Collaborative research in myositis-related disorders: MIHRA, a global shared community model.

Myositis International Health and Research Collaborative Alliance (MIHRA) is a newly formed purpose-built non-profit charitable research organization dedicated to accelerating international clinical trial readiness, global professional and lay education, career development and rare disease advocacy in IIM-related disorders. In its long form, the name expresses the community's scope of engagement and intent. In its abbreviation, MIHRA, conveys linguistic roots across many languages, that reflects the IIM community's spirit with meanings such as kindness, community, goodness, and peace. MIHRA unites the global multi-disciplinary community of adult and pediatric healthcare professionals, researchers, patient advisors and networks focused on conducting research in and providing care for pediatric and adult IIM-related disorders to ultimately find a cure. MIHRA serves as a resourced platform for collaborative efforts in investigator-initiated projects, consensus guidelines for IIM assessment and treatment, and IIM-specific career development through connecting research networks.MIHRA's infrastructure, mission, programming and operations are designed to address challenges unique to rare disease communities and aspires to contribute toward transformative models of rare disease research such as global expansion and inclusivity, utilization of community resources, streamlining ethics and data-sharing policies to facilitate collaborative research. Herein, summarises MIHRA operational cores, missions, vision, programming and provision of community resources to sustain, accelerate and grow global collaborative research in myositis-related disorders.

[Nutritional Status of Institutionalized Elderly and Its Relationship with Functional Status During 2019]. / Estado nutricional de personas mayores institucionalizadas y su relación con el estado funcional durante el año 2019.

Aging is associated with physiological, economic, and psychological changes that can compromise nutritional and functional status. AIM: To determine the nutritional status of institutionalized older people living in a long-term nursing home "Fundación las Rosas" (FLR), the largest long-stay establishment in Chile, in 2019, and its relationship with functionality. METHODS: Descriptive study of analysis of secondary data in 1646 older adults institutionalized in FLR (60% women). The information collected was weight, height, Body mass index (BMI), Barthel Index, Mini-Mental State Examination, area, macrozone, sex, age, and date of admission to FLR. Logistic regression models of functionality and nutritional status, unadjusted and adjusted, were performed. RESULTS: The percentage of normal-weight people was 40.3%; 38.1% presented some degree of malnutrition due to deficit, and 9.5% presented severe malnutrition (BMI≤18.5 kg/m2). 70% of people present total dependency. The low educational level reached 73%. Logistic regressions determined that people who were overweight, 70 years of age or older, had a low level of education, and cognitive impairment were positively associated with dependency, excluding bedridden people, with the strongest associations being not having any level of schooling and having cognitive impairment. The persons of low weight, with cognitive impairment, and with a low educational level were positively associated with institutionalized bedridden elderly, the strongest associations being not having any level of schooling and having cognitive impairment. CONCLUSIONS: In this study, malnutrition due to deficit and excess are positively associated with decreased functionality, and a low educational level is associated with dependency and being bedridden.

A pilot study to evaluate the safety and efficacy of treprostinil in the treatment of calcinosis in systemic sclerosis.

OBJECTIVES: We evaluated the safety and efficacy of oral treprostinil in preventing progression of SSc-associated calcinosis. METHODS: This prospective open-label study enrolled 12 SSc patients meeting 2013 ACR/EULAR classification criteria with confirmed clinical and radiographic evidence of one or more calcinosis deposit in the hands. Patients received oral treprostinil for 1 year. Primary endpoints were safety/tolerability and percentage of patients without radiographic progression of calcinosis at 1 year (<25% increase in Scleroderma Clinical Trials Consortium radiographic score). Secondary endpoints included 1-year changes in Scleroderma HAQ (SHAQ), Cochin Hand Functional Scale, Medical Outcomes Survey Short Form 36 (SF-36), Raynaud Condition Score and patient/physician assessment of calcinosis severity. RESULTS: Twelve female patients were enrolled, half with diffuse cutaneous disease; median age was 55 years (range 35-68 years). Five patients completed the study. Seven patients withdrew due to intolerable adverse effects (n = 3), intercurrent unrelated illness (n = 2, cirrhosis, cancer), progressive SSc (n = 1) and personal reasons (n = 1). Most patients developed headaches and gastrointestinal adverse effects. Four of 11 (36%) patients with 1-year follow-up hand radiographs experienced progression of calcinosis. Of five who completed treatment, calcinosis was stable in four (80%) with progression in one. Based on SF-36 Physical and Mental Component and Domain scores, transition question and SF-6D utility score, all patients who finished the trial reported overall improvement or no change compared with baseline. CONCLUSION: Oral treprostinil was poorly tolerated in SSc patients with calcinosis. Of five patients who completed treatment, most (80%) had documented stability of calcinosis on hand radiographs at 1 year. CLINICALTRIALS.GOV IDENTIFIER: NCT02663895.

