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! # Ola via Alexandros G.Sfakianakis on Inoreader

Τετάρτη, 14 Ιουνίου 2017

Protocol for the development of a Core Outcome Set (COS) for hemorrhoidal disease: an international Delphi study

Abstract

Purpose

Over the last decade, many studies were performed regarding treatment options for hemorrhoidal disease. Randomised controlled trials (RCTs) should have well-defined primary and secondary outcomes. However, the reported outcome measures are numerous and diverse. The heterogeneity of outcome definition in clinical trials limits transparency and paves the way for bias. The development of a core outcome set (COS) helps minimizing this problem. A COS is an agreed minimum set of outcomes that should be measured and reported in all clinical trials of a specific disease. The aim of this project is to generate a COS regarding the outcome of treatment after hemorrhoidal disease.

Methods

A Delphi study will be performed by an international steering group healthcare professionals and patients with the intention to create a standard outcome set for future clinical trials for the treatment of hemorrhoidal disease. First, a literature review will be conducted to establish which outcomes are used in clinical trials for hemorrhoidal disease. Secondly, both healthcare professionals and patients will participate in several consecutive rounds of online questionnaires and a face-to-face meeting to refine the content of the COS.

Discussion

Development of a COS for hemorrhoidal disease defines a minimum outcome-reporting standard and will improve the quality of research in the future.



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Variation in Pediatric Post-Ablation Care: A Survey of the Pediatric and Congenital Electrophysiology Society (PACES)

Abstract

Although catheter ablation is a standard treatment for pediatric arrhythmias, there are no consensus guidelines for follow-up care. This study describes the variation in post-ablation practices identified through a survey of the pediatric and congenital electrophysiology society (PACES). Pediatric and congenital electrophysiology society members were invited to participate in an online survey of post-ablation practices in September 2014. Survey questions targeted routine post-ablation practices for three common arrhythmia substrates: atrioventricular nodal reentry tachycardia, concealed accessory pathways (AP), and manifest APs. Significant practice variation was defined as <90% concordance among respondents. There were 70 respondents from 67 centers, 29 (41%) in practice for <10 years. Uniform practices included aspirin after left side ablation by 65 (93%), immediate post-procedure ECG by 63 (90%), and performance of outpatient follow-up in 69 (99%) including ECG in 97–100% depending on substrate. The majority, 57 (81%), have standardized follow-up independent of substrate. Post-procedural observation is highly variable, with 25 (36%) discharging patients on the day of ablation, 22 (33%) observing patients in hospital overnight, and 21 (30%) basing hospitalization on pre-defined criteria. Immediate post-procedure echo is performed after all ablations in only 16 (23%). Discharge from outpatient care occurs at a median time of 12 months for each arrhythmia substrate. Common post-ablation practices are evident among pediatric electrophysiologists. However, they report significant variation in post-procedure monitoring practices and testing. The rationale for these variances, and their impact on costs and outcomes, should be defined.



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Impact of tissue adhesives on the prevention of anastomotic leakage of colonic anastomoses: an in vivo study

Abstract

Background

Tissue adhesives (TA) may be useful to strengthen colorectal anastomoses, thereby preventing anastomotic leakage (AL). Previous studies have identified cyanoacrylate (CA) TAs as the most promising colonic anastomotic sealants. This study investigates the protective effects of sealing colonic anastomoses with various CAs.

Materials and methods

Fifty-five Wistar rats underwent laparotomy and transection of the proximal colon. An anastomosis was created with 4 interrupted sutures followed by either application of Histoacryl Flexible, Omnex, Glubran 2, or no TA seal. An additional control group was included with a 12-suture anastomosis and no TA seal. After 7 days, the rats were sacrificed and scored for the presence of AL as the main outcome. Secondary outcomes were the occurrence of bowel obstruction, adhesions, and anastomotic bursting pressure. Histological evaluation was performed.

Results

The highest AL rate was found in the Glubran 2 group (7/11), followed by the 4-sutures group without TA (5/11), and the Omnex group (5/11). Histoacryl Flexible showed the lowest AL rate (2/11). In the control group, only one rat showed signs of AL. Histologically, the highest influx of inflammatory cells was found in the 4-suture group without TA and for Omnex and Glubran 2. Histoacryl Flexible caused more mature collagen deposition when compared to the other TA groups.

Conclusions

Histoacryl Flexible showed the lowest leakage rate compared to the other TA groups and to the 4-suture control group. Glubran 2 showed the highest AL rate and a high inflammatory response. Histoacryl Flexible was associated with the presence of more mature collagen and seems to promote anastomotic healing.



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Study protocol on the role of intestinal microbiota in colorectal cancer treatment: a pathway to personalized medicine 2.0

Abstract

Purpose

Investigate in patients with metastatic and/or irresectable colorectal cancer treated with systemic treatment with capecitabine or TAS-102 whether:

  1. Intestinal microbiota composition can act as a predictor for response.

  2. Intestinal microbiota composition changes during systemic treatment and its relation to chemotoxicity.

Background

Gut microbiota and host determinants evolve in symbiotic and dependent relationships resulting in a personal ecosystem. In vitro studies showed prolonged and increased response to 5-fluorouracil, a fluoropyrimidine, in the presence of a favorable microbiota composition. Capecitabine and TAS-102 are both fluoropyrimidines used for systemic treatment in colorectal cancer patients.

Methods

An explorative prospective multicenter cohort study in the Maastricht University Medical Centre+ and Zuyderland Medical Centre will be performed in 66 patients. Before, during, and after three cycles of systemic treatment with capecitabine or TAS-102, fecal samples and questionnaires (concerning compliance and chemotoxicity) will be collected. The response will be measured by CT/MRI using RECIST-criteria. Fecal microbiota composition will be analyzed with 16S rRNA next-generation sequencing. The absolute bacterial abundance will be assessed with quantitative polymerase chain reaction. Multivariate analysis will be used for statistical analysis.

Conclusions

We aim to detect a microbiota composition that predicts if patients with metastatic and/or irresectable colorectal cancer will respond to systemic treatment and/or experience zero to limited chemotoxicity. If we are able to identify a favorable microbiota composition, fecal microbiota transplantation might be the low-burden alternative to chemotherapy switch in the future.



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Colorectal surgery and surgical site infection: is a change of attitude necessary?

Abstract

Introduction

Surgical site infection (SSI) can be as high as 30% in patients undergoing colorectal surgery and is associated with an increase in morbidity and mortality. The aim of this study is to evaluate the impact of a set of simple preventive measures that have resulted in a reduction in surgical site infection in colorectal surgery.

Applied method

Prospective study with two groups of patients treated in the colorectal unit of the "Clinico Universitario Lozano Blesa" hospital in Zaragoza. One group was subject to our measures from February to May 2015. The control group was given conventional treatment within a time period of 3 months before the set of measures were implemented.

Results

One hundred forty-nine patients underwent a major colorectal surgical procedure. Seventy (47%) belonged to the control group and were compared to the remaining 79 patients (53% of the total), who were subject to our treatment bundle in the period tested. Comparing the two groups revealed that our set of measures led to a general reduction in SSI (31.4 vs. 13.6%, p = 0.010) and in superficial site infection (17.1 vs. 2.5%, p = 0.002). As a consequence, the postoperative hospital stay was shortened (10.0 vs. 8.0 days, p = 0.048). However, it did not, the number of readmissions nor the re-operation rate. SSI was clearly related to open surgery.

Conclusions

The preventive set of measures applied in colorectal surgery led to a significant reduction of the SSI and of the length of hospital stay.



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Percutaneous endoscopic sigmoidopexy using T-fasteners for management of sigmoid volvulus

Abstract

Background

Sigmoid volvulus (SV) is the third leading cause of large bowel obstruction after colonic neoplasms and diverticular disease. SV has traditionally been managed via endoscopic detorsion and decompression followed by non-emergent surgical resection owing to the high risk of recurrence. Most cases of SV occur in elderly debilitated patients with multiple comorbidities and may not be candidates for surgical resection. Endoscopic sigmoidopexy has been described as an alternative to surgical resection. Here, we describe our experience with endoscopic sigmoidopexy using T-fasteners.

Methods

Three patients with recurrent SV that were identified as poor surgical candidates by our colorectal surgery team underwent endoscopic sigmoidopexy. The patients received preoperative bowel preparation. A colonoscope was inserted and the site of the volvulus was visualized and assessed for adequate decompression. Subsequently, four points of fixation were identified and T-fasteners were deployed.

Results

Two patients underwent successful sigmoidopexy without any complications or recurrence on follow-up. One patient developed post procedure pneumoperitoneum that was successfully treated conservatively; however, he passed away from their underlying comorbidities.

Conclusion

Overall, preliminary results for sigmoidopexy using T-fasteners have been promising, offering a potential option to prevent recurrence in high risk patients unsuitable for surgical intervention.



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Progastrin: a potential predictive marker of liver metastasis in colorectal cancer

Abstract

Background and aims

Staging of colorectal cancer often fails to discriminate outcomes of patients with morphologically similar tumours that exhibit different clinical behaviours. Data from several studies suggest that the gastrin family of growth factors potentiates colorectal cancer tumourigenesis. The aim of this study was to investigate whether progastrin expression may predict clinical outcome in colorectal cancer.

Methods

Patients with colorectal adenocarcinoma of identical depth of invasion who had not received neoadjuvant therapy were included. The patients either had stage IIa disease with greater than 3-year disease-free survival without adjuvant therapy or stage IV disease with liver metastases on staging CT. Progastrin expression in tumour sections was scored with reference to the intensity and area of immunohistochemical staining.

Results

Progastrin expression by stage IV tumours was significantly greater than stage IIa tumours with mean progastrin immunopositivity scores of 2.1 ± 0.2 versus 0.5 ± 0.2, respectively (P < 0.001).

Conclusions

This is the first study to show that progastrin expression may be predictive of aggressive tumour behaviour in patients with colorectal cancer and supports its clinical relevance and potential use as a biomarker.



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Familial hypocalciuric hypercalcemia type 1 due to a novel homozygous mutation of the calcium-sensing receptor gene



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Administration of Exogenous Melatonin After the Onset of Systemic Inflammation Is Hardly Beneficial

Abstract

Melatonin improves survival and functional impairment including hemolysis, thrombocytopenia, and hypotension when administered in a prophylactic manner or early after initiation of sepsis or endotoxemia. In the present study, melatonin was given not before first symptoms of systemic inflammation became manifest. Lipopolysaccharide was infused at a rate of 0.5 mg/kg × h to induce systemic inflammation in male Wistar rats. Melatonin (single dose 3 mg/kg × 15 min) was intravenously administered 180 and 270 min after starting of the lipopolysaccharide infusion. Systemic and vital parameters (e.g., systemic blood pressure and breathing rate) as well as blood and plasma parameters (acid-base parameters; electrolytes; parameters of tissue injury such as glucose concentration, lactate concentration, hemolysis, and aminotransferase activities; parameters of thromboelastometry; and platelet count) were determined in regular intervals. Infusion of lipopolysaccharide led to characteristic symptoms of severe systemic inflammation including hypotension, metabolic acidosis and hypoglycemia, electrolyte and hemostatic disturbances, thrombocytopenia, and hemolysis. Melatonin neither decreased mortality nor reduced lipopolysaccharide-dependent changes to vital, blood, and plasma parameters. Even though melatonin may have a beneficial effect in early stages of systemic inflammation, it can hardly be an option in therapy of manifest sepsis or endotoxemia in an intensive care unit.



