The Psychosocial Impact of Undifferentiated Connective Tissue Disease on Patient Health and Well-Being: A Qualitative Study.

METHODS: We identified 20 adult patients with UCTD enrolled in the UCTD and Overlap Registry at our tertiary care level hospital. A licensed clinical social worker administered a 30-minute semistructured interview by telephone. The standardized questionnaire consisted of 14 open-ended questions on UCTD. A team of physicians, research coordinators, and a social worker used grounded theory to analyze the qualitative data and identify themes. RESULTS: Among 14/20 study participants (100% female; mean age, 53.6 ± 13.2 years [range, 27-74 years]), all had at least an associate's/bachelor's degree; 9 (64%) were White. The mean disease duration was 14.5 ± 13.5 years (range, 0.5-44 years). Nine study participants (64%) were engaged in counseling or mindfulness training. Ten specific psychosocial themes and categories emerged, including the need for professional guidance and peer and family support to increase awareness, reduce isolation, and promote self-efficacy. CONCLUSIONS: Emerging themes from semistructured interviews of women with UCTD at a major academic center suggest the need for psychosocial interventions (e.g., patient support groups, educational materials, peer counselors) to help UCTD patients manage and cope with their illness. Future studies evaluating the psychosocial impact of UCTD diagnosis on diverse cohorts are needed.

Evaluation of the relationship between microalbuminuria and 25-(OH) vitamin D levels in patients with type 2 diabetes mellitus.

BACKGROUND: 25-(OH) vitamin D (VD) deficiency has been described as potential risk factor for the development of diabetes in many epidemiological studies. 25-(OH) VD deficiency and insulin resistance associated with this deficiency are common findings in patients with type 2 diabetes mellitus. The objective of this study is to evaluate the relationship between 25-(OH) VD levels and microalbuminuria. METHODS: The patients with type 2 diabetes mellitus aged between 40 and 65 years, who were admitted to the diabetes outpatient clinics of our hospital, were evaluated in two different groups. The first group consisted of 119 patients with insufficient 25-(OH) VD levels (10-30 ng/mL) and the second group consisted of 121 patients with 25-(OH) VD deficiency (≤10 ng/mL). The relationship between 25-(OH) VD levels and the level of microalbuminuria was evaluated in the two groups. RESULTS: The mean 25-(OH) VD level was 11.5 ng/mL and the mean HbA1c level was 9.1%. When the patient groups were evaluated according to 25-(OH) VD levels, HbA1c values were significantly higher in patients with a 25-(OH) VD level of 10 ng/mL or lower (p = .039). 25-(OH) VD levels were not significantly different between patients with different stages of renal failure (p = .119), whereas the level of microalbuminuria was significantly different (p = .030). CONCLUSIONS: This study found that the level of microalbuminuria was significantly higher in patients with 25-(OH) vitamin D deficiency compared to patients with 25-(OH) VD insufficiency.

Association between sarcopenia and erectile dysfunction in males with type II diabetes mellitus.

BACKGROUND: The prevalence rates for both sarcopenia and erectile dysfunction (ED) gradually increase in middle-aged and elderly diabetic male population and they impair physical functioning, sexual functioning, and quality of life. The aim of the present study was to evaluate the sarcopenia in patients with diabetic ED. METHODS: The study included 98 male patients with type II diabetes mellitus (DM) aged 18-80 years. Blood chemistry and hormone levels were obtained. The International Index of Erectile Function (IIEF-5) questionnaire was administered to the patients. The patients were divided into three groups according to the IIEF-5 score; a score of 5-10 points indicated severe ED, a score of 11-20 indicated moderate ED, and a score of 21-25 points indicated no ED. The muscle mass, handgrip strength, timed up and go test, upper mid-arm circumference, calf circumference, and body mass index were obtained. The statistical analysis was performed using MedCalc Statistical Software version 12.7.7. All parameters were compared between the three groups. RESULTS: Of 98 patients included in the study, 84 patients had severe sarcopenia, 13 had moderate sarcopenia, while only one patient had normal muscle mass. The mean age was 56.59 ± 11.46 years. When patients were divided into three groups according to IIEF-5 score, 38 had severe ED, 39 had moderate ED, and 21 had no ED. There was a significant difference between the three groups in terms of handgrip strength, timed up and go test scores, upper mid-arm circumference, and calf circumference (p < .05 for all). CONCLUSIONS: Although muscle mass remains unchanged, muscle strength and physical performance decrease in diabetic ED patients. Diabetic patients with severe and moderate ED have lower muscle strength and physical performance.

