Parsing the thyroid cytopathology suspicious for malignancy diagnosis through molecular-derived risk of malignancy and other related parameters: Insights into nodule characteristics and practice patterns.

INTRODUCTION: Thyroid cytopathology cases with suspicious for malignancy (SFM) diagnosis often result in resection. However, molecular testing offers details that may provide additional insights. In this study, the molecular profiles of SFM cases from two institutions that routinely used ThyroSeq v3 (TSV3) were examined. MATERIALS AND METHODS: Following institutional review board approval, SFM thyroid cytopathology cases with TSV3 results were retrieved from the databases of two institutions. Molecular information including molecular-derived risk of malignancy (MDROM), cytologic-histologic correlation data, and other related parameters were calculated. Statistical comparisons were made with a p <.05 considered significant. RESULTS: The core data set comprised 114 SFM cases that passed TSV3 quality assurance. All TSV3 results were reported as positive or negative for genomic alterations and all except five cases provided a probability of malignancy estimate. The overall combined baseline MDROM of 75.7% (95% CI, 70.0-81.4) was comparable to the risk of malignancy (74%) published in the Bethesda System. There was a statistically significant difference between the combined MDROMs of resected and unresected cohorts (79.0% vs 58.6%; p = .0153). Interestingly, the MDROMs of the resected cohorts from the two institutions were statistically different (75.0% vs 85.3%; p = .020). Cytologic-histologic correlation revealed malignant outcome in 88.5% of resected cases. CONCLUSIONS: Molecular analyses of SFM cases demonstrated higher risk genomic alterations that were associated with histologically overt neoplasms, resulting in increased malignancy outcome compared to baseline. MDROM analysis revealed differences in the cytopathologic practice patterns regarding follicular-patterned neoplasms at the two institutions.

Pentoxifylline ameliorates subclinical atherosclerosis progression in patients with type 2 diabetes and chronic kidney disease: a randomized pilot trial.

BACKGROUND: Diabetic kidney disease (DKD) is associated with a higher risk of cardiovascular disease (CVD). Pentoxifylline (PTF), a nonselective phosphodiesterase inhibitor with anti-inflammatory, antiproliferative, and antifibrotic actions, has demonstrated renal benefits in both clinical trials and meta-analyses. The present work aimed to study the effects of PTF on the progression of subclinical atherosclerosis (SA) in a population of patients with diabetes and moderate to severe chronic kidney disease (CKD). METHODS: In this open-label, randomized controlled, prospective single-center pilot study the evolution of carotid intima-media thickness (CIMT) and ankle-brachial index (ABI) were determined in 102 patients with type 2 diabetes mellitus and CKD assigned to PTF, aspirin or control groups during 18 months. We also determined the variations in the levels of inflammatory markers and Klotho (KL), a protein involved in maintaining cardiovascular health, and their relationship with the progression of SA. RESULTS: Patients treated with PTF presented a better evolution of CIMT, increased KL mRNA levels in peripheral blood cells (PBCs) and reduced the inflammatory state. The progression of CIMT values was inversely related to variations in KL both in serum and mRNA expression levels in PBCs. Multiple regression analysis demonstrated that PTF treatment and variations in mRNA KL expression in PBCs, together with changes in HDL, were significant determinants for the progression of CIMT (adjusted R2 = 0.24, P < 0.001) independently of traditional risk factors. Moreover, both variables constituted protective factors against a worst progression of CIMT [OR: 0.103 (P = 0.001) and 0.001 (P = 0.005), respectively]. CONCLUSIONS: PTF reduced SA progression assessed by CIMT variation, a beneficial effect related to KL gene expression in PBCs. TRIAL REGISTRATION: The study protocol code is PTF-AA-TR-2009 and the trial was registered on the European Union Drug Regulating Authorities Clinical Trials (EudraCT #2009-016595-77). The validation date was 2010-03-09.

Clinical characteristics and impact on patient-reported outcomes and quality of life of people with ambulatory secondary progressive multiple sclerosis: DISCOVER study.

