significant time × group interaction was detected for any ES biomarker, including 2-AG (F(2,88) = 0.17, p = 0.844) and AEA (F(2,88) = 1.20, p = 0.306); both groups showed comparable within-group decreases in 2-AG, 2-LG and 2-OG. The intervention significantly improved CRF [between-group difference + 81.6 m at 12 weeks (F(2,78) = 7.88, p = 0.001)], exceeding the established minimal clinically important difference. None of the exploratory muscular fitness outcomes reached statistical significance; the arm curl test showed a borderline non-significant interaction (F(2,78) = 2.83, p = 0.065). CONCLUSION: A 12-week internet-based combined exercise and iCBT intervention significantly improved CRF in adults with mild-to-moderate depression. We did not find evidence of an intervention-specific effect on plasma ES biomarkers. These findings support the inclusion of internet-delivered exercise and psychological interventions in comprehensive treatment strategies for depression. TRIAL REGISTRATION: ClinicalTrials.gov NCT05849792 (registered 6 May 2023).

Humans↗

PubMed2026

Synaptic vesicle glycoprotein 2A PET imaging in parkinsonian α-synucleinopathies: a systematic review.

Synaptic dysfunction is increasingly recognized as an early and biologically relevant component of α-synucleinopathies. However, conventional imaging biomarkers mainly assess dopaminergic dysfunction, glucose metabolism, or structural damage rather than presynaptic density itself. Synaptic vesicle glycoprotein 2A (SV2A) PET enables in vivo assessment of presynaptic terminal integrity and may provide complementary information in Parkinson's disease (PD), Parkinson's disease dementia/dementia with Lewy bodies (PDD/DLB), and multiple system atrophy (MSA). This systematic review synthesized the available evidence on SV2A-targeted PET in parkinsonian α-synucleinopathies, focusing on regional imaging patterns, clinical associations, longitudinal findings, and methodological determinants of interpretation. Seventeen reports were included. In PD, the most recurrent finding was reduced SV2A binding in the substantia nigra, although additional involvement of brainstem, caudate, striatal, thalamic, raphe, or cortical regions was reported in selected cohorts. In PDD/DLB, abnormalities appeared broader and more cortical, with evidence of association between cortical SV2A binding and cognitive performance. In MSA, one study suggested a distinct infratentorial and cerebellar pattern with potential relevance for phenotypic stratification. SV2A PET is a promising research biomarker for biological characterization of synucleinopathies. However, the field remains limited by small cohorts, methodological heterogeneity, variable quantification strategies, limited longitudinal evidence, and potential cohort overlap. Multicentre validation and harmonized protocols are required before clinical translation.

Humans↗

PubMed2026

Early proteomic and metabolic signatures of liver and eye in OAT-deficient mice.

Ornithine aminotransferase (OAT) deficiency causes hyperornithinemia and gyrate atrophy (GA) of the choroid and retina, a rare inherited retinal degeneration. To understand the early molecular changes that make the eye susceptible to damage, we performed quantitative proteomic and metabolomic profiling of liver, retina, and retinal pigment epithelium and choroid (RPE/Cho) from OAT-deficient (Oatrhg) mice prior to detectable vision impairment. In addition to reduced OAT expression and elevated ornithine, methylation-related metabolites such as N(6)-methyl-lysine were altered in all examined tissues of Oatrhg mice. In the liver, excess ornithine was directed into urea cycle metabolism, together with altered expression of detoxification enzymes and histone H2B proteins. In contrast, the retina showed minimal proteomic changes but pronounced alterations in amino acid pathways that support glutamate homeostasis. The RPE/Cho demonstrated the most extensive proteomic changes, particularly in mitochondrial metabolism, cytoskeleton, and extracellular matrix, along with changes in metabolites involved in lysine metabolism, energy metabolism, and antioxidant capacity. Incubation with 13C lysine demonstrated that lysine was primarily degraded in RPE/Cho but not the retina, and ornithine enhanced lysine degradation in an OAT-dependent manner. Together, these findings highlight common and tissue-specific impacts of OAT on the liver and ocular tissues and provide insight into early molecular changes that contribute to the selective vulnerability of the eye in GA. Proteomics data are available via ProteomeXchange (PXD063614) and metabolomics data via MassIVE repository (MSV000101103).

