Active Treatment Research Articles

DNA-sensing inflammasomes cause recurrent atherosclerotic stroke.

The risk of early recurrent events after stroke remains high despite currently established secondary prevention strategies1. Risk is particularly high in patients with atherosclerosis, with more than 10% of patients experiencing early recurrent events1,2. However, despite the enormous medical burden of this clinical phenomenon, the underlying mechanisms leading to increased vascular risk and recurrent stroke are largely unknown. Here, using a novel mouse model of stroke-induced recurrent ischaemia, we show that stroke leads to activation of the AIM2 inflammasome in vulnerable atherosclerotic plaques via an increase of circulating cell-free DNA. Enhanced plaque inflammation post-stroke results in plaque destabilization and atherothrombosis, finally leading to arterioarterial embolism and recurrent stroke within days after the index stroke. We confirm key steps of plaque destabilization also after experimental myocardial infarction and in carotid artery plaque samples from patients with acute stroke. Rapid neutrophil NETosis was identified as the main source of cell-free DNA after stroke and NET-DNA as the causative agent leading to AIM2 inflammasome activation. Neutralization of cell-free DNA by DNase treatment or inhibition of inflammasome activation reduced the rate of stroke recurrence after experimental stroke. Our findings present an explanation for the high recurrence rate after incident ischaemic events in patients with atherosclerosis. The detailed mechanisms uncovered here provide clinically uncharted therapeutic targets for which we show high efficacy to prevent recurrent events. Targeting DNA-mediated inflammasome activation after remote tissue injury represents a promising avenue for further clinical development in the prevention of early recurrent events.

A Meta-Analysis of Interpersonal and Psychodynamic Psychotherapies for Posttraumatic Stress Disorder.

Established trauma-focused cognitive-behavioral therapies for posttraumatic stress disorder (PTSD) have remission rates of approximately 30%-40%. Alternatively, interpersonal psychotherapy (IPT) and psychodynamic psychotherapy (PDT) focus on disrupted attachment, mentalization, and social connection in PTSD and may help some patients. The authors conducted a meta-analysis on these interpersonal and affect-oriented approaches to treating PTSD. Building on a prior meta-analysis, the authors searched for randomized controlled trials (RCTs) comparing IPT or PDT with other established PTSD treatments or control conditions for adults diagnosed as having PTSD. Random-effects meta-analyses were conducted to assess outcome effect sizes and dropout rates. RCTs were rated via the Randomized Controlled Trial Psychotherapy Quality Rating Scale. Ten RCTs (eight of IPT) comparing IPT or PDT with control (k=7) or active treatment (k=4) conditions were identified, nine of which were of adequate quality. IPT (k=5) and PDT (k=2), when analyzed together, were superior to control conditions overall (g=-1.14, p=0.011 [as was IPT alone: g=-0.88, p=0.034]) and to waitlist (g=-1.49) and treatment-as-usual (g=-0.70) groups. Effect sizes, however, may have been inflated by outliers or publication bias. IPT (k=3) and PDT (k=1), when analyzed together, were equally efficacious compared with other active PTSD treatments (primarily exposure-based psychotherapies), as was IPT alone, and had lower dropout rates (relative risk=0.63, p=0.049 for IPT and PDT analyzed together; relative risk=0.61, p=0.098 for IPT alone). Affect-focused therapies hold promise in the treatment of PTSD. IPT has demonstrated efficacy in multiple trials, whereas the evidence base for PDT is sparse.

Measuring the individualization potential of treatment individualization rules: Application to rules built with a new parametric interaction model for parallel-group clinical trials.

For personalized medicine, we propose a general method of evaluating the potential performance of an individualized treatment rule in future clinical applications with new patients. We focus on rules that choose the most beneficial treatment for the patient out of two active (nonplacebo) treatments, which the clinician will prescribe regularly to the patient after the decision. We develop a measure of the individualization potential (IP) of a rule. The IP compares the expected effectiveness of the rule in a future clinical individualization setting versus the effectiveness of not trying individualization. We illustrate our evaluation method by explaining how to measure the IP of a useful type of individualized rules calculated through a new parametric interaction model of data from parallel-group clinical trials with continuous responses. Our interaction model implies a structural equation model we use to estimate the rule and its IP. We examine the IP both theoretically and with simulations when the estimated individualized rule is put into practice in new patients. Our individualization approach was superior to outcome-weighted machine learning according to simulations. We also show connections with crossover and N-of-1 trials. As a real data application, we estimate a rule for the individualization of treatments for diabetic macular edema and evaluate its IP.

