Identification of subgroups of early breast cancer patients at high risk of nonadherence to adjuvant hormone therapy: results of an italian survey.

The aim of this study was the identification of subgroups of patients at higher risk of nonadherence to adjuvant hormone therapy for breast cancer. Using recursive partitioning and amalgamation (RECPAM) analysis, the highest risk was observed in the group of unmarried, employed women, or housewives. This result might be functional in designing tailored intervention studies aimed at improvement of adherence. Background: Adherence to adjuvant endocrine therapy (HT) is suboptimal among breast cancer patients. A high rate of nonadherence might explain differences in survival between clinical trial and clinical practice. Tailored interventions aimed at improving adherence can only be implemented if subgroups of patients at higher risk of poor adherence are identified. Because no data are available for Italy, we undertook a large survey on adherence among women taking adjuvant HT for breast cancer. Patients and Methods: Patients were recruited from 10 cancer clinics in central Italy. All patients taking HT for at least 1 year were invited, during one of their follow-up visit, to fill a confidential questionnaire. The association of sociodemographic and clinical characteristics of participants with adherence was assessed using logistic regression. The RECPAM method was used to evaluate interactions among variables and to identify subgroups of patients at different risk of nonadherence. Results: A total of 939 patients joined the study and 18.6% of them were classified as nonadherers. Among possible predictors, only age, working status, and switching from tamoxifen to an aromatase inhibitor were predictive of nonadherence in multivariate analysis. RECPAM analysis led to the identification of 4 classes of patients with a different likelihood of nonadherence to therapy, the lowest being observed in retired women with a low level of education, the highest in the group of unmarried, employed women, or housewives. Conclusion: The identification of these subgroups of “real life” patients with a high prevalence of nonadherers might be functional in designing intervention studies aimed at improving adherenc

PP165—Evaluation of JNJ-26489112, a Novel Antiepileptic Drug: A Placebo-Controlled, Exploratory Study

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Current Methods to Unravel the Functional Properties of Lysosomal Ion Channels and Transporters

open18siA distinct set of channels and transporters regulates the ion fluxes across the lysosomal membrane. Malfunctioning of these transport proteins and the resulting ionic imbalance is involved in various human diseases, such as lysosomal storage disorders, cancer, as well as metabolic and neurodegenerative diseases. As a consequence, these proteins have stimulated strong interest for their suitability as possible drug targets. A detailed functional characterization of many lysosomal channels and transporters is lacking, mainly due to technical difficulties in applying the standard patch-clamp technique to these small intracellular compartments. In this review, we focus on current methods used to unravel the functional properties of lysosomal ion channels and transporters, stressing their advantages and disadvantages and evaluating their fields of applicability.openFesta M.; Minicozzi V.; Boccaccio A.; Lagostena L.; Gradogna A.; Qi T.; Costa A.; Larisch N.; Hamamoto S.; Pedrazzini E.; Milenkovic S.; Scholz-Starke J.; Ceccarelli M.; Vitale A.; Dietrich P.; Uozumi N.; Gambale F.; Carpaneto A.Festa, M.; Minicozzi, V.; Boccaccio, A.; Lagostena, L.; Gradogna, A.; Qi, T.; Costa, A.; Larisch, N.; Hamamoto, S.; Pedrazzini, E.; Milenkovic, S.; Scholz-Starke, J.; Ceccarelli, M.; Vitale, A.; Dietrich, P.; Uozumi, N.; Gambale, F.; Carpaneto, A

Homeostatic control of slow vacuolar channels by luminal cations and evaluation of the channel-mediated tonoplast Ca2+ fluxes in situ

