Indications for flexible fiberoptic bronchoscopy and its safety in the very elderly

Aim. To evaluate the indications and the safety of fiberoptic bronchoscopy (FOB) with bronchoalveolar lavage (BAL), protected specimen brushing (PSB), endobronchial biopsy (EBB), and transbronchial biopsy (TBB) in a population of very elderly patients. Methods. We performed a retrospective study of all adult patients, aged 50 years or older, who underwent FOB in the Bronchology Unit of the University of Parma Hospital between 1 January, 2003 and 31 April, 2005. Bronchoscopy records of 436 consecutive patients, including 191 patients, 75 yrs of age and older ("very elderly"; =>75 yrs), were reviewed. Results. Patients aged 75 years were no different with regard to gender, BMI, baseline FEV1/FVC ratio, baseline SaO2, and blood pressure. The primary indication in patients aged <75 years, was to assist in the diagnosis of a pulmonary mass of unknown aetiology (33%) and to remove secretions in the very elderly patients (31%). Indications for FOB and sampling procedures in the two groups were similar. Approximately 30% of patients in each group required supplemental oxygen during the procedure and fever occurred in 9.2% and 10.3% of patients, respectively.Hypertension and bleeding were relatively rare and did not occur more often in the very elderly. Conclusions. Indication for FOB did not vary with age and adverse events in both groups were uncommon and generally not severe

A beacon in the dark: COVID-19 course in CVID patients from two European countries: Different approaches, similar outcomes

Background: CVID patients present an increased risk of prolonged SARS-CoV-2 infection and re-infection and a higher COVID-19-related morbidity and mortality compared to the general population. Since 2021, different therapeutic and prophylactic strategies have been employed in vulnerable groups (vaccination, SARS-CoV-2 monoclonal antibodies and antivirals). The impact of treatments over the last 2 years has not been explored in international studies considering the emergence of viral variants and different management between countries. Methods: A multicenter retrospective/prospective real-life study comparing the prevalence and outcomes of SARS-CoV-2 infection between a CVID cohort from four Italian Centers (IT-C) and one cohort from the Netherlands (NL-C), recruiting 773 patients. Results: 329 of 773 CVID patients were found positive for SARS-CoV-2 infection between March 1st, 2020 and September 1st 2022. The proportion of CVID patients infected was comparable in both national sub-cohorts. During all waves, chronic lung disease, “complicated” phenotype, chronic immunosuppressive treatment and cardiovascular comorbidities impacted on hospitalization, whereas risk factors for mortality were older age, chronic lung disease, and bacterial superinfections. IT-C patients were significantly more often treated, both with antivirals and mAbs, than NL-C patients. Outpatient treatment, available only in Italy, started from the Delta wave. Despite this, no significant difference was found for COVID-19 severity between the two cohorts. However, pooling together specific SARS-CoV-2 outpatient treatments (mAbs and antivirals), we found a significant effect on the risk of hospitalization starting from Delta wave. Vaccination with ≥ 3 doses shortened RT-PCR positivity, with an additional effect only in patients receiving antivirals. Conclusions: The two sub-cohorts had similar COVID-19 outcomes despite different treatment approaches. This points out that specific treatment should now be reserved for selected subgroups of CVID patients, based on pre-existing conditions

Re-irradiation with carbon ion radiotherapy for pelvic rectal cancer recurrences in patients previously irradiated to the pelvis

Background/Aim: Re-irradiation of locally recurrent rectal cancer poses challenges due to the proximity of critical organs, such as the bowel. This study aimed at evaluating the safety and efficacy of re-irradiation with Carbon Ion Radiotherapy (CIRT) in rectal cancer patients with local recurrence. Patients and Methods: Between 2014 and 2018, 14 patients were treated at the National Center of Oncological Hadrontherapy (CNAO Foundation) with CIRT for locally recurrent rectal cancer. Results: All patients concluded the treatment. No G≥3 acute/late reaction nor pelvic infections were observed. The 1-year and 2-year local control rates were, 78% and 52%, respectively, and relapse occurred close to the bowel in 6 patients. The 1-year and 2-year overall survival rates were 100% and 76.2% each; while the 1-year and 2-year metastasis free survival rates were 64.3% and 43%. Conclusion: CIRT as re-irradiation for locally recurrent rectal cancer emerges as a safe and valid treatment with an acceptable rate of morbidity of surrounding healthy tissue

Reduced Reactivation from Dormancy but Maintained Lineage Choice of Human Mesenchymal Stem Cells with Donor Age

