Headwaters’ Isotopic Signature as a Tracer of Stream Origins and Climatic Anomalies: Evidence from the Italian Alps in Summer 2018

Glaciers are shrinking due to global warming, resulting in a diminishing contribution of ice and snowmelt to headwaters and subsequent consequences to freshwater ecosystems. Within this context, we tested whether water-stable isotopes are spatio-temporal tracers of (i) water in high altitude periglacial environments, being the isotopic signature of surface water inherited from the snow/icemelt, groundwater, and rainfall; and (ii) regional (year-specific) meteorological conditions, being the isotopic signature of precipitations affected by air temperature, humidity and aqueous vapour origin, ascribing stable isotopes to the list of "essential climate variables" (ECVs). To this end, we investigated the ionic and isotopic composition (δ18O and δ2H) of six high-altitude streams and one pond in the Italian Alps (Noce and Sarca basins) during the ablation season in 2018. Differences between habitat types (pond, kryal, rhithral, krenal) were detected. More negative values of δ18O and δ2H were recorded in the kryal and glacio-rhithral sites, dominated by ice and snowmelt, in early summer. Less negative values were recorded in these sites in late summer, as well as in the krenal sites, which were dominated by groundwater and rainfall inputs. The isotopic results also show that the complex alpine orography influences air masses and moisture, ultimately resulting in isotopic differences in the precipitations of neighboring but distinct catchments (Sarca and Noce basins). On average, less negative values were recorded in the Sarca basin, characterized by a higher contribution of precipitation of Mediterranean origin. In general, isotopic results of the entire water population appeared to be strongly influenced by the regional climatic anomaly of 2018, which was anomalously warm. Therefore, the study will provide additional information for the climate change debate, proposing water isotopes as ECVs for assessing change in a warmer future

First record of Pseudostigmatidae (Insecta: Odonata) in the Northeast Region of Brazil

We record the first occurrence of Mecistogaster amalia (Burmeister, 1839) for the state of Rio Grande do Norte, Brazil, which is the first record of this genus and family for the whole Northeast Region of Brazil. This record is based on four collected samples and extends by more than 1,500 km to the north, the area known of distribution of this species

Multimodality Treatment with Conventional Transcatheter Arterial Chemoembolization and Radiofrequency Ablation for Unresectable Hepatocellular Carcinoma

Background/Aims: To evaluate the efficacy of multimodality treatment consisting of conventional transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (RFA) in patients with non-resectable and non-ablatable hepatocellular carcinoma (HCC). Methods: In this retrospective study, 85 consecutive patients with HCC (59 solitary, 29 multifocal HCC) received TACE followed by RFA between 2001 and 2010. The mean number of tumors per patient was 1.6 +/- 0.7 with a mean size of 3.0 +/- 0.9 cm. Both local efficacy and patient survival were evaluated. Results: Of 120 treated HCCs, 99 (82.5%) showed a complete response (CR), while in 21 HCCs (17.5%) a partial response was depicted. Patients with solitary HCC revealed CR in 91% (51/56); in patients with multifocal HCC (n = 29) CR was achieved in 75% (48 of 64 HCCs). The median survival for all patients was 25.5 months. The 1-, 2-, 3- and 5-year survival rates were 84.6, 58.7, 37.6 and 14.6%, respectively. Statistical analysis revealed a significant difference in survival between Barcelona Clinic Liver Cancer (BCLC) A (73.4 months) and B (50.3 months) patients, while analyses failed to show a difference for Child-Pugh score, Cancer of Liver Italian Program (CLIP) score and tumor distribution pattern. Conclusion: TACE combined with RFA provides an effective treatment approach with high local tumor control rates and promising survival data, especially for BCLC A patients. Randomized trials are needed to compare this multimodality approach with a single modality approach for early-stage HCC. Copyright (C) 2011 S. Karger AG, Base

p 159analysis of early tumor shrinkage and depth of response in metastatic pancreatic cancer patients treated with first line modified folfirinox or gemcitabine nab paclitaxel

n/

A New SteatoScore in the Evaluation of Non-Alcoholic Liver Disease in Oncologic Patients

