Connective Tissue Disease Research Articles

Histological differences related to autophagy in the minor salivary gland between primary and secondary types of Sjögren’s syndrome

Some forms of Sjögren’s syndrome (SS) follow a clinical course accompanied by systemic symptoms caused by lymphocyte infiltration and proliferation in the liver, kidneys, and other organs. To better understand the clinical outcomes of SS, here we used minor salivary gland tissues from patients and examine their molecular, biological, and pathological characteristics. A retrospective study was performed, combining clinical data and formalin-fixed paraffin-embedded (FFPE) samples from female patients over 60 years of age who underwent biopsies at Okayama University Hospital. We employed direct digital RNA counting with nCounter® and multiplex immunofluorescence analysis with a PhenoCycler™ on the labial gland biopsies. We compared FFPE samples from SS patients who presented with other connective tissue diseases (secondary SS) with those from stable SS patients with symptoms restricted to the exocrine glands (primary SS). Secondary SS tissues showed enhanced epithelial damage and lymphocytic infiltration accompanied by elevated expression of autophagy marker genes in the immune cells of the labial glands. The close intercellular distance between helper T cells and B cells positive for autophagy-associated molecules suggests accelerated autophagy in these lymphocytes and potential B cell activation by helper T cells. These findings indicate that examination of FFPE samples from labial gland biopsies can be an effective tool for evaluating molecular histological differences between secondary and primary SS through multiplexed analysis of gene expression and tissue imaging.

Spontaneous pneumothorax in children: a radiological perspective.

Spontaneous pneumothorax is a common clinical condition due to several etiologies. Appropriate radiologic assessment helps avoid re-imaging and guide individualized management. To describe the etiologic factors of spontaneous pneumothorax in children from a radiological perspective. Thirty-nine children with spontaneous pneumothorax were evaluated according to their demographic characteristics, the presence of underlying lung diseases, and imaging findings. Twenty-one patients without underlying lung disease were assessed as primary spontaneous pneumothorax; eight of these 21 patients (38.9%) had subpleural air cysts in the apices/upper lobes of the lung on chest computed tomography (CT). In the remaining 18 patients with secondary spontaneous pneumothorax, the most common causes were respiratory diseases (33.3%), infectious lung diseases (33.3%), interstitial lung diseases (27.7%), and connective tissue diseases (5.5%). The mean age of children with secondary spontaneous pneumothorax was lower than that of children with primary spontaneous pneumothorax (P = 0.002). Recurrences occurred in 11 patients (52.3%) with primary spontaneous pneumothorax and three patients (16.6%) with secondary spontaneous pneumothorax. Bilateral pneumothorax was observed in three of the 18 patients with secondary spontaneous pneumothorax. Identifying the etiologic factors of spontaneous pneumothorax may help clinicians plan how to reduce the risk of recurrence. Radiologists should keep in mind the possible underlying diseases and assess imaging methods in children with spontaneous pneumothorax for subpleural air cysts and be suspicious about an underlying disease in cases of bilateral pneumothorax and in younger patients.

Detection and differentiation of antinuclear antibodies in serum of dengue suspected patients with or without systemic autoimmune disease in Kolkata, India

ABSTRACT The pathophysiology of dengue may be influenced by antibodies released during infection. Several autoimmune diseases are accompanied by antinuclear antibodies (ANAs) but 8–10% of the general population have positive ANA tests. To test the hypothesis that an ANA-positive test indicates an immune dysregulated state that modifies the risk for certain clinical disorders in people with or without an autoimmune disease, we examined the various ANA profiles and their relationships to various autoimmune disorders, as well as the severity of these relationships, in patients infected with dengue fever. Enzyme-linked immunosorbent assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR) methods were used. Indirect immunofluorescence assay (IIFA) and line immunoassay (LIA) were performed to detect and differentiate the ANAs among dengue infected patients. Out of 135 dengue virus-positive patients, 94.07% were positive by ELISA and 5.93% positive by RT-PCR method. ANAs by IIFA and LIA were detected in 54.8% and 18.5% of the dengue positive patients, respectively, and 10.3% and 7.1% of the 126 dengue negative patients, respectively. This study showed that dengue was associated with an increased risk of autoimmune myositis and mixed connective tissue disease (MCTD), a rare complication of dengue. The risk of other autoimmune diseases did not seem to increase after DENV infection.

