87,238 research outputs found
Innovative treatments for severe refractory asthma: how to choose the right option for the right patient?
No full textFrancesco Menzella,1 Carla Galeone,1 Francesca Bertolini,2 Claudia Castagnetti,1 Nicola Facciolongo1 1Department of Medical Specialties, Pneumology Unit, IRCCS- Arcispedale Santa Maria Nuova, Reggio Emilia, Italy; 2Department of Animal Science, Iowa State University, Ames, IA, USA Abstract: The increasing understanding of the molecular biology and the etiopathogenetic mechanisms of asthma helps in identification of numerous phenotypes and endotypes, particularly for severe refractory asthma. For a decade, the only available biologic therapy that met the unmet needs of a specific group of patients with severe uncontrolled allergic asthma has been omalizumab. Recently, new biologic therapies with different mechanisms of action and targets have been approved for marketing, such as mepolizumab. Other promising drugs will be available in the coming years, such as reslizumab, benralizumab, dupilumab and lebrikizumab. Moreover, since 2010, bronchial thermoplasty has been successfully introduced for a limited number of patients. This is a nonpharmacologic endoscopic procedure which is considered a promising therapy, even though several aspects still need to be clarified. Despite the increasing availability of new therapies, one of the major problems of each treatment is still the identification of the most suitable patients. This sudden abundance of therapeutic options, sometimes partially overlapping with each other, increases the importance to identify new biomarkers useful to guide the clinician in selecting the most appropriate patients and treatments, without forgetting the drug-economic aspects seen in elevated direct cost of new therapies. The aim of this review is, therefore, to update the clinician on the state of the art of therapies available for refractory asthma and, above all, to give useful directions that will help understand the different choices that sometimes partially overlap and to dispel the possible doubts that still exist. Keywords: severe asthma, phenotypes, monoclonal antibodies, IL-5, bronchial thermoplasty, biomarker
Progetto di residenze in forma aggregata, con annessi servizi, in un contesto della città consolidata.
No full textParental Decisional Regret after Primary Distal Hypospadias Repair: Family and Surgery Variables, and Repair Outcomes
No full textPurpose Decisional regret is defined as distress after making a health care choice and can be an issue for parents electing distal hypospadias repair for their sons. We assessed the influence on decisional regret of variables related to the family, surgery and outcomes. Materials and Methods Charts for 372 patients undergoing primary distal hypospadias repair between 2005 and 2012 were reviewed, and validated questionnaires, including the Decisional Regret Scale, Pediatric Penile Perception Score and Dysfunctional Voiding and Incontinence Scoring System, were administered to parents. Results Data were available for 172 of 372 families (response rate 46.2%). Of 323 parents 128 (39.6%) presented with moderately strong decisional regret, with good agreement within couples. Predictors of decisional regret included intermediate parental educational level (OR 3.19, 95% CI 1.52–6.69), patient not being the first born (OR 2.01, 95% CI 1.07–3.78), family history of hypospadias (OR 4.42, 95% CI 1.96–9.97), initial desire to avoid surgery (OR 2.07, 95% CI 1.04–4.12), younger age at followup (OR 0.81, 95% CI 0.72–0.91), presence of lower urinary tract symptoms (OR 4.92, 95% CI 1.53–15.81) and lower Pediatric Penile Perception Score (OR 0.86, 95% CI 0.75–0.99). Decisional regret was unrelated to parental desire to avoid circumcision, surgical variables, development of complications and duration of followup. Conclusions Decisional regret is a problem in a significant proportion of parents electing distal hypospadias repair for their sons. In our experience family variables seemed to be predictors of decisional regret, while surgical variables did not. Predictors of decisional regret included worse parental perception of penile appearance and the presence of lower urinary tract symptoms. However, the latter could be unrelated to surgery. Irrespective of the duration of followup, decisional regret seems decreased in parents of older patients
Surgical management of penile amputation in children
No full textAbstract Purpose: Penile amputation in children is rare. If the amputated organ cannot be salvaged, standard treatment options include sex reassignment or creation of a penoid with a musculocutaneous flap. We describe our experience with phallic reconstruction after amputation. Methods: Between 2005 and 2007, we observed 3 patients with penile amputation. All presented a flat pubic scar and a severe urethral stricture for which urinary diversion had been performed in two.The first step of the procedure was penile augmentation. The latter included dissection and advancement of the residual erectile tissue by either division of the suspensory ligament (n = 2) or detachment of the corpora cavernosafromthepubicbones.Then,meataladvancementwasattemptedandcombinedwithastagedoral mucosa urethroplasty, if necessary. Finally, skin coverage was achieved using local flaps (n = 2) or a free graft harvested from the inguinal region. In 2 patients, a pseudoglans was sculptured from the pubic scar. Results: Innocasetheprocedurecouldbeperformedinasinglestage.Inonepatient,2additionalcosmetic revisions wererequired.Goodpenileaugmentationwasachievedinallthe3cases.Allpatientspresentedat least nocturnal erections and reported to be satisfied with the cosmetic results. Conclusions: Our experience suggests that an attempt to phallic reconstruction by retrieval of any residual erectile tissue might be worthwhile before embarking on a penile replacement. In a few cases, this may allow recreation of a penis with good cosmesis and functio
