Rationale and design of the Biventricular Evaluation of Gliflozins effects In chroNic Heart Failure: BEGIN-HF study.

AIMS: Sodium-glucose cotransporter type 2 inhibitors (SGLT-2i) represent a unique class of anti-hyperglycaemic agents for type 2 diabetes mellitus that selectively inhibit renal glucose reabsorption, thereby increasing urinary excretion of glucose. Several studies have demonstrated the cardioprotective effects of SGLT-2i in patients with heart failure (HF), unrelated to its glucosuric effect. It is unclear whether the benefits of SGLT-2i therapy also rely on the improvement of left ventricular (LV) and/or right ventricular (RV) function in patients with HF. This study aimed to evaluate the effect of SGLT-2i on LV and RV function through conventional and advanced echocardiographic parameters with a special focus on RV function in patients with HF. METHODS AND RESULTS: The Biventricular Evaluation of Gliflozins effects In chroNic Heart Failure (BEGIN-HF) study is an international multicentre, prospective study that will evaluate the effect of SGLT-2i on echocardiographic parameters of myocardial function in patients with chronic stable HF across the left ventricular ejection fraction (LVEF) spectrum. Patients with New York Heart Association Class II/III symptoms, estimated glomerular filtration rate > 25 mL/min/1.73 m2 , age > 18 years, and those who were not previously treated with SGLT-2i will be included. All patients will undergo conventional, tissue-derived imaging (TDI), and strain echocardiography in an ambulatory setting, at time of enrolment and after 6 months of SGLT-2i therapy. The primary endpoint is the change in LV function as assessed by conventional, TDI, and myocardial deformation speckle tracking parameters. Secondary outcomes include changes in RV and left atrial function as assessed by conventional and deformation speckle tracking echocardiography. Univariate and multivariate analyses will be performed to identify predictors associated with primary and secondary endpoints. CONCLUSIONS: The BEGIN-HF will determine whether SGLT-2i therapy improves LV and/or RV function by conventional and advanced echocardiography in patients with HF irrespective of LVEF.

Psychosomatic syndromes are associated with IL-6 pro-inflammatory cytokine in heart failure patients.

Psychosomatic syndromes have emerged as an important source of comorbidity in cardiac patients and have been associated with increased risk for adverse outcomes in patients with heart failure (HF). Understanding of the mechanisms underlying this connection is limited, however immune activity represents a possible pathway. While there have been numerous studies connecting immune activity to psychosomatic psychopathology, there is a lack of research on patients with HF. We examined forty-one consecutive outpatients affected by HF. We assessed psychosomatic psychopathology using the Diagnostic Criteria for Psychosomatic Research (DCPR) and the Patient Health Questionnaire-15 (PHQ-15). The Psychosocial Index (PSI) was used for assessing stress and psychosocial dimensions. Depression was evaluated with Beck Depression Inventory-II (BDI-II). Circulating levels of proinflammatory cytokines IL-6 and TNF-alpha were ascertained. Univariate and multivariable regression models were used to test for associations between inflammatory cytokines and psychosomatic psychopathology (i.e., DCPR syndromes, PHQ-15) and psychological dimensions (i.e., BDI-II, PSI). A significant positive correlation was found between IL-6 levels and psychosomatic psychopathology even when controlling for any confounding variables (i.e., Body-mass index (BMI), New York Heart Association (NYHA) class, smoking habits, alcohol consumption, statin use, aspirin use, beta blockers use, age, and gender). In contrast, the associations between TNF-alpha levels were non-significant. These findings can contribute to research in support of a psychoneuroimmune connection between psychosomatic psychopathology and HF. Findings also suggest the possibility that elevated IL-6 levels are more relevant for the pathogenesis of psychosomatic syndromes than for depression in patients with HF.

COVID-19 Biomarkers in research: Extension of the OncoMX cancer biomarker data model to capture biomarker data from other diseases.