BACKGROUND: People with secondary progressive multiple sclerosis (pwSPMS) experience increasing disability, which impacts negatively on their health-related quality of life (HRQoL). Our aims were to assess the impact of secondary progressive multiple sclerosis (SPMS) on functional status and HRQoL and describe the clinical profile in this population. METHODS: DISCOVER is an observational, cross-sectional, multicenter study with retrospective data collection in real-world clinical practice in Spain. Sociodemographic and clinical variables, functional and cognitive scales, patient-reported outcomes (PROs), and direct healthcare, and non-healthcare and indirect costs were collected. RESULTS: A total of 297 evaluable pwSPMS with a EDSS score between 3-6.5 participated: 62.3 % were female and 18.9 % had active SPMS. At the study visit, 77 % of them presented an Expanded Disability Scale Score (EDSS) of 6-6.5. Nearly 40 % did not receive any disease-modifying treatment. Regarding the working situation, 61.6 % were inactive due to disability. PROs: 99.3 % showed mobility impairment in EuroQoL-5 Dimensions-5 Levels, and about 60 % reported physical impact on the Multiple Sclerosis Impact Scale-29. Fatigue was present in 76.1 %, and almost 40 % reported anxiety or depression. The Symbol Digit Modalities Test was used to assess cognitive impairment; 80 % of the patients were below the mean score. Participants who presented relapses two years before and had high EDSS scores had a more negative impact on HRQoL. PwSPMS with a negative impact on HRQoL presented a higher cost burden, primarily due to indirect costs. CONCLUSIONS: PwSPMS experience a negative impact on their HRQoL, with a high physical impact, fatigue, cognitive impairment, and a high burden of indirect costs.

Real-World Study of Serum Neurofilament Light Chain Levels in Ocrelizumab-Treated People with Relapsing Multiple Sclerosis.

Serum neurofilament light chain (sNfL) levels have been proposed as a biomarker of the clinical activity, disability progression, and response to treatment of people with multiple sclerosis (PwMS); however, questions remain about its implementation in clinical practice. Ocrelizumab (OCR) has proven effective in improving clinical and radiological outcomes and reducing sNfL levels. This real-life study followed the sNfL levels of 30 PwMS treated for 12 months with OCR and evaluated the usefulness of this biomarker for their short-term prognosis, considering expanded disability status scale (EDSS), annualized relapse rate (ARR), radiological activity, and NEDA-3 values. OCR reduced ARR in 83% of PwMS and radiological activity in 80%. EDSS was maintained, while NEDA-3 was achieved in 70% at 12 months. OCR produced an early reduction in sNfL levels (at 3 months). At baseline, greater MRI-evaluated radiological activity was associated with higher sNfL levels. sNfL levels over the first 12 months of treatment did not predict a suboptimal response or sustained control of the disease. Longer-term studies are needed to explore the predictive usefulness of sNfL levels in PwMS treated with high-efficacy drugs.

Impact of Driver Mutations on Metastasis-Free Survival in Uveal Melanoma: A Meta-Analysis.

The prognosis of uveal melanoma is significantly influenced by the risk of metastasis, which varies according to clinical and genetic features. Driver mutations can predict the likelihood of disease progression and survival, although the data in the literature are inconsistent. This meta-analysis aimed to evaluate the prognostic significance of driver mutations, including GNAQ, GNA11, BAP1, and SF3B1, in the advancement of uveal melanoma. A comprehensive search of databases yielded relevant studies, and data from 13 studies (848 eyes) were synthesized to assess the impact of these mutations on metastasis-free survival. The BAP1 mutation and negative immunohistochemistry were associated with a higher risk of metastasis (logHR = 1.44, 95% CI 1.05-1.83). GNAQ, GNA11, and SF3B1 mutations did not show a significant increase in risk. In summary, BAP1 has proven to reliably predict the likelihood of disease progression in uveal melanoma, while further studies are needed to establish the significance of other driver mutations.

Preclinical characterization of endotoxin-induced uveitis models using OCT, PET/CT and proteomics.

