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Background: Asthma is a chronic inflammatory condition of the airways with a complex pathophysiology. Stratification of asthma subtypes into phenotypes and endotypes should move the field forward, making treatment more effective and personalized. Eosinophils are the key inflammatory cells involved in severe eosinophilic asthma. Given the health threat posed by eosinophilic asthma, there is a need for reliable biomarkers to identify affected patients and treat them properly with novel biologics. microRNAs (miRNAs) are a promising diagnostic tool. Objective: The aim of this study was to identify serum miRNAs that can phenotype asthma patients. Methods: Serum miRNAs of patients with eosinophilic asthma (N=40) and patients with noneosinophilic asthma (N=36) were evaluated using next-generation sequencing, specifically miRNAs-seq, and selected miRNAs were validated using RT-qPCR. Pathway enrichment analysis of deregulated miRNAs was performed. Results: Next-generation sequencing revealed 15 miRNAs that were expressed differentially between eosinophilic and noneosinophilic asthma patients, although no differences were observed in the miRNome between atopic and nonatopic asthma patients. Of the 15 miRNAs expressed differentially between eosinophilic and noneosinophilic asthma patients, hsa-miR-26a-1-3p and hsa-miR-376a-3p were validated by RT-qPCR. Expression levels of these 2 miRNAs were higher in eosinophilic than in noneosinophilic asthma patients. Furthermore, expression values of hsa-miR-26a-1-3p correlated inversely with peripheral blood eosinophil count, and hsa-miR-376a-3p expression values correlated with FeNO values and the number of exacerbations. Additionally, in silico pathway enrichment analysis revealed that these 2 miRNAs regulate signaling pathways associated with the pathogenesis of asthma. Conclusion: hsa-miR-26a-1-3p and hsa-miR-376a-3p could be used to differentiate between eosinophilic and noneosinophilic asthma.

Clonal hematopoiesis, especially that of indeterminate potential (CHIP), has been associated with age-related diseases, such as those contributing to a more severe COVID-19. Four studies have attempted to associate CHIP with COVID-19 severity without conclusive findings. In the present work, we explore the association between CHIP and COVID-19 mortality. Genomic DNA extracted from peripheral blood of COVID-19 patients (n = 241 deceased, n = 239 survivors) was sequenced with the Myeloid Solutions™ panel of SOPHiA Genetics. The association between clonality and age and clonality and mortality was studied using logistic regression models adjusted for sex, ethnicity, and comorbidities. The association with mortality was performed with patients stratified into four groups of age according to the quartiles of the distribution: 60–74 years, 75–84 years, 85–91 years, and 92–101 years. Clonality was found in 38% of the cohort. The presence of CHIP variants, but not the number, significantly increased with age in the entire cohort of COVID-19 patients, as well as in the group of survivors (p p = 0.020). We confirmed the well-established linear relationship between age and clonality in the cohort of COVID-19 patients and found a significant association between pathogenic/likely pathogenic CHIP and mortality in patients from 75 to 84 years that needs to be further validated.

Background and aimsThis study aimed to assess the role of plasmatic fibroblast growth factor 23 (FGF23) as a prognostic marker after an acute coronary syndrome (ACS).MethodsThis prospective and multicentric study included 1,190 patients with ACS. FGF23 plasma levels and other components of mineral metabolism (calcidiol, parathormone [PTH], klotho, and phosphate), lipids, troponin, high-sensitivity C-reactive protein, N-terminal-pro-brain natriuretic peptide and estimated glomerular filtration rate (eGFR) were measured at discharge. The primary outcome was a combination of acute ischemic events, heart failure (HF) and death. Secondary outcomes were the separate components of the primary outcome.ResultsMedian follow-up was 5.44 (3.03-7.46) years. 294 patients developed the primary outcome. Patients with FGF23 levels below the median were predominantly males, younger, and with lower load of cardiovascular risk factors. Calcidiol and PTH levels were lower among them. Multivariable analysis showed that FGF23 (HR 1.18 [1.08-1.29], p2.ConclusionsFGF23 is a strong, independent predictor of HF and death among patients with ACS. This effect is homogeneous across different subgroups of population and not limited to patients with chronic kidney disease (CKD).

