Undifferentiated Connective Tissue Disease Research Articles

UCTD and SLE patients show increased levels of oxidative and DNA damage together with an altered kinetics of DSB repair.

Immunological tolerance is a critical feature of the immune system; its loss might lead to an abnormal response of lymphocytes causing autoimmune diseases. One of the most important groups belonging to autoimmune disorders is the connective tissue diseases (CTD). CTD are classified among systemic rheumatic diseases and include pathologies such as systemic lupus erythematosus (SLE), and undifferentiated CTD (UCTD). In this study, we evaluated oxidative and genome damage in peripheral blood lymphocytes from patients with SLE and UCTD, further classified on the basis of disease activity and the presence/absence of a serological profile. Oxidative damage was evaluated in cell membrane using the fluorescent fatty acid analogue BODIPY581/591 C11. The percentage of oxidised lymphocytes in both SLE and UCTD patients was higher than in the control group, and the oxidative stress correlated positively with both disease activity and autoantibody profile. The γH2AX focus assay was used to quantify the presence of spontaneous double strand breaks (DSBs), and to assess the abilities of DSBs repair system after T cells were treated with mitomycin C (MMC). Subjects with these autoimmune disorders showed a higher number of γH2AX foci than healthy controls, but no correlation with diseases activity and presence of serological profile was observed. In addition, patients displayed an altered response to MMC-induced DSBs, which led their peripheral cells to greatly increase apoptosis. Taken together our results confirmed an interplay among oxidative stress, DNA damage and impaired DNA repair, which are directly correlated to the aggressiveness and clinical progression of the diseases. We propose the evaluation of these molecular markers to better characterise SLE and UCTD, aiming to improve the treatment plan and the quality of the patients' life.

Дисплазія сполучної тканини як провокуючий фактор важкості пієлонефриту в дітей

Актуальність. Останніми десятиріччями все більшу увагу привертає патологія різних органів і систем людини, асоційована з дисплазією сполучної тканини (ДСТ), через часте формування на її фоні патології різних систем організму, зокрема з боку нирок. Мета дослідження — з’ясування ролі недиференційованої дисплазії сполучної тканини (НДСТ) у важкості перебігу пієлонефриту (ПН) у дітей та пошук можливих молекулярно­генетичних маркерів, асоційованих із порушенням фібрилогенезу в дітей із різними варіантами перебігу ПН. Матеріали та методи. Обстежено 60 дітей із ПН. За результатами катамнестичного спостереження вони були розподілені на 2 групи: І — 30 дітей із хронічним пієлонефритом (ХрПН), у катамнезі яких діагностувались 3 епізоди рецидиву ПН і більше впродовж 2 років, ІІ — 30 дітей із ПН, в яких впродовж 2 років не відмічалось рецидивів ПН. Контрольну групу становили 42 здорові дитини. Дітям проводилося рутинне обстеження, встановлювались клініко­лабораторні маркери порушення фібрилогенезу (фенотипові ознаки ДСТ, вміст оксипроліну (Оп) у плазмі крові та сечі) та молекулярно­генетичне тестування локусів ТТ та СТ поліморфного локусу rs565470 гена COL4A2 та локусів AA та AG поліморфного локусу rs605143 гена колагену COL4A1. Результати. У дітей із ХрПН вірогідно частіше відмічались фенотипові ознаки недиференційованої дисплазії сполучної тканини порівняно з даними дітей із гострим ПН (ГПН). Практично у всіх обстежених із ХрПН були вірогідно підвищені показники вільної та зв’язаної фракцій Оп у плазмі крові (47,14 ± 0,03 мкмоль/л та 40,08 ± 0,03 мкмоль/л відповідно), вірогідно відрізняючись від даних дітей із ГПН (17,65 ± 0,01 мкмоль/л та 17,22 ± 0,02 мкмоль/л), серед яких ці показники були підвищені тільки у 12,0 та 16,0 % дітей відповідно. У 97,0 % дітей із ХрПН визначався підвищений рівень Оп у сечі, що перевищувало частоту його виділення із сечею в дітей із ГПН (10 %). Установлена вірогідна вища частота «дикого» генотипу АА — rs605143 гена колагену COL4A1 у дітей із ХрПн порівняно з даними осіб загальнопопуляційної контрольної групи (21,4 проти 4,8 %, p < 0,05). Розрахунки показали, що носійство цього генотипу в п’ять разів збільшує ризик розвитку ХрПН (OR 5,105, 95% CI 0,12–0,87), а наявність у дитини генотипу ТТ поліморфного локусу rs565470 гена колагену COL4A2 зменшує ризик розвитку рецидивування ПН (OR 0,14, 95% CI 0,02–1,19). Висновки. Наявність НДСТ у дитини відіграє важливу роль у процесі хронізації пієлонефриту, тому наявність ознак НДСТ є прогностично неблагополучною. З метою прогнозування генетично детермінованої схильності до хронізації ПН рекомендується проведення молекулярно­генетичного тестування генотипів AA та AG поліморфного локусу rs605143 гена колагену COL4A1 та генотипів ТТ та ТС поліморфного локусу rs565470 гена колагену COL4A2.