Reduction of N-Acetylglucosaminyltransferase-I Activity Promotes Neuroblastoma Invasiveness and EGF-Stimulated Proliferation In Vitro

Aberrant N-glycosylation has been associated with progression of the pediatric cancer neuroblastoma (NB) but remains understudied. Here we investigated oligomannose N-glycans in NB by genetic editing of MGAT1 in a human NB cell line, BE(2)-C, called BE(2)-C(MGAT1−/−). Lectin binding studies confirmed that BE(2)-C(MGAT1−/−) had decreased complex and increased oligomannose N-glycans. The relevance of 2D and 3D cell cultures was demonstrated for cell morphology, cell proliferation, and cell invasion, thereby highlighting the necessity for 3D cell culture in investigating cancerous properties. Western blotting revealed that oligomannosylated EGFR had increased autophosphorylation. Proliferation was decreased in BE(2)-C(MGAT1−/−) using 2D and 3D cultures, but both cell lines had similar proliferation rates using 3D cultures without serum. Upon EGF treatment, BE(2)-C(MGAT1−/−), but not BE(2)-C, showed increased proliferation, and furthermore, the mutant proliferated much faster than BE(2)-C under 3D conditions. Cell spheroid invasiveness was greatly increased in BE(2)-C(MGAT1−/−) compared with BE(2)-C. Moreover, invasiveness was reduced in both cell lines with either EGF or RhoA activator treatment, regardless of the N-glycan population. Thus, this study further extends our earlier findings that oligomannose N-glycans enhance NB cell invasiveness, and that EGF stimulation of oligomannosylated EGFR greatly enhances cell proliferation rates, underlining the role of oligomannose N-glycans in the promotion of NB.

Neuroplasticity in Parkinson's disease.

Parkinson's disease (PD) is the second most frequent neurodegenerative disorder, affecting millions of people and rapidly increasing over the last decades. Even though there is no intervention yet to stop the neurodegenerative pathology, many efficient treatment methods are available, including for patients with advanced PD. Neuroplasticity is a fundamental property of the human brain to adapt both to external changes and internal insults and pathological processes. In this paper we examine the current knowledge and concepts concerning changes at network level, cellular level and molecular level as parts of the neuroplastic response to protein aggregation pathology, synapse loss and neuronal loss in PD. We analyse the beneficial, compensatory effects, such as augmentation of nigral neurons efficacy, as well as negative, maladaptive effects, such as levodopa-induced dyskinesia. Effects of physical activity and different treatments on neuroplasticity are considered and the opportunity of biomarkers identification and use is discussed.

Oculomotor nerve palsy caused by imidacloprid at initial diagnosis: A case report.

Amid the pervasive deployment of imidacloprid, the incidence of poisoning from this compound has risen markedly. Those afflicted with imidacloprid poisoning typically exhibit symptoms ranging from headaches, dizziness, nausea, and abdominal pain, to impaired consciousness and breathlessness, yet instances of ocular paralysis induced by this toxin have not previously been documented. When the pesticide spray inadvertently made contact with the patient's eyes, they were seared with a burning sensation and discomfort. Subsequent to this incident, on the second day, the individual began to experience diplopia in the right eye and found it arduous to elevate his eyelids, indicating a challenge in achieving full extension. Based on the medical history, symptoms, and signs, the patient was diagnosed with oculomotor nerve palsy caused by imidacloprid. The treatment involved intravenous dexamethasone to reduce inflammatory response in the eye tissue; oral pantoprazole enteric-coated tablets to suppress acid production and protect the stomach; Xuesaitong administered intravenously to improve blood supply to the eye and promote metabolism of toxins; vitamin C, cobamamide, and vitamin B1 for nerve nutrition and antioxidant effects; local application of tobramycin-dexamethasone eye drops for anti-inflammatory purposes; and repeated flushing of the conjunctival sac with saline. Finally, the patient improved and was discharged. After active treatment, the patient finally improved diplopia and ptosis. This report marks the first documentation of oculomotor nerve palsy induced by imidacloprid, featuring diplopia, and blepharoptosis without substantial limitation of ocular motility. Following therapeutic intervention, the patient showed marked improvement and was discharged from the hospital, providing a point of reference for the treatment of analogous cases in future clinical practice. It also serves as a reminder for the public to take appropriate precautions when using imidacloprid.