Chronic obstructive sialadenitis (COS) is a recurring inflammation of the salivary gland. To date, there are no known predisposing factors for COS. Given the advances seen in radiology and sialendoscopy, we must update our knowledge of COS, analyzing factors that can favor its development.We prospectively analyzed 333 patients who underwent sialendoscopy between 2012 and 2021. Epidemiologic, radiologic, and sialendoscopy-related factors were correlated. Suspected diagnosis was established based on the clinical and radiologic data. The final diagnosis was determined on the basis of sialendoscopic findings.The most common etiology of COS was stricture (40.8%). Lack of papilla distensibility (LPD) was also described as an etiology. COS was related to patient gender and age. Submandibular gland involvement was significantly more associated with lithiasis and LPD, while COS of the parotid gland was most frequently caused by stricture. Radioiodine sialadenitis and Sjögren's syndrome were significantly associated with stricture. MR sialography (MR-Si) showed the best overall sensitivity and specificity.In our series, stricture was the most common cause of COS. We describe LPD as a frequent cause of COS in this series; ours is the first study to report this finding. There was a significant association between the salivary gland involved, patient sex and age, and the cause of COS. MR-Si showed the greatest diagnostic yield.

OBJECTIVE: To describe the trial results reporting behaviour of leading European non-commercial sponsors by country and over time. STUDY DESIGN AND SETTING: Cross-sectional analysis describing results reporting rates to the European Clinical Trials Registry among the top sponsors across Europe as of May 2021 and a comparison of reporting trends for a cohort of major sponsors between January 2018 and May 2021. RESULTS: Fifty-nine highly active sponsors from 10 countries and 9 collaborative groups had 1,916 trials due to report, representing 14% of all due trials on the registry (n=13,709); of these, 1,058 had reported results (55.2%). Sponsors in the UK, Belgium and Germany had the highest compliance at 94%, 69% and 58%; those in Spain, France and the Netherlands, had the lowest, ranging from 4% to 21%. Collaborative groups had a reporting rate of 50%. In the major sponsors cohort (n=49), those with no reporting to the registry decreased from 27 (55%) in 2018 to 10 (20%) in 2021. Thirteen of these sponsors (27%) reached a 90-100% reporting rate in 2021 compared to 0 in 2018. CONCLUSION: Compliance with EU regulations by non-commercial sponsors is highly variable between nations. Enforcement of EU reporting regulations should be prioritized.

ADAM10 is the main α-secretase acting in the non-amyloidogenic processing of APP. We hypothesized that certain rare ADAM10 variants could increase the risk for AD by conferring the age-related downregulation of α-secretase. The ADAM10 gene was sequenced in 103 AD cases (82% familial) and 96 cognitively preserved nonagenarians. We examined rare variants (MAF < 0.01) and determined their potential association in the AD group with lower CSF protein levels, as analyzed by means of ELISA, and Western blot (species of 50 kDa, 55 kDa, and 80 kDa). Rare variants were found in 15.5% of AD cases (23% early-onset, 8% late-onset) and in 12.5% of nonagenarians, and some were group-specific. All were intronic variants except Q170H, found in three AD cases and one nonagenarian. The 3′UTR rs74016945 (MAF = 0.01) was found in 6% of the nonagenarians (OR 0.146, p = 0.057). Altogether, ADAM10 total levels or specific species were not significantly different when comparing AD with controls or carriers of rare variants versus non-carriers (except a Q170H carrier exhibiting low levels of all species), and did not differ according to the age at onset or APOE genotype. We conclude that ADAM10 exonic variants are uncommon in AD cases, and the presence of rare intronic variants (more frequent in early-onset cases) is not associated with decreased protein levels in CSF.

Objective Predominance of bone loss in cortical sites with relative preservation of trabecular bone, even in postmenopausal women, has been described in primary hyperparathyroidism (PHPT). The aim of this study was to evaluate bone microarchitectural differences using dual-energy x-ray absorptiometry (DXA), trabecular bone score (TBS), and DXA-based 3-dimensional (3D) modeling (3D-DXA) between postmenopausal women diagnosed with PHPT (PM-PHPT) and healthy postmenopausal controls. Methods This retrospective study included 44 women with PM-PHPT (9 of whom had fractures) and 48 healthy women matched by age, body mass index, and years since menopause treated at Hospital Universitario Fundacion Jimenez Diaz between 2008 and 2017. The bone mineral density (BMD) of the lumbar spine (LS), femoral neck, total hip (TH), and 1/3 radius was assessed using DXA, and trabecular volumetric BMD (vBMD), cortical vBMD, integral vBMD, cortical thickness, and cortical surface BMD at TH were assessed using a 3D-DXA software and TBS at LS. Results The mean adjusted BMD values at LS, the femoral neck, and TH; TBS at LS; and TH 3D-DXA parameters (trabecular vBMD, integral vBMD, cortical thickness, and cortical surface BMD) were significantly reduced in women with PM-PHPT compared with those in the controls. However, differences in mean cortical vBMD were not statistically significant (P = .078). There were no significant differences in mean BMD, TBS, or the 3D-DXA parameters between patients with fractures and those without fractures. The 25-hydroxyvitamin D level appeared to be associated with TBS but not with DXA and 3D-DXA measurements. Conclusion PM-PHPT has significant involvement of the trabecular and cortical compartments of the bone, as determined by DXA, TBS, and 3D-DXA.

