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1.
Artículo en Inglés | MEDLINE | ID: mdl-37862223

RESUMEN

OBJECTIVES: Shoulder pain is common but current clinical classification has limited utility. We aimed to determine whether groups of ultrasound-based shoulder pathologies exist and to evaluate outcomes according to identified groups and individual pathologies. METHODS: Prospective study of a community-based cohort with shoulder pain referred for their first ultrasound scan at a single radiology unit, with subsequent routine clinical care. Patient-reported outcomes were collected at baseline, 2 weeks and 6 months; standardised ultrasound reporting was employed. Latent class analysis (LCA) identified ultrasound pathology-based groups. Multiple linear regression analysis explored associations between baseline pathologies, subsequent treatment and shoulder pain and disability index (SPADI). Short-term response to corticosteroid injections was investigated. RESULTS: Of 500 participants (mean age 53.6; 52% female), 330 completed follow-up. LCA identified 4 groups: bursitis with (33%) or without (27%) acromioclavicular joint degeneration, rotator cuff tear (21%), no bursitis/tear (19%). Total SPADI was higher at baseline for cuff tears (mean 55.1 vs 49.7-51.3; overall p= 0.005), but accounting for this, groups did not differ at 6 months (43.5 vs 38.5-40.5; p= 0.379). Baseline SPADI was the only predictor of 6-month SPADI retained by penalised modelling; neither LCA-derived US groups nor individual pathologies were selected. Response to baseline injection at week 2 did not differ between groups (mean SPADI 40.1-43.8; p= 0.423). CONCLUSION: Ultrasound-based classification (groups or individual pathologies) of shoulder pain did not predict medium-term outcomes using current treatments. The role of routine diagnostic ultrasound for shoulder pain needs consideration; it may be useful if evidence-based therapies for specific pathologies are established.

2.
Cancer Chemother Pharmacol ; 92(4): 325-328, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37452859

RESUMEN

BACKGROUND: Dubin-Johnson syndrome is a rare benign autosomal recessive condition that causes an isolated increase of conjugated bilirubin in the serum. Impaired biliary excretion is due to mutation in the multiple drug-resistance protein 2 gene (MRP2). CASE PRESENTATION: We describe the case of a 4-year-old girl being treated for acute lymphoblastic leukaemia who had a history of conjugated hyperbilirubinaemia and persistently elevated bilirubin levels on initiation of chemotherapy. During treatment for leukaemia, she was diagnosed with Dubin-Johnson syndrome for the underlying condition. Following administration of vincristine at the recommended dose of 1.5 mg/m2, an abnormally high vincristine exposure was observed (AUC > 200 µg/L*h), approximately 3 times higher than previously reported exposures in a comparable clinical setting. Vincristine dose reductions were applied on subsequent cycles of treatment and resulted in markedly reduced drug exposures, within the normal target range. CONCLUSION: This case provided a rare opportunity to assess the impact of MRP2 mutations associated with Dubin-Johnson syndrome on the pharmacokinetics of vincristine and strongly indicates that a marked dose reduction should be recommended. Clinicians should be made aware of the potential for altered drug disposition for agents such as vincristine in patients with this rare genetic condition.


Asunto(s)
Ictericia Idiopática Crónica , Leucemia-Linfoma Linfoblástico de Células Precursoras , Femenino , Humanos , Niño , Preescolar , Ictericia Idiopática Crónica/tratamiento farmacológico , Ictericia Idiopática Crónica/genética , Ictericia Idiopática Crónica/complicaciones , Vincristina , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Proteína 2 Asociada a Resistencia a Múltiples Medicamentos , Bilirrubina/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética
3.
J Infect ; 87(3): 230-241, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37331429

