RESUMO
BACKGROUND: Teleguidance on portable devices opens the possibility of joint self-imaging in persons with hemophilia (PWH). AIMS: Determine the feasibility of patient self-imaging with/without teleguidance. METHODS: Adult PWH received ultrasound teaching including 11 views for hemarthrosis detection in ankles, elbows, and knees. The patients acquired five randomly selected views with the Butterfly/IQ probe without assistance at 2, 6-8 weeks, and 3-4 months later, followed by teleguidance. Image acquisition was timed, patients identified anatomic landmarks, and image quality was graded. Questionnaires assessed the imaging experience. Hemophilia Joint Health Score (HJHS) indicated arthropathy status. RESULTS: Of 132 PWH, 10 (median age 52 years) opted for study inclusion. Most had severe Hemophilia A, were white/non-Hispanic, with at least a high school degree and, overall, similar to the other 122 PWH. At 2 and 6 weeks after training, ~80% images were acquired correctly compared with 53% at 12 weeks. Accuracy of landmark recognition was ~55%. With teleguidance, all images were acquired correctly, with near-perfect image quality (P ≤ .01 compared with the 3-4 month time point). Median HJHS of scanned joints was 11.5 at each time point, demonstrating a similar spectrum of arthropathic changes. Median time of image acquisition was fast, and similar with or without teleguidance (median 01:04 [mm:ss] vs median 01:02), but differed slightly between arthropathic and non-arthropathic joints. Study participants and the imaging facilitator rated that it was easy to navigate mobile technology and acquire images with teleguidance. CONCLUSION: Mobile ultrasound with teleguidance for joint self-imaging is feasible and warrants further exploration.
Assuntos
Articulação do Cotovelo , Hemofilia A , Adulto , Humanos , Pessoa de Meia-Idade , Hemofilia A/complicações , Hemofilia A/diagnóstico por imagem , Projetos Piloto , Hemartrose/diagnóstico , Ultrassonografia/métodos , Articulações/diagnóstico por imagemRESUMO
OBJECTIVES: The Joint tissueActivity and Damage Exam (JADE) is a point-of-care (POC) musculoskeletal ultrasound (MSKUS) protocol for non-radiologists to evaluate hemophilic arthopathy. Our aim was to determine the consistency of cross-sectional analyses of direct tissue measurements (JADE protocol) and clinical Hemophilia Joint Health Score [HJHS] and functional joint assessments (arc) at three clinic visits. METHODS: We prospectively studied adults (n = 44) with hemophilia (A or B) of any severity and arthropathy at 3 North American sites. We assessed HJHS, total arc, and JADE parameters (bilateral elbows, ankles, and knees) at study entry, at ≈12-18 months, and at ≈24-36 months, and used MSKUS to evaluate painful episodes between study visits. JADE measurements included osteochondral alterations, cartilage thickness, and soft tissue expansion at sentinel positions. Associations between joint HJHS and total arc with each JADE variable were examined with random intercept models. RESULTS: At each visit increasing HJHS and decreasing total arc were associated in the expected direction with increasing length of OAs and soft tissue expansion in all joints, and decreasing cartilage thickness in the knee. However, HJHS associations with cartilage thickness were U-shaped for elbow and ankle (i.e. cartilage thinning and thickening). Associations between total arc and cartilage thickness followed a similar curve. (Near) normal levels of both joint parameters (HJHS and total arc) were associated with normal ranges of cartilage thickness. JADE views were also helpful to detect hemarthrosis in association with joint pains. CONCLUSIONS: POC MSKUS applying direct tissue measurements using the JADE protocol provided reproducible cross-sectional associations with joint health outcomes on three visits. These findings advance protocol validation and enable iterative adaptations resulting in JADE protocol version 2.
