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International audience; AIMS: To evaluate the current management and survival of patients with left-sided infective endocarditis (IE) complicated by congestive heart failure (CHF) in the ESC-EORP European Endocarditis (EURO-ENDO) registry. METHODS AND RESULTS: Among the 3116 patients enrolled in this prospective registry, 2449 (mean age: 60 years, 69% male) with left-sided (native or prosthetic) IE were included in this study. Patients with CHF (n~=~698, 28.5%) were older, with more comorbidity and more severe valvular damage (mitro-aortic involvement, vegetations >10\,mm and severe regurgitation/new prosthesis dehiscence) than those without CHF (all p\,≤q\,0.019). Patients with CHF experienced higher 30-day and 1-year mortality than those without (20.5% vs. 9.0% and 36.1% vs. 19.3%, respectively) and CHF remained strongly associated with 30-day (odds ratio[OR] 2.37, 95% confidence interval [CI] [1.73-3.24; p\,10\,mm, severe valvular regurgitation and/or new prosthetic dehiscence, perivalvular complication, and prosthetic IE (OR 0.22, 95% CI 0.12-0.38; p\

Irritable bowel syndrome (IBS) is one of the most frequent disorders in clinical practice, with a mean 7.6-10.8% worldwide prevalence. A study showed that 6.1% of patients with diarrhea-predominant IBS (IBS-D) had severe exocrine pancreatic insufficiency (EPI). We aimed to identify the prevalence of EPI based on fecal elastase stool testing (Fel-1) in IBS-D and the clinical characteristics that may predict the diagnosis of EPI.Patients aged18 years presenting to tertiary hospital outpatient clinics with IBS-D completed validated questionnaires and gave a stool sample where Fel-1 concentration was measured. Patients with Fel-1 100 µg/g represented EPI and 100 to 200 µg/g underwent testing for pancreatic pathology with laboratory and endoscopic ultrasound (EUS) evaluation.One hundred forty patients (mean age 60 years, females 75.7%) were studied. EPI was found in 5% (95% CI 2.2-10.4), and pancreatic steatosis was the main EUS finding (71%). Dyspepsia was an independent factor associated with EPI (OR 34.7; 95% CI 4.95-366.37, p = 0.0007). After pancreatic enzyme replacement therapy (PERT), patients showed a significant improvement in the Bristol stool scale (p 0.0001), bowel movements per day (p 0.005), distension score (0.0009), pain score (0.0277) and IBS severity (0.0034).EPI is present in 5% of patients who fulfill Rome IV criteria for D-IBS, and dyspepsia was an independent symptom strongly associated with EPI. Pancreatic steatosis was the main endoscopic ultrasound finding. After PERT therapy, patients had significantly improved stool frequency, stool consistency, abdominal pain, distension and IBS severity score.

Breast cancer is the most frequent cancer diagnosed in women worldwide. Accurate lymph node staging is essential for both prognosis (of early-stage disease) and treatment (for regional control of disease) in patients with breast cancer. The sentinel lymph nodes are the regional nodes that directly drain lymph from the primary tumor. No imaging modality is accurate enough to detect lymph node metastases when a primary breast cancer is at an early stage (I or II), but sentinel lymph node biopsy is a highly reliable method for screening axillary nodes and for identifying metastatic (including micro-metastatic) disease in regional lymph nodes. Despite the widespread use of sentinel lymph node biopsy for early-stage breast cancer, relevant variations have been described regarding practical aspects of the procedure, and some variability has initially been reported regarding the rates of intraoperative sentinel lymph node identification and of false-negative findings, most likely because of differences in the size of the populations being investigated and in lymphatic mapping techniques. Nevertheless, using adequate learning curves and once a multidisciplinary team is experienced with the procedure, improved levels of accuracy are achieved.

BackgroundOne key contributor to lumbar stenosis is thickening of the ligamentum flavum (LF), a process still poorly understood. Wild-type transthyretin amyloid (ATTRwt) has been found in the LF of patients undergoing decompression surgery, suggesting that amyloid may play a role. However, it is unclear whether within patients harboring ATTRwt, the amount of amyloid is associated with LF thickness.MethodsFrom an initial cohort of 324 consecutive lumbar stenosis patients whose LF specimens from decompression surgery were sent for analysis (2018-2019), 33 patients met the following criteria: (1) Congo red-positive amyloid in the LF; (2) ATTRwt by mass spectrometry-based proteomics; and (3) an available preoperative MRI. Histological specimens were digitized, and amyloid load quantified through Trainable Weka Segmentation (TWS) machine learning. LF thicknesses were manually measured on axial T2-weighted preoperative MRI scans at each lumbar level, L1-S1. The sum of thicknesses at every lumbar LF level (L1-S1) equals “lumbar LF burden.”ResultsPatients had a mean age of 72.7 years (range 59-87), were mostly male (61%) and white (82%); and predominantly had surgery at L4-L5 levels (73%). Amyloid load was positively correlated with LF thickness (R=0.345, p=0.0492) at the levels of surgical decompression. Furthermore, amyloid load was positively correlated with lumbar LF burden (R=0.383, p=0.0279).ConclusionsAmyloid load is positively correlated with LF thickness and lumbar LF burden across all lumbar levels, in a dose-dependent manner. Further studies are needed to validate these findings, uncover the underlying pathophysiology, and pave the way towards using therapies that slow LF thickening.

