Ultrasound-guided hydrodilatation for adhesive capsulitis: capsule-preserving versus capsule-rupturing technique.

OBJECTIVE: To compare the clinical efficacy of capsule-rupturing versus capsule-preserving ultrasound-guided hydrodilatation in patients with shoulder adhesive capsulitis (AC). To determine potential factors affecting the outcome over a 6-month follow-up. MATERIALS AND METHODS: Within a 2-year period, 149 consecutive patients with AC were prospectively enrolled and allocated into (i) group-CR, including 39 patients receiving hydrodilatation of the glenohumeral joint (GHJ) with capsular rupture and (ii) group-CP, including 110 patients treated with GHJ hydrodilatation with capsular preservation. Demographics, affected shoulder, and AC grade were recorded. Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire and visual analog scale (VAS) were used for clinical assessment at baseline/1/3/6 months. Comparisons were performed with Mann-Whitney U test and Kolmogorov-Smirnov test. Linear regression was used to identify predictors of outcome. P value < 0.05 defined significance. RESULTS: DASH and VAS scores in both groups improved significantly compared to baseline (P < 0.001) and were significantly lower in the CP compared to CR group at all time-points following intervention (P < 0.001). Capsule rupture was a significant predictor of DASH score at all time-points (P < 0.001). DASH scores correlated to initial DASH score at all time-points (P < 0.001). DASH/VAS scores at 1 month were correlated to the AC grade (P = 0.025/0.02). CONCLUSION: GHJ hydrodilatation results in pain elimination and functional improvement till the mid-term in patients with AC, with improved outcome when adopting the capsule-preserving compared to the capsule-rupturing technique. Higher initial DASH score is predictive of impaired functionality in the mid-term.

Ultrasound-Guided Hydrodistension for Adhesive Capsulitis: Is There Any Adjunct Effect of Immediate Post-Procedural Manipulation Over Instructed Physical Therapy?

OBJECTIVES: To compare the additive value of immediate post-procedural manipulation versus physiotherapy, following ultrasound (US)-guided hydrodistention of the glenohumeral joint (GHJ) in patients with adhesive capsulitis (AC) and define predictors of outcome. METHODS: Within a 19-month period, 161 consecutive patients with AC were prospectively enrolled and allocated to two groups according to treatment, based on patients' individual preferences: 1) group-I, US-guided hydrodistension plus immediate post-procedural manipulations and 2) group-II, US-guided hydrodistension plus supervised physiotherapy program. The Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire and a visual analog scale (VAS) were used for clinical assessment at baseline (immediately after treatment), 1, 3, and 6 months. Comparisons were performed with Mann-Whitney U test and Kolmogorov-Smirnov test. Linear regression was used to identify predictors of outcome. P value <.05 defined significance. RESULTS: GHJ hydrodistension with manipulation or physiotherapy was linked to clinical improvement at all follow-up time-points. DASH scores of group-I remained constantly lower than DASH scores of group-II at all time-points (P < .001). VAS scores were lower in group-I than group-II at 1 and 3 months (P < .001 and P = .0019, respectively). Both groups had improved to a similar degree with respect to pain at 6 months (P = .29). The performance of post-interventional manipulations was predictive of improved shoulder functionality (as assessed with DASH scores) at all time-points, while low-grade disease and milder symptoms at presentation were associated with improved short-term pain. CONCLUSIONS: Immediate post-procedural manipulations appeared to be superior to physiotherapy following GHJ hydrodistension for AC in terms of shoulder functionality during a 6-month follow-up period. Post-interventional manipulations, the stage of AC and lower DASH and VAS scores at presentations were predictive of improved outcome.

Ultrasound-guided hydrodistension for adhesive capsulitis: a longitudinal study on the effect of diabetes on treatment outcomes.

