Treatment selection for esophageal cancer: evaluation from a nationwide database

Abstract

Background

Most elderly patients poorly tolerate the standard treatment for esophageal cancer; however, little information is available regarding the appropriateness of non-standard esophageal cancer treatments for those patients. This study aims to analyze the treatment costs and completion rates of patients undergoing a real-world treatment for esophageal cancer to elucidate the treatment selection and its quality.

Materials and methods

We analyzed treatment costs and completion rates for patients with esophageal cancer and analyzed these data relative to patient age and center volumes. Patients with esophageal cancer [UICC, TMN, Clinical stage II/III (excluding T4)] who were diagnosed in 2013 were analyzed. Patients were classified into five groups defined as follows: surgical therapy, chemotherapy, concurrent chemoradiotherapy (CCRT), modified concurrent chemoradiotherapy (mCRT), and radiotherapy (RT).

Results

Mean and median age of patients who received surgery and CCRT were comparable; however, patients who underwent mCRT and RT tended to be older. Medical costs associated with surgery were higher than costs associated with other non-surgical treatments. Cost and completion rate of chemoradiotherapy did not differ between CCRT and mCRT; however, both had higher completion rates compared to that of RT. Surgical expenses tended to be the highest in low-volume centers and the lowest in high-volume centers.

Conclusion

Treatment of esophageal cancer at high-volume centers seems well balanced compared with medium- to low-volume centers. mCRT was widely performed and comparable in medical cost to CCRT, although additional clinical impacts were unclear.

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Complex versus Standard Fittings: Part 2

In Part 2 of this three part series, the concept of Exception Discovery is introduced. The discussion focuses on situations where hearing thresholds may drive hearing aid fittings that are not as optimal as an approach focused on the quality of the patient's remaining hearing.

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Clinical routine assessment of palliative care symptoms and concerns and caregiver burden in glioblastoma patients: an explorative field study

Abstract

The implementation of self-reported outcome measurements into clinical routine was tested to help facilitate early access to palliative care (PC) for glioblastoma (GBM)-patients. Measures detail PC symptoms and concerns and caregiver burden. Between January 2014 and December 2016, a total of 337 GBM-patients were discussed during meetings of the neuro-oncology tumor board to examine further treatment options. Each patient, along with their caregivers, was requested to participate in self-assessment using the palliative outcome scale (POS) and the Zarit Burden Interview (ZBI). Analyses encompassed summary statistics, non-parametric tests, visual graphic analysis, content analysis and assessing the utilization of the specialized PC consulting service (SPCCS). Ninety-five (28%) GBM-patients and 71 (21%) caregivers completed the self-assessment. Of these, 20 patients and 12 caregivers repeated the assessment at least once more during follow-up. POS total scores were similar in the group of patients with initial diagnosis [10 (0–31)] and those with later disease stages like recurrent diagnosis [9 (0–25)], but ZBI total scores differed [14 (0–51) vs. 24 (2–62)]. Single item analysis demonstrated that anxiety and worries about the future predominated. Caregivers were torn between high engagement in caring and feeling overburdened. Still, requests for the SPCCS showed no increase. Actual implementation of measures like POS and ZBI for detecting PC concerns and caregiver burden with GBM-patients in the field remains challenging as indicated by the limited response rate and lack of increased requests for the SPCCS. Modified clinical routines including strengthening awareness of PC, and allowing proxy-assessment might help to overcome barriers.

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Biosorptive Removal of Copper(II) by Bacillus cereus Isolated from Contaminated Soil of Electroplating Industry in India

Abstract

Heavy metal contamination is one of the major environmental issues around the globe and hence, this work aims to apply microbes to remove these toxic inorganic pollutants. Bacillus cereus KTSMBNL 81 isolated from electroplating industry waste-contaminated soil has been identified by biochemical and 16S rRNA sequencing analysis. B. cereus has been applied for the uptake of Cu(II) ions from the aqueous solution and the effects of various physicochemical parameters influencing Cu(II) biosorption namely, initial Cu(II) ion concentration (100–400 mg L⁻¹), pH of the solution (2–10), temperature (25–45 °C), and contact time (0–26 h), were investigated. Maximum Cu(II) removal (89%) was observed at the following conditions: initial pH 6.0, temperature 35 °C, contact time 26 h, and initial Cu(II) concentration of 100 mg L⁻¹. FTIR spectrum of the biomass indicated the presence of carboxyl, hydroxyl, and amino groups that might be responsible for biosorption of Cu(II) and the SEM-EDX results showed a distinct change in the surface morphology after the biosorption of Cu(II) ions. XRD pattern confirmed the crystalline nature of the organism. The results demonstrated that the B. cereus KTSMBNL 81 is very effective, tolerant, economical, and environment-friendly sorbent for removing Cu(II) ions from aqueous solutions.

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Dacomitinib potentiates the efficacy of conventional chemotherapeutic agents via inhibiting the drug efflux function of ABCG2 in vitro and in vivo

ATP-binding cassette subfamily G member 2 (ABCG2), a member of the ABC transporter superfamily proteins, mediates multidrug resistance (MDR) by transporting substrate anticancer drugs out of cancer cells and d...

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FAK-ERK activation in cell/matrix adhesion induced by the loss of apolipoprotein E stimulates the malignant progression of ovarian cancer

Extracellular matrix (ECM) is a mediator of tumor progression. However, whether the alterations of the intraperitoneal ECM prior to tumor establishment affects the malignant progression of ovarian cancer remai...

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EACMFS Awards

The Council of EACMFS wishes to ensure that all members of the Association are aware of the current awards and prizes that are available. These are designed to provide educational support and also to allow the opportunity for trainees and those who have recently achieved specialist status to visit units outside their own departments.

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Announcements

Dear Colleagues,

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Editorial Board

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Sealed osteons in animals and humans: low prevalence and lack of relationship with age

Abstract

Sealed osteons are unusual variants of secondary osteons that have received little attention, especially in non-human bones. Sealed osteons are characterized by central canals that are plugged with bone tissue. As with other variants of secondary osteons (e.g. drifting, dumbbell, multi-canal), understanding how and why sealed osteons form can shed light on the mechanisms that regulate normal bone remodeling and how this process can be perturbed with aging and some diseases. In a recent microscopic evaluation of human tibiae obtained after traumatic amputations, 4–5% of the osteons were sealed. It is suggested that this high prevalence reflects occasional localized microscopic ischemia from normal osteonal remodeling; hence sealed osteons are implicated in human skeletal fragility. Therefore, osteon prevalence would be expected to correlate with the bone remodeling seen with aging; for example, showing positive relationships between sealed osteons and the population density of typical secondary osteons (OPD). We evaluated the prevalence of partially sealed (80–99% sealed) and fully sealed osteons with respect to age and variations in OPD in 10 adult human femora (34–71 years) and in various non-human appendicular bones of mature animals that were not of advanced age, including deer calcanei, equine radii and equine third metacarpals. An additional sample of 10 bilateral human femora with unilateral non-cemented total hip replacements (F,+HR) and non-implanted contralateral femora (F,−HR) were evaluated (10 patients; 52–94 years). In non-human bones, sealed + partially sealed osteons were rare (~0.1%) even when having relatively high OPD. When considering sealed + partially sealed osteons in femora from patients without any HR, results showed that 1.6% of the osteons were sealed or partially sealed, which was much lower than anticipated, but this is 10- to 20-fold more than in any of the non-human bones. Additionally, in all bones, sealed + partially sealed osteons were significantly smaller than typical secondary osteons (mean diameters: 125 vs. 272 μm; P < 0.005). In the patients with HR, the percentage of sealed + partially sealed osteons: (i) did not correlate with age, (ii) showed no significant difference between F,−HR and F,+HR (1.9 vs. 2.1%; P = 0.2), and (iii) was positively correlated with OPD (r = 0.67, P = 0.001), which differs from the very weak or lack of correlations in the non-human bones and the other human femur sample. The lack of an age-related relationship, in addition to the very low prevalence of sealed + partially sealed osteons are inconsistent with the idea that they contribute to reduced bone quality seen in aging humans. The small size of sealed and partially sealed osteons, regardless of species affiliation, suggests that they represent closing cones at the termini of some osteons. Available evidence suggests that osteons of primates might have a greater capacity for branching that is associated with closing cones, which might explain the 10–20 times higher prevalence of sealed + partially sealed osteons in the human bones examined in this study.

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The remarkable vocal anatomy of the koala (Phascolarctos cinereus): insights into low-frequency sound production in a marsupial species

Abstract

Koalas are characterised by a highly unusual vocal anatomy, with a descended larynx and velar vocal folds, allowing them to produce calls at disproportionately low frequencies. Here we use advanced imaging techniques, histological data, classical macroscopic dissection and behavioural observations to provide the first detailed description and interpretation of male and female koala vocal anatomy. We show that both males and females have an elongated pharynx and soft palate, resulting in a permanently descended larynx. In addition, the hyoid apparatus has a human-like configuration in which paired dorsal, resilient ligaments suspend the hyoid apparatus from the skull, while the ventral parts tightly connect to the descended larynx. We also show that koalas can retract the larynx down into the thoracic inlet, facilitated by a dramatic evolutionary transformation of the ventral neck muscles. First, the usual retractors of the larynx and the hyoid have their origins deep in the thorax. Secondly, three hyoid muscles have lost their connection to the hyoid skeleton. Thirdly, the genioglossus and geniohyoid muscles are greatly increased in length. Finally, the digastric, omohyoid and sternohyoid muscles, connected by a common tendinous intersection, form a guiding channel for the dynamic down-and-up movements of the ventral hyoid parts and the larynx. We suggest that these features evolved to accommodate the low resting position of the larynx and assist in its retraction during call production. We also confirm that the edges of the intra-pharyngeal ostium have specialised to form the novel, extra-laryngeal velar vocal folds, which are much larger than the true intra-laryngeal vocal folds in both sexes, but more developed and specialised for low frequency sound production in males than in females. Our findings illustrate that strong selection pressures on acoustic signalling not only lead to the specialisation of existing vocal organs but can also result in the evolution of novel vocal structures in both sexes.

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EMCrit RACC Podcast 218 – Physostigmine with Bryan Hayes

Physostigmine for Anticholinergic toxicity

EMCrit Project by Scott Weingart.

