Childhood-onset of primary Sjögren's syndrome: phenotypic characterization at diagnosis of 158 children.

OBJECTIVES: To characterize the phenotypic presentation at diagnosis of childhood-onset primary SS. METHODS: The Big Data Sjögren Project Consortium is an international, multicentre registry using worldwide data-sharing cooperative merging of pre-existing clinical SS databases from the five continents. For this study, we selected those patients in whom the disease was diagnosed below the age of 19 years according to the fulfilment of the 2002/2016 classification criteria. RESULTS: Among the 12 083 patients included in the Sjögren Big Data Registry, 158 (1.3%) patients had a childhood-onset diagnosis (136 girls, mean age of 14.2 years): 126 (80%) reported dry mouth, 111 (70%) dry eyes, 52 (33%) parotid enlargement, 118/122 (97%) positive minor salivary gland biopsy and 60/64 (94%) abnormal salivary US study, 140/155 (90%) positive ANA, 138/156 (89%) anti-Ro/La antibodies and 86/142 (68%) positive RF. The systemic EULAR Sjögren's syndrome disease activity index (ESSDAI) domains containing the highest frequencies of active patients included the glandular (47%), articular (26%) and lymphadenopathy (25%) domains. Patients with childhood-onset primary SS showed the highest mean ESSDAI score and the highest frequencies of systemic disease in 5 (constitutional, lymphadenopathy, glandular, cutaneous and haematological) of the 12 ESSDAI domains, and the lowest frequencies in 4 (articular, pulmonary, peripheral nerve and CNS) in comparison with patients with adult-onset disease. CONCLUSIONS: Childhood-onset primary SS involves around 1% of patients with primary SS, with a clinical phenotype dominated by sicca features, parotid enlargement and systemic disease. Age at diagnosis plays a key role in modulating the phenotypic expression of the disease.

Post-COVID-19 syndrome in patients with primary Sjögren's syndrome after acute SARS-CoV-2 infection.

OBJECTIVES: To analyse the frequency and characteristics of post-COVID-19 syndrome in patients with primary Sjögren's syndrome (pSS) affected by acute SARS-CoV-2 infection. METHODS: By the first week of April 2021, all centres included in the Big Data Sjögren Consortium were contacted asking for patients included in the Registry diagnosed with SARSCoV-2 infection according to the ECDC guidelines. According to the NICE definitions, symptoms related to COVID-19 were classified as acute COVID-19 (signs and symptoms for up to 4 weeks), ongoing symptomatic COVID-19 (presence of signs and symptoms from 4 to 12 weeks) and post-COVID-19 syndrome (signs and symptoms that continue for > 12 weeks not explained by an alternative diagnosis after a protocolized study). RESULTS: We identified 132 patients who were followed a mean follow-up of 137.8 days (ranging from 5 days to 388 days) after being diagnosed with COVID-19. In the last visit, 75 (57%) patients remained symptomatic: 68 (52%) remained symptomatic for more than 4 weeks fulfilling the NICE definition for ongoing symptomatic post-COVID-19, and 38 (29%) remained symptomatic for more than 12 weeks fulfilling the definition of post-COVID-19 syndrome. More than 40% of pSS patients reported the persistence of four symptoms or more, including anxiety/depression (59%), arthralgias (56%), sleep disorder (44%), fatigue (40%), anosmia (34%) and myalgias (32%). Age-sex adjusted multivariate analysis identified raised LDH levels (OR 10.36), raised CRP levels (OR 7.33), use of hydroxychloroquine (OR 3.51) and antiviral agents (OR 3.38), hospital admission (OR 8.29), mean length of hospital admission (OR 1.1) and requirement of supplemental oxygen (OR 6.94) as factors associated with a higher risk of developing post-COVID-19 syndrome. A sensitivity analysis including hospital admission in the adjusted model confirmed raised CRP levels (OR 8.6, 95% CI 1.33-104.44) and use of hydroxychloroquine (OR 2.52, 95% CI 1.00-6.47) as the key independent factors associated with an enhanced risk of developing post-COVID-19 syndrome. CONCLUSIONS: This is the first study that analyses the frequency and characteristics of post-COVID-19 syndrome in patients affected by a systemic autoimmune disease. We found that 57% of patients with pSS affected by COVID-19 remain symptomatic after a mean follow-up of 5 months. The risk of developing post-COVID-19 syndrome in patients who required hospitalisation was 8-times higher than in non-hospitalised patients, with baseline raised CRP levels and the use of hydroxychloroquine being independent risk factors for post-COVID-19.

