Search

Background: X-linked hypophosphatemia (XLH) is a rare disorder characterized by elevated levels of fibroblast growth factor 23 (FGF-23), leading to hypophosphatemia and complications in diagnosis due to its clinical heterogeneity. Metabolomic analysis, which examines metabolites as the final products of cellular processes, is a powerful tool for identifying in vivo biochemical changes, serving as biomarkers of pathological abnormalities, and revealing previously uncharted metabolic pathways., Methods: A multicenter cross-sectional case-control study of adult patients diagnosed with XLH was conducted. Serum metabolomic analysis was performed with an Ultra-Performance Liquid Chromatography equipment (UPLC) coupled to a high-resolution mass spectrometer (MS). An analysis of metabolic pathways using MetaboAnalyst version 5.0 and a quantitative enrichment analysis (QEA) was performed. We employed multivariate statistical models, including a principal component analysis (PCA) and an orthogonal partial least squares discriminant analysis (OPLS-DA) regression model., Results: A cohort of 20 XLH patients and 19 control subjects were recruited. A total of 104 metabolites were identified. The differential metabolites identified included glycine, taurine, hypotaurine, phosphoethanolamine, pyruvate, guanidoacetic acid, serine, succinate, 2-aminobutyric acid, glutamine, 2-hydroxyvaleric acid, methionine, ornithine, phosphorylcholine, hypoxanthine, lysine, and N-methylnicotinamide. Enrichment analysis identified disturbances in key metabolic pathways, including phosphatidylethanolamine biosynthesis, sphingolipid metabolism, and phosphatidylcholine biosynthesis. Additionally, pathways related to cysteine metabolism, glycolysis, and pyruvate metabolism., Conclusions: This study identified significant differences in the metabolic profiles of individuals with XLH compared to healthy controls. These findings enhance understanding of potential pathogenic mechanisms and offer a metabolic basis for further in-depth investigations into XLH.

Background: Hereditary transthyretin amyloidosis (ATTRv) is an autosomal-dominant systemic disease, where amyloid fibrils accumulate especially in the peripheral and autonomic nervous systems and in the heart. The aim of the present work was to outline the follow-up and type of management received by asymptomatic carriers (ACs) and Coutinho stage 1 ATTRv patients in Spain. Methods: A cross-sectional, non-interventional study was conducted throughout seven experienced hospitals in Spain. A total of 86 ACs without neurological symptoms and 19 Coutinho stage 1 ATTRv patients diagnosed 12 months before their enrollment were included. Clinical and demographic data, red flags, and neurological and cardiological evaluations were gathered. In addition, site variables were collected from four centers to describe the clinical management of ATTRv. Results: ATTRv clinical management varied depending on the center setting but was primarily overseen by neurology and internal medicine, which were responsible for the holistic follow-up of ACs and patients. Routinely, neurologists, neurophysiologists, cardiologists, and internal medicine conducted the follow-up. Specialties involved in initial AC assessment were neurophysiologists and cardiologists in 100% of cases, neurologists (75%), internists and geneticists (50%), and ophthalmologists (25%). A review of the medical tests performed proved an exhaustive management of the study population. Stable patients were followed up every 6 months, while those under evolution were monitored every 3-6 months. The frequency of monitoring of ACs was annual, and carriers classified with doubtful disease onset were visited every 3-6 months. Conclusions: The EMPATIa study provides valuable insights into the management of ATTRv in a real-world clinical setting in highly experienced hospitals in Spain. It demonstrates that multidisciplinary practice and enhanced disease awareness may lead to a reduction in diagnostic delay.

Background/objectives: The direct bridge to urgent heart transplant (HT) with venoarterial extracorporeal membrane oxygenation (VA-ECMO) support has been associated with high morbidity and mortality. The objective of this study is to analyze the morbidity and mortality of patients transplanted with VA-ECMO and compare the presumed differences between various eras over a 17-year timeline., Methods: This is a prospective, observational study on consecutive patients stabilized with VA-ECMO and transplanted with VA-ECMO from July 2007 to December 2023 at a reference center (98 patients). Objective variables were mortality and morbidity from renal failure, venous thromboembolic disease (VTD), primary graft dysfunction (PGD), the need for tracheostomy, severe myopathy, reoperation, post-transplant ECMO, vascular complications, and sepsis/infection., Results: The percentage of patients who reached transplantation without the need for mechanical ventilation has increased over the periods studied. No significant differences were found between the study periods in 30-day mortality ( p = 0.822), hospital discharge ( p = 0.972), one-year mortality ( p = 0.706), or five-year mortality ( p = 0.797). Survival rates in these periods were 84%, 75%, 64%, and 61%, respectively. Comorbidities were very frequent, with an average of 3.33 comorbidities per patient. The most frequent were vascular complications (58%), the need for post-transplant ECMO (57%), and myopathy (55%). The development of myopathy and the need for post-transplant ECMO were higher in recent periods ( p = 0.004 and p = 0.0001, respectively)., Conclusions: VA-ECMO support as a bridge to HT allows hospital discharge for 3 out of 4 transplanted patients. This survival rate has not changed over the years. The comorbidities associated with this device are frequent and significant.

Third-trimester ultrasound has low sensitivity to small for gestational age (SGA) and adverse perinatal outcomes (APOs). The objective of this study was to compare, in terms of cost-effectiveness, two routine third-trimester surveillance protocols for the detection of SGA and evaluate the added value of a Doppler study for the prediction of APO. This was a retrospective observational study of low-risk pregnancies that were followed by a two growth scans protocol (P2) at 32 and 38 weeks or by a single growth scan at 36 weeks (P1). Ultrasound scans included an estimated fetal weight (EFW) in all cases and a Doppler evaluation in most cases. A total of 1011 pregnancies were collected, 528 with the P2 protocol and 483 with the P1 protocol. While the two models presented no differences for the detection of SGA in terms of sensitivity (47.89% vs. 50% p = 0.85) or specificity (94.97 vs. 95.86% p = 0.63), routine performance of two growth scans (P2) led to a 35% cost increase. The accuracy of EFW for the detection of SGA showed a noteworthy improvement when reducing the interval to labor, and the only parameter with predictive capacity of APO was the cerebroplacental ratio at 38 weeks. In low-risk pregnancies, the higher costs of a two-scan growth surveillance protocol at the third trimester are not justified by an increase in diagnostic effectivity.

