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Wildfires shape ecosystems globally, yet little is known on their effects on wildlife distribution and spatial behaviour. We used bats as models to test the effects of fire on ecosystems because they are multi‐habitat specialists and feature ecological and life traits such as behavioural plasticity and longevity that make them able to respond to both short‐ and long‐term environmental changes. We aimed at testing the effects of a severe wildfire on a Mediterranean bat assemblage in terms of occupancy, activity and individual fitness. Here, we measure the effects of fire on activity levels and occupancy by a Mediterranean bat assemblage at the Vesuvius National Park, in Southern Italy, over 4 years, encompassing a year when a severe wildfire occurred. By comparing bat occurrence and activity at burnt versus unburnt sites with a Before‐After/Control‐Impact approach, we found that bat responses to wildfires are species specific and depend on the time elapsed since the fire. Species that rely more strongly on forest areas showed a strong short‐term adverse response in terms of occupancy and activity, while species adapted to open habitats showed no response 1 year after the wildfire. However, most species showed a general positive effect due to the passage of fire 2 years after its occurrence, probably because of vegetation regrowth. The wildfire event was also associated with reduced reproduction in at least one species, and to worse individual body conditions 1 year after the wildfire. Our results show that most bats in a Mediterranean ecosystem show resilience to the occurrence of fire, yet many species show negative short‐term responses by altering their spatial behaviour and decreasing their investment in reproduction. Future increases in fire occurrence and intensity due to climate change may alter bat assemblages and impair population viability in the long term, hampering the fundamental ecosystem services provided by structured bat communities. [ABSTRACT FROM AUTHOR]

The introduction of modern forwarders to Apennines forest operations must account for the traditional forwarding units used by local logging contractors. They generally use the same machine for extraction and intermediate off-road transportation on mountain trails, inaccessible to heavy road vehicles. Conventional forwarders are not designed for fast transportation on trail and cannot replace conventional. This research set up a long-term follow-up study to determine the use pattern of three conventional tractor-trailer units (Forwarder, forestry trailer and articulated truck). The goal of this study was to gauge the potential of these machines. In particular, the study determined for both machine types: monthly usage, incidence of travelling time over total time, distance covered and travel speed. The null hypothesis was that use pattern, average travel distance and speed distribution did not differ between traditional tractor and trailer units and high-speed forwarders. For this purpose, Global Positioning System/Global System for Mobile Communications data loggers were installed for continuous real-time collection of the main work data, including position, status, speed and fuel consumption. The study showed that new forwarders could actually travel at a speed higher than 24 km h-1, and they performed both extraction and intermediate transportation. They were capable of independent relocation, which made them suitable for small-scale forestry. Both machine types were used intensively, but the annual usage of forwarders was almost twice as large as that of tractor-trailer units. Furthermore, forwarders had a 27% higher hourly productivity and a 50% higher fuel consumption per hour, compared with tractor-trailer units. [ABSTRACT FROM AUTHOR]

• Bats adjust spatial behaviour according to forest structure and management. • Plecotus auritus prefer high forest and avoid coppice and artificial stands. • Forest and trail network management warrant attention to preserve this species. Landscape management is a key tool for wildlife conservation. This is especially important in protected areas, where conservation, local resource harvesting such as timber harvesting, and public accessibility are potentially conflicting needs that eventually influence wildlife ecology and behaviour. We studied the spatial behaviour of a forest specialist, the brown long-eared bat (Plecotus auritus), and tested how this species copes with: i) habitat structure shaped by forest management practices (past coppice, high forest and conifer plantations) , and ii) the occurrence of gaps within the forest matrix opened by people to make space for pastures and hiking trails. We radio-tagged 17 bats for 3 consecutive nights each, to track their movements in a beech-dominated forest landscape in central Italy, and assessed their spatial behaviour in relation to the landscape by adopting two different approaches. First, we applied habitat selection analyses to test whether specific land use classes were disproportionately used by bats over land class availability within the landscape. Second, we related individual-based foraging and commuting locations to landscape structure, predicting activity-specific probabilities in response to land use composition and spatial patterning. Brown long-eared bats most preferred high forest stands, whereas all other land classes were least preferred such as coppice, conifer stands, and pastures. Predictive models indicate that commuting and foraging, besides being both more likely to occur within high forest, were differently affected by landscape features. Commuting long-eared bats flew along and closer to trails and open areas compared to random sites, while such habitat features were barely used for foraging. On such bases, due to the great importance of high forest, we highlight that long time may be needed to functionally convert coppice into high forest, and that previous forest management may have long-lasting effects on forest-specialist taxa. Similarly, the use of non-native conifers, once favoured for their high timber productivity, should be avoided within protected areas aiming at conserving forest bats. Trails and clearings might also be planned strategically to exploit their potential role of ecological corridor between core forest areas and favour bat commuting. [ABSTRACT FROM AUTHOR]

Myotis capaccinii is one of the most endangered Mediterranean bats. We radio tracked 21 adult individuals to assess foraging range and analyse micro-habitat selection around a nursery roost in central Italy. Habitats were characterized by development of riparian vegetation, distance between banks, degree of water clutter and levels of water pollution (expressed by macro-benthic bioindicators). Diet was also analysed to see whether prey rarity might account for species decline. Myotis capaccinii proved highly mobile: the maximum straight line distance between roost location and the farthest foraging fix recorded on one night was c. 21 km, whereas this variable averaged 7.5 km for the entire study. In general, the species preferred calm waters bordered by well-developed riparian vegetation and large (>5 m) inter-bank distances. Such factors determined the overall quality of foraging sites. Although diet was dominated by pollution-tolerant insects such as Chironomus midges, bats preferred less polluted waters. Our study also confirmed the occurrence of piscivory in this bat. Of the factors potentially responsible for species endangerment, the most likely are general habitat degradation, that is alteration of riparian vegetation and pollution, and cave roost loss. Given the large ecological niche overlap, increasing Myotis daubentonii may be outcompeting M. capaccinii. The most urgent actions to preserve M. capaccinii are extensive restoration of riparian vegetation and strict roost protection. Our study offers indications about where, and how, restoration of riparian vegetation may translate into best conservation results. [ABSTRACT FROM AUTHOR]

In recent years, many cryptic species of bats have been discovered thanks to the application of molecular techniques. The several long-eared bat species (genus Plecotus) occurring in Europe show a marked morphological similarity and occur in sympatry, so that when confusion may arise, molecular approaches have prime importance to establish the actual specific identity. Italy represents a diversity hotspot for bats in Europe, hosting 35 species, among them four Plecotus species. In this study we report on the first confirmed record of the Balkan's long-eared bat Plecotus kolombatovici for peninsular Italy, review previous unconfirmed records and analyse the species' potential distribution in the country using a modelling approach. The species' potential distribution is strongly associated with warm summer temperatures and relatively high winter precipitations, typical of Mediterranean climate. The modelling exercise we did highlights that P. kolombatovici may occur in much of the Italian territory, including the Tyrrhenian coast and on many islands that border it. We therefore argue that P. kolombatovici presence has been so far overlooked due to the morphological resemblance of this species with the grey long-eared bat P. austriacus. Comprehensive surveys are needed to ascertain the actual distribution and establish the conservation status in Italy of this poorly known species to adopt effective legal and practical conservation measures. [ABSTRACT FROM AUTHOR]