PurposeThe aims of this study were to evaluate the reproducibility of a new multi-parametric steatoscore (new SteatoScore) in oncologic patients with non-alcoholic fatty liver disease (NAFLD) and to compare it with computed tomography (CT). Materials and MethodsFifty-one (31 men, 20 women) oncologic patients, with a mean age and weight of 63.9 years and 78.33 kg, respectively, were retrospectively enrolled in the study. Patients underwent ultrasound (US) and computed tomography (CT) examinations as part of their oncologic follow-up protocol. US examinations were performed by using a 3.5-MHz convex probe. During the US examination, three standardized clips were obtained in each patient. Two operators performed all measurements, one of whom repeated the processing twice in 1 year. Hepatic/renal ratio (HR), attenuation rate (AR), diaphragm visualization (DV), hepatic/portal vein ratio (HPV), and portal vein wall visualization (PVW) were acquired and calculated by using Matlab and inserted in a multi-parametric algorithm called new SteatoScore. On unenhanced CT scan, hepatic attenuation (HA), liver-spleen difference (L-S), and liver/spleen ratio (L/S) were measured by placement of a region of interest (ROI) within liver and spleen parenchyma, avoiding areas with vessels and biliary ducts. ResultsThe intra-observer variability was greater than the inter-observer one, with intraclass correlation coefficient (ICC) values of 0.94 and 0.97, respectively. Correlation between single US and CT parameters provided an agreement in no case exceeding 50%. New SteatoScore showed high reproducibility, and high coefficient of correlation with L-S (R = -0.64; p < 0.0001) and L/S (R = -0.62; p < 0.0001) at CT. ConclusionNew SteatoScore has a high reproducibility and shows a good correlation with unenhanced CT in evaluation of oncologic patients with NAFLD

Baseline computed-tomography (CT)-evaluated sarcopenia predicts toxicity from first-line chemotherapy in metastatic gastric cancer (mGC) patients

Introduction: The impact of sarcopenia as a predictor of poor prognosis and its association with chemotherapy toxicity have been explored in different cancer types but remain controversial in mGC. Our aim was to explore the correlation between sarcopenia, evaluated at baseline CT scan, and toxicity and efficacy of first-line therapy. Methods: We retrospectively analyzed pre-treatment CT scans from 78 mGC patients treated with first-line doublet chemotherapy comprising oxaliplatin and 5-fluorouracil/leucovorin or capecitabine (trastuzumab was administered in case of HER2-positive disease). Sarcopenia was defined according to previously published criteria (Martin L et al. J Clin Oncol 2013) by the use of the skeletal muscle index (SMI) and body mass index (BMI), according to gender-specific cut-off values. SMI was calculated as follows: cross-sectional skeletal muscle area (SMA) measured at the level of the third lumbar vertebra / (height)2 (m2). Toxicities were graded according to NCI CTCAE v.4.0. Association between the presence of sarcopenia and different adverse events was evaluated by Chi-square test. Correlation with response rate (RR, evaluated according to RECIST criteria 1.1), progression-free survival (PFS) and overall survival (OS) was assessed by the use of the log-rank test. Results: Sarcopenia was evident in 34 (44%) patients. We observed a significant association between the presence of sarcopenia at baseline assessment and a higher risk of severe (i.e. grade 3-4) neutropenia (38% versus 18%; p = 0.048) and a higher risk of any grade mucosal toxicities (56% versus 34%; p = 0.045). None of the other investigated clinical factors (comprising age, gender, performance status, sites of metastases and previous surgery on primary tumor) was associated with the risk of toxicity. Neither sarcopenia nor the other evaluated clinical parameters were associated with outcome as measured by RR, PFS, and OS: the only exception was performance status, which was confirmed a major prognostic determinant in terms of PFS and OS. Conclusion: Our experience identified sarcopenia as a potential determinant of the risk of hematologic and mucosal toxicities from first-line platinum plus fluoropyrimidine chemotherapy in mGC patients. Sarcopenia was apparently not associated with benefit from treatment and survival, but larger studies are needed to address this issue. Strategies aiming at improving the nutritional status of mGC patients are warranted to optimize the risk-to-benefit ratio of available treatments

The risk stratification of adverse neonatal outcomes in women with gestational diabetes (STRONG) study

