Search Results for: Il ruolo dell’imaging nel sanguinamento gastrointestinale: linea guida

Introduction
Cerebral palsy (CP), the most common physical disability in children, imposes substantial economic and psychological burdens on families and society. The clinical management of CP remains challenging due to the limited efficacy of current treatments and the heterogeneity of its aetiologies and clinical presentations. This study aims to investigate the functional changes and identify influencing factors in Chinese children with CP. Through analysis of neuroimaging and genetic data, this study seeks to inform the development of preventive and therapeutic strategies and guide healthcare decision-making for this population.

Methods and analysis
This prospective cohort study aims to recruit 2051 children with CP across China. Baseline data will include demographic and clinical characteristics. Participants will undergo comprehensive assessments, including motor, cognitive, language, social, behavioural, nutritional, pain, sleep and quality-of-life domains, with regular follow-up evaluations. Trio whole-exome sequencing and detailed neuroimaging and musculoskeletal imaging will also be performed. This study will also assess caregivers’ quality of life and emotional burden. Mendelian randomisation will be adopted to evaluate genetic contributions to functional outcomes and their causal relationship with health metrics. Analytical methods will include correlation analysis, logistic regression (binary and multivariate), linear and non-linear mixed-effects models and structural equation modelling.

Ethics and dissemination
Ethics approval was granted by the Research Ethics Committee of Guangzhou Women and Children’s Medical Center (No.2023-346A01). All study procedures will adhere to the approved protocol. Study findings will be disseminated through peer-reviewed publications and conference presentations.

Trial registration number
ChiCTR2300079017.

La guida dell’Istituto sui cibi e le regole da rispettare

Circulation, Ahead of Print. BACKGROUND:Pathological cardiac remodeling after myocardial infarction (MI) is a leading cause of heart failure and sudden death. The detailed mechanisms underlying the transition to heart failure after MI are not fully understood. Disruptions in the endoplasmic reticulum (ER)–mitochondria connectivity, along with mitochondrial dysfunction, are substantial contributors to this remodeling process. In this study, we aimed to explore the impact of mitochondrial tumor suppressor 1A (Mtus1A) on cardiac remodeling subsequent to MI and elucidate its regulatory role in ER-mitochondria interactions.METHODS:Single-nucleus RNA sequencing analysis was performed to delineate the expression patterns of Mtus1 in human cardiomyocytes under ischemic stress. MI models were induced in mice by left coronary artery ligation and replicated in vitro using primary neonatal rat ventricular myocytes exposed to oxygen glucose deprivation. Cardiac-specific deletion of Mtus1 was achieved by crossing floxed Mtus1 mice with the Myh6-MerCreMer mice. The impact of Mtus1A, a mitochondrial isoform of Mtus1, on cardiac function and the molecular mechanisms were investigated in both in vivo and in vitro settings. Mitochondria-associated ER membranes coupling levels were evaluated by transmission electron microscopy and live-cell imaging. Protein interactions involving Mtus1A were explored through immunoprecipitation–mass spectrometry, coimmunoprecipitation, and proximity ligation assay. The roles of Mtus1A and Fbxo7 (F-box protein 7) were validated in a murine MI model using adeno-associated virus serotype 9 (AAV9).RESULTS:Bioinformatics analysis revealed a significant downregulation of Mtus1 expression in human cardiomyocytes under ischemic conditions, indicating its potential role in stress response. The predominant isoform in murine cardiomyocytes, Mtus1A, showed reduced expression in the left ventricle of mice after MI, which is consistent with the decreased levels of its orthologs in heart tissues from patients with MI. Cardiac-specific knockout of Mtus1 in mice exacerbated cardiac dysfunction after MI. Both in vitro and in vivo studies demonstrated the vital role of Mtus1A in modulating mitochondria-associated ER membranes coupling and preserving mitochondrial function. Mechanistically, Mtus1A functions as a scaffold protein that maintains the formation of inositol 1,4,5-trisphosphate receptor 1 (IP3R1)–glucose-regulated protein 75 (Grp75)–voltage-dependent anion channel 1 (VDAC1) complex through its amino acid sequence 189-219. In addition, Mtus1A protein is stabilized by K6-linked ubiquitination through the E3 ubiquitin ligase Fbxo7. Mtus1A overexpression in mice mitigated MI-induced cardiac dysfunction and remodeling by maintaining ER-mitochondria connectivity.CONCLUSIONS:Our study demonstrates that Mtus1A is crucial for modulating MI-induced cardiac remodeling by preserving ER-mitochondria communication and ameliorating mitochondrial function in cardiomyocytes. Mtus1A may serve as a potential therapeutic target for treating heart failure after MI.

