Genetic characteristics involved in COVID-19 severity. The CARGENCORS case-control study and meta-analysis.

Pre-existing coronary artery disease (CAD), and thrombotic, inflammatory, or virus infectivity response phenomena have been associated with COVID-19 disease severity. However, the association of candidate single nucleotide variants (SNVs) related to mechanisms of COVID-19 complications has been seldom analysed. Our aim was to test and validate the effect of candidate SNVs on COVID-19 severity. CARGENCORS (CARdiovascular GENetic risk score for Risk Stratification of patients positive for SARS-CoV-2 [COVID-19] virus) is an age- and sex-matched case-control study with 818 COVID-19 cases hospitalized with hypoxemia, and 1636 controls with COVID-19 treated at home. The association between severity and SNVs related to CAD (n = 32), inflammation (n = 19), thrombosis (n = 14), virus infectivity (n = 11), and two published to be related to COVID-19 severity was tested with adjusted logistic regression models. Two external independent cohorts were used for meta-analysis (SCOURGE and UK Biobank). After adjustment for potential confounders, 14 new SNVs were associated with COVID-19 severity in the CARGENCORS Study. These SNVs were related to CAD (n = 10), thrombosis (n = 2), and inflammation (n = 2). We also confirmed eight SNVs previously related to severe COVID-19 and virus infectivity. The meta-analysis showed five SNVs associated with severe COVID-19 in adjusted analyses (rs11385942, rs1561198, rs6632704, rs6629110, and rs12329760). We identified 14 novel SNVs and confirmed eight previously related to COVID-19 severity in the CARGENCORS data. In the meta-analysis, five SNVs were significantly associated to COVID-19 severity, one of them previously related to CAD.

Patients' preferences for fracture risk communication: the Risk Communication in Osteoporosis (RICO) study.

The RICO study indicated that most patients would like to receive information regarding their fracture risk but that only a small majority have actually received it. Patients globally preferred a visual presentation of fracture risk and were interested in an online tool showing the risk. PURPOSE: The aim of the Risk Communication in Osteoporosis (RICO) study was to assess patients' preferences regarding fracture risk communication. METHODS: To assess patients' preferences for fracture risk communication, structured interviews with women with osteoporosis or who were at risk for fracture were conducted in 11 sites around the world, namely in Argentina, Belgium, Canada at Hamilton and with participants from the Osteoporosis Canada Canadian Osteoporosis Patient Network (COPN), Japan, Mexico, Spain, the Netherlands, the UK, and the USA in California and Washington state. The interviews used to collect data were designed on the basis of a systematic review and a qualitative pilot study involving 26 participants at risk of fracture. RESULTS: A total of 332 women (mean age 67.5 ± 8.0 years, 48% with a history of fracture) were included in the study. Although the participants considered it important to receive information about their fracture risk (mean importance of 6.2 ± 1.4 on a 7-point Likert scale), only 56% (i.e. 185/332) had already received such information. Globally, participants preferred a visual presentation with a traffic-light type of coloured graph of their FRAX® fracture risk probability, compared to a verbal or written presentation. Almost all participants considered it important to discuss their fracture risk and the consequences of fractures with their healthcare professionals in addition to receiving information in a printed format or access to an online website showing their fracture risk. CONCLUSIONS: There is a significant communication gap between healthcare professionals and patients when discussing osteoporosis fracture risk. The RICO study provides insight into preferred approaches to rectify this communication gap.

Sequential management of postmenopausal health and osteoporosis: An update.

Increased life expectancy means that women are now in a hypoestrogenic state for approximately one-third of their lives. Overall health and specifically bone health during this period evolves in accordance with aging and successive exposure to various risk factors. In this review, we provide a summary of the approaches to the sequential management of osteoporosis within an integrative model of care to offer physicians a useful tool to facilitate therapeutic decision-making. Current evidence suggests that pharmacologic agents should be selected based on the risk of fractures, which does not always correlate with age. Due to their effect on bone turnover and on other hormone-regulated phenomena, such as hot flushes or breast cancer risk, we position hormone therapy and selective estrogen receptor modulators as an early postmenopause intervention for the management of postmenopausal osteoporosis. When the use of these agents is not possible, compelling evidence supports antiresorptive agents as first-line treatment of postmenopausal osteoporosis in many clinical scenarios, with digestive conditions, kidney function, readiness for compliance, or patient preferences playing a role in choosing between bisphosphonates or denosumab during this period. For patients at high risk of osteoporotic fracture, the "anabolic first" approach reduces that risk. The effect on bone health with these bone-forming agents or with denosumab should be consolidated with the subsequent use of antiresorptive agents. Regardless of the strategy, follow-up and treatment should be maintained indefinitely to help prevent fractures.

