Integrated Membrane Process in Organic Media: Combining Organic Solvent Ultrafiltration, Nanofiltration, and Reverse Osmosis to Purify and Concentrate the Phenolic Compounds from Wet Olive Pomace.

Phenolic compounds from a hydroalcoholic extract of wet olive pomace were purified and concentrated by an integrated membrane process in organic media. First, UF010104 (Solsep BV) and UP005 (Microdyn Nadir) membranes were tested to be implemented in the ultrafiltration stage, with the aim of purifying the extract and obtaining a permeate enriched in phenolic compounds. Despite the high flux observed with the UF010104 membrane (20.4 ± 0.7 L·h-1·m-2, at 2 bar), the UP005 membrane was selected because of a more suitable selectivity. Even though some secoiridoids were rejected, the permeate stream obtained with this membrane contained high concentrations of valuable simple phenols and phenolic acids, whereas sugars and macromolecules were retained. Then, the ultrafiltration permeate was subjected to a nanofiltration step employing an NF270 membrane (DuPont) for a further purification and fractionation of the phenolic compounds. The permeate flux was 50.2 ± 0.2 L·h-1·m-2, working at 15 bar. Hydroxytyrosol and some phenolic acids (such as vanillic acid, caffeic acid, and ferulic acid) were recovered in the permeate, which was later concentrated by reverse osmosis employing an NF90 membrane. The permeate flux obtained with this membrane was 15.3 ± 0.3 L·h-1·m-2. The concentrated phenolic mixture that was obtained may have important applications as a powerful antioxidant and for the prevention of diabetes and neurodegenerative diseases.

Safety and effectiveness of direct-acting antiviral drugs in the treatment of hepatitis C in patients with inflammatory bowel disease.

BACKGROUND AND AIMS: Hepatitis C virus (HCV) management in Inflammatory Bowel Disease (IBD) is uncertain. The ECCO guidelines 2021 recommended HCV treatment but warn about the risk of IBD reactivation. We aimed to evaluate 1) the effectiveness and safety of direct-acting antivirals (DAAs) in IBD; 2) the interaction of DAAs with IBD drugs. METHODS: Multicentre study of IBD patients and HCV treated with DAAs. Variables related to liver diseases and IBD, as well as adverse events (AEs) and drug interactions, were recorded. McNemar's test was used to assess differences in the proportion of active IBD during the study period. RESULTS: We included 79 patients with IBD and HCV treated with DAAs from 25,998 IBD patients of the ENEIDA registry. Thirty-one (39.2 %) received immunomodulators/biologics. There were no significant differences in the percentage of active IBD at the beginning (n = 11, 13.9 %) or at the 12-week follow-up after DAAs (n = 15, 19 %) (p = 0.424). Sustained viral response occurred in 96.2 % (n = 76). A total of 8 (10.1 %) AEs occurred and these were unrelated to activity, type of IBD, liver fibrosis, immunosuppressants/biologics, and DAAs. CONCLUSIONS: We demonstrate a high efficacy and safety of DAAs in patients with IBD and HCV irrespective of activity and treatment of IBD.

[Combined histiocytosis of the Langerhans group (Langerhans cell histiocytosis and Erdheim-Chester disease) in a 64-year-old man with BRAF and NRAS mutations: a case report]. / Histiocitosis combinada de tipo Langerhans (Histiocitosis de células de Langerhans y enfermedad de Erdheim-Chester) en varón de 64 años con mutaciones en BRAF y NRAS: a propósito de un caso.

We present a case of a 64-year-old male with a history of Crohn's disease who presented with an episode of acute abdominal pain. He was being investigated for a dermatological lesion. A skin and lung biopsy both revealed histiocytosis of the "L" (Langerhans) group. The skin biopsy showed a proliferation of histiocytic cells expressing Langerin, CD1a and S100 and the molecular study was positive for the BRAF p.V600E mutation. In the lung biopsy, a proliferation of histiocytic cells was found, which were positive for CD68 and S100 and negative for Langerin and CD1a; mutations in NRAS c.38G>A in exon 2 (p.G13D) were also detected.

