Factors influencing dry mouth in patients with primary Sjögren syndrome: usefulness of the ESSPRI index

To evaluate health-related quality of life in a large series of primary SS patients using the recently-proposed ESSPRI questionnaire and to evaluate the relationship between the intensity of oral dryness and other signs and symptoms frequently found in these patients. METHODS: We evaluated 90 primary SS patients seen consecutively; all fulfilled the current classification criteria. All patients completed the ESSPRI questionnaire. We compared the mean values of the ESSPRI-dry mouth item with other ESSPRI items related to sicca features, general symptoms, quality of life, quality of sleep, psychological and psychiatric features, extraglandular involvement, laboratory features and immunological markers and cardiovascular risk factors. Multivariate regression analysis with a backwards stepwise selection method was performed to identify those variables that were independently associated with dry mouth. RESULTS: Mean intensity of oral dryness measured by the corresponding ESSPRI item was 7.17±0.23. Oral dryness correlated with age both at diagnosis and at study inclusion (p=0.013), but not with gender or with time of disease evolution. No significant correlation was found with the SF-36, HAQ and FIQ questionnaires. We found a significant correlation between the intensity of oral dryness and the quality of sleep (p=0.001), anxiety and depression measured by the GH28 (p=0.004 and 0.024, respectively), and a statistically-significant trend for anxiety and depression measured by the HADS (p=0.08 and 0.07, respectively). No significant correlation was found with the main extraglandular and immunological features; however, a significant correlation between oral dryness and hypertension (p=0.019), type II diabetes mellitus (p=0.005) and hypercholesterolemia (p=0.011) was found. Multivariate regression analysis shows that fatigue measured by ESSPRI (p=0.049), sleep quality (p=0.008) and hypercholesterolemia (p=0.008) were independently associated with dry mouth. CONCLUSION: We report on the usefulness of the ESSPRI index in evaluating HRQOL associated with oral dryness in primary SS patients. Oral dryness correlated with age and the other sicca symptoms measured by ESSPRI, but not with the main systemic and immunological SS features. In contrast, oral dryness was strongly correlated with fatigue, pain, psychological distress, poor sleep and vascular risk factors. A multidisciplinary therapeutic approach may be the best way of minimizing oral dryness and its consequences in primary SS patient

Association of Candidate Gene Polymorphisms With Chronic Kidney Disease: Results of a Case-Control Analysis in the Nefrona Cohort

Chronic kidney disease (CKD) is a major risk factor for end-stage renal disease, cardiovascular disease and premature death. Despite classical clinical risk factors for CKD and some genetic risk factors have been identified, the residual risk observed in prediction models is still high. Therefore, new risk factors need to be identified in order to better predict the risk of CKD in the population. Here, we analyzed the genetic association of 79 SNPs of proteins associated with mineral metabolism disturbances with CKD in a cohort that includes 2, 445 CKD cases and 559 controls. Genotyping was performed with matrix assisted laser desorption ionizationtime of flight mass spectrometry. We used logistic regression models considering different genetic inheritance models to assess the association of the SNPs with the prevalence of CKD, adjusting for known risk factors. Eight SNPs (rs1126616, rs35068180, rs2238135, rs1800247, rs385564, rs4236, rs2248359, and rs1564858) were associated with CKD even after adjusting by sex, age and race. A model containing five of these SNPs (rs1126616, rs35068180, rs1800247, rs4236, and rs2248359), diabetes and hypertension showed better performance than models considering only clinical risk factors, significantly increasing the area under the curve of the model without polymorphisms. Furthermore, one of the SNPs (the rs2248359) showed an interaction with hypertension, being the risk genotype affecting only hypertensive patients. We conclude that 5 SNPs related to proteins implicated in mineral metabolism disturbances (Osteopontin, osteocalcin, matrix gla protein, matrix metalloprotease 3 and 24 hydroxylase) are associated to an increased risk of suffering CKD

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Calcificaciones ectópicas: mecanismos, similitudes y diferencias