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A phase Ib study of everolimus combined with metformin for patients with advanced cancer

Summary

Background The efficacy to monotherapy with the mTOR inhibitor everolimus in advanced cancer is often limited due to therapy resistance. Combining everolimus with metformin may decrease the chance of therapy resistance. Methods Patients received everolimus and metformin in a 3 + 3 dose-escalation scheme. Objectives were to determine the dose-limiting toxicities (DLTs), maximum tolerated dose, toxic effects, pharmacokinetics and anti-tumour efficacy. Results 9 patients received study treatment for a median duration of 48 days (range: 4–78). 6 patients discontinued due to toxicity and 3 patients because of progressive disease. At the starting dose level of 10 mg everolimus qd and 500 mg metformin bid, 3 out of 5 patients experienced a DLT. After de-escalation to 5 mg everolimus qd and 500 mg metformin bid, considerable toxicity was still observed and patient enrollment was terminated. In pharmacokinetic analyses, metformin was eliminated slower when co-administered with everolimus than as single-agent. After 9 weeks of treatment, 3 patients were still on study and all had stable disease. Conclusion The combination of everolimus and metformin is poorly tolerated in patients with advanced cancer. The pharmacokinetic interaction between everolimus and metformin may have implications for diabetic cancer patients that are treated with these drugs. Our results advocate for future clinical trials with combinations of other mTOR inhibitors and biguanides.



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Demonstration that a Klebsiella pneumoniae subsp. pneumoniae isolated from an insect ( Nezara viridula ) harbors a plasmid-borne type IV secretion system

Abstract

Previously, we reported the isolation of Klebsiella pneumoniae subspecies pneumoniae strain Kp 5-1 from a southern green stink bug (Nezara viridula) that is a significant pest of numerous economically important crops. We subsequently sequenced the strains whole genome. Here, we report the presence of a functional plasmid-borne type IV secretion (TFSS) system that was identified using genomic mining of the annotated genome. Comparison of the Kp 5-1 resident 186 kb plasmid (pKp 5-1) with nine other Klebsiella with plasmids of comparable size from clinical and environmental strains revealed putative TFSS with identities ranging from 70 to 99%. A primer set was designed at the pKp 5-1 region that shared homology with traC of the conjugation capable F-plasmid. The 2.4 kb amplified PCR product was cloned, sequenced, and used in hybridization experiments verify that the predicted gene was extra-chromosomally located. Based on biparental mating experimental results, a K. pneumoniae Kp 5-1 derivative transformed with the non-self-transmissible pMMB207αβ (an IncQ RSF1010 derivative) mobilized the vector into the parental strain with transfer frequencies of 10−3 transconjugants/donor. Identification of a TFSS in strain Kp 5-1 is significant since in other systems the mobilization capacity is involved in dissemination of plasmids that may confer antibiotic resistance and/or the delivery of virulence proteins into host cells, and thus may have an important role in the fitness of this strain as well. This is the first report that both compared and demonstrated functionality of a plasmid-harbored TFSS in a K. pneumoniae isolated from a N. viridula.



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A phase Ib study of everolimus combined with metformin for patients with advanced cancer

Summary

Background The efficacy to monotherapy with the mTOR inhibitor everolimus in advanced cancer is often limited due to therapy resistance. Combining everolimus with metformin may decrease the chance of therapy resistance. Methods Patients received everolimus and metformin in a 3 + 3 dose-escalation scheme. Objectives were to determine the dose-limiting toxicities (DLTs), maximum tolerated dose, toxic effects, pharmacokinetics and anti-tumour efficacy. Results 9 patients received study treatment for a median duration of 48 days (range: 4–78). 6 patients discontinued due to toxicity and 3 patients because of progressive disease. At the starting dose level of 10 mg everolimus qd and 500 mg metformin bid, 3 out of 5 patients experienced a DLT. After de-escalation to 5 mg everolimus qd and 500 mg metformin bid, considerable toxicity was still observed and patient enrollment was terminated. In pharmacokinetic analyses, metformin was eliminated slower when co-administered with everolimus than as single-agent. After 9 weeks of treatment, 3 patients were still on study and all had stable disease. Conclusion The combination of everolimus and metformin is poorly tolerated in patients with advanced cancer. The pharmacokinetic interaction between everolimus and metformin may have implications for diabetic cancer patients that are treated with these drugs. Our results advocate for future clinical trials with combinations of other mTOR inhibitors and biguanides.



http://ift.tt/2rj9XuX

Liver segmentation: indications, techniques and future directions

Abstract

Objectives

Liver volumetry has emerged as an important tool in clinical practice. Liver volume is assessed primarily via organ segmentation of computed tomography (CT) and magnetic resonance imaging (MRI) images. The goal of this paper is to provide an accessible overview of liver segmentation targeted at radiologists and other healthcare professionals.

Methods

Using images from CT and MRI, this paper reviews the indications for liver segmentation, technical approaches used in segmentation software and the developing roles of liver segmentation in clinical practice.

Results

Liver segmentation for volumetric assessment is indicated prior to major hepatectomy, portal vein embolisation, associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) and transplant. Segmentation software can be categorised according to amount of user input involved: manual, semi-automated and fully automated. Manual segmentation is considered the "gold standard" in clinical practice and research, but is tedious and time-consuming. Increasingly automated segmentation approaches are more robust, but may suffer from certain segmentation pitfalls. Emerging applications of segmentation include surgical planning and integration with MRI-based biomarkers.

Conclusions

Liver segmentation has multiple clinical applications and is expanding in scope. Clinicians can employ semi-automated or fully automated segmentation options to more efficiently integrate volumetry into clinical practice.

Teaching points

Liver volume is assessed via organ segmentation on CT and MRI examinations.

Liver segmentation is used for volume assessment prior to major hepatic procedures.

Segmentation approaches may be categorised according to the amount of user input involved.

Emerging applications include surgical planning and integration with MRI-based biomarkers.



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Overexpressed PRAME is a potential immunotherapy target in sarcoma subtypes

Abstract

Background

PRAME (preferentially expressed antigen in melanoma), a member of the cancer-testis antigen family, has been shown to have increased expression in solid tumors, including sarcoma, and PRAME-specific therapies are currently in development for other cancers such as melanoma.

Methods

To map the landscape of PRAME expression in sarcoma, we used publicly available data from The Cancer Genome Atlas (TCGA) and the Cancer Cell Line Encyclopedia (CCLE) projects and determined which sarcoma subtypes and subsets are associated with increased PRAME expression. We also analyzed how PRAME expression correlates with survival and expression of markers related to antigen presentation and T cell function. Furthermore, tumor and normal tissue expression comparisons were performed using data from the genotype-tissue expression (GTEx) project.

Results

We found that uterine carcinosarcoma highly overexpresses the PRAME antigen, and synovial sarcomas and multifocal leiomyosarcomas also show high expressions suggesting that PRAME may be an effective target of immunotherapies of these tumors. However, we also discovered that PRAME expression negatively correlates with genes involved in antigen presentation, and in synovial sarcoma MHC class I antigen presentation deficiencies are also present, potentially limiting the efficacy of immunotherapies of this malignancy.

Conclusions

We determined that uterine carcinosarcoma, synovial sarcoma, and leiomyosarcoma patients would potentially benefit from PRAME-specific immunotherapies. Tumor escape through loss of antigen presentation needs to be further studied.



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Intact Transition Epitope Mapping (ITEM)

Abstract

Intact transition epitope mapping (ITEM) enables rapid and accurate determination of protein antigen-derived epitopes by either epitope extraction or epitope excision. Upon formation of the antigen peptide-containing immune complex in solution, the entire mixture is electrosprayed to translate all constituents as protonated ions into the gas phase. There, ions from antibody–peptide complexes are separated from unbound peptide ions according to their masses, charges, and shapes either by ion mobility drift or by quadrupole ion filtering. Subsequently, immune complexes are dissociated by collision induced fragmentation and the ion signals of the "complex-released peptides," which in effect are the epitope peptides, are recorded in the time-of-flight analyzer of the mass spectrometer. Mixing of an antibody solution with a solution in which antigens or antigen-derived peptides are dissolved is, together with antigen proteolysis, the only required in-solution handling step. Simplicity of sample handling and speed of analysis together with very low sample consumption makes ITEM faster and easier to perform than other experimental epitope mapping methods.

Graphical Abstract



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Possible involvement of central oxytocin in cisplatin-induced anorexia in rats

Abstract

During cancer chemotherapy, drugs such as 5-HT3 receptor antagonists have typically been used to control vomiting and anorexia. We examined the effects of oxytocin (OXT), which has been linked to appetite, on cisplatin-induced anorexia in rats. Fos-like immunoreactivity (Fos-LI) expressed in the supraoptic nucleus (SON), the paraventricular nucleus (PVN), the area postrema and the nucleus of the solitary tract (NTS) after intraperitoneal (ip) administration of cisplatin. We also examined the fluorescence intensity of OXT-mRFP1 after ip administration of cisplatin in OXT-mRFP1 transgenic rats. The mRFP1 fluorescence intensity was significantly increased in the SON, the PVN, and the NTS after administration of cisplatin. The cisplatin-induced anorexia was abolished by OXT receptor antagonist (OXTR-A) pretreatment. In the OXT-LI cells, cisplatin-induced Fos expression in the SON and the PVN was also suppressed by OXTR-A pretreatment. These results suggested that central OXT may be involved in cisplatin-induced anorexia in rats.



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MR Imaging Features of Intestinal Phytobezoar

Abstract

Purpose

The aim of this study is to explore MR features and imaging mechanism of intestinal phytobezoar and to deepen the understanding of intestinal phytobezoar.

Methods

Eighteen cases of intestinal phytobezoar (including 15 cases in small intestine and 3 cases in colon) underwent MR examinations. Summing-up and analyzing MR features combinded with intraoperative findings.

Results

All 18 cases of intestinal phytobezoar showed irregular shape low signal on T2-weighted image, which was named coke sign in this study. And on T1-weighted image showed as follows: (i) 12 cases of intestinal phytobezoar (11 in small intestine and 1 in ascending colon) showed internal low signal and peripheral ring-like high signal, which was named empty shell sign in this study, (ii) 4 cases of intestinal phytobezoar (3 in jejunum and 1 in ileum) showed mixed slightly higher signal, and (iii) 2 cases of intestinal phytobezoar (both in colon) showed slightly low signal.

Conclusions

Intestinal phytobezoar presented coke sign on T2-weighted image and complicated signal, more often empty shell sign on T1-weighted image. Correct diagnosis of an intestinal phytobezoar has an instructive value in selection of treatment strategy.



