Clinical profile of Spanish hepatitisC virus-infected treatment-naïve patients with compensated cirrhosis in the CREST study. / Perfil clínico de los pacientes españoles con hepatitisC naïve con cirrosis compensada tratados en el estudio CREST.

BACKGROUND AND AIM OF THE STUDY: There are still patients with hepatitisC in Spain who have yet to be diagnosed, but their clinical profile is unclear. In 2021, 21.93% of patients diagnosed had cirrhosis and were mostly treatment-naïve. METHODS: This sub-analysis describes the clinical profile of the 60Spanish treatment-naïve patients with compensated cirrhosis who were included in the CREST study. MAJOR RESULTS: Sixty percent of patients were male, median age 56years, and 33% had a history of drug use. Almost three-quarters (71.3%) had more than one comorbidity and 78.3% took concomitant medication. At treatment initiation, median platelet count was 139×103/µL and FibroScan® 17kPa. No virological failure was observed and no patient discontinued treatment due to adverse events. No clinically significant changes were noted during or after treatment in the median platelet, albumin, bilirubin, and transaminase levels. CONCLUSIONS: Treatment with glecaprevir/pibrentasvir for 8weeks in this cohort of treatment-naïve patients with compensated cirrhosis in Spain was safe and effective. This information reinforces the use of this short antiviral regimen even when there is compensated cirrhosis, simplifying the approach to hepatitisC among those patients still to be diagnosed and treated in Spain.

Myocardial infarction and haemorrhagic stroke as a rare presentation of acute aortic dissection: a fatal case report.

Background: Type A acute aortic dissection (AAD) is an extremely severe condition, having a high risk of mortality. Initial diagnosis can be deceptive, especially in patients with other confounding presentations. Case summary: We present the case of a 60-year-old male with a history of endovascular aortic repair for abdominal aortic dissection, in whom a diagnosis of AAD was made, but almost missed, after he presented with stroke signs and left coronary myocardial infarction. Thorough clinical evaluation and point-of-care ultrasound (POCUS) were fundamental to the diagnosis of the underlying condition, which showed the intimal flap in the ascending aorta, aortic insufficiency, and a dissected left common carotid artery. The diagnosis was confirmed with a head and thoracic computed tomography scan, which also showed bilateral haemorrhagic strokes. Treatment options can be limited in patients with AAD with associated complications. After a careful multidisciplinary evaluation, life-sustaining therapy was withdrawn and the patient passed away. Discussion: Our case depicts the diagnosis challenge presented by patients with AAD. We emphasize the importance of clinical suspicion and POCUS examination for the diagnosis of the underlying condition, as it is frequently missed during first evaluation. We discuss the available literature regarding the prevalence and described mechanisms by which AAD can associate occlusion myocardial infarction, which more commonly involves the right coronary artery, as well as haemorrhagic stroke. We briefly mention management options, which are limited and controversial.

Calcifilaxis en una paciente en hemodiálisis: complicación grave con elevada mortalidad / Calciphylaxis in a hemodialysis patient: a serious complication with high mortality

Descripción del caso: Paciente con enfermedad renal crónica terminal en tratamiento de hemodiálisis desde hace 1 año. Acude a sesión de hemodiálisis refiriendo lesiones cutáneas muy dolorosas con aspecto necrótico de 2 semanas de evolu-ción en extremidades inferiores distales sugestivas de calcifi-laxis. Dados los antecedentes clínicos de fibrilación auricular paroxística, anticoagulada con acenocumarol y los factores de riesgo que presenta, se inician medidas inmediatas dado el mal pronóstico de dicha enfermedad. Descripción/evaluación del plan de cuidados: Se suspende tratamiento con acenocumarol iniciando anticoagulación con heparina de bajo peso molecular, también se suspenden los suplementos de vitamina D. Se inicia administración de bifos-fonatos como inhibidores del calcio, de tiosulfato de sodio como vasodilatador y quelante del fósforo. Se instaura pauta de analgesia siendo uno de los objetivos más importantes del plan de cuidados, el control del dolor, con la administración de opiáceos, antiinflamatorios no esteroideos o mórficos. Aunque fue de difícil manejo, el papel de enfermería ha sido fundamental para procurar el máximo confort. También fue muy importante la vigilancia y el cuidado de las lesiones para prevenir infecciones y controlar la enfermedad observándose una adversa y rápida evolución a pesar de las terapias coad-yuvantes, puesto que cuando se diagnosticó ya presentaba lesiones necróticas. Conclusiones: La calcifilaxis es una complicación poco fre-cuente pero grave que suele observarse en pacientes con enfermedad renal crónica, sobre todo en hemodiálisis. Eltratamiento es multidisciplinar y es importante identificar precozmente a estos pacientes. Desgraciadamente, como en nuestro caso, los resultados no son siempre favorables.(AU)

