Survival rates and extra-regional migration patterns of children and adolescents with cancer in Italy: The 30-year experience of the Italian Association of Pediatric Hematology and Oncology (AIEOP) with the Italian hospital-based registry of pediatric cancer (Mod. 1.01).

Since the 1970s, Italian pediatric oncologists have collaborated through the Italian Association for Pediatric Hematology Oncology (AIEOP) network using a common centralized system for the registration of childhood cancer, known as Model 1.01 (Mod. 1.01). In this study, we report on recruitment trends, extra-regional migration and changes in outcome over time in the Italian population of children (0-14 years) and adolescents (15-19 years) registered and treated within the national AIEOP network in the period between 1989 and 2017. In almost 30 years, a cohort of 43,564 patients with a neoplasia diagnosis was registered in Mod. 1.01. The analysis of national extra-regional migration showed that patients tend to migrate from the South to the North and, to a lesser extent, to the Center of the country. During the study period, migration apparently decreased, especially for lymphohematopoietic diseases, whereas it remained substantial for solid tumors. Our data showed a progressive and significant increase in the cumulative survival 5 years after diagnosis since the 1990s, reaching almost 84% for all patients diagnosed in the last decade. Survival rates of Mod. 1.01 patients are similar to those provided by the main national and international reports showing childhood cancer surveillance estimates. The AIEOP Mod 1.01 has proved to be an invaluable tool from both an epidemiological and a health policy point of view, allowing us, in this study, to examine the survival experience of the largest cohort of Italian pediatric cancer patients with a very long follow-up.

Risk-adapted treatment of acute promyelocytic leukemia: results from the International Consortium for Childhood APL.

Pediatric acute promyelocytic leukemia (APL) can be cured with all-trans retinoic acid (ATRA) and anthracycline. However, most published trials have employed high cumulative doses of anthracyclines. Here, we report the outcome of newly diagnosed APL patients enrolled in the International Consortium for Childhood APL (ICC-APL-01) trial, which reduced anthracycline exposure but extended that of ATRA. The study recruited 258 children/adolescents with molecularly/cytogenetically proven APL. Patients were stratified into standard-risk (SR) and high-risk (HR) groups according to baseline white blood cell counts (<10 × 109/L or ≥10 × 109/L); both groups received identical induction treatment with ATRA and 3 doses of idarubicin. Two or 3 blocks of consolidation therapy were administered to SR and HR patients, respectively, while maintenance therapy with low-dose chemotherapy and ATRA cycles was given to all patients for 2 years. The cumulative dose of daunorubicin equivalent anthracyclines in SR and HR patients was lower than that of previous studies (355 mg/m2 and 405 mg/m2, respectively). Hematologic remission was obtained in 97% of patients; 8 children died of intracranial hemorrhage in the first 2 weeks following diagnosis. Five-year overall and event-free survival for the whole cohort were 94.6% and 79.9%, respectively; they were 98.4% and 89.4% in SR patients and 84.3% and 74.2% in HR patients (P = .002 and P = .043, respectively). These data demonstrate that extended use of ATRA coupled to a risk-adapted consolidation can achieve high cure rates in childhood APL and limit anthracycline exposure. The trial was registered at www.clinicaltrials.gov as EudractCT 2008-002311-40.

The Maize MID-COMPLEMENTING ACTIVITY Homolog CELL NUMBER REGULATOR13/NARROW ODD DWARF Coordinates Organ Growth and Tissue Patterning.