Influence of the age at diagnosis in the disease expression of primary Sjögren syndrome. Analysis of 12,753 patients from the Sjögren Big Data Consortium.

OBJECTIVES: To analyse how the main components of the disease phenotype (sicca symptoms, diagnostic tests, immunological markers and systemic disease) can be driven by the age at diagnosis of primary Sjögren's syndrome (pSS). METHODS: By January 2021, the participant centres had included 12,753 patients from 25 countries that fulfilled the 2002/2016 classification criteria for pSS. The age at diagnosis was defined as the time when the attending physician confirmed fulfilment of the criteria. Patients were clustered according to age at diagnosis. 50 clusters with more than 100 observations (from 27 to 76 years) were used to study the influence of the age at diagnosis in the disease expression. RESULTS: There was a consistent increase in the frequency of oral dryness according to the age at diagnosis, with a frequency of <90% in patients diagnosed at the youngest ages and >95% in those diagnosed at the oldest ages. The smooth curves that best fitted a linear model were the frequency of dry mouth (adjusted R2 0.87) and the frequency of abnormal oral tests (adjusted R2 0.72). Therefore, for each 1-year increase in the age at diagnosis, the frequency of dry mouth increased by 0.13%, and the frequency of abnormal oral diagnostic tests by 0.11%. There was a consistent year-by-year decrease in the frequency of all autoantibodies and immunological markers except for cryoglobulins. According to the linear models, for each 1-year increase in the age at diagnosis, the frequency of a positive result decreased by 0.57% (for anti-Ro antibodies), 0.47% (for RF) and 0.42% (for anti-La antibodies). The ESSDAI domains which showed a more consistent decrease were glandular and lymph node involvement (for each 1-year increase in the age at diagnosis, the frequency of activity decreased by 0.18%), and constitutional, cutaneous, and haematological involvements (the frequency decreased by 0.09% for each 1-year increase). In contrast, other domains showed an ascending pattern, especially pulmonary involvement (for each 1-year increase in the age at diagnosis, the frequency of activity increased by 0.22%), and peripheral nerve involvement (the frequency increased by 0.09% for each 1-year increase). CONCLUSIONS: The influence of the age at diagnosis on the key phenotypic features of pSS is strong, and should be considered critical not only for designing a personalised diagnostic approach, but also to be carefully considered when analysing the results of diagnostic tests and immunological parameters, and when internal organ involvement is suspected at diagnosis.

Impact of the COVID-19 pandemic on stress, resilience and depression in health professionals: a cross-sectional study.

AIM: To describe the impact of the COVID-19 pandemic on stress, resilience and depression in health professionals from a public hospital in Barcelona, Spain after the first peak of pandemic. BACKGROUND: The COVID-19 pandemic in Spain has pushed boundaries in health systems and, especially, for health professionals. Analysis of resilience as an individual resource and it is essential to understand the mechanisms that make staff react unfavourably to stressors caused by the pandemic. DESIGN: A descriptive cross-sectional study was designed. PARTICIPANTS: Health professionals supervised by the nursing department, including registered nurses, health care assistants, health technicians, final year nurse student nurses, foreign nurses, and other nurse-related health workers. METHODS: The study complies with the STROBE checklist for cross-sectional studies. An online survey was administered to all health professionals supervised by the nursing department between 6 and 27 May 2020. The survey included the ER-14 Resilience Scale, the widely-used PHQ-9 depression scale, the Spanish version of the Nursing Stress Scale, and an ad-hoc questionnaire to obtain sociodemographic and occupational variables. RESULTS: A total of 686 participants answered the survey. Resilience was high or very high in health professionals, with an inverse correlation with stress and depression scores. Personal on fixed shifts showed better resilience. The most stressed health professionals were full-time registered nurses, followed by health care assistants. Up to 25% of nursing professionals had depression. CONCLUSION: Our study showed a high degree of resilience among nurse professionals despite the overwhelming nature of the COVID-19 pandemic. Relevant signs of depression and stress were detected among participants. Occupational factors heavily influenced nurses' resilience, stress and depression. IMPLICATIONS FOR NURSING & HEALTH POLICY: Government policy shifts are needed in Spain to improve nurses' workforce conditions, enhance the ratio of nurses to patient numbers, and avoid workforce losses. Maintaining the resilience of health professionals would assist in improving their health and their capacity to possible future emergency situations.