A comprehensive review of dermatomyositis treatments - from rediscovered classics to promising horizons.

INTRODUCTION: Dermatomyositis (DM) is a rare inflammatory disease with diverse cutaneous and systemic manifestations, often associated with myositis-specific antibodies. Managing patients with refractory DM, or individuals presenting pecific complications, like calcinosis or rapidly progressive interstitial lung disease, presents unique challenges. AREAS COVERED: This review explores current and promising treatment options for DM, drawing from clinical studies, case series, and case reports that consider the underlying disease pathophysiology. EXPERT OPINION: Recent advancements have improved our understanding and management of DM. The discovery of distinct DM autoantibodies and their correlation with specific clinical phenotypes has transformed patient categorization and enhanced our knowledge of the pathogenesis of the disease. Intravenous immunoglobulin, a well-established treatment in dermatomyositis, has regained prominence and a large randomized clinical trial has reaffirmed its efficacy, confirming it as an effective therapeutic option in this group of patients. Identification of the type I interferon pathway as a key pathogenic mechanism in DM has opened up new avenues for more effective treatment strategies. Blocking the JAK/STAT pathway offers potential for improved management of refractory patients and prevention of highly morbid complications. These recent advancements have significantly impacted the management and care of dermatomyositis patients, enabling tailored approaches, targeted interventions, and improved outcomes for individuals affected by this complex condition.

Relapsing polychondritis: Best Practice & Clinical Rheumatology.

Relapsing polychondritis (RP) is an uncommon inflammatory disorder that predominantly targets cartilaginous structures. The disease frequently affects the nose, ears, airways, and joints, but it can also impact organs that aren't primarily cartilage-based, such as blood vessels, skin, inner ear, and eyes. Given its infrequent occurrence and recurrent symptoms, patients often experience delays in proper diagnosis. Lately, based on the organs involved, the disease's diverse manifestations have been categorized into specific clinical groups, based on the most likely organ involvement including auricular, nasal, pulmonary, and musculoskeletal. More recently the discovery of a new disease, called (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) VEXAS syndrome, due to mutations in UBA1 gene, identified the cause of 8 % of the patients with a clinical diagnosis of RP. VEXAS is likely the cause of a previously described "hematologic subgroup" in RP. This discovery is proof of concept that RP is likely more than one disease (Beck et al., Dec 31 2020; Ferrada et al., 2021). People diagnosed with RP face numerous hurdles, with the quality of their lives and overall prognosis being affected. Diagnosing the condition is particularly challenging due to its fluctuating symptoms, the absence of specific markers, and the lack of universally recognized classification criteria. For a correct diagnosis, it's imperative for healthcare professionals to identify its unique clinical patterns. Moreover, there are no approved metrics to gauge the disease's severity, complicating patient management. This review seeks to equip clinicians with pertinent insights to better diagnose and attend to these complex patients.

Mammalian Target of Rapamycin Pathway Assessment in Antiphospholipid Antibody-Positive Patients with Livedo.