Assuntos
Hemofilia A , Adulto , Humanos , Hemofilia A/complicações , Hemofilia A/diagnóstico por imagem , Estudos Transversais , Hemartrose/complicações , Articulação do Joelho/diagnóstico por imagem , Artralgia/complicaçõesRESUMO
INTRODUCTION: Haemophilia patients experience painful joint episodes which may or may not be associated with haemarthrosis. We sought to validate a questionnaire developed by the Canadian Haemophilia Society using point-of-care musculoskeletal ultrasound (POC MSKUS) to confirm haemarthrosis. METHODS: The questionnaire comprised of 20 questions (10 each associated with haemarthrosis and arthritis pain) and was administered to adult haemophilia patients reporting to the Haemophilia Treatment Centre (University of California San Diego). We confirmed the presence (or absence) of haemarthrosis using POC MSKUS [Joint Activity and Damage Exam (JADE)]. We fitted univariate and multivariate generalized estimating equations to identify symptoms associated with haemarthrosis. RESULTS: We evaluated 79 painful episodes in 32 patients [median age = 38 years (range 21-74)]. POC MSKUS detected haemarthrosis in 36 (46%) episodes. The strongest predictor for haemarthrosis pain was 'like a balloon swelling with water' (odds ratio [OR] 2.88 [CI .68;12.10]); 'no feeling of sponginess with movement' (OR .24[CI .07;.76]) was the strongest for arthritic pain. We identified four questions with the strongest OR for differentiating haemarthrosis pain from arthritic pain to develop an algorithm for haemarthrosis prediction. Answering these questions in "yes/no" fashion yielded estimates of the probability of haemarthrosis CONCLUSION: Objective diagnosis of haemarthrosis by MSKUS facilitated the development of a symptom-based prediction tool for diagnosis of haemarthrosis. The tool requires further validation and will be particularly helpful in situations where MSKUS is not readily available.
Assuntos
Hemofilia A , Comportamento de Utilização de Ferramentas , Adulto , Idoso , Artralgia , Canadá , Hemartrose/diagnóstico por imagem , Hemartrose/etiologia , Hemofilia A/complicações , Hemofilia A/diagnóstico , Humanos , Pessoa de Meia-Idade , Dor/complicações , Adulto JovemRESUMO
INTRODUCTION: The reasons for the high prevalence of hypertension in persons with haemophilia (PWH) are poorly understood. AIM: To examine the roles of diabetes, Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV) in the etiology of hypertension for PWH. METHODS: Retrospective cross-sectional design. Adult PWH (n = 691) were divided into two groups: (A) free of diabetes, HCV and HIV; (B) with diabetes and/or HCV positivity and/or HIV positivity. Each group was matched by race and age with random samples from the general population of the US (National Health and Nutrition Examination Surveys, NHANES) and outpatients at the Veterans Affairs Medical Center (VAMC) in San Diego. Generalized additive models (GAMs) were fitted for graphical analysis of hypertension risk over the lifespan. RESULTS: In Group A, PWH had the highest prevalence of hypertension compared to NHANES and VAMC, especially in young adults. In Group B, diabetes increased the risk of hypertension for all three cohorts (PWH, NHANES and VAMC), especially for PWH. In PWH, hypertension risk was also increased by HIV, in NHANES by HCV, and in VAMC by HCV and HIV. CONCLUSION: Diabetes conferred the greatest risk of hypertension for all three cohorts. However, curves of hypertension in relation to age revealed that diabetes, HCV and HIV modulated hypertension risk differently in PWH. PWH experienced a disproportionally high risk increase with diabetes. Therefore, haemophilia care should include screening for hypertension and diabetes at a young age.