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GeneReviews®

Related Articles

GeneReviews®

Book. 1993

Authors: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A

Abstract
CLINICAL CHARACTERISTICS: Individuals with X-linked dystonia-parkinsonism (XDP) have dystonia of varying severity and parkinsonism. XDP afflicts primarily Filipino men and, rarely, women. The mean age of onset in men is 39 years; the clinical course is highly variable with parkinsonism as the initial presenting sign, overshadowed by dystonia as the disease progresses. Features of parkinsonism include resting tremor, bradykinesia, rigidity, postural instability, and severe shuffling gait. The dystonia develops focally, most commonly in the jaw, neck, trunk, and eyes, and less commonly in the limbs, tongue, pharynx, and larynx, the most characteristic being jaw dystonia often progressing to neck dystonia. Individuals with pure parkinsonism have non-disabling symptoms that are only slowly progressive; those who develop a combination of parkinsonism and dystonia can develop multifocal or generalized symptoms within a few years and die prematurely from pneumonia or intercurrent infections. Female carriers are mostly asymptomatic, though a small minority may manifest dystonia, parkinsonism, or chorea.
DIAGNOSIS/TESTING: The diagnosis of XDP is suspected in a male with typical clinical findings, family history consistent with X-linked inheritance, and maternal ancestral roots from the Panay Islands in the Philippines. Molecular genetic testing for variants that tag a disease-associated haplotype of the multilocus transcript system termed TAF/DYT3 is required to confirm the diagnosis in those with no known family history of XDP, very early symptoms, and/or a phenotype of pure parkinsonism, pure tremor, or chorea without dystonia. Olfactory testing indicates olfactory dysfunction early in the disease and may be used to support the diagnosis when molecular genetic testing is not available.
MANAGEMENT: Treatment of manifestations: Pharmacologic agents are used to treat dystonia or parkinsonism or both. Anticholinergic agents, benzodiazepines, and sometimes neuroleptics are used in the early stages of dystonia; zolpidem and tetrabenazine are used after dystonia becomes multifocal or generalized. Botulinum toxin injections improve focal dystonia but may worsen swallowing in individuals with preexisting dysphagia. Parkinsonism is treated with levodopa and dopamine agonists to control tremor. Bilateral pallidal deep brain stimulation may be used to treat advanced disease and medically refractory dystonia, although it may have less effect on parkinsonism. Prevention of secondary complications: Swallowing evaluation to guide diet modification and swallowing techniques to minimize risk of aspiration. Physical therapy, coupled with maximal medical and surgical therapy, may help delay immobility and its complications. Surveillance: Annual clinical evaluations in males with the disease-related haplotype who are not yet symptomatic, biannual evaluation for symptomatic males to monitor medications, and periodic swallowing evaluation, especially in those with subjective dysphagia.
GENETIC COUNSELING: XDP is inherited in an X-linked manner. Approximately 94% of affected individuals have a known family history of the condition. De novo occurrence of the disease-related haplotype associated with the disorder has not been observed to date. Males with XDP pass the TAF1/DYT3 disease-associated haplotype to all of their daughters and none of their sons. Women who are carriers have a 50% chance of transmitting the TAF1/DYT3 disease-associated haplotype in each pregnancy: males who inherit the TAF1/DYT3 disease-associated haplotype will be affected; females who inherit the TAF1/DYT3 disease-associated haplotype are mostly asymptomatic, although a small percentage may manifest symptoms. Carrier evaluation of at-risk female relatives is possible if the TAF1/DYT3 disease-associated haplotype has been identified in the family. Once the TAF1/DYT3 disease-associated haplotype has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic diagnosis for XDP are possible. Caution should be exercised in interpreting the results of prenatal testing as the c.94C>T (p.Arg32Cys) variant that marks the disease haplotype has not been proven to be the molecular cause of XDP.

PMID: 20301662

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Alcohol consumption and risk of hematological malignancies: A meta-analysis of prospective studies

Abstract

Current convincing evidence suggests that alcohol intake increases the risk of several carcinomas, which might subsequently lead to a recommendation towards limiting alcohol consumption. However, there are accumulating data worth meta-analyzing that show a different effect on the risk of hematological malignancies. Eligible cohort studies were sought in PubMed database up to August 31, 2016. Separate analyses were performed by subtype of hematological malignancy (non-Hodgkin lymphoma [NHL] and subtypes, Hodgkin lymphoma [HL], leukemia and subtypes), time status (ever, current, former), level of consumption (light, moderate, heavy), alcoholic beverage (total alcohol, beer, liquor, wine), and gender. Moderate and heavy alcohol consumption were significantly associated with reduced risk of NHL (relative risk [RR]=0.85, 95% confidence interval [CI]: 0.80-0.90 and RR=0.73, 95%CI: 0.60-0.89, respectively); a protective trend was also shown for light alcohol intake (RR=0.93, 95%CI:0.87-1.00). Specifically, beer consumption was associated with reduced NHL risk (RR=0.88, 95%CI: 0.81-0.95). However, the association regarding other alcoholic beverages seemed null. The beneficial effects of alcohol mainly pertained to Diffuse Large B-Cell Lymphoma (DLBCL) (RR=0.83, 95%CI:0.77-0.89) and Follicular Lymphoma (FL) (RR=0.85, 95%CI:0.78-0.93). There was also no association between alcohol consumption and risk of HL or leukemias. In contrast to most solid malignancies, alcohol seems to confer a protective effect on NHL risk, especially on DLBCL and FL subtypes, with beer being notably beneficial. This article is protected by copyright. All rights reserved.

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Evaluation of the benefit and use of the new terminology in endometrial cytology reporting system

Objective

The introduction and establishment of a new classification system for endometrial cytology, the "New Terminology in Endometrial Cytology (NTEMC) system," which is based on the Bethesda System for uterine cervical cytology, has recently been reported. However, the clinical management for new categories in the NTEMC system, particularly atypical endometrial cells (ATEC), has not been clarified. The objective of the present study is to determine how the ATEC category should be treated and whether the introduction of the system has decreased the number of unnecessary endometrial biopsies.

Methods

Fifty-nine cases were diagnosed as "suspicious positive" according to the three-tier reporting (TTR) system, which was adopted in Japan. The specimens were re-evaluated according to the NTEMC system. Thirty-seven of the 59 patients underwent endometrial biopsy. We correlated the pathological diagnosis with the NTEMC system category.

Results

The 59 cases were classified according to the NTEMC system as follows: 36 cases were classified as ATEC of undetermined significance (ATEC-US), 21 cases were classified as ATEC for which atypical endometrial hyperplasia or worse cannot be excluded (ATEC-A), and 2 cases were classified as endometrial hyperplasia. The ratio of atypical endometrial hyperplasia or malignancy in ATEC-US category was significantly lower than that in ATEC-A category. Fifteen cases in ATEC-US category did not show atypical endometrial hyperplasia lesions or malignancy after 3 months.

Conclusions

These data suggest that patients with ATEC-US results can be followed up for at least three months, and the introduction of the NTEMC system decreased the number of unnecessary endometrial biopsies.

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Immediate biopsy of cervical cytology-negative and non-HPV-16/18 oncogenic types positive patients

Background

According to the American Society of Colposcopy and Cervical Pathology (ASCCP), a co-test is recommended for patients one year after the detection of non-HPV 16/18 viral types in association with a negative cervical cytology. In this study, we used immediate colposcopy to evaluate the risks to the patient during the one year waiting period.

Methods

We included 544 Hpv-positive/cervical cytology-negative patients who underwent cervical cancer screening from June 2015 to June 2017. Cytological specimens were classified using the Bethesta method on a liquid based preparation. We used the Hybrid Capture 2 system to define HPV DNA. Biopsies were performed on all patients under colposcopy.

Results

Three hundred and seventy-five patients had HPV types 16/18 and 169 had non-HPV-16/18 oncogenic types. Of the 169 patients who had non-HPV-16/18 oncogenic types, 151 (89%) had no dysplasia, 16 (9.4%) had CIN 1, and 2 (1.1%) had CIN 2/CIN 3.

Conclusion

For the patients who had cervical cytology negative/non-HPV-16/18 positive, we detected that 1.1% of these women had CIN 2-3. For this reason, by chasing the algorithm recommended by guidelines, gynecologists take risk missing a diagnosis of CIN 2 plus lesion in 1.1% of patients.

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The rs1024611 in the CCL2 gene and risk of gynecological cancer in Asians: a meta-analysis

Abstract

Background

The -2518A/G (rs1024611) polymorphism of the CCL2 (C-C motif chemokine ligand 2), also known as MCP-1 (monocyte chemotactic protein-1) gene, has been reported to be associated with increased gynecological cancer risk, but the results are conflicting.

Methods

In this analysis, 1089 cases and 1553 controls from six publications were used to investigate the association between CCL2-2518A/G (rs1024611) polymorphism and the risk of gynecological cancer with a meta-analytic approach. Studies published on EBSCO, EMBASE, Web of Science, PubMed, SpringerLink, ScienceDirect, Weipu, and CNKI databases were identified (last update was on November 3, 2015). Six articles focused on the association between CCL2-2518A/G (rs1024611) polymorphism, and gynecological cancer risk was selected and data were extracted. The cancer type included endometrial cancer (n = 1), breast cancer (n = 2), ovarian cancer (n = 2), and cervical cancer (n = 1). All statistical analyses were performed using the STATA version 12.0 software.

Results

The meta-analysis showed that CCL2-2518A/G (rs1024611) polymorphism is associated with risk of gynecological cancer (GG vs AG + AA, OR = 1.55, 95%CI = 1.07–2.24, P < 0.05; AA vs GG, OR = 0.59 95%CI = 0.38–0.92, P < 0.05). Notably, the subgroup analysis demonstrated that the genotype AA is associated with a reduced gynecological cancer risk in Asians, but an increased risk when compared to AG in Europeans.

Conclusions

Our data demonstrated the CCL2-2518A/G (rs1024611) polymorphism is significantly associated with risk of gynecological cancer, and the association differs by ethnicity.

