A high level of lncFGD5-AS1 inhibits epithelial-to-Mesenchymal transition by regulating the miR-196a-5p/SMAD6/BMP axis in gastric Cancer.

BACKGROUND: Long non-coding RNA (lncRNA) was a vital factor in the progression and initiation of human cancers. This study found a new lncRNA, FGD5-AS1, which can inhibit EMT process, proliferation, and metastasis in vitro and in vivo. METHODS: qRT-PCR was employed to test the expression of lncFGD5-AS1 in 30 gastric cancer patients' cancer tissue and para-cancer tissue. Overexpressed lncFGD5-AS1 cells shown sharply decrease of proliferation, migration, and epithelial-mesenchymal transition (EMT). miR-196a-5p/SMAD6 was confirmed as downstream molecular mechanism of lncFGD5-AS1 by expression correlation analysis and mechanism experiments. In vivo study illustrated overexpression of lncFGD5-AS1 suppression tumor growth. RESULTS: LncFGD5-AS1 served as a ceRNA of miR-196a-5p to release its inhibition on SMAD6, a conventional inhibitor on the BMP pathway. Comparing with normal gastric cancer cells, FGD5-AS1 overexpressed group had fewer migration cells, lower cell viability, and lower EMT transformation rate. Meanwhile, xenografts nude mice injecting with overexpressed-FGD5-AS1 cells also shown smaller tumor weight and volume. CONCLUSION: In conclusion, this research supported the first evidence that FGD5-AS1 suppressed proliferation and metastasis in gastric cancer by regulating miR-196a-5p/SMAD6/BMP axis and suggested a potential therapeutic candidate for gastric cancer.

Expression of Cyclin D1 protein in residual tumor after neoadjuvant chemotherapy for breast cancer.

PURPOSE: Hormone receptor (HR)-positive breast cancer (BC) shows a poor response to neoadjuvant chemotherapy (NACT). New treatment targets like the Cyclin D1-CDK4/CDK6 complex are promising adjuvant/post-neoadjuvant therapeutic strategies. Evaluating Cyclin D1 overexpression in residual tumor could recognize those patients that benefit most from such post-neoadjuvant treatment. In this study, we determined Cyclin D1 expression in residual BC after NACT. Secondary aims were to correlate Cyclin D1 expression levels with clinicopathological parameters and to assess its prognostic value after NACT. METHODS: We retrospectively assessed the nuclear expression of Cyclin D1 on tissue microarrays with residual tumor from 284 patients treated in the neoadjuvant GeparTrio (n = 186) and GeparQuattro (n = 98) trials. Evaluation was performed with a standardized immunoreactive score (IRS) after selecting a cut-off value. RESULTS: A high expression level (IRS ≥ 6) of Cyclin D1 was found in 37.3% of the assessed specimens. An increased Cyclin D1 expression was observed in HR-positive tumors, compared to HR-negative tumors (p = 0.02). Low Cyclin D1 levels correlated with clinical tumor stage 1-3 (p = 0.03). Among patients with HR-positive/Her2-negative tumors and high Cyclin D1 expression, a better disease-free survival (DFS) was graphically suggested, but not significant (p = 0.21). CONCLUSION: Our study demonstrates a measurable nuclear expression of Cyclin D1 in post-neoadjuvant residual tumor tissue of HR-positive BC. Cyclin D1 expression was not prognostic for DFS after NACT. Our results and defined cut-off suggest that the marker can be used to stratify tumors according to protein expression levels. Based on this, a prospective evaluation is currently performed in the ongoing Penelope-B trial.

Clinicopathologic and prognostic factors in short- and long-term surviving dogs with protein-losing enteropathy.