OBJECTIVE: The effect of diabetes on adhesive capsulitis (AC) and its impact on the outcomes of ultrasound (US)-guided hydrodistension of the glenohumeral joint are still unclear. We aimed to identify predictors of US-guided hydrodistension outcomes, while assessing the performance of the method in diabetic compared to non-diabetic patients. MATERIALS AND METHODS: A total of 135 patients with AC who underwent US-guided hydrodistension were prospectively included. Demographics and factors linked to chronic inflammation and diabetes were recorded and patients were followed-up for 6 months. Functionality and pain were evaluated with the Disabilities of the Arm, Shoulder and Hand (DASH) and the Visual Analogue Scale (VAS) score. Statistical analysis was performed with Mann-Whitney U test, linear, and binary logistic regression. RESULTS: Diabetes was identified in 25/135 patients (18.5%). Diabetic patients had worse DASH and VAS score at presentation (P < 0.0001) and presented with a higher grade of AC (P < 0.0001) and lower range of motion (P < 0.01) compared to non-diabetics. Higher DASH (P = 0.025) and VAS scores (P = 0.039) at presentation were linked to worse functionality at 6 months. Presence and duration of diabetes, and the number of hydrodistension repeats, correlated with worse VAS and DASH scores at 6 months. The number of procedure repeats was the only independent predictor of complete pain resolution at 6 months (OR 0.418, P = 003). CONCLUSION: Diabetes is linked to more severe AC at presentation and worse outcomes in patients undergoing US-guided hydrodistension. In resistant cases, repeating the intervention is independently linked to worse outcomes for at least 6 months post-intervention.

Influence of diabetes on response to ultrasound guided hydrodistension treatment of adhesive capsulitis: a retrospective study.

BACKGROUND: Diabetes is associated with microvascular and macrovascular complications. Although it is less recognized, diabetes also has an important role in the development of musculoskeletal disorders. Our objective was to evaluate the effect of type 2 diabetes (T2D) on the severity of adhesive capsulitis of the shoulder (AC) and on the efficacy of ultrasound guided hydrodistension treatment. METHODS: We conducted a retrospective longitudinal observational study, of patients with AC who underwent ultrasound guided hydrodistension at our Centre. Severity was measured with DASH (Disabilities of Arm, Shoulder and Hand) score and pain was evaluated with a score between 0 and 10. The association of T2D with baseline characteristics of AC, and with outcomes at 6-12 months was analyzed using linear and logistic regression models. RESULTS: We evaluated 120 ultrasound guided hydrodistension treatments of AC, 85 in patients without diabetes and 35 in patients with T2D. Patients with diabetes had a higher prevalence of dyslipidemia, hypertension and higher HbA1c values. The average duration of diabetes was 4.8 years (2.0, 7.9). The baseline characteristics of AC were not significantly different between patients with and without diabetes. Patients with T2D relapsed more frequently and required more reinterventions than patients without diabetes (20.0% vs 4.7%, p = 0.008), had higher post-intervention pain scale values [4.0 (0.0-5.0) vs 0.0 (0.0-5.0), p = 0.022] and higher post-intervention DASH score [0.8 (0.0-1.8) vs 0.0 (0.0-0.8), p = 0.038]. CONCLUSION: Although baseline characteristics of AC in patients with diabetes were similar to those without diabetes, patients with diabetes had a worse response to treatment, more frequent relapses and a greater need for new interventions.

Erasmus Syndrome: An Underrecognized Entity.

We present a case of a 33-year-old male who worked as a plumber and a locksmith. The patient presented with diffuse myalgia and asthenia, skin sclerosis and puffy fingers, Raynaud's phenomenon, exertional dyspnea and erectile dysfunction. The presence of specific autoantibodies enabled the diagnosis of systemic sclerosis. Chest-computed tomography revealed upper lobe consolidation. After extensive evaluation, the multidisciplinary interstitial lung disease team concluded that the patient also had advanced silicosis. After a year, there was significant clinical, radiologic, and functional deterioration of the lung disease. The patient was referred for lung transplant. Silica inhalation is the cause of silicosis but is also implicated in the development of systemic sclerosis (Erasmus syndrome). Although they share a common risk factor, it is rare to find both diseases co-existing. We present this case of a young patient where both diseases presented aggressively in order to raise awareness to this association.