Animals↗

PubMed2026

Effects of exercise snacking on neuromuscular performance in insufficiently active adults: A systematic review and meta-analysis.

OBJECTIVE: To examine the effects of exercise snacking (ES) on neuromuscular performance in insufficiently active adults. METHODS: Six databases were searched from inception to July 17, 2026. Randomized controlled trials and non-randomized studies of interventions involving insufficiently active adults undertaking ES interventions were included. Outcomes were functional performance, muscular strength, and muscular power. A three-level random-effects meta-analysis was performed. Risk of bias was assessed with RoB 2 or ROBINS-I, and certainty of evidence was evaluated using GRADE. RESULTS: Nine studies (13 reports) involving 313 participants were included. In the primary three-level model, ES showed a small positive overall effect on neuromuscular performance (g = 0.37, 95% CI 0.16-0.58, p = 0.001), which remained supported under trial-clustered robust inference with small-sample adjustment. Domain-specific estimates for muscular power/velocity, functional performance, and muscular strength were positive but imprecise and were not statistically supported after small-sample robust adjustment. Robust moderator tests provided no evidence of between-subgroup differences, and the certainty of evidence was low for all outcomes. CONCLUSION: Current low-certainty evidence suggests that ES may produce a small improvement in overall neuromuscular performance. However, domain-specific effects remain uncertain because of the limited number of independent trials, and the overall prediction interval crossed zero, indicating uncertainty across future populations and settings. Larger, preregistered randomized controlled trials are needed to confirm these preliminary findings.

Adult↗

PubMed2026

Omics in hereditary optic neuropathies: A systematic review of clinical studies with an integrated point of view.

Hereditary optic neuropathies are characterized by bilateral visual loss due to the degeneration of retinal ganglion cells, resulting in optic nerve degeneration and atrophy. Although the genetic origin of the main isolated and syndromic hereditary optic neuropathies has been characterized, the clinical phenotypes exhibit significant and poorly understood variability in both penetrance and expressivity. Additionally, the genetic and environmental factors that influence the onset of these optic neuropathies remain poorly understood, with limited biomarkers to predict disease progression or as readouts for therapeutic trials. Data-driven omics strategies allow deep phenotyping to improve our understanding of pathophysiological mechanisms and to search for new biomarkers and therapeutic targets. We explore whether the omics strategies applied to patients with hereditary optic neuropathies have provided such new insights. MEDLINE, Web of Science and EMBASE databases were screened for studies with terms relating to hereditary optic neuropathies, transcriptomics, epigenomics, proteomics, metabolomics and lipidomics in clinical studies exploring patients' samples. Out of 1244 references identified, 22 articles were included after double-masked data curation. These articles focused only on the 3 main forms of hereditary optic neuropathies, namely, OPA1-related dominant optic atrophy (n = 4), Leber hereditary optic neuropathy (n = 13), and Wolfram syndrome (n = 5). While the methodological designs and results of these studies were highly heterogeneous, they revealed molecular alterations that we have attempted to discuss at the integrated multi-omics level. This data integration highlighted several common pathophysiological mechanisms such as energetic impairment, endoplasmic reticulum stress, proteotoxic and oxidative stresses, lipid remodeling and altered amino acid and purine metabolisms, while suggesting potential new biomarkers and therapeutic targets. These findings underscore the potential of integrated multi-omics approaches to deepen our understanding of the phenotypic complexity of hereditary optic neuropathies and to support the development of innovative diagnostic and therapeutic strategies.

Humans↗

PubMed2026

Resistance versus concurrent training with three assigned protein targets in middle-aged and older women: a randomized 2 × 3 factorial trial.