Background: Intermittent treatment with tyrosine kinase inhibitors (TKIs) is an option for elderly chronic myeloid leukemia (CML) patients who are often candidates for life-long treatment., Materials and Methods: The Italian phase III multicentric randomized Optimize TKIs Multiple Approaches (OPTkIMA) study aimed to evaluate if a progressive de-escalation of TKIs is able to maintain the molecular remission (MR) 3.0 and to improve Health-Related Quality of Life (HRQoL) in CML elderly patients., Results: A total of 215 patients in stable MR 3.0 /MR 4.0 were randomized to receive an intermittent TKI schedule 1 month ON-1 month OFF for 3 years (FIXED arm; n = 111) vs. a progressive de-escalation TKI dose up to one-third of the starting dose at the 3rd year (PROGRESSIVE arm; n = 104). Two hundred three patients completed the 3rd year of OPTkIMA study. At the last follow-up, MR 3.0 loss was 27% vs. 46% (P = .005) in the FIXED vs PROGRESSIVE arm, respectively. None of these patients experienced disease progression. The 3-year probability of maintaining the MR 3.0 was 59% vs. 53%, respectively (P = .13). HRQoL globally improved from the baseline to the 3rd year, without any significant difference between the 2 arms. After the 3rd year, the proportion of patients who was address to TKI discontinuation in the 2 arms was 36% (FIXED) vs. 58% (PROGRESSIVE) (P = .03)., Conclusions: The intensification of intermittent TKI therapy is associated with a higher incidence of MR 3.0 loss, but those patients who maintain the MR 3.0 molecular response at the end of the study have been frequently considered eligible for TFR. The HRQoL generally improved during the de-escalation therapy in both randomization arms., Competing Interests: Disclosures AI: Speaker honoraria – AOP, BMS, GSK, Incyte, Novartis and Pfizer. CB: Speaker's Bureau – Novartis, Incyte and Pfizer AB: Advisory Board and Consultancy - Novartis, Incyte, BMS, Pfizer. GR: Speaker's Bureau and Advisory Boards - Incyte, Novartis and Pfizer. MT: Speaker's Bureau – Novartis, Incyte and BMS. AMR: research funding - AstraZeneca, European Hematology Association, Transcan2-ERANET and Italian Association for Cancer Research (Fondazione AIRC); honoraria - Amgen, Celgene, Janssen and Takeda. All the other Authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The reliability and safety of front-line ultrasonography guided core needle biopsy (UG-CNB) performed with specific uniform approach have never been evaluated in a large series of patients with lymphadenopathies suspected of lymphoma. The aim of this study was to assess the overall accuracy of UG-CNB in the lymph node histological diagnosis, using a standard reference based on pathologist consensus, molecular biology, and/or surgery. We retrospectively checked the findings concerning the application of lymph node UG-CNB from four Italian clinical units that routinely utilized 16-gauge diameter modified Menghini needle under power-Doppler ultrasonographic guidance. A data schedule was sent to all centers to investigate the information regarding techniques, results, and complications of lymph node UG-CNB in untreated patients over a 12-year period. Overall, 1000 (superficial target, n = 750; deep-seated target, n = 250) biopsies have been evaluated in 1000 patients; other 48 biopsies (4.5%), screened in the same period, were excluded because inadequate for a confident histological diagnosis. Most patients were suffering from lymphomas (aggressive B-cell non-Hodgkin lymphoma [aBc-NHL], 309 cases; indolent B-cell [iBc]-NHL, 279 cases; Hodgkin lymphoma [HL], 212 cases; and nodal peripheral T-cell [NPTC]-NHL, 30 cases) and 100 cases from metastatic carcinoma; 70 patients had non-malignant disorders. The majority of CNB results met at least one criterion of the composite reference standard. The overall accuracy of the micro-histological sampling was 97% (95% confidence interval: 95%-98%) for the series. The sensitivity of UG-CNB for the detection of aBc-NHL was 100%, for iBc-NHL 95%, for HL 93%, and for NPTC-NHL 90%, with an overall false negative rate of 3.3%. The complication rate was low (6% for all complications); no patient suffered from biopsy-related complications of grade >2 according to the Common Terminology Criteria for Adverse Events. Lymph node UG-CNB as mini-invasive diagnostic procedure is effective with minimal risk for the patient., (© 2023 The Authors. Hematological Oncology published by John Wiley & Sons Ltd.)

The Transplant Centers belonging to Gruppo Italiano per il Trapianto di Midollo Osseo (GITMO) conducted a survey with the aim of evaluating the effect of SARS-CoV2 pandemic on the allogeneic transplant activity in Italy. The pandemic period from 1/3/2020 to 31/7/2020 was compared with the same period in 2019. Overall, in 2020 there was a 2.4% reduction in the number of allo-HCT cases compared to 2019. Interestingly, this deflection did not affect the acute leukemia cases (+5.7% in 2020). The use of peripheral blood-derived stem cells (+10.7%) and cryopreservation (97.4% of the centers) was highly adopted in 2020. Despite the sanitary emergency, almost all of the surveyed centers declared no impact of SARS-CoV2 pandemic on the transplant timing and outcomes, and the sanitary policy was positively evaluated by the majority of centers. The emergency measures ensured that only a minority of the allo-HCT patients had been infected by SARS-CoV2; however, a mortality of 42.1% among the allo-HCT patients hospitalized for COVID-19 was recorded. This survey gives us the information that the GITMO Group reacted positively to the pandemic. Thanks to the emergency strategies, the Italian allo-HCT activity continued safely, showing only a minor deflection and offering the same probability of cure to the transplanted patients., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Artificial light at night (ALAN) is a pervasive form of pollution largely affecting wildlife, from individual behaviour to community structure and dynamics. As nocturnal mammals, bats are often adversely affected by ALAN, yet some "light-opportunistic" species exploit it by hunting insects swarming near lights. Here we used two potentially competing pipistrelle species as models, Kuhl's (Pipistrellus kuhlii) and common (Pipistrellus pipistrellus) pipistrelles, both known to forage in artificially illuminated areas. We set our study in a mountainous area of central Italy, where only recently did the two species become syntopic. We applied spatial modelling and radiotracking to contrast potential vs. actual environmental preferences by the two pipistrelles. Species distribution models and niche analysis showed a large interspecific niche overlap, including a preference for illuminated areas, presenting a potential competition scenario. Pipistrellus pipistrellus association with ALAN, however, was weakened by adding P. kuhlii as a biotic variable to the model. Radiotracking showed that the two species segregated habitats at a small spatial scale and that P. kuhlii used artificially illuminated sites much more frequently than P. pipistrellus, despite both species potentially being streetlamp foragers. We demonstrate that ALAN influences niche segregation between two potentially competing species, confirming its pervasive effects on species and community dynamics, and provide an example of how light pollution and species' habitat preferences may weave a tapestry of complex ecological interactions., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Aims: The use of beta-blocker therapy in cardiac amyloidosis (CA) is debated. We aimed at describing patterns of beta-blocker prescription through a nationwide survey., Methods and Results: From 11 referral centres, we retrospectively collected data of CA patients with a first evaluation after 2016 (n = 642). Clinical characteristics at first and last evaluation were collected, with a focus on medical therapy. For patients in whom beta-blocker therapy was started, stopped, or continued between first and last evaluation, the main reason for beta-blocker management was requested. Median age of study population was 77 years; 81% were men. Arterial hypertension was found in 58% of patients, atrial fibrillation (AF) in 57%, and coronary artery disease in 16%. Left ventricular ejection fraction was preserved in 62% of cases, and 74% of patients had advanced diastolic dysfunction. Out of the 250 CA patients on beta-blockers at last evaluation, 215 (33%) were already taking this therapy at first evaluation, while 35 (5%) were started it, in both cases primarily because of high-rate AF. One-hundred-nineteen patients (19%) who were on beta-blocker at first evaluation had this therapy withdrawn, mainly because of intolerance in the presence of heart failure with advanced diastolic dysfunction. The remaining 273 patients (43%) had never received beta-blocker therapy. Beta-blockers usage was similar between CA aetiologies. Patients taking vs. not taking beta-blockers differed only for a greater prevalence of arterial hypertension, coronary artery disease, AF, and non-restrictive filling pattern (P < 0.01 for all) in the former group., Conclusions: Beta-blockers prescription is not infrequent in CA. Such therapy may be tolerated in the presence of co-morbidities for which beta-blockers are routinely used and in the absence of advanced diastolic dysfunction., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Mesotherapy (local intradermal therapy, LIT) is a technique used to slowly spread drugs in tissues underlying the site of injection to prolong the pharmacological effect with respect to intramuscular injection. Recommendations for proper medical use of this technique have been made for pain medicine and rehabilitation, chronic venous disease, sport medicine, musculoskeletal disorders, several dermatological conditions, skin ageing, and immune-prophylaxis. Although mesotherapy is considered a valid technique, unresolved questions remain, which should be answered to standardize methodology and dosing regimen as well as to define the right indications in clinical practice. New randomized controlled trials are needed to test single products (dose, frequency of administration, efficacy and safety). Even infiltration of substances for dermo-cosmetic purposes must be guided by safety and efficacy tests before being proposed by mesotherapy. In this article, we put forth a preclinical and clinical research plan and a health technology assessment as a call to action by doctors, researchers and scientific societies to aid national health authorities in considering mesotherapy for prevention, treatment and rehabilitation paths., Competing Interests: Prof. Dr. Silvia Natoli reports personal fees from Grunenthal Italia, grants from Grunenthal Italia, personal fees from Mylan, personal fees from Angelini, personal fees from Sandoz, outside the submitted work. All the other authors declare no conflicts of interest., (© 2021 Mammucari et al.)