OBJECTIVE: In antiphospholipid antibody (aPL) nephropathy, activation of the mammalian target of rapamycin (mTOR) contributes to endothelial cell proliferation, a key finding of aPL microvascular disease. Here, we examined mTOR activation in the skin of aPL-positive patients with livedo. METHODS: Three patient groups with livedo were studied: (1) persistently aPL-positive with systemic lupus erythematosus (SLE); (2) persistently aPL-positive without SLE; and (3) aPL-negative SLE (control). After collecting aPL-related medical history, two 5-mm skin biopsies of livedo were performed on each patient: (1) peripheral (erythematous-violaceous lesion); and (2) central (nonviolaceous area). We stained specimens for phosphorylated protein kinase B (p-AKT) and phosphorylated S6 ribosomal protein (p-S6RP) as mTOR activity markers, CD31 to identify endothelial cells, and Ki-67 to show cellular proliferation. We counted cells in the epidermis and compared mTOR-positive cell counts between peripheral and central samples, and between patient groups, using Freidman test and Wilcoxon signed-rank test. RESULTS: Ten patients with livedo reticularis were enrolled: 4 aPL-positive without SLE (antiphospholipid syndrome [APS] classification met, n = 3), 4 aPL-positive SLE (APS classification met, n = 3), and 2 aPL-negative SLE (control). In all aPL-positive patients, epidermal p-AKT and p-S6RP staining were significantly increased in both peripheral and central skin samples when compared to aPL-negative SLE controls; both were more pronounced in the lower basal layers of epidermis. CONCLUSION: Our study demonstrates increased mTOR activity in livedoid lesions of aPL-positive patients with or without SLE compared to aPL-negative patients with SLE, with more prominent activity in the lower basal layers of the epidermis. These findings may serve as a basis for further investigating the mTOR pathway in aPL-positive patients.

Pregnancy outcomes in antiphospholipid antibody positive patients: prospective results from the AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking (APS ACTION) Clinical Database and Repository ('Registry').

OBJECTIVES: To describe the outcomes of pregnancies in antiphospholipid antibody (aPL)-positive patients since the inception of the AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking Registry. METHODS: We identified persistently aPL-positive patients recorded as 'pregnant' during prospective follow-up, and defined 'aPL-related outcome' as a composite of: (1) Preterm live delivery (PTLD) at or before 37th week due to pre-eclampsia (PEC), eclampsia, small-for-gestational age (SGA) and/or placental insufficiency (PI); or (2) Otherwise unexplained fetal death after the 10th week of gestation. The primary objective was to describe the characteristics of patients with and without aPL-related composite outcomes based on their first observed pregnancies following registry recruitment. RESULTS: Of the 55 first pregnancies observed after registry recruitment among nulliparous and multiparous participants, 15 (27%) resulted in early pregnancy loss <10 weeks gestation. Of the remaining 40 pregnancies: (1) 26 (65%) resulted in term live delivery (TLD), 4 (10%) in PTLD between 34.0 weeks and 36.6 weeks, 5 (12.5%) in PTLD before 34th week, and 5 (12.5%) in fetal death (two associated with genetic anomalies); and (2) The aPL-related composite outcome occurred in 9 (23%). One of 26 (4%) pregnancies with TLD, 3/4 (75%) with PTLD between 34.0 weeks and 36.6 weeks, and 3/5 (60%) with PTLD before 34th week were complicated with PEC, SGA and/or PI. Fifty of 55 (91%) pregnancies were in lupus anticoagulant positive subjects, as well as all pregnancies with aPL-related composite outcome. CONCLUSION: In our multicentre, international, aPL-positive cohort, of 55 first pregnancies observed prospectively, 15 (27%) were complicated by early pregnancy loss. Of the remaining 40 pregnancies, composite pregnancy morbidity was observed in 9 (23%) pregnancies.

Characteristics of Patients With Antiphospholipid Antibody Positivity in the APS ACTION International Clinical Database and Repository.