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CrosstalkNet: A visualization tool for differential co-expression networks and communities

Variations in physiological conditions can rewire molecular interactions between biological compartments, which can yield novel insights into gain or loss of interactions specific to perturbations of interest. Networks are a promising tool to elucidate intercellular interactions, yet exploration of these large-scale networks remains a challenge due to their high dimensionality. To retrieve and mine interactions, we developed CrosstalkNet, a user friendly, web-based network visualization tool that provides a statistical framework to infer condition-specific interactions coupled with a community detection algorithm for bipartite graphs to identify significantly dense subnetworks. As a case study, we used CrosstalkNet to mine a set of 54 and 22 gene expression profiles from breast tumor and normal samples, respectively, with epithelial and stromal compartments extracted via laser microdissection. We show how CrosstalkNet can be used to explore large-scale co-expression networks and obtain insights into the biological processes that govern crosstalk between different tumor compartments.

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Tamoxifen metabolism and efficacy in breast cancer- a prospective multicentre trial

Purpose: Levels of endoxifen, the most active metabolite of tamoxifen, vary by the highly polymorphic cytochrome P450 (CYP) 2D6 enzyme. We prospectively investigated tamoxifen efficacy by serum endoxifen levels and the tamoxifen activity score (TAS). Experimental Design: A prospective observational multicentre study including postmenopausal women with an oestrogen-receptor (ER)-positive breast cancer receiving first line tamoxifen, 20mg daily in the neo-adjuvant or metastatic setting recruited between February 2009 and May 2014. The primary endpoint was the objective response rate (ORR) using RECIST criteria 1.0. Secondary endpoints were clinical benefit (CB), progression-free survival (PFS) and tolerability of tamoxifen. The main analysis used logistic regression to relate ORR to serum endoxifen levels after 3 months. Endpoints were also related to other tamoxifen metabolites and to TAS. Results: Endoxifen levels were available for 247 of all 297 patients (83%) of which 209 with target lesions (85%). Median follow-up time for PFS was 32.5 months, and 62% progressed. ORR and CB were 45% and 84%, respectively. ORR was not related to endoxifen, the odds ratio of ORR was 1.008 per µg/l increase in endoxifen (95% CI 0.971-1.046, p=0.56). In general, none of the endpoints was associated with endoxifen levels, tamoxifen metabolites, or TAS. Conclusions: Under the pre-specified assumptions, the results from this prospective clinical trial do not suggest therapeutic drug monitoring of endoxifen to be of clinical value in postmenopausal women treated with tamoxifen for breast cancer in the neo-adjuvant or metastatic setting.

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Pediatric Eating Behaviors as the Intersection of Biology and Parenting: Lessons from the Birds and the Bees

Abstract

Purpose of Review

Current feeding advice to prevent pediatric obesity focuses on caregiver feeding behaviors. This review integrates newer data showing that child appetitive traits also have a genetic component.

Recent Findings

Caregiver feeding behaviors robustly correlate with child eating behaviors; however, there is also a strong heritable component.

Summary

The satiety cascade delineates the biological drive underlying hunger, satiation, and satiety. Innate individual differences exist for the components of the satiety cascade, which may explain the heritability of child eating behaviors. However, given the correlation of caregiver feeding behaviors with child eating behaviors, any etiological model should include both genetic/biological components and environmental. Integrating the biological etiology of child eating behaviors into the current environmental model has implications for tailoring feeding advice which needs to move from a "one size fits all" approach to one that is tailored to individual differences in children's biological drives to appetite.

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Using Technology in Global Otolaryngology

Technology is integral to the diverse diagnostics and interventions of Otolaryngology. Historically, major advances in this field derive from advances of associated technologies. Challenges of visualization and surgical access are increasingly overcome by integrating endoscopic, electronic, and robotic instruments. Otolaryngology is often limited to urban areas and large academic centers, making it difficult to allocate care and resources to many underserved populations. The widespread use of technology has important implications in regards to global access to this field as telemedicine is most effectively applied to specialties that are heavily reliant on data and visuals that may be electronically disseminated.

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Herbert cannulated bone screw osteosynthesis in anterior mandibular fractures treatment: a comparative study with lag screw and mini-plate

Publication date: Available online 19 February 2018
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Yehia El-Mahallawy., Haytham Al-Mahalawy.
PurposeHerbert bone screw is a successful minimally invasive mean of fracture fixation that is used routinely in orthopedic surgery. The aim of this study was to evaluate the clinical and radiographic performance of Herbert bone screw in the treatment of anterior mandibular fractures and compare it with the commonly established treatment modalities; lag screw and 2.0-mm miniplates.Materials and methodsThis study implemented a randomized clinical trial and enrolled a sample of patients with anterior mandible fractures. The primary predictor variable was treatment group categorized as Herbert bone screw (HBS), lag screw (LS), or miniplate (MP) fixation of the fracture. The primary outcome variables were the presence of interfragmentary mobility and radiodensitometric appraisal of fracture healing progression. The secondary outcome was the postoperative clinical evaluation. Other variables collected were grouped into demographic, fracture location, and intra-operative clinical data. All of the recorded data were documented, tabulated, computed, and analyzed. Statistical significance was set at 5% level.ResultsTwenty-one patients were selected and randomly allocated into the three groups based on the fixation modality utilized. There were no significant differences in demographic data for the 3 groups. There were no statistically significant differences in clinical evaluation outcomes. However, there was a statistically significant difference in the gain of mean postoperative bone density between the HBS and MP groups (P=0.012), and between LS and MP groups (P=0.045), but not between HBS and LS groups.ConclusionHerbert cannulated bone screw osteosynthesis provides a successful and minimally invasive treatment modality for the management of anterior mandibular fractures.



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Maxillary Interdental Osteotomies Have Low Morbidity For Alveolar Crestal Bone And Adjacent Teeth: A Cbct Image-Based Study

Publication date: Available online 19 February 2018
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Daniel B. Rodrigues, Paulo S.F. Campos, Larry M. Wolford, Jaqueline Ignácio, João R. Gonçalves
PurposeMaxillary segmentation involving interdental osteotomies may have an adverse effect on the inter-dental crestal bone and adjacent teeth. The purpose of this study was to evaluate the effect of interdental osteotomies on surrounding osseous and dental structures, including adjacent teeth, using cone beam computed tomography (CBCT) technology, in patients submitted to segmental maxillary osteotomies.Patients and methodsThis retrospective cohort study evaluated interdental osteotomy sites between the lateral incisors and canines in patients treated with three-piece Le Fort I osteotomies. CBCT scans were assessed using Kodac Dental Imaging software at the time intervals, T0 (presurgery), T1 (immediate post-surgery), and T2 (post-surgery minimum of 11 months). The statistical analysis using a linear regression model was adjusted to compare the variables at the different time intervals. Injury to dental structures was assessed by radiological evidence of dental damage, requirement for endodontic treatment or tooth loss.ResultsThere were 94 interdental osteotomy sites in 47 patients evaluated in this study. The mean inter-radicular distance at T0 was 2.5 mm. There was a statistically significant increase in the inter-radicular distance (T1-T0) of 0.72 mm and a reduction of the alveolar bone crest height (T2-T0) of 0.19 mm (p < 0.001) for group 2. There was a weak correlation for this increase in the inter-radicular distance with changes in alveolar crest bone height. Potential complications associated with the interdental osteotomies such as iatrogenic damage to tooth structure, need for endodontic treatment, or tooth loss were not encountered in any patients.ConclusionsThere is very low morbidity for the interdental alveolar crest and the integrity of teeth adjacent to the interdental osteotomies for patients subjected to maxillary segmentation between lateral incisors and canines.



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Fiber-reinforced resin fixed prostheses on four short implants in severely atrophic maxillae: 1-year results of a prospective cohort study

Publication date: Available online 19 February 2018
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Florian Wagner, Rudolf Seemann, Mauro Marincola, Rolf Ewers
PurposeThe aim of this paper was to report the 1-year outcomes of fixed full arch fiber-reinforced resin bridges on short implants in atrophic maxillary jaws.MethodsA prospective cohort study was designed and patients with severely atrophic maxillae, corresponding to Cawood and Howell class V and VI were included. The mesial and distal peri-implant bone levels were assessed on panoramic radiographs that were taken at the time of implant insertion (baseline) and during follow-up visits.ResultsA total of 18 patients with 72 implants inserted in atrophic maxillary jaws were included in this study. All patients had a follow-up visit one year after loading. The cumulative one-year patient-based implant survival rate (CSR) was 88.8%, the cumulative one-year implant-based survival rate 97.2%, respectively.The marginal bone level was -0.5±0.5mm at the time of loading (n=72) and -0.8±0.6mm (n=72) after one year. The MBL depended significantly on the depth at the time of insertion. No prosthetic failure such as chipping or fracture occurred within the first year of loading.ConclusionProsthetic rehabilitation of atrophic maxillae with prostheses supported by four 4.0 x 5.0 mm or 3.0 x 8.0 mm implants seems to be a viable and cost-effective treatment option in the short-term.



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Cervical lymph node metastatic status and adjuvant therapy predict the prognosis of salivary duct carcinoma

Publication date: Available online 19 February 2018
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Kai Qian, Lu Di, Kai Guo, Xiaoke Zheng, Qinghai Ji, Zhuoying Wang
PurposeSalivary duct carcinoma (SDC) is an aggressive malignancy and is not yet fully understood. We designed this retrospective study to investigate the factors affecting the prognosis of salivary duct carcinoma and the effects of adjuvant therapies on clinical outcomes in patients.Materials and methodsPatients with major salivary gland duct carcinoma treated surgically between 2006 and 2016 were enrolled in the retrospective cohort study. Demographic data, clinical pathological characteristics and follow-up results were obtained. The prognostic indicators of overall survival (OS), locoregional failure-free survival (LRFFS) and distant metastasis-free survival (DMFS) were analyzed using the Kaplan–Meier method and the Cox Proportional Hazard Model.ResultsThe study sample comprised 66 patients, the majority of whom were male (81.8%). The 5-year OS, LRFFS and DMFS for all patients were 52.5, 63.9, and 51.3%, respectively. Univariate analysis showed that stages N2-3, lymph node involvement levels IV and V, ≥8 positive lymph nodes and extranodal extension were all negative prognostic indicators for OS. The only significant indicator in the multivariate analysis was the number of positive lymph nodes. Multivariate analysis revealed that extracapsular invasion and no adjuvant radiotherapy were risk factors for LRFFS, whereas lesions involving both glands and ≥8 positive lymph nodes were prognostic factors for DMFS. Further subgroup analysis showed that radiotherapy was only useful for patients with locally advanced lesions under local control.ConclusionCervical lymph node metastatic status is an important factor in predicting the prognosis of SDC patients. Adjuvant radiotherapy is useful for local control, especially for patients with stage T4 disease, but will not benefit OS and DMFS.



