CONQUER Scleroderma: association of gastrointestinal tract symptoms in early disease with resource utilization.

OBJECTIVES: SSc is associated with increased health-care resource utilization and economic burden. The Collaborative National Quality and Efficacy Registry (CONQUER) is a US-based collaborative that collects longitudinal follow-up data on SSc patients with <5 years of disease duration enrolled at scleroderma centres in the USA. The objective of this study was to investigate the relationship between gastrointestinal tract symptoms and self-reported resource utilization in CONQUER participants. METHODS: CONQUER participants who had completed a baseline and 12-month Gastrointestinal Tract Questionnaire (GIT 2.0) and a Resource Utilization Questionnaire (RUQ) were included in this analysis. Patients were categorized by total GIT 2.0 severity: none-to-mild (0-0.49); moderate (0.50-1.00), and severe-to-very severe (1.01-3.00). Clinical features and medication exposures were examined in each of these categories. The 12-month RUQ responses were summarized by GIT 2.0 score categories at 12 months. RESULTS: Among the 211 CONQUER participants who met the inclusion criteria, most (64%) had mild GIT symptoms, 26% had moderate symptoms, and 10% severe GIT symptoms at 12 months. The categorization of GIT total severity score by RUQ showed that more upper endoscopy procedures and inpatient hospitalization occurred in the CONQUER participants with severe GIT symptoms. These patients with severe GIT symptoms also reported the use of more adaptive equipment. CONCLUSION: This report from the CONQUER cohort suggests that severe GIT symptoms result in more resource utilization. It is especially important to understand resource utilization in early disease cohorts when disease activity, rather than damage, primarily contributes to health-related costs of SSc.

Analysis of Hand Joint Space Morphology in Women and Men with Hereditary Hemochromatosis.

Hereditary hemochromatosis (HH) causes unbalanced iron deposition in many organs including the joints leading to severe cartilage loss and bone damage in the metacarpophalangeal joints (MCPJ). High-resolution peripheral quantitative computed tomography (HR-pQCT) and its joint space width (JSW) quantification algorithm quantifies in vivo 3D joint morphology. We therefore aimed to (i) determine feasibility and performance of the JSW algorithm in HH, (ii) quantify joint space morphology, and (iii) investigate the relationship between morphological and clinical parameters in HH. Here, we performed an exploratory study on 24 HH patients and sex- and age-matched controls using HR-pQCT imaging of MCPJ. Mineralized bone structure was automatically segmented from the grayscale image data and periosteal surface bone masks and joint space masks were generated. Mean, minimal, and maximal joint space width (JSW; JSW.MIN; JSW.MAX), JSW heterogeneity (JSW.SD), JSW asymmetry (JSW.AS), and joint space volume (JSV) were computed. Demographics and, for HH patients, disease-specific parameters were recorded. Segmentation of JS was very good with 79.7% of MCPJs successfully segmented at first attempt and 20.3% requiring semi-manual correction. HH men showed larger JSV at all MCPs (+ 25.4% < JSV < + 41.8%, p < 0.05), larger JSW.MAX at MCP 3-4 (+ 14%, 0.006 < p < 0.062), and wider JSW (+ 13%, p = 0.043) at MCP 4 relative to HH women. Compared to controls, both HH men and HH women showed larger JSW.AS and smaller JSW.MIN at all MCP levels, reaching significance for HH men at MCP 2 and 3 (JSW.AS: + 323% < JSW.AS < + 359%, 0.020 < p < 0.043; JSW.MIN: - 216% < JSW.MIN < - 225%, p < 0.043), and for women at MCP 3 (JSW.AS: + 180%, p = 0.025; JSW.MIN: - 41.8%, p = 0.022). Time since HH diagnosis was correlated positively with MCP 4 JSW.AS and JSW.SD (0.463 < ρ < 0.499, p < 0.040), and the number of phlebotomies since diagnosis was correlated with JSW.SD at all MCPs (0.432 < ρ < 0.535, p < 0.050). HR-pQCT-based JSW quantification in MCPJ of HH patients is feasible, performs well even in narrow JS, and allows to define the microstructural joint burden of HH.

