Prognostic Value of Ambulatory Blood Pressure Monitoring in Refractory Hypertension : A Prospective Study

The objective of this study was to establish whether ambulatory blood pressure offers a better estimate of cardiovascular risk than does its clinical blood pressure counterpart in refractory hypertension. This prospective study assessed the incidence of cardiovascular events over time during an average follow-up of 49 months (range, 6 to 96). Patients were referred to specialized hypertension clinics (86 essential hypertension patients who had diastolic blood pressure >100 mm Hg during antihypertensive treatment that included three or more antihypertensive drugs, one being a diuretic). Twenty-four-hour ambulatory blood pressure monitoring (ABPM) was performed at the time of entrance. End-organ damage was monitored yearly, and the incidence of cardiovascular events was recorded. Patients were divided into tertiles of average diastolic blood pressure during activity according to the ABPM, with the lowest tertile 97 mm Hg (HT, n=28). While significant differences in systolic and diastolic ambulatory blood pressures were observed among groups, no differences were observed at either the beginning or at the time of the last evaluation for office blood pressure. During the last evaluation, a progression in the end-organ damage score was observed for the HT group but not for the two other groups. Twenty-one of the patients had a new cardiovascular event; the incidence of events was significantly lower for the LT group (2.2 per 100 patient-years) than it was for the MT group (9.5 per 100 patient-years) or for the HT group (13.6 per 100 patient-years). The probability of event-free survival was also significantly different when comparing the LT group with the other two groups (LT versus MT log-rank, P<.04; LT versus HT log-rank, P<.006). The HT group was an independent risk factor for the incidence of cardiovascular events (relative risk, 6.20; 95% confidence interval, 1.38 to 28.1, P<.02). Higher values of ambulatory blood pressure result in a worse prognosis in patients with refractory hypertension, supporting the recommendation that ABPM is useful in stratifying the cardiovascular risk in patients with refractory hypertension.Redon Mas, Josep, [email protected]

HAART as a Strategy for Reduction of HIV-1 Transmission in Sub-Saharan Africa: Survival and Virus Load Parameters from the Drug Resource Enhancement against AIDS and Malnutrition Program

Background: The concept of universal antiretroviral use as a strategy for reduction of new cases of HIV infection has been evaluated in mathematical models as a potential approach to curtailing the Sub-Saharan African epidemic. In order to further substantiate such models, additional strategic parameters based on robust patient data should be considered, including survival of HIV-infected populations under HAART and subject infectivity as determined by HIV RNA levels. Methods: A retrospective cohort study was conducted in a population of patients enrolled in DREAMcenters throughout sub-Saharan Africa in order to determine survival under HAART. Cox regression analysis was performed evaluating parameters associated with survival such as CD4 cell count, viral load, body mass index (BMI) and hemoglobin (HB) levels. DREAM criteria for HAART initiation included (1) WHO stage 3-4 regardless of CD4 cell value (2) 100,000 copies in any subject. Virus load response to HAART was assessed in a subset of patients. Results: Adult non-pregnant patients who accessed DREAM centers from 1/2002 to 7/2009 were evaluated. A total of 34,295 patients (22,249 females/12,041 males) were included. Median age was 34 years (IQR:29-42) and median observation time 476 days (IQR:206 –950). Baseline median viral load, CD4 cell counts, HB and BMI values were 4.4 (IQR:3.6-5.0), 243 (IQR:109-416), 10.8 (IQR:9.2-12.4), and 20.3 (IQR:18.3-22.7).Over time 23,795 patients initiated HAART. Cox survival analysis (adjusted for Viral Load and HB) according to CD4 cell strata was performed. The relative risk of death in the lowest CD4 stratum (500) was 3.3 [2.7 –4.1]. Survival estimates at >7 years of HAART ranged from 50% to 95% according to baseline CD4 cell count and HB levels. In a subset of 13,405 subjects who received HAART for >6 months with at least 2 virus load measures available, 55.9% achieved < 50 copies/ml and an additional 19.7% achieved levels < 400 copies/ml (75.6% total). Final median virus load value was 58 (IQ: 0 –2000). Conclusions: Contrary to more conservative estimates used in mathematical modeling studies, patients in our cohort demonstrated a significant survival benefit even within the lowest CD4 cell stratum. Patients on HAART had low potential infectivity as measured by plasma virus load. Cohort data from African patients can contribute to the further refinement of predictive models

