Search Results for: L'imaging nella urolitiasi

Introduction
Up to one-fifth of breast cancer survivors will develop chronic breast cancer-related lymphoedema (BCRL). To date, complex physical decongestion therapy (CDT) is the gold standard of treatment. However, it is mainly symptomatic and often ineffective in preventing BCRL progression. Lymphovenous anastomosis (LVA) and vascularised lymph node transfer (VLNT) are microsurgical techniques that aim to restore lymphatic drainage. This international randomised trial aims to evaluate advantages of microsurgical interventions plus CDT versus CDT alone for BCRL treatment.

Methods and analysis
The effectiveness of LVA and/or VLNT in combination with CDT, which may be combined with liposuction, versus CDT alone will be evaluated in routine practice across the globe. Patients with BCRL will be randomly allocated to either surgical or conservative therapy. The primary end point of this trial is the patient-reported quality of life (QoL) outcome ‘lymphoedema-specific QoL’, which will be assessed 15 months after randomisation. Secondary end points are further patient-reported outcomes (PROs), arm volume measurements, economic evaluations and imaging at different time points. A long-term follow-up will be conducted up to 10 years after randomisation. A total of 280 patients will be recruited in over 20 sites worldwide.

Ethics and dissemination
This study will be conducted in compliance with the Declaration of Helsinki and the International Council for Harmonisation-Good Clinical Practice (ICH-GCP) E6 guideline. Ethical approval has been obtained by the lead ethics committee ‘Ethikkommission Nordwest- und Zentralschweiz’ (2023-00733, 22 May 2023). Ethical approval from local authorities will be sought for all participating sites. Regardless of outcomes, the findings will be published in a peer-reviewed medical journal. Metadata detailing the dataset’s type, size and content will be made available, along with the full study protocol and case report forms, in public repositories in compliance with the Findability, Accessibility, Interoperability and Reuse principles.

Trial registration number
NCT05890677.

Circulation, Ahead of Print. BACKGROUND:Although cell therapy has emerged as a promising approach to promote neovascularization, its effects are mostly limited to capillaries. To generate larger or stable vessels, layering of mural cells such as smooth muscle cells (SMCs) or pericytes is required. Recently, direct reprogramming approaches have been developed for generating SMCs. However, such reprogrammed SMCs lack genuine features of contractile SMCs, a native SMC phenotype; thus, their therapeutic and vessel-forming potential in vivo was not explored. Therefore, we aimed to directly reprogram human dermal fibroblasts toward contractile SMCs (rSMCs) and investigated their role for generating vascular mural cells in vivo and their therapeutic effects on ischemic disease.METHODS:We applied myocardin and all-transretinoic acid with specific culture conditions to directly reprogram human dermal fibroblasts into rSMCs. We characterized their phenotype as contractile SMCs through quantitative reverse-transcriptase polymerase chain reaction, flow cytometry, and immunostaining. We then explored their contractility using a vasoconstrictor, carbachol, and through transmission electron microscope and bulk RNA sequencing. Next, we evaluated whether transplantation of rSMCs improves blood flow and induces vessel formation as mural cells in a mouse model of hind-limb ischemia with laser Doppler perfusion imaging and histological analysis. We also determined their paracrine effects.RESULTS:Our novel culture conditions using myocardin and all-transretinoic acid efficiently reprogrammed human dermal fibroblasts into SMCs. These rSMCs displayed characteristics of contractile SMCs at the mRNA, protein, and cellular levels. Transplantation of rSMCs into ischemic mouse hind limbs enhanced blood flow recovery and vascular repair and improved limb salvage. Histological examination showed that vascular density was increased and the engrafted rSMCs were incorporated into the vascular wall as pericytes and vascular SMCs, thereby contributing to formation of stabler and larger microvessels. Quantitative reverse-transcriptase polymerase chain reaction analysis revealed that these transplanted rSMCs exerted pleiotropic effects, including angiogenic, arteriogenic, vessel-stabilizing, and tissue regenerative effects, on ischemic limbs.CONCLUSIONS:A combination of myocardin and all-transretinoic acid in defined culture conditions efficiently reprogrammed human fibroblasts into contractile and functional SMCs. The rSMCs were shown to be effective for vascular repair and contributed to neovascularization through mural cells and various paracrine effects. These human rSMCs could represent a novel source for cell-based therapy and research.