Calcinosis in scleroderma.

PURPOSE OF REVIEW: To provide an update on the available literature regarding the epidemiology, pathophysiology, diagnosis, and treatment of calcinosis cutis in patients with systemic sclerosis (SSc). RECENT FINDINGS: We identified observational studies that describe the frequency of calcinosis in SSc and associated clinical features; molecular studies exploring potential pathogenic mechanisms; and case reports and case series describing new diagnostic approaches and treatments. SUMMARY: Calcinosis cutis is the deposition of insoluble calcium in the skin and subcutaneous tissues. It represents a major clinical problem in patients with SSc affecting at least one quarter of patients. It is associated with longer disease duration, digital ulcers, acro-osteolysis, positive anticentromere antibody, and positive anti-PM/Scl antibody. Although pathogenesis is unknown, there is evidence supporting local trauma, chronic inflammation, vascular hypoxia, and dysregulation of bone matrix proteins as potential mechanisms. Diagnosis can be made clinically or with plain radiography. Several pharmacologic therapies have been tried for calcinosis with variable and modest results, but surgical excision of calcium deposits remains the mainstay of treatment.

Intestinal pseudo-obstruction in patients with systemic sclerosis: an analysis of the Nationwide Inpatient Sample.

OBJECTIVE: Intestinal pseudo-obstruction is a rare gastrointestinal complication in patients with SSc without large studies examining its prevalence or outcomes. We aimed to compare outcomes in SSc patients with intestinal pseudo-obstruction to patients with intestinal pseudo-obstruction secondary to other causes, and SSc patients without intestinal pseudo-obstruction. METHODS: This is a case-control study using the Healthcare Cost and Utilization Project Nationwide Inpatient Sample for the period 2002-2011. We included patients with the previously validated International Classification of Diseases-Clinical Modification-9 code 710.1 for SSc in combination with codes for intestinal pseudo-obstruction, and determined length of hospitalization and the risks for surgical procedures, use of total parenteral nutrition (TPN) and in-hospital mortality. RESULTS: A total of 193 610 SSc hospitalizations occurred in the USA between 2002 and 2011, of which 5.4% (n = 10 386) were associated with a concurrent intestinal pseudo-obstruction diagnosis (cases). In-hospital mortality was 7.3%. In multivariate analyses, cases were more likely to die during the inpatient stay and to receive TPN than patients with idiopathic intestinal pseudo-obstruction (control group 1), patients with intestinal pseudo-obstruction and diabetes (control group 2), and SSc patients without intestinal pseudo-obstruction (control group 3). Cases had longer in-hospital stay than control groups 2 and 3, and were less likely to undergo surgical procedures than control groups 1 and 2. CONCLUSION: Intestinal pseudo-obstruction is a rare cause of hospitalization in patients with SSc, but is associated with high in-hospital mortality in comparison with other SSc patients and those with intestinal pseudo-obstruction secondary to other causes.

Calcinosis: pathophysiology and management.