RESUMEN

BACKGROUND: This was the first study to investigate the reactogenicity and immunogenicity of heterologous or fractional second dose COVID-19 vaccine regimens in adolescents. METHODS: A phase II, single-blind, multi-centre, randomised-controlled trial recruited across seven UK sites from September to November 2021, with follow-up visits to August 2022. Healthy 12-to-16 years olds were randomised (1:1:1) to either 30 µg BNT162b2 (BNT-30), 10 µg BNT162b2 (BNT-10), or NVX-CoV2373 (NVX), 8 weeks after a first 30 µg dose of BNT162b2. The primary outcome was solicited systemic reactions in the week following vaccination. Secondary outcomes included immunogenicity and safety. 'Breakthrough infection' analyses were exploratory. FINDINGS: 148 participants were recruited (median age 14 years old, 62% female, 26% anti-nucleocapsid IgG seropositive pre-second dose); 132 participants received a second dose. Reactions were mostly mild-to-moderate, with lower rates in BNT-10 recipients. No vaccine-related serious adverse events occurred. Compared to BNT-30, at 28 days post-second dose anti-spike antibody responses were similar for NVX (adjusted geometric mean ratio [aGMR]) 1.09 95% confidence interval (CI): 0.84, 1.42] and lower for BNT-10 (aGMR 0.78 [95% CI: 0.61, 0.99]). For Omicron BA.1 and BA.2, the neutralising antibody titres for BNT-30 at day 28 were similar for BNT-10 (aGMR 1.0 [95% CI: 0.65, 1.54] and 1.02 [95% CI: 0.71, 1.48], respectively), but higher for NVX (aGMR 1.7 [95% CI: 1.07, 2.69] and 1.43 [95% CI: 0.96, 2.12], respectively). Compared to BNT-30, cellular immune responses were greatest for NVX (aGMR 1.73 [95% CI: 0.94, 3.18]), and lowest for BNT-10 (aGMR 0.65 [95% CI: 0.37, 1.15]) at 14 days post-second dose. Cellular responses were similar across the study arms by day 236 post-second dose. Amongst SARS-CoV-2 infection naïve participants, NVX participants had an 89% reduction in risk of self-reported 'breakthrough infection' compared to BNT-30 (adjusted hazard ratio [aHR] 0.11 [95% CI: 0.01, 0.86]) up until day 132 after second dose. BNT-10 recipients were more likely to have a 'breakthrough infection' compared to BNT-30 (aHR 2.14 [95% CI: 1.02, 4.51]) up to day 132 and day 236 post-second dose. Antibody responses at 132 and 236 days after second dose were similar for all vaccine schedules. INTERPRETATION: Heterologous and fractional dose COVID-19 vaccine schedules in adolescents are safe, well-tolerated and immunogenic. The enhanced performance of the heterologous schedule using NVX-CoV2373 against the Omicron SARS-CoV-2 variant suggests this mRNA prime and protein-subunit boost schedule may provide a greater breadth of protection than the licensed homologous schedule. FUNDING: National Institute for Health Research and Vaccine Task Force. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number registry: 12348322.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Humanos , Adolescente , Femenino , Masculino , Vacunas contra la COVID-19/efectos adversos , Vacuna BNT162 , Infección Irruptiva , COVID-19/prevención & control , SARS-CoV-2 , Método Simple Ciego , Vacunación , Inmunogenicidad Vacunal , Anticuerpos Antivirales , Anticuerpos Neutralizantes
4.
Cureus ; 15(2): e34908, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36938209

RESUMEN

Chondroblastomas are rare primary bone tumours typically affecting the epiphyses and less frequently the apophyses of the growing skeleton. Most cases are treated by intralesional curettage with or without local adjuvants and this technique can produce good long-term outcomes. Herein, we describe a case of chondroblastoma of the greater trochanter in a 12-year-old male child that was treated by intralesional curettage and grafting with calcium phosphate bone cement (Neocement Inject® P, Bioceramed, Loures, Portugal). A brief review of the literature is also presented.

5.
Gen Hosp Psychiatry ; 81: 57-67, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36805333

RESUMEN

BACKGROUND: The Medicare-enrolled population is heterogeneous across race, ethnicity, age, dual eligibility, and a breadth of chronic health, mental and behavioral health, and disability-related conditions, which may be differentially impacted by the COVID-19 pandemic. OBJECTIVE: To quantify changes in all-cause mortality prior-to and in the first year of the COVID-19 pandemic across Medicare's different sociodemographic and health-condition subpopulations. METHODS: This observational, population-based study used stratified bivariate regression to investigate Medicare fee-for-service subpopulation differences in pre-pandemic (i.e., 2019 versus 2016) and pandemic-related (2020 versus 2019) changes in all-cause mortality. RESULTS: All-cause mortality in the combined Medicare-Advantage (i.e., managed care) and fee-for-service beneficiary population improved by a relative 1% in the ten years that preceded the COVID-19 pandemic, but then escalated by a relative 15.9% in 2020, the pandemic's first year. However, a closer look at Medicare's fee-for-service subpopulations reveals critical differences. All-cause mortality had actually been worsening prior to the pandemic among most psychiatric and disability-related condition groups, all race and ethnicity groups except White Non-Hispanic, and Medicare-Medicaid dual-eligible (i.e., low-income) beneficiaries. Many of these groups then experienced all-cause mortality spikes in 2020 that were over twice that of the overall Medicare fee-for-service population. Of all 61 chronic health conditions studied, beneficiaries with schizophrenia were the most adversely affected, with all-cause mortality increasing 38.4% between 2019 and 2020. CONCLUSION: This analysis reveals subpopulation differences in all-cause mortality trends, both prior to and in year-one of the COVID-19 pandemic, indicating that the events of 2020 exacerbated preexisting health-related inequities.