Assuntos
Diabetes Mellitus , Infecções por HIV , Hemofilia A , Hepatite C , Hipertensão , Veteranos , Adulto Jovem , Humanos , Hemofilia A/complicações , Hemofilia A/epidemiologia , Hepacivirus , Estudos Transversais , Inquéritos Nutricionais , Estudos Retrospectivos , Fatores de Risco , Hipertensão/complicações , Hipertensão/epidemiologia , Hepatite C/complicações , Hepatite C/epidemiologia , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Diabetes Mellitus/epidemiologia , Prevalência , HIVRESUMO
INTRODUCTION: Persons with haemophilia (PWH) have a higher prevalence of hypertension compared to the general population, which cannot be explained entirely by the usual cardiovascular risk factors. Neutralizing antibodies (inhibitors) against clotting factors might have some relation to cardiovascular disease in PWH. However, whether inhibitors facilitate hypertension is unknown. AIM: We investigated the relationship between hypertension/blood pressure and inhibitors in PWH. Additional goals were to determine the relationships with haemophilia type, race, and viral status. METHODS: Records were extracted retrospectively for PWH (age ≥18 years) between 2003 and 2014 from four Hemophilia Treatment Centers in North America and included demographics, weight, height, haemophilia type/severity, HCV and HIV infection status, hypertension, use of anti-hypertensive medications, and inhibitor status. We fitted semiparametric generalized additive models (GAMs) to describe adjusted curves of blood pressure (BP) against age. RESULTS: Among 691 PWH, 534 had haemophilia A and 157 had haemophilia B, with a median age of 39 years (range 18 to 79). Forty-four PWH (6.5%) had a history of inhibitors, without evidence for a higher prevalence of hypertension or higher BP. A higher prevalence of hypertension and higher BP were noted for haemophilia A (vs. haemophilia B), coinfection with HCV/HIV (vs. uninfected), or moderate haemophilia (vs. severe haemophilia). CONCLUSION: While there was no signal to suggest that a history of inhibitors is associated with hypertension, differences based on haemophilia type, severity, and viral infection status were identified, encouraging prospective investigations to better delineate haemophilia-specific risk factors for hypertension.
Assuntos
Infecções por HIV , Hemofilia A , Hemofilia B , Hepatite C , Hipertensão , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Hemofilia A/complicações , Hemofilia A/epidemiologia , Hemofilia B/complicações , Hemofilia B/epidemiologia , Pressão Sanguínea , Estudos Retrospectivos , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Estudos Prospectivos , Fatores de Risco , Hipertensão/complicações , Hipertensão/epidemiologia , Hepatite C/complicaçõesRESUMO
INTRODUCTION: Ageing patients with haemophilia (PWH) develop cardiovascular risk factors impacting care. Little is known about the prevalence of diabetes in PWH and its relation to other comorbidities. AIM: To examine the risk of diabetes for adult PWH compared to men from the general United States population (National Health and Nutrition Examination Surveys [NHANES]) and outpatients attending a Veterans Affairs Medical Center (VAMC) clinic. METHODS: Retrospective cross-sectional design. PWH from four haemophilia centres (n = 690) were matched with random samples from NHANES and VAMC. Diabetes (yes/no) was the outcome, while age, body mass index (BMI), race and Hepatitis C (HCV; by serology) and human immunodeficiency virus (HIV) positivity were covariates. We fitted semiparametric generalized additive models (GAMs) in order to compare diabetes risk between cohorts. RESULTS: Younger PWH were at lower risk of diabetes than NHANES or VAMC subjects irrespective of BMI. However, the risk of diabetes rose in older PWH and was closely associated with HCV. For HCV-negative subjects, the risk of diabetes was considerably lower for PWH than NHANES and VAMC subjects. The difference persisted after controlling for BMI and age, indicating that the low risk of diabetes in PWH cannot be explained by lean body mass alone. CONCLUSION: Since many ageing PWH are HCV positive and therefore at heightened risk for diabetes, it is important to incorporate diabetes screening into care algorithms in Haemophilia Treatment Centers, especially since PWH are not always followed in primary care clinics.
Assuntos
Diabetes Mellitus , Hemofilia A , Hepatite C , Adulto , Idoso , Estudos Transversais , Diabetes Mellitus/epidemiologia , Hemofilia A/complicações , Hemofilia A/epidemiologia , Hepatite C/complicações , Hepatite C/epidemiologia , Humanos , Masculino , Inquéritos Nutricionais , Estudos Retrospectivos , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
Functional, usable, and maintainable open-source software is increasingly essential to scientific research, but there is a large variation in formal training for software development and maintainability. Here, we propose 10 "rules" centered on 2 best practice components: clean code and testing. These 2 areas are relatively straightforward and provide substantial utility relative to the learning investment. Adopting clean code practices helps to standardize and organize software code in order to enhance readability and reduce cognitive load for both the initial developer and subsequent contributors; this allows developers to concentrate on core functionality and reduce errors. Clean coding styles make software code more amenable to testing, including unit tests that work best with modular and consistent software code. Unit tests interrogate specific and isolated coding behavior to reduce coding errors and ensure intended functionality, especially as code increases in complexity; unit tests also implicitly provide example usages of code. Other forms of testing are geared to discover erroneous behavior arising from unexpected inputs or emerging from the interaction of complex codebases. Although conforming to coding styles and designing tests can add time to the software development project in the short term, these foundational tools can help to improve the correctness, quality, usability, and maintainability of open-source scientific software code. They also advance the principal point of scientific research: producing accurate results in a reproducible way. In addition to suggesting several tips for getting started with clean code and testing practices, we recommend numerous tools for the popular open-source scientific software languages Python, R, and Julia.
