Bridging aortic valve surgery to 21st century. what can a surgeon do

Aortic valve stenosis is the most clinically relevant valvular heart disease in the elderlies. Surgical aortic valve replacement (SAVR) represented, for decades, the standard of care for the treatment of severe aortic stenosis. Although SAVR still represents a valid option in this clinical scenario, transcatheter aortic valve implantation proved to be superior to medical therapy and comparable to SAVR in several randomized trials in patients at high or intermediate operative risk. At the same time, the growing aging population carrying on greater morbidities and high risk profiles has led to the development of minimally invasive technologies, as rapid deployment aortic valve replacement or Sutureless, to minimize surgical impact on patients. The Heart Team is nowadays tasked to determine the best option tailored for each patient considering patient-related factors and mastering all the surgical options in terms of both different techniques and types of available valves. Nevertheless, some open issues need to be already answered as: which has the longest durability, which the lower complication rate and the lower overall mortality. The aim of this review is to briefly resume the main features of these different options and explore what kind of open questions these newer-generation prosthetic valves and delivery devices carry

Premalignant laryngeal lesions: twenty-year experience in specialized service

Introduction Premalignant lesions are considered both a hyperplastic and dysplastic stage of epithelial lesions in the glottic larynx that may or may not progress into an invasive carcinoma. The evolution of laryngoscopic procedures in outpatients has provided better access to important information for safe and easy diagnosis of laryngeal pathologies. Objective The goal of this study was to determine the accuracy of the preoperative exam for diagnosis of premalignant laryngeal lesions and their connection with benign diseases of the vocal folds, as well as to assess their epidemiologic characteristics. Methods This is a retrospective and longitudinal cohort study performed through the review of surgical records of patients who underwent laryngeal microsurgery performed by a single surgeon from 1990 to 2009. Results Preoperative assessment of outpatients was 64.4% accurate. Vocal fold cysts were the most frequently associated benign lesions. The patients who apparently had premalignant lesions represented 10.57% of those who underwent laryngeal microsurgery. Premalignant lesions prevailed in men (69.49%) age from 41 to 50 years (32.20%). Conclusion Although the evolution of laryngoscopic procedures in outpatients has provided better access to important information for safe and easy diagnosis of laryngeal pathologies, about one-third of premalignant lesions are diagnosed just during the laryngeal microsurgery. Cysts were the most prevalent concomitant benign lesion of the vocal folds. Males were more prevalent than females and the predominant age bracket was between 41 and 50 years

IKZF1 alterations are not associated with outcome in 498 adults with B-precursor ALL enrolled in the UKALL14 trial

IKZF1 deletions (ΔIKZF1) are commonly detected in B-precursor acute lymphoblastic leukemia (ALL; B-ALL) and are widely assumed to have a significant impact on outcome. We compared the ability of multiplex ligand-dependent probe amplification (MLPA) and polymerase chain reaction (PCR) to detect ΔIKZF1 and to determine the impact on event-free survival of patients with precursor B-ALL aged 23 to 65 years recruited to the completed trial UKALL14 (ISRCTN 66541317). From 655 recruits with BCR-ABL1+ and BCR-ABL1− B-ALL, all available diagnostic DNA samples (76% of the recruited population) were screened by multiplex end point PCR covering 4 deletions: dominant-negative (DN) Δ4-7 or the loss of function Δ2-7, Δ4-8, and Δ2-8 (n = 498), MLPA (n = 436), or by both (n = 420). Although patients with BCR-ABL1− ΔIKZF1 were more likely to have minimal residual disease at the end of induction, we did not find any impact of ΔIKZF1 (including subgroup analysis for DN or loss-of-function lesions) or the IKZF1plus genotype on event-free, overall survival, or relapse risk by univariable or multivariable analyses. Consistent with the technical approach, MLPA not only detected a wider range of deletions than PCR but also failed to detect some PCR-detected lesions. The main difference between our study and others reporting an association between ΔIKZF1 and outcome is the older age of participants in our population. The impact of ΔIKZF1 in ALL may be less marked in an older population of patients. Our study underscores the need for analyses in large, harmonized data sets. This trial was registered at www.clinicaltrials.gov as #NCT01085617

The role of diet and exercise and of glucosamine sulfate in the prevention of knee osteoarthritis: Further results from the PRevention of knee Osteoarthritis in Overweight Females (PROOF) study