Nailfold capillaroscopy in systemic diseases: short overview for internal medicine.

Nailfold capillaroscopy (NFC) is now one of the main imaging tools in systemic sclerosis and imposed over time as an easy, non-invasive method for the nailfold microvascular bed assessment. In qualitative NFC normal pattern is characterized by homogeneous, parallel fashion arrangement of the last capillaries row as well as by capillaries with hairpin or non-specific variations like tortuous and/ or crossing shape. Nailfold capillaroscopy is strongly recommended for evaluation of all patients with Raynaud phenomenon. Appearance of giant capillaries is chronologically the first relevant finding for scleroderma spectrum disorders development (systemic sclerosis, dermatomyositis, undifferentiated and mixed connective tissue disease). Collapses of the giant loops generate microhemorrhages and further capillary loss with subsequent hypoxia, and neoangiogenesis seen as ramified/ bushy capillaries. Nailfold capillaroscopy is indicated especially in systemic sclerosis, being also included in the classification criteria. Based on these major NFC pathologic findings (giant capillaries, microhemorrhages, avascularity and neoangiogenesis), three evolutive stages were described in systemic sclerosis, namely the early, active, and late scleroderma pattern. In other connective tissue diseases than those scleroderma-related, like systemic lupus erythematosus, psoriatic arthritis, or antiphospholipid syndrome, the interest for capillaroscopy is growing, but the attempts of defining specific characteristics failed until now. Besides qualitative NFC, semiquantitative and quantitative capillaroscopic assessments were proposed for more accurate evaluation. Lately, automated systems are under development. There is still need of more studies to sustain the nailfold capillaroscopy validity as diagnostic and prognostic test.

Breathing for 2

(N Engl J Med. 2021;384:61–68) This feature contained details about 1 patient’s case, with a clinician’s commentary interspersed throughout. The case was that of a 29-year-old woman at 26 weeks gestation with undifferentiated connective tissue disease, presenting with cough, and shortness of breath.

Polycystic ovary syndrome: epidemiologic assessment of prevalence of systemic rheumatic and autoimmune diseases.

