Predictive Factors and Pattern of Locoregional Recurrence After Prophylactic Central Neck Dissection in Papillary Thyroid Carcinoma

© 2014, Society of Surgical Oncology. Background: Prophylactic central neck dissection (pCND) at the time of the total thyroidectomy (TT) remains controversial in clinically nodal-negative (cN0) papillary thyroid carcinoma. Our study was designed to examine the predictive factors and pattern of locoregional recurrence (LRR) after pCND in the context of the postoperative stimulated Tg (sTg) level. Results: After a follow-up of 66.6 ± 38.6 months, 14 (4.1 %) suffered from LRR. The duration to first LRR was 36.4 ± 21.7 months. The estimated 5- and 10-year LRR rates were 5.1 and 6.1 %, respectively. Of these 14 LRR, 3 (21.4 %) involved the central compartment alone, 9 (64.3 %) involved the lateral compartment alone, and 2 (14.3 %) involved both central and lateral compartments. After adjusting for other clinicopathological factors, postablation sTg level ≥ 1 µg/L (hazard ratio 265.109, 95 % confidence interval 1.132–62075.644, p = 0.045) was the only independent predictor of LRR. Conclusions: Annualized risk of LRR after pCND was approximately 1 % in the first 5 years and 0.2 % in the subsequent 5 years. Most (78.6 %) LRRs involved the lateral compartment. Postablation sTg ≥ 1 µg/L significantly predicted risk of LRR. Methods: A total of 341 patients who underwent TT and unilateral pCND were analyzed. Patients with an identifiable lesion on ultrasonography or whole-body scan within 6 months of surgery were excluded. LRR was defined as an identifiable lesion on USG, which was later confirmed by cytology/histology. Preablation sTg level was taken 2 months after surgery, whereas postablation sTg level was taken 8 months after surgery. Cox regression was used in the univariate and multivariate analyses to identify significant independent factors for LRR.postprin

White blood cell count and risk of incident lung cancer in the UK Biobank

Background The contribution of measurable immunological/inflammatory parameters to lung cancer development remains unclear, particularly among never-smokers. We investigated the relationship between total and differential white blood cell (WBC) counts and incident lung cancer risk overall and among subgroups defined by smoking status and sex in the United Kingdom (UK). Methods We evaluated 424,407 adults aged 37-73 years from the UK Biobank. Questionnaires, physical measurements, and blood were administered/collected at baseline in 2006-2010. Complete blood cell counts were measured using standard methods. Lung cancer diagnoses and histological classifications were obtained from cancer registries. Multivariable Cox regression models were used to estimate the hazard ratio (HR) and 95% confidence intervals (CI) of incident lung cancer in relation to quartiles (Q) of total WBC and subtype-specific counts, with Q1 as the reference. Results There were 1,493 incident cases diagnosed over an average 7-year follow-up. Overall, the highest quartile of total WBC count was significantly associated with elevated lung cancer risk (HRQ4=1.67, 95% CI:1.41-1.98). Among women, increased risks were found in current-smokers (ncases/n=244/19,464, HRQ4=2.15, 95% CI:1.46-3.16), former-smokers (ncases/n=280/69,198, HRQ4=1.75, 95% CI:1.24-2.47), and never-smokers without environmental tobacco smoke exposure (ncases/n=108/111,294, HRQ4=1.93, 95% CI:1.11-3.35). Among men, stronger associations were identified in current-smokers (ncases/n=329/22,934, HRQ4=2.95, 95% CI:2.04-4.26) and former-smokers (ncases/n= 358/71,616, HRQ4=2.38, 95% CI:1.74-3.27) but not in never-smokers. Findings were similar for lung adenocarcinoma and squamous cell carcinoma and were driven primarily by elevated neutrophil fractions. Conclusions Elevated WBCs could potentially be one of many important markers for increased lung cancer risk, especially among never-smoking women and ever-smoking men

Treatment threshold for intra-operative hypotension in clinical practice-a prospective cohort study in older patients in the UK

