Impact of lung function changes after induction radiochemotherapy on resected T4 non-small cell lung cancer outcome.

BACKGROUND: Induction radiochemotherapy, followed by resection, for T4 non-small cell lung cancer, has shown promising long-term survival but may be associated with increased postoperative morbidity and death, depending on patient selection. Here, we determined the effect of induction radiochemotherapy on pulmonary function and whether postinduction pulmonary function changes predict hospital morbidity and death and long-term survival. METHODS: A consecutive prospective cohort of 72 patients with T4 N0-2 M0 non-small cell lung cancer managed by radiochemotherapy, followed by resection, is reported. All patients underwent thoracoabdominal computed tomography or fusion positron emission tomography-computed tomography, brain imaging, mediastinoscopy, echocardiography, ventilation-perfusion scintigraphy, and pulmonary function testing before and after induction therapy. Resection was performed if the postoperative forced expiratory volume in 1 second and diffusion capacity of the lung for carbon monoxide exceeded 30% predicted and if the postoperative maximum oxygen consumption exceeded 10 mL/kg/min. RESULTS: The postoperative 90-day mortality rate was 8% (lobectomy, 2%; pneumonectomy, 21%; p=0.01). All deaths after pneumonectomy occurred after right-sided procedures. The 3-year and 5-year survival was 50% (95% confidence interval, 36% to 62%) and 45% (95% confidence interval, 31% to 57%) and was significantly associated with completeness of resection (p=0.004) and resection type (pneumonectomy vs lobectomy, p=0.01). There was no correlation between postinduction pulmonary function changes and postoperative morbidity or death or long-term survival in patients managed by lobectomy or pneumonectomy. CONCLUSIONS: In properly selected patients with T4 N0-2 M0 non-small cell lung cancer, resection after induction radiochemotherapy can be performed with a reasonable postoperative mortality rate and long-term survival, provided the resection is complete and a right-sided pneumonectomy is avoided. Postinduction pulmonary function changes did not correlate with postoperative morbidity or death or with long-term outcome.

Fatal intrahepatic hemorrhage after nadroparin use for total hip arthroplasty.

Low-molecular-weight heparins have become the predominant choice for deep venous thrombosis prophylaxis and treatment. However, their use may cause bleeding complications. Intrahepatic bleeding is exceptional and only very few cases have been described. The authors present a unique case of fatal intrahepatic hematoma complicating nadroparin use in a 65-year-old woman with a hepatic cyst who was admitted to hospital for unilateral total hip arthroplasty. At autopsy, hemoperitoneum (2,000 ml of blood and clots) was evident. A ruptured sub-capsular hematoma involving the right lobe of the liver was observed. The hemorrhage within the cyst induced by the nadroparin use was likely responsible for the subsequent hepatic hematoma, liver rupture, and death. This case highlights the need for pathologists and surgeons to be aware of the possibility of intrahepatic hematoma in patients who have received low-molecular-weight heparins, undergone major surgery and present postoperative hemodynamic instability, especially in those with preoperative diagnosis of hepatic cyst.

Malignant gastroduodenal obstruction: palliation with self-expanding metallic stents.

PURPOSE: To evaluate the feasibility, efficacy, and tolerance of self-expanding metallic stent insertion under fluoroscopic guidance for palliation of symptoms related to malignant gastroduodenal obstruction. MATERIALS AND METHODS: Seventy-two patients (38 men, 34 women) aged 25-98 years (mean, 62 years) with duodenal (n = 43), antropyloric (n = 13), surgical gastrojejunostomy (n = 10), or pyloroduodenal (n = 6) malignant obstruction were referred for insertion of self-expanding metallic stents over a 6-year period. Stent insertion was performed with use of a peroral or transgastric approach when necessary (n = 11). RESULTS: Stents were successfully inserted in 70 of the 72 patients (97%) and provided symptom relief in 65 patients (90%). Inserted stents were mainly uncovered vascular (n = 55) or enteral (n = 10) Wallstents. One hundred eight stents were initially inserted: one, two, three, or four stents were indicated in 43, 17, nine, and one patient, respectively. Mean follow-up was 119 days (range, 4-513 days). Mean stent patency was 113 days (range, 4-513 days). Mean survival of patients was 120 days. During follow-up, stent obstruction occurred in seven patients as a result of tumoral overgrowth (n = 5) or ingrowth (n = 2). Complications occurred in 12 of the 72 patients (17%), including stent migration (n = 8), stent fracture (n = 1), duodenal perforation (n = 1), and death related to general anesthesia (n = 1). CONCLUSION: Despite a significant complication rate, self-expanding metallic stent insertion under fluoroscopic guidance appears to be a feasible and useful technique in the palliative management of malignant gastroduodenal obstruction.