Ca2+, Mg2+, and K+ activities in red beet (Beta vulgaris L.) vacuoles were evaluated using conventional ion-selective microelectrodes and, in the case of Ca2+, by non-invasive ion flux measurements (MIFE) as well. The mean vacuolar Ca2+ activity was ∼0.2 mM. Modulation of the slow vacuolar (SV) channel voltage dependence by Ca2+ in the absence and presence of other cations at their physiological concentrations was studied by patch-clamp in excised tonoplast patches. Lowering pH at the vacuolar side from 7.5 to 5.5 (at zero vacuolar Ca2+) did not affect the channel voltage dependence, but abolished sensitivity to luminal Ca2+ within a physiological range of concentrations (0.1–1.0 mM). Aggregation of the physiological vacuolar Na+ (60 mM) and Mg2+ (8 mM) concentrations also results in the SV channel becoming almost insensitive to vacuolar Ca2+ variation in a range from nanomoles to 0.1 mM. At physiological cation concentrations at the vacuolar side, cytosolic Ca2+ activates the SV channel in a voltage-independent manner with Kd=0.7–1.5 μM. Comparison of the vacuolar Ca2+ fluxes measured by both the MIFE technique and from estimating the SV channel activity in attached patches, suggests that, at resting membrane potentials, even at elevated (20 μM) cytosolic Ca2+, only 0.5% of SV channels are open. This mediates a Ca2+ release of only a few pA per vacuole (∼0.1 pA per single SV channel). Overall, our data suggest that the release of Ca2+ through SV channels makes little contribution to a global cytosolic Ca2+ signal

Amphibians in Zootaxa: 20 years documenting the global diversity of frogs, salamanders, and caecilians

Zootaxa is a mega-journal that since its inception, 20 years ago, has contributed to the documentation of the planet?s biodiversity. Its role concerning terrestrial vertebrates has been crucial especially for amphibians, which are the most threatened class of vertebrates. As current editors of the Amphibia section, we reviewed the state of knowledge of taxonomic publications on amphibians over the last two decades (from 2001 to 2020). Our review reveals that 2,533 frogs, 259 salamanders, and 55 caecilians have been named in these 20 years, mainly in the tropical regions of South America, Asia, and Africa. More than half (57%) of these species descriptions were published in only 10 journals. At least 827 species of the new amphibians (29% of the total) were described in Zootaxa. This mega-journal has served also as a place of publication for monographs and systematic reviews, in addition to short articles documenting the vocalizations of anurans and the morphology of embryos and larvae. Its efficient evaluation process, the freedom of manuscript length, including full-color figures, and free of cost for the authors, has made Zootaxa a favorite for amphibian researchers. In an era of accelerating rates of biodiversity loss, documenting, describing, naming, and proposing evolutionary scenarios for species is, more than ever, an urgent task.Fil: Rivera Correa, Mauricio. Universidad de Antioquia; ColombiaFil: Baldo, Juan Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas | Universidad Nacional de Misiones. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas; ArgentinaFil: Vera Candioti, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - Tucumán. Unidad Ejecutora Lillo; ArgentinaFil: Goyannes Dill Orrico, Victor. Universidade Estadual de Santa Cruz; BrasilFil: Blackburn, David C.. University Of Florida. Florida Museum Of History; Estados UnidosFil: Castroviejo Fisher, Santiago. Pontificia Universidade Católica do Rio Grande do Sul; BrasilFil: Chan, Kin Onn. National University of Singapore; SingapurFil: Gambale, Priscilla. Universidade Federal de Goiás; BrasilFil: Gower, David J.. Natural History Museum; Reino UnidoFil: Quah, Evan S. H.. National University of Singapore; SingapurFil: Rowley, Jodi J. L.. University of New South Wales; AustraliaFil: Twomey, Evan. Goethe Universitat Frankfurt; AlemaniaFil: Vences, Miguel. Technische Universitat Carolo Wilhelmina Zu Braunschweig.; Alemani

No impact of NRAS mutation on features of primary and metastatic melanoma or on outcomes of checkpoint inhibitor immunotherapy: An italian melanoma intergroup (IMI) study