INTRODUCTION: The aim of the present study was to investigate the differences in the characteristics of short- and long-term surviving dogs with protein-losing enteropathy (PLE) and to identify factors that predict its outcome. We retrospectively reviewed the medical records of 59 client- owned dogs with PLE diagnosed at three different hospitals between January 2009 and November 2013. The dogs were classified as either short-term (= 6 months; STs) or long-term (> 6 months; LTs) survivors. Clinical and clinicopathological variables were investigated between the groups and receiver operating characteristic (ROC) curve analysis was performed. Nineteen dogs were classified as STs and 40 as LTs. Body weight and blood urea nitrogen concentrations were significantly higher in the STs at diagnosis (P < 0.05). At 1 month after initiation of immunosuppressive therapy (data- driven cut-off, T1), chronic canine enteropathy clinical activity index (CCECAI) scores were higher (P < 0.01) and albumin, serum total protein and total cholesterol concentrations were lower (P < 0.01) in the STs. ROC curve analysis showed that CCECAI > 5 evaluated at T1 was the best predictor of poor outcome. Although the severity of clinical signs and the majority of clinicopathological findings at diagnosis did not influence the outcome, survival time was shorter in the dogs with high CCECAI scores at T1 and which did not respond to therapy.

INTRODUCTION: Le présent travail avait pour buts d'étudier quels sont les différences de symptômes chez les chiens survivant à court et à long terme à une d'entéropathie exsudative (PLE) et d'identifier les facteurs ayant une valeur pronostique. On a étudié pour cela les dossiers médicaux de 59 chiens sur lesquels une entéropathie exsudative avait été diagnostiquée dans trois cliniques différentes entre janvier 2009 et novembre 2013. Les chiens ont été classés comme survivants à court terme (= 6 mois; STs) respectivement à long terme (= 6 mois; LTs). Les variations cliniques et clinico-pathologiques entre les groupes ont été relevées et une courbe ROC a été établie. Dixneuf chiens ont été classés comme STs et 40 comme LTs. Le poids corporel et la concentration sanguine d'urée était significativement plus élevée (P < 0.05) chez les STs que chez les LTs. Un mois après le début d'une immunosuppression (cut-off établi sur la base des données disponibles, T1), le score clinique d'activité pour une entéropathie chronique chez le chien (CCEAI) était plus élevé chez les STs que chez les LTs(P < 0.01), les valeur sanguines d'albumine, de protéines totales et de cholestérine totale par contre plus basses (P < 0.01). Dans l'analyse par la courbe ROC, un CCEAI > 5 à T1 s'est avéré être un indice fiable quant à une évolution de courte ou de longue durée. Bien que l'étendue des symptômes cliniques et la quantité des découvertes clinico-pathologiques n'aient pas influencé le pronostic, le taux de survie des chiens avec un CCEAI élevé à T1 et de ceux qui n'avaient pas répondu au traitement a été plus faible.

[What happens to children and adolescents with mental disorders? Findings from long-term outcome research]. / Was wird aus Kindern und Jugendlichen mit psychischen Störungen?

Research on the long-term outcome of mental disorders originating in childhood and adolescence is an important part of developmental psychopathology. After a brief sketch of relevant terms of outcome research, the first part of this review reports findings based on heterotypic cohort studies. The major second part of this review presents findings based on long-term outcome studies dealing with homotypic diagnostic groups. In particular, the review focuses on the course and prognosis of ADHD, anxiety disorders, depression, conduct disorders, eating disorders, autism spectrum disorders, schizophrenia, and selective mutism. Findings mainly support the vulnerability hypothesis regarding mental disorders with early manifestation in childhood and adolescence as frequent precursors of mental disorders in adulthood. The discussion focuses on the impact of early manifesting disorders in the frame of general mental morbidity and of the effect of interventions, which is not yet sufficiently discernible.

Individuals With Higher CD4/CD8 Ratio Exhibit Increased Risk of Acute Respiratory Distress Syndrome and In-Hospital Mortality During Acute SARS-CoV-2 Infection.