Aims: To assess the risk of adverse neonatal outcomes in women with gestational diabetes (GDM) by identifying subgroups of women at higher risk to recognize the characteristics most associated with an excess of risk. Methods: Observational, retrospective, multicenter study involving consecutive women with GDM. To identify distinct and homogeneous subgroups of women at a higher risk, the RECursive Partitioning and AMalgamation (RECPAM) method was used. Overall, 2736 pregnancies complicated by GDM were analyzed. The main outcome measure was the occurrence of adverse neonatal outcomes in pregnancies complicated by GDM. Results: Among study participants (median age 36.8 years, pre-gestational BMI 24.8 kg/m2), six miscarriages, one neonatal death, but no maternal death was recorded. The occurrence of the cumulative adverse outcome (OR 2.48, 95% CI 1.59–3.87), large for gestational age (OR 3.99, 95% CI 2.40–6.63), fetal malformation (OR 2.66, 95% CI 1.00–7.18), and respiratory distress (OR 4.33, 95% CI 1.33–14.12) was associated with previous macrosomia. Large for gestational age was also associated with obesity (OR 1.46, 95% CI 1.00–2.15). Small for gestational age was associated with first trimester glucose levels (OR 1.96, 95% CI 1.04–3.69). Neonatal hypoglycemia was associated with overweight (OR 1.52, 95% CI 1.02–2.27) and obesity (OR 1.62, 95% CI 1.04–2.51). The RECPAM analysis identified high-risk subgroups mainly characterized by high pre-pregnancy BMI (OR 1.68, 95% CI 1.21–2.33 for obese; OR 1.38 95% CI 1.03–1.87 for overweight). Conclusions: A deep investigation on the factors associated with adverse neonatal outcomes requires a risk stratification. In particular, great attention must be paid to the prevention and treatment of obesity

Efficacy and safety of combination therapy with everolimus and sorafenib for recurrence of hepatocellular carcinoma after liver transplantation.

