Risk Factors Associated with In-Hospital Mortality for Patients with Acute Abdomen After Cardiac Surgery.

OBJECTIVES: Management of acute abdomen (AA) differs due to the heterogeneity of underlying pathophysiology. Complications of AA and its overall outcome after cardiac surgery are known to be associated with poor results. The aim of this retrospective analysis was to evaluate risk factors for AA in patients undergoing cardiac surgery. METHODS: Between December 2011 and December 2014, a total of 131 patients with AA after cardiac surgery were identified and retrospectively analyzed using our institutional database. Statistical analysis of risk factors concerning in-hospital mortality of mentioned patient cohort was performed using IBM SPSS Statistics. RESULTS: Overall in-hospital mortality was 54.2% (71/131). Analyzing in-hospital non-survivors (NS) versus in-hospital survivors (S) peripheral artery disease (28.2% vs. 11.7%; p = 0.03), the need for assist device therapy (33.8% vs. 16.7%; p = 0.03) and the requirement of hemodialysis (67.6% vs. 23.3%; p < 0.01) were significantly higher in NS. Furthermore, lactic acid values at onset of symptoms were shown to be significantly higher in NS (5.7 ± 5.7 mmol/L vs. 2.8 ± 2.9 mmol/L; p < 0.01). Assured diagnosis of mesenterial ischemia was strongly associated with worse outcome (odds ratio 10.800, 95% confidence interval 2.003-58.224; p = 0.006). CONCLUSION: In conclusion, in critically ill patients after performed cardiac surgery peripheral vascular disease, need for supportive hemodynamic assist device systems and occurrence of renal failure are risk factors associated with worsen outcome. Additionally, rise of lactic acid could potentially be associated with onset of intestinal malperfusion and should be taken into account in therapeutic decisions preventing fatal mesenterial ischemia.

Effects of Natura 2000 on nontarget bird and butterfly species based on citizen science data.

The European Union's Natura 2000 (N2000) is among the largest international networks of protected areas. One of its aims is to secure the status of a predetermined set of (targeted) bird and butterfly species. However, nontarget species may also benefit from N2000. We evaluated how the terrestrial component of this network affects the abundance of nontargeted, more common bird and butterfly species based on data from long-term volunteer-based monitoring programs in 9602 sites for birds and 2001 sites for butterflies. In almost half of the 155 bird species assessed, and particularly among woodland specialists, abundance increased (slope estimates ranged from 0.101 [SD 0.042] to 3.51 [SD 1.30]) as the proportion of landscape covered by N2000 sites increased. This positive relationship existed for 27 of the 104 butterfly species (estimates ranged from 0.382 [SD 0.163] to 4.28 [SD 0.768]), although most butterflies were generalists. For most species, when land-cover covariates were accounted for these positive relationships were not evident, meaning land cover may be a determinant of positive effects of the N2000 network. The increase in abundance as N2000 coverage increased correlated with the specialization index for birds, but not for butterflies. Although the N2000 network supports high abundance of a large spectrum of species, the low number of specialist butterflies with a positive association with the N2000 network shows the need to improve the habitat quality of N2000 sites that could harbor open-land butterfly specialists. For a better understanding of the processes involved, we advocate for standardized collection of data at N2000 sites.