Uveitis is a group of inflammatory ocular pathologies. Endotoxin-Induced Uveitis (EIU) model represent a well-known model induced by administration of Lipopolysaccharide (LPS). The aim is to characterize two models of EIU through two routes of administration with novel noninvasive imaging techniques. 29 rats underwent Intraocular Pressure (IOP) measurements, Optical Coherence Tomography (OCT), proteomic analysis, and Positron Emission Tomography and Computed Tomography (PET/CT). Groups included healthy controls (C), BSS administered controls (Ci), systemically induced EIU with LPS (LPSs), and intravitreally induced EIU with LPS (LPSi) for IOP, OCT, and proteomic studies. For 18F-FDG PET/CT study, animals were divided into FDG-C, FDG-LPSs and FDG-LPSi groups and scanned using a preclinical PET/CT system. LPSi animals exhibited higher IOP post-induction compared to C and LPSs groups. LPSi showed increased cellular infiltrate, fibrotic membranes, and iris inflammation. Proinflammatory proteins were more expressed in EIU models, especially LPSi. PET/CT indicated higher eye uptake in induced models compared to FDG-C. FDG-LPSi showed higher eye uptake than FDG-LPSs but systemic uptake was higher in FDG-LPSs due to generalized inflammation. OCT is valuable for anterior segment assessment in experimental models. 18F-FDG PET/CT shows promise as a noninvasive biomarker for ocular inflammatory diseases. Intravitreal induction leads to higher ocular inflammation. These findings offer insights for future inflammatory disease research and drug studies.

Mesenchymal neoplasms of the tongue: A clinicopathologic study of 93 cases.

Neoplasms of the tongue are relatively common, and the vast majority are epithelial in phenotype. Although uncommon, a diverse and distinctive array of mesenchymal neoplasms arises in this anatomic site. To increase our understanding of these lesions, we reviewed our experience of MNs of the tongue and described their clinicopathologic features. The pathology archives from 2005 to 2021 and the consultation files of one of the authors were queried for all MNs of the tongue. We reviewed the histologic slides and ancillary studies and obtained clinical data from the available medical records. Ninety-three cases were identified, and they form the study cohort - to our knowledge, this is the largest series of mesenchymal neoplasms of the tongue. Forty-eight patients were female, and forty-five were male, with a mean age of 51 years (range: 1-94 years). The tumors included 43 (46.2%) hemangiomas, 14 (15%) granular cell tumors, 8 (9%) lipomas, 4 (4.3%) schwannomas, 4 (4.3%) solitary fibrous tumors - all with low risk of progression based on risk stratification criteria, 2 (2.2%) lymphangiomas, 3 (3.2%) Kaposi sarcomas, 2 (2.2%) chondromas, 2 (2.2%) myofibromas, 1 (1.1%) solitary circumscribed neuroma, 1 (1.1%) perineurioma, 1 (1.1%) neurofibroma, 1 (1.1%) ectomesenchymal chondromyxoid tumor, 1 (1.1%) atypical glomus tumor with a NOTCH2 rearrangement and TLL2 mutation, 1 (1.1%) spindle cell rhabdomyosarcoma, 1 (1.1%) pleomorphic fibroblastic sarcoma, 1 (1.1%) malignant rhabdoid tumor, 1 (1.1%) leiomyosarcoma, 1 (1.1%) angiosarcoma, and 1 (1.1%) alveolar soft part sarcoma. Most of the patients underwent surgical excision, and 1 patient (with hemangioma) underwent embolization. On follow-up, the patient with spindle cell rhabdomyosarcoma developed postoperative numbness at the surgical site and was disease-free through 17 months of follow-up. The patient with leiomyosarcoma declined adjuvant radiation and developed metastasis to the lung at 22 months. The patient with alveolar soft part sarcoma had metastases to the lung at the time of diagnosis and received adjuvant chemotherapy. The remaining patients had no local or distant recurrence. MNs of the tongue are usually benign and characterized by either endothelial, adipocytic, or schwannian differentiation. The mainstay of treatment is surgical excision with the extent of excision determined by tumor type. Adjuvant therapy is reserved for high-grade sarcomas.

Utility of the Milan System for Reporting Salivary Gland Cytopathology in fine needle aspiration cytology of minor salivary gland lesions.

