Changes in bone quality after switching from a TDF to a TAF based ART: A pilot randomized study

BackgroundThe impact of tenofovir disoproxil fumarate (TDF) antiretroviral (ART) regimens on bone health has been characterized mostly by bone mineral density (BMD), but recently also by bone quality (BQ). The aim of this pilot study is to assess the changes in BMD and BQ after switch from TDF to tenofovir alafenamide (TAF) ART.MethodsHIV individuals receiving TDF-based ART were randomized to switch to Bictegravir-TAF-Emtricitabine or to remain in the same regimen. At baseline and 24-weeks after randomization, participants underwent bone mineral density (BMD) by DXA and BQ assessment using bone microindentation, a validated technique that measures bone tissue quality expressed as bone material strength index (BMSi). A panel of plasma bone turnover biomarkers were measured by ELISA at the same time-points. Values are expressed as median [interquartile range] and non-parametric tests were used where appropriate.ResultsA total of 24 HIV individuals were included in the study, 19 of which were men (80%). Median age at baseline was 43 years (IQR 38-54). Half of individuals were allocated in the TDF group while the other half changed to TAF treatment. No differences at baseline between both groups were detected in any parameter. Non-significant changes nor in lumbar or femoral BMD at week 24 was found in any regimen. In contrast, there was an increase in BMSi in the TAF arm at 24 weeks, and thus an improvement in BQ[81.6 (79-83) to 86 (80-88) (+5.1%);p=0.041], whereas the TDF arm remained stable from 82 (76-85) at baseline to 82 (73-83);p=0.812. Hence, at week 24 there were significant differences in BQ between arms (p=0.049). A reduction in bone formation markers was found at week 24 in both regimens: N-terminal propeptide of type-1 collagen decreased a 20% (-35 - -0.6); p=0.031 with TAF and -16% (-25 - -5); p=0.032 with TDF. Also a decrease in bone resorption marker C-telopeptide with TAF was detected [-10% (-19 - -5);p=0.028] but not with TDF (p=0.232), suggesting a less metabolically active bone after switching to TAF.ConclusionA bone quality improvement was found after switching from a TDF to a TAF based ART independently of BMD, suggesting that the bone health benefits of TAF may extend beyond BMD. Future research should be directed to confirm these findings and to identify the underlying mechanisms of ART related bone toxicity

Professional Liability in Plastic Surgery: A Change of Scenario in Medical Professional Liability in Spain

Background:The epidemic of complaints and/or litigation, both in and out of court, for cases of alleged malpractice has increased dramatically. In Spain, claims related to plastic surgery are gaining more and more interest. Methods:The Council of Medical Associations of Catalonia database was used to analyze claims related to plastic surgery from 1986 to 2021. Results:1039 claims (9.8% over 10,567 total claims) were studied. Both the total number of claims (P = 0.016; R-2=0.16) and the number of claims for plastic surgery (P < 0.0005; R-2=0.732) showed an upward trend during the period of study. In the period from 2000 to 2021, the behavior was different; while the number of total claims stabilized (P = 0.352; R-2 = 0.043), plastic surgery claims continued to show a time-related tendency to increase (P < 0.0005; R-2=0.484). The distribution was 50.12% out of court. Ten unique procedures accounted for 84.5% of the total number of claims. Liability was observed in 21.46% of the closed claims, with differences between civil (20.34%), criminal (6.89%), and out-of-court (25.53%) procedures. Regarding compensation amounts, out-of-court cases had an average of 33,169.44 euros paid; civil cases, 29,153.37 euros; and criminal cases, 37,186.88 euros. Conclusions:The increase in the number of cases can only be related to an increase in the activity carried out by plastic surgeons. There has been a change in Spain in terms of the most sought-after medical specialty, with plastic surgery having displaced the perennially most sought-after specialty, orthopedic surgery and traumatology