Background
Prostate cancer (PCa) is the most common male malignancy in the western world. Many men (40%) are diagnosed with localised low or intermediate-risk PCa, which is suitable for active surveillance (AS). AS affords careful monitoring to identify changes in otherwise non-life-threatening cancers. While AS reduces overtreatment (and quality of life impact), long-term compliance can be poor, with many men undergoing radical treatment after starting AS.

Methods and analysis
Finasteride in Active Surveillance for men with low and intermediate-risk prostate cancer (FINESSE) is a prospective, open-label, two-arm, phase 3 trial, in which men with low or intermediate PCa are randomised (1:1) to receive AS with or without finasteride (5 mg once a day for 2 years). Randomisation is stratified by age and PCa risk. AS includes regular prostate-specific antigen testing, MRI scans and the offer of repeat biopsy (at 3 years, or if imaging suggests progression). Additional MRI scans and/or biopsies will be performed for biochemical or clinical indications. We aim to recruit 550 men (aged 50 to 75 years) from up to eight sites. Active outpatient follow-up will be for 3–5 years (depending on date recruited), followed by passive registry-based follow-up for up to 10 years. Primary outcome is adherence to AS. Secondary outcomes include rates and type of disease progression, treatments received (for PCa and benign prostatic enlargement), overall and PCa-specific mortality, an understanding of patients/professionals views of this approach and health-related quality of life. An external panel of experts blinded to allocation will review all AS cessation and progression events. Trial pathologist’s and radiologist’s, blinded to allocation, will review representative cases. Analysis is Intention to Treat.

Ethics and dissemination
The study received Health Research Authority and South-Central Oxford Research Ethics Committee (14/12/2021: 21/SC/0349) and CTA/MHRA (29/12/2021: 21304/0274/001–0001) approvals. Results will be made available to providers and researchers via publicly accessible scientific journals.

Trial registration number
ISRCTN16867955

Stroke, Ahead of Print. BACKGROUND:Infarct growth rate is remarkably heterogeneous in acute ischemic stroke, reflecting diverse clinical-physiological phenotypes. We compared different methods of estimating infarct growth rate in patients with acute ischemic stroke undergoing thrombectomy using multimodal computed tomography (CT) stroke imaging.METHODS:Secondary analysis of the international ESCAPE-NA1 trial (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischemic Stroke) which evaluated the effect of nerinetide in patients with large vessel occlusion undergoing thrombectomy. Infarct growth rate was estimated leveraging each component of multimodal stroke CT imaging: (1) 10 minus baseline Alberta Stroke Program Early CT Score (ASPECTS) divided by hours elapsed from symptom onset on noncontrast CT (ASPECTS decay per hour); (2) collateral status on multiphase CT angiography (mCTA), and (3) hypoperfusion intensity ratio on CT perfusion. Patients were dichotomized into intermediate and slow progressors (since fast progressors were likely to be excluded from ESCAPE-NA1 based on trial enrollment criteria) according to median ASPECTS decay, presence of good versus moderate/poor mCTA collaterals, and median hypoperfusion intensity ratio, respectively. Associations between progressor phenotypes and 90-day modified Rankin Scale score were assessed across neuroimaging modalities using adjusted logistic regression analyses.RESULTS:Among 1105 patients enrolled in ESCAPE-NA1 between 2017 and 2019, 619 (56.0%) were assessed for progressor phenotypes using noncontrast CT, 1084 (98.1%) with mCTA, and 415 (37.6%) with CT perfusion. Median ASPECTS decay per hour was 1.05 (interquartile range, 0.05–1.85), 188/1084 (17%) patients had good collateral status on mCTA, and the median hypoperfusion intensity ratio was 0.44 (interquartile range, 0.28–0.59). Intermediate progressors showed worse functional outcomes compared with slow progressors only in CT perfusion strata: adjusted common odds ratio for modified Rankin Scale ordinal shift analysis of 1.69 (95% CI, 1.14–2.49). No significant association between progressor phenotypes and 90-day modified Rankin Scale was seen when the noncontrast CT and the mCTA approaches were used.CONCLUSIONS:Stroke progressor phenotypes based on CT perfusion criteria (using the hypoperfusion intensity ratio approach) were associated with clinical outcomes, while stroke progressor phenotypes based on noncontrast CT (ASPECTS decay) and mCTA (collateral status) criteria were not.

