Maternal smoking and high BMI disrupt thyroid gland development.

BACKGROUND: Maternal lifestyle factors, including smoking and increased body weight, increase risks of adult diseases such as metabolic syndrome and infertility. The fetal thyroid gland is essential for the control of fetal metabolic rate, cardiac output, and brain development. Altered fetal thyroid function may contribute to increased disease onset later in life. Here, we investigated the impact of maternal smoking and high maternal weight on human fetal thyroid function during the second trimester. METHODS: Thyroid glands and plasma were collected from fetuses electively terminated in the second trimester (normally progressing pregnancies). Plasma total triiodothyronine (T3) and total thyroxine (T4) were measured by solid-phase extraction-liquid chromatography-tandem mass spectrometry. Fetal plasma thyroid-stimulating hormone (TSH) levels were measured using a multiplex assay for human pituitary hormones. Histology and immunolocalization of thyroid developmental markers were examined in thyroid sections. Transcript levels of developmental, functional, apoptotic, and detoxification markers were measured by real-time PCR. Statistical analyses were performed using multivariate linear regression models with fetal age, sex, and maternal smoking or maternal body mass index (BMI) as covariates. RESULTS: Maternal smoking was associated with significant changes in fetal plasma T4 and TSH levels during the second trimester. Smoke-exposed thyroids had reduced thyroid GATA6 and NKX2-1 transcript levels and altered developmental trajectories for ESR2 and AHR transcript levels. Maternal BMI > 25 was associated with increased fetal thyroid weight, increased plasma TSH levels, and abnormal thyroid histology in female fetuses. Normal developmental changes in AHR and ESR1 transcript expression were also abolished in fetal thyroids from mothers with BMI > 25. CONCLUSIONS: For the first time, we show that maternal smoking and high maternal BMI are associated with disturbed fetal thyroid gland development and endocrine function in a sex-specific manner during the second trimester. These findings suggest that predisposition to post-natal disease is mediated, in part, by altered fetal thyroid gland development.

A Systematic Review of the Outcomes of Microsurgical Toe Transfer for Metacarpal and Metacarpal-Like Hand Deformity.

Background: Thumb and multiple finger amputations may result in a metacarpal and a metacarpal-like hand deformity. Toe-to-hand transfer is a recognised treatment strategy for this deformity but has risks and is resource intensive. The aim of this study is to conduct a systematic review of the outcomes of toe-to-hand transfer for traumatic metacarpal and metacarpal-like hand deformity in adult patients. Methods: Multi-database searching with index and free text terms, duplicate standardised screening and extraction, and quality assessment was performed. The inclusion and exclusion criteria were prespecified. We included any randomised controlled trials, cohort studies, case-control studies, as well as interrupted time series, before and after intervention studies. Results: Screening of 548 articles yielded 20 studies eligible that included 19 retrospective observational studies and one before and after intervention study. A total of 171 patients underwent 274 toe transfers for metacarpal and metacarpal-like hand deformity. No study compared toe-transfer to a control group or to a prosthesis. The before and after intervention study demonstrated significant improvement in activities of daily living, work, aesthetics and satisfaction. Additionally, no significant donor site morbidity occurred in the heterogenous sample. Outcomes from remaining studies at risk of bias suggest that those with a lesser severity of injury and at least two toe transfers score higher in functional tests and scoring systems. Conclusions: There is limited confidence in the effectiveness of toe transfer for metacarpal and metacarpal-like hand deformity. The available evidence indicates that toe transfer(s) may restore acceptable function permitting activities of daily living, return to original or sedentary occupation and affords satisfaction. Level of Evidence: Level III (Therapeutic).

Maternal Smoking Dysregulates Protein Expression in Second Trimester Human Fetal Livers in a Sex-Specific Manner.