Apresentamos o caso de um homem de 33 anos que trabalhava como canalizador e serralheiro. Apresentava mialgias e astenia, esclerose cutânea e puffy fingers, fenómeno de Raynaud, dispneia de esforço e disfunção erétil. A presença de autoanticorpos específicos permitiu o diagnóstico de esclerose sistémica. A tomografia computadorizada de tórax revelou consolidações dos lobos superiores. Após extensa avaliação, o grupo multidisciplinar de doenças do interstício concluiu que o doente tinha também silicose avançada. Após um ano, houve agravamento clínico, radiológico e funcional significativo da doença pulmonar. O doente foi encaminhado para transplante pulmonar. A inalação de sílica é a causa da silicose, mas também está implicada no desenvolvimento da esclerose sistémica (síndrome de Erasmus). Embora tenham um fator de risco comum, é raro encontrar as duas doenças simultaneamente. Apresentamos o caso de um doente jovem em que ambas as doenças se apresentaram de forma agressiva para alertar sobre esta associação.

Long-Term Outcomes of Ultrasound-Guided Hydrodistension for Adhesive Capsulitis: A Prospective Observational Study.

Ultrasound-guided hydrodistention has been established as an effective minimally invasive treatment option for glenohumeral joint adhesive capsulitis (AC). Nonetheless, the long-term outcomes of the procedure have not yet been established. A total of 202 patients with AC were prospectively recruited and followed up for a total of 2 years. Pain and functionality were assessed with the use of the visual analogue scale (VAS) and the disabilities of the arm, shoulder, and hand (DASH) score, respectively, at the beginning and the end of the follow-up period. The relapse of AC over the 2-year period and the effect of diabetes were also evaluated in the treatment cohort. The Mann-Whitney U test was used to compare mean scores at the two time points, and Cox survival analysis and χ2 test were used to assess the effect of diabetes on AC relapse. VAS and DASH scores were significantly lower at 2 years compared with the beginning of the follow-up period (p < 0.001). Diabetes was diagnosed in 38/202 patients (18.8%) and was found to be significantly associated with recurrence of the disease (p < 0.001). In conclusion, in this observational study, we have demonstrated that ultrasound-guided hydrodistention is linked to excellent long-term outcomes for the treatment of AC, which are significantly worse in patients with diabetes.

The role of MRI and Ultrasonography in Diagnosis and Treatment of Glenohumeral Joint Adhesive Capsulitis.

Adhesive capsulitis is a common disorder of the glenohumeral joint. Delayed diagnosis is the result of overlapping signs and symptoms with other disorders affecting the shoulder. Typically, the disease shows gradual progression of pain and loss of the range of motion. The hallmark of the physical examination is limitation of both passive and active motion without any associated degenerative changes on plain radiographs. Conservative and/or surgical treatments have shown conflicting results. Poor outcome may be related to co-morbid factors mainly including prolonged immobilization, rotator cuff pathology and diabetes mellitus among others. This review will present the current literature data on the natural history and pathophysiology of the disease, and will highlight the role of imaging in the prompt and accurate diagnosis as well as in the imaged-guided treatment with emphasis on ultrasonography.

Retinal and choroidal thickness changes in systemic lupus erythematosus patients: a longitudinal study.

BACKGROUND/OBJECTIVES: To prospectively evaluate changes in peripapillary retinal nerve fibre layer (pRNFL), in all macular layers and in choroidal thickness (CT) in a cohort of systemic lupus erythematosus (SLE) patients without ophthalmologic manifestations. To associate those changes with ophthalmic characteristics, disease activity state, medication and systemic comorbidities. SUBJECTS/METHODS: Prospective cohort study of 68 previously diagnosed SLE patients. In two study visits (V1 and V2) at least 12 months apart, patients underwent a complete ophthalmologic examination including spectral domain-optical coherence tomography (SD-OCT) and an autoimmune disease specialist assessment. Automatic retinal segmentation was performed. pRNFL was determined globally and in the six peripapillary sectors and each macular layer thickness was determined in the nine early treatment diabetic retinopathy study (ETDRS) subfields. CT was manually measured at 13 locations in the posterior pole. Only one eye per patient was randomly selected for inclusion. Generalised linear mixed effects models were employed. RESULTS: Sixty-five patients completed the study. The median follow-up time was twelve months. At V2, pRNFL was significantly thinner globally (p = 0.006) and in the temporal inferior sector (p = 0.017). Patients under chronic medication with anticoagulants or antihypertensives had significantly thinner pRNFL in some locations. No significant changes were observed in macular layers or choroidal thickness between study visits. CONCLUSIONS: SLE patients presented early SD-OCT signs of neurodegeneration, evidenced by a progressive reduction in pRNFL thickness. Regardless of study visit, baseline chronic medication with anticoagulants or antihypertensives was associated with lower pRNFL thickness, accounting for a deleterious effect of cardiovascular risk factors.