Stroke, Ahead of Print. BACKGROUND:Although the relationship between cervical carotid tortuosity and cardiovascular risk in patients with Loeys-Dietz syndrome has been studied, it is unclear whether cervical carotid tortuosity influences the risk of neurovascular events.METHODS:This is a single-institution retrospective cohort study. Cervical carotid tortuosity and morphology were assessed in patients with Loeys-Dietz syndrome who underwent baseline computed tomography/magnetic resonance imaging of the cervical and cerebral arteries from 2010 to 2022. The primary end point was a composite of adverse neurovascular events (multiple vessel cervical artery dissection, ischemic stroke, intracerebral hemorrhage, and any neurovascular intervention) at 5- and 10-year follow-ups. Independent risk factors were identified using univariate and multivariate logistic regression analyses. Single-variable predictors of 5- and 10-year outcomes were analyzed via receiver operating curve analyses. Cutoff values were determined per the Youden J index. Stratification analyses were performed for ages

Background
The determinants of the response to checkpoint immunotherapy in hepatocellular carcinoma (HCC) remain poorly understood. The organisation of the immune response in the tumour microenvironment (TME) is expected to govern immunotherapy outcomes but spatial immunotypes remain poorly defined.

Objective
We hypothesised that the deconvolution of spatial immune network architectures could identify clinically relevant immunotypes in HCC.

Design
We conducted highly multiplexed imaging mass cytometry on HCC tissues from 101 patients. We performed in-depth spatial single-cell analysis in a discovery and validation cohort to deconvolute the determinants of the heterogeneity of HCC immune architecture and develop a spatial immune classification that was tested for the prediction of immune checkpoint inhibitor (ICI) therapy.

Results
Bioinformatic analysis identified 23 major immune, stroma, parenchymal and tumour cell types in the HCC TME. Unsupervised neighbourhood detection based on the spatial interaction of immune cells identified three immune architectures with differing involvement of immune cells and immune checkpoints dominated by either CD8 T-cells, myeloid immune cells or B- and CD4 T-cells. We used these to define three major spatial HCC immunotypes that reflect a higher level of intratumour immune cell organisation: depleted, compartmentalised and enriched. Progression-free survival under ICI therapy differed significantly between the spatial immune types with improved survival of enriched patients. In patients with intratumour heterogeneity, the presence of one enriched area governed long-term survival.

Background
PARP inhibitors (PARPi) have been licensed for the maintenance therapy of patients with metastatic pancreatic cancer carrying pathogenic germline BRCA1/2 mutations. However, mutations in BRCA1/2 are notably rare in pancreatic cancer.

Objective
There is a significant unmet clinical need to broaden the utility of PARPi.

Design
RNA sequencing was performed to screen potential targets for PARPi sensitivity. The synthetic lethal effects were verified in patient-derived xenograft (PDX), xenograft and patient-derived organoid models. Mechanisms were explored via LC-MS/MS, coimmunoprecipitation, laser microirradiation, immunofluorescence, the homologous recombination (HR) or non-homologous end joining (NHEJ) reporter system, in situ proximity ligation assay and live-cell time-lapse imaging analyses.