PURPOSE OF REVIEW: This article reviews the most updated literature regarding the epidemiology, pathophysiology, diagnosis, and treatment of calcinosis cutis in patients with systemic sclerosis (SSc). RECENT FINDINGS: Our review identified observational studies that describe the frequency of calcinosis in SSc and associated clinical features, genetic studies in animal models of heritable disorders leading to calcium deposition, and case series and case reports describing new diagnostic approaches and therapeutic interventions. SUMMARY: Calcinosis cutis is the deposition of calcium in the skin and subcutaneous tissues. It affects almost one quarter of patients with SSc, and is associated with longer disease duration, digital ulcers, acroosteolysis, positive anticentromere antibody, and positive anti-PM/Scl antibody. Local trauma, chronic inflammation, and vascular hypoxia have been proposed as potential pathomechanisms. The development of mouse models that mimic heritable ectopic mineralization disorders are contributing to the understanding of the process of calcification. Diagnosis can be made clinically or with plain radiography. Experimental diagnostic studies include ultrasonography, multidetector computed tomography, and dual-energy computed tomography. Several pharmacologic therapies have been tried for calcinosis with variable results, but surgical excision of calcium deposits remains the mainstay of treatment.

Recurrent hepatocellular carcinoma and poorer overall survival in patients undergoing left-sided compared with right-sided partial hepatectomy.

GOALS: We aimed to determine the incidence and predictors of recurrent hepatocellular carcinoma (HCC) after partial hepatectomy. BACKGROUND: Liver transplantation is the preferred treatment for selected patients with HCC, but access to donor organs is limited. Partial hepatectomy is another accepted treatment option; however, postoperative recurrence is frequently observed. METHODS: This is a retrospective cohort study of 107 consecutive patients who underwent partial hepatectomy for HCC between January 1993 and February 2011 at a US University Medical Center. Study endpoints were recurrent HCC, death, loss to follow-up, or last visit without HCC. RESULTS: The study cohort was 78% male with a median age of 61 years and 59% Asians. A total of 50 patients developed recurrent HCC (46.7%) after a median follow-up of 12 (1 to 69) months postresection. Recurrent HCC was significantly higher in patients with left-sided resection (41% at year 1, 54% at year 2, 62% at year 3, 81% at year 4, and 90% at year 5) compared with right-sided resection (18% at year 1, 34% at year 2, 36% at year 3, 44% at year 4, and 72% at year 5). In multivariate Cox proportional hazards model also inclusive of anatomic resection and TNM stage 3/4, left-sided resection was significantly associated with increased HCC recurrence (hazard ratio, 2.13; P=0.02; 95% confidence interval, 1.08-4.2) compared with right-sided resection. CONCLUSIONS: HCC recurrence rate is higher among those undergoing left-sided resection: 54% at year 2 and 81% at year 4. Liver transplantation should be considered in patients who are at high risk for recurrence.

Surgical treatment of systemic sclerosis--is it justified to offer peripheral sympathectomy earlier in the disease process?

PURPOSE: Systemic sclerosis (SSc) is a rare connective tissue disease associated with significant digital vasculopathy. Peripheral sympathectomy is frequently offered late in the disease process after severe digital ischemia has already occurred with patients being symptomatic for numerous years. The purpose of the present study was to analyze the results of peripheral sympathectomy in patients with a confirmed diagnosis of SSc. PATIENTS AND METHODS: A retrospective analysis of 17 patients (26 hands) who underwent peripheral sympathectomy between January 2003 and September 2013 was performed. Data regarding patient demographics, clinical features, and postoperative outcomes were retrieved. Of note, preoperative pain was present in all patients with a mean duration of 9.6 years prior to peripheral sympathectomy. RESULTS: Pain improvement/resolution was seen in 24 hands (92.3%). Digital ulcers healed in all patients with only two patients (two hands; 7.7%) requiring surgical intervention for ulcer recurrence 6 months and 4.5 years later. Minor complications were seen in seven hands (26.9%); including infection, wound opening, and stitch abscess, but none required surgical intervention. Seven of eight patients queried would have preferred surgical treatment at an earlier point in the disease process. CONCLUSION: Peripheral sympathectomy is a well-tolerated procedure in patients with SSc and is associated with predictable pain relief and ulcer healing in the majority of patients. In light of these findings it seems prudent to offer surgical treatment not as a last resort but rather earlier in the disease process to decrease the duration that patients suffer pain.

Primary surgical resection versus liver transplantation for transplant-eligible hepatocellular carcinoma patients.