Assuntos
Biologia Computacional/estatística & dados numéricos , Design de Software , Software , Linguagens de Programação , Análise de RegressãoRESUMO
PURPOSE: Factors leading to mechanical complications following insertion of central venous access devices (CVADs) in children are poorly understood. We aimed to quantify the rates and elucidate the mechanisms of these complications. METHODS: Retrospective (2016-2021) review of children (< 18 years old) receiving a CVAD. Data, reported as number of cases (%) and median (IQR), were analysed by Fisher's exact test, chi-squared test and logistic regression analysis. RESULTS: In total, 317 CVADs (245 children) were inserted. Median age was 5.0 (8.9) years, with 116 (47%) females. There were 226 (71%) implantable port devices and 91 (29%) Hickman lines. Overall, 54 (17%) lines had a mechanical complication after 0.4 (0.83) years from insertion: fracture 19 (6%), CVAD migration 14 (4.4%), occlusion 14 (4.4%), port displacement 6 (1.9%), and skin tethering to port device 1 (0.3%). Younger age and lower weight were associated with higher risk of complications (p < 0.0001). Hickman lines had a higher incidence of complications compared to implantable port devices [24/91 (26.3%) vs 30/226 (13.3%); p = 0.008]. CONCLUSION: Mechanical complications occur in 17% of CVADs at a median of < 6 months after insertion. Risk factors include younger age and lower weight. Implantable port devices have a lower complications rate. LEVEL OF EVIDENCE: Level 4: case-series with no comparison group.
Assuntos
Cateterismo Venoso Central , Cateteres Venosos Centrais , Adolescente , Cateterismo Venoso Central/efeitos adversos , Cateteres de Demora/efeitos adversos , Cateteres Venosos Centrais/efeitos adversos , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Masculino , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: Painful arthropathy is a long-term complication in patients with hemophilia (PWH), affecting mobility and quality of life. A major barrier for the appraisal of joint health is the absence of point-of-care (POC) imaging modalities to promptly identify and manage arthropathic changes. Accordingly, we developed the Joint tissue Activity and Damage Exam (JADE) POC musculoskeletal ultrasound (MSKUS) protocol. JADE is validated for haemophilic joint tissue recognition with high intra/inter-rater and inter-operator reliability. AIMS: Evaluate associations of JADE with clinical (Hemophilia Joint Health Score, [HJHS]) and functional (total arc [combined flexion and extension range of motion [ROM]]) parameters. METHODOLOGY: In this multi-centre prospective study, we recruited PWH A or B with at least one arthropathic joint. We evaluated joint health (both elbows, knees, and ankles) by comparing JADE measurements (soft tissue and cartilage thickness, and osteochondral alterations) with HJHS and total arc. RESULTS: Of 44 PWH, most had hemophilia A (35/44), were severe (36/44) and had a median age of 36 years. Increasing HJHSs and declining total arc, indicating worsening arthropathy, were associated with JADE measurements in the expected direction, including (1) increasing length of osteochondral alterations, (2) diminished cartilage thickness, and (3) greater soft tissue expansion. The ankles had the highest proportion of joints without measurable (missing) cartilage. In multivariable models MSKUS measurements explained 68% and 71% of the variation in HJHS and total arc respectively for the elbow, 55% and 29% respectively for the knee, and 50% and 73% for the ankle. CONCLUSIONS: This study highlights the associations of direct intra-articular ultrasonography measurements using the JADE protocol with clinical and functional parameters. Our findings underscore the clinical value of POC MSKUS using the JADE protocol as a complementary instrument for the diagnosis and management of haemophilic arthropathy.