Experiences and meaningfulness of breast cancer survivorship care in improving the quality of life of immigrant women: A qualitative systematic review

Introduction: Holistic healthcare approaches tailored to people’s needs can enhance quality of life. However, needs of immigrant women in breast cancer survivorship have received little attention. Language barriers can result in significant challenges to accessing healthcare and difficulty in translating information from healthcare providers into self-management. The purpose of this review was to examine the experiences and meaningfulness of breast cancer survivorship care in improving the quality of life for immigrant breast cancer survivors. Methods: A qualitative systematic review using a systematic search of peer-reviewed and non-peer-reviewed articles of empirical research was conducted. Articles about immigrant women who were diagnosed, treated, and completed their initial course of breast cancer treatment were included. Exclusion criteria were non-immigrant women, men, younger than 18 years, no breast cancer diagnosis, not currently undergoing active or advanced treatment, and not receiving palliative or end-of-life care. Thematic synthesis and qualitative systematic review included studies of survivorship care targeting breast cancer treatment and post-treatment. Articles were obtained from PubMed/MEDLINE, CINAHL, Embase, PsycINFO, Web of Science, and Google Scholar searches, with findings configured according to the JBI methodology. Results: Twenty studies, most of moderate- to high-quality were included. The thematic synthesis identified two overall themes regarding breast cancer survivorship care, as well as subthemes for both. The subthemes of the first theme, challenges and experiences accessing and using healthcare services, were inadequate insurance and benefits, less acculturation and decision-making, discrimination and differential treatment, and influencing sociocultural factors. The subthemes of the second theme, facilitators and barriers to accessing and using healthcare services, included ineffective knowledge and communication, lack of continuity and information, cultural and language barriers, limited access to services, and quality of care. Conclusions: Supporting and engaging immigrant women throughout their breast cancer journey is critical. To do so requires integrating advancements in survivorship care as a systematic approach to lead to a better quality of life and improving patient-reported outcomes.

‘Just because I have prostate cancer doesn’t mean that I can’t do things’ – men’s experiences of the acceptability of an exercise intervention for prostate cancer during treatment

BackgroundStructured exercise has an important role in mitigating the extensive side effects caused by ongoing prostate cancer treatments, specifically androgen deprivation therapy (ADT) and radiation therapy (RT). Little is known about men’s experiences of, and preferences for, structured exercise programmes during active cancer treatment. This study aimed to inform the acceptability of a 6-month supervised intervention that emphasised increasing and varied intensities of aerobic and resistance exercise, by exploring the experiences of men who participated.MethodsIndividual semi-structured interviews were conducted with an interviewer independent of the exercise study and data was analysed using a descriptive qualitative design.ResultsTwelve prostate cancer patients were interviewed including participants who completed (n = 9) and withdrew from (n = 3) the intervention. Four main themes captured how men experienced the intervention: (1) Navigating the Unknown: Building confidence amidst vulnerability (subtheme- pushing the limits), (2) Building Trust: The credibility and approach of the exercise instructor (subtheme- appropriateness of supervised vs. independent exercise), (3) Flexibility in Delivery, (4) Finding Purpose: Exercise as a means of escapism and regaining control during treatment.ConclusionWhile an initial lack of self-confidence can be a barrier to exercise participation, exercise programmes have the potential to provide psychosocial benefits, rebuild confidence and empower men throughout their cancer treatment and into recovery. Structured exercise is acceptable during treatment including RT and can offer a form of escapism and sense of control for men navigating their cancer journey. Trust building, flexible delivery and credibility alongside a challenging exercise prescription are important facilitators of acceptability for men. Strategies to embed exercise from the point of diagnosis through ADT and RT should reflect men’s experiences of exercise during treatment.Trial registrationThe trial has been registered on ClinicalTrials.gov as of the 14th of December 2021 (NCT05156424).

