Association of Implementation of a Comprehensive Preconception-to-Pregnancy Management Plan With Pregnancy Outcomes Among Chinese Pregnant Women With Type 1 Diabetes: The CARNATION Study

OBJECTIVETo investigate the effect on pregnancy outcome of integrating a comprehensive management plan for patients with type 1 diabetes (T1D) into the World Health Organization universal maternal care infrastructure.RESEARCH DESIGN AND METHODSA comprehensive preconception-to-pregnancy management plan for women with T1D was implemented in 11 centers from 8 Chinese cities from 2015 to 2017. Sequential eligible pregnant women (n = 133 out of 137 initially enrolled) with T1D and singleton pregnancies attending these management centers formed the prospective cohort. The main outcome was severe adverse pregnancy outcome comprising maternal mortality, neonatal death, congenital malformations, miscarriage in the second trimester, and stillbirth. We compared pregnancy outcomes in this prospective cohort with two control groups with the same inclusion and exclusion criteria: a retrospective cohort (n = 153) of all eligible pregnant women with T1D attending the same management centers from 2012 to 2014 and a comparison cohort (n = 116) of all eligible pregnant women with T1D receiving routine care from 2015 to 2017 in 11 different centers from 7 cities.RESULTSThe rate of severe adverse pregnancy outcome was lower in the prospective cohort (6.02%) than in either the retrospective cohort (18.30%; adjusted odds ratio [aOR] 0.31 [95% CI 0.13–0.74]) or the contemporaneous comparison cohort (25.00%; aOR 0.22 [95% CI 0.09–0.52]).CONCLUSIONSThe substantial improvements in the prospective cohort are evidence of a potentially clinically important effect of the comprehensive management plan on pregnancy outcomes among Chinese pregnant women with pregestational T1D. This supports the development of similar approaches in other countries.     

Detecting EGFR alterations in clinical specimens—pitfalls and necessities

We investigated the epidermal growth factor receptor (EGFR) status in early stage lung cancer in Southern Sweden, a population for which there are no previous reports on the EGFR mutation frequency. Three hundred fifty small cell lung cancers, adenocarcinomas (AC), squamous cell carcinomas (SqCC), and large cell carcinomas were analyzed using a combination of techniques for the analysis of protein expression, gene copy numbers, and mutations. Immunohistochemical (IHC) staining with antibodies for the EGFR mutations L858R and del E746-A750 revealed intratumoral heterogeneity and several discrepant cases when compared to mutation-specific polymerase chain reaction (PCR)-based analysis. The frequencies of these two mutations, when considering IHC staining with mutation-specific antibodies in a cohort of 298 cases and subsequent confirmation by PCR, were 10 % in AC and <2 % in SqCC. Furthermore, screening by sequencing of EGFR in a cohort of 52 lung AC and squamous carcinomas demonstrated a more diverse mutation spectrum, not covered by the mutation-specific antibodies. High expression of total EGFR protein was correlated to high gene copy numbers but did not reflect the mutational status of the tumors. We believe that the mutation spectra in a Southern Swedish population is too diverse to be covered by the mutation-specific antibodies, and we also raise some other issues regarding the use of the mutation-specific antibodies, for example concerning heterogeneous expression of the mutated protein, optimal antibody dilution, and discrepancies between staining results and PCR.     

Saturation recovery-prepared magnetic resonance angiography for assessment of left atrial and esophageal anatomy

Objectives:Magnetic resonance angiography (MRA) has been established as an important imaging method in cardiac ablation procedures. In pulmonary vein (PV) isolation procedures, MRA has the potential to minimize the risk of severe complications, such as atrio-esophageal fistula, by providing detailed information on esophageal position relatively to cardiac structures. However, traditional non-gated, first-pass (FP) MRA approaches have several limitations, such as long breath-holds, non-uniform signal intensity throughout the left atrium (LA), and poor esophageal visualization. The aim of this observational study was to validate a respiratory-navigated, ECG-gated (EC), saturation recovery-prepared MRA technique for simultaneous imaging of LA, LA appendage, PVs, esophagus, and adjacent anatomical structures.Methods:Before PVI, 106 consecutive patients with a history of AF underwent either conventional FP-MRA (n = 53 patients) or our new EC-MRA (n = 53 patients). Five quality scores (QS) of LA and esophagus visibility were assessed by two experienced readers. The non-parametric Mann–Whitney U-test was used to compare QS between FP-MRA and EC-MRA groups, and linear regression was applied to assess clinical contributors to image quality.Results:EC-MRA demonstrated significantly better image quality than FP-MRA in every quality category. Esophageal visibility using the new MRA technique was markedly better than with the conventional FP-MRA technique (median 3.5 [IQR 1] vs median 1.0, p < 0.001). In contrast to FP-MRA, overall image quality of EC-MRA was not influenced by heart rate.Conclusion:Our ECG-gated, respiratory-navigated, saturation recovery-prepared MRA technique provides significantly better image quality and esophageal visibility than the established non-gated, breath-holding FP-MRA. Image quality of EC-MRA technique has the additional advantage of being unaffected by heart rate.Advances in knowledge:Detailed information of cardiac anatomy has the potential to minimize the risk of severe complications and improve success rates in invasive electrophysiological studies. Our novel ECG-gated, respiratory-navigated, saturation recovery-prepared MRA technique provides significantly better image quality of LA and esophageal structures than the traditional first-pass algorithm. This new MRA technique is robust to arrhythmia (tachycardic, irregular heart rates) frequently observed in AF patients.     