Assuntos
Hemofilia A , Artropatias , Adulto , Hemartrose/diagnóstico por imagem , Hemartrose/etiologia , Hemofilia A/complicações , Humanos , Artropatias/diagnóstico por imagem , Artropatias/etiologia , Articulação do Joelho/diagnóstico por imagem , Sistemas Automatizados de Assistência Junto ao Leito , Estudos Prospectivos , Qualidade de Vida , Reprodutibilidade dos Testes , UltrassonografiaRESUMO
Methamphetamine use, sexual relationship power (SRP), and partner violence (PV) are associated with increased risk of sexually transmitted infections (STIs) among women. The objective of our study was to examine the association of recent PV and SRP on STIs by partner type among HIV-negative, heterosexual women who use methamphetamine in San Diego, CA. Using baseline survey data from 209 women enrolled in FASTLANE II, an HIV behavioral intervention trial, we conducted logistic regression analyses to examine associations between PV, SRP, and self-reported lifetime STIs (e.g., chlamydia, gonorrhea). Models focused on PV perpetrated within the past 2 months by: (1) spouse, live-in, or steady sexual partners and (2) casual or anonymous sexual partners. Seventy-eight percent of women reported lifetime physical PV and 57% reported lifetime sexual PV. In the past 2 months, 19.6% reported physical and/or sexual violence by a spouse, live-in, or steady sexual partner, and 7.2% reported physical and/or sexual PV by a casual or anonymous partner. Median SRP score was 2.36 (interquartile range: 2.02-2.68). Twenty-six percent of women reported ever being diagnosed with ≥ 1 STI. While recent physical violence and sexual violence were not associated with STI history among women in steady relationships, women who reported recent sexual violence by casual/anonymous partners were approximately 8 times more likely to ever have an STI compared with those with no history of recent PV by casual/anonymous partners (AOR: 7.70; 95% CI: 1.32, 44.84). SRP was not associated with lifetime STIs among women who reported either partner type. Our findings support a relationship between recent sexual violence perpetrated by casual/anonymous partners and women's STI history. Women who use methamphetamine need help in navigating partner violence experiences. Risk reduction interventions to support this marginalized population are needed.
Assuntos
Metanfetamina , Poder Psicológico , Parceiros Sexuais , Infecções Sexualmente Transmissíveis , Maus-Tratos Conjugais , Transtornos Relacionados ao Uso de Substâncias , Adulto , California/epidemiologia , Feminino , Humanos , Masculino , Fatores de Risco , Parceiros Sexuais/psicologia , Infecções Sexualmente Transmissíveis/epidemiologia , Maus-Tratos Conjugais/estatística & dados numéricos , Transtornos Relacionados ao Uso de Substâncias/epidemiologiaRESUMO
INTRODUCTION: Evidence suggests that toxic iron is involved in haemophilic joint destruction. AIM: To determine whether joint iron deposition is linked to clinical and imaging outcomes in order to optimize management of haemophilic joint disease. METHODS: Adults with haemophilia A or haemophilia B (n = 23, ≥ age 21) of all severities were recruited prospectively to undergo assessment with Hemophilia Joint Health Scores (HJHS), pain scores (visual analogue scale [VAS]) and magnetic resonance imaging (MRI) at 3T using conventional MRI protocols and 4-echo 3D-UTE-Cones sequences for one affected arthropathic joint. MRI was scored blinded by two musculoskeletal radiologists using the International Prophylaxis Study Group (IPSG) MRI scale. Additionally, UTE-T2* values of cartilage were quantified. Correlations between parameters were performed using Spearman rank correlation. Two patients subsequently underwent knee arthroplasty, which permitted linking of histological findings (including Perl's reaction) with MRI results. RESULTS: MRI scores did not correlate with pain scores or HJHS. Sixteen joints had sufficient cartilage for UTE-T2* analysis. T2* values for cartilage correlated inversely with HJHS (rs = -0.81, P < 0.001) and MRI scores (rs = -0.52, P = 0.037). This was unexpected since UTE-T2* values decrease with better joint status in patients with osteoarthritis, suggesting that iron was present and responsible for the effects. Histological analysis of cartilage confirmed iron deposition within chondrocytes, associated with low UTE-T2* values. CONCLUSIONS: Iron accumulation can occur in cartilage (not only in synovium) and shows a clear association with joint health. Cartilage iron is a novel biomarker which, if quantifiable with innovative joint-specific MRI T2* sequences, may guide treatment optimization.