Diabetes: a silent player in musculoskeletal interventional radiology response.

Diabetes has an important role in the development of several musculoskeletal disorders, such as adhesive capsulitis of the shoulder (ACs) and stenosing flexor tenosynovitis of the finger (SfTf). The etiopathophysiology of ACs and SfTf in diabetic patients is associated with both chronic hyperglycemia, increased amounts of visceral adiposity and chronic inflammation. Chronic hyperglycemia stimulates the creation of cross-links between collagen molecules, impairing degradation and resulting in the build-up of excessive collagen deposits in the cartilage, ligaments, tendon sheaths and tendons. Increased adipocytes in diabetic patients secrete proteins and cytocines such as TNF-α, IL-6 and IL-13 which result in overproduction of pro-inflammatory factors, destruction of normal tissue architecture and fibrosis. Both hyperglycemia and adipocytes inhibit efferocytosis, limiting natural resolution. Recently, multiple image-guided interventional radiology musculoskeletal treatment options have been developed, such as ultrasound-guided glenohumeral capsule hydrodistension for ACs and ultrasound-guided percutaneous pulley release for trigger finger. Diabetes can negatively influence outcomes in patients with ACs and SfTf and may impact the decision of which specific procedure technique should be employed. Further studies are necessary to define how diabetes influences response to interventional radiology treatments of these disorders, as well as the extent to which control of blood sugar levels can contribute towards the personalization and optimization of patient follow up.

Catatonia in Anti-N-Methyl-D-Aspartate (NMDA) Receptor Encephalitis Misdiagnosed as Schizophrenia.

Anti-N-Mmethyl-D-aspartate receptor encephalitis is an autoimmune disease of the central nervous system with prominent neurologic and psychiatric features. Symptoms appear progressively and sometimes with an exclusively psychiatric initial presentation. The patient's evaluation should be meticulous, and we should use all the diagnostic tests required for the exclusion of entities that can mimic this disease. We report the diagnostic investigation of a case of anti-N-methyl-D-aspartate receptor encephalitis in a patient with a previous diagnosis of schizophrenia with poor response to antipsychotics. The aim of this case report is to highlight the importance of close surveillance for neuropsychiatric symptoms, especially catatonia, and to recognize autoimmune encephalitis in the differential diagnosis of psychotic disorders with neurological symptoms and resistance or intolerance to antipsychotics. A prompt diagnosis will contribute to a faster onset of therapy and an overall improvement in prognosis.

A encefalite anti-receptor N-metil-D-aspartato é uma doença auto-imune do sistema nervoso central com características neurológicas e psiquiátricas proeminentes. Os sintomas surgem progressivamente e por vezes com uma apresentação inicial exclusivamente psiquiátrica. A avaliação do doente deve ser meticulosa e devem ser realizados todos os meios complementares de diagnóstico necessários à exclusão das entidades que podem mimetizar aquela patologia. Apresenta-se a evolução diagnóstica de um caso de encefalite anti-receptor N-metil-D-aspartato num doente com diagnóstico prévio de esquizofrenia sem resposta à terapêutica anti-psicótica. Pretende-se com este caso realçar a importância de uma vigilância apertada para sintomas neuropsiquiátricos, especialmente no caso de catatonia, e de ter em consideração as encefalites auto-imunes no diagnóstico diferencial de quadros psicóticos associados a sintomas neurológicos e resistência ou intolerância a anti-psicóticos. Um diagnóstico célere contribuirá para a instituição de terapêutica atempadamente e uma melhoria global do prognóstico.

The Microbiome of the Nose-Friend or Foe?

