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The aging population poses challenges such as loneliness, decreased mobility, and medical conditions. To tackle these issues, a proposed robot platform offers personalized well-being behavior change suggestions. Developed through a user-centered process involving surveys and focus groups, and tested with a first prototype, the system is ideal for individuals with "special social needs". Technical results indicate that emotion recognition is valuable, with attention and valence being key metrics, but user acceptance and quality of facial/speech analysis for elderly users remain challenges.

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Envejecimiento Saludable , Robótica , Humanos , Anciano , Emociones , Envejecimiento , Grupos Focales

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Complementary to the quickly advancing understanding of the swimming of microorganisms, we demonstrate rather simple design principles for systems that can mimic swimming by body shape deformation. For this purpose, we developed a microswimmer that could be actuated and controlled by fast temperature changes through pulsed infrared light irradiation. The construction of the microswimmer has the following features: (i) it is a bilayer ribbon with a length of 80 or 120 [Formula: see text]m, consisting of a thermo-responsive hydrogel of poly-N-isopropylamide coated with a 2-nm layer of gold and equipped with homogeneously dispersed gold nanorods; (ii) the width of the ribbon is linearly tapered with a wider end of 5 [Formula: see text]m and a tip of 0.5 [Formula: see text]m; (iii) a thickness of only 1 and 2 [Formula: see text]m that ensures a maximum variation of the cross section of the ribbon along its length from square to rectangular. These wedge-shaped ribbons form conical helices when the hydrogel is swollen in cold water and extend to a filament-like object when the temperature is raised above the volume phase transition of the hydrogel at [Formula: see text]. The two ends of these ribbons undergo different but coupled modes of motion upon fast temperature cycling through plasmonic heating of the gel-objects from inside. Proper choice of the IR-light pulse sequence caused the ribbons to move at a rate of 6 body length/s (500 [Formula: see text]m/s) with the wider end ahead. Within the confinement of rectangular container of 30 [Formula: see text]m height and 300 [Formula: see text]m width, the different modes can be actuated in a way that the movement is directed by the energy input between spinning on the spot and fast forward locomotion.

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INTRODUCTION: Trauma leadership skills are increasingly being addressed in trauma courses, but few resources are available to systematically observe and debrief trainees' performances. The authors therefore translated their previously developed, extensive Taxonomy of Trauma Leadership Skills (TTLS) into a practical observation tool that is tailored to the vocabulary of clinician instructors and their workflow and workload during simulation-based training. METHODS: In 2016 to 2018, the TTLS was subjected to practical evaluation in an iterative process of 2 stages. In the first stage, testing panels of trauma specialists observed excerpts from videotaped simulations and indicated from the list of elements which behaviors they felt were being shown. Any ambiguities or redundancy were addressed by rephrasing or combining elements. In the second stage, iterations were used in actual scenario training to observe and debrief trainees' performances. The instructors' recommendations resulted in further improvements of clarity, ease of use, and usefulness, until no new suggestions were raised. RESULTS: The resultant "TTLS-Shortened for Observation and Reflection in Training" was given a simpler structure and more concrete and self-explanatory benchmarks. It contains 6 skill categories for evaluation, each with 4 to 6 benchmark behaviors. CONCLUSIONS: The TTLS-Shortened for Observation and Reflection in Training is an important addition to other trauma assessment tools because of its specific focus on leadership skills. It helps set concrete performance expectations, simplify note taking, and target observations and debriefings. One central challenge was striking a balance between its conciseness and specificity. The authors reflected on how the decisions for the resultant structure ease and leverage the conduct of observations and performance debriefing.

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Liderazgo , Entrenamiento Simulado , Competencia Clínica , Grupo de Atención al Paciente

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The number of people with diabetes is increasing in every European country and as with all chronic diseases, coping with diabetes is a long-term process. Self-Management and supporting behaviour change are aspects when dealing with diabetes. The POWER2DM (Funded by the EU Horizon 2020 research and innovation programme under grant agreement No 689444) system combines treatment planning and self-management activities by providing interventions to change a patient's lifestyle towards a healthier, diabetes-appropriate life. FHIR3 allows for data exchange.