Efectos de Natura 2000 sobre las Especies No Focales de Aves y Mariposas con Base en Datos de Ciencia Ciudadana Resumen La red Natura 2000 (N2000) de la Unión Europea está entre las redes internacionales más grandes de áreas protegidas. Uno de sus objetivos es asegurar el estado de un conjunto predeterminado de especies de aves y mariposas (focales). Sin embargo, las especies no focales también pueden beneficiarse con la N2000. Evaluamos cómo el componente terrestre de esta red afecta la abundancia de las especies de aves y mariposas no focales más comunes con base en los datos de programas de monitoreo voluntario a largo plazo en 9,602 sitios para aves y en 2,001 sitios para mariposas. En casi la mitad de las 155 especies de aves evaluadas, particularmente entre aquellas especies especialistas en zonas boscosas, la abundancia incrementó (los estimaciones de la pendiente variaron desde 0.101 [DS 0.042] hasta 3.51 [DS 1.30]) conforme incrementó la proporción del paisaje cubierto por sitios de la N2000. Esta relación positiva existió en 27 de las 104 especies de mariposas (con una variación de estimaciones desde 0.382 [DS 0.163] hasta 4.28 [DS 0.768]), aunque la mayoría de las especies de mariposas fueron generalistas. Cuando se consideraron las covarianzas de cobertura de suelo estas relaciones positivas no fueron evidentes para la mayoría de las especies, lo que significa que la cobertura de suelo puede ser una determinante de los efectos positivos de la red N2000. El incremento en la abundancia conforme aumentó la cobertura de la N2000 estuvo correlacionado con el índice de especialización de las aves, pero no el de las mariposas. Aunque la red N2000 sostiene la abundancia alta de un espectro amplio de especies, el bajo número de mariposas especialistas con una asociación positiva a la red N2000 demuestra la necesidad de mejorar la calidad del hábitat de los sitios N2000 que podrían albergar a mariposas especialistas de campo abierto. Para un mejor entendimiento de los procesos involucrados, promovemos una recolección estandarizada de datos en los sitios de la red N2000.

Risk factors associated with 30-day mortality for out-of-center ECMO support: experience from the newly launched ECMO retrieval service.

Out-of-hospital extracorporeal membrane oxygenation (ECMO) implantation and ECMO transport have become a growing field useful for emergent treatment of heart or lung failure with increasing number of centers launching such service. This study was designed to present risk factors predicting 30-day mortality for patients receiving ECMO support in a newly launched ECMO retrieval service. From 01/2015 till 01/2017 28 consecutive patients received ECMO support in peripheral hospitals using a miniaturized portable Cardiohelp System® (Maquet, Rastatt Germany) for heart, lung or heart/lung failure as a bridge-to-decision as a part of our newly launched ECMO retrieval service. Outcomes and predictors for 30-day mortality were presented. The mean age was 56 ± 15 (maximum 78) years. The mean ECMO support duration was 97 ± 100 h, whereas 11 patients (40%) were weaned off support and discharged from hospital. Presence of hemolysis (p = 0.041), renal failure (p = 0.016), lower platelet count before ECMO implantation (p = 0.001), and higher lactate 24 h after initiation of support (p = 0.006) were factors associated with 30-day mortality. Initial success of an ECMO retrieval service depends on logistic organization and clinical management. Taking into consideration highly deleterious effects of hemodynamic malperfusion of end organs, rapid initiation of ECMO support is a vital factor for survival. This is highlighted by predictive factors of early mortality that are associated with peripheral organ failure or complications.

French Endocrine Society Guidance on endocrine side effects of immunotherapy.

The management of cancer patients has changed due to the considerably more frequent use of immune checkpoint inhibitors (ICPIs). However, the use of ICPI has a risk of side effects, particularly endocrine toxicity. Since the indications for ICPI are constantly expanding due to their efficacy, it is important that endocrinologists and oncologists know how to look for this type of toxicity and how to treat it when it arises. In view of this, the French Endocrine Society initiated the formulation of a consensus document on ICPI-related endocrine toxicity. In this paper, we will introduce data on the general pathophysiology of endocrine toxicity, and we will then outline expert opinion focusing primarily on methods for screening, management and monitoring for endocrine side effects in patients treated by ICPI. We will then look in turn at endocrinopathies that are induced by ICPI including dysthyroidism, hypophysitis, primary adrenal insufficiency and fulminant diabetes. In each chapter, expert opinion will be given on the diagnosis, management and monitoring for each complication. These expert opinions will also discuss the methodology for categorizing these side effects in oncology using 'common terminology criteria for adverse events' (CTCAE) and the difficulties in applying this to endocrine side effects in the case of these anti-cancer therapies. This is shown in particular by certain recommendations that are used for other side effects (high-dose corticosteroids, contraindicated in ICPI for example) and that cannot be considered as appropriate in the management of endocrine toxicity, as it usually does not require ICPI withdrawal or high-dose glucocorticoid intake.

Adenocarcinoma classification: patterns and prognosis.