Efficacy of antihypertensive treatment for target organ protection in patients with masked hypertension (ANTI-MASK): a multicentre, double-blind, placebo-controlled trial

Masked hypertension is associated with target organ damage (TOD) and adverse health outcomes, but whether antihypertensive treatment improves TOD in patients with masked hypertension is unproven. In this multicentre, randomised, double-blind, placebo-controlled trial at 15 Chinese hospitals, untreated outpatients aged 30-70 years with an office blood pressure (BP) of <140/<90mm Hg and 24-h, daytime or nighttime ambulatory BP of ≥130/≥80, ≥135/≥85, or ≥120/≥70mm Hg were enrolled. Patients had ≥1 sign of TOD: electrocardiographic left ventricular hypertrophy (LVH), brachial-ankle pulse wave velocity (baPWV) ≥1400cm/s, or urinary albumin-to-creatinine ratio (ACR) ≥3.5mg/mmol in women and ≥2.5mg/mmol in men. Exclusion criteria included secondary hypertension, diabetic nephropathy, serum creatinine ≥176.8μmol/L, and cardiovascular disease within 6 months of screening. After stratification for centre, sex and the presence of nighttime hypertension, eligible patients were randomly assigned (1:1) to receive antihypertensive treatment or placebo. Patients and investigators were masked to group assignment. Active treatment consisted of allisartan starting at 80mg/day, to be increased to 160mg/day at month 2, and to be combined with amlodipine 2.5mg/day at month 4, if the ambulatory BP remained uncontrolled. Matching placebos were used likewise in the control group. The primary endpoint was the improvement of TOD, defined as normalisation of baPWV, ACR or LVH or a ≥20% reduction in baPWV or ACR over the 48-week follow-up. The intention-to-treat analysis included all randomised patients, the per-protocol analysis patients who fully adhered to the protocol, and the safety analysis all patients who received at least one dose of the study medication. This study is registered with ClinicalTrials.gov, NCT02893358. Between February 14, 2017, and October 31, 2020, 320 patients (43.1% women; mean age±SD 53.7±9.7 years) were enrolled. Baseline office and 24-h BP averaged 130±6.0/81±5.9mm Hg and 136±8.6/84±6.1mm Hg, and the prevalence of elevated baPWV, ACR and LVH were 97.5%, 12.5%, and 7.8%, respectively. The 24-h BP decreased on average (±SE) by 10.1±0.9/6.4±0.5mm Hg in 153 patients on active treatment and by 1.3±0.9/1.0±0.5mm Hg in 167 patients on placebo. Improvement of TOD occurred in 79 patients randomised to active treatment and in 49 patients on placebo: 51.6% (95% CI 43.7%, 59.5%) versus 29.3% (22.1, 36.5%; p<0.0001). Per-protocol and subgroup analyses were confirmatory. Adverse events were generally mild and occurred in 38 (25.3%) and 43 (26.4%) patients randomised to active treatment and placebo, respectively (p=0.83). Our results suggest that antihypertensive treatment improves TOD in patients with masked hypertension, highlighting the need of treatment. However, the long-term benefit in preventing cardiovascular complications still needs to be established. Salubris China.

Clinical stage IIA/B seminoma - to do or not to do: the role of retroperitoneal lymphadenectomy

About 10% of patients with seminomatous testicuar germ cell tumors are diagnosed with clinical stage II/B. The current guideline recommended treatment options include systemic chemotherapy with 3 cycles PEB or radiation therapy with 30 Gy for CS IIA and 36 Gy for CS IIB. Despite a high cure rate of 90-94% and 82-90% for CS IIA and CS IIB, respectively, both options are associated with a high rate of treatment-associated long-term toxicities. A significantly increased risk for the development of secondary malignancies, cardiovascular and metabolic disease as well as an increased for treatment-associated mortality has been proven in various studies. Primary nerve sparing retroperitoneal lymph node dissection (nsRPLND) has been evaluated in 5 prospective and retrospective clinical studies and it has emerged as a valid treatment alternative. The relapse-rate after a median follow-up of 25-33 months is in the range of 11-30%, so that 70-90% of patients are cured without being subjected to chemotherapy and potential long-term toxicities. All relapsing patients have been cured with secondary salvage chemotherapy. The frequency of significant surgery-associated complications is low with 3-13%. Therapeutic success depends on the surgical experience of the various surgeons and the chosen template, so that this type of surgical interventions should only be performed in centres of excellence with dedicated surgeons. Preoperative evaluation of the new biomarker miR371 has been shown to predict the presence of metastatic disease with an accuracy of around 100% so that this marker might be used in daily routine prior to active treatment in CS IIA/B seminomas.