A Case Report of Mixed Connective Tissue Disease Predominantly Manifesting as Systemic Sclerosis in a Middle-Aged Nepali Woman

Introduction: Mixed connective tissue disease (MCTD) is a rare systemic autoimmune disorder, first described in 1972, that presents with overlapping features of systemic lupus erythematosus, systemic sclerosis, and polymyositis. The diagnosis of MCTD is complex and often delayed due to its varied clinical manifestations and the requirement of serological confirmation, particularly the presence of anti-U1 RNP antibodies. Despite its global prevalence, data on MCTD are limited, especially in the South Asian population.  Case Report: We present the case of a 42-year-old Nepali woman with a decade-long history of myalgia, muscle weakness, and joint pain, initially misdiagnosed as rheumatoid arthritis. Over time, she developed Raynaud phenomenon, dysphagia, and progressive muscle weakness, which prompted further investigation. Serological testing revealed elevated levels of anti-U1 RNP antibodies and a positive antinuclear antibody (ANA) titer, confirming the diagnosis of MCTD according to the Alarcón-Segovia criteria. The patient was successfully managed with a regimen of corticosteroids, hydroxychloroquine, and nifedipine, resulting in significant symptomatic improvement.  Discussion: This case underscores the diagnostic challenges associated with MCTD, a condition that may present with nonspecific symptoms and mimic other rheumatic diseases. The prolonged diagnostic journey of this patient highlights the need for heightened clinical suspicion and comprehensive serological testing in patients with overlapping connective tissue disease features. Furthermore, the case contributes to the limited body of literature on MCTD in the South Asian population, emphasizing the importance of early recognition and tailored management strategies to improve patient outcomes.  Conclusion: MCTD is a complex and under-recognized autoimmune disorder, particularly in the South Asian context. This case report highlights the importance of considering MCTD in the differential diagnosis of patients with multi-systemic involvement and underscores the role of serological testing in confirming the diagnosis. Early diagnosis and appropriate management are crucial in mitigating disease progression and improving the quality of life for patients with MCTD.

Association of Combined Autoreactivity to Sm/RNP Common Motif and U1 RNP With Mixed Connective Tissues Disease and Systemic Lupus Erythematosus.

This study aimed to evaluate the clinical features in patients with suspected connective tissue disease who tested positive for anti-Sm/RNP common motif antibody with or without associated anti-RNP antibody. The titers of anti-Sm/RNP and anti-RNP antibodies were measured by the multiplex solid-phase bioassays (Bio-Rad). Clinical manifestations were compared among the three subgroups (RNP only, Sm/RNP only, and double positive for RNP and Sm/RNP). Patients were further evaluated for the diagnosis of mixed connective tissue disease (MCTD) and/or systemic lupus erythematosus (SLE) using accepted classification criteria. A total of 133 patients were included in this study. The rates of inflammatory arthritis and Raynaud phenomenon were significantly higher in patients testing positive for both anti-RNP and anti-Sm/RNP antibodies compared to anti-RNP only or anti-Sm/RNP only (69.1% vs 28.8% vs 25.0%, P < 0.0001 for arthritis and 59.5% vs 23.3% vs 37.5%, P = 0.0005 for Raynaud phenomenon). Area under the curve (AUC) values were 0.68 (95% confidence interval [CI] 0.59-0.77, P < 0.0001) for anti-Sm/RNP titers and 0.65 (95% CI 0.55-0.74, P = 0.0039) for anti-RNP titers with inflammatory arthritis. AUC values were 0.67 (95% CI 0.58-0.77, P = 0.0002) for anti-Sm/RNP titers and 0.59 (95% CI 0.49-0.69, P = 0.0352) for anti-RNP titers with Raynaud phenomenon. The odds ratios for the diagnosis of MCTD and SLE were significantly higher in patients with double positivity compared to those testing solely positive for anti-RNP antibody. Anti-Sm/RNP common motif autoreactivity when combined with anti-RNP antibody positivity identifies those patients who are closely related with certain clinical manifestations and who are associated with well-defined connective tissue disease such as MCTD or SLE.