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Myopericytoma of the Lip: A Case Report of the Rare Lesion

Publication date: Available online 19 February 2018
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Eric Strayer, Roger Throndson, Cecilia Clement, Keith McDaniel
Myopericytomas are rare benign tumors that show a distinctive, concentric perivascular proliferation of oval-to-spindle shaped myoid appearing cells that are predominantly arranged concentrically around thin-walled vascular channels.¹ These lesions are similar in histologic appearance to hemangiopericytomas, myofibromas and glomus tumors. The myopericytoma is usually found in the distal extremities, but a handful of reports have shown the lesion to be present in the oral cavity.² Review of literature to date only shows four other reported cases of myopericytomas occurring in the lips. Here we describe a case of myopericytoma in the lower lip of a 42 year old female.



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How Does the Remodeling Capacity of Children Affect the Morphological Changes of Fractured Mandibular Condylar Processes After Conservative Treatment?

Publication date: Available online 19 February 2018
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Shiping Chang, Yan Yang, Yang Liu, Jingfu Wang, Wuyang Zhang, Qin Ma
PurposeOur aim was to explore how the remodeling capacity of children's mandibular condyles affected the morphological changes of fractured condyles after conservative treatment.MethodsA retrospective study was designed and performed on children and some adult patients with mandibular condylar fractures. Computed tomographic (CT) imaging was reviewed for all patients to analyze the morphological changes and risk factors of traumatic temporomandibular joint ankylosis.ResultsFrom 2012 to 2017, there were 81 patients younger than 18 and 10 adult patients who accepted treatment in our department. There were 23 young patients (aged < 18 years) with 41 fractured condyles and 10 adults with 14 fractured condyles who were managed with conservative treatment, and the morphological changes were analyzed with the aid of Mimics 19.0 software. The fractured condyles with intracapsular fractures completed the remodeling progress within 3-4 months and condyles with neck or base fractures took more than 6 months. Differentely, we found no remodeling in adults. Three of the 81 young patients suffered temporomandibular joint ankylosis. Each case was analyzed regarding the risk factors, morphological changes, and remodeling features. Finally, the common points of these cases were summarized.ConclusionsThe shape of fractured condyles can remold after conservative treatment in young patients, instead of bony fusion between the fractured fragments compared with the adult patients.



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Factors influencing post-surgical diplopia in orbital floor fractures and prevalence of other complications in a serie of cases

Publication date: Available online 19 February 2018
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Marina Alexandra Gavin Clavero, M Victoria Simón Sanz, Andrea Mur Til, Úrsula María Jariod Ferrer
PurposeWe have conducted a review of the orbital fractures treated in our hospital for a period of four years. We have reviewed its several complications, and especially the relationship of postsurgical diplopia with different pre-surgical variables: age, sex, type of fracture, fracture area, coronal and sagittal diameter of the fracture, fractured floor area, time to surgery, existence of muscular herniation and muscle entrapment.Patients and methodsFractures involving the orbital floor still remain a controversial issue in terms of surgical treatment and the time required from trauma to surgery. Surgical indications are divided into aesthetic and functional, and they greatly differ from one medical center to another. It has been observed that the variables that influence postoperative complications vary in the different studies reviewed. Post-surgical diplopia is one of the most important complications, and its relationship with pre-surgical variables has been the focus of this study. For the purpose of the present study, a bivariate and a multivariate analysis has been performed, accepting as significant the value p <0.05.Resultsaccording to the multivariate analysis, post-surgical diplopia is only associated with trap door fractures, regardless of all other variables, especially if these fractures are operated after 48 hours. In addition, the bivariate analysis has also reported that fractures involving muscular herniation result in less diplopia and a better prognosis if operated before 48 hours. Notwithstanding, these results are not statistically significant.ConclusionSurgery before 48 hours statistically improves fractures with real muscular entrapment, and improves (although not statistically significantly) patients with muscular herniation.



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Author response to “do we need to keep playing this tune?”

We thank Dr. Weinberger for the interest in our publication "Dexamethasone for inpatient childhood asthma exacerbations is as effective as short-acting corticosteroid treatment."1 The growing number of studies in this area reflects the importance of refining our approach to treating children with acute asthma exacerbations, the most common reason for childhood hospitalizations in the U.S.2 We believe our report fills an important knowledge gap by answering the question whether a two-dose dexamethasone regimen is as effective as short-acting systemic corticosteroid for hospitalized children.

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Results of an asthma education program delivered via telemedicine in rural schools

Asthma morbidity is high among low-income children living in rural U.S. regions, yet few interventions have been designed to reduce asthma burden among rural populations.

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Erratum

In the editorial, "Is eosinophilic esophagitis a member of the atopic march?" (Ann Allergy Asthma Immunol. 2018;120(2):113–114), on page 113, "see page XXX in this issue" should have read "see pages 131–137 in this issue" to reference the CME Review article "The atopic march: Critical evidence and clinical relevance" (Ann Allergy Asthma Immunol. 2018;120(2):131–137). The online version of the editorial has been corrected to reflect this change.

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Stimulus dependent neural oscillatory patterns show reliable statistical identification of Autism Spectrum Disorder in a face perceptual decision task

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social interaction and communication as well as by repetitive and restrictive behaviors and interests (American Psychiatric Association, 2013). Given the heterogeneity of this spectrum (Walsh et al., 2011) it is of paramount importance to identify experimental paradigms that are able to target cognitive processes that can be translated into the development of disease related biomarkers. Impaired attentional allocation to social features (including joint attention) (Amaral et al., 2015) or face processing deficits (Tavares et al., 2016) include the type of cognitive processes that might be targeted.

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Occurrence of Thalamic High Frequency Oscillations in Patients with Different Tremor Syndromes

Abnormal oscillatory activity in the basal ganglia plays a pivotal role in the pathophysiology of movement disorders. In particular, an increase of beta activity (15-30Hz) in the subthalamic nucleus (STN) has been suggested to underlie slowing of movement in Parkinson's disease (PD) (Kühn et al., 2009; Ray et al., 2008). Beta oscillations are modulated by dopaminergic medication (Brown et al., 2001; Levy et al., 2002; Priori et al., 2004) and voluntary movement (Cassidy et al., 2002; Levy et al., 2002).

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Creatine kinase level and its relationship with quantitative electromyographic characteristics in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that involves both upper and lower motor neurons and eventually leads to muscle weakness, muscle atrophy, bulbar palsy, and respiratory failure. Creatine kinase (CK) is an enzyme that catalyzes the reversible conversion of creatine and utilizes adenosine triphosphate (ATP) to generate phosphocreatine and adenosine diphosphate. This enzyme is important in tissues and cells that rapidly consume ATP, particularly skeletal muscle.

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Long-term neurophysiological and clinical response in patients with chronic inflammatory demyelinating polyradiculoneuropathy treated with subcutaneous immunoglobulin

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare immune-mediated disorder presenting with sub-acute onset and progressive symmetrical weakness over at least 2 months, involving proximal and distal limb muscles, associated with hypo/areflexia and impaired sensory functions (Latov, 2014; Koller et al., 2005).

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Cost Analysis of Channeled, Distal Chip Laryngoscope for In-office Laryngopharyngeal Biopsies

Given that financial considerations play an increasingly prominent role in clinical decision-making, we sought (1) to determine the cost-effectiveness of in-office biopsy for the patient, the provider, and the health-care system, and (2) to determine the diagnostic accuracy of in-office biopsy.

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The Effect of Parkinson Disease Tremor Phenotype on Cepstral Peak Prominence and Transglottal Airflow in Vowels and Speech

The physiological manifestations of Parkinson disease are heterogeneous, as evidenced by disease subtypes. Dysphonia has been well documented as an early and progressively significant impairment associated with the disease. The purpose of this study was to investigate how acoustic and aerodynamic measures of vocal function were affected by Parkinson tremor subtype (phenotype) in an effort to better understand the heterogeneity of voice impairment severity in Parkinson disease.

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Assessment of tumor margins in head and neck cancer using a 3D-navigation system based on PET/CT image-fusion – a pilot study

Determination of tumor margins in patients with squamous cell carcinoma of the head and neck (SCCHN) is mostly based on preoperative magnetic resonance imaging (MRI) or computed tomography scans (CT). Local recurrence of disease is often correlated with the presence of positive resection margins after surgical treatment. Positron emission tomography/computed tomography (PET/CT) imaging plays a crucial role in the assessment of patients with SCCHN. The purpose of this study was to determine whether PET/CT could predict tumor extension.

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Endoscopic Endonasal Transtuberculum Sellae Approach for the Resection of Suprasellar Intrainfundibular Epidermoid Cyst

J Neurol Surg B
DOI: 10.1055/s-0038-1624590

A 49-year-old female presented with intense headaches of 3 months duration. Brain magnetic resonance imaging (MRI) was performed and showed a sellar–suprasellar lesion extending into the third ventricle. A presumptive diagnosis of a craniopharyngioma was made. Since the patient did not have any visual deficits, she opted for conservative management. Four months later, she started to have progressive deterioration of vision; thus, surgery was indicated.The patient underwent endoscopic endonasal resection of the lesion through a transtuberculum sellae approach. The patient was positioned supine with the head slightly extended and the face turned to the right side. Following the essence of a binostril four-hand technique, a total gross resection of the lesion was achieved and multilayer skull base reconstruction was performed utilizing collagen matrix and nasoseptal flap; with no intraoperative complications.The patient's postoperative course was uneventful with the improvement in her vision, and she was discharged on postoperative day 4 with no new neurological deficits. Histopathological examination confirmed the diagnosis of an epidermoid cyst. Postoperative pituitary gland function was within normal limits except for mild diabetes insipidus for which she is on DDAVP 0.1 mg twice daily. At 4 years follow-up, the patient was doing well, her vision was normalized, and brain MRI revealed no evidence of residual or recurrent lesion.The link to the video can be found at: https://youtu.be/OqDFpa_Xq78.
[...]

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  open access Full text

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Influence of orthodontic appliance-derived artifacts on 3-T MRI movies

Magnetic resonance imaging (MRI) has been used to study configurations of speech organs in the resting state. However, MRI is sensitive to metals, and numerous types of metallic appliances, most of which have ...

