Maternal smoking and high BMI disrupt thyroid gland development

This study was supported by grants from the Medical Research Council (MR/L010011/1) (to PAF & PJOS), the Natural Science and Engineering Research Council of Canada (NSERC) for TK and SHK, and NHS Endowment Grant (to PF).Peer reviewedPublisher PD

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

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

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. The liver is essential for detoxification and homeostasis by metabolizing and/or assisting in the excretion of a wide range of xenotoxicants including alcohol, drugs, and tobacco smoke constituents. In the human the fetal liver is active and because 70% of its blood supply is directly from the fetomaternal interface, it is directly exposed to potentially harmful agents from the maternal circulation. Tobacco smoke contains a mixture of ∼5000 chemicals and the human fetal liver responds to maternal smoking by up-regulating phase I and phase II enzyme transcripts (1). Strikingly, the human fetal liver also expresses transcripts and proteins associated with altering steroid hormone function/activity in the mother and fetus. These include CYP19A1 (2), CYP3A7 (2, 3), and SULT enzymes (2, 4). The fetal liver is the main hematopoietic organ during the second trimester in humans (5) and also secrets high levels of α-fetoprotein (AFP), sex-hormone binding globulin (6), IGF-I, and IGF-II (7). It is clear, therefore, that the human fetal liver functions in the development and protection of the fetus and in the regulation of steroid hormone levels/actions during pregnancy. Maternal smoking is associated with diverse negative outcomes for the health of the neonate [including reduced birth weight, premature delivery, and stillbirth (8, 9)] and predisposition of the offspring to long-term health risks [including metabolic syndrome (10, 11), reduced fertility (12, 13), and psychosomatic problems (15)]. Approximately 30% of women continue to smoke once pregnant (16) and it remains one of the most important modifiable risk factors during pregnancy. Maternal smoking restricts the fetal oxygen supply and increases carbon monoxide burden to the conceptus but also disrupts fetal development through other mechanisms; previous studies from this group have identified some of these mechanisms such as endocrine signaling (1, 17) but a greater understanding of how maternal smoking links to disease in the offspring is required. Given the importance of the fetal liver to human fetal development and its susceptibility to maternal smoking we have, for the first time, used a proteomics approach to identify proteins and pathways that are dysregulated in the human fetal liver by maternal smoking