Organogenesis occurs through cell division, expansion, and differentiation. How these cellular processes are coordinated remains elusive. The maize (Zea mays) leaf provides a robust system to study cellular differentiation due to its distinct tissues and cell types. The narrow odd dwarf (nod) mutant displays defects at both the cellular and tissue level that increase in severity throughout growth. nod mutant leaves have reduced size due to fewer and smaller cells compared with the wild type. The juvenile-to-adult transition is delayed, and proximal distal-patterning is abnormal in this mutant. Differentiation of specialized cells such as those forming stomata and trichomes is incomplete. Analysis of nod-1 sectors suggests that NOD plays a cell-autonomous function in the leaf. We cloned nod positionally and found that it encodes CELL NUMBER REGULATOR13 (CNR13), the maize MID-COMPLEMENTING ACTIVITY homolog. CNR13/NOD is localized to the membrane and is enriched in dividing tissues. Transcriptome analysis of nod mutants revealed overrepresentation of cell wall, hormone metabolism, and defense gene categories. We propose that NOD coordinates cell activity in response to intrinsic and extrinsic cues.

The Arabidopsis SWR1 chromatin-remodeling complex is important for DNA repair, somatic recombination, and meiosis.

All processes requiring interaction with DNA are attuned to occur within the context of the complex chromatin structure. As it does for programmed transcription and replication, this also holds true for unscheduled events, such as repair of DNA damage. Lesions such as double-strand breaks occur randomly; their repair requires that enzyme complexes access DNA at potentially any genomic site. This is achieved by chromatin remodeling factors that can locally slide, evict, or change nucleosomes. Here, we show that the Swi2/Snf2-related (SWR1 complex), known to deposit histone H2A.Z, is also important for DNA repair in Arabidopsis thaliana. Mutations in genes for Arabidopsis SWR1 complex subunits photoperiod-independent Early Flowering1, actin-related protein6, and SWR1 complex6 cause hypersensitivity to various DNA damaging agents. Even without additional genotoxic stress, these mutants show symptoms of DNA damage accumulation. The reduced DNA repair capacity is connected with impaired somatic homologous recombination, in contrast with the hyper-recombinogenic phenotype of yeast SWR1 mutants. This suggests functional diversification between lower and higher eukaryotes. Finally, reduced fertility and irregular gametogenesis in the Arabidopsis SWR1 mutants indicate an additional role for the chromatin-remodeling complex during meiosis. These results provide evidence for the importance of Arabidopsis SWR1 in somatic DNA repair and during meiosis.

[The contribution of the Italian Association of paediatric haematology and oncology (AIEOP)]. / Il contributo dell'Associazione italiana di ematologia e oncologia pediatrica (AIEOP).

Since 1972, children affected by cancer took advantage from multi-centric diagnostic and therapeutic protocols produced by the Italian Association of paediatric haematology and oncology (AIEOP). At the beginning, these protocols were used in few well-trained centres, later in almost all Italian haemato-oncological centres. The need of a careful monitoring of his own activity induced AIEOP to achieve, in 1989, an Italian hospital- based registry (database Mod.1.01) of malignant tumours diagnosed and treated in the participating centres, with the aim to quantify the number of cases diagnosed and treated in the different centres, the agreement (or not) to official diagnostic- therapeutic protocols, and the extraregional migration. The database Mod.1.01, which is available via web to the current 55 AIEOP centres since 2000, recruits annually about 1,400 children (0-14 years) and 200 adolescents (15-19 years). While the first accounts for over 90% of expected subjects, the latter are only 25%. Leukaemias (30% of cases) are the most frequent childhood cancers, followed by central nervous system (CNS) tumours and lymphomas, 18% of cases both. In children, leukaemias (34%) are prevalent, mostly acute lymphoblastic leukaemia (26%), followed by CNS tumours (18%); in adolescents, lymphomas (30%) are prevalent, mostly Hodgkin lymphomas (22%), followed by bone sarcomas (16%). The recruitment of registered cases in AIEOP protocols is overall good both for children (70%) and for adolescents (60%), achieving outstanding results in leukaemia protocols. Extraregional migration of patients for diagnosis and therapy is decreasing over time, being currently about 20%, higher in adolescents, in solid tumours, and in residents in South Italy and in the islands. On the contrary, an increase of subjects born and resident abroad who are hospitalised in AIEOP centres for diagnosis and treatment, accounting at present for 5% of all cases, was observed. The results confirm that the database Mod.1.01 can be a valid tool able to contribute to epidemiologic research on childhood cancer in Italy.