Recently, multiple studies regarding the human microbiota and its role on the development of disease have emerged. Current research suggests that the nasal cavity is a major reservoir for opportunistic pathogens, which can then spread to other sections of the respiratory tract and be involved in the development of conditions such as allergic rhinitis, chronic rhinosinusitis, asthma, pneumonia, and otitis media. However, our knowledge of how nasal microbiota changes originate nasopharyngeal and respiratory conditions is still incipient. Herein, we describe how the nasal microbiome in healthy individuals varies with age and explore the effect of nasal microbiota changes in a range of infectious and immunological conditions. We also describe the potential health benefits of human microbiota modulation through probiotic use, both in disease prevention and as adjuvant therapy. Current research suggests that patients with different chronic rhinosinusitis phenotypes possess distinct nasal microbiota profiles, which influence immune response and may be used in the future as biomarkers of disease progression. Probiotic intervention may also have a promising role in the prevention and adjunctive treatment of acute respiratory tract infections and allergic rhinitis, respectively. However, further studies are needed to define the role of probiotics in the chronic rhinosinusitis.

Neurodegeneration in systemic lupus erythematosus: layer by layer retinal study using optical coherence tomography.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic, autoimmune and multisystemic disease. Recent studies with functional and structural magnetic resonance imaging and cognitive tests report an unexpectedly high frequency of central nervous system involvement, even in patients with asymptomatic SLE. The purpose of this study was to identify early signs of retinal neurodegeneration by comparing the thickness of the peripapillary retinal nerve fiber layer (pRNFL) and all macular layers between patients with SLE without ophthalmologic manifestations and healthy controls. The effect of disease duration and systemic comorbidities was also studied. METHODS: Cross-sectional study, in which all participants underwent a complete ophthalmologic evaluation including retinal segmentation analysis with spectral domain-optical coherence tomography. Patients with SLE also received a detailed autoimmune disease specialist evaluation to assess the disease activity state and systemic involvement. For pRNFL thickness, the global and six peripapillary sectors were determined. Each macular layer thickness was determined in the nine Early Treatment Diabetic Retinopathy Study (ETDRS) subfields. A multiple linear regression analysis was performed to control for the effect of potential demographic, ophthalmic and systemic confounders. A second multivariable analysis, including patients with SLE only, was performed to assess the effect of disease-specific variables on the outcome measures. RESULTS: Sixty-eight eyes of 68 patients with SLE and 50 eyes of 50 healthy controls were considered. The pRNFL was significantly thinner in the SLE group globally (p = 0.026) and in the temporal superior (p = 0.007) and temporal (p = 0.037) sectors. In patients with SLE, chronic medication for hypercholesterolemia, hypertension and anticoagulants were associated with a significant thinning of the pRNFL. Patients with SLE presented significant thinning in the photoreceptor layer in five ETDRS areas (p < 0.05). Shorter disease duration was associated with greater photoreceptor thinning in all ETDRS subfields. Neuropsychiatric SLE, higher disease activity and cardiovascular risk factors were associated with a thinner photoreceptor layer. No differences were observed in overall retinal thickness or the remaining macular layers. CONCLUSION: Patients with SLE present early signs of retinal neurodegeneration, as evidenced by a reduction in the photoreceptor layer and pRNFL. These signs are more pronounced in patients with higher cardiovascular risk burden or neuropsychiatric involvement.

Gestação de Substituição em Portugal: Orientações para a prática clínica

Introdução: A aprovação na Assembleia da República, em dezembro de 2021, da lei aplicável à Gestação de Substituição, suscita a reflexão acerca dos aspetos práticos em que o regime se concretizará e das orientações necessárias para os profissionais de saúde envolvidos. Por esse motivo, foram definidos como objetivos: analisar um conjunto de recomendações para a prática clínica no âmbito da Gestação de Substituição em países com experiência no procedimento e promover uma discussão com peritos na área da Procriação Medicamente Assistida. Material e Métodos: Foi realizada uma análise documental das publicações e documentos oficiais sobre o tema que serviu de base para o estudo de desenho qualitativo baseado em grupos focais com diferentes profissionais -médicos e psicólogos- com experiência em Procriação Medicamente Assistida. A discussão foi concretizada através de sessões via Zoom®, realizadas separadamente com os dois grupos focais. Resultados: Na discussão os peritos fizeram as suas apreciações e propostas de melhoria em relação à versão inicial do documento resultante da análise documental. Conclusão: Obteve-se uma versão consolidada do conjunto de orientações para os profissionais de saúde com as dimensões a avaliar e acompanhar junto da gestante e parte beneficiária na Gestação de Substituição.