BACKGROUND: Hepatocellular carcinoma (HCC) is a leading cause of mortality worldwide. Existing studies comparing outcomes after liver transplantation (LT) versus surgical resection among transplant-eligible patients are conflicting. AIM: The purpose of this study was to compare long-term survival between consecutive transplant-eligible HCC patients treated with resection versus LT. METHODS: The present retrospective matched case cohort study compares long-term survival outcomes between consecutive transplant-eligible HCC patients treated with resection versus LT using intention-to-treat (ITT) and as-treated models. Resection patients were matched to LT patients by age, sex, and etiology of HCC in a 1:2 ratio. RESULTS: The study included 171 patients (57 resection and 114 LT). Resection patients had greater post-treatment tumor recurrence (43.9 vs. 12.9 %, p < 0.001) compared to LT patients. In the as-treated model of the pre-model for end stage liver disease (MELD) era, LT patients had significantly better 5-year survival compared to resection patients (100 vs. 69.5 %, p = 0.04), but no difference was seen in the ITT model. In the multivariate Cox proportional hazards model, inclusive of age, sex, ethnicity, tumor stage, and MELD era (pre-MELD vs. post-MELD), treatment with resection was an independent predictor of poorer survival (HR 2.72; 95 % CI, 1.08-6.86). CONCLUSION: Transplant-eligible HCC patients who received LT had significantly better survival than those treated with resection, suggesting that patients who can successfully remain on LT listing and actually undergo LT have better outcomes.

Vascular, Soft Tissue, and Musculoskeletal Imaging in Systemic Sclerosis.

This review examines the role of various imaging techniques in assessing vascular and musculoskeletal manifestations in Systemic Sclerosis (SSc). Imaging modalities, such as thermography, capillaroscopy, ultrasound, optical coherence tomography, laser speckle contrast analysis, radiography, computed tomography, and MRI, offer valuable insights into SSc-related complications. Findings suggest that these techniques aid in diagnosing conditions like Raynaud phenomenon, digital ulcers, calcinosis, acro-osteolysis, and hand contractures. However, each modality has its advantages and limitations, necessitating a multimodal approach for comprehensive evaluation and accurate diagnosis of SSc-related manifestations.

Acute calcific tendinitis of the longus colli: A case report.

Acute calcific longus colli tendinitis is a differential diagnosis of neck pain. Typical presentation consists in a triad of symptoms including acute onset neck pain, neck stiffness and odynophagia. Computed tomography (CT) is the gold standard for acute calcific longus colli tendinitis diagnosis and the main radiological findings include prevertebral soft tissue swelling and the presence of amorphous calcifications. The case involves a 39-year-old female who presented to the emergency department with acute unilateral cervical pain that resulted in acute calcific longus colli tendinitis.

Patient Experience of Systemic Sclerosis-Related Calcinosis: An International Study Informing Clinical Trials, Practice, and the Development of the Mawdsley Calcinosis Questionnaire.

Systemic sclerosis (SSc) -related calcinosis can be a debilitating, constantly painful, poorly understood vascular complication of calcium hydroxyapatite deposition in soft tissue structures that affects approximately 40% of both limited and diffuse cutaneous SSc subtypes. This publication describes the iterative and multitiered international qualitative investigations that yielded remarkable insights into natural history, daily experience, and complications of SSc-calcinosis providing pivotal information for health management. Patient-driven question development and field testing, according to Food and Drug Administration guidance, propelled the development of a patient-reported outcome measure for SSc-calcinosis, the Mawdsley Calcinosis Questionnaire.

Incidence of hepatocellular carcinoma among US patients with cirrhosis of viral or nonviral etiologies.