Epigenetic regulation of repetitive elements is attenuated by prolonged heat stress in Arabidopsis.

Epigenetic factors determine responses to internal and external stimuli in eukaryotic organisms. Whether and how environmental conditions feed back to the epigenetic landscape is more a matter of suggestion than of substantiation. Plants are suitable organisms with which to address this question due to their sessile lifestyle and diversification of epigenetic regulators. We show that several repetitive elements of Arabidopsis thaliana that are under epigenetic regulation by transcriptional gene silencing at ambient temperatures and upon short term heat exposure become activated by prolonged heat stress. Activation can occur without loss of DNA methylation and with only minor changes to histone modifications but is accompanied by loss of nucleosomes and by heterochromatin decondensation. Whereas decondensation persists, nucleosome loading and transcriptional silencing are restored upon recovery from heat stress but are delayed in mutants with impaired chromatin assembly functions. The results provide evidence that environmental conditions can override epigenetic regulation, at least transiently, which might open a window for more permanent epigenetic changes.

Outcomes, health costs and use of antiplatelet agents in 7,082 patients admitted for an acute coronary syndrome occurring in a large community setting.

PURPOSE: To assess the outcomes of patients admitted for ACS and the prescription pattern of antiplatelets of patients discharged alive. METHODS: From the ARNO Observatory database, we performed a record linkage analysis of hospital discharge and prescription databases, which included 2,758,872 subjects of 7 Italian Local Health Authorities. The accrual period lasted from January 1 to December 31, 2008. Discharge records and prescription patterns were analyzed for 1 year before and after the accrual period. RESULTS: Of 2,758,872 subjects, 7,082 (2.6‰) were hospitalized for ACS. Mean age was 72±13 years, females and diabetics accounted for 36% and 25% of the cases. Of the 7,082 patients, in-hospital death occurred in 6.9%. Of the survivors, 64.5% was treated medically, 35.5% with PCI. Of the patients discharged alive, 65.8% were treated with an antiplatelet, 21.9% aspirin alone, 33.1% aspirin plus a thienopyridine (mostly clopidogrel), 10.5% a thienopyridine alone. Dual antiplatelet treatment was prescribed more frequently in patients treated with PCI than in those treated medically (57.3% vs 19.7%, p<0.0001). At least one re-hospitalization occurred in 58.6% (18.5% for a recurrent episode of ACS, 24.8% for other CV reasons, 15.3% for non CV reasons). Prescription continuity to antiplatelets was observed in 68.0% and 60.3% of the patients, respectively at 6 and 12 months after discharge. CONCLUSION: In a large community setting, the prescription rate of antiplatelets after ACS seems to be far from the guidelines recommendation. Rates of 1 year re-hospitalizations after ACS remain high, recurrence of ACS accounted for just one third of the cases.

Imprinting of the polycomb group gene MEDEA serves as a ploidy sensor in Arabidopsis.

Balanced maternal and paternal genome contributions are a requirement for successful seed development. Unbalanced contributions often cause seed abortion, a phenomenon that has been termed "triploid block." Misregulation of imprinted regulatory genes has been proposed to be the underlying cause for abnormalities in growth and structure of the endosperm in seeds with deviating parental contributions. We identified a mutant forming unreduced pollen that enabled us to investigate direct effects of unbalanced parental genome contributions on seed development and to reveal the underlying molecular mechanism of dosage sensitivity. We provide evidence that parent-of-origin-specific expression of the Polycomb group (PcG) gene MEDEA is causally responsible for seed developmental aberrations in Arabidopsis seeds with increased paternal genome contributions. We propose that imprinted expression of PcG genes is an evolutionary conserved mechanism to balance parental genome contributions in embryo nourishing tissues.

Appearance of HbeAg in an occult persistent hepatitis B virus infection.