HIV infection is associated with upregulated circulating levels of the inflammaging miR-21-5p.

BACKGROUND: HIV infection produces a chronic inflammation which leads to early aging of people living with HIV. Even though antiretroviral treatments (ART) have significantly increased HIV patient survival, an underlying chronic inflammation persists leading to HIV-related comorbidities. In this context, changes in microRNAs (miRNAs) expression may contribute to this inflammatory response. This study aims to detect differential expression of circulating miRNAs in treatment-naïve HIV-infected individuals compared to uninfected controls and evaluation of altered miRNAs after one year of ART. METHODS: Serum from patients and controls was collected at baseline and after 48-weeks on ART in HIV-treated patients. Circulating miRNAs were analysed using next generation sequencing. RESULTS: A total of 32 HIV patients and 10 controls were recruited. Of HIV+ individuals, 7 were long-term non-progressors (elite controllers), a group of HIV-infected individuals that spontaneously control the infection. Higher circulating levels of miR-21-5p, and lower levels of miR-6503-3p and miR-3135b were detected in HIV+ progressors. After one year of ART, these miRNAs remain altered. Moreover, miR-21-5p and miR-6503-3p were also altered in elite controllers compared to control group. In silico analyses showed that miR-21-5p target pathways are related to inflammation mechanisms and immune system. CONCLUSION: miR-21-5p circulating levels are involved in inflammation and oxidative stress mechanisms in HIV patients even after one year of ART or in elite controllers.

Fracture risk reduction and safety by osteoporosis treatment compared with placebo or active comparator in postmenopausal women: systematic review, network meta-analysis, and meta-regression analysis of randomised clinical trials.

OBJECTIVE: To review the comparative effectiveness of osteoporosis treatments, including the bone anabolic agents, abaloparatide and romosozumab, on reducing the risk of fractures in postmenopausal women, and to characterise the effect of antiosteoporosis drug treatments on the risk of fractures according to baseline risk factors. DESIGN: Systematic review, network meta-analysis, and meta-regression analysis of randomised clinical trials. DATA SOURCES: Medline, Embase, and Cochrane Library to identify randomised controlled trials published between 1 January 1996 and 24 November 2021 that examined the effect of bisphosphonates, denosumab, selective oestrogen receptor modulators, parathyroid hormone receptor agonists, and romosozumab compared with placebo or active comparator. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials that included non-Asian postmenopausal women with no restriction on age, when interventions looked at bone quality in a broad perspective. The primary outcome was clinical fractures. Secondary outcomes were vertebral, non-vertebral, hip, and major osteoporotic fractures, all cause mortality, adverse events, and serious cardiovascular adverse events. RESULTS: The results were based on 69 trials (>80 000 patients). For clinical fractures, synthesis of the results showed a protective effect of bisphosphonates, parathyroid hormone receptor agonists, and romosozumab compared with placebo. Compared with parathyroid hormone receptor agonists, bisphosphonates were less effective in reducing clinical fractures (odds ratio 1.49, 95% confidence interval 1.12 to 2.00). Compared with parathyroid hormone receptor agonists and romosozumab, denosumab was less effective in reducing clinical fractures (odds ratio 1.85, 1.18 to 2.92 for denosumab v parathyroid hormone receptor agonists and 1.56, 1.02 to 2.39 for denosumab v romosozumab). An effect of all treatments on vertebral fractures compared with placebo was found. In the active treatment comparisons, denosumab, parathyroid hormone receptor agonists, and romosozumab were more effective than oral bisphosphonates in preventing vertebral fractures. The effect of all treatments was unaffected by baseline risk indicators, except for antiresorptive treatments that showed a greater reduction of clinical fractures compared with placebo with increasing mean age (number of studies=17; ß=0.98, 95% confidence interval 0.96 to 0.99). No harm outcomes were seen. The certainty in the effect estimates was moderate to low for all individual outcomes, mainly because of limitations in reporting, nominally indicating a serious risk of bias and imprecision. CONCLUSIONS: The evidence indicated a benefit of a range of treatments for osteoporosis in postmenopausal women for clinical and vertebral fractures. Bone anabolic treatments were more effective than bisphosphonates in the prevention of clinical and vertebral fractures, irrespective of baseline risk indicators. Hence this analysis provided no clinical evidence for restricting the use of anabolic treatment to patients with a very high risk of fractures. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019128391.