Survey of management of first-ever seizures in a hospital based community

Résumé Contexte: Bon nombre d'études épidémiologiques concernant les premières crises comitiales ont été effectuées principalement sur des populations générales. Cependant, les patients admis dans un hôpital peuvent présenter des éléments cliniques différents. Nous avons donc mené une étude prospective auprès de sujets dans une population hospitalière ayant subi une première crise d'épilepsie, afin d'étudier leur pronostic et le rôle des examens complémentaires (examen neurologique, imagerie cérébrale, examens sanguins, EEG) dans le choix de l'administration d'une médication antiépileptique. Méthodes : Sur une période d'une année, nous avons suivi 177 patients adultes, admis consécutivement, ayant présenté une crise d'épilepsie dont l'évaluation aiguë a été effectuée dans notre hôpital. Pendant 6 mois, nous avons pratiqué pour chaque patient un suivi du traitement antiépileptique, des récidives de crises et d'un éventuel décès. Résultats : L'examen neurologique était anormal dans 72.3% des cas, l'imagerie cérébrale dans 54.8% et les examens sanguins dans 57.1%. L'EEG a montré des éléments épileptiformes dans 33.9% des cas. L'étiologie la plus fréquemment représentée était constituée par des intoxications. Un traitement antiépileptique a été prescrit chez 51% des patients. 31.6% des sujets suivis à six mois ont subi une récidive ; la mortalité s'est élevée à 17.8%. Statistiquement, l'imagerie cérébrale, l'EEG et l'examen neurologique étaient des facteurs prédictifs indépendants pour l'administration d'antiépileptiques, et l'imagerie cérébrale le seul facteur associé au pronostic. Conclusions : Les patients évalués en aigu dans un hôpital pour une première crise comitiale présentent un profil médical sous-jacent, qui explique probablement leur mauvais pronostic. L'imagerie cérébrale s'est avérée être le test paraclinique le plus important dans la prévention du traitement et du pronostic. Mots-clés : première crise d'épilepsie, étiologie, pronostic, récidive, médication antiépileptique, population hospitalière Summary Background: Epidemiological studies focusing on first-ever seizures have been carried out mainly on community based populations. However, since hospital populations may display varying clinical features, we prospectively analysed patients with first-ever seizure in a hospital based community to evaluate prognosis and the role of complementary investigations in the decision to administer antiepileptic drugs (AED). Methods: Over one year, we recruited 177 consecutive adult patients with a first seizure acutely evaluated in our hospital. During six months' follow-up data relating to AED treatment, recurrence of seizures and death were collected for each patient. Results:. Neurological examination was abnormal in 72.3%, neuroimaging in 54.8% and biochemical tests in 57.1%. Electroencephalogram (EEG) showed epileptiform features in 33.9%. Toxicity represented the most common aetiology. AED was prescribed in 51% of patients. Seizure recurrence at six months involved 31.6% of patients completing the follow-up; mortality was 17.8%. Statistical analysis showed that brain CT, EEG and neurological examination are independent predictive factors for AED administration, but only CT scan is associated with outcome. Conclusions: Patients evaluated acutely for first- ever seizure in a hospital setting have severe underlying clinical conditions apparently related to their relatively poor prognosis. Neuroimaging represents the most important paraclinical test in predicting both treatment administration and outcome.

Family Size Evolution in Drosophila Chemosensory Gene Families: A Comparative Analysis with a Critical Appraisal of Methods