Epidemiological profile and north-south gradient driving baseline systemic involvement of primary Sjögren's syndrome.

OBJECTIVE: To characterize the systemic phenotype of primary Sjögren's syndrome at diagnosis by analysing the EULAR-SS disease activity index (ESSDAI) scores. METHODS: The Sjögren Big Data Consortium is an international, multicentre registry based on worldwide data-sharing cooperative merging of pre-existing databases from leading centres in clinical research in Sjögren's syndrome from the five continents. RESULTS: The cohort included 10 007 patients (9352 female, mean 53 years) with recorded ESSDAI scores available. At diagnosis, the mean total ESSDAI score was 6.1; 81.8% of patients had systemic activity (ESSDAI score ≥1). Males had a higher mean ESSDAI (8.1 vs 6.0, P < 0.001) compared with females, as did patients diagnosed at <35 years (6.7 vs 5.6 in patients diagnosed at >65 years, P < 0.001). The highest global ESSDAI score was reported in Black/African Americans, followed by White, Asian and Hispanic patients (6.7, 6.5, 5.4 and 4.8, respectively; P < 0.001). The frequency of involvement of each systemic organ also differed between ethnic groups, with Black/African American patients showing the highest frequencies in the lymphadenopathy, articular, peripheral nervous system, CNS and biological domains, White patients in the glandular, cutaneous and muscular domains, Asian patients in the pulmonary, renal and haematological domains and Hispanic patients in the constitutional domain. Systemic activity measured by the ESSDAI, clinical ESSDAI (clinESSDAI) and disease activity states was higher in patients from southern countries (P < 0.001). CONCLUSION: The systemic phenotype of primary Sjögren's syndrome is strongly influenced by personal determinants such as age, gender, ethnicity and place of residence, which are key geoepidemiological players in driving the expression of systemic disease at diagnosis.

Autoimmune congenital heart block and primary Sjögren's syndrome: characterisation and outcomes of 49 cases.

OBJECTIVES: To characterise autoimmune congenital heart block (CHB) associated with a maternal diagnosis of primary Sjögren's syndrome (pSS) confirmed either before, concomitant or after the first pregnancy complicated with CHB. METHODS: The following inclusion criteria were applied: (i) Mothers with positive Ro/La autoantibodies detected previously or at the time of diagnosis of the first case of CHB; (ii) diagnosis of CHB confirmed by fetal echocardiography; (iii) AV block diagnosed in uterus, at birth or within the neonatal period (0-27 days after birth) (8); (iv) absence of anatomical cardiac abnormalities which might be causal of AV block; and (v) maternal fulfillment of the 2002 SS criteria before, during or after having a pregnancy complicated with CHB. RESULTS: We identified 49 cases of autoimmune CHB in children born from 44 mothers who had a mean age at the time of pregnancy of 30.3 years (range 18 to 41). At the time of diagnosis of autoimmune CHB, all mothers had positive anti-Ro antibodies and 28/44 (64%) were positive for anti-La antibodies. Only 10 (22%) mothers with affected pregnancies had a diagnosis of primary SS at the time of diagnosis of the first pregnancy complicated by CHB (a mean of 4 years before, ranging from 1 to 10 years). In 6 (14%) mothers, primary SS was diagnosed during pregnancy or less than 12 months after the delivery/termination. In the remaining 28 (64%) mothers, pSS was confirmed 1-5 years after CHB diagnosis (n=19, 68%), 6-10 years after (n=2, 7%), or more than 10 years after the first case of CHB was diagnosed (n=7, 25%). CHB was diagnosed in uterus in all cases but two. AV block was initially incomplete in 11 fetuses and complete in 36 (no available data in 2 cases). Among the 35 (71%) surviving children with CHB, 5 (14%) developed other features of neonatal lupus. After the index pregnancy, 12 women had 20 subsequent pregnancies: five were complicated by a CHB (recurrence rate of CHB of 25%). The 4 women who had recurrent CHB were double-positive for anti-Ro and anti-La antibodies, and all had a confirmed pSS before having the first index case of CHB. CONCLUSIONS: In pSS, autoimmune CHB could be one of the first "indirect" signs of the disease in women of childbearing-age, in whom the diagnosis is confirmed several years later. Some maternal characteristics could be related with recurrent CHB, such as having an already-confirmed diagnosis of pSS and carrying the two Ro/La autoantibodies.