Heavy metals (HMs) are natural elements present in the Earth's crust, characterised by a high atomic mass and a density more than five times higher than water. Despite their origin from natural sources, extensive usage and processing of raw materials and their presence as silent poisons in our daily products and diets have drastically altered their biochemical balance, making them a threat to the environment and human health. Particularly, the food chain polluted with toxic metals represents a crucial route of human exposure. Therefore, the impact of HMs on human health has become a matter of concern because of the severe chronic effects induced by their excessive levels in the human body. Chelation therapy is an approved valid treatment for HM poisoning; however, despite the efficacy demonstrated by chelating agents, various dramatic side effects may occur. Numerous data demonstrate that dietary components and phytoantioxidants play a significant role in preventing or reducing the damage induced by HMs. This review summarises the role of various phytochemicals, plant and herbal extracts or probiotics in promoting human health by mitigating the toxic effects of different HMs.

(1) Background: High dose gradients and manual steps in brachytherapy treatment procedures can lead to dose errors which make the use of in vivo dosimetry (IVD) highly recommended for verifying brachytherapy treatments. A new procedure was presented to obtain a calibration factor which allows fast and robust calibration of plastic scintillation detector (PSD) probes for the geometry of a compact phantom using Monte Carlo simulations. Additionally, characterization of PSD energy, angular, and temperature dependences was performed. (2) Methods: PENELOPE/PenEasy code was used to obtain the calibration factor. To characterize the energy dependence of the PSD, the signal was measured at different radial and transversal distances. The sensitivity to the angular position was characterized in axial and azimuthal planes. (3) Results: The calibration factor obtained allows for an absorbed dose to water determination in full scatter conditions from ionization measured in a mini polymethylmethacrylate (PMMA) phantom. The energy dependence of the PSD along the radial distances obtained was (2.3 ± 2.1)% ( k = 1). The azimuthal angular dependence measured was (2.6 ± 3.4)% ( k = 1). The PSD response decreased by (0.19 ± 0.02)%/°C with increasing detector probe temperature. (4) Conclusions: The energy, angular, and temperature dependence of a PSD is compatible with IVD.

Introduction: Rehabilitation can improve outcomes after reverse shoulder arthroplasty (RSA). However, low adherence to rehabilitation and compliance rates are some of the main barriers. To address this public health issue, the goal of this research was to pilot test and evaluate the effectiveness of a chatbot to promote adherence to home rehabilitation in patients undergoing RSA., Methods: A randomized pilot trial including patients undergoing RSA and early postoperative rehabilitation was performed. The control group received standard home rehabilitation; the experimental group received the same intervention supervised with a chatbot, with automated interactions that included messages to inform, motivate, and remember the days and exercises for 12 weeks. Compliance with rehabilitation and clinical measures of shoulder function, pain, and quality of life were assessed., Results: 31 patients (17 experimental) with an average age of 70.4 (3.6) completed the intervention. Compliance was higher in the experimental group (77% vs. 65%; OR95% = 2.4 (0.5 to 11.4)). Statistically significant between-group differences with a CI of 95% were found in the QuickDASH questionnaire and self-reported quality of life. No differences were found in the rest of the measures., Conclusions: This pilot study suggests that the chatbot tool can be useful in promoting compliance with early postoperative home rehabilitation in patients undergoing RSA. Future randomized trials with adequate power are warranted to determine the clinical impact of the proposal.

The lockdown and de-escalation process following the COVID-19 pandemic led to a period of new normality. This study aimed to assess the confinement impact on the mental health of peripartum women, as their psychological well-being may be particularly vulnerable and thus affect their offspring's development. A cross-sectional epidemiological study was conducted among women who gave birth during strict confinement (G0) and the new normality period (G1), in which a self-administered paper-based questionnaire assessed 15 contextual factors and the General Health Questionnaire-12 (GHQ-12). For each item, it was verified whether the positive screening rate differed in each confinement phase, and a risk factor study was conducted. For G0, significantly higher positive screening and preterm birth rates were observed in the positive screening group. In the case of G1, maternal age (>35 years), decreased physical activity, and normal weight were found to be protective factors against distress. This study underscores the heightened mental health risk for postpartum women during major psychosocial upheavals (war, economic crisis, natural disasters, or pandemics), along with their resilience as the positive screening rate decreases with the new normality. Findings encourage adopting strategies to identify high-risk women and promote effective measures, such as promoting physical activity.

Within the practice of pain management, one of the most commonly encountered events is low back pain. Lumbar radiculopathy (LR) is a pain syndrome caused by the compression or irritation of the nerve roots in the lower back due to lumbar disc herniation, vertebra degeneration, or foramen narrowing. Symptoms of LR include low back pain that propagates toward the legs, numbness, weakness, and loss of reflexes. The aim of this study is to assess the long-term effectiveness of quantum molecular resonance disc decompression and its combination with a percutaneous microdiscectomy using Grasper© forceps (QMRG) in patients with persistent lumbar radiculopathy (LR) in relation to patient physical stress status. The main outcome measures of this prospective observational study were DN4, NRS, ODI, SF12, PGI, CGI, and MOS Sleep Scale. An improvement 12 months post-intervention was observed in patients without physical stress, presenting better overall results. The mean change was over the minimal clinically important difference in 64.3% of outcome measures studied for the whole sample. QMRG appears to be an effective treatment option for LR, but a reduction in physical stress is needed to ensure long-term effectiveness.

Broadly neutralizing antibodies (bnAbs) bind and neutralize diverse HIV isolates and demonstrate protective effects in primate models and humans against specific isolates. To develop an effective HIV vaccine, it is widely believed that inducing these antibodies is crucial. However, the high somatic hypermutation in bnAbs and the limited affinity of HIV Env proteins for bnAb germline precursors suggest that extended antigen exposure is necessary for their production. Consequently, HIV vaccine research is exploring complex sequential vaccination strategies to guide the immune response through maturation stages. In this context, the exploration of the factors linked to the generation of these antibodies across diverse age groups becomes critical. In this study, we assessed the anti-HIV-1 neutralization potency and breadth in 108 aviremic adults and 109 aviremic children under 15 years of age who were receiving ART. We used a previously described minipanel of recombinant viruses and investigated the factors associated with neutralization in these individuals. We identified individuals in both groups who were capable of neutralizing viruses from three different subtypes, with greater cross-neutralization observed in the adult group (49.0% vs. 9.2%). In both groups, we observed an inverse association between neutralization breadth and the CD4+/CD8+ ratio, as well as a direct association with the time to ART initiation. However, we found no association with time post-infection, cumulative ART duration, or CD8+ cell levels. The present study demonstrates that children receiving antiretroviral therapy generate broadly neutralizing responses to HIV-1, albeit with lower magnitude compared to adults. We also observed that neutralization breadth is associated with CD4+/CD8+ levels and time to treatment initiation in both children and adults living with HIV-1. Our interpretation of these results is that a delay in ART initiation could have prolonged the antigenic stimulation associated with viral replication and thus facilitate the capacity to elicit long-lasting broadly neutralizing responses. These results corroborate prior findings that show that HIV-1-neutralizing responses can persist for years, even at low antigen levels, implying an HIV-1 vaccine may induce lasting neutralizing antibody response.