Guidelines recommend surgery for left-sided infective endocarditis (LSIE) that is associated with large vegetations. Given that most patients who undergo surgery also have other indications (heart failure and/or uncontrolled infection), it is not settled whether surgery should be routinely recommended in patients with large vegetations but no other predictors of poor outcome.A total of 726 patients with definitive LSIE were included in our analysis. The mean age was 64.9 years, and 61% were male. Multivariate analysis of all patients was performed to determine whether vegetation size is related to death in LSIE. Then patients were divided into two groups according to vegetation size: group A (10 mm, n = 420) and group B (≤10 mm, n = 306). Univariate and multivariate analyses of group A patients were carried out to identify the variables related to death in this group. The impact of surgery on mortality in group A patients without heart failure or uncontrolled local infection (n = 139) was assessed.Age, Staphylococcus aureus, perivalvular complications, heart failure, kidney failure, and septic shock, but not vegetation size, were associated with death. Patients with large vegetations showed increased mortality (31.7% in group A vs 24.8% in group B; P = .045). Group A had more valve rupture and valve regurgitation than group B, but heart failure (55% vs 53%; P = .678), stroke (22% vs 17.0%, P = .091), systemic embolism (39% vs 32%; P = .074), perivalvular complication (28% vs 28%; P = .865), and septic shock (15% vs 13%; P = .288) were similar in both groups. In patients from group A without heart failure or uncontrolled infection, mortality was similar with and without surgery (n = 139; n = 70 with surgery and n = 69 without surgery; mortality, 18.6% vs 11.6%, respectively; P = .251).Large vegetations identify patients with poor outcomes in the context of LSIE. However, surgery is not associated with a better prognosis in patients with large vegetations if they do not present with another predictor of poor outcome such as heart failure or uncontrolled infection. These findings challenge whether vegetation size alone should be an indication for surgery in LSIE.

The humoral arm of innate immunity includes diverse molecules with antibody-like functions, some of which serve as disease severity biomarkers in coronavirus disease 2019 (COVID-19). The present study was designed to conduct a systematic investigation of the interaction of human humoral fluid-phase pattern recognition molecules (PRMs) with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Of 12 PRMs tested, the long pentraxin 3 (PTX3) and mannose-binding lectin (MBL) bound the viral nucleocapsid and spike proteins, respectively. MBL bound trimeric spike protein, including that of variants of concern (VoC), in a glycan-dependent manner and inhibited SARS-CoV-2 in three in vitro models. Moreover, after binding to spike protein, MBL activated the lectin pathway of complement activation. Based on retention of glycosylation sites and modeling, MBL was predicted to recognize the Omicron VoC. Genetic polymorphisms at the MBL2 locus were associated with disease severity. These results suggest that selected humoral fluid-phase PRMs can play an important role in resistance to, and pathogenesis of, COVID-19, a finding with translational implications.

Appropriate patient/caregiver training and continuity of care after hospital discharge are key factors for the success of home enteral nutrition (HEN). This study aims to assess the effects of a specific patient support program (PSP) on the nutrition status, health-related quality of life (HRQoL), and healthcare resource utilization and associated costs of patients with HEN.Observational study of adult patients with HEN enrolled in a PSP. Sociodemographic variables (baseline), HRQoL (NutriQoL) and nutrition status (Mini Nutritional Assessment [MNA]) (baseline, 6 months after PSP enrollment), and use of unplanned HEN-related healthcare resources (6 months prior to or after PSP enrollment) were recorded. HEN-related resource cost was estimated from total resources used (all patients) and each resource cost. Data were analyzed with Stata program (v. 14), considering P0.05 as significant.Forty-three patients were included in the study (mean age, 72 years [SD = 21]; 54% women; mean HEN duration, 4 years [SD = 5]). A total of 401 calls were recorded in the PSP, 7% made proactively by the patient. HRQoL and nutrition status remained stable during the study period (NutriQoL baseline, 64; 6-months, 66; P = 0.3737; MNA baseline, 10; 6-months, 10; P = 0.0675). Unplanned resources amounted to €6229 (US $5563) and €4711 (US $4207) before and after PSP enrollment, respectively. Cost savings, representing €1518 (US $1356), were related to fewer emergency visits.Health advice provided through a PSP and close patient monitoring in the hospital can help to maintain patients' nutrition status and HRQoL and to reduce the use of certain unplanned HEN-related resources, leading to cost savings.