Scientists, medical researchers, and health care workers have mobilized worldwide in response to the outbreak of COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; SCoV2). Preliminary data have captured a wide range of host responses, symptoms, and lingering problems post-recovery within the human population. These variable clinical manifestations suggest differences in influential factors, such as innate and adaptive host immunity, existing or underlying health conditions, co-morbidities, genetics, and other factors. As COVID-19-related data continue to accumulate from disparate groups, the heterogeneous nature of these datasets poses challenges for efficient extrapolation of meaningful observations, hindering translation of information into clinical applications. Attempts to utilize, analyze, or combine biomarker datasets from multiple sources have shown to be inefficient and complicated, without a unifying resource. As such, there is an urgent need within the research community for the rapid development of an integrated and harmonized COVID-19 Biomarker Knowledgebase. By leveraging data collection and integration methods, backed by a robust data model developed to capture cancer biomarker data we have rapidly crowdsourced the collection and harmonization of COVID-19 biomarkers. Our resource currently has 138 unique biomarkers. We found multiple instances of the same biomarker substance being suggested as multiple biomarker types during our extensive cross-validation and manual curation. As a result, our Knowledgebase currently has 265 biomarker type combinations. Every biomarker entry is made comprehensive by bringing in together ancillary data from multiple sources such as biomarker accessions (canonical UniProtKB accession, PubChem Compound ID, Cell Ontology ID, Protein Ontology ID, NCI Thesaurus Code, and Disease Ontology ID), BEST biomarker category, and specimen type (Uberon Anatomy Ontology) unified with ontology standards. Our preliminary observations show distinct trends in the collated biomarkers. Most biomarkers are related to the immune system (SAA,TNF-∝, and IP-10) or coagulopathies (D-dimer, antithrombin, and VWF) and a few have already been established as cancer biomarkers (ACE2, IL-6, IL-4 and IL-2). These trends align with proposed hypotheses of clinical manifestations compounding the complexity of COVID-19 pathobiology. We explore these trends as we put forth a COVID-19 biomarker resource that will help researchers and diagnosticians alike. All biomarker data are freely available from https://data.oncomx.org/covid19 .

Cardiac Tumors.

Cardiac tumors (CTs) are extremely rare, with an incidence of approximately 0.02% in autopsy series. Primary tumors of the heart are far less common than metastatic tumors. CTs usually present with any possible clinical combination of heart failure, arrhythmias, or embolism. Echocardiography remains the first diagnostic approach when suspecting a CT which, on the other side, frequently appears unexpectedly during an echocardiographic examination. Yet, cardiac tomography and especially magnetic resonance imaging may offer several adjunctive opportunities in the diagnosis of CTs. Early and exact diagnosis is crucial for the following therapy and outcome of CTs.

Liver disease and heart failure.

INTRODUCTION: Several systemic conditions, inflammatory disease, infections and alcoholism, may affect both the heart and the liver. Common conditions, such as the non-alcoholic fatty liver disease (NAFLD), may increase the risk of cardiac dysfunction. Patients with acute decompensated HF (ADHF) may develop acute ischemic hepatitis and, chronic HF patients may develop congestive hepatopathy (CH). EVIDENCE ACQUISITION: Laboratory anomalies of hepatic function may predict the outcome of patients with advanced HF and the evaluation of both cardiac and hepatic function is very important in the management of these patients. In clinically apparent ischemic hepatitis more than 90% of patients have some right-sided HF. There are systemic disorders characterized by the accumulation of metals or by metabolism defects that may affect primarily the liver but also the heart leading to symptomatic hypertrophic cardiomyopathy (HCM). EVIDENCE SYNTHESIS: Abnormal LFTs indicate the mechanism of liver injury: liver congestion or liver ischemia. In AHF, it's important an adequate evaluation of heart and liver function in order to choose the treatment in order to ensure stable hemodynamic as well as optimal liver function. CONCLUSIONS: Measurements of LFTs should be recommended in the early phase of ADHF management. Physicians with interest in HF should be trained in the evaluation of LFTs. It's very important for cardiologists to know the systemic diseases affecting both heart and liver and the first imaging or laboratory findings useful for a diagnosis. it is very important for internists, nephrologists, cardiologists, primary physicians and any physicians with interest in treating HF to recognize such signs and symptoms belong to rare diseases and liver diseases that could be mistaken for HF.

Minimally invasive surgical versus transcatheter aortic valve replacement: A multicenter study.