Case description: Patient with end-stage renal disease undergoing hemodialysis treatment for 1 year. The patient presents to the hemodialysis session with extremely painful necrotic-looking skin lesions on the distal lower extremities, suggestive of calciphylaxis, which have been present for 2 weeks. Given the patient’s medical history of paroxysmal atrial fibrillation and anticoagulation with acenocoumarol, along with the risk factors present, immediate measures are initiated due to the poor prognosis of this condition. Description/evaluation of the care plan: Acenocoumarol treatment is discontinued, and anticoagulation with low molecular weight heparin is initiated. Vitamin D supplements are also discontinued. Bisphosphonates are started as calcium inhibitors, sodium thiosulfate is administered as a vasodilator, and phosphate binder. An analgesic regimen is established, with pain control being one of the most important goals of he care plan. This includes the administration of opioids, nonsteroidal anti-inflammatory drugs, or morphine. Although challenging, the nursing role has been crucial in providing maximum comfort. Close monitoring and wound care are also important to prevent infections and control the disease, although an adverse and rapid progression was observed despite the adjunctive therapies, as necrotic lesions were already present at the time of diagnosis. Conclusions: Calciphylaxis is a rare but serious complication often observed in patients with chronic kidney disease, especially in those undergoing hemodialysis. Treatment is multidisciplinary, and early identification of these patients is important. Unfortunately, as in our case, the outcomes are not always favorable.(AU)

Valoración de la fragilidad en un centro de diálisis. ¿Son más frágiles los pacientes con diabetes? / Fragility assessment in a dialysis center. Are patients with diabetes more fragile than others?

Introducción: El incremento en la inclusión de personas de edad avanzada a los programas de hemodiálisis se relaciona con un aumento de la prevalencia de fragilidad, considerada predictora de discapacidad y asociada a eventos adversos de salud. Dado su carácter reversible, es importante hacer un cribaje para mejorar la práctica clínica.Objetivo: Evaluar el grado de fragilidad y estado funcional del paciente en nuestra unidad de hemodiálisis y analizar las diferencias entre diabéticos y no diabéticos. Material y Método: Estudio observacional de corte transversal. La fragilidad se midió utilizando el fenotipo de Fried y la valoración funcional mediante las escalas Barthel, Lawton, Downton y la Short Physical Performance Battery. Se evaluó comorbilidad y riesgo de caídas con las escalas Charlson y Downton respectivamente. Se comparó entre grupos de diabéticos y no diabéticos y se analizó la relación entre la fragilidad y la edad, dependencia, comorbilidad y riesgo de caídas.Resultados: Se incluyeron 128 pacientes. El 45% tenían Diabetes. Los pacientes con diabetes tenían una edad media mayor que los no diabéticos (74,2±11 vs 67,8±15 años) y mayor comorbilidad (Charlson 8,2±2,2 vs 5,8±2,4). El 25% de los pacientes presentaron fragilidad, observando una tendencia que sugirió mayor fragilidad, peor capacidad funcional y mayor grado de dependencia en los pacientes diabéticos, aunque de forma no significativa. Conclusiones: Una cuarta parte de la población estudiada presenta fragilidad, con una tendencia más acusada a padecerla los pacientes diabéticos, que podría estar relacionada con mayor edad, mayor comorbilidad y menor capacidad funcional que los no diabéticos.(AU)

Introduction: The increase in the inclusion of elderly people in hemodialysis programs is connected to a rise in the prevalence of their frailty, considered as well as a prediction of disability and often associated with adverse health events. Given its reversible nature, screening is essential to improve clinical practice.Objective: To assess the frailty index and the patient functional status in our hemodialysis unit, as well as analyze the differences between diabetics and non-diabetics.Material and Method: Observational cross-sectional study. Frailty was measured using the Fried phenotype and functional assessment using the Barthel, Lawton, Downton, and Short Physical Performance Battery scales. Comorbidity and fall risk were evaluated with the Charlson and Downton scales, respectively. Diabetic and nondiabetic groups were compared, as well as the relationship between frailty and age, dependency, comorbidity, and fall hazard was analyzed. Results: A hundred and twenty-eight patients were included in the study. 45% had diabetes. Diabetic patients had a higher average age than nondiabetics (74.2±11 vs 67.8±15 years) and higher comorbidity (Charlson 8.2±2.2 vs 5.8±2.4). Twenty-five percent of the patients had frailty, observing a trend that suggests higher frailty, worse functional capacity, and a higher degree of dependency in diabetic patients, although not significantly.Conclusions: A quarter of the sampled analyzed presents frailty, with a more pronounced tendency to suffer from it in the case of diabetic patients, which could be related to older age, higher comorbidity, and less functional capacity than non-diabetic people.(AU)

Hiperpotasemia severa tras realización de ileostomía en un paciente en hemodiálisis crónica / Severe hyperkalaemia after ileostomy in a patient on chronic hemodialysis

Descripción del caso: Paciente que ingresa por anemia y de-terioro de la función renal. Se diagnostica neoplasia de recto infiltrante tras realización de colonoscopia e inicia tratamiento renal sustitutivo tras colocación de catéter temporal. Previa-mente a la realización de la ileostomía se somete a radiotera-pia neoadyuvante. Tres meses después presenta hiperpotase-mia severa persistente. Encontramos pocos casos descritos en la literatura al respecto, pero parece estar relacionado con la interrupción del tránsito intestinal.Descripción/evaluación del plan de cuidados: Se hace refuer-zo dietético, se modifican los parámetros de la hemodiálisis (HD) y se inicia tratamiento con resinas, pero no se norma-liza el potasio hasta el cierre de la ileostomía. Resolver la hi-perpotasemia fue el objetivo imperioso del plan de cuidados, además del manejo de la ansiedad y el apoyo al paciente en el autocuidado de su estoma. Parece ser que la alteración de la homeostasia se debió al déficit de secreción intestinal de potasio en el colon. Se aceleró el proceso de restauración de la continuidad intestinal con el cierre de la ileostomía, confir-mándose la sospecha. Conclusiones: La hiperpotasemia en los pacientes en tratamien-to en hemodiálisis puede estar relacionada con la cirugía de co-lon. Nuestro caso demuestra la importancia de la secreción de potasio en el tracto intestinal para mantener la homeostasis en los pacientes con insuficiencia renal crónica terminal. (AU)