Mycosis fungoides (MF) represents the most common type of cutaneous lymphoma. In the majority of patients, the disease has a slow evolution and a protracted course; however, a subset of patients shows poor oncologic outcomes. Unfortunately, there are no reliable prognostic markers for MF, and the currently available treatments are only effective in a minority of patients. This study aimed to evaluate the expression and clinical significance of PARP-1 and CAF-1/p60 in MF. Sixty-four MF representatives of the different stages of disease were assessed by immunohistochemistry for PARP-1 and CAF-1/p60. The association of PARP-1 and CAF-1/p60 with the MF stage and outcome was assessed by using Fisher's exact test and Kaplan-Meier survival analysis with the Log-rank test; a p value < 0.05 was considered significant. PARP-1 was overexpressed in 57.9% of MF and was significantly associated with a MF stage > II (p = 0.034) but not with the risk of death (p = 0.237). CAF-1/p60 was overexpressed in 26.8% of MF and was significantly associated with decreased overall survival (p < 0.001) but not with the MF stage (p = 1). A significant association was found between PARP-1 overexpression and CAF-1/p60 overexpression (p = 0.0025). Simultaneous overexpression of PARP-1 and CAF-1/p60 was significantly associated with decreased overall survival (p < 0.001), although less strongly than CAF-1/p60 alone (χ 2  = 14.916 vs 21.729, respectively). In MF, PARP-1 is overexpressed in advanced stages, while CAF-1/p60 is overexpressed in the cases with shorter overall survival, appearing as a significant prognostic marker. A role for PARP-1 inhibitors and anti-CAF-1/p60 targeted therapy may be reasonably hypothesized in MF.

HLA molecules are important for immunoreactivity in allogeneic hematopoietic stem cell transplantation (HSCT). The Gruppo Italiano Trapianto di Cellule Staminali e Terapie Cellulari, Italian Bone Marrow Donor Registry, and Associazione Italiana di Immunogenetica e Biologia dei Trapianti promoted a retrospective observational study to evaluate HLA matching and the impact of allelic HLA mismatching and non-HLA factors on unrelated Italian HSCT outcomes. From 2012 to 2015, 1788 patients were enrolled in the study. The average donor age was 29 years and the average recipient age was 49 years. As a conditioning regimen, 71% of the patients received myeloablative conditioning. For GVHD prophylaxis, 76% received either antithymocyte or anti-T lymphocyte globulin, cyclosporine A, and methotrexate. Peripheral blood was the stem cell source in 80%. The median duration of follow-up was 53 months. Regarding HLA matching, 50% of donor-recipient pairs were 10/10 matched, 38% had 1 mismatch, and 12% had 2 or more mismatches. A total of 302 pairs shared Italian origin. Four-year overall survival (OS), progression-free survival, GVHD-free relapse-free survival, and relapse rates were 49%, 40%, 22%, and 34%, respectively. The 4-year NRM was 27%, and the 100-day cumulative incidence of grade ≥II acute GVHD (aGVHD) was 26%. In multivariate analysis, 9/10 and ≤8/10 HLA allele-matched pairs were associated with worse OS (P = .04 and .007, respectively), NRM (P = .007 and P < .0001, respectively), and grade III-IV aGVHD (P = .0001 and .01, respectively). Moreover, the incidences of grade II-IV aGVHD (P = .001) and chronic GVHD (P = .002) were significantly lower in Italian pairs. In conclusion, 10/10 HLA matching is a favorable prognostic factor for unrelated HSCT outcome in the Italian population. Moreover, the presence of 2 HLA-mismatched loci was associated with a higher NRM (P < .0001) and grade II-IV aGVHD (P = .006) and a poorer OS (P = .001) compared with 1 HLA-mismatched locus in early or intermediate disease phases. Finally, we found that Italian donor and recipient origin is a favorable prognostic factor for GVHD occurrence., (Copyright © 2020 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Hyperphosphatemia is a risk factor for vascular calcifications (VCs), which are part of the chronic kidney disease-mineral and bone disorders (CKD-MBD). Vitamin K-dependent proteins such as matrix Gla protein (MGP) and bone Gla proteins (BGP, or osteocalcin) can inhibit VCs and regulate bone mineralization. In this analysis of the Vitamin K Italian (VIKI) study, the relationship between vitamin K status, vertebral fractures (VFs) and VCs in 387 hemodialysis (HD) patients with (N = 163; 42.1%) or without N = 224; 57.9%) sevelamer was evaluated. Levels of vitamin K vitamers K1 and K2 or menaquinones (MK; MK4-7), total and undercarboxylated (uc) forms for both BGP and MGP were determined. Although no differences in clinical characteristics were noted, lower levels of MK4 (0.45 versus 0.6 ng/mL, p = .01) and a greater MK4 deficiency was observed in sevelamer-treated patients (13.5% versus 5.4%, p = .005). Multivariate logistic regression revealed that MK4 deficiency was associated with sevelamer use (odds ratio [OR] = 2.64, 95% confidence interval [CI] 1.25-5.58, p = .011) and aortic calcification (OR = 8.04, 95% CI 1.07-60.26, p = .04). In the same logistic model, sevelamer amplified the effect of total BGP levels on the odds of VFs in patients with total BGP <150 μg/L compared with those with total BGP ≥150 μg/L (OR = 3.15, 95% CI 1.46-6.76, p = .003). In contrast, there was no such effect in those untreated (total BGP <150 μg/L versus total BGP ≥150 μg/L: OR = 1.21, 95% CI 0.66-2.23, p = .54]; p = .049 for effect modification by sevelamer). Sevelamer may interfere with MK4 levels in HD patients and interact with low BGP levels to increase bone fractures in CKD patients. © 2020 American Society for Bone and Mineral Research (ASBMR)., (© 2020 American Society for Bone and Mineral Research (ASBMR).)

Background: Intermittent treatment with TKIs is an option for the great majority (70%-80%) of CML patients who do not achieve a stable deep molecular response and are not eligible for treatment discontinuation. For these patients, the only alternative is to assume TKI continuously, lifelong., Methods: The Italian phase III multicentric randomized OPTkIMA study started in 2015, with the aim to evaluate if a progressive de-escalation of TKIs (imatinib, nilotinib, and dasatinib) is able to maintain the molecular response (MR 3.0 ) and to improve Health Related Quality of Life (HRQoL)., Results: Up to December 2018, 166/185 (90%) elderly CML patients in stable MR 3.0 /MR 4.0 completed the first year of any TKI intermittent schedule 1 month ON and 1 month OFF. The first year probability of maintaining the MR 3.0 was 81% and 23.5% of the patients who lost the molecular response regained the MR 3.0 after resuming TKI continuously. Patients' HRQoL at baseline was better than that of matched peers from healthy population. Women was the only factor independently associated with worse baseline HRQoL (p > 0.0001). Overall, global HRQoL worsened at 6 (p < 0.001) but returned to the baseline value at 12 months and it was statistically significantly worse in women (p = 0.001)., Conclusions: De-escalation of any TKI by 1 month ON/OFF schedule maintains the MR 3.0 /MR 4.0 in 81% of the patients during the first 12-24 months. No patients progressed to accelerated/blastic phase, all the patients (23.5%) losing MR 3.0 regained the MR 3.0 and none suffered from TKI withdrawn syndrome. The study firstly report on HRQoL in elderly CML patients moving from a continuous daily therapy to a de-escalated intermittent treatment., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Intracardiac thrombosis is reported to occur frequently in cardiac amyloidosis (CA). However, data regarding arterial thrombo-embolic events (AEs) in CA are limited. We aimed at assessing prevalence, clinical characteristics and predictors of AEs in a large multicentric CA cohort., Methods and Results: Four-hundred-six consecutive CA patients (134 AL, 73 ATTRm and 199 ATTRwt) from 5 Italian referral centres were retrospectively evaluated and followed-up for a median time of 19 months. Thirty-one patients (7.6%) suffered from an AE, of whom 10 (32.2%) were in sinus rhythm and had no history of AF. There were no significant differences in terms of age, gender and type of CA between patients with or without AEs. Fourteen (7.6%) of 185 patients on anticoagulation had an AE despite therapy. Anticoagulation therapy did not appear to fully protect from the risk of events (HR 1.23, 95%CI 0.52-2.92, p  = .64). The only predictor of AEs, in particular among CA patients in sinus rhythm, was a CHA2DS2-VASC score ≥ 3 (HR 2.84, 95%CI 1.02-7.92, p  = .05 in overall population; HR 10.13, 95%CI 1.12-91.19, p  = .04 in patients in sinus rhythm)., Conclusions: In our large, multicentric, real-world cohort, prevalence and incidence rate of AEs was high. A consistent proportion of events occurred despite anticoagulation therapy or in patients in sinus rhythm. A higher CHA2DS2-VASc score might identify patients at risk of AEs also among those in sinus rhythm.

Introduction: Mesotherapy, also known as local intradermal therapy, widely used all over the world, is a technique used to inject substances into the surface layer of the skin. There are no international guidelines for the correct use of this technique and in many countries, it is still applied empirically without valid patient consent. The Italian society of mesotherapy has planned a study to assess the rationale and clinical applications based on current evidence., Methods: An independent steering committee, based on the available scientific literature, has formulated a series of clinical questions. 21 experts responded by writing an evidence-based document. From this document 30 statements were obtained which were presented to 114 experts using the Delphi method., Results: 28 statements reached a broad agreement on definition, technique, pharmacological rationale, indications and some crucial ethical aspect., Conclusions: Although further studies are needed to establish the clinical role of this technique in each field of application, our statements recommend the correct application according to the needs of the individual patient in full respect of ethics.