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Body mass index and age at natural menopause: an international pooled analysis of 11 prospective studies

Abstract

Current evidence on the association between body mass index (BMI) and age at menopause remains unclear. We investigated the relationship between BMI and age at menopause using data from 11 prospective studies. A total of 24,196 women who experienced menopause after recruitment was included. Baseline BMI was categorised according to the WHO criteria. Age at menopause, confirmed by natural cessation of menses for ≥ 12 months, was categorised as < 45 years (early menopause), 45–49, 50–51 (reference category), 52–53, 54–55, and ≥ 56 years (late age at menopause). We used multinomial logistic regression models to estimate multivariable relative risk ratios (RRRs) and 95% confidence intervals (CI) for the associations between BMI and age at menopause. The mean (standard deviation) age at menopause was 51.4 (3.3) years, with 2.5% of the women having early and 8.1% late menopause. Compared with those with normal BMI (18.5–24.9 kg/m²), underweight women were at a higher risk of early menopause (RRR 2.15, 95% CI 1.50–3.06), while overweight (1.52, 1.31–1.77) and obese women (1.54, 1.18–2.01) were at increased risk of late menopause. Overweight and obesity were also significantly associated with around 20% increased risk of menopause at ages 52–53 and 54–55 years. We observed no association between underweight and late menopause. The risk of early menopause was higher among obese women albeit not significant (1.23, 0.89–1.71). Underweight women had over twice the risk of experiencing early menopause, while overweight and obese women had over 50% higher risk of experiencing late menopause.

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Cost Analysis of Channeled, Distal Chip Laryngoscope for In-office Laryngopharyngeal Biopsies

Publication date: Available online 19 February 2018
Source:Journal of Voice
Author(s): Sonya Marcus, Micah Timen, Gregory R. Dion, Mark A. Fritz, Ryan C. Branski, Milan R. Amin
ObjectiveGiven that financial considerations play an increasingly prominent role in clinical decision-making, we sought (1) to determine the cost-effectiveness of in-office biopsy for the patient, the provider, and the health-care system, and (2) to determine the diagnostic accuracy of in-office biopsy.Study DesignRetrospective, financial analyses were performed.MethodsPatients who underwent in-office (Current Procedural Terminology Code 31576) or operative biopsy (CPT Code 31535) for laryngopharyngeal lesions were included. Two financial analyses were performed: (1) the average cost of operating room (OR) versus in-office biopsy was calculated, and (2) a break-even analysis was calculated to determine the cost-effectiveness of in-office biopsy for the provider. In addition, the diagnostic accuracy of in-office biopsies and need for additional biopsies or procedures was recorded.ResultsOf the 48 patients included in the current study, 28 underwent in-office biopsy. A pathologic sample was obtained in 26 of 28 (92.9%) biopsies performed in the office. Of these patients, 16 avoided subsequent OR procedures. The average per patient cost was $7000 and $11,000 for in-office and OR biopsy, respectively. Break-even analysis demonstrated that the provider could achieve a profit 2 years after purchase of the necessary equipment.ConclusionIn-office laryngopharyngeal biopsies are accurate and, overall, more cost-effective than OR biopsies. Purchase of the channeled, distal chip laryngoscope and biopsy forceps to perform in-office biopsies can be profitable for a provider with a videolaryngoscopy tower. In-office biopsy should be considered the initial diagnostic tool for suspected laryngopharyngeal malignancies noted on videolaryngoscopy.



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The Effect of Parkinson Disease Tremor Phenotype on Cepstral Peak Prominence and Transglottal Airflow in Vowels and Speech

Publication date: Available online 19 February 2018
Source:Journal of Voice
Author(s): Brittany R. Burk, Christopher R. Watts
ObjectivesThe physiological manifestations of Parkinson disease are heterogeneous, as evidenced by disease subtypes. Dysphonia has been well documented as an early and progressively significant impairment associated with the disease. The purpose of this study was to investigate how acoustic and aerodynamic measures of vocal function were affected by Parkinson tremor subtype (phenotype) in an effort to better understand the heterogeneity of voice impairment severity in Parkinson disease.Study DesignThis is a prospective case-control study.MethodsThirty-two speakers with Parkinson disease assigned to tremor and nontremor phenotypes and 10 healthy controls were recruited. Sustained vowels and connected speech were recorded from each speaker. Acoustic measures of cepstral peak prominence (CPP) and aerodynamic measures of transglottal airflow (TAF) were calculated from the recorded acoustic and aerodynamic waveforms.ResultsSpeakers with a nontremor dominant phenotype exhibited significantly (P < 0.05) lower CPP and higher TAF in vowels compared with the tremor dominant phenotype and control speakers, who were not different from each other. No significant group differences were observed for CPP or TAF in connected speech.ConclusionsWhen producing vowels, participants with nontremor dominant phenotype exhibited reduced phonation periodicity and elevated TAF compared with tremor dominant and control participants. This finding is consistent with differential limb-motor and cognitive impairments between tremor and nontremor phenotypes reported in the extant literature. Results suggest that sustained vowel production may be sensitive to phonatory control as a function of Parkinson tremor phenotype in mild to moderate stages of the disease.



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Convergent molecular defects underpin diverse neurodegenerative diseases

In our ageing population, neurodegenerative disorders carry an enormous personal, societal and economic burden. Although neurodegenerative diseases are often thought of as clinicopathological entities, increasing evidence suggests a considerable overlap in the molecular underpinnings of their pathogenesis. Such overlapping biological processes include the handling of misfolded proteins, defective organelle trafficking, RNA processing, synaptic health and neuroinflammation. Collectively but in different proportions, these biological processes in neurons or non-neuronal cells lead to regionally distinct patterns of neuronal vulnerability and progression of pathology that could explain the disease symptomology. With the advent of patient-derived cellular models and novel genetic manipulation tools, we are now able to interrogate this commonality despite the cellular complexity of the brain in order to develop novel therapeutic strategies to prevent or arrest neurodegeneration. Here, we describe broadly these concepts and their relevance across neurodegenerative diseases.

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miRNA-124-3p/neuropilin-1(NRP-1) axis plays an important role in mediating glioblastoma growth and angiogenesis

Abstract

Glioblastoma Multiforme (GBM) is the most lethal brain malignancy which involves multi-gene abnormality. Unfortunately, effective therapy against GBM is still lacking. Previously, we found that NRP-1 and its downstream NRP-1/GIPC1 pathway played an important role in GBM. In this study, we further investigated the upstream signaling of NRP-1 to understand how it is regulated. Firstly, we identified that hsa-miR-124-3p was miRNA differentially expressed in GBM and in normal brain tissues by high-throughput sequencing. Then, by dual luciferase reporter gene, we found miR-124-3p can specially bind to the 3'UTR region of the NRP-1 thus suppresses its expression. Moreover, miR-124–3p overexpression significantly inhibited GBM cell proliferation, migration and tumor angiogenesis which resulted in GBM apoptosis and cell cycle arrest, putatively via NRP-1 mediated PI3K/Akt/NFκB pathways activation in GBM cells. Meanwhile, miR-124-3p overexpression also suppressed tumor growth and reduced tumor angiogenesis when targeted by NRP-1 in a PDX model. Furthermore, NRP-1 mAb exerted synergistic inhibitory effects with miR-124–3p overexpression in GBM. Thus, we discovered that miR-124-3p acts as the upstream suppressor of NRP-1 which promotes GBM cell development and growth by PI3K/Akt/NFκB pathway. The miR-124-3p/NRP-1/GIPC1 pathway as a new pathway has a vital role in GBM, and it could be considered as the potential target for malignant gliomas in future. This article is protected by copyright. All rights reserved.

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Tobacco-attributable burden of cancer according to socioeconomic position in France

Abstract

Smoking is a major preventable cause of cancers and is increasingly concentrated among the most deprived individuals leading to increasing socioeconomic inequalities in the incidence of cancers linked to smoking. We aimed to estimate the tobacco-attributable cancer burden according to socioeconomic position in France. The analysis was restricted to cancer sites for which tobacco smoking was recognized as a risk factor. Cancer cases by sex, age group and European Deprivation Index (EDI) among people aged 30–74 between 2006 and 2009 were obtained from cancer registries covering approximately 20% of the French population. The tobacco-attributable burden of cancer according to EDI was estimated applying the population attributable fraction (PAF) computed with the Peto-Lopez method. The PAF increased from 56% in the least deprived EDI quintile to 70% in the most deprived EDI quintile among men and from 26% to 38% among women. In total, 28% of the excess cancer cases in the four most deprived EDI quintiles in men and 43% in women could be prevented if smoking in these 4 EDI quintiles was similar to that of the least deprived EDI quintile. A substantial smoking-attributable burden of cancer by socioeconomic position was observed in France. The results highlight the need for policies reducing tobacco consumption. More comprehensive interventions integrating the various dimensions of health determinants and proportionate according to socioeconomic position may essentially contribute to the reduction of socioeconomic inequalities in cancer. This article is protected by copyright. All rights reserved.

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Low T3 syndrome as a predictor of poor prognosis in chronic lymphocytic leukemia

Abstract

Low triiodothyronine (T3) state is associated with poor prognosis in critical acute and prolonged illness. However, the information on thyroid dysfunction and cancer is limited. The aim of our study was to evaluate the prognostic value of low T3 syndrome in chronic lymphocytic leukemia (CLL). Two hundred and fifty-eight patients with detailed thyroid hormone profile at CLL diagnosis were enrolled. Low T3 syndrome was defined by low free T3 (FT3) level accompanied by normal-to-low free tetraiodothyronine (FT4) and thyroid-stimulating hormone (TSH) levels. A propensity score-matched method was performed to balance the baseline characteristics. Multivariate Cox regression analyses screened the independent prognostic factors related to time-to-first-treatment (TTFT) and cancer-specific survival (CSS). Area under the curve (AUC) assessed the predictive accuracy of CLL-International Prognostic Index (IPI) together with low T3 syndrome. The results showed that 37 (14.34%) patients had low T3 syndrome, which was significantly associated with unfavorable TTFT and CSS in the propensity-matched cohort, and it was an independent prognostic indicator for both TTFT and CSS. Serum FT3 level was positively related to protein metabolism and anemia, and inversely related to inflammatory state. Patients with only low FT3 demonstrated better survival than those with synchronously low FT3 and FT4, while those with synchronously low FT3, FT4 and TSH had the worst clinical outcome. Low T3 syndrome together with CLL-IPI had larger AUCs compared with CLL-IPI alone in TTFT and CSS prediction. In conclusion, low T3 syndrome may be a good candidate for predicting prognosis in future clinical practice of CLL. This article is protected by copyright. All rights reserved.

