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.

Big data-based parathyroid hormone (PTH) values emphasize need for age correction.

PURPOSE: We aimed to study the relationship between aging and increased parathyroid hormone (PTH) values. METHODS: We performed a retrospective cross-sectional study with data from patients who underwent outpatient PTH measurements performed by a second-generation electrochemiluminescence immunoassay. We included patients over 18 years of age with simultaneous PTH, calcium, and creatinine measurements and 25-OHD measured within 30 days. Patients with glomerular filtration rate < 60 mL/min/1.73 m2, altered calcemia, 25-OHD level < 20 ng/mL, PTH values > 100 pg/mL or using lithium, furosemide or antiresorptive therapy were excluded. Statistical analyses were performed using the RefineR method. RESULTS: Our sample comprised 263,242 patients for the group with 25-OHD ≥ 20 ng/mL, that included 160,660 with 25-OHD ≥ 30 ng/mL. The difference in PTH values among age groups divided by decades was statistically significant (p < 0.0001), regardless of 25-OHD values, ≥ 20 or ≥ 30 ng/mL. In the group with 25-OHD ≥ 20 ng/mL and more than 60 years, the PTH values were 22.1-84.0 pg/mL, a different upper reference limit from the reference value recommended by the kit manufacturer. CONCLUSION: We observed a correlation between aging and PTH increase, when measured by a second-generation immunoassay, regardless of vitamin D levels, if greater than 20 ng/mL, in normocalcemic individuals without renal dysfunction.

Seroprevalence of ANTI-SARS-CoV-2 antibodies in patients with inflammatory bowel disease.

Patients with inflammatory bowel disease (IBD) treated with biologic and/or immunosuppressant drugs are at increased risk for opportunistic infections. Seroprevalence studies can confirm the diagnosis of SARS-CoV-2 infections as well as the associated risk factors. This is a descriptive study which primary endpoints were to highlight the prevalence of SARS-CoV-2 antibodies in a cohort of IBD patients in March 2021, and to analyze seroconversion in patients with known COVID-19 infection and its relationship with IBD treatments. Patients filled in a questionnaire about symptoms of COVID-19 infection and clinical information about their IBD. All included patients were tested for SARS-CoV-2 antibodies. 392 patients were included. Among patients with clinical infection, 69 patients (17,65%) were IgG-positive, 286 (73,15%) IgG-negative and 36 (9,21%) indeterminate. In relation to seroconversion among patients under biologic treatment, 13 patients of the 23 with a previous positive CRP developed antibodies (56.5%). However, when the influence of immunosuppressive treatment on the probability of developing antibodies was analyzed, no significant differences were seen between those patients with or without treatment (77.8% vs. 77.1%, p = 0.96). In our cohort of IBD patients, after one year of pandemic, there were 18.64% IgG positive patients, a higher prevalence than the general population (15.7%).

Angiotensin-(1-7), a protective peptide against vascular aging.

Vascular aging is a complex and multifaceted process that provokes profound molecular, structural, and functional changes in the vasculature. Eventually, these profound aging alterations make arteries more prone to vascular disease, including hypertension, atherosclerosis and other arterial complications that impact the organism beyond the cardiovascular system and accelerate frailty. For these reasons, preventing or delaying the hallmarks of vascular aging is nowadays a major health goal, especially in our aged societies. In this context, angiotensin(Ang)-(1-7), a major player of the protective branch of the renin-angiotensin system, has gained relevance over recent years as growing knowledge on its anti-aging properties is being unveiled. Here, we briefly review the main actions of Ang-(1-7) against vascular aging. These include protection against vascular cell senescence, anti-inflammatory and antioxidant effects together with the induction of cytoprotective systems. Ang-(1-7) further ameliorates endothelial dysfunction, a hallmark of vascular aging and disease, attenuates fibrosis and calcification and promotes protective angiogenesis and repair. Although further research is needed to better understand the anti-aging properties of Ang-(1-7) on the vasculature, this heptapeptide arises as a promising pharmacological tool for preventing vascular aging and frailty.