Reference Intervals for Bone Impact Microindentation in Healthy Adults: A Multi-Centre International Study.

Impact microindentation (IMI) is a novel technique for assessing bone material strength index (BMSi) in vivo, by measuring the depth of a micron-sized, spherical tip into cortical bone that is then indexed to the depth of the tip into a reference material. The aim of this study was to define the reference intervals for men and women by evaluating healthy adults from the United States of America, Europe and Australia. Participants included community-based volunteers and participants drawn from clinical and population-based studies. BMSi was measured on the tibial diaphysis using an OsteoProbe in 479 healthy adults (197 male and 282 female, ages 25 to 98 years) across seven research centres, between 2011 and 2018. Associations between BMSi, age, sex and areal bone mineral density (BMD) were examined following an a posteriori method. Unitless BMSi values ranged from 48 to 101. The mean (± standard deviation) BMSi for men was 84.4 ± 6.9 and for women, 79.0 ± 9.1. Healthy reference intervals for BMSi were identified as 71.0 to 97.9 for men and 59.8 to 95.2 for women. This study provides healthy reference data that can be used to calculate T- and Z-scores for BMSi and assist in determining the utility of BMSi in fracture prediction. These data will be useful for positioning individuals within the population and for identifying those with BMSi at the extremes of the population.

Early Neurobehavioral Characterization of the CD Mouse Model of Williams-Beuren Syndrome.

Williams-Beuren syndrome (WBS) is a neurodevelopmental disorder caused by a chromosomic microdeletion (7q11.23). WBS has been modeled by a mouse line having a complete deletion (CD) of the equivalent mouse locus. This model has been largely used to investigate the etiopathological mechanisms of WBS, although pharmacological therapies have not been identified yet. Surprisingly, CD mice were so far mainly tested in adulthood, despite the developmental nature of WBS and the critical relevance of early timing for potential treatments. Here we provide for the first time a phenotypic characterization of CD mice of both sexes during infancy and adolescence, i.e., between birth and 7 weeks of age. CD pups of both sexes showed reduced body growth, delayed sensory development, and altered patterns of ultrasonic vocalizations and exploratory behaviors. Adolescent CD mice showed reduced locomotion and acoustic startle response, and altered social interaction and communication, the latter being more pronounced in female mice. Juvenile CD mutants of both sexes also displayed reduced brain weight, cortical and hippocampal dendritic length, and spine density. Our findings highlight the critical relevance of early neurobehavioral alterations as biomarkers of WBS pathology, underlying the importance of adolescence for identifying novel therapeutic targets for this neurological disorder.

Current situation of shared decision making in osteoporosis: A comprehensive literature review of patient decision aids and decision drivers.

Background and Aims: Osteoporosis is a systemic skeletal disease characterized by low bone mass and microstructural deterioration of bone tissues, resulting in bone fragility and increased fracture risk. It is the most common bone-related disease in the population. However, the proportion of patients who start treatment but discontinue it during the first year is very high (around 50%). Endeavors are made to promote patient participation in treatment by implementing patient decision aids (PDA), whose function is to help the patient make disease-related decisions. We aim to summarize the characteristics of the currently available PDA for osteoporosis, as well as deciding factors. Methods: Comprehensive review of the literature. Results: Currently, eleven PDAs can be found for osteoporosis. These PDA have different characteristics or options such as information about treatments tailored to patient needs, graphic information of the results (to facilitate understanding), personal histories (learning), tests to check the knowledge acquired, provision of evidence, clinical practice guidelines or a final summary to share with their doctor. Only five of these PDAs can be considered complete since they provide relevant disease information and therapeutic options to the patient, promote patient's reflection and foment patient-physician discussion. Conclusions: This study provides an update on the current state of decision making on osteoporosis and available PDA, which can help engage the patient through shared decision-making by considering, among other things, patient preferences. Physicians should consider PDA, as it may promote adherence and effectiveness of treatment.