Occult hepatitis B virus infection (OBI) is characterized by the presence of ongoing viral replication with very low levels of viremia (<200 IU/ml), and negativity for HBsAg, while the so-called 'false' OBI with higher levels of HBV-DNA that are negative for HBsAg are usually due to the occurrence of mutations of the HBsAg sequence that may alter the recognition by some immunoassays. We describe here a case of occult HBV infection that combines both aspects. A male patient with severe systemic diseases, positive for anti-HBc and anti-HBs and negative for all other HBV markers, including HBsAg, since at least 4 years, showed a positivity for HBeAg at a follow-up control in November 2008; HBV-DNA testing by real-time PCR evidenced very low levels of viremia (<40 IU/ml), direct sequencing of the surface antigen-coding and Pol/RT coding regions allowed the identification of genotype D, serotype adw2, one immune escape mutation (G145R) and no drug resistance mutations. The positivity for HBeAg could be attributed to a superinfection in a naturally immune subject or to reactivation of a latent infection; the mutated virus had a reduced fitness and was therefore able to replicate only at low levels, resulting in a mild form of occult HBV infection.

Antidepressant drug prescription and risk of abnormal bleeding: a case-control study.

This study assessed the risk of any bleeding abnormalities, including the risk of gastrointestinal bleeding, associated with antidepressant exposure. We used a case-control methodology. Case patients were individuals admitted with a diagnosis of abnormal bleeding. Control subjects were individuals admitted on the same date without evidence of abnormal bleeding. During the study period, 11,025 case patients were admitted for bleeding abnormalities (matched with 21,846 eligible control subjects), and 1008 were admitted for gastrointestinal bleeding (matched with 1990 eligible control subjects). With respect to any bleeding abnormalities, antidepressants as a group were not associated with an increased risk (adjusted odds ratio [OR], 0.99; 95% confidence interval [CI], 0.90-1.08). Similarly, selective serotonin reuptake inhibitors as a group, the group of tricyclic and related antidepressants, and the group of other antidepressants were not associated with an increased risk of bleeding. With respect to gastrointestinal bleeding abnormalities, antidepressants as a group were associated with a modestly increased risk (adjusted OR, 1.34; 95% CI, 1.01-1.80). Whereas the group of tricyclic and related antidepressants was not associated with an increased risk of bleeding, the group of selective serotonin reuptake inhibitors was associated with a nonsignificant trend toward an increased risk of bleeding (adjusted OR, 1.31; 95% CI, 0.91-1.88) and the group of other antidepressants with a statistically significant increase in the risk of bleeding (adjusted OR, 1.74; 95% CI, 1.04-2.93). In a population with a low baseline risk of bleeding, we detected a significant increase in the risk of gastrointestinal bleeding only.

Drug utilisation profile in the Italian paediatric population.

OBJECTIVE: In order to evaluate the prescribing pattern in the Italian paediatric population, prescriptions involving 923,353 children under 14 years old and dispensed during 2006 by the retail pharmacies of 22 Italian local health units were analysed. MATERIALS AND METHODS: A total of 561,237 children (61%) received at least one drug prescription. The prescription prevalence rate was highest in children 3 years of age (78%), decreased with increasing age and was higher in boys than in girls (chi(2)=655; p<<0.001). Each treated child received an average of 3.2 prescriptions and 4.8 boxes. RESULTS: Antibiotics and anti-asthmatics were the more prescribed therapeutic classes and represented 80% of prescriptions. Amoxicillin+clavulanic acid was the most prescribed drug (24% of the overall population; 17% of all boxes), followed by inhaled beclometasone and amoxicillin. A total of 620 different drugs were prescribed and the ten leading drugs represented 64% of the prescribed boxes. Six of the ten most prescribed drugs were the same in all age groups. Wide differences were found in the prevalence rate between the different local health units; these ranged between 50.1 and 68.4% (p<<0.001). The prescription prevalence increased in the 2000-2002 period (from 62.2 to 68.3%) and slightly decreased afterwards. CONCLUSION: Despite some limitations, the systematic monitoring of prescriptions is a valuable tool for evaluating the appropriateness of the care.