Systemic phenotype related to primary Sjögren's syndrome in 279 patients carrying isolated anti-La/SSB antibodies.

OBJECTIVES: To evaluate the systemic phenotype associated with the presence of isolated anti-La/SSB antibodies in a large international registry of patients with primary Sjögren's syndrome (pSS) fulfilling the 2002 classification criteria. METHODS: The Big Data Sjögren Project Consortium is an international, multicentre registry created in 2014. Baseline clinical information from leading centres on clinical research in SS of the 5 continents was collected. Combination patterns of anti-Ro/SSA-La/SSB antibodies at the time of diagnosis defined the following four immunological phenotypes: double positive (combined Ro/SSA and La/SSB,) isolated anti-Ro/SSA, isolated anti-La/SSB, and immunonegative. RESULTS: The cohort included 12,084 patients (11,293 females, mean 52.4 years) with recorded ESSDAI scores available. Among them, 279 (2.3%) had isolated anti-La/SSB antibodies. The mean total ESSDAI score at diagnosis of patients with pSS carrying isolated anti-La/SSB was 6.0, and 80.4% of patients had systemic activity (global ESSDAI score ≥1) at diagnosis. The domains with the highest frequency of active patients were the biological (42.8%), glandular (36.8%) and articular (31.2%) domains. Patients with isolated anti-La/SSB showed a higher frequency of active patients in all ESSDAI domains but two (articular and peripheral nerve) in comparison with immune-negative patients, and even a higher absolute frequency in six clinical ESSDAI domains in comparison with patients with isolated anti-Ro/SSA. In addition, patients with isolated anti-La/SSB showed a higher frequency of active patients in two ESSDAI domains (pulmonary and glandular) with respect to the most active immunological subset (double-positive antibodies). Meanwhile, systemic activity detected in patients with isolated anti-La/SSB was overwhelmingly low. Even in ESSDAI domains where patients with isolated anti-La/SSB had the highest frequencies of systemic activity (lymphadenopathy and muscular), the percentage of patients with moderate or high activity was lower in comparison with the combined Ro/SSA and La/SSB group. CONCLUSIONS: Patients carrying isolated La/SSB antibodies represent a very small subset of patients with a systemic SS phenotype characterised by a significant frequency of active patients in most clinical ESSDAI domains but with a relative low frequency of the highest severe organ-specific involvements. Primary SS still remains the best clinical diagnosis for this subset of patients.

Systemic manifestations of primary Sjögren's syndrome out of the ESSDAI classification: prevalence and clinical relevance in a large international, multi-ethnic cohort of patients.