Social and ideological determinants of COVID-19 vaccination status in Spain.

OBJECTIVES: This study analysed the association between social and ideological determinants with COVID-19 vaccine accessibility and hesitancy in the Spanish adult population. STUDY DESIGN: This was a repeated cross-sectional study. METHODS: The data analysed are based on monthly surveys conducted by the Centre for Sociological Research between May 2021 and February 2022. Individuals were classified according to their COVID-19 vaccination status into (1) vaccinated (reference group); (2) willing to vaccinate but not vaccinated, proxy of lack of vaccine accessibility; and (3) hesitant, proxy of vaccine hesitancy. Independent variables included social (educational attainment, gender) and ideological determinants (voting in the last elections, importance attached to the health vs the economic impact of the pandemic, and political self-placement). We estimated odds ratio (OR) and 95% confidence interval (CI) conducting one age-adjusted multinomial logistic regression model for each determinant and then stratified them by gender. RESULTS: Both social and ideological determinants had a weak association with the lack of vaccine accessibility. Individuals with medium educational attainment had higher odds of vaccine hesitancy (OR = 1.44, CI 1.08-1.93) compared with those with high educational attainment. People self-identified as conservative (OR = 2.90; CI 2.02-4.15) and those who prioritised the economic impact (OR = 3.80; CI 2.62-5.49) and voted for parties opposed to the Government (OR = 2.00; CI 1.54-2.60) showed higher vaccine hesitancy. The stratified analysis showed a similar pattern for both men and women. CONCLUSIONS: Considering the determinants of vaccine uptake and hesitancy could help to design strategies that increase immunisation at the population level and minimise health inequities.

Overcoming Barriers to Tumor Genomic Profiling through Direct-to-Patient Outreach.

PURPOSE: To overcome barriers to genomic testing for patients with rare cancers, we initiated a program to offer free clinical tumor genomic testing worldwide to patients with select rare cancer subtypes. EXPERIMENTAL DESIGN: Patients were recruited through social media outreach and engagement with disease-specific advocacy groups, with a focus on patients with histiocytosis, germ cell tumors (GCT), and pediatric cancers. Tumors were analyzed using the MSK-IMPACT next-generation sequencing assay with the return of results to patients and their local physicians. Whole-exome recapture was performed for female patients with GCTs to define the genomic landscape of this rare cancer subtype. RESULTS: A total of 333 patients were enrolled, and tumor tissue was received for 288 (86.4%), with 250 (86.8%) having tumor DNA of sufficient quality for MSK-IMPACT testing. Eighteen patients with histiocytosis have received genomically guided therapy to date, of whom 17 (94%) have had clinical benefit with a mean treatment duration of 21.7 months (range, 6-40+). Whole-exome sequencing of ovarian GCTs identified a subset with haploid genotypes, a phenotype rarely observed in other cancer types. Actionable genomic alterations were rare in ovarian GCT (28%); however, 2 patients with ovarian GCTs with squamous transformation had high tumor mutational burden, one of whom had a complete response to pembrolizumab. CONCLUSIONS: Direct-to-patient outreach can facilitate the assembly of cohorts of rare cancers of sufficient size to define their genomic landscape. By profiling tumors in a clinical laboratory, results could be reported to patients and their local physicians to guide treatment. See related commentary by Desai and Subbiah, p. 2339.

Tic disorders and premonitory urges: validation of the Spanish-language version of the Premonitory Urge for Tics Scale in children and adolescents.

INTRODUCTION: Most people with persistent tics report an unpleasant sensation (premonitory urge) before the tic. In recent years, interest in these sensory phenomena has increased due to their important role in behavioural therapy. However, instruments for assessing these sensations remain scarce. Among the available instruments, the Premonitory Urge for Tics Scale (PUTS) is the most widely used. METHODS: We examined the psychometric properties and factor structure of the Spanish-language version of the PUTS in a sample of 72 children and adolescents with Tourette syndrome or persistent tic disorders. We analysed data from the total sample and by age group (children up to 10 years old and children/adolescents over 10). RESULTS: The PUTS presented good internal consistency and moderate correlations between items on the scale (except for item 1). Divergent validity was good, test-retest reliability was adequate, and a bifactorial structure was identified (one dimension related to mental phenomena reported in obsessive-compulsive disorder, and another related to the quality and frequency of premonitory urges). These results were replicated in both age groups, with lower divergent validity and test-retest reliability in the younger group. CONCLUSIONS: The Spanish-language version of the PUTS is a valid, reliable tool for assessing premonitory urges in both children and adolescents, especially after the age of 10.

