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.

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.

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.

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.

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.