Benefit of dual-chamber pacing with Closed Loop Stimulation in tilt-induced cardio-inhibitory reflex syncope (BIOSync trial): study protocol for a randomized controlled trial

Ritme cardíac; Síncope reflex neurològic; Prova de la taula d’inclinacióRitmo cardíaco; Síncope reflejo neuromediado; Prueba de la mesa inclinadaCardiac pacing; Neuro-mediated reflex syncope; Tilt-Table testBackground: The efficacy of dual-chamber cardiac pacing in neuro-mediated reflex syncope with a cardio-inhibitory response to the Tilt-Table test (TT) has not been definitively assessed so far. The lack of reproducibility of results from previous studies may be partially explained by discrepancies in subject selection and some weaknesses in design and methods. The European Society of Cardiology (ESC) has set a class IIb indication to pacemaker implantation in this population recommending further research. Methods/design: The BIOSync study is a multicenter, patient- and outcome-assessor-blind, randomized, parallel-arm, placebo-controlled trial with the objective of assessing the clinical benefit of cardiac pacing in patients with frequently recurrent reflex syncope, suspected (but not proven) to be triggered by asystolic pauses as showing a VASIS 2B response to the TT (>3-s pause regardless of blood pressure drop). The primary and secondary endpoints are time to first post-implantation recurrence of syncope or the combination of pre-syncope or syncope, respectively. One hundred and twenty-eight consenting patients will be 1:1 randomized to dual-chamber cardiac pacing 'on' or 'off' after pacemaker implantation, and followed up until the first adjudicated primary endpoint event for a maximum of 2 years. The so-called Closed Loop Stimulation function on top of dual-chamber pacing is the pacing mode selected in the study active arm. Participating patients are asked to self-report syncopal symptoms at least every 3 months with self-administered questionnaires addressed to an independent Adjudication Committee. Patients and members of the Adjudicating Committee are blinded to randomization. The study is designed to detect a 40% relative reduction in the 2-year incidence of syncopal recurrences with 80% statistical power. Discussion: The BIOSync study is designed to definitively assess the benefit of pacing against placebo in reflex syncope patients with a cardio-inhibitory response to the TT. The study will also provide important information on the efficiency of the TT in appropriately selecting reflex syncope patients for cardiac pacing.All study-related costs are being directly supported by the sponsor of the study (BIOTRONIK SE & Co. KG, Berlin, Germany). No further funding is provided

Air Temperature Distribution and Energy-balance Modelling of a Debris-covered Glacier

Near-surface air temperature is an important determinant of the surface energy balance of glaciers and is often represented by a constant linear temperature gradients (TGs) in models. Spatiotemporal variability in 2 m air temperature was measured across the debris-covered Miage Glacier, Italy, over an 89 d period during the 2014 ablation season using a network of 19 stations. Air temperature was found to be strongly dependent upon elevation for most stations, even under varying meteorological conditions and at different times of day, and its spatial variability was well explained by a locally derived mean linear TG (MG–TG) of −0.0088°C m−1. However, local temperature depressions occurred over areas of very thin or patchy debris cover. The MG–TG, together with other air TGs, extrapolated from both on- and off-glacier sites, were applied in a distributed energy-balance model. Compared with piecewise air temperature extrapolation from all on-glacier stations, modelled ablation, using the MG–TG, increased by 4% using the environmental ‘lapse rate’. Ice melt under thick debris was relatively insensitive to air temperature, while the effects of different temperature extrapolation methods were strongest at high elevation sites of thin and patchy debris cover

Clinicopathological predictors of recurrence in nodular and superficial spreading cutaneous melanoma: A multivariate analysis of 214 cases

Abstract Background Nodular melanoma (NM) accounts for most thick melanomas and because of their frequent association with ulceration, fast growth rate and high mitotic rate, contribute substantially to melanoma-related mortality. In a multicentric series of 214 primary melanomas including 96 NM and 118 superficial spreading melanoma (SSM), histopathological features were examined with the aim to identify clinicopathological predictors of recurrence. Methods All consecutive cases of histopathologically diagnosed primary invasive SSM and NM during the period 2005–2010, were retrieved from the 12 participating Italian Melanoma Intergroup (IMI) centers. Each center provided clinico-pathological data such as gender, age at diagnosis, anatomical site, histopathological conventional parameters, date of excision and first melanoma recurrence. Results Results showed that NM subtype was significantly associated with Breslow thickness (BT) at multivariate analysis: [BT 1.01–2 mm (OR 7.22; 95% CI 2.73–19.05), BT 2.01–4 mm (OR 7.04; 95% CI 2.54–19.56), and BT > 4 mm (OR 51.78; 95% CI 5.65–474.86) (p  5 mitoses/mm2 (OR 4.87; 95% CI 1.77–13.40) (p = 0.002)]. The risk of recurrence was not significantly associated with NM histotype while BT [BT 1.01–2.00 mm (HR 1.55; 95% CI 0.51–4.71), BT 2.01–4.00 mm (HR 2.42; 95% CI 0.89–6.54), BT > 4.00 mm. (HR 3.13; 95% CI 0.95–10.28) (p = 0.05)], mitotic rate [MR > 2 mitoses/mm2 (HR 2.34; 95% CI, 1.11–4.97) (p = 0.03)] and the positivity of lymph node sentinel biopsy (SNLB) (HR 2.60; 95% CI 1.19–5.68) (p = 0.007) were significantly associated with an increased risk of recurrence at multivariate analysis. Conclusions We found that NM subtype was significantly associated with higher BT and MR but it was not a prognostic factor since it did not significantly correlate with melanoma recurrence rate. Conversely, increased BT and MR as well as SNLB positivity were significantly associated with a higher risk of melanoma recurrence