Background: CD4/CD8 ratio has been used as a quantitative prognostic risk factor in patients with viral infections. This study aims to assess the association between in-hospital mortality and at admission CD4/CD8 ratio among individuals with acute SARS-CoV-2 infection. Methods: This is a longitudinal cohort study with data of all consecutive patients admitted to the COVID-19 unit at Hospital del Mar, Barcelona, Spain for ≥48 h between March to May 2020. The CD4+ CD8+ T-cell subset differentiation was assessed by flow cytometry at admission as well as a complete blood test. Patients were classified according to CD4/CD8 ratio tertiles. The primary outcome was in-hospital mortality and the secondary outcome was acute respiratory distress (ARDS). Results: A total of 338 patients were included in the cohort. A high CD4/CD8 ratio (third tertile) was associated with a higher in-hospital mortality [adjusted Cox model hazard ratio (HR) 4.68 (95%CI 1.56-14.04, p = 0.006), reference: second tertile HR 1]. Similarly, a high CD4/CD8 ratio (third tertile) was associated with a higher incidence of ARDS [adjusted logistic regression model OR 1.97 (95%CI 1.11-3.55, p = 0.022) reference: second tertile HR 1]. There was a trend of higher in-hospital mortality and incidence of ARDS in patients within the first tertile of CD4/CD8 ratio compared with the second one, but the difference was not significant. No associations were found with total lymphocyte count or inflammatory parameters, including D-dimer. Conclusion: CD4/CD8 ratio is a prognostic factor for the severity of COVID-19, reflecting the negative impact on prognosis of those individuals whose immune response has abnormal CD8+ T-cell expansion during the early response to the infection.

[Metabolic Tumor Imaging in Head and Neck Oncology]. / Metabolische Tumorbildgebung bei muskosalen Kopf- und Hals-Karzinomen.

Metabolic Tumor Imaging in Head and Neck Oncology Abstract. Fluorodeoxyglucose with position emission tomography combined with CT or MRI (FDG-PET) has become an important diagnostic and staging method in head and neck squamous cell carcinoma. Some regard FDG-PET merely as a tool able of displaying cancer cells as bright spots on imaging. However, quantification of FDG uptake can be used as a surrogate marker for tumor aggressiveness and predict tumor response before (chemo)-radiation. The FDG uptake of the primary tumor can also predict surgical outcome measures such as depth of invasion, occult nodal metastasis, or bone invasion for oral cancer and/or organ preservation in hypopharyngeal cancer.

Development of childhood asthma prediction models using machine learning approaches.

BACKGROUND: Respiratory symptoms are common in early life and often transient. It is difficult to identify in which children these will persist and result in asthma. Machine learning (ML) approaches have the potential for better predictive performance and generalisability over existing childhood asthma prediction models. This study applied ML approaches to predict school-age asthma (age 10) in early life (Childhood Asthma Prediction in Early life, CAPE model) and at preschool age (Childhood Asthma Prediction at Preschool age, CAPP model). METHODS: Clinical and environmental exposure data was collected from children enrolled in the Isle of Wight Birth Cohort (N = 1368, ∼15% asthma prevalence). Recursive Feature Elimination (RFE) identified an optimal subset of features predictive of school-age asthma for each model. Seven state-of-the-art ML classification algorithms were used to develop prognostic models. Training was performed by applying fivefold cross-validation, imputation, and resampling. Predictive performance was evaluated on the test set. Models were further externally validated in the Manchester Asthma and Allergy Study (MAAS) cohort. RESULTS: RFE identified eight and twelve predictors for the CAPE and CAPP models, respectively. Support Vector Machine (SVM) algorithms provided the best performance for both the CAPE (area under the receiver operating characteristic curve, AUC = 0.71) and CAPP (AUC = 0.82) models. Both models demonstrated good generalisability in MAAS (CAPE 8-year = 0.71, 11-year = 0.71, CAPP 8-year = 0.83, 11-year = 0.79) and excellent sensitivity to predict a subgroup of persistent wheezers. CONCLUSION: Using ML approaches improved upon the predictive performance of existing regression-based models, with good generalisability and ability to rule in asthma and predict persistent wheeze.

