The role of tenascin-C in tissue injury and tumorigenesis

The extracellular matrix molecule tenascin-C is highly expressed during embryonic development, tissue repair and in pathological situations such as chronic inflammation and cancer. Tenascin-C interacts with several other extracellular matrix molecules and cell-surface receptors, thus affecting tissue architecture, tissue resilience and cell responses. Tenascin-C modulates cell migration, proliferation and cellular signaling through induction of pro-inflammatory cytokines and oncogenic signaling molecules amongst other mechanisms. Given the causal role of inflammation in cancer progression, common mechanisms might be controlled by tenascin-C during both events. Drugs targeting the expression or function of tenascin-C or the tenascin-C protein itself are currently being developed and some drugs have already reached advanced clinical trials. This generates hope that increased knowledge about tenascin-C will further improve management of diseases with high tenascin-C expression such as chronic inflammation, heart failure, artheriosclerosis and cancer

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Acupuncture or low frequency infrared treatment for low back pain in Chinese patients: a discrete choice experiment

Acupuncture is a popular but controversial treatment option for low back pain. In China, it is practised as traditional Chinese medicine; other treatment strategies for low back pain are commonly practised as Western medicine. Research on patient preference for low back-pain treatment options has been mainly conducted in Western countries and is limited to a willingness-to-pay approach. A stated-preference, discrete choice experiment was conducted to determine Chinese patient preferences and trade-offs for acupuncture and low frequency infrared treatment in low back pain from September 2011 to August 2012 after approval from the Department of Scientific Research in the study settings. Eight-six adult outpatients who visited the ‘traditional medicine department’ at a traditional Chinese medicine hospital and the ‘rehabilitation department’ at a Western medicine hospital in Guangdong Province of China for chronic low back pain during study period participated in an interview survey. A questionnaire containing 10 scenarios (5 attributes in each scenario) was used to ask participants' preference for acupuncture, low frequency infrared treatment or neither option. Validated responses were analysed using a nested-logit model. The decision on whether to receive a therapy was not associated with the expected utility of receiving therapy, female gender and higher out-of-pocket payment significantly decreased chance to receive treatments. Of the utility of receiving either acupuncture or low frequency infrared treatment, the treatment sensation was the most important attribute as an indicator of treatment efficacy, followed by the maximum efficacy, maintenance duration and onset of efficacy, and the out-of-pocket payment. The willingness-to-pay for acupuncture and low frequency infrared treatment were about $618.6 and$592.4 USD per course respectively, demonstrated patients' demand of pain management. The treatment sensation was regarded as an indicator of treatment efficacy and the most important attribute for choosing acupuncture or low frequency infrared treatment. The high willingness-to-pay demonstrated patients' demand of pain management. However, there may be other factors influencing patients' preference to receive treatments

The 2021 WHO catalogue of Mycobacterium tuberculosis complex mutations associated with drug resistance: a genotypic analysis.

Background: Molecular diagnostics are considered the most promising route to achievement of rapid, universal drug susceptibility testing for Mycobacterium tuberculosis complex (MTBC). We aimed to generate a WHO-endorsed catalogue of mutations to serve as a global standard for interpreting molecular information for drug resistance prediction. Methods: In this systematic analysis, we used a candidate gene approach to identify mutations associated with resistance or consistent with susceptibility for 13 WHO-endorsed antituberculosis drugs. We collected existing worldwide MTBC whole-genome sequencing data and phenotypic data from academic groups and consortia, reference laboratories, public health organisations, and published literature. We categorised phenotypes as follows: methods and critical concentrations currently endorsed by WHO (category 1); critical concentrations previously endorsed by WHO for those methods (category 2); methods or critical concentrations not currently endorsed by WHO (category 3). For each mutation, we used a contingency table of binary phenotypes and presence or absence of the mutation to compute positive predictive value, and we used Fisher's exact tests to generate odds ratios and Benjamini-Hochberg corrected p values. Mutations were graded as associated with resistance if present in at least five isolates, if the odds ratio was more than 1 with a statistically significant corrected p value, and if the lower bound of the 95% CI on the positive predictive value for phenotypic resistance was greater than 25%. A series of expert rules were applied for final confidence grading of each mutation. Findings: We analysed 41 137 MTBC isolates with phenotypic and whole-genome sequencing data from 45 countries. 38 215 MTBC isolates passed quality control steps and were included in the final analysis. 15 667 associations were computed for 13 211 unique mutations linked to one or more drugs. 1149 (7·3%) of 15 667 mutations were classified as associated with phenotypic resistance and 107 (0·7%) were deemed consistent with susceptibility. For rifampicin, isoniazid, ethambutol, fluoroquinolones, and streptomycin, the mutations' pooled sensitivity was more than 80%. Specificity was over 95% for all drugs except ethionamide (91·4%), moxifloxacin (91·6%) and ethambutol (93·3%). Only two resistance mutations were identified for bedaquiline, delamanid, clofazimine, and linezolid as prevalence of phenotypic resistance was low for these drugs. Interpretation: We present the first WHO-endorsed catalogue of molecular targets for MTBC drug susceptibility testing, which is intended to provide a global standard for resistance interpretation. The existence of this catalogue should encourage the implementation of molecular diagnostics by national tuberculosis programmes. Funding: Unitaid, Wellcome Trust, UK Medical Research Council, and Bill and Melinda Gates Foundation

Example of one scenario of choices presented to participants.

<p>Example of one scenario of choices presented to participants.</p

Characteristics of the 86 included participants.

<p>(Note)</p><p>^(a) Proportion of out-of-pocket payment to the cost fo current treatment;</p><p>^(b) 1 Chinese Yuan (CNY) = 0.1575 American Dollar (USD) in August 2012.</p><p>Characteristics of the 86 included participants.</p

Attributes and levels included in the discrete choice experiment.

<p>(Note)</p><p>*1 Chinese Yuan (CNY) = 0.1575 American Dollar (USD) in August 2012, and 0.1637 in August 2013. The out-of-pocket payment ranked was $18.9,$94.5 and $157.5 USD in August 2012.</p><p>Attributes and levels included in the discrete choice experiment.</p

Covariates associated with choosing either therapy in the nested-logit model.

<p>(Note)</p><p>* Statistical significance (p<0.05); CNY: Chinese Yuan (1 CNY = 0.1575 USD in August 2012). Monthly family income rank equalled to $157.5,$472.5–787.5, and >$787.5 USD in August 2012.</p><p>Covariates associated with choosing either therapy in the nested-logit model.</p