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Diabetes Mellitus , Automanejo , Enfermedad Crónica , Europa (Continente) , Humanos , Estilo de Vida , Autocuidado

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PURPOSE: Acute kidney injury (AKI) is a severe complication in medical and surgical intensive care units accounting for a high morbidity and mortality. Incidence, risk factors, and prognostic impact of this deleterious condition are well established in this setting. Data concerning the neurocritically ill patients is scarce. Therefore, aim of this study was to determine the incidence of AKI and elucidate risk factors in this special population. METHODS: Patients admitted to a specialized neurocritical care unit between 2005 and 2011 with a length of stay above 48 hours were analyzed retrospectively for incidence, cause, and outcome of AKI (AKI Network-stage ≥2). RESULTS: The study population comprised 681 neurocritically ill patients from a mixed neurosurgical and neurological intensive care unit. The prevalence of chronic kidney disease (CKD) was 8.4% (57/681). Overall incidence of AKI was 11.6% with 36 (45.6%) patients developing dialysis-requiring AKI. Sepsis was the main cause of AKI in nearly 50% of patients. Acute kidney injury and renal replacement therapy are independent predictors of worse outcome (hazard ratio [HR]: 3.704; 95% confidence interval [CI]: 1.867-7.350; P < .001; and HR: 2.848; CI: 1.301-6.325; P = .009). Chronic kidney disease was the strongest independent risk factor (odds ratio: 12.473; CI: 5.944-26.172; P < .001), whereas surgical intervention or contrast agents were not associated with AKI. CONCLUSIONS: Acute kidney injury in neurocritical care has a high incidence and is a crucial risk factor for mortality independently of the underlying neurocritical condition. Sepsis is the main cause of AKI in this setting. Therefore, careful prevention of infectious complications and considering CKD in treatment decisions may lower the incidence of AKI and hereby improve outcome in neurocritical care.

Asunto(s)

Lesión Renal Aguda/mortalidad , Cuidados Críticos/estadística & datos numéricos , Insuficiencia Renal Crónica/mortalidad , Terapia de Reemplazo Renal/mortalidad , Sepsis/mortalidad , Lesión Renal Aguda/etiología , Anciano , Cuidados Críticos/métodos , Resultados de Cuidados Críticos , Enfermedad Crítica/mortalidad , Femenino , Mortalidad Hospitalaria , Humanos , Incidencia , Unidades de Cuidados Intensivos/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Insuficiencia Renal Crónica/complicaciones , Estudios Retrospectivos , Factores de Riesgo , Sepsis/complicaciones

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In this work, the concentration polarization layer (CPL) of sulphate in a cross-flow membrane system was measured in-situ using Raman microspectroscopy (RM). The focus of this work is to introduce RM as a new tool for the study of mass transfer inside membrane channels in reverse osmosis (RO) and nanofiltration (NF) generally. Specifically, this work demonstrates how to use RM for locally resolved measurement of sulphate concentration in a cross-flow flat-sheet NF membrane flow cell with channel dimensions similar to commonly applied RO/NF spiral wound modules (channel height about 0.7 mm). Concentration polarization profiles of an aqueous magnesium sulphate solution of 10 gsulphate·L-1 were obtained at operating pressure of 10 bar and cross-flow velocities of 0.04 and 0.2 m·s-1. The ability of RM to provide accurate concentration profiles is discussed thoroughly. Optical effects due to refraction present one of the main challenges of the method by substantially affecting signal intensity and depth resolution. The concentration profiles obtained in this concept study are consistent with theory and show reduced CPL thickness and membrane wall concentration with increasing cross-flow velocity. The severity of CP was quantified to reach almost double the bulk concentration at the lower velocity.

RESUMEN

The number of people with diabetes is increasing in every European country and like all chronic diseases it cannot be cured. However, patient empowerment is an acknowledged strategy for improving the patients' health situation. This paper describes the Action Plan Engine developed as a tool for diabetes patients in the POWER2DM project. The Action Plan Engine offers a guided workflow based on treatment goals and activities. A periodic review evaluates how successful a patient has fulfilled these goals and activities. Part of the evaluation is detailed feedback, in particular about 170 interventions based on Behaviour Change Techniques in order to change a patient's lifestyle behaviour towards a healthier, diabetes-appropriate lifestyle. Additionally, the Action Plan Engine offers decision trees for coping with barriers regarding glucose monitoring, exercise, carbohydrate, insulin and stress.

Asunto(s)

Terapia Conductista , Automonitorización de la Glucosa Sanguínea , Diabetes Mellitus , Glucemia , Diabetes Mellitus/terapia , Europa (Continente) , Humanos , Estilo de Vida , Poder Psicológico