OBJECTIVES: Treatment of aortic valve stenosis is evolving, indications for transcatheter approach (TAVI) have increased but also surgical valve replacement has changed with the use of minimally invasive approaches. Comparisons between TAVI and surgery have rarely been done with minimally invasive techniques (mini-SAVR) in the surgical arm. Aim of the present study is to compare mini-SAVR and TAVI in a multicenter recent cohort. METHODS: Evaluated were 2904 patients undergone mini-SAVR (2407) or TAVI (497) in 10 different centers in the period 2011-2016. The Heart Team approved treatment for complex cases. The primary outcome is the incidence of 30-day mortality following mini-SAVR and TAVI. Secondary outcomes are the occurrence of major complications following both procedures. Propensity matched comparisons was performed based on multivariable logistic regression model. RESULTS: In the overall population TAVI patients had increased surgical risk (median EuroSCORE II 3.3% vs. 1.7%, p ≤ 0.001) and 30-day mortality was higher (1.5% and 2.8% in mini-SAVR and TAVI respectively, p = 0.048). Propensity score identified 386 patients per group with similar baseline profile (median EuroSCORE II ~3.0%). There was no difference in 30-day mortality (3.4% in mini-SAVR and 2.3% in TAVI; p = 0.396) and stroke, surgical patients had more blood transfusion, kidney dysfunction and required longer ICU and hospital length of stay while TAVI patients had more permanent pace maker insertion. CONCLUSIONS: Mini-SAVR and TAVI are both safe and effective to treat aortic stenosis in elderly patients with comorbidities. A joint evaluation by the heart-team is essential to direct patients to the proper approach.

Quality-of-life analysis of the MITO-8, MaNGO, BGOG-Ov1, AGO-Ovar2.16, ENGOT-Ov1, GCIG study comparing platinum-based versus non-platinum-based chemotherapy in patients with partially platinum-sensitive recurrent ovarian cancer.

Background: MITO-8 showed that prolonging platinum-free interval by introducing non-platinum-based chemotherapy (NPBC) does not improve prognosis of patients with partially platinum-sensitive recurrent ovarian cancer. Quality of life (QoL) was a secondary outcome. Patients and methods: Ovarian cancer patients recurring or progressing 6-12 months after previous platinum-based chemotherapy (PBC) were randomized to receive PBC or NPBC as first treatment. QoL was assessed at baseline, third and sixth cycles, with the EORTC C-30 and OV-28 questionnaires. Mean changes and best response were analysed. Progression-free survival, response rate, and toxicity are also reported for proper interpretation of data. All analyses were based on intention-to-treat. Results: Out of the 215 patients, 151 (70.2%) completed baseline questionnaire, balanced between the arms; thereafter, missing rate was higher in the NPBC arm. At mean change analysis, C30 scores were prevalently worse in the NPBC than PBC arm, statistical significance being attained for emotional functioning, global health status/QoL, fatigue, and dyspnoea (effect sizes ranging from 0.30 to 0.51). Conversely, as for OV28 scale, the other chemotherapy side-effects item was significantly worse with PBC at three and six cycles, with a larger effect size (0.70 and 0.54, respectively). At best response analysis, improvement of emotional functioning and pain and worsening of peripheral neuropathy and other chemotherapy side-effects were significantly more frequent in the PBC arm. Progression-free survival (median 9 versus 5 months, P = 0.001) and objective response rate (51.6% versus 19.4%, P = 0.0001) were significantly better with PBC. Allergy, blood cell count, alopecia, nausea, musculoskeletal, and neurological side-effects were more frequent and severe with PBC; hand-foot skin reaction, rash/desquamation, mucositis, and vascular events were more frequent with NPBC. Conclusion: MITO-8 QoL analysis shows that deterioration of some functioning and symptom scales is lower with PBC, with improvement of emotional functioning and pain, despite worsening of toxicity-related items. ClinicalTrials.gov: NCT00657878.

Nonfluoroscopic mapping reduces radiation exposure in ablation of atrial fibrillation.