Scalp melanomas (SM) have been previously associated with poor overall and melanoma-specific survival rates. The aim of this study was to describe and compare the clinicopathological characteristics and survival outcomes of SM and non-scalp cutaneous head and neck melanoma (CHNM). An observational multi-center retrospective study was designed based on patients with CHNM followed in two tertiary care hospitals. A hundred and fifty-two patients had CHNM, of which 35 (23%) had SM. In comparison with non-scalp CHNM, SM were more frequently superficial spreading and nodular subtypes, had a thicker Breslow index median (2.1 mm vs. 0.85 mm), and a higher tumor mitotic rate (3 vs. 1 mitosis/mm 2 ) ( p < 0.05). SM had a higher risk of recurrence and a higher risk of melanoma-specific death ( p < 0.05). In the multivariate analysis, scalp location was the only prognostic factor for recurrence, and tumor mitotic rate was the only prognostic factor for melanoma-specific survival. We encourage routinely examining the scalp in all patients, especially those with chronic sun damage.

Cardiac resynchronization therapy (CRT) via biventricular pacing (BiVP-CRT) is considered a mainstay treatment for symptomatic heart failure patients with reduced ejection fraction and wide QRS. However, up to one-third of patients receiving BiVP-CRT are considered non-responders to the therapy. Multiple strategies have been proposed to maximize the percentage of CRT responders including two new physiological pacing modalities that have emerged in recent years: His bundle pacing (HBP) and left bundle branch area pacing (LBBAP). Both pacing techniques aim at restoring the normal electrical activation of the ventricles through the native conduction system in opposition to the cell-to-cell activation of conventional right ventricular myocardial pacing. Conduction system pacing (CSP), including both HBP and LBBAP, appears to be a promising pacing modality for delivering CRT and has proven to be safe and feasible in this particular setting. This article will review the current state of the art of CSP-based CRT, its limitations, and future directions.

Wilson disease (WD) is a rare copper metabolism disorder caused by mutations in the ATP7B gene. It usually affects young individuals and can produce hepatic and/or neurological involvement, potentially affecting health-related quality of life (HRQoL). We assessed HRQoL in a cohort of Spanish patients with WD and evaluated disease impact on several domains of patients' lives, treatment adherence, drug preference and satisfaction, and healthcare resource utilisation in a cross-sectional, retrospective, multicentric, observational study. A total of 102 patients were included: 81.4% presented isolated liver involvement (group H) and 18.6% presented neurological or mixed involvement (group EH). Up to 30% of patients reported a deteriorated emotional status with anxiety and depression, which was greater in the EH subgroup; the use of neuropsychiatric drugs was high. Over 70% of the patients were satisfied with their current treatment but complained about taking too many pills, stating they would consider switching to another more patient-friendly treatment if available. The Simplified Medication Adherence Questionnaire revealed only 22.5% of patients were fully adherent to therapy, suggesting that alternative therapies are needed. This real-world study, even though is highly enriched with hepatic patients and mild disease, shows that WD impacts patients' HRQoL, especially in the emotional domain.

Anthracyclines are widely used in the treatment of many solid cancers, but their efficacy is limited by cardiotoxicity. As the number of pediatric cancer survivors continues to rise, there has been a concomitant increase in people living with anthracycline-induced cardiotoxicity. Accordingly, there is an ongoing need for new models to better understand the pathophysiological mechanisms of anthracycline-induced cardiac damage. Here we generated induced pluripotent stem cells (iPSCs) from two pediatric oncology patients with acute cardiotoxicity induced by anthracyclines and differentiated them to ventricular cardiomyocytes (hiPSC-CMs). Comparative analysis of these cells (CTX hiPSC-CMs) and control hiPSC-CMs revealed that the former were significantly more sensitive to cell injury and death from the anthracycline doxorubicin (DOX), as measured by viability analysis, cleaved caspase 3 expression, oxidative stress, genomic and mitochondrial damage and sarcomeric disorganization. The expression of several mRNAs involved in structural integrity and inflammatory response were also differentially affected by DOX. Functionally, optical mapping analysis revealed higher arrythmia complexity after DOX treatment in CTX iPSC-CMs. Finally, using a panel of previously identified microRNAs associated with cardioprotection, we identified lower levels of miR-22-3p, miR-30b-5p, miR-90b-3p and miR-4732-3p in CTX iPSC-CMs under basal conditions. Our study provides valuable phenotype information for cellular models of cardiotoxicity and highlights the significance of using patient-derived cardiomyocytes for studying the associated pathogenic mechanisms.

Objective: Only a few studies assessing the sleep effects of low doses of melatonin (aMT) have been performed in the past, most of them in adults, and only one in subjects with attention-deficit/hyperactivity disorder (ADHD). The aim of this study was to provide evidence of the changes induced by aMT doses as low as 1 mg in the sleep pattern of pediatric patients with ADHD under treatment with methylphenidate (MPH)., Methods: Children and adolescents (7-15 years) with ADHD who were receiving extended-release MPH were recruited. A seven-week sleep diary was collected prior to starting a four-week treatment with 1 mg of aMT (30 min before bedtime). Seven-day actigraphic assessments of sleep were performed before and after treatment., Results: Twenty-seven patients (17 males, 62.96%) participated in the study, who had been receiving MPH for 1.57 (1.11) months. A significant increase in sleep duration (TST) was observed after one month of treatment (463 (49) min to 485 (41) min; p < 0.040), with nonsignificant improvements in sleep-onset latency (SOL), nocturnal awakenings, or sleep efficiency. Only minor adverse effects were reported., Conclusion: Low doses of melatonin (1 mg) are able to increase TST in children and adolescents with ADHD receiving treatment with psychostimulants, with an adequate tolerability profile. Further placebo-controlled trials adjusting the time of aMT administration to the individual circadian profile should explore the effects of low doses of this hormone to shorten SOL in this population of patients.

Background: Chronic kidney disease (CKD) is a common complication of a non-kidney solid organ transplant (NKSOT). Identifying predisposing factors is crucial for an early approach and correct referral to nephrology., Methods: This is a single-center retrospective observational study of a cohort of CKD patients under follow-up in the Nephrology Department between 2010 to 2020. Statistical analysis was performed between all the risk factors and four dependent variables: end-stage renal disease (ESKD); increased serum creatinine ≥50%; renal replacement therapy (RRT); and death in the pre-transplant, peri-transplant, and post-transplant periods., Results: 74 patients were studied (7 heart transplants, 34 liver transplants, and 33 lung transplants). Patients who were not followed-up by a nephrologist in the pre-transplant ( p < 0.027) or peri-transplant ( p < 0.046) periods and those who had the longest time until an outpatient clinic follow-up (HR 1.032) were associated with a higher risk of creatinine increase ≥50%. Receiving a lung transplant conferred a higher risk than a liver or heart transplant for developing a creatinine increase ≥50% and ESKD. Peri-transplant mechanical ventilation, peri-transplant and post-transplant anticalcineurin overdose, nephrotoxicity, and the number of hospital admissions were significantly associated with a creatinine increase ≥50% and developing ESKD., Conclusions: Early and close follow-up by a nephrologist was associated with a decrease in the worsening of renal function.