Systemic treatment in sarcoidosis: Experience over two decades.

OBJECTIVE: The aim of this study was to evaluate the frequency of systemic treatment in a cohort of sarcoidosis patients and identify presenting clinical features as predictive factors of the need for systemic immunosuppressive therapy. METHODS: Retrospective study of 342 patients diagnosed and followed-up from January 1999 to December 2019 in a University Hospital in Northern Spain. The diagnosis of sarcoidosis was established according to ATS/ERS/WASOG criteria. A comparative analysis was performed between treated and untreated patients. Predictive factors of treatment prescription according to initial clinical manifestations were identified (multivariate analysis). RESULTS: Mean age at diagnosis was 47.7±15.1 years, with a slight female predominance (51.8%) and Caucasian majority (94.2%). The main clinical manifestation was thoracic involvement (88.3%). Extrathoracic manifestations were detected in 68.4% cases, mainly cutaneous (34.2%), articular (27.8%) and ocular (17.8%). A total of 207 (60.5%) patients required systemic treatment. Glucocorticoid therapy was the most widely used (60.5%). Conventional immunosuppressive therapy in 25.4%, more frequently MTX (21.9%). Biologic therapy was prescribed in 12.9%, especially adalimumab (9.1%). Male gender (OR: 1.65; 95%CI: 1.06-2.56), intrathoracic (OR: 2.41; 95%CI: 1.22-4.76), ocular (OR: 4.14; 95%CI: 2.01-8.52), parotid (OR: 1.60; 95%CI: 1.39-1.94), neurological (OR: 5.00; 95%CI: 1.68-14.84), and renal (OR: 1.59; 95%CI: 1.38-1.94) involvement were identified as risk factors associated with the need of systemic treatment. CONCLUSION: Most patients (60.5%) of sarcoidosis in our series required systemic therapy. An association between certain characteristics at initial presentation (male gender, lung, ocular, parotid, neurological and renal involvement) and the need of systemic treatment was identified.

[Impact on the incidence of gastrointestinal perforation during the COVID-19 pandemic in the Costa del Sol healthcare system area]. / Impacto en la incidencia de perforación gastrointestinal durante la pandemia de COVID-19 en el área sanitaria Costa del Sol.

INTRODUCTION AND AIMS: Gastrointestinal perforation is a surgical emergency that is associated with a high mortality rate and requires special care. During the pandemic, there has been competition with COVID-19 patients for health resources, especially ICU bed availability. The primary aim of our study was to compare the incidence of gastrointestinal perforation during the COVID-19 pandemic, with cases registered before the pandemic. MATERIALS AND METHODS: A retrospective, observational, single center, cohort study was conducted that included patients that underwent emergency surgery for gastrointestinal perforation in the periods during the pandemic (6 months) and before the pandemic (12 months). Sociodemographic characteristics, comorbidities, duration of hospital and ICU stay, status at discharge, and perforation site were compared. RESULTS: The study included 67 subjects (33 in the pre-pandemic period and 34 in the pandemic period). There were no significant differences regarding sex, age, or comorbidity. The perforation rate per emergency intervention was 4-times higher during the pandemic. There was an increase in the number of patients that were foreigners (4 [11%]) and nonresidents (6, [17%]). ICU admissions decreased (6 [19%]) but ICU stay increased to 137 h. Hospital stay increased by 5 days and delay in care increased 4.5 h. The number of deaths was higher (from 5 [15.2%] to 10 [29.4%]). Four patients with perforations were positive for COVID-19, were admitted to the ICU, and died. CONCLUSIONS: During the COVID-19 pandemic there was an increase in the incidence of gastrointestinal perforations at our healthcare system area; symptoms were more advanced, and mortality was higher.