Autoimmune Optic Neuropathy

Autoimmune optic neuropathy represents a chronic, heterogeneous disease that is usually accompanied by bilateral vision loss and is caused by injury occurring through autoimmune mechanisms. Autoimmune optic neuropathy can occur as a component of autoimmune or collagen vascular diseases, as well as it can be seen in an isolated way. Plasmapheresis and monoclonal antibodies are used together with steroids in the treatment of autoimmune optic neuropathy, the pathophysiology of which is not yet fully understood despite advances in existing laboratory and imaging devices. This rare clinical picture usually results in vision loss when it is not properly diagnosed, treated quickly and effectively.

Novel deep-learning analysis for connective tissue disease -related interstitial lung disease extent assessment on CT: a preliminary cross-sectional study.

Physician's evaluation of interstitial lung disease (ILD) extension with high-resolution computed tomography (HRCT) has limitations such as lack of objectivity and reproducibility. This study aimed to investigate the utility of computer-based deep-learning analysis using QZIP-ILD® software (DL-QZIP) compared with conventional approaches in connective tissue disease (CTD) -related ILD. Patients with CTD-ILD visiting our Rheumatology Centre between December 2020 and April 2024 were recruited. Quantitative scores, including the percentage of lung involvement in ground-glass opacity (QGG), total fibrotic lesion (QFIB), and overall ILD extension encompassing both QGG and QFIB (QILD), calculated by DL-QZIP, were compared with semiquantitative visual method, employing intraclass correlation coefficients (ICC). We compared the capability of QILD scores to distinguish patients with forced vital capacity (FVC) % <70 in both methods determined by the area under the curve (AUC) by the receiver-operating characteristic curve analysis and DeLong's test. Eighty patients (median age, 66 years; 14 men) were included. Median QGG, QFIB, and QILD scores were 3.45%, 2.19%, and 5.35% using DL-QZIP, and 3.25%, 4.06%, and 8.48% using visual method, respectively. Correlations between DL-QZIP and visual method were 0.75 for QGG, 0.61 for QFIB, and 0.75 for QILD. The AUC of QILD scores for FVC% <70 was significantly higher with DL-QZIP (0.833) compared with visual method (0.660) (p < 0.01). QZIP-ILD® demonstrates superior capability in distinguishing patients with a radiological scenario correlated to severe physiological impairment, while showing relatively good correlations in quantifying the extent on HRCT compared with conventional method in CTD-ILD.

Double-negative T cells in pediatric rheumatic diseases.

Double-negative (CD4-CD8-) T (DNT) cells have been implicated in Autoimmune Lymphoproliferative Syndrome (ALPS), where their expansion inside the circulating pool of T cells represents a diagnostic criterion. Recent experimental evidence has supported the immunomodulatory roles of DNT cells, and studies in adult patients have suggested that they may be altered in some immune-mediated conditions. This study aimed to retrieve available data on circulating DNT cells in pediatric rheumatic disorders that do not arise in the context of ALPS through a systematic literature review of three scientific databases (PubMed, Scopus, and Web of Science). The final output of the systematic literature search consisted of eight manuscripts, including cross-sectional (n=6) and longitudinal (n=2) studies. Overall, the pooled population of patients includes children affected with pediatric Systemic Lupus Erythematosus (n=104), Juvenile Idiopathic Arthritis (n=92), Behçet's disease (n=15), mixed connective tissue disease (n=8), Juvenile Dermatomyositis (n=6), and Kawasaki disease/multisystem inflammatory disease in children (n=1 and n=14, respectively); moreover, one study also included 11 children with a high titer of antinuclear antibody but no diagnosis of rheumatic disease. All studies except one included a control group. The number of DNT cells were increased in most studies of children with rheumatic diseases. Even if such a limited number of studies and their great heterogeneity in several methodological aspects do not allow for reliable conclusions about the relevance of DNT cells in specific rheumatic conditions in children, this cell population deserves further investigation in this pathological setting through well-designed clinical studies.