Background In March 2020, the COVID‐19 pandemic forced the Spanish government to declare a state of emergency. A stringent lockdown was enforced, restricting access to healthcare services, including chiropractic. Reduced access to care provision in combination with psychological stress, social isolation and physical inactivity during the lockdown were shown to negatively influence pain conditions. However, data on strategies to mitigate the impact of the pandemic on these conditions are lacking. Methods Upon easing of restrictions in May 2020, 51 chiropractic clinics throughout Spain pseudo‐randomly invited patients, recruiting a total of 385 participants. During a 14‐day period, participants were exposed to in‐person chiropractic care in either one (n = 177) or multiple encounters (n = 109) or to no care (n = 99). The effects of access to chiropractic care on patients’ pain‐related and psychological outcomes were assessed online through validated self‐reported questionnaires before and after the period of care. Coprimary outcomes included pain intensity, pain interference and pain cognitions. Results When comparing to participants without access to care, pain intensity and interference were significantly decreased at follow‐up, irrespective of the number of encounters. Kinesiophobia was also significantly reduced at follow‐up, though only after multiple encounters. The relationship between fear of movement, changes in pain intensity and interference was mediated by catastrophizing. Conclusion Access to in‐person chiropractic care may provide pain relief, associated with reductions in interference and pain cognitions. Prioritizing in‐person care for patients with maladaptive pain cognitions may help dampen the detrimental consequences of the pandemic on physical and psychological well‐being.

Aims: There are controversial data on the ability of the components of mineral metabolism (vitamin D, phosphate, parathormone [PTH], fibroblast growth factor-23 [FGF23], and klotho) to predict cardiovascular events. In addition, it is unknown whether they add any prognostic value to other well-known biomarkers. Methods and results: In 969 stable coronary patients, we determined plasma levels of all the aforementioned components of mineral metabolism with a complete set of clinical and biochemical variables, including N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity troponin I (hs-TnI), and high-sensitivity C-reactive protein. Secondary outcomes were ischaemic events (any acute coronary syndrome, stroke, or transient ischaemic attack) and heart failure or death. The primary outcome was a composite of the secondary outcomes. Median follow-up was 5.39 years. Age was 60 (52–72) years. Median glomerular filtration rate was 80.4 (65.3–93.1) mL/min/1.73 m2. One-hundred and eighty-five patients developed the primary outcome. FGF23, PTH, hs-TnI, and NT-proBNP were directly related with the primary outcome on univariate Cox analysis, while Klotho and calcidiol were inversely related. On multivariate analysis, only PTH (HR 1.058 [CI 1.021–1.097]; P = 0.002) and NT-proBNP (HR 1.020 [CI 1.012–1.028]; P 85.5 RU/mL) (P, This work was supported by grants from Instituto de Salud Carlos III (ISCIII) and Fondos FEDER (Fondo Europeo de Desarrollo Regional) European Union (PI05/0451, PI14/1567, PI17/01615, and PI17/01495); Spanish Society of Cardiology; Spanish Society of Arteriosclerosis; RECAVA (Red Temática de Investigación Cooperativa en Enfermedades Cardiovasculares) (RD06/0014/0035); and Instituto de Salud Carlos III FEDER (FJD biobank: RD09/0076/00101). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