BACKGROUND: Radiofrequency catheter ablation (RFCA) of atrial fibrillation is an effective and definitive treatment. The methods used to guide RFCA have evolved over the years from a purely electrophysiological approach, in which anatomical lesions were guided solely by fluoroscopy and angiographic imaging of the pulmonary veins, to an approach guided by modern nonfluoroscopic electroanatomical mapping, integrated or not with computed tomography (CT). The aim of this study was, therefore, to compare radiation exposure of RFCA based on a fast three-dimensional nonfluoroscopic mapping system with 'traditional' mapping integrated with CT imaging. METHODS: Thirty consecutive patients with atrial fibrillation who underwent RFCA were treated with two different approaches: 3D-Fast-Anatomical-Mapping and One-Map tool (FAM-One Map group, 21 patients) vs. 3D-Fast-Anatomical-Mapping integrated with CT images (MERGE-CT group, nine patients). Fluoroscopy time and radiation doses (expressed in milliGray) were compared. RESULTS: No statistically significant difference was detectable between FAM-One Map group and MERGE-CT group considering RFCA success rates and fluoroscopy times. Radiation exposure was higher in the MERGE-CT group (965 ±â€Š138  mGy MERGE-CT group vs. 532 ±â€Š216  mGy FAM-One Map group, P < 0.001) because of supplemental radiation exposures due to CT imaging (470 ±â€Š126  mGy). CONCLUSION: A fast nonfluoroscopic electroanatomical mapping system may reduce radiation exposure in RFCA of atrial fibrillation, with preserved success rates.

Bullous lung disease and neurofibromatosis type-1.

Lung interstitial diseases and bullae are described as possible complications of neurofibromatosis type-1 (NF-1), a genetic disorder inherited as a autosomal-dominant trait. We report the case of a 16-year-old male non-smoker with NF-1, who presented with pneumothorax caused by ruptured lung bullae. The case of this young patient, successfully treated by video-assisted thoracoscopic resection of bullae, supports the concept that pulmonary alterations may be part of the NF-1 syndrome, rather than as an unrelated complication.

Prevalence of heavy smokers in the year 2000 in the province of Varese, Italy.

BACKGROUND: Knowing the prevalence of heavy smokers (HS) by gender and age is a pre-requisite for bringing into effect public health measures against smoking-related diseases. Smoking prevalence data is available for the Italian Regions, however it is generally unknown for the Italian Provinces. METHODS: In the year 2000 a survey of smoking prevalence was conducted by 47 general practitioners (GPs), by personal interview, in a large sample of the Varese Province population 45-74 years of age (28,034 subjects; 13,528 men, 14,506 women). Each surveyed subject was categorised either as ever HS (current/former smoker of at least 10 pack-years) or as non HS. The information on smoking habit collected by the GPs was anonymously pooled for analysis. Prevalence figures of smoking were tabulated by gender and by 5-year age-strata. RESULTS: In the population 45-74 years of age the percentage of ever HS overall was 22.3% (34.4% of men; 11.0% of women). The prevalence of ever HS in both sexes combined progressively decreased with advancing age, from 23.6% (45-49 year stratum) to 19.5% (70-74 year stratum). Current HS were 24.5% of men and 9.5% of women. CONCLUSIONS: The year 2000 survey on smoking habit, showing 22.3% prevalence of ever HS in age range 45-74 years, is the first conducted in the Varese Province using a large population sample. The data on heavy cigarette smoking presented in this paper, stratified by gender and age, may be used to monitor changes in the smoking habit and in the incidence of smoking-related illnesses at the provincial level.

Efficacy of the combination of cisplatin with either gemcitabine and vinorelbine or gemcitabine and paclitaxel in the treatment of locally advanced or metastatic non-small-cell lung cancer: a phase III randomised trial of the Southern Italy Cooperative Oncology Group (SICOG 0101).