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Reply to “Excess amyloid beta can be degraded in healthy humans”

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Computed tomography analysis of frontal cell prevalence according to the International Frontal Sinus Anatomy Classification

Background

The International Frontal Sinus Anatomy Classification (IFAC) is an international consensus document published in 2016 to standardize the nomenclature of cells in the region of the frontal recess and frontal sinus. The IFAC was designed to be surgically relevant and anatomically precise. The current study was undertaken to assess the prevalence of the frontal cell variants as defined by the IFAC, as well as to determine the interrater reliability of the IFAC.

Methods

Three independent reviewers examined triplanar nondiseased maxillofacial computed tomography (CT) scans to assess the anatomy of the frontal recess according to the IFAC system. The prevalence of each cell type was assessed and interrater reliability was measured using an intraclass correlation coefficient (ICC).

Results

One hundred CT scans (200 sides) were examined. Of the 200 sides, 96.5% contained an agger nasi cell (ICC, 0.82; 95% confidence interval [CI], 0.77-0.86), 30.0% contained a supra agger cell (ICC, 0.89; 95% CI, 0.86-0.92), 20.0% contained a supra agger frontal cell (ICC 0.80; 95% CI 0.74-0.84), 72.0% contained a supra bulla cell (ICC, 0.81; 95% CI, 0.76-0.85), 5.5% contained a supra bulla frontal cell (ICC, 0.71; 95% CI, 0.63-0.77), 28.5% contained a supraorbital ethmoid cell (ICC, 0.78; 95% CI, 0.72-0.83), and 30.0% contained a frontal septal cell (ICC, 0.80; 95% CI, 0.74-0.84). The ICC was good to excellent for identification of all frontal cell types.

Conclusions

This study describes the normative distribution of frontal recess cells in a nondiseased population according to IFAC and demonstrates favorable interrater reliability of the classification system.

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The impact of video nasal endoscopy on patient satisfaction

Background

Video nasal endoscopy has significant associated expense for practices, but its use has been justified by the benefit it provides to the examiner. No study has examined the perceived benefit to the patient. In this study, the impact of video endoscopy on patient satisfaction is evaluated.

Methods

A prospective, randomized, single-blinded study was performed on new patients receiving care in the rhinology clinics of a tertiary-care center. Patients were randomized into the standard endoscopic examination (SEE) or video endoscopic examination (VEE) groups. SEE patients had their examination performed with the physician viewing the exam through the eyepiece, without a video camera, and subsequently had their examination explained. VEE patients had their examination performed with a video camera attached to the scope, recorded, and then used for the explanation. All patients were asked to complete the 22-item Sino-Nasal Outcome Test (SNOT-22) and the 18-item Patient Satisfaction Questionnaire Short-Form (PSQ-18). Statistical analysis was performed to identify differences between cohorts.

Results

There was no significant demographic difference between groups. SNOT-22 total and domain scores were similar between both groups (p > 0.05). VEE patients had significantly higher general satisfaction (p = 0.048) and communication (p = 0.028) domains within the PSQ-18. There was no difference between other domains (p > 0.05).

Conclusion

VEE is a valuable tool for otolaryngologists and patients. Further studies evaluating variance in patient compliance and symptomatology may provide further justification for its use.

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Baseline and changes in serum uric acid independently predict 11-year incidence of metabolic syndrome among community-dwelling women

Abstract

Introduction

Metabolic syndrome (MetS) is associated with an increased risk of major cardiovascular events. In women, increased serum uric acid (SUA) levels are associated with MetS and its components. However, whether baseline and changes in SUA predict incidence of MetS and its components remains unclear.

Methods

The subjects comprised 407 women aged 71 ± 8 years from a rural village. We have identified participants who underwent a similar examination 11 years ago, and examined the relationship between baseline and changes in SUA, and MetS based on the modified criteria of the National Cholesterol Education Program's Adult Treatment Panel (NCEP-ATP) III report.

Results

Of these subjects, 83 (20.4%) women at baseline and 190 (46.7%) women at follow-up had MetS. Multiple linear regression analysis was performed to evaluate the contribution of each confounding factor for MetS; both baseline and changes in SUA as well as history of cardiovascular disease, low-density lipoprotein cholesterol, and estimated glomerular filtration ratio (eGFR) were independently and significantly associated with the number of MetS components during an 11-year follow-up. The adjusted odds ratios (ORs) (95% confidence interval) for incident MetS across tertiles of baseline SUA and changes in SUA were 1.00, 1.47 (0.82–2.65), and 3.11 (1.66–5.83), and 1.00, 1.88 (1.03–3.40), and 2.49 (1.38–4.47), respectively. In addition, the combined effect between increased baseline and changes in SUA was also a significant and independent determinant for the accumulation of MetS components (F = 20.29, p < 0.001). The ORs for incident MetS were significant only in subjects with age ≥ 55 years, decline in eGFR, and no baseline MetS.

Conclusions

These results suggested that combined assessment of baseline and changes in SUA levels provides increased information for incident MetS, independent of other confounding factors in community-dwelling women.

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The Global Spine Care Initiative: applying evidence-based guidelines on the non-invasive management of back and neck pain to low- and middle-income communities

Abstract

Purpose

The purpose of this review was to develop recommendations for the management of spinal disorders in low-income communities, with a focus on non-invasive pharmacological and non-pharmacological therapies for non-specific low back and neck pain.

Methods

We synthesized two evidence-based clinical practice guidelines for the management of low back and neck pain. Our recommendations considered benefits, harms, quality of evidence, and costs, with attention to feasibility in medically underserved areas and low- and middle-income countries.

Results

Clinicians should provide education and reassurance, advise patients to remain active, and provide information about self-care options. For acute low back and neck pain without serious pathology, primary conservative treatment options are exercise, manual therapy, superficial heat, and nonsteroidal anti-inflammatory drugs (NSAIDs). For patients with chronic low back and neck pain without serious pathology, primary treatment options are exercise, yoga, cognitive behavioral therapies, acupuncture, biofeedback, progressive relaxation, massage, manual therapy, interdisciplinary rehabilitation, NSAIDs, acetaminophen, and antidepressants. For patients with spinal pain with radiculopathy, clinicians may consider exercise, spinal manipulation, or NSAIDs; use of other interventions requires extrapolation from evidence regarding effectiveness for non-radicular spinal pain. Clinicians should not offer treatments that are not effective, including benzodiazepines, botulinum toxin injection, systemic corticosteroids, cervical collar, electrical muscle stimulation, short-wave diathermy, transcutaneous electrical nerve stimulation, and traction.

Conclusion

Guidelines developed for high-income settings were adapted to inform a care pathway and model of care for medically underserved areas and low- and middle-income countries by considering factors such as costs and feasibility, in addition to benefits, harms, and the quality of underlying evidence. The selection of recommended conservative treatments must be finalized through discussion with the involved community and based on a biopsychosocial approach. Decision determinants for selecting recommended treatments include costs, availability of interventions, and cultural and patient preferences.

Graphical abstract

These slides can be retrieved under Electronic Supplementary Material.

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Type V osteogenesis imperfecta undergoing surgical correction for scoliosis

Abstract

Purpose

The objective of this article is to report a case of type V osteogenesis imperfecta (OI) undergoing posterior instrumented fusion for scoliosis. Type V OI is a moderately severe dysplasia causing primary defects in endochondral bone ossification or mineralisation. It is characterised by hyperplastic callus (HPC) formation, interosseous membrane calcifications, poor bone quality and spinal deformities including scoliosis. Data on the surgical management of spinal deformities in this patient group are lacking.

Case report

A 16-year-old patient with a confirmed diagnosis of type V OI presented with a progressive scoliosis. The patient underwent a T3–L4 posterior instrumented correction and fusion utilising pedicle screws, pedicle hooks and sub-laminar wiring. At 4 months after surgery, the pedicle hooks pulled out and required partial metalwork removal after CT scanning confirmed bony union and no evidence of HPC formation. The patient was successfully discharged with satisfactory correction, confirmed bony union, no neurologic complication and absence of any hyperplastic callus formation.

Conclusion

Type V OI patients requiring surgical intervention for scoliosis correction can safely undergo posterior instrumented fusion using sublaminar wiring and pedicle hook/screw constructs without apparent risk of HPC formation around neural elements. Surgery in this patient group remains challenging due to the associated poor bone quality.

Level of evidence

V.

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ISSLS PRIZE IN BASIC SCIENCE 2018: Growth differentiation factor-6 attenuated pro-inflammatory molecular changes in the rabbit anular-puncture model and degenerated disc-induced pain generation in the rat xenograft radiculopathy model

Abstract

Purpose

To elucidate the effects of growth differentiation factor-6 (GDF6) on: (i) gene expression of inflammatory/pain-related molecules and structural integrity in the rabbit intervertebral disc (IVD) degeneration model, and (ii) sensory dysfunction and changes in pain-marker expression in dorsal nerve ganglia (DRGs) in the rat xenograft radiculopathy model.

Methods

Forty-six adolescent rabbits received anular-puncture in two non-consecutive lumbar IVDs. Four weeks later, phosphate-buffered saline (PBS) or GDF6 (1, 10 or 100 µg) was injected into the nucleus pulposus (NP) of punctured discs and followed for 4 weeks for gene expression analysis and 12 weeks for structural analyses. For pain assessment, eight rabbits were sacrificed at 4 weeks post-injection and NP tissues of injected discs were transplanted onto L5 DRGs of 16 nude rats to examine mechanical allodynia. The rat DRGs were analyzed immunohistochemically.

Results

In GDF6-treated rabbit NPs, gene expressions of interleukin-6, tumor necrosis factor-α, vascular endothelial growth factor, prostaglandin-endoperoxide synthase 2, and nerve growth factor were significantly lower than those in the PBS group. GDF6 injections resulted in partial restoration of disc height and improvement of MRI disc degeneration grades with statistical significance in rabbit structural analyses. Allodynia induced by xenograft transplantation of rabbit degenerated NPs onto rat DRGs was significantly reduced by GDF6 injection. Staining intensities for ionized calcium-binding adaptor molecule-1 and calcitonin gene-related peptide in rat DRGs of the GDF6 group were significantly lower than those of the PBS group.