Management of splenic and/or hepatic pseudoaneurysm following abdominal trauma in pediatric patients. / Manejo del pseudoaneurisma esplénico y/o hepático después de un traumatismo abdominal en pediatría.

INTRODUCTION: Splenic and hepatic pseudoaneurysm (PA) is a rare arteriovenous injury that may occur following abdominal trauma. The most frequent complication of PA is late rupture, which can lead to hemodynamic instability. The objective of this study was to describe our experience in the management of visceral PA. MATERIAL AND METHODS: A retrospective study of patients under 15 years of age with blunt abdominal trauma associated with splenic and/or hepatic injury treated from 2012 to 2020 was carried out. PA formation and management were analyzed. All patients underwent CT-scan, which allowed trauma grade to be established, and also control contrast-enhanced ultrasonography (CEUS) in the first week following trauma. If PA was confirmed, angiography ± percutaneous embolization were performed. RESULTS: A total of 32 patients with blunt trauma were included. Mean age was 8.7 ± 3.2 years (2-15 years). 68.7% (n = 22) of patients were male. Median trauma grade was grade III (grades II-IV). 33.3% (n = 5/15) of patients developed splenic PA, and 5.8% (n = 1/17) of patients developed hepatic PA, with mean diagnostic time being 3.7 ± 3 (3-8) days. PA formation was associated with higher severity scores, with a mean difference of 15.6 ± 5.3 (95% CI: 4.37:26.14 p < 0.008). All PA cases - except for one, which required urgent splenectomy - were treated with embolization (85.7%) (n = 5/6). CONCLUSION: Visceral PA is underdiagnosed, with an incidence higher than reported. Imaging studies (CEUS) are required prior to discharge in the presence of severe trauma. Treatment remains controversial, but we recommend percutaneous embolization, with splenectomy being reserved for unstable patients.

INTRODUCCION: Los pseudoaneurismas (PA) esplénicos y hepáticos son lesiones arteriovenosas raras que se pueden desarrollar tras un traumatismo abdominal. La rotura tardía es su complicación más frecuente que puede conducir a inestabilidad hemodinámica. El objetivo del presente es presentar nuestra experiencia en el manejo de los PA viscerales. METODOLOGIA: Estudio retrospectivo en pacientes menores de 15 años con traumatismo abdominal cerrado con lesión esplénica y/o hepática, entre 2012-2020. Se analizó el desarrollo de PA y el manejo realizado. En todos los pacientes se realizó tomografía computarizada estableciendo el grado del traumatismo, y estudio control en la primera semana postratumatismo mediante ecografía con contraste (CEUS). Si se confirmaba un PA se procedió a angiograma ± embolización percutánea. RESULTADOS: Un total de 32 pacientes con traumatismo cerrado, edad media 8,7 ± 3,2 años (2-15 años), 68,7% (n = 22) hombres y mediana de grado de traumatismo grado III (grado II-IV), 33,3% (n = 5/15) desarrollaron un PA esplénico y 5,8% (n = 1/17) desarrollaron un PA hepático con tiempo diagnóstico medio de 3,7 ± 3 (3-8) días. El desarrollo de PA se asoció a mayor puntuación en el índice de severidad con una diferencia de medias de 15,6 ± 5,3 (CI 95% 4,37:26,14 p < 0,008). Todos los PA se trataron mediante embolización un 85,7% (n = 5/6) excepto una esplenectomía urgente. CONCLUSION: Los PA viscerales están infradiagnosticados, con una incidencia mayor a la reportada. Consideramos que un estudio de imagen (CEUS) debe ser realizado previo al alta en los traumatismos severos. El tratamiento sigue siendo controversial: sin embargo, recomendamos la embolización percutánea reservando la esplenectomía para paciente inestables.

Effect of antibiotics on mechanical properties of Bordetella pertussis examined by atomic force microscopy.