Gene turnover rates and the evolution of gene family sizes are important aspects of genome evolution. Here, we use curated sequence data of the major chemosensory gene families from Drosophila-the gustatory receptor, odorant receptor, ionotropic receptor, and odorant-binding protein families-to conduct a comparative analysis among families, exploring different methods to estimate gene birth and death rates, including an ad hoc simulation study. Remarkably, we found that the state-of-the-art methods may produce very different rate estimates, which may lead to disparate conclusions regarding the evolution of chemosensory gene family sizes in Drosophila. Among biological factors, we found that a peculiarity of D. sechellia's gene turnover rates was a major source of bias in global estimates, whereas gene conversion had negligible effects for the families analyzed herein. Turnover rates vary considerably among families, subfamilies, and ortholog groups although all analyzed families were quite dynamic in terms of gene turnover. Computer simulations showed that the methods that use ortholog group information appear to be the most accurate for the Drosophila chemosensory families. Most importantly, these results reveal the potential of rate heterogeneity among lineages to severely bias some turnover rate estimation methods and the need of further evaluating the performance of these methods in a more diverse sampling of gene families and phylogenetic contexts. Using branch-specific codon substitution models, we find further evidence of positive selection in recently duplicated genes, which attests to a nonneutral aspect of the gene birth-and-death process.

Immunological aspects of Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (copd) is a major cause of illness and death throughout the world. It affects about 10% of the general population, but its prevalence among heavy smokers can reach 50%.COPD is the fourth leading cause of death in most industrialized countries, and it is projected to be the third leading cause of death worldwide by 2020. Tobacco smoking is the primary risk factor for the development of COPD, but other factors, such as burning biomass fuels for cooking and heating, are important causes of COPD in many developing countries....

Gender differences in cancer patients with acute venous thromboembolism.

BACKGROUND: The outcome of cancer patients with acute venous thromboembolism (VTE) may differ according to gender. METHODS: We used the RIETE database to compare the rate of VTE (pulmonary embolism [PE] or deep vein thrombosis [DVT]) recurrences), major bleeding and mortality during the course of anticoagulation, according to gender. RESULTS: As of August 2014, 11,055 patients with active cancer were enrolled in RIETE, of whom 5,104 (46%) were women. During the course of anticoagulation (mean: 142 days), 505 patients developed recurrent VTE, 429 bled and 2730 died. Compared with men, women had a significantly lower rate of fatal bleeding (risk ratio [RR]: 0.69; 95% CI: 0.47-0.99) and death (RR: 0.90; 95% CI: 0.83-0.97), and a non-significantly lower rate of PE recurrences (RR 0.83; 95% CI: 0.65-1.06) and major bleeding (RR: 0.89; 95% CI: 0.74-1.08). CONCLUSIONS: During the course of anticoagulation, cancer women with VTE had a better outcome than men.

La fureur divine et son détournement en Nb 25

The story Numbers of 25 which reports the incident of Baal Peor is one among several texts in the book of Numbers focusing on divine wrath, its cause and its consequences. The present article offers a detailed analysis of the account which is difficult to understand because of certain jumps in the plot and because of its allusive style. Scholars mostly agree with the idea that the story grew in two or three stages. A lot of commentators believe that the original story contains only the apostasy of Peor caused by the Moabites (vv. 1-5). A subsequent story would focus on Pinchas' action against Zimri and Kospi, and a third layer is linked to the story of the war between Israel and Midian (Numbers 31). The problem of this theory however is that it seems impossible to reconstruct an original story about the matter of Peor; one does not find a satisfying end within vv. 1-5. Furthermore, v. 5, which belongs to the first, "Moabite", section, is already linked to the theme of Midian which dominates the second and the third passage. Moreover, the assemblage of different themes and motifs seem having been done with care: Regarding the two abuses of Israel reported in the story--idolatry and intermarriage--, they often go together in late polemical Deuteronomistic and post-Deuteronomistic layers (Ezra-Nehemiah). The double focus on Midian and Moab could both be polemically directed against certain Moses traditions found in the books of Exodus and Deuteronomy (concerning Moses' marriage with a Midianite women on the one hand and his stay and death and burial in Moab - in the vicinity of Beth Peor - on the other hand). As in several ANE traditions also in the Hebrew Bible the motif of "divine wrath" serves to interpret fatal historical events; in Num 25 as in other Biblical stories however it is doubtful whether the alleged incident (the plague) really have taken place and the story's plot is anchored in ancient Israel's history.

European cancer mortality predictions for the year 2016 with focus on leukemias.