Introduction: Plasma is always supersaturated in hydroxyapatite, because if not the bone would not be formed. However ectopic calcifications do not occur massively and, their formation mechanism is still poorly understood. In this work three cases of different ectopic calcifications are presented and similarities and differences are analyzed in order to deepen in their formation mechanism. Patients and Methods: Three patients with ectopic calcifications were selected. A patient with hip calcification as a result of necrosis produced by a blow, a patient with a autoimmune overlap syndrome having multiple calcifications in several areas of the body and one patient with calcifying tendinitis of the shoulder. Mineralogical studies of samples taken from each patient were performed using scanning electron microscopy with microanalysis by X-ray dispersive energy. Urinary phytate levels in each patient were also determined. Results: The presence of organic matter and no spherulitic carbonated hydroxyapatite with bone-like compact structure was detected in the patient with hip calcification. In the other two patients the presence of organic matter calcified with carbonated hydroxyapatite with a lot of spherulites or spheroidal carboxyapatite objects was observed. In all cases the urinary phytate levels correspond to low values (about 0.5 μM). Discussion: This study confirms that in all cases, if an ectopic calcification is generated this is due to a previous tissue injury. The morphology of that calcification will depend on the size and status of the available space where is generated. So, if it comes in regions of dense tissues, with little empty space and without excessive fluid renewal, it will lead to compact carboxyapatite structures that nucleate directly on organic matter . If the region has more or less open cavities fluid-filled, spherulitic or spheroidal amorphous structures are formed. The role of crystallization inhibitors and immune system in the development of these deposits is also discussed.Introducción: El plasma está siempre sobresaturado en hidroxiapatita, ya que si no fuera así el hueso no se podría formar. A pesar de ello las calcificaciones ectópicas no se dan de forma masiva, siendo su mecanismo de desarrollo todavía poco conocido. En este trabajo se presentan tres casos de calcificación ectópica muy diferentes, con el fin de profundizar en su mecanismo de formación, analizando analogías y diferencias. Pacientes y Métodos: Se seleccionaron tres pacientes con calcificaciones ectópicas: un paciente con calcificación de cadera resultado de la necrosis de la misma producida por un fuerte golpe. Un paciente con Síndrome de Solapamiento autoinmune que presenta calcificaciones múltiples en varias zonas del cuerpo y un paciente con tendinitis calcificante del hombro. Se efectuaron estudios mineralógicos de muestras extraídas de cada paciente mediante microscopía electrónica de barrido y microanálisis por energía dispersiva de Rayos X. Se determinó también los niveles de fitato urinario en cada paciente. Resultados: En el paciente con calcificación en la cadera se detectó la presencia de materia orgánica e hidroxiapatita carbonatada no esferulítica de estructura compacta similar al hueso. En los otros dos pacientes se observó la presencia de materia orgánica calcificada con hidroxiapatita carbonatada junto con gran cantidad de esferulitos o bien objetos esferoidales de carboxiapatita. En todos los casos los valores de fitato urinario correspondieron a valores bajos (alrededor de 0.5 μM). Discusión: Este estudio confirma que en cualquier caso, si se genera una calcificación ectópica es porque se ha producido una lesión tisular previa. La morfología de dicha calcificación dependerá del tamaño y disposición del espacio en la que se genere. Así, si se trata de regiones de tejido denso, con poco espacio vacío y sin excesiva renovación de líquido, dará lugar a estructuras compactas de carboxiapatita nucleada directamente sobre la materia orgánica. Si se trata de zonas con cavidades mas o menos abiertas y llenas de líquido, se formarán estructuras amorfas esferulíticas o esferoidales. Se discute también el papel de los inhibidores de la cristalización y del sistema inmunitario en la evolución de estos depósitos

Factors influencing dry mouth in patients with primary Sjögren syndrome: usefulness of the ESSPRI index