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Cooperative strategy for a dynamic ensemble of classification models in clinical applications: the case of MRI vertebral compression fractures

Abstract

Purpose

In clinical practice, the constructive consultation among experts improves the reliability of the diagnosis and leads to the definition of the treatment plan for the patient. Aggregation of the different opinions collected by many experts can be performed at the level of patient information, abnormality delineation, or final assessment.

Methods

In this study, we present a novel cooperative strategy that exploits the dynamic contribution of the classification models composing the ensemble to make the final class assignment. As a proof of concept, we applied the proposed approach to the assessment of malignant infiltration in 103 vertebral compression fractures in magnetic resonance images.

Results

The results obtained with repeated random subsampling and receiver operating characteristic analysis indicate that the cooperative system statistically improved ( \(p<0.01\) ) the classification accuracy of individual modules as well as of that based on the manual segmentation of the fractures provided by the experts.

Conclusions

The performances have been also compared with those obtained with those of standard ensemble classification algorithms showing superior results.



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Long-term survival after multidisciplinary therapy for residual gallbladder cancer with peritoneal dissemination: a case report

Abstract

Background

Although surgical resection is the only curative treatment for gallbladder cancer (GBC), concomitant peritoneal dissemination is considered far beyond the scope of resection. We report a long-term survivor with a residual GBC with multiple peritoneal disseminations who underwent an extended resection after effective chemotherapy.

Case presentation

A 59-year-old male underwent an open cholecystectomy for Mirizzi syndrome at a local hospital. Because of severe inflammation, the gallbladder was perforated during surgery, ending in a piecemeal resection. A pathological examination revealed GBC with positive margins, and the patient was referred to our hospital 1 month after surgery for further treatment. A multidetector-row computed tomography (MDCT) showed three hypoattenuated tumours: a tumour (3.9 cm) at the left medial segment corresponding to the gallbladder bed, a tumour (1.8 cm) around the hepatic flexure of the transverse colon, and a tumour (1.0 cm) at the stump of the cystic duct. Percutaneous needle biopsy was performed, which provided histologic evidence of adenocarcinoma. Thus, the patient had a rapidly progressive local relapse with limited peritoneal dissemination, labelled ycT3N0M1, stage IVB disease according to the UICC system. After the administration of 3 cycles of gemcitabine plus cisplatin combination chemotherapy, the size of all tumours and the CA19-9 level decreased significantly. Since the patient's general condition and liver function reserve were satisfactory, we decided the initial unresectable scenario to perform surgical therapy. After portal vein embolization, right hepatectomy, resection of the extrahepatic bile duct, partial duodenectomy, and partial colectomy were performed. Operative time was 555 min, and intraoperative blood loss was 1654 mL. Pathologic diagnosis of residual gallbladder carcinoma with peritoneal dissemination was confirmed, and the surgical margins were tumour-free. The patient was discharged on postoperative day 29, with a Clavien-Dindo IIIa complication (abdominal wall abscess). Postoperative adjuvant chemotherapy with tegafur/gimeracil/oteracil was administered during 1 year after surgery. The patient is doing well 6 years after the second surgery without evidence of disease.

Conclusions

Although specific clinical factors were associated with a favourable outcome in this patient, the present report suggests that multidisciplinary therapy may be a promising option in selected patients with distant metastatic GBC.



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Epidemiologie akuter Leukämien in Deutschland

Zusammenfassung

Der Beitrag gibt einen Überblick über die Epidemiologie akuter Leukämien in Deutschland, basierend auf den Daten aus 8 deutschen epidemiologischen Krebsregistern und dem deutschen Kinderkrebsregister. Von den gut 1000 jährlichen Neuerkrankungen an akuter lymphatischer Leukämie (ALL) betreffen etwa 45 % Kinder unter 15 Jahren, während die jährlich rund 4100 Erkrankungen an akuter myeloischer Leukämie (AML) vor allem im höheren Lebensalter auftreten; das mediane Erkrankungsalter liegt bei 72 Jahren. In den letzten 10 Jahren zeigten sich insgesamt keine wesentlichen Veränderungen der Inzidenzraten. Die Fünfjahresüberlebenswahrscheinlichkeiten liegen im Kindesalter bei etwa 92 % (ALL) bzw. 74 % (AML), gehen aber mit steigendem Diagnosealter deutlich zurück. Die altersstandardisierten Inzidenzraten für Deutschland sind mit Ergebnissen aus Europa, den USA und Australien vergleichbar, während die entsprechenden Überlebenswahrscheinlichkeiten innerhalb Europas im oberen Bereich und auch höher als in den USA liegen.



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Groundwater contamination with 2,6-dichlorobenzamide (BAM) and perspectives for its microbial removal

Abstract

The pesticide metabolite 2,6-dichlorobenzamide (BAM) is very persistent in both soil and groundwater and has become one of the most frequently detected groundwater micropollutants. BAM is not removed by the physico-chemical treatment techniques currently used in drinking water treatment plants (DWTP); therefore, if concentrations exceed the legal threshold limit, it represents a sizeable problem for the stability and quality of drinking water production, especially in places that depend on groundwater for drinking water. Bioremediation is suggested as a valuable strategy for removing BAM from groundwater by deploying dedicated BAM-degrading bacteria in DWTP sand filters. Only a few bacterial strains with the capability to degrade BAM have been isolated, and of these, only three isolates belonging to the Aminobacter genus are able to mineralise BAM. Considerable effort has been made to elucidate degradation pathways, kinetics and degrader genes, and research has recently been presented on the application of strain Aminobacter sp. MSH1 for the purification of BAM-contaminated water. The aim of the present review was to provide insight into the issue of BAM contamination and to report on the current status and knowledge with regard to the application of microorganisms for purification of BAM-contaminated water resources. This paper discusses the prospects and challenges for bioaugmentation of DWTP sand filters with specific BAM-degrading bacteria and identifies relevant perspectives for future research.



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Correlation of cardio-metabolic parameters with vitamin D status in healthy premenopausal women

Abstract

Purpose

Vitamin D has been associated with metabolic disorders and increasing risk of cardiovascular diseases, with conflicting results. Aim of our study was to evaluate the relationship, if any, between cardio-metabolic risk factors and serum 25(OH)D concentrations in healthy women in premenopausal age.

Methods

We enrolled 200 healthy women, aged 19–50 years (mean age ± SD, 38 ± 11 years). In each subject, we measured serum 25(OH)D in relation to metabolic biomarkers and cardiovascular parameters.

Results

A status of vitamin D deficiency was found in 48% of the study population, while 38% showed levels higher than 30 ng/ml. Fasting glucose and insulin levels were significantly higher in subjects with vitamin D deficiency/insufficiency (P = 0.034 and P = 0.049, respectively) as well as HOMA-IR (P = 0.05). HDL cholesterol was significantly lower (P = 0.024) and intima–media thickness (IMT) higher (P = 0.014) in the vitamin D deficient/insufficient subjects. Moreover, serum 25(OH)D levels inversely correlated with insulin levels (P = 0.0001) and intima–media thickness (P = 0.015), and directly with serum HDL cholesterol (P = 0.010). At univariate regression analysis, the parameters that were significantly associated with vitamin D levels were insulin (P = 0.050), HDL cholesterol (P = 0.016), and intima–media thickness (P = 0.015). At multivariate analysis adjusted for age and BMI, vitamin D was still significantly associated with HDL cholesterol and intima–media thickness.

Conclusions

A positive association between vitamin D and HDL cholesterol was found in healthy women without any evidence of metabolic disorders, with a significant inverse correlation between vitamin D and IMT. These results suggest a possible protective role of 25(OH)D in cardiovascular disorders.



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Detecting and identifying offset gaze

Abstract

A number of experiments have demonstrated that observers can accurately identify stimuli that they fail to detect (Rollman and Nachmias, 1972; Harris and Fahle, 1995; Allik et al. 1982, 2014). Using a 2x2AFC double judgements procedure, we demonstrated an analogous pattern of performance in making judgements about the direction of eye gaze. Participants were shown two faces in succession: one with direct gaze and one with gaze offset to the left or right. We found that they could identify the direction of gaze offset (left/right) better than they could detect which face contained the offset gaze. A simple Thurstonian model, under which the detection judgement is shown to be more computationally complex, was found to explain the empirical data. A further experiment incorporated metacognitive ratings into the double judgements procedure to measure observers' metacognitive awareness (Meta-d') across the two judgements and to assess whether observers were aware of the evidence for offset gaze when detection performance was at and below threshold. Results suggest that metacognitive awareness is tied to performance, with approximately equal Meta-d' across the two judgements, when sensitivity is taken into account. These results show that both performance and metacognitive awareness rely not only on the strength of sensory evidence but also on the computational complexity of the decision, which determines the relative distance of that evidence from the decision axes.



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General practitioners’ perceptions of the current status and pharmacists’ contribution to primary care in Iceland

Abstract

Background For the past several years pharmacists' responsibilities have expanded globally from traditional tasks of dispensing medications to collaborating with other health care professionals in patient care. Similar developments have not occurred in outpatient settings in Iceland. Objective The aim of this study was to explore Icelandic general practitioners' views on the current status of primary care, their perceptions of pharmacists as a health care profession, and their attitudes towards future GP-pharmacist collaboration in primary care in Iceland. Setting Twelve primary care clinics in Iceland. Methods Semi-structured in-depth interviews were conducted with general practitioners from different primary care clinics in Iceland. A purposive and snowball sampling technique was used to select participants. All interviews were recorded and transcribed verbatim. The transcripts were categorized by themes and then analyzed using conventional content analysis. Main outcome measure General practitioners' attitudes towards pharmacists. Results Twenty general practitioners from twelve different primary care clinics in Iceland were interviewed. There are several unmet needs regarding medicines and patient monitoring in the Icelandic health care system. General practitioners suggested ways in which these gaps may be addressed and pharmacist-led clinical service was one of the suggestions. Currently, their communication with pharmacists in the primary sector solely surrounds practical non-clinical issues. Due to increasing polypharmacy and multimorbidity, they suggested that pharmacists should be more involved in patient care. Conclusions General practitioners believe that pharmacist-led clinical service can increase the quality of patient therapy. To improve communication between these health care providers, pharmacists must also re-professionalize (strengthening the profession´s status through new responsibilities and tasks), not having a conflict of interest and showing that they have expertise in patient care.



http://ift.tt/2st8Pt5

Triple-Bit Quantization with Asymmetric Distance for Image Content Security

Abstract

With the rapid growth of the number of images on the Internet, it has become more necessary to ensure the content security of images. The key problem is retrieving relevant images from the large database. Binary embedding is an effective way to improve the efficiency of calculating similarities for image content security as binary code is storage efficient and fast to compute. It tries to convert real-valued signatures into binary codes while preserving similarity of the original data, and most binary embedding methods quantize each projected dimension to one bit (presented as 0/1). As a consequence, it greatly decreases the discriminability of original signatures. In this paper, we first propose a novel triple-bit quantization strategy to solve the problem by assigning 3-bit to each dimension. Then, asymmetric distance algorithm is applied to re-rank candidates obtained from Hamming space for the final nearest neighbors. For simplicity, we call the framework triple-bit quantization with asymmetric distance (TBAD). The inherence of TBAD is combining the best of binary codes and real-valued signatures to get nearest neighbors quickly and concisely. Moreover, TBAD is applicable to a wide variety of embedding techniques. Experimental comparisons on BIGANN set show that the proposed method can achieve remarkable improvement in query accuracy compared to original binary embedding methods.



http://ift.tt/2tmhpGi

The pathway to consultation for rheumatoid arthritis: exploring anticipated actions between the onset of symptoms and face-to-face encounter with a healthcare professional

Abstract

Background

When people first experience symptoms of rheumatoid arthritis (RA) they often delay seeking medical attention resulting in delayed diagnosis and treatment. This research assesses behaviours people might engage in prior to, or instead of, seeking medical attention and compares these with behaviours related to illnesses which are better publicised.