To compare the efficacy of 4 different analgesic regimens that include music and nitrous oxide during the treatment of renal lithiasis with ambulatory extracorporeal shock wave lithotripsy (ESWL).A single-centre, longitudinal, prospective, randomized, open and parallel group study was conducted. Patients with renal lithiasis were included and were randomized to Group A (basal analgesia: midazolam (1 mg), fentanyl (0.05 mg) and dexketoprofen (50 mg)), Group B (basal analgesia and nitrous oxide), Group C (basal analgesia and music) and Group D (basal analgesia, nitrous oxide and music). For the measurement of pain, a visual analogue scale ranging from 0 (no pain) to 100 (maximum pain imaginable) was used. Patient satisfaction was assessed using a Likert questionnaire. The epidemiological data of the patients in terms of lithiasis, previous clinical and ESWL sessions, and pain measured with the VAS before, during (maximum) at the end of the session and at discharge were recorded. Data on complications were also collected, as was the patients' subjective evaluation of the treatment and their satisfaction. The ESWL procedure was performed with a Storz Modulith SLX-F2® lithotripter. A maximum of 4000 waves were applied at a frequency of 1.5 Hz.Eighty patients were included (20 per group). None of the analgesia guidelines proved to be superior to the others for pain control during the ESWL session. Patients younger than 50 years had significantly higher values for the maximum VAS. Only 13.75% of patients required rescue analgesia. A total of 77.5% described their experience as good, very good or excellent, regardless of the assigned group.The addition of nitrous oxide and/or music did not result in a statistically significant improvement over the basal analgesia regimen of midazolam, fentanyl and dexketoprofen; however, the degree of patient satisfaction was very high.

small-cell lung cancer (SCLC) is one of the most lethal malignancies. Its management is complex due to the lack of biomarkers and limited therapies. Galectin-1 (Gal-1) plays a major role in cancer development and progression. The aim of this study is to assess whether Gal-1 has a predictive role in the disease evolution and its therapeutic potential.The expression level of Gal-1 was examined by using a public RNA-sequencing (77 SCLC patients) and in-house immunohistochemistry (IHC) performed on biopsies from 81 patients. Survival curves and Cox regression analysis were used to assess the prognostic potential of Gal-1. In addition, a SCLC-PDX model was carried out and treated with either OTX008, an inhibitor of Gal-1, or vehicle to assess the effects of Gal-1 inhibition on this disease in vivo.Galectin-1 gene (LGALS1) expression showed a strong negative correlation with outcome in SCLC patients with advanced disease (p = 0.007). IHC unveiled that overall survival (OS) was significantly lower among extensive-stage SCLC (ES-SCLC) patient group with increased level of Gal-1 and platelet-to-lymphocyte ratio (PLR) (HR=3.07, 95% CI: 1.62, 5.79, p 0.001). The SCLC-PDX model showed a significant reduction in tumor size (tumor growth inhibition [TGI] index 73%) without side effects.in this study, high levels of Gal-1 and PLR were associated with poorer OS in SCLC patients, supporting their utility as clinical prognostic biomarkers. Moreover, the in vivo model suggests the inhibition of Gal-1 as a novel potential therapy for this disease with very poor prognosis.

Resumen: Antecedentes y objetivo: La mortalidad de los pacientes en hemodiálisis es alta. Una tasa de ultrafiltración horaria ajustada por peso (UFR/W) elevada se ha asociado con episodios de hipotensión arterial y con mayor riesgo de muerte y/o eventos cardiovasculares. Material y métodos: Hemos evaluado la asociación entre UFR/W y mortalidad en 215 pacientes en hemodiálisis prevalentes seguidos durante 28 ± 6,12 meses. Se estimaron características clínicas basales y UFR/W media a lo largo del seguimiento. Resultados: La UFR/W media fue 9,0 ± 2,4 y los terciles 7,1 y 10,1 mL/kg/h. Se categorizó a la población en función del tiempo que habían estado con UFR/W igual o superior a los puntos de corte descritos en la literatura como relacionados con mayor mortalidad (10,0 mL/kg/h y 13,0 mL/kg/h). Los pacientes con mayor UFR/W fueron más jóvenes, con mayor ganancia de peso interdiálisis y porcentaje de reducción de peso, pero con menor peso seco, inicial y final. Durante el seguimiento, fallecieron 46 (21,4%) personas de las cuales la mayoría eran > 70 años, diabéticas o con enfermedad cardiovascular. No hubo diferencias en la mortalidad entre los grupos de UFR/W ni en la UFR/W entre los fallecidos y no fallecidos. En comparación con estudios previos donde describieron la asociación entre UFR/W y mortalidad, en nuestra población había más prevalencia de medicación protectora cardiovascular y no se observaron UFR/W tan altas. Conclusión: En nuestro medio, la UFR/W más elevada se observó en pacientes más jóvenes y de menor peso y no se asoció con mayor mortalidad. Abstract: Background and aims: Mortality among hemodialysis patients remains high. An elevated ultrafiltration rate adjusted by weight (UFR/W) has been associated with hypotension and higher risk of death and/or cardiovascular events. Methods: We evaluated the association between UFR/W and mortality in 215 hemodialysis patients. The mean follow-up was 28 ± 6.12 months. We collected patientś baseline characteristics and mean UFR/W throughout the follow-up. Results: Mean UFR/W was 9.0 ± 2,4 and tertiles 7.1 y 10.1 mL/kg/h. We divided our population according to the percentage of sessions with UFR/W above the limits described in the literature associated with increased mortality (10.0 mL/kg/h and 13.0 mL/kg/h). Patients with higher UFR/W were younger, with higher interdialytic weight gain and weight reduction percentage but lower dry, pre and post dialysis weight. Throughout the follow-up, 46 (21.4%) patients died, the majority over 70 years old, diabetic or with cardiovascular disease. There were neither differences regarding mortality between groups nor differences in UFR/W among patients who died and those who did not. Contrary to previous studies, we did not find an association between UFR/W and mortality, maybe due to a higher prevalence in the use of cardiovascular protection drugs and lower UFR/W. Conclusions: The highest UFR/W were observed in younger patients with lower weight and were not associated with an increased mortality.