RESUMEN

AIMS: Chronic kidney disease (CKD) is a common complication after liver transplantation (LT). The etiology of CKD is broad and may only be assessed accurately by renal histology. The current study aimed to analyze the safety of renal biopsy in daily clinical practice as well as its usefulness regarding management of CKD after LT. METHODS: We performed a retrospective analysis of clinical data and renal biopsies obtained from patients with severe renal impairment (overt proteinuria, progressive deterioration of renal function) after LT with respect to safety, etiology of renal disease, and therapeutic consequences. RESULTS: Renal biopsies were obtained from 14 patients at median (minimum-maximum) 3 (0.2-12) years after LT. No major complications associated with renal biopsy were observed. Histomorphological alterations were varied (nephrosclerosis, n = 5; IgA-glomerulonephritis, n = 4; tenofovir-associated nephropathy, membranoproliferative glomerulonephritis type 1, membranous glomerulonephritis, amyloid A amyloidosis, and calcineurin inhibitor nephropathy, n = 1, respectively). The diagnosis of specific renal diseases other than calcineurin-inhibitor nephrotoxicity facilitated specific treaments and avoided unnecessary modification of immunosuppression in the majority of patients. CONCLUSIONS: Renal biopsy in patients with CKD after LT seems safe and may offer specific therapeutic options. Furthermore, unnecessary changes of immunosuppression can be avoided in a considerable number of patients.

Asunto(s)

Riñón/patología , Trasplante de Hígado/efectos adversos , Insuficiencia Renal Crónica/patología , Adulto , Anciano , Progresión de la Enfermedad , Femenino , Humanos , Inmunosupresores/efectos adversos , Riñón/fisiopatología , Masculino , Persona de Mediana Edad , Proteinuria/etiología , Proteinuria/patología , Proteinuria/fisiopatología , Insuficiencia Renal Crónica/etiología , Insuficiencia Renal Crónica/fisiopatología , Insuficiencia Renal Crónica/terapia , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento

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INTRODUCTION: Whereas medical shift handovers are increasingly recognized to fulfil important functions beyond information transfer, studies suggest that shift handovers continue to be variably used for reflection, learning or discussion. Little is known of the dynamics of incorporating such functions into ICU shift handovers, resulting in a challenge for the design of educational programs whose underlying philosophies align with the specific requirements of the ICU. METHODS: Intensivists, residents and fellows (n = 21) from three ICUs were interviewed to determine perceptions of handover functionality and the boundaries to what must or can be achieved in handover conversations. Interviews were analyzed to isolate training requirements and factors that challenge interactions. RESULTS: The analysis revealed that ICU physicians value three functions for shift handovers: information transfer, enhancing shared understanding and decision-making, and learning. The functions towards which physicians are oriented were found to be affected by situational characteristics of cases, individuals, teams, and the unit workflow. Whereas some factors are helpful cues for determining communication needs, others raise dilemmas and misaligned expectations with regards to what can be achieved in the handover. DISCUSSION: Our findings add to the growing case for the education of handovers in complex settings to involve more than information transfers. As residents gain experience, training should be gradually shifted towards more fluid and adaptable approaches to the handover and residents' ability to engage in joint reflections and discussions. Challenges for engaging in such interactions need to be alleviated, in order to allow the redefinition of handovers as potential sources of safety and learning, rather than error.

Asunto(s)

Educación Médica/métodos , Pase de Guardia , Percepción , Médicos/psicología , Centros Médicos Académicos/organización & administración , Educación Médica/normas , Docentes Médicos , Humanos , Unidades de Cuidados Intensivos/organización & administración , Planificación de Atención al Paciente , Seguridad del Paciente/normas , Médicos/normas , Investigación Cualitativa

RESUMEN

OBJECTIVE: End-stage renal disease associates with catabolism and sarcopenia. Hypothetically, peroral supplemental nutrition over 6 months prevents catabolism in hemodialysis patients. DESIGN: Prospective randomized pilot study (ClinicalTrials.gov Identifier: NCT00687050). SUBJECTS: Twenty-three hemodialysis patients (15 males and 7 females) with or without human immunodeficiency virus (HIV) infection of 2 ambulatory hemodialysis centers. INTERVENTION: HIV-positive hemodialysis patients (n = 7, Group 1) were started on supplemental nutrition drinks (250 kcal/day), HIV-negative hemodialysis patients (n = 16, Group 2) were randomized to supplemental nutrition drinks (250 kcal/day) or received none. MAIN OUTCOME MEASURES: Body impedance analysis, anthropometric measures, magnetic resonance imaging results for mid-iliopsoas muscle cross-sectional area and laboratory parameters including albumin, cytokines at baseline, and at 6 months follow-up. RESULTS: Seven patients in Group 1 (mean age: 50.6 ± 9.6 years) and 16 patients in Group 2 (mean age: 54.0 ± 13.3 years) were recruited. Serum creatinine (Group 1: 6.4 ± 3.0 mg/dL; Group 2: 10.7 ± 2.5 mg/dL; P < .01), Body impedance analysis-derived phase angle alpha (Group 1: 5.1 ± 1.2; Group 2: 6.9 ± 1.6; P < .01), mid-arm circumference (Group 1: 26.1 ± 1.3 cm; Group 2: 29.6 ± 2.4 cm; P < .01) were less in Group 1 versus Group 2 patients at baseline suggesting that HIV-positive hemodialysis patients had a poorer nutritional status at baseline. At 6-month follow-up, mortality was higher in Group 1 patients (29%) than in Group 2 patients (6%). There was no significant treatment effect on nutritional status in survivors of Group 1 or in the supplemental nutrition arm of Group 2 when compared with baseline or to untreated controls. CONCLUSIONS: A new oral supplemental nutrition over 6 months had no treatment effect in surviving HIV-positive hemodialysis patients or in maintenance hemodialysis patients without HIV infection. The limitations of this study were small study size and unexpected high mortality among HIV-positive hemodialysis patients.