Oxygen saturation and lactate are markers of tissue hypoxia; they are obtained from central venous and mixed venous sample of the pulmonary artery. The simultaneous behavior of these parameters in the postoperative period of cardiac surgery is unknown.To characterize the lactate and oxygen saturation of the venous-arterial circuit of the postoperative patient from cardiac surgery.Design: Analytical cross-sectional. In consecutive patients after cardiac surgery, serum lactate and oxygen saturation of the venous-arterial circuit were obtained. The variables were reported with median (25.75 percentiles). They were analyzed with Kruskal-Wallis ANOVA and respective adjustment, Spearman correlation, the descriptive Bland-Altman statistic and intraclass correlation coefficient (95% confidence interval). A p0.05 was considered significant.244 blood samples from 61 patients were studied. Women 30 (49%). (Oxygen saturation) [lactate] were: arterial 98 (95.3, 99.4%) and 1.7 (1.1, 2.1); peripheral venous 85 (75.4, 94%) and [1.9 (1.35, 2.3)]; central venous 68.8 (58.74, 70.2%) and 1.8 (1.3, 2.3); mixed central venous 66.8 (61.2, 73.1%) and 1.8 (1.3, 2.2), p0.05. The best intraclass correlation coefficient for oxygen saturation were from central vein to mixed central vein 0.856 (0.760,0.914); and lactate: 0.954 (0.923, 0.972).The oxygen saturation differs in the venous-arterial circuit unlike lactate where they are similar. The best values of the intraclass correlation coefficient for lactate and oxygen saturation were those obtained in central vein and mixed central vein.La saturación de oxígeno y el lactato son marcadores de hipoxia tisular, se obtienen de muestra venosa mezclada en arteria pulmonar o venosa central. Se desconoce el comportamiento simultáneo de estos parámetros en el postoperatorio de cirugía cardiaca.Caracterizar la saturación de oxígeno y lactato del circuito venoso-arterial del paciente postoperado de cirugía cardiaca.Diseño transversal analítico. En pacientes consecutivos postoperados de cirugía cardiaca se obtuvieron lactato sérico y saturación de oxígeno del circuito venoso-arterial. Las variables se informaron con mediana (percentiles 25 y 75). Se analizaron con ANOVA de Kruskal-Wallis y ajuste respectivo, correlación de Spearman, el estadístico descriptivo de Bland-Altman y coeficiente de correlación intraclase (intervalo de confianza al 95%). Una p0.05 se consideró significativa.Se estudiaron 244 muestras sanguíneas de 61 pacientes. Mujeres 30 (49%). Saturación de oxígeno y lactato fueron: arterial 98 (95.3, 99.4)% y 1.7 (1,1, 2.1); venosa periférica 85 (75.4, 94)% y 1.9 (1.35, 2.3); venosa central 68.8 (58.74, 70.2)% y 1.8 (1.3, 2.3); venosa central mezclada 66.8 (61.2, 73.1)% y 1.8 (1.3, 2.2), p0.05. El mejor coeficiente de correlación intraclase para la saturación de oxígeno fue de vena central a vena central mezclada: 0.856 (0.760, 0.914); del lactato: 0.954 (0.923, 0.972).La saturación de oxígeno difiere en el circuito venoso-arterial a diferencia del lactato, donde son similares. Los mejores valores del coeficiente de correlación intraclase para el lactato y la saturación de oxígeno fueron los obtenidos en vena central y vena central mezclada.

The aim of this study was to investigate the relationship between nasal airway obstruction (NAO) and symptoms of orofacial pain, including temporomandibular joint pathology and primary headaches. This study was a retrospective analysis of consecutive patients seeking care for chronic orofacial pain at 14 North American treatment centers. The standardized evaluation protocol followed for all patients included cone beam computed tomography (CBCT), a comprehensive clinical examination, and a thorough review of the patient's subjective complaints and health history, including pain and sleep pathology. The primary conditions of interest in this study were the following 5 types of NAO: nasal valve compromise (NVC), deviated septum, septal swell body, concha bullosa, and inferior turbinate soft tissue hypertrophy. Descriptive statistics and regression analysis were performed to determine comorbidities between orofacial pain symptoms and NAO observed on CBCT images. The study population consisted of 1393 patients, 253 men (18.2%) and 1140 women (81.8%). The mean age of the patients was 43.3 (SD 18.1) years. NVC was the most prevalent type of NAO found in the study population (n = 1006; 72.2%). NVC showed a statistically significant comorbidity with capsulitis (odds ratio, 3.73) as well as facial and cervical myositis (odds ratio, 6.97). To the author's knowledge, this is first time that these comorbidities have been identified. NAO had a high comorbidity with orofacial pain. Specifically, NVC was a major contributor to NAO. An understanding of the mechanisms of orofacial pain as well as the effects of improper (mouth) breathing, adaptive forward head posture, muscular fatigue, parafunction, and temporomandibular joint pathology will help the clinician to evaluate the role a patient's nose may be playing in orofacial pain.

ObjectiveTo evaluate the prognostic impact of urgent cardiac surgery on the prognosis of left-sided infective endocarditis (LSIE) and its relationship to the basal risk of the patient and to the surgical indication.Methods605 patients with LSIE and formal surgical indication were consecutively recruited between 2000 and 2020 among three tertiary centres: 405 underwent surgery during the active phase of the disease and 200 did not despite having indication. The prognostic impact of urgent surgery was evaluated by multivariable analysis and propensity score analysis. We studied the benefit of surgery according to baseline mortality risk defined by the ENDOVAL score and according to surgical indication.ResultsSurgery is an independent predictor of survival in LSIE with surgical indication both by multivariable analysis (OR 0.260, 95% CI 0.162 to 0.416) and propensity score (mortality 40% vs 66%, pConclusionsSurgery during active LSIE seems to significantly reduce in-hospital mortality. The higher the risk, the higher the improvement in outcome.