OBJECTIVES: To analyse the frequency and characterise the systemic presentation of primary Sjögren's syndrome (SS) out of the ESSDAI classification in a large international, multi-ethnic cohort of patients. METHODS: The Big Data Sjögren Project Consortium is an international, multicentre registry based on world-wide data-sharing and cooperative merging of pre-existing clinical SS databases from leading centres in clinical research in SS from the five continents. A list of 26 organ-by-organ systemic features not currently included in the ESSDAI classification was defined according to previous studies; these features were retrospectively recorded. RESULTS: Information about non-ESSDAI features was available in 6331 patients [5,917 female, mean age at diagnosis 52 years, mainly White (86.3%)]. A total of 1641 (26%) patients had at least one of the ESSDAI systemic features. Cardiovascular manifestations were the most frequent organ-specific group of non-ESSDAI features reported in our patients (17% of the total cohort), with Raynaud's phenomenon being reported in 15%. Patients with systemic disease due to non-ESSDAI features had a lower frequency of dry mouth (90.7% vs. 94.1%, p<0.001) and positive minor salivary gland biopsy (86.7% vs. 89%, p=0.033), a higher frequency of anti-Ro/SSA (74.7% vs. 68.7%, p<0.001), anti-La/SSB antibodies (44.5% vs. 40.4%, p=0.004), ANA (82.7% vs. 79.5%, p=0.006), low C3 levels (17.4% vs. 9.7%, p<0.001), low C4 levels (14.4% vs. 9.6%, p<0.001), and positive serum cryoglobulins (8.6% vs. 5.5%, p=0.001). Systemic activity measured by the ESSDAI, clinESSDAI and DAS was higher in patients with systemic disease out of the ESSDAI in comparison with those without these features (p<0.001 for all comparisons). CONCLUSIONS: More than a quarter of patients with primary SS may have systemic manifestations not currently included in the ESSDAI classification, with a wide variety of cardiovascular, digestive, pulmonary, neurological, ocular, ENT (ear, nose, and throat), cutaneous and urological features that increase the scope of the systemic phenotype of the disease. However, the individual frequency of each of these non-ESSDAI features was very low, except for Raynaud's phenomenon.

How immunological profile drives clinical phenotype of primary Sjögren's syndrome at diagnosis: analysis of 10,500 patients (Sjögren Big Data Project).

OBJECTIVES: To evaluate the influence of the main immunological markers on the disease phenotype at diagnosis in a large international cohort of patients with primary Sjögren's syndrome (SjS). METHODS: The Big Data Sjögren Project Consortium is an international, multicentre registry created in 2014. As a first step, baseline clinical information from leading centres on clinical research in SjS of the 5 continents was collected. The centres shared a harmonised data architecture and conducted cooperative online efforts in order to refine collected data under the coordination of a big data statistical team. Inclusion criteria were the fulfillment of the 2002 classification criteria. Immunological tests were carried out using standard commercial assays. RESULTS: By January 2018, the participant centres had included 10,500 valid patients from 22 countries. The cohort included 9,806 (93%) women and 694 (7%) men, with a mean age at diagnosis of primary SjS of 53 years, mainly White (78%) and included from European countries (71%). The frequency of positive immunological markers at diagnosis was 79.3% for ANA, 73.2% for anti-Ro, 48.6% for RF, 45.1% for anti- La, 13.4% for low C3 levels, 14.5% for low C4 levels and 7.3% for cryoglobulins. Positive autoantibodies (ANA, Ro, La) correlated with a positive result in salivary gland biopsy, while hypocomplementaemia and especially cryoglo-bulinaemia correlated with systemic activity (mean ESSDAI score of 17.7 for cryoglobulins, 11.3 for low C3 and 9.2 for low C4, in comparison with 3.8 for negative markers). The immunological markers with a great number of statistically-significant associations (p<0.001) in the organ-by-organ ESS- DAI evaluation were cryoglobulins (9 domains), low C3 (8 domains), anti-La (7 domains) and low C4 (6 domains). CONCLUSIONS: We confirm the strong influence of immunological markers on the phenotype of primary SjS at diagnosis in the largest multi-ethnic international cohort ever analysed, with a greater influence for cryoglobulinaemic-related markers in comparison with Ro/La autoantibodies and ANA. Immunological patterns play a central role in the phenotypic expression of the disease already at the time of diagnosis, and may guide physicians to design a specific personalised management during the follow-up of patients with primary SjS.