Introduction: Transfusion plays a main role in supportive treatment for patients who receive an allogeneic hematopoietic stem cell transplantation (HSCT). In this study, we compare the transfusion requirements of patients undergoing different modalities of HSCT according to different time periods. The objective is to assess the evolution of HSCT transfusion requirements over time, from a single institution., Methods: The clinical charts and transfusion records of patients who underwent HSCT of different modalities at La Fe University Hospital during a twelve-year period were reviewed (2009-2020). For analysis, we divided the overall time into three periods: 1 from 2009 to 2012, 2 from 2013 to 2016 and 3 from 2017 to 2020. The study included 855 consecutive adult HSCT: 358 HLA-matched related donors (MRD), 134 HLA-matched unrelated donors (MUD), 223 umbilical cord blood transplantation (UCBT) and 140 haploidentical transplants (Haplo-HSCT)., Results: There were no significant differences in RBC and PLT requirements or transfusion independence among the three time periods for MUD and Haplo-HSCT. However, the transfusion burden increased significantly for MRD HSCT during the 2017-2020 period., Conclusion: despite HSCT modalities having evolved and changed over time, overall transfusion requirements have not significantly decreased and continue to be a cornerstone of transplantation-supportive care.

Background: This study aims to analyse whether in acute heart failure (AHF) with iron deficiency (ID), the administration of ferric carboxymaltose (FCM) produces a greater benefit in renal dysfunction., Methods: A total of 812 consecutive patients admitted for AHF and ID were studied. Untreated (n:272) and treated (n:540) patients were compared. The six-month prevalence of a combined event (readmission for HF, all-cause death, and emergency department visit for decompensation) was analysed. Three grades of renal dysfunction (KDIGO) were compared, Group 1 (grades 1 and 2), Group 2 (grades 3a and 3b), and Group 3 (grades 4 and 5)., Results: There were differences in sex distribution (untreated group: males 39.7% vs. treated group: males 51.9%; p < 0.001). Sex-adjusted combined event analysis showed a greater benefit in Group 1 (OR: 0.31, 95% CI:0.19-0.5; p < 0.001) and Group 2 (OR: 0.23, 95% CI:0.14-0.38; p < 0.001), but not in Group 3 (OR: 0.51, 95% CI:0.17-0.55; p : 0.237)., Conclusions: The administration of FCM in patients with AHF and ID reduces the combined event analysed. The benefit is greater when renal dysfunction is present, except in very advanced degrees where no significant benefit is obtained.

Hydrosalpinx is a condition with a crucial prognostic role in reproduction, and its diagnosis by a non-invasive technique such as ultrasound is key in achieving an adequate reproductive assessment while avoiding unnecessary laparoscopies. The aim of the present systematic review and meta-analysis is to synthetize and report the current evidence on transvaginal sonography (TVS) accuracy to diagnose hydrosalpinx. Articles on the topic published between January 1990 and December 2022 were searched in five electronic databases. Data from the six selected studies, comprising 4144 adnexal masses in 3974 women, 118 of which were hydrosalpinxes, were analyzed as follows: overall, TVS had a pooled estimated sensitivity for hydrosalpinx of 84% (95% confidence interval (CI) = 76-89%), specificity of 99% (95% CI = 98-100%), positive likelihood ratio of 80.7 (95% CI = 33.7-193.0), and negative likelihood ratio of 0.16 (95% CI = 0.11-0.25) and DOR of 496 (95% CI = 178-1381). The mean prevalence of hydrosalpinx was 4%. The quality of the studies and their risk of bias were assessed using QUADAS-2, evidencing an overall acceptable quality of the selected articles. We concluded that TVS has a good specificity and sensitivity for diagnosing hydrosalpinx.

Historically, donor infection with hepatitis-C virus (HCV) has been a barrier to kidney transplantation. However, in recent years, it has been reported that HCV positive kidney donors transplanted into HCV negative recipients offer acceptable mid-term results. However, acceptance of HCV donors, especially viremic, has not broadened in the clinical practice. This is an observational, multicenter, retrospective study including kidney transplants from HCV positive donors into negative recipients reported to the Spanish group from 2013 to 2021. Recipients from viremic donors received peri-transplant treatment with direct antiviral agents (DAA) for 8-12 weeks. We included 75 recipients from 44 HCV non-viremic donors and 41 from 25 HCV viremic donors. Primary non function, delayed graft function, acute rejection rate, renal function at the end of follow up, and patient and graft survival were not different between groups. Viral replication was not detected in recipients from non-viremic donors. Recipient treatment with DAA started pre-transplant avoids ( n = 21) or attenuates ( n = 5) viral replication but leads to non-different outcomes to post-transplant treatment with DAA ( n = 15). HCV seroconversion was more frequent in recipients from viremic donors (73% vs. 16%, p < 0.001). One recipient of a viremic donor died due to hepatocellular carcinoma at 38 months. Donor HCV viremia seems not to be a risk factor for kidney transplant recipients receiving peri-transplant DAA, but continuous surveillance should be advised.

The fetal-to-neonatal transition poses an extraordinary challenge for extremely low birth weight (ELBW) infants, and postnatal stabilization in the delivery room (DR) remains challenging. The initiation of air respiration and the establishment of a functional residual capacity are essential and often require ventilatory support and oxygen supplementation. In recent years, there has been a tendency towards the soft-landing strategy and, subsequently, non-invasive positive pressure ventilation has been generally recommended by international guidelines as the first option for stabilizing ELBW in the delivery room. On the other hand, supplementation with oxygen is another cornerstone of the postnatal stabilization of ELBW infants. To date, the conundrum concerning the optimal initial inspired fraction of oxygen, target saturations in the first golden minutes, and oxygen titration to achieve desired stability saturation and heart rate values has not yet been solved. Moreover, the retardation of cord clamping together with the initiation of ventilation with the patent cord (physiologic-based cord clamping) have added additional complexity to this puzzle. In the present review, we critically address these relevant topics related to fetal-to-neonatal transitional respiratory physiology, ventilatory stabilization, and oxygenation of ELBW infants in the delivery room based on current evidence and the most recent guidelines for newborn stabilization.