Cessation of Immunomodulatory Medication Use in Dermatomyositis: A Single-Center Cohort Study.

OBJECTIVE: To determine the frequency with which adults with dermatomyositis (DM) are able to discontinue systemic immunomodulatory therapy and factors associated with medication cessation. METHODS: We studied a cohort of adult DM patients seen in a rheumatology/dermatology clinic between 2013 and 2020. All patients had exposure to at least 1 systemic immunomodulatory medication for a minimum of 3 months and were followed until medications were discontinued for at least 12 months. Survival analysis was performed using Kaplan-Meier curves with log-rank analyses, and multivariate analysis was done using Cox proportional hazards models. RESULTS: A total of 246 DM patients were followed up for a median time of ∼7 years (47-134 months). Forty-seven patients (19%) discontinued all immunomodulatory medications with a median follow-up of ∼3 years (interquartile range 22-108 months) following DM onset. Log-rank analysis demonstrated that those with anti-MDA5 autoantibodies discontinued medications faster compared with those without autoantibodies (P = 0.03). Multivariate modeling showed that clinically amyopathic patients were 2.7-fold (95% confidence interval [95% CI] 1.34-5.59) more likely to discontinue medications than those with muscle disease. Those with anti-MDA5, anti-NXP2, and anti-SAE1 antibodies had increased likelihood of medication cessation with hazard ratios of 9.83 (95% CI 2.00-48.2), 8.92 (95% CI 1.69-47.0), and 10.8 (95% CI 2.06-56.6), respectively, when compared with the autoantibody-negative group. CONCLUSION: Approximately 20% of adult DM patients discontinued immunomodulatory medications over a median 7-year follow-up. Those with clinically amyopathic disease, anti-MDA5, anti-NXP2, and anti-SAE1 antibodies have a higher likelihood of medication cessation.

Circulating serum microRNAs including senescent miR-31-5p are associated with incident fragility fractures in older postmenopausal women with type 2 diabetes mellitus.

Fragility fractures are an important hallmark of aging and an increasingly recognized complication of Type 2 diabetes (T2D). T2D individuals have been found to exhibit an increased fracture risk despite elevated bone mineral density (BMD) by dual x-ray absorptiometry (DXA). However, BMD and FRAX-scores tend to underestimate fracture risk in T2D. New, reliable biomarkers are therefore needed. MicroRNAs (miRNAs) are secreted into the circulation from cells of various tissues proportional to local disease severity. Serum miRNA-classifiers were recently found to discriminate T2D women with and without prevalent fragility fractures with high specificity and sensitivity (AUC > 0.90). However, the association of circulating miRNAs with incident fractures in T2D has not been examined yet. In 168 T2D postmenopausal women in the AGES-Reykjavik cohort, miRNAs were extracted from baseline serum and a panel of 10 circulating miRNAs known to be involved in diabetic bone disease and aging was quantified by qPCR and Ct-values extracted. Unadjusted and adjusted Cox proportional hazard models assessed the associations between serum miRNAs and incident fragility fracture. Additionally, Receiver operating curve (ROC) analyses were performed. Of the included 168 T2D postmenopausal women who were on average 77.2 ±â€¯5.6 years old, 70 experienced at least one incident fragility fracture during the mean follow-up of 5.8 ±â€¯2.7 years. We found that 3 serum miRNAs were significantly associated with incident diabetic fragility fracture: while low expression of miR-19b-1-5p was associated with significantly lower risk of incident fragility fracture (HR 0.84 (95% CI: 0.71-0.99, p = 0.0323)), low expression of miR-203a and miR-31-5p was each significantly associated with a higher risk of incident fragility fracture per unit increase in Ct-value (miR-203a: HR 1.29 (95% CI: 1.12-1.49), p = 0.0004, miR-31-5p HR 1.27 (95% CI: 1.06-1.52), p = 0.009). Hazard ratios of the latter two miRNAs remained significant after adjustments for age, body mass index (BMI), areal bone mineral density (aBMD), clinical FRAX or FRAXaBMD. Women with miR-203a and miR-31-5p serum levels in the lowest expression quartiles exhibited a 2.4-3.4-fold larger fracture risk than women with miR-31-5p and miR-203a serum expressions in the highest expression quartile (0.002 ≤ p ≤ 0.039). Women with both miR-203a and miR-31-5p serum levels below the median had a significantly increased fracture risk (Unadjusted HR 3.26 (95% CI: 1.57-6.78, p = 0.001) compared to those with both expression levels above the median, stable to adjustments. We next built a diabetic fragility signature consisting of the 3 miRNAs that showed the largest associations with incident fracture (miR-203a, miR-31-5p, miR-19b-1-5p). This 3-miRNA signature showed with an AUC of 0.722 comparable diagnostic accuracy in identifying incident fractures to any of the clinical parameters such as aBMD, Clinical FRAX or FRAXaBMD alone. When the 3 miRNAs were combined with aBMD, this combined 4-feature signature performed with an AUC of 0.756 (95% CI: 0.680, 0.823) significantly better than aBMD alone (AUC 0.666, 95% CI: 0.585, 0.741) (p = 0.009). Our data indicate that specific serum microRNAs including senescent miR-31-5p are associated with incident fragility fracture in older diabetic women and can significantly improve fracture risk prediction in diabetics when combined with aBMD measurements of the femoral neck.