Stroke, Ahead of Print. BACKGROUND:The impact of covert cerebrovascular disease on falls in the general population is not well-known. Here, we determine the time to a first fall following incidentally detected covert cerebrovascular disease during a clinical neuroimaging episode.METHODS:This longitudinal cohort study assessed computed tomography (CT) and magnetic resonance imaging from 2009 to 2019 of patients aged >50 years registered with Kaiser Permanente Southern California which is a healthcare organization combining health plan coverage with coordinated medical services, excluding those with before stroke/dementia. We extracted evidence of incidental covert brain infarcts (CBI) and white matter hyperintensities/hypoattenuation (WMH) from imaging reports using natural language processing. We examined associations of CBI and WMH with falls requiring medical attention, using Cox proportional hazards regression models with adjustment for 12 variables including age, sex, ethnicity multimorbidity, polypharmacy, and incontinence.RESULTS:We assessed 241 050 patients, mean age 64.9 (SD, 10.42) years, 61.3% female, detecting covert cerebrovascular disease in 31.1% over a mean follow-up duration of 3.04 years. A recorded fall occurred in 21.2% (51 239/241 050) during follow-up. On CT, single fall incidence rate/1000 person-years (p-y) was highest in individuals with both CBI and WMH on CT (129.3 falls/1000 p-y [95% CI, 123.4–135.5]), followed by WMH (109.9 falls/1000 p-y [108.0–111.9]). On magnetic resonance imaging, the incidence rate was the highest with both CBI and WMH (76.3 falls/1000 p-y [95% CI, 69.7–83.2]), followed by CBI (71.4 falls/1000 p-y [95% CI, 65.9–77.2]). The adjusted hazard ratio for single index fall in individuals with CBI on CT was 1.13 (95% CI, 1.09–1.17); versus magnetic resonance imaging 1.17 (95% CI, 1.08–1.27). On CT, the risk for single index fall incrementally increased for mild (1.37 [95% CI, 1.32–1.43]), moderate (1.57 [95% CI, 1.48–1.67]), or severe WMH (1.57 [95% CI, 1.45–1.70]). On magnetic resonance imaging, index fall risk similarly increased with increasing WMH severity: mild (1.11 [95% CI, 1.07–1.17]), moderate (1.21 [95% CI, 1.13–1.28]), and severe WMH (1.34 [95% CI, 1.22–1.46]).CONCLUSIONS:In a large population with neuroimaging, CBI and WMH are independently associated with greater risks of an index fall. Increasing severities of WMH are associated incrementally with fall risk across imaging modalities.

Question
What is the effect of Choosing Wisely recommendations on physiotherapists’ intentions to refer for imaging and use electrotherapy for low back pain?

Design
Three-arm parallel-group online randomised controlled trial.

Participants
Physiotherapists who treat people with low back pain.

Intervention
Participants were randomised to receive: (a) two original Australian Physiotherapy Association Choosing Wisely recommendations about low back pain, (b) two optimised versions of these recommendations based on previous research and (c) no recommendations. Participants were then directed to read three clinical vignettes of a person with low back pain and respond to questions regarding each vignette.

