161 research outputs found

    Correlation of disability with quality of life in patients with multiple sclerosis treated with natalizumab: primary results and post hoc analysis of the TYSabri ImPROvement study (PROTYS).

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    BACKGROUND In patients with multiple sclerosis (MS), relapses and disability progression have been associated with decreased health-related quality of life (HRQoL). METHODS PROTYS, a prospective, multicentre, single-arm, observational study in seven Swiss MS centres, evaluated correlations between change in disability status (measured through the Expanded Disability Status Scale (EDSS)) and HRQoL changes (measured through the global Multiple Sclerosis International Quality of Life (MusiQoL) index questionnaire) in 35 patients with relapsing remitting MS on natalizumab for 1‚ÄČyear. In addition, several other scales were also used, such as: Multiple Sclerosis Intimacy and Sexuality Questionnaire-19, EuroQoL-5 Dimension, and Fatigue Scale of Motor and Cognitive Function. A post hoc analysis further assessed the association between HRQoL changes after 1‚ÄČyear and the MusiQoL subscores and other patient-reported outcome (PRO) measures. RESULTS At 1‚ÄČyear, patients were categorised into 'EDSS improved' (6/35), 'EDSS stable' (28/35) and 'EDSS worsened' (1/35). Mean disability scores decreased for 'EDSS improved' and 'EDSS stable' but increased for 'EDSS worsened'. Mean MusiQoL index score for 'EDSS improved' increased from 61.2 at baseline to 66.3 at 1‚ÄČyear, while the 'EDSS stable' group increased from 67.9 to 70.8. No meaningful statistical relationship was observed between EDSS group and changes in MusiQoL score. For the post hoc analysis, patients were categorised in 'MusiQoL improved' (n=21) and 'MusiQoL worsened' (n=14) groups. MusiQoL subscores for 'symptoms,' 'psychological well-being' and 'activities of daily living', as well as scores for several related PRO measures, correlated with improvement of the MusiQoL global index. There was no correlation between the changes in MusiQoL global index and EDSS score. CONCLUSIONS Natalizumab treatment for 1‚ÄČyear resulted in either improved or stable EDSS status in most patients, and although no significant relationship was observed between global HRQoL change and EDSS change, several domains of HRQoL seemed to improve with natalizumab treatment. TRIAL REGISTRATION NUMBER NCT02386566

    Open radiofrequency ablation as upfront treatment for locally advanced pancreatic cancer: Requiem from a randomized controlled trial

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    Background: Local ablation of pancreatic cancer has been suggested as an option to manage locally advanced pancreatic cancer (LAPC) although no robust evidence has been published to date to support its application. The aim of this study is to compare overall survival (OS) and progression-free survival (PFS) in patients receiving both radiofrequency ablation (RFA) and conventional chemoradiotherapy (CHRT) with patients receiving CHRT only. Methods: This is a multicentre prospective randomized controlled trial (RCT). Patients with LAPC diagnosed by the Pancreas-Ablation-Team-Verona were randomly assigned to open RFA (Group A) or CHRT (Group B). Survival analyses were performed using the Kaplan-Meier method and compared using the log-rank test. Statistical significance was set at p < 0.05. Results: One hundred LAPC patients were enrolled from January 2014 to August 2016. 33% of patients in Group A did not receive the designated procedure because of intraoperative findings of liver (18.7%) or peritoneal metastases (43.8%), or technical contraindications (37.5%). We did not observe any statistically significant survival benefit from RFA compared to CHRT, neither in terms of OS (medians of 14.2 months and 18.1 months, respectively, p = 0.639) nor PFS (medians of 8 months and 6 months respectively, p = 0.570). Mortality was nil and RFA-related morbidity was 15.6%. In 13% of subjects, conversion to surgery occurred (2 after RFA and 11 after CHRT). Conclusions: This is the first RCT evaluating the impact of upfront RFA in the multimodal treatment of LAPC. Compared to CHRT, RFA alone did not provide any advantage in terms of OS or PFS. It could be considered as a therapeutic option for LAPC within a multimodal context and after neoadjuvant therapies

    Asthma in patients admitted to emergency department for COVID-19: prevalence and risk of hospitalization

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    Impact of transposable elements on the evolution of complex living systems and their epigenetic control

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    Transposable elements (TEs) contribute to genomic innovations, as well as genome instability, across a wide variety of species. Popular designations such as ‚Äėselfish DNA‚Äô and ‚Äėjunk DNA,‚Äô common in the 1980s, may be either inaccurate or misleading, while a more enlightened view of the TE-host relationship covers a range from parasitism to mutualism. Both plant and animal hosts have evolved epigenetic mechanisms to reduce the impact of TEs, both by directly silencing them and by reducing their ability to transpose in the genome. However, TEs have also been co-opted by both plant and animal genomes to perform a variety of physiological functions, ranging from TE-derived proteins acting directly in normal biological functions to innovations in transcription factor activity and also influencing gene expression. Their presence, in fact, can affect a range of features at genome, phenotype, and population levels. The impact TEs have had on evolution is multifaceted, and many aspects still remain unexplored. In this review, the epigenetic control of TEs is contextualized according to the evolution of complex living systems

    Spray application of BcBmp3-dsRNA delivered by layered double hydroxide (LDH) clay nanosheets reduces virulence of Botrytis cinerea on Lactuca sativa: first results.