Enhanced passivity of reinforcing steel in cementitious materials with thermally-activated red mud

Red mud (RM) is a solid waste from aluminium industry that can be used as an emerging supplementary cementitious material, and it has beneficial effects on the corrosion resistance of reinforcing steel in concrete. However, the low reactivity of RM reduces the comprehensive performance of cementitious materials, thereby limiting its widespread application in concrete. In this study, RM was thermally activated and the phase transformation behavior of the thermally-activated RM (TA-RM) was studied. Additionally, the passivation behavior of steel in extract solutions and mortars containing RM with and without thermal activation was investigated using electrochemical methods, surface characterization techniques and compositional analysis. The results showed that the reactivity of RM was effectively improved by the thermal activation treatment due to the phase transformation, and the enhanced steel passivity was observed in both extract solution and mortar with TA-RM. Compared to steel exposed to extract solutions, the mortar containing TA-RM could provide an additional protection for the embedded steel by forming a compact steel-mortar interface, further improving its passivation ability.

Association of rheumatoid factor, anti-citrullinated protein antibodies and shared epitope with clinical response to initial treatment in patients with early rheumatoid arthritis: data from a randomised controlled trial

ObjectivesTo investigate whether rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPAs) and shared epitope (SE) allele-related genetic markers associate with treatment response to abatacept, certolizumab pegol or tocilizumab versus active conventional...

Effects of semaglutide, empagliflozin and their combination on renal diffusion-weighted MRI and total kidney volume in patients with type 2 diabetes: a post hoc analysis from a 32 week randomised trial.

The apparent diffusion coefficient (ADC) derived from diffusion-weighted MRI (DWI-MRI) has been proposed as a measure of changes in kidney microstructure, including kidney fibrosis. In advanced kidney disease, the kidneys often become atrophic; however, in the initial phase of type 2 diabetes, there is an increase in renal size. Glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors both provide protection against progression of kidney disease in diabetes. However, the mechanisms are incompletely understood. To explore this, we examined the effects of semaglutide, empagliflozin and their combination on renal ADC and total kidney volume (TKV). This was a substudy of a randomised clinical trial on the effects of semaglutide and empagliflozin alone or in combination. Eighty patients with type 2 diabetes and high risk of CVD were randomised into four groups (n=20 in each) receiving either tablet placebo, empagliflozin, a combination of semaglutide and tablet placebo (herein referred to as the 'semaglutide' group), or the combination of semaglutide and empagliflozin (referred to as the 'combination-therapy' group). The semaglutide and the combination-therapy group had semaglutide treatment for 16 weeks and then had either tablet placebo or empagliflozin added to the treatment, respectively, for a further 16 weeks; the placebo and empagliflozin groups were treated with the respective monotherapy for 32 weeks. We analysed the effects of treatment on changes in ADC (cortical, medullary and the cortico-medullary difference [ΔADC; medullary ADC subtracted from cortical ADC]), as well as TKV measured by MRI. Both semaglutide and empagliflozin decreased cortical ADC significantly compared with placebo (semaglutide: -0.20×10-3 mm2/s [95% CI -0.30, -0.10], p<0.001; empagliflozin: -0.15×10-3 mm2/s [95% CI -0.26, -0.04], p=0.01). No significant change was observed in the combination-therapy group (-0.05×10-3 mm2/s [95%CI -0.15, 0.05]; p=0.29 vs placebo). The changes in cortical ADC were not associated with changes in GFR, albuminuria, TKV or markers of inflammation. Further, there were no changes in medullary ADC in any of the groups compared with placebo. Only treatment with semaglutide changed ΔADC significantly from placebo, showing a decrease of -0.13×10-3 mm2/s (95% CI -0.22, -0.04; p=0.01). Compared with placebo, TKV decreased by -3% (95% CI -5%, -0.3%; p=0.04), -3% (95% CI -5%, -0.4%; p=0.02) and -5% (95% CI -8%, -2%; p<0.001) in the semaglutide, empagliflozin and combination-therapy group, respectively. The changes in TKV were associated with changes in GFR, albuminuria and HbA1c. In a population with type 2 diabetes and high risk of CVD, semaglutide and empagliflozin significantly reduced cortical ADC compared with placebo, indicating microstructural changes in the kidneys. These changes were not associated with changes in GFR, albuminuria or inflammation. Further, we found a decrease in TKV in all active treatment groups, which was possibly mediated by a reduction in hyperfiltration. Our findings suggest that DWI-MRI may serve as a promising tool for investigating the underlying mechanisms of medical interventions in individuals with type 2 diabetes but may reflect effects not related to fibrosis. European Union Drug Regulating Authorities Clinical Trials Database (EudraCT) 2019-000781-38.