Dental caries is a biofilm-mediated disease that represents a worldwide oral health issue. Streptococcus mutans has been ascertained as the main cariogenic pathogen responsible for human dental caries, with a high ability to form biofilms, regulated by the quorum sensing. Diarylureas represent a class of organic compounds that show numerous biological activities, including the antimicrobial one. Two small molecules belonging to this class, specifically to diphenylureas, BPU (1,3-bis[3,5-bis(trifluoromethyl)phenyl]urea) and DMTU (1,3-di- m -tolyl-urea), showed interesting results in studies regarding the antimicrobial activity against the cariogenic bacterium S. mutans . Since there are not many antimicrobials used for the prevention and treatment of caries, further studies on these two interesting compounds and other diarylureas against S. mutans may be useful to design new effective agents for the treatment of caries with generally low cytotoxicity.

Multiple myeloma is a hematologic neoplasm caused by an uncontrolled clonal proliferation of neoplastic plasma cells (nPCs) in the bone marrow. The development and survival of this disease is tightly related to the bone marrow environment. Proliferation and viability of nPCs depend on their interaction with the stromal cells and the extracellular matrix components, which also influences the appearance of drug resistance. Recapitulating these interactions in an in vitro culture requires 3D environments that incorporate the biomolecules of interest. In this work, we studied the proliferation and viability of three multiple myeloma cell lines in a microgel consisting of biostable microspheres with fibronectin (FN) on their surfaces. We also showed that the interaction of the RPMI8226 cell line with FN induced cell arrest in the G0/G1 cell cycle phase. RPMI8226 cells developed a significant resistance to dexamethasone, which was reduced when they were treated with dexamethasone and bortezomib in combination.

Background: Randomized clinical trials and meta-analyses, primarily from Asian countries, have reported good effectiveness with high-dose dual therapy (HDDT) including a proton pump inhibitor (PPI) and amoxicillin when prescribed as H. pylori first-line or rescue treatment. However, combining amoxicillin with PPIs in the 1990s in several European countries yielded suboptimal results., Methods: An international, multicenter, prospective non-interventional Registry (Hp-EuReg) aimed to evaluate the decisions and outcomes of H. pylori management by European gastroenterologists. All infected adult cases treated with HDDT were registered at e-CRF AEG-REDCap platform until June 2021. Sixty patients were prescribed with HDDT (98% compliance), 19 of them received a first-line therapy and 41 a rescue treatment (second- to sixth-line)., Results: Overall HDDT effectiveness was 52% (per-protocol) and 51% (modified intention-to-treat). First-line and rescue treatment lines were equally effective, but the effectiveness was worse when patients had previously received metronidazole, tetracycline, or rifabutin. Adding bismuth to HDDT in rescue treatment did not yield better results. The incidence of adverse events was 30%, diarrhea being the most common (20% of patients); no serious adverse events were reported., Conclusion: Although HDDT is safe and has good compliance, it is not a good option in European first-line or rescue H. pylori treatment, even when adding bismuth.

(1) Background: In brachytherapy, there are still many manual procedures that can cause adverse events which can be detected with in vivo dosimetry systems. Plastic scintillator dosimeters (PSD) have interesting properties to achieve this objective such as real-time reading, linearity, repeatability, and small size to fit inside brachytherapy catheters. The purpose of this study was to evaluate the performance of a PSD in postoperative endometrial brachytherapy in terms of source dwell time accuracy. (2) Methods: Measurements were carried out in a PMMA phantom to characterise the PSD. Patient measurements in 121 dwell positions were analysed to obtain the differences between planned and measured dwell times. (3) Results: The repeatability test showed a relative standard deviation below 1% for the measured dwell times. The relative standard deviation of the PSD sensitivity with accumulated absorbed dose was lower than 1.2%. The equipment operated linearly in total counts with respect to absorbed dose and also in count rate versus absorbed dose rate. The mean (standard deviation) of the absolute differences between planned and measured dwell times in patient treatments was 0.0 (0.2) seconds. (4) Conclusions: The PSD system is useful as a quality assurance tool for brachytherapy treatments.

In order to harness the potential of metanephroi allotransplantation to the generation of a functional kidney graft on demand, we must achieve further growth post-transplantation. Sildenafil citrate (SC) is widely known as a useful inductor of angiogenesis, offering renoprotective properties due to its anti-inflammatory, antifibrotic, and antiapoptotic effects. Here, we performed a laparoscopic metanephroi allotransplantation after embedding sildenafil citrate into the retroperitoneal fat of non-immunosuppressed adult rabbit hosts. Histology and histomorphometry were used to examine the morphofunctional changes in new kidneys 21 days post-transplantation. Immunofluorescence of E-cadherin and renin and erythropoietin gene expression were used to assess the tubule integrity and endocrine functionality. After the metanephroi were embedded in a 10 µM SC solution, the new kidneys' weights become increased significantly. The E-cadherin expression together with the renin and erythropoietin gene expression revealed its functionality, while histological mature glomeruli and hydronephrosis proved the new kidneys' excretory function. Thus, we have described a procedure through the use of SC that improves the outcomes after a metanephroi transplantation. This study gives hope to a pathway that could offer a handsome opportunity to overcome the kidney shortage.

Background: The frequency of cognitive impairment (CI) reported in neuromyelitis optica spectrum disorder (NMOSD) is highly variable, and its relationship with demographic and clinical characteristics is poorly understood. We aimed to describe the cognitive profile of NMOSD patients, and to analyse the cognitive differences according to their serostatus; furthermore, we aimed to assess the relationship between cognition, demographic and clinical characteristics, and other aspects linked to health-related quality of life (HRQoL). Methods: This cross-sectional study included 41 patients (median age, 44 years; 85% women) from 13 Spanish centres. Demographic and clinical characteristics were collected along with a cognitive z-score (Rao’s Battery) and HRQoL patient-centred measures, and their relationship was explored using linear regression. We used the Akaike information criterion to model which characteristics were associated with cognition. Results: Fourteen patients (34%) had CI, and the most affected cognitive domain was visual memory. Cognition was similar in AQP4-IgG-positive and -negative patients. Gender, mood, fatigue, satisfaction with life, and perception of stigma were associated with cognitive performance (adjusted R2 = 0.396, p < 0.001). Conclusions: The results highlight the presence of CI and its impact on HRQoL in NMOSD patients. Cognitive and psychological assessments may be crucial to achieve a holistic approach in patient care.