Case description: Patient admitted for anaemia and deterioration of renal function. Infiltrating rectal neoplasia was diagnosed after colonoscopy. Renal replacement therapy was started after placing a tunneled venous catheter. Prior to ileostomy, neoadjuvant radiotherapy was performed. Three months later, persistent severe hyperkalaemia appeared. Few cases have been described in the literature, but there seems to be a relationship with the interruption of intestinal transit.Description/evaluation of the care plan: Dietary reinforce-ment was performed, hemodialysis parameters were modi-fied and treatment with resins was started, but potassium did not normalise until the ileostomy was closed. Resolving the hyperkalaemia was the main focus of the care plan, in addition to anxiety management and supporting the patient in stoma self-care. It was suggested that the alteration of homeosta-sis was due to a deficit of intestinal potassium secretion in the colon. The process of restoring intestinal continuity was accelerated with the closure of the ileostomy, confirming the suspicion.Material and Method: Hyperkalaemia in hemodialysis patients may be related to colon surgery. Our case demonstrates the importance of potassium secretion in the intestinal tract to maintain homeostasis in patients with end-stage renal failure. (AU)

Long-Term Outcome of Critically Ill Advanced Cancer Patients Managed in an Intermediate Care Unit.

Background: To analyze the long-term outcomes for advanced cancer patients admitted to an intermediate care unit (ImCU), an analysis of a do not resuscitate orders (DNR) subgroup was made. Methods: A retrospective observational study was conducted from 2006 to January 2019 in a single academic medical center of cancer patients with stage IV disease who suffered acute severe complications. The Simplified Acute Physiology Score 3 (SAPS 3) was used as a prognostic and severity score. In-hospital mortality, 30-day mortality and survival after hospital discharge were calculated. Results: Two hundred and forty patients with stage IV cancer who attended at an ImCU were included. In total, 47.5% of the cohort had DNR orders. The two most frequent reasons for admission were sepsis (32.1%) and acute respiratory failure (excluding sepsis) (38.7%). Mortality in the ImCU was 10.8%. The mean predicted in-hospital mortality according to SAPS 3 was 51.9%. The observed in-hospital mortality was 37.5% (standard mortality ratio of 0.72). Patients discharged from hospital had a median survival of 81 (30.75−391.25) days (patients with DNR orders 46 days (19.5−92.25), patients without DNR orders 162 days (39.5−632)). The observed mortality was higher in patients with DNR orders: 52.6% vs. 23.8%, p 0 < 0.001. By multivariate logistic regression, a worse ECOG performance status (3−4 vs. 0−2), a higher SAPS 3 Score and DNR orders were associated with a higher in-hospital mortality. By multivariate analysis, non-invasive mechanical ventilation, higher bilirubin levels and DNR orders were significantly associated with 30-day mortality. Conclusion: For patients with advanced cancer disease, even those with DNR orders, who suffer from acute complications or require continuous monitoring, an ImCU-centered multidisciplinary management shows encouraging results in terms of observed-to-expected mortality ratios.

Recovery of parathyroid function in patients with thyroid cancer treated by total thyroidectomy: An analysis of 685 patients with hypoparathyroidism at discharge of surgery.

OBJECTIVE: We aimed to study the predictive factors for recovery of parathyroid function in hypoparathyroid patients after total thyroidectomy for thyroid cancer. METHODS: We designed a retrospective, multicentre and nation-wide analysis of patients with total thyroidectomy who were seen in twenty endocrinology departments from January to March 2018. We selected patients with histologically proven thyroid cancer and retrieved information related to surgical procedure and thyroid cancer features. Survival analysis and Cox regression analysis were used to study the relationship between these variables and the recovery of parathyroid function. RESULTS: From 685 patients with hypoparathyroidism at discharge of surgery, 495 (72.3%) recovered parathyroid function over time. Kaplan-Meier analysis showed that this recovery was significantly related to the presence of specialized surgical team (P<0.001), identification of parathyroid glands at surgery (P<0.001), papillary histopathology (P=0.040), and higher levels of postoperative calcium (Ca) (P<0.001) and parathyroid hormone (PTH) (P<0.001). Subjects with gross extrathyroidal extension (P=0.040), lymph node metastases (P=0.004), and surgical re-intervention after initial surgery (P=0.024) exhibited a significant risk of persistence of hypoparathyroidism. Multivariate Cox regression analysis showed that the significant and independent factors for recovery of parathyroid function were postoperative concentrations of Ca (P=0.038) and PTH (P=0.049). The presence of lymph node metastases was a negative predictor of recuperation of parathyroid function (P=0.042) in this analysis. CONCLUSION: In patients with thyroid cancer, recovery of parathyroid function after total thyroidectomy was directly related to postoperative Ca and PTH concentrations, and inversely related to lymph node metastases.

Late Recovery of Parathyroid Function After Total Thyroidectomy: A Case-Control Study.