Asunto(s)

Caquexia/prevención & control , Infecciones por VIH/terapia , Fallo Renal Crónico/terapia , Apoyo Nutricional , Diálisis Renal/efectos adversos , Adolescente , Adulto , Anciano , Composición Corporal , Proteína C-Reactiva/metabolismo , Caquexia/complicaciones , Impedancia Eléctrica , Femenino , Estudios de Seguimiento , Infecciones por VIH/complicaciones , Humanos , Interleucina-1beta/sangre , Interleucina-6/sangre , Fallo Renal Crónico/complicaciones , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Músculo Esquelético/metabolismo , Evaluación Nutricional , Estado Nutricional , Proyectos Piloto , Estudios Prospectivos , Sarcopenia/complicaciones , Sarcopenia/prevención & control , Albúmina Sérica/metabolismo , Factor de Necrosis Tumoral alfa/sangre , Adulto Joven

RESUMEN

Background Chronic metabolic acidosis is a frequent comorbidity in chronic kidney disease, especially in patients undergoing dialysis. Recent study data suggest that treatment of acidosis during dialysis with bicarbonate may result in increased levels of serum bicarbonate, which is associated with increased mortality. Methods We aimed to evaluate the current management of chronic metabolic acidosis in Germany: have recent study results been transferred into daily routine and are nephrologists aware of these new study data? Therefore, we did a survey with 17 questions among 2096 German nephrologists. 280 valid responses were returned and analysed with descriptive statistics. Results Blood gas analysis was done weekly (27 % of respondents), monthly (20 %), every 3 months (19 %), less frequently (5 %) or not routinely (3 %). It was done by most respondents prior to the dialysis session (83 %) and by some (20 %) also afterwards or during the session (3 %). 20 % did blood gas analysis "as required".Oral bicarbonate was discontinued at start of dialysis by 66 % of nephrologists; 22 % of these do generally not use it and 44 % usually discontinue it but might continue if required. 34 % of responding nephrologists continue oral bicarbonate when starting dialysis but might adjust dose. Discussion Recent study data might have to be better promoted among nephrologists. Although KDIGO guidelines recommend at least monthly blood gas analysis, about one quarter of nephrologists stated to do it less frequently. Furthermore, blood gas analysis was rarely done after dialysis treatment and thus, important information about success or failure of bicarbonate correction was not obtained. If alkalotic episodes after dialysis treatment would be detected this way, regular oral bicarbonate might be an option for correction of metabolic acidosis.

Asunto(s)

Acidosis/mortalidad , Acidosis/prevención & control , Adhesión a Directriz/estadística & datos numéricos , Pautas de la Práctica en Medicina/estadística & datos numéricos , Pautas de la Práctica en Medicina/normas , Diálisis Renal/normas , Enfermedad Crónica , Medicina Basada en la Evidencia , Alemania/epidemiología , Adhesión a Directriz/normas , Humanos , Guías de Práctica Clínica como Asunto , Prevalencia , Diálisis Renal/mortalidad , Factores de Riesgo , Bicarbonato de Sodio/administración & dosificación , Tasa de Supervivencia , Resultado del Tratamiento

RESUMEN

PURPOSE: Good leadership is essential for optimal trauma team performance, and targeted training of leadership skills is necessary to achieve such leadership proficiency. To address the need for a taxonomy of leadership skills that specifies the skill components to be learned and the behaviors by which they can be assessed across the five phases of trauma care, the authors developed the Taxonomy of Trauma Leadership Skills (TTLS). METHOD: Critical incident interviews were conducted with trauma team leaders and members from different specialties-emergency physicians, trauma surgeons, anesthesiologists, and emergency ward nurses-at three teaching hospitals in the Netherlands during January-June 2013. Data were iteratively analyzed for examples of excellent leadership skills at each phase of trauma care. Using the grounded theory approach, elements of excellent leadership skills were identified and classified. Elements and behavioral markers were sorted and categorized using multiple raters. In a two-round verification process in late 2013, the taxonomy was reviewed and rated by trauma team leaders and members from the multiple specialties for its coverage of essential items. RESULTS: Data were gathered from 28 interviews and 14 raters. The TTLS details 5 skill categories (information coordination, decision making, action coordination, communication management, and coaching and team development) and 37 skill elements. The skill elements are captured by 67 behavioral markers. The three-level taxonomy is presented according to five phases of trauma care. CONCLUSIONS: The TTLS provides a framework for teaching, learning, and assessing team leadership skills in trauma care and other complex, acute care situations.