Lung cancer is the most frequent human malignancy and the principal cause of cancer-related death worldwide. Adenocarcinoma is now the main histologic type, accounting for almost half of all the cases. The 2015 World Health Organization has adopted the classification recently developed by the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society. This new adenocarcinoma classification has incorporated up-to-date advances in radiological, molecular and oncological knowledge, providing univocal diagnostic criteria and terminology. For resection specimens, new entities have been defined such as adenocarcinoma in situ and minimally invasive adenocarcinoma to designate adenocarcinomas, mostly nonmucinous and ≤ 3 cm in size, with either pure lepidic growth or predominant lepidic growth with ≤ 5 mm invasion, respectively. For invasive adenocarcinoma, the new classification has introduced histological subtyping according to the predominant pattern of growth of the neoplastic cells: lepidic (formerly non mucinous brochioloalveolar adenocarcinoma), acinar, papillary, micropapillary, and solid. Of note, micropapillary pattern is a brand new histologic subtype. In addition, four variants of invasive adenocarcinoma are recognized, namely invasive mucinous (formerly mucinous brochioloalveolar adenocarcinoma), colloid, fetal, and enteric. Importantly, three variants that were considered in the previous classification have been eliminated, specifically mucinous cystadenocarcinoma, signet ring cell, and clear cell adenocarcinoma. This review presents the changes introduced by the current histological classification of lung adenocarcinoma and its prognostic implications.

Efficacy and safety of a T-type calcium channel blocker in patients with neuropathic pain: A proof-of-concept, randomized, double-blind and controlled trial.

BACKGROUND: T-type calcium channels have been shown to play an important role in the initiation and maintenance of neuropathic pain and represent a promising therapeutic target for new analgesic treatments. Ethosuximide (ETX), an anticonvulsant and a T-type channel blocker has shown analgesic effect in several chronic pain models but has not yet been evaluated in patients with neuropathic pain. METHODS: This proof-of-concept, multicentre, double-blind, controlled and randomized trial compared the efficacy and safety of ETX (given as add-on therapy) to an inactive control (IC) in 114 patients with non-diabetic peripheral neuropathic pain. After a 7-day run-in period, eligible patients aged over 18 years were randomly assigned (1:1) to ETX or IC for 6 weeks. The primary outcome was the difference between groups in the pain intensity (% of change from the baseline to end of treatment) assessed in the intention-to-treat population. This study is registered with EudraCT (2013-004801-26) and ClinicalTrials.gov (NCT02100046). RESULTS: The study was stopped during the interim analysis due to the high number of adverse events in the active treatment group. ETX failed to reduce total pain and showed a poor tolerance in comparison to IC. In the per-protocol analysis, ETX significantly reduced pain intensity by 15.6% (95% CI -25.8; -5.4) from baseline compared to IC (-7.8%, 95% CI -14.3; -1.3; p = 0.033), but this result must be interpreted with caution because of a small subgroup of patients. CONCLUSION: Ethosuximide did not reduce the severity of neuropathic pain and induces, at the doses used, many adverse events. SIGNIFICANCE: This article shows that ETX is not effective to treat neuropathic pain. Nevertheless, per-protocol analysis suggests a possible analgesic effect of ETX. Thus, our work adds significant knowledge to preclinical and clinical data on the benefits of T-type calcium channel inhibition for the treatment of neuropathic pain.

Safety of leucodepleted salvaged blood in oncological surgery: an in vitro model.

Intra-operative blood cell salvage (IOCS) is mainly avoided in onco surgery due to the suspicion that it could increase metastasis' risk. We simulated IOCS followed by leucodepletion: HCT116 (human colorectal cancer) cells were inoculated into packed red blood cells units, and their distribution was evaluated, step-by-step, by flow cytometry and immunohistochemistry. Most of HCT116 cells were lost during washing, and almost completely removed after filtration. IOCS plus leucodepletion could be of great advantage for oncological patients, where allogenic blood transfusion could influence tumour progression.

Impact of 2013 ASCO/CAP guidelines on HER2 determination of invasive breast cancer: A single institution experience using frontline dual-color FISH.