Morphea-like tattoo reaction in a patient with systemic sclerosis: Case report and review of the literature

Background: Morphea-like tattoo reactions are rare phenomena, with few cases reported in the literature. We present a case of a morphea-like tattoo reaction and a literature review of such reactions for comparison. Case Description: A 38-year-old woman with known history of systemic sclerosis presented with abnormal healing and skin thickening over a red tattoo. Histopathological examination revealed sclerosing dermatitis, consistent with morphea-like tattoo reaction. Treatment included topical clobetasol and oral mycophenolate mofetil. Methods: A literature search of PubMed and EMBASE was performed in August 2023 for known morphea-like tattoo reactions. No time or language filters were applied. Results: A total of six articles were included. Case reports of morphea-like tattoo reactions in patients with no significant past medical history comprise five articles. One review article notes that red tattoo ink with and without cinnabar is associated with adverse skin reactions. Conclusions: Morphea-like tattoo reactions can be triggered by ingredients of tattoo ink, possibly due to local hypersensitivity or the Koebner phenomenon. We encourage high clinical suspicion for morphea-like tattoo reactions when a patient with known history of connective tissue disease presents with skin changes around a tattoo.

Antinuclear Antibodies in Systemic Lupus Erythematous – Their Complex Role and Clinical Significance in Diagnosis

Antinuclear antibodies (ANA) are a wide group of proteins directed against autologous cellular components, primarily nucleic acids and histones. Their levels are assessed using immunofluorescence on Hep-2 cells or a solid-phase ANA screening immunoassay to subsequently obtain titer value with positive cut-point of ≥1:80. Studies show that ANA can be found in 13% of general population, but typically they are associated with autoimmune conditions and inflammatory connective tissue diseases for example: systemic lupus erythematosus (SLE), sjögren's syndrome, rheumatoid arthritis, mixed connective tissue disease, juvenile idiopathic arthritis, systemic sclerosis, inflammatory myopathies. ANA detection is especially important for SLE, where 2 antibody types - anti-Sm and anti-dsDNA - serve as an entry diagnostic criterion. With increasing patient screening for those antibodies, it is important to determine that alone, positive ANA assays cannot confirm nor deny any disease and to classify their presence as a marker of a disease it is required to satisfy additional additive criteria approved in 2019 by European League Against Rheumatism/American College of Rheumatology. SLE diagnosis can be made when patient collects 10 points from clinical or immunologic domains described by EULAR/ACR, which makes SLE diagnosis challenging and therefore, describing the guidelines is vital to remain cautious about overestimation of the position positive ANA values hold in clinical practice.In conclusion the positive ANA test may be a basis for diagnosis, when additional symptoms occur, but alone does not hold any diagnostic significance and may lead to unnecessary stress for patient.

Fever of unknown origin in pediatrics: causes and clinical characteristics in a single centre experience

BackgroundFever of unknown origin (FUO) is a common condition worldwide in children that remains a diagnostic challenge. The causes of FUO vary depending on the patient's age, residency, and the time of study. Therefore, this study aimed to identify the common aetiologies of FUO at Alexandria University Children’s Hospital under the current diagnostic abilities and newly emerging diseases.MethodsThe current prospective observational study included all children fulfilling the definition of FUO admitted at Alexandria University Children's Hospital from January 2020 to December 2021 using a steps approach for investigations.ResultsA total of 110 children with fever of unknown origin (FUO) were included in this study; the average duration of fever was 36.76 ± 31.73 days. In most of the enrolled cases 105/110 (95.4%) the definite etiology of FUO was identified. The common causes were collagen vascular diseases (30.9%), infectious diseases (28.2%), miscellaneous conditions (19.1%), and malignancy (17.3%). Among collagen vascular diseases, systemic lupus erythematosus (SLE) (47.1%) and systemic onset juvenile idiopathic arthritis (sJIA) (38.2%) were the most common. In the infectious category, Katayama fever (16.1%), brucellosis (12.9%), and urinary tract infection (UTI) (12.9%) were the most frequently observed. Post-Covid MIS-C (52.4%) was the most common in the miscellaneous category. Children in the infectious category had significantly higher neutrophil [5.76 (2.28–7.92) × 10^3/µl] and lymphocytic counts [ 4.2 (2.04–5.91) × 10^3/µl]; (P < 0.001 and < 0.010 respectively). Moreover, in the collagen category the median lymphocytic count was lower [1.95 (1.47–2.73) × 10^3/µl] with a significantly (P < 0.010) higher neutrophil/ lymphocyte ratio [2.30 (1.53–3.91)].ConclusionCollagen vascular diseases, infectious diseases, miscellaneous, and malignancy were the most common causes of FUO. Katayama fever, urinary tract infections (UTI), and brucellosis were the most common causes in the infectious category. Post-Covid MIS-C and hemophagocytic lymphohistiocytosis were the most common diagnoses in the miscellaneous category.