Outcome measures
Primary outcomes were physiotherapists’ intentions to refer for imaging and use electrotherapy for low back pain. Secondary outcomes were physiotherapists’ intentions to use other treatments for low back pain, the influence of the recommendations on decision-making in the vignettes and familiarity with the recommendations.

Results
723 participants opened the survey and 473 (65%) provided complete responses. Across all vignettes, there were no statistically significant differences in intentions to refer for imaging or use electrotherapy between those who received Choosing Wisely recommendations versus no recommendation (imaging ORs ranging from 0.7 (95% CI 0.5 to 1.0) to 0.9 (0.6 to 1.4); electrotherapy ORs ranging from 0.9 (0.5 to 1.7) to 1.1 (0.7 to 2.0)). Similarly, no significant differences were observed between those who received optimised versus original recommendations for all three vignettes.

Conclusion
Our study suggests simply presenting Choosing Wisely recommendations to physiotherapists does not influence their intentions to refer for imaging or use electrotherapy for low back pain, even if the language of the recommendations is optimised.

Introduction
Adolescent idiopathic scoliosis (AIS) is an acquired deformity that develops in 2–4% of otherwise healthy children during adolescent growth, substantially reducing their quality of life and creating a life-long burden of disease. Despite many years of dedicated research, the cause and mechanism of AIS are still unknown and no effective curative treatments are available for children suffering from this spinal and chest deformity. To date, all etiological studies focused on children with an already established scoliosis. EARLYBIRD aims to uncover the earliest pathoanatomical changes in AIS, by studying longitudinal spinal growth in children at increased risk for scoliosis development with MRI, starting before adolescence.

Methods and analysis
This prospective observational cohort study will follow two groups: 60 adolescent girls (8–10 years old) who have an older sibling or parent diagnosed with AIS (cohort 1) and 60 adolescents with 22q11.2 deletion syndrome, a genetic microdeletion associated with 50% scoliosis prevalence (cohort 2). Data collection will be completely radiation-free and occur at baseline and yearly during adolescence up to 15 years of age in girls and up to 16 in boys. A comprehensive physical examination, a dedicated spine and chest MRI as well as a standing three-dimensional (3-D) spinal ultrasound will be obtained at each time point. The main parameter will be the longitudinal changes in segmental axial rotation during growth in subjects that do and do not develop AIS. Secondary endpoints are longitudinal changes in 3-D morphology of the bone and intervertebral discs (IVDs) during normal spinal development and during scoliosis development, determining biomarkers for bone growth, implementing radiation-free imaging methods for spinal monitoring in adolescent patients at risk for scoliosis development and use these for spinal skeletal maturity and patient-specific spinal biomechanical analyses.

Ethics and dissemination
This protocol has been approved by the Medical Ethics Committee NedMed and is registered on clinicaltrials.gov (NCT05924347). Written informed consent will be obtained from all parents/legal representatives. Key findings will be disseminated via peer-reviewed journals and presentation at conferences. This study is funded by the European Research Council.