Asunto(s)
COVID-19 , Medicare , Humanos , Estados Unidos/epidemiología , Anciano , Pandemias , Salud Mental , Enfermedad Crónica
6.
Lancet Rheumatol ; 5(10): e611-e621, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38251485

RESUMEN

BACKGROUND: Vascular fibrosis is a key manifestation of systemic sclerosis that leads to the narrowing of small and medium arteries, causing vascular clinical manifestations including digital ulcers and pulmonary arterial hypertension. We investigated the potential of the MRI-based Digital Artery Volume Index (DAVIX) as a surrogate outcome measure of vascular fibrosis by using it to quantify and predict the burden of digital ulcer disease in patients with systemic sclerosis. METHODS: Two independent cohorts of patients participating in the prospective observational study STRIKE were consecutively enrolled from the Scleroderma Clinic of the Leeds Teaching Hospitals Trust, Leeds, UK. Eligible patients were aged 18 years or older and fulfilled the very early diagnosis of systemic sclerosis (VEDOSS) or the 2013 American College of Rheumatology (ACR)-European Alliance of Associations for Rheumatology (EULAR) systemic sclerosis classification criteria. DAVIX was calculated as the percentage mean of the ratio of digital artery volume to finger volume in the four fingers of the dominant hand. Data were collected at baseline and 12-month follow-up, and the primary outcome was the presence of digital ulcers at 12-month follow-up. FINDINGS: Between Feb 7, 2018, and April 11, 2022, we included 85 patients in the exploratory cohort and 150 in the validation cohort. In the exploratory cohort, the mean age was 54·5 years (SD 11·6), 75 (88%) of 85 patients were women, ten (12%) were men, and 69 (82%) were White. In the validation cohort, the mean age was 53·5 years (SD 13·8), 136 (91%) of 150 patients were women, 14 (9%) were men, and 127 (85%) were White. In the exploratory cohort, DAVIX was significantly lower in patients with previous or active digital ulcers (0·34% [IQR 0·16-0·69]) than in those without digital ulcer disease (0·65% [0·42-0·88]; p=0·015); this finding was substantiated in the validation cohort (0·43% [0·20-0·73] vs 0·73% [0·53-0·97]; p<0·0001). Patients who developed new digital ulcers during 12-month follow-up had a lower DAVIX (0·23% [0·10-0·66]) than those who did not (0·65% [0·45-0·91]; p=0·0039). DAVIX was negatively correlated with disease duration (r=-0·415; p<0·0001), the ratio of forced vital capacity to the diffusing capacity of the lungs for carbon monoxide (r=-0·334; p=0·0091), nailfold capillaroscopy pattern (r=-0·447; p<0·0001), and baseline modified Rodnan skin score (r=-0·305; p=0·014) and was positively correlated with the diffusing capacity of carbon monoxide (r=0·368; p=0·0041). DAVIX was negatively correlated with change in score on the Scleroderma Health Assessment Questionnaire-Disability Index (r=-0·308; p=0·024), Visual Analogue Scale (VAS) Raynaud's (r=-0·271; p=0·044), and VAS digital ulcers (r=-0·291; p=0·044). INTERPRETATION: DAVIX is a promising surrogate outcome measure of digital ulcer disease in patients with systemic sclerosis. The ability of DAVIX to non-invasively predict future digital ulcers and worsening of patient-reported outcomes could aid patient enrichment and stratification in clinical trials. Clinically, DAVIX could offer insights into the assessment of vascular activity. The sensitivity of DAVIX to change over time and with treatment will establish its value as an imaging outcome measure of vascular disease. FUNDING: National Institute for Health Research Biomedical Research Centre and University of Leeds Industry Engagement Accelerator Fund.


Asunto(s)
Esclerodermia Localizada , Esclerodermia Sistémica , Úlcera Cutánea , Masculino , Humanos , Femenino , Persona de Mediana Edad , Monóxido de Carbono , Estudios Prospectivos , Esclerodermia Sistémica/complicaciones , Arteria Cubital , Imagen por Resonancia Magnética , Evaluación de Resultado en la Atención de Salud , Fibrosis
7.
Br J Radiol ; 95(1136): 20220278, 2022 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-35704452

RESUMEN

The detailed anatomy of the rectus femoris and corresponding injury appearances were first described in 1995. Since then, there has been little published to change our understanding of this complex anatomical area. More recent anatomical dissection work in 2004 and 2006 alluded to the presence of an altered configuration of the proximal tendon anatomy. Whilst widely accepted that the proximal rectus femoris muscle has two distinct tendon slips, the authors in 2006 described a third separate tendon slip arising from the anterior femoral capsule and this has been widely termed the 'capsular head'. We provide evidence that imaging features corroborate this revised anatomical concept. Whilst the clinical relevance of these findings is yet to be established, it remains important that our understanding of the radiological anatomy in this area advances with the forward growth of imaging clarity. In this review, we revisit anatomical concepts and present atypical injury cases that may be explained by the presence of a separate capsular head.