Association of Inflammatory Marker C-Reactive Protein and Interleukin-6 with Stages 3-5 of Chronic Kidney Disease

Background: Despite different strategy to retard the progression of CKD, majority still progress to ESRD. Other than conventional risk factors inflammation is considered as one of the reversible factors responsible for CKD progression which can be intervened. Therefore, we have studied the level of inflammatory marker CRP and IL-6 at stages 3-5 of CKD patients and their association with CKD stage progression determined by eGFR. Methods: We have conducted a cross sectional study among 150 CKD patients and 32 healthy controls at OPD of Nephrology department of National Institute of Kidney Diseases and Urology, Dhaka from January`2016 to December`2016. Purposive sampling method was the tool for case selection and CKD was defined as eGFR &lt;60ml/min/1.73m2. AKI, history of dialysis, kidney transplant, patients having acute infection, malignancy or liver disease, received chemotherapy or immunotherapy (&lt;6 months) and patients with connective tissue disease were the exclusion criteria. Fasting blood glucose, Hb%, serum Ca++, serum PO4, serum total cholesterol and serum triglyceride level were measured for both case and controls. eGFR has been calculated using MDRD equation. For the cases CRP had been measured on two occasions at an interval of one and half month. Those cases who had raised CRP level in both occasions were selected for measurement of IL-6 from second sample. CRP had been measured by turbidimetry method using fully automated chemistry analyzer. IL-6 had been measured using enzyme linked immunosorbent assay (ELISA) based on the Biotin double antibody sandwich technology. Scatter diagram and multiple regression models were used to examine the association between CRP and IL-6 with stage 3-5 of CKD denoted by eGFR. Results: The mean of CRP were 9.5±2.7 mg/L in CKD patients vs. 2.9±0.5 mg/L in controls without CKD and the mean of IL-6 were 29.5±13.0 pg/ml in CKD patients vs. 3.3±0.3 pg/ml in controls without CKD. Both were elevated and significant statistically (p=.001). Scatter diagram showing correlation coefficient (r value) -0.592 and -0.615 for eGFR vs. CRP and eGFR vs. IL-6 respectively which indicate both are negatively correlated with eGFR. But IL-6 had a more strong negative correlation. Multiple regression analysis shows regression co efficient (B) for CRP and IL-6 is -1.251 and -2.826 respectively after taking into account other factors which can alter eGFR level (age, Hb%, serum Calcium, S. Total Cholesterol, S.PO4, S. Triglyceride) that indicates in the prediction of eGFR, IL-6 had significant negative association than CRP after adjusting the conventional factors responsible for CKD progression. Conclusion: Our data suggest that though CRP and IL-6 both are significantly raised in advanced CKD stage 3-5, IL-6 is more rapidly increasing and more strongly associated than CRP with the severity of CKD measured by eGFR.

Coronary Artery Aneurysm or Ectasia as a Form of Coronary Artery Remodeling: Etiology, Pathogenesis, Diagnostics, Complications, and Treatment.