Methods

Thirty-one qualitative interviews with members of the general public explored intended actions in relation to two hypothetical RA vignettes (with and without joint swelling) and two non-RA vignettes (bowel cancer and angina). The interviews were audio-recorded and transcribed. Analysis focused on intended information gathering and other self-management behaviours in the interval between symptom onset and help-seeking.

Results

Participants were more likely to envision self-managing symptoms when confronted with the symptoms of RA compared to the other vignettes. Participants would look for information to share responsibility for decision making and get advice and reassurance. Others saw no need for information seeking, perceived the information available as untrustworthy or, particularly in the case of bowel cancer and angina, would not want to delay seeking medical attention. Participants further anticipated choosing not to self-manage the symptoms; actively monitoring the symptoms (angina/ bowel cancer) or engaging in self-treatment of symptom(s).

Discussion

These results help define targets for interventions to increase appropriate help-seeking behaviour for people experiencing the initial symptoms of RA, such as educational interventions directed at allied healthcare professionals from whom new patients may seek information on self-management techniques, or the development of authoritative and accessible informational resources for the general public.



http://ift.tt/2sADHr1

Systematic review of oral manifestations related to hyperparathyroidism

Abstract

Objectives

We sought to identify oral symptoms found in hyperparathyroidism and compare their rate of occurrence, as well as potential variations in sequelae between primary, secondary, and tertiary hyperparathyroidism.

Materials and methods

Database searches were performed through EMBASE and PubMed, with a continual handsearch for relevant articles. PRISMA guidelines were followed.

Results

Two hundred five articles including 245 patients were analyzed with data extraction. The average age was 34.02 years old (age range 1–83), with 91 male and 154 female patients (1:1.7 M/F ratio). Patients presented with symptoms including facial asymmetry or swelling (167/214 cases; 78.0%), oral pain (30/214; 14.0%), systemic symptoms (25/214; 11.7%), referrals or incidental findings (16/214; 7.5%), and neuropathy (6/214; 2.8%) independently and in combination together. Bony pathology occurred most often in the mandible (100/245 cases; 40.8%), while 72 cases were in the maxilla (29.4%) and 73 cases in both jaw bones (29.8%).

Conclusions

Our data collection identifies a wide variation in the presentation of hyperparathyroidism. In order to be more certain of oral maladies from hyperparathyroidism, studies with large patient populations need to be conducted at healthcare centers to clarify the oral outcomes of hyperparathyroidism.

Clinical relevance

What was thought to be a characteristic finding of HPT, mandibular radiolucency occurred in only a minor portion of cases. Furthermore, the pathognomonic sign of HPT on radiograph, loss of lamina dura, was only the third most common presentation. Bone pathology was most commonly reported in literature, but should not be assumed the only oral sequelae of hyperparathyroidism.



http://ift.tt/2rrQ6Oc

Laryngotracheal Involvement in Systemic Light Chain Amyloidosis

Abstract

Laryngotracheal amyloid deposition is an uncommon manifestation of systemic light chain amyloidosis. Diagnostic imaging, such as CT, is useful for suggesting the possibility of amyloidosis and delineating the extent of the lesions for surgical management; however, the diagnosis is confirmed with the histologic finding of amorphous eosinophilic material which stains positively for Congo red and may show apple green birefringence on polarization. These features are exemplified in this sine qua non radiology-pathology correlation article.



http://ift.tt/2s0H09J

Nd:YAG laser therapy for rectal and vaginal venous malformations

Abstract

Background

Limited therapeutic options exist for rectal and vaginal venous malformations (VM). We describe our center's experience using Nd:YAG laser for targeted ablation of abnormal veins to treat mucosally involved pelvic VM.

Methods

Records of patients undergoing non-contact Nd:YAG laser therapy of pelvic VM at a tertiary children's hospital were reviewed. Symptoms, operative findings and details, complications, and outcomes were evaluated.

Results

Nine patients (age 0–24) underwent Nd:YAG laser therapy of rectal and/or vaginal VM. Rectal bleeding was present in all patients and vaginal bleeding in all females (n = 5). 5/7 patients had extensive pelvic involvement on MRI. Typical settings were 30 (rectum) and 20–25 W (vagina), with 0.5–1.0 s pulse duration. Patients underwent the same-day discharge. Treatment intervals ranged from 14 to 180 (average = 56) weeks, with 6.1-year mean follow-up. Five patients experienced symptom relief with a single treatment. Serial treatments managed recurrent bleeding successfully in all patients, with complete resolution of vaginal lesions in 40% of cases. No complications occurred.

Conclusions

Nd:YAG laser treatment of rectal and vaginal VM results in substantial improvement and symptom control, with low complication risk. Given the high morbidity of surgical resection, Nd:YAG laser treatment of pelvic VM should be considered as first line therapy.



http://ift.tt/2rhhZ7L

Real-time optical flow-based video stabilization for unmanned aerial vehicles

Abstract

This paper describes the development of a novel algorithm to tackle the problem of real-time video stabilization for unmanned aerial vehicles (UAVs). There are two main components in the algorithm: (1) By designing a suitable model for the global motion of UAV, the proposed algorithm avoids the necessity of estimating the most general motion model, projective transformation, and considers simpler motion models, such as rigid transformation and similarity transformation; (2) to achieve a high processing speed, optical flow-based tracking is employed in lieu of conventional tracking and matching methods used by state-of-the-art algorithms. These two new ideas resulted in a real-time stabilization algorithm, developed over two phases. Stage I considers processing the whole sequence of frames in the video while achieving an average processing speed of 50 fps on several publicly available benchmark videos. Next, Stage II undertakes the task of real-time video stabilization using a multi-threading implementation of the algorithm designed in Stage I.



http://ift.tt/2s0MGk4

Predictors of the response to etanercept in patients with juvenile idiopathic arthritis without systemic manifestations within 12 months: results of an open-label, prospective study conducted at the National Scientific and Practical Center of Children's Health, Russia

Abstract

Background

The aim of this study was to investigate the efficacy of etanercept treatment and to identify predictors of response to therapy within 12 months in patients with juvenile idiopathic arthritis (JIA) without systemic manifestations.

Methods

A total of 197 juvenile patients were enrolled in this study. Response to therapy was assessed using the ACRPedi 30/50/70/90 criteria, the Wallace criteria, and the Juvenile Arthritis Disease Activity Score 71 (JADAS-71). Univariate and multivariate logistic regression analyses were performed to identify potential baseline factors associated with treatment response in different JIA categories.

Results

One year after treatment initiation, 179 (90.9%) patients achieved ACRPedi30; 177 (89.8%) patients achieved ACRPedi50; 168 (85.3%) patients achieved ACRPedi70; and 135 (68.5%) patients achieved ACRPedi90 response. A total of 132 (67.0%) and 92 (46.7%) patients achieved inactive disease according to the Wallace criteria and the JADAS-71 cut-off point, respectively. Excellent response (achieving ACRPedi90 and clinically inactive disease according both to the Wallace criteria and the JADAS71 cut-off point) was associated with persistent oligoarticular JIA category, shorter disease duration before the start of etanercept, a lower number of DMARDs used before the introduction of etanercept, a lower number of joints with limited motion, and lower C-reactive protein at baseline. Poor response (failure to achieve ACR 70 or active disease according to both the Wallace criteria and JADAS71 even when ACR 70 was achieved) was associated with the polyarticular or enthesitis-related JIA categories, higher disease duration before the start of etanercept, and older age at disease onset.

Conclusion

Almost half (45.7%) of the patients who initiated etanercept treatment achieved an excellent response (inactive disease and ACRPedi90) after 1 year. What may be novel is our finding that the response to etanercept therapy was strongly associated with the JIA category. The response to etanercept therapy was also associated with the disease duration before the start of etanercept treatment.



http://ift.tt/2rwgfqm

Epileptische Anfälle und Epilepsie nach einem Schlaganfall

Zusammenfassung

Nach einem Schlaganfall treten bei 3–6 % der Patienten – nach Hämorrhagien mehr also nach Ischämien – innerhalb von 7 Tagen akut symptomatische und bei 10–12 % nach mehr als 7 Tagen unprovozierte epileptische Anfälle auf. Aufgrund dieser geringen Inzidenzen ist eine primärprophylaktische Gabe von Antiepileptika in der Regel nicht erforderlich. Das Risiko eines weiteren akut symptomatischen Anfalls liegt bei 10–20 %, diese niedrige Rate spricht gegen eine antiepileptische Sekundärprophylaxe in der akuten Phase. Im klinischen Alltag wird diese dennoch häufig initiiert. Das Antiepileptikum sollte dann aber rasch wieder abgesetzt werden, da das langfristige Risiko eines weiteren unprovozierten Anfalls bei ca. 30 % liegt. Nach einem unprovozierten Anfall nach einem Schlaganfall beträgt das Risiko eines Anfallsrezidivs in den folgenden 10 Jahren etwa 70 %, dies definiert eine Epilepsie. Daher wird in diesem Fall in der Regel eine sekundärprophylaktische Behandlung mit einem Antiepileptikum empfohlen.



http://ift.tt/2s0PNZn

Effect of antimony (Sb) addition on the linear and non-linear optical properties of amorphous Ge–Te–Sb thin films

Abstract

Non-crystalline thin films of Ge20Te80−xSbx (x = 0, 2, 4, 6, 10) systems were deposited on glass substrate using thermal evaporation technique. The optical coefficients were accurately determined by transmission spectra using Swanepoel envelope method in the spectral region of 400–1600 nm. The refractive index was found to increase from 2.38 to 2.62 with the corresponding increase in Sb content over the entire spectral range. The dispersion of refractive index was discussed in terms of the single oscillator Wemple–DiDomenico model. Tauc relation for the allowed indirect transition showed decrease in optical band gap. To explore non-linearity, the spectral dependence of third order susceptibility of a-Ge–Te–Sb thin films was evaluated from change of index of refraction using Miller's rule. Susceptibility values were found to enhance rapidly from 10−13 to 10−12 (esu), with the red shift in the absorption edge. Non-linear refractive index was calculated by Fourier and Snitzer formula. The values were of the order of 10−12 esu. At telecommunication wavelength, these non-linear refractive index values showed three orders higher than that of silica glass. Dielectric constant and optical conductivity were also reported. The prepared Sb doped thin films on glass substrate with observed improved functional properties have a noble prospect in the application of nonlinear optical devices and might be used for a high speed communication fiber. Non-linear parameters showed good agreement with the values given in the literature.



