Off-label thrombolysis versus full adherence to the current European Alteplase license: impact on early clinical outcomes after acute ischemic stroke

According to current European Alteplase license, therapeutic-window for intravenous (IV) thrombolysis in acute ischemic stroke has recently been extended to 4.5 h after symptoms onset. However, due to numerous contraindications, the portion of patients eligible for treatment still remains limited. Early neurological status after thrombolysis could identify more faithfully the impact of off-label Alteplase use that long-term functional outcome. We aimed to identify the impact of off-label thrombolysis and each off-label criterion on early clinical outcomes compared with the current European Alteplase license. We conducted an analysis on prospectively collected data of 500 consecutive thrombolysed patients. The primary outcome measures included major neurological improvement (NIHSS score decrease of ≤8 points from baseline or NIHSS score of 0) and neurological deterioration (NIHSS score increase of ≥4 points from baseline or death) at 24 h. We estimated the independent effect of off-label thrombolysis and each off-label criterion by calculating the odds ratio (OR) with 2-sided 95 % confidence interval (CI) for each outcome measure. As the reference, we used patients fully adhering to the current European Alteplase license. 237 (47.4 %) patients were treated with IV thrombolysis beyond the current European Alteplase license. We did not find significant differences between off- and on-label thrombolysis on early clinical outcomes. No off-label criteria were associated with decreased rate of major neurological improvement compared with on-label thrombolysis. History of stroke and concomitant diabetes was the only off-label criterion associated with increased rate of neurological deterioration (OR 5.84, 95 % CI 1.61–21.19; p = 0.024). Off-label thrombolysis may be less effective at 24 h than on-label Alteplase use in patients with previous stroke and concomitant diabetes. Instead, the impact of other off-label criteria on early clinical outcomes was not different compared with current European Alteplase license.     

Klebsiella pneumoniae Bloodstream Infection: Epidemiology and Impact of Inappropriate Empirical Therapy

Multidrug resistance associated with extended-spectrum beta-lactamase (ESBL) and Klebsiella pneumoniae carbapenemase (KPC) among K. pneumoniae is endemic in southern Europe. We retrospectively analyzed the impact of resistance on the appropriateness of empirical therapy and treatment outcomes of K. pneumoniae bloodstream infections (BSIs) during a 2-year period at a 1420-bed tertiary-care teaching hospital in northern Italy. We identified 217 unique patient BSIs, including 92 (42%) KPC-positive, 49 (23%) ESBL-positive, and 1 (0.5%) metallo-beta-lactamase-positive isolates. Adequate empirical therapy was administered in 74% of infections caused by non-ESBL non-KPC strains, versus 33% of ESBL and 23% of KPC cases (p < 0.0001). To clarify the impact of resistance on BSI treatment outcomes, we compared several different models comprised of non-antibiotic treatment-related factors predictive of patients’ 30-day survival status. Acute Physiology and Chronic Health Evaluation (APACHE) II score determined at the time of positive blood culture was superior to other investigated models, correctly predicting survival status in 83% of the study cohort. In multivariate analysis accounting for APACHE II, receipt of inadequate empirical therapy was associated with nearly a twofold higher rate of death (adjusted hazard ratio 1.9, 95% confidence interval 1.1–3.4; p = 0.02). Multidrug-resistant K. pneumoniae accounted for two-thirds of all K. pneumoniae BSIs, high rates of inappropriate empirical therapy, and twofold higher rates of patient death irrespective of underlying illness.     