Survival of children with cancer in Italy, 1989-98. A report from the hospital based registry of the Italian Association of Paediatric Haematology and Oncology (AIEOP).

We describe the survival patterns of 10,791 Italian children (age 0-14) diagnosed with cancer during 1989-1998 and who were included in the hospital-based registry of the Italian Association of Paediatric Haematology and Oncology. Five-year cumulative survival percentages were 76% for lymphoproliferative disorders and 68% for solid tumours. Survival rates in 1994-1998 significantly improved for acute lymphocytic leukaemia (ALL), acute non-lymphocytic leukaemia, Hodgkin's lymphoma and Wilms' tumour. Gender and age were determinants of survival for some specific types of cancer. Girls with ALL and neuroblastoma exhibited a significant advantage (hazard ratio HR 0.72, 0.62-0.83) and disadvantage (HR 0.73, 0.59-0.90) over boys, respectively. Children with a Wilms' tumour diagnosed above age 3 had a worse prognosis than younger children (HR 2.3, 1.4-4.1). The persisting gender-related difference in survival rate for ALL requires understanding as to whether it is attributable to delays in the adoption of more recent therapeutic protocols, while the corresponding findings for Wilms' tumour and neuroblastoma deserve further biological interpretation.

The 'Survivorship Passport' for childhood cancer survivors.

BACKGROUND: Currently, there are between 300,000 and 500,000 childhood cancer survivors (CCSs) in Europe. A significant proportion is at high risk, and at least 60% of them develop adverse health-related outcomes that can appear several years after treatment completion. Many survivors are unaware of their personal risk, and there seems to be a general lack of information among healthcare providers about pathophysiology and natural history of treatment-related complications. This can generate incorrect or delayed diagnosis and treatments. METHOD: The Survivorship Passport (SurPass) consists of electronic documents, which summarise the clinical history of the childhood or adolescent cancer survivor. It was developed by paediatric oncologists of the PanCare and SIOPE networks and IT experts of Cineca, together with parents, patients, and survivors' organisations within the European Union-funded European Network for Cancer research in Children and Adolescents. It consists of a template of a web-based, simply written document, translatable in all European languages, to be given to each CCS. The SurPass provides a summary of each survivor's clinical history, with detailed information about the original cancer and of treatments received, together with personalised follow-up and screening recommendations based on guidelines published by the International Guidelines Harmonization Group and PanCareSurFup. RESULTS: The SurPass data schema contains a maximum of 168 variables and uses internationally approved nomenclature, except for radiotherapy fields, where a new classification was defined by radiotherapy experts. The survivor-specific screening recommendations are mainly based on treatment received and are automatically suggested, thanks to built-in algorithms. These may be adapted and further individualised by the treating physician in case of special disease and survivor circumstances. The SurPass was tested at the Istituto Giannina Gaslini, Italy, and received positive feedback. It is now being integrated at the institutional, regional and national level. CONCLUSIONS: The SurPass is potentially an essential tool for improved and more harmonised follow-up of CCS. It also has the potential to be a useful tool for empowering CCSs to be responsible for their own well-being and preventing adverse events whenever possible. With sufficient commitment on the European level, this solution should increase the capacity to respond more effectively to the needs of European CCS.

Massive pulmonary embolism.