The clinical characteristics of patients with postoperative hypoparathyroidism who recover parathyroid function more than 12 months after surgery have not been studied. We aimed to evaluate whether the intensity of replacement therapy with calcium and calcitriol is related to the late recovery of parathyroid function. We compared the demographic, surgical, pathological, and analytical features of two groups of patients: cases, i. e., late recovery patients (those who recover parathyroid function>1 year after thyroidectomy, n=40), and controls, i. e., patients with permanent hypoparathyroidism (n=260). Replacement therapy with calcium and calcitriol was evaluated at discharge of surgery, 3-6 months, 12 months, and last visit. No significant differences were found in clinical, surgical, pathological, or analytical characteristics between cases and controls. The proportion of cases who required treatment with calcium plus calcitriol at 12 months was significantly lower than that found in controls (p<0.001). Furthermore, daily calcium and calcitriol doses in controls were significantly higher than those in cases at 3-6 months (p=0.014 and p=0.004, respectively) and at 12 months (p<0.001 and p=0.043, respectively). In several models of logistic regression analysis therapy with calcium and calcitriol at 12 months was negatively related to late recovery of parathyroid function. Although delayed recuperation of parathyroid function after total thyroidectomy is uncommon (13%), follow-up beyond 12 months is necessary in patients with postoperative hypoparathyroidism, especially in those whose needs of treatment with Ca and calcitriol are reducing over time.

Permanent postoperative hypoparathyroidism: an analysis of prevalence and predictive factors for adequacy of control in a cohort of 260 patients.

BACKGROUND: Recent guidelines for the treatment of hypoparathyroidism emphasize the need for long-term disease control, avoiding symptoms and hypocalcaemia. Our aim has been to analyze the prevalence of poor disease control in a national cohort of patients with hypoparathyroidism, as well as to evaluate predictive variables of inadequate disease control. METHODS: From a nation-wide observational study including a cohort of 1792 patients undergoing total thyroidectomy, we selected 260 subjects [207 women and 53 men, aged (mean ± SD) 47.2±14.8 years] diagnosed with permanent hypoparathyroidism. In every patient demographic data and details on surgical procedure, histopathology, calcium (Ca) metabolism, and therapy with Ca and calcitriol were retrospectively collected. A patient was considered not adequately controlled (NAC) if presented symptoms of hypocalcemia or biochemical data showing low serum Ca levels or high urinary Ca excretion. RESULTS: Two hundred and twenty-one (85.0%) patients were adequately controlled (AC) and 39 (15.0%) were NAC. Comparison between AC and NAC patients did not show any significant difference in demographic, surgical, and pathological features. Rate of hospitalization during follow-up was significantly higher among NAC patients in comparison with AC patients (35.9% vs. 10.9%, P<0.001). Dose of oral Ca and calcitriol were also significantly higher in NAC subjects. In a subgroup of 129 patients with serum parathyroid hormone (PTH) levels available, we found that NAC patients exhibited significantly lower postoperative PTH concentrations than AC patients [median (interquartile range) 3 (1.9-7.8) vs. 6.9 (3.0-11) pg/mL; P=0.009]. CONCLUSIONS: In a nation-wide cohort of 260 subjects with definitive hypoparathyroidism, 15% of them had poor disease control. These patients required higher doses of oral Ca and calcitriol, had higher rate of hospitalization during follow-up and showed lower PTH concentrations in the postoperative period.

Correction to: Prevalence and risk factors for hypoparathyroidism following total thyroidectomy in Spain: a multicentric and nation-wide retrospective analysis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Prevalence and risk factors for hypoparathyroidism following total thyroidectomy in Spain: a multicentric and nation-wide retrospective analysis.

PURPOSE: The prevalence of postoperative hypoparathyroidism has been studied in registries and in surgical series with highly variable and imprecise results. However, the frequency of this hormonal deficiency in the clinical practice of endocrinologists is not known with accuracy. We aimed to assess the prevalence and risk factors of hypoparathyroidism in patients undergoing total thyroidectomy in Spain. METHODS: We designed a retrospective, multicentre and nation-wide protocol including all patients with total thyroidectomy who were seen in the endocrinology clinic of the participant centers from January to March 2018. Prevalence of hypoparathyroidism was evaluated at discharge of surgery, 3-6 months after surgery, 12 months after surgery and at last visit. Twenty hospitals participated in the study. RESULTS: Of 1792 patients undergoing total thyroidectomy, 866 (48.3%) developed postoperative hypoparathyroidism at discharge of surgery. Most of them recover parathyroid function over time. Prevalence of hypoparathyroidism at 3-6 months, 12 months and at last visit was 22.9%, 16.7% and 14.5%, respectively. The risk of developing definitive hypoparathyroidism was related to the presence of parathyroid tissue at histology, lymph node dissection, and two-stage thyroidectomy. Patients with thyroid cancer, with higher postoperative calcium levels and treated by expert surgical teams exhibited lower risk of developing permanent hypoparathyroidism. CONCLUSIONS: Although most patients with postsurgical hypoparathyroidism recover parathyroid function, the prevalence of permanent disease in clinical practice is non negligible (14.5%). Postoperative calcium, extent and timing of surgery, the presence of cancer, expert surgical team, and parathyroid tissue at histology are predictors of permanent hypoparathyroidism.