Impact of the COVID-19 pandemic on acute appendicitis in children.

BACKGROUND AND OBJECTIVES: Since the COVID-19 pandemic confinement was established in Spain on March 9, 2020, the number of visits to the pediatric Emergency Department (ED) has decreased dramatically, probably due to the fear of parents becoming infected in the hospital environment. The aim of this work was to analyze the medium-term consequences during the first 9 months after the onset of the COVID-19 pandemic in children with acute appendicitis (AA). MATERIAL AND METHODS: A retrospective study was performed on children operated on for AA in our institution between 2017 and 2020, who were distributed in two groups according to the date of surgery: COVID-19 group (after March 9, 2020) and control group (before March 9, 2020). Demographic variables, associated symptoms, time from symptoms onset, hospital stay, rate of complicated AA and postoperative complications were analyzed. RESULTS: A total of 1274 patients were included (288 COVID group; 986 control group), without demographic differences. Time from symptom onset was significantly longer in COVID-19 group (34.5 vs. 24.2h; p=0.021), although no differences in associated symptoms were observed between both groups. COVID-19 group presented a higher rate of complicated AA (20.1% vs. 14%; OR: 1.55; CI 95% [1.10-2.18]; p=0.008), a longer hospital stay (3.5 vs. 2.8 days; p=0.042) as well as a higher rate of postoperative complications (21.5% vs. 15.7%; OR: 1.47; CI 95% [(1.06-2.04)]; p=0.008). CONCLUSION: In our experience there was a negative medium-term effects of the COVID-19 pandemic on children with acute appendicitis: delayed ED visits, increased rate of complicated AA, increased hospital stay and increased postoperative complications.

Simple template-based optimization for pediatric total lymphoid irradiation (TLI) radiotherapy treatments.

Total lymphoid irradiation (TLI) is used in the management of pediatric allogeneic hematopoietic stem cell transplantation (HSCT. This work aims to simplify the treatment planning process for TLI via a proposed template using the volumetric modulated arc therapy (VMAT) technique. Fifteen pediatric patients were planned, prescribed to 8 Gy in 4 fractions. Cost functions included in the template were the ones for the planning target volume (PTV), and conformality cost function (CCF) for the rest of the patient's volume. Conformity index (CI), homogeneity index (HI), conformation number (CN), gradient index (GI), integral dose, and doses to the organs at risk achieved with the template were reported. Cost function influence over various indexes was studied by Wilcoxon signed ranks test. Same 15 patients were planned with 3-dimensional conventional radiotherapy (3D-CRT) technique for comparison. Mean CI and HI were 1.33 and 0.13, respectively, which indicates good dose conformation and homogeneity. Mean CN and GI values were 0.69 and 4.51, respectively. Mean PTV coverage was reached (V100% > 95%). No correlation between the CCF and indexes values was found (p > 0.05). Doses to organs at risk (OARs) were as low as possible without losing PTV coverage. VMAT plan showed higher levels of conformation and similar homogeneity as 3D-CRT plans. Doses to OARs were inferior with VMAT except for the right kidney. The proposed template simplifies the planning of TLI treatments, and it is able to create acceptable plans with little modification in order to reduce doses to certain organs like the kidneys or the heart. VMAT technique showed higher conformation and lower doses to OAR compared to 3D-CRT.

Differences in the response in the dermis of the tails of young and old SD rats to treatment with bipolar RF.