Multiple primary melanomas (MPM) refer to the occurrence of more than one synchronous or metachronous melanoma in the same individual. The aim of this study was to identify the frequency of MPM and describe the clinical and histopathologic characteristics of patients with MPM. An observational single-center retrospective study was designed based on a cohort of melanoma patients followed in a tertiary care hospital. Fifty-eight (8.9%) patients developed MPM. Most patients were men (65.5%) and the median age at the time of diagnosis of the first melanoma was 71 years old. The median time of diagnosis of the second melanoma from the first melanoma was 10.9 months, and 77.6% of second melanomas were diagnosed within the first 5 years. In total, 29 (50%) and 28 (48.3%) first and second melanomas were located in the trunk, respectively. Concordance of anatomic site between primary and subsequent melanoma was found in 46.6% of the patients. Proportion of in situ melanomas was increasingly higher in subsequent melanomas (from 36.21% of first melanomas to 100% of fifth melanomas). An increasing rate of melanomas with histological regression was observed within subsequent melanomas (from 60.3% of first melanomas to 80% of third melanomas). Our results support the importance of careful long-term follow-up with total body examination in melanoma patients.

The purpose of this study was to identify clinical, analytical, and sociodemographic variables associated with the need for hospital admission in people over 50 years infected with SARS-CoV-2 and to assess whether diabetes mellitus conditions the risk of hospitalization. A multicenter case-control study analyzing electronic medical records in patients with COVID-19 from 1 March 2020 to 30 April 2021 was conducted. We included 790 patients: 295 cases admitted to the hospital and 495 controls. Under half ( n = 386, 48.8%) were women, and 8.5% were active smokers. The main comorbidities were hypertension (50.5%), dyslipidemia, obesity, and diabetes (37.5%). Multivariable logistic regression showed that hospital admission was associated with age above 65 years (OR from 2.45 to 3.89, ascending with age group); male sex (OR 2.15, 95% CI 1.47-3.15), fever (OR 4.31, 95% CI 2.87-6.47), cough (OR 1.89, 95% CI 1.28-2.80), asthenia/malaise (OR 2.04, 95% CI 1.38-3.03), dyspnea (4.69, 95% CI 3.00-7.33), confusion (OR 8.87, 95% CI 1.68-46.78), and a history of hypertension (OR 1.61, 95% CI 1.08-2.41) or immunosuppression (OR 4.97, 95% CI 1.45-17.09). Diabetes was not associated with increased risk of hospital admission (OR 1.18, 95% CI 0.80-1.72; p = 0.38). Diabetes did not increase the risk of hospital admission in people over 50 years old, but advanced age, male sex, fever, cough, asthenia, dyspnea/confusion, and hypertension or immunosuppression did.

Antibiotic resistance is one of the major challenges that humankind shall face in the short term. (Bacterio)phage therapy is a valuable therapeutic alternative to antibiotics and, although the concept is almost as old as the discovery of phages, its wide application was hindered in the West by the discovery and development of antibiotics in the mid-twentieth century. However, research on phage therapy is currently experiencing a renaissance due to the antimicrobial resistance problem. Some countries are already adopting new ad hoc regulations to favor the short-term implantation of phage therapy in clinical practice. In this regard, the Phage Therapy Work Group from FAGOMA (Spanish Network of Bacteriophages and Transducing Elements) recently contacted the Spanish Drugs and Medical Devices Agency (AEMPS) to promote the regulation of phage therapy in Spain. As a result, FAGOMA was asked to provide a general view on key issues regarding phage therapy legislation. This review comes as the culmination of the FAGOMA initiative and aims at appropriately informing the regulatory debate on phage therapy.

Epidemiological trends show a dramatic increase in the prevalence of fungal infections, and in the isolation of multidrug-resistant species, such as Candida auris. CHROMagar TM Candida (CC; CHROMagar, Paris, France) and other chromogenic media, which are widely used in the clinical laboratory because they allow a rapid identification of most Candida species. Recently, CHROMagar TM Candida Plus (CC-Plus; CHROMagar, Paris, France) was developed to detect and differentiate C. auris in addition to other major clinical Candida species, such as C. albicans , C . tropicalis , C. glabrata , or C. krusei. C. auris colonies display a differential light blue color with a blue halo. A multicentric study was designed to evaluate the performance of the CC-Plus medium in the detection of Candida species in patients' surveillance and environmental samples from three Spanish hospitals with active C. auris outbreaks. A total of 364 patients' surveillance samples and 212 environmental samples were tested. Samples were inoculated in CC and CC-Plus in parallel, and the plates were read at 24 and 48 h. All recovered colonies were presumptively identified according to colony color described by manufacturer, and the definitive identification was performed by mass spectrometry at 48 h. A total of 134 C. auris isolates were obtained (101 from patients' surveillance samples, and 33 from environmental samples). Sensitivity, specificity, and predictive positive and negative values were 99.5%, 100%, 100%, and 99.1%, respectively, for the main clinical Candida species, showing that CC-Plus is comparable to CC, with the advantage of being able to differentiate C. auris from C. parapsilosis . Furthermore, CC-Plus was able to detect one C. albicans , one C. glabrata , and eight C. auris that did not grow in CC. Additionally, the yeast colonies were generally larger, suggesting that this novel medium could be a richer medium, and suitable for surveillance and environmental cultures of C. auris and other clinically relevant Candida species.

Patients with immune-mediated inflammatory diseases (IMIDs), such as rheumatoid arthritis and inflammatory bowel disease, are at increased risk of infection. International guidelines recommend vaccination to limit this risk of infection, although live attenuated vaccines are contraindicated once immunosuppressive therapy has begun. Biologic therapies used to treat IMIDs target the immune system to stop chronic pathogenic process but may also attenuate the protective immune response to vaccines. Here, we review the current knowledge regarding vaccine responses in IMID patients receiving treatment with biologic therapies, with a focus on the interleukin (IL)-12/23 inhibitors. B cell-depleting therapies, such as rituximab, strongly impair vaccines immunogenicity, and tumor necrosis factor (TNF) inhibitors and the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) fusion protein abatacept are also associated with attenuated antibody responses, which are further diminished in patients taking concomitant immunosuppressants. On the other hand, integrin, IL-6, IL-12/23, IL-17, and B-cell activating factor (BAFF) inhibitors do not appear to affect the immune response to several vaccines evaluated. Importantly, treatment with biologic therapies in IMID patients is not associated with an increased risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or developing severe disease. However, the efficacy of SARS-CoV-2 vaccines on IMID patients may be reduced compared with healthy individuals. The impact of biologic therapies on the response to SARS-CoV-2 vaccines seems to replicate what has been described for other vaccines. SARS-CoV-2 vaccination appears to be safe and well tolerated in IMID patients. Attenuated but, in general, still protective responses to SARS-CoV-2 vaccination in the context of certain therapies warrant current recommendations for a third primary dose in IMID patients treated with immunosuppressive drugs.