Background Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) is still associated with a dismal outcome. Combination therapy with everolimus (EVL) and vascular endothelial growth factor inhibitor sorafenib (SORA) is based on the role of both b-Raf and mammalian target of rapamycin/protein kinase B pathways in the pathogenesis of HCC and is being investigated in clinical practice. Methods This was a single-center retrospective analysis on LT recipients with unresectable HCC recurrence and undergoing combination therapy with EVL and SORA. Patients were included if they were switched to EVL+SORA at any time after surgery. Primary endpoint was overall survival (OS) after both LT and recurrence, and response to treatment based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST) in the intention-to-treat (ITT) population. Secondary analysis was safety of combination therapy with EVL and SORA in the population of patients who received ≥1 dose of the study drug. Results Seven patients (100% male; median age 53 years [interquartile range (IQR) 9 years]) were considered for analysis. HCC recurrence was diagnosed at a median (IQR) interval since LT of 9 (126) months, and patients were administered EVL+SORA at a median interval since LT of 11 (126) months. Baseline immunosuppression was with tacrolimus (TAC) in 2 patients (28.6%), cyclosporine (CsA) in 2 (28.6%), and EVL monotherapy in 3 (42.8%). At a median (IQR) follow-up of 6.5 (14) months, 5 patients (71.4%) were alive, 4 of them (57.1%) with tumor progression according to the mRECIST criteria. Median (IQR) time to progression was 3.5 (12) months. Two patients died at a median (IQR) follow-up of 5 (1) months owing to tumor progression in 1 patient (14.3%) and sepsis in the other (14.3%). EVL monotherapy was achieved in 6 patients (85.7%), whereas 1patient (14.3%) could not withdraw from calcineurin inhibitor owing to acute rejection. Treatment complications were: hand-foot syndrome in 5 patients (71.4%), hypertension in 1 (14.3%), alopecia in 1 (14.3%), hypothyroidism in 1 (14.3%), diarrhea in 2 (28.6%), pruritus in 1 (14.3%), abdominal pain in 1 (14.3%), rash in 1 (14.3%), asthenia in 3 (42.8%), anorexia in 3 (42.8%), and hoarseness in 2 (28.6%). Adverse events led to temporary SORA discontinuation in 2 patients (28.6%) and to SORA dose reduction in 3 (42.8%). Conclusions Treatment of HCC recurrence after LT with a combination regimen of EVL+ SORA is challenging because of SORA-related complications. Longer follow-up periods and larger series are needed to better capture the impact of such combination treatment on tumor progression and patient survival.BACKGROUND: Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) is still associated with a dismal outcome. Combination therapy with everolimus (EVL) and vascular endothelial growth factor inhibitor sorafenib (SORA) is based on the role of both b-Raf and mammalian target of rapamycin/protein kinase B pathways in the pathogenesis of HCC and is being investigated in clinical practice. METHODS: This was a single-center retrospective analysis on LT recipients with unresectable HCC recurrence and undergoing combination therapy with EVL and SORA. Patients were included if they were switched to EVL+SORA at any time after surgery. Primary endpoint was overall survival (OS) after both LT and recurrence, and response to treatment based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST) in the intention-to-treat (ITT) population. Secondary analysis was safety of combination therapy with EVL and SORA in the population of patients who received ≥1 dose of the study drug. RESULTS: Seven patients (100% male; median age 53 years [interquartile range (IQR) 9 years]) were considered for analysis. HCC recurrence was diagnosed at a median (IQR) interval since LT of 9 (126) months, and patients were administered EVL+SORA at a median interval since LT of 11 (126) months. Baseline immunosuppression was with tacrolimus (TAC) in 2 patients (28.6%), cyclosporine (CsA) in 2 (28.6%), and EVL monotherapy in 3 (42.8%). At a median (IQR) follow-up of 6.5 (14) months, 5 patients (71.4%) were alive, 4 of them (57.1%) with tumor progression according to the mRECIST criteria. Median (IQR) time to progression was 3.5 (12) months. Two patients died at a median (IQR) follow-up of 5 (1) months owing to tumor progression in 1 patient (14.3%) and sepsis in the other (14.3%). EVL monotherapy was achieved in 6 patients (85.7%), whereas 1patient (14.3%) could not withdraw from calcineurin inhibitor owing to acute rejection. Treatment complications were: hand-foot syndrome in 5 patients (71.4%), hypertension in 1 (14.3%), alopecia in 1 (14.3%), hypothyroidism in 1 (14.3%), diarrhea in 2 (28.6%), pruritus in 1 (14.3%), abdominal pain in 1 (14.3%), rash in 1 (14.3%), asthenia in 3 (42.8%), anorexia in 3 (42.8%), and hoarseness in 2 (28.6%). Adverse events led to temporary SORA discontinuation in 2 patients (28.6%) and to SORA dose reduction in 3 (42.8%). CONCLUSIONS: Treatment of HCC recurrence after LT with a combination regimen of EVL+ SORA is challenging because of SORA-related complications. Longer follow-up periods and larger series are needed to better capture the impact of such combination treatment on tumor progression and patient survival

First interim analysis of the GIDEON (Global Investigation of therapeutic DEcisions in hepatocellular carcinoma and Of its treatment with sorafeNib) non‐interventional study

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/92068/1/j.1742-1241.2012.02940.x.pd

Cardiac resynchronization therapy using endocardial versus trans-coronary sinus, epicardial left ventricular pacing: the Epi-Endo study

Aims: Some studies have suggested that cardiac resynchronization therapy (CRT) using endocardial left ventricular (LV) pacing (Endo-CRT) is superior to a conventional transvenous, epicardial CRT (Epi-CRT). To determine whether, in CRT recipients, endocardial LV pacing is haemodynamically superior to trans-coronary vein (trans-CV) LV epicardial pacing. Methods and results: At implantation patients (n=16; aged 68.9±8.32 years; 13 male) underwent Epi-CRT and Endo-CRT in basal, mid and apical myocardial segments, delivered using the trans-CS lead and an intra-cavitary, roving EP catheter to achieve juxtapositions of the epicardial and endocardial side of the LV free wall respectively. Myocardial scar was quantified using cardiovascular magnetic resonance. An acute haemodynamic response (AHR) was defined as a ≥10% increase in the maximal rate of rise of LV pressure (%LV dP/dtmax) in relation to RV pacing (DOO). When the 84 paired segments were taken together, the %ΔLV dP/dtmax was higher with Endo-CRT than with Epi-CRT (9.9±8,6% vs 7.9±8.3% respectively,