In recent years, the coevolution of microorganisms with current antibiotics has increased the mechanisms of bacterial resistance, generating a major health problem worldwide. Bordetella pertussis is a bacterium that causes whooping cough and is capable of adopting different states of virulence, i.e. virulent or avirulent states. In this study, we explored the nanomechanical properties of both virulent and avirulent B. pertussis as exposed to various antibiotics. The nanomechanical studies highlighted that only virulent B. pertussis cells undergo a decrease in their cell elastic modulus and height upon antimicrobial exposure, whereas their avirulent counterparts remain unaffected. This study also permitted to highlight different mechanical properties of individual cells as compared to those growing in close contact with other individuals. In addition, we analyzed the presence on the bacterial cell wall of Filamentous hemagglutinin adhesin (FHA), the major attachment factor produced by virulent Bordetella spp., under different virulence conditions by Force Spectroscopy.

Clinical and pathological features of Merkel cell carcinoma: A 4-year follow-up observational retrospective study in Spain.

BACKGROUND: Merkel cell carcinoma (MCC) is a malignant skin cancer with a 5-year survival rate of approximately 50%. Knowledge of MCC has increased in recent years mostly due to improved diagnosis techniques. In Spain there is lack of information regarding the incidence and tumour characteristics, and the treatment approaches are not standardised. The objective of this study was to provide information of the clinical and epidemiological characteristics of MCC patients in Spain. METHODS: Retrospective, observational study involving 192 patients from 25 Spanish hospitals. Evaluated variables included overall survival and incidence rate of Merkel cell polyomavirus, in patients diagnosed from 2012 to 2016. RESULTS: The Spanish incidence rate was estimated 0.32/100,000 inhabitants/year, with variations according to geographical regions, being slightly higher in areas with greater sunlight exposure. In total, 61.5% of tumours showed expansive growth (progressive growth of the tumour), 78.6% showed localisation in UV-exposed skin. 97.4% of patients were diagnosed by excisional biopsy. Surgery was the first line treatment in 96.6% of patients, radiotherapy in 24.6%, and chemotherapy in 6.3%. These treatments were not mutually exclusive. Median overall survival was 38.3 months (78.4% at 12 months and 60% at 24 months). MCPyV was present in 33.8% of patients. CONCLUSION: The incidence of MCC in Spain is one of the highest in Europe, with a slight predominance in men. The sample has shown that a biopsy is available for diagnosis in most cases. Moreover, the treatment is surgical when the tumour is localized and is associated with lymphadenectomy, and/or it is radiotherapy if widespread.

Evaluation of serum omentin-1 and apelin concentrations in patients with hidradenitis suppurativa.

INTRODUCTION: Recent studies suggest a role of adipokines in the pathogenesis of hidradenitis suppurativa (HS). Omentin-1 and apelin are two recently identified adipokines that have been involved in the regulation of metabolic and inflammatory responses. AIM: To investigate serum omentin-1 and apelin levels in patients with HS and to assess their associations with metabolic parameters, disease severity and HS risk. MATERIAL AND METHODS: This case-control study included 139 non-diabetic individuals (78 HS patients and 61 ageand sex-matched controls). Serum concentrations of omentin-1 and apelin and the homeostasis model assessment of insulin resistance (HOMA-IR) were measured in all participants. RESULTS: Serum omentin-1 concentrations were significantly higher in HS patients compared to controls, whereas apelin serum levels did not significantly differ between both groups. These differences in omentin-1 concentrations remained significant even after adjusting for age, sex, and body mass index (BMI). The results of logistic regression analysis showed that increased omentin-1 plasma levels were an independent risk factor for HS. However, we found no association between serum levels of both omentin-1 and apelin with HS severity. CONCLUSIONS: Our results show that patients with HS have raised omentin-1 serum levels, which are associated with HS risk.

Subcutaneous sarcoidosis: A case series of 19 patients.