Nowadays, the evaluation of elderly patients' eligibility for allogeneic stem cell transplantation (allo-SCT) is crucial. We evaluated the feasibility and efficacy of a multidimensional geriatric assessment, the Fondazione Italiana Linfomi (FIL) score, on a cohort of 228 patients older than 60 years submitted to allo-SCT in Italy and France from 2008 to 2018. Based on FIL score, available in 215 patients, 125 (58%) patients were classified as "fit" and 90 as "unfit/frail." The hematopoietic cell transplantation-specific comorbidity index (HCT-CI) was measured in 222 patients (97%); 71 (32%) patients had HCT-CI 0, 75 (34%) patients scored 1-2, and 76 (34%) ≥3. A total of 121 (53%) patients died after a median follow-up of 36 months. FIL score was found to highly predict survival, due to an excess of NRM in unfit/frail group, and confirmed its independent prognostic role on OS (HR: 0.37; 95% CI: 0.25-0.55; p < 0.0001). On the contrary, the HCI-CI failed in allo-SCT outcome prediction (HR: 1.06; 95% CI: 0.96-1.16; p = 0.27). In summary, a comprehensive geriatric assessment with FIL score seems to add significant prognostic information in elderly patients submitted to allo-SCT. The pretransplant adoption of this easy-to-use tool could help the patients' selection and management.

Background: Several small studies on patients with COVID-19 and haematological malignancies are available showing a high mortality in this population. The Italian Hematology Alliance on COVID-19 aimed to collect data from adult patients with haematological malignancies who required hospitalisation for COVID-19., Methods: This multicentre, retrospective, cohort study included adult patients (aged ≥18 years) with diagnosis of a WHO-defined haematological malignancy admitted to 66 Italian hospitals between Feb 25 and May 18, 2020, with laboratory-confirmed and symptomatic COVID-19. Data cutoff for this analysis was June 22, 2020. The primary outcome was mortality and evaluation of potential predictive parameters of mortality. We calculated standardised mortality ratios between observed death in the study cohort and expected death by applying stratum-specific mortality rates of the Italian population with COVID-19 and an Italian cohort of 31 993 patients with haematological malignancies without COVID-19 (data up to March 1, 2019). Multivariable Cox proportional hazards model was used to identify factors associated with overall survival. This study is registered with ClinicalTrials.gov, NCT04352556, and the prospective part of the study is ongoing., Findings: We enrolled 536 patients with a median follow-up of 20 days (IQR 10-34) at data cutoff, 85 (16%) of whom were managed as outpatients. 440 (98%) of 451 hospitalised patients completed their hospital course (were either discharged alive or died). 198 (37%) of 536 patients died. When compared with the general Italian population with COVID-19, the standardised mortality ratio was 2·04 (95% CI 1·77-2·34) in our whole study cohort and 3·72 (2·86-4·64) in individuals younger than 70 years. When compared with the non-COVID-19 cohort with haematological malignancies, the standardised mortality ratio was 41·3 (38·1-44·9). Older age (hazard ratio 1·03, 95% CI 1·01-1·05); progressive disease status (2·10, 1·41-3·12); diagnosis of acute myeloid leukaemia (3·49, 1·56-7·81), indolent non-Hodgin lymphoma (2·19, 1·07-4·48), aggressive non-Hodgkin lymphoma (2·56, 1·34-4·89), or plasma cell neoplasms (2·48, 1·31-4·69), and severe or critical COVID-19 (4·08, 2·73-6·09) were associated with worse overall survival., Interpretation: This study adds to the evidence that patients with haematological malignancies have worse outcomes than both the general population with COVID-19 and patients with haematological malignancies without COVID-19. The high mortality among patients with haematological malignancies hospitalised with COVID-19 highlights the need for aggressive infection prevention strategies, at least until effective vaccination or treatment strategies are available., Funding: Associazione italiana contro le leucemie, linfomi e mieloma-Varese Onlus., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Aging is a risk factor for the development of multiple chronic diseases, including cardiovascular disease, cancer and dementia. Life expectancy has increased in certain countries but this phenomenon is associated with a reduction of years of healthy life. Aging is associated with a number of physical and functional changes, especially sarcopenia. Sarcopenia is a clinical condition associated with a decrease in skeletal muscle and muscle strength, however, sarcopenia is a reversible condition. On the basis of the current scientific literature, sarcopenia could more appropriately capture an individual's vulnerability to negative health-related outcomes since it represents an early form of the chronic diseases. Recognition of this clinical condition can improve the management of older individuals in many different clinical settings. Despite the limitations of the indirect methods used to study body composition, the Italian College of the Academic Nutritionists ME/49 recommends that health authorities and health professionals around the world should make a greater effort to diagnose sarcopenia earlier and to manage it more effectively. In line with the development of cancer screening, the use of two diagnostic tools for sarcopenia (BIA and DXA) should be implemented.

Objective: Current guidelines recommend precautionary disqualification from competitive sports in patients with hypertrophic cardiomyopathy (HCM). We assessed the incidence of cardiovascular events in a cohort of patients with HCM engaged in long-term exercise programmes and competitive sport., Methods: We reviewed data on 88 consecutive athletes diagnosed with HCM, from 1997 to 2017; 92% male, 98% Caucasian, median age 31 (IQR: 19-44) years. All participated in regular exercise programmes and competitive sport at study entry.We performed follow-up evaluation after 7±5 (1-21) years. 61 (69%) of the athletes had substantially reduced or stopped exercise and sport (ie, HCM-detrained), and 27 had continued with regular training and sport competitions (HCM-trained). At baseline evaluation, both groups were similar for age, gender balance, symptoms, ECG abnormalities, extent of left ventricular hypertrophy, arrhythmias and risk profile for sudden cardiac death/arrest., Results: During the follow-up period, two participants suffered sudden cardiac arrest or death (0.3% per year) both outside of sport participation. In addition, 19 (22%) reported symptoms (syncope in 3, palpitations in 10, chest pain in 4 and dyspnoea in 2). The Kaplan-Meier analyses of freedom from combined sudden cardiac arrest/death and symptoms (log-rank test p=0.264) showed no differences between HCM-trained and detrained patients., Conclusion: In this adult cohort of low-risk HCM athletes, voluntary decision to pursue in participation in competitive sport events was not associated with increased risk for major cardiac events or clinical worsening compared with decision to reduce or withdraw from exercise programmes and sport. Similar results may not be seen in younger or racially diverse athlete populations, or in patients with more severe HCM phenotypes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: The aim of this study was to assess the diagnostic accuracy of bone scintigraphy in a large multicenter cohort of patients with cardiac amyloidotic involvement and Phe64Leu transthyretin (TTR) mutation., Background: Diagnostic accuracy of bone scintigraphy for transthyretin-related cardiac amyloidosis (TTR-CA) is considered extremely high, enabling this technique to be the noninvasive diagnostic standard for TTR-CA. Nevertheless, this approach has not been systematically validated across the entire spectrum of TTR mutations., Methods: A total of 55 patients with Phe64Leu TTR mutation were retrospectively analyzed and evaluated between 1993 and 2018 at 7 specialized Italian tertiary centers. Cardiac involvement was defined as presence of an end-diastolic interventricular septum thickness ≥12 mm, without other possible causes of left ventricular hypertrophy (i.e., arterial hypertension or valvulopathies). A technetium-99m (99mTc)-diphosphonate (DPD) or 99mTc-hydroxyl-methylene-diphosphonate (HMDP) bone scintigraphy was reviewed, and visual scoring was evaluated according to Perugini's method., Results: Among 26 patients with definite cardiac involvement, 19 underwent 99mTc-DPD or 99mTc-HMDP bone scintigraphy. Of them, 17 (89.5%) patients had low or absent myocardial bone tracer uptake, whereas only 2 (10.5%) showed high-grade myocardial uptake. The sensitivity and the accuracy of bone scintigraphy in detecting TTR-CA were 10.5% and 37%, respectively. Patients with cardiac involvement and low or absent bone tracer uptake were similar to those with high-grade myocardial uptake in terms of age, sex, and electrocardiographic and echocardiographic findings., Conclusions: The sensitivity of bone scintigraphy (DPD and HMDP) in detecting TTR-CA is extremely low in patients with Phe64Leu TTR mutation, suggesting the need to assess diagnostic accuracy of bone scintigraphy to identify cardiac involvement across a wider spectrum of TTR mutations., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Intradermal therapy, known as mesotherapy, is a technique used to inject a drug into the surface layer of the skin. In particular, it involves the use of a short needle to deposit the drug in the dermis. The intradermal microdeposit modulates the drug's kinetics, slowing absorption and prolonging the local mechanism of action. It is successfully applied in the treatment of some forms of localized pain syndromes and other local clinical conditions. It could be suggested when a systemic drug-sparing effect is useful, when other therapies have failed (or cannot be used), and when it can synergize with other pharmacological or nonpharmacological therapies. Despite the lack of randomized clinical trials in some fields of application, a general consensus is also reached in nonpharmacological mechanism of action, the technique execution modalities, the scientific rationale to apply it in some indications, and the usefulness of the informed consent. The Italian Mesotherapy Society proposes this position paper to apply intradermal therapy based on scientific evidence and no longer on personal bias., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2020 Massimo Mammucari et al.)