Coronary artery aneurysm or ectasia (CAAE) is a term that includes both coronary artery ectasia (CAE) and coronary artery aneurysm (CAA), despite distinct phenotypes and definitions. This anomaly can be found in 0.15-5.3% of coronary angiography. CAE is a diffuse dilatation of the coronary artery at least 1.5 times wider than the diameter of the normal coronary artery in a patient with a length of over 20 mm or greater than one-third of the vessel. CAE can be further subdivided into diffuse and focal dilations by the number and the length of the dilated vessels. Histologically, it presents with extensive destruction of musculoelastic elements, marked degradation of collagen and elastic fibers, and disruption of the elastic lamina. Conversely, CAA is a focal lesion manifesting as focal dilatation, which can be fusiform (if the longitudinal diameter is greater than the transverse) or saccular (if the longitudinal diameter is smaller than the transverse). Giant CAA is defined as a 4-fold enlargement of the vessel diameter and is observed in only 0.02% of patients after coronary. An aneurysmal lesion can be either single or multiple. It can be either a congenital or acquired phenomenon. The pathophysiological mechanisms responsible for the formation of CAAE are not well understood. Atherosclerosis is the most common etiology of CAAE in adults, while Kawasaki disease is the most common in children. Other etiological factors include systemic connective tissue diseases, infectious diseases, vasculitis, congenital anomalies, genetic factors, and idiopathic CAA. Invasive assessment of CAAE is based on coronary angiography. Coronary computed tomography (CT) is a noninvasive method that enables accurate evaluation of aneurysm size and location. The most common complications are coronary spasm, local thrombosis, distal embolization, coronary artery rupture, and compression of adjacent structures by giant coronary aneurysms. The approach to each patient with CAAE should depend on the severity of symptoms, anatomical structure, size, and location of the aneurysm. Treatment methods should be carefully considered to avoid possible complications of CAAE. Simultaneously, we should not unnecessarily expose the patient to the risk of intervention or surgical treatment. Patients can be offered conservative or invasive treatment. However, there are still numerous controversies and ambiguities regarding the etiology, prognosis, and treatment of patients with coronary artery aneurysms. This study summarizes the current knowledge about this disease's etiology, pathogenesis, and management.

Connective Tissue and Autoimmune Diseases Associated With Postsurgical Breast Augmentation: An Updated Review.

This review provides an updated overview of the association between breast augmentation and connective tissue diseases (CTDs). A narrative review of recent literature was conducted. Various autoimmune disorders, such as Raynaud's syndrome, rheumatoid arthritis (RA), and Sjögren's syndrome, have been reported in association with breast implants, particularly silicone implants. Symptoms can be diverse and systemic, including fatigue, joint stiffness, muscle pain, skin rashes, and neurological and gastrointestinal issues. Explantation has shown promise in alleviating symptoms, but the exact pathogenesis remains unclear. Recent studies emphasize the need for informed consent, vigilant monitoring, and multidisciplinary management. The association between breast implants and CTDs remains contentious. While advancements in implant technology have improved patient outcomes, concerns about long-term health implications persist. Continuous research is necessary to elucidate the mechanisms underlying these potential risks and to develop informed patient care guidelines. In this narrative review, we discuss the history of breast implants, illness associated with breast augmentation, and treatment of CTDs and autoimmune diseases associated with breast augmentation.

MDS-508 IDH1 Somatic Mutations Are More Commonly Observed Among Patients With Concomitant Myelodysplastic Syndromes and Connective Tissue Disease

MDS-508 IDH1 Somatic Mutations Are More Commonly Observed Among Patients With Concomitant Myelodysplastic Syndromes and Connective Tissue Disease

Multiancestry transferability of a polygenic risk score for diverticulitis

ObjectivePolygenic risk scores (PRS) for diverticular disease must be evaluated in diverse cohorts. We sought to explore shared genetic predisposition across the phenome and to assess risk stratification in individuals...

Lnsights into Adjuvant Systemic Treatment Selection for Patients with Stage III Melanoma: Data from the Dutch Cancer Registry.

Patient demographics and shared decision making might influence the choice of adjuvant therapy for stage III melanoma. To identify factors for treatment selection of patients diagnosed with stage III melanoma to better understand current treatment decisions and improve further treatment counseling. Data from 2007 patients diagnosed with stage III melanoma, between December 2018 and 2021, sourced from the Dutch Cancer Registry, were analyzed. Among the cohort, 48.7% received no therapy, 45.8% received checkpoint inhibition, and 5.5% received targeted therapy (TT). Patients foregoing therapy were significantly older [67.0 years (range 53.0-77.0) vs. 62.0 year (range 52.0-72.0)], had poorer performance scores (PS), and higher Charlson Comorbidity Index scores compared to those receiving therapy (p<0.001). Patients undergoing therapy had significantly higher median Breslow thickness (3.3mm vs. 2.2mm) and higher prevalence of ulceration (49.9% vs. 38.1%). Those with connective tissue disease and/or congestive heart disease were more likely to receive TT [odds ration (OR) 8.1; 95% confidence interval (CI) 1.7-37.6 and OR 9.3; 95% CI 1.2-72.2, respectively]. Median treatment time among strata for disease recurrence was 4.26months (3.69-4.82) for immunotherapy and 3.1months (0.85-5.36) for TT (p=0.298). Patients who developed recurrent disease were equal across treatment types (p=0.656). The number of patients with grade 3 complications was different for each treatment type [immunotherapy: 17.8% vs. TT: 37.3% (p<0.001)]. Age, PS, and Breslow thickness seem to influence adjuvant treatment decisions. Clinicians' preference for immunotherapy might play a role in counseling BRAF-positive patients for adjuvant therapy, this however, cannot be confirmed in this dataset. Overall, only a small proportion of patients completed adjuvant treatment.