The Effects of Calcium Supplementation on Verified Coronary Heart Disease Hospitalization and Death in Postmenopausal Women: A Collaborative Meta‐Analysis of Randomized Controlled Trials

Calcium supplementation, particularly with vitamin D, has been an approved public health intervention to reduce fracture risk. Enthusiasm for this intervention has been mitigated by meta‐analyses suggesting that calcium supplementation with or without vitamin D increases myocardial infarction (MI) risk; however, concern has been raised over the design of these meta‐analyses. We, therefore, undertook a meta‐analysis of randomized controlled trials with placebo or no‐treatment control groups to determine if these supplements increase all‐cause mortality and coronary heart disease (CHD) risk including MI, angina pectoris and acute coronary syndrome, and chronic CHD verified by clinical review, hospital record, or death certificate in elderly women. The Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE databases were searched from January 1, 1966, to May 24, 2013, for potentially eligible studies, reference lists were checked, and trial investigators were contacted where additional unpublished data were required. The search yielded 661 potentially eligible reports of which 18 met the inclusion criteria and contributed information on 63,563 participants with 3390 CHD events and 4157 deaths. Two authors extracted the data independently with trial data combined using random‐effects meta‐analysis to calculate the relative risk (RR). Five trials contributed CHD events with pooled relative RR of 1.02 (95% confidence interval [CI], 0.96–1.09; p = 0.51). Seventeen trials contributed all‐cause mortality data with pooled RR of 0.96 (95% CI, 0.91–1.02; p = 0.18). Heterogeneity among the trials was low for both primary outcomes (I² = 0%). For secondary outcomes, the RR for MI was 1.08 (95% CI, 0.92–1.26; p = 0.32), angina pectoris and acute coronary syndrome 1.09 (95% CI, 0.95–1.24; p = 0.22) and chronic CHD 0.92 (95% CI, 0.73–1.15; p = 0.46). In conclusion, current evidence does not support the hypothesis that calcium supplementation with or without vitamin D increases coronary heart disease or all‐cause mortality risk in elderly women. © 2014 American Society for Bone and Mineral Research.     

The risk of revision in total knee arthroplasty is not affected by previous high tibial osteotomy: A 15-year follow-up of 32,476 total knee arthroplasties in the Norwegian Arthroplasty Register

Background and purpose — Previous studies have found different outcomes after revision of knee arthroplasties performed after high tibial osteotomy (HTO). We evaluated the risk of revision of total knee arthroplasty with or without previous HTO in a large registry material.Patients and methods — 31,077 primary TKAs were compared with 1,399 TKAs after HTO, using Kaplan-Meier 10-year survival percentages and adjusted Cox regression analysis.Results — The adjusted survival analyses showed similar survival in the 2 groups. The Kaplan-Meier 10-year survival was 93.8% in the primary TKA group and 92.6% in the TKA-post-HTO group. Adjusted RR was 0.97 (95% CI: 0.77–1.21; p = 0.8).Interpretation — In this registry-based study, previous high tibial osteotomy did not appear to compromise the results regarding risk of revision after total knee arthroplasty compared to primary knee arthroplasty.High tibial osteotomy (HTO) is a well-established joint preserving procedure for the treatment of medial knee osteoarthritis. The goal is to achieve unloading of the affected medial compartment of the knee to prevent or postpone the need for an artificial knee joint. This is performed by slightly overcorrecting the knee joint from varus malalignment to valgus or neutral position. Osteotomy was a standard treatment option for unicompartmental knee osteoarthritis in earlier years before knee arthroplasty was a surgical option, but osteotomy lost importance in the 1980s because of the success of knee replacement surgery (Smith et al. 2013). However, there has been an increase in osteotomies during the last 15 years, especially in younger patients in some countries (Seil et al. 2013). National arthroplasty registers have demonstrated higher risk of revision for knee arthroplasty in younger patients (under the age of 60) (NAR 2014, SKAR 2013). The 2 most commonly used methods for HTO are lateral closing wedge and medial opening wedge osteotomy. Both methods have shown improvement in knee pain and function (Naudie et al. 1999, van Raaij et al. 2008, Efe et al. 2011, W-Dahl et al. 2012). Nevertheless, some patients later require a second procedure, a total knee arthroplasty (Naudie et al. 1999), depending on the degree of osteoarthritis, their level of pain and function, and the degree of correction achieved. Although total knee arthroplasty appears to be technically more challenging after HTO in cases with severe overcorrection, bone stock loss, altered joint line (Figures 1 and ​and2),2), or patella infera, only a few studies have found inferior results compared to primary TKA (Windsor et al. 1988, Parvizi et al. 2004, Haslam et al. 2007, Farfalli et al. 2012). The aim of this study was to evaluate the risk of revision after TKA, comparing primary TKA with and without previous high tibial osteotomy using data from the Norwegian Arthroplasty Register (NAR).Open in a separate windowFigure 1.Example of extra-articular malalignment after high tibial osteotomy (HTO) with opening wedge technique. The red line on the left radiograph (a) indicates the mechanical axis lateral to the knee joint. The radiograph to the right (b) indicates the extra-articular angulation of the tibia in the osteotomy area.Open in a separate windowFigure 2.Example of intra-articular malalignment after high tibial osteotomy (WTO) with closing wedge technique. The solid red line indicates that the tibial plateau has been elevated medially and is not perpendicular to the tibial axis.