To evaluate health-related quality of life in a large series of primary SS patients using the recently-proposed ESSPRI questionnaire and to evaluate the relationship between the intensity of oral dryness and other signs and symptoms frequently found in these patients. METHODS: We evaluated 90 primary SS patients seen consecutively; all fulfilled the current classification criteria. All patients completed the ESSPRI questionnaire. We compared the mean values of the ESSPRI-dry mouth item with other ESSPRI items related to sicca features, general symptoms, quality of life, quality of sleep, psychological and psychiatric features, extraglandular involvement, laboratory features and immunological markers and cardiovascular risk factors. Multivariate regression analysis with a backwards stepwise selection method was performed to identify those variables that were independently associated with dry mouth. RESULTS: Mean intensity of oral dryness measured by the corresponding ESSPRI item was 7.17±0.23. Oral dryness correlated with age both at diagnosis and at study inclusion (p=0.013), but not with gender or with time of disease evolution. No significant correlation was found with the SF-36, HAQ and FIQ questionnaires. We found a significant correlation between the intensity of oral dryness and the quality of sleep (p=0.001), anxiety and depression measured by the GH28 (p=0.004 and 0.024, respectively), and a statistically-significant trend for anxiety and depression measured by the HADS (p=0.08 and 0.07, respectively). No significant correlation was found with the main extraglandular and immunological features; however, a significant correlation between oral dryness and hypertension (p=0.019), type II diabetes mellitus (p=0.005) and hypercholesterolemia (p=0.011) was found. Multivariate regression analysis shows that fatigue measured by ESSPRI (p=0.049), sleep quality (p=0.008) and hypercholesterolemia (p=0.008) were independently associated with dry mouth. CONCLUSION: We report on the usefulness of the ESSPRI index in evaluating HRQOL associated with oral dryness in primary SS patients. Oral dryness correlated with age and the other sicca symptoms measured by ESSPRI, but not with the main systemic and immunological SS features. In contrast, oral dryness was strongly correlated with fatigue, pain, psychological distress, poor sleep and vascular risk factors. A multidisciplinary therapeutic approach may be the best way of minimizing oral dryness and its consequences in primary SS patient

Factors influencing dry mouth in patients with primary Sjögren syndrome: usefulness of the ESSPRI index

To evaluate health-related quality of life in a large series of primary SS patients using the recently-proposed ESSPRI questionnaire and to evaluate the relationship between the intensity of oral dryness and other signs and symptoms frequently found in these patients. METHODS: We evaluated 90 primary SS patients seen consecutively; all fulfilled the current classification criteria. All patients completed the ESSPRI questionnaire. We compared the mean values of the ESSPRI-dry mouth item with other ESSPRI items related to sicca features, general symptoms, quality of life, quality of sleep, psychological and psychiatric features, extraglandular involvement, laboratory features and immunological markers and cardiovascular risk factors. Multivariate regression analysis with a backwards stepwise selection method was performed to identify those variables that were independently associated with dry mouth. RESULTS: Mean intensity of oral dryness measured by the corresponding ESSPRI item was 7.17±0.23. Oral dryness correlated with age both at diagnosis and at study inclusion (p=0.013), but not with gender or with time of disease evolution. No significant correlation was found with the SF-36, HAQ and FIQ questionnaires. We found a significant correlation between the intensity of oral dryness and the quality of sleep (p=0.001), anxiety and depression measured by the GH28 (p=0.004 and 0.024, respectively), and a statistically-significant trend for anxiety and depression measured by the HADS (p=0.08 and 0.07, respectively). No significant correlation was found with the main extraglandular and immunological features; however, a significant correlation between oral dryness and hypertension (p=0.019), type II diabetes mellitus (p=0.005) and hypercholesterolemia (p=0.011) was found. Multivariate regression analysis shows that fatigue measured by ESSPRI (p=0.049), sleep quality (p=0.008) and hypercholesterolemia (p=0.008) were independently associated with dry mouth. CONCLUSION: We report on the usefulness of the ESSPRI index in evaluating HRQOL associated with oral dryness in primary SS patients. Oral dryness correlated with age and the other sicca symptoms measured by ESSPRI, but not with the main systemic and immunological SS features. In contrast, oral dryness was strongly correlated with fatigue, pain, psychological distress, poor sleep and vascular risk factors. A multidisciplinary therapeutic approach may be the best way of minimizing oral dryness and its consequences in primary SS patient