Intra-operative hypotension frequently complicates anaesthesia in older patients and is implicated in peri-operative organ hypoperfusion and injury. The prevalence and corresponding treatment thresholds of hypotension are incompletely described in the UK. This study aimed to identify prevalence of intra-operative hypotension and its treatment thresholds in UK practice. Patients aged ≥ 65 years were studied prospectively from 196 UK hospitals within a 48-hour timeframe. The primary outcome was the incidence of hypotension (mean arterial pressure 20%; systolic blood pressure 20% reduction in systolic blood pressure from baseline and 77.5% systolic blood pressure <100 mmHg. The mean (SD) blood pressure triggering vasopressor therapy was mean arterial pressure 64.2 (11.6) mmHg and the mean (SD) stated intended treatment threshold from the survey was mean arterial pressure 60.6 (9.7) mmHg. A composite adverse outcome of myocardial injury, kidney injury, stroke or death affected 345 patients (7.3%). In this representative sample of UK peri-operative practice, the majority of older patients experienced intra-operative hypotension and treatment was delivered below suggested thresholds. This highlights both potential for intra-operative organ injury and substantial opportunity for improving treatment of intra-operative hypotension

Fluoxetine: a case history of its discovery and preclinical development

Introduction: Depression is a multifactorial mood disorder with a high prevalence worldwide. Until now, treatments for depression have focused on the inhibition of monoaminergic reuptake sites, which augment the bioavailability of monoamines in the CNS. Advances in drug discovery have widened the therapeutic options with the synthesis of so-called selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine. Areas covered: The aim of this case history is to describe and discuss the pharmacokinetic and pharmacodynamic profiles of fluoxetine, including its acute effects and the adaptive changes induced after long-term treatment. Furthermore, the authors review the effect of fluoxetine on neuroplasticity and adult neurogenesis. In addition, the article summarises the preclinical behavioural data available on fluoxetine’s effects on depressive-like behaviour, anxiety and cognition as well as its effects on other diseases. Finally, the article describes the seminal studies validating the antidepressant effects of fluoxetine. Expert opinion: Fluoxetine is the first selective SSRI that has a recognised clinical efficacy and safety profile. Since its discovery, other molecules that mimic its mechanism of action have been developed, commencing a new age in the treatment of depression. Fluoxetine has also demonstrated utility in the treatment of other disorders for which its prescription has now been approved

Optimal drug combinations and minimal hitting sets

<p>Abstract</p> <p>Background</p> <p>Identifying effective drug combinations that significantly improve over single agents is a challenging problem. Pairwise combinations already represent a huge screening effort. Beyond two drug combinations the task seems unfeasible.</p> <p>Results</p> <p>In this work we introduce a method to uncover drug combinations with a putative effective response when presented to a heterogeneous population of malignant agents (strains), such as cancer cell lines or viruses. Using data quantifying the effect of single drugs over several individual strains, we search for minimal drug combinations that successfully target all strains. We show that the latter problem can be mapped to a minimal hitting set problem in mathematics. We illustrate this approach using data for the NCI60 panel of tumor derived cell lines, uncovering 14 anticancer drug combinations.</p> <p>Conclusion</p> <p>The drug-response graph and the associated minimal hitting set method can be used to uncover effective drug combinations in anticancer drug screens and drug development programs targeting heterogeneous populations of infectious agents such as HIV.</p

Treatment threshold for intra‐operative hypotension in clinical practice—a prospective cohort study in older patients in the UK

Intra-operative hypotension frequently complicates anaesthesia in older patients and is implicated in peri-operative organ hypoperfusion and injury. The prevalence and corresponding treatment thresholds of hypotension are incompletely described in the UK. This study aimed to identify prevalence of intra-operative hypotension and its treatment thresholds in UK practice. Patients aged ≥ 65 years were studied prospectively from 196 UK hospitals within a 48-hour timeframe. The primary outcome was the incidence of hypotension (mean arterial pressure 20%; systolic blood pressure 20% reduction in systolic blood pressure from baseline and 77.5% systolic blood pressure <100 mmHg. The mean (SD) blood pressure triggering vasopressor therapy was mean arterial pressure 64.2 (11.6) mmHg and the mean (SD) stated intended treatment threshold from the survey was mean arterial pressure 60.6 (9.7) mmHg. A composite adverse outcome of myocardial injury, kidney injury, stroke or death affected 345 patients (7.3%). In this representative sample of UK peri-operative practice, the majority of older patients experienced intra-operative hypotension and treatment was delivered below suggested thresholds. This highlights both potential for intra-operative organ injury and substantial opportunity for improving treatment of intra-operative hypotension