Results
Targeting protein for Xenopus kinesin-like protein 2 (TPX2) is an exploitable vulnerability. TPX2 was downregulated in PDX models sensitive to PARPi, and TPX2 inhibition conferred synthetic lethality to PARPi both in vitro and in vivo. Mechanistically, TPX2 functions in a cell cycle-dependent manner. In the S/G2 phase, ATM-mediated TPX2 S634 phosphorylation promotes BRCA1 recruitment to double-strand breaks (DSBs) for HR repair, whereas non-phosphorylated TPX2 interacts with 53BP1 to recruit it for NHEJ. The balance between phosphorylated and non-phosphorylated TPX2 determines the DSB repair pathway choice. During mitosis, TPX2 phosphorylation enhances Aurora A activity, promoting mitotic progression and chromosomal stability. Targeting TPX2 S634 phosphorylation with a cell-penetrating peptide causes genomic instability and mitotic catastrophe and enhances PARPi sensitivity. Additionally, the inhibition of TPX2 or S634 phosphorylation combined with gemcitabine further sensitised pancreatic cancer to PARPi.

Conclusions
Our findings revealed the dual-functional significance of TPX2 in controlling DNA DSB repair pathway choice and mitotic progression, suggesting a potential therapeutic strategy involving PARPi for patients with pancreatic cancer.

E’ partner del progetto ‘European cancer imaging – Eucaim’

Objectives
The Wells rule is often used in primary care to rule out pulmonary embolism (PE), but its efficiency is low as many referred patients do not have PE. In this study, we evaluated in primary care an alternative and potentially more efficient diagnostic strategy—the YEARS algorithm; a simplified three-item version of the Wells rule combined with a pretest probability adjusted D-dimer interpretation.

Design
In this comprehensive prospective diagnostic validation study, primary care patients suspected of PE were enrolled by their general practitioner. All three YEARS items were collected in addition to D-dimer results, and patients were followed for 3 months to establish the final diagnosis.

Setting
Primary care in the Netherlands.

Participants
753 patients with suspected acute PE were included. Five patients (0.7%) were lost to follow-up.

Main outcome measures
Failure rate (number of PE cases among patients classified by the algorithm as ‘PE ruled-out’) and efficiency (fraction of patients classified as ‘PE probable/further imaging needed’).

Results
Prevalence of PE was 5.5% (41/748 patients). In total, 603 patients were classified as ‘PE ruled-out’ by the YEARS algorithm (532 with zero YEARS items and a D-dimer

Introduction
Artificial Intelligence Ready and Equitable for Diabetes Insights (AI-READI) is a data collection project on type 2 diabetes mellitus (T2DM) to facilitate the widespread use of artificial intelligence and machine learning (AI/ML) approaches to study salutogenesis (transitioning from T2DM to health resilience). The fundamental rationale for promoting health resilience in T2DM stems from its high prevalence of 10.5% of the world’s adult population and its contribution to many adverse health events.

Methods
AI-READI is a cross-sectional study whose target enrollment is 4000 people aged 40 and older, triple-balanced by self-reported race/ethnicity (Asian, black, Hispanic, white), T2DM (no diabetes, pre-diabetes and lifestyle-controlled diabetes, diabetes treated with oral medications or non-insulin injections and insulin-controlled diabetes) and biological sex (male, female) (Clinicaltrials.org approval number STUDY00016228). Data are collected in a multivariable protocol containing over 10 domains, including vitals, retinal imaging, electrocardiogram, cognitive function, continuous glucose monitoring, physical activity, home air quality, blood and urine collection for laboratory testing and psychosocial variables including social determinants of health. There are three study sites: Birmingham, Alabama; San Diego, California; and Seattle, Washington.

Ethics and dissemination
AI-READI aims to establish standards, best practices and guidelines for collection, preparation and sharing of the data for the purposes of AI/ML, including guidance from bioethicists. Following Findable, Accessible, Interoperable, Reusable principles, AI-READI can be viewed as a model for future efforts to develop other medical/health data sets targeted for AI/ML. AI-READI opens the door for novel insights in understanding T2DM salutogenesis. The AI-READI Consortium are disseminating the principles and processes of designing and implementing the AI-READI data set through publications. Those who download and use AI-READI data are encouraged to publish their results in the scientific literature.