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    Recently novel strategies based on the use of RNA interference (RNAi) are rising up in the crop protection scenario. Spray-induced gene silencing (SIGS) is a potential strategy for plant disease management, whereby nucleotide sequence-specific double-stranded RNA (dsRNA) can be sprayed onto a crop and it could represent a potential alternative to conventional fungicides. SIGS could give rise to transient silencing without producing genetically modified organisms (GMO) neither requiring transformation method for plants. Nevertheless, the instability of naked dsRNA sprayed on plants is a major challenge towards its practical application. To overcome this limiting aspect, nanocarriers for dsRNA delivery can be used to extend its stability and durability. We previously shown that topical application of a BcBmp3-dsRNA construct mediated both in vitro and in vivo knockdown of B. cinerea transcripts on Lactuca sativa. Our dsRNA construct was loaded on non-toxic, degradable, layered double hydroxide clay nanosheets for a sustained release on the leaf surface under ambient conditions. We prepared LDH by a modified non-aqueous method and the BcBmp3-dsRNA/LDH optimal ratio was assessed by the gel retardation assay. Lettuce plants were sprayed with either water, LDH, or BcBmp3-dsRNA/LDH complex on day 0. B. cinerea was inoculated using a conidial suspension 7 days after spray treatment. A significant reduction of gray mould severity was observed as assessed by a rating scale and by calculating the McKinney index. Our results suggest a possible development of SIGS approach for the management of B. cinerea disease, although further experiments are needed to fully understand this potential

    Correction to: Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial

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    Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial

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    BackgroundTocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients.MethodsA multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival.ResultsIn the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6-24.0, P=0.52) and 22.4% (97.5% CI: 17.2-28.3, P<0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline.ConclusionsTocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline.Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092)

    Expression of homeobox genes during in vitro culture of Lactuca sativa

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    Lettuce, Lactuca sativa, is one of the main leafy vegetable crops, interesting as a source of phytonutrients. It is extensively studied for biotechnological applications based on in vitro regeneration. However, in lettuce, histological studies of adventitious morphogenesis during the regeneration process are lacking. Analogously, the genes involved in the initiation of adventitious shoots or embryos are unknown. Here, we used cotyledon explants of a cos lettuce (‚ÄėRomana‚Äô) to define the histological events of in-vitro morphogenesis at different times, and to investigate the nature of the regeneration pathway. Furthermore, we isolated three homeobox genes, LsWUSCHEL1-LIKE (LsWUS1L), LsWUS2L, and LsSHOOT MERISTEMLESS1-LIKE (LsSTM1L), to evaluate their transcription activity during the ontogenesis of the adventitious structures. De novo morphogenesis quickly proceeded through embryogenic and organogenic pathways, with some developmental abnormalities. The expression of LsWUS1L gradually increased during the in vitro culture of cotyledon explants. Remarkably, we detected high expression of both LsWUS2L and LsSTM1L genes after four days of culture, when the very early stages of morphogenesis were only noticeable through histological analysis. These findings suggest a key role of these genes in the rapid recruitment of the founder cells of adventitious structures

    US-Guided Percutaneous Radiofrequency Ablation of Locally Advanced Pancreatic Adenocarcinoma: A 5-Year High-Volume Center\ua0Experience