INTRODUCTION: Salivary gland lesions are routinely evaluated by fine-needle aspiration cytology (FNAC) preoperatively. The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) has standardized salivary gland FNAC reporting. Its application in major salivary glands (MSGs) has been well-established; however, its utility in minor salivary glands (MiSGs) is not well-known. We studied the utility of MSRSGC in MiSG FNAC. MATERIALS AND METHODS: A retrospective search of MiSG FNACs from 2 academic institutions (2006-2023) was performed. FNACs were classified using the MSRSGC. Histologic data were reviewed and recorded. The risk of malignancy (ROM), risk of neoplasia (RON), diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. RESULTS: The series included 43 MiSG FNAC (24 males and 18 females), with a mean age of 55 years (range 10-92). Aspirated sites included the following: palate, buccal space, floor of mouth, lip, tongue, and maxillary sinus. FNACs were classified as nondiagnostic (1), nonneoplastic (3), atypia of undetermined significance (6), benign neoplasm (9), salivary gland neoplasm of uncertain malignant potential (15), suspicious for malignancy, (2) and malignant (7). The risk of neoplasia and risk of malignancy were 87% and 39%. The diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 100%, respectively. CONCLUSIONS: Milan System for Reporting Salivary Gland Cytopathology offers valuable information for stratifying MiSG lesions. However, the distribution and the range of diagnostic entities encountered differ somewhat from those in MSGs. For instance, mucinous cyst contents may warrant unique consideration in MiSG; while an atypical classification is recommended in MSGs, the high prevalence of mucoceles in MiSG may tilt this group toward benignity.

Ataxia-telangiectasia in Latin America: clinical features, immunodeficiency, and mortality in a multicenter study.

Ataxia-telangiectasia (AT) is a rare genetic disorder leading to neurological defects, telangiectasias, and immunodeficiency. We aimed to study the clinical and immunological features of Latin American patients with AT and analyze factors associated with mortality. Referral centers from 9 Latin American countries participated in this retrospective cohort study, and 218 patients were included. Median (IQR) ages at symptom onset and diagnosis were 1.0 (1.0-2.0)  and 5.0 (3.0-8.0) years, respectively. Most patients presented recurrent airway infections, which was significantly associated with IgA deficiency. IgA deficiency was observed in 60.8% of patients and IgG deficiency in 28.6%. T- and B-lymphopenias were also present in most cases. Mean survival was 24.2 years, and Kaplan-Meier 20-year-survival rate was 52.6%, with higher mortality associated with female gender and low IgG levels. These findings suggest that immunologic status should be investigated in all patients with AT.

Identification and functional characterization of fish IL-17 receptors suggest important roles in the response to nodavirus infection.

Th17 is a lymphocyte T helper (Th) subpopulation relevant in the control and regulation of the immune response characterized by the production of interleukin (IL)-17. This crucial cytokine family acts through their binding to the IL-17 receptors (IL-17R), having up to six members. Although the biology of fish Th17 is well-recognized, the molecular and functional characterization of IL-17 and IL-17R has been limited. Thus, our aim was to identify and characterize the IL-17R repertory and regulation in the two main Mediterranean cultured fish species, the gilthead seabream (Sparus aurata) and the European sea bass (Dicentrarchus labrax). Our in silico results showed the clear identification of six members in each fish species, from IL-17RA to IL-17RE-like, with well-conserved gene structure and protein domains with their human orthologues. All of them showed wide and constitutive transcription in naïve tissues but with highest levels in mucosal tissues, namely skin, gill or intestine. In leucocytes, T mitogens showed the strongest up-regulation in most of the il17 receptors though il17ra resulted in inhibition by most stimulants. Interestingly, in vivo nodavirus infection resulted in alterations on the transcription of il17 receptors. While nodavirus infection led to some increments in the il17ra, il17rb, il17rc and il17rd transcripts in the susceptible European sea bass, many down-regulations were observed in the resistant gilthead seabream. Our data identify the presence and conservation of six coding IL-17R in gilthead seabream and European sea bass as well as their differential regulation in vitro and upon nodavirus infection. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-024-00225-1.

Fall assessment and intervention among community-dwelling older people in a primary health care center in Spain: a best practice implementation project.