Neuroblastoma RAS Viral Oncogen Homolog (NRAS) mutant melanoma is usually considered more aggressive and more responsive to checkpoint inhibitor immunotherapy (CII) than NRAS wildtype. We retrospectively recruited 331 metastatic melanoma patients treated with CII as first line: 162 NRAS-mutant/BRAF wild-type and 169 wt/wt. No substantial differences were observed among the two cohorts regarding the melanoma onset and disease-free interval. Also, overall response to CII, progression-free survival and overall survival were similar in the two groups. Therefore, our data do not show increased aggressiveness and higher responsiveness to CII in NRAS-mutant melanoma. The controversy in the published data could be due to different patient characteristics and treatment heterogeneity. We believe our data adds evidence to clear up these controversial issues. Aims: It is debated whether the NRAS-mutant melanoma is more aggressive than NRAS wildtype. It is equally controversial whether NRAS-mutant metastatic melanoma (MM) is more responsive to checkpoint inhibitor immunotherapy (CII). 331 patients treated with CII as first-line were retrospectively recruited: 162 NRAS-mutant/BRAF wild-type (mut/wt) and 169 wt/wt. We compared the two cohorts regarding the characteristics of primary and metastatic disease, disease-free interval (DFI) and outcome to CII. No substantial differences were observed between the two groups at melanoma onset, except for a more frequent ulceration in the wt/wt group (p = 0.03). Also, the DFI was very similar in the two cohorts. In advanced disease, we only found lung and brain progression more frequent in the wt/wt group. Regarding the outcomes to CII, no significant differences were reported in overall response rate (ORR), disease control rate (DCR), progression free survival (PFS) or overall survival (OS) (42% versus 37%, 60% versus 59%, 12 (95% CI, 7-18) versus 9 months (95% CI, 6-16) and 32 (95% CI, 23-49) versus 27 months (95% CI, 16-35), respectively). Irrespectively of mutational status, a longer OS was significantly associated with normal LDH, <3 metastatic sites, lower white blood cell and platelet count, lower neutrophil-to-lymphocyte (N/L) ratio. Our data do not show increased aggressiveness and higher responsiveness to CII in NRAS-mutant MM

Recommendations for diagnosis and treatment of methemoglobinemia

Methemoglobinemia is a rare disorder associated with oxidization of divalent ferro-iron of hemoglobin (Hb) to ferri-iron of methemoglobin (MetHb). Methemoglobinemia can result from either inherited or acquired processes. Acquired forms are the most common, mainly due to the exposure to substances that cause oxidation of the Hb both directly or indirectly. Inherited forms are due either to autosomal recessive variants in the CYB5R3 gene or to autosomal dominant variants in the globin genes, collectively known as HbM disease. Our recommendations are based on a systematic literature search. A series of questions regarding the key signs and symptoms, the methods for diagnosis, the clinical management in neonatal/childhood/adulthood period, and the therapeutic approach of methemoglobinemia were formulated and the relative recommendations were produced. An agreement was obtained using a Delphi-like approach and the experts panel reached a final consensus >75% of agreement for all the questions.Genetics of disease, diagnosis and treatmen

Summary of joint European Hematology Association (EHA) and EuroBloodNet recommendations on diagnosis and treatment of methemoglobinemia

Genetics of disease, diagnosis and treatmen

Recommendations regarding splenectomy in hereditary hemolytic anemias.

Hereditary hemolytic anemias are a group of disorders with a variety of causes, including red cell membrane defects, red blood cell enzyme disorders, congenital dyserythropoietic anemias, thalassemia syndromes and hemoglobinopathies. As damaged red blood cells passing through the red pulp of the spleen are removed by splenic macrophages, splenectomy is one possible therapeutic approach to the management of severely affected patients. However, except for hereditary spherocytosis for which the effectiveness of splenectomy has been well documented, the efficacy of splenectomy in other anemias within this group has yet to be determined and there are concerns regarding short- and long-term infectious and thrombotic complications. In light of the priorities identified by the European Hematology Association Roadmap we generated specific recommendations for each disorder, except thalassemia syndromes for which there are other, recent guidelines. Our recommendations are intended to enable clinicians to achieve better informed decisions on disease management by splenectomy, on the type of splenectomy and the possible consequences. As no randomized clinical trials, case control or cohort studies regarding splenectomy in these disorders were found in the literature, recommendations for each disease were based on expert opinion and were subsequently critically revised and modified by the Splenectomy in Rare Anemias Study Group, which includes hematologists caring for both adults and children