Transverse testicular ectopia discovered following reduction of an inguinal hernia.

Transverse testicular ectopia is a rare condition in which both testicles occupy a single hemiscrotum. The aberrant positioning may lead to vascular compromise or impaired temperature regulation, which elevate the risks for torsion, infertility and testicular cancer. Definitive therapy consists of orchiectomy or orchiopexy. We report a case of a 10-month-old boy with an incarcerated inguinal hernia who was discovered to have transverse testicular ectopia following hernia reduction. The patient was treated with herniorrhaphy and open transseptal orchiopexy.

¿Cómo son los últimos meses de vida de los pacientes con insuficiencia renal crónica avanzada en los que se desestima el tratamiento con hemodiálisis o con diálisis peritoneal? / What are the last months of life like for advanced chronic renal failure patients who are not considered candidates for treatment with haemodialysis or peritoneal dialysis?

OBJETIVO: Objetivo primario. Determinar la supervivencia y los factores predictores de supervivencia en pacientes con insuficiencia renal crónica avanzada (IRCA) desestimados para tratamiento renal sustitutivo (TRS). Objetivos secundarios. Describir: a) las características sociodemográficas de los pacientes y del cuidador principal; b) la etiología de la nefropatía y la comorbilidad asociada; c) variables clínicas de los pacientes cuando son incluidos en el programa; d) la evolución clínica en términos de tensión arterial (TA), número de episodios de sobrecarga hídrica, tratamientos recibidos, frecuencia de hospitalizaciones, causas de las mismas, lugar y causa del fallecimiento; e) la evolución de los parámetros analíticos; f) el grado de información del diagnóstico y del pronóstico del paciente y de la familia, y g) la actividad asistencial realizada por los equipos de soporte de atención paliativa domiciliaria (ESAPD) durante el seguimiento. Material y MÉTODO: DISEÑO: Estudio descriptivo longitudinal de cohorte histórica. Ámbito. ESAPD áreas 1, 5 y 7 de Madrid. Sujetos a estudio. Pacientes con IRCA que han sido considerados y desestimados para TRS. Criterios de selección.1) Pacientes con IRCA que han sido considerados y desestimados para depuración extrarrenal, y 2) el paciente y/o cuidador y/o familia acepta el seguimiento de la enfermedad por el ESAPD y/o por su médico de Atención Primaria. Tamaño de la muestra. Se seleccionaron todas las historias clínicas de los archivos desde la creación de los respectivos ESAPD, desde 1997 hasta diciembre del 2009. Variables analizadas.1) Respuesta principal: tiempo de supervivencia; 2) variables secundarias: 2.1) sociodemográficas paciente y cuidador principal; edad, sexo; cuidador principal: estado civil, parentesco; 2.2) variables relacionadas con la enfermedad renal; etiología de la nefropatía, motivo de exclusión de TRS, comorbilidad; 2.3) variables clínicas; grado de control TA a lo largo de la evolución de la enfermedad; se recoge la TA en sucesivas visitas; presencia o ausencia de alguno de los siguientes síntomas al inicio del programa: edemas, dolor, estreñimiento, prurito, disnea, insomnio, ansiedad, tristeza y deterioro cognitivo; número de episodios sobrecarga hídrica; causa de salida del programa; lugar del fallecimiento; causa del fallecimiento y síntomas presentes en situación de últimos días; 2.4) variables terapéuticas; número de fármacos al inicio del programa; número de fármacos a la salida del programa de los pacientes cuyo motivo de salida era el exitus; tipo de fármacos; número de transfusiones realizadas; 2.5) variables de ingresos hospitalarios; número de ingresos hospitalarios; causas de hospitalización; 2.6) variables analíticas; grado de control a lo largo de la enfermedad de parámetros analíticos hasta el fallecimiento; 2.7) variables del grado de información del diagnóstico y del pronóstico; 2.8) variables de actividad asistencial; número de visitas domiciliarias realizadas al paciente. RESULTADOS: N: 102 pacientes. Edad media: 79,62 (9,94) años. Etiología IRCA más frecuentes: vascular 37, no filiada 32, diabética 15.comorbilidad: SCG riesgo bajo 17, SCG riesgo medio 35, SCG riesgo alto 50. Ponderación media del índice de Charlson: 6,88 (2,5). Causa desestimación TRS: comorbilidad 47,5%, edad 25,7%, decisión paciente 22,8%, otras 4%. Grado información diagnóstico paciente y cuidador 57,9 y 94,4%, respectivamente. Grado información pronóstica paciente y cuidador 11,8 y 90%, respectivamente. Síntomas más frecuentes en primera visita: disnea 33,3%, prurito 30,4%, insomnio 34,3%, tristeza 36,3 y edemas 43,1%. Mediana consumo fármacos al inicio: 10, al final de seguimiento: 11. Número de transfusiones: 5. Número de ingresos hospitalarios: 50, por sobrecarga hídrica: 35, comorbilidad: 12, oliguria: 3. Causa exitus: IRCA 72,9%, enfermedad intercurrente 27,1%. Localización exitus: domicilio 39, hospital agudos 31, unidad cuidados paliativos 13, urgencias 2. Media visitas por ESAPD: 11,32, mediana: 6,5. Mediana supervivencia: 4 meses, supervivencia al año: 25%. Factores predictores de supervivencia: creatinina primera visita HZ 1,106 (IC 95% 1,01-1,20), p = 0,024; edad 71-80 años, HZ 4,42 (IC 95% 1,60-12,21), edad>81 años, HZ 2,97 (IC 95% 1,16-7,61). No se asoció a supervivencia niveles TA, volumen diuresis, niveles sodio, potasio, calcio, fósforo ni hemoglobina. CONCLUSIONES: Los pacientes con IRCA en los que se desestimó TRS y que fueron seguidos en su domicilio por unidades de cuidados paliativos a domicilio tuvieron una mediana de supervivencia de 4 meses, siendo la edad y la función renal residual factores predictores de supervivencia, sin que la comorbilidad ni los niveles de electrólitos, TA ni el volumen de diuresis se asocien a supervivencia. Durante el seguimiento la causa más frecuente de ingreso hospitalario fue la sobrecarga hídrica. La mayoría de los pacientes fallecieron por la progresión de la IRCA, en su domicilio o en una unidad de cuidados paliativos de media-larga estancia