BACKGROUND: Evidence is limited regarding whether assigned protein targets modify responses to resistance training (RT) alone or to the same RT program plus cycling (concurrent training [CT]) in middle-aged and older women. This randomized 2 × 3 factorial trial examined bioelectrical impedance analysis (BIA)-derived skeletal muscle mass (SMM; primary outcome), other body composition outcomes, muscular and functional performance, and cycle-derived estimated VO₂max. METHODS: In this randomized 2 × 3 factorial trial, 108 women aged 40-77 years were assigned to 12 weeks of supervised RT or CT (identical RT followed by cycling) and protein targets of 0.8, 1.6, or 2.2 g·kg-1·d-1. Baseline-adjusted ANCOVA tested training × protein interactions and marginal training and protein effects. Complete-case analyses included 83 participants. RESULTS: For SMM, no training-condition × protein-target interaction (p = 0.856), marginal protein-target effect (p = 0.726), or marginal training-condition effect (p = 0.273) was detected. CT had a lower baseline-adjusted week-12 BFP than RT (adjusted difference, -2.04 percentage points; 95% CI, -2.94 to -1.14; p < 0.001). RT had a higher baseline-adjusted week-12 leg-press estimated 1-RM than CT (CT - RT: -6.68 kg; 95% CI, -8.32 to -5.04; p < 0.001), whereas CT had a higher baseline-adjusted week-12 cycle-derived estimated VO₂max (adjusted difference, 4.53 mL·kg-1·min-1; 95% CI, 3.80 to 5.25; p < 0.001). No detectable marginal protein-target effects or training-condition × protein-target interactions were observed for the key secondary outcomes. CONCLUSIONS: No detectable differences in SMM or key secondary outcomes were attributable to assigned protein target. Compared with RT, CT favored estimated aerobic fitness and BFP, whereas RT favored leg-press strength. Because CT included additional cycling and greater exercise exposure, these differences cannot be attributed solely to training modality. Null protein findings do not establish equivalence among doses.

Humans↗

PubMed2026

Seventeen-year follow-up of hypophosphatasia diagnosed in middle-aged siblings harboring a novel intronic and a rare missense ALPL gene mutation.

Hypophosphatasia (HPP) is the rare inborn-error-of-metabolism that features impaired mineralization of the skeleton and teeth due to a deactivating mutation or mutations of the gene ALPL which encodes the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP). We report 17-year follow-up of twin sisters and a brother referred in middle-age for painful proximal femoral "stress fractures" and then diagnosed with HPP. They reported generalized muscle and bone pain, metatarsal fractures, arthropathy and, since childhood, tooth loss. Their concordant findings were explained by compound heterozygosity in ALPL for a rare maternal missense mutation (c.1403C > T, p.Ala468Val) in exon 12, together with a novel presumably paternal change (c.863-14G > A) predicting a cryptic mRNA splice site in intron 8. Fractures continued during follow-up until one sister received a three-and-one-half-year course of hydroxyapatite-targeted TNSALP supplementation therapy (asfotase alfa) during which substantial improvement occurred in her clinical, biochemical, and functional parameters as well as quality of life. Following subsequent unplanned treatment cessation she suffered significant clinical deterioration, including new fractures and loss of mobility. Her bone histopathology documented osteomalacia. Treatment resumption restored its benefits. Among ten asymptomatic family members evaluated in this four-generation kindred, eight were carriers heterozygous for either ALPL mutation. Those harboring the maternal missense defect manifested mild hypophosphatasemia, suggesting a dominant-negative mutation effect. This experience underscores the importance of in-depth phenotyping and then clinical follow-up to characterize ALPL variant combinations, and for maintaining effective asfotase alfa treatment.

Humans↗

PubMed2026

Comparative safety of lipid-lowering drugs alone or in combination: insights from a systematic review and network meta-analysis.

BACKGROUND AND AIMS: Although the safety profile of lipid-lowering therapies (LLTs) is known, there are no comprehensive comparative assessments. We aimed to compare the risk of muscle-related events, diabetes, liver dysfunction, and cognitive disorders among LLTs through a network meta-analysis. METHODS AND RESULTS: Databases were searched from inception to May 2025. Eligible studies included adult patients, using statins, ezetimibe, PCSK9 monoclonal antibodies (PCSK9mAbs), inclisiran, bempedoic acid, or their combinations as intervention, reporting the information about any of the selected adverse events, a total sample size of ≥200 subjects, and had ≥1 month of intervention. Pooled estimates were assessed by fixed effects model within a frequentist setting. Pooled relative risks (RR) and their 95% confidence interval were estimated. A total of 303,397 subjects from 153 RCTs were included. Bempedoic acid ranked the lowest risk of myalgia (vs PCSK9mAbs, RR 0.80 [0.69, 0.93]). PCSK9mAbs were associated with lower incidence of creatine kinase (CK) elevation, diabetes, and liver dysfunction comparing to statins (statins vs PCSK9mAbs, RR 1.44 [1.14, 1.81], RR 1.13 [1.05, 1.22], and RR 1.38 [1.17, 1.62], respectively). In terms of muscle-related events and cognitive disorders, no significant risk differences were found among treatments and their combinations. CONCLUSIONS: PCSK9mAbs appear to have a more favourable safety profile regarding the risk of CK elevation, diabetes, and liver dysfunction. Bempedoic acid seem to be a better choice for subjects with high risk of myalgia. This information can be valuable when selecting therapy for specific patient subgroups at higher risk of certain adverse events.