Durable responses to trastuzumab deruxtecan in patients with leptomeningeal metastases from breast cancer with variable HER2 expression.

Emerging data suggest that trastuzumab deruxtecan (T-DXd) is an active treatment for brain metastases from HER2 + breast cancer. We aimed to characterize the activity of T-DXd in the treatment of leptomeningeal metastases (LM) from a range of HER2-altered cancers. We reviewed neuro-oncology clinic records between July 2020 and December 2023 to identify patients who received T-DXd to treat LM. Of 18 patients identified, 6 had HER2 + breast cancer, 8 had HER2-low/negative breast cancer, 2 had HER2 + gastroesophageal cancer, and 2 had HER2-mutant non-small cell lung cancer (NSCLC). 10/18 (56%) patients had cytologically confirmed LM by CSF cytology or circulating tumor cell (CTC) capture. A partial response (PR) on MRI using the EORTC/RANO-LM Revised-Scorecard occurred in 4/6 (67%) patients with HER2 + breast LM, 2/8 (25%) patients with HER2-low/negative breast cancer, and 0/4 (0%) patients with HER2 + gastroesophageal cancer or HER2-mutant NSCLC. Median overall survival after initiating T-DXd was 5.8 months. Survival after initiating T-DXd was numerically longer for HER2 + breast cancer patients compared with HER2-low/negative breast and HER2-altered non-breast cancer patients (13.9 months vs. 5.2 months and 4.6 months, respectively). Landmark analysis showed that patients with radiologic LM response to T-DXd by 2.5 months had longer survival than non-responders (14.2 months vs. 2.6 months, HR 0.18, 95% CI 0.05-0.63, p < 0.05), and landmark analyses at 3.5 and 4.5 months after starting T-DXd showed a similar but nonsignificant trend. T-DXd induces LM responses in a subset of patients, and such responses may be associated with prolongation of survival. Prospective trials are needed to clarify the role of T-DXd in treating LM and which patients are most likely to benefit.

Plasma EV-miRNAs as Potential Biomarkers of COVID-19 Vaccine Immune Response in Cancer Patients

Cancer patients, prone to severe COVID-19, face immune challenges due to their disease and treatments. Identifying biomarkers, particularly extracellular vesicle (EV)-derived microRNAs (miRNAs), is vital for comprehending their response to COVID-19 vaccination. Therefore, this study aimed to investigate specific EV-miRNAs in the plasma of cancer patients under active treatment who received the COVID-19 booster vaccine. The selected miRNAs (EV-hsa-miR-7-5p, EV-hsa-miR-15b-5p, EV-hsa-miR-24-3p, EV-hsa-miR-145- 5p, and EV-hsa-miR-223-3p) are involved in regulating SARS-CoV-2 spike protein and cytokine release, making them potential biomarkers for vaccination response. The study involved 54 cancer patients. Plasma and serum samples were collected at pre-boost vaccination, and at 3 and 6 months post-boost vaccination. Anti-spike antibody levels were measured. Additionally, RNA was extracted from EVs isolated from plasma and the expression levels of miRNAs were assessed. The results showed a significantly positive antibody response after COVID-19 boost vaccination. The expression levels of EV-hsa-miR-7-5p, EV-hsa-miR-15b-5p, EV-hsa-miR-24-3p, and EV-hsa-miR-223-3p increased significantly after 6 months of COVID-19 booster vaccination. Interestingly, an increased expression of certain EV-hsa-miRNAs was positively correlated. Bioinformatic analysis revealed that these correlated miRNAs play a critical role in regulating the targets present in antiviral responses and cytokine production. These findings suggest that EV-hsa-miR-15b-5p, EV-hsa-miR-24-3p, and EV-hsa-miR-223-3p may be crucial in immune response induced by mRNA vaccines.