SinicView: A visualization environment for comparisons of multiple nucleotide sequence alignment tools

BACKGROUND: Deluged by the rate and complexity of completed genomic sequences, the need to align longer sequences becomes more urgent, and many more tools have thus been developed. In the initial stage of genomic sequence analysis, a biologist is usually faced with the questions of how to choose the best tool to align sequences of interest and how to analyze and visualize the alignment results, and then with the question of whether poorly aligned regions produced by the tool are indeed not homologous or are just results due to inappropriate alignment tools or scoring systems used. Although several systematic evaluations of multiple sequence alignment (MSA) programs have been proposed, they may not provide a standard-bearer for most biologists because those poorly aligned regions in these evaluations are never discussed. Thus, a tool that allows cross comparison of the alignment results obtained by different tools simultaneously could help a biologist evaluate their correctness and accuracy. RESULTS: In this paper, we present a versatile alignment visualization system, called SinicView, (for Sequence-aligning INnovative and Interactive Comparison VIEWer), which allows the user to efficiently compare and evaluate assorted nucleotide alignment results obtained by different tools. SinicView calculates similarity of the alignment outputs under a fixed window using the sum-of-pairs method and provides scoring profiles of each set of aligned sequences. The user can visually compare alignment results either in graphic scoring profiles or in plain text format of the aligned nucleotides along with the annotations information. We illustrate the capabilities of our visualization system by comparing alignment results obtained by MLAGAN, MAVID, and MULTIZ, respectively. CONCLUSION: With SinicView, users can use their own data sequences to compare various alignment tools or scoring systems and select the most suitable one to perform alignment in the initial stage of sequence analysis

Site-specific incorporation of phosphotyrosine using an expanded genetic code.

Access to phosphoproteins with stoichiometric and site-specific phosphorylation status is key to understanding the role of protein phosphorylation. Here we report an efficient method to generate pure, active phosphotyrosine-containing proteins by genetically encoding a stable phosphotyrosine analog that is convertible to native phosphotyrosine. We demonstrate its general compatibility with proteins of various sizes, phosphotyrosine sites and functions, and reveal a possible role of tyrosine phosphorylation in negative regulation of ubiquitination

Introducing EMMIE: An evidence rating scale to encourage mixed-method crime prevention synthesis reviews

Objectives This short report describes the need for, and the development of, a coding system to distil the quality and coverage of systematic reviews of the evidence relating to crime prevention interventions. The starting point for the coding system concerns the evidence needs of policymakers and practitioners. Methods The coding scheme (EMMIE) proposed builds on previous scales that have been developed to assess the probity, coverage and utility of evidence both in health and criminal justice. It also draws on the principles of realist synthesis and review. Results The proposed EMMIE scale identifies five dimensions to which systematic reviews intended to inform crime prevention should speak. These are the Effect of intervention, the identification of the causal Mechanism(s) through which interventions are intended to work, the factors that Moderate their impact, the articulation of practical Implementation issues, and the Economic costs of intervention

A low density of 0.8 g/cc for the Trojan binary asteroid 617 Patroclus

The Trojan population consists of two swarms of asteroids following the same orbit as Jupiter and located at the L4 and L5 Lagrange points of the Jupiter-Sun system (leading and following Jupiter by 60 degrees). The asteroid 617 Patroclus is the only known binary Trojan (Merline et al. 2001). The orbit of this double system was hitherto unknown. Here we report that the components, separated by 680 km, move around the system centre of mass, describing roughly a circular orbit. Using the orbital parameters, combined with thermal measurements to estimate the size of the components, we derive a very low density of 0.8 g/cc. The components of Patroclus are therefore very porous or composed mostly of water ice, suggesting that they could have been formed in the outer part of the solar system.Comment: 10 pages, 3 figures, 1 tabl