BACKGROUND: Current cancer mortality statistics are important for public health decision making and resource allocation. Age standardized rates and numbers of deaths are predicted for 2016 in the European Union. PATIENTS AND METHODS: Population and death certification data for stomach, colorectum, pancreas, lung, breast, uterus, prostate, leukemia and total cancers were obtained from the World Health Organisation database and Eurostat. Figures were derived for the EU, France, Germany, Italy, Poland, Spain and the UK. Projected numbers of deaths by age group were obtained for 2016 by linear regression on estimated numbers of deaths over the most recent time period identified by a joinpoint regression model. RESULTS: Projected total cancer mortality trends for 2016 in the EU are favourable in both sexes with rates of 133.5/100,000 men and 85.2/100,000 women (8% and 3% falls since 2011, due to population ageing) corresponding to 753,600 and 605,900 deaths in men and women for a total number of 1,359,500 projected cancer deaths (+3% compared to 2011). In men lung, colorectal and prostate cancer fell 11%, 5% and 8% since 2011. Breast and colorectal cancer trends in women are favourable (8% and 7% falls, respectively), but lung and Pancreatic cancer rates rose 5% and 4% since 2011 reaching rates of 14.4 and 5.6/100,000 women. Leukemia shows favourable projected mortality for both sexes and all age groups with stronger falls in the younger age groups, rates are 4.0/100,000 men and 2.5/100,000 women, with respectively falls of 14% and 12%. CONCLUSION: The 2016 predictions for EU cancer mortality confirm the favourable trends in rates particularly for men. Lung cancer is likely to remain the leading site for female cancer rates. Continuing falls in mortality, larger in children and young adults, are predicted in leukemia, essentially due to advancements in management and therapy, and their subsequent adoption across Europe.

High-Resolution Magnetic Resonance Imaging Can Reliably Detect Orbital Tumor Recurrence after Enucleation in Children with Retinoblastoma.

PURPOSE: Orbital tumor recurrence is a rare but serious complication in children with retinoblastoma, leading to a high risk of metastasis and death. Therefore, we assume that these recurrences have to be detected and treated as early as possible. Preliminary studies used magnetic resonance imaging (MRI) to evaluate postsurgical findings in the orbit. In this study, we assessed the diagnostic accuracy of high-resolution MRI to detect orbital tumor recurrence in children with retinoblastoma in a large study cohort. DESIGN: Consecutive retrospective study (2007-2013) assessing MRI findings after enucleation. PARTICIPANTS: A total of 103 MRI examinations of 55 orbits (50 children, 27 male/23 female, mean age 16.3±12.4 months) with a median time of 8 months (range, 0-93) after enucleation for retinoblastoma. METHODS: High-resolution MRI using orbital surface coils was performed on 1.5 Tesla MRI systems to assess abnormal orbital findings. MAIN OUTCOME MEASURES: Five European experts in retinoblastoma imaging evaluated the MRI examinations regarding the presence of abnormal orbital gadolinium enhancement and judged them as "definitive tumor," "suspicious of tumor," "postsurgical condition/scar formation," or "without pathologic findings." The findings were correlated to histopathology (if available), MRI, and clinical follow-up. RESULTS: Abnormal orbital enhancement was a common finding after enucleation (100% in the first 3 months after enucleation, 64.3% >3 years after enucleation). All histopathologically confirmed tumor recurrences (3 of 55 orbits, 5.5%) were correctly judged as "definitive tumor" in MRI. Two orbits from 2 children rated as "suspicious of tumor" received intravenous chemotherapy without histopathologic confirmation; further follow-up (67 and 47 months) revealed no sign of tumor recurrence. In 90.2%, no tumor was suspected on MRI, which was clinically confirmed during follow-up (median follow-up after enucleation, 45 months; range, 8-126). CONCLUSIONS: High-resolution MRI with orbital surface coils may reliably distinguish between common postsurgical contrast enhancement and orbital tumor recurrence, and therefore may be a useful tool to evaluate orbital tumor recurrence after enucleation in children with retinoblastoma. We recommend high-resolution MRI as a potential screening tool for the orbit in children with retinoblastoma to exclude tumor recurrence, especially in high-risk patients within the critical first 2 years after enucleation.

The Proteolytic Activation of (H3N2) Influenza A Virus Hemagglutinin Is Facilitated by Different Type II Transmembrane Serine Proteases.