BACKGROUND: The passing of the years is marked by intrinsic (chronological) and extrinsic aging, caused by photoaging, which is characterized by a decrease in collagen and the deposition of abnormal elastic fibers in the dermis. The use of bipolar radiofrequency (RF) increases fibroblast proliferation and differentiation, accompanied by collagen synthesis and a subsequent increase in connective tissue, and it is not known whether the biological effects of this type of radiofrequency on the dermis are similar regardless of the age of the individual or whether such effects are altered by the aging process itself. AIMS: The objective was to perform a histological study of the changes in the tail dermis of young and old rats after submitting them to bipolar RF, to determine cell proliferation and volume of connective tissue. METHODS: One part of the rat tail was fixed in formol and processed for light microscopy and another part processed for electron microscopy. RESULTS: The number of fibroblasts/unit area and cells positive to nuclear proliferation antigen was higher in young animals. Significant differences were observed regarding expression of HSP-47 protein, and the value was always lower in old rats. No significant differences were observed in the percentage of connective tissue. No histological alterations were observed in any rats. CONCLUSION: Treatment with RF increased the number of fibroblasts located in the connective tissue of the young rats. In addition, the effect of a single treatment on the population of fibroblasts in young animals was sufficient to activate the synthesis of new collagen.

Hyperbaric oxygen and radiation therapy: a review.

About 5% of cancer patients treated with radiotherapy will have severe late-onset toxicity. Hyperbaric oxygen therapy (HBOT) has been used as a treatment for radiation injuries for decades, with many publications presenting data from small series or individual cases. Moreover, we know that the hypoxic areas of tumours are more resistant to radiation. HBOT increases the oxygen tension in tissues and, theoretically, it should enhance the efficiency of radiotherapy. To better understand how HBOT works, we carried out this bibliographic review. We found Grade B and C evidence that at pressures exceeding 2 absolute atmospheres (ata), HBOT reduced late-onset radiation injuries to the head and neck, bone, prostate and bladder. It also appeared to prevent osteoradionecrosis after exodontia in irradiated areas. Finally, HBOT at 2 ata increased the effectiveness of radiation in head and neck tumours and achieved promising results in the local control of high-grade gliomas.

Prevalencia de resistencia transmitida a drogas antirretrovirales en pacientes con infección por VIH en Chile (2014-2018)

Background: Transmitted drug resistance (TDR) occurs in patients with HIV infection who are not exposed to antiretroviral drugs but who are infected with a virus with mutations associated with resistance. Aim: To determine the prevalence of TDR and characterize HIV reverse transcriptase and protease mutation patterns. Material and Methods: HIV infected antiretroviral treatment-naive patients treated in three centers between 2014 and 2018 were studied. A genotyping study was carried out. The HIVdb Program (Stanford University) and the World Health Organization (WHO) TDR surveillance mutation list were used to register resistance-associated mutations. Results: We enrolled 220 patients aged a median of 29 (interquartile range (IQR) 24-34) years, 99% men. Median CD4 count was 365 cells/μL (IQR 250-499 cells/μL) and median viral load was 39.150 copies/mL (IQR 9,270 −120,000). The overall prevalence of RTD was 10.45% (95% CI 6.7-15.2, N = 23/220). The higher frequency of TDR was against non-nucleoside reverse transcriptase inhibitors, reaching 9.0% (95% CI 5.6-13.6), followed by nucleoside reverse transcriptase inhibitors reaching 1.8% (95% CI 0.49-4.5) and protease inhibitors reaching 0.45% (95% CI 0.01-2.5). The mutations in reverse transcriptase were M41L, L210W, D67N, K70E, M184V, K103N (6.36%, 95% CI 3.5-10.4), G190A, E138A, K101E, and I84V in protease. Conclusions: These results should prompt a change in recommendations for starting antiretoviral therapy, especially in first-line regimens that include non-nucleoside reverse transcriptase inhibitors.

[Prevalence of transmitted drug resistance in HIV-infected treatment-naive patients in Chile]. / Prevalencia de resistencia transmitida a drogas antirretrovirales en pacientes con infección por VIH en Chile (2014-2018).