OBJECTIVES The rate of eosinophilic esophagitis (EoE) diagnosis is increasing. This study aims to determine the incidence of EoE in the pediatric population residing in the southwestern Madrid and to analyze whether absolute monthly pollen counts, modified or not by the principal atmospheric pollutants, are associated with it. METHODS A cross-sectional study on prospectively recruited patients was designed to calculate the incidence of EoE in children aged under 15 years who were diagnosed between September 2014 and August 2016 in twelve hospitals. We collected demographic and symptoms data, date of onset of symptoms, date of medical consultation, and date of endoscopic diagnosis of each included patient. Relative risk estimation was performed to assess the association between the incidence of diagnosis and monthly pollen counts and levels of atmospheric pollutants. All these models were adjusted for the number of total patients that underwent endoscopy at first time. RESULTS One hundred forty-eight patients were included. The most frequent symptoms were abdominal pain [42.57%], dysphagia [42.57%], and impaction [39%-86%]. The median overall monthly incidence was 1.13 [interquartile rank: 0.97-1.43] cases/100,000 children, and the annual mean was 15.2. The overall analysis of the relationship between incidence and absolute monthly counts, corrected for the number of first-time endoscopies performed, revealed no statistically significant association with pollen and air pollutants. There was a higher frequency of diagnosis during the pollination period of Cupressaceae [relative risk 1.647; 95% CI (1.192-2.276) p

Background: Trochanteric bursitis or greater trochanteric pain syndrome is a common disorder and frequent cause of lateral hip pain. It can lead to severe functional impairment with increase morbidity and poor quality of life. The purpose of the current study was to identify and evaluate relationship between health-related factors, as prognostic indicators, and clinical outcomes. Methods: A single-centre, prospective study was conducted and 60 patients (62 hips) were included with a minimum 12 months of follow-up. Clinical outcomes were evaluated using Hip Outcome Scale, Single Assessment Numeric Evaluation and Visual Analogue Scale. Radiological assessments and health-related factors were documented in an attempt to understand their validity as predictors of clinical outcomes. Complications and recurrence rates were also analyzed. Results: Univariate model revealed that an increased BMI ( p = 0.001; OR = 1.05; 95% CI, 1.02–1.07); number of previous corticosteroid infiltrations ( p = 0.001; OR = 1.28, 95% CI, 1.11–1.48); longer time from symptom onset to surgery ( p = 0.001; OR = 1.19; 95% CI, 1.12–1.28); smoker status ( p = 0.001; OR 11.2; 95% CI, 3.30–44.2); and the presence of prior lumbosacral fusion (LSF) ( p = 0.001; OR 13.8; 95% CI, 2.96–101); were prognostic factors predisposing for poor clinical outcomes. Among prognostic health-related factors were medical comorbidities such as emotional distress ( p Conclusions: Better overall physical function was predicted by lower number of corticosteroid infiltrations, shorter time span from symptom onset to surgery, non-smoker status and the absence of prior lumbosacral fusion. Obesity, smoking, the presence of emotional distress, fibromyalgia and hypothyroidism seem to increase the risk of poor clinical outcomes. A proper selection and/or correction of modifiable prognostic factors could reduce the incidence of endoscopic treatment failure and, as a consequence, improve patient outcomes and quality of life. However, future efforts should focus on experimental and randomised studies to fully determine these associations.