BACKGROUND: Acute massive pulmonary embolism (PE) carries an exceptionally high mortality rate. We explored how often adjunctive therapies, particularly thrombolysis and inferior vena caval (IVC) filter placement, were performed and how these therapies affected the clinical outcome of patients with massive PE. METHODS AND RESULTS: Among 2392 patients with acute PE and known systolic arterial blood pressure at presentation, from the International Cooperative Pulmonary Embolism Registry (ICOPER), 108 (4.5%) had massive PE, defined as a systolic arterial pressure <90 mm Hg, and 2284 (95.5%) had non-massive PE with a systolic arterial pressure > or =90 mm Hg. PE was first diagnosed at autopsy in 16 patients (15%) with massive PE and in 29 patients (1%) with non-massive PE (P<0.001). The 90-day mortality rates were 52.4% (95% CI, 43.3% to 62.1%) and 14.7% (95% CI, 13.3% to 16.2%), respectively. In-hospital bleeding complications occurred in 17.6% versus 9.7% and recurrent PE within 90 days in 12.6% and 7.6%, respectively (P<0.001). In patients with massive PE, thrombolysis, surgical embolectomy, or catheter embolectomy were withheld in 73 (68%). Thrombolysis was performed in 33 patients, surgical embolectomy in 3, and catheter embolectomy in 1. Thrombolytic therapy did not reduce 90-day mortality (thrombolysis, 46.3%; 95% CI, 31.0% to 64.8%; no thrombolysis, 55.1%; 95% CI, 44.3% to 66.7%; hazard ratio, 0.79; 95% CI, 0.44 to 1.43). Recurrent PE rates at 90 days were similar in patients with and without thrombolytic therapy (12% for both; P=0.99). None of the 11 patients who received an IVC filter developed recurrent PE within 90 days, and 10 (90.9%) survived at least 90 days. IVC filters were associated with a reduction in 90-day mortality (hazard ratio, 0.12; 95% CI, 0.02 to 0.85). CONCLUSIONS: In ICOPER, two thirds of the patients with massive PE did not receive thrombolysis or embolectomy. Counterintuitively, thrombolysis did not reduce mortality or recurrent PE at 90 days. The observed reduction in mortality from IVC filters requires further investigation.

Estudio relacional de las necesidades de soporte según los servicios de lugar de vida utilizados / Relational study of support needs according to life services used

El objetivo del presente estudio es valorar la relación existente entre el grado de atención requerida por los diferentes usuarios y el servicio de lugar de vida que están utilizando. Para ello se ha realizado un estudio con 388 personas. Las variables estudiadas incluyen el diagnóstico, la edad, el sexo, la situación económica y la Escala ENAR-CPB. El porcentaje de hombres es superior al de mujeres. Los jóvenes son tratados principalmente en los pisos supervisados. Mayoritariamente se atienden esquizofrenias paranoides, sobre todo en las residencias. Las depresiones mayores están sobre todo en el propio domicilio y los trastornos límites de la personalidad son atendidos principalmente en pisos supervisados. Las personas que viven en una residencia son por lo general más dependientes que las que viven en pisos supervisados o en su propio domicilio. Es importante ajustar lo más posible el recurso de lugar de vida a las capacidades y necesidades reales de la persona, pero la situación económica personal marca la diferencia entre el hecho de ir a vivir a un piso supervisado o mantenerse en el propio domicilio. (AU)

This study was conducted with the aim of evaluating the relationship existing between the degree of care required by users of different mental health services and the services provided in the place they are using. The study was performed on a 388-person sample. The variables studied included diagnosis, age, sex, economic circumstances, and the ENAR-CPB scale. In all resources, the percentage of men with support outnumbered that of women. On the other hand, young people were found to mostly be living in supportive housing. The majority in all resources suffered from paranoid schizophrenia, especially in long-term care facilities. Clients with severe depression generally lived in their own homes, while those with borderline personality disorder were mainly attended in supportive housing. The residences clients were more dependent than those living whether in supportive housing or in their own home. It is important to relate the housing resource to a person's real capabilities and needs as much as possible; however, it is economic capacity what determines whether a person lives in a supportive housing unit or in their own home. (AU)

[Best practices on peritoneal dialysis: the audit of Lazio Region]. / Best practices in dialisi peritoneale: l'audit della regione Lazio.