Asunto(s)

Competencia Clínica , Educación Médica Continua/normas , Evaluación Educacional/estadística & datos numéricos , Liderazgo , Grupo de Atención al Paciente/organización & administración , Médicos/normas , Centros Traumatológicos , Humanos , Relaciones Interprofesionales , Países Bajos

RESUMEN

The immune response after influenza vaccination is impaired in HIV-infected individuals and can be enhanced by a second dose. The durability of the antibody protection and its clinical benefit is not known. We investigated clinical symptoms and antibody titres against H1N1 influenza A following no dose, 1 dose, or 2 doses of an ASO3-adjuvanted H1N1 vaccine in HIV-infected patients. Seroprotection was found in 7.9%, 52.2%, and 57.3% of patients who received no dose, 1 dose, and 2 doses of the vaccine, respectively (p-value for group comparison < 0.001), after a median of 8.2 ± 1.6 months. Clinical symptoms suggestive of an influenza-like illness were slightly more frequently reported in the unvaccinated group. Vaccinated HIV-infected patients were more likely to be seroprotected at follow-up, but there was no difference comparing those who had received 1 or 2 doses of the vaccine.

Asunto(s)

Anticuerpos Antivirales/sangre , Infecciones por VIH/complicaciones , Subtipo H1N1 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/administración & dosificación , Vacunas contra la Influenza/inmunología , Gripe Humana/prevención & control , Vacunación/métodos , Adyuvantes Inmunológicos/administración & dosificación , Adulto , Anciano , Combinación de Medicamentos , Femenino , Infecciones por VIH/virología , VIH-1/aislamiento & purificación , Humanos , Esquemas de Inmunización , Gripe Humana/virología , Masculino , Persona de Mediana Edad , Polisorbatos/administración & dosificación , Escualeno/administración & dosificación , alfa-Tocoferol/administración & dosificación

RESUMEN

The pathogenesis and therapy of Shigatoxin 2 (Stx2)-mediated kidney failure remain controversial. Our aim was to test whether, during an infection with Stx2-producing E. coli (STEC), Stx2 exerts direct effects on renal tubular epithelium and thereby possibly contributes to acute renal failure. Mice represent a suitable model because they, like humans, express the Stx2-receptor Gb3 in the tubular epithelium but, in contrast to humans, not in glomerular endothelia, and are thus free of glomerular thrombotic microangiopathy (TMA). In wild-type mice, Stx2 caused acute tubular dysfunction with consequent electrolyte disturbance, which was most likely the cause of death. Tubule-specific depletion of Gb3 protected the mice from acute renal failure. In vitro, Stx2 induced secretion of proinflammatory cytokines and apoptosis in human tubular epithelial cells, thus implicating a direct effect of Stx2 on the tubular epithelium. To correlate these results to human disease, kidney biopsies and outcome were analysed in patients with Stx2-associated kidney failure (n = 11, aged 22-44 years). The majority of kidney biopsies showed different stages of an ongoing TMA; however, no glomerular complement activation could be demonstrated. All biopsies, including those without TMA, showed severe acute tubular damage. Due to these findings, patients were treated with supportive therapy without complement-inhibiting antibodies (eculizumab) or immunoadsorption. Despite the severity of the initial disease [creatinine 6.34 (1.31-17.60) mg/dl, lactate dehydrogenase 1944 (753-2792) U/l, platelets 33 (19-124)/nl and haemoglobin 6.2 (5.2-7.8) g/dl; median (range)], all patients were discharged after 33 (range 19-43) days with no neurological symptoms and no dialysis requirement [creatinine 1.39 (range 0.84-2.86) mg/dl]. The creatinine decreased further to 0.90 (range 0.66-1.27) mg/dl after 24 months. Based on these data, one may surmise that acute tubular damage represents a separate pathophysiological mechanism, importantly contributing to Stx2-mediated acute kidney failure. Specifically in young adults, an excellent outcome can be achieved by supportive therapy only.