BACKGROUND: Triplet regimens were occasionally reported to produce a higher response rate (RR) than doublets in locally advanced or metastatic non-small-cell lung cancer (NSCLC). This trial was conducted to assess (i) whether the addition of cisplatin (CDDP) to either gemcitabine (GEM) and vinorelbine (VNR) or GEM and paclitaxel (PTX) significantly prolongs overall survival (OS) and (ii) to compare the toxicity of PTX-containing and VNR-containing combinations. PATIENTS AND METHODS: Stage III or IV NSCLC patients were randomly assigned to (i) GEM 1000 mg/m(2) and VNR 25 mg/m(2) on days 1 and 8 (GV arm); (ii) GEM 1000 mg/m(2) and PTX 125 mg/m(2) on days 1 and 8 (GT arm); (iii) GV plus CDDP 50 mg/m(2) on days 1 and 8 (PGV arm); and (iv) GT plus CDDP 50 mg/m(2) on days 1 and 8 (PGT arm). Treatments were repeated every 3 weeks for a maximum of six cycles. RESULTS: A total of 433 (stage III, 160; stage IV, 273) patients were randomly allocated to the study. RR was 48% [95% confidence interval (CI), 42% to 54%] for triplets and 35% (95% CI, 32% to 38%) for doublets (P = 0.004). Median progression-free survival (6.1 versus 5.5 months, P = 0.706) and median OS (10.7 versus 10.5 months, P = 0.379) were similar. CDDP significantly increased the occurrence of severe neutropenia (35% versus 13%), thrombocytopenia (14% versus 4%), anaemia (9% versus 3%), vomiting (6% versus 0.5%), and diarrhoea (6% versus 2%). Conversely, frequency of severe neutropenia (30% versus 17%) and thrombocytopenia (11% versus 6%) was significantly higher with VNR-containing regimens. CONCLUSIONS: Adding CDDP to GV or GT significantly increased RR, but did not prolong the OS of patients. Among doublets, the GT regimen should be preferred in view of its better safety profile.

[Longitudinal changes of pulmonary function in workers with high wood dust exposure levels]. / Studio longitudinale della funzionalità polmonare in esposti ad alti livelli di polvere di legno.

BACKGROUND: It is well know that wood dust exposure can induce sino-nasal cancers, rhinitis and asthma; induction of chronic bronchial obstruction, pulmonary fibrosis and lung cancer are also suggested, but data are often inconclusive and in disagreement. OBJECTIVES: The study evaluated the decrease in lung function in a group of 31 non-smokers exposed to high levels of wood dust (> 5 mg/m3 also) and in 2 non-smokering control groups with comparable lung function tests at first examination: 39 mechanical workers without respiratory hazards (group 1) and 30 forestry workers (group 2). METHODS: Assessment of lung function was repeated at least 5 times during 11.2 +/- 2.4 years for wood workers and 12.3 +/- 4.2 years for group 1 (n.s.) and 15.0 +/- 2.6 years for group 2 (p < 0.0005). Linear regression for annual loss of VC and FEV1 was calculated from observed data for each subject. RESULTS: No significant differences were observed in VC loss or FEV1 loss between woodworkers and control group1 (20.67 +/- 16.9 vs 19.0 +/- 23.2 and 31.37 +/- 22.3 vs 36.2 +/- 22.4 ml/year respectively), while control group 2 showed an accelerated (p < 0.005) VC and FEV1 loss (32.8 +/- 22.1 and 46.6 +/- 21.2 ml/years respectively). In conclusion, the study did not show any alterations in the longitudinal decrease in pulmonary function due to high wood dust exposure levels, perhaps due to the poor inhalability of wood particles that are mostly trapped in the nose; further studies are needed to investigate chronic effects of wood dust exposure on development of Chronic Obstructive Pulmonary Disease, pulmonary fibrosis and also lung cancer.

Biweekly oxaliplatin combined with oral capecitabine (OXXEL regimen) as first-line treatment of metastatic colorectal cancer patients: a Southern Italy Cooperative Oncology Group phase II study.

Oxaliplatin 100 mg/m(2) iv on day 1, and capecitabine 1,000 mg/m(2) orally bid from day 1 (evening) to day 11 (morning) were administered every 2 weeks (OXXEL regimen) to 38 patients as first-line treatment for metastatic colorectal carcinoma. A total of 318 cycles were administered, with a median of 8 (range, 4-12) cycles per patient. Response rate (RR) was 45% (95% confidence interval (CI), 29%-62%), with 7 complete responses and 10 partial responses; furthermore, 12 patients showed a stable disease, so that a disease control was achieved in 29 (76%) patients. RR was greater among patients with performance status 0 (52%), without weight loss (52%), younger than 65 years (50%), and previously unexposed to adjuvant chemotherapy (48%), while no correlation was found with the actually delivered oxaliplatin dose intensity. Overall, haematological side effects were negligible, with no case of grade 4 toxicity, and only one patient suffering from an episode of grade 3 neutropenic fever. Severe anaemia occurred in 4 (11%) patients, and grade 3 neuropathy affected 9 (24%) patients. Median progression-free survival was 7.9 (95% CI, 6.2-9.6) months, and median overall survival has not been reached yet. In conclusion, the OXXEL regimen resulted safe and active, and it deserves further evaluation in metastatic colorectal cancer patients.