Impact of pediatric inflammatory bowel disease on caregivers' work productivity: A multicenter study by the SEGHNP.

Pediatric inflammatory bowel disease (PIBD) poses significant challenges not only to patients but also to their families, particularly affecting the work productivity of caregivers. This Spanish multicenter study aims to elucidate the extent of this impact. A cross-sectional, multicenter study was conducted between February 2021 and June 2023, involving parents or caregivers of PIBD patients aged 10-18 years. The study utilized the Work Productivity and Activity Impairment (WPAI) questionnaires alongside assessing disease activity and socioeconomic status to quantify work productivity loss and its economic implications. The study included 370 patients from 37 centers, highlighting a significant loss of work productivity among caregivers, especially mothers. The global unemployment rate was notably higher in this group compared to national averages (22.9% vs. 13.8%), particularly among females (30.7% vs. 13.7%), with absenteeism and presenteeism rates (26.4% and 39.9%) significantly impacting the caregivers' ability to work. The study also identified active disease and treatment with biologics or steroids as risk factors for increased work productivity loss. Caregivers of children with inflammatory bowel disease face considerable challenges in maintaining employment, with a notable economic impact due to lost work hours. The findings underscore the need for targeted support and interventions to assist these families, suggesting potential areas for policy improvement and support mechanisms to mitigate the socioeconomic burden of PIBD on affected families.

Cognitive, Neuropsychological and Biological Effects of Oxygen–Ozone Therapy on Frailty: A Study Protocol for a 5-Week, Randomized, Placebo-Controlled Trial

Cognitive frailty (CF) is a heterogeneous syndrome that is becoming one of the most serious health problems as the world’s population age is increasing. Elucidating its biological mechanisms as well as prevention and treatments is becoming increasingly significant, particularly in view of the associated health costs. We presented the study protocol of a research project funded by the Italian Ministry of Health (grant number RF-2016-02363298) aiming to investigate the cognitive and neuropsychological effects of a 5-week treatment with therapy based on the regenerative properties of ozone (O3) in a cohort of subjects stratified according to CF scores. We also studied the potential effects of O3 on blood-based biomarkers indicative of specific biological systems that may be altered in CF. Seventy-five older persons were recruited and randomly assigned to receive the active treatment (150 cc of oxygen-O2-O3 mixture at the concentration of 30 µg of O3 per cc of O2), O2, or the placebo (air) for 5 weeks. The main endpoints were the change in the scores of clinical scales from baseline (T0) to weeks 3 (T3), 9 (T9), and 15 (T15) after treatment and the change in biomarker levels resulting from transcriptomics, proteomics, and metabolomic patterns at the same times. The positive results from this study could have important clinical implications.

A prospective, randomised, controlled, double blinded, cross-over study on the effect of a single session of pulsed electromagnetic field therapy on signs of hip osteoarthritis in dogs

BackgroundCanine coxofemoral joint osteoarthritis is a common, painful and debilitating condition. The objective of this study was to evaluate if any measurable changes in pain or lameness occurred in this patient group immediately after a single treatment with pulsed electromagnetic field therapy. Eight dogs with coxofemoral joint osteoarthritis presenting with signs of pain and lameness were prospectively recruited to this randomised, controlled, double blinded, cross-over study. Subjects attended the research facility on two occasions for one active and one placebo treatment with pulsed electromagnetic field therapy. The immediate effect of one pulsed electromagnetic field therapy treatment on pain and lameness was measured subjectively with the Helsinki Chronic Pain Index and Visual Analogue Scale and objectively using a pressure sensitive walkway.ResultsA statistically significant difference (P = 0.03) for change in stride length in the affected limb was recorded for subjects between the active and placebo treatments with pulsed electromagnetic field therapy. Within the active treatment results, there was a statistically significant change in the measurement for reach (P = 0.04) and stride length (P = 0.047) which got shorter in the affected limb post treatment. For the subjective outcome measures, there was no statistically significant difference between the active and placebo treatments for the evening of the treatment day or the next morning from pre-treatment values. Within the placebo treatment results a statistically significant change (improvement) was detected in Visual Analogue Score (P = 0.03) between pre-treatment and the next morning values.ConclusionsThe findings of this study do not show demonstrable improvement in owner assessed pain levels or temporospatial performance in dogs with coxofemoral joint osteoarthritis immediately after a single application of pulsed electromagnetic field therapy.