Background and objectives: The PRevention of knee Osteoarthritis in Overweight Females (PROOF) study (ISRCTN 42823086) described a trend for a decrease in the incidence of knee osteoarthritis (OA) by a tailored diet and exercise program (DEP) or by oral glucosamine sulfate in women at risk for the disease, using a composite clinical and/or radiological outcome. The aim of this updated post-hoc analysis was to re-assess the results according to more precise techniques and take advantage of the 2×2 factorial design. Methods: A total of 407 overweight (BMI ≥ 27 kg/m2) women of 50-60 years of age with no diagnosis of knee OA were randomized to: (1) no DEP + placebo (Control, N = 102), (2) DEP + placebo (DEP, N = 101), (3) glucosamine sulfate + no DEP (GS, N = 102), and (4) DEP + glucosamine sulfate (DEP + GS, N =102) and followed for 2.5 years, with standardized postero-anterior, semiflexed (MTP) view knee radiographs at baseline and end of the study. DEP consisted of a tailored low fat and/or low caloric diet and easy to implement physical activities. Glucosamine was given as oral crystalline glucosamine sulfate 1500 mg once daily, double-blinded vs. placebo. Incident knee OA was defined as radiographic progression of ≥1 mm minimum joint space narrowing (mJSN) in the medial tibiofemoral compartment, as previously assessed by the visual (manual) technique and by a new semi-automated method. Logistic regression analysis was used to calculate the odds ratio for the effect of the interventions. Results: After 2.5 years, 11.8% of control subjects developed knee OA. This incidence was decreased with glucosamine sulfate, either alone or in combination with the DEP, but not by the DEP alone. Since there was no statistical interaction between treatments, the 2×2 factorial design allowed analysis of patients receiving glucosamine sulfate (= 204) vs. those not receiving it (= 203), similarly for those on the DEP (= 203) or not (= 204). Glucosamine sulfate significantly decreased the risk of developing knee OA: odds ratio (OR) = 0.41 (95% CI: 0.20-0.85, P = 0.02) by the manual JSN assessment method and OR = 0.42 (95% CI: 0.20-0.92, P = 0.03) by the semi-automated technique. Conversely, there was no decrease in risk with the DEP. Conclusions: Glucosamine sulfate decreased the risk of developing radiographic knee OA over 2.5 years in overweight, middle-aged women at risk, as determined by medial mJSN progression. Conversely a tailored diet and exercise program exerted no preventive effect, possibly because of the lower than expected effect on weight loss

Effects of aircraft noise on annoyance, sleep disorders, and blood pressure among adult residents near the Orio al Serio International Airport (BGY), Italy

Introduzione: Il rumore aeroportuale pu\uf2 causare effetti extra-uditivi quali annoyance, disturbi del sonno, ipertensione, patologie cardiovascolari e alterazioni delle abilit\ue0 cognitive nei bambini. Obiettivi: Condurre un\u2019indagine trasversale tra gli adulti residenti in prossimit\ue0 dell\u2019Aeroporto Internazionale di Orio al Serio (BGY), per studiare l\u2019associazione tra rumore aeroportuale, annoyance, disturbi del sonno, pressione arteriosa e ipertensione. Metodi: Soggetti di et\ue0 45-70 anni sono stati suddivisi, sulla base della residenza, in tre zone acustiche di rumore aeroportuale: <60 (Riferimento), 60-65 (Zona A) e 65-75 dBA (Zona B). Un campione di soggetti \ue8 stato invitato a sottoporsi a intervista e misurazioni della pressione arteriosa. Per analizzare variabili quantitative e categoriche, sono stati utilizzati modelli di regressione lineare multipla e di Poisson robusta, rispettivamente. Risultati: Tra giugno e settembre 2013 sono stati reclutati 400 soggetti (166 nella Zona di Riferimento, 164 nella Zona A e 70 nella Zona B). Rispetto al riferimento, sono stati rilevati elevati punteggi di annoyance (diurni e notturni) nelle Zone A (+2,7) e B (+4,0) (p<0,001) e circa il doppio di soggetti fortemente infastiditi in entrambe le zone (p<0,001). Anche i disturbi del sonno riferiti nel mese precedente erano pi\uf9 frequenti nelle Zone A e B. I disturbi del sonno considerati complessivamente corrispondevano a 19,9% nella Zona di Riferimento, 29,9% nella Zona A e 35,7% nella Zona B (p<0,001). Conclusioni: \uc8 stata evidenziata una forte associazione tra rumore aeroportuale, annoyance e disturbi del sonno. Non \ue8 stata riscontrata alcuna relazione con i livelli di pressione arteriosa e la prevalenza di ipertensione.Background: Aircraft noise may cause several non-auditory health effects, including annoyance, sleep disorders, hypertension, cardiovascular diseases, and impaired cognitive skills in children. Objectives: To perform a cross-sectional study among adult residents near the Orio al Serio International Airport (BGY), Italy to investigate the association between aircraft noise, annoyance, sleep disorders, blood pressure levels, and prevalence of hypertension. Methods: Residential addresses of subjects aged 45-70 years were geocoded and classified in three groups according to noise levels: <60 (Reference), 60-65 (Zone A), and 65-75 dBA (Zone B). A sample of subjects was invited to undergo a personal interview and blood pressure measurements. Multiple linear and robust Poisson regression models were used to analyze quantitative and categorical variables, respectively. Results: Between June and September 2013, we enrolled 400 subjects (166 in the Reference Zone, 164 in Zone A, and 70 in Zone B). Compared to the Reference Zone, we found elevated adjusted annoyance scores (day and night) in Zone A (+2.7) and Zone B (+4.0) (p<0.001) and about doubled proportions of severely annoyed subjects (p<0.001). Reported sleep disorders in the previous month were also more frequent in Zones A and B. Sleep disorders in general were 19.9% in the Reference Zone, 29.9% in Zone A, and 35.7% in Zone B (p<0.001). Conclusions: We found a strong association between aircraft noise levels, annoyance, and sleep disorders among adult residents near the Orio al Serio International Airport. We found no relationship with blood pressure levels and prevalence of hypertension