OBJECTIVE: To describe the baseline characteristics of patients with positivity for antiphospholipid antibodies (aPLs) who were enrolled in an international registry, the Antiphospholipid Syndrome (APS) Alliance for Clinical Trials and International Networking (APS ACTION) clinical database and repository, overall and by clinical and laboratory subtypes. METHODS: The APS ACTION registry includes adults who persistently had positivity for aPLs. We evaluated baseline sociodemographic and aPL-related (APS classification criteria and "non-criteria") characteristics of patients overall and in subgroups (aPL-positive without APS, APS overall, thrombotic APS only, obstetric APS only, and both thrombotic APS/obstetric APS). We assessed baseline characteristics of patients tested for the presence of three aPLs (lupus anticoagulant [LAC] test, anticardiolipin antibody [aCL], and anti-ß2 -glycoprotein I [anti-ß2 GPI]) antibodies by aPL profiles (LAC only, single, double, and triple aPL positivity). RESULTS: The 804 aPL-positive patients assessed in the present study had a mean age of 45 ± 13 years, were 74% female, and 68% White; additionally, 36% had other systemic autoimmune diseases. Of these 804 aPL-positive patients, 80% were classified as having APS (with 55% having thrombotic APS, 9% obstetric APS, and 15% thrombotic APS/obstetric APS). In the overall cohort, 71% had vascular thrombosis, 50% with a history of pregnancy had obstetric morbidity, and 56% had experienced at least one non-criteria manifestation. Among those with three aPLs tested (n = 660), 42% were triple aPL-positive. While single-, double-, and triple aPL-positive subgroups had similar frequencies of vascular, obstetric, and non-criteria events, these events were lowest in the single aPL subgroup, which consisted of aCLs or anti-ß2 GPI only. CONCLUSION: Our study demonstrates the heterogeneity of aPL-related clinical manifestations and laboratory profiles in a multicenter international cohort. Within single aPL positivity, LAC may be a major contributor to clinical events. Future prospective analyses, using standardized core laboratory aPL tests, will help clarify aPL risk profiles and improve risk stratification.

The Relationship Between Osteoarthritis and Sarcopenia in Geriatric Diabetic Patients.

Objectives: Osteoarthritis is a common disease affecting the quality of life in the elderly population. Osteoarthritis is a painful condition commonly encountered in patients aged 65 years and older and it may cause muscle weakness. Sarcopenia is a condition that has an increasing prevalence in the elderly population. The present study evaluated the relationship between sarcopenia and osteoarthritis. Methods: The study included 100 patients aged 65 years and older who were diagnosed with diabetes mellitus. The patients were divided into two groups as Group 1 and Group 2. Group 1 was composed of 50 patients with diabetes and osteoarthritis and Group 2 was composed of 50 patients with diabetes but without osteoarthritis. A detailed medical history was obtained from all patients and all patients underwent physical examination. The get-up and go test was performed, handgrip strength was measured with a hand dynamometer, bioimpedance analysis was performed, and mid-upper arm circumference, calf circumference and waist circumference were measured, and laboratory tests including complete blood count, biochemical nutritional parameters, liver and kidney function tests, and erythrocyte sedimentation rate were ordered. The Kellgren and Lawrence grading system was used to evaluate the severity of osteoarthritis and the skeletal muscle mass index was used to evaluate the muscle mass. These parameters were compared between the two groups. Results: Of the study participants, 1% had severe sarcopenia, 22% had moderate sarcopenia, and 77% did not have sarcopenia. Albumin (p=0.013), magnesium (p=0.038), total protein (0.004), erythrocyte sedimentation rate (p=0.047), hemoglobin level (p=0.018), muscle strength (p=0.046), height (p=0.033), and muscle mass (p<0.05) were significantly different in patients with osteoarthritis compared to patients without osteoarthritis. Patients with osteoarthritis achieved poorer results on the get-up and go test (p=0.014), and mid-upper arm circumference (p=0.028), and calf circumference (p=0.016) were lower in this group. There was a negative moderate correlation between the muscle mass and the Kellgren and Lawrence grade (p<0.05, r: -0.405), whereas there was a positive moderate correlation between sarcopenia index and the Kellgren and Lawrence grade (p<0.05, r: 0.320) in patients with osteoarthritis. Conclusion: The present study is the first to evaluate the relationship between sarcopenia and osteoarthritis in geriatric diabetic patients. The present study found a significant relationship between osteoarthritis and sarcopenia in geriatric patients with type II diabetes mellitus. The authors suggest that pain associated with osteoarthritis results in immobility, decrease in functional performance, and thus development of sarcopenia.