Polycystic ovary syndrome (PCOS) causes anovulation and hyperandrogenism. Hormonal imbalance is known to contribute to systemic autoimmune diseases. To examine the frequency of certain rheumatic diseases in PCOS. This retrospective study utilized and analyzed electronic medical records from January 2004 through February 2020. A diagnosis of PCOS and specified rheumatic diseases was searched using ICD-9 and ICD-10 codes. A total of 754 adult patients with PCOS and 1,508 age- and body mass index-matched patients without PCOS were included. Frequencies of the rheumatic diseases were compared between PCOS and non-PCOS subjects or literature data. The prevalence of rheumatoid arthritis (RA) was found to be 2.25% (17/737) in the PCOS patients, numerically higher than 1.26% (19/1489) in the non-PCOS subjects. The difference was significant with a confidence level of 90% (1.04-3.15) but not at 95% with an odds ratio of 1.808 (95% CI = 0.934-3.4, p = 0.0747). When compared with the literature data from the US female population, the prevalence of RA in PCOS patients was significantly higher (2.25% vs. 1.40%, p < 0.0001). Among the autoimmune diseases examined, both systemic sclerosis (0.40% vs. 0.0%, p = 0.0369) and undifferentiated connective tissue disease (0.53% vs. 0.0%, p = 0.0123) were significantly more frequent in the PCOS patients than the non-PCOS. Additionally, PCOS patients had a significantly higher frequency of osteoarthritis than non-PCOS patients (5.44% vs. 2.92%, p = 0.0030) with an odds ratio of 1.913 (95% CI = 1.239-2.955). We have shown unprecedentedly that certain rheumatic diseases are more prevalent in PCOS. This study provides important insight into autoimmunity in association with PCOS. Key Points • Polycystic ovary syndrome is postulated to cause systemic autoimmune disease due to its hormonal imbalance. • We conducted the first epidemiologic assessment of the prevalence of systemic autoimmune diseases. • Certain autoimmune and rheumatic diseases are more prevalent in polycystic ovary syndrome.

CLINICAL SIGNIFICANCE OF LAMININ AND ELASTINE LEVELS IN CHILDREN WITH UNDIFFERENTIATED CONNECTIVE TISSUE DISEASE

This research aims to study levels of laminin and elastine in 64 children with undifferentiated connective tissue disease (UCTD). All the children underwent clinical, laboratory and instrumental examination. It was found that changes in the levels of laminin and elastin are directly related to the severity of UCTD in children. Thus, clinical values of laminin and elastin levels can serve as additional criteria of UCTD severity. Using them, along with early detection of the phenotypic and visceral signs, helps prevent the development of severe forms of the disease.

AB0411 CHALLENGES IN THE MANAGEMENT OF MIXED CONNECTIVE TISSUE DISEASE: A RETROSPECTIVE ANALYSIS OF THE MCTD COHORT IN A TERTIARY REFERRAL CENTRE

Background:As a rare, complex, and heterogeneous disease, mixed connective tissue disease (MCTD) represents a challenge for clinical practice.Objectives:We aimed to unravel potential pitfalls including correct referral diagnosis, fulfilment of diagnostic criteria, distinction from other CTDs, disease course and activity, and treatment modalities.Methods:We analysed the prospectively collected MCTD cohort at our tertiary referral centre. The patients’ medical histories were investigated for fulfilment of Sharp’s (1), Kasukawa’s (2), and Alarcón-Segovia’s (3) diagnostic MCTD criteria. We defined overlap syndromes as simultaneous fulfilment of clinical as well as immunological criteria of two defined rheumatic diseases. Disease conversion was defined as emergence of new symptoms and autoantibodies consistent with another rheumatic disease. Remission was defined by simultaneous systemic lupus erythematosus disease activity index 2000 (SLEDAI-2 K) of 0 and European League Against Rheumatism scleroderma trial and research (EUSTAR) activity index &lt;2.5. Disease phenotype and disease activity were monitored over time and all patients were evaluated for fulfilment of classification criteria of various connective tissue diseases.Results:Out of 85 patients initially referred as MCTD, only one third fulfilled the diagnostic MCTD criteria. Most of the remaining patients had undifferentiated CTD (29%) or overlap syndromes (20%). In our final cohort of 33 MCTD patients, 6 (48%) also met the classification criteria of systemic sclerosis, 13 (39%) those of systemic lupus erythematosus (SLE), 6 (18%) those of rheumatoid arthritis, and 3 (9%) those of primary myositis. Over the median observation period of 4.6 (1.6, 9.9) years, only two patients (6%) underwent disease conversion from MCTD to SLE and no patient converted towards other diseases. The number of patients in remission increased from 6 (18%) to 15 (45%) due to introduction of immune modulatory treatment. Combination therapy was favoured in most cases (17 patients, 52%), whereas monotherapy was less frequent (12 patients, 36%), and only 4 (12%) patients remained without immune modulators until the end of the follow-up period. Hydroxychloroquine, prednisone, and methotrexate were the most frequently used medications in our cohort.Conclusion:Our study showed a high risk for misdiagnosis for patients with MCTD. Phenotype conversion was a very rare event. As a multi-organ disease, MCTD required prolonged (combined) immunosuppressive therapy to achieve remission. The establishment of an international registry with longitudinal data from observational multi-centre cohorts might represent a first step to address the many unmet needs of MCTD.