The diffusion of peritoneal methodology can not be something out of the real organizational context and the regional directive can not be the only means to encourage the diffusion. There is the need to provide effective and sustainable levels of assistance through a clinical scientific support and sharing of best-practises. On one side, the aim is to provide an aid by the centers with great expertise in the methodology, recognized as reference points; on the other side, to establish the shared K.P.I.s (Key Performance Index), to asses the clinical effectiveness and measure the objectives to be achieved, through a modality of valuation to establish the real applicability. For this purpose, a scientific board was founded, composed by the heads of UU.OO, that provide the peritoneal dialysis, to determine which aspects to investigate and identify factors of supply improvement. The selected method was the clinical audit. The analysis of the 2011 data has allowed us to capture the situation of the peritoneal dialysis in the Lazio Region. The formative procedure has enabled the centers to share and standardize protocols and therapeutic procedures, identify the strengths of peritoneal dialysis in the Lazio Region and define the KPIs through whose compare and monitor the centers over time. The conclusive analysis of the audit has enabled to identify a series of activities to be undertaken together in order to improve the situation of the peritoneal dialysis in the Lazio Region. In the following years, surveys will be carried out to verify the KPIs trend.

Prognostic role of echocardiography among patients with acute pulmonary embolism and a systolic arterial pressure of 90 mm Hg or higher.

BACKGROUND: The prognostic role of echocardiographic right ventricular (RV) dysfunction for predicting mortality in patients with acute pulmonary embolism and a preserved systemic arterial pressure remains controversial. METHODS: We evaluated 1035 patients with pulmonary embolism from the International Cooperative Pulmonary Embolism Registry who (1) presented with systolic systemic arterial pressure of 90 mm Hg or higher and (2) who underwent echocardiography within 24 hours of a diagnosis of pulmonary embolism, showing presence (n = 405) or absence (n = 630) of RV hypokinesis. The main outcome measure was the cumulative survival rate through 30 days in patients with and without RV hypokinesis. RESULTS: In patients with RV hypokinesis, the initial systolic systemic pressure was lower (125 +/- 22 mm Hg vs 131 +/- 22 mm Hg; P<.001), and the initial heart rate was higher (104 +/- 21 beats per minute vs 99 +/- 22 beats per minute; P<.001) than in patients without RV hypokinesis. Cancer was less often present (14.1% vs 22.5%, P = .001). The 30-day survival rates in patients with and without RV hypokinesis were 83.7% (95% confidence interval [CI], 79.3%-87.0%) and 90.6% (95% CI, 88.0%-92.6%), respectively (log-rank P value <.001). The univariate hazard ratio of RV hypokinesis for predicting 30-day mortality was 2.11 (95% CI, 1.41-3.16; P<.001). Right ventricular hypokinesis remained an independent predictor of 30-day mortality (hazard ratio, 1.94; 95% CI, 1.23-3.06) after adjusting for univariately significant predictors, including cancer, congestive heart failure, chronic lung disease, age older than 70 years, systolic arterial pressure of 100 mm Hg or lower, administration of thrombolytic therapy, and heart rate greater than 100 beats per minutes. CONCLUSION: Among patients with pulmonary embolism who present with a systolic arterial pressure greater than or equal to 90 mm Hg, echocardiographic RV hypokinesis is an independent predictor of early death.

Gefitinib in pretreated non-small-cell lung cancer (NSCLC): analysis of efficacy and correlation with HER2 and epidermal growth factor receptor expression in locally advanced or metastatic NSCLC.

PURPOSE: To evaluate the correlation between HER2 expression and gefitinib (ZD 1839, Iressa; AstraZeneca, London, United Kingdom) efficacy in terms of response rate, time to progression (TTP), and overall survival (OS) time. PATIENTS AND METHODS: Patients with pretreated advanced non-small-cell lung cancer (NSCLC) received gefitinib at a daily dose of 250 mg until disease progression. Tumor tissue specimens obtained at the time of primary diagnosis were collected to determine HER2/epidermal growth factor receptor (EGFR) status by immunohistochemistry. RESULTS: From February 2001 to June 2002, 63 consecutive patients were enrolled onto the study. The overall disease control rate was 58.7% (partial response [PR], 15.9%; stable disease [SD], 42.8%), median TTP was 3.3 months, and median OS was 4.1 months. Among the 43 patients in whom EGFR/HER2 status was determined, we observed six PRs (14%) and 18 SDs (42%). Disease control, including PR and SD, was 40% in the 15 patients overexpressing HER2 and 64.3% in the 28 patients not overexpressing HER2 (P =.126). No difference was found between the two groups in terms of TTP (3.5 v 3.7 months, respectively) and OS (5.7 v 6.8 months, respectively). In addition, we did not find any difference in TTP, OS, toxicity, and symptom outcome in the group of patients overexpressing both HER2 and EGFR compared with patients who had no overexpression of HER2 CONCLUSION: According to these data, efficacy, toxicity, and symptom outcome in patients with NSCLC treated with gefitinib do not seem to be related to HER2 expression.