Introducción : La aprobación por el Parlamento portugués, en diciembre de 2021, de la ley aplicable a la Gestación Subrogada, plantea la reflexión sobre los aspectos prácticos en los que se implementará el esquema y las directrices necesarias para los profesionales de la salud involucrados. Por este motivo, se definieron los siguientes objetivos: analizar un conjunto de recomendaciones para la práctica clínica en el ámbito de la gestación subrogada en países con experiencia en el procedimiento y promover un debate con expertos en el campo de la Reproducción Médicamente Asistida. Material y Métodos : Se realizó un análisis documental de publicaciones y documentos oficiales sobre el tema, que sirvió de base para el estudio de diseño cualitativo basado en focus group con diferentes profesionales -médicos y psicólogos- con experiencia en Reproducción Médicamente Asistida. La discusión se realizó a través de sesiones via Zoom®, celebradas por separado con los dos focus group. Resultados : En la discusión, los expertos realizaron sus apreciaciones y propuestas de mejora respecto a la versión inicial del documento resultante del análisis documental. Conclusión : Se obtuvo una versión consolidada del conjunto de directrices para los profesionales de la salud con las dimensiones para evaluar y dar seguimiento a la madre sustituta y a los beneficiarios en la Gestación Subrogada.

Introduction: The approval by the Portuguese Parliament, in December 2021, of the law applicable to Surrogate Pregnancy, raises reflection on the practical aspects in which the scheme will be implemented and the necessary guidelines for health professionals involved. For this reason, the following objectives were defined: to analyze a set of recommendations for clinical practice in surrogacy in countries with experience in the procedure and to promote a discussion with experts in Medically Assisted Reproduction. Material and Methods: A documental analysis of publications and official documents on the theme was conducted. This served as a basis for the qualitative design study based on focus groups with different professionals -physicians, and psychologists- with experience in Medically Assisted Reproduction. The discussion was realized through sessions via Zoom®, held separately with the two focus groups. Results : In the debate, the experts made their appreciation and proposals for improvement concerning the initial version of the document resulting from the document analysis. Conclusion : A consolidated version of the set of guidelines for health professionals was obtained with the dimensions to evaluate and follow up with the surrogate and beneficiaries in Surrogacy.

Pharmacodynamic evaluation of novel Catechol-O-methyltransferase inhibitors.

Currently, peripheral COMT inhibitors have an important role in the treatment of Parkinson's disease, and central COMT inhibitors have a potential role in the treatment of various neuropsychiatric disorders, such as attention deficit hyperactivity disorder. Adverse reactions, low bioavailability and short elimination half-lives have prompted the development of new selective COMT inhibitors. The objective of this study was to evaluate the pharmacodynamic properties of novel tight-binding COMT inhibitors (NC, NE, NDE, NCAPE, CNCAFBn, CNCAPE, NCAFBn, CNCAPA, CNCABA and CNCAHA) and compared to standard inhibitors tolcapone and entacapone. The activity of soluble (S) and membrane bound (MB) COMT from rat liver and brain was assessed in the presence of varying concentrations of each inhibitor. NE and NC behaved most potently against liver S-COMT, and CNCAPE was the most potent inhibitor against brain MB-COMT. The cytotoxicity of tolcapone and CNCAPE in human neuroblastoma SK-N-SH cells and human liver adenocarcinoma SK-HEP-1 cells was also assessed. At lower concentrations, CNCAPE did not reduce cell viability, suggesting that CNCAPE may have a potential therapeutic role as a centrally active COMT inhibitor.

Choroidal thickness changes in systemic lupus erythematosus patients.