Antiphospholipid Antibody Profile Stability Over Time: Prospective Results From the APS ACTION Clinical Database and Repository.

OBJECTIVE: The APS ACTION Registry studies long-term outcomes in persistently antiphospholipid antibody (aPL)-positive patients. Our primary objective was to determine whether clinically meaningful aPL profiles at baseline remain stable over time. Our secondary objectives were to determine (1) whether baseline characteristics differ between patients with stable and unstable aPL profiles, and (2) predictors of unstable aPL profiles over time. METHODS: A clinically meaningful aPL profile was defined as positive lupus anticoagulant (LAC) test and/or anticardiolipin (aCL)/anti-ß2 glycoprotein-I (anti-ß2-GPI) IgG/M ≥ 40 U. Stable aPL profile was defined as a clinically meaningful aPL profile in at least two-thirds of follow-up measurements. Generalized linear mixed models with logit link were used for primary objective analysis. RESULTS: Of 472 patients with clinically meaningful aPL profile at baseline (median follow-up 5.1 yrs), 366/472 (78%) patients had stable aPL profiles over time, 54 (11%) unstable, and 52 (11%) inconclusive. Time did not significantly affect odds of maintaining a clinically meaningful aPL profile at follow-up in univariate (P = 0.906) and multivariable analysis (P = 0.790). Baseline triple aPL positivity decreased (OR 0.25, 95% CI 0.10-0.64, P = 0.004) and isolated LAC test positivity increased (OR 3.3, 95% CI 1.53-7.13, P = 0.002) the odds of an unstable aPL profile over time. CONCLUSION: Approximately 80% of our international cohort patients with clinically meaningful aPL profiles at baseline remain stable at a median follow-up of 5 years; triple aPL-positivity increase the odds of a stable aPL profile. These results will guide future validation studies of stored blood samples through APS ACTION Core Laboratories.

Is there a role for immunosuppression in antiphospholipid syndrome?

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by thrombosis, pregnancy morbidity, or nonthrombotic manifestations in patients with persistently positive antiphospholipid antibodies (aPL). Conventional APS treatment focuses on antithrombotic strategies, which are usually ineffective for the microvascular and nonthrombotic manifestations of aPL. Using a case-based presentation, this review focuses on the role of immunosuppression in nonobstetric APS, including B-cell inhibition (rituximab, belimumab, and bortezomib), complement inhibition (eculizumab), mechanistic target of rapamycin inhibition (sirolimus), vascular endothelial cell modulation (defibrotide), statins, and traditional rheumatologic disease-modifying agents (hydroxychloroquine, mycophenolate mofetil, azathioprine, and cyclophosphamide).

Impact of antiphospholipid syndrome iBook on medical students' improvement of knowledge: An international randomized controlled study.

OBJECTIVE: iBook on Antiphospholipid Syndrome (APS) did not exist before our work, and hence the utility of an Apple iBook as a teaching method in APS for medical students has never been assessed. Our objective was to evaluate medical students' improvement of knowledge and satisfaction with an interactive APS iBook, in comparison with conventional teaching methods. METHODS: An iBook designer with the guidance of a medical team developed the APS iBook in both French and English. Second-year medical students, naïve of APS knowledge, were enrolled from two institutions. For the "teaching intervention", participants were randomly assigned to three groups: a) APS iBook with interactive capability; b) printed copy of the APS iBook material; and c) classroom lecture presentation of the APS iBook material by a physician-scientist experienced in APS. The participants filled a standardized medical questionnaire about APS before and after teaching interventions to determine the relative change of knowledge. Participants were asked to fill out a standardized satisfaction survey. After 20 weeks of the intervention, recall capability of students was tested. RESULTS: A total of 233 second-year medical students were enrolled (iBook group: 73; print group: 79, and lecture group: 81). Relative change of knowledge was not different between the iBook group and the printed material group; additionally, it was significantly higher in the lecture group than the two other methods. Satisfaction was significantly higher in both the lecture and the iBook groups than the print group, on several dimensions including overall quantitative satisfaction, subjective enhanced knowledge, interactivity, quality of content, comprehensibility, and pleasure of learning. Recall capability of students (n=109, 47%) was not significantly different among groups. CONCLUSION: The APS iBook is as effective as printed material in improving medical student's knowledge, although a classroom lecture was the most effective method when compared to self-learning methods. Among self-learning methods, medical students are more satisfied with the APS iBook, whereas the recall capability was not different among groups. These results suggest that the APS iBook will help medical students in their curriculum and increase the awareness of APS among the community.