OBJECTIVE: Primary OBJECTIVE: To determine survival and survival predictive factors in advanced chronic renal failure (ACRF) patients not considered candidates for renal replacement therapy (RRT). Secondary OBJECTIVES: To describe: a) the sociodemographic characteristics of the patients and the main caregiver; b) the aetiology and associated comorbidity of the nephropathy; c) the clinical variables of patients when they are included in the programme; d) the clinical outcome in terms of blood pressure (BP), episodes of fluid overload, treatments received, frequency of hospitalisation, causes of hospitalisation, place and cause of death; e) the evolution of analytical parameters; f) the degree of information about diagnosis and prognosis given to the patient and family, and g) care activity provided by the domiciliary palliative care support team (DPCST) during follow-up. Material and method: DESIGN: Longitudinal descriptive study of a historical cohort. Scope. DPCST of Madrid areas 1, 5 and 7. Study subjects. Patients with ACRF not considered candidates for RRT. Selection criteria.1) patients with ACRF considered and rejected for extra-renal depuration, and 2) the patient and/or caregiver and/or family had accepted follow-up by the DPCST and/or his or her Primary Care physician. Sample size. All clinical histories from the archives of the DPCSTs were selected, from 1997 up to December 2009. Variables analysed.1) Main answer: time of survival; 2) secondary variables: 2.1) sociodemographic characteristics of patient and caregiver: age and gender; main caregiver: marital status, kinship; 2.2) variables related to the renal disease: the aetiology of the nephropathy, reason for exclusion from RRT, comorbidity; 2.3) CLINICAL VARIABLES: degree of BP control during evolution of disease; measurements from several visits were collected; at initiation of programme, the presence or absence of the following was recorded: oedema, pain, constipation, pruritus, dyspnoea, insomnia, anxiety, sadness and cognitive deterioration; number of episodes of fluid overload; cause for exiting the programme; place of death; cause of death and symptoms observed in last days situation; 2.4) therapeutic variables: number of medications at beginning of programme, number of medications at time of exiting the programme, when cause of exit was death; type of medications; number of transfusions received; 2.5) variables of hospital admission: number of admissions; causes of admission; 2.6) analytical variables: degree of control of analytical parameters during illness until death; 2.7) variables on the degree of information about diagnosis and prognosis; 2.8) variables of care activity: number of domiciliary visits to the patient. RESULTS: N: 102 PATIENTS: Mean age: 76.92 (9.94) years. Aetiology ACRF: vascular 37, unknown origin 32, diabetic 15.comorbidity: low risk SCG 17; medium risk SCG 35; high risk SCG 50. Median Charlson comorbidity index: 6.88 (2.5). Cause for rejection for RRT: comorbidity 47.5%, age 25.7%, patient's decision 22.8%, others 4%. Degree of information about diagnosis to patient and caregiver: 57.9 and 94.4%, respectively. Degree of information about prognosis to patient and caregiver: 11.8 and 90%, respectively. Symptoms on first visit: dyspnoea 33.3%, pruritus 30.4%, insomnia 34.3%, sadness 36.3%, oedema 43.1%. Average medications at beginning of follow-up: 10. At the end: 11. Number of transfusions: 5. Number of hospital admissions: 50; caused by fluid overload: 35, comorbidity: 12, oliguria: 3. Cause of death: ACRF 72.9%, intercurrent illness 27.1%. Place of death: home 39, acute hospitalization ward 31, palliative care ward 13, emergency room 2. Average of visits by DPCST: 11.32, median 6.5. Average survival: 4 months, survival at one year: 25%. Predictive survival factors: creatinine on first visit HZ 1.106 (95% CI 1.01-1.20), p=.024; age 71-80 years, HZ 4.42 (95% CI 1.60-12.21), age>81 years, HZ 2.97 (95% CI 1.16-7.61). The following were not associated with survival rates: BP, volume of diuresis, levels of sodium, potassium, calcium, phosphorus and haemoglobin. CONCLUSIONS: ACRF patients rejected for RRT receiving domiciliary follow-up by palliative care teams had an average survival of 4 months; age and residual renal function were predictive factors for survival, whereas comorbidity, electrolyte levels, BP and diuresis were not. During follow-up, the most frequent cause of hospital admission was fluid overload. Most patients died because of disease progression, at home or in a palliative care medium-long term hospital ward

Sustained interleukin-1ß exposure modulates multiple steps in glucocorticoid receptor signaling, promoting split-resistance to the transactivation of prominent anti-inflammatory genes by glucocorticoids.