P170 The validity and utility of the SLE-key® rule-out serological test when applied in a selected cohort of patients with SLE and other connective tissue diseases

Abstract Background/Aims We aimed to establish the validity of the SLE-key® rule-out test and analyse its utility in distinguishing systemic lupus erythematosus (SLE) from other autoimmune rheumatic connective tissue diseases. Methods We used data from the Lupus Extended Autoimmune Phenotype (LEAP) study, which included a representative cross-sectional sample of patients with a variety of rheumatic connective tissue diseases, including SLE, mixed connective tissue disease (MCTD), inflammatory myositis, systemic sclerosis, primary Sjögren’s syndrome and undifferentiated connective tissue disease (UCTD). The modified 1997 ACR criteria were used to classify patients with SLE. Banked serum samples were sent to Immune-Array’s CLIA- certified laboratory Veracis (Richmond, VA) for testing. Patients were assigned test scores between 0 and 1 where a score of 0 was considered a negative rule-out test (i.e. SLE cannot be excluded) whilst a score of 1 was assigned for a positive rule-out test (i.e. SLE excluded). Performance measures were used to assess the test’s validity and measures of association determined using linear regression and Spearman’s correlation. Results Our study included a total of 155 patients of whom 66 had SLE. The mean age in the SLE group was 44.2 years (SD 13.04). 146 patients (94.1%) were female. 84 (54.2%) patients from the entire cohort had ACR SLE scores of ≤ 3 whilst 71 (45.8%) had ACR SLE scores ≥ 4. The mean ACR SLE total score for the SLE patients was 4.85 (SD 1.67), ranging from 2 to 8, with mean disease duration of 12.9 years. The Sensitivity of the SLE-Key® Rule-Out test in diagnosing SLE from other connective tissue diseases was 54.5%, specificity was 44.9%, PPV 42.4% and NPV 57.1 %. 45% of the SLE patients had a positive rule-out test. SLE could not be ruled out in 73% of the MCTD patients whilst 51% of the UCTD patients had a positive Rule-Out test and &amp;gt;85% of the inflammatory myositis patients had a negative rule-out test. ROC analysis generated an AUC of 0.525 illustrating weak class separation capacity. Linear regression established a negative correlation between the SLE-key Rule-Out score and ACR SLE total scores. Spearman’s correlation was run to determine the relationship between ACR SLE total scores and SLE-key rule-out score and showed very weak negative correlation (rs = -0.0815, n = 155, p = 0.313). Conclusion Our findings demonstrate that when applied in clinical practice in a rheumatology CTD clinic setting, the SLE-key® rule-out test does not accurately distinguish SLE from other CTDs. The development of a robust test that could achieve this would be pivotal. It is however important to highlight that the test was designed to distinguish healthy subjects from SLE patients and not for the purpose of differentiating SLE from other connective tissue diseases. Disclosure S. Achieng: None. J.A. Reynolds: None. I.N. Bruce: Other; I.N.B is a National Institute for Health Research (NIHR) Senior Investigator and is funded by the NIHR Manchester Biomedical Research Centre. M. Bukhari: None.

Role of Osteopontin as a Potential Biomarker of Pulmonary Arterial Hypertension in Patients with Systemic Sclerosis and Other Connective Tissue Diseases (CTDs).

Pulmonary arterial hypertension (PAH) is a severe complication of connective tissue diseases (CTD). Its early diagnosis is essential to start effective treatment. In the present paper, we aimed to evaluate the role of plasma osteopontin (OPN) as a candidate biomarker of PAH in a cohort of CTD patients. OPN is a pleiotropic protein involved in inflammation and fibrogenesis and, therefore, potentially promising in this specific clinical context. We performed a cross-sectional observational study on a cohort of 113 CTD patients (females N = 101, 89.4%) affected by systemic sclerosis N = 88 (77.9%), mixed connective tissue disease N = 10 (8.8%), overlap syndrome N = 10 (8.8%) or undifferentiated connective tissue disease N = 5 (4.4%). CTD-PAH patients showed significantly higher OPN plasma values than patients with CTD alone (241.0 (188.8–387.2) vs. 200.7 (133.5–281.6) ng/mL; p = 0.03). Although OPN levels were directly correlated with age and inversely with glomerular filtration rate, they remained associated with PAH at multivariate analysis. In conclusion, OPN was significantly associated with PAH among patients with CTD, suggesting it may have a role as a non-invasive disease biomarker of PAH.