The Burden of Comorbidity and Complexity in Sarcoidosis: Impact of Associated Chronic Diseases.

PURPOSE: To evaluate comorbidity, complexity and poor outcomes in patients with sarcoidosis and to compare those scores with a control group. METHODS: 218 consecutive patients were diagnosed with sarcoidosis according to the ATS/ERS/WASOG criteria; extrathoracic involvement was evaluated using the 2014 WASOG organ assessment instrument. Sarcoidosis patients were compared with an age- and gender-matched control group of primary care outpatients without sarcoidosis. Comorbidities were assessed retrospectively using the Charlson Comorbidity Index (CCI); complexity was evaluated according to the classification into Clinical Risk Groups (CRG) and severity levels. RESULTS: The cohort included 142 women and 76 men; the mean age was 47.1 years at diagnosis of sarcoidosis and 55.9 years at the last visit. Patients with a CCI > 1 had a higher frequency of calcium/vitamin D abnormalities (p < 0.001), kidney involvement (p = 0.005) and a higher mortality rate (p < 0.001) compared with patients with a CCI ≤ 1. Patients with a CRG ≥ 6 had a higher frequency of extrathoracic involvement (p = 0.039), calcium/vitamin D abnormalities (p = 0.019) and treatment with glucocorticoids (p = 0.032) compared with patients with a CRG < 6. 11% patients died after a mean follow-up of 102.3 months. Country of birth, kidney involvement and extrathoracic disease were significantly associated with death. Patients with sarcoidosis had a higher frequency of liver (p < 0.001), pulmonary (p = 0.002) and autoimmune disease (p = 0.011) and cancer (p = 0.007) compared with the control group. CONCLUSION: We found higher rates of comorbidity and complexity in patients with sarcoidosis compared with a control group. Liver, pulmonary, autoimmune and neoplastic diseases were the main comorbidities found in patients with sarcoidosis.

Influence of geolocation and ethnicity on the phenotypic expression of primary Sjögren's syndrome at diagnosis in 8310 patients: a cross-sectional study from the Big Data Sjögren Project Consortium.

OBJECTIVES: To analyse the influence of geolocation and ethnicity on the clinical presentation of primary Sjögren's syndrome (SjS) at diagnosis. METHODS: The Big Data Sjögren Project Consortium is an international, multicentre registry designed in 2014. By January 2016, 20 centres from five continents were participating. Multivariable logistic regression analyses were performed. RESULTS: We included 7748 women (93%) and 562 men (7%), with a mean age at diagnosis of primary SjS of 53 years. Ethnicity data were available for 7884 patients (95%): 6174 patients (78%) were white, 1066 patients (14%) were Asian, 393 patients (5%) were Hispanic, 104 patients (1%) were black/African-American and 147 patients (2%) were of other ethnicities. SjS was diagnosed a mean of 7 years earlier in black/African-American compared with white patients; the female-to-male ratio was highest in Asian patients (27:1) and lowest in black/African-American patients (7:1); the prevalence of sicca symptoms was lowest in Asian patients; a higher frequency of positive salivary biopsy was found in Hispanic and white patients. A north-south gradient was found with respect to a lower frequency of ocular involvement in northern countries for dry eyes and abnormal ocular tests in Europe (OR 0.46 and 0.44, respectively) and Asia (OR 0.18 and 0.49, respectively) compared with southern countries. Higher frequencies of antinuclear antibodies (ANAs) were reported in northern countries in America (OR=1.48) and Asia (OR=3.80) while, in Europe, northern countries had lowest frequencies of ANAs (OR=0.67) and Ro/La (OR=0.69). CONCLUSIONS: This study provides the first evidence of a strong influence of geolocation and ethnicity on the phenotype of primary SjS at diagnosis.

Glycaemia Fluctuations Improvement in Old-Age Prediabetic Subjects Consuming a Quinoa-Based Diet: A Pilot Study.

