Cancers, Vol. 10, Pages 56: Cancer Stem Cells, Bone and Tumor Microenvironment: Key Players in Bone Metastases

Cancers, Vol. 10, Pages 56: Cancer Stem Cells, Bone and Tumor Microenvironment: Key Players in Bone Metastases

Cancers doi: 10.3390/cancers10020056

Authors: Ilaria Roato Riccardo Ferracini

Tumor mass is constituted by a heterogeneous group of cells, among which a key role is played by the cancer stem cells (CSCs), possessing high regenerative properties. CSCs directly metastasize to bone, since bone microenvironment represents a fertile environment that protects CSCs against the immune system, and maintains their properties and plasticity. CSCs can migrate from the primary tumor to the bone marrow (BM), due to their capacity to perform the epithelial-to-mesenchymal transition. Once in BM, they can also perform the mesenchymal-to-epithelial transition, allowing them to proliferate and initiate bone lesions. Another factor explaining the osteotropism of CSCs is their ability to recognize chemokine gradients toward BM, through the CXCL12–CXCR4 axis, also known to be involved in tumor metastasis to other organs. Moreover, the expression of CXCR4 is associated with the maintenance of CSCs’ stemness, and CXCL12 expression by osteoblasts attracts CSCs to the BM niches. CSCs localize in the pre-metastatic niches, which are anatomically distinct regions within the tumor microenvironment and govern the metastatic progression. According to the stimuli received in the niches, CSCs can remain dormant for long time or outgrow from dormancy and create bone lesions. This review resumes different aspects of the CSCs’ bone metastastic process and discusses available treatments to target CSCs.

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Optimising gestational weight gain and improving maternal and infant health outcomes through antenatal dietary, lifestyle and physical activity advice: the OPTIMISE randomised controlled trial protocol

Introduction

Obesity represents a significant health burden, and WHO recognises the importance of preventing weight gain and subsequent development of obesity among adults who are within the healthy weight range. Women of reproductive age have demonstrated high rates of weight gain during pregnancy placing them at risk of becoming overweight or obese. We will evaluate the effects of dietary and physical activity advice on maternal, fetal and infant health outcomes, among pregnant women of normal body mass index (BMI).

Methods and analysis

We will conduct a randomised controlled trial, consenting and randomising women with a live singleton pregnancy between 10⁺⁰ and 20⁺⁰ weeks and BMI 18.5–24.9 kg/m² at first antenatal visit, from a tertiary maternity hospital. Women randomised to the Lifestyle Advice Group will receive three face-to-face sessions (two with a research dietitian and one with a trained research assistant) and three telephone calls over pregnancy, in which they will be provided with dietary and lifestyle advice and encouraged to make change using a SMART goals approach. Women randomised to the Standard Care Group will receive routine antenatal care. The primary outcome is infant birth weight >4 kg. Secondary outcomes will include adverse infant and maternal outcomes, maternal weight change, maternal diet and physical activity changes, maternal quality of life and emotional well-being, fetal growth and costs of healthcare. We will recruit 624 women to detect a reduction from 8.72% to 3.87% (alpha 0.05 (two-tailed); power 70%) in infants with birth weight >4 kg. Analyses will be intention to treat with estimates reported as relative risks and 95% CIs.

Ethics and dissemination

Ethical approval has been obtained from the Women’s and Children’s Hospital ethics committee. Findings will be disseminated widely via journal publication and conference presentation(s), and participants informed of results.

Trial registration number

ACTRN12614000583640.

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Domestic violence: a cross-sectional study among pregnant women in different regions of Sri Lanka

Objectives

The aims of this study were to assess the regional differences in domestic violence among pregnant women in the capital district and in the tea plantation sector of Sri Lanka, to explore potential contributory factors and to assess whether healthcare workers addressed domestic violence and disclosure among survivors.

Design

A cross-sectional study was carried out using interviewer-administered Abuse Assessment Screen.

Setting

Fifty-seven antenatal clinic centres in the capital district and 30 in the tea plantation sector.

Participants

Pregnant women between 6 and 40 weeks of gestational age. In the capital district, 1375 women were recruited from antenatal clinic centres in the urban (n=25) and in the rural areas (n=32), and 800 women from 30 centres in the tea plantation sector. The response rate in the capital district was 95.6% and 96.7% in the tea plantation sector.

Results

Among the total sample of pregnant women (n=2088), the prevalence of ‘ever abused’ was 38.6%, and the prevalence of ‘currently abused’ was 15.9%. ‘Ever abused’ (31.5% vs 50.8%) and ‘currently abused’ (10% vs 25.8%) were significantly higher (P<0.001) among the women living in the tea plantation sector. ‘Ever abused’ was associated with living in the tea plantation sector, being employed, living far from gender-based violence care centre and of Muslim ethnicity, after adjusting for age, education and family income. Only 38.8% of all participants had been asked by healthcare workers about abuse. Living in the tea plantation sector and lower level of education were associated with not being asked. Among those who reported ‘ever abused’, only 8.7% had disclosed the experience to a healthcare worker.

Conclusion

Domestic violence was prevalent and highest among women in the tea plantation sector compared with the capital district. The capacity of healthcare workers in addressing domestic violence should be increased.

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Factors associated with insufficient awareness of breast cancer among women in Northern and Eastern China: a case-control study

Objectives

To investigate the awareness and knowledge level of breast cancer among Chinese participants.

Design

Case–control study.

Settings

This study was based on the database of the minister-affiliated hospital key project of the Ministry of Health of the People’s Republic of China that included 21 Chinese hospitals between April 2012 and April 2013.

Participants

Matched study was designed among 2978 participants with Han ethnicity aged between 25 and 70.

Primary and secondary outcome measures

Student’s t-test, Pearson’s ² test, reliability analysis, exploratory factor analysis, and univariate and multivariate logistic regression analyses were performed to know the level of breast cancer knowledge and find the breast cancer awareness-associated factors.

Results

80.0% (2383/2978) of the participants had poor awareness level of breast cancer. In-depth knowledge of breast cancer such as early symptoms and risk factors was poorly found among them. Television broadcast and relatives or friends with breast cancers were the main sources of information about breast cancer. Of all participants, 72.8% (2167/2978) had heard about breast cancer as a frequent cancer affecting women, and 63.3% (1884/2978) knew that family history of breast cancer was a risk factor for breast cancer. Over half of them were aware that a breast lump could be a symptom of breast cancer. Multivariate analysis identified the following variables that predicted awareness of breast cancer: young age (OR=0.843, 95% CI 0.740 to 0.961), occupation (agricultural worker) (OR=12.831, 95% CI 6.998 to 23.523), high household social status (OR=0.644, 95% CI 0.531 to 0.780), breast hyperplasia history (OR=1.684, 95% CI 1.273 to 2.228), high behavioural prevention score (OR=4.407, 95% CI 3.433 to 5.657).