BACKGROUND: Transmitted drug resistance (TDR) occurs in patients with HIV infection who are not exposed to antiretroviral drugs but who are infected with a virus with mutations associated with resistance. AIM: To determine the prevalence of TDR and characterize HIV reverse transcriptase and protease mutation patterns. MATERIAL AND METHODS: HIV infected antiretroviral treatment-naive patients treated in three centers between 2014 and 2018 were studied. A genotyping study was carried out. The HIVdb Program (Stanford University) and the World Health Organization (WHO) TDR surveillance mutation list were used to register resistance-associated mutations. RESULTS: We enrolled 220 patients aged a median of 29 (interquartile range (IQR) 24-34) years, 99% men. Median CD4 count was 365 cells/µL (IQR 250-499 cells/µL) and median viral load was 39.150 copies/mL (IQR 9,270 -120,000). The overall prevalence of RTD was 10.45% (95% CI 6.7-15.2, N = 23/220). The higher frequency of TDR was against non-nucleoside reverse transcriptase inhibitors, reaching 9.0% (95% CI 5.6-13.6), followed by nucleoside reverse transcriptase inhibitors reaching 1.8% (95% CI 0.49-4.5) and protease inhibitors reaching 0.45% (95% CI 0.01-2.5). The mutations in reverse transcriptase were M41L, L210W, D67N, K70E, M184V, K103N (6.36%, 95% CI 3.5-10.4), G190A, E138A, K101E, and I84V in protease. CONCLUSIONS: These results should prompt a change in recommendations for starting antiretoviral therapy, especially in first-line regimens that include non-nucleoside reverse transcriptase inhibitors.

Dose and time effects of solar-simulated ultraviolet radiation on the in vivo human skin transcriptome.

BACKGROUND: Terrestrial ultraviolet (UV) radiation causes erythema, oxidative stress, DNA mutations and skin cancer. Skin can adapt to these adverse effects by DNA repair, apoptosis, keratinization and tanning. OBJECTIVES: To investigate the transcriptional response to fluorescent solar-simulated radiation (FSSR) in sun-sensitive human skin in vivo. METHODS: Seven healthy male volunteers were exposed to 0, 3 and 6 standard erythemal doses (SED). Skin biopsies were taken at 6 h and 24 h after exposure. Gene and microRNA expression were quantified with next generation sequencing. A set of candidate genes was validated by quantitative polymerase chain reaction (qPCR); and wavelength dependence was examined in other volunteers through microarrays. RESULTS: The number of differentially expressed genes increased with FSSR dose and decreased between 6 and 24 h. Six hours after 6 SED, 4071 genes were differentially expressed, but only 16 genes were affected at 24 h after 3 SED. Genes for apoptosis and keratinization were prominent at 6 h, whereas inflammation and immunoregulation genes were predominant at 24 h. Validation by qPCR confirmed the altered expression of nine genes detected under all conditions; genes related to DNA repair and apoptosis; immunity and inflammation; pigmentation; and vitamin D synthesis. In general, candidate genes also responded to UVA1 (340-400 nm) and/or UVB (300 nm), but with variations in wavelength dependence and peak expression time. Only four microRNAs were differentially expressed by FSSR. CONCLUSIONS: The UV radiation doses of this acute study are readily achieved daily during holidays in the sun, suggesting that the skin transcriptional profile of 'typical' holiday makers is markedly deregulated. What's already known about this topic? The skin's transcriptional profile underpins its adverse (i.e. inflammation) and adaptive molecular, cellular and clinical responses (i.e. tanning, hyperkeratosis) to solar ultraviolet radiation. Few studies have assessed microRNA and gene expression in vivo in humans, and there is a lack of information on dose, time and waveband effects. What does this study add? Acute doses of fluorescent solar-simulated radiation (FSSR), of similar magnitude to those received daily in holiday situations, markedly altered the skin's transcriptional profiles. The number of differentially expressed genes was FSSR-dose-dependent, reached a peak at 6 h and returned to baseline at 24 h. The initial transcriptional response involved apoptosis and keratinization, followed by inflammation and immune modulation. In these conditions, microRNA expression was less affected than gene expression.

TLI in pediatric patients.