Asunto(s)
Músculo Cuádriceps , Tendones , Atletas , Diagnóstico por Imagen , Fémur , Humanos , Músculo Cuádriceps/anatomía & histología , Músculo Cuádriceps/diagnóstico por imagen , Tendones/anatomía & histología
8.
Br J Radiol ; 95(1132): 20210940, 2022 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-35148205

RESUMEN

OBJECTIVES: To validate reliability of slice-encoding for metal artefact correction (SEMAC)-MRI findings in prosthesis loosening detection by comparing them to surgical outcomes (gold standard) in symptomatic patients following hip arthroplasties. To evaluate periprosthetic anatomical structures in symptomatic patients to identify an alternative cause of hip symptoms. METHODS: We prospectively followed 47 symptomatic patients (55 hips, 39 painful hips - group P and 16 control hips - group C) at our institution from 2011 to 2016. We acquired 1.5 T MRI conventional and SEMAC-MRI images for all patients. Two consultants scored MRI for osteolysis and marrow oedema zone-wise using predefined signal characteristics and settled scoring variations by consensus. We used Spearman Rank-Order Correlation for correlation analysis and used OMERACT (Outcome Measures in Rheumatology) filter pillars to validate SEMAC-MRI findings. RESULTS: Eleven patients needed revision surgery, all from group P. None from group C required revision surgery. Remaining 28 hips in the group P were managed conservatively pain completely resolved in 21 hips, eight hips had trochanteric bursitis, eight had extraarticular cause and the remaining five hips had spontaneous pain resolution. We found moderate-to-weak correlation between SEMAC-MRI findings for prosthesis loosening and revision surgery outcomes. Sensitivity, Specificity, PPV and NPV in Group P were (72.7, 64.3, 44.4, 85.7%) in T1W-SEMAC, (90.9, 46.4, 40.0, 92.9%) in STIR-SEMAC and (36.3, 78.5, 40.0, 75.8%) in PDW-SEMAC. CONCLUSION: Negative SEMAC-MRI results can effectively exclude prosthesis loosening confirmed on revision surgery and SEMAC-MRI can detect alternative cause of hip pain accurately. ADVANCES IN KNOWLEDGE: Negative SEMAC-MRI in painful THA patients can effectively exclude prosthesis loosening as a cause.


Asunto(s)
Artroplastia de Reemplazo de Cadera , Prótesis de Cadera , Artralgia , Artroplastia de Reemplazo de Cadera/efectos adversos , Artefactos , Prótesis de Cadera/efectos adversos , Humanos , Aumento de la Imagen/métodos , Imagen por Resonancia Magnética/métodos , Metales , Estudios Prospectivos , Falla de Prótesis , Reoperación , Reproducibilidad de los Resultados
9.
Pediatr Neurol ; 128: 20-24, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-35032886

RESUMEN

BACKGROUND: We aimed to describe the clinical presentation, risk of bleeding and recurrent thrombosis, and perioperative anticoagulant management of children with cerebral venous thrombosis (CVT) and an associated head or neck infection. METHODS: In this subgroup analysis of the EINSTEIN-Jr study, we included children with CVT and an associated head or neck infection who received therapeutic anticoagulants with either low-molecular-weight heparin (with or without subsequent vitamin K antagonists) or rivaroxaban for a period of 3 months. Analyses are descriptive. RESULTS: Of 74 included children, 59 (80%) had otomastoiditis, 21 (28%) a central nervous system infection, 18 (24%) sinusitis, and 9 (12%) another upper respiratory tract infection; 29 (39%) had infection of multiple regions of the head or neck. All 74 children received antibiotics and therapeutic anticoagulants; 41 (55%) underwent surgery, of whom 34 were diagnosed with CVT preoperatively. Anticoagulation was started before surgery in 12 children and interrupted 0-1 days prior to surgery. Anticoagulation was (re)started in all 34 children at a median of 1 day (interquartile range: 0-1) postoperatively, in therapeutic doses in 94%. Overall, one child (1%, 95% confidence interval: 0-7) had recurrent thrombosis, and one (1%, 95% confidence interval: 0-7) had major bleeding; neither was associated with surgery. At 3 months, no children had died, 3 (4%) had persistent focal neurologic deficits, and 2 (3%) had impaired vision. CONCLUSIONS: Children with CVT and an associated head or neck infection administered therapeutic anticoagulants generally had low risks of bleeding and thrombotic complications, including those who had surgical interventions with delay or interruption of anticoagulation.