Lupus anticoagulant (LA) can be a cause of thrombosis and/or pregnancy morbidities, producing antiphospholipid syndrome (APS). An increase in thrombin generation (TG) is correlated with prothrombotic status. Several changes in TG-derived parameters have been reported in APS patients.Evaluate whether the TG phenotype of APS can also be described in LA subjects without clinical manifestations of APS, and to investigate the possible influence of both LA potency and antiphospholipid (aPL) profile on it.TG was analyzed in 153 cases of LA and 41 healthy controls. We have observed prolongation of both lag time (3.7 min vs 2.32 min, p 0.001) and time to peak (6.48 min vs 5.27 min, p 0.001), increased peak height (221.7 nM vs 182.7 nM, p 0.001), slightly higher ETP (221.7 nM·min vs 182.7 nM·min, p = 0.041), and higher velocity index (100.7 nM/min vs 74.53 nM/min, p = 0.001) in LA subjects compared to controls. After adding thrombomodulin (TM), ETP%inh was significantly lower in LA group (37.90% vs 59.90%, p 0.001) showing resistance to TM/activated protein C (APC). Significant differences were found in lag time, time to peak and ETP%inh according to the potency and aPL profile.Previously described differences in TG-derived parameters in APS patients have been confirmed in incidental LA subjects: prolonged lag time and time to peak, slightly higher ETP, higher peak height, and less sensitivity to TM/APC. High LA potency and triple-positive aPL profile enhance differences in lag time, time to peak and, especially, increase APC resistance, but no effect in ETP was observed.

Purpose To describe the visual, refractive, topographic and aberrometric outcomes of six different accelerated cross-linking (ACXL) protocols in progressive keratoconus (KC) at 12 months. # Material and methods This observational retrospective study included 62 eyes of 49 patients with progressive KC that received one of the following accelerated cross-linking protocols: Group I (8 patients, 5.4 J/cm2, 15mWx12min, pulsed), Group II (11 patients, 5.4 J/cm2, 6mWx15min, continuous), Group III (16 patients, 5.4 J/cm2, 9mWx10min, continuous), Group IV (13 patients, 5.4 J/cm2, 30mWx6min, pulsed), Group V (8 patients, 7.2 J/cm2, 15mWx16min, pulsed) and Group VI (6 patients, 7.2 J/cm2, 30mWx8min, pulsed). Best corrected visual acuity (BCVA), sphere, refractive cylinder, spherical equivalent (SE), maximum keratometry (Kmax), mean keratometry (Km), flat keratometry (K1), steep keratometry (K2), thinnest pachymetry, total aberrations, high order aberrations (RMS-HOA), spherical aberration, coma and trefoil were studied previously and at 12 months. Intragroup and intergroup statistical analysis was performed. Postoperative complications were noted. # Results 11 patients were females(22,45%) and 38 males(77,55%). Improvement in the BCVA was observed in all groups (P > 0.05). Kmax reduced in all patients and was statistically significant in groups II (p = 0.041), III (p = 0.017), IV (p = 0.018) and V (p = 0.018). Flattening of the Km was significant in groups II (p = 0.028), IV (p = 0.008) and V (p = 0.028), as well as the K1 in groups IV(p = 0.01) and V(p = 0.028) and K2 in group IV(p = 0.036). There was no significant difference in the thinnest pachymetry in any of the groups. Total aberrations, RMS-HOA, spherical aberration and coma reduced in all groups with statistical significance in Group V (P = 0.016). Two patients in Group I had anterior stromal scarring and one patient in Group V presented an unexpected overflattening. Progression was noticed in one patient in Group II. # Conclusions Accelerated CXL protocols included in this study can be considered effective and safe procedures in stopping the progression of keratoconus at 12 months. Improvement in BCVA and wavefront analysis is observed, but results are limited by the number of patients. Caution should be taken when applying high radiance and long duration protocols to prevent undesirable events.