Conclusion

Most women were aware of breast cancer as a disease, but their in-depth knowledge of it was poor. More publicity and education programmes to increase breast cancer awareness are necessary and urgent, especially for the ageing women and agricultural workers.

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Evaluation of a complex intervention (Engager) for prisoners with common mental health problems, near to and after release: study protocol for a randomised controlled trial

Introduction

The ‘Engager’ programme is a ‘through-the-gate’ intervention designed to support prisoners with common mental health problems as they transition from prison back into the community. The trial will evaluate the clinical and cost-effectiveness of the Engager intervention.

Methods and analysis

The study is a parallel two-group randomised controlled trial with 1:1 individual allocation to either: (a) the Engager intervention plus standard care (intervention group) or (b) standard care alone (control group) across two investigation centres (South West and North West of England). Two hundred and eighty prisoners meeting eligibility criteria will take part. Engager is a person-centred complex intervention delivered by practitioners and aimed at addressing offenders’ mental health and social care needs. It comprises one-to-one support for participants prior to release from prison and for up to 20 weeks postrelease. The primary outcome is change in psychological distress measured by the Clinical Outcomes in Routine Evaluation-Outcome Measure at 6 months postrelease. Secondary outcomes include: assessment of subjective met/unmet need, drug and alcohol use, health-related quality of life and well-being-related quality of life measured at 3, 6 and 12 months postrelease; change in objective social domains, drug and alcohol dependence, service utilisation and perceived helpfulness of services and change in psychological constructs related to desistence at 6 and 12 months postrelease; and recidivism at 12 months postrelease. A process evaluation will assess fidelity of intervention delivery, test hypothesised mechanisms of action and look for unintended consequences. An economic evaluation will estimate the cost-effectiveness.

Ethics and dissemination

This study has been approved by the Wales Research Ethics Committee 3 (ref: 15/WA/0314) and the National Offender Management Service (ref: 2015–283). Findings will be disseminated to commissioners, clinicians and service users via papers and presentations.

Trial registration number

ISRCTN11707331; Pre-results.

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Pregnancy diet and offspring asthma risk over a 10-year period: the Lifeways Cross Generation Cohort Study, Ireland

Objective

The association of maternal pregnancy diet with offspring asthma risk have been reported. However, literature on longitudinal patterns of asthma risk relative to intrauterine nutrient exposure is limited. We aimed to establish whether vegetable, oily fish and vitamin D intake during pregnancy are associated with childhood asthma risk over a 10-year period in the Irish Republic.

Design

Mother–child pairs (n=897) from the Lifeways prospective birth cohort, with data on nutrient intake during pregnancy and asthma status, respectively, were eligible for inclusion in the analysis. Data on socioeconomic and morbidity indicators over 10 years of follow-up on mothers and the index child were collected through self-administered questionnaires. Asthma status as diagnosed by the general practitioner at any time point over 10 years was related to maternal vegetable, oily fish and vitamin D intake during pregnancy, while adjusting for gestational age, socioeconomic status, smoking at delivery, breast feeding, season of birth and supplement use. Data were modelled with a marginal model on correlated observations over time within individuals.

Results

In the fully adjusted model, asthma was inversely associated with higher daily average intake of oily fish (OR 0.23 per serving/day, 95% CI 0.04 to 1.41) and of vegetables (OR 0.96 per serving/day, 95% CI 0.88 to 1.05), but the confidence limits overlapped 1. A higher daily vitamin D intake was associated with reduced odds of asthma (OR 0.93 per μg/day, 95% CI 0.89 to 0.98).

Conclusion

This analysis suggests higher daily average intake of vitamin D in pregnancy is associated with asthma risk in offspring over the first 10 years of life.

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Regional disparities in the intimate partner sexual violence rate against women in Parana State, Brazil, 2009-2014: an ecological study

Objective

Evaluate disparities in a Brazilian state by conducting an analysis to determine whether socioeconomic status was associated with the reported intimate partner sexual violence (IPSV) rates against women.

Design

A retrospective, ecological study.

Settings

Data retrieved from the Notifiable Diseases Information System database of the Ministry of Health of Brazil.

Participants

All cases of IPSV (n=516) against women aged 15–49 years reported in the Notifiable Diseases Information System between 2009 and 2014.

Outcome measures

The data were evaluated through an exploratory analysis of spatial data.

Results

We identified a positive spatial self-correlation in the IPSV rate (0.7105, P≤0.001). Five high–high-type clusters were identified, predominantly in the Metropolitan, West, South Central, Southwest, Southeast and North Central mesoregions, with only one cluster identified in the North Pioneer mesoregion. Our findings also indicated that the associations between the IPSV rate and socioeconomic predictors (women with higher education, civil registry of legal separations, economically active women, demographic density and average female income) were significantly spatially non-stationary; thus, the regression coefficients verified that certain variables in the model were associated with the IPSV rate in some regions of the state. In addition, the geographically weighted regression (GWR) model improved the understanding of the associations between socioeconomic indicators and the IPSV notification rate, showing a better adjustment than the ordinary least square (OLS) model (OLS vs GWR model: R²: 0.95 vs 0.99; Akaike information criterion: 4117.90 vs 3550.61; Moran’s I: 0.0905 vs –0.0273, respectively).

Conclusions

IPSV against women was heterogeneous in the state of Paraná. The GWR model showed a better fit and enabled the analysis of the distribution of each indicator in the state, which demonstrated the utility of this model for the study of IPSV dynamics and the indication of local determinants of IPSV notification rates.

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Which patients benefit specifically from short-term psychodynamic psychotherapy (STPP) for depression? Study protocol of a systematic review and meta-analysis of individual participant data

Introduction

Short-term psychodynamic psychotherapy (STPP) is an empirically supported treatment that is often used to treat depression. However, it is largely unclear if certain subgroups of depressed patients can benefit specifically from this treatment method. We describe the protocol for a systematic review and meta-analysis of individual participant data (IPD) aimed at identifying predictors and moderators of STPP for depression efficacy.