Impact of the grade and jet-flow direction of residual aortic regurgitation after valve-sparing root replacement

ObjectivesTo investigate the impact of the grade and jet direction of residual aortic regurgitation (rAR) after valve-sparing root replacement (VSRR). MethodsThe study enrolled 248 adult patients who underwent VSRR between 1995 and 2021. The patients were divided into groups based on the postoperative rAR. Patients with rAR were further categorized according to rAR grade and jet direction. The primary endpoint was the development of aortic regurgitation of moderate or greater (≥moderate) severity and/or the need for valve replacement during the follow-up, analyzed by a multivariable competing risk analysis. The secondary endpoints included the occurrence of rAR and overall survival. ResultsThe median age of the patients was 36.5 years, and 79.8% had been diagnosed with connective tissue disease. After VSRR, 146 patients did not present with rAR; however, 102 had rAR (77 with minimal central, 18 with minimal eccentric, and 7 with mild rAR). The 5-year and 8-year incidence rates of the primary endpoint were 14.6% and 17.9%, respectively. rAR was a significant risk factor (P = .001), and eccentricity and mild rAR seemed to have important roles. The risk factors for rAR included dilated root, preoperative moderate regurgitation, and redo sternotomy. Overall survival was influenced only by age. ConclusionsrAR after VSRR operation could be a risk factor for AR progression. Minimal central rAR generally has a tolerable clinical course; however, patients with even minimal eccentric AR may develop AR progression, so active surveillance and timely management might be required. Furthermore, early VSRR can help reduce the rAR.

54206 A Hispanic dermatology-rheumatology clinic: enhancing healthcare care beyond connective tissue diseases.

54206 A Hispanic dermatology-rheumatology clinic: enhancing healthcare care beyond connective tissue diseases.

Clinical effectiveness of genetic testing guidelines in patients with thoracic aortic aneurysms

ObjectiveTo analyze the effectiveness of the current genetic testing guidelines for patients with thoracic aortic aneurysms. MethodsWe evaluated genetic tests for thoracic aortic disease (TAD) from 2012 to 2023 in patients aged 18 and older with a thoracic aorta diameter greater than 4 cm. Mutation rates were compared by American College of Cardiology/American Heart Association testing criteria met by patients: age younger than 60 years, syndromic features of connective tissue diseases (CTDs), family history, or none. Results were classified as pathogenic, variants of uncertain significance (VUS), or negative. Genes tested were analyzed in 2 categories: primary (strongly associated with heritable diseases) or secondary (less strongly associated). ResultsIn total, 1034 patients were included: 42.4% aged younger than 60 years, 19.1% with syndromic features of CTD, 41.8% with family history, and 30.7% meeting no criteria. Overall, 3.97% had pathogenic mutations, and 27.27% had VUS. Mutation rates were greatest in patients with syndromic features of CTD (13.2%), followed by patients aged younger than 60 years (5.48%), with a family history (4.63%), and with no criteria met (2.21%). Primary genes had pathogenic mutation rates of 3.29% and VUS rates of 12.19%. Secondary genes had lower pathogenic rates (0.68%) but greater VUS (17.5%). Mutation rates in primary genes peaked at 22% in patients meeting all criteria, whereas those younger than 60 years without family history or syndromic features of CTD had the lowest rate (0.54%). ConclusionsRefining genetic testing guidelines to incorporate multiple patient criteria could enhance risk stratification and support informed decision-making in genetic testing for TAD. Limiting testing to genes strongly associated with TAD could lower VUS rates.