Corticosteroids and hip fracture risk in elderly respiratory patients: EPIC-Greece cohort

INTRODUCTION: In an ageing population the prevalence of osteoporosis and chronic respiratory diseases is expected to increase in the near future. Interestingly, several forms of corticosteroids, drugs implicated in osteoporosis pathogenesis, are prescribed to respiratory patients without taking into consideration their age and risk for osteoporotic fractures. The aim of this study was to investigate the risk for hip fracture of the elder individuals who are taking corticosteroids for respiratory disease, including inhalers. MATERIAL AND METHODS: Data on incident hip fractures were collected through the active follow-up for all individuals participating in the Greek segment of the European Prospective Investigation into Cancer and Nutrition (EPIC-Greece) study who were 60 years or older at recruitment and reported "a doctor's diagnosis" of respiratory disease. Socio-demographic, life-style, health status data and use of corticosteroids were recorded from the baseline and follow-up questionnaires. Cox regression models were applied to estimate hazard ratios (HRs) adjusting for relevant confounders. RESULTS: We observed an increase in hip fracture risk with corticosteroid intake overall (HR: 1.68, 95% CI: 0.85-3.34). Increased risk persisted when we restricted our analysis to participants taking any form of corticosteroids for obstructive lung disease (HR: 1.40, 95% CI: 0.64-3.06) and to those using only inhalers (HR: 1.58, 95% CI: 0.71-3.50). However, these positive associations did not reach the nominal level of significance probably due to the small number of participants with hip fractures during follow-up. CONCLUSION: Hip fracture risk should be taken into consideration when recommending corticosteroids to the elder respiratory patients, including inhalers

Epidemiology of interstitial lung diseases in Greece

SummaryIntroductionFew data are available on the epidemiology of interstitial lung diseases (ILDs), especially after the current classification of idiopathic interstitial pneumonias. The aim of this study is to provide data on the epidemiology of ILDs in Greece, under the ATS/ERS international consensus.MethodsDepartments of Pneumonology were contacted and asked to complete a questionnaire for every case of ILD that was alive on 2004 as well as for every new case from 1st January 2004 to 31st December 2004. Questions on the patients' demographic data, the exact diagnosis and the procedures used to establish the diagnosis were included. Centers covering about 60% of the Greek population have been analyzed.ResultsA total of 967 cases have been registered. The estimated prevalence of ILDs is 17.3 cases per 100,000 inhabitants. The estimated annual incidence of ILDs is 4.63 new cases per 100,000 inhabitants. The most frequent disease is sarcoidosis (34.1%), followed in decreasing order by idiopathic pulmonary fibrosis (19.5%), ILD associated with collagen vascular diseases (12.4%), cryptogenic organizing pneumonia (5.3%), histiocytosis (3.8%), and hypersensitivity pneumonitis (2.6%). Unclassified ILD or not otherwise specified accounted for the 8.5% of prevalent cases.ConclusionsThese data suggest that sarcoidosis and idiopathic pulmonary fibrosis are the most frequent ILDs in our population. In comparison with the few previous reports, interesting dissimilarities have been observed

Long-Term Safety of Repeated Blood-Brain Barrier Opening via Focused Ultrasound with Microbubbles in Non-Human Primates Performing a Cognitive Task