Assuntos
Cartilagem/diagnóstico por imagem , Hemofilia A/complicações , Hemossiderina/efeitos adversos , Artropatias/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Adulto , Humanos , MasculinoRESUMO
OBJECTIVES: Musculoskeletal ultrasound (US) is used increasingly to examine hemophilic arthropathy. However, quantitative algorithms to document findings are lacking. We developed and sought to validate a protocol quantifying hemophilic joint abnormalities. METHODS: Thirty-one patients with hemophilia were examined serially for 2 years with musculoskeletal US (≈600 joint examinations and ≈6000 images). Based on the spectrum of pathologies, a quantitative algorithm, named Joint Tissue Activity and Damage Examination (JADE), was developed for soft tissue and osteochondral measurements, including power Doppler, using nominal group techniques. To study intra- and inter-rater reliability, 8 musculoskeletal US-experienced hemophilia providers performed anatomic landmark recognition and tissue measurements on 86 images with arthropathic changes, with repetition 1 month later. Twenty-three musculoskeletal US-inexperienced providers performed similar assessments. Inter-operator reliability was established by 6 musculoskeletal US-experienced hemophilia providers, each acquiring images and JADE assessments of 3 hemophilic arthropathic joints. A radiologist and musculoskeletal sonographer functioned as adjudicators. The statistical analysis was performed with the intraclass correlation coefficient (ICC), Fleiss κ, and Cohen κ where appropriate. RESULTS: The musculoskeletal US-experienced providers showed excellent intra-and inter-rater reliability for tissue measurements (ICCs, 0.94-0.96). Agreement was good to excellent for landmark recognition (Fleiss κ, 0.87-0.94). Inter-operator reliability was excellent for measurements and landmark recognition (ICC, 0.90; Fleiss κ, 1.0). Agreement with adjudicators was mostly good to excellent. Musculoskeletal US-inexperienced providers showed excellent inter-rater reliability for measurements (ICC, 0.96) and moderate agreement for landmark recognition (Fleiss κ, 0.58). CONCLUSIONS: The JADE protocol appears feasible for quantifying hemophilic intra-articular abnormalities. Musculoskeletal US-trained hemophilia providers showed high intra-rater, inter-rater, and inter-operator reliability, supporting JADE as a protocol for clinical management and research.
Assuntos
Hemofilia A/complicações , Artropatias/complicações , Artropatias/diagnóstico por imagem , Ultrassonografia/métodos , Adulto , Feminino , Humanos , Articulações/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos TestesRESUMO
OBJECTIVES: Point-of-care musculoskeletal ultrasound (US) is increasingly used by hemophilia providers to guide management; however, pathologic tissue differentiation with US is uncertain. We sought to determine the extent to which point-of-care musculoskeletal US can identify and discriminate pathologic soft tissue changes in hemophilic arthropathy. METHODS: Thirty-six adult patients with hemophilia A/B were prospectively enrolled. Point-of-care musculoskeletal US examinations were performed on arthropathic joints (16 knees, 10 ankles, and 10 elbows) using standard views by a musculoskeletal US-trained and certified hematologist, who recorded abnormal intra-articular soft tissue accumulation. Within 3 days, magnetic resonance imaging was performed using conventional and multiecho ultrashort echo time sequences. Soft tissue identification (synovial proliferation with or without hemosiderin, fat, and/or blood products) was performed by a musculoskeletal radiologist. Findings obtained with both imaging modalities were compared and correlated in a blinded fashion. RESULTS: There was perfect agreement between the modalities on the presence of abnormal soft tissue (34 of 36 cases). However, musculoskeletal US was unable to discriminate between coagulated blood, synovium, intrasynovial or extrasynovial fat tissue, or hemosiderin deposits because of wide variations in echogenicity. CONCLUSIONS: Musculoskeletal US is valuable for point-of-care imaging to determine the presence of soft tissue accumulation in discrete areas. However, because of limitations of musculoskeletal US in discriminating the nature of pathologic soft tissues and detecting hemosiderin, magnetic resonance imaging will be required if such discrimination is clinically important.