Thrombotic Microangiopathy Associated with Macrophage Activation Syndrome: A Multinational Study of 23 Patients

To describe the clinical characteristics, treatment, and outcomes of a multinational cohort of patients with macrophage activation syndrome (MAS) and thrombotic microangiopathy (TMA). International pediatric rheumatologists were asked to collect retrospectively the data of patients with the co-occurrence of MAS and TMA. Clinical and laboratory features of patients with systemic juvenile idiopathic arthritis (sJIA)-associated MAS and TMA were compared with those of an historical cohort of patients with sJIA and MAS. Twenty-three patients with MAS and TMA were enrolled: 17 had sJIA, 2 systemic lupus erythematosus, 1 juvenile dermatomyositis, 1 mixed connective tissue disease, and 2 undifferentiated connective tissue disease. Compared with the historical cohort of MAS, patients with sJIA with coexistent MAS and TMA had higher frequencies of renal failure and neurologic involvement, hemorrhage, jaundice, and respiratory symptoms, as well as more severe anemia and thrombocytopenia, higher levels of alanine aminotransferase, lactate dehydrogenase, bilirubin and D-dimer, and lower levels of albumin and fibrinogen. They also required admission to the intensive care unit more frequently. Among patients tested, complement abnormalities and reduced ADAMTS13 activity were observed in 64.3% and 44.4% of cases, respectively. All patients received glucocorticoids. Treatment for TMA included plasma-exchange, eculizumab, and rituximab. The possible coexistence of MAS and TMA in rheumatic diseases may be underrecognized. This association should be considered in patients with MAS who develop disproportionate anemia, thrombocytopenia, and lactate dehydrogenase increase, or have multiorgan failure.

A prospective cohort study comparing the performance of interferon gamma release assays in autoimmune skin diseases

A prospective cohort study comparing the performance of interferon gamma release assays in autoimmune skin diseases

Breastfeeding in women with rheumatic diseases

ObjectiveMany rheumatologists and women with rheumatic disease worry that the disease or treatment will prevent breast feeding. International guidelines establish, however, that most antirheumatic medications are compatible with breast feeding....

Selexipag Therapy for Raynaud Phenomenon-induced Severe Digital Ischemia in Intravenous Epoprostenol Responders With Connective Tissue Disease.

Raynaud phenomenon (RP) in connective tissue disease (CTD) can be resistant to oral vasodilator therapy, resulting in uncontrollable digital ischemia. Intravenous (IV) prostanoids are often used, but the benefit can be transient and not all patients respond. Selexipag is an orally active selective IP-type prostanoid receptor agonist used in pulmonary arterial hypertension. We describe 2 patients where selexipag significantly reduced digital ischemia after failure of other oral vasodilating agents. Subject 1 with undifferentiated CTD had impressive healing of her fingers (Figure 1) and subject 2 with systemic sclerosis (SSc) had a …

Troubling Tenosynovitis: When a Serious Sign Persists

A 42-year-old woman was admitted to the hospital with 5 days of diffuse joint pain and swelling associated with prolonged morning stiffness and intermittent fevers up to 38.7°C. The review of systems was negative for rashes, mouth sores, pleuritic chest pain, alopecia, dysuria, vaginal discharge, diarrhea or vomiting, cough or shortness of breath, recent travel, sick contacts, or tick exposure. Her medical history was significant for a 2-year history of an undifferentiated connective tissue disease, which presented with inflammatory arthritis, palpable skin rashes (biopsy showed immunoglobulin G and immunoglobulin M granular deposition along the basement membrane zone, suggestive of a connective tissue disease), positive antinuclear antibodies, positive SS-A and SS-B, low total complement, low C3 and C4, and positive rheumatoid factor with negative anticyclic citrullinated peptide antibodies.