Stroke, Ahead of Print. BACKGROUND:National studies on reversible cerebral vasoconstriction syndrome (RCVS) point to differences between Asian and European patients. We investigated geographic variations in neurological complications, outcomes, and causes.METHODS:We conducted an exploratory analysis of pooled individual patient data from the Reversible Cerebral Vasoconstriction Syndrome International Collaborative network, a multicenter observational cohort study including patients with definite RCVS from 2 French, 32 Italian, 1 South Korean, and 1 Taiwanese centers. Data on demographics, precipitants, symptoms, imaging, treatment, and outcomes were collected. The primary end point was RCVS-associated brain lesions, including ischemic stroke, cortical subarachnoid hemorrhage, intracerebral hemorrhage, posterior reversible encephalopathy syndrome, and subdural hematoma. Secondary end points included unfavorable 3-month outcomes (modified Rankin Scale score ≥1) and causes (idiopathic versus secondary). Odds ratios and 95% CIs were calculated using multivariable logistic regression, adjusting for potential confounders.RESULTS:From 2009 to 2021, we included 1127 patients (528 European and 599 Asian). Recruitment occurred either through emergency settings or outpatient clinics, with most Asian patients recruited from outpatient clinics (65.8%) and most European patients from emergency settings (99.8%). Brain lesions were more frequent in European patients (29.2% versus 6.3%; odds ratio, 4.09 [95% CI, 2.66–6.30]). In a sensitivity analysis restricted to hospitalized patients (n=651), the association persisted. Unfavorable 3-month outcomes (5.5% versus 1.7%; odds ratio, 3.01 [95% CI, 1.35–6.68]) and secondary RCVS (50.4% versus 10.9%; odds ratio, 7.09 [95% CI, 5.14–9.76]) were also associated with European residency.CONCLUSIONS:RCVS presentations vary across regions, with higher lesion rates, more secondary forms, and worse outcomes in European patients. While these exploratory results may reflect selection bias from differing health care structures, further research is needed to determine the contribution of genetic, environmental, and societal factors.

Stroke, Ahead of Print. BACKGROUND:Familial hypercholesterolemia (FH) is characterized by elevated levels of LDL-C (low-density lipoprotein cholesterol) since birth. However, the association between FH and cerebrovascular diseases, including cerebral small vessel disease (CSVD), is controversial. To investigate the association between FH and CSVD, we compared the prevalence and severity of CSVD neuroradiological findings between patients with FH and control participants.METHODS:Patients with FH who visited the lipid clinic and underwent brain magnetic resonance imaging at the National Cerebral and Cardiovascular Center in Japan from November 2006 to April 2021 and control participants who voluntarily underwent brain magnetic resonance imaging as a checkup between December 2000 and December 2010 at the Health Science Center Shimane, Japan, were enrolled into the study. The prevalence and severity of CSVD neuroradiological findings were investigated in patients with FH and control participants, and potential risk factors for CSVD development were identified using multivariable logistic and quasi-Poisson regression analyses.RESULTS:A total of 151 patients with FH and 3172 control participants were enrolled in this study. FH was identified as an independent risk factor of prevalent lacunes (adjusted odds ratio, 1.60 [95% CI, 1.03–2.51];P=0.039) and increased number of lacunes (1.67 times [95% CI, 1.17–2.31];P=0.003). Furthermore, FH was also an independent risk factor of prevalent cerebral microbleeds (adjusted odds ratio, 9.42 [95% CI, 5.81–15.28];P

Stroke, Ahead of Print. Recently, 6 randomized controlled trials of endovascular treatment (EVT) versus medical management in anterior circulation large vessel occlusion with large-core documented significant benefit of EVT on functional outcome. Moreover, one trial reported the benefit of EVT in the large-core category (Alberta Stroke Program Early Computed Tomography Score, 0–2). These results are considered paradoxical by some as they contradict the prevailing view that the presence of a large core precludes the possibility of good outcomes following reperfusion. They, in turn, led some investigators to question the applicability of the core/penumbra model in the case of large-core stroke and even its overall validity, specifically regarding the notion that the core reliably predicts tissue infarction. Here, we discuss the trial results and propose alternative explanations for the large-core paradox. First, although EVT does improve outcomes as compared with medical management, overall outcomes remain poor in ≈80% of the treated population. Second, the assessment of core extent on imaging, particularly with computed tomography, is potentially inaccurate, especially in the early time window. Third, consistent with observational studies, some randomized controlled trial substudies suggest that the benefit of EVT in this population derives at least in part from the salvage of penumbra, which appears to have been present in a large percentage of enrolled patients. Fourth, the markedly reduced perfusion that prevails within large cores facilitates the early development of vasogenic edema. This heterogeneity of tissue injury may, in turn, lead to an overestimation of true core/neuronal death as estimated with computed tomography and magnetic resonance imaging. Assessing patients with apparent large core should consider these notions when discussing eligibility for EVT. Early reperfusion of large-core patients is expected to both target any residual penumbra and prevent the development of vasogenic edema within the severely hypoperfused areas. These considerations underscore the need for more reliable methods to identify irreversible neuronal injury inside the imaging-based estimated core.

