Feasibility of a screening algorithm for chronic thromboembolic pulmonary hypertension: The OSIRIS study.

INTRODUCTION: Chronic thromboembolic pulmonary hypertension (CTEPH) is a long-term sequel to pulmonary embolism (PE) whose incidence varies according to different published studies. We have carried out this study to determine its incidence within 2 years after index pulmonary embolism and to study limitations to an early diagnosis. MATERIAL AND METHODS: OSIRIS is a multicentre, longitudinal cohort study. Patients were followed for 3, 6, 12, and 24 months after pulmonary embolism using a structured three-step algorithm. A physician-centered questionnaire at least one positive response in a screening proceeded to the second step, transthoracic echocardiography. The third step consisted of ventilation/perfusion lung scintigraphy and right heart catheterisation. A transthoracic echocardiography was performed in patients without positive response in the screening questionnaire after 2 years. CTEPH diagnosis required haemodynamic confirmation by right heart catheterisation and mismatched perfusion defects on lung scintigraphy. RESULTS: A total of 1191 patients were enrolled in 18 Spanish hospitals. Cumulative CTEPH incidence after 2-years PE was: 2.49 % (95 % CI: 1.68-3.56) and the incidence rate of CTEPH was 1.1 cases per 1000 person-months (95 % CI: 0.725; 1.60). The CTEPH algorithm presented a lack of adherence of 29 %; patient and physician preferences posed barriers to the triage algorithm The screening questionnaire, in patients who completed the follow-up, shows a specificity of 91.3 % (89.0-93.2 %) and negative predictive value of 99.4 % (98.4-99.8 %).. CONCLUSIONS: OSIRIS provides practiced clinical based data on the chronic thromboembolic pulmonary hypertension incidence and identified barriers to the implementation of a 3-step triage algorithm for its detection. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT03134898.

Stress-induced protein disaggregation in the endoplasmic reticulum catalysed by BiP.

Protein synthesis is supported by cellular machineries that ensure polypeptides fold to their native conformation, whilst eliminating misfolded, aggregation prone species. Protein aggregation underlies pathologies including neurodegeneration. Aggregates' formation is antagonised by molecular chaperones, with cytoplasmic machinery resolving insoluble protein aggregates. However, it is unknown whether an analogous disaggregation system exists in the Endoplasmic Reticulum (ER) where ~30% of the proteome is synthesised. Here we show that the ER of a variety of mammalian cell types, including neurons, is endowed with the capability to resolve protein aggregates under stress. Utilising a purpose-developed protein aggregation probing system with a sub-organellar resolution, we observe steady-state aggregate accumulation in the ER. Pharmacological induction of ER stress does not augment aggregates, but rather stimulate their clearance within hours. We show that this dissagregation activity is catalysed by the stress-responsive ER molecular chaperone - BiP. This work reveals a hitherto unknow, non-redundant strand of the proteostasis-restorative ER stress response.

Hipocalcemia grave y deterioro cognitivo en paciente con hipoparatiroidismo y esclerosis sistémica. A propósito de un caso / Cognitive impairment and severe hypocalcemia in a patient with hypoparathyroidism and systemic sclerosis. Report of a case

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Home blood pressure in poorly controlled hypertension: relationship with ambulatory blood pressure and organ damage.

OBJECTIVES: (1) To assess whether home blood pressure measurement is a reliable alternative to ambulatory blood pressure monitoring for the evaluation of treated patients with inadequate blood pressure control at the clinic; and (2) to evaluate the relationship between home blood pressure and several target-organ damage markers. BASIC METHODS: A cross-sectional study was performed in 225 treated hypertensive patients with persistently high blood pressure values at the clinic (systolic blood pressure 140 mmHg and/or diastolic blood pressure 90 mmHg). All study participants underwent clinic blood pressure measurement, 24-h ambulatory blood pressure and home blood pressure monitoring. A subgroup of patients underwent the following procedures: carotid echography (n=74), microalbuminuria determination (n=88) and echocardiography (n=43). We defined out-of-clinic normotension as an average ambulatory or home blood pressure less than 135 mmHg (systolic) and 85 mmHg (diastolic). MAIN RESULTS: The sensitivity, specificity and positive and negative predictive values of the home blood pressure method for predicting out-of-clinic normotension (with the ambulatory method used as reference), expressed as percentages, were 50, 87, 64 and 79%, respectively. Systolic home blood pressure correlated significantly with left ventricular mass (r=0.33, P<0.05) and microalbuminuria (r=0.24, P<0.05). Similar correlation coefficients were found for systolic ambulatory blood pressure (r=0.32, P<0.05 and r=0.24, P<0.05, respectively). Clinic blood pressure did not correlate with either left ventricular mass or microalbuminuria (r=0.19, P=0.09 and r=0.19, P=0.24, respectively). Diastolic home blood pressure, but not ambulatory blood pressure, correlated negatively with mean carotid intima-media thickness (r=-0.27, P<0.05). CONCLUSION: Our results suggest that, in patients with poorly controlled hypertension at the clinic, home blood pressure represents a complementary test rather than an alternative to ambulatory blood pressure, and correlates with several target-organ damage markers.