PURPOSE: Hematopoietic progenitor cell transplantation (HSCT) is a procedure used in different hematological diseases as part of the curative treatment, so the investigators propose a system of conditioning of reduced intensity based on total lymphoid irradiation (TLI) as an alternative to the classic total body irradiation (TBI) followed by haploidentical transplantation in patients compatible with a single HLA haplotype, as an alternative to patients who do not have an HLA compatible donor. MATERIALS AND METHODS: A cohort of 25 patients with hematological disease underwent haploidentical HSCT from February 2015 to May 2018, conditioned with TLI from day - 10 (2-4 days of treatment) followed by thiotepa (5 mg/kg/12 h) and melphalan (70 mg/m2/day) prior to HSCT and prophylaxis with ciclosporin (1.5 mg/kg/12 h). 2 Gy/fraction was administered to complete 8 Gy with IMRT and VMAT technique. RESULTS: 12% rejection of the transplant was obtained with acute GVHD < II (48%) and chronic GVHD 12%. No acute toxicity was recorded in irradiated patients and 56% survival of patients at the end of follow-up. CONCLUSION: Conditioning the haploidentical transplant with TLI, IMRT, and VMAT techniques compared with TBI and RT3D-C techniques is a feasible technique that helps inducing the necessary immunosuppression in patients with a high risk of graft rejection, minimal adverse effects, low incidence of GVHD, and high survival rate.

Are there enough radiation oncologists to lead the new Spanish radiotherapy?

AIM: Radiation oncology services in Spain are undergoing a process of technical modernization, but-in a context of increasing demand by an ageing population-it is unclear whether there are enough radiation oncologists to staff the newly equipped units. This study aims to assess the number of specialists working in radiation oncology services in Spain relative to current and future needs. MATERIALS AND METHODS: In the second half of 2017, the Commission on Infrastructures of the Spanish Society for Radiation Oncology (SEOR) sent a questionnaire on radiation oncology staff to the heads of all 122 public (n = 76, 62%) and private (n = 46, 38%) radiation oncology services in Spain. Data collected were the number of professionals, their position, and their year of birth for specialists and residents in each service. In the descriptive analysis, for continuous variables we calculated means, standard deviations and ranges for each Spanish region and work post. For qualitative variables, we constructed frequency tables. All analyses were performed with R statistical software, version 3.5.1. RESULTS: The survey response rate was 100% among service heads across all 122 centers. The total number of radiation oncologists working in these centers is 721, or 15.4 per million population, with considerable variations between regions. Given the national recommendations to have 20 radiation oncologists per million population, there is currently a deficit of 204 specialists. If the 163 upcoming retirements are also taken into account, there will be 367 fewer radiation oncologists than required to meet the 25% increase in indications for radiotherapy projected for 2025. CONCLUSIONS: The classic model for calculating staff needs based on the number of treatments is outdated, and recommendations should be revised to reflect the current reality. A new model should integrate the most complex technological advances and emerging plans in radiotherapy, without neglecting the other activities carried out in radiation oncology services that are not directly linked to patient care.

Exploration of environmental contaminants in honeybees using GC-TOF-MS and GC-Orbitrap-MS.

This study reports an analytical approach by gas chromatography and high-resolution mass spectrometry (HRMS) intended to be used for investigation of non-targeted environmental contaminants in honeybees. The approach involves a generic extraction and analysis with two GC-HRMS systems: time-of-flight and Orbitrap analyzers, GC-TOF-MS, and GC-Orbitrap-MS operated in electron-impact ionization (EI) mode. The workflow for screening of non-targeted contaminants consisted of initial peak detection by deconvolution and matching the first-stage mass spectra EI-MS with a nominal mass spectral library. To gain further confidence in the structural characterization of the contaminants under investigation, molecular formula of representative ions (molecular and fragment ions) was provided for those with an accurate mass scoring (error < 5 ppm). This methology was applied for screening environmental contaminants in 75 samples of adult honeybee. This approach has provided the tentative identification of environmental contaminants belonging to different chemical groups, among them, PAHs, phthalates and synthetic musks. Residues of veterinary treatments used in apiculture were also detected in the honeybee samples.

Loss of hamster Leydig cells during regression after exposure to a short photoperiod.