Mesenchymal stem cells (MSC) are promising for cell-based regeneration therapies but up to date it is still controversial whether their function is maintained throughout ageing. Aim of this study was to address whether frequency, activation in vitro, replicative function, and in vitro lineage choice of MSC is maintained throughout ageing to answer the question whether MSC-based regeneration strategies should be restricted to younger individuals. MSC from bone marrow aspirates of 28 donors (5–80 years) were characterized regarding colony-forming unit-fibroblast (CFU-F) numbers, single cell cloning efficiency (SSCE), osteogenic, adipogenic and chondrogenic differentiation capacity in vitro. Alkaline phosphatase (ALP) activity, mineralization, Oil Red O content, proteoglycan- and collagen type II deposition were quantified. While CFU-F frequency was maintained, SSCE and early proliferation rate decreased significantly with advanced donor age. MSC with higher proliferation rate before start of induction showed stronger osteogenic, adipogenic and chondrogenic differentiation. MSC with high osteogenic capacity underwent better chondrogenesis and showed a trend to better adipogenesis. Lineage choice was, however, unaltered with age. Conclusion: Ageing influenced activation from dormancy and replicative function of MSC in a way that it may be more demanding to mobilize MSC to fast cell growth at advanced age. Since fast proliferation came along with high multilineage capacity, the proliferation status of expanded MSC rather than donor age may provide an argument to restrict MSC-based therapies to certain individuals

Age-related changes in rat bone-marrow mesenchymal stem cell plasticity

<p>Abstract</p> <p>Background</p> <p>The efficacy of adult stem cells is known to be compromised as a function of age. This therefore raises questions about the effectiveness of autologous cell therapy in elderly patients.</p> <p>Results</p> <p>We demonstrated that the expression profile of stemness markers was altered in BM-MSCs derived from old rats. BM-MSCs from young rats (4 months) expressed Oct-4, Sox-2 and NANOG, but we failed to detect Sox-2 and NANOG in BM-MSCs from older animals (15 months). Chondrogenic, osteogenic and adipogenic potential is compromised in old BM-MSCs. Stimulation with a cocktail mixture of bone morphogenetic protein (BMP-2), fibroblast growth factor (FGF-2) and insulin-like growth factor (IGF-1) induced cardiomyogenesis in young BM-MSCs but not old BM-MSCs. Significant differences in the expression of gap junction protein connexin-43 were observed between young and old BM-MSCs. Young and old BM-MSCs fused with neonatal ventricular cardiomyocytes in co-culture and expressed key cardiac transcription factors and structural proteins. Cells from old animals expressed significantly lower levels of VEGF, IGF, EGF, and G-CSF. Significantly higher levels of DNA double strand break marker γ-H2AX and diminished levels of telomerase activity were observed in old BM-MSCs.</p> <p>Conclusion</p> <p>The results suggest age related differences in the differentiation capacity of BM-MSCs. These changes may affect the efficacy of BM-MSCs for use in stem cell therapy.</p

State Britain and the art of (Im)proper democratic protest

The installation of Mark Wallinger’s State Britain in the Duveen Galleries of Tate Britain recreated Brian Haw’s protest opposite the Houses of Parliament, which had largely been dismantled by the police under the Serious Organised Crime and Police Act 2005. Wallinger’s work bisected a boundary created by the Act inside which the police could be given greater than usual powers to control demonstrations. The intersection exemplified how, when understood in terms of the performative after Jacques Derrida, art may unsettle the ways in which both the law and aesthetics work to protect the political establishment. aesthetics work to protect the political establishment

RECURRENT PREGNANCY LOSS IS ASSSOCIATED TO LEAKY GUT: A NOVEL PATHOGENIC MODEL OF ENDOMETRIUM INFLAMMATION ?