PURPOSE: To compare choroidal thickness (CT) between patients with systemic lupus erythematosus (SLE) without ophthalmologic manifestations and a control group. To study the effects in CT of disease duration, activity index, medication and systemic comorbidities. METHODS: Cross-sectional study where spectral-domain optical coherence tomography with enhanced depth imaging was used to measure CT in 13 locations, subfoveally and at 500-µm intervals along a horizontal and a vertical section from the fovea. Linear regression models were used. RESULTS: Sixty-eight SLE patients and fifty healthy controls were enrolled. CT multivariable analysis revealed lower values in SLE patients (12.93-26.73 µm thinner) in all locations, except the inferior quadrants (6.48-10.44 µm thicker); however, none of these results reached statistical significance. Contrary to the control group, the normal topographic variation in CT between macular quadrants and from the center to the periphery was not observed in the SLE group. Multivariable analysis in the SLE group alone revealed a significant negative association with anticoagulants (50.10-56.09 µm thinner) and lupus nephritis (40.79-58.63 µm thinner). Contrary to controls, the CT of SLE patients did not respond to changes in mean arterial pressure. CONCLUSION: CT in SLE appears to be thinner, particularly in the subset of patients with nephritis and taking anticoagulants, suggesting more advanced systemic vascular disease. Choroidal responses to hemodynamic changes may also be altered in SLE.

The role of ophthalmic imaging in central nervous system degeneration in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disorder that can involve any organ system. Central nervous system involvement can be a severe life threatening complication, ultimately resulting in severe neurodegenerative changes. Magnetic resonance imaging suggests that neurodegeneration, which may have deleterious effects on brain function, may occur early in SLE and experimental models suggest that neuroprotection may be feasible and beneficial. The retina is an extension of the brain. Recent ophthalmic imaging technologies are capable of identifying early changes in retinal and choroidal morphology and circulation that may reflect CNS degeneration. However, their utility in monitoring CNS involvement in SLE has been poorly studied as these have only been performed in small cohorts, in a cross-sectional design, non-quantitatively and without correlation to disease activity. The authors aim to review the current understanding of neurodegeneration associated with SLE, with particular focus on the visual pathway. We describe the neuropathology of the visual system in SLE and the evidence for retinal and choroidal neurodegenerative and microvascular changes using optical coherence tomography technology. We aim to describe the potential role of optical imaging modalities in NPSLE diagnosis and their likely impact on the study of neuronal function.

Ultrasound detects subclinical joint inflammation in the hands and wrists of patients with systemic lupus erythematosus without musculoskeletal symptoms.

OBJECTIVES: To assess the prevalence and severity of ultrasonographic abnormalities of the hand and wrist of asymptomatic patients with systemic lupus erythematosus (SLE) and compare these findings with those from patients with SLE with musculoskeletal signs or symptoms and healthy controls. METHODS: We conducted a prospective cross-sectional study that evaluated bilaterally, with grey-scale and power Doppler (PD) ultrasound (US), the dorsal hand (2nd to 5th metacarpophalangeal and 2nd to 5th proximal interphalangeal joints) and wrist (radiocarpal, ulnocarpal and intercarpal joints) of 30 asymptomatic patients with SLE, 6 symptomatic patients with SLE and 10 controls. Synovial hypertrophy (SH) and intra-articular PD signal were scored using semiquantitative grading scales (0-3). Individual scores were graded as normal (SH≤1 and PD=0) or abnormal (SH≥2 or PD≥1). Global indexes for SH and PD were also calculated. US findings were correlated with clinical and laboratory data and disease activity indexes. RESULTS: US detected SH (score ≥1) in 77% asymptomatic patients with SLE, mostly graded as minimal (score 1: 63%). 23% of the asymptomatic patients with SLE showed abnormal US PD findings (SH≥2 or PD≥1). SH was present in all symptomatic patients with SLE, mostly graded as moderate (grade 2: 67%), and with associated PD signal (83%). SH (score 1) was identified in 50% of controls, however, none presented abnormal US PD findings. SH index in the asymptomatic SLE group was higher than in the control group (2.0 (0-5) vs 0.5 (0-2), median (range), p=0.01) and lower than in the symptomatic SLE group (7.0 (4-23), median (range), p<0.001). No significant correlation was demonstrated between US PD findings and clinical or laboratory variables and disease activity indexes. CONCLUSION: A small subgroup of asymptomatic patients with SLE may present subclinical joint inflammation. Global US scores and PD signal may be important in disease evaluation and therapeutic monitoring.

Thoracic manifestations of connective tissue diseases.