Spanish National Registry of Major Osteoporotic Fractures (REFRA) seen at Fracture Liaison Services (FLS): objectives and quality standards.

REFRA-FLS is a new registry in Spain aimed at identifying individuals over 50 years of age with a fragility fracture. Using this registry, we found hip fracture is the most prevalent fracture. Treatment for osteoporosis was 87.7%, with 65.3% adherence. REFRA-FLS provides fundamental data in the study of fragility fractures. PURPOSE: Fragility fractures are a growing public health concern in modern-aged societies. Fracture Liaison Services (FLS) have been shown to successfully lower rates of secondary fractures. A new registry (REFRA-FLS) has been created to monitor quality indicators of FLS units in Spain and to explore the occurrence and characteristic of fragility fractures identified by these centers. METHODS: We conducted a prospective cohort study based on fragility fractures recorded in the REFRA-FLS registry. Participants were individuals 50 years or above who suffered a low energy fragility fracture identified by the 10 participating FLS units during the study period. The type of FLS unit, the characteristics of the individuals at baseline, along with patient outcomes as quality indicators among those who completed 1 year of follow-up were analyzed. RESULTS: A total of 2965 patients and 3067 fragility fractures were identified, and the most frequent locations were hip (n = 1709, 55.7%) and spine (n = 492, 16.0%). A total of 43 refractures (4.5%) and 46 deaths (4.9%) were observed among 948 individuals in the follow-up analyses. Time from fracture to evaluation was less than 3 months in 76.7% of individuals. Osteoporosis treatment was prescribed in 87.7%, and adherence was 65.3% in Morisky-Green test. CONCLUSION: Our results provide a comprehensive picture of fragility fractures identified in FLS units from Spain. Overall, quality indicators are satisfactory although a much higher use of DXA would be desirable. As the registry grows with the incorporation of new FLS units and longer follow-up, incoming analyses will provide valuable insight.

Bone loss induced by cancer treatments in breast and prostate cancer patients

Cancer and cancer therapies are a major factor risk for osteoporosis due to bone loss and deterioration of bone microarchitecture. Both factors contribute to a decrease in bone strength and, consequently, increased bone fragility and risk of fracture. Cancer-associated bone loss is a multifactorial process, and optimal interdisciplinary management of skeletal health, accurate assessment of bone density, and early diagnosis are essential when making decisions aimed at reducing bone loss and fracture risk in patients who have received or are receiving treatment for cancer. In this document, a multidisciplinary group of experts collected the latest evidence on the pathophysiology of osteoporosis and its prevention, diagnosis, and treatment with the support of the Spanish scientific society SEOM. The aim was to provide an up-to-date and in-depth view of osteoporotic risk and its consequences, and to present a series of recommendations aimed at optimizing the management of bone health in the context of cancer. (AU)

Correction to: Bone loss induced by cancer treatments in breast and prostate cancer patients

In the sentence beginning ‘In this document…’ in the Abstract section of this article, the text ‘In this document, a multidisciplinary group of experts collected the latest evidence on the pathophysiology of osteoporosis and its prevention, diagnosis, and treatment with the support of the Spanish scientific societies SEOM, SER, SEIOMM, and SECOT’ should have read ‘In this document, a multidisciplinary group of experts collected the latest evidence on the pathophysiology of osteoporosis and its prevention, diagnosis, and treatment with the support of the Spanish scientific society SEOM’. (AU)

Bone loss induced by cancer treatments in breast and prostate cancer patients.