INTRODUCTION: The implementation of fall prevention programs in the community is complex. Although there is solid scientific evidence that supports the effectiveness of such programs, there are multiple barriers that should be addressed using multifaceted strategies. AIMS: The aim of this project was to increase compliance with evidence-based recommendations regarding fall risk screening and preventive interventions among older adults in a primary health care setting. METHODS: This project used a pre-/post-implementation clinical audit based on the JBI Evidence Implementation Framework. Eight audit criteria were derived from JBI evidence summaries. The sample size was 62 patients aged 70 years or older. Data collection methods included a review of medical records and a questionnaire. A baseline audit was conducted and five barriers to best practice were identified. Strategies were then developed to increase compliance with the evidence-based recommendations, guided by JBI's Getting Research into Practice (GRiP) analysis. A follow-up audit was conducted in July 2022 to evaluate changes in compliance with best practices. RESULTS: The baseline audit showed 0% compliance with best practice recommendations for seven out of eight audit criteria. Five barriers were identified: (1) absence of fall risk screening tools, (2) lack of fall prevention intervention protocols, (3) insufficient reporting of fall episodes in the records, (4) need for staff training, and (5) high staff turnover. Following the implementation of a fall risk assessment and intervention protocol, along with staff training, seven out of eight audit criteria increased from 0% to between 22.6% and 100%. CONCLUSIONS: This evidence-based implementation project improved nursing practice in relation to compliance with best practice interventions to prevent falls. SPANISH ABSTRACT: http://links.lww.com/IJEBH/A229.

In-hospital versus after-discharge complete revascularization in patients with ST segment elevation myocardial infarction and multivessel disease. REVIVA-ST trial.

INTRODUCTION: Complete revascularization (CR) in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease (MVD), is associated with a reduction in major adverse cardiovascular events (MACE). However, there is uncertainty about whether nonculprit-lesion revascularization should be performed, during index hospitalization or delayed, especially regarding health care resources utilization. In this study, we aimed to evaluate the impact of in-hospital nonculprit-lesion revascularization vs. delayed (after discharge) revascularization on the length of index hospitalization. METHODS: In this single-center study, we randomly assigned patients with STEMI and MVD who underwent successful culprit-lesion PCI to a strategy of either CR during in-hospital admission or a delayed CR after discharge. The first primary endpoint was the length of hospital stay. The second endpoint was the composite of cardiovascular death, myocardial infarction or ischemia-driven revascularization at 12 months (MACE). RESULTS: From January 2018 to December 2022, we enrolled 258 patients (131 allocated to CR during in-hospital admission and 127 to an after-discharge CR). We found a significant reduction in the length of hospital stay in those assigned to after-discharge CR strategy [4 days (3-5) versus 7 days (5-9); p = 0.001]. At 12-month of follow-up, no differences were found in the occurrence of MACE, 7 (5.34%) patients in in-hospital CR and 4 (3.15%) in after-discharge CR strategy; (hazard ratio, 0.59; 95% confidence interval, 0.17 to 2.02; p = 0.397). CONCLUSIONS: In STEMI patients with MVD, an after-discharge CR strategy reduces the length of index hospitalization without an increased risk of MACE after 12 months of follow-up. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT04743154.

FGF23 as a Potential Pathophysiological Factor in Peripheral Arterial Disease Associated with Chronic Kidney Disease.

Fibroblast growth factor 23 (FGF23) levels are often elevated in chronic kidney disease (CKD). FGF23 and inflammation are common characteristics in CKD, and both are associated with worse disease progression and the occurrence of complications. The existence of an interaction between FGF23 and inflammation has been suggested, each of which influences the expression and activity of the other, leading to a vicious feedback loop with adverse outcomes, including cardiovascular disease and mortality. In this work, we determined circulating FGF23 levels in a group of patients with CKD stages 3 and 4 subjected to elective femoral endarterectomy due to established peripheral artery disease (PAD), a condition resulting from an athero-inflammatory process, and we studied its associations with different inflammatory markers and mediators. We evaluated its association with serum tumor necrosis factor (TNF)α, interleukin (IL) 6, and IL10, as well as with the gene expression levels of these parameters and A disintegrin and metalloproteinase domain-containing protein (ADAM) 17 in femoral vascular tissue and peripheral blood circulating cells (PBCCs). We also analyzed its association with serum concentrations of C-reactive protein (CRP), the systemic immune inflammation index (SII), and the neutrophil-to-lymphocyte ratio (NLR). Finally, we determined the vascular immunoreactivity of protein TNFα in a subgroup of patients. FGF23 concentrations were independently associated with circulating and PBCC mRNA levels of TNFα. Worst kidney function and diabetes were also found to be contributing to FGF23 levels. Patients with higher levels of FGF23 also had greater vascular immunoreactivity for TNFα.