Focused Ultrasound (FUS) coupled with intravenous administration of microbubbles (MB) is a non-invasive technique that has been shown to reliably open (increase the permeability of) the blood-brain barrier (BBB) in multiple in vivo models including non-human primates (NHP). This procedure has shown promise for clinical and basic science applications, yet the safety and potential neurological effects of long term application in NHP requires further investigation under parameters shown to be efficacious in that species (500kHz, 200–400 kPa, 4–5μm MB, 2 minute sonication). In this study, we repeatedly opened the BBB in the caudate and putamen regions of the basal ganglia of 4 NHP using FUS with systemically-administered MB over 4–20 months. We assessed the safety of the FUS with MB procedure using MRI to detect edema or hemorrhaging in the brain. Contrast enhanced T1-weighted MRI sequences showed a 98% success rate for openings in the targeted regions. T2-weighted and SWI sequences indicated a lack edema in the majority of the cases. We investigated potential neurological effects of the FUS with MB procedure through quantitative cognitive testing of’ visual, cognitive, motivational, and motor function using a random dot motion task with reward magnitude bias presented on a touchpanel display. Reaction times during the task significantly increased on the day of the FUS with MB procedure. This increase returned to baseline within 4–5 days after the procedure. Visual motion discrimination thresholds were unaffected. Our results indicate FUS with MB can be a safe method for repeated opening of the BBB at the basal ganglia in NHP for up to 20 months without any long-term negative physiological or neurological effects with the parameters used

Pirfenidone in idiopathic pulmonary fibrosis:expert panel discussion on the management of drug-related adverse events

Pirfenidone is currently the only approved therapy for idiopathic pulmonary fibrosis, following studies demonstrating that treatment reduces the decline in lung function and improves progression-free survival. Although generally well tolerated, a minority of patients discontinue therapy due to gastrointestinal and skin-related adverse events (AEs). This review summarizes recommendations based on existing guidelines, research evidence, and consensus opinions of expert authors, with the aim of providing practicing physicians with the specific clinical information needed to educate the patient and better manage pirfenidone-related AEs with continued pirfenidone treatment. The main recommendations to help prevent and/or mitigate gastrointestinal and skin-related AEs include taking pirfenidone during (or after) a meal, avoiding sun exposure, wearing protective clothing, and applying a broad-spectrum sunscreen with high ultraviolet (UV) A and UVB protection. These measures can help optimize AE management, which is key to maintaining patients on an optimal treatment dose.Correction in: Advances in Therapy, Volume 31, Issue 5, pp 575-576 , doi: 10.1007/s12325-014-0118-8</p

Non-invasive, Focused Ultrasound-Facilitated Gene Delivery for Optogenetics

Optogenetics, a widely used technique in neuroscience research, is often limited by its invasive nature of application. Here, we present a noninvasive, ultrasound-based technique to introduce optogenetic channels into the brain by temporarily opening the blood-brain barrier (BBB). We demonstrate the efficiency of the method developed and evaluate the bioactivity of the non-invasively introduced channelrhodopsin channels by performing stimulation in freely behaving mice

A posteriori error estimates for fully discrete schemes for the time dependent Stokes problem

The final publication is available at Springer via http://dx.doi.org/10.1007/s10092-018-0259-2This work is devoted to a posteriori error analysis of fully discrete finite element approximations to the time dependent Stokes system. The space discretization is based on popular stable spaces, including Crouzeix–Raviart and Taylor–Hood finite element methods. Implicit Euler is applied for the time discretization. The finite element spaces are allowed to change with time steps and the projection steps include alternatives that is hoped to cope with possible numerical artifices and the loss of the discrete incompressibility of the schemes. The final estimates are of optimal order in L∞(L2) for the velocity error

The protective effect of dietary folate intake on gastric cancer is modified by alcohol consumption: A pooled analysis of the StoP Consortium