Ovarian cancer is the most lethal gynecological cancer, and despite years of research, with the exception of a BRCA mutation driving the use of PARP inhibitors, no new prognostic/predictive biomarkers are clinically available. Improvement in biomarker selection and validation may derive from the systematic inclusion of translational analyses into the design of clinical trials. In the era of personalized medicine, the prospective centralized collection of high-quality biological material, expert pathological revision, and association to well-controlled clinical data are important or even essential added values to clinical trials. Here, we present the academic experience of the MITO (Multicenter Italian Trial in Ovarian Cancer) group, including gynecologists, pathologists, oncologists, biostatisticians, and translational researchers, whose effort is dedicated to the care and basic/translational research of gynecologic cancer. In our ten years of experience, we have been able to collect and process, for translational analyses, formalin-fixed, paraffin-embedded blocks from more than one thousand ovarian cancer patients. Standard operating procedures for collection, shipping, and processing were developed and made available to MITO researchers through the coordinating center's web-based platform. Clinical data were collected through dedicated electronic case report forms hosted in a web-based electronic platform and stored in a central database at the trial's coordinating center, which performed all the analyses related to the proposed translational researches. During this time, we improved our strategies of block management from retrospective to prospective collection, up to the design of a prospective collection with a quality check for sample eligibility before patients' accrual. The final aim of our work is to share our experience by suggesting a guideline for the process of centralized collection, revision processing, and storing of formalin-fixed, paraffin-embedded blocks for translational purposes.

Rationale & Objective: Data for the association of sex with chronic kidney disease (CKD) progression are conflicting, a relationship this study sought to examine., Study Design: Pooled analysis of 4 Italian observational cohort studies., Setting & Participants: 1,311 older men and 1,024 older women with estimated glomerular filtration rate (eGFR)<45mL/min/1.73m 2 followed up in renal clinics., Predictor: Sex., Outcomes: End-stage kidney disease (ESKD), defined as maintenance dialysis or kidney transplantation, as the primary outcome; all-cause mortality and eGFR decline as secondary outcomes., Analytical Approach: Cox proportional hazard analysis to estimate the relative risk for ESKD and mortality and linear mixed models to estimate the rate of eGFR decline., Results: Age, systolic blood pressure, and use of renin-angiotensin system inhibitors were similar in men and women. Baseline eGFRs were 27.6±10.2 in men and 26.0±10.6mL/min/1.73m 2 in women (P<0.001), while median proteinuria was lower in women (protein excretion, 0.45 [IQR, 0.14-1.10] g/d) compared with men (0.69 [IQR 0.19-1.60] g/d; P<0.001). During a median follow-up of 4.2 years, 757 developed ESKD (59.4% men) and 471 died (58.4% men). The adjusted risks for ESKD and mortality were higher in men (HRs of 1.50 [95% CI, 1.28-1.77] and 1.30 [95% CI, 1.06-1.60], respectively). This finding was consistent across CKD stages. We observed a significant interaction between sex and proteinuria, with the risk for ESKD in men being significantly greater than for women at a level of proteinuria of ∼0.5g/d or greater. The slope of decline in eGFR was steeper in men (-2.09; 95% CI, -2.21 to-1.97mL/min/1.73m 2 per year) than in women (-1.79; 95% CI, -1.92 to-1.66mL/min/1.73m 2 per year; P<0.001). Although sex differences in eGFR decline were not different across CKD stages (P=0.3), the difference in slopes between men and women was progressively larger with proteinuria >0.5g/d (P = 0.04)., Limitations: Residual confounding; only whites were included., Conclusions: Excess renal risk in men may, at least in part, be related to higher levels of proteinuria in men compared with women., (Copyright © 2019 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: World Kidney Day (WKD) was promoted by the Italian Kidney Foundation and the Italian Society of Nephrology for raising awareness, detection, prevention, and treatment of kidney diseases. The Italian WKD focused on the "School Project" by screening students attending the fifth year of high school. The main goal of the "School Project" was to assess in healthy adolescents the presence of hypertension (HTN) and proteinuria; as well as to evaluate potential interrelations between overweight, obesity (both measured with different anthropometric methods), blood pressure (BP) levels, and proteinuria. The ancillary goal was to have an estimate of awareness on some nephrology topics., Methods: The study population consisted of 17- to 19-year-old students. HTN was defined as systolic BP (SBP) ≥140 mm Hg and/or diastolic BP (DBP) ≥90 mm Hg. Isolated systolic hypertension (ISH) was defined as SBP ≥140 mm Hg and DBP <90 mm Hg; isolated diastolic hypertension as SBP <140 mm Hg and DBP ≥90 mm Hg; systolic and diastolic hypertension as SBP ≥140 mm Hg and DBP ≥90 mm Hg; pre-hypertension as SBP >120 mm Hg but <140 mm Hg or DBP >80 mm Hg but <90 mm Hg; and optimal BP as SBP ≤120 mm Hg and DBP ≤80 mm Hg. Urine tests were performed with a dipstick; the subjects were regarded as proteinuric when the urine dipstick was positive (proteinuria ≥30 mg/dL). Body weight, height, and waist circumference (WC) were measured; body mass index (BMI), waist-to-height ratio (WHtR), and conicity index (Ci) were calculated. According to the BMI, the following classifications were adopted: underweight (<18.5 kg/m2), normal weight (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), class-I obesity (30-34.9 kg/m2), class-II obesity (35-39.9 kg/m2), class-III obesity (≥40 kg/m2)., Results: Data from 12,125 students (45.6% males) were evaluated. HTN was found in 1,349 participants (11.1%; 61.1% male), and ISH was present in 7.4%. Overweight (24.1%) and class-I (6%), -II (3.6%), and -III (1%) obesity were present in hypertensive participants. Compared to participants with normal BP, hypertensive participants had a higher BMI (p < 0.001), WC (p < 0.001), and WHtR (p < 0.001); whereas the Ci was not different (p = 0.527). Multivariate linear regression analysis showed that both WC and BMI were predictors of abnormal SBP and DBP (p < 0.001) both in males and females. Proteinuria was present in 14.8, 13.8, 14.7, and 14.7% of all normal weight, overweight, obese, and all subjects, respectively. In addition, no association was found between body weight, proteinuria, and BP., Conclusion: This study shows that overweight and obesity were significantly associated to HTN in Italian adolescents. BMI and WC were predictors of SBP and DBP. The occurrence of proteinuria was quite similar to that of HTN, but it was not associated with anthropometric indicators or HTN., (© 2020 The Author(s) Published by S. Karger AG, Basel.)

Several papers authored by international experts have proposed recommendations on the management of BCR-ABL1+ chronic myeloid leukemia (CML). Following these recommendations, survival of CML patients has become very close to normal. The next, ambitious, step is to bring as many patients as possible into a condition of treatment-free remission (TFR). The Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA; Italian Group for Hematologic Diseases of the Adult) CML Working Party (WP) has developed a project aimed at selecting the treatment policies that may increase the probability of TFR, taking into account 4 variables: the need for TFR, the tyrosine kinase inhibitors (TKIs), the characteristics of leukemia, and the patient. A Delphi-like method was used to reach a consensus among the representatives of 50 centers of the CML WP. A consensus was reached on the assessment of disease risk (EUTOS Long Term Survival [ELTS] score), on the definition of the most appropriate age boundaries for the choice of first-line treatment, on the choice of the TKI for first-line treatment, and on the definition of the responses that do not require a change of the TKI (BCR-ABL1 ≤10% at 3 months, ≤1% at 6 months, ≤0.1% at 12 months, ≤0.01% at 24 months), and of the responses that require a change of the TKI, when the goal is TFR (BCR-ABL1 >10% at 3 and 6 months, >1% at 12 months, and >0.1% at 24 months). These suggestions may help optimize the treatment strategy for TFR., (© 2019 by The American Society of Hematology.)