Method and analysis

We will conduct a systematic literature search in multiple bibliographic databases (PubMed, PsycINFO, Embase.com, Web of Science and Cochrane’s Central Register of Controlled Trials), ‘grey literature’ databases (GLIN and UMI ProQuest) and a prospective trial register (http://www.controlled-trials.com). We will include studies reporting (a) outcomes on standardised measures of (b) depressed (c) adult patients (d) receiving STPP. We will next invite the authors of these studies to share the participant-level data of their trials and combine these data to conduct IPD meta-analyses. The primary outcome for this study is post-treatment efficacy as assessed by a continuous depression measure. Potential predictors and moderators include all sociodemographic variables, clinical variables and psychological patient characteristics that are measured before the start of treatment and are assessed consistently across studies. One-stage IPD meta-analyses will be conducted using mixed-effects models.

Ethics and dissemination

Institutional review board approval is not required for this study. We intend to submit reports of the outcomes of this study for publication to international peer-reviewed journals in the fields of psychiatry or clinical psychology. We also intend to present the outcomes at international scientific conferences aimed at psychotherapy researchers and clinicians. The findings of this study can have important clinical implications, as they can inform expectations of STPP efficacy for individual patients, and help to make an informed choice concerning the best treatment option for a given patient.

PROSPERO registration number

CRD42017056029.

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Pathways and cost-effectiveness of routine lung cancer inpatient care in rural Anhui, China: a retrospective cohort study protocol

Introduction

Routine inpatient care (RIC) for patients with cancer forms various pathways of clinical procedures. Although most individual procedures comprising the pathways have been tested via clinical trials, little is known about the collective cost and effectiveness of the pathways as a whole. This study aims at exploring RIC pathways for patients with lung cancer from rural Anhui, China, and their determinants and economic impacts.

Methods and analysis

The study adopts a retrospective cohort design and proceeds in five steps. Step 1 defines the four main categories of study variables, including clinical procedures, direct cost and effectiveness of procedures, and factors affecting use of these procedures and their cost and effectiveness. Step 2 selects a cohort of 5000 patients with lung cancer diagnosed between 1 July 2015 and 30 June 2016 from rural Anhui by clustered random sampling. Step 3 retrieves the records of all the inpatient care episodes due to lung cancer and extracts data about RIC procedures, proximate variables (eg, Karnofsky Performance Status, Lung Function Score) of patient outcomes and related factors (eg, stage of cancer, age, gender), by two independent clinician researchers using a web-based form. Step 4 estimates the direct cost of each of the RIC procedures using micro-costing and collects data about ultimate patient outcomes (survival and progression-free survival) through a follow-up survey of patients and/or their close relatives. Step 5 analyses the data collected and explores pathways of RIC procedures and their relations with patient outcomes, costs, cost:effect ratios, and a whole range of clinical and sociodemographic factors using multivariate regression and path models.

Ethics and dissemination

The study protocol has been approved by an authorised ethics committee of Anhui Medical University (reference number: 20170312). Findings from the study will be disseminated through conventional academic routes such as peer-reviewed publications and presentations at regional, national and international conferences.

Trial registration number

ISRCTN25595562.

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Efficacy and safety of ginkgo preparations for attention deficit hyperactivity disorder: a systematic review protocol

Introduction

Attention deficit hyperactivity disorder (ADHD) is one of the most commonly diagnosed and treated childhood psychiatric disorders. The analogous diagnosis adopted in Europe is hyperkinetic disorder, which is defined in the WHO’s International Classification of Diseases 10th edition (ICD-10). Hyperkinetic disorder includes more severe conditions. Ginkgo preparations are used in the treatment of ADHD. The present study will assess the efficacy and safety of ginkgo preparations in the treatment of ADHD in the currently published literature.

Materials and methods

All prospective randomised controlled trials (RCTs) will be included in this systematic review. Patients diagnosed with ADHD according to American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders fourth edition (DSM-IV), Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5), ICD-10 or Chinese Classification and Diagnosis of Mental Diseases third edition (CMDD) will be included. A comprehensive search for RCTs to evaluate the effectiveness and tolerance of ginkgo preparations will be performed. The primary outcomes are the ADHD Rating Scale-IV and Revised Conners’ Parent Rating Scale. The secondary outcomes are quality of life evaluated by the KINDL scale, adverse effects/events, Conners’ Teacher Rating Scale, Strengths and Weaknesses of ADHD Symptoms and Normal Behaviour Scale and Fremdbeurteilungsbogen für Hyperkinetische Störungen. Exclusion criteria are the following: (1) case reports, not randomised trial, non-comparative studies and (2) patients who were not diagnosed based on DSM-IV, DSM-5, ICD-10 or CMDD. The following databases will be searched from their inception until January 2018: Medline, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, China Biology Medicine Disc, China National Knowledge Infrastructure Database, Wanfang Database and Chinese Scientific Journals Database. Two authors will independently perform the study selection, extract the data and assess the study quality and risk of bias.

Ethics and dissemination

This systematic review does not require ethics approval. It will be published in a peer-reviewed journal.

PROSPERO registration number

CRD42017077190.

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Antibodies, Vol. 7, Pages 12: A Polar Sulfamide Spacer Significantly Enhances the Manufacturability, Stability, and Therapeutic Index of Antibody–Drug Conjugates

Antibodies, Vol. 7, Pages 12: A Polar Sulfamide Spacer Significantly Enhances the Manufacturability, Stability, and Therapeutic Index of Antibody–Drug Conjugates

Antibodies doi: 10.3390/antib7010012

Authors: Jorge Verkade Marloes Wijdeven Remon van Geel Brian Janssen Sander van Berkel Floris van Delft

Despite tremendous efforts in the field of targeted cancer therapy with antibody–drug conjugates (ADCs), attrition rates have been high. Historically, the priority in ADC development has been the selection of target, antibody, and toxin, with little focus on the nature of the linker. We show here that a short and polar sulfamide spacer (HydraSpace™, AE Oss, the Netherland) positively impacts ADC properties in various ways: (a) efficiency of conjugation; (b) stability; and (c) therapeutic index. Different ADC formats are explored in terms of drug-to-antibody ratios (DAR2, DAR4) and we describe the generation of a DAR4 ADC by site-specific attachment of a bivalent linker–payload construct to a single conjugation site in the antibody. A head-to-head comparison of HydraSpace™-containing DAR4 ADCs to marketed drugs, derived from the same antibody and toxic payload components, indicated a significant improvement in both the efficacy and safety of several vivo models, corroborated by in-depth pharmacokinetic analysis. Taken together, HydraSpace™ technology based on a polar sulfamide spacer provides significant improvement in manufacturability, stability, and ADC design, and is a powerful platform to enable next-generation ADCs with enhanced therapeutic index.