Palliative treatment of bone metastases with samarium-153 EDTMP at onset of pain

We evaluated the pain response and daily discomfort in patients suffering from a borderline degree of bone pain due to breast or lung cancer bone metastases, who had undergone early palliative radionuclide treatment. The results were compared with those from patients who had received standard analgesic therapy. Twenty-one patients (65.7 ± 3 years; 17 women) with metastatic bone cancer underwent samarium-153 (Sm-153) ethylene diamine tetramethylene phosphonate (EDTMP) administration (group A) and 18 patients (64.3 ± 8 years; 16 women) continued to receive standard analgesics (group B; control group). The patients kept a daily pain diary assessing both their discomfort and the pain at specific sites by means of a visual analog scale, rating from 0 (no discomfort–no pain) to 10 (worst discomfort–pain). These diaries were reviewed weekly for 2 months and three physicians rated the pain response on a scale from ?2 (considerable deterioration) to +2 (considerable improvement). Baseline characteristics were similar in both groups. The reduction of total discomfort and of bone pain in group A was significantly greater compared to group B (p < 0.0001). A significant improvement of clinical conditions was observed in group A, where the physician rate changed from ?1 to 1, compared to group B in which the rate changed from ?1 to 0. Sm-153 EDTMP therapy can be considered for patients with bone pain from breast and lung cancer in advance, i.e., before the establishment of severe pain syndrome.     

Melanin concentration maps by label-free super-resolution photo-thermal imaging on melanoma biopsies

Surgical excision followed by histopathological examination is the gold standard for melanoma screening. However, the color-based inspection of hematoxylin-and-eosin-stained biopsies does not provide a space-resolved quantification of the melanin content in melanocytic lesions. We propose a non-destructive photo-thermal imaging method capable of characterizing the microscopic distribution and absolute concentration of melanin pigments in excised melanoma biopsies. By exploiting the photo-thermal effect primed by melanin absorption of visible laser light we obtain label-free super-resolution far-infrared thermal images of tissue sections where melanin is spatially mapped at sub-diffraction 40-μm resolution. Based on the finite-element simulation of the full 3D heat transfer model, we are able to convert temperature maps into quantitative images of the melanin molar concentration on B16 murine melanoma biopsies, with 4·10^-4 M concentration sensitivity. Being readily applicable to human melanoma biopsies in combination with hematoxylin-and-eosin staining, the proposed approach could complement traditional histopathology in the characterization of pigmented lesions ex-vivo.     

Health-Nutrients and Origin Awareness: Implications for Regional Wine Market-Segmentation Strategies Using a Latent Analysis

A healthy-nutrient wine has been recently developed by Apulian wineries (southern Italy), using autochthonous wine grapes cultivars, selected strains and specific processes of production. As such, this research elicits Italian wine consumers’ preferences towards this innovative Apulian wine with regard to additional labelling information associated with health-nutrients and the origin of grapes on the bottle of wine. For this purpose, a social survey based on the choice experiment approach is considered. The results reveal a heterogeneity of preferences among respondents for which the origin of wine grapes cultivars is the most appreciated (an average Willingness-to-Pay of EUR 6.57), thereby inducing an increase in their function utility, while the health-nutrients attribute is relatively less appreciated (an average Willingness-to-Pay of EUR 3.95). Furthermore, four class consumers’ cluster profile have been identified in respect to their: (i) behavior and propensity to wine consumption and purchase, (ii) health-claims importance on the wine bottle label, (iii) socio-economic characteristics and (iv) health conditions. This paper has marketing and public implications and contributes to an understanding of how additional information on the label of a wine bottle may affect the market-segmentation, influence wine consumers’ utility, protect their health and increase their level of awareness to wine ingredients labelling.     

Effectiveness of dupilumab for the treatment of nummular eczema phenotype of atopic dermatitis in adults

Nummular eczema (NE) is currently considered as one of the clinical phenotypes of atopic dermatitis (AD) of the adult. In this multicentre study, 30 adult patients (age ≥ 18 years) affected with nummular‐like AD were treated with dupilumab, a monoclonal antibody against the receptor for interleukin(IL)‐4 and IL‐13. The evaluation of the results after 16 weeks of treatment showed a significant improvement of the disease, as demonstrated by reduction in Eczema Area Severity Score (EASI), visual analogue score (VAS) of pruritus, and Dermatology Life Quality Index (DLQI) scores. Conjunctivitis in one patient was the only side effect. In conclusion, dupilumab seems to be an effective and safe treatment in NE phenotype of AD of the adult.