Asunto(s)

Lesión Renal Aguda/patología , Infecciones por Escherichia coli/patología , Toxina Shiga II/metabolismo , Escherichia coli Shiga-Toxigénica/patogenicidad , Lesión Renal Aguda/microbiología , Lesión Renal Aguda/terapia , Adulto , Animales , Biopsia , Línea Celular , Estudios de Cohortes , Creatinina/metabolismo , Modelos Animales de Enfermedad , Epitelio/microbiología , Epitelio/patología , Infecciones por Escherichia coli/microbiología , Infecciones por Escherichia coli/terapia , Femenino , Globósidos/metabolismo , Humanos , Túbulos Renales/microbiología , Túbulos Renales/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Toxina Shiga II/genética , Microangiopatías Trombóticas , Resultado del Tratamiento , Adulto Joven

RESUMEN

BACKGROUND: Dysregulation of the autonomic nervous system is frequent in subjects with cardiovascular disease. The contribution of different forms of renovascular hypertension and the mechanisms contributing to autonomic dysfunction in hypertension are incompletely understood. Here, murine models of renovascular hypertension with preserved (2-kidneys-1 clip, 2K1C) and reduced (1-kidney-1 clip, 1K1C) kidney mass were studied with regard to autonomic nervous system regulation (sympathetic tone: power-spectral analysis of systolic blood pressure; parasympathetic tone: power-spectral analysis of heart rate) and baroreflex sensitivity of heart rate by spontaneous, concomitant changes of systolic blood pressure and pulse interval. Involvement of the renin-angiotensin system and the rho-kinase pathway were determined by application of inhibitors. RESULTS: C57BL6N mice (6 to 11) with reduced kidney mass (1K1C) or with preserved kidney mass (2K1C) developed a similar degree of hypertension. In comparison to control mice, both models presented with a significantly increased sympathetic tone and lower baroreflex sensitivity of heart rate. However, only 2K1C animals had a lower parasympathetic tone, whereas urinary norepinephrine excretion was reduced in the 1K1C model. Rho kinase inhibition given to a subset of 1K1C and 2K1C animals improved baroreflex sensitivity of heart rate selectively in the 1K1C model. Rho kinase inhibition had no additional effects on autonomic nervous system in either model of renovascular hypertension and did not change the blood pressure. Blockade of AT1 receptors (in 2K1C animals) normalized the sympathetic tone, decreased resting heart rate, improved baroreflex sensitivity of heart rate and parasympathetic tone. CONCLUSIONS: Regardless of residual renal mass, blood pressure and sympathetic tone are increased, whereas baroreflex sensitivity is depressed in murine models of renovascular hypertension. Reduced norepinephrine excretion and/or degradation might contribute to sympathoactivation in renovascular hypertension with reduced renal mass (1K1C). Overall, the study helps to direct research to optimize medical therapy of hypertension.

Asunto(s)

Barorreflejo/fisiología , Hipertensión Renovascular/fisiopatología , Sistema Nervioso Simpático/fisiopatología , Quinasas Asociadas a rho/antagonistas & inhibidores , Animales , Presión Sanguínea/fisiología , Modelos Animales de Enfermedad , Frecuencia Cardíaca/fisiología , Hipertensión Renovascular/enzimología , Hipertensión Renovascular/orina , Isoquinolinas/farmacología , Riñón/cirugía , Ratones , Ratones Endogámicos C57BL , Sistema Nervioso Parasimpático/fisiopatología , Piperidinas/farmacología

RESUMEN

BACKGROUND: Illicit drug abuse is an independent risk factor for chronic kidney disease, but the pathogenic consequences of long-term exposure to illicit drugs and contaminants under unsterile conditions remains unclear. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: All deceased persons (n 5 129) who underwent forensic autopsy because of suspected connection with illicit drug abuse between January 1, 2009, and April 30, 2011, in Frankfurt/Main, Germany. PREDICTOR: Clinical characteristics and patterns of drug abuse. OUTCOMES: Histopathologic alterations of the kidney. MEASUREMENTS: Hematoxylin and eosin, periodic acid-Schiff, Sirius, and Congo Red stainings and immunoglobulin A immunohistochemistry of all cases; additional histochemical stainings or immunohistochemistry and electron microscopy in selected cases. RESULTS: Individuals were mostly white (99.2%), were male (82.2%), and had intravenous drug use (IVDU) (81.4%). Median age at death was 39 years and duration of drug abuse was 17 years. The majority (79.1%) took various drugs in parallel as assessed by toxicologic analysis. Despite a young age, the deceased had a high burden of comorbid conditions, especially cardiovascular disease, liver cirrhosis, and infections. Evaluation of the kidneys demonstrated a broad spectrum of pathologic alterations predominated by arteriosclerotic and ischemic damage, mild interstitial inflammation, calcification of renal parenchyma, and interstitial fibrosis and tubular atrophy, with hypertensive-ischemic nephropathy as the most common cause of nephropathy. Interstitial inflammation (OR, 16.59; 95% CI, 3.91-70.39) and renal calcification (OR, 2.43; 95% CI, 1.03- 5.75) were associated with severe IVDU, whereas hypertensive and ischemic damage were associated with cocaine abuse (OR, 6.00; 95% CI, 1.27-28.44). Neither specific glomerular damage indicative for heroin and hepatitis C virus-related disease nor signs of analgesic nephropathy were found. LIMITATIONS: White population, lack of a comparable control group, incomplete clinical data, and absence of routine immunohistochemistry and electron microscopy. CONCLUSIONS: Illicit drug abuse is associated with a broad but unspecific spectrum of pathologic alterations of the kidneys. Cocaine abuse has a deleterious role in this setting by promoting hypertensive and ischemic damage.