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

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. 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. 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.

AB019. Response to tofacitinib in a case of refractory TIF-1 positive amyopathic dermatomyositis with arthritis

A 47-year-old woman with a previous diagnosis of undifferentiated connective tissue disease presented to our clinic for evaluation of rash and joint pains. She had a significant history of severe fatigue, musculoskeletal and joint pains. She described her joint pain as constant, stating it severely impacted her activities of daily living, but denied muscle weakness. She was previously diagnosed with systemic lupus erythematosus (SLE), and treated unsuccessfully with low dose systemic steroids and antimalarial therapy. Upon examination, she was found to have heliotrope eruption, Gottron’s sign and Gottron’s papules, fulfilling EULAR/ACR classification criteria for dermatomyositis. On the myositis panel she tested positive for antibodies to TIF1 and NXP2, confirming the diagnosis. She was also found to have RF positive but CCP negative arthropathy, without evidence of radiographic erosions. She was responsive to prednisone but either skin or joint symptoms remained refractory to several steroid-sparing agents including hydroxychloroquine, mycophenolate mofetil, methotrexate, intravenous immunoglobulin and eventually infliximab. With subsequent visits, she reported worsening of joint pain, despite improvement of cutaneous burden of disease on mycophenolate mofetil. In the setting of debilitating joint pain, she was started on tofacitinib 11 mg PO daily in addition to hydroxychloroquine 200 mg PO BID with discontinuation of mycophenolate mofetil. After two months of treatment she reported 90% improvement in symptoms, with resolution of joint pains and no recurrences of her rash, and was able to return to baseline functional status. Teaching points: (I) overlap syndrome with dermatomyositis has been previously reported in a case report showing 19% overlap with other connective tissue diseases, including rheumatoid arthritis; (II) the overlap of the two conditions can be extremely debilitating to patients, with few options for complete symptom resolution; (III) tofacitinib is an inhibitor of Janus kinase 1 (JAK1) and Janus kinase 3 (JAK3) and works by inhibiting JAK signaling for many pro-inflammatory cytokines. Maximizing this mechanism can be a novel approach to treating recalcitrant immune-mediated inflammatory diseases.

Efficacy and safety of mycophenolate mofetil in the treatment of rheumatic disease-related interstitial lung disease: a narrative review.

Mycophenolate mofetil (MMF) is an antimetabolite with a potent inhibitory effect on proliferation of T and B lymphocytes used since the early 1990s for the prevention of acute allograft rejection after organ transplant. MMF is also widely used for the treatment of a variety of rheumatic diseases (RDs) and their pulmonary involvement. Interstitial lung disease (ILD) is a heterogeneous group of progressive fibrotic diseases of the lung, which is often secondary to RD and represents a major cause of morbidity and mortality. MMF is considered the main alternative to cyclophosphamide as a first-line agent to treat RD-related ILD or as possible maintenance therapy after cyclophosphamide, with a lower rate of side-effects. However, as for other immunosuppressive agents, the use of MMF in RD-ILD is supported by poor scientific evidence. In this narrative review, we describe the available data and recent advances on the effectiveness and safety of MMF for the treatment of ILD related to RD, including rheumatoid arthritis, systemic sclerosis, primary Sjögren syndrome, systemic lupus erythematosus, idiopathic inflammatory myopathies, undifferentiated connective tissue disease, interstitial pneumonia with autoimmune features and antineutrophil cytoplasmic antibody-associated vasculitis.