Clinical treatment with glucocorticoids (GC) can be complicated by cytokine-induced glucocorticoid low-responsiveness (GC-resistance, GCR), a condition associated with a homogeneous reduction in the expression of GC-receptor- (GR-) driven anti-inflammatory genes. However, GR level and phosphorylation changes modify the expression of individual GR-responsive genes differently. As sustained IL-1ß exposure is key in the pathogenesis of several major diseases with prevalent GCR, we examined GR signaling and the mRNA expression of six GR-driven genes in cells cultured in IL-1ß and afterwards challenged with GC. After a GC challenge, sustained IL-1ß exposure reduced the cytoplasmic GR level, GR(Ser203) and GR(Ser211) phosphorylation, and GR nuclear translocation and led to selective GCR in the expression of the studied genes. Compared to GC alone, in a broad range of GC doses plus sustained IL-1ß, FKBP51 mRNA expression was reduced by 1/3, TTP by 2/3, and IRF8 was completely knocked down. In contrast, high GC doses did not change the expression of GILZ and DUSP1, while IGFBP1 was increased by 5-fold. These effects were cytokine-selective, IL-1ß dose- and IL-1R1-dependent. The integrated gain and loss of gene functions in the "split GCR" model may provide target cells with a survival advantage by conferring resistance to apoptosis, chemotherapy, and GC.

Ordering human CD34+CD10-CD19+ pre/pro-B-cell and CD19- common lymphoid progenitor stages in two pro-B-cell development pathways.

Studies here respond to two long-standing questions: Are human "pre/pro-B" CD34(+)CD10(-)CD19(+) and "common lymphoid progenitor (CLP)/early-B" CD34(+)CD10(+)CD19(-) alternate precursors to "pro-B" CD34(+)CD19(+)CD10(+) cells, and do the pro-B cells that arise from these progenitors belong to the same or distinct B-cell development pathways? Using flow cytometry, gene expression profiling, and Ig V(H)-D-J(H) sequencing, we monitor the initial 10 generations of development of sorted cord blood CD34(high)Lineage(-) pluripotential progenitors growing in bone marrow S17 stroma cocultures. We show that (i) multipotent progenitors (CD34(+)CD45RA(+)CD10(-)CD19(-)) directly generate an initial wave of Pax5(+)TdT(-) "unilineage" pre/pro-B cells and a later wave of "multilineage" CLP/early-B cells and (ii) the cells generated in these successive stages act as precursors for distinct pro-B cells through two independent layered pathways. Studies by others have tracked the origin of B-lineage leukemias in elderly mice to the mouse B-1a pre/pro-B lineage, which lacks the TdT activity that diversifies the V(H)-D-J(H) Ig heavy chain joints found in the early-B or B-2 lineage. Here, we show a similar divergence in human B-cell development pathways between the Pax5(+)TdT(-) pre/pro-B differentiation pathway that gives rise to infant B-lineage leukemias and the early-B pathway.

Mechanisms of relaxation induced by flavonoid ayanin in isolated aorta rings from Wistar rats

Introduction: This study shows the relaxant effect induced by ayanin in aorta rings from Wistar rats linked to nitric oxide/cyclic-GMP pathway. This flavonoid is the prevalent compound obtained from Croton schiedeanus Schlecht (Euphorbiaceae), specie used in Colombian folk medicine for the treatment of arterial hypertension. Objectives: To identify possible action mechanisms of vascular relaxation induced by ayanin (quercetin 3,4',7-trimethyl ether).Methodology: Isolated aorta rings from Wistar rats obtained at the Animal House of the University of Salamanca were contracted with KCl (80 mM) or phenylephrine (PE, 10-6 M) and exposed to ayanin (10-6-10-4 M). Then, the effect of ayanin was assessed in deendothelized rings contracted with PE and in intact rings contracted with PE previously incubated with: ODQ (10-6 M), L-NAME (10-4 M), L-NAME plus D- and L-arginine (10-4 M), indomethacin (5x10-6 M), dipyridamole (3x10-7 M), glibenclamide (10-6 M), propranolol (10-6 M), verapamil (10-7 M) or atropine (3x10-5 M). In addition, the relaxant effect of acetylcholine (Ach, 10-8-3x10-4 M), and sodium nitroprusside (SNP, 10-9-3x10-5 M) was assessed in the presence and absence of ayanin (10-6 M).Results: Ayanin induced a greater concentration-dependent relaxation in vessels contracted with phenylephrine (pEC50: 5.84±0.05), an effect significantly reduced by deendothelization and by both ODQ and L-NAME. L-arginine was able to reverse the effect of L-NAME. Indomethacin weakly inhibited ayanin response. Dipyridamole, glibenclamide, propranolol, verapamil, and atropine did not affect ayanin relaxation. Ayanin did not have any effect on the relaxation elicited by acetylcholine (ACh), while weakly decreasing the relaxation induced by sodium nitroprusside (SNP).Conclusion: Ayanin induces endothelium-dependent relaxation in the rat aorta mainly related to nitric oxide/cGMP pathway, according to the response observed in the presence of L-NAME, L-arginine and ODQ.