PURPOSE: The new ASCO/CAP guidelines published in 2013 (AC2013) significantly modified the scoring criteria for HER2-FISH, introducing the most controversial change to the HER2-equivocal category. We retrospectively evaluated the impact of AC2013 in a cohort of consecutive invasive breast cancers (IBCs) analyzed with frontline dual-color FISH. METHODS: 2788 consecutive IBCs were reclassified based on the AC2013 guidelines. Clinico-pathological features of equivocal IBCs were compared with HER2-negative and HER2-positive IBCs. FISH HER2-equivocal cases underwent reflex tests: HER2-IHC, RARA-FISH, and SMS-FISH. Overall and disease-free survivals were evaluated in AC2007 HER2-positive patients treated with trastuzumab and in patients that became eligible for target-therapy according to AC2013. RESULTS: Two-hundred HER2-negative cases (7.2%) were classified differently, following AC2013: 0.3% (8/2788) became HER2-positive and 6.9% (192/2788) HER2-equivocal. AC2013, compared with AC2007, significantly increased initial HER2-equivocal cases (6.9%vs1.6%, p < 0.001). AC2013 equivocal-IBCs affected older patients and showed pathological features between HER2-negative and HER2-positive IBCs. After reflex tests, 102 of the 190 equivocal cases (53.7%) were reclassified as HER2-positive, 51 (26.8%) as negative and 37 (19.5%) as equivocal. IHC tested negative in 44.7% of cases, whereas SMS-FISH showed the highest percentage of positive results (45.8%). Clinical outcomes showed no statistically significant differences. CONCLUSION: Overall, 80.5% of FISH-equivocal cases were solved with at least one reflex test and 3.6% of patients became AC2013 HER2-positive, therefore eligible for target-therapy, but showed clinical outcomes similar to HER2-positive patients treated with trastuzumab. Our data belittle the clinical impact of AC2013 HER2-equivocal reclassification; further prospective randomized clinical studies are necessary to support these findings.

Optimization of multi-environment trials for genomic selection based on crop models.

KEY MESSAGE: We propose a statistical criterion to optimize multi-environment trials to predict genotype × environment interactions more efficiently, by combining crop growth models and genomic selection models. Genotype × environment interactions (GEI) are common in plant multi-environment trials (METs). In this context, models developed for genomic selection (GS) that refers to the use of genome-wide information for predicting breeding values of selection candidates need to be adapted. One promising way to increase prediction accuracy in various environments is to combine ecophysiological and genetic modelling thanks to crop growth models (CGM) incorporating genetic parameters. The efficiency of this approach relies on the quality of the parameter estimates, which depends on the environments composing this MET used for calibration. The objective of this study was to determine a method to optimize the set of environments composing the MET for estimating genetic parameters in this context. A criterion called OptiMET was defined to this aim, and was evaluated on simulated and real data, with the example of wheat phenology. The MET defined with OptiMET allowed estimating the genetic parameters with lower error, leading to higher QTL detection power and higher prediction accuracies. MET defined with OptiMET was on average more efficient than random MET composed of twice as many environments, in terms of quality of the parameter estimates. OptiMET is thus a valuable tool to determine optimal experimental conditions to best exploit MET and the phenotyping tools that are currently developed.

Post-training Beliefs, Intentions, and Use of Prolonged Exposure Therapy by Clinicians in the Veterans Health Administration.

To examine how changes in beliefs during the training process predict adoption of prolonged exposure therapy (PE) by veterans health administration clinicians who received intensive training in this evidence-based treatment. Participants completed a 4-day PE workshop and received expert consultation as they used PE with two or more training cases. Participants were surveyed prior to the workshop, after the workshop, after case consultation (n = 1.034), and 6 months after training (n = 810). Hierarchical regression was used to assess how pre-training factors, and changes in beliefs during different stages of training incrementally predicted post-training intent to use PE and how many patients clinicians were treating with PE 6 months after training. Post-training intent to use PE was high (mean = 6.2, SD = 0.81 on a 1-7 scale), yet most participants treated only 1 or 2 patients at a time with PE. Pre-training factors predicted intent to use and actual use of PE. Changes in beliefs during the workshop had statistically significant yet modest effects on intent and use of PE. Changes in beliefs during case consultation had substantial effects on intent and actual use of PE. Pre-training factors and changes in beliefs during training (especially during case consultation) influence clinicians' adoption of PE. Use of PE was influenced not only by its perceived clinical advantages/disadvantages, but also by contextual factors (working in a PTSD specialty clinic, perceived control over one's schedule, and ability to promote PE to patients and colleagues).