Assuntos
Hemofilia A/complicações , Artropatias/complicações , Artropatias/diagnóstico por imagem , Articulações/diagnóstico por imagem , Ultrassonografia/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema Musculoesquelético/diagnóstico por imagem , Sistemas Automatizados de Assistência Junto ao Leito , Estudos Prospectivos , Índice de Gravidade de Doença , Adulto JovemRESUMO
For many taxa and systems, species richness peaks at midelevations. One potential explanation for this pattern is that large-scale changes in climate and geography have, over evolutionary time, selected for traits that are favored under conditions found in contemporary midelevation regions. To test this hypothesis, we use records of historical temperature and topographic changes over the past 65 Myr to construct a general simulation model of plethodontid salamander evolution in eastern North America. We then explore possible mechanisms constraining species to midelevation bands by using the model to predict plethodontid evolutionary history and contemporary geographic distributions. Our results show that models that incorporate both temperature and topographic changes are better able to predict these patterns, suggesting that both processes may have played an important role in driving plethodontid evolution in the region. Additionally, our model (whose annotated source code is included as a supplement) represents a proof of concept to encourage future work that takes advantage of recent advances in computing power to combine models of ecology, evolution, and earth history to better explain the abundance and distribution of species over time.
Assuntos
Filogenia , Temperatura , Urodelos , Animais , Clima , Geografia , América do Norte , Estados UnidosRESUMO
OBJECTIVE: Hemophilic arthropathy is associated with pronounced vascular joint remodeling. Also, compared to the general population, PWH have a higher prevalence of hypertension not explained by usual risk factors. As vascular remodeling in various vascular beds is a hallmark of hypertension, we hypothesized that vascular joint remodeling is associated with elevated blood pressures and hypertension. METHODS: Elbows, knees, and ankles of 28 adult PWH were evaluated for vascular abnormalities with MSKUS/PD, as well as for radiographic and clinical status and pain. Logistic and linear regression models were fitted to examine associations between hypertension, blood pressure, and PD score. RESULTS: The extent of vascular abnormalities was associated with hypertension and blood pressures. Hypertensive patients had a higher PD score compared to nonhypertensive patients, and the risk of hypertension increased steeply with PD score. SBP was also strongly associated with PD score, while DBP was only weakly associated. CONCLUSIONS: Vascular remodeling in hemophilic joints is associated with hypertension and elevated blood pressures. As hypertension is a grave risk factor for intracranial hemorrhage, a prominent cause of mortality in hemophilia patients, future studies are needed to address the causal pathways between vascular joint remodeling and blood pressure.
Assuntos
Hemofilia A/complicações , Hipertensão/patologia , Remodelação Vascular , Adulto , Humanos , Artropatias , Articulações/irrigação sanguínea , Articulações/diagnóstico por imagem , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: Subdural haematoma (SDH) is rare following spinal anaesthesia and has not been reported previously in an infant. Non-accidental injury is the commonest cause of subdural haematoma in infants. METHODS: We describe two cases of SDH following spinal anaesthesia in infants. RESULTS: In both cases, forensic investigation was commenced and no evidence of child abuse was found. Both children are well 2 years after diagnosis. CONCLUSION: Paediatric health workers should be aware of the possibility of SDH after spinal anaesthesia and consider this as a differential diagnosis when investigating possible non-accidental injury in an infant.