CONTEXT: Maternal smoking during pregnancy has adverse effects on the offspring (eg, increased likelihood of metabolic syndrome and infertility), which may involve alterations in fetal liver function. OBJECTIVE: Our aim was to analyze, for the first time, the human fetal liver proteome to identify pathways affected by maternal smoking. DESIGN: Fetal liver proteins extracted from elective second trimester pregnancy terminations (12-16 weeks of gestation) were divided in four balanced groups based on sex and maternal smoking. SETTING AND PARTICIPANTS: Livers were collected from 24 morphologically normal fetuses undergoing termination for nonmedical reasons and analyzed at the Universities of Aberdeen and Glasgow. MAIN OUTCOME MEASURES: Protein extracts were resolved by 2D-PAGE and analyzed with SameSpots software. Ingenuity pathway analysis was used to investigate likely roles of dysregulated proteins identified by tandem liquid chromatography/mass spectroscopy. RESULTS: Significant expression differences between one or more groups (fetal sex and/or maternal smoking) were found in 22 protein spots. Maternal smoking affected proteins with roles in post-translational protein processing and secretion (ERP29, PDIA3), stress responses and detoxification (HSP90AA1, HSBP1, ALDH7A1, CAT), and homeostasis (FTL1, ECHS1, GLUD1, AFP, SDHA). Although proteins involved in necrosis and cancer development were affected in both sexes, pathways affecting cellular homeostasis, inflammation, proliferation, and apoptosis were affected in males and pathways affecting glucose metabolism were affected in females. CONCLUSIONS: The fetal liver exhibits marked sex differences at the protein level, and these are disturbed by maternal smoking. The foundations for smoke-induced post-natal diseases are likely to be due to sex-specific effects on diverse pathways.

Variation in caecal intubation rates between screening and symptomatic patients.

BACKGROUND: The caecal intubation rate (CIR) is an important quality standard for endoscopists, as well as for national bowel cancer screening programmes; however, individuals undergoing colonoscopy for bowel screening and symptomatic patients represent different groups, and their characteristics may affect colonoscopy performance. OBJECTIVE: To compare colonoscopists' performance, as assessed by the CIR, in symptomatic patients compared to individuals undergoing colonoscopy for bowel cancer screening. METHODS: Retrospective audit of CIRs for all patients undergoing colonoscopy at our institution during the year 2008. We retrieved the data from an endoscopy reporting software database and from the local bowel cancer screening programme database. Demographic data was extracted, as well as details of known factors that may affect completion of colonoscopy, such as poor bowel preparation, presence of diverticular disease, polyps, tumour and strictures. The unadjusted CIRs for colonoscopists participating in the screening programme were compared between the bowel screening and the symptomatic patient groups. RESULTS: Five screening colonoscopists performed 1056 colonoscopies, of which 488 were bowel screening procedures. The overall CIR was significantly lower in the symptomatic, compared to the screening, individuals (88.5% versus 93%, P < 0.02). No significant differences were observed between the two groups for risk factors that could impair the CIR. The CIR was <90% for two of the five colonoscopists in symptomatic patients, and just under 90% for one colonoscopist in screening individuals. Multivariate analysis revealed that non-screening colonoscopy was an independent predictor for an incomplete procedure (OR 1.8; 95% CI 1.2-2.8). CONCLUSIONS: The CIR, a key quality performance indicator for colonoscopy, is lower in symptomatic patients compared to individuals undergoing colorectal cancer screening. These results suggested that CIR should be monitored independently in screening and non-screening colonoscopies.

Is periprocedural CK-MB a better indicator of prognosis after emergency and elective percutaneous coronary intervention compared with post-procedural cardiac troponins?

A best evidence topic in interventional cardiac surgery was written according to a structured protocol. The question we addressed related to the elevation of markers of cardiac damage associated with percutaneous coronary intervention (PCI). We explored and compared the clinical and prognostic relevance of the elevation of creatinine kinase-myocardial band (CK-MB) and cardiac troponin (cTn) levels during the periprocedural period and the post-procedural period, respectively, following an emergency or elective PCI. We found in excess of 390 papers after a systematic literature search, of which 10 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. From the best evidence available it appears that the monitoring of cardiac biomarkers following a PCI can provide important clinical information about the health of the myocardium, as well as prognostic information on short to mid-term outcomes of mortality up to 3 years. The narrow evidence base advocates the use of periprocedural CK-MB monitoring, recommending that an elevation in CK-MB is a significant predictor of adverse events. Troponins remain a precise and reliable marker of cardiac damage; however, current evidence argues that cTn holds little prognostic relevance until the degree of elevation is almost five times the upper limit of normal (ULN). Thus, the best evidence recommends the use of periprocedural CK-MB routinely during PCI to provide clinical and prognostic information about the degree of myocardial injury and risk of post-procedural morbidity and mortality.