Identification of consistent QTL and candidate genes associated with seed traits in common bean by combining GWAS and RNA-Seq.

KEY MESSAGE: Association analysis, colocation study with previously reported QTL, and differential expression analyses allowed the identification of the consistent QTLs and main candidate genes controlling seed traits. Common beans show wide seed variations in shape, size, water uptake, and coat proportion. This study aimed to identify consistent genomic regions and candidate genes involved in the genetic control of seed traits by combining association and differential expression analyses. In total, 298 lines from the Spanish Diversity Panel were genotyped with 4,658 SNP and phenotyped for seven seed traits in three seasons. Thirty-eight significant SNP-trait associations were detected, which were grouped into 23 QTL genomic regions with 1,605 predicted genes. The positions of the five QTL regions associated with seed weight were consistent with previously reported QTL. HCPC analysis using the SNP that tagged these five QTL regions revealed three main clusters with significantly different seed weights. This analysis also separated groups that corresponded well with the two gene pools described: Andean and Mesoamerican. Expression analysis was performed on the seeds of the cultivar 'Xana' in three seed development stages, and 1,992 differentially expressed genes (DEGs) were detected, mainly when comparing the early and late seed development stages (1,934 DEGs). Overall, 91 DEGs related to cell growth, signaling pathways, and transcriptomic factors underlying these 23 QTL were identified. Twenty-two DEGs were located in the five QTL regions associated with seed weight, suggesting that they are the main set of candidate genes controlling this character. The results confirmed that seed weight is the sum of the effects of a complex network of loci, and contributed to the understanding of seed phenotype control.

Levodopa-Induced Dyskinesias are Frequent and Impact Quality of Life in Parkinson's Disease: A 5-Year Follow-Up Study.

BACKGROUND: Levodopa-induced dyskinesias (LID) are frequent in Parkinson's disease (PD). OBJECTIVE: To analyze the change in the frequency of LID over time, identify LID related factors, and characterize how LID impact on patients' quality of life (QoL). PATIENTS AND METHODS: PD patients from the 5-year follow-up COPPADIS cohort were included. LID were defined as a non-zero score in the item "Time spent with dyskinesia" of the Unified Parkinson's Disease Rating Scale-part IV (UPDRS-IV). The UPDRS-IV was applied at baseline (V0) and annually for 5 years. The 39-item Parkinson's disease Questionnaire Summary Index (PQ-39SI) was used to asses QoL. RESULTS: The frequency of LID at V0 in 672 PD patients (62.4 ± 8.9 years old; 60.1% males) with a mean disease duration of 5.5 ± 4.3 years was 18.9% (127/672) and increased progressively to 42.6% (185/434) at 5-year follow-up (V5). The frequency of disabling LID, painful LID, and morning dystonia increased from 6.9%, 3.3%, and 10.6% at V0 to 17.3%, 5.5%, and 24% at V5, respectively. Significant independent factors associated with LID (P < 0.05) were a longer disease duration and time under levodopa treatment, a higher dose of levodopa, a lower weight and dose of dopamine agonist, pain severity and the presence of motor fluctuations. LID at V0 (ß = 0.073; P = 0.027; R2 = 0.62) and to develop disabling LID at V5 (ß = 0.088; P = 0.009; R2 = 0.73) were independently associated with a higher score on the PDQ-39SI. CONCLUSION: LID are frequent in PD patients. A higher dose of levodopa and lower weight were factors associated to LID. LID significantly impact QoL.