The time course of health-related Quality of Life in rectal cancer patients undergoing combined modality treatment

Background and purposeThis exploratory prospective observational study investigated the changes in Health-related Quality of Life (HRQoL) in rectal cancer patients (RCPs), from diagnosis to one-year-post-surgery follow-up and explored the role of physical symptoms and psychological determinants on HRQoL at the different time points. Materials and methodsWe assessed HRQoL, psychological distress, coping, affectivity, alexithymia and social support in 43 RCPs treated with preoperative (chemo)radiation and surgery, at three different assessment time points: diagnosis (T0), one month after the end of preoperative treatment (T1), one month after resection surgery (T2), and at follow-up (T3). ResultsThe data showed that HRQoL decreased during active treatments, especially between T1 and T2 (p = 0.005), before increasing again at follow-up (p = 0.002).Baseline intestinal symptoms (p < 0.001) and negative affectivity trait (p = 0.03) significantly predicted HRQoL at T0. Baseline pain (p < 0.001), intestinal (p = 0.003) and urinary (p = 0.009) symptoms at T1 significantly predicted HRQoL at T1. A fatalistic coping style at T1 (p = 0.013), psychological distress (p = 0.003), mouth symptoms (p = 0.001) at T2 significantly predicted HRQoL at T2. Similarly, a fatalistic coping style at T1 (p = 0.006), psychological distress (p = 0.004), mouth (p = 0.002) and pain symptoms (p = 0.002) at T3 significantly predicted HRQoL at T3. ConclusionSeveral physical and psychological factors are involved in the changes occurring after diagnosis in RCPs’ HRQoL. While cancer-related symptoms and treatment-related physical side effects are the main predictors of HRQoL at diagnosis and during active treatments, early psychological reactions have a higher predictive weight in post-treatment HRQoL.These data emphasise the importance of active screening, early diagnosis, and preventive psychological interventions immediately after diagnosis to improve HRQoL and psychological health outcomes.

Evaluating predictive equations for energy requirements throughout breast cancer trajectory: A comparative study

Background & AimsAccurately estimating resting energy requirements is crucial for optimizing energy intake, particularly in the context of patients with varying energy needs, such as individuals with cancer. We sought to evaluate the agreement between resting energy expenditure (REE) predicted by 40 equations and that measured by reference methods in women undergoing active breast cancer treatment stage (I-IV) and post-completion (i.e., survivors). MethodsData from 4 studies were combined. REE values estimated from 40 predictive equations identified by a systematic search were compared with REE assessed by indirect calorimetry (IC) using a metabolic cart (MC-REE N=46) or a whole-room indirect calorimeter (WRIC-REE N=44). Agreement between methods was evaluated using Bland-Altman and Lin's concordance coefficient correlation (Lin's CCC). Results90 participants (24 % survivors, 61.1% had early-stage breast cancer I or II, mean age: 56.8 ± 11 years; body mass index: 28.7 ± 6.4 kg/m2) were included in this analysis. Mean MC-REE and WRIC-REE values were 1389 ± 199 kcal/day and 1506 ± 247 kcal/day, respectively. Limits of agreement were wide for all equations compared to both MC and WRIC (∼ 300kcal for both methods), including the most commonly used ones, such as Harris-Benedict and Mifflin ST. Jeor equations; none had a bias within ±10% of measured REE, and all had low agreement per Lin's CCC analysis (< 0.90). The Korth equation exhibited the best performance against WRIC and the Lvingston-Kohlstadt equation against MC. Similar patterns of bias were observed between survivors and patients and between patients with stages I-III versus IV cancer. ConclusionMost equations failed to accurately predict REE at the group level, and none were effective at the individual level. This inaccuracy has significant implications for women with or surviving breast cancer, who may experience weight gain, maintenance, or loss due to inaccurate energy needs estimations. Therefore, our research underscores the need for further efforts to improve REE estimation.