MiRNA profiling of whole trabecular bone: identification of osteoporosis-related changes in MiRNAs in human hip bones

Background MicroRNAs (miRNAs) are important regulators of gene expression, with documented roles in bone metabolism and osteoporosis, suggesting potential therapeutic targets. Our aim was to identify miRNAs differentially expressed in fractured vs nonfractured bones. Additionally, we performed a miRNA profiling of primary osteoblasts to assess the origin of these differentially expressed miRNAs. Methods Total RNA was extracted from (a) fresh femoral neck trabecular bone from women undergoing hip replacement due to either osteoporotic fracture (OP group, n = 6) or osteoarthritis in the absence of osteoporosis (Control group, n = 6), matching the two groups by age and body mass index, and (b) primary osteoblasts obtained from knee replacement due to osteoarthritis (n = 4). Samples were hybridized to a microRNA array containing more than 1900 miRNAs. Principal component analysis (PCA) plots and heat map hierarchical clustering were performed. For comparison of expression levels, the threshold was set at log fold change > 1.5 and a p-value < 0.05 (corrected for multiple testing). Results Both PCA and heat map analyses showed that the samples clustered according to the presence or absence of fracture. Overall, 790 and 315 different miRNAs were detected in fresh bone samples and in primary osteoblasts, respectively, 293 of which were common to both groups. A subset of 82 miRNAs was differentially expressed (p < 0.05) between osteoporotic and control osteoarthritic samples. The eight miRNAs with the lowest p-values (and for which a validated miRNA qPCR assay was available) were assayed, and two were confirmed: miR-320a and miR-483-5p. Both were over-expressed in the osteoporotic samples and expressed in primary osteoblasts. miR-320a is known to target CTNNB1 and predicted to regulate RUNX2 and LEPR, while miR-483-5p down-regulates IGF2. We observed a reduction trend for this target gene in the osteoporotic bone. Conclusions We identified two osteoblast miRNAs over-expressed in osteoporotic fractures, which opens novel prospects for research and therapy

What do we know about Immunity to SARS-CoV-2? Implications for Public Health Policies

Additional support from ISGlobal’s Antoni Plasència and Josep M. AntóAs the COVID-19 pandemic progresses, so does our knowledge of the magnitude, type and durability of the immune response to SARS-CoV-2 as a result of natural infection or vaccination. This information is crucial since it will largely define the strategies we need to implement in order to protect individuals and populations. With this in mind, the GCMSC presents its second report, where they review the current knowledge on immunity to SARS-CoV-2 and the implications in terms of public health policies

Post-Acute COVID Syndrome (PACS): Definition, Impact and Management

Additional support from ISGlobal’s Antoni Plasència and Josep M. AntóA variety of studies suggest that up to 10-15% of all patients with COVID-19 may present persistent symptomatology weeks or even months after the original infection. Given the accumulated burden of COVID-19 in Catalonia, Spain, we speculate that over 90,000 patients could have been or are currently affected by persistent symptoms or sequelae. The Multidisciplinary Collaborative Group for the Scientific Monitoring of COVID-19 (GCMSC) presents its third report where they propose a clear set of case definitions of Post-Acute COVID syndrome (PACS) and its sub-categories and recommend a comprehensive medical examination to characterise the clinical features and complications when assessing PACS

Risk Factors for Amoxicillin-Clavulanate Resistance in Community-Onset Urinary Tract Infections Caused by Escherichia coli or Klebsiella pneumoniae : The Role of Prior Exposure to Fluoroquinolones