Subcutaneous sarcoidosis is a rare variant of this disease, whose relationship with systemic disease is still controversial. Our objective was to describe the clinical characteristics of a series of patients with subcutaneous sarcoidosis and to investigate the relationship between these skin lesions and the disease's activity, severity, and prognosis. Nineteen patients with biopsy-confirmed subcutaneous sarcoidosis between 2009 and 2019 were selected. Mean age at diagnosis was 53 years. Lung involvement was detected in 10 patients (52.6%), mainly in stages I and II. Only two patients (10.5%) had additional systemic signs and five patients (26%) suffered from other autoimmune diseases simultaneously. Six patients (31.6%) had elevated angiotensin-converting enzyme levels (mean level 174.5 U/L). Eight patients (42%) received treatment, mainly systemic corticosteroids, and all patients except for one had a favorable clinical outcome. Subcutaneous sarcoidosis is frequently associated with a mild form of systemic disease, and the prognosis seems favorable regardless of treatment. Sarcoid nodules could be an early finding of systemic disease, allowing for less invasive procedures for histological confirmation.

Epidemiology of sarcoidosis in northern Spain, 1999-2019: A population-based study.

BACKGROUND: The incidence of sarcoidosis varies widely worldwide. The aim of this study was to estimate the incidence of sarcoidosis in a population-based cohort from northern Spain. METHODS: Patients diagnosed with sarcoidosis at Marqués de Valdecilla University Hospital, corresponding to the central Cantabria that encompasses Santander city and the surroundings, between January 1999 and December 2019were assessed. The diagnosis of sarcoidosis was established according to ATS/ERS/WASOG criteria as follows: compatible clinical and radiological presentation, histopathologic confirmation, and exclusion of other granulomatous diseases. Demographic and clinical data were collected. The incidence of sarcoidosis between 1999-2019 was estimated by sex, age, and year of diagnosis. RESULTS: A total of 234 patients were included, with a male/female ratio of 0.81. The mean age of the cohort at diagnosis was 48.43 ± 14.83 years and 129 (55.1%) were women. Incidence during the period of study was 3.58 per 100,000 populations (95% confidence interval: 3.13 - 4.07). No gender predominance was observed. An increase in age at diagnosis over time was found in the linear regression analysis. Thoracic affection was found in 180 patients (76.9%). Most common extra-thoracic areas affected were skin (34.2%), joints (30.8%) and eyes (15.4%). CONCLUSIONS: The incidence of sarcoidosis estimated in this study was similar to that of other Mediterranean countries. No gender predominance was observed. Consistent with previous studies, male presented an incidence peak 10 years earlier than female. A second peak between ages 60-69 years was identified in both sexes.

Interaction of cationic surfactants with DPPC membranes: effect of a novel Nα-benzoylated arginine-based compound.

Cationic amino acid-based surfactants are known to interact with the lipid bilayer of microorganism resulting in cell death through a disruption of the membrane topology. To elucidate the interaction of a cationic surfactant synthesized in our lab, investigations involving Nα-benzoyl-arginine decyl amide (Bz-Arg-NHC10), and model membranes composed by 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) were done. Bz-Arg-NHC10was able to penetrate into DPPC monolayers up to a critical pressure of 59.6 mN m-1. Differential scanning calorimetry revealed that as the concentration of Bz-Arg-NHC10 increased, the main transition temperature of DPPC slightly decreased. Atomic force microscopy (AFM) in situ experiments performed on supported DPPC bilayers on mica allowed monitoring the changes induced by Bz-Arg-NHC10. DPPC bilayer patches were partially removed, mainly in borders and bilayer defects for 50 µM Bz-Arg-NHC10 solution. Increasing the concentration to 100 µM resulted in a complete depletion of the supported bilayers. Surface plasmon resonance (SPR) experiments, carried out with fully DPPC bilayers covered chips, showed a net increase of the SPR signal, which can be explained by Bz-Arg-NHC10 adsorption. When patchy DPPC bilayers were formed on the substrate, a SPR signal net decrease was obtained, which is consistent with the phospholipids' removal observed in the AFM images. The results obtained suggest that the presence of the benzoyl group attached to the polar head of our compound would be the responsible of the increased antimicrobial activity against gram-negative bacteria when compared with other arginine-based surfactants.