Клинико-прогностическое значение определения эластина и ламинина при недифференцированной дисплазии соединительной ткани у детей

Aim: to determine clinical prognostic relevance of elastin and laminin in children with undifferentiated connective tissue disease (UCTD). Patients and Methods: 47 children with UCTD aged 3–6 were enrolled. The diagnosis was verified by ruling out genetic disorders via analyzing family tree, genetic consultation, etc. Phenotypic and visceral signs were interpreted based on "Congenital and multifactorial connective tissue diseases in children" guidelines (2016). The results of cardiovascular and urinary tract ultrasound were analyzed. Serum levels of elastin and laminin were measured by the sandwich ELISA using high-sensitive kits. All tests were performed at admission and after two years. Results: prognostic relevance (prognostic coefficient) of individual phenotypic and visceral signs and lab tests and prognostic threshold value (the sum of prognostic coefficients indicating high, moderate, or low risk of UCTD progression) were determined. It was demonstrated that measuring elastin and laminin levels improves the efficacy of UCTD progression risk assessment. This phenomenon was supported by the values of their prognostic coefficient, which were comparable to the values of significant phenotypic and visceral signs. Furthermore, the accuracy of prognosis based on the use of a set of prognostic indicators (phenotypic, visceral, and biochemical) was supported by the escalation of dysplasia signs. After two years, disease progression was reported in 36 out of 38 children with a moderate and high risk of UCTD progression as identified by the initial evaluation. Conclusion: given the relevance of elastin and laminin in dysplasia pathogenesis, these parameters are considered informative to assess the risk of dysplasia progression in children aged 3–6. It is reasonable to use elastin and laminin levels as additional criteria to evaluate the risk of UCTD progression. KEYWORDS: undifferentiated connective tissue disease, prediction, children, phenotypic signs, laminin, elastin, risk of progression, cardiovascular system, urinary system. FOR CITATION: Cherkasov N.S., Doronina T.N., Prakhov A.V., Lutsenko Yu.A. Clinical prognostic relevance of elastin and laminin in children with undifferentiated connective tissue disease. Russian Journal of Woman and Child Health. 2021;4(4):351–354 (in Russ.). DOI: 10.32364/2618-8430-2021-4-4-351-354.

Hot-Melt Extrusion: An Emerging Technique for Solubility Enhancement of Poorly Water-Soluble Drugs.

The solubility of the drug is a significant aspect to be considered during manufacturing of pharmaceutical products. Poor aqueous solubility of drugs imparts depleted bioavailability. In this regard, several techniques are available for enhancing drug solubility or dissolution. However, only few of them are scalable and industrially applicable. Hot-melt extrusion (HME) is one such technique that has been widely used in the industry. It is a single-step, continuous manufacturing, and scalable method that has proved successful in improving the solubility of poorly soluble drugs. This review highlights the numerous pharmaceutical applications of HME, such as formulations of sterile implants, taste masking of unpleasant drugs, cocrystallization, salt formation, sustained and controlled release formulations, etc. It also describes various hydrophilic and hydrophobic carriers utilized in HME. This review also briefly discusses the recent advances in HME and gives an update on the currently available marketed products. The opportunities and challenges in future development of pharmaceutical products by HME technique are also discussed.

Applying SLICC and ACR/EULAR systemic lupus erythematosus classification criteria in a cohort of patients with undifferentiated connective tissue disease.

New classification criteria for SLE have recently been developed. How these criteria affect the classification of patients with the SLE-mimicking condition UCTD is poorly understood. This study investigated the reclassification of UCTD patients using newly derived SLE criteria. Patients with UCTD were identified within a single academic medical center using ICD9/10 codes. Medical record review was performed to confirm UCTD diagnosis and identify disease features present at diagnosis. The SLICC and ACR/EULAR criteria were applied, after which we compared the proportion of patients reclassified as SLE and determined which disease features were associated with reclassification. A total of 129 patients were included in the study. When applying the SLICC and ACR/EULAR criteria, 18 (14.0%) and 26 patients (20.2%) were reclassified as SLE. Comparison with McNemar's test trended toward statistical significance (p = 0.057). Cohen's kappa coefficient was 0.62 (p < 0.001), indicating substantial agreement between these criteria. Disease features associated with reclassification as SLE were renal involvement, leukopenia, thrombocytopenia, anti- dsDNA antibody, hypocomplementemia, non-scarring alopecia (SLICC), and arthritis (ACR/EULAR). Both the SLICC and ACR/EULAR criteria exhibit increased SLE classification. These newer classification criteria could be used to increase the number of SLE patients in future clinical studies.