COVID-19 Pandemic: Consensus guidelines for preferred practices in an aesthetic clinic.

Strict infection control measures in response to the current COVID-19 pandemic are expected to remain for an extended period. In aesthetic clinics, most procedures are provided on one to one basis by the physician or therapist. In such a scenario, guidelines detailing the infection control measures for aesthetic clinics are of particular importance. An online meeting of an international group of experts in the field of aesthetic medicine, with experience in administration of an aesthetic clinic, was convened. The meeting aimed to provide a set of consensus guidelines to protect clinic staff and patients from SARS-CoV-2 infection. Consensus guidelines for "preferred practices" were provided for scheduling of patients, patient evaluation and triaging, and for safety precautions about the different procedures. Procedures were categorized into low-risk, moderate risk, and high-risk based on the likelihood of transmission of SARS-CoV-2 virus from the patient to the treating physician or therapist. While not intended to be complete or exhaustive, these guidelines provide sound infection control measures for aesthetic practices. Since guidelines regarding safety measures and use of PPEs may vary from country to country, the local guidelines should also be followed to prevent COVID-19 infection in aesthetic clinics.

Vision Loss Associated with Hyaluronic Acid Fillers: A Systematic Review of Literature.

BACKGROUND: With the global increase in the use of injectable fillers, more cases with serious adverse events such as skin ischemia and vision loss are being reported. This article aims to review the role of HA fillers, as a subgroup separate from fat graft and non-HA fillers, in causing vision loss and to elucidate various features and outcomes of post-HA filler vision loss. METHODS: The preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines were used to report this review. A total of 29 articles presenting 60 unique cases of post-HA filler vision loss were identified in the literature. Based on various inclusion and exclusion criteria, 26 articles with details of 44 cases were included in this study. RESULTS: The majority of cases were seen in women and in the 20-40 years age group. The maximum number of cases was reported from Korea, followed by China. Nearly half of the cases reported after HA filler-related visual complications had partial loss of sight, hence 'partial vision loss' and 'complete vision loss' were used as differentiating descriptive terms to the degree of 'blindness.' Nearly all the cases were unilateral, with immediate onset of visual signs and symptoms. The nose, glabella, and forehead were the most commonly implicated areas, while no cases of post-HA filler vision loss were reported from lower face anatomical areas, including the chin, jawline, and lips. Partial vision loss after HA filler has a better prognosis than complete vision loss. HA filler volumes as low as 0.2 ml can cause permanent, complete vision loss, which is suggestive of the embolic nature of HA filler blockage. Ophthalmic artery occlusion (OAO) and central retinal artery occlusion (CRAO) were the two most commonly involved arterial obstruction patterns followed by branch retinal artery occlusion (BRAO). BRAO is the most favorable involved arterial pattern for a chance of recovery after HA filler-related vision loss while CRAO and OAO patterns carry a very poor prognosis. CONCLUSION: Post-HA filler vision loss is nearly always of immediate onset. Partial vision loss after HA filler injection with the involvement of smaller branches of the retina, other than central retinal artery or ophthalmic artery, has more favorable visual outcomes. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Homocysteine in neurological disease: a marker or a cause?