http://ift.tt/2tlUomZ

A density functional study of chalcopyrite MgGeSb 2

Abstract

The structural, electronic, elastic, dynamic and optical properties of the ternary chalcopyrite compound MgGeSb2 were studied by using the density functional theory (DFT) framework for different exchange–correlation functionals. The obtained equilibrium structural parameters are in good agreement with the available theoretical result. After considering the electronic band structure and electronic density of states (DOS) calculation; this compound is a semiconductor as suggested in the previous work. However; all considered functionals underestimate considerably the electronic band gap energies compared with the experimental results. We have predicted single-crystal elastic constants and related properties such as Young's modulus, Poisson ratio, shear modulus and bulk modulus. Optical properties such as the dielectric function, refractive index, extinction index have been calculated in the range of 0–20 eV. The obtained results can facilitate an assessment of possible applications of MgGeSb2.



http://ift.tt/2soecca

Criteria for failure and worsening after surgery for lumbar disc herniation: a multicenter observational study based on data from the Norwegian Registry for Spine Surgery

Abstract

Purpose

In clinical decision-making, it is crucial to discuss the probability of adverse outcomes with the patient. A large proportion of the outcomes are difficult to classify as either failure or success. Consequently, cutoff values in patient-reported outcome measures (PROMs) for "failure" and "worsening" are likely to be different from those of "non-success". The aim of this study was to identify dichotomous cutoffs for failure and worsening, 12 months after surgical treatment for lumbar disc herniation, in a large registry cohort.

Methods

A total of 6840 patients with lumbar disc herniation were operated and followed for 12 months, according to the standard protocol of the Norwegian Registry for Spine Surgery (NORspine). Patients reporting to be unchanged or worse on the Global Perceived Effectiveness (GPE) scale at 12-month follow-up were classified as "failure", and those considering themselves "worse" or "worse than ever" after surgery were classified as "worsening". These two dichotomous outcomes were used as anchors in analyses of receiver operating characteristics (ROC) to define cutoffs for failure and worsening on commonly used PROMs, namely, the Oswestry Disability Index (ODI), the EuroQuol 5D (EQ-5D), and Numerical Rating Scales (NRS) for back pain and leg pain.

Results

"Failure" after 12 months for each PROM, as an insufficient improvement from baseline, was (sensitivity and specificity): ODI change <13 (0.82, 0.82), ODI% change <33% (0.86, 0.86), ODI final raw score >25 (0.89, 0.81), NRS back-pain change <1.5 (0.74, 0.86), NRS back-pain % change <24 (0.85, 0.81), NRS back-pain final raw score >5.5 (0.81, 0.87), NRS leg-pain change <1.5 (0.81, 0.76), NRS leg-pain % change <39 (0.86, 0.81), NRS leg-pain final raw score >4.5 (0.91, 0.85), EQ-5D change <0.10 (0.76, 0.83), and EQ-5D final raw score >0.63 (0.81, 0.85). Both a final raw score >48 for the ODI and an NRS >7.5 were indicators for "worsening" after 12 months, with acceptable accuracy.

Conclusion

The criteria with the highest accuracy for defining failure and worsening after surgery for lumbar disc herniation were an ODI percentage change score <33% for failure and a 12-month ODI raw score >48. These cutoffs can facilitate shared decision-making among doctors and patients, and improve quality assessment and comparison of clinical outcomes across surgical units. In addition to clinically relevant improvements, we propose that rates of failure and worsening should be included in reporting from clinical trials.



http://ift.tt/2t1WFV0

Comparison of efficacy of transversus abdominis plane block and iliohypogastric/ilioinguinal nerve block for postoperative pain management in patients undergoing inguinal herniorrhaphy with spinal anesthesia: a prospective randomized controlled open-label study

Abstract

Purposes

The purpose of this study was to compare the effects of lateral abdominal transversus abdominis plane block (TAP block) and iliohypogastric/ilioinguinal nerve block (IHINB) under ultrasound guidance for postoperative pain management of inguinal hernia repair. Secondary purposes were to compare the complication rates of the two techniques and to examine the effects of TAP block and IHINB on chronic postoperative pain.

Methods

This was a prospective randomized controlled open-label study. After approval of the Research Ethics Board, a total of 90 patients were allocated to three groups of 30 by simple randomized sampling as determined with a priori power analysis. Peripheral nerve blocks (TAP block or IHINB) were administered to patients following subarachnoid block according to their allocated group. Patient pain scores, additional analgesic requirements and complication rates were recorded periodically and compared.

Results

Pain scores were significantly lower in the study groups (p < 0.001, p < 0.001, p < 0.001, p = 0.002, p < 0.001, p < 0.001 for 1, 2, 4, 6, 24, and 48 h and at 1 and 6 months, respectively). First pain declaration times were significantly longer in the study groups (TAP block group [GT] 266.6 ± 119.7 min; IHINB group [GI] 247.2 ± 128.7 min; and control group [GC] 79.1 ± 66.2 min; p < 0.001). At 24 h, the numeric rating scale scores of GT were significantly lower than GI (p = 0.048). Additional analgesic requirements of GT and GI patients were found to be significantly lower than GC patients (p = 0.001, p < 0.001, p = 0.006, p = 0.002, p = 0.001, p < 0.001 for 1, 2, 4, 6, 24, and 48 h, respectively).

Conclusion

We conclude that administration of TAP block or IHINB for patients undergoing inguinal herniorrhaphy reduces the intensity of both acute and chronic postoperative pain and additional analgesic requirements.



http://ift.tt/2rhfPEX

Cerebral venous sinus thrombosis in Behçet’s disease: a retrospective case-control study

Abstract

The objective of the study is to investigate the clinical features of Behçet's disease (BD) complicated with cerebral venous sinus thrombosis (CVST). We retrospectively analyzed the clinical features of age- and gender-matched BD patients with and without CVST. Of the 840 BD patients enrolled, 21 (2.5%, 11 female, mean age 30.3 ± 9.5) were diagnosed as CVST. Eighteen patients (85.7%) developed neurologic manifestations after BD onset, with an average interval of 47.6 months (SD 36.1). Onset of neurologic symptoms was mostly progressive (89.5%), with headache (95.2%) being the most common symptom. Intracranial hypertension occurred in 17 cases (89.5%). Thrombosis was detected mostly in transverse (71.4%) and superior sagittal (66.7%) sinuses, with more frequently (66.7%) dual or multiple sinuses involved. In addition, extra cranial thrombosis was presented in 11 cases. Cerebral infarction was presented in four cases. Compared with BD patients without CVST, the prevalence of extra cranial vascular involvement (52.4 versus 20.6%; P = 0.005) and BDCAF 2006 score (3.7 ± 1.4 versus 1.8 ± 1.3; P = 1.7863 × 10−7) was higher in BD patients with CVST. During a median 7-month follow-up (range 0.3–88.8 months), 18 patients (85.7%) achieved remission following glucocorticoid, immunosuppressant therapy, anticoagulants, and dehydration, although 3 patients experienced (14.3%) flare. No death was reported. CVST is rare complication of BD and predominately progressively developed in active BD and after BD onset. It typically features intracranial hypertension syndrome and is frequently complicated with extra cranial thrombosis; thus, systemic thrombus screening is highly recommended. Promptly, diagnosis and aggressive treatment are keys to improve the prognosis.



http://ift.tt/2t1Uvo9

Isolated transient vertigo: posterior circulation ischemia or benign origin?

Abstract

Background

Isolated transient vertigo can be the only symptom of posterior circulation ischemia. Thus, it is important to differentiate isolated vertigo of a cerebrovascular origin from that of more benign origins, as patients with cerebral ischemia have a much higher risk for future stroke than do those with 'peripheral' vertigo. The current study aims to identify risk factors for cerebrovascular origin of isolated transient vertigo, and for future cerebrovascular events.

Methods

From the files of 339 outpatients with isolated transient vertigo we extracted history, clinical and technical findings, diagnosis, and follow-up information on subsequent stroke or transient ischemic attack (TIA). Risk factors were analyzed using multivariate regression models (logistic or Cox) and reconfirmed in univariate analyses.

Results

On first presentation, 48 (14.2%) patients received the diagnosis 'probable or definite cerebrovascular vertigo'. During follow-up, 41 patients suffered stroke or TIA (event rate 7.9 per 100 person years, 95% confidence interval (CI) 5.5–10.4), 26 in the posterior circulation (event rate 4.8 per 100 person years, 95% CI 3.0–6.7). The diagnosis was not associated with follow-up cerebrovascular events. In multivariate models testing multiple potential determinants, only the presentation mode was consistently associated with the diagnosis and stroke risk: patients who presented because of vertigo (rather than reporting vertigo when they presented for other reasons) had a significantly higher risk for future stroke or TIA (p = 0.028, event rate 13.4 vs. 5.4 per 100 person years) and for future posterior circulation stroke or TIA (p = 0.044, event rate 7.8 vs. 3.5 per 100 person years).

Conclusions

We here report for the first time follow-up stroke rates in patients with transient isolated vertigo. In such patients, the identification of those with cerebrovascular origin remains difficult, and presentation mode was found to be the only consistent risk factor. Confirmation in an independent prospective sample is needed.



http://ift.tt/2ssvrK8

Genetic population diversity of European eel Anguilla anguilla elvers in two Egyptian water bodies, Rosetta (Rachid) estuary and Burullus Lake

Abstract

The European eel Anguilla anguilla is a species of great economic importance for Egypt. Its long trans-Atlantic migrations for semelparous spawning then larval homing provides a possible way for worldwide mixing of populations. Its natural habitats in Egypt, as in other Mediterranean countries, are under heavy load of pollution due to anthropogenic activities. Hence, a major priority should be given to assess the genetic diversity within/among eels' populations as a step towards revealing populations' status, identification of possible conservation units, and, subsequently, implementation of proper conservation and management strategies for them. For this, A. anguilla elvers were collected from Rosetta estuary and Burullus coastal lagoon in the North of Egypt. Sequencing of the barcode region of the cytochrome c oxidase subunit 1 gene (COI) was carried out for all collected elvers. The sequences were analyzed using various genetic, phylogenetic, and population analyses to assess their variability. A total of 33 haplotypes were identified, 14 of which were unique to Burullus Lake, and 11 to Rosetta estuary. Very low fixation (F st  = 0–0.04) was found for A. anguilla populations in Egypt and worldwide, except for the Turkish and Czech ones (F st  = 0.47–0.62 and 0.18–0.41, respectively). Both Egyptian populations showed signs of recent populations' expansion, besides low, non-significant raggedness values. The results suggested Burullus Lake and Rosetta estuary as separate conservation units for A. anguilla in Egypt. These units require special attention for proper protection and management of the existing eel diversity and permitting sustainability in the activities dealing with eel's fishing and aquaculture.



http://ift.tt/2s0ureF

Transcriptome comparative analysis between the cytoplasmic male sterile line and fertile line in soybean ( Glycine max (L.) Merr.)