A Fast and Efficient Decellularization Method for Tissue Slices

The study and use of decellularized extracellular matrix (dECM) in tissue engineering, regenerative medicine, and pathophysiology have become more prevalent in recent years. To obtain dECM, numerous decellularization procedures have been developed for the entire organ or tissue blocks, employing either perfusion of decellularizing agents through the tissue's vessels or submersion of large sections in decellularizing solutions. However, none of these protocols are suitable for thin tissue slices (less than 100 μm) or allow side-by-side analysis of native and dECM consecutive tissue slices. Here, we present a detailed protocol to decellularize tissue sections while maintaining the sample attached to a glass slide. This protocol consists of consecutive washes and incubations of simple decellularizing agents: ultrapure water, sodium deoxycholate (SD) 2%, and deoxyribonuclease I solution 0.3 mg/mL (DNase I). This novel method has been optimized for a faster decellularization time (2-3 h) and a better correlation between dECM properties and native tissue-specific biomarkers, and has been tested in different types of tissues and species, obtaining similar results. Furthermore, this method can be used for scarce and valuable samples such as clinical biopsies

Development of a physiomimetic model of acute respiratory distress syndrome by using ECM hydrogels and organ-on-a-chip devices

Acute Respiratory Distress Syndrome is one of the more common fatal complications in COVID-19, characterized by a highly aberrant inflammatory response. Pre-clinical models to study the effect of cell therapy and anti-inflammatory treatments have not comprehensively reproduced the disease due to its high complexity. This work presents a novel physiomimetic in vitro model for Acute Respiratory Distress Syndrome using lung extracellular matrix-derived hydrogels and organ-on-a-chip devices. Monolayres of primary alveolar epithelial cells were cultured on top of decellullarized lung hydrogels containing primary lung mesenchymal stromal cells. Then, cyclic stretch was applied to mimic breathing, and an inflammatory response was induced by using a bacteriotoxin hit. Having simulated the inflamed breathing lung environment, we assessed the effect of an anti-inflammatory drug (i.e., dexamethasone) by studying the secretion of the most relevant inflammatory cytokines. To better identify key players in our model, the impact of the individual factors (cyclic stretch, decellularized lung hydrogel scaffold, and the presence of mesenchymal stromal cells) was studied separately. Results showed that developed model presented a more reduced inflammatory response than traditional models, which is in line with what is expected from the response commonly observed in patients. Further, from the individual analysis of the different stimuli, it was observed that the use of extracellular matrix hydrogels obtained from decellularized lungs had the most significant impact on the change of the inflammatory response. The developed model then opens the door for further in vitro studies with a better-adjusted response to the inflammatory hit and more robust results in the test of different drugs or cell therapy

Coordinated response to imported vaccine-derived poliovirus infection, Barcelona, Spain, 2019-2020

In 2019, the Public Health Agency of Barcelona, Spain, was notifi ed of a vaccine-derived poliovirus infection. The patient had an underlying common variable immunodefi ciency and no signs of acute fl accid paralysis. We describe the ongoing coordinated response to contain the infection, which included compassionate-use treatment with pocapavir

Haemolytic anaemia in an HIV-infected patient with severe falciparum malaria after treatment with oral artemether-lumefantrine

Intravenous (i.v.) artesunate is now the recommended first-line treatment of severe falciparum malaria in adults and children by WHO guidelines. Nevertheless, several cases of haemolytic anaemia due to i.v. artesunate treatment have been reported. This paper describes the case of an HIV-infected patient with severe falciparum malaria who was diagnosed with haemolytic anaemia after treatment with oral artemether-lumefantrine

description of the methodological approach

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Lilliput

Catalog for the exhibition Lilliput held at the Seton Hall University Walsh Gallery, June 8 - July 24, 2009. Curated by Jeanne Brasile and Asha Ganpat. Includes an essay by Jeanne Brasile and Asha Ganpat. Includes color illustrations