Hyperhomocysteinemia is increasingly recognized as an independent risk factor for several cerebral, vascular, ocular, and agerelated disorders. Whether it is a cause or a consequence or a mere marker necessitates further clarification. This review focuses on the pathophysiological aspects of homocysteine's involvement in neurodegenerative and neuropsychiatric disorders and complications. The pharmacological agents (antiepileptic drugs, L-DOPA) augment the homocysteine levels, thus, raising concern for physicians. The mechanisms underlying the enhanced homocysteine levels and its related pathophysiological cascades remain poorly understood, inspite of numerous epidemiological and research studies that have been carried out in recent years. This article will review the current understanding of these underlying mechanisms and the research being carried with homocysteine as a core molecule.

Modulatory effect of curcumin on methionine-induced hyperlipidemia and hyperhomocysteinemia in albino rats.

The present study was designed to investigate the antioxidant effect of curcumin on methionine-induced hyperlipidemia and hyperhomocysteinemia in Wistar rats (200-250 g) of either sex. The vehicle control rats were treated with 1% Tween 80 in normal saline (2 ml/kg, po) for 30 days. Hyperlipidemia and hyperhomocysteinemia was induced by methionine administration (1 g/kg, po) for 30 days. A significant increase in total cholesterol, triglycerides, low density lipoprotein cholesterol (LDL-C) and homocysteine levels in serum and thiobarbituric acid reactive substances (TBARS) levels in heart homogenates were observed with a concomitant decrease in serum high density lipoprotein (HDL-C) levels in pathogenic control (i.e. group II) rats, as compared to vehicle control (i.e. group I) rats. Further, curcumin (200 mg/kg, p.o.) treatment in methionine treated rats for 30 days significantly decreased the total cholesterol, triglycerides, LDL-C and homocysteine levels in serum and TBARS levels in heart homogenates and increased serum HDL-C levels, as compared to pathogenic control (i.e. group II) rats. The results of biochemical observations were supplemented by histopathological examination of rat's aortic section. The results of test drug were comparable to that obtained with folic acid (100 mg/kg, p.o.). The results suggest that curcumin has significant antihyperlipidemic and antihyperhomocysteinemic effect against methionine-induced hyperlipidemia and hyperhomocysteinemia in rats.

Prevention of nausea and vomiting after middle ear surgery: combination of ondansetron and dexamethasone is the right choice.

OBJECTIVE: To determine the efficacy of a combination of ondansetron and dexamethasone in preventing postoperative nausea and vomiting after middle ear surgery compared with ondansetron alone. DESIGN: A prospective, randomized, double-blind study with prestudy power analysis performed to determine the sample size. SETTING: A tertiary teaching hospital. METHOD: One hundred patients undergoing tympanomastoidectomy under general anesthesia were included in the study. Patients in group O (n = 50) received ondansetron 4 mg and those in group OD (n = 50) received ondansetron 4 mg with dexamethasone 8 mg 30 minutes before the end of surgery. All patients were monitored for nausea score, episodes of vomiting, and rescue antiemetic requirement in 48 hours after surgery. The total number of complete responders was calculated. Patients' satisfaction at the end of the study period was also estimated. RESULTS: In patients receiving combination antiemetic (group OD), the nausea score was significantly less (p < .01) at 6, 12, and 24 hours after surgery. The total incidence of vomiting was reduced from 28% in group O to 6% in group OD. Rescue antiemetic requirement was significantly less (p < .01) in group OD. The number of complete responders significantly improved in the combination group (92% vs 62%). The patients were also found to be more satisfied in this group. CONCLUSION: Prophylaxis with a combination of ondansetron and dexamethasone decreased the incidence of nausea and vomiting after middle ear surgery to a minimum and improved patients' satisfaction significantly in the postoperative period.