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Recognise evidence based medicines to help smokers quit, including nicotine replacement therapy, varenicline buprop… https://t.co/jhIeUxDxmN

Recognise evidence based medicines to help smokers quit, including nicotine replacement therapy, varenicline buprop… https://t.co/jhIeUxDxmN

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A Trend in Sudden Sensorineural Hearing Loss: Data from a Population-Based Study

This is the first study reporting on the incidence and clinical aspects of sudden sensorineural hearing loss (SSNHL) in South Korea. Using Health Insurance Review and Assessment Service data from 2011 to 2015, the monthly incidence of unilateral SSNHL and incidence according to patients’ sex, age, and month of diagnosis were investigated. The monthly incidence of unilateral SSNHL increased over the 5-year study period, with a mean annual incidence of 17.76 cases/ 100,000 of the population. The incidence increased with age, with most patients presenting in their 60s. There was a slight female preponderance, with a male-to-female ratio of 1: 1.35. Most new patients were diagnosed in October, and the fewest in January. In conclusion, this large-scale study indicates that unilateral SSNHL has a higher incidence among the elderly, women, and in autumn (i.e., along with colder weather).
Audiol Neurotol 2017;22:311–316

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health technology; +156 new citations

156 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

health technology

These pubmed results were generated on 2018/02/20

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

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Computational analysis identifies putative prognostic biomarkers of pathological scarring in skin wounds

Pathological scarring in wounds is a prevalent clinical outcome with limited prognostic options. The objective of this study was to investigate whether cellular signaling proteins could be used as prognostic b...

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Editorial Board

Publication date: 1 March 2018
Source:Experimental Cell Research, Volume 364, Issue 1





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Mechano-growth factor protects against mechanical overload induced damage and promotes migration of growth plate chondrocytes through RhoA/YAP pathway

Publication date: Available online 20 February 2018
Source:Experimental Cell Research
Author(s): Xingzhi Jing, Yaping Ye, Yuan Bao, Jinming Zhang, Junming Huang, Rui Wang, Jiachao Guo, Fengjing Guo
Epiphyseal growth plate is highly dynamic tissue which is controlled by a variety of endocrine, paracrine hormones, and by complex local signaling loops and mechanical loading. Mechano growth factor (MGF), the splice variant of the IGF-I gene, has been discovered to play important roles in tissue growth and repair. However, the effect of MGF on the growth plate remains unclear. In the present study, we found that MGF mRNA expression of growth plate chondrocytes was upregulated in response to mechanical stimuli. Treatment of MGF had no effect on growth plate chondrocytes proliferation and differentiation. But it could inhibit growth plate chondrocytes apoptosis and inflammation under mechanical overload. Moreover, both wound healing and transwell assay indicated that MGF could significantly enhanced growth plate chondrocytes migration which was accompanied with YAP activation and nucleus translocation. Knockdown of YAP with YAP siRNA suppressed migration induced by MGF, indicating the essential role of YAP in MGF promoting growth plate chondrocytes migration. Furthermore, MGF promoted YAP activation through RhoA GTPase mediated cytoskeleton reorganization, RhoA inhibition using C3 toxin abrogated MGF induced YAP activation. Importantly, we found that MGF promoted focal adhesion(FA) formation and knockdown of YAP with YAP siRNA partially suppressed the activation of FA kinase, implying that YAP is associated with FA formation. In conclusion, MGF is an autocrine growth factor which is regulated by mechanical stimuli. MGF could not only protect growth plate chondrocytes against damage by mechanical overload, but also promote migration through activation of RhoA/YAP signaling axis. Most importantly, our findings indicate that MGF promote cell migration through YAP mediated FA formation to determine the FA-cytoskeleton remodeling.



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Indomethacin induced glioma apoptosis involving ceramide signals

Publication date: Available online 19 February 2018
Source:Experimental Cell Research
Author(s): Cheng-Yi Chang, Jian-Ri Li, Chih-Cheng Wu, Jiaan-Der Wang, Ching-Ping Yang, Wen-Ying Chen, Wen-Yi Wang, Chun-Jung Chen
Nonsteroidal anti-inflammatory drugs (NSAIDs) are increasingly implicated in the prevention and treatment of cancers apart from their known inhibitory effects on eicosanoid production. One of the NSAIDs, indomethacin, in particular shows promising antineoplastic outcome against glioma. To extend such finding, we here studied in human H4 and U87 glioma cells the possible involvement of the ceramide/protein phosphatase 2A (PP2A)/Akt axis in the indomethacin-induced apoptosis. We found that the induced apoptosis was accompanied by a series of biochemical events, including intracellular ceramide generation, PP2A activation, Akt dephosphorylation, Mcl-1 and FLICE inhibiting protein (FLIP) transcriptional downregulation, Bax mitochondrial distribution, and caspase 3 activation. Such events were also duplicated with a cell-permeable C2-ceramide and Akt inhibitor LY294002. Pharmacological inhibition of ceramide synthase by fumonisin B1 and PP2A by okadaic acid moderately attenuated indomethacin-induced Akt dephosphorylation along with the apoptosis. Results suggested that the ceramide/PP2A/Akt axis is involved in the apoptosis and a possible cyclooxygenase-independent target for indomethacin. Furthermore, apoptosis regulatory proteins such as Mcl-1 and FLIP are potential downstream effectors of this axis and their downregulation could turn on the apoptotic program.



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Reversible Dilation of Cerebral Macrovascular Changes in MELAS Episodes

Abstract

Purpose

To investigate the cerebral macrovascular changes as well as the relationship of large vessels and cerebral blood flow (CBF) in mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) using magnetic resonance angiography (MRA) and arterial spin labeling (ASL) perfusion MR imaging (MRI).

Methods

A total of 20 patients diagnosed with MELAS (12 males, 8 females; mean age, 23.3 years) underwent conventional MRI, time-of-flight (TOF) MRA and three dimensional ASL. Follow-up scans were performed in 10 patients. The changes of cerebral arteries and branches on MRA images from both acute and recovery patients were independently evaluated by two radiologists. Lesion distribution and CBF were observed on the integrated maps of MRA and ASL.