Rac3 Expression and its Clinicopathological Significance in Patients With Bladder Cancer.

Background: Ras-related C3 botulinum toxin substrate 3 (Rac3) is overexpressed in malignancies and promotes tumor progression. However, the correlations between Rac3 expression and the clinicopathological characteristics and prognoses of patients with bladder cancer (BC) remain unclear. Methods: Data from The Cancer Genome Atlas (TCGA) were used to analyze Rac3 expression in BC and normal bladder tissues and validated using the Oncomine database, quantitative real-time PCR (qRT-PCR) and western blot. The Kaplan-Meier method was used to analyze the relationship between Rac3 expression and the prognosis of patients with BC. Cox univariate and multivariate analyses of BC patients overall survival (OS) were performed. Signaling pathways that potentially mediate Rac3 activity in BC were then analyzed by gene set enrichment analysis (GSEA). Results: The Rac3 expression in BC tissues was significantly higher than that in normal bladder tissues. Rac3 expression was significantly correlated with grade and stage. Overexpression of Rac3 was associated with a poor prognosis. GSEA showed that the cell cycle, DNA replication, p53 signaling pathway and mismatch repair were differentially enriched in the high Rac3 expression phenotype. The qRT-PCR and western blot results confirmed that the Rac3 expression in BC tissues was higher than that in normal bladder tissues. Conclusion: Rac3 is highly expressed in BC, which is related to the advanced clinicopathological variables and adverse prognosis of patients with BC. These results provide a new therapeutic target for BC.

[Communicating Prognosis and Expectations in Advanced Disease - A Balancing Act in Practice]. / Kommunikation von Prognose und Erwartungen bei fortgeschrittenen Erkrankungen ­ eine Gratwanderung in der Praxis.

Communicating Prognosis and Expectations in Advanced Disease - A Balancing Act in Practice Abstract. To prepare the end of life, to plan important things, to spend the remaining time of life not only with medical treatments, but to live - these are frequently expressed wishes of people with progressive diseases. Prognostic statements are feared by professionals. At the same time, when talking about what lies ahead for those affected, professionals very often make over-optimistic promises. A broader definition of the term prognosis as well as a careful handling of expectations can help to define realistic goals together.

'I Don't Have a Crystal Ball' - Why Do Doctors Tend to Avoid Prognostication?

Uncertainty, fear to harm the patient, discomfort handling the discussion and lack of time are the most cited barriers to prognostic disclosure. Physicians can be reassured that patients desire the truth about prognosis and can manage the discussion without harm, including the uncertainty of the information, if approached in a sensitive manner. Conversational guides could provide support in preparing such difficult conversations. Communicating 'with realism and hope' is possible, and anxiety is normal for both patients and clinicians during prognostic disclosure. As a clinician pointed out: 'I had asked a mentor once if it ever got easier. - No. But you get better at it.'

Prognostic value of main pulmonary artery diameter to ascending aorta diameter ratio in patients with advanced heart failure.

OBJECTIVES AND BACKGROUND: In this study we assessed the prognostic value of main pulmonary artery diameter and its ratio to ascending aorta diameter (P/Ao ratio) in advanced heart failure patients. METHODS: Patients with advanced heart failure who were candidates for heart transplantation were retrospectively evaluated. The clinical information, cardiac catheterisation results, and computed tomography images were gathered from institutional database system. The observed and predicted probabilities for survival were analysed in a nomogram. RESULTS: The P/Ao ratio was found to be a strong predictor for MACE both in traditional multivariable Cox proportional hazard regression modelling (increase in P/Ao ratio per 2 SD, HR:2.72, 95% CI 1.14-6.48, p = 0.024) and ridge regression analysis (increase in P/Ao ratio per 2SD, HR:3.45, 95% CI 1.53-7.74, p = 0.003). Prediction model showed statistically significant correlation between the observed and predicted probabilities for 1-year survival. CONCLUSION: In patients with advanced heart failure, computed tomography derived P/Ao ratio might be a prognostic predictor during follow up.