Selective intrauterine growth restriction in monochorionic twins : changing patterns in umbilical artery Doppler flow and outcomes

Objectives: To describe changes in umbilical artery (UA) Doppler flow in monochorionic diamniotic (MCDA) twins affected by selective intrauterine growth restriction (sIUGR), to correlate Doppler findings with pregnancy course and perinatal outcome, and to report postnatal follow-up. Methods: This was a retrospective study of 140 MCDA twins with sIUGR. UA end-diastolic flow, defined as Doppler waveform pattern Type I (persistently positive), Type II (persistently absent or persistently reversed) or Type III (intermittently absent or intermittently reversed), was recorded at first examination and monitored weekly until double or single intrauterine fetal death (IUFD), bipolar cord coagulation or delivery. All neonates had an early neonatal brain scan, magnetic resonance imaging, when indicated, and neurological assessment during infancy. Rates (per 100 person-weeks) and hazard ratios (HR) of IUFD in the IUGR twin in each pregnancy were calculated considering UA Doppler pattern as a time-dependent variable. Results: At first examination, there were 65 cases with UA Doppler waveform pattern Type I, 62 with Type II and 13 with Type III. Of the 65 Type-I cases, 48 (74%) remained stable, while 17 (26%) changed to either Type II absent (14%), Type II reversed (9%) or Type III (3%). Of 62 Type-II cases (47 with absent and 15 with reversed flow), 33 (53%) remained stable (18 with absent and all 15 with reversed flow). The 29 Type-II absent cases which changed became Type II reversed (24/47, 51%) or Type III (5/47, 11%). All 13 Type-III cases remained stable. Compared with Type I, the risk of IUFD (adjusted for estimated fetal weight discordance and amniotic fluid deepest vertical pocket) was highest when the pregnancy was or became Type II reversed (HR, 9.5; 95% CI, 2.7\u201332.7) or Type II absent (HR, 4.3; 95% CI, 1.3\u201314.3). Mild neurological impairment was more prevalent in the IUGR twin than in the large cotwin (7% vs 1%, P = 0.02). Conclusions: Risk stratification based on UA Doppler is useful for planning ultrasound surveillance. However, patterns can change over time, with important consequences for management and outcome

Gli1/DNA interaction is a druggable target for Hedgehog-dependent tumors

Hedgehog signaling is essential for tissue development and stemness, and its deregulation has been observed in many tumors. Aberrant activation of Hedgehog signaling is the result of genetic mutations of pathway components or other Smo-dependent or independent mechanisms, all triggering the downstream effector Gli1. For this reason, understanding the poorly elucidated mechanism of Gli1-mediated transcription allows to identify novel molecules blocking the pathway at a downstream level, representing a critical goal in tumor biology. Here, we clarify the structural requirements of the pathway effector Gli1 for binding to DNA and identify Glabrescione B as the first small molecule binding to Gli1 zinc finger and impairing Gli1 activity by interfering with its interaction with DNA. Remarkably, as a consequence of its robust inhibitory effect on Gli1 activity, Glabrescione B inhibited the growth of Hedgehog-dependent tumor cells in vitro and in vivo as well as the self-renewal ability and clonogenicity of tumor-derived stem cells. The identification of the structural requirements of Gli1/DNA interaction highlights their relevance for pharmacologic interference of Gli signaling

Enhanced Software for Scheduling Space-Shuttle Processing

The Ground Processing Scheduling System (GPSS) computer program is used to develop streamlined schedules for the inspection, repair, and refurbishment of space shuttles at Kennedy Space Center. A scheduling computer program is needed because space-shuttle processing is complex and it is frequently necessary to modify schedules to accommodate unanticipated events, unavailability of specialized personnel, unexpected delays, and the need to repair newly discovered defects. GPSS implements constraint-based scheduling algorithms and provides an interactive scheduling software environment. In response to inputs, GPSS can respond with schedules that are optimized in the sense that they contain minimal violations of constraints while supporting the most effective and efficient utilization of space-shuttle ground processing resources. The present version of GPSS is a product of re-engineering of a prototype version. While the prototype version proved to be valuable and versatile as a scheduling software tool during the first five years, it was characterized by design and algorithmic deficiencies that affected schedule revisions, query capability, task movement, report capability, and overall interface complexity. In addition, the lack of documentation gave rise to difficulties in maintenance and limited both enhanceability and portability. The goal of the GPSS re-engineering project was to upgrade the prototype into a flexible system that supports multiple- flow, multiple-site scheduling and that retains the strengths of the prototype while incorporating improvements in maintainability, enhanceability, and portability