The treatment strategy of multiple sclerosis (MS) is a highly controversial debate. Currently, there are up to 19 drugs approved. However, there is no clear evidence to guide fundamental decisions such as what treatment should be chosen in first place, when treatment failure or suboptimal response should be considered, or what treatment should be considered in these cases. The "escalation strategy" consists of starting treatment with drugs of low side-effect profile and low efficacy, and "escalating" to drugs of higher efficacy-with more potential side-effects-if necessary. This strategy has prevailed over the years. However, the evidence supporting this strategy is based on short-term studies, in hope that the benefits will stand in the long term. These studies usually do not consider the heterogeneity of the disease and the limited effect that relapses have on the long-term. On the other hand, "early intense therapy" strategy refers to starting treatment with drugs of higher efficacy from the beginning, despite having a less favorable side-effect profile. This approach takes advantage of the so-called "window of opportunity" in hope to maximize the clinical benefits in the long-term. At present, the debate remains open. In this review, we will critically review both strategies. We provide a summary of the current evidence for each strategy without aiming to reach a definite conclusion.

The aim of this cross-sectional study was to explore the spatial extent of pain and its association with clinical symptoms, psychological features, and pain sensitization in people with frozen shoulder (FS). Forty-eight individuals with FS completed pain drawings (PDs) and reported their clinical symptoms including pain intensity (Visual Analogue Scale) and shoulder disability (Shoulder Pain and Disability Index). Moreover, pain sensitization measurements (pressure pain thresholds, temporal summation, conditioned pain modulation, and Central Sensitization Inventory (CSI)) were assessed. Psychological features were assessed by Pain Catastrophizing Scale (PCS) and Pain Vigilance and Awareness Questionnaire. Pain frequency maps were generated, Margolis rating scale was used for pain location, and Spearman correlation coefficients were computed. The mean (SD) pain extent was 12.5% (6.7%) and the most common painful area was the anterolateral shoulder region (100%). Women presented a more widespread pain distribution compared with men. Significant positive associations were obtained between pain extent and current pain intensity (rs = 0.421, p < 0.01), PCS (rs = 0.307, p < 0.05) and CSI (rs = 0.358, p < 0.05). The anterolateral region of the shoulder was the most common painful area in people with FS. Women with FS presented more extended areas of pain; and a more widespread distribution of pain was correlated with higher levels of pain, pain catastrophizing and pain sensitization.

Autosomal dominant mutations in the TWNK gene, which encodes a mitochondrial DNA helicase, cause adult-onset progressive external ophthalmoplegia (PEO) and PEO-plus presentations. In this retrospective observational study, we describe clinical and complementary data from 25 PEO patients with mutations in TWNK recruited from the Hospital 12 de Octubre Mitochondrial Disorders Laboratory Database. The mean ages of onset and diagnosis were 43 and 63 years, respectively. Family history was positive in 22 patients. Ptosis and PEO (92% and 80%) were the most common findings. Weakness was present in 48%, affecting proximal limbs, neck, and bulbar muscles. Exercise intolerance was present in 28%. Less frequent manifestations were cardiac (24%) and respiratory (4%) involvement, neuropathy (8%), ataxia (4%), and parkinsonism (4%). Only 28% had mild hyperCKemia. All 19 available muscle biopsies showed signs of mitochondrial dysfunction. Ten different TWNK mutations were identified, with c.1361T>G (p.Val454Gly) and c.1070G>C (p.Arg357Pro) being the most common. Before definitive genetic confirmation, 56% of patients were misdiagnosed (36% with myasthenia, 20% with oculopharyngeal muscle dystrophy). Accurate differential diagnosis and early confirmation with appropriately chosen complementary studies allow genetic counseling and the avoidance of unnecessary treatments. Thus, mitochondrial myopathies must be considered in PEO/PEO-plus presentations, and particularly, TWNK is an important cause when positive family history is present.

Wilson disease (WD) is a rare disorder caused by mutations in ATP7B , which leads to the defective biliary excretion of copper. The subsequent gradual accumulation of copper in different organs produces an extremely variable clinical picture, which comprises hepatic, neurological psychiatric, ophthalmological, and other disturbances. WD has a specific treatment, so that early diagnosis is crucial to avoid disease progression and its devastating consequences. The clinical diagnosis is based on the Leipzig score, which considers clinical, histological, biochemical, and genetic data. However, even patients with an initial WD diagnosis based on a high Leipzig score may harbor other conditions that mimic the WD's phenotype (Wilson-like). Many patients are diagnosed using current available methods, but others remain in an uncertain area because of bordering ceruloplasmin levels, inconclusive genetic findings and unclear phenotypes. Currently, the available biomarkers for WD are ceruloplasmin and copper in the liver or in 24 h urine, but they are not solid enough. Therefore, the characterization of biomarkers that allow us to anticipate the evolution of the disease and the monitoring of new drugs is essential to improve its diagnosis and prognosis.

Statins could increase the effectiveness of Helicobacter pylori eradication therapies due to their anti-inflammatory effect. The aim of this study was to analyze the impact of this therapeutic association in real life. This is a multicenter, prospective, non-interventional study aimed at evaluating the management of H. pylori by European gastroenterologists. Patients were registered in an e-CRF by AEG-REDCap from 2013 to 2020. The association between statin use and H. pylori eradication effectiveness was evaluated through multivariate analysis. Overall, 9988 and 705 patients received empirical and culture-guided treatment, respectively. Overall, statin use was associated with higher effectiveness in the empirical group (OR = 1.3; 95%CI = 1.1-1.5), but no association was found with first-line treatment effectiveness (N = 7738); as an exception, statin use was specifically associated with lower effectiveness of standard triple therapy (OR = 0.76; 95%CI = 0.59-0.99). In the rescue therapy empirical group (N = 2228), statins were associated with higher overall effectiveness (OR = 1.9; 95%CI = 1.4-2.6). However, sub-analyses by treatment schemes only confirmed this association for the single-capsule bismuth quadruple therapy (OR = 2.8; 95%CI = 1.3-5.7). No consistent association was found between statin use and H. pylori therapy effectiveness. Therefore, the addition of statins to the usual H. pylori treatment cannot be currently recommended to improve cure rates.

Recently the European Working Group on Sarcopenia in Older People (EWGSOP2) has updated diagnostic criteria for sarcopenia, which consist of one or more measures of muscle strength, muscle mass, and physical performance, plus an initial screening test called SARC-F. The main objective was to compare the number of cases of sarcopenia, using the different measurements and screening options. A cross-sectional study was conducted on Spanish older adults ( n = 272, 72% women). Combining the different measures proposed by the steps described in the EWGSOP2 algorithm, 12 options were obtained (A-L). These options were studied in each of the three models: (1) using SARC-F as initial screening; (2) not using SARC-F; and (3) using SARC-CalF instead of SARC-F. A χ 2 independence test was statistically significant (χ 2 (6) = 88.41, p < 0.001), and the association between the algorithm used and the classification of sarcopenia was moderate (Cramer's V = 0.226). We conclude that the different EWGSOP2 measurement options imply case-finding differences in the studied population. Moreover, when applying the SARC-F, the number of people classified as sarcopenic decreases. Finally, when SARC-CalF is used as screening, case finding of sarcopenic people decreases. Thus, clinical settings should consider these outcomes, since these steps can make preventive and therapeutic interventions on sarcopenia vary widely.