Oxaliplatin plus high-dose folinic acid and 5-fluorouracil i.v. bolus (OXAFAFU) versus irinotecan plus high-dose folinic acid and 5-fluorouracil i.v. bolus (IRIFAFU) in patients with metastatic colorectal carcinoma: a Southern Italy Cooperative Oncology Group phase III trial.

PURPOSE: The primary end point of this phase III trial was to compare the response rate (RR) of oxaliplatin (OXA) plus levo-folinic acid (l-FA) and 5-fluorouracil (5-FU) bolus with that of irinotecan (IRI) plus l-FA and 5-FU bolus in advanced colorectal carcinoma. PATIENTS AND METHODS: Patients with measurable metastatic colorectal carcinoma were randomly allocated to receive: IRI 200 mg/m(2) on day 1, l-FA 250 mg/m(2) intravenously plus 5-FU 850 mg/m(2) on day 2 (IRIFAFU); or OXA 100 mg/m(2) on day 1, l-FA 250 mg/m(2) plus 5-FU 1050 mg/m(2) on day 2 [OXAFAFU high dose (hd)]. Cycles were given every 2 weeks. After a planned interim analysis, OXA was reduced to 85 mg/m(2) and 5-FU to 850 mg/m(2) [OXAFAFU low dose (ld)]. RESULTS: Two hundred and seventy-four patients (IRIFAFU, 135; OXAFAFUhd, 71; OXAFAFUld, 68) were treated. Forty-two confirmed responses were achieved with IRIFAFU, 29 with OXAFAFUhd and 32 with OXAFAFUld. The response rate with OXAFAFU [44%; 95% confidence interval (CI) 35% to 52%] was significantly higher (P=0.029) than that of IRIFAFU (31%; 95% CI 23% to 40%). Occurrence of grade > or =3 neutropenia with OXAFAFUld was similar to that for IRIFAFU (29% versus 31%), while severe diarrhoea was significantly lower (12% versus 24%). Median failure-free survival (7 versus 5.8 months; P=0.046) and overall survival of patients (18.9 versus 15.6 months; P=0.032) were significantly prolonged with OXAFAFU. CONCLUSIONS: OXAFAFU was more active and less toxic than IRIFAFU, and it should be preferred in the first-line treatment of advanced colorectal cancer patients.

Molecular regulation of blastocyst formation.

Preimplantation development encompasses the interval from insemination until embryo implantation and thus includes the 'freeliving' period of oviduct and uterine development. Formation of the blastocyst is required for implantation and establishment of pregnancy, and is a principal determinant of embryo quality prior to embryo transfer. Development through this period is regulated by the expression of specific gene families that encode for cell polarity, cell junctional, cytoskeletal, ion transporter, and water channel gene products that direct the acquisition of cell polarity and differentiation of the outer cells of the early embryo. This results in the formation of the trophectoderm, which is the first epithelium of development. This review considers the roles of each of these gene families in trophectoderm differentiation and blastocyst formation. The principal hypothesis under investigation is that blastocyst formation is regulated by a Na/K-ATPase-generated trans-trophectoderm ion gradient that promotes the accumulation of water across the epithelium. This, combined with the formation of the tight junction seal controlling paracellular movement of water between adjacent trophectoderm cells, results in the formation of a fluid-filled blastocyst cavity and the expansion of the blastocyst. Results from recent experiments, however, have cast some doubt on the role of Na/K-ATPase in mediating these events and have defined water channels or Aquaporins (AQPs) as physiological mediators of fluid movement across the trophectoderm. In addition, studies have now implicated mitogen-activated protein kinase (MAPK) signaling as an important mediator of development to the blastocyst stage. Such studies define the physiology of blastocyst formation and serve to support the application of assisted reproductive technologies (ART) to both human and animal species.

Independent evolution of heavy metal-associated domains in copper chaperones and copper-transporting atpases.