Implementation of a virtual community of practice to promote the empowerment of middle-aged people with multimorbidity: study protocol of a randomised controlled trial.

INTRODUCTION: Empowering people living with multimorbidity (multiple chronic conditions) to gain greater confidence in managing their health can enhance their quality of life. Education focused on self-management is a key tool for fostering patient empowerment and is mostly provided on an individual basis. Virtual communities of practice (VCoP) present a unique opportunity for online education in chronic condition self-management within a social context. This research aims to evaluate the effectiveness/cost-effectiveness of individualised, online self-management education compared with VCoP among middle-aged individuals living with multiple chronic conditions. METHODS AND ANALYSIS: People aged 30-60, living with ≥2 chronic conditions and receiving care in primary care (PC) centres and outpatient hospital-based clinics in Madrid and Canary Islands will enrol in an 18-month parallel-design, blinded (intervention assessment and data analysts), pragmatic (adhering to the intention-to-treat principle), individually randomised trial. The trial will compare two 12-month web-based educational offers of identical content; one delivered individually (control) and the other with online social interaction (VCoP, intervention). Using repeated measures mixed linear models, with the patient as random effect and allocation groups and time per group as fixed effects, we will estimate between-arm differences in the change in Patient Activation Measure from baseline to 12 months (primary endpoint), including measurements at 6-month and 18-month follow-up. Other outcomes will include measures of depression and anxiety, treatment burden, quality of life. In addition to a process evaluation of the VCoP, we will conduct an economic evaluation estimating the relative cost-effectiveness of the VCoP from the perspectives of both the National Health System and the Community. ETHICS AND DISSEMINATION: The trial was approved by Clinical Research Ethics Committees of Gregorio Marañón University Hospital in Madrid/Nuestra Señora Candelaria University Hospital in Santa Cruz de Tenerife. The results will be disseminated through workshops, policy briefs, peer-reviewed publications and local/international conferences. TRIAL REGISTRATION NUMBER: NCT06046326.

[Translated article] Current situation and evolution of the availability of drugs in the pediatric population in Spain.

OBJECTIVE: To analyze the characteristics of the new medicines approved in the pediatric population in the last 3 years, both those with studies only in the pediatric population and those that extend their indication in this population group, as well as the current situation in relation to their marketing and financing. METHODS: Descriptive observational study of all drugs that include an indication in the pediatric population in Spain (by extension of the indications of drugs already authorized or because they are new drugs that already include an indication in this population group), from January 2019 to March 2022. RESULTS: During the study period, 129 drugs included their indication in the pediatric population. 13.9% of them are not marketed, 46.5% are in a situation of non-financing, under study or without a request for financing, and 4.6% are financed for a specific pediatric subpopulation. 52.7% are original drugs, 4.7% are generic, 38.8% are biological, 3.8% are biosimilar, and 17.8% are orphan drugs. 57.36% of these medicines obtain the pediatric indication due to extension of the indication and 42.64% obtain it because they are new medicines that already include their studies in the pediatric population. CONCLUSIONS: Drugs with authorized indications are increasingly available in the pediatric population and the trend is to extend the indication of authorized drugs to the adult population. However, barriers in terms of financing and marketing need to be expedite and overcome to facilitate access to them.

Exploring the atypia of undetermined significance: Malignant ratio, ThyroSeq v3 positive call rate, molecular-derived risk of malignancy, and risk of malignancy as possible quality metric tools in thyroid cytology.