Viral load strategy: impact on risk behaviour and serocommunication of men who have sex with men in specialized care.

BACKGROUND: Incidence and prevalence of HIV are continuously high in German men, who have sex with men (MSM). Different transmission risk minimizing strategies have been observed. The viral load strategy rates patients unlikely to be sexually infectious if their viral load under effective therapy is stably suppressed during 6 months and no other sexually transmitted infections are present. OBJECTIVES: We aim to objectify the current popularity of the viral load strategy, the adherence to basic conditions and its impact on risk behaviour and serocommunication. Until now, no data on a German sample of HIV-positive MSM in regular specialized outpatient care are available. METHODS: Cross-sectional study with group comparisons between user group and non-user-group of the viral load strategy. Self-report questionnaires were conducted with 269 sexually active German HIV+MSM under effective treatment in specialized outpatient care. Structured interviews gathered additional information about approach to and realization of definite action levels concerning sexual risk behaviour and transmission risk minimizing strategies. RESULTS: Twenty-seven of 269 participants (10%) affirmed knowledge of having an undetectable viral load and stated this to be criteria for unprotected sexual behaviour. This subgroup reported more unprotected insertive (P = 0.018) and receptive anal intercourse (P = 0.042), more anonymous sex partners (P = 0.008) and less consistent safer sex. Analysing serocommunication, less addressing HIV/AIDS in general (P = 0.043) and less disclosing to sex partners (P = 0.023) was found, especially in anonymous settings. Differentiating serocommunication characteristics, a focus on seroguessing was depicted. CONCLUSIONS: The user group of the viral load strategy is small. But a less frequent, more reactive and assumptive serocommunication leads to an imprecise information exchange paired with higher frequency of risky behaviour, especially in anonymous settings, where frank serocommunication is often avoided. The targeted group of the viral load strategy diverges greatly from the user group.

[Enlarged blind spot and reduced visual evoked potentials due to melanocytoma of the optic disc]. / Vergrößerter blinder Fleck und auffällige visuell evozierte Potenziale bei melanozytärem Tumor der Papille.

A 59-year-old male patient presented with clinical characteristics of a melanocytoma of the optic disc in the right eye. Using functional tests, such as visual acuity, visual fields, visual evoked potentials (VEP) and imaging procedures (e.g., fundus photography and spectral domain optical coherence tomography) the findings were documented. Best corrected visual acuity was 25/20 in both eyes. Ophthalmoscopy showed a slightly prominent and pigmented tumor in the upper third of the optic disc. Comparing both eyes, an enlarged blind spot and a reduction of VEP were detectable.

Adverse event potentially due to an interaction between ibrutinib and verapamil: a case report.

WHAT IS KNOWN AND OBJECTIVE: Ibrutinib is a recently approved oral anticancer agent with pharmacokinetics that is very sensitive to metabolic inhibition. We report a serious side effect of ibrutinib potentially attributable to interaction with the moderate CYP3A4 inhibitor verapamil. CASE DESCRIPTION: A patient with mantle cell lymphoma was admitted to our emergency department with severe diarrhoea. During a prescription review, the clinical pharmacist identified a potential drug interaction between ibrutinib and verapamil present in a branded combination product also containing trandolapril. Ibrutinib was discontinued for 5 days, and verapamil was stopped. Lercanidipine 10 mg daily was prescribed as an alternative antihypertensive drug. The patient was discharged after 3 days with symptomatic treatment for his diarrhoea. Three months later, the patient maintained control with ibrutinib and olmesartan, but without verapamil. WHAT IS NEW AND CONCLUSION: This is the first description of a serious side effect of ibrutinib likely due to an interaction with the CYP3A4 inhibitor verapamil. Prescriptions of ibrutinib must be carefully checked to identify possible interactions with CYP3A4 inhibitors and patients monitored accordingly.

Urban mining as a contribution to the resource strategy of the Canton of Zurich.