Human-induced alterations of ecosystems and environmental conditions often lead to changes in the geographical range of plants and animals. While modelling exercises may contribute to understanding such dynamics at large spatial scales, they rarely offer insights into the mechanisms that prompt the process at a local scale. Savi's pipistrelle (Hypsugo savii) is a vespertilionid bat widespread throughout the Mediterranean region. The species' recent range expansion towards northeastern Europe is thought to be induced by urbanization, yet no study actually tested this hypothesis, and climate change is a potential alternative driver. In this radio-telemetry study, set in the Vesuvius National Park (Campania region, Southern Italy) we provide insights into the species' thermal physiology and foraging ecology and investigate their relationships with potential large-scale responses to climate, and land use changes. Specifically, we test whether H. savii i) exploits urbanisation by selecting urban areas for roosting and foraging, and ii) tolerates heatwaves (a proxy for thermophily) through a plastic use of thermoregulation. Tolerance to heatwaves would be consistent with the observation that the species' geographic range is not shifting but expanding northwards. Tracked bats roosted mainly in buildings but avoided urban habitats while foraging, actively selecting non-intensive farmland and natural wooded areas. Hypsugo H. savii showed tolerance to heat, reaching the highest body temperature ever recorded for a free-ranging bat (46.5 °C), and performing long periods of overheating. We conclude that H. savii is not a strictly synurbic species because it exploits urban areas mainly for roosting, and avoids them for foraging: this questions the role of synurbization as a range expansion driver. On the other hand, the species' extreme heat tolerance and plastic thermoregulatory behaviour represent winning traits to cope with heatwaves typical of climate change-related weather fluctuations., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduced species represent a threat to native wildlife worldwide, due to predation, competition, and disease transmission. Concurrent introduction of parasites may also add a new dimension of competition, i.e. parasite-mediated competition, through spillover and spillback dynamics. Urban areas are major hotspots of introduced species, but little is known about the effects of urban habitat structure on the parasite load and diversity of introduced species. Here, we investigated such environmental effects on the ectoparasite load, richness, and occurrence of spillback in two widespread invasive parakeets, Psittacula krameri and Myiopsitta monachus, in the metropolitan area of Rome, central Italy. We tested 231 parakeets and found that in both species parasite load was positively influenced by host abundance at local scale, while environmental features such as the amount of natural or urban habitats, as well as richness of native birds, influenced parasite occurrence, load, and richness differently in the two host species. Therefore, we highlight the importance of host population density and habitat composition in shaping the role of introduced parakeets in the spread of both native and introduced parasites, recommending the monitoring of urban populations of birds and their parasites to assess and manage the potential occurrence of parasite-mediated competition dynamics as well as potential spread of vector-borne diseases.

Background: In recent years, novel anticoagulant drugs have been introduced in the clinical armamentarium and have progressively gained momentum. Although their use is increasing among CKD patients, some skepticism about their risk-benefit ratio still persists. We sought to investigate the safety and effectiveness of rivaroxaban in a cohort of moderate-to-advanced CKD patients., Methods: This observational, retrospective, longitudinal study involved 347 consecutive CKD stage 3b-4 (according to NKF-KDOQI guidelines) patients enrolled from 8 cardiac outpatient clinics between March 2015 and October 2017. All patients received anticoagulation (100 warfarin vs. 247 rivaroxaban) as part of their non-valvular atrial fibrillation management at the attending physician's discretion. Clinical effectiveness (defined as the occurrence of ischemic stroke, venous thromboembolism, or transient ischemic attack) and safety (intracranial hemorrhage, gastrointestinal or other bleeding) were assessed separately., Results: Over a mean follow-up period of 16 ± 0.3 months, 25 stroke episodes (15 hemorrhagic, and 10 ischemic) occurred in 24 warfarin treated patients vs. none in the rivaroxaban arm. There were 5 vs. 0 episodes of deep venous thrombosis and 8 vs. 2 major episodes of bleeding in the warfarin and rivaroxaban groups, respectively. In contrast, the proportion of minor episodes of bleeding was similar between groups., Conclusion: Rivaroxaban seems a safe and effective therapeutic option in CKD stage 3b-4 patients. However, future randomized controlled trials are needed to definitively establish the role of rivaroxaban in CKD patients.

In recent years, bats have been found to harbour many viruses, raising several questions about their role as reservoirs and potential disseminators of zoonotic viruses. We investigated the presence of six virus families in bats in three regions of Central-Southern Italy. Astroviruses were identified in seven of 13 bat species. Sequence analysis revealed marked genetic heterogeneity among the astroviruses identified, with nucleotide identity ranging between 60.26% and 87.62%. Astrovirus diversity was not associated with the bat species, the geographic areas or the bat colony, suggesting the circulation of several astrovirus strains in Italian ecosystems. Genetic diversification and interspecies transmission appear common in bat astroviruses and could provide, potentially, the bases for transmission to humans and other mammals. Yet overemphasizing this risk might have detrimental consequences for bat conservation and preservation of the important ecosystem services bats provide., (© 2018 Blackwell Verlag GmbH.)

Managing biological invasions requires rapid, cost-effective assessments of introduced species' occurrence, and a good understanding of the species' vegetation associations. This is particularly true for species that are elusive or may spread rapidly. Finlayson's squirrel (Callosciurus finlaysonii) is native to Thailand and southeastern Asia, and two introduced populations occur in peninsular Italy. One of the two introduced populations is rapidly expanding, but neither effective monitoring protocols nor reliable information on vegetation associations are available. To fill this gap, we conducted visual surveys and hair tube sampling in a periurban landscape of southern Italy to compare the effectiveness of these two methods in assessing presence of Finlayson's squirrel. We also determined the species' association with vegetation types at detection locations and nesting sites. Both visual and hair tube sampling effectively assessed the species' presence, but hair tubes resulted in fewer false absences. Moreover, when we controlled for the costs of labor and equipment, hair tubes were 33.1% less expensive than visual sampling. Presence of squirrels and their nests was positively correlated with shrub species richness, indicating that the occurrence of forests with well-developed understory may inhibit the spread of the species.

A surface extract of the aerial parts of Salvia chamaedryoides afforded 13 diterpenes (1-13), with seven compounds (1, 3, 4, 7-9, 12) described for the first time. The structures of the new compounds were established using 1D and 2D NMR spectroscopic methods, HRESIMS, and ECD data. The potential hypoglycemic effects of the crude extract, fractions, and pure compounds from S. chamaedryoides were investigated by inhibition of α-glucosidase and α-amylase enzymes. The extract and its fractions showed a moderate dose-dependent inhibition; the pure compounds exhibited differential inhibitory activity against these two enzymes. Molecular modeling studies were also performed to suggest the interaction mode of compound 3 in the α-glucosidase enzyme active site. The antimicrobial activity of the purified compounds was investigated against 26 clinical pathogens. No activity was detected for the Gram-negative species tested nor on Candida albicans and C. glabrata, while variable susceptibilities were observed using Gram-positive staphylococcal and enterococcal species.

Background: The recent multicenter, randomized, open-label INDEPENDENT study demonstrated that sevelamer improves survival in new to hemodialysis (HD) patients compared with calcium carbonate. The objective of this study was to determine the cost-effectiveness of sevelamer versus calcium carbonate for patients new to HD, using patient-level data from the INDEPENDENT study., Study Design: Cost-effectiveness analysis., Setting and Population: Adult patients new to HD in Italy., Model, Perspective, Timeframe: A patient-level cost-effectiveness analysis was conducted from the perspective of the Servizio Sanitario Nazionale, Italy's national health service. The analysis was conducted for a 3-year time horizon. The cost of dialysis was excluded from the base case analysis., Intervention: Sevelamer was compared to calcium carbonate., Outcomes: Total life years (LYs), total costs, and the incremental cost per LY gained were calculated. Bootstrapping was used to estimate confidence intervals around LYs, costs, and cost-effectiveness and to calculate the cost-effectiveness acceptability curve., Results: Sevelamer was associated with a gain of 0.26 in LYs compared to calcium carbonate, over the 3-year time horizon. Total drug costs were €3,282 higher for sevelamer versus calcium carbonate, while total hospitalization costs were €2,020 lower for sevelamer versus calcium carbonate. The total incremental cost of sevelamer versus calcium carbonate was €1,262, resulting in a cost per LY gained of €4,897. The bootstrap analysis demonstrated that sevelamer was cost effective compared with calcium carbonate in 99.4 % of 10,000 bootstrap replicates, assuming a willingness-to-pay threshold of €20,000 per LY gained., Limitations: Data on hospitalizations was taken from a post hoc retrospective chart review of the patients included in the INDEPENDENT study. Patient quality of life or health utility was not included in the analysis., Conclusions: Sevelamer is a cost-effective alternative to calcium carbonate for the first-line treatment of hyperphosphatemia in new to HD patients in Italy.