Asunto(s)
Anticoagulantes/uso terapéutico , Trombosis Intracraneal/tratamiento farmacológico , Trombosis Intracraneal/microbiología , Trombosis de la Vena/tratamiento farmacológico , Trombosis de la Vena/microbiología , Infecciones del Sistema Nervioso Central/complicaciones , Niño , Preescolar , Estudios de Cohortes , Femenino , Heparina de Bajo-Peso-Molecular/uso terapéutico , Humanos , Masculino , Mastoiditis/complicaciones , Rivaroxabán/uso terapéutico , Sinusitis/complicaciones
10.
J Ultrasound ; 25(1): 115-119, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33502663

RESUMEN

The rotator interval (RI) is a critical but complex anatomical structure for which musculoskeletal ultrasound provides an excellent imaging evaluation. In the patients with restricted and painful movements, the RI may not be visualised optimally as the conventional 'Modified Crass' positions may not be achievable. It can also be difficult to optimally evaluate the anterior supraspinatus and subscapularis tendons in such patients. We describe a simple shoulder position obviating need of pronounced supraspinatus stretch for better evaluation of the rotator interval and adjoining rotator cuff structures.


Asunto(s)
Articulación del Hombro , Hombro , Humanos , Manguito de los Rotadores/diagnóstico por imagen , Hombro/diagnóstico por imagen , Articulación del Hombro/diagnóstico por imagen , Tendones/diagnóstico por imagen , Ultrasonografía
11.
AJR Am J Roentgenol ; 217(6): 1390-1400, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34161130

RESUMEN

Rotator cuff tears are the most likely source of shoulder pain in adults and may cause protracted disability. Management of rotator cuff tears is associated with considerable costs. Accurate diagnosis can guide surgical planning and help achieve a favorable clinical outcome. Although radiography remains the initial imaging test for shoulder injury, the roles of MRI and ultrasound (US) as first-line imaging after radiography are evolving. This article leverages current literature and the practical experience of subspecialty musculoskeletal radiologists from different institutions in describing a practical approach to imaging rotator cuff pathology. Both MRI and US are accurate for identifying rotator cuff tears, but each has advantages and shortcomings. As both modalities currently represent reasonable first-line approaches, considerable practice variation has evolved. Given the low cost of US, imagers should strive to optimize the quality of shoulder US examinations and to build referrer confidence in this modality. The roles of direct CT and MR arthrography as well as imaging evaluation of the postoperative rotator cuff are also considered. Through careful selection among the available imaging modalities and optimal performance and interpretation of such examinations, radiologists can positively contribute to the diagnosis and treatment of patients with rotator cuff injuries.


Asunto(s)
Imagen por Resonancia Magnética/métodos , Lesiones del Manguito de los Rotadores/diagnóstico por imagen , Ultrasonografía/métodos , Humanos , Manguito de los Rotadores/diagnóstico por imagen
12.
Br J Radiol ; 94(1121): 20210198, 2021 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-33793317

RESUMEN

There has been some concern expressed by UK regulator, the Professional Standards Authority regarding the risks arising from Independent sonographer practices. The Professional Standards Authority presented evidence demonstrating that there are instances of harm occurring because of errors made by non-radiologists performing musculoskeletal ultrasound (MSKUS), particularly MSKUS-guided interventions. This document summarises British Society of Skeletal Radiologists position for Musculoskeletal use of ultrasound in UK, representing the agreed consensus of experts from the British Society of Skeletal Radiologists Ultrasound committee. The purpose of this position statement is to review the current practices affecting the delivery of MSKUS. Recommendations are given for education and training, audit and clinical governance, reporting, and medicolegal issues.


Asunto(s)
Consenso , Radiología/normas , Sociedades Médicas/normas , Ultrasonido/educación , Ultrasonografía/normas , Humanos , Errores Médicos , Sistema Musculoesquelético/diagnóstico por imagen , Ultrasonografía Intervencional/normas , Reino Unido
14.
Blood Adv ; 4(24): 6250-6258, 2020 12 22.
Artículo en Inglés | MEDLINE | ID: mdl-33351120