Introdución: Este estudio muestra el efecto vasodilatador inducido por ayanina en anillos de aorta de ratas Wistar vinculado con la vía óxido nítrico/GMP-cíclico. Este flavonoide es el compuesto mayoritario aislado de Croton schiedeanus Schlecht (Euphorbiaceae), especie utilizada en la medicina popular colombiana para el tratamiento de la hipertensión arterial. Objetivos: Identificar los posibles mecanismos vasodilatadores inducidos por la ayanina (quercetin 3,4',7-trimetileter). Metodología: Se adicionó ayanina (10-6 - 10-4 M) a anillos aislados de aorta procedentes de ratas Wistar contraídos con KCl (80 mM) o fenilefrina (10-6 M). Luego se evaluó el efecto de la ayanina en anillos sin endotelio contraídos con fenilefrina y en anillos íntegros, contraídos con fenilefrina, previamente incubados con: ODQ (10-6 M), L-NAME (10-4 M), L-NAME más L- o D-arginina (10-4 M), indometacina (5x10-6 M), dipiridamol (3x10-7 M), glibenclamida (10-6 M), propranolol (10-6 M), verapamilo (10-7 M) o atropina (3x10-5 M). Además se examinó la relajación inducida por acetilcolina (Ach, 10-8-3x10-4 M) y nitroprusiato de sodio (SNP, 10-9-3x10-5 M) en presencia y ausencia de ayanina (10-6 M). Resultados: La ayanina produjo una mayor relajación en los anillos contraídos con fenilefrina (pEC50: 5.84±0.05), efecto que se redujo en anillos sin endotelio o en anillos íntegros preincubados con ODQ y L-NAME. L-arginina fue capaz de revertir la respuesta inducida por L-NAME. La indometacina inhibió discretamente la relajación generada por la ayanina. El dipyridamol, la glibenclamida, el propranolol, el verapamilo y la atropina no modificaron el efecto de la ayanina. La ayanina no afectó la relajación inducida por la acetilcolina y débilmente disminuyó la inducida por el nitroprusiato de sodio...

Mesenteric Th1 polarization and monocyte TNF-alpha production: first steps to systemic inflammation in rats with cirrhosis.

A systemic inflammatory state with increased circulating tumor necrosis factor alpha (TNF-alpha) has been related to the bacterial infection susceptibility and hemodynamic derangement of patients with cirrhosis. We compared the activation status of immune cell subpopulations defined by 4-color cytometry in mesenteric and peripheral lymph nodes and blood of rats with CCl(4)-cirrhosis to define the immune response initiation site, the T-cell and monocyte contribution to pro-inflammatory cytokine production, as well as the pathogenic role of enteric bacteria in the cirrhosis immune response. Th1 cells and monocytes were expanded in the mesenteric nodes (P < .001) and blood (P < .001) of rats with cirrhosis, and activated to produce interferon gamma (P < .0001) and TNF-alpha (P < .0001), respectively. The greater numbers of recently activated CD134(+) Th cells in mesenteric nodes compared with blood, the correlation between their numbers in mesenteric nodes and blood (r = 0.66, P < .001), and the expansion of activated CD45RC(-) Th cells, which are unable to re-enter lymph nodes, in mesenteric nodes but not in blood or axillary nodes points to mesenteric nodes as the origin site of activated Th cells. Abrogation of bacterial translocation by bowel decontamination reduced the number of activated Th cells and monocytes, and normalized interferon gamma production by Th cells and TNF-alpha production by monocytes in mesenteric nodes and blood, respectively. In conclusion, in cirrhosis, enteric bacteria start off an orchestrated immune response cascade in mesenteric nodes involving Th1 polarization and monocyte activation to TNF-alpha production. Later, the recirculation of these activated effector immune cells into blood promotes systemic inflammation.

Tumour necrosis factor-alpha expression by activated monocytes and altered T-cell homeostasis in ascitic alcoholic cirrhosis: amelioration with norfloxacin.

BACKGROUND/AIMS: To investigate the distribution and activation state of circulating monocytes and T-cell subsets, their contribution to tumour necrosis factor-alpha (TNFalpha) production, and their potential relationship with bacterial products of enteric origin in alcoholic cirrhosis. METHODS: Peripheral blood monocytes and T-lymphocytes from 60 cirrhotic patients and 24 controls were characterized by four-color flow-cytometry after labelling of differentiation antigens and cytokines, before and after a 4-week course of norfloxacin or placebo. RESULTS: Monocytes from ascitic patients showed increased number, enhanced CD80 and HLA-DR surface levels, and spontaneous intracytoplasmic TNFalpha expression, when compared to non-ascitic patients and controls. Blood TNFalpha levels directly correlated with the amount of TNFalpha expressed by monocytes. In ascitic patients, there was a collapse of virgin CD4(+) and CD8(+) T-cell subsets; and, an expansion of activated CD4(+) T-cells. The above abnormalities were mainly restricted to ascitic patients with high serum levels of lypolysaccharide-binding-protein. Norfloxacin normalized the number of monocytes, reduced their activated phenotype and ability to produce TNFalpha and improved the abnormal T-cell homeostasis. CONCLUSIONS: In ascitic cirrhosis with high lipolysaccharide-binding-protein, monocytes are spontaneously activated to produce TNFalpha and are major contributors to the elevated serum TNFalpha. The T-cell compartment is profoundly depleted. Enteric bacterial products play a relevant role in these immune cellular abnormalities.