The aim of the present study was to evaluate the changes that occur in hamster Leydig cells during regression. Animals were divided into control, mild regression (MR), strong regression (SR) and total regression (TR) groups. Leydig cells were characterised by light and electron microscopy. Terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling (TUNEL) and proliferating cell nuclear antigen (PCNA) antibodies were used to detect apoptosis and proliferation respectively. Three types of Leydig cells (A, B and C) could be differentiated. Type A cells were small in size compared with Leydig cells from animals exposed to a long photoperiod, which was a result of a decreased cytoplasm and nucleus. Type B cells were even smaller than Type A cells in regression groups. Type C exhibited cytoplasm vacuolisation. The percentage of Type C cells from the control group was much lower than in the MR, SR and TR groups. (P<0.05). In the SR and TR groups, there was a significant decrease in the percentage of Type B cells compared with the control and MR groups (P<0.05). The total number of Leydig cells decreased during testicular regression (P<0.05). The total number of Type A and B cells was significantly lower in the MR, SR and TR groups compared with the control group (P<0.05). There were no significant differences in the proliferation and apoptosis index in the groups studied. The findings of the present study indicate that there are three types of Leydig cells (A, B and C) in all hamsters studied and that regression causes an increase in the number of Type C cells, so that the reduction in the number Leydig cells during the phases of regression studied must be the result of necrosis and/or necroptosis.

Infrastructure and equipment for radiation oncology in the Spanish National Health System: analysis of external beam radiotherapy 2015-2020.

PURPOSE: Planning for radiation oncology requires reliable estimates of both demand for radiotherapy and availability of technological resources. This study compares radiotherapy resources in the 17 regions of the decentralised Spanish National Health System (SNHS). MATERIALS AND METHODS: The Sociedad Española de Oncología Radioterápica (SEOR) performed a cross-sectional survey of all Spanish radiation oncology services (ROS) in 2015. We collected data on SNHS radiotherapy units, recording the year of installation, specific features of linear accelerators (LINACs) and other treatment units, and radiotherapeutic techniques implemented by region. Any machine over 10 years old or lacking a multileaf collimator or portal imaging system was considered obsolete. We performed a k-means clustering analysis using the Hartigan-Wong method to test associations between the gross domestic regional product (GDRP), the number of LINACs per million population and the percentage of LINACs over 10 years old. RESULTS: The SNHS controls 72 (61%) of the 118 Spanish ROS and has 180 LINACs, or 72.5% of the total public and private resources. The mean rate of LINACs per million population is 3.9 for public ROS, and 42% (n = 75) of the public accelerators were obsolete in 2015: 61 due to age and 14 due to technological capability. There was considerable regional variation in terms of the number and technological capacity of radiotherapy units; correlation between GRDP and resource availability was moderate. CONCLUSION: Despite improvements, new investments are still needed to replace obsolete units and increase access to modern radiotherapy. Regular analysis of ROS in each Spanish region is the only strategy for monitoring progress in radiotherapy capacity.

Nutrient sensor O-GlcNAc transferase controls cancer lipid metabolism via SREBP-1 regulation.

Elevated O-GlcNAcylation is associated with disease states such as diabetes and cancer. O-GlcNAc transferase (OGT) is elevated in multiple cancers and inhibition of this enzyme genetically or pharmacologically inhibits oncogenesis. Here we show that O-GlcNAcylation modulates lipid metabolism in cancer cells. OGT regulates expression of the master lipid regulator the transcription factor sterol regulatory element binding protein 1 (SREBP-1) and its transcriptional targets both in cancer and lipogenic tissue. OGT regulates SREBP-1 protein expression via AMP-activated protein kinase (AMPK). SREBP-1 is critical for OGT-mediated regulation of cell survival and of lipid synthesis, as overexpression of SREBP-1 rescues lipogenic defects associated with OGT suppression, and tumor growth in vitro and in vivo. These results unravel a previously unidentified link between O-GlcNAcylation, lipid metabolism and the regulation of SREBP-1 in cancer and suggests a crucial role for O-GlcNAc signaling in transducing nutritional state to regulate lipid metabolism.