Comparison of real world and core laboratory lupus anticoagulant results from the Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION) clinical database and repository.

BACKGROUND: Variability remains a challenge in lupus anticoagulant (LA) testing. OBJECTIVE: To validate LA test performance between Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION) Core laboratories and examine agreement in LA status between Core and local/hospital laboratories contributing patients to this prospective registry. METHODS: Five Core laboratories used the same reagents, analyzer type, protocols, and characterized samples for LA validation. Non-anticoagulated registry samples were retested at the corresponding regional Core laboratories and anticoagulated samples at a single Core laboratory. Categorical agreement and discrepancies in LA status between Core and local/hospital laboratories were analyzed. RESULTS: Clotting times for the reference/characterized plasmas used for normalized ratios were similar between Core laboratories (CV <4%); precision and agreement for LA positive/negative plasma were similar (all CV ≤5%) in the four laboratories that completed both parts of the validation exercise; 418 registry samples underwent LA testing. Agreement for LA positive/negative status between Core and local/hospital laboratories was observed in 87% (115/132) non-anticoagulated and 77% (183/237) anticoagulated samples. However, 28.7% (120/418) of samples showed discordance between the Core and local/hospital laboratories or equivocal LA results. Some of the results of the local/hospital laboratories might have been unreliable in 24.7% (41/166) and 23% (58/252) of the total non-anticoagulated and anticoagulated samples, respectively. Equivocal results by the Core laboratory might have also contributed to discordance. CONCLUSIONS: Laboratories can achieve good agreement in LA performance by use of the same reagents, analyzer type, and protocols. The standardized Core laboratory results underpin accurate interpretation of APS ACTION clinical data.

The adjusted global antiphospholipid syndrome score (aGAPSS) and the risk of recurrent thrombosis: Results from the APS ACTION cohort.

OBJECTIVES: To assess whether patients with antiphospholipid syndrome (APS) and history of recurrent thrombosis have higher levels of adjusted Global AntiphosPholipid Syndrome Score (aGAPSS) when compared to patients without recurrent thrombosis. METHODS: In this cross-sectional study of antiphospholipid antibody (aPL)-positive patients, we identified APS patients with a history of documented thrombosis from the AntiPhospholipid Syndrome Alliance For Clinical Trials and InternatiOnal Networking (APS ACTION) Clinical Database and Repository ("Registry"). Data on aPL-related medical history and cardiovascular risk factors were retrospectively collected. The aGAPSS was calculated at Registry entry by adding the points corresponding to the risk factors: three for hyperlipidemia, one for arterial hypertension, five for positive anticardiolipin antibodies, four for positive anti-ß2 glycoprotein-I antibodies and four for positive lupus anticoagulant test. RESULTS: The analysis included 379 APS patients who presented with arterial and/or venous thrombosis. Overall, significantly higher aGAPSS were seen in patients with recurrent thrombosis (arterial or venous) compared to those without recurrence (7.8 ±â€¯3.3 vs. 6 ±â€¯3.9, p<0.05). When analyzed based on the site of the recurrence, patients with recurrent arterial, but not venous, thrombosis had higher aGAPSS (8.1 ± SD 2.9 vs. 6 ±â€¯3.9; p<0.05). CONCLUSIONS: Based on analysis of our international large-scale Registry of aPL-positive patients, the aGAPSS might help risk stratifying patients based on the likelihood of developing recurrent thrombosis in APS.