Connective tissue diseases (CTDs) comprise several immunologic systemic disorders, each of which associated with a particular set of clinical manifestations and autoimmune profile. CTDs may cause numerous thoracic abnormalities, which vary in frequency and pattern according to the underlying disorder. The CTDs that most commonly involve the respiratory system are progressive systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis, Sjögren syndrome, polymyositis, dermatomyositis, and mixed connective tissue disease. Pulmonary abnormalities in this group of patients may result from CTD-related lung disease or treatment complications, namely drug toxicity and opportunistic infections. The most important thoracic manifestations of CTDs are interstitial lung disease and pulmonary arterial hypertension, with nonspecific interstitial pneumonia being the most common pattern of interstitial lung disease. High-resolution computed tomography is a valuable tool in the initial evaluation and follow-up of patients with CTDs. As such, general knowledge of the most common high-resolution computed tomographic features of CTD-related lung disease allows the radiologist to contribute to better patient management.

Overcoming resistance: virologic response to a salvage regimen with the combination of ritonavir plus indinavir.

PURPOSE: To explore the possibility of overcoming resistance to protease inhibitors (PIs) and to determine the resistance cutoff values that continue to predict treatment failure with a dual PI regimen. METHOD: We performed a prospective study of 53 patients who had failed in several PIs and who were included in a ritonavir (RTV) plus indinavir (IDV) salvage regimen. Median HIV RNA level decrease was evaluated according to resistance assays and indinavir trough levels. RESULTS: Eighty-seven percent of patients had previously failed on an IDV-containing regimen. Overall, median HIV RNA decrease was -1.25 log(10) copies/mL after 3 months on therapy. A significant blunted virologic response was observed only in isolates with more than 12 substitutions including the V82A (-0.75 vs. -1.3 log(10) copies/mL; p =.04), or in isolates with more than 30 fold-increase in the IC(50) (-0.43 vs. -1.2 log(10) copies/mL). Higher drug levels were observed in patients with resistant isolates who achieved an HIV RNA decrease greater than 1 log (1742 vs. 1100 ng/mL). CONCLUSION: Our preliminary data suggest the possibility of overcoming resistance with the combination of RTV plus IDV. They also suggest the need for establishing new resistance cutoff values when using PIs in combination.

Association between alcohol and cardiovascular disease: Mendelian randomisation analysis based on individual participant data.

OBJECTIVE: To use the rs1229984 variant in the alcohol dehydrogenase 1B gene (ADH1B) as an instrument to investigate the causal role of alcohol in cardiovascular disease. DESIGN: Mendelian randomisation meta-analysis of 56 epidemiological studies. PARTICIPANTS: 261 991 individuals of European descent, including 20 259 coronary heart disease cases and 10 164 stroke events. Data were available on ADH1B rs1229984 variant, alcohol phenotypes, and cardiovascular biomarkers. MAIN OUTCOME MEASURES: Odds ratio for coronary heart disease and stroke associated with the ADH1B variant in all individuals and by categories of alcohol consumption. RESULTS: Carriers of the A-allele of ADH1B rs1229984 consumed 17.2% fewer units of alcohol per week (95% confidence interval 15.6% to 18.9%), had a lower prevalence of binge drinking (odds ratio 0.78 (95% CI 0.73 to 0.84)), and had higher abstention (odds ratio 1.27 (1.21 to 1.34)) than non-carriers. Rs1229984 A-allele carriers had lower systolic blood pressure (-0.88 (-1.19 to -0.56) mm Hg), interleukin-6 levels (-5.2% (-7.8 to -2.4%)), waist circumference (-0.3 (-0.6 to -0.1) cm), and body mass index (-0.17 (-0.24 to -0.10) kg/m(2)). Rs1229984 A-allele carriers had lower odds of coronary heart disease (odds ratio 0.90 (0.84 to 0.96)). The protective association of the ADH1B rs1229984 A-allele variant remained the same across all categories of alcohol consumption (P=0.83 for heterogeneity). Although no association of rs1229984 was identified with the combined subtypes of stroke, carriers of the A-allele had lower odds of ischaemic stroke (odds ratio 0.83 (0.72 to 0.95)). CONCLUSIONS: Individuals with a genetic variant associated with non-drinking and lower alcohol consumption had a more favourable cardiovascular profile and a reduced risk of coronary heart disease than those without the genetic variant. This suggests that reduction of alcohol consumption, even for light to moderate drinkers, is beneficial for cardiovascular health.