Introduction
A quarter of breast cancers show human epidermal growth factor-2 (HER2) overexpression, where targeted therapy dramatically improves survival. However, cancer therapy-related cardiac dysfunction (CTRCD) occurs in up to 15% of patients. With the interruption of HER2 therapy, if necessary, and the initiation of heart failure therapy (HFT), HER2 CTRCD recovers in over 80% of cases. The need to continue HFT in ‘recovered’ HER2 CTRCD following completion of HER2 therapy is unclear and there are potential significant impacts on patient’s quality of life (QoL). The Randomised Controlled Trial for the Safety of Withdrawal of Pharmacological Treatment for Recovered HER2 Targeted Therapy Related Cardiac Dysfunction (HER-SAFE) aims to evaluate whether HFT can be safely withdrawn in non-high cardiovascular (CV) risk patients with ‘recovered’ HER2 CTRCD.

Methods and analysis
This is a multicentre, open-label randomised controlled trial investigating whether withdrawal of HFT is non-inferior to continuation in non-high CV risk, breast cancer survivors with recovered HER2 CTRCD after cancer treatment completion. The primary endpoint is the incidence of guideline-defined cardiac dysfunction or clinical heart failure. Secondary endpoints include changes in cardiac blood biomarkers, cardiovascular magnetic resonance (CMR)-derived strain and tissue mapping and heart failure symptom questionnaires. The study will recruit 90 participants who will undergo serial clinical assessment over 12 months with advanced cardiovascular imaging (CMR scans with automated analysis at baseline, 6 and 12 months), cardiac biomarker measurement (six time points over 12 months), plus complete heart failure QoL and medication disutility questionnaires. This is the first multicentre study to address this significant clinical issue.

Ethics and dissemination
This study was approved by the research ethics committee (London—London Bridge, 23/LO/0152). The results will be disseminated in peer-reviewed scientific journals.

Trial registration number
NCT05880160.

Functional lumen imaging probe (FLIP) Panometry provides assessment of the esophagogastric junction (EGJ) opening and esophageal body contractile activity during an endoscopic procedure and is increasing being incorporated in comprehensive esophageal motility assessments. We aimed to provide a standardized approach and vocabulary to the procedure and interpretation and update the motility classification scheme.

Many medical schools offer courses designed to “train the eye,” bringing students and physicians into museums to look carefully at art. Just as for decades images of artworks graced the covers of JAMA, reminding us medicine is an art while stimulating our visual imaginations, such courses invite us to describe accurately what we see. The implications for physicians, from dermatologists who must recognize rashes based on appearance to radiologists who must discern patterns on imaging to make diagnoses, are perhaps more obvious than the subtleties of perspective and composition. The same kind of close attention is characteristic of poetry, as the poem “Joanne” vividly demonstrates: the keenly observed details are striking and reveal more than mere depictions of objects and people. The comparison between the pink gown the speaker is given to wear in the mammography suite and the sunset enveloping Joanne is not just lovingly rendered, but also evokes the vulnerability and need for comfort undergoing evaluation of a breast lump engenders. The recurring colors of pinks and reds suggest not just searching for warmth and reassurance, but also returning for repeated surveillance. The speaker scrawling “I wuz here” on a childhood chalkboard is at once startlingly clear-eyed, but also reminds us how, when we identify with patients, we ourselves may feel as exposed and helpless as children. Ultimately, it is not just opening our eyes to see what is before us that encounters with art and poetry teach, but also that the very act of close observation sparks empathy.