Background: High rates of amoxicillin-clavulanate (AMC) resistance among Enterobacterales isolated from urinary tract infections (UTIs) were observed in our area. The aim of this study was to identify risk factors associated with AMC resistance in patients with community-onset UTI in emergency departments (EDs). Methods: A retrospective study was performed of all ED patients with positive urine cultures for Escherichia coli or Klebsiella pneumoniae in a Spanish tertiary-care hospital. Results: 330 urine cultures in all were included: 261 (79.1%) for E. coli and 69 (20.90%) for K. pneumonia. Rates of AMC resistance were 14.94% and 34.78%, respectively. UTI was clinically confirmed in 212 (64.24%) cases. Previous antimicrobial exposure was independently associated with AMC resistance development in E. coli and K. pneumoniae urinary isolates (OR = 2.94, 95% CI = 1.55-5.58). Analyses of infected patients revealed that previous exposure to fluoroquinolones (OR = 3.33, 95% CI = 1.10-10.12, p = 0.034) and to AMC (OR = 5.68, 95% CI = 1.97-16.44, p = 0.001) was significantly associated with isolation of AMC-resistant strains. Conclusions: Prior antibiotic exposure, particularly to AMC or fluoroquinolones, was the only independent risk factor associated with development of AMC resistance in E. coli and K. pneumoniae urinary isolates from patients attending the ED

BA.5 Omicron subvariant in Catalonia: Current impact and recommendations for booster vaccination strategies

Additional support from ISGlobal’s Antoni Plasència and Josep M. AntóCirculation of the Omicron BA.5 subvariant has led to a considerable increase in cases and also in hospitalisations (but not severe cases or deaths) in recent weeks in Catalonia, the rest of Spain and many other countries. Based on scientific evidence and the current epidemiological situation, the Multidisciplinary Collaborative Group for the Scientific Monitoring of COVID-19 (GCMSC) has conducted an analysis of the impact of the BA-5 subvariant in Catalonia and, with the support of the COVID-19 Scientific Advisory Committee (CCAC) attached to the Department of Health of the Government of Catalonia, has issued a series of recommendations for booster vaccination strategies

Genetic analysis of high bone mass cases from the BARCOS cohort of spanish postmenopausal women

The aims of the study were to establish the prevalence of high bone mass (HBM) in a cohort of Spanish postmenopausal women (BARCOS) and to assess the contribution of LRP5 and DKK1 mutations and of common bone mineral density (BMD) variants to a HBM phenotype. Furthermore, we describe the expression of several osteoblast-specific and Wnt-pathway genes in primary osteoblasts from two HBM cases. A 0.6% of individuals (10/1600) displayed Z-scores in the HBM range (sum Z-score >4). While no mutation in the relevant exons of LRP5 was detected, a rare missense change in DKK1 was found (p.Y74F), which cosegregated with the phenotype in a small pedigree. Fifty-five BMD SNPs from Estrada et al. [NatGenet 44:491-501,2012] were genotyped in the HBM cases to obtain risk scores for each individual. In this small group of samples, Z-scores were found inversely related to risk scores, suggestive of a polygenic etiology. There was a single exception, which may be explained by a rare penetrant genetic variant, counterbalancing the additive effect of the risk alleles. The expression analysis in primary osteoblasts from two HBM cases and five controls suggested that IL6R, DLX3, TWIST1 and PPARG are negatively related to Z-score. One HBM case presented with high levels of RUNX2, while the other displayed very low SOX6. In conclusion, we provide evidence of lack of LRP5 mutations and of a putative HBM-causing mutation in DKK1. Additionally, we present SNP genotyping and expression results that suggest additive effects of several genes for HBM

COVID-19 Immunisation Strategy: Priority Populations

Additional support from ISGlobal’s Antoni Plasència and Josep M. AntóWith a limited initial supply of COVID-19 vaccines doses and an expected delay for the universal vaccination of those eligible to receive it, it is relevant to analyse how best to prioritise the first available doses to achieve the greatest impact, both in terms of protecting individuals and minimising community transmission. Ethical issues are key in guiding a fair distribution. Different scenarios on vaccine implementation are summarised in this report. After a critical review of the documents and considering that these criteria are applied to Spanish citizens, the members of theGCMSC establish a priority vaccination list based on ethical principles and adapted to our count