The pathophysiology of hyperuricemia in essential hypertension: a pilot study.

We have examined whether hyperuricemia in essential hypertension may be related to an increased insulin secretion thereby enhancing the tubular reabsorption of sodium and thus uric acid. Insulin hypersecretion, as elicited by the oral glucose tolerance test (OGTT), increased a mean of 5-fold in 12 essential hypertensive patients. Urinary uric acid to creatinine ratio significantly diminished by a mean of 62% after the OGTT. Simultaneously, urinary sodium to creatinine ratio decreased by a mean of 54%. These results suggest that insulin may mediate uric acid underexcretion due to its tubular sodium retaining effect in essential hypertensive patients.

Prevalence of left ventricular hypertrophy in patients with mild hypertension in primary care: impact of echocardiography on cardiovascular risk stratification.

BACKGROUND: Left ventricular hypertrophy (LVH) is an important predictor of cardiovascular risk, and its detection contributes to risk stratification. The aims of the present study were to estimate the prevalence of echocardiographic LVH and to evaluate the influence of echocardiography (ECHO) on cardiovascular risk stratification in hypertensive patients presenting in primary care. METHODS: In this cross-sectional study, 250 patients recently diagnosed with mild hypertension underwent clinical evaluation including electrocardiography (ECG), microalbuminuria measurement, 24-h blood pressure monitoring and ECHO. Level of cardiovascular risk was stratified, initially using routine procedures including ECG to assess target organ damage and then again after detection of LVH by ECHO. RESULTS: The frequency of echocardiographic LVH was 32%, substantially higher than that detected by ECG (9%). Initial cardiovascular risk stratification yielded the following results: 30% low risk, 49% medium risk, 16% high risk, and 5% very high risk subjects. The detection of LVH by ECHO provoked a significant change in the risk strata distribution, particularly in those patients initially classified as being at medium risk. In this group, 40% of subjects were reclassified as high risk subjects according to ECHO information. The new classification was as follows: 23% low risk, 30% medium risk, 42% high risk, and 5% very high risk subjects. CONCLUSIONS: A substantial proportion of mildly hypertensive patients presenting in primary care have LVH determined by ECHO. Our results suggest that this procedure could significantly improve cardiovascular risk stratification in those patients with multiple risk factors, but no evidence of target organ damage by routine investigations.

Hipersensibilidad al alopurinol: tratamiento desensibilizante / Hypersensitivity to alopurinol: desensitizing treatment

Introducción: La incidencia de episodios adversos relacionados con la administración de alopurinol es menor del 5 por ciento. Entre un 1 y un 2 por ciento de los enfermos tratados con alopurinol presenta un síndrome de hipersensibilidad que comporta una mortalidad próxima al 25 por ciento. Hemos recogido nuestra experiencia con la desensibilización oral al alopurinol en pacientes con intolerancia a este fármaco y que lo precisaban para normalizar la uricemia. Pacientes y métodos: Seis pacientes con gota primaria e insuficiencia renal moderada tuvieron que suspender la administración de alopurinol por erupción cutánea con características alérgicas. Los 6 pacientes aceptaron un programa de desensibilización oral con una dosis creciente de alopurinol (primer día, 50 µg; día 91, 300 mg). Resultados: Los 6 pacientes toleraron la administración de alopurinol oral tras el régimen de desensibilización, llegando a alcanzar una dosis de 300 mg/día. La uricemia se normalizó en todos y no presentaron nuevos episodios de artritis gotosa aguda. Tres enfermos, al recibir una dosis de 100-200 mg/día, experimentaron una nueva reacción cutánea que obligó a suspender el tratamiento. Tras iniciar una pauta de desensibilización más lenta los 3 enfermos toleraron dosis habituales de alopurinol (300 mg/día). Conclusiones: La desensibilización oral al alopurinol es un procedimiento eficaz y sencillo, indicado en pacientes con reacciones alérgicas a este fármaco y que requieren invariablemente su administración. (AU)

Neumonía cavitada en un paciente infectado por el virus de la inmunodeficiencia humana / Cavitated pneumonia in a patient with human immunodeficiency virus infection

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