Abstract

To further elucidate the molecular mechanism and fertility restoration of cytoplasmic male sterility (CMS) in soybean, a comparative transcriptome analysis was conducted between the CMS line NJCMS1A, restorer line NJCMS1C and their hybrid F1 progeny (NJCMS1A × NJCMS1C) using RNA-Seq strategy. After pairwise comparative analysis of these soybean lines, 294, 222, and 288 differentially expressed genes (DEGs) were identified, respectively. Further bioinformatic analysis indicated that these DEGs were involved in diverse molecular functions and metabolic pathways. qRT-PCR analysis validated that the gene expression pattern in RNA-Seq was reliable. These results significantly showed that the male sterility and fertility restoration in NJCMS1A might be related to a series of the abnormal of growth development and metabolic processes, such as pollen development, DNA methylation process, pollen viability, cell wall development, programmed cell death, as well as carbohydrate and energy metabolism. This study could facilitate our understanding of the molecular mechanisms and fertility restoration behind CMS in soybean.



http://ift.tt/2rqUWv8

Power difference template for action recognition

Abstract

This paper proposes power difference template as a new spatial-temporal representation for action recognition. Specifically, spatial power features are first extracted according to the transform of Gaussian convolution on gradients between logarithmic and exponential domain. Using the forward–backward frame power difference method, we thus present normalized projection histogram (NPH) to characterize segmented action spatial features by normalizing histogram of the 2D horizontal–vertical projections. Furthermore, from the perspective of energy conservation, motion kinetic velocity (MKV) is introduced as a supplement for representing temporal relationships of power features by supposing that the variation of power is produced by motion in the form of kinetic energy. Our power difference template fusing NPH and MKV is further integrated to a bag of word model for training and testing under a support vector machine framework. Experiments on KTH, UCF Sports, UCF101 and HMDB datasets demonstrate the effectiveness of the proposed algorithm.



http://ift.tt/2rvpAPn

Controversies in the role of postmastectomy radiotherapy in breast cancer patients with one to three positive axillary nodes and safety of integrating radiotherapy and breast reconstruction



http://ift.tt/2t1SWXB

Auditory brainstem responses after electrolytic lesions in bilateral subdivisions of the medial geniculate body of tree shrews

Abstract

This study aimed to establish a tree shrew model of bilateral electrolytic lesions in the medial geniculate body (MGB) to determine the advantages of using a tree shrew model and to assess the pattern of sound processing in tree shrews after bilateral electrolytic damage in different parts of the MGB. The auditory brainstem responses (ABRs) of a normal control group (n = 30) and an electrical damage group (n = 30) were tested at 0 h, 24 h, 48 h, 72 h, 7 days, 15 days, and 30 days after surgery. (1) The bilateral ablations group exhibited a significant increase in the ABR threshold of the electrolytic damage group between pre- and post-operation. (2) There were significant increases in the I-VI latencies at 0 h after MGBd and MGBm lesions and at 24 h after MGBv lesion. (3) The amplitudes of wave VI were significantly decreased at 24 h and 48 h after MGBd lesion, at 72 h and 7 days after MGBm lesion, and at 24 h, 48 h, 72 h, and 7 days after MGBv lesion. (1) The electrolytic damage group suffered hearing loss that did not recover and appeared to be difficult to fully repair after bilateral ablation. (2) The latencies and amplitudes of responses in the MGB following bilateral electrolytic lesion were restored to pre-operation levels after 15–30 days, suggesting that a portion of the central nuclei lesion was reversible. (3) The tree shrew auditory animal model has many advantages compared to other animal models, such as greater complexity of brain structure and auditory nuclei fiber connections, which make the results of this experiment more useful for clinical diagnoses compared with studies using rats and guinea pigs.



http://ift.tt/2rrkKHs

Comparison of the Simple Patient-Centric Atopic Dermatitis Scoring System PEST with SCORAD in Young Children Using a Ceramide Dominant Therapeutic Moisturizer

Abstract

Introduction

Patient eczema severity time (PEST) is a new atopic dermatitis (AD) scoring system based on patients' own perception of their disease. Conventional scales such as SCORing of atopic dermatitis (SCORAD) reflect the clinician's observations during the clinic visit. Instead, the PEST score captures eczema severity, relapse and recovery as experienced by the patient or caregiver on a daily basis, promoting patient engagement, compliance with treatment and improved outcomes. This study aims to determine the correlation between carer-assessed PEST and clinician-assessed SCORAD in paediatric AD patients after 12 weeks of treatment using a ceramide-dominant therapeutic moisturizer.

Methods

Prospective, open-label, observational, multi-centre study in which children with AD aged 6 months to 6 years were treated with a ceramide dominant therapeutic moisturizer twice daily for 12 weeks; 58 children with mild-to-moderate AD were included. Correlation between the 7-day averaged PEST and SCORAD scores for assessment of AD severity was measured within a general linear model. PEST and SCORAD were compared in week 4 and week 12.

Results

At week 12, a moderate correlation was found between the SCORAD and PEST scores (r = 0.51). The mean change in SCORAD and PEST scores from baseline to week 12 was −11.46 [95% confidence interval (CI) −14.99 to −7.92, p < 0.0001] and −1.33 (95% CI −0.71 to −0.10, p < 0.0001) respectively. PEST demonstrated greater responsiveness to change (33.3% of scale) compared to SCORAD (13.8% of scale).

Conclusion

The PEST score correlates well with the SCORAD score and may have improved sensitivity when detecting changes in the severity of AD. The ceramide-dominant therapeutic moisturizer used was safe and effective in the management of AD in young children.

Funding

Hyphens Pharma Pte Ltd.

Trial Registration

clinicaltrials.gov identifier, NCT02073591.



http://ift.tt/2s08Zq1

Synergistic hydrolysis of xylan using novel xylanases, β-xylosidases, and an α- l -arabinofuranosidase from Geobacillus thermodenitrificans NG80-2

Abstract

Lignocellulosic biomass from various types of wood has become a renewable resource for production of biofuels and biobased chemicals. Because xylan is the major component of wood hemicelluloses, highly efficient enzymes to enhance xylan hydrolysis can improve the use of lignocellulosic biomass. In this study, a xylanolytic gene cluster was identified from the crude oil-degrading thermophilic strain Geobacillus thermodenitrificans NG80-2. The enzymes involved in xylan hydrolysis, which include two xylanases (XynA1, XynA2), three β-xylosidases (XynB1, XynB2, XynB3), and one α-l-arabinofuranosidase (AbfA), have many unique features, such as high pH tolerance, high thermostability, and a broad substrate range. The three β-xylosidases were highly resistant to inhibition by product (xylose) accumulation. Moreover, the combination of xylanase, β-xylosidase, and α-l-arabinofuranosidase exhibited the largest synergistic action on xylan degradation (XynA2, XynB1, and AbfA on oat spelt or beechwood xylan; XynA2, XynB3, and AbfA on birchwood xylan). We have demonstrated that the proposed enzymatic cocktail almost completely converts complex xylan to xylose and arabinofuranose and has great potential for use in the conversion of plant biomass into biofuels and biochemicals.



http://ift.tt/2rqWoxD

Treatment of Refractory Colorectal Cancer: Regorafenib vs. TAS-102

Abstract

Purpose of Review

This paper reviews the development, mechanism of action, clinical efficacy, and safety of regorafenib and TAS-102. Through this review, we aimed to help clinicians make an appropriate choice in patients who progressed after standard therapies.

Recent Findings

Regorafenib and TAS-102 have shown superior survival results compared with placebo in refractory metastatic colorectal cancer (mCRC). In the phase III CORRECT study, regorafenib showed significant improvement in overall survival (OS) and progression-free survival (PFS). TAS-102 was associated with OS and PFS benefit as well in the phase III RECOURSE study. However, the toxicity profiles were quite different between the two agents.

Summary

Regorafenib and TAS-102 are approved for the management of refractory mCRC. Optimal treatment sequence for using these two novel agents is not defined yet. Safety profiles and patient's condition should be considered before using these two agents in clinical settings. Further investigation is needed to identify the predictive biomarkers of both agents. These results will allow patients to benefit more from regorafenib and TAS-102.



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miR-183 and miR-21 expression as biomarkers of progression and survival in tongue carcinoma patients

Abstract

Objectives

Micro RNAs (miRNAs) have a major role in human cancerogenesis.The current study investigated the prognostic significance of miR-183 and miR-21 expression in tongue carcinoma patients.

Material and method

For qPCR of miR-183 and miR-21 expression, total RNA isolated from 60 fresh-frozen tissue of tongue carcinomas was converted into cDNA by TaqMan MicroRNA Reverse Transcription Kit and quantified by TaqMan MicroRNAs Expression Assays. Fold changes in the miRNAs expression, normalized to RNU6B, were determined using 2−ΔΔCt method, and dichotomized into high and low according to cut-off values derived from ROC curve analysis.

Results

miR-183 emerged as promising discriminatory biomarker of poor outcome. Tissue over-expression of miR-183, observed in 68.3% of tongue carcinomas, was associated with clinical stage (p = 0.037), tumor size (p = 0.036), and high alcohol intake (p = 0.034).The patients with miR-183 over-expression had significantly shorter overall survival (p = 0.006) and a 5.666 times higher risk of poor outcome (p = 0.005), while miR-21 over-expression carried a tendency towards poorer survival (p = 0.073). However, multivariate analysis revealed that the recurrences were independent adverse prognostic factors, while miR-183 over-expression lost its significance.

Conclusion

Our results suggests that over-expression of miR-183 in tumor tissue could be a potential marker of clinical stage and a poor survival of tongue carcinoma patients and may be associated with high alcohol consumption.

Clinical relevance

Oncogenic miRNAs, such as the investigated miR-183 and miR-21, could be novel prognostic biomarkers of tumor progression and adverse clinical outcome in oral cancer, as well as novel therapeutic targets in cancer.



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Bird migration



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Dermatophyten und Meerschweinchen

Zusammenfassung

Hintergrund

Dermatophytosen durch Trichophyton (T.) benhamiae – v. a. bei Kindern – zeigen seit einigen Jahren eine erhöhte Inzidenz. Die Übertragung erfolgt meist durch Meerschweinchen, die als Haustiere gehalten werden. Über die Prävalenz des Erregers bei käuflich erhältlichen Tieren ist bislang nichts bekannt.

Zielstellung

Es sollte deshalb untersucht werden, wie hoch der Anteil von Tieren in Berliner Zoohandlungen ist, die entweder symptomatisch infiziert oder asymptomatische Träger von T. benhamiae sind.

Methoden

Es wurden 59 Meerschweinchen, die in 15 verschiedenen Zoohandlungen zum Verkauf standen, mit der MacKenzie-Brush-Technik großflächig und mit einer Abstrichmethode lokal beprobt und mittels Polymerasekettenreaktion (PCR) und Kultur auf das Vorhandensein von Dermatophyten untersucht.