Fungal diseases and antifungal resistance continue to increase, including those caused by rare or emerging species. However, the majority of the published in vitro susceptibility data are for the most common fungal species. We reviewed the literature in order to pool reference minimal inhibitory concentration (MIC) data (Clinical and Laboratory Standards Institute-CLSI and European Committee on Antimicrobial Susceptibility-EUCAST) for rare/non-prevalent Candida and other yeast species. MIC results were compared with those for Candida albicans , C. glabrata , and C. krusei . Data were listed for twenty rare and emerging Candida spp., including C. auris , as well as two Cryptococcus spp., two Trichosporon spp., Saccharomyces cerevisiae and five Malassezia spp. The best detectors of antimicrobial resistance are the breakpoints, which are not available for the less common Candida species. However, epidemiological cutoff values (ECVs/ECOFFs) have been calculated using merely in vitro data for both reference methods for various non-prevalent yeasts and recently the CLSI has established ECVs for other Candida species. The ECV could identify the non-wild type (NWT or mutants) isolates with known resistance mechanisms. Utilizing these ECVs, we were able to report additional percentages of NWT, especially for non-prevalent species, by analyzing the MIC distributions in the literature. In addition, since several antifungal drugs are under development, we are listing MIC data for some of these agents.

Pneumocystis pneumonia (PcP) is a disease produced by the opportunistic infection of the fungus Pneumocystis jirovecii . As delayed or unsuitable treatments increase the risk of mortality, the development of rapid and accurate diagnostic tools for PcP are of great importance. Unfortunately, current standard methods present severe limitations and are far from adequate. In this work, a time-competitive, sensitive and selective biosensor based on DNA-gated nanomaterials for the identification of P. jirovecii is presented. The biosensor consists of a nanoporous anodic alumina (NAA) scaffold which pores are filled with a dye reporter and capped with specific DNA oligonucleotides. In the presence of P. jirovecii genomic DNA, the gated biosensor is open, and the cargo is delivered to the solution where it is monitored through fluorescence spectroscopy. The use of capping oligonucleotides able to form duplex or triplex with P. jirovecii DNA is studied. The final diagnostic tool shows a limit of detection (LOD) of 1 nM of target complementary DNA and does not require previous amplification steps. The method was applied to identify DNA from P. jirovecii in unmodified bronchoalveolar lavage, nasopharyngeal aspirates, and sputum samples in 60 min. This is a promising alternative method for the routinely diagnosis of Pneumocystis pneumonia.

: Oxidative stress is an imbalance between production and accumulation of oxygen reactive species and/or reactive nitrogen species in cells and tissues, and the capacity of detoxifying these products, using enzymatic and non-enzymatic components, such as glutathione. Oxidative stress plays roles in several pathological processes in the nervous system, such as neurotoxicity, neuroinflammation, ischemic stroke, and neurodegeneration. The concepts of oxidative stress and rare diseases were formulated in the eighties, and since then, the link between them has not stopped growing. The present review aims to expand knowledge in the pathological processes associated with oxidative stress underlying some groups of rare diseases: Friedreich's ataxia, diseases with neurodegeneration with brain iron accumulation, Charcot-Marie-Tooth as an example of rare neuromuscular disorders, inherited retinal dystrophies, progressive myoclonus epilepsies, and pediatric drug-resistant epilepsies. Despite the discrimination between cause and effect may not be easy on many occasions, all these conditions are Mendelian rare diseases that share oxidative stress as a common factor, and this may represent a potential target for therapies.

Almost one third of patients do not achieve type 2 diabetes remission after bariatric surgery or are unable to sustain this effect long term. Our objective was to delve further into the dynamic responses of diabetes after bariatric surgery and to evaluate the "time-within-remission range" as a variable of metabolic control. A descriptive cohort study was done using a computerised multicentre and multidisciplinary registry. All data were adjusted by propensity score. A total of 1186 subjects with a follow-up of 4.5 ± 2.5 years were included. Type of surgery, diabetes remission, recurrence of diabetes, "time-within-remission range" and key predictors of diabetes outcomes were assessed. All patients (70% women, 51.4 ± 9.2 years old, body mass index (BMI) 46.3 ± 6.9 kg/m 2 ) underwent primary bariatric procedures. "Time-within-remission range" were 83.3% (33.3-91.6) after gastric bypass, 68.7% (7.1-87.5) after sleeve gastrectomy and 90% (83.3-92.8) after malabsorptive techniques ( p < 0.001 for all). Duration of diabetes, baseline HbA1c and insulin treatment were significantly negatively correlated with the "time-within-remission range". The association of bariatric techniques with "time-within-remission range", using gastric bypass as a reference, were: odds ratio (OR) 3.70 (2.34-5.84), p < 0.001 for malabsorptive techniques and OR 0.55 (0.40-0.75), p < 0.001 for sleeve gastrectomy. Characteristics of type 2 diabetes powerfully influence the outcomes of bariatric surgery. The "time-within-remission range" unveils a superiority of gastric bypass compared to sleeve gastrectomy., Competing Interests: The authors declare no conflicts of interest.

The objective was to investigate the usefulness of the "liquid biopsy" of aqueous humor (AH) to predict the clinical response after intravitreal injections (IVT) of anti-VEGF agents for treating diabetic macular edema (DME). For this purpose, AH samples obtained during the first anti-VEGF IVT from 31 type two diabetic patients were analyzed. Patients were classified into three groups according to their anti-VEGF response: rapid responders ( n = 11), slow responders ( n = 11), and non-responders ( n = 9). In addition, patients ( n = 7) who showed good response to corticosteroids but a delayed or no response to anti-VEGF therapy were analyzed. Levels of 17 different cytokines, chemokines, and growth factors in AH were measured using a multiplex immunoassay. We found higher concentrations of VEGF in rapid responders to anti-VEGF therapy compared to non-responders. In addition, slow responders to anti-VEGF treatment showed higher levels of inflammatory markers than rapid responders, but did not reach statistical significance. Finally, those patients who responded to corticosteroids but not to anti-VEGF therapy showed significantly lower levels of VEGF than patients with rapid response ( p = 0.01). In conclusion, "liquid biopsy" of AH could be useful to determine whether the predominant pathogenic event is primarily angiogenic or inflammatory in nature. This approach would allow physicians to select a more rational and cost-effective treatment. Further studies to validate these preliminary results are warranted.