Background: Degenerative spine disease is a common cause of low back pain in people age 65 years or older. Nonsurgical treatment is tried first, but if it is unsuccessful, surgery is advocated. This has special connotations for both underlying disease and the biomechanical characteristics of osteoporotic bone. We conducted an observational study to investigate the clinical and radiological outcome in patients in this age group with poor bone quality and degenerative lumbar instability treated with fusion using perforated pedicle screws augmented with polymethylmethacrylate (PMMA). Methods: We collected prospective data on treatment, outcome, and patient characteristics from our institution9s database. The primary outcome was a change in pain and physical function measured by the visual analog scale, the Core Outcome Measures Index, and the Oswestry Disability Index. Control participants were also analyzed for secondary complications such as hardware mobilization, fusion (as apparent on radiographs), and adjacent fractures or adjacent degenerative disc disease. Results: We included 89 patients who underwent surgery between October 2015 and February 2018 at a mean age of 78 years (range, 67–88 years) and were then monitored for at least 12 months (range, 12–40 months). Findings on pain and function questionnaires showed improvement at 6 months after surgery, maintained at the final evaluation; 90% of patients had final score increases of ≥15 points. No patient developed clinical complications secondary to PMMA leakages. One patient had nonunion and screw breakage. No other patient had clinical or radiological nonunion. Of the control participants, 6 had adjacent disc disease, with 2 of them requiring instrumentation extension. Six deep infections required surgical revision without removal of material. Conclusion: PMMA-augmented cannulated pedicle screw instrumentation in spine fusion effectively and safely treats degenerative lumbar disease in patients who are age 65 years or older with poor bone quality.

Objectives: Eosinophilic esophagitis (EoE) is a chronic esophageal disease characterized by eosinophilic inflammation. Proton-pump inhibitors (PPI) induce disease remission but no predictive factors of PPI-responsiveness have been identified yet. So, a biomarker must be found to differentiate between responders (PPI-R) and nonresponder patients (PPI-NR) to PPI. Aims were to identify any molecular biomarker that could predict PPI responsiveness and to study molecular remission after PPI therapy. Methods: This prospective study enrolled 39 controls and 43 pediatric children with EoE from 2 hospitals, and they were treated with esomeprazole for 8 to 12 weeks. After therapy, patients were classified as either PPI-R or PPI-NR. Biopsies were collected and RNA, microRNAs, and proteins were isolated from them, measuring levels by qPCR and Western blot (WB). Also, miRNAs were evaluated in serum. Results: We found several esophageal miRNAs with different expression values between PPI-R and PPI-NR children, which can be used to discriminate them (area under curve = 0.90). No useful serum miRNAs were, however, identified. Also, these miRNAs were dysregulated in responder patients before and after PPI therapy. Moreover, we corroborated in this child population, that PPI-R displayed a significant decrease in eotaxin-3, IL-5, IL-13, periostin, and major basic protein (P

Introduction Mortality risk prediction for Intermediate Respiratory Care Unit's (IRCU) patients can facilitate optimal treatment in high-risk patients. While Intensive Care Units (ICUs) have a long term experience in using algorithms for this purpose, due to the special features of the IRCUs, the same strategics are not applicable. The aim of this study is to develop an IRCU specific mortality predictor tool using machine learning methods. Methods Vital signs of patients were recorded from 1966 patients admitted from 2007 to 2017 in the Jimenez Diaz Foundation University Hospital's IRCU. A neural network was used to select the variables that better predict mortality status. Multivariate logistic regression provided us cut-off points that best discriminated the mortality status for each of the parameters. A new guideline for risk assessment was applied and mortality was recorded during one year. Results Our algorithm shows that thrombocytopenia, metabolic acidosis, anemia, tachypnea, age, sodium levels, hypoxemia, leukocytopenia and hyperkalemia are the most relevant parameters associated with mortality. First year with this decision scene showed a decrease in failure rate of a 50%. Conclusions We have generated a neural network model capable of identifying and classifying mortality predictors in the IRCU of a general hospital. Combined with multivariate regression analysis, it has provided us with an useful tool for the real-time monitoring of patients to detect specific mortality risks. The overall algorithm can be scaled to any type of unit offering personalized results and will increase accuracy over time when more patients are included to the cohorts.