BACKGROUND & AIMS: We aimed to identify risk factors for hepatocellular carcinoma (HCC) in patients with cirrhosis in the United States. We performed a prospective study to identify associations between etiologies of cirrhosis and ethnicity with HCC incidence. METHODS: We used convenience sampling to select a cohort of 379 patients with cirrhosis who visited the liver clinic at the Stanford University Medical Center from 2001 to 2009 (65% male, 75% white or Hispanic, and 20% Asian). Study end points were HCC diagnosis by histology or noninvasive criteria, liver transplantation, or last screening without HCC. Patients were followed up, with ultrasound or computed tomographic imaging analyses and measurements of serum levels of α-fetoprotein, approximately every 6 months, for a median time of 34 months (range, 6-99 mo). RESULTS: The etiologies of cirrhosis in the cohort were 68% hepatitis C, 7% hepatitis B, and 25% nonviral. Forty-four patients (12%) were diagnosed with HCC during the follow-up period. Patients with cirrhosis related to viral hepatitis had a statistically significantly higher incidence of HCC than those with nonviral diseases in Kaplan-Meier analysis (P = .04). There was no statistically significant difference in HCC incidence between Asian and non-Asian patients. In a multivariate Cox proportional hazards model that included age, sex, ethnicity, etiology, and Child-Pugh-Turcotte score, viral cirrhosis was associated significantly with HCC, compared with nonviral cirrhosis (hazard ratio, 3.6; 95% confidence interval, 1.3-10.1; P = .02) but Asian ethnicity was not. CONCLUSIONS: In a diverse cohort of patients in the United States with cirrhosis, a viral etiology of cirrhosis was associated with increased incidence of HCC, but Asian ethnicity was not. These findings indicate the importance of cirrhosis etiology in determining risk for HCC.

Subcutaneous calcinosis: Is it different between systemic sclerosis and dermatomyositis?

Calcinosis cutis is the deposition of insoluble calcium in the skin and subcutaneous tissues. It is a manifestation of several autoimmune connective tissue diseases, most frequently with systemic sclerosis and juvenile dermatomyositis, followed by adult dermatomyositis. Autoimmune connective tissue disease-associated calcinosis is of the dystrophic subtype, which occurs at sites of damaged tissue in the setting of normal serum calcium and phosphate levels. In juvenile dermatomyositis, calcinosis is considered a marker of ongoing disease activity and possibly inadequate treatment, while in adult dermatomyositis, it is a hallmark of skin damage due to chronic rather than active disease. Calcinosis is associated with long disease duration in systemic sclerosis and dermatomyositis, anti-polymyositis/sclerosis autoantibodies in systemic sclerosis and NXP-2 and melanoma differentiation-associated gene 5 in dermatomyositis. Calcinosis in systemic sclerosis occurs most frequently in the hands, particularly the fingers, whereas in dermatomyositis, it affects mainly the trunk and extremities. The primary mineral component of calcinosis is hydroxyapatite in systemic sclerosis and carbonate apatite in dermatomyositis. Calcinosis in dermatomyositis and systemic sclerosis share some pathogenic mechanisms, but vascular hypoxia seems to play a more important role in systemic sclerosis, whereas the release of calcium from mitochondria in muscle cells damaged by myopathy may be a primary mechanism contributing to dermatomyositis-related calcinosis. Multiple treatment strategies for dermatomyositis and systemic sclerosis-related calcinosis have been used with variable results. Early aggressive treatment of underlying myositis in patients with dermatomyositis may improve long-term outcomes of calcinosis. A better understanding of the pathogenesis of calcinosis is needed to improve treatment options.

Performance of the 2017 EULAR/ACR criteria for idiopathic inflammatory myopathies in a cohort of patients from Latin America.

We aimed to determine the performance of the 2017 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for idiopathic inflammatory myopathies (IIMs) in a cohort of Chilean patients. This single-center retrospective study included 151 patients with a clinical diagnosis of IIM. Patients were classified according to the 2017 EULAR/ACR classification criteria for IIM, and its performance was compared to the Bohan & Peter (B&P) classification criteria. A total of 135 patients (89.4%) met the EULAR/ACR criteria, and 140 (92.7%) patients met the B&P criteria. A total of 130 patients had IIM according to both the criteria; concordance rate was 29.2% for definite IIM, 6.2% for probable IIM, and 1.5% for possible IIM. The kappa coefficient of agreement was weak between the 2 classification criteria (κ = 0.39, SD 0.15-0.64). Against gold standard expert physician's diagnosis, sensitivity, and specificity of EULAR/ACR criteria was 0.86 and 0.85 to diagnose dermatomyositis, respectively, and 0.73 and 0.87 to diagnose polymyositis. The EULAR/ACR criteria showed good sensitivity and identified more patients with probable or definite IIM than the B&P criteria in a single-center cohort of patients with IIM in South America. The sensitivity of the EULAR/ACR criteria was slightly higher in patients with dermatomyositis, but lower in patients with polymyositis, than that of the B&P criteria.