Asunto(s)

Insuficiencia Renal Crónica/epidemiología , Abuso de Sustancias por Vía Intravenosa/epidemiología , Adulto , Trastornos Relacionados con Cocaína/epidemiología , Trastornos Relacionados con Cocaína/patología , Femenino , Humanos , Inmunohistoquímica , Riñón/patología , Masculino , Persona de Mediana Edad , Insuficiencia Renal Crónica/patología , Factores de Riesgo , Abuso de Sustancias por Vía Intravenosa/patología

RESUMEN

PURPOSE: In membrane-based therapeutic plasma exchange (TPE), regional citrate anticoagulation (RCA) is associated with difficulties because of citrate accumulation and consequent, potentially significant, metabolic complications, especially when using fresh frozen plasma (FFP) as replacement fluid. We modified the technical setup of a commercially available continuous veno-venous hemodialysis RCA module (multiFiltrate Ci-Ca®) to establish an RCA-protocol for TPE. METHODS: Description of the modified technical setup and retrospective analysis of the feasibility of the RCA-protocol for TPE in all patients treated between 2009 and 2010. RESULTS: 411 consecutive TPE with RCA were performed in 42 patients, all using FFP as replacement fluid. Median procedure characteristics were: blood flow 160 ml/min, filtrate flow 36 ml/min, duration 93 min, processed total plasma volume 3600 mL. Trisodium citrate was infused at a rate of 0.43 mmol/min to achieve post-filter ionized calcium levels of <0.4 mmol/l. Calcium substitution rate was 0.19 mmol/min to maintain physiologic iCa levels. RCA was well tolerated with no significant differences in pH, iCa, bicarbonate or potassium after repeated sessions. Clotting events complicated 7.3% of the procedures. Adverse events occurred in 3.4% of TPE procedures; none was severe or fatal. No significant differences were observed comparing the rate of adverse events to those observed in TPE using standard anticoagulation at our center (4.8%). CONCLUSIONS: We describe for the first time a modified protocol for RCA in TPE using an integrated citrate module. Based on our experience, this RCA protocol is a feasible alternative for anticoagulation in TPE with FFP, especially in patients with a high risk of bleeding.

Asunto(s)

Ácido Cítrico , Intercambio Plasmático , Anticoagulantes/uso terapéutico , Citratos , Ácido Cítrico/uso terapéutico , Humanos , Estudios Retrospectivos

RESUMEN

Rho-family GTPases like RhoA and Rac-1 are potent regulators of cellular signaling that control gene expression, migration and inflammation. Activation of Rho-GTPases has been linked to podocyte dysfunction, a feature of chronic kidney diseases (CKD). We investigated the effect of Rac-1 and Rho kinase (ROCK) inhibition on progressive renal failure in mice and studied the underlying mechanisms in podocytes. SV129 mice were subjected to 5/6-nephrectomy which resulted in arterial hypertension and albuminuria. Subgroups of animals were treated with the Rac-1 inhibitor EHT1846, the ROCK inhibitor SAR407899 and the ACE inhibitor Ramipril. Only Ramipril reduced hypertension. In contrast, all inhibitors markedly attenuated albumin excretion as well as glomerular and tubulo-interstitial damage. The combination of SAR407899 and Ramipril was more effective in preventing albuminuria than Ramipril alone. To study the involved mechanisms, podocytes were cultured from SV129 mice and exposed to static stretch in the Flexcell device. This activated RhoA and Rac-1 and led via TGFß to apoptosis and a switch of the cells into a more mesenchymal phenotype, as evident from loss of WT-1 and nephrin and induction of α-SMA and fibronectin expression. Rac-1 and ROCK inhibition as well as blockade of TGFß dramatically attenuated all these responses. This suggests that Rac-1 and RhoA are mediators of podocyte dysfunction in CKD. Inhibition of Rho-GTPases may be a novel approach for the treatment of CKD.