Ergebnisse

Bei >90 % der untersuchten Tiere konnte T. benhamiae nachgewiesen werden. Davon zeigten nur 9 % Symptome einer Tinea, die anderen Tiere waren asymptomatische Träger.

Schlussfolgerung

Bei Meerschweinchen, die in Zoohandlungen erworben werden, ist die Wahrscheinlichkeit, dass sie Träger des Erregers sind, der durch Körperkontakt auf den Menschen übertragen werden kann, sehr hoch. Meist ist der Befall bei den Tieren nicht zu erkennen, da diese keine klinischen Symptome zeigen. Es ist deshalb empfehlenswert, die Tiere zunächst beim Tierarzt vorzustellen und auf Hautpilze untersuchen zu lassen.



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Tinea barbae profunda durch Trichophyton mentagrophytes nach Thailand-Reise

Zusammenfassung

Die Tinea barbae ist eine sehr seltene Dermatophytose. Hier wird eine Tinea barbae profunda als Folge einer Reise nach Südostasien beschrieben. Ein Geschäftsmann erkrankte nach einer Thailand-Reise an einer foudroyant verlaufenden abszedierenden Infektion im Oberlippen- und Bartbereich. Die anfängliche Therapie mit Aciclovir p. o. und Ciprofloxacin p. o., später Ampicillin + Sulbactam i. v., war erfolglos. In einer Probeexzision war histologisch mittels Grocott-Gomori-Methenamin-Silber-Färbung Pilzmyzel erkennbar. Daraufhin wurde mit Terbinafin 250 mg über ca. 4 Wochen behandelt, topisch mit 1 % Ciclopiroxolamin-haltiger Creme. In der Pilzkultur wuchs Trichophyton (T.) mentagrophytes. Zwischenzeitlich erkrankte die deutsche Ehefrau des Patienten an einer Tinea faciei. Aus Hautschuppen von der Wange ließ sich ebenfalls Tmentagrophytes anzüchten. Der zoophile Dermatophyt war identisch mit anderen aktuell in Deutschland gefundenen zoophilen Stämmen von Tmentagrophytes, die ebenfalls in Thailand erworben wurden. Der Patient hatte in Thailand Kontakt zu Female Sexworkern, die als potenzielle Infektionsquelle der Dermatophytose angesehen werden können. Tierkontakt bestand nicht. Die Infektionskette der Dermatophytose aus Thailand reichte wahrscheinlich von der thailändischen Sexworkerin über den hier vorgestellten Patienten bis zu seiner Ehefrau in Deutschland. Dieser Infektionsweg ist erst seit 1 bis 2 Jahren bekannt, bislang wurden in Deutschland, der Schweiz und Österreich jedoch ausschließlich pubogenitale Infektionen (Tinea genitalis profunda) durch Tmentagrophytes nach Südostasien-Reisen beschrieben. Zur Behandlung müssen oral verabreichte Antimykotika eingesetzt werden, an erster Stelle kommt Terbinafin in Betracht, alternativ Fluconazol oder Itraconazol.



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Präoperative Gendiagnostik und Bildgebung bei kindlichen Phäochromozytomen und Paragangliomen



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Der Schatten der Transparenz



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Somatic mutations of the coding microsatellites within the beta-2-microglobulin gene in mismatch repair-deficient colorectal cancers and adenomas

Abstract

In colorectal cancers (CRCs) with tumour mismatch repair (MMR) deficiency, genes involved in the host immune response that contain microsatellites in their coding regions, including beta-2-microglobulin (B2M), can acquire mutations that may alter the immune response, tumour progression and prognosis. We screened the coding microsatellites within B2M for somatic mutations in MMR-deficient CRCs and adenomas to determine associations with tumour subtypes, clinicopathological features and survival. Incident MMR-deficient CRCs from Australasian Colorectal Cancer Family Registry (ACCFR) and the Melbourne Collaborative Cohort Study participants (n = 144) and 63 adenomas from 41 MMR gene mutation carriers from the ACCFR were screened for somatic mutations within five coding microsatellites of B2M. Hazard ratios (HR) and 95% confidence intervals (CI) for overall survival by B2M mutation status were estimated using Cox regression, adjusting for age at CRC diagnosis, sex, AJCC stage and grade. B2M mutations occurred in 30 (20.8%) of the 144 MMR-deficient CRCs (29% of the MLH1-methylated, 17% of the Lynch syndrome and 9% of the suspected Lynch CRCs). No B2M mutations were identified in the 63 adenomas tested. B2M mutations differed by site, stage, grade and lymphocytic infiltration although none reached statistical significance (p > 0.05). The HR for overall survival for B2M mutated CRC was 0.65 (95% CI 0.29–1.48) compared with B2M wild-type. We observed differences in B2M mutation status in MMR-deficient CRC by tumour subtypes, site, stage, grade, immune infiltrate and for overall survival that warrant further investigation in larger studies before B2M mutation status can be considered to have clinical utility.



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Therapeutic Utility of Opioids for Restless Legs Syndrome

Abstract

Restless legs syndrome (RLS) is a sensorimotor neurologic disorder characterized by an unpleasant urge to move the legs, often accompanied by leg dysesthesias. Symptoms predominate in the evening or at night and often cause significant distress and disruption of sleep. Several non-opioid classes of drugs provide initial relief from the symptoms of RLS. Among these, however, the efficacy of dopamine agonists can wane over time or even paradoxically 'augment' the severity of symptoms during the course of long-term treatment. Opioids can alleviate RLS symptoms, even in patients who have become refractory to, or do not tolerate, other drugs. In a carefully selected group of patients with severe RLS that has not been effectively managed with other therapies, opioids may be an appropriate treatment.



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Neoadjuvant Therapy for Breast Cancer: Established Concepts and Emerging Strategies

Abstract

In the last decade, the systemic treatment approach for patients with early breast cancer has partly shifted from adjuvant treatment to neoadjuvant treatment. Systemic treatment administration started as a 'one size fits all' approach but is currently customized according to each breast cancer subtype. Systemic treatment in a neoadjuvant setting is at least as effective as in an adjuvant setting and has several additional advantages. First, it enables response monitoring and provides prognostic information; second, it downstages the tumor, allowing for less extensive surgery, improved cosmetic outcomes, and reduced postoperative complications such as lymphedema; and third, it enables early development of new treatment strategies by using pathological complete remission as a surrogate outcome of event-free and overall survival. In this review we give an overview of the current standard of neoadjuvant systemic treatment strategies for the three main subtypes of breast cancer: hormone receptor-positive, triple-negative, and human epidermal growth factor receptor 2-positive. Additionally, we summarize drugs that are under investigation for use in the neoadjuvant setting.



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Biomarkers in pancreatic ductal adenocarcinoma

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is currently the third most frequent form of malignancy. The role of biomarkers in the diagnostic and therapeutic strategy of cancer is constantly expanding. Translational research is already changing paradigms in tumours encompassing from early diagnosis to precision medicine in advanced disease. Nomenclature for molecular subtypes of tumours is gradually gaining acceptance and there are growing expectations it will further go from the bench to the bedside. However, the clinical relevance of biomarkers in PDAC is still far behind the relevance of biomarkers in other solid tumours. This article is part of a wider project (GALLgo) involving over forty specialists devoted to the multidisciplinary management of PDAC which concluded in recommendations based on scientific evidence. The aim of the present article is to review the diagnostic, prognostic and predictive biomarkers, either in localised or advanced disease, which have been lately subjected to study and analysis and others currently available for PDAC in order to give strength-graded recommendations linked to quality of evidence that can be used as guidelines in routine clinical practice.



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Quality of life after whole brain radiotherapy compared with radiosurgery of the tumor bed: results from a randomized trial

Abstract

Background

A recent randomized trial (NCT01535209) demonstrated no difference in neurocognitive function between stereotactic radiotherapy of the tumor bed (SRT-TB) and whole brain radiotherapy (WBRT) in patients with resected single brain metastasis. Patients treated with SRT-TB had lower overall survival compared with the WBRT arm. Here, we compared the health-related quality of life (HRQOL) in patients who received WBRT vs. SRT-TB.

Methods

A self-reported questionnaire was used to assess HRQOL (EORTC QLQ-C30 with the QLQ-BN20 module) before RT, 2 months after RT, and every 3 months thereafter. HRQOL results are presented as mean scores and compared between groups.

Results

Of 59 randomized patients, 37 (64%) were eligible for HRQOL analysis, 15 received SRT-TB, and 22 had WBRT. There were no differences between groups in global health status and main function scales/symptoms (except for drowsiness and appetite loss, which were worse with WBRT 2 months after RT). Global health status decreased 2 and 5 months after RT, but significantly only for SRT-TB (p = 0.025). Physical function decreased significantly 5 months after SRT-TB (p = 0.008). Future uncertainty worsened after RT, but significantly only for SRT-TB after 2 months (p = 0.036). Patients treated with WBRT had significant worsening of appetite, hair loss, and drowsiness after treatment.

Conclusions

Despite higher symptom burden after WBRT attributed to the side effects of RT (such as appetite loss, drowsiness, and hair loss), global health status, physical functioning, and future uncertainty favored WBRT compared with SRT-TB. This may be related to the compromised brain tumor control with omission of WBRT.



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Präkanzerosen von Ösophagus, Magen und Kolon

Zusammenfassung

Unter den onkologisch wichtigen Präkanzerosen von Ösophagus, Magen und Kolon haben in Deutschland Adenokarzinome der Speiseröhre die niedrigste Prävalenz. Bei der Beurteilung ihrer Präkanzerose, dem Barrett-Ösophagus, stellt die Sicherung des Dysplasiegrads, der maßgeblich das weitere Vorgehen bestimmt, aufgrund der heterogen verteilten und endoskopisch nicht gut diskriminierbaren Areale mit niedrig- und hochgradiger intraepithelialer Neo‑/Dysplasie eine besondere Herausforderung dar. Zudem besteht hinsichtlich dessen histomorphologischer Einordung eine relevante Interobservervariabilität. Endoskopisch sichtbare adenomatöse Präkanzerosen des Magens sind eher selten. Die in die sog. präkanzeröse Kaskade des Magens einzuordnenden Läsionen bedürfen zur optimalen Risikostratifizierung einer standardisierten endoskopisch-bioptischen Sicherung. Unter den Präkanzerosen des Kolons können die serratierten Läsionen histomorphologisch eine Herausforderung darstellen.



