Documento de consenso: Recomendaciones para el manejo de la enfermedad ósea metabólica en pacientes con virus de la inmunodeficiencia humana

Objective

To provide practical recommendations for the evaluation and treatment of metabolic bone disease in human immunodeficiency virus (HIV) patients.

Participants

Members of scientific societies related to bone metabolism and HIV: Grupo de Estudio de Sida (GeSIDA), Sociedad Española de Endocrinología y Nutrición (SEEN), Sociedad Española de Investigación Ósea y del Metabolismo Mineral (SEIOMM), and Sociedad Española de Fractura Osteoporótica (SEFRAOS).

Methods

A systematic search was carried out in PubMed, and papers in English and Spanish with a publication date before 28 May 2013 were included. Recommendations were formulated according to GRADE system (Grading of Recommendations, Assessment, Development, and Evaluation) setting both their strength and the quality of supporting evidence. Working groups were established for each major part, and the final resulting document was later discussed in a face-to-face meeting. All the authors reviewed the final written document and agreed with its content.

Conclusions

The document provides evidence-based practical recommendations on the detection and treatment of bone disease in HIV-infected patients.     

Test–retest repeatability of [18F]Flortaucipir PET in Alzheimer’s disease and cognitively normal individuals

The aim of this study was to investigate the test–retest (TRT) repeatability of various parametric quantification methods for [¹⁸F]Flortaucipir positron emission tomography (PET). We included eight subjects with dementia or mild cognitive impairment due to Alzheimer’s disease and six cognitively normal subjects. All underwent two 130-min dynamic [¹⁸F]Flortaucipir PET scans within 3 ± 1 weeks. Data were analyzed using reference region models receptor parametric mapping (RPM), simplified reference tissue method 2 (SRTM2) and reference logan (RLogan), as well as standardized uptake value ratios (SUVr, time intervals 40–60, 80–100 and 110–130 min post-injection) with cerebellar gray matter as reference region. We obtained distribution volume ratio or SUVr, first for all brain regions and then in three tau-specific regions-of-interest (ROIs). TRT repeatability (%) was defined as |retest–test|/(average (test + retest)) × 100. For all methods and across ROIs, TRT repeatability ranged from (median (IQR)) 0.84% (0.68–2.15) to 6.84% (2.99–11.50). TRT repeatability was good for all reference methods used, although semi-quantitative models (i.e. SUVr) performed marginally worse than quantitative models, for instance TRT repeatability of RPM: 1.98% (0.78–3.58) vs. SUVr_80–100: 3.05% (1.28–5.52), p < 0.001. Furthermore, for SUVr_80–100 and SUVr_110–130, with higher average SUVr, more variation was observed. In conclusion, while TRT repeatability was good for all models used, quantitative methods performed slightly better than semi-quantitative methods.     

A single-center pilot validation study of a new chronic GVHD skin scoring system.

The use of a quantifiable and reproducible measurement tool for skin manifestations of chronic graft-versus-host disease (cGVHD) is key for the successful assessment and documentation of therapeutic response. Skin scoring methods for use in clinical trials have not been validated for application in patients suffering from cGVHD. For this purpose we performed a prospective single-center pilot study to validate a skin-scoring tool developed at our institution for evaluating cutaneous involvement of cGVHD approximately 10 years ago. It combines percentage of involved body surface area (BSA) divided into 10 separate anatomic regions with manifestations of cGVHD coded from 0 (normal skin) to 4 (hidebound skin, unmovable sclerosis). Sixteen patients were examined separately by 4 trained physicians 3 times on 2 consecutive days for a total of 192 individual skin assessments; intraobserver and interobserver reliability were calculated. Good to excellent intraclass correlation coefficients (ICC) were obtained in almost all scores including erythematous lesions in areas with scores 3 and 4 for all observers. Moderate to good interrater reliability for observers 1 to 4 was seen in lesions with scores 0, 3, and 4, respectively. A marked improvement of interrater reliability in all scores and examinations was observed when ICCs were calculated only for the more experienced observers 1 to 3. This New Chronic GVHD Skin score is a reproducible, accurate, feasible, and inexpensive tool for use in selected clinical trials of chronic cutaneous GVHD. Further studies with larger patient numbers and validation of this new tool for assessment of treatment response are warranted.     

Acute Exposure to the Mitochondrial Complex I Toxin Rotenone Impairs Synaptic Long‐Term Potentiation in Rat Hippocampal Slices

Aims: To evaluate the acute effects of the mitochondrial complex I inhibitor rotenone on rat hippocampal synaptic plasticity. Methods: Electrophysiological field potential recordings were used to measure basal synaptic transmission and synaptic plasticity in rat coronal hippocampal slices. Synaptic long‐term potentiation (LTP) was induced by high‐frequency stimulation (100 Hz, 1 second × 3 at an interval of 20 seconds). In addition, mitochondrial complex I function was measured using MitoSOX imaging in mitochondrial preparations. Results: Acute exposure of hippocampal slices to 50 nM rotenone for 1 h did not alter basal CA3–CA1 synaptic transmission though 500 nM rotenone significantly reduced basal synaptic transmission. However, 50 nM rotenone significantly impaired LTP and this rotenone's effect was prevented by co‐application of rotenone plus the ketones acetoacetate and β‐hydroxybutyrate (1 mM each). Finally, we measured mitochondrial function using MitoSOX imaging in mitochondrial preparations and found that 50 nM rotenone partially reduced mitochondrial function whereas 500 nM rotenone completely eliminated mitochondrial function. Conclusions: Our findings suggest that mitochondrial activity driven by complex I is a sensitive modulator of synaptic plasticity in the hippocampus. Acute exposure of the hippocampus to rotenone eliminates complex I function and in turn impairs LTP.     

Systematic analysis of research underfunding in maternal and perinatal health

Background  Little published evidence supports the widely held contention that research in pregnancy is underfunded compared with other disease areas.
Objectives  To assess absolute and relative government and charitable funding for maternal and perinatal research in the UK and internationally.
Search strategy, selection criteria, data collection, and analysis  Major research funding bodies and alliances were identified from an Internet search and discussions with opinion leaders/senior investigators. Websites and annual reports were reviewed for details of strategy, research spend, grants awarded, and allocation to maternal and/or perinatal disease using generic and disease-specific search terms.
Main results  Within the imprecision in the data sets, ≤1% of health research spend in the UK was on maternal/perinatal health. Other countries fared better with 1–4% investment, although nonexclusive categorisation may render this an overestimate. In low-resource settings, government funders focused on infectious disease but not maternal and perinatal health despite high relative disease burden, while global philanthropy concentrated on service provision rather than research. Although research expenditure has been deemed as appropriate for 'reproductive health' disease burden in the UK, there are no data on the equity of maternal/perinatal research spend against disease burden, which globally may justify a manyfold increase.
Author's conclusions  This systematic review of research expenditure and priorities from national and international funding bodies suggests relative underinvestment in maternal/perinatal health. Contributing factors include the low political priority given to women's health, the challenging nature of clinical research in pregnancy, and research capacity dearth as a consequence of chronic underinvestment.