Results

In 14 patients with clinical onsets, increased CBF was observed in all stroke-like lesions. Dilations of a single artery (four middle cerebral arteries, two posterior cerebral arteries) were found in six patients. Dilations of multiple arteries (two anterior cerebral arteries, seven middle cerebral arteries, six posterior cerebral arteries) were found in seven patients. Normal angiography was shown in one acute patient. Cortical terminal branches feeding the lesion areas were more obviously dilated than the main trunks. The dilated vessels returned to normal on follow-up scans concurrently with decreased CBF in nine patients who were resuscitated from episode attacks. Vasodilation was even seen in one preclinical patient who suffered a recurrent episode 50 days later.

Conclusion

Reversible dilation of cerebral macrovascular changes could be a new feature of MELAS and a presumed reason for fluctuant CBF. It would shed new light on the mitochondrial angiopathy.

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Establishment of reference intervals for the salivary cortisol circadian cycle, by electrochemiluminescence (ECLIA), in healthy adults

Publication date: Available online 19 February 2018
Source:Clinical Biochemistry
Author(s): Nadia Gagnon, Isabelle Fréchette, Pierre-Luc Mallet, Jean Dubé, Ghislaine Houde, Guy D. Fink
ObjectivesTo determine salivary cortisol reference intervals in a healthy adult population, at 6 different time points during a 24-hour (h) period.MethodsIn a prospective study, salivary cortisol concentrations were measured upon waking, one-hour post-waking and at specific times of the day: at 12 h00, 16 h00, 20 h00 and midnight. Samples were analyzed by the first and second-generation electrochemiluminescence assays (ECLIA) from Roche Cobas Cortisol®.ResultsSalivary cortisol values were obtained from 134 healthy volunteers. Reference intervals for the first-generation assay were 6.14–33.19 nmol/L (95% prediction interval) at waking, 5.42–28.06 nmol/L one-hour post-waking, 3.62–16.23 nmol/L at 12 h00, 2.78–15.27 nmol/L at 16 h00, 2.08–14.90 nmol/L at 20 h00 and 2.09–16.92 nmol/L at midnight. Mean salivary cortisol values were 14.63 nmol/L at waking and 6.44 nmol/L at midnight. Reference intervals for the second-generation assay were 1.50–22.02 nmol/L (2.5th to 97.5th percentiles) at waking, 1.50–20.87 nmol/L one-hour post-waking, 1.50–12.51 nmol/L at 12 h00, 1.50–13.03 nmol/L at 16 h00, 1.50–9.52 nmol/L at 20 h00 and 1.50–6.28 nmol/L at midnight. Values for the second-generation assay at all 6 different time points were almost half of the first-generation assay. The second-generation assay showed a better correlation with LC-MS/MS (r = 0,97).ConclusionOur study confirms that reference intervals for salivary cortisol are not comparable across first and second-generation Roche Cobas Cortisol® assays. Furthermore, the second-generation assay has a better correlation with LC-MS/MS and a better analytical performance (accuracy and precision).



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An imaging system from @Columbia identifies #breastcancer pts responding to neoadjuvant chemotherapy - analysing bl… https://t.co/sY8sS1n2aR

An imaging system from @Columbia identifies #breastcancer pts responding to neoadjuvant chemotherapy - analysing bl… https://t.co/sY8sS1n2aR

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Angioedema in Chronic Spontaneous Urticaria Is Underdiagnosed and Has a Substantial Impact: Analyses From ASSURE-CSU

Abstract

Background

ASSURE-CSU revealed differences in physician and patient reporting of angioedema. This post-hoc analysis was conducted to evaluate the actual rate of angioedema in the study population and explore differences between patients with and without angioedema.

Methods

This international observational study assessed 673 patients with inadequately controlled chronic spontaneous urticaria (CSU). Physicians abstracted angioedema data from medical records, which were compared with patient-reported data. Patients in the Yes-angioedema category had angioedema reported in the medical record and a patient-reported source. For those in the No-angioedema category, angioedema was reported in neither the medical record nor a patient-reported source. Those in the Misaligned category had angioedema reported in only one source. Statistical comparisons between Yes-angioedema and No-angioedema categories were conducted for measures of CSU activity, health-related quality of life (HRQoL), productivity, and healthcare resource utilisation (HCRU). Regression analyses explored the relationship between Dermatology Life Quality Index (DLQI) score and angioedema, adjusting for important covariates.

Results

Among evaluable patients, 259 (40.3%), 173 (26.9%), and 211 (32.8%) were in the Yes-angioedema, No-angioedema, and Misaligned category, respectively. CSU activity and impact on HRQoL, productivity, and HCRU were greater for Yes-angioedema patients than No-angioedema patients. After covariate adjustment, mean DLQI score was significantly higher (indicating worse HRQoL) for patients with angioedema versus no angioedema (9.88 vs. 7.27, P < 0.001). The Misaligned category had similar results with Yes-angioedema on all outcomes.

Conclusions

Angioedema in CSU seems to be under-reported but has significant negative impacts on HRQoL, daily activities, HCRU, and work compared with no angioedema.

This article is protected by copyright. All rights reserved.

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Novel targeted therapies and immunotherapy for advanced thyroid cancers.

Related Articles

Novel targeted therapies and immunotherapy for advanced thyroid cancers.

Mol Cancer. 2018 Feb 19;17(1):51

Authors: Naoum GE, Morkos M, Kim B, Arafat W

Abstract
Thyroid cancer is a frequently encountered endocrine malignancy. Despite the favorable prognosis of this disease, 15-20% of differentiated thyroid cancer (DTC) cases and most anaplastic types, remain resistant to standard treatment options, including radioactive iodine (RAI). In addition, around 30% of medullary thyroid cancer (MTC) cases show resistance after surgery. The evolving understanding of disease-specific molecular therapeutic targets has led to the approval of two targeted therapies (Sorafenib and Lenvatinib) for RAI refractory DTC and another two drugs (Vandetanib and Cabozantinib) for MTC. These advanced therapies exert their effects by blocking the MAPK pathway, which has been widely correlated to different types of thyroid cancers. While these drugs remain reserved for thyroid cancer patients who failed all treatment options, their ability to improve patients' overall survival remain hindered by their low efficacy and other molecular factors. Among these factors is the tumor's ability to activate parallel proliferative signaling pathways other than the cascades blocked by these drugs, along with overexpression of some tyrosine kinase receptors (TKR). These facts urge the search for novel different treatment strategies for advanced thyroid cases beyond these drugs. Furthermore, the growing knowledge of the dynamic immune system interaction with tumor microenvironment has revolutionized the cancer immune therapy field. In this review, we aim to discuss the molecular escape mechanisms of thyroid tumors from these drugs. We also highlight novel therapeutic options targeting other pathways than MAPK, including PI3K pathway, ALK translocations and HER2/3 receptors and their clinical impact. We also aim to discuss the usage of targeted therapy in restoring thyroid tumor sensitivity to RAI, and finally turn to extensively discuss the role of immunotherapy as a potential alternative treatment option for advanced thyroid diseases.