BACKGROUND: The atypia of undetermined significance (AUS) category is heterogeneous, leading to variations in its use. To prevent excessive usage, the AUS rate should be ≤10%. Although this recommendation aims to maintain diagnostic quality, it lacks supporting data. The AUS:Malignant (AUS:M) ratio has been proposed as a metric tool to evaluate AUS use. Furthermore, integrating ThyroSeq v3 (TSV3) positive call rate (PCR) and the molecular-derived risk of malignancy (MDROM) have been put forward as performance improvement tools. The authors reviewed their AUS:M ratios, TSV3 PCR, MDROM, and ROM. METHODS: Thyroid aspirates evaluated in the laboratory (from August 2022 to September 2023) by seven cytopathologists (CPs) were identified. AUS:M ratio, MDROM, ROM, and TSV3 PCR results for the laboratory and each CP were recorded and analyzed. RESULTS: A total of 2248 aspirates were identified (462 AUS and 80 malignant). The AUS:M ratio for the laboratory was 5.8 (CPs range, 2.8 to 7.3). The TSV3 PCR for the laboratory was 23% (CPs range, 11% to 41%). The MDROM for the laboratory was 19% (CPs range, 9% to 31%), whereas the ROM was 36% (CPs range, 29% to 50%). Linear regression analysis of AUS:M ratio versus TSV3 PCR and MDROM demonstrated a moderate positive correlation but a weak negative correlation to the ROM. Deviations from established targets were attributed to multiple factors. CONCLUSION: The findings of this study underscore the importance of using a combination of metrics to evaluate diagnostic practices. By dissecting the practice patterns of each CP, the authors can measure different aspects of their performance and provide individualized feedback.

Clinical value of questionnaires & physical tests for patellofemoral pain: Validity, reliability and predictive capacity.

OBJECTIVES: To determine the most appropriate method of functional assessment for "patellofemoral pain" (PFP)/"chondromalacia patella" for its diagnostic value, (validity, reliability, sensitivity, specificity, predictive value and clinical applicability); to outline initial interpretations of the questionnaires and their appropriateness, through the cut-off points determined in their scores based on physical test and Magnetic Resonance Imaging (MRI); to establish which methods should be used in conjunction with each other to obtain clinical diagnoses that are robust effective and efficient. METHODS: (1)Intra- and inter-observer reliability and of the relationship among PFP questionnaires/physical tests validated. (2)Predictive capacity of the questionnaires. Subject: 113 knees with PFP, assessed using "Knee-injury-and-Osteoarthritis Outcome-Score-for-Patellofemoral-pain-and-osteoarthritis" (KOOS-PF), "Kujala-Patellofemoral-Score" (KPS), "Victorian-Institute-of-Sports-Assessment-for-Patellar-tendons-questionnaire" (VISA-P), and the physical tests: "patellar-palpation", "patellar-tilt", "patellar-apprehension", "Clarke" and "squat". RESULTS: Questionnaires correlations themselves was 0.78

[Early cortical atrophy in REM sleep behavior disorder]. / Atrofia cortical precoz en el trastorno de conducta del sueño REM.

INTRODUCTION: The presence of cortical atrophy (focal or diffuse) prior to the development of symptoms of cognitive impairment could predict the earliest cases of neurodegenerative disease in patients with REM sleep behavior disorder (RSBD). We reviewed the usefulness of cranial CT and MRI as early markers of cortical atrophy in patients with RSBD at our center. PATIENTS AND METHODS: Retrospective observational descriptive analysis of patients diagnosed with RSBD from October 2012 to October 2022. All with cranial CT or MRI, evaluated by a neuroradiologist. RESULTS: 54 patients were included, 21 women (38.88%), 33 men (61.12%), mean age at diagnosis of RSBD: 69.04±12.625 years. Of the 54 patients, 44 (81.48%) had imaging tests consistent with their age, and 10 had atrophy greater than expected for their age. Of the 54 patients, 21 (38.88%) with a diagnosis of neurodegenerative disease, 33 (61.12%) persist as idiopathic, almost all with more than 5years of evolution (range of 1 to 10years of evolution without diagnosis). Of the 10 (18.52%) patients with greater atrophy, all were diagnosed with neurodegenerative disease (8 in 1year, 2 in 8years). CONCLUSIONS: Almost half of our series have developed a neurodegenerative disease in the first 10years of evolution. The majority of them presented global cortical atrophy measured by the GCA scale in the first year of diagnosis, without other neurological symptoms. Patients who did not show cortical atrophy at diagnosis have not yet developed the neurodegenerative disease in 10years of evolution. In our experience, the absence of cortical atrophy on cranial MRI or CT (measured by scales such as GCA) at the diagnosis of RSBD seems to predict slower progression cases. These data should be corroborated with larger series.