Humans↗

PubMed2026

Indications, Techniques and Complications Associated With Pterygoid Implants: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Pterygoid implants represent a graftless option for rehabilitation of patients with posterior maxillary atrophy, engaging the dense cortical bone of the pterygomaxillary complex. Despite clinical growth, a comprehensive synthesis of indications, surgical techniques, and complications is lacking. This review evaluated the prevalence of complications, implant survival rates, and marginal bone loss (MBL) associated with pterygoid implant placement. METHODS: The reporting of this review follows PRISMA 2020 guidelines. Six electronic databases (PubMed, Ovid, Scopus, WoS, CENTRAL, and Dentistry & Oral Sciences Source) were searched from 1 January 2020 to 31 December 2025. Included criteria comprised randomized and non-randomized clinical studies reporting outcomes of pterygoid implants (≥ 13 mm) in adult patients with posterior maxillary atrophy (minimum 10 implants). Risk of bias was assessed using JBI critical appraisal checklists. Proportions were pooled using the Freeman-Tukey double arcsine transformation under a random-effects model. Certainty of evidence was assessed using GRADE. RESULTS: Seventeen studies reporting 846 patients and 1915 pterygoid implants were included. The pooled survival rate was 97.9% (95% CI: 97.1%-98.6%; I2 = 0%; 14 studies) and the overall failure rate was 2.1% (95% CI: 1.4%-3.0%). Early failure rate was 0.9% (95% CI: 0.0%-3.0%; I2 = 59.5%). Late failure and MBL were summarized narratively. Certainty of evidence was low to very low. CONCLUSIONS: Pterygoid implants demonstrate excellent survival (97.9%) and low failure rates (2.1%), primarily early, supporting their reliability as a graftless solution for posterior maxillary atrophy. Complications appear infrequent though heterogeneously reported. Low evidence certainty necessitates prospective studies with standardized outcome reporting.

Humans↗

PubMed2026

Associations Between Health-Related Physical Fitness and Accelerometry-Based Energy Expenditure in Physiotherapy Workers.

BACKGROUND AND PURPOSE: Although it has been assumed that higher physical activity (PA) levels will contribute to better physical fitness (PF) performance, the interplay between these two has yet to be investigated. Moreover, the majority of studies have been presented in children and adolescents, and older adults, while little is known about the correlation in the adult working population of physiotherapists. Therefore, the main purpose of the study was to examine associations between objectively measured PA and health-related PF. METHODS: We recruited 50 physiotherapists (72.6% women) from several public and private settings in the city of Zagreb. The SenseWearArmbandPro3 (SWA), a triaxial accelerometer placed on the nondominant hand for 7 consecutive days, was used to capture total energy expenditure (TEE) and active EE (AEE). Cardiorespiratory fitness included the Harvard step test, and muscular fitness was composed of sit-ups in 60 sec and the Handgrip strength. Flexibility was evaluated using the Toe-touch test. RESULTS: TEE and AEE were moderately and positively correlated with the Harvard step test (r = 0.65 and 0.62, p < 0.001), sit-ups (r = 0.70 and 0.59, p < 0.001), and the Handgrip strength test (r = 0.74 and 0.64, p < 0.001). No significant correlation with the Toe-touch test was observed (r = -0.25 and -0.19, p > 0.05). When models were adjusted for age, weaker, but significant positive correlations remained. DISCUSSION: The findings suggest that both cardiorespiratory and muscular fitness are positively associated with PA, whereas no statistically significant association with flexibility was detected. Thus, it is not surprising that we obtained moderate to almost strong correlations between TEE and AEE with cardiorespiratory and muscular fitness. CONCLUSIONS: In physiotherapists, TEE and AEE yield moderate correlations with health-related PF, especially for cardiorespiratory and muscular fitness.

Humans↗

PubMed2026

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 = 41) from a randomized controlled trial who underwent ultra-high-field 7 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↗