Conclusion

GDF6 injection may change the pathological status of degenerative discs and attenuate degenerated IVD-induced pain.

Graphical Abstract

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ISSLS PRIZE IN CLINICAL SCIENCE 2018: longitudinal analysis of inflammatory, psychological, and sleep-related factors following an acute low back pain episode—the good, the bad, and the ugly

Abstract

Study design

Prospective longitudinal study.

Objective

To determine whether systemic cytokines and C-reactive protein (CRP) during an acute episode of low back pain (LBP) differ between individuals who did and did not recover by 6 months and to identify sub-groups based on patterns of inflammatory, psychological, and sleep features associated with recovery/non-recovery.

Summary of background data

Systemic inflammation is observed in chronic LBP and may contribute to the transition from acute to persistent LBP. Longitudinal studies are required to determine whether changes present early or develop over time. Psychological and/or sleep-related factors may be related.

Methods

Individuals within 2 weeks of onset of acute LBP (N = 109) and pain-free controls (N = 55) provided blood for assessment of CRP, tumor necrosis factor (TNF), interleukin-6 (IL-6) and interleukin-1β, and completed questionnaires related to pain, disability, sleep, and psychological status. LBP participants repeated measurements at 6 months. Biomarkers were compared between LBP and control participants at baseline, and in longitudinal (baseline/6 months) analysis, between unrecovered (≥pain and disability), partially recovered (reduced pain and/or disability) and recovered (no pain and disability) participants at 6 months. We assessed baseline patterns of inflammatory, psychological, sleep, and pain data using hierarchical clustering and related the clusters to recovery (% change in pain) at 6 months.

Results

CRP was higher in acute LBP than controls at baseline. In LBP, baseline CRP was higher in the recovered than non-recovered groups. Conversely, TNF was higher at both time-points in the non-recovered than recovered groups. Two sub-groups were identified that associated with more ("inflammatory/poor sleep") or less ("high TNF/depression") recovery.

Conclusions

This is the first evidence of a relationship between an "acute-phase" systemic inflammatory response and recovery at 6 months. High inflammation (CRP/IL-6) was associated with good recovery, but specific elevation of TNF, along with depressive symptoms, was associated with bad recovery. Depression and TNF may have a two-way relationship.

Graphical abstract

These slides can be retrieved under Electronic Supplementary Material.

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Correction to: 12. Deutscher Wirbelsäulenkongress Jahrestagung der Deutschen Wirbelsäulengesellschaft, 30. November – 2. Dezember 2017, Stuttgart

Abstract

Unfortunately, the abstract from V.

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EUROSPINE 2017 FULL PAPER AWARD: Time to remove our rose-tinted spectacles: a candid appraisal of the relative success of surgery in over 4500 patients with degenerative disorders of the lumbar spine, hip or knee

Abstract

Purpose

Studies comparing the outcome of spine surgery with that of large-joint replacement report equivocal findings. The patient-reported outcome measures (PROMs) used in such studies are typically generic and may not be sufficiently sensitive to the successes/failures of treatment. This study compared different indices of "success" in patients undergoing surgery for degenerative disorders of the lumbar spine, hip, or knee, using a validated, multidimensional, and joint-specific PROM.

Methods

Preoperatively and 12 months postoperatively, 4594 patients (3937 lumbar spine, 368 hip, 269 knee) undergoing first-time surgery completed a PROM that included the Core Outcome Measures Index (COMI) for the affected joint. The latter comprises a set of single items on pain, function, symptom-specific well-being, quality of life, and disability—all in relation to the specified joint problem. Other single-item ratings of treatment success were made 12 months postoperatively.

Results

In multiple regression analyses, controlling for confounders, the mean improvement in COMI at 12 months was greatest for the hip patients and lowest for those with degenerative spinal deformity (= the statistical reference group) (p < 0.05). Compared with spinal deformity, the odds of achieving "success" were: higher for hip (OR 4.6; 95% CI 2.5–8.5) and knee (OR 4.0; 95% CI 2.1–7.7) (no difference between spine subgroups) for "satisfaction with care"; higher for hip (OR 16.9; 95% CI 7.3–39.6), knee (OR 6.3; 95% CI 3.4–11.6), degenerative spondylolisthesis (OR 1.6; 95% CI 1.2–2.2), and herniated disc (OR 1.7; 95% CI 1.2–2.4) for "global treatment outcome"; and higher for hip (OR 13.8; 95% CI 8.8–21.6), knee (OR 5.3; 95% CI 3.6–7.8), degenerative spondylolisthesis (OR 1.6; 95% CI 1.3–2.1), and herniated disc (1.5; 95% CI 1.1–2.0) for "patient-acceptable symptom state". Patient-rated complications were the greatest in degenerative spinal deformity (29%) and the lowest in hip (18%).

Conclusions

The current study is the largest of its kind and the first to use a common, but joint-specific instrument to report patient-reported outcomes after surgery for degenerative disorders of the spine, hip, or knee. The findings provide a sobering account of the significantly poorer outcomes after spine surgery compared with large-joint replacement. Further work is required to hone the indications and patient selection criteria for spine surgery. The data should be used to lobby research funding-bodies, governmental agencies, industry, and charitable foundations to invest more in spine research/registries, in the hope of ultimately improving spine outcomes.

Graphical abstract

These slides can be retrieved under Electronic Supplementary Material.

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The tumour-stroma ratio in colon cancer; the biological role and its prognostic impact

Abstract

The tumour microenvironment consists of a complex mixture of non-neoplastic cells including fibroblasts, immune cells and endothelial cells embedded in the proteins of the extracellular matrix. The tumour microenvironment plays an active role in tumour behaviour. By interacting with cancer cells, it influences disease progression and the metastatic capacity of the tumour. Tumours with a high amount of stroma correspond to poor patient prognosis. The tumour-stroma ratio (TSR) is a strong independent prognostic tool in colon cancer and provides additional value to the current clinically used TNM classification. The TSR is assessed on conventional haematoxylin and eosin stained paraffin sections at the invasive front of the tumour. Here we review studies demonstrating the prognostic significance of the TSR in solid epithelial tumours with a focus on colon cancer. Moreover, the biological role of the tumour microenvironment during tumour progression and invasion will be discussed as well as the attempts to target the tumour stroma for therapeutic purposes. We suggest that the TSR can be implemented with little effort and without additional costs in current routine pathology diagnostics owing to its simplicity and reliability.

This article is protected by copyright. All rights reserved.

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Factors in Removing Job Restrictions for Cancer Survivors in the United Kingdom Royal Air Force

Abstract

Purpose To identify personal, occupational and clinical factors associated with the lifting of restrictions on duties among Royal Air Force (RAF) personnel who have returned to work after surviving primary cancer treatment. Methods A retrospective cohort of 205 RAF personnel aged 18–58 with cancer diagnosed between 2001 and 2011 was followed-up until May 2012. Personal, occupational, and clinical information was extracted from occupational health and primary care records. Predictors of the lifting of (a) employment restrictions on UK duties at 18 months after diagnosis and (b) the lifting of all deployment restrictions at the end of the study were analysed using logistic and Cox regression models. Results At 18 months, 62% of the cancer survivors had restrictions on their UK duties lifted. The positive independent predictors of unrestricted UK duties are testicular cancer (OR 5.34; 95% CI 1.21–23.6) and no treatment being required (16.8; 1.11–255.2). The lifting of all employment restrictions and return to full deployability was achieved by 41% of the participants (median time 2.1 years), with testicular cancer (HR 2.69; 95% CI 1.38–5.26) and age at diagnosis (1.05; 1.01–1.09) being the positive independent predictors of faster lifting of all restrictions. Conclusion Diagnostic group, prognosis and type of treatment are not the only predictor of employment outcome after cancer. Patient-centred factors such as smoking, age, fatigue, job status, job type and length of employment are also important predictors of return to pre-morbid job function in cancer survivors in the RAF.

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Experimental study on TGF-β1-mediated CD147 expression in oral submucous fibrosis

Abstract

Objective

Although previous evidence indicates that CD147 is closely involved in the progression of organ fibrosis and various signaling pathways have been proven to regulate its expression, the role of CD147 in oral submucous fibrosis (OSF) remain largely unknown.

Methods

In the present study, we investigated the expression of CD147 and transforming growth factor β1 (TGF-β1) in human samples of an OSF tissue array by immunohistopathology. Pearson's correlation analysis was conducted to explore the correlation between CD147 and TGF-β1. Immunofluorescence and Western blotting were used to investigate to levels of CD147 in Human Oral Keratinocytes (HOKs) followed by TGF-β1 or LY2157299, an inhibitor of TGF-β1 receptor and arecoline stimulation.

Results

We found that CD147 was highly expressed in both HOKs and the fibrotic oral mucosa and that this expression was correlated with TGF-β1 expression. Additionally, CD147 levels were significantly associated with the fibrosis stage. The TGF-β1 signaling pathway was found to be mainly responsible for CD147 up-regulation after arecoline treatment whereas inhibition of TGF-β1 down-regulated CD147 expression.

Conclusion

Our findings suggest arecoline promotes CD147 expression via the TGF-β1 signaling pathway in HOKs, whereas overexpression of CD147 may promote OSF progression.

This article is protected by copyright. All rights reserved.

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Mutations in BAG3 cause adult-onset Charcot-Marie-Tooth disease

Introduction

Charcot-Marie-Tooth disease (CMT) is an umbrella term for more than 90 different genetic causes of inherited peripheral neuropathies (http://hihg.med.miami.edu/code/http/cmt/public_html/index.html#/) and has an estimated prevalence of 1 in 2500. Most cases present within the first two decades of life but increasing axonal genetic subtypes (CMT2) first present in adulthood. Identifying additional genes causing CMT2 is important because these can identify molecular pathways involved in axonal degeneration and enable development of rational therapies for these and related disorders.

We have used whole exome sequencing (WES) to identify two families with CMT2 caused by mutations in the Bcl2-associated athanogene 3 (BAG3). Mutations in BAG3 have previously been shown to cause a myofibrillar myopathy1 2 often associated with cardiomyopathy that usually presents in childhood. Children have been reported with peripheral neuropathy in addition to myopathy3 and/or cardiomyopathy.4

Genetic testing

Genomic...