Copper chaperones are small cytoplasmic proteins that bind intracellular copper (Cu) and deliver it to Cu-dependent enzymes such as cytochrome oxidase, superoxide dismutase, and amine oxidase. Copper chaperones are similar in sequence and structure to the Cu-binding heavy metal-associated (HMA) domains of Cu-transporting ATPases (Cu-ATPases), and the genes for copper chaperones and Cu-ATPases are often located in the same operon. Phylogenetic analysis shows that Cu chaperones and HMA domains of Cu-ATPases represent ancient and distinct lineages that have evolved largely independently since their initial separation. Copper chaperone-Cu-ATPase operons appear to have evolved independently in different prokaryotic lineages, probably due to a strong selective pressure for coexpression of these genes.

How prevalent are hospital-based palliative care programs? Status report and future directions.

In the United States, the majority of deaths occur in the hospital but the dying process there is at best unsatisfactory and more likely inadequate for both patients and caregivers. The development of hospital-based palliative care programs (HBPCPs) can vastly improve inpatient end-of-life care. This study is the first to examine the prevalence and characteristics of HBPCPs in the United States, thus providing a snapshot of the characteristics of these HBPCPs. It also serves as a baseline and benchmark against which future development and patterns of HBPCPs can be compared. Phase 1: Data were obtained from the American Hospital Association (AHA) 1998 Annual Survey, on the existence of end-of-life care (EOLC) and pain management (PM) services in U.S. hospitals. Phase 2: A focused survey further assessed programs in Phase 1 and was sent to all registered hospitals that responded affirmatively to the AHA survey questions as having either a PM service, an EOLC service, or both. In phase 1, 1,751 (36%) hospitals reported having a PM service and 719 (15%) had an EOLC service, for a total of 2,015 unique hospitals that had one or both. For Phase 2, 1,120 of 2,015 responded (56%). Of these, 337 (30%) hospitals reported having an HBPCP, and another 228 (20.4%) had plans to establish one. HBPCPs are most commonly structured as inpatient consultation service and hospital-based hospice. They tend to be based in oncology, general medicine, and geriatrics. We also assessed reasons for consultation, patient characteristics, and future development needs. These findings can help guide future funding, educational, and programming efforts in hospital-based palliative care.

Juvenile chronic myelogenous leukemia: report of the Italian Registry. Associazione Italiana di Ematologia Oncologia Pediatrica (AIEOP).

BACKGROUND: Since juvenile chronic myeloid leukemia (JCML) represents no more than 2% of leukemia in children, clinical and investigative experience of this disorder has been limited. In order to evaluate the diagnostic criteria currently applied, to provide centralized facilities for blood culture and to collect data on treatment, and to propose a uniform treatment protocol in our country, a National Registry for JCML was recently established in the "Associazione Italiana di Ematologia Oncologia Pediatrica" (AIEOP). PATIENTS: Out of the 24 cases reported from 9/35 centres, 22 were considered sufficiently documented and were enrolled in the Registry. Clonogenic assay on marrow and peripheral blood cells was performed in all available cases. RESULTS: Common features were non-specific clinical (fever, splenomegaly, hepatomegaly, lymphadenomegaly) and hematologic alterations (anemia, thrombocytopenia, leukocytosis usually < 50 x 10(9)/l, monocytosis, circulating immature granulocytes, increased HbF, normal karyotype). In 11 out of 11 cases, in vitro blood cultures showed the spontaneous growth of CFU-C in the absence of any exogenous source of colony-stimulating activity. Twelve of the 22 patients (55%) are alive (probability of survival 47.7%); most patients were treated according to an acute myeloid leukemia-directed schedule; 5/7 children treated with interferon were alive with disease after a median time of 29 months from diagnosis (range 8-95 months); 4/5 children who underwent bone marrow transplantation were alive in complete remission 10, 24, 42 and 118 months, after the diagnosis. Age < 1 year at presentation was the most significant prognostic factor in terms of probability of survival (80% vs 28%; p = 0.0024). CONCLUSIONS: JCML must be considered in young children for whom acute leukemia has been suspected but ruled out; in vitro cultures should be considered mandatory to confirm the diagnosis. Age less than one year at the presentation was associated with prolonged survival. Only bone marrow transplantation was followed by prolonged disease-free survival, whereas intensive chemotherapy seemed not very effective and potentially associated with life-threatening complications. Interferon therapy appears to be a promising alternative to chemotherapy while the value of unrelated marrow donor is explored.