Circulation, Ahead of Print. BACKGROUND:Dilated cardiomyopathy (DCM) appears to be diagnosed twice as often in male than in female patients. This could be attributed to underdiagnosis in female patients or sex differences in susceptibility. Up to 30% of cases have an autosomal dominant monogenic cause, where equal sex prevalence would be expected. The aim of this systematic review, meta-analysis, and population study was to assess the sex ratio in patients with DCM, stratified by genetic status, and evaluate whether this is influenced by diagnostic bias.METHODS:A literature search identified DCM patient cohorts with discernible sex ratios. Exclusion criteria were studies with a small (n

Introduction
Stroke is a major cause of acquired disability globally, yet the neural mechanisms driving motor recovery post-stroke remain elusive. Recent research has underscored the growing significance of subcortical pathways in neural plasticity and motor control. Among these, the cortico-reticulospinal tract (CRST) has gained attention in rehabilitation due to its unique ascending and descending structural features as well as its cellular properties which position it as an excellent candidate to compensate for inadequate motor control post-stroke. However, the optimal strategies to harness the CRST for motor recovery remain unknown. Non-invasive modulation of the CRST presents a promising though challenging, therapeutic opportunity. Acoustic startle priming (ASP) training and intermittent theta burst stimulation (iTBS) are emerging as potential methods to regulate CRST function. This study aims to investigate the feasibility of segmentally modulating the cortico-reticular and reticulospinal tracts through ASP and iTBS while evaluating the resulting therapeutic effects.

Methods and analysis
This is a randomised, blinded interventional trial with three parallel groups. A total of 36 eligible participants will be randomly assigned to one of three groups: (1) iTBS+ASP group, (2) iTBS+non-ASP group, (3) sham iTBS+ASP group. The trial comprises four phases: baseline assessment, post-first intervention assessment, assessment after 3 weeks of intervention and a 4-week follow-up. The primary outcomes are the changes in the Fugl-Meyer Assessment-Upper Extremity and Modified Ashworth Scale after the 3-week intervention. Secondary outcomes include neurophysiological metrics and neuroimaging results from diffusion tensor imaging and resting-state functional MRI.

Ethics and dissemination
The trial is registered with the Chinese Clinical Trial Registry (Registration No. ChiCTR2400085220) and Medical Ethics Committee of Tongji Hospital, affiliated with Tongji Medical College, Huazhong University of Science and Technology (Registration No.TJ-IRB20231109). It will be conducted in the Departments of Rehabilitation Medicine and Radiology at Tongji Hospital in Wuhan, China. The findings will be disseminated through peer-reviewed journal publications and presentations at scientific conferences.

Trial registration number
ChiCTR2400085220.

Objective
To examine longitudinal trends in infertility management in women attending general practice.

Design
Cohort study using the national general practice dataset, MedicineInsight.

Setting
Australian general practice.

Intervention(s)
Not applicable.

Participants
The cohort included 2 552 339 women aged 18–49 years with one or more general practice clinical encounters between January 2011 and December 2021.

Primary and secondary outcome measures(s)
The primary outcome assessed was the proportion of women who had a clinical encounter related to infertility, stratified by year and age group. Second, the proportions of women receiving relevant clinical management actions, including selected pathology tests, imaging ordered and selected medications, were calculated. Univariable logistic regression analyses compared the likelihood of women having a documented clinical encounter related to infertility and receiving selected management actions based on individual characteristics. We also examined practice-level variation in the proportion receiving selected management for infertility by stratifying proportions based on practice site.

Results
A total of 2 552 339 women had one or more clinical encounters with their general practitioner (GP) between January 2011 and December 2021, of which 27 671 (1.1%) had a clinical encounter related to infertility management. The rate of infertility encounters increased from 3.4 per 1000 in 2011 to 5.7 per 1000 in 2021. Over episodes of care, half (50.9%) of women presenting for an infertility encounter had at least one specified pathology test, and almost a quarter (23.1%) had a specified imaging test. A relatively small proportion of infertility encounters (5.4%) resulted in prescribing of a selected infertility medication by the GP.
Large variation in clinical management (pathology, imaging and medication prescribing) was evident according to both individual characteristics and also at the clinical-practice level. Factors associated with increased likelihood of being provided infertility medications included younger age, holding a Commonwealth concession card (indicating low income), lower socioeconomic status and living outside a major city.

Conclusions
Clinical encounters related to infertility are increasing in primary care, with large variation evident in corresponding clinical management. These findings support the development of clinical practice guidelines to enhance standardised and equitable approaches towards the management of infertility in primary care.