Right heart thrombi in pulmonary embolism: results from the International Cooperative Pulmonary Embolism Registry.

OBJECTIVES: This study was designed to investigate the prevalence and prognostic significance of right heart thrombi (RHTh) in pulmonary embolism. BACKGROUND: Most reports about patients with RHTh are small case series. We analyzed data referring to RHTh among 2,454 consecutive pulmonary embolism patients enrolled in the International Cooperative Pulmonary Embolism Registry. METHODS: Of the 2,454 patients, 1,113 had results available from baseline echocardiography. We compared the 42 patients with RHTh versus 1,071 without RHTh. RESULTS: Patients with RHTh had shorter duration of symptoms (2.2 +/- 2.9 days vs. 4.3 +/- 6.0 days, p = 0.013), lower systolic blood pressure (BP) (116.0 +/- 28.8 vs. 125.7 +/- 25.0 mm Hg, p = 0.008), and more frequent right ventricular hypokinesis (64% vs. 40%, p = 0.002) and congestive heart failure (26% vs. 13%, p = 0.024); but they had similar age (62.9 vs. 62.5 years), arterial oxygen pressure (71.3 +/- 26.0 vs. 69.5 +/- 30.5 mm Hg), and prevalence of cancer (14% vs. 19%). The overall mortality rate at 14 days and at three months was higher in patients with RHTh (21% vs. 11%, p = 0.032, and 29% vs. 16%, p = 0.036). The difference in early mortality was observed almost entirely within the subgroup of patients treated with heparin alone (23.5% vs. 8%, p = 0.02), despite similar clinical severity at presentation (systolic BP 122.2 +/- 24.2 vs. 127.8 +/- 24.1 mm Hg, hypotension in 5.9% vs. 3.4% patients). CONCLUSIONS: Among patients with acute pulmonary embolism, RHTh is usually found in those more hemodynamically compromised but is also a marker of worse prognosis in initially apparently stable patients treated with heparin alone.

Overt hepatic encephalopathy in Italy: clinical outcomes and healthcare costs.

PURPOSE: Hepatic encephalopathy (HE) is a recurrent severe complication of progressive hepatic cirrhosis. The aim of this study is to evaluate the average annual direct healthcare costs for the treatment of patients with overt HE in Italy. PATIENTS AND METHODS: This retrospective, observational study analyzed information from the database of ARNO Observatory. Patients with at least one hospitalization due to overt HE in the period from January 1, 2011 to December 31, 2011, were selected and observed during the year following the hospitalization. Costs for drugs, diagnostic and therapeutic procedures, and hospitalizations were estimated from the Italian National Health Service perspective. RESULTS: Out of a population of 2,678,462 subjects, 381 patients were identified, of whom, 21.5% died during the first hospitalization and 5.8% during the follow-up; the survival rate was 72.7% at the end of the observation period. The direct healthcare costs per patient amounted to €13,393/year (15,295 USD) (88% for hospitalizations, 8% for drugs, and 4% for diagnostic procedures). During the follow-up, 42.5% of patients had at least one rehospitalization due to HE. Patients readmitted for HE had an average annual cost of €21,272 (24,293 USD), almost doubled if compared to patients without readmissions (€12,098 [13,816 USD]). CONCLUSION: This analysis showed that patients with HE had relevant direct healthcare costs, in which hospitalizations were the most important cost drivers.