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Particle Size and Concentration Dependent Ecotoxicity of Nano- and Microscale TiO 2 —Comparative Study by Different Aquatic Test Organisms of Different Trophic Levels

Abstract

A comprehensive ecotoxicity assessment of three different nanosized TiO2 (with 16, 36 and 89 nm particle diameter) and one microscale TiO2 suspension (with 3264 nm particle diameter) was carried out with a special emphasis on the relation between product characteristics and toxic effect. The applied test battery included the combination of modified standardized tests (Aliivibrio fischeri bioluminescence inhibition test, Lemna minor growth inhibition test), and nonstandardized bioassays with unconventional physiological endpoints (Tetrahymena pyriformis phagocytic activity, the Daphnia magna heartbeat rate). Based on the lowest significant effect values, the tested aquatic organisms were the most sensitive to the microscale TiO2 suspension (with 3264 nm particle size). Although the three nanoscale TiO2 particles were aggregated in the A. fischeri and the L. minor growth media, significant inhibition rates were experienced at 0.1 and at 1 μg L─1 concentration of nTiO2 suspensions with 16 and 36 nm primary particle size, respectively. Larger aggregates may have also high impact on biological organisms. In case of the D. magna heartbeat rate test rapid agglomeration was avoided, but lower responses were found compared to other investigated systems. The short term T. pyriformis phagocytic activity test demonstrated outstanding sensitivity; three TiO2 suspensions were significantly toxic even at 0.1 μg L─1. The consequences of our study clearly indicated that nanoscale TiO2 may have an impact on the aquatic ecosystem which is strongly influenced by aggregation. The effect of exposure duration and concentration as contributing factors in nano-titanium dioxide mediated toxicity was also demonstrated.



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A simplified surgical technique for recurrent inguinal hernia repair following total extraperitoneal patch plastic

Abstract

Purpose

To present a new and alternative method for surgical treatment of recurrent inguinal hernia after total extraperitoneal patch plastic (TEP).

Methods

From January 2005 to September 2015, 35 patients (34 male, 1 female; mean age 65 ± 12.6 years) with recurrent inguinal hernia following TEP were operated at the Kliniken Essen-Mitte using a simplified method consisting of re-fixation of the primary mesh to the inguinal ligament by an anterior approach.

Results

The mean operating time was 47 ± 22 min. All complications were minor with an overall incidence of 6%. After a mean follow-up of 54 months one re-recurrence was observed.

Conclusions

This Simplified Hernia Repair is safe and avoids additional foreign body implantation. Therefore, it is our method of choice for recurrent inguinal hernias after TEP.



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Earlier Pulmonary Valve Replacement in Down Syndrome Patients Following Tetralogy of Fallot Repair

Abstract

The association between Down syndrome and pulmonary hypertension could contribute to more severe pulmonary regurgitation after tetralogy of Fallot repair and possibly earlier pulmonary valve replacement. We compared cardiac magnetic resonance measures of pulmonary regurgitation and right ventricular dilation as well as timing of pulmonary valve replacement between those with and without Down syndrome after tetralogy of Fallot repair. Review of our surgical database from 2000 to 2015 identified patients with tetralogy of Fallot with pulmonary stenosis. Those with Down syndrome were compared to those without. The primary outcome of interest was time from repair to pulmonary valve replacement. Secondary outcomes included pulmonary regurgitation and indexed right ventricular volume on cardiac magnetic resonance imaging. The cohort of 284 patients included 35 (12%) with Down syndrome. Transannular patch repair was performed in 210 (74%). Down syndrome showed greater degree of pulmonary regurgitation (55 ± 14 vs. 37 ± 16%, p = 0.01) without a significantly greater rate of right ventricular dilation (p = 0.09). In multivariable analysis, Down syndrome (HR 2.3, 95% CI 1.2–4.5, p = 0.02) and transannular patch repair (HR 5.5, 95% CI 1.7–17.6, p = 0.004) were significant risk factors for valve replacement. Those with Down syndrome had significantly lower freedom from valve replacement (p = 0.03). Down syndrome is associated with an increased degree of pulmonary regurgitation and earlier pulmonary valve replacement after tetralogy of Fallot repair. These patients require earlier assessment by cardiac magnetic resonance imaging to determine timing of pulmonary valve replacement and evaluation for and treatment of preventable causes of pulmonary hypertension.



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Band gap dependence of semiconducting nano-wires on cross-sectional shape and size

Abstract

Applicability of three different thermodynamic models based on classical (Qi model) as well as quantum approach (Lu et al. and Jiang et al. models) have been discussed to search out the exact description of band gap variation with size in semiconducting nanowires. All considered models showed an increment in the band gap as diametric size of the wire decreases. To study band gap and the band edge shift of nanowires, a novel approach has been proposed by incorporating shape effect with size in Jiang et al. model due to its accuracy or consistency with the experimental results. Hence a unified model without any adjustable parameter has been established for studying the combined effect of size and shape on band edges shift [∆Ec (D), ∆Ev (D)] and the band gap expansion [∆EG (D)] of the semiconducting nanowires. Present study reveals that for small-sized nanowires band gap expansion and edge shift is not only governed by size but also varies with the cross-sectional shape. Band gap expansion and edge shift showed rising behavior due to the enhancement in surface area.



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Multiconfiguration Dirac–Fock calculation of Kα transition energies in beryllium like titanium

Abstract

We report calculations of energy levels and radiative rates for Kα transitions among the lowest 40 fine-structure levels in Be-like Ti XIX. The wavelengths, oscillator strengths, radiative rates and lifetimes for all possible Kα transitions have been calculated using the multiconfiguration Dirac–Fock method. The accuracy of the results is determined through extensive comparisons with existing laboratory measurements and theoretical results. These results can be used to analyze the previous experimental results and guide the design of the future experiments.



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Post-operative strictures in anorectal malformation: trends over 15 years

Abstract

Aim

For decades, paediatric surgeons have employed the standard posterior sagittal anorectoplasty (PSARP) approach to deal with patients with anorectal malformations (ARM). In recent years, we noted an apparent increase in the incidence of anal stricture after surgical repair of ARM following the introduction of laparoscopic pull-through and techniques aiming to preserve the internal sphincter—the internal sphincter sparing approach (ISSA). We decided to analyse our data to find out if these new trends had added to the problem of post-operative strictures.

Methods

All patients with ARM at our institution from January 2000 to December 2015 were identified. A retrospective case note review was carried out. Data collected included patient demographics, type of ARM, operative details, and post-operative outcomes.

Results

114 patients were identified. Ten patients were excluded. Of the remaining 104 children, 48 (46%) were female. Median age was 8.3 (range 1.2–16.8) years. Types of ARM were as follows: perineal fistula (15 patients), anterior stenotic anus (12), imperforate anus without fistula (10), vestibular fistula (32), rectourethral (bulbar) fistula (11), rectourethral (prostatic) fistula (14), rectovesical fistula (7), and cloaca (3). Twenty-seven patients with a perineal fistula or anterior stenotic anus underwent perineal procedures that were variably described by the different operating surgeons. The majority (15 patients) had an anoplasty, 5 had anal transposition, 5 had limited PSARP, and 2 patients had ISSA. Two patients with a cloacal anomaly underwent open cloacal reconstruction. Of the remaining 75 patients, 45 had a PSARP approach, 6 had a laparoscopic-assisted pull-through, and 18 had ISSA. Four girls with vestibular fistula had anal transposition and two boys with imperforate anus without fistula had anoplasty. 15 (14%) children developed anal stricture. Stricture incidence differed according to operation type. PSARP was the most commonly performed procedure, with only 6% developing a stricture. In contrast, 30% of ISSA patients and 50% of children who had laparoscopic pull-through developed a stricture. Strictures also occurred in 11 and 12% of children having anal transposition and anoplasty, respectively.

Conclusion

The laparoscopic-assisted pull-through involves tunnelling the sphincter muscle complex. We found that often the tunnels were not wide enough, resulting in narrowing not just at the ano-cutaneous junction but also at the deeper level. 50% developed strictures. We have modified our technique by ensuring that the tunnels are generous enough to allow the rectum to be pulled through without any resistance. ISSA unfortunately resulted in 30% of our patients developing strictures. This approach, started in 2004, was, therefore, abandoned in 2013. The standard Pena's PSARP, with or without a laparotomy, has stood the test of time. Any modification of this approach must be carefully thought through and audited meticulously. Strictures can cause significant morbidity, which may need several revisions, and the resulting redo anoplasties run the risk of sphincter damage, ironically which the newer modifications of ISSA were trying to conserve.



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Clinical relevance of P-glycoprotein activity on peripheral blood mononuclear cells and polymorphonuclear neutrophils to methotrexate in systemic lupus erythematosus patients

Abstract

To elucidate the relationship between P-glycoprotein activity on peripheral blood leukocytes of systemic lupus erythematosus (SLE) patients with lupus arthritis and the clinical response to methotrexate. An observational study was made in patients with SLE according to ACR criteria 1997 who had arthralgia and arthritis and received methotrexate for ≥3 months. Methotrexate responders and non-responders were compared according to the Clinical Disease Activity Index. Mononuclear cells and polymorphonuclear neutrophils were isolated from SLE patients and P-glycoprotein expression was measured using the relative fluorescence index and percentage of positive cells. The chi-square test was used to compare P-glycoprotein activity between responders and non-responders. Thirty-two patients with a mean age of 45.4 ± 10.7 years were included: 34.4% had a response to methotrexate and 65.6% did not. Mean relative fluorescence units of both mononuclear cells and polymorphonuclear neutrophils were significantly lower in patients with a good response (7.0 ± 4.3 vs. 9.6 ± 3.8; p = 0.041 and 4.2 ± 3.5 vs. 7.6 ± 4.0; p = 0.004). The prevalence of low fluorescence levels (<6 relative fluorescence units), signifying higher P-glycoprotein activity of both mononuclear cells and polymorphonuclear neutrophils, was higher in methotrexate responders than in non-responders (27.3 vs. 4.8%; p = 0.10 and 81.8 vs. 23.8%; p = 0.003, respectively). In SLE patients with joint involvement treated with methotrexate, P-glycoprotein activity was higher in responders to methotrexate than in non-responders. Further studies are required to determine the mechanisms behind this finding and whether P-glycoprotein activity mediates alterations in methotrexate efficacy.



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Angiostrongylus cantonensis : An optimized cultivation of this parasitic nematode under laboratory conditions

Abstract

Angiostrongylus cantonensis (A. cantonensis), a parasitic nematode, is the important neurotropic pathogen which causes human angiostrongyliasis. It has a complex life-cycle and severe parasite-host interaction in contrast to free-living nematode. Establishment of a well-suited life-cycle and in vitro cultivation of A. cantonensis in the laboratory will be one of the key techniques to elucidate the mechanism of parasite-host interaction. However, the low survival and growth rate of worms is still to be the problem. We optimized the known life-cycle of A. cantonensis in the laboratory, showing that small in size, easy to breed, and high compatibility of Biomphalaria straminea precede the common snails as an intermediate host of A. cantonensis. Furthermore, the egg hatching rate in Ham's F-12 medium reached approximately 80% using the eggs of mature female adult worms. We also demonstrated that the survival of larvae could be sustained for more than 30 days by in vitro cultivation of L1 larvae in DMEM with mixed antibiotics (100 units/mL of penicillin G potassium, 50 μg/mL of streptomycin sulfate, and 0.5 μg/mL of amphotericin B) and L3, L4, and L5 larvae in Waymouth's medium with 20% fetal calf serum and mixed antibiotics. Infective L1 and L3 larvae kept high infective rate to the snail and rat after cultivation in these media, respectively. It will provide the basis for studying on genetic manipulations for functional genes, new drug screening, and the mechanism of parasite-host interaction of parasitic nematodes.



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