Background: Recurrent pregnancy loss (RPL) occurs in 3\u20135% in about 30% of cases no cause can be found. Women with RPL show higher prevalence of undiagnosed gut disorders. Furthermore, in endometrial tissues of RPL women, higher expression of pro-inflammatory cytokines and Nalp-3 inflammasome has been observed. Aim of this study was to investigate whether an abnormal gut permeability might occur in RPL women and allow passage into systemic circulation of pro-inflammatory molecules able to induce endometrial inflammation. Methods: 70 women with idiopathic RPL and 30 healthy women were recruited at the Recurrent Pregnancy Loss Outpatient Unit of the Gemelli Hospital of Rome from March 2013 to February 2017. Enrolled women underwent 51Cr-ethylene-diamine-tetraacetic acid absorption test to evaluate intestinal permeability. Sera obtained from enrolled women were analysed for lipopolysaccharide (LPS) by ELISA. Anxiety and depression state were evaluated by administering STAI-Y and Zung-SDS tests, respectively. Of all recruited individuals, 35 women with idiopathic RPL and 20 healthy controls accepted to undergo diagnostic hysteroscopy and endometrial biopsy. Endometrial lysates were investigated for inflammasome Nalp-3 by Western blot analysis, and caspase-1, IL-1\u3b2 and IL-18 by ELISA, respectively. Results: Higher prevalence of abnormal intestinal permeability (P &lt; 0.0001), increased circulating levels of LPS (P &lt; 0.05), anxiety (P &lt; 0.05) and depression (P &lt; 0.05) were observed in RLP women compared to controls. Endometrial expression of Nalp-3, caspase-1 and IL-1\u3b2 was significantly increased in RPL group (P &lt; 0.0001; P &lt; 0.05 and P &lt; 0.001, respectively). IL-18 endometrial levels were not found to be higher in RPL cases. Statistically significant association between higher intestinal permeability and abnormally increased expression of endometrial Nalp-3, was observed in RPL (P &lt; 0.01). Furthermore, higher LPS serum levels, a bacterial-derived activator of Nalp-3 complex, was shown to be statistically associated to abnormal endometrial expression of Nalp-3 inflammasome (P &lt; 0.01) in RPL women. Conclusions: In women with RLP, leaky gut might occur and allow passage into circulation of immune triggers, potentially able to elicit endometrial innate immune response and, thus, to contribute to miscarriage pathogenesis. Diagnosis and treatment of intestinal disorders underlying leaky gut might improve endometrial environment and pregnancy outcome

Heating, current drive and energetic particle studies on JET in preparation of ITER operation

This paper summarizes the recent work on JET in the three areas of heating, current drive and energetic particles. The achievements have extended the possibilities of JET, have a direct connection to ITER operation and provide new and interesting physics. Toroidal rotation profiles of plasmas heated far off axis with little or no refuelling or momentum input are hollow with only small differences on whether the power deposition is located on the low field side or on the high field side. With LH current drive the magnetic shear was varied from slightly positive to negative. The improved coupling (through the use of plasma shaping and CD4) allowed up to 3.4 MW of PLH in internal transport barrier (ITB) plasmas with more than 15 MW of combined NBI and ICRF heating. The q-profile with negative magnetic shear and the ITB could be maintained for the duration of the high heating pulse (8 s). Fast ions have been produced in JET with ICRF to simulate alpha particles: by using third harmonic 4He heating, beam injected 4He at 120 kV were accelerated to energies above 2 MeV, taking advantage of the unique capability of JET to use NBI with 4He and to confine MeV class ions. ICRF heating was used to replicate the dynamics of alpha heating and the control of an equivalent Q = 10 `burn' was simulated

Particle and Energy Transport in the SOL of DIII-D and NSTX

The far scrape-off layer (SOL) radial transport and plasma-wall contact is mediated by intermittent and ELM-driven transport. Experiments to characterize the intermittent transport and ELMs have been performed in both DIII-D and NSTX under similar conditions. Both intermittent transport and ELMs are comprised of filaments of hot, dense plasma (n{sub e} {approx} 1 x 10{sup 13} cm{sup -3}, T{sub e} {approx} 400 eV) originating at the edge, transport both particles and heat into the SOL by convection, increasing wall interaction and causing sputtering and impurity release. Both intermittent filaments and ELMs leave the pedestal region at speeds of {approx}0.5-3 km/s, losing heat and particles by parallel transport as they travel through the SOL. The intermittency shows many similarities in NSTX and DIII-D, featuring similar size (2-5 cm), large convective radial velocity, ''holes'' inside and peaks outside the LCFS which quickly decay and slow down with radius. Whereas in DIII-D the intermittency decays in both intensity and frequency in H-mode, it chiefly decays in frequency in NSTX. In the low collisionality (v* = {pi}R{sub q{sub 95}}/{lambda}C) (v* {approx} 0.1, N{sub G} {approx} 0.3) case, the ELMs impact the walls quite directly and account for {approx}90% of the wall particle flux, decreasing to {approx}30% at (v* {approx} 1.0, N{sub G} &gt; 0.6)