RESUMEN

Anticoagulant treatment of pediatric cerebral venous thrombosis has not been evaluated in randomized trials. We evaluated the safety and efficacy of rivaroxaban and standard anticoagulants in the predefined subgroup of children with cerebral venous thrombosis (CVT) who participated in the EINSTEIN-Jr trial. Children with CVT were randomized (2:1), after initial heparinization, to treatment with rivaroxaban or standard anticoagulants (continued on heparin or switched to vitamin K antagonist). The main treatment period was 3 months. The primary efficacy outcome, symptomatic recurrent venous thromboembolism (VTE), and principal safety outcome, major or clinically relevant nonmajor bleeding,were centrally evaluated by blinded investigators. Sinus recanalization on repeat brain imaging was a secondary outcome. Statistical analyses were exploratory. In total, 114 children with confirmed CVT were randomized. All children completed the follow-up. None of the 73 rivaroxaban recipients and 1 (2.4%; CVT) of the 41 standard anticoagulant recipients had symptomatic, recurrent VTE after 3 months (absolute difference, 2.4%; 95% confidence interval [CI], -2.6% to 13.5%). Clinically relevant bleeding occurred in 5 (6.8%; all nonmajor and noncerebral) rivaroxaban recipients and in 1 (2.5%; major [subdural] bleeding) standard anticoagulant recipient (absolute difference, 4.4%; 95% CI, -6.7% to 13.4%). Complete or partial sinus recanalization occurred in 18 (25%) and 39 (53%) rivaroxaban recipients and in 6 (15%) and 24 (59%) standard anticoagulant recipients, respectively. In summary, in this substudy of a randomized trial with a limited sample size, children with CVT treated with rivaroxaban or standard anticoagulation had a low risk of recurrent VTE and clinically relevant bleeding. This trial was registered at clinicaltrials.gov as #NCT02234843.


Asunto(s)
Tromboembolia Venosa , Trombosis de la Vena , Anticoagulantes/efectos adversos , Niño , Hemorragia , Humanos , Rivaroxabán/efectos adversos , Trombosis de la Vena/tratamiento farmacológico
15.
J Clin Invest ; 130(10): 5272-5286, 2020 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-32865517

RESUMEN

Human natural killer cell deficiency (NKD) arises from inborn errors of immunity that lead to impaired NK cell development, function, or both. Through the understanding of the biological perturbations in individuals with NKD, requirements for the generation of terminally mature functional innate effector cells can be elucidated. Here, we report a cause of NKD resulting from compound heterozygous mutations in minichromosomal maintenance complex member 10 (MCM10) that impaired NK cell maturation in a child with fatal susceptibility to CMV. MCM10 has not been previously associated with monogenic disease and plays a critical role in the activation and function of the eukaryotic DNA replisome. Through evaluation of patient primary fibroblasts, modeling patient mutations in fibroblast cell lines, and MCM10 knockdown in human NK cell lines, we have shown that loss of MCM10 function leads to impaired cell cycle progression and induction of DNA damage-response pathways. By modeling MCM10 deficiency in primary NK cell precursors, including patient-derived induced pluripotent stem cells, we further demonstrated that MCM10 is required for NK cell terminal maturation and acquisition of immunological system function. Together, these data define MCM10 as an NKD gene and provide biological insight into the requirement for the DNA replisome in human NK cell maturation and function.


Asunto(s)
Células Asesinas Naturales/inmunología , Proteínas de Mantenimiento de Minicromosoma/genética , Mutación , Enfermedades de Inmunodeficiencia Primaria/genética , Enfermedades de Inmunodeficiencia Primaria/inmunología , Alelos , Puntos de Control del Ciclo Celular/genética , Puntos de Control del Ciclo Celular/inmunología , Diferenciación Celular/genética , Diferenciación Celular/inmunología , Línea Celular , Codón sin Sentido , Daño del ADN/genética , Daño del ADN/inmunología , Resultado Fatal , Femenino , Técnicas de Silenciamiento del Gen , Heterocigoto , Humanos , Células Madre Pluripotentes Inducidas/inmunología , Células Madre Pluripotentes Inducidas/metabolismo , Células Madre Pluripotentes Inducidas/patología , Lactante , Células Asesinas Naturales/metabolismo , Células Asesinas Naturales/patología , Masculino , Proteínas de Mantenimiento de Minicromosoma/metabolismo , Modelos Inmunológicos , Mutación Missense , Linaje , Enfermedades de Inmunodeficiencia Primaria/patología
16.
J Thromb Haemost ; 18(7): 1672-1685, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32246743

RESUMEN

BACKGROUND: Recently, the randomized EINSTEIN-Jr study showed similar efficacy and safety for rivaroxaban and standard anticoagulation for treatment of pediatric venous thromboembolism (VTE). The rivaroxaban dosing strategy was established based on phase 1 and 2 data in children and through pharmacokinetic (PK) modeling. METHODS: Rivaroxaban treatment with tablets or the newly developed granules-for-oral suspension formulation was bodyweight-adjusted and administered once-daily, twice-daily, or thrice-daily for children with bodyweights of ≥30, ≥12 to <30, and <12 kg, respectively. Previously, these regimens were confirmed for children weighing ≥20 kg but only predicted in those <20 kg. Based on sparse blood sampling, the daily area under the plasma concentration-time curve [AUC(0-24)ss ] and trough [Ctrough,ss ] and maximum [Cmax,ss ] steady-state plasma concentrations were derived using population PK modeling. Exposure-response graphs were generated to evaluate the potential relationship of individual PK parameters with recurrent VTE, repeat imaging outcomes, and bleeding or adverse events. A taste-and-texture questionnaire was collected for suspension-recipients. RESULTS: Of the 335 children (aged 0-17 years) allocated to rivaroxaban, 316 (94.3%) were evaluable for PK analyses. Rivaroxaban exposures were within the adult exposure range. No clustering was observed for any of the PK parameters with efficacy, bleeding, or adverse event outcomes. Results were similar for the tablet and suspension formulation. Acceptability and palatability of the suspension were favorable. DISCUSSION: Based on this analysis and the recently documented similar efficacy and safety of rivaroxaban compared with standard anticoagulation, we conclude that bodyweight-adjusted pediatric rivaroxaban regimens with either tablets or suspension are validated and provide for appropriate treatment of children with VTE.