Cancer and cancer therapies are a major factor risk for osteoporosis due to bone loss and deterioration of bone microarchitecture. Both factors contribute to a decrease in bone strength and, consequently, increased bone fragility and risk of fracture. Cancer-associated bone loss is a multifactorial process, and optimal interdisciplinary management of skeletal health, accurate assessment of bone density, and early diagnosis are essential when making decisions aimed at reducing bone loss and fracture risk in patients who have received or are receiving treatment for cancer. In this document, a multidisciplinary group of experts collected the latest evidence on the pathophysiology of osteoporosis and its prevention, diagnosis, and treatment with the support of the Spanish scientific society SEOM. The aim was to provide an up-to-date and in-depth view of osteoporotic risk and its consequences, and to present a series of recommendations aimed at optimizing the management of bone health in the context of cancer.

Development and external validation of a 1- and 5-year fracture prediction tool based on electronic medical records data: The EPIC risk algorithm.

OBJECTIVES: We aimed to develop and validate a fracture risk algorithm for the automatic identification of subjects at high risk of imminent and long-term fracture risk. RESEARCH, DESIGN, AND METHODS: A cohort of subjects aged 50-85, between 2007 and 2017, was extracted from the Catalan information system for the development of research in primary care database (SIDIAP). Participants were followed until the earliest of death, transfer out, fracture, or 12/31/2017. Potential risk factors were obtained based on the existing literature. Cox regression was used to model 1 and 5-year risk of hip and major fracture. The original cohort was randomly split in 80:20 for development and internal validation purposes respectively. External validation was explored in a cohort extracted from the Spanish database for pharmaco-epidemiological research in primary care. RESULTS: A total of 1.76 million people were included from SIDIAP (50.7 % women with mean age of 65.4 years). Hip and major fracture incidence rates were 3.57 [95%CI 3.53 to 3.60] and 11.61 [95%CI 11.54 to 11.68] per 1000 person-years, respectively. The derived model included 19 risk factors. Internal validity showed good results on calibration and discrimination. The 1-year C-statistic for hip and major fracture were 0.851 (95%CI 0.853 to 0.864), and 0.717 (95%CI 0.742 to 0.749) respectively. The 5-year C-statistic for hip and major fracture were 0.849 (95%CI 0.847 to 0.852) and 0.724 (95%CI 0.721 to 0.727) respectively. External validation showed good performance for hip and major fracture risk prediction. CONCLUSIONS: We have developed and validated a clinical prediction tool for 1- and 5-year hip and major osteoporotic fracture risks using electronic primary care data. The proposed algorithm can be automatically estimated at the population level using the available primary care records. Future work is needed on the cost-effectiveness of its use for population-based screening and targeted prevention of osteoporotic fractures.

Clinical description and genetic analysis of a novel familial skeletal dysplasia characterized by high bone mass and lucent bone lesions.

High bone mass (HBM) disorders are a clinically and genetically heterogeneous subgroup of rare skeletal dysplasias. Here we present a case of a previously unreported familial skeletal dysplasia characterized by HBM and lucent bone lesions that we aimed to clinically characterize and genetically investigate. For phenotyping, we reviewed past clinical records and imaging tests, and performed physical examination (PE), bone densitometry, and mineral panels in affected individuals, including a male proband, his son and daughter, in addition to unaffected controls, including the proband's wife and brother. Affected individuals also underwent impact microindentation (IMI). In an effort to elucidate the disorder's molecular etiology, whole exome sequencing (WES) was performed in all individuals to filter for rare variants present only in affected ones. The cases displayed a unique skeletal phenotype with a mix of sclerotic features and lucent bone lesions, and high IMI values. Bone mineral density was very elevated in the proband and his daughter. The proband's daughter also exhibited idiopathic scoliosis (IS), in addition to mild thrombocytopenia and mild structural thyroid abnormalities, which were the only extra-skeletal abnormalities identified. WES analysis yielded 5 rare putative pathogenic variants in affected members in genes that are associated with bone metabolism including: SEM4AD, TBX18, PTCH1, PTK7, and ADGRE5. The PTK7 variant appeared as possibly implicated in the development of IS while the TBX18 and SEMA4D variants stood out as the strongest candidates for the lucent bone lesions and HBM, respectively, given their high predicted pathogenicity and putative role in bone biology. Variant functionality should be addressed in the future to assess their implication in skeletal metabolism as it is the first time that mutations in TBX18 and SEMA4D have been associated to bone developmental lesions and mineral metabolism in a clinical setting.