Background: Recurrent wheezing (RW) is frequently developed in infants that have suffered bronchiolitis (BCH) during first months of life, but the immune mechanism underlying is not clear. The goal was to analyze the innate immune response that characterizes BCH and RW. Methods: Ninety-eight and seventy hospitalized infants with BCH or RW diagnosis, respectively, were included. Nasopharyngeal aspirate (NPA) was processed. Cellular pellet was employed to evaluate type 2 innate lymphoid cells (ILC2) by flow cytometry and mRNA expression assays by semi-quantitative real-time PCR (qRT-PCR). In supernatant, twenty-seven pro-inflammatory and immunomodulatory factors, as well as lipid mediators and nitrites, were evaluated by ELISA and Luminex. Results: Bronchiolitis patients showed higher ILC2 percentage compared with RW (P < .05). Also, ST2+ /ILC2 percentage was higher in the BCH group than in the RW group (P < .01). TLR3, IL33, IFNG, IL10, and FLG mRNA levels were significantly increased in BCH vs RW (P < .05). In supernatant, no significant differences were reached, observing similar levels of parameters linked to vascular damage, monocyte activation, and fibroblast growth. Prostaglandin E2 and cysteinyl leukotrienes C4 were evaluated; a significant difference was only found in their ratio. Conclusion: Bronchiolitis is associated with elevated nasal percentage of ILC2. This cellular population could be the key element in the differential immune response between BCH and RW which share some mechanisms such us monocyte activation, vascular damage, and fibroblast repair. Lipid mediators could play a role in the evolution of the disease later in life through innate lymphoid cells. This study has been partially supported by FIS (Fondo de Investigación Sanitaria—Spanish Health Research Fund) Grants PI15/00803, FI16/00036, PI15CIII/00028, and FEDER Funds (Fondo Europeo de Desarrollo Regional); Alfonso X El Sabio University Grant: VIII Convocatoria Santander‐UAX; and CIBER de Enfermedades Respiratorias (CIBERES), a Carlos III Institute of Health Initiative. Sí

SUMMARYBackgroundKBG syndrome is a highly variable neurodevelopmental disorder and clinical diagnostic criteria have changed as new patients have been published. Both loss-of-function sequence variants and large deletions (CNVs) involving ANKRD11 have been involved in KBG, but no genotype-phenotype correlation has been reported to date. This study presents the clinical and molecular characteristics of 67 new patients with KBG syndrome and the results of the first genotype-phenotype correlation leveraging data on 273 patients previously published.Methods67 patients with KBG syndrome were recruited through a Spanish collaborative effort and were assessed using a custom phenotypic questionnaire. The frequency of all features was calculated. Manifestations present in >50% of the patients and a “severity score” were used to perform a genotype-phenotype correlation in the 340 KBG patients.ResultsNeurodevelopmental delay (95%), comorbidites (82.8%), macrodontia (80.9%), triangular face (71%), characteristic ears (76%), nose (75.9%) and eyebrows (67.3%) were the most prevalent features in the 67 patients. The genotype-phenotype correlation yielded significant associations with the triangular face (71.1% in patients with sequence variants vs 45.2% in CNVs, p=0.015), short stature (62.5% variants in exon 9 vs. 27.8% outside; p=0.009) and macrodontia (with larger deletions, p=0.028), ID/ADHD/ASD (70.4% in c.1903_1907del vs. 89.4%; p=0.012) and a higher phenotypic score in patients with sequence variants compared with CNVs (p=0.005).ConclusionsWe present a detailed phenotypic description of KBG syndrome in the largest series of patients reported to date, provide evidence of a genotype-phenotype correlation between some KBG features and specific ANKRD11 aberrations, and propose updated clinical diagnostic criteria based on our findings.

The purpose of this paper was to describe the characteristics of salivary calculi and their relationship to epidemiological factors, through a cross-sectional study. We analysed 100 calculi obtained in 2017–2021. Patient data including age, time since onset of symptoms, gland involved, and site of location in the salivary system were studied. The calculi were studied to determine their morphological features using scanning electron microscopy and energy dispersive plain radiographic analysis. Most of the calculi had formed in the submandibular gland (SG) (82%). The mean age of patients at onset was 45.83 years; patients presenting parotid gland (PG) stones were somewhat older (p = 0.031). The mean time since the onset of symptoms was longer in PG calculi (p = 0.038). The most common lithiasis site was the main duct (74%), followed by the hilum (22%). Hilar stones were the largest (p < 0.05) and heaviest (p = 0.028). Octacalcium phosphate (OCP) was the most common crystalline phase (Cp) founded, followed by hydroxyapatite (HA) and whitlockite (WH). Specifically, OCP had a higher presence in PG calculi (p = 0.029) and WH was the most common phase in SG calculi (p = 0.017). The most prevalent site of lithiasis was the main duct, and the largest and heaviest calculi were found in the SG. PG stones were associated with a longer history of symptoms and older age. OCP was the most frequent Cp of the calculi studied, and the main Cp in PG stones. WH was the predominant Cp in SG stones. The Cp of the calculi was not influenced by location, patient age, or time of symptoms.