Stroke, Ahead of Print. BACKGROUND:We investigated the relationship between white matter hyperintensity (WMH) multispot pattern lesions, a supporting magnetic resonance imaging marker of cerebral amyloid angiopathy (CAA), and positron emission tomography–based amyloid-β burden across a range of cerebrovascular amyloid deposition.METHODS:Twenty-one nondemented subjects (11 patients with probable CAA; median age, 71 [63–77] years; 82% males; and 10 healthy subjects; median age, 63.5 [61–68] years; 50% males) underwent brain magnetic resonance imaging and 11C-Pittsburgh compound B-positron emission tomography imaging. WMH multispot lesions were evaluated on FLAIR sequences. The association between whole cortex 11C-Pittsburgh compound B binding and WMH multispot lesions count was assessed using Kendall tau, adjusting for key markers of CAA through a hierarchical residualization approach.RESULTS:The unadjusted analysis showed a positive correlation between WMH multispot lesions count and whole cortex 11C-Pittsburgh compound B binding (tau-b=0.495;P=0.0017). Sequential adjustments for the presence of severe magnetic resonance imaging-visible perivascular spaces in the centrum semiovale, lobar cerebral microbleeds, age, and total WMH burden led to a progressive decline in correlation. The largest reduction occurred after adjusting for age (tau-b=0.307;P=0.0484) indicating its role as a potential confounder. In the fully adjusted model, the association remained significant (tau-b=0.316;P=0.0423), suggesting a partially independent relationship between WMH multispot lesions count and whole cortex amyloid burden. The results were consistent in a subanalysis within the probable CAA.CONCLUSIONS:This pilot study suggests a positive association between cerebrovascular amyloid deposition and WMH multispot lesions in CAA, with potential pathophysiological and clinical implications. These exploratory observations require confirmation in larger studies.

In a randomized trial, MRI and contrast-enhanced mammography detected more cancers than did ultrasound.

Stroke, Ahead of Print. BACKGROUND:In acute ischemic stroke, infarcted tissue gradually becomes detectable on noncontrast computed tomography (NCCT) as a hypodensity representing vasogenic edema. We studied whether subtle NCCT density changes are also present in penumbral tissue.METHODS:This observational cohort study included patients with stroke with anterior circulation occlusions from the CRISP2 study (CT Perfusion to Predict Response to Recanalization in Ischemic Stroke Project 2) who were transferred from a primary to a comprehensive stroke center for consideration of endovascular thrombectomy. Patients received baseline NCCT and computed tomography perfusion at the referring hospital and magnetic resonance imaging at the receiving hospital. We created baseline relative NCCT images, which compare voxel density to the corresponding area in the contralateral hemisphere. We analyzed the relative density of rNCCT in the core and penumbra (based on computed tomography perfusion in referring hospitals). We also assessed the correlation between relative density and the degree of hypoperfusion in the penumbra, defined as the time-to-maximum of the tissue residue function. We studied the association between penumbral changes and functional outcomes on the full distribution of the modified Rankin Scale score at 90 days.RESULTS:From the 314 patients, 162 met inclusion criteria with a median (interquartile range) age of 73 (61–83) years, penumbra volume of 78 (52–113) mL, and core volume of 0.6 (0–13.0) mL; 54% were men. The relative density was reduced by a median of 1.8% (P