Background: Brentuximab vedotin (BV) has demonstrated an extraordinary efficacy in heavily pretreated classical Hodgkin lymphoma (cHL) patients, targeting CD30-positive cells; however, limited data have been reported on the efficacy of BV in cHL patients failing allogeneic stem cell transplantation (allo-SCT). The aim of this study was to retrospectively evaluate the efficacy and safety of BV in a multicenter setting of cHL relapsing or progressing after allo-SCT., Methods: Sixteen BV-naïve patients with recurrent cHL after allo-SCT were included in a compassionate use program and treated with intravenous BV at the dose of 1.8 mg/kg of body weight every 3 weeks for a maximum of 16 cycles., Results: The objective response rate was 69%. Five patients (31%) had complete remission, and 6 (37%) had partial remission. Stable disease was observed in 4 patients (25%), and progressive disease was observed in 1 (6%). After median follow-up of 26 months (range: 5-30 months), median progression-free survival (PFS), overall survival (OS), and duration of response were 7, 25, and 5 months, respectively. The 2-year PFS and OS were 20% and 61%, respectively. Grade 3-4 hematological adverse events included anemia (15%), thrombocytopenia (12%), and neutropenia (18%). Grade 3 peripheral sensory neuropathy occurred in 2 patients (12%)., Conclusion: BV therapy is an effective and safe approach for achieving transient disease control in cHL patients with failed allo-SCT. To improve disease control, future studies should explore the combination of BV with targeted agents., (©AlphaMed Press.)

Competition may lead to changes in a species' environmental niche in areas of sympatry and shifts in the niche of weaker competitors to occupy areas where stronger ones are rarer. Although mainland Mediterranean (Rhinolophus euryale) and Mehely's (R. mehelyi) horseshoe bats mitigate competition by habitat partitioning, this may not be true on resource-limited systems such as islands. We hypothesize that Sardinian R. euryale (SAR) have a distinct ecological niche suited to persist in the south of Sardinia where R. mehelyi is rarer. Assuming that SAR originated from other Italian populations (PES)--mostly allopatric with R. mehelyi--once on Sardinia the former may have undergone niche displacement driven by R. mehelyi. Alternatively, its niche could have been inherited from a Maghrebian source population. We: a) generated Maxent Species Distribution Models (SDM) for Sardinian populations; b) calibrated a model with PES occurrences and projected it to Sardinia to see whether PES niche would increase R. euryale's sympatry with R. mehelyi; and c) tested for niche similarity between R. mehelyi and PES, PES and SAR, and R. mehelyi and SAR. Finally we predicted R. euryale's range in Northern Africa both in the present and during the Last Glacial Maximum (LGM) by calibrating SDMs respectively with SAR and PES occurrences and projecting them to the Maghreb. R. mehelyi and PES showed niche similarity potentially leading to competition. According to PES' niche, R. euryale would show a larger sympatry with R. mehelyi on Sardinia than according to SAR niche. Such niches have null similarity. The current and LGM Maghrebian ranges of R. euryale were predicted to be wide according to SAR's niche, negligible according to PES' niche. SAR's niche allows R. euryale to persist where R. mehelyi is rarer and competition probably mild. Possible explanations may be competition-driven niche displacement or Maghrebian origin.

Purpose: Acromegaly usually occurs as a sporadic disease, but it may be a part of familial pituitary tumor syndromes in rare cases. Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene have been associated with a predisposition to familial isolated pituitary adenoma. The aim of the present study was to evaluate the AIP gene in a patient with gigantism and in her relatives., Methods: Direct sequencing of AIP gene was performed in fourteen members of the family, spanning among three generations., Results: The index case was an 18-year-old woman with gigantism due to an invasive GH-secreting pituitary adenoma and a concomitant tall-cell variant of papillary thyroid carcinoma. A novel germline mutation in the AIP gene (c.685C>T, p.Q229X) was identified in the proband and in two members of her family, who did not present clinical features of acromegaly or other pituitary disorders. Eleven subjects had no mutation in the AIP gene. Two members of the family with clinical features of acromegaly refused either the genetic or the biochemical evaluation. The Q229X mutation was predicted to generate a truncated AIP protein, lacking the last two tetratricopeptide repeat domains and the final C-terminal α-7 helix., Conclusions: We identified a new AIP germline mutation predicted to produce a truncated AIP protein, lacking its biological properties due to the disruption of the C-terminus binding sites for both the chaperones and the client proteins of AIP.

Epidemiologic investigation of invasive fungal diseases (IFDs) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) may be useful to identify subpopulations who might benefit from targeted treatment strategies. The Gruppo Italiano Trapianto Midollo Osseo (GITMO) prospectively registered data on 1858 consecutive patients undergoing allo-HSCT between 2008 and 2010. Logistic regression analysis was performed to identify risk factors for proven/probable IFD (PP-IFD) during the early (days 0 to 40), late (days 41 to 100), and very late (days 101 to 365) phases after allo-HSCT and to evaluate the impact of PP-IFDs on 1-year overall survival. The cumulative incidence of PP-IFDs was 5.1% at 40 days, 6.7% at 100 days, and 8.8% at 12 months post-transplantation. Multivariate analysis identified the following variables as associated with PP-IFDs: transplant from an unrelated volunteer donor or cord blood, active acute leukemia at the time of transplantation, and an IFD before transplantation in the early phase; transplant from an unrelated volunteer donor or cord blood and grade II-IV acute graft-versus-host disease (GVHD) in the late phase; and grade II-IV acute GVHD and extensive chronic GVHD in the very late phase. The risk for PP-IFD was significantly higher when acute GVHD was followed by chronic GVHD and when acute GVHD occurred in patients undergoing transplantation with grafts from other than matched related donors. The presence of PP-IFD was an independent factor in long-term survival (hazard ratio, 2.90; 95% confidence interval, 2.32 to 3.62; P < .0001). Our findings indicate that tailored prevention strategies may be useful in subpopulations at differing levels of risk for PP-IFDs., (Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Livestock farming produces atmospheric emissions that may pose a risk to workers and a disturbance to the population. Emissions into the atmosphere produced by livestock farming consist of gases such as ammonia, dust, compounds such as aliphatic hydrocarbons and bio-aerosols formed by microorganisms. Some gases, such as ammonia and hydrogen sulphide, have foul odours and are thus potentially annoying to the population. Gaseous or volatile molecules produced by livestock installations and related activities may have several adverse effects on health and environment. The most significant exposure certainly relates to workers in the confined spaces of farms, rather than to residents in the surrounding areas. In this article we examine potential hazards to farm workers and to the population living in the vicinity of livestock farms, arising from emissions into the atmosphere.

Ambrosia artemisiifolia is a potentially allergenic annual herbaceous plant coming from North America and widespread in Italy, where it can be easily seen since May-April. Its pollination is mainly windborne and each plant is able to produce billions of pollen grains. The pollen peaks are in the hottest days in the absence of rain and wind. In susceptible individuals, the great amount of pollen produced by this species may cause rhinitis and severe asthma attacks. Some allergic subjects can manifest disorders already at a concentration of a few granules per cubic metre. Chemical control is often practiced on a large scale and uses herbicides. A major risk is the result of the unprofessional use of chemicals by the population, especially in residential or very busy areas (eg railways, urban areas). In this paper we propose preventive measures of chemical hazards that may be resulting from the excessive use of plant protection products.

Background: Cardiac disease remains the major cause of death among ESRD patients. Indeed, the risk of cardiovascular events in ESRD is reported to be at least 3.4 fold higher than that of the general population. Moreover, annual mortality rates among ESRD patients on hemodialysis approximate 20%, with cardiovascular disease accounting for almost half of this mortality profile. Despite this knowledge, so far we have been unable to identify treatable pathogenetic factors among ESRD patients to help reverse these poor cardiovascular outcomes. The difficulty to prognosticate cardiovascular mortality in ESRD remains elusive. However, in 2011, our group, for the first time, had demonstrated that cyclic variations of arterial stiffness as measured by pulse wave velocity (PWV) before and after hemodialysis determined mortality differences within an ESRD cohort. We have therefore examined the impact of individual patient-level translational PWV changes over time on mortality outcomes in an Italian ESRD cohort., Study Design and Setting: Prospective observational study, 2007-2010, in an Italian ESRD cohort who underwent in-center outpatient conventional thrice weekly hemodialysis., Methods: PWV was measured by the foot-to-foot method and repeated after six months. Coronary artery calcification (CAC) was measured at 0, 12 and 24 months. Routine clinical data and patient demographics were recorded and mortality outcomes were analyzed., Results: Between 2007 and 2010, 466 Italian ESRD patients, 229 males and 237 females, age 19-97 (65.6) years, were followed up for 28.9 months. 128 patients (74M:54F) died. The major causes of death were acute myocardial infarction (AMI) in 47 (37%) patients (age 70, 26M:21F) and sudden death (SD) in 29 (23%) patients (age 72, 19M:10F). Paired PWV data was available in 308 surviving patients and in 106 patients who died. Baseline PWV was lower in surviving vs dead patients 8.46 +/- 1.8 vs 9.43 +/- 3.75 (p=0.0005). Repeat PWV values were unchanged in the 308 survivors (8.46 +/- 1.8 vs 8.53 +/- 1.85, p=0.5, NS). Repeat PWV values increased in the 106 patients who died from 9.43 +/- 3.75 to 12.11 +/- 4.18 (p<0.0001). Of the 29 patients who died from SD, death occurred <12 hours after the last dialysis (ATLD) in 7, >24 hours ATLD in 20 and >48 hours ATLD in 17. Of the 47 patients who died from AMI, 6 died <12 hours ATLD, 35 died >24 hours ATLD and 23 died >48 hours ATLD. Of the 14 ESRD patients in the cohort that died from hyperkalemia, 3 died <12 hours ATLD, 11 died >24 hours ATLD, and 7 died >48 hours ATLD. CAC data scatter did not allow for adequate statistical subgroup analysis but overall, baseline CAC values were higher in the AMI/SD dead patients vs surviving patients., Conclusions: This is the first report to show a scalable and direct relationship between translational follow up PWV changes after six months versus observed cardiovascular mortality in an ESRD cohort. We have shown, for the first time, that penultimate PWV, better than baseline PWV, predicted cardiovascular mortality in this ESRD cohort. Moreover, higher proportions of the ESRD deaths from AMI, SD and hyperkalemia occurred during the long inter-dialytic (weekend) period when ESRD patients went for 3 days without hemodialysis. We propose that PWV be monitored among all new ESRD patients, and be repeated after six months of initiation of chronic hemodialysis. Our group had earlier demonstrated in 2012 that daily dialysis reduced PWV in chronic hemodialysis patients. From these study findings, we have proposed that ESRD patients who exhibit elevated initial PWV values, or more so, ESRD patients who demonstrate accelerated PWV values after six months on maintenance chronic hemodialysis should be converted to daily hemodialysis protocol. Furthermore, such patients may require more intense cardiovascular analysis by cardiologists. Further research into new preventative or therapeutic options in this area of ESRD care is warranted.