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Chitotriosidase: shucking the role of microglia in amyotrophic lateral sclerosis

Cerebrospinal fluid (CSF) chitotriosidase concentration reflects microglial activation in the spinal cord of patients with amyotrophic lateral sclerosis (ALS).

Chitin is a long-chain insoluble carbohydrate polymer that is one of the most abundant organic materials in the biosphere, second only to cellulose.1 It occurs as a key structural molecule in the exoskeleton of invertebrates and cell walls of fungi. It builds up the shells of oysters and clams. Its durable properties are the subject of intense study in biotechnology and materials science. There has been a long-standing assumption that chitin plays no role in vertebrate biology, but this is starting to change; expression of chitin in vertebrate tissues has been verified, and potential biological functions of the polymer in higher organisms are just being unravelled.1

Chitinases constitute a widely expressed family of hydrolases that cleave chitins. Insects produce chitinases to facilitate moulting. Micro-organisms produce them to digest...

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Clinical utility of amyloid PET imaging with (18)F-florbetapir: a retrospective study of 100 patients

Background and objective

Amyloid-positron emission tomography (PET) imaging (API) detects amyloid-beta pathology early in the course of Alzheimer's disease (AD) with high sensitivity and specificity. (18)F-florbetapir (Amyvid) is an amyloid-binding PET ligand with a half-life suitable for clinical use outside of the research setting. How API affects patient investigation and management in the 'real-world' arena is unknown. To address this, we retrospectively documented the effect of API in patients in the memory clinic.

Methods

We reviewed the presenting clinical features, the pre-API and post-API investigations, diagnosis and outcomes for the first 100 patients who had API as part of their routine work-up at the Imperial Memory Centre, a tertiary referral clinic in the UK National Health Service.

Results

API was primarily used to investigate patients with atypical clinical features (56 cases) or those that were young at onset (42 cases). MRI features of AD did not always predict positive API (67%), and 6 of 23 patients with MRIs reported as normal were amyloid-PET positive. There were significantly more cases categorised as non-AD dementia post-API (from 11 to 23). Patients investigated when API was initially available had fewer overall investigations and all patients had significantly fewer investigations in total post-API.

Conclusions

API has a clear impact on the investigation of young-onset or complex dementia while reducing the overall burden of investigations. It was most useful in younger patients, atypical presentations or individuals with multiple possible causes of cognitive impairment.

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Pragmatic approach to muscle MRI biomarkers in motor neuron disease

A rapid whole body muscle MRI protocol is sensitive to disease progression in motor neuron disease.

As part of the evolution of neuromuscular medicine, there has been a move towards tools that can objectively measure change in the disease without relying on relatively insensitive or subjective clinical measures. Motor neuron disease (MND) has a wide array of potential clinical phenotypes and disease progression can be unpredictable between individuals.1 Clinical instruments to measure MND have well-defined limitations.2 3 For these reasons, it is necessary to develop objective non-clinical measures of disease progression in MND.

In their JNNP paper, Dr Jenkins and colleagues have advanced muscle MRI as a potential biomarker of MND progression.4 The authors performed whole body T2-weighted imaging on a cohort of patients with MND and demonstrated an increase in muscle T2 signal over a 4-month observation period and a correlation between muscle...

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Opioid K receptor variant is associated with a delayed onset of dyskinesias in Parkinsons disease

Risk factors for levodopa-induced dyskinesias (LIDs) in Parkinson's disease (PD) include young age at onset, disease progression and individual dose of levodopa.1 Nevertheless, established risk factors do not fully explain the marked individual variability in the time elapsing between levodopa initiation and the onset of LIDs, and genetic predisposition is likely to play a critical role. To identify the genetic determinants modulating the time at onset of LIDs, we investigated 10 polymorphisms previously associated with LIDs in PD. Among these variants, we selected those additionally associated with addictive disorders, based on the recent hypothesis that pathophysiological mechanisms underlying LIDs share similarities with non-motor hyper-dopaminergic states, such as addictive disorders (including impulse control disorders).2

Clinical records of consecutive outpatients diagnosed with PD, attending our clinic from April 2009 to April 2011 and contributing to the 'Parkinson Institute Biobank', were retrospectively reviewed. We included only patients who were free...

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Marriage and risk of dementia: systematic review and meta-analysis of observational studies

Background

Being married is associated with healthier lifestyle behaviours and lower mortality and may reduce risk for dementia due to life-course factors. We conducted a systematic review and meta-analysis of studies of the association between marital status and the risk of developing dementia.

Methods

We searched medical databases and contacted experts in the field for relevant studies reporting the relationship, adjusted for age and sex, between marital status and dementia. We rated methodological quality and conducted random-effects meta-analyses to summarise relative risks of being widowed, divorced or lifelong single, compared with being married. Secondary stratified analyses with meta-regression examined the impact of clinical and social context and study methodology on findings.

Results

We included 15 studies with 812 047 participants. Compared with those who are married, lifelong single (relative risk=1.42 (95% CI 1.07 to 1.90)) and widowed (1.20 (1.02 to 1.41)) people have elevated risk of dementia. We did not find an association in divorced people.

Further analyses showed that less education partially confounds the risk in widowhood and worse physical health the elevated risk in lifelong single people. Compared with studies that used clinical registers for ascertaining dementia diagnoses, those which clinically examined all participants found higher risk for being unmarried.

Conclusions

Being married is associated with reduced risk of dementia than widowed and lifelong single people, who are also underdiagnosed in routine clinical practice. Dementia prevention in unmarried people should focus on education and physical health and should consider the possible effect of social engagement as a modifiable risk factor.

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Sleep and REM sleep behaviour disorder in Parkinsons disease with impulse control disorder

Introduction

Because the association between rapid eye movement sleep behaviour disorder (RBD) and impulse control disorders (ICDs) in Parkinson's disease (PD) has been debated, we assessed the sleep characteristics and the frequency of RBD using video-polysomnography (v-PSG) in patients with PD with versus without ICDs.

Methods

Eighty non-demented patients with PD consecutively identified during routine evaluation at three movement disorders centres were enrolled in a case–control study. Forty patients (22 men; mean age: 62.6±9.7 years, Hoehn & Yahr: 2.1±0.6) with one or more current ICDs were age-matched and sex-matched with 40 patients with no history of ICDs (22 men, mean age: 64.9±7.8 years, Hoehn & Yahr: 2.2±0.6). They underwent a detailed sleep interview followed by a full-night in-lab v-PSG. Sleep was scored blindly to ICDs condition and RBD diagnosis included a clinical complaint of enacted dreams and/or documented behaviour during rapid eye movement (REM) sleep, with the presence of quantified REM sleep without atonia (RSWA).

Results

Patients with ICDs had a higher arousal index and higher RSWA than those without ICDs (51.9%±28.2%vs 32.2±27.1%, p=0.004). In addition, RBD was more frequent in the ICD group (85%vs53%, p=0.0001). RBD was still associated with ICDs in a multivariate regression analysis including age of onset, PD duration and severity, treatment duration, levodopa-equivalent and dopamine agonist-equivalent daily doses and antidepressant use (OR: 4.9 (95% CI 1.3 to 18.5), p=0.02).

Conclusions

This large, controlled series of patients with PD with ICDs assessed by v-PSG confirms the association between ICDs and RBD. Increased surveillance of symptoms of ICDs should be recommended in patients with PD with RBD.

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Chitotriosidase (CHIT1) is increased in microglia and macrophages in spinal cord of amyotrophic lateral sclerosis and cerebrospinal fluid levels correlate with disease severity and progression

Objectives

Neurochemical markers of amyotrophic lateral sclerosis (ALS) that reflect underlying disease mechanisms might help in diagnosis, staging and prediction of outcome. We aimed at determining the origin and differential diagnostic and prognostic potential of the putative marker of microglial activation chitotriosidase (CHIT1).

Methods

Altogether 316 patients were included, comprising patients with sporadic ALS, ALS mimics (disease controls (DCo)), frontotemporal lobar degeneration (FTLD), Creutzfeldt-Jakob disease (CJD), Alzheimer's disease (AD), Parkinson's disease (PD) and healthy controls (Con). CHIT1 and neurofilament levels were determined in cerebrospinal fluid (CSF) and blood and analysed with regard to diagnostic sensitivity and specificity and prognostic performance. Additionally, postmortem tissue was analysed for CHIT1 expression.

Results

In ALS, CHIT1 CSF levels were higher compared with Con (p<0.0001), DCo (p<0.05) and neurodegenerative diseases (AD p<0.05, PD p<0.01, FTLD p<0.0001) except CJD. CHIT1 concentrations were correlated with ALS disease progression and severity but not with the survival time, as did neurofilaments. Serum CHIT1 levels were not different in ALS compared with any other study group. In the spinal cord of patients with ALS, but not Con, AD or CJD cases, CHIT1 was expressed in the corticospinal tract and CHIT1 staining colocalised with markers of microglia (IBA1) and macrophages (CD68).

Conclusions

CHIT1 concentrations in the CSF of patients with ALS may reflect the extent of microglia/macrophage activation in the white matter of the spinal cord. CHIT1 could be a potentially useful marker for differential diagnosis and prediction of disease progression in ALS and, therefore, seems suitable as a supplemental marker for patient stratification in therapeutic trials.

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Default mode network neurodegeneration reveals the remote effects of ischaemic stroke

Introduction

Dementia is estimated to occur in 15%–30% patients after ischaemic stroke.1 Stroke may initiate or accelerate neurodegeneration associated with cognitive impairment.1 Brain atrophy is an important marker of neurodegeneration, preceding the emergence of cognitive symptoms in Alzheimer's disease (AD).2 Atrophy occurs in distributed regions that collectively mirror known brain networks, including the default mode network (DMN). Atrophy and dysfunction within the DMN is evident in healthy ageing, accelerated in pathological ageing2 and evident in acute and subacute stroke.3 Lesion location rarely predicts long-term outcome in stroke. Network-wide changes may better explain neurodegeneration and conversion to dementia after stroke. Atrophy after stroke has not been well investigated and has been limited to cross-sectional studies and regional volume changes.

Structural covariance is an increasingly popular method of examining network-wide correlations in morphometric estimates of brain structure, such as cortical...

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