UNLABELLED: Cleavage of influenza virus hemagglutinin (HA) by host cell proteases is necessary for viral activation and infectivity. In humans and mice, members of the type II transmembrane protease family (TTSP), e.g., TMPRSS2, TMPRSS4, and TMPRSS11d (HAT), have been shown to cleave influenza virus HA for viral activation and infectivityin vitro Recently, we reported that inactivation of a single HA-activating protease gene,Tmprss2, in knockout mice inhibits the spread of H1N1 influenza viruses. However, after infection ofTmprss2knockout mice with an H3N2 influenza virus, only a slight increase in survival was observed, and mice still lost body weight. In this study, we investigated an additional trypsin-like protease, TMPRSS4. Both TMPRSS2 and TMPRSS4 are expressed in the same cell types of the mouse lung. Deletion ofTmprss4alone in knockout mice does not protect them from body weight loss and death upon infection with H3N2 influenza virus. In contrast,Tmprss2(-/-)Tmprss4(-/-)double-knockout mice showed a remarkably reduced virus spread and lung pathology, in addition to reduced body weight loss and mortality. Thus, our results identified TMPRSS4 as a second host cell protease that, in addition to TMPRSS2, is able to activate the HA of H3N2 influenza virusin vivo IMPORTANCE: Influenza epidemics and recurring pandemics are responsible for significant global morbidity and mortality. Due to high variability of the virus genome, resistance to available antiviral drugs is frequently observed, and new targets for treatment of influenza are needed. Host cell factors essential for processing of the virus hemagglutinin represent very suitable drug targets because the virus is dependent on these host factors for replication. We reported previously thatTmprss2-deficient mice are protected against H1N1 virus infections, but only marginal protection against H3N2 virus infections was observed. Here we show that deletion of two host protease genes,Tmprss2andTmprss4, strongly reduced viral spread as well as lung pathology and resulted in increased survival after H3N2 virus infection. Thus, TMPRSS4 represents another host cell factor that is involved in cleavage activation of H3N2 influenza virusesin vivo.

Les Sentències catòliques del diví poeta Dant (1545) d’en Jaume Ferrer de Blanes: edició crítica del text

Procurador reial i nobiliari, cosmògraf, joier, lapidari, mercader i escriptor, i al capdavall, un ciutadà català honrat, en Ferrer (Vidreres, ~1445 – Blanes, 1529) va marxar de ben jove, primer, a la cort de Nàpols, al servei del rei en Ferran I, i després a la cort de Sicília, al servei de la reina na Joana de Sicília. Acabada aquesta peripècia italiana va tornar a Blanes al servei del vescomte de Cabrera i de Bas fins que va morir a la mateixa vila al 1529. Un seu criat, disset anys més tard, va editar uns papers esparsos que havia trobat a can Ferrer, les (sic) Sentèncias cathòlicas del diví poeta Dant florentí, compilades per lo prudentíssim mossèn Jaume Ferrer de Blanes, incloent-hi tres parts. La primera, Conclusions, és un sumari destinat a mostrar (sic) «Entre totas las cosas necessàries a l’home per aconseguir lo seu fi y beatitut eterna principalment són tres»; la segona, Meditació, és una reflexió a fi d’il•luminar els misteris sobre la passió i mort de Jesucrist a (sic) «lo santíssim loch de Calvari»; la tercera, Letras, és un conjunt de dotze documents, entre cartes i d’altres textos, «fetas a mossèn Jaume Ferrer, respostes e regles per ell ordenades en cosmographia y en art de navegar». En Ferrer, home de grans recursos, fa un recorregut per tots els coneixements que havia acumulat al llarg de la seva vida, de Dant Alighieri a Ptolemeu i del marquès de Santillana a Albert Gran o a Aristòtil, fent servir fragments de la Commedia, dels Proverbios, de la Bíblia i de moltes altres autoritats científiques i filosòfiques, en català, italià, espanyol, llatí i, també, set mots en arameu

Statistical Analysis of an SEIR Epidemic Model

This thesis was focussed on statistical analysis methods and proposes the use of Bayesian inference to extract information contained in experimental data by estimating Ebola model parameters. The model is a system of differential equations expressing the behavior and dynamics of Ebola. Two sets of data (onset and death data) were both used to estimate parameters, which has not been done by previous researchers in (Chowell, 2004). To be able to use both data, a new version of the model has been built. Model parameters have been estimated and then used to calculate the basic reproduction number and to study the disease-free equilibrium. Estimates of the parameters were useful to determine how well the model fits the data and how good estimates were, in terms of the information they provided about the possible relationship between variables. The solution showed that Ebola model fits the observed onset data at 98.95% and the observed death data at 93.6%. Since Bayesian inference can not be performed analytically, the Markov chain Monte Carlo approach has been used to generate samples from the posterior distribution over parameters. Samples have been used to check the accuracy of the model and other characteristics of the target posteriors.