PMID: 29455653 [PubMed - in process]

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What Makes Us Vibe?

We like other people in part because they think the way we do—but we may also think alike as a result of being friends

-- Read more on ScientificAmerican.com

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Scottish GPs resign from BMA in protest at new contract

A group of GPs in Scotland are resigning from the BMA in protest at the agreement of a new contract that they claim will have a “devastating” effect on patients in rural areas.Although the contract...

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Quantitative, clinically relevant acoustic measurements of focal embouchure dystonia

ABSTRACT

Background: Focal embouchure dystonia impairs orofacial motor control in wind musicians and causes professional disability. A paucity of quantitative measures or rating scales impedes the objective assessment of treatment efficacy.

Objectives: We quantified specific features of focal embouchure dystonia using acoustic measures and developed a metric to assess severity across multiple domains of symptomatic impairment.

Methods: We recruited 9 brass musicians with and 6 without embouchure dystonia. The following 4 domains of symptomatic dysfunction in focal embouchure dystonia were identified: pitch inaccuracy, sound instability and tremor, sound breaks, and timing variability. Musicians performed sustained tones and sequences, and then acoustic variables within each domain were quantified. A composite brass acoustic severity score composed of these variables was validated against clinical global impressions of severity.

Results: Musicians with dystonia performed worse in acoustic domains of pitch inaccuracy (median: dystonia = 100%, control = 62%), instability (median shimmer: dystonia = 3%, control = 2%), and breaks (median: dystonia = 0.34%, control = 0.05%). Tremor in embouchure dystonia was 5 to 8 Hz, intermittent, and variable in amplitude. Rhythmic variability did not differ between groups. Participants with embouchure dystonia had different patterns of impairment across variables. Composite severity scores strongly predicted clinical global impression of severity (R² = 0.95).

Conclusions: Acoustic variables distinguish musicians with embouchure dystonia from controls and reflect different types of symptomatic impairments. Our composite acoustic severity score predicts severity of clinical global impression for musicians with different patterns of symptomatic impairment and may provide a foundation for developing a clinical rating scale. © 2018 International Parkinson and Movement Disorder Society

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MoCA for cognitive screening in Parkinson's disease: Beware of floor effect

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Lifetime exposure to estrogen and progressive supranuclear palsy: Environmental and Genetic PSP study

ABSTRACT

Background

Studies suggesting a protective effect of estrogen in neurodegenerative diseases prompted us to investigate this relationship in progressive supranuclear palsy (PSP).

Methods

This case-control study evaluated the self-reported reproductive characteristics and estrogen of 150 women with PSP and 150 age-matched female controls who participated in the Environmental Genetic-PSP study. Conditional logistic regression models were generated to examine associations of PSP with estrogen.

Results

There was no association between years of estrogen exposure duration and PSP. There was a suggestion of an inverse association between composite estrogen score and PSP that did not reach statistical significance (P = .06). Any exposure to estrogen replacement therapy halved the risk of PSP (odds ratio = 0.52; 95% confidence interval = 0.30-0.92; P = .03). Among PSP cases, earlier age at menarche was associated with better performance on Hoehn and Yahr stage (β = −0.60; SE = 0.26; P = .02) and Unified Parkinson's Disease Rating Scale II score (β = −5.19; SE = 2.48; P = .04) at clinical examination.

Conclusions

This case-control study suggests a protective role of lifetime estrogen exposure in PSP. Future studies will be needed to confirm this association. © 2018 International Parkinson and Movement Disorder Society

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Reply: MoCA for cognitive screening in Parkinson's disease: Beware of floor effect

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3-T MR Imaging of Proximal Femur Microarchitecture in Subjects with and without Fragility Fracture and Nonosteoporotic Proximal Femur Bone Mineral Density.

3-T MR Imaging of Proximal Femur Microarchitecture in Subjects with and without Fragility Fracture and Nonosteoporotic Proximal Femur Bone Mineral Density.

Radiology. 2018 Feb 19;:170138

Authors: Chang G, Rajapakse CS, Chen C, Welbeck A, Egol K, Regatte RR, Saha PK, Honig S

Abstract
Purpose To determine if 3-T magnetic resonance (MR) imaging of proximal femur microarchitecture can allow discrimination of subjects with and without fragility fracture who do not have osteoporotic proximal femur bone mineral density (BMD). Materials and Methods Sixty postmenopausal women (30 with and 30 without fragility fracture) who had BMD T scores of greater than -2.5 in the hip were recruited. All subjects underwent dual-energy x-ray absorptiometry to assess BMD and 3-T MR imaging of the same hip to assess bone microarchitecture. World Health Organization Fracture Risk Assessment Tool (FRAX) scores were also computed. We used the Mann-Whitney test, receiver operating characteristics analyses, and Spearman correlation estimates to assess differences between groups, discriminatory ability with parameters, and correlations among BMD, microarchitecture, and FRAX scores. Results Patients with versus without fracture showed a lower trabecular plate-to-rod ratio (median, 2.41 vs 4.53, respectively), lower trabecular plate width (0.556 mm vs 0.630 mm, respectively), and lower trabecular thickness (0.114 mm vs 0.126 mm) within the femoral neck, and higher trabecular rod disruption (43.5 vs 19.0, respectively), higher trabecular separation (0.378 mm vs 0.323 mm, respectively), and lower trabecular number (0.158 vs 0.192, respectively), lower trabecular connectivity (0.015 vs 0.027, respectively) and lower trabecular plate-to-rod ratio (6.38 vs 8.09, respectively) in the greater trochanter (P < .05 for all). Trabecular plate-to-rod ratio, plate width, and thickness within the femoral neck (areas under the curve [AUCs], 0.654-0.683) and trabecular rod disruption, number, connectivity, plate-to-rod ratio, and separation within the greater trochanter (AUCs, 0.662-0.694) allowed discrimination of patients with fracture from control subjects. Femoral neck, total hip, and spine BMD did not differ between and did not allow discrimination between groups. FRAX scores including and not including BMD allowed discrimination between groups (AUCs, 0.681-0.773). Two-factor models (one MR imaging microarchitectural parameter plus a FRAX score without BMD) allowed discrimination between groups (AUCs, 0.702-0.806). There were no linear correlations between BMD and microarchitectural parameters (Spearman ρ, -0.198 to 0.196). Conclusion 3-T MR imaging of proximal femur microarchitecture allows discrimination between subjects with and without fragility fracture who have BMD T scores of greater than -2.5 and may provide different information about bone quality than that provided by dual-energy x-ray absorptiometry. © RSNA, 2018.