Two-Year Outcome From Combining Cryoballoon Ablation and Left Atrial Appendage Closure: CLACBAC Study.

Objective: Catheter ablation combined with left atrial appendage closure (LAAC) has emerged as a promising strategy for atrial fibrillation (AF) patients at high risk for stroke or with contraindications for oral anticoagulants (OACs). But the evidence for the long-term safety and efficacy of a combined procedure using cryoballoon ablation (CBA) with LAAC is still insufficient. Methods: From October 2015 to December 2017, a total of 76 consecutive non-valvular, drug-refractory AF patients who underwent a combined procedure of CBA and LAAC are included. Peri- and post-procedural safety and efficacy were evaluated through scheduled follow-ups and transesophageal echocardiography (TEE). Results: A total of 74 patients (97.4%) underwent the combined procedure and achieved instant pulmonary vein isolation and satisfactory LAAC. With a mean follow-up time of 23.7 ± 11.0 months, the recurrence of atrial arrhythmia was recorded in 35 patients (48.0%). In addition, a survival analysis shows a non-significant higher recurrence in persistent AF (p = 0.48). The overall OAC withdrawal rate was 97.2%, and one patient (1.4%) had a lethal hemorrhagic stroke while on single antiplatelet therapy. For safety concerns, the overall mortality was 2.7%, which resulted from one case of myocardial infarction on OAC and one hemorrhagic stroke, as mentioned. No other major hemorrhagic events occurred. Among the 72 patients (94.7%) who underwent TEE, one patient (1.4%) had device-related thrombosis and one patient (1.4%) had prominent residual flow (over 3 mm). Both were prescribed long-term OACs without severe complications occurring. Conclusions: Combining CBA with LAAC in a single procedure achieved considerable long-term safety and efficacy, providing a promising strategy for AF management.

Stadien des Prostatakarzinoms und Unmet Medical Need.

Männer mit Prostatakarzinom haben eine gute Prognose, wenn die Erkrankung in einem frühen Stadium erkannt und behandelt wird. In späteren Stadien steigt das Progressions- und Mortalitätsrisiko hingegen deutlich. Das gilt auch für das nicht-metastasierte kastrationsresistente Prostatakarzinom (M0CRPC, nm-CRPC), bei dem das Progressionsrisiko insbesondere bei kurzer PSA-Verdopplungszeit deutlich erhöht ist. Für entsprechende Patienten gab es lange - außer der klassischen Androgendeprivation - keine Therapieoptionen.

Diabetes care in figures: current pitfalls and future scenario.

Diabetes mellitus (DM) epidemic-on a global scale-is a major and snowballing threat to public health, healthcare systems and economy, due to the cascade of pathologies triggered in a long-term manner after the DM manifestation. There are remarkable differences in the geographic disease spread and acceleration of an increasing DM prevalence recorded. Specifically, the highest initial prevalence of DM was recorded in the Eastern-Mediterranean region in 1980 followed by the highest acceleration of the epidemic characterised by 0.23% of an annual increase resulted in 2.3 times higher prevalence in the year 2014. In contrast, while the European region in 1980 demonstrated the second highest prevalence, the DM epidemic developments were kept much better under control compared to all other regions in the world. Although both non-modifiable and modifiable risk factors play a role in DM predisposition, cross-sectional investigations recently conducted amongst elderly individuals demonstrate that ageing as a non-modifiable risk factor is directly linked to unhealthy lifestyle as a well-acknowledged modifiable risk factor which, in turn, may strongly promote ageing process related to DM even in young populations. Consequently, specifically modifiable risk factors should receive a particular attention in the context of currently observed DM epidemic prognosed to expand significantly over 600 million of diabetes-diseased people by the year 2045. The article analyses demographic profiles of DM patient cohorts as well as the economic component of the DM-related crisis and provides prognosis for future scenarios on a global scale. The innovative approach by predictive diagnostics, targeted prevention and treatments tailored to the person in a suboptimal health condition (before clinical onset of the disease), as the medicine of the future is the most prominent option to reverse currently persisting disastrous trends in diabetes care. The key role of biomedical sciences in the future developments of diabetes care is discussed.