Chronic heart failure (CHF) is frequently associated with the involuntary loss of body weight and muscle wasting, which can determine the course of the disease and its prognosis. While there is no gold standard malnutrition screening tool for their detection in the CHF population, several bioelectrical and imaging methods have been used to assess body composition in these patients (such as Dual Energy X-Ray Absorptiometry and muscle ultrasound, among other techniques). In addition, numerous nutritional biomarkers have been found to be useful in the determination of the nutritional status. Nutritional considerations include the slow and progressive supply of nutrients, avoiding high volumes, which could ultimately lead to refeeding syndrome and worsen the clinical picture. If oral feeding is insufficient, hypercaloric and hyperproteic supplementation should be considered. β-Hydroxy-β-methylbutyrate and omega-3 polyunsaturated fatty acid administration prove to be beneficial in certain patients with CHF, and several interventional studies with micronutrient supplementation have also described their possible role in these subjects. Taking into account that CHF is sometimes associated with gastrointestinal dysfunction, parenteral nutritional support may be required in selected cases. In addition, potential therapeutic options regarding nutritional state and muscle wasting have also been tested in clinical studies. This review summarises the scientific evidence that demonstrates the necessity to carry out a careful nutritional evaluation and nutritional treatment to prevent or improve cardiac cachexia and sarcopenia in CHF, as well as improve its course SI

Comorbid depression and anxiety is linked to worse outcomes such as increased impairment, distress, and morbidity, as well as worse treatment outcomes. Transdiagnostic variables such as cognitive fusion are considered potential factors for explaining comorbidity. The aim of this study was to analyze the differences between symptom profiles of caregivers (comorbid, depressive, anxiety, and subclinical) in terms of demographic and contextual factors, stress variables, and cognitive fusion. Individual interviews were conducted with 553 caregivers of a relative with dementia. Sociodemographic variables, stressors, cognitive fusion, and depressive and anxiety symptoms were assessed. Caregivers were grouped into four symptom profiles, comorbid (n = 303), depressed (n = 40) anxiety (n = 86), and subclinical (n = 124), based on their depressive and anxiety symptoms. The likelihood of presenting a comorbid profile relative to the subclinical profile was higher in female caregivers. In addition, higher frequency of disruptive behaviors of the care recipient was a risk factor for presenting a comorbid profile relative to the other three profiles, and higher scores in cognitive fusion were a risk factor of comorbidity relative to the other profiles (anxiety, depressive, and subclinical). The findings suggest that the likelihood of presenting comorbid symptomatology is higher for female caregivers and those reporting higher levels of cognitive fusion and higher frequency of disruptive behaviors. These characteristics may describe a vulnerable profile of dementia family caregivers. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The serum fraction of platelet-rich fibrin (hyperacute serum) has been shown to improve cartilage cell proliferation in in vitro osteoarthritic knee joint models. We hypothesize that hyperacute serum may be a potential regenerative therapeutic for osteoarthritic knees. In this study, the cytokine milieu at the synovial fluid of osteoarthritic knee joints exposed to hyperacute serum intraarticular injections was investigated. Patients with knee osteoarthritis received three injections of autologous hyperacute serum, synovial fluid was harvested before each injection and clinical monitoring was followed-up for 6 months. Forty osteoarthritic-related cytokines, growth factors and structural proteins from synovial fluid were quantified and analysed by Multivariate Factor Analysis. Hyperacute serum provided symptomatic relief regarding pain and joint stability for OA patients. Both patients “with” and “without effusion knees” had improved VAS, KOOS and Lysholm-Tegner scores 6 months after of hyperacute serum treatment. Synovial fluid analysis revealed two main clusters of proteins reacting together as a group, showing strong and significant correlations with their fluctuation patterns after hyperacute serum treatment. In conclusion, hyperacute serum has a positive effect in alleviating symptoms of osteoarthritic knees. Moreover, identified protein clusters may allow the prediction of protein expression, reducing the number of investigated proteins in future studies.

In Spain, the 2021/22 influenza season overlapped with the sixth wave of the 2019 coronavirus disease pandemic (COVID-19). Influenza is a major public health problem associated with high morbidity and mortality. The objectives of this study were to determine the knowledge, perceptions and practices of influenza vaccination in the Spanish population, coinciding with the COVID-19 pandemic, with special attention paid to people over 65 years of age. A cross-sectional study was carried out by conducting 2211 telephone interviews. It was observed that 81.6% of people ≥ 65 years were vaccinated annually or with some frequency compared to 35.5% of those under 65 years (p < 0.001). Fifty percent of Spaniards showed an intention to be vaccinated in the 2021/22 campaign, during the SARS-CoV2 pandemic. In the case of people ≥ 65 years old, this figure was 83% compared to 42% of those under 65 years old (p < 0.001). Significant predictors of intention to be vaccinated were age of 65 years or older (OR 1.8, 95% CI 1.3–2.5), female sex (OR 1.9, 95% CI 1.5–2.4), belonging to risk groups (OR 2.2, 95% CI 1.6–3.1) and having been previously vaccinated (OR 29.7, 95% CI 22.5–39.2). The main reasons for deciding to be vaccinated were the need to be protected against the virus and to be vaccinated annually. On the other hand, lack of recommendation and considering the influenza vaccine as not necessary were the main reasons for not getting vaccinated. In addition, health personnel stood out as the main source of information (32.9%) compared to traditional media (26.9%) and public administration (12.3%). This study aimed to assess and analyse the factors influencing willingness to receive influenza vaccines in the COVID-19 era among Spanish adults, as well as the main information channels and strategies to encourage vaccination.