Change in calcinosis over 1 year using the scleroderma clinical trials consortium radiologic scoring system for calcinosis of the hands in patients with systemic sclerosis.

INTRODUCTION: Calcinosis cutis is a debilitating complication of systemic sclerosis (SSc). We previously developed a radiographic scoring system to assess severity of calcinosis affecting the hands in patients with SSc. We sought to further validate our radiographic scoring system to assess for change over 1 year and to identify factors associated with improvement or progression. MATERIALS AND METHODS: Baseline and 1-year antero-posterior hand radiographs were obtained in 39 SSc patients with calcinosis prospectively enrolled at 6 centers within the US, Canada, Mexico and Australia. Two readers (one radiologist and one rheumatologist) scored all radiographs using the calcinosis scoring system and a 5-point Likert scale (1 = A lot better, 2 = A little better, 3=No change, 4 = A little worse, 5 = A lot worse) on follow-up. By maximizing the Kappa coefficient of agreement between grouped Likert scale (better/no change/worse) and the percentage of change of calcinosis in the radiographic scoring system, we defined progressive calcinosis as >25% increase in score from baseline at 1-year, stable calcinosis as change in score between -25% to 25%, and improvement of calcinosis as decrease in score by >25%. Nineteen SSc patients from an independent cohort were used for validation. RESULTS: Inter-rater reliability of the calcinosis scoring system was high with intra-class correlation coefficient of 0.93 (0.89-0.95). The median percentage of change from baseline to 1 year was 12.8% (range -89.3 to 290.2%). Sixteen patients (41%) experienced progression of calcinosis over 1 year; 18 (46%) remained stable; and 5 (13%) had improvement. Patients with progressive calcinosis had lower T-score on bone densitometry (-3.3 vs -1.7, p = 0.044) and higher prevalence of loss of digital pulp on physical exam (56% vs 22%, p = 0.027), with a trend towards lower baseline modified Rodnan skin score (mRSS) (3.8 vs. 5.9, p = 0.057), than patients who did not progress. Patients who experienced improvement in calcinosis had lower prevalence of digital pitting scars (20% vs 71%, p = 0.047) than patients whose calcinosis did not improve. In multivariable analysis, loss of digital pulp remained a predictor of calcinosis progression (OR 5.8, p = 0.023, CI 1.27 - 26.36). In the validation cohort, 2 (11%) patients improved, 10 (53%) remained stable, and 7 (37%) progressed. CONCLUSIONS: We confirmed the excellent inter-rater reliability of our radiographic calcinosis scoring system and demonstrated its usefulness to detect change over time. Approximately 40% of patients experienced progression of calcinosis over 1 year. Loss of digital pulp was predictive of progressive calcinosis providing further evidence that digital ischemia contributes to the progression of calcinosis.

A narrative review of imaging in calcinosis associated with systemic sclerosis.

Calcinosis is dystrophic calcification of the soft tissue which can lead to painful and debilitating disease. It is commonly seen in patients with systemic sclerosis (SSc). Imaging can assist in diagnosis, quantification of disease, and better pathophysiologic understanding of calcinosis. Traditionally, X-rays have been the most frequently used imaging modality for diagnosis; however, advances in ultrasound (US), computed tomography (CT), positron emission tomography (PET), and magnetic resonance imaging (MRI) have led to greater ability to characterize these lesions and surrounding structures. This narrative review aims to describe the use of imaging for calcinosis in patients with SSc. Key Points • Imaging is useful in the diagnosis of calcinosis, assessment of disease severity, and disease monitoring. • X-ray is commonly used and offers high sensitivity and specificity, but both ultrasound and CT-scans are alternatives when greater anatomic detail is sought regarding surrounding structures. • Investigational imaging modalities include dual energy CT-scans, cinematic rendering CT-scans, and PET- CT scans. • Conventional MRI scans have less sensitivity and specificity for detection of calcinosis.