Introduction: Serum concentrations of potassium (K) and calcium (Ca) influence ionic currents and play an important role in the duration of ventricular action potential. Further, the influence of alkalosis in reducing ionized calcium has been well known for a long time. The aim of this study was to assess the effects of different dialysate electrolytes and bicarbonate concentrations on changes of QTc interval in patients on chronic hemodialysis., Methods: The study hemodialysis sessions were performed in 22 patients, with different electrolyte and bicarbonate concentrations in dialysate. Tested dialysate concentrations were K of 2 and 3 mmol/L; Ca 1.25, 1.5 and 1.75 mmol/L; and bicarbonate 30 and 34 mmol/L. An electrocardiogram (ECG) was recorded 1 hour before, at the end and every hour for 4 hours after each study dialysis session. QTc interval was measured from the beginning of the QRS complex to the end of a T wave on a 12-lead ECG. Blood was collected and K, total Ca, ionic Ca and pH evaluated., Results: At the end of the study hemodialysis session with dialysate containing low K (2 mmol/L), low Ca (1.25 mmol/L) and high bicarbonate concentration (34 mmol), mean QTc interval was significantly prolonged compared with that recorded with dialysate containing high K (3 mmol/L), high Ca (1.75 mmol/L) and bicarbonate (30 mmol) (40 ± 10 milliseconds vs. 2 ± 2 milliseconds; p<0.01). Dialysate with low concentration of low Ca, K and high concentration of bicarbonate was an independent predictor of QTc; the combination of low Ca and K and high bicarbonate strongly increased the risk of prolonged QTc interval., Conclusion: The present pilot study shows that changes in QTc interval during hemodialysis depend on both electrolyte and bicarbonate concentrations in dialysate.

The barbastelle (Barbastella barbastellus) is a rare forest bat with a wide distribution in Europe. Here, we combine results from the analysis of two mtDNA fragments with species distribution modelling to determine glacial refugia and postglacial colonization routes. We also investigated whether niche conservatism occurs in this species. Glacial refugia were identified in the three southern European peninsulas: Iberia, Italy and the Balkans. These latter two refugia played a major role in the postglacial colonization process, with their populations expanding to England and central Europe, respectively. Palaeo-distribution models predicted that suitable climatic conditions existed in the inferred refugia during the last glacial maximum (LGM). Nevertheless, the overlap between the current and the LGM distributions was almost inexistent in Italy and in the Balkans, meaning that B. barbastellus populations were forced to shift range between glacial and interglacial periods, a process that probably caused some local extinctions. In contrast, Iberian populations showed a 'refugia within refugium' pattern, with two unconnected areas containing stable populations (populations that subsisted during both glacial and interglacial phases). Moreover, the match between LGM models and the refugial areas determined by molecular analysis supported the hypothesis of niche conservatism in B. barbastellus. We argue that geographic patterns of genetic structuring, altogether with the modelling results, indicate the existence of four management units for conservation: Morocco, Iberia, Italy and UK, and Balkans and central Europe. In addition, all countries sampled possessed unique gene pools, thus stressing the need for the conservation of local populations., (© 2012 Blackwell Publishing Ltd.)

Background and Objectives: High levels of fibroblast growth factor 23 are associated with mortality, CKD progression, and calcification in CKD patients. The aim of this pilot study is to assess whether a very-low-protein diet (0.3 g/kg per day) with a consequent low intake of phosphorus would reduce fibroblast growth factor 23 compared with a low-protein diet (0.6 g/kg per day) in CKD patients not yet on dialysis., Design, Setting, Participants, & Measurements: A prospective, randomized, controlled crossover study was performed in which 32 patients were randomized into two groups. Group A (16 patients) received a very-low-protein diet (0.3 g/kg body wt per day) supplemented with ketoanalogues during the first week and a low-protein diet during the second week, and group B (16 patients) received a low-protein diet during the first week and a very-low-protein diet during the second week. Fibroblast growth factor 23, seric, and urinary phosphate levels were measured at baseline and the end of each study period., Results: After only 1 week of the very-low-protein diet, reductions in fibroblast growth factor 23 levels (33.5%), serum phosphate (12%), and urinary phosphate (34%) with the very-low-protein diet compared with the low-protein diet were observed. Serum and urinary phosphate levels and protein intake were significant determinants of fibroblast growth factor 23 (95% confidence interval=1.04-1.19, 1.12-1.37, and 1.51-2.23, respectively)., Conclusions: A very-low-protein diet supplemented with ketoanalogues reduced fibroblast growth factor 23 levels in CKD patients not yet on dialysis.

Background: Haemodialysis patients are ageing and have with a high rate of comorbidities. The impact of this novel clinical setting on intact parathyroid hormone (iPTH) is not well established., Methods: For this observational, prospective multicentre cohort study, incident haemodialysis patients were recruited in 40 Italian centres and followed up for a mean period of 18 +/- 6.7 months. Clinical characteristics and biochemistry were recorded at baseline. Comorbid conditions were scored by the Charlson comorbidity index (CCI)., Results: Data of 411 patients (mean age: 66.5 +/- 14.8 years; 17.3% >80 years old) were recorded. The mean CCI was 4.17 +/- 2.8. In patients with CCI >0, an inverse correlation was observed between CCI (excluding age) and iPTH (P = 0.00002). Independently of CCI, patients with iPTH <150 pg/ml had 76% as high as the risk of all-cause mortality. After multivariable adjustment, the combination of the first tertile of iPTH with second and third tertiles of CCI was significantly associated with all-cause mortality (RR = 3.83, P = 0.02; RR = 3.79, P = 0.01, respectively)., Conclusions: Incident haemodialysis patients suffer from a high rate of clinical complications. In these patients, low iPTH and high CCI are often associated and very likely responsible for an adverse outcome.

Arterial hypertension and proteinuria are risk factors for chronic kidney disease. A mobile clinic was parked in a central plaza of 11 Italian cities to check blood pressure (BP), prescribe antihypertensive drugs, assess for proteinuria, and provide awareness about hypertension. Among 3757 patients, 56% were hypertensive, 37% were not diabetic nor proteinuric with BP >or=140/90 mm Hg, 17% were diabetic or proteinuric with BP >or=130/80 mm Hg, and 11% were on treatment with BP at target. Among 1204 treated patients, 400 (33%) had controlled BP. Among all 2114 hypertensive patients, only 1344 (64%) were aware of their hypertension. Awareness was greater among treated patients at target (99%). As many as 523 (14%) patients had proteinuria >or=30 mg/dL. The authors conclude that awareness of people walking in the street about their BP and proteinuria is insufficient. Mobile screening clinics may increase public awareness and detection of hypertension and proteinuria in the general community and detect patients at risk for chronic kidney disease.

We evaluated safety and efficacy of imatinib (600 mg) in 36 c-KIT+ acute myeloid leukemia patients not amenable to receive conventional chemotherapy. No patient achieved complete remission. One patient obtained a hematologic improvement (platelet increase with transfusion independence). Median overall survival was 3 months (0.5-44+). Non-hematologic toxicity was overall mild.