ABO blood group system modulates the inflammatory response and has been implicated in COVID-19. Group O protects against SARS-CoV-2 infection, but there are no data regarding post-COVID-19 syndrome (PCS). Our aim was to assess this possible association.Case-control study in a community setting, with subjects who had experienced mild COVID-19. Cases were PCS+, controls were PCS-, and the exposure variable, group O. We collected age, sex, BMI, smoking, comorbidities, inflammatory markers, anti-SARS-CoV-2 IgG antibodies, blood type and clinical data. Five composite inflammatory indices were developed. Multivariate analyses were performed.We analysed 121 subjects (56.2% women), mean age 45.7 ± 16 years. Blood group frequencies were 41.5%, 7.9%, 5.9%, and 44.5% for A, B, AB and O, respectively. Thirty-six patients were PCS+, without significant differences between cases and controls. Compared to non-O, a higher prevalence of PCS (Group O has shown a consistent relationship with PCS, characterised by a more intense inflammatory burden than the other blood groups. Blood group O could be part of the immunological link between acute COVID-19 and PCS.

Susceptibility to organophosphates was evaluated in 2 populations of Culex quinquefasciatus from the department of Atlantico, Colombia. Bioassays for temephos, malathion, and pirimiphos-methyl were performed with 3rd-stage larvae and adult females of Cx. quinquefasciatus from the municipalities of Soledad and Puerto Colombia, following the methods of the World Health Organization and Centers for Disease Control and Prevention, respectively. The median lethal concentration (LC50) and 90% lethal concentration (LC90) resistance ratios (RRLC50 and RRLC90) were determined for each insecticide in the field populations evaluated, using the Cartagena strain as the susceptible control. Relative to LC50 and LC90 of the Cartagena strain, the population from Puerto Colombia was moderately resistant to temephos (RRLC50 5.7-fold) and malathion (RRLC50 8.6-fold, RRLC90 9-fold) and susceptible to pirimiphos-methyl (RRLC50 and RRLC90 < 5-fold). The population from Soledad was susceptible to temephos and pirimiphos-methyl (RRLC50 and RRLC90 < 5-fold) and showed moderate resistance to malathion (RRLC50 7.5-fold). It is important to emphasize that routine monitoring of insecticide resistance in Cx. quinquefasciatus helps us detect resistance early and improve the effectiveness of control strategies.

Prolactin (PRL) is a pleiotropic hormone with a key role in pregnancy. In fetal membranes, PRL can regulate the secretion of pro-inflammatory factors, which induces the activation of matrix metalloproteinases (MMPs). The increase and activation of MMPs deregulate the turnover of the extracellular matrix in the fetal membranes, altering its structure and function, causing premature rupture of the membranes and preterm labor. In this work, we evaluate the effect of PRL upon the secretion of MMP-1, MMP-2, MMP-9, MMP-13, and the tissue inhibitors of metalloproteinases (TIMPs) in human fetal membranes after lipopolysaccharide (LPS) challenge. Nine fetal membranes from healthy non-laboring cesarean deliveries at term were cultured in a 2-independent chamber system and pre-treated with 250, 500, 1000 or 4000 ng/ml of PRL for 24 h, then choriodecidual region was stimulated with 500 ng/ml of LPS plus fresh PRL for 24 h. The MMPs and TIMPs secretion were quantified by ELISA, additionally MMP-2 and MMP-9 gelatinolytic activity was measured by zymography. LPS induced the MMP-9 and MMP-1 secretion, but no MMP-2 or MMP-13 in comparison with basal levels. PRL co-treatment decreased the MMP-2, MMP-9 and MMP-1 secretion induced by LPS. The active forms were present in the tissue extract, showing a response consistent with the secretion profile. TIMP-1 and TIMP-2 secretion was decreased after LPS treatment and the PRL co-treatment reverts this effect. The present results support that PRL may favor the balance between these factors involved in the structural maintenance of fetal membranes in an inflammatory event.

INTRODUCTION Early graft loss is a devastating kidney transplant complication associated with high mortality and an increased risk of sensitization to antigens from the failed graft. Moreover, if rapid re-transplantation were to occur, given that the human leukocyte antigen antibodies identification may not be reliable until several weeks after transplantation, the recipient's immunological status would be uncertain. Hence, there could be an increased immunological risk. To date, there is no information on whether a rapid re-transplantation after early graft loss, without a new reliable anti-HLA determination, is safe. METHODS We retrospectively analysed the number of rejections and the graft survival of re-transplanted patients with early graft loss (defined as graft failure before 30 days from transplant) from our centre between June 2003 and November 2019. The studied population was divided into rapid re-transplantation (performed within 30 days of early graft loss) and late re-transplantation (performed beyond those 30 days). RESULTS Forty-seven patients were re-transplanted after early graft loss. There were nine rapid re-transplantation cases with an 89% five-year graft survival and one antibody-mediated rejection episode. Furthermore, we identified 38 cases of late re-transplantation with a 69% five-year graft survival, 4 T cell-mediated, and 11 antibody-mediated rejections. CONCLUSIONS Rapid re-transplantation appears to be safe and does not entail increased rejection risk, nor does it impact long-term graft survival when compared to late re-transplantation.