PMID: 29457963 [PubMed - as supplied by publisher]

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Liver Imaging Reporting and Data System: Patient Outcomes for Category 4 and 5 Nodules.

Liver Imaging Reporting and Data System: Patient Outcomes for Category 4 and 5 Nodules.

Radiology. 2018 Feb 19;:170748

Authors: Choi SH, Byun JH, Lim YS, Lee SJ, Kim SY, Won HJ, Shin YM, Kim PN

Abstract
Purpose To determine the outcomes after initial therapy in patients with chronic liver disease and retrospectively assigned Liver Imaging Reporting and Data System (LI-RADS; version 2014) category 4 (LR-4) and 5 (LR-5) nodules at gadoxetate disodium-enhanced MR imaging. Materials and Methods In this retrospective study, 260 patients with a single LR-4 (n = 132) or LR-5 (n = 128) nodule who were assigned a LI-RADS category were included. Patients were identified between January 2012 and December 2012, and were initially treated by resection, liver transplant, radiofrequency ablation (RFA), or transcatheter arterial chemoembolization (TACE) according to the Barcelona Clinic Liver Cancer staging system. Follow-up continued until August 31, 2016. The incidences of local tumor recurrence (ILRs) and distant tumor recurrence (IDRs) and recurrence-free survival (RFS) were compared between the LR-4 and LR-5 patients. For each category, ILRs, IDRs, and RFS were compared across the four treatments. Results LR-5 patients were more frequently treated by surgical resection than LR-4 patients (72.7% [93 of 128] vs 41.7% [55 of 132], respectively; P < .001), but less frequently treated by RFA (19.5% [25 of 128] vs 30.3% [40 of 132], respectively; P = .047) and TACE (6.3% [eight of 128] vs 22.0% [29 of 132], respectively; P < .001). ILRs and IDRs were not significantly different between LR-4 and LR-5 patients according to the type of treatment (0%-48.3% [14 of 29] vs 0%-25.0% [two of eight], P $ .423; 0%-55.2% [16 of 29] vs 0%-37.5% [three of eight], P $ .447, respectively). There was no difference in RFS between the two categories (36.3 months vs 41.7 months, respectively; P = .084). Liver transplant showed no local or distant tumor recurrence in either category. Resection showed higher RFS and lower ILR and IDR than RFA and TACE in both LR-4 and LR-5 patients. Conclusion Patients with LR-4 nodules had ILRs and IDRs similar to patients with LR-5 nodules when stratified by treatment type. RFS was also similar between patients with LR-4 and LR-5 nodules. Among the four initial treatments, liver transplant and resection showed better local tumor control, with longer RFS than RFA or TACE. © RSNA, 2018 Online supplemental material is available for this article.

PMID: 29457964 [PubMed - as supplied by publisher]

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Text-mined phenotype annotation and vector-based similarity to improve identification of similar phenotypes and causative genes in monogenic disease patients

Abstract

The genetic diagnosis of rare monogenic diseases using exome/genome sequencing requires the true causal variant(s) to be identified from tens of thousands of observed variants. Typically a virtual gene panel approach is taken whereby only variants in genes known to cause phenotypes resembling the patient under investigation are considered. With the number of known monogenic gene-disease pairs exceeding 5000, manual curation of personalised virtual panels using exhaustive knowledge of the genetic basis of the human monogenic phenotypic spectrum is challenging.

We present improved probabilistic methods for estimating phenotypic similarity based on Human Phenotype Ontology annotation. A limitation of existing methods for evaluating a disease's similarity to a reference set is that reference diseases are typically represented as a series of binary (present/absent) observations of phenotypic terms. We evaluate a quantified disease reference set, using term frequency in phenotypic text descriptions to approximate term relevance.

We demonstrate an improved ability to identify related diseases through the use of a quantified reference set, and that vector space similarity measures perform better than established information content-based measures. These improvements enable the generation of bespoke virtual gene panels, facilitating more accurate and efficient interpretation of genomic variant profiles from individuals with rare Mendelian disorders. These methods are available online at https://atlas.genetics.kcl.ac.uk/~jake/cgi-bin/patient_sim.py

This article is protected by copyright. All rights reserved

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The BRCA2 c.68-7T > A variant is not pathogenic: A model for clinical calibration of spliceogenicity

Abstract

Although the spliceogenic nature of the BRCA2 c.68-7T > A variant has been demonstrated, its association with cancer risk remains controversial. In this study, we accurately quantified by real-time PCR and digital PCR the BRCA2 isoforms retaining or missing exon 3. In addition, the combined odds ratio for causality of the variant was estimated using genetic and clinical data, and its associated cancer risk was estimated by case-control analysis in 83,636 individuals. Co-occurrence in trans with pathogenic BRCA2 variants was assessed in 5,382 families. Exon 3 exclusion rate was 4.5-fold higher in variant carriers (13%) than controls (3%), indicating an exclusion rate for the c.68-7T > A allele of approximately 20%. The posterior probability of pathogenicity was 7.44 × 10⁻¹¹⁵. There was neither evidence for increased risk of breast cancer (OR 1.03; 95% CI 0.86-1.24), nor for a deleterious effect of the variant when co-occurring with pathogenic variants. Our data provide for the first time robust evidence of the non-pathogenicity of the BRCA2 c.68-7T > A. Genetic and quantitative transcript analyses together inform the threshold for the ratio between functional and altered BRCA2 isoforms compatible with normal cell function. These findings might be exploited to assess the relevance for cancer risk of other BRCA2 spliceogenic variants.

This article is protected by copyright. All rights reserved

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“First, do no harm” is true for NHS management too

McCartney is spot on in her column about the reasons for the current NHS crisis.1 Huge amounts of money been wasted on initiatives like the internal market, the white elephant Darzi centres, and the...