Genetic Analysis in a Familial Case With High Bone Mineral Density Suggests Additive Effects at Two Loci.

Osteoporosis is the most common bone disease, characterized by a low bone mineral density (BMD) and increased risk of fracture. At the other end of the BMD spectrum, some individuals present strong, fracture-resistant, bones. Both osteoporosis and high BMD are heritable and their genetic architecture encompasses polygenic inheritance of common variants and some cases of monogenic highly penetrant variants in causal genes. We have investigated the genetics of high BMD in a family segregating this trait in an apparently Mendelian dominant pattern. We searched for rare causal variants by whole-exome sequencing in three affected and three nonaffected family members. Using this approach, we have identified 38 rare coding variants present in the proband and absent in the three individuals with normal BMD. Although we have found four variants shared by the three affected members of the family, we have not been able to relate any of these to the high-BMD phenotype. In contrast, we have identified missense variants in two genes, VAV3 and ADGRE5, each shared by two of out of three affected members, whose loss of function fits with the phenotype of the family. In particular, the proband, a woman displaying the highest BMD (sum Z-score = 7), carries both variants, whereas the other two affected members carry one each. VAV3 encodes a guanine-nucleotide-exchange factor with an important role in osteoclast activation and function. Although no previous cases of VAV3 mutations have been reported in humans, Vav3 knockout (KO) mice display dense bones, similarly to the high-BMD phenotype present in our family. The ADGRE5 gene encodes an adhesion G protein-coupled receptor expressed in osteoclasts whose KO mouse displays increased trabecular bone volume. Combined, these mouse and human data highlight VAV3 and ADGRE5 as novel putative high-BMD genes with additive effects, and potential therapeutic targets for osteoporosis. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Locus coeruleus activation during environmental novelty gates cocaine-induced long-term hyperactivity of dopamine neurons.

A key feature of the brain is the ability to handle novelty. Anything that is new will stimulate curiosity and trigger exploration. Novelty preference has been proposed to predict increased sensitivity to cocaine. Different brain circuits are activated by novelty, but three specific brain regions are critical for exploring a novel environment: the noradrenergic neurons originating from the locus coeruleus (LC), the dopaminergic neurons from the ventral tegmental area (VTA), and the hippocampus. However, how exploring a novel environment can interfere with the reward system and control cocaine impact on VTA dopamine neuron plasticity is unclear. Here, we first investigated the effects of exposure to a novel environment on the tonic electrophysiological properties of VTA dopamine neurons. Then, we explored how exposure to a novel environment controls cocaine-evoked plasticity in dopamine neurons. Our findings indicate that LC controls VTA dopamine neurons under physiological conditions but also after cocaine.

Comparison of Hospitalized Coronavirus Disease 2019 and Influenza Patients Requiring Supplemental Oxygen in a Cohort Study: Clinical Impact and Resource Consumption.

BACKGROUND: To compare clinical characteristics, outcomes, and resource consumption of patients with coronavirus disease 2019 (COVID-19) and seasonal influenza requiring supplemental oxygen. METHODS: Retrospective cohort study conducted at a tertiary-care hospital. Patients admitted because of seasonal influenza between 2017 and 2019, or with COVID-19 between March and May 2020 requiring supplemental oxygen were compared. Primary outcome: 30-day mortality. Secondary outcomes: 90-day mortality and hospitalization costs. Attempted sample size to detect an 11% difference in mortality was 187 patients per group. RESULTS: COVID-19 cases were younger (median years of age, 67; interquartile range [IQR] 54-78 vs 76 [IQR 64-83]; P < .001) and more frequently overweight, whereas influenza cases had more hypertension, immunosuppression, and chronic heart, respiratory, and renal disease. Compared with influenza, COVID-19 cases had more pneumonia (98% vs 60%, <.001), higher Modified Early Warning Score (MEWS) and CURB-65 (confusion, blood urea nitrogen, respiratory rate, systolic blood pressure, and age >65 years) scores and were more likely to show worse progression on the World Health Organization ordinal scale (33% vs 4%; P < .001). The 30-day mortality rate was higher for COVID-19 than for influenza: 15% vs 5% (P = .001). The median age of nonsurviving cases was 81 (IQR 74-88) and 77.5 (IQR 65-84) (P = .385), respectively. COVID-19 was independently associated with 30-day (hazard ratio [HR], 4.6; 95% confidence interval [CI], 2-10.4) and 90-day (HR, 5.2; 95% CI, 2.4-11.4) mortality. Sensitivity and subgroup analyses, including a subgroup considering only patients with pneumonia, did not show different trends. Regarding resource consumption, COVID-19 patients had longer hospital stays and higher critical care, pharmacy, and complementary test costs. CONCLUSIONS: Although influenza patients were older and had more comorbidities, COVID-19 cases requiring supplemental oxygen on admission had worse clinical and economic outcomes.