Stroke, Ahead of Print. BACKGROUND:Spontaneous aneurysmal subarachnoid hemorrhage induces early blood-brain barrier permeability dysfunction, although its clinical relevance and underlying mechanisms remain poorly understood. We aimed to evaluate the association between blood-brain barrier disruption, quantified with dynamic contrast–enhanced magnetic resonance imaging at the end of the early brain injury period, circulating neuroinflammatory mediators, and long-term clinical outcomes.METHODS:We analyzed a prospective cohort of subarachnoid hemorrhage patients who underwent dynamic contrast–enhanced magnetic resonance imaging at a median (interquartile range) of 4 (2–6) days after clinical onset. Permeability maps were used to obtain K-trans values as a measure of increased blood-brain barrier permeability in the whole brain, gray matter, and white matter. Circulating neuroinflammatory molecules, including IL (interleukin) 8 and PDGF (platelet-derived growth factor), were measured using Multiplex-ELISA in blood samples collected concurrently with magnetic resonance imaging acquisition. Poor clinical outcome was defined as a modified Rankin Scale score of >2 at 90 days. Associations between K-trans values, neuroinflammatory mediators, and clinical outcomes were assessed using univariate and multivariate regression models.RESULTS:From 153 patients initially screened, 96 were finally included (63% females; median age, 55 years; 43% premorbid hypertension; 32% World Federation of Neurosurgical Societies grade 4–5; 31% poor outcome). In adjusted linear regression analyses, higher K-trans values were significantly associated with increased IL-8 (P=0.001) and PDGF (P=0.018) levels. In univariate analysis, K-trans values in white matter were significantly higher in patients with poor clinical outcome (median [interquartile range], 2.5 [2.07–6.09] ×10−3·min−1) compared with good clinical outcome (median [interquartile range], 2.0 [1.60–2.42] ×10−3·min−1;P

Stroke, Ahead of Print. BACKGROUND:Multiple recent randomized trials have demonstrated the benefit of thrombectomy over medical management alone in adult patients with large vessel occlusion (LVO) stroke and large infarct on baseline imaging. Cohort studies have also identified improved functional outcomes in pediatric patients who received thrombectomy. However, the role of thrombectomy in pediatric stroke with large baseline infarct remains uncertain.METHODS:A case-control study was undertaken using pooled data from 3 cohort studies of pediatric stroke (Save ChildS, Save ChildS Pro, Pediatric LVO Stroke Study). Pediatric patients of age 1 to 18 years with acute anterior circulation LVO stroke presenting within 24 hours since last seen well with an Alberta Stroke Program Early Computed Tomography (CT) Score of 0 to 5 on CT or magnetic resonance imaging were included. Isolated M2 occlusion or focal cerebral arteriopathy–inflammatory subtype cases were excluded. Thrombectomy-treated patients were compared with patients who received medical management alone. The primary clinical outcome was the pediatric modified Rankin Scale score at 90 days, compared between groups using ordinal logistic regression.RESULTS:Of 56 pediatric patients with anterior circulation LVO and low Alberta Stroke Program Early CT Score presenting between January 1, 2000 and August 31, 2023 from 45 centers across Europe, North America, and Australia, 40 patients were eligible for inclusion (female: n=14, 35.0%; mean age, 9.1 years; range, 1.5–17; SD, 5.27). Thrombectomy-treated patients (n=24) had significantly better pediatric modified Rankin Scale scores at 90 days than medical management alone patients (n=16; odds ratio, 3.68 [95% CI, 1.11–12.21];P=0.034). There was no significant difference between groups in the rate of symptomatic intracranial hemorrhage (P=0.806).CONCLUSIONS:In this multicentre case-control study, pediatric patients (age, 1–18 years) with anterior circulation LVO stroke and low Alberta Stroke Program Early CT Score who received thrombectomy had significantly better functional outcomes than those treated with medical management alone. Exclusion of pediatric patients from thrombectomy based on low Alberta Stroke Program Early CT Score alone may not be appropriate.