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    The aim of this study was to investigate the safety and effectiveness of percutaneous radiofrequency ablation (RFA) in locally advanced pancreatic cancer (LAPC) of the pancreatic body by assessing the overall survival of patients and evaluating the effects of the procedure in the clinical and radiological follow-up.Zusammenfassung Ziel\u2002Ziel dieser Studie war es, die Sicherheit und Wirksamkeit der perkutanen Radiofrequenzablation (RFA) bei lokal fortgeschrittenem Pankreaskarzinom (LAPC) zu untersuchen, indem das Gesamt\ufcberleben der Patienten beurteilt wurde und die Auswirkungen des Verfahrens in der klinischen und radiologischen Nachsorge bewertet wurden. Material und Methoden\u2002Patienten mit inoperablem LAPC nach fehlgeschlagener Radiochemotherapie \ufcber mindestens 6 Monate wurden retrospektiv eingeschlossen. Die perkutane RFA wurde nach einer vorl\ue4ufigen Ultraschall (US)-Machbarkeitsbewertung durchgef\ufchrt. Eine kontrastverst\ue4rkte Computertomografie (CT) und eine Probenentnahme f\ufcr CA 19-9 wurden vor dem Verfahren und 24 Stunden sowie 30 Tage danach durchgef\ufchrt, um die Auswirkungen der Ablation zu beurteilen. Die Patienten wurden nach Entlassung unter Ber\ufccksichtigung der beiden wichtigsten Endpunkte nachbeobachtet: verfahrensbedingte Komplikationen und Tod. Ergebnisse\u2002Es wurden 35 Patienten eingeschlossen und 5 ausgeschlossen. Alle Patienten wurden der RFA unterzogen, wobei keine verfahrensbezogenen Komplikationen gemeldet wurden. Die durchschnittliche Tumorgr\uf6 fe betrug vor der Behandlung 49\u200amm. Das mittlere Ausma f der abgetragenen nekrotischen Zone betrug 32\u200amm, mit einer mittleren Ausdehnung von 65\u200a% im Vergleich zur gesamten Tumorgr\uf6 fe. Die Tumordichte war einen Tag nach dem Eingriff statistisch signifikant reduziert (p\u200a&lt;\u200a0,001). Die mittleren CA-19-9-Werte vor dem Eingriff und 24 Stunden bzw. 30 Tage danach betrugen 285,8\u200aU/ml, 635,2\u200aU/ml bzw. 336,0\u200aU/ml, mit einer Abnahme oder Stabilit\ue4t der Werte in der 30-Tage-Auswertung bei 80\u200a% der F\ue4lle. Die mittlere cberlebenszeit betrug 310 (65\u2013718) Tage. Schlussfolgerung\u2002Die perkutane RFA der LAPC ist eine durchf\ufchrbare Technik bei Patienten, die nicht operiert werden k\uf6nnen, mit gro fen Debulking-Effekten und einer sehr niedrigen Komplikationsrate

    Outcomes of Primary Chemotherapy for Borderline Resectable and Locally Advanced Pancreatic Ductal Adenocarcinoma

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    IMPORTANCE Chemotherapy is the recommended induction strategy in borderline resectable and locally advanced pancreatic ductal adenocarcinoma. However, the associated results on an intention-to-treat basis are poorly understood. OBJECTIVE To investigate pragmatically the treatment compliance, conversion to surgery, and survival outcomes of patients with borderline resectable and locally advanced pancreatic ductal adenocarcinoma undergoing primary chemotherapy. DESIGN, SETTING, AND PARTICIPANTS This prospective study took place in a national referral center for pancreatic diseases in Italy. Consecutive patients with borderline resectable and locally advanced pancreatic ductal adenocarcinoma were enrolled at the time of diagnosis (January 2013 through December 2015) and followed up to June 2018. EXPOSURES The chemotherapy regimen, assigned based on multidisciplinary evaluation,was delivered either at a hub center or at spoke centers. By convention, primary chemotherapywas considered completed after 6 months. After restaging, surgical candidateswere selected based on radiologic and biochemical response. All surgerieswere carried out at the hub center. MAIN OUTCOMES AND MEASURES Rates of receipt and completion of chemotherapy, rates of conversion to surgery, and disease-specific survival. RESULTS Of 680 patients, 267 (39.3%) had borderline resectable and 413 (60.7%) had locally advanced pancreatic ductal adenocarcinoma. Overall, 66 patients (9.7%)were lost to follow-up. The rate of chemotherapy receiptwas 92.9%(n = 570). The chemotherapeutic regimens most commonly used included FOLFIRINOX (fluorouracil, leucovorin, oxaliplatin, and irinotecan) (260 [45.6%]) and gemcitabine plus nanoparticle albumin-bound\u2013paclitaxel (123 [21.6%]). Nineteen patients (3.3%) receiving chemotherapy died within 6 months, mainly for disease progression. The treatment completion ratewas 71.6%(408 of 570). The overall rate of resectionwas 15.1% (93 of 614) (borderline resectable, 60 of 249 [24.1%]; locally advanced, 33 of 365 [9%]; resection:exploration ratio, 63.3%). Independent predictors of resectionwere age, borderline resectable disease, chemotherapy completion, radiologic response, and biochemical response. The median survival for the whole cohortwas 12.8 (95%CI, 11.7-13.9) months. Factors independently associated with survivalwere completion of chemotherapy, receipt of complementary radiation therapy, and resection. In patients who underwent resection, the median survivalwas 35.4 (95%CI, 27.0-43.7) months for initially borderline resectable and 41.8 (95%CI, 27.5-56.1) months for initially locally advanced disease.No pretreatment and posttreatment factorswere associated with survival after pancreatectomy. CONCLUSIONS AND RELEVANCE This pragmatic observational cohort study with an intention-to-treat design provides real-world evidence of outcomes associated with the most current primary chemotherapy regimens used for borderline resectable and locally advanced pancreatic ductal adenocarcinoma
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