Dietary folate intake has been identified as a potentially modifiable factor of gastric cancer (GC) risk, although the evidence is still inconsistent. We evaluate the association between dietary folate intake and the risk of GC as well as the potential modification effect of alcohol consumption. We pooled data for 2829 histologically confirmed GC cases and 8141 controls from 11 case–control studies from the international Stomach Cancer Pooling Consortium. Dietary folate intake was estimated using food frequency questionnaires. We used linear mixed models with random intercepts for each study to calculate adjusted odds ratios (OR) and 95% confidence interval (CI). Higher folate intake was associated with a lower risk of GC, although this association was not observed among participants who consumed >2.0 alcoholic drinks/day. The OR for the highest quartile of folate intake, compared with the lowest quartile, was 0.78 (95% CI, 0.67–0.90, P-trend = 0.0002). The OR per each quartile increment was 0.92 (95% CI, 0.87–0.96) and, per every 100 μg/day of folate intake, was 0.89 (95% CI, 0.84–0.95). There was a significant interaction between folate intake and alcohol consumption (P-interaction = 0.02). The lower risk of GC associated with higher folate intake was not observed in participants who consumed >2.0 drinks per day, ORQ4v Q1 = 1.15 (95% CI, 0.85–1.56), and the OR100 μg/day = 1.02 (95% CI, 0.92–1.15). Our study supports a beneficial effect of folate intake on GC risk, although the consumption of >2.0 alcoholic drinks/day counteracts this beneficial effect. © 2024 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.This study was funded by the Associazione Italiana per la Ricerca sul Cancro (Project number 21378, Investigator Grant). NL and SM are funded under the Unidade de Investigação em Epidemiologia – Instituto de Saúde Pública da Universidade do Porto (EPIUnit; UIDB/04750/2020) financed by national funds from the Foundation for Science and Technology – FCT (Portuguese Ministry of Science, Technology and Higher Education) and the Laboratório para a Investigação Integrativa e Translacional em Saúde Populacional (ITR; LA/P/0064/2020). SM also received funding under the scope of the project “NEON-PC – Neuro-oncological complications of prostate cancer: longitudinal study of cognitive decline” (POCI-01-0145-FEDER-032358; Ref. PTDC/SAU-EPI/32358/2017) funded by FEDER through the Operational Program Competitiveness and Internationalization, and national funding from FCT, and the EPIUnit – Junior Research – Prog Financing (UIDP/04750/2020). This research was supported in part by the Intramural Research Program of the US National Cancer Institute. The study was also supported by the Italian Ministry of Health through the project “Interaction of genomic and dietary aspects in gastric cancer risk: the global StoP project” (Grant number RF-2021-12373951). This research was funded by the AICO/2021/347 grants for consolidated research groups from the Generalitat Valenciana. MHW and CSR also received funding from National Institutes of Health (ZIA CP010212 - Molecular mechanisms of infection-related cancer). [Correction added on 29 May 2024, after first online publication: The funding information has been updated.]

KIM-1 as a blood-based marker for early detection of kidney cancer: a prospective nested case-control study

Purpose: Renal cell carcinoma (RCC) has the potential for cure with surgery when diagnosed at an early stage. Kidney injury molecule-1 (KIM-1) has been shown to be elevated in the plasma of RCC patients. We aimed to test whether plasma KIM-1 could represent a means of detecting RCC prior to clinical diagnosis. Experimental Design: KIM-1 concentrations were measured in pre-diagnostic plasma from 190 RCC cases and 190 controls nested within a population-based prospective cohort study. Cases had entered the cohort up to five years before diagnosis, and controls were matched on cases for date of birth, date at blood donation, sex, and country. We applied conditional logistic regression and flexible parametric survival models to evaluate the association between plasma KIM-1 concentrations and RCC risk and survival. Results: The incidence rate ratio (IRR) of RCC for a doubling in KIM-1 concentration was 1.71 (95% confidence interval [CI]: 1.44-2.03, p-value = 4.1x10-23), corresponding to an IRR of 63.3 (95% CI: 16.2-246.9) comparing the 80th to the 20th percentile of the KIM-1 distribution in this sample. Compared with a risk model including known risk factors of RCC (age, sex, country, body mass index and tobacco smoking status), a risk model additionally including KIM-1 substantially improved discrimination between cases and controls (area under the receiver operating characteristic curve of 0.8 compared to 0.7). High plasma KIM-1 concentrations were also associated with poorer survival (p=0.0053). Conclusions: Plasma KIM-1 concentrations could predict RCC incidence up to 5 years prior to diagnosis and were associated with poorer survival