This study aimed to observe if quinoa could produce a benefit on postprandial glycemia that would result in less progression to type 2 diabetes (T2D). A cross-over design pilot clinical study with a nutritional intervention for 8 weeks was performed: 4 weeks on a regular diet (RD) and 4 weeks on a quinoa diet (QD). Nine subjects aged ≥65 years with prediabetes were monitored during the first 4 weeks of RD with daily dietary records and FreeStyle Libre®. Subsequently, participants started the QD, where quinoa and 100% quinoa-based products replaced foods rich in complex carbohydrates that they had consumed in the first 4 weeks of RD. The glycemic measurements recorded by the sensors were considered as functions of time, and the effects of nutrients consumed at the intended time period were analyzed by means of a function-on-scalar regression (fosr) model. With QD participants, decreased body weight (−1.6 kg, p = 0.008), BMI (−0.6 kg/m2p = 0.004) and waist circumference (−1.5 cm, p = 0.015) were observed. Nutrients intake changed during QD, namely, decreased carbohydrates (p = 0.004) and increased lipids (p = 0.004) and some amino acids (p < 0.05). The fosr model showed a reduction in postprandial glycemia in QD despite intrapersonal differences thanks to the joint action of different nutrients and the suppression of others consumed on a regular diet. We conclude that in an old age and high T2D-risk population, a diet rich in quinoa reduces postprandial glycemia and could be a promising T2D-preventive strategy.

Immune checkpoint inhibitor-associated sarcoidosis: A usually benign disease that does not require immunotherapy discontinuation.

OBJECTIVE: To analyse the clinical patterns of sarcoidosis triggered by immune checkpoint inhibitors (ICIs) in patients with cancer. PATIENTS AND METHODS: The ImmunoCancer International Registry is a big data-sharing multidisciplinary network from 18 countries dedicated to evaluating the clinical research of immune-related adverse events related to cancer immunotherapies. RESULTS: We identified 32 patients with biopsy-proven sarcoidosis. Underlying cancer included mainly melanoma (n = 24). Cancer immunotherapy consisted of monotherapy in 19 cases (anti-PD-1 in 18 and ipilimumab in 1) or combined ipilimumab + nivolumab in 13. The time median interval between initiation of ICI and sarcoidosis diagnosis was 3 months (range, 2-29 months). The use of combined ICI was associated with a shorter delay in developing sarcoidosis symptoms. The disease was symptomatic in 19 (59%) cases with mostly cutaneous, respiratory and general symptoms. The organs involved included mainly the mediastinal lymph nodes (n = 32), the lungs (n = 11), the skin (n = 10) and the eyes (n = 5). Pulmonary computed tomography studies showed bilateral hilar lymphadenopathy in all cases. There was no severe manifestation. Specific systemic therapy was required in only 12 patients (37%): oral glucocorticoids in 9, and hydroxychloroquine in 3. ICIs were held in 25 patients (78%) and definitively discontinued in 18 (56%) patients. Seven patients continued ICI treatment with a second flare in one case. In six additional patients, an ICI was reintroduced with no harm, and sarcoidosis relapsed in one of them. CONCLUSION: Our study shows that ICI-related sarcoidosis seems to have a specific profile, possibly more benign than that of idiopathic sarcoidosis, and does not necessarily imply ICI discontinuation.

Spanish Validation of the "User Reported Measure of Care Coordination" Questionnaire for Older People with Complex, Chronic Conditions.

INTRODUCTION: Older people with complex, chronic conditions often receive insufficient or inefficient care provision, and few instruments are able to measure their perception of care provision. The "User Reported Measure of Care Coordination" instrument has been satisfactorily used to evaluate chronic care provision and integration. The aim of this study is to validate this instrument in Spanish. METHODS: The questionnaire was adapted and validated in two phases: translation and cultural adaptation of the questionnaire and psychometric property measurement. Study population were chronic care conditions patients. RESULTS: A total of 332 participants completed test re-test as part of the questionnaire validation process. The final version of the questionnaire had 6 domains: Health and Well-being (D1), Health day to day (D2), Social Services (D3), Planned Care (D4), Urgent Care (D5), and Hospital Care (D6). Cronbach's alpha for the overall questionnaire was 0.86, indicating good internal consistency. When analyzing each domain, only Planned Care (D4) and Urgent Care (D5) had Cronbach's Alphas slightly lower than 0.7, although this could be related to the low number of items in each domain. A good temporal stability was observed for the distinct subscales and items, with intraclass correlation coefficients varying from 0.412 to 0.929 (p < 0.05). CONCLUSION: The adapted version of the "User Reported Measure of Care Coordination" into Spanish proved to be a practical tool for use in our daily practice and an efficient instrument for assessment of care coordination in chronic, complex conditions in older people across services and levels of care.