Erratum: Additional chromosomal abnormalities in Philadelphia-positive clone: Adverse prognostic influence on frontline imatinib therapy: A GIMEMA Working Party on CML analysis (Blood (2012) 120:4 (761-767))
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La modellizzazione dell'inquinamento atmosferico in aree urbane su scala locale: un esempio di applicazione in un quartiere di Torino
No full textMulti-sensor and Multi-frequency Data Fusion for Structural Health Monitoring
No full textThe increasing need to evaluate the health state of existing bridges has pushed the researchers towards the study and development of innovative monitoring approaches. Among these, the high frequency GNSS (Global Navigation Satellite Systems) receivers have the potential to be a valuable support for the monitoring of structural displacement. Displacement data obtained from GNSS receivers can be combined and integrated with data measured from other sensors according to data fusion techniques in order to achieve a deeper knowledge of the structural behavior. In this context, the present paper investigates the potential of data fusion for the structural health monitoring by combining GNSS data with measures acquired with a traditional accelerometer-based monitoring system. The adopted data fusion approach is based on the Kalman filter. Structural displacements can be estimated from measured accelerations through a double integration procedure which, however, can introduce non-removable errors. Displacements measured by the GNSS receiver, although acquired with sampling rates lower than those of traditional monitoring systems, can be employed to adjust the post processed displacements and remove the uncertainties introduced with the integration procedure. Furthermore, the integration of measured accelerations and GNSS data holds the potential to identify residual displacements, which are often challenging to detect through acceleration post-processing alone. The effectiveness of this data fusion approach is examined with reference to the case study of a steel footbridge
Changes in the fecal microbiota associated with a broad‐spectrum antimicrobial administration in hospitalized neonatal foals with probiotics supplementation
Get PDFThere is a wide array of evidence across species that exposure to antibiotics is associated with dysbiosis, and due to their widespread use, this also raises concerns also in medicine. The study aimed to determine the changes on the fecal microbiota in hospitalized neonatal foals administered with broad‐spectrum antimicrobials and supplemented probiotics. Fecal samples were collected at hospital admission (Ta), at the end of the antimicrobial treatment (Te) and at discharge (Td). Feces were analysed by next‐generation sequencing of the 16S rRNA gene on Illumina MiSeq. Seven foals treated with IV ampicillin and amikacin/gentamicin were included. The mean age at Ta was 19 h, the mean treatment length was 7 days and the mean time between Te and Td was 4.3 days. Seven phyla were identified: Actinobacteria, Bacteroidetes, Firmicutes, Fusobacteria, Proteobacteria, TM7 and Verrucomicrobia. At Ta, Firmicutes (48.19%) and Proteobacteria (31.56%) were dominant. The alpha diversity decreased from Ta to Te, but it was the highest at Td. The beta diversity was higher at Ta than at Te and higher at Td than at Te. An increase in Akkermansia over time was detected. The results suggest that the intestinal microbiota of neonatal foals rapidly returns to a high diversity after treatment. It is possible that in foals, the effect of antimicrobials is strongly influenced or overshadowed by the time‐dependent changes in the developing gut microbiota
Dosing Strategies for Improving the Risk-Benefit Profile of Ponatinib in Patients With Chronic Myeloid Leukemia in Chronic Phase
Get PDFThe treatment of chronic myeloid leukemia (CML) has been advanced by the development of small-molecule tyrosine kinase inhibitors (TKIs), which target the fusion protein BCR-ABL1 expressed by the Philadelphia chromosome. Ponatinib is a 3rd generation TKI that binds BCR-ABL1 with high affinity and inhibits most BCR-ABL1 mutants, including the T315I mutation. The approved starting dose of ponatinib is 45 mg once daily (full dose), however, the need for a full dose, especially in patients with dose adjustments due to tolerability problems, remains undemonstrated. Lower starting doses of ponatinib (30 mg or 15 mg once daily) for patients “with lesser degrees of resistance or multiple intolerances, especially those with an increased cardiovascular risk profile” has been recommended by the 2020 European LeukemiaNet. However, the available literature and guidance on the use of ponatinib at low dosage are limited. The objective of this paper is to describe how we select ponatinib dosage for CML patients in chronic phase in our clinical practice based on the available evidence and our clinical experience. We propose dosing regimens for the optimal starting dose for six generic cases of CML patients in chronic phase eligible for the switch to ponatinib and provide an algorithm to guide ponatinib dosing during treatment
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