Assuntos
Raquianestesia/efeitos adversos , Hematoma Subdural/etiologia , Hérnia Inguinal/cirurgia , Humanos , Lactente , MasculinoRESUMO
Hemophilic arthropathy is a debilitating condition that can develop as a consequence of frequent joint bleeding despite adequate clotting factor replacement. The mechanisms leading to repeated spontaneous bleeding are unknown. We investigated synovial, vascular, stromal, and cartilage changes in response to a single induced hemarthrosis in the FVIII-deficient mouse. We found soft-tissue hyperproliferation with marked induction of neoangiogenesis and evolving abnormal vascular architecture. While soft-tissue changes were rapidly reversible, abnormal vascularity persisted for months and, surprisingly, was also seen in uninjured joints. Vascular changes in FVIII-deficient mice involved pronounced remodeling with expression of α-Smooth Muscle Actin (SMA), Endoglin (CD105), and vascular endothelial growth factor, as well as alterations of joint perfusion as determined by in vivo imaging. Vascular architecture changes and pronounced expression of α-SMA appeared unique to hemophilia, as these were not found in joint tissue obtained from mouse models of rheumatoid arthritis and osteoarthritis and from patients with the same conditions. Evidence that vascular changes in hemophilia were significantly associated with bleeding and joint deterioration was obtained prospectively by dynamic in vivo imaging with musculoskeletal ultrasound and power Doppler of 156 joints (elbows, knees, and ankles) in a cohort of 26 patients with hemophilia at baseline and during painful episodes. These observations support the hypothesis that vascular remodeling contributes significantly to bleed propagation and development of hemophilic arthropathy. Based on these findings, the development of molecular targets for angiogenesis inhibition may be considered in this disease.
Assuntos
Fator VIII/genética , Hemartrose/patologia , Hemofilia A/patologia , Neovascularização Patológica/patologia , Remodelação Vascular , Actinas/genética , Actinas/metabolismo , Animais , Tornozelo/irrigação sanguínea , Tornozelo/patologia , Modelos Animais de Doenças , Articulação do Cotovelo/irrigação sanguínea , Articulação do Cotovelo/metabolismo , Articulação do Cotovelo/patologia , Endoglina , Fator VIII/metabolismo , Expressão Gênica , Hemartrose/genética , Hemartrose/metabolismo , Hemofilia A/genética , Hemofilia A/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Articulação do Joelho/irrigação sanguínea , Articulação do Joelho/metabolismo , Articulação do Joelho/patologia , Camundongos , Camundongos Endogâmicos BALB C , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismoAssuntos
Anestésicos/efeitos adversos , Encéfalo/efeitos dos fármacos , Comportamento Infantil/efeitos dos fármacos , Desenvolvimento Infantil/efeitos dos fármacos , Síndromes Neurotóxicas/etiologia , Fatores Etários , Animais , Encéfalo/crescimento & desenvolvimento , Criança , Pré-Escolar , Humanos , Síndromes Neurotóxicas/fisiopatologia , Síndromes Neurotóxicas/psicologia , Segurança do Paciente , Medição de Risco , Fatores de RiscoRESUMO
Lamins A and C, alternatively spliced products of the LMNA gene, are key components of the nuclear lamina. The two isoforms are found in similar amounts in most tissues, but we observed an unexpected pattern of expression in the brain. Western blot and immunohistochemistry studies showed that lamin C is abundant in the mouse brain, whereas lamin A and its precursor prelamin A are restricted to endothelial cells and meningeal cells and are absent in neurons and glia. Prelamin A transcript levels were low in the brain, but this finding could not be explained by alternative splicing. In lamin A-only knockin mice, where alternative splicing is absent and all the output of the gene is channeled into prelamin A transcripts, large amounts of lamin A were found in peripheral tissues, but there was very little lamin A in the brain. Also, in knockin mice expressing exclusively progerin (a toxic form of prelamin A found in Hutchinson-Gilford progeria syndrome), the levels of progerin in the brain were extremely low. Further studies showed that prelamin A expression, but not lamin C expression, is down-regulated by a brain-specific microRNA, miR-9. Expression of miR-9 in cultured cells reduced lamin A expression, and this effect was abolished when the miR-9-binding site in the prelamin A 3' UTR was mutated. The down-regulation of prelamin A expression in the brain could explain why mouse models of Hutchinson-Gilford progeria syndrome are free of central nervous system pathology.