Vitamin D has shown to play a role in multiple diseases due to its skeletal and extraskeletal actions. Furthermore, vitamin D deficiency has become a worldwide health issue. Few supplementation guidelines mention calcifediol treatment, despite being the direct precursor of calcitriol and the biomarker of vitamin D status. This 1-year, phase III-IV, double-blind, randomized, controlled, multicenter clinical trial assessed the efficacy and safety of calcifediol 0.266 mg soft capsules in vitamin D-deficient postmenopausal women, compared to cholecalciferol. Results reported here are from a prespecified interim analysis, for the evaluation of the study's primary endpoint: the percentage of patients with serum 25-hydroxyvitamin D (25(OH)D) levels above 30 ng/ml after 4 months. A total of 303 patients were enrolled, of whom 298 were included in the intention-to-treat (ITT) population. Patients with baseline levels of serum 25(OH)D

Background: The molecular mechanisms underlying the potential health benefits of a ketogenic diet are unknown and could be mediated by epigenetic mechanisms. Objective: To identify the changes in the obesity-related methylome that are mediated by the induced weight loss or are dependent on ketosis in subjects with obesity underwent a very-low calorie ketogenic diet (VLCKD). Methods: Twenty-one patients with obesity (n ¼ 12 women, 47.9 ± 1.02 yr, 33.0 ± 0.2 kg/m2 ) after 6 months on a VLCKD and 12 normal weight volunteers (n ¼ 6 women, 50.3 ± 6.2 yrs, 22.7 ± 1.5 kg/m2 ) were studied. Data from the Infinium MethylationEPIC BeadChip methylomes of blood leukocytes were obtained at time points of ketotic phases (basal, maximum ketosis, and out of ketosis) during VLCKD (n ¼ 10) and at baseline in volunteers (n ¼ 12). Results were further validated by pyrosequencing in representative cohort of patients on a VLCKD (n ¼ 18) and correlated with gene expression. Results: After weight reduction by VLCKD, differences were found at 988 CpG sites (786 unique genes). The VLCKD altered methylation levels in patients with obesity had high resemblance with those from normal weight volunteers and was concomitant with a downregulation of DNA methyltransferases (DNMT)1, 3a and 3b. Most of the encoded genes were involved in metabolic processes, protein metabolism, and muscle, organ, and skeletal system development. Novel genes representing the top scoring associated events were identified, including ZNF331, FGFRL1 (VLCKD-induced weight loss) and CBFA2T3, C3orf38, JSRP1, and LRFN4 (VLCKD-induced ketosis). Interestingly, ZNF331 and FGFRL1 were validated in an independent cohort and inversely correlated with gene expression. Conclusions: The beneficial effects of VLCKD therapy on obesity involve a methylome more suggestive of normal weight that could be mainly mediated by the VLCKD-induced ketosis rather than weight loss. This work was supported by the PronoKal Group® and grants from the Fondo de Investigacion Sanitaria as well as PI17/01287, PI20/00628 and PI20/00650 research projects and CIBERobn from the Instituto de Salud Carlos III (ISCIII)-Subdireccion General de Evaluacion y Fomento de la Investigación; Fondo Europeo de Desarrollo Regional (FEDER) Ana B Crujeiras is funded by a research contract “Miguel Servet” (CP17/00088) from the ISCIII, co-financed by the European Regional Development Fund (FEDER) and Xunta de Galicia-GAIN (IN607B2020). The funding source had no involvement in the study design or interpretation of the results

BACKGROUND AND AIM Atrial fibrillation is a major cause of death and disability due to stroke. Vitamin K antagonist drugs are effective for prevention, but they have a narrow therapeutic range and multiple pharmacological interactions. In recent years, new therapeutic alternatives have been searched to minimize complications. The main objective is to evaluate the risk of gastrointestinal bleeding in anticoagulated patients and compare the classic treatment with new anticoagulants. METHODS We conducted a retrospective cohort study to determine the risk of gastrointestinal bleeding in patients treated with acenocoumarol/dabigatran/rivaroxaban, between 2012 and 2016. We compared the classic with the new anticoagulant group, and a multivariate logistic regression analysis was used to determinate the risk factors of gastrointestinal bleeding. RESULTS A total of 1213 patients were selected, 52.7% male patients, a mean age of 72.6 years old (± 14.563). 73.6% had atrial fibrilation. 14.5% of patients used acetylsalicylic acid, and 4% clopidogrel. 67.2% had a high-risk CHADS-2 Score, and 36.9% a high-risk HAS-BLED Score. We determined a 5.6% (68) of gastrointestinal bleeding, without differences according to anticoagulant used. The multivariate model showed a greater risk for digestive hemorrhage in patients with a previous hemorrhagic event (odds ratio [OR] = 2.422 95% confidence interval [CI]: 1.101-5.327) and the concomitant therapy with clopidogrel (OR = 2.373 95% CI: 0.996-5.652). CONCLUSIONS No differences were found in the risk of gastrointestinal bleeding between the different anticoagulants. A previous gastrointestinal bleeding were considered independent risk factor. The HAS-BLED score should be taken into account to make clinical decisions about to prescribe anticoagulant treatment.