Asunto(s)

Podocitos/efectos de los fármacos , Podocitos/metabolismo , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/metabolismo , Proteína de Unión al GTP rac1/metabolismo , Proteína de Unión al GTP rhoA/metabolismo , Albuminuria/metabolismo , Albuminuria/prevención & control , Animales , Isoquinolinas/uso terapéutico , Masculino , Ratones , Piperidinas/uso terapéutico , Pironas/uso terapéutico , Quinolinas/uso terapéutico , Ramipril/uso terapéutico , Insuficiencia Renal Crónica/patología , Proteína de Unión al GTP rac1/antagonistas & inhibidores , Proteína de Unión al GTP rhoA/antagonistas & inhibidores

RESUMEN

BACKGROUND: Immune response rates following influenza vaccination are often lower in HIV-infected individuals. Low vitamin D levels were correlated with weak immune response in cancer patients and are known to be lower in HIV-infected patients. METHODS: Diagnostic study to determine immune response against the H1N1v component after a single, intramuscular dose of the 2010/11 seasonal, trivalent influenza vaccine (TIV) in adult HIV-infected and healthy controls scheduled for influenza vaccination (ClinicalTrials.gov Identifier: NCT01017172). Influenza A/H1N1 antibody titers (AB) were determined before and 21 days after vaccination by hemagglutination inhibition assay. RESULTS: Immune response was not different between HIV-infected patients (n = 36) and healthy controls (n = 42) who were previously naïve to the H1N1v component of the TIV. Comparing HIV-infected patients (n = 55) and healthy controls (n = 63) who had received 1 or 2 doses of an AS03 adjuvanted H1N1 vaccine in the previous winter season (2009/10), seroconversion rate and the geometric mean AB titer after TIV of the HIV-infected patients were more than twice as high compared to healthy controls. This difference was mainly driven by the 2-dose schedule for HIV patients in 2009/10. Vitamin D levels were lower in HIV patients but did not correlate with immune response. CONCLUSION: HIV-infected patients who had received 1 or 2 doses of an adjuvanted H1N1 vaccine in the previous year (2009/10) had a significant higher seroconversion rate following TIV as compared to healthy controls, indicating a stronger memory cell response due to the 2-dose schedule.

Asunto(s)

Síndrome de Inmunodeficiencia Adquirida/inmunología , VIH-1 , Subtipo H1N1 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/inmunología , Adulto , Anticuerpos Antivirales/sangre , Femenino , Humanos , Vacunas contra la Influenza/administración & dosificación , Masculino , Persona de Mediana Edad

RESUMEN

OBJECTIVE: Uncontrolled hypertension under antihypertensive multidrug regimen is not necessarily always true resistance. Incomplete adherence is one of several possible causes of uncontrolled hypertension. Nonadherence remains largely unrecognized and is falsely interpreted as treatment resistance, as it is difficult to confirm or exclude objectively. This is the first study assessing adherence in patients with apparent resistant hypertension systematically via toxicological urine screening. METHODS: All patients referred from primary care physicians because of uncontrolled hypertension between 2004 and 2011 were analysed. Adherence was assessed in all patients with uncontrolled hypertension despite the concurrent use of at least four antihypertensive agents by using liquid chromatography-mass spectrometry analysis for antihypertensive drugs or their corresponding metabolites in urine. RESULTS: A total of 375 patients with uncontrolled hypertension were referred. After optimization of drug therapy and exclusion of white coat hypertension, 108 patients met criteria for resistant hypertension. Of those, 15 patients had secondary causes of hypertension and 17 achieved goal blood pressure with quadruple antihypertensive therapy. Of the remaining 76 patients, 40 patients (53%) were found to be nonadherent. Among nonadherent patients, 30% had complete and 70% had incomplete adherence; 85% of the latter had taken less than 50% of drugs prescribed. Lack of adherence was almost evenly distributed between different classes of antihypertensive drugs. CONCLUSION: Low adherence was the most common cause of poor blood pressure control in patients with apparent resistant hypertension, being twice as frequent as secondary causes of hypertension. Incomplete adherence was far more common than complete nonadherence; thus, assessment of adherence in patients on multiple drug regime is only reliable when all drugs are included in assessment. Assessing adherence by toxicological urine screening is a useful tool in detecting low adherence, especially in the setting of multidrug regimen as a cause of apparently resistant hypertension.

Asunto(s)

Antihipertensivos/uso terapéutico , Hipertensión/tratamiento farmacológico , Cooperación del Paciente , Anciano , Antihipertensivos/administración & dosificación , Cromatografía Líquida de Alta Presión , Quimioterapia Combinada , Femenino , Humanos , Hipertensión/orina , Masculino , Persona de Mediana Edad , Espectrometría de Masa por Ionización de Electrospray