Urinalysis: diagnostic performance of urine dipstick compared to an automated microscopic method

Introduction: Urinalysis is one of the most important clinical laboratory tests because numerous pathologies can manifest or be suspected through this test. Although the previous reports mention that urinary microscopy is a fundamental part of urinalysis for diagnostic support of various conditions, there is a debate about the utility of this test section in a certain patient population. The aim of this study was to determine the diagnostic performance of the urinary dipstick analysis and the potential risks of false-negative (FN) results. Material and methods: This is a retrospective and observational study, and urinalysis information was obtained from non-hospitalized patients. The dipstick and microscopic analyses were performed using the Clinitek-ATLAS (index test) and iQ200-SPRINT (reference standard) devices. Dipstick or microscopy analyses were positive if ≥ 1 parameters were abnormal. A Bayesian hierarchal beta-binomial model was carried out for each performance parameter. Risk analysis was performed as proposed in the literature. Results: Five hundred and fifty-two patients were included in the study. The posterior median at group level was 94% (credible interval 95% [CrI 95%] 89.9-97%) for sensitivity (Se), 57.1% (CrI 95%, 50.1-64.1%) for specificity, and 5.8% (CrI 95%, 2.59-9.64%) for FN rate (FNR). The posterior probability Se > 90% was 95.9% at a group level. The risk analysis found only low-risk false-negative events. Conclusions: The performance of the dipstick analysis was appropriate, with a good certainty of Se > 90% and a FNR < 10% at the operator level. Omission of microscopic analysis can be a safe action in a patient with a negative dipstick since FNs with a clinical impact are not expected

Visualization of Murine Intranasal Dosing Efficiency Using Luminescent Francisella tularensis: Effect of Instillation Volume and Form of Anesthesia

Intranasal instillation is a widely used procedure for pneumonic delivery of drugs, vaccine candidates, or infectious agents into the respiratory tract of research mice. However, there is a paucity of published literature describing the efficiency of this delivery technique. In this report we have used the murine model of tularemia, with Francisella tularensis live vaccine strain (FTLVS) infection, to evaluate the efficiency of pneumonic delivery via intranasal dosing performed either with differing instillation volumes or different types of anesthesia. FTLVS was rendered luminescent via transformation with a reporter plasmid that constitutively expressed the Photorhabdus luminescens lux operon from a Francisella promoter. We then used an IVIS Spectrum whole animal imaging system to visualize FT dissemination at various time points following intranasal instillation. We found that instillation of FT in a dose volume of 10 µl routinely resulted in infection of the upper airways but failed to initiate infection of the pulmonary compartment. Efficient delivery of FT into the lungs via intranasal instillation required a dose volume of 50 µl or more. These studies also demonstrated that intranasal instillation was significantly more efficient for pneumonic delivery of FTLVS in mice that had been anesthetized with inhaled (isoflurane) vs. parenteral (ketamine/xylazine) anesthesia. The collective results underscore the need for researchers to consider both the dose volume and the anesthesia type when either performing pneumonic delivery via intranasal instillation, or when comparing studies that employed this technique

The role of spectrophotometry in the diagnosis of melanoma

Background. Spectrophotometry (SPT) could represent a promising technique for the diagnosis of cutaneous melanoma (CM) at earlier stages of the disease. Starting from our experience, we further assessed the role of SPT in CM early detection. Methods. During a health campaign for malignant melanoma at National Cancer Institute of Naples, we identified a subset of 54 lesions to be addressed to surgical excision and histological examination. Before surgery, all patients were investigated by clinical and epiluminescence microscopy (ELM) screenings; selected lesions underwent spectrophotometer analysis. For SPT, we used a video spectrophotometer imaging system (Spectroshade® MHT S.p.A., Verona, Italy). Results. Among the 54 patients harbouring cutaneous pigmented lesions, we performed comparison between results from the SPT screening and the histological diagnoses as well as evaluation of both sensitivity and specificity in detecting CM using either SPT or conventional approaches. For all pigmented lesions, agreement between histology and SPT classification was 57.4%. The sensitivity and specificity of SPT in detecting melanoma were 66.6% and 76.2%, respectively. Conclusions. Although SPT is still considered as a valuable diagnostic tool for CM, its low accuracy, sensitivity, and specificity represent the main hamper for the introduction of such a methodology in clinical practice. Dermoscopy remains the best diagnostic tool for the preoperative diagnosis of pigmented skin lesions