• Several cardiovascular/hemostatic disturbances haves been reported in patients with COVID-19, but the real frequency and their potential association with the pathogenic mechanisms of SARS-CoV-19 still remain to be defined. • We investigated the relative frequency of acute coronary syndrome, deep venous thrombosis, pulmonary embolism, stroke and upper gastrointestinal bleeding in COVID patents attending emergency departments (EDs), before hospitalization and compared them with frequencies in the general ED population attending 50 Spanish EDs. • We found that the risk of pulmonary embolism is clearly increased in COVID patients, with an OR of 4.53 with respect to non-COVID patients (95% confidence interval 4.03- 5.10). Additionally, the diagnosis of pulmonary embolism was 2 fold more frequent among ED comers in 2020 compared to 2019, suggesting a SARS-CoV-2 role in such increment of cases.. The remaining entities studied were not found to be unequivocally increased in the present study and need further investigation.

Objectives: To picture the psychological impact on the general population consulting the Emergency Medical System (EMS) of Catalonia for psychological assistance due to the COVID-19.Methods: Calls received to the 061 emergency phone number between the months of March and June 2020 (period of lockdown and de-escalation) were analyzed. The reason, most prevalent psychological symptoms, presence of psychological antecedents, and type of intervention that was carried out were analyzed.Results: A total of 2,516 calls were analyzed. Weeks 6, 7, 8 and 9 of lockdown saw the highest volume of calls (298, 314, 282 and 290 daily calls, respectively). The main profile of the affected person was women, under the age of 50 who are responsible for others. Psychologically, they present symptoms of depression (7.33%) and anxiety (39.44%). The greatest impacts on mental health throughout lockdown seem to be related to an increase of interpersonal conflict (8.8% < 11.2%), work-related problems (1.7% < 4.6%), and problems of psychological distress (6.5% < 17.0%).Conclusion: The information obtained enables us to better understand the possible evolution of the impacts on mental health derived from the lockdown.

To examine glycaemic status, and the impact of at-admission HbA1c levels on outcome, in a large group of participants hospitalized for COVID-19.We inclued 515 participants with confirmed COVID-19 infection, with or without known diabetes, who met the following additional criteria: 1) age 18 years, 2) HbAMean age was 70 years, 98.8% were of white race, 49% were female, 31% had known diabetes (KD), an additional 7% met the HbA1c criterion for diabetes, and 13.6% died. In participants with KD, FPG and HbA1c levels were not associated with mortality in adjusted analyses; however, in participants without KD, whereas FPG showed direct association with mortality, HbA1c showed slight inverse association.There was a very high prevalence of people without KD with HbA1c levels above normal at-admission. This alteration does not seem to have been related to blood glucose levels.

Objective: To describe the population of patients with cleft lip and/or palate (CL/P) in terms of cleft phenotypes, gender, age, ethnic group, family history, clinical presentation (syndromic vs nonsyndromic), some environmental and behavioral factors, and some clinical features. Design: Descriptive retrospective study. Setting: Patients attending the genetics counseling practice in Operation Smile Foundation, Bogotá, Colombia, for over 8 years. Participants: No screening was conducted. All patients requiring clinical genetics assessment in Operation Smile Foundation were included in the study. Results: Left cleft lip and palate (CLP) and nonsyndromic forms were the most frequent types of malformations in this population. Psychomotor retardation and heart disease were the most frequent comorbidities in these patients. A low proportion of mothers exposed to passive smoking during pregnancy was observed and low birth weight accounted for an important number of cases. Aarskog, velocardiofacial, and orofaciodigital syndromes were the most frequent syndromic forms of CLP in this population. Conclusions: In this study, the most frequent type of CL/P was the nonsyndromic complete left CLP. Aarskog, velocardiofacial, and orofaciodigital syndromes were the most frequent syndromic forms of CL/P in this population.

Objectives Postpartum mothers with gestational diabetes may remain with either type 2 diabetes mellitus, impaired glucose tolerance or impaired fasting glucose. Our aim in this study was to identify maternal variables that could predict 1 or more of these conditions. Methods In 193 singleton pregnancies with gestational diabetes, we applied bivariate logistic regression and receiver-operating characteristic curves to data from the index glucose-challenge test that allowed the diagnosis of gestational diabetes. Results Receiver-operating characteristic curves of fasting glucose from the index glucose-challenge test predicted impaired fasting glucose and type 2 diabetes mellitus combined, with a sensitivity of 100%, false-positive rate of 40.5%, area under the curve of 0.849, p=0.004 and positive predictive value 45%, and with a cutoff point of 4.7 mmol/L. Conclusions At the time of diagnosis of gestational diabetes during pregnancy, a basal glucose level of ≥4.7 mmol/L on index glucose-challenge test indicates a 45% probability of either type 2 diabetes mellitus or impending diabetes early postpartum.