Urban mining is increasingly being recognised as an important component of resource strategies of public authorities, not only because it contributes to environmental protection, but also because it is a source of valuable recyclable materials. We demonstrate that the sustainable livelihoods (SL) framework can be used for public policy making in waste management by presenting the approach and experiences of a review study termed 'urban mining potential analysis' and its application to antimony, copper, gypsum, gold and rare earth elements. This article uses the rare earth element (REE) group to illustrate and present an overview over information and knowledge gaps concerning urban mining. The analysis shows that rare earth element recycling can be more environmentally friendly than primary production, particularly if the latter comes from countries with weak enforcement of environmental legislation. On the other hand REE recycling often cannot compete with large scale primary production because market prices do not reflect the social and environmental impacts of production, and because the avoided impacts of waste decontamination and reduced waste production are not considered. The urban mining potential analysis can be used to support decision making and the setting of priorities for future research and public action. The findings of the study and expert opinions based thereon contribute to the selection of measures and the formulation of public waste management and resource strategies in general.

Insulin-like growth factor I and risk of epithelial invasive ovarian cancer by tumour characteristics: results from the EPIC cohort.

BACKGROUND: Prospective studies on insulin-like growth factor I (IGF-I) and epithelial ovarian cancer (EOC) risk are inconclusive. Data suggest risk associations vary by tumour characteristics. METHODS: We conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) to evaluate IGF-I concentrations and EOC risk by tumour characteristics (n=565 cases). Multivariable conditional logistic regression models were used to estimate associations. RESULTS: We observed no association between IGF-I and EOC overall or by tumour characteristics. CONCLUSIONS: In the largest prospective study to date was no association between IGF-I and EOC risk. Pre-diagnostic serum IGF-I concentrations may not influence EOC risk.

[Brown, white, beige: the color of fat and new therapeutic perspectives for obesity...]. / Brun, blanc, beige: la couleur du gras et nouvelles perspectives thérapeutiques de l'obésité

Three articles published in the NEJM in 2009 have renewed the interest for brown adipose tissue (BAT) in humans. This review reports interesting new findings on adipocyte cell types that have been presented at the last meeting of the Endocrine Society in Houston, TX, in June 2012. Many studies have focused on identifying factors involved in brown adipocyte lineage, the site of adaptive thermogenesis. Indeed, the role of the transcription factors, such as PRDM16, in brown adipocyte differentiation has been unambiguously established. Very recently, the concept of "beigeing", defined as the occurrence of thermogenic brown adipocytes in white adipose tissue, has emerged, leading to the identification, by Bruce Spiegelman's group, of a new muscular hormone, called irisin, which is able to stimulate the "beigeing". This finding should convey toward the discovery of new mutations involved in the pathogenesis of obesity and lipodystrophies, and should be translated into innovative therapeutic perspectives. Finally, the nature of BAT innervation has been clarified and the presence of an autoregulatory loop between BAT and notably hypothalamic paraventricular nuclei via the sensory and sympathetic nervous systems has been delineated. These feedback circuits appear to be crucial to control BAT thermogenic activity.

[New pathophysiological mechanisms of metabolic syndrome: implication of orphan nuclear receptors?]. / Nouveaux mécanismes physiopathologiques du Syndrome Métabolique: implication des récepteurs nucléaires orphelins?

This review focuses on a number of new data on biology and pathophysiology of the metabolic syndrome (MetS) and the involvement of nuclear receptors that have been presented during the last Endocrine Society meeting, held in Houston in June 2012. Several studies have reported beneficial effects of various orphan nuclear receptors, including SHP (Small Heterodimeric Partner, NR0B2) and LXR (Liver X Receptor, NR1H3 and NR1H2), on various components of MetS. By using an inactivation model of SHP, David Moore has shown that SHP exerts "antidiabetic" effects but associated with hepatic steatosis development. He also showed that DLPC (dilauroyl phosphatidylcholine), an unconventional phospholipid, exhibited anti-diabetic properties through its binding to LRH-1 (Liver Receptor Homolog-1, NR5A2), a molecular partner of SHP. Interestingly, Carolyn Cummins investigated LXR α and ß isoforms knock-out mice and provided experimental evidence for the detailed mechanisms involved in the deleterious metabolic effects of glucocorticoids, pointing out to the functional interaction between LXRß, and the glucocorticoid receptor. These new and original studies open new therapeutic opportunities for the management of metabolic disorders in humans by selective modulators of these receptors.