Abdominal aortic aneurysm screening program using hand-held ultrasound in primary healthcare.

We determined the feasibility of abdominal aortic aneurysm (AAA) screening program led by family physicians in public primary healthcare setting using hand-held ultrasound device. The potential study population was 11,214 men aged ≥ 60 years attended by three urban, public primary healthcare centers. Participants were recruited by randomly-selected telephone calls. Ultrasound examinations were performed by four trained family physicians with a hand-held ultrasound device (Vscan®). AAA observed were verified by confirmatory imaging using standard ultrasound or computed tomography. Cardiovascular risk factors were determined. The prevalence of AAA was computed as the sum of previously-known aneurysms, aneurysms detected by the screening program and model-based estimated undiagnosed aneurysms. We screened 1,010 men, with mean age of 71.3 (SD 6.9) years; 995 (98.5%) men had normal aortas and 15 (1.5%) had AAA on Vscan®. Eleven out of 14 AAA-cases (78.6%) had AAA on confirmatory imaging (one patient died). The total prevalence of AAA was 2.49% (95%CI 2.20 to 2.78). The median aortic diameter at diagnosis was 3.5 cm in screened patients and 4.7 cm (p<0.001) in patients in whom AAA was diagnosed incidentally. Multivariate logistic regression analysis identified coronary heart disease (OR = 4.6, 95%CI 1.3 to 15.9) as the independent factor with the highest odds ratio. A screening program led by trained family physicians using hand-held ultrasound was a feasible, safe and reliable tool for the early detection of AAA.

Therapeutic approach to IgG4-related disease: A systematic review.

To review the reported evidence on the therapeutic management of IgG4-related disease (IgG4-RD) in clinical practice.A systematic search of the literature was conducted. The primary outcome measured was the rate of efficacy of first-line therapeutic approaches. Secondary outcomes measured included the rate of disease relapse, the outcome of untreated patients, the rate of patients without drug therapy at the end of follow-up, the rate of side effects, and mortality. The MOOSE, AHRQ, STROBE, and GRACE recommendations/statements were followed.The results of the systematic search strategy yielded 62 studies that included a total of 3034 patients. Complete information about first-line therapeutic regimens was detailed in 1952 patients, including glucocorticoid-based regimens in 1437 (74%), drug-free regimens in 213 (11%), and other therapies in 38 (2%). No therapy (wait and see management) was reported in 264 (13%) patients. The efficacy of monotherapy with glucocorticoids was specified in 1220 patients, of whom 97% had a therapeutic response. Relapses, however, were reported in 464/1395 (33%) patients despite typically short follow-up periods. Therapeutic efficacy was reported in 219/231 (95%) of relapses treated with glucocorticoids, 56/69 (81%) of those treated with azathioprine, 16/22 (72%) of those treated with other immunosuppressive agents, and in the 9 cases treated with rituximab (100%). In 14 studies, the authors detailed the outcome of 159/246 patients with wait-and-see management; spontaneous improvement or resolution was reported in 68 (43%) cases. Wide heterogeneity was observed with respect to the first-line therapeutic approaches used for the different organ-specific disease subsets, including significant differences in the mean dose of glucocorticoids used.Nearly 70% of reported IgG4-RD patients are treated with oral glucocorticoids in monotherapy. However, the therapeutic management is heavily influenced by geographical, epidemiological, and clinical factors, especially with respect to the predominant organ affected. The frequency of glucocorticoid failure to induce sustained remissions both during and after treatment and the assessment of glucocorticoid toxicity in IgG4-RD require further study.