Obesity and Gestational Diabetes Mellitus (GDM) are the most frequent pathologies affecting mothers and offspring during pregnancy. Both conditions have shown a sustained increase in their prevalence in recent years, and they worsen the outcome of pregnancy and the long-term health of mothers. Obesity increases the risk of GDM and pre-eclampsia during pregnancy and elevates the risk of developing metabolic syndrome in later life. Offspring of obese mothers have an increased risk of obstetric morbidity and mortality and, consistent with the developmental origins of health and disease, a long term risk of childhood obesity and metabolic dysfunction. On the other hand, GDM also increases the risk of pre-eclampsia, caesarean section, and up to 50% of women will develop type 2 diabetes later in life. From a fetal point of view, it increases the risk of macrosomia, large-for-gestational-age fetuses, shoulder dystocia and birth trauma. The insulin resistance and inflammatory mediators released by a hypoxic trophoblast are mainly responsible for the poor pregnancy outcome in obese or GDM patients. The adequate management of both pathologies includes modifications in the diet and physical activity. Drug therapy should be considered when medical nutrition therapy and moderate physical activity fail to achieve treatment goals. The antenatal prediction of macrosomia is a challenge for physicians. The timing and the route of delivery should consider adequate metabolic control, gestational age, and optimal conditions for a vaginal birth. The best management of these pathologies includes pre-conception planning to reduce the risks during pregnancy and improve the quality of life of these patients.

Introduction: COVID-19 is a highly contagious disease that has easily spread worldwide. Outpatient maintenance hemodialysis seems to entail an increased risk of contagion, and previous reports inform of increased mortality among this population. Methods: We retrospectively analyzed clinical and laboratory parameters, outcomes, and management once discharged of CKD-5D patients infected with SARS-CoV-2 from our health area. Results: Out of the 429 CKD-5D population, 36 were diagnosed with SARS-CoV-2 infection (8%): 34 on in-center hemodialysis and 2 on peritoneal dialysis. Five were asymptomatic. The most common symptom was fever (70%), followed by dyspnea and cough. History of cardiovascular disease and elevation of LDH and C-reactive protein during admission were associated with higher mortality. Thirteen patients died (36%), 8 patients were admitted to an ICU, and survival was low (38%) among the latter. The mean time to death was 12 days. Most discharged patients got negative rRT-PCR in nasopharyngeal swabs within 26 days of diagnosis. However, there is a portion of cured patients that continue to have positive results even more than 2 months after the initial presentation. Conclusions: Patients on dialysis have an increased mortality risk if infected with SARS-CoV-2. Preventive measures have proven useful. Thus, proper ones, such as universal screening of the population and isolation when required, need to be generalized. Better de-isolation criteria are necessary to ensure an appropriate use of public health resources.

Background The role of vitamin D status in COVID-19 patients is a matter of debate. Objectives To assess serum 25-hydroxyvitamin D (25OHD) levels in hospitalized patients with COVID-19 and to analyze the possible influence of vitamin D status on disease severity. Methods Retrospective case–control study of 216 COVID-19 patients and 197 population-based controls. Serum 25OHD levels were measured in both groups. The association of serum 25OHD levels with COVID-19 severity (admission to the intensive care unit, requirements for mechanical ventilation, or mortality) was also evaluated. Results Of the 216 patients, 19 were on vitamin D supplements and were analyzed separately. In COVID-19 patients, mean ± standard deviation 25OHD levels were 13.8 ± 7.2 ng/mL, compared with 20.9 ± 7.4 ng/mL in controls (P Conclusions 25OHD levels are lower in hospitalized COVID-19 patients than in population-based controls and these patients had a higher prevalence of deficiency. We did not find any relationship between vitamin D concentrations or vitamin deficiency and the severity of the disease.

The prevalence of pediatric respiratory diseases in Spain is 23%. Inhalation is the preferred route of administration but there are frequent errors in the performance of the inhalation technique leading a poor control of the disease. The aim of this research was to detect errors in the execution of the inhalation technique at a Pediatric Pulmonology Unit in a hospital of Aragón (Spain). In order to improve the administration of inhaled medication, an educational intervention for 1 year by nursing was conducted. This interventional study, including children aged 1 to 15 years with an inhalation therapy and who attended the Pediatric Pulmonology Unit, was conducted between September 2017 and September 2018. Logistic Regression models were conducted in SPSS. This study involved 393 children (61.1% boys). Before the intervention, 39.4% achieved a correct inhalation technique increasing up to 62.1% after the intervention. Those who had their first visit to the Unit, young children and girls had a higher risk of incorrect performance than those with subsequent visits, older children, and boys, respectively. The most common errors in the inhalation technique were not performing adequate apnoea after inhaling and not rinsing the mouth at the end of the procedure. The education given by nurses to pediatric patients improved the inhalation technique, achieving better control of the disease and use of the health system. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Aminobisphosphonates are widely used in the treatment of osteoporosis. They have a high affinity for hydroxyapatite, binding primarily to resorbing surfaces, but also to forming surfaces and to some extent to resting surfaces. They inhibit osteoclasts, thereby decreasing remodelling units. Consequently, they increase bone mass and reduce stress risers. This decreases the risk of fractures. If this decrease is sufficient, they can be temporarily withdrawn (drug holidays), which prevents serious complications (atypical femoral fracture). They probably reduce mortality. Virtually all patients with osteoporosis can benefit from them at some point in the course of their disease (at the beginning of treatment or after the administration of anabolics, selective estrogen receptor modulators or denosumab). If well tolerated orally, alendronate and risedronate are preferable. Otherwise, zoledronate is preferred. Their efficacy vs. cost-safety-convenience ratio makes aminobisphosphonates reference drugs in the field of osteoporosis.