Colloid (mucinous non-cystic) carcinoma of the pancreas: A case report.

Colloid carcinoma (CC) of the pancreas, also known as mucinous non-cystic carcinoma, is a rare histological variant of pancreatic cancer. The present study reports the case of a 65-year-old male with a pancreatic head tumor 4.6×3.1 cm in size. The tumor had not invaded the superior mesenteric or celiac arteries. Laboratory data showed elevated alkaline phosphatase, γ-gluytamyl transpeptidase and cancer antigen 19-9 (CA19-9) levels. The patient underwent a pancreaticoduodenectomy (PD), and the pathology revealed CC extending to the submucosa of the duodenum, with mild atypical hyperplasia of the pancreatic duct. The patient was negative for circulating tumor cells, indicating a good prognosis. The CA19-9 concentration decreased to within the normal range following surgery. The present study reports a rare case of CC of the pancreas presenting with obstructive jaundice, in which a PD procedure was performed. Primary surgical treatment with curative intent is the optimal management and this subtype of pancreatic cancer is associated with a better prognosis compared with pancreatic ductal adenocarcinoma.

[Follow-up care of patients after heart attack]. / Nachsorge von Herzinfarktpatienten in der Hausarztpraxis.

Survivors of a myocardial infarction are at increased risk for future cardiac events, including recurrent infarction, heart failure, arrhythmia, stroke, and sudden cardiac death. The primary care physician needs to be aware of the potential risks and complications facing these patients. Secondary preventive measures after myocardial infarction include an optimal medical therapy (dual antiplatelet therapy, Statin, ACE-inhibitor, and in most cases a beta-blocker) and life style modifications (quit smoking, regular physical activity, Mediterranean-style diet). Patients should be informed about how to recognize and react to cardiac symptoms.

Acuracidade da distribuição diamétrica entre métodos de projeção em Floresta Ombrófila Mista / Accuracy of the diameter distribution of projection methods in Araucaria's Forest

O estudo tem como objetivo avaliar a acuracidade das projeções diamétricas em uma Floresta Ombrófila Mista, empregando os modelos da Matriz de Transição e Razão de Movimentação, aplicados em três amplitudes temporais (2, 3 e 4 anos), sendo utilizados duas amplitudes de classes diamétricas (5 e 10cm). Os dados utilizados no estudo são oriundos de parcelas permanentes instaladas na Floresta Nacional de São Francisco de Paula - RS. A eficiência das projeções foi verificada com base nos valores observados, adotando-se os testes de Kolmogorov Smirnov e a análise de variância. Embora tenham sido influenciadas pelas Propriedades Markovianas, as projeções realizadas mostraram eficiência para descrever a estrutura futura da floresta, sendo o modelo da Razão de Movimentação o que gerou as projeções mais eficientes se comparada às projeções da Matriz de Transição. A amplitude temporal de 4 anos, associada à amplitude de classe diamétrica de 5cm, apresentou o resultado mais acurado do estudo, superestimando em 1,7% o número total de indivíduos da floresta.

This study aims to evaluate accuracy of projections in diametric Araucaria Forest, using models of the transition matrix and movement ratio, applied in three temporal amplitude (2, 3 and 4 years), and two employees amplitudes diameter classes (5 and 10cm). The information used in the study are from permanent plots established in the National Forest of São Francisco de Paula - RS. The efficiency of the projections was verified based on observed values, using Kolmogorov Smirnov test and analysis of variance. Although they have been influenced by the Markovian properties, projections carried out showed efficiency to describe the future structure of the forest, but the model the movement ratio projections generated more efficient compared to those described by the transition matrix. The time span of 4 years applied the range of 5cm diameter class had the most accurate results of the study overestimated by 1.7% the total number of individuals in the forest.