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IJMS, Vol. 19, Pages 613: Anti-Renal Fibrotic Effect of Exercise Training in Hypertension

IJMS, Vol. 19, Pages 613: Anti-Renal Fibrotic Effect of Exercise Training in Hypertension

International Journal of Molecular Sciences doi: 10.3390/ijms19020613

Authors: Ching Huang Yi-Yuan Lin Ai-Lun Yang Tang-Wei Kuo Chia-Hua Kuo Shin-Da Lee

The purpose of this study was to evaluate the effects of exercise training on renal fibrosis in hypertensive rats. Masson’s trichrome staining and Western blotting were performed on the excised renal cortex from sixteen male spontaneously hypertensive rats (SHR), which were randomly divided into either a sedentary hypertensive group (SHR) or exercise hypertensive group (SHR-EX, running on an exercise treadmill for 60 min/day, 5 sessions/week, for 12 weeks), and from eight male Wistar-Kyoto rats which served as a sedentary normotensive group (WKY). The systolic blood pressure (SBP) and renal fibrosis in hypertensive rats improved after exercise training. The inflammatory-related protein levels of interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2), as well as the fibrotic-related protein levels of transforming growth factor-beta (TGF-β), phospho-Smad2/3 (p-Smad2/3), connective tissue growth factor (CTGF), matrix metalloproteinase-9 (MMP-9), and matrix metalloproteinase-2 (MMP-2) were decreased in the SHR-EX group when compared with the SHR group. Exercise training suppressed the hypertension-induced renal cortical inflammatory and fibrotic pathways in hypertensive rat models. These findings might indicate a new therapeutic effect for exercise training to prevent renal fibrosis in hypertensive nephropathy.

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health technology; +156 new citations

156 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

health technology

These pubmed results were generated on 2018/02/20

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

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Correction: Effects of UV-B radiation on the infectivity of Magnaporthe oryzae and rice disease-resistant physiology in Yuanyang terraces

Photochem. Photobiol. Sci., 2018, Advance Article
DOI: 10.1039/C8PP90006J, Correction

Open Access

  This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.

Xiang Li, Yongmei He, Chunmei Xie, Yanqun Zu, Fangdong Zhan, Xinyue Mei, Yang Xia, Yuan Li
To cite this article before page numbers are assigned, use the DOI form of citation above.
The content of this RSS Feed (c) The Royal Society of Chemistry

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Porphyromonas gingivalis: the gift of community involvement

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Fat halo sign

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Percutaneous microwave ablation for local control of metastatic renal cell carcinoma

Abstract

Purpose

The purpose of the article is to evaluate the safety and oncologic efficacy of microwave ablation for metastatic renal cell carcinoma (mRCC).

Materials and methods

From September 2011 to December 2016, 33 mRCC were ablated in 18 patients using percutaneous microwave ablation. Sites of mRCC include retroperitoneum (n = 12), contralateral kidney (n = 6), liver (n = 6), lung (n = 5), adrenal gland (n = 5). Technical success, local, and distant tumor progression, and complications were assessed at immediate and follow-up imaging. The Kaplan–Meier method was used for survival analysis.

Results

Technical success was achieved for 33/33 (100%) mRCC tumors. Ablation provided durable local control for 28/30 (93%) mRCC tumors in 17 patients at a median duration of clinical and imaging follow-up of 1.6 years (IQR 0.7–3.6) and 0.8 years (IQR 0.5–2.7), respectively. In-hospital and perioperative mortality was 0%. There were 5 (15%) procedure-related complications including one high-grade event (Clavien–Dindo III). Four patients have died from mRCC at a median of 1.3 years (range 0.7–5.1) following ablation. Estimated OS (95% CI number still at risk) at 1, 2, and 5 years were 86% (53–96%, 11), 75% (39–92%, 8), and 75% (39–92%, 3), respectively.

Conclusions

Microwave ablation of oligometastatic renal cell carcinoma is safe and provides durable local control in appropriately selected patients.

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Machine Learning Algorithms Utilizing Quantitative CT Features May Predict Eventual Onset of Bronchiolitis Obliterans Syndrome After Lung Transplantation

Publication date: Available online 19 February 2018
Source:Academic Radiology
Author(s): Eduardo J. Mortani Barbosa, Maarten Lanclus, Wim Vos, Cedric Van Holsbeke, William De Backer, Jan De Backer, James Lee
Rationale and ObjectivesLong-term survival after lung transplantation (LTx) is limited by bronchiolitis obliterans syndrome (BOS), defined as a sustained decline in forced expiratory volume in the first second (FEV1) not explained by other causes. We assessed whether machine learning (ML) utilizing quantitative computed tomography (qCT) metrics can predict eventual development of BOS.Materials and MethodsPaired inspiratory-expiratory CT scans of 71 patients who underwent LTx were analyzed retrospectively (BOS [n = 41] versus non-BOS [n = 30]), using at least two different time points. The BOS cohort experienced a reduction in FEV1 of >10% compared to baseline FEV1 post LTx. Multifactor analysis correlated declining FEV1 with qCT features linked to acute inflammation or BOS onset. Student t test and ML were applied on baseline qCT features to identify lung transplant patients at baseline that eventually developed BOS.ResultsThe FEV1 decline in the BOS cohort correlated with an increase in the lung volume (P = .027) and in the central airway volume at functional residual capacity (P = .018), not observed in non-BOS patients, whereas the non-BOS cohort experienced a decrease in the central airway volume at total lung capacity with declining FEV1 (P = .039). Twenty-three baseline qCT parameters could significantly distinguish between non-BOS patients and eventual BOS developers (P < .05), whereas no pulmonary function testing parameters could. Using ML methods (support vector machine), we could identify BOS developers at baseline with an accuracy of 85%, using only three qCT parameters.ConclusionsML utilizing qCT could discern distinct mechanisms driving FEV1 decline in BOS and non-BOS LTx patients and predict eventual onset of BOS. This approach may become useful to optimize management of LTx patients.



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Many CCGs are failing to boost mental health funding, BMA warns

Many clinical commissioning groups (CCGs) in England are failing to increase spending on mental health services in line with national policy commitments, a report from the BMA has found.1The...

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Hydroxychloroquine should not be used for hand osteoarthritis, say researchers

Hydroxychloroquine is no more effective than placebo in reducing the symptoms of hand osteoarthritis, a study published in the Annals of Internal Medicine has found.1 The UK researchers said that...

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