Asunto(s)
Rivaroxabán , Tromboembolia Venosa , Adolescente , Adulto , Anticoagulantes/efectos adversos , Coagulación Sanguínea , Niño , Preescolar , Hemorragia/inducido químicamente , Humanos , Lactante , Recién Nacido , Rivaroxabán/efectos adversos , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/tratamiento farmacológico
17.
Mod Rheumatol ; 30(4): 617-625, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31314615

RESUMEN

Objectives: To investigate muscle stiffness and strength in rheumatoid arthritis patients compared to healthy controls.Methods: A sample of 80 RA patients from three discrete groups: 1 - newly diagnosed treatment-naïve RA (n = 29), 2 - active RA for at least 1 year (n = 18) and 3 - in remission RA for at least 1 year (n = 33), was compared to 40 healthy controls. Shear wave velocity (SWV) was measured using shear wave elastography as a surrogate for tissue stiffness in multiple muscles. All participants performed isometric grip strength, timed get-up-and-go test, 30-s chair stand test and isokinetic knee extension/flexion (60°/s). The difference in SWV amongst the groups was tested using one-way ANOVA, and the correlation between SWV and muscle strength results were calculated using Pearson's coefficients.Results: The mean age ± SD was 61.2 ± 12.8 for RA patients and 61.5 ± 10.5 years for controls. SWV was not significantly different amongst the groups on all muscles (p > .05). In comparison to controls, the new and active RA groups showed a significantly lower isokinetic strength by -29% (p = .013) and -28% (p = .040), fewer chair stands by -28% (p = .001) and -44% (p < .001), longer walking times by -25% (p = .025) and -30% (p = .001), respectively, and weaker grip strength by -45% for both (p < .001). The muscle strength in the remission RA groups was not significantly lower, except in the isokinetic knee strength (-21%; p = .027). The correlations between SWE and the muscle assessment results were weak and insignificant (r < 0.30; p > .05).Conclusion: Significant muscle weakness was demonstrated in patients with RA disease. However, muscle stiffness was normal and not associated with muscle strength.


Asunto(s)
Artritis Reumatoide/diagnóstico por imagen , Diagnóstico por Imagen de Elasticidad , Debilidad Muscular/diagnóstico por imagen , Adulto , Anciano , Artritis Reumatoide/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fuerza Muscular , Debilidad Muscular/patología , Músculo Esquelético/diagnóstico por imagen
18.
Lancet Haematol ; 7(1): e18-e27, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31699660

RESUMEN

BACKGROUND: Treatment of venous thromboembolism in children is based on data obtained in adults with little direct documentation of its efficacy and safety in children. The aim of our study was to compare the efficacy and safety of rivaroxaban versus standard anticoagulants in children with venous thromboembolism. METHODS: In a multicentre, parallel-group, open-label, randomised study, children (aged 0-17 years) attending 107 paediatric hospitals in 28 countries with documented acute venous thromboembolism who had started heparinisation were assigned (2:1) to bodyweight-adjusted rivaroxaban (tablets or suspension) in a 20-mg equivalent dose or standard anticoagulants (heparin or switched to vitamin K antagonist). Randomisation was stratified by age and venous thromboembolism site. The main treatment period was 3 months (1 month in children <2 years of age with catheter-related venous thromboembolism). The primary efficacy outcome, symptomatic recurrent venous thromboembolism (assessed by intention-to-treat), and the principal safety outcome, major or clinically relevant non-major bleeding (assessed in participants who received ≥1 dose), were centrally assessed by investigators who were unaware of treatment assignment. Repeat imaging was obtained at the end of the main treatment period and compared with baseline imaging tests. This trial is registered with ClinicalTrials.gov, number NCT02234843 and has been completed. FINDINGS: From Nov 14, 2014, to Sept 28, 2018, 500 (96%) of the 520 children screened for eligibility were enrolled. After a median follow-up of 91 days (IQR 87-95) in children who had a study treatment period of 3 months (n=463) and 31 days (IQR 29-35) in children who had a study treatment period of 1 month (n=37), symptomatic recurrent venous thromboembolism occurred in four (1%) of 335 children receiving rivaroxaban and five (3%) of 165 receiving standard anticoagulants (hazard ratio [HR] 0·40, 95% CI 0·11-1·41). Repeat imaging showed an improved effect of rivaroxaban on thrombotic burden as compared with standard anticoagulants (p=0·012). Major or clinically relevant non-major bleeding in participants who received ≥1 dose occurred in ten (3%) of 329 children (all non-major) receiving rivaroxaban and in three (2%) of 162 children (two major and one non-major) receiving standard anticoagulants (HR 1·58, 95% CI 0·51-6·27). Absolute and relative efficacy and safety estimates of rivaroxaban versus standard anticoagulation estimates were similar to those in rivaroxaban studies in adults. There were no treatment-related deaths. INTERPRETATION: In children with acute venous thromboembolism, treatment with rivaroxaban resulted in a similarly low recurrence risk and reduced thrombotic burden without increased bleeding, as compared with standard anticoagulants. FUNDING: Bayer AG and Janssen Research & Development.