Circulating microRNA profiling is altered in the acute respiratory distress syndrome related to SARS-CoV-2 infection.

One of the hallmarks of SARS-CoV-2 infection is an induced immune dysregulation, in some cases resulting in cytokine storm syndrome and acute respiratory distress syndrome (ARDS). Several physiological parameters are altered as a result of infection and cytokine storm. Among them, microRNAs (miRNAs) might reflect this poor condition since they play a significant role in immune cellular performance including inflammatory responses. Circulating miRNAs in patients who underwent ARDS and needed mechanical ventilation (MV+; n = 15) were analyzed by next generation sequencing in comparison with patients who had COVID-19 poor symptoms but without intensive care unit requirement (MV-; n = 13). A comprehensive in silico analysis by integration with public gene expression dataset and pathway enrichment was performed. Whole miRNA sequencing identified 170 differentially expressed miRNAs between patient groups. After the validation step by qPCR in an independent sample set (MV+ = 10 vs. MV- = 10), the miR-369-3p was found significantly decreased in MV+ patients (Fold change - 2.7). After integrating with gene expression results from COVID-19 patients, the most significant GO enriched pathways were acute inflammatory response, regulation of transmembrane receptor protein Ser/Thr, fat cell differentiation, and regulation of biomineralization and ossification. In conclusion, miR-369-3p was altered in patients with mechanical ventilation requirement in comparison with COVID-19 patients without this requirement. This miRNA is involved in inflammatory response which it can be considered as a prognosis factor for ARDS in COVID-19 patients.

Frailty in kidney transplant candidates: a comparison between physical frailty phenotype and FRAIL scales.

BACKGROUND: Frailty is common among advanced chronic kidney disease (CKD) patients who are kidney transplant (KT) candidates, and predisposes to poor outcomes after transplantation. However, frailty is not routinely measured during pretransplant work-up and it is unknown which metric should be used in this specific population. Our aim was to establish frailty prevalence in KT candidates according to different frailty scales. METHODS: Prospective longitudinal study of 451 KT candidates evaluated for frailty by both Physical Frailty Phenotype (PFP) and FRAIL scale at the time of inclusion on the KT waiting list. Clinical and functional characteristics including sociodemographics, comorbidities, disability and nutritional status were recorded. Agreement between PFP and FRAIL scales as well as dissonant patients were analyzed. RESULTS: Mean age was 60.9 years and 31.7% were female. Comorbidity burden among patients was high, with 36.9% and 16.2% presenting with diabetes and ischemic coronary disease, respectively. Disabilities were also frequent. More than 70% of patients presented with ≥ 1 PFP criteria while this percentage for ≥ 1 FRAIL criteria was 45.4%. Agreement between PFP and FRAIL was not good (kappa index 0.317). There were 132 patients who were pre-frail or frail according to PFP but non-frail according to the FRAIL scale and they presented with fewer comorbidities and less disability. CONCLUSIONS: Frailty is frequent in advanced CKD patients, although its prevalence may vary according to different scales. Agreement between PFP and FRAIL scale is not good, and FRAIL scale might misclassify as robust patients those frail/prefrail patients who are in better health conditions.