Asunto(s)
Anticoagulantes/uso terapéutico , Rivaroxabán/uso terapéutico , Tromboembolia Venosa/tratamiento farmacológico , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Factores de Riesgo
19.
Int J Rheum Dis ; 22(10): 1891-1899, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31364284

RESUMEN

AIM: To investigate muscle stiffness changes in patients treated for giant cell arteritis (GCA) with high-dose oral glucocorticoids. METHODS: Using ultrasound elastography, shear wave velocity (SWV) was measured in the quadriceps, hamstrings and biceps brachii muscles of 14 patients with GCA (4 male, mean age ± SD, 68.2 ± 4.3 years) within the first 2 weeks of initiating glucocorticoid treatment (baseline) and repeated after 3 and 6 months treatment. Muscle strength and performance tests were performed at each visit. Baseline measures were compared with those from 14 healthy controls. Linear mixed models were used to test for change in patient measures over time. RESULTS: At baseline, muscle SWV in patients was not significantly different from controls. With glucocorticoid treatment, there was a reduction in SWV in the leg but not the arm muscles. SWV decreased by a mean of 14% (range 8.3%-17.3%; P = .001) after 3 months and 18% (range 10.2%-25.3%; P < .001) after 6-months in the quadriceps and hamstrings during the resting position. The baseline, 3 and 6 months mean SWV (±SD) for the vastus lateralis were 1.62 ± 0.16 m/s, 1.40 ± 0.10 m/s and 1.31 ± 0.06 m/s, respectively (P < .001). In the patient group as a whole, there was no significant change in muscle strength. However, there were moderate correlations (r = .54-.69) between exhibiting weaker muscle strength at follow-up visits and a greater reduction in SWV. CONCLUSION: Glucocorticoid therapy in patients with GCA was associated with a significant reduction in proximal leg muscle stiffness during the first 6 months. Future research should study a larger sample of patients for a longer duration to investigate if diminished muscle stiffness precedes signs of glucocorticoid-induced myopathy.


Asunto(s)
Diagnóstico por Imagen de Elasticidad/métodos , Arteritis de Células Gigantes/tratamiento farmacológico , Fuerza Muscular/efectos de los fármacos , Músculo Esquelético/diagnóstico por imagen , Prednisolona/administración & dosificación , Administración Oral , Anciano , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Arteritis de Células Gigantes/diagnóstico , Arteritis de Células Gigantes/fisiopatología , Glucocorticoides/administración & dosificación , Humanos , Pierna , Masculino , Persona de Mediana Edad , Fuerza Muscular/fisiología , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/fisiopatología , Proyectos Piloto , Estudios Retrospectivos , Factores de Tiempo
20.
Semin Musculoskelet Radiol ; 23(3): 324-344, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31163506

RESUMEN

This article consists of a series of clinical cases presented during the ESSR Quiz session at the 25th Annual Meeting of the European Society of Musculoskeletal Radiology in Amsterdam 2018. The first section contains the clinical information and an initial set of images for each case. The second section reveals the answers along with additional imaging followed by a short discussion about the pathologic processes presented. This article provides self-assessment and at the same time refreshes the reader's knowledge about some common and not-so-common clinical conditions that a radiologist may encounter during clinical practice.


Asunto(s)
Enfermedades Óseas/diagnóstico por imagen , Diagnóstico por Imagen/métodos , Artropatías/diagnóstico por imagen , Enfermedades de la Columna Vertebral/diagnóstico por imagen , Adolescente , Adulto , Anciano , Niño , Europa (Continente) , Femenino , Antebrazo/diagnóstico por imagen , Humanos , Articulaciones/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Cuello/diagnóstico por imagen , Pelvis/diagnóstico por imagen , Radiología , Sociedades Médicas , Columna Vertebral/diagnóstico por imagen , Pared Torácica/diagnóstico por imagen
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