Thrombolysis for massive pulmonary embolism in pregnancy: a case report

Mortality from pulmonary embolism (PE) in pregnancy might be related to challenges in targeting the right population for prevention. Such targeting could help ensure that the correct diagnosis is suspected and adequately investigated, and allow the initiation of the timely and best possible treatment of this disease. In the literature to date only 18 case reports of thrombolysis in pregnant women with PE have been reported, and showed beneficial effects for both mother and fetus in terms of mortality and complications with acceptable bleeding risks. We present here the case of a pregnant patient with massive PE who underwent successful thrombolysis. A 26-year-old pregnant (at 24 weeks) woman was admitted 4 h after onset of sudden acute dyspnea and chest pain. An immediate electrocardiogram showed a typical S1-Q3-T3 pattern. The echocardiogram showed a distended right ventricle with free-wall hypokinesia and displacement of the interventricular septum toward the left ventricle. Thrombolysis with recombinant tissue plasminogen activator (alteplase 10 mg bolus, then 90 mg over 2 h) was administered. Pelvic examination and ultrasound showed regular fetal heart beat, and regular placental and liquid presence. No problems developed for the mother or fetus in the subsequent days or at discharge. In conclusion, in pregnant patients with life-threatening massive PE, thrombolytic therapy can be administered, and the use of echocardiographic, laboratory, and clinical data can be useful tools to achieve a rapid diagnosis and make a therapeutic decision, but additional studies need to be performed to further define its use

External versus internal fixation for bicondylar tibial plateau fractures: systematic review and meta-analysis.

BACKGROUND: It is uncertain whether external fixation or open reduction internal fixation (ORIF) is optimal for patients with bicondylar tibial plateau fractures. MATERIALS AND METHODS: A systematic review using Ovid MEDLINE, Embase Classic, Embase, AMED, the Cochrane Library, Open Grey, Orthopaedic Proceedings, WHO International Clinical Trials Registry Platform, Current Controlled Trials, US National Institute for Health Trials Registry, and the Cochrane Central Register of Controlled Trials. The search was conducted on 3rd October 2014 and no language limits were applied. Inclusion criteria were all clinical study designs comparing external fixation with open reduction internal fixation of bicondylar tibial plateau fractures. Studies of only one treatment modality were excluded, as were those that included unicondylar tibial plateau fractures. Treatment effects from studies reporting dichotomous outcomes were summarised using odds ratios. Continuous outcomes were converted to standardized mean differences to assess the treatment effect, and inverse variance methods used to combine data. A fixed effect model was used for meta-analyses. RESULTS: Patients undergoing external fixation were more likely to have returned to preinjury activities by six and twelve months (P = 0.030) but not at 24 months follow-up. However, external fixation was complicated by a greater number of infections (OR 2.59, 95 % CI 1.25-5.36, P = 0.01). There were no statistically significant differences in the rates of deep infection, venous thromboembolism, compartment syndrome, or need for re-operation between the two groups. CONCLUSION: Although external fixation and ORIF are associated with different complication profiles, both are acceptable strategies for managing bicondylar tibial plateau fractures

Assessment of interactions between 205 breast cancer susceptibility loci and 13 established risk factors in relation to breast cancer risk, in the Breast Cancer Association Consortium.

BACKGROUND: Previous gene-environment interaction studies of breast cancer risk have provided sparse evidence of interactions. Using the largest available dataset to date, we performed a comprehensive assessment of potential effect modification of 205 common susceptibility variants by 13 established breast cancer risk factors, including replication of previously reported interactions. METHODS: Analyses were performed using 28 176 cases and 32 209 controls genotyped with iCOGS array and 44 109 cases and 48 145 controls genotyped using OncoArray from the Breast Cancer Association Consortium (BCAC). Gene-environment interactions were assessed using unconditional logistic regression and likelihood ratio tests for breast cancer risk overall and by estrogen-receptor (ER) status. Bayesian false discovery probability was used to assess the noteworthiness of the meta-analysed array-specific interactions. RESULTS: Noteworthy evidence of interaction at ≤1% prior probability was observed for three single nucleotide polymorphism (SNP)-risk factor pairs. SNP rs4442975 was associated with a greater reduction of risk of ER-positive breast cancer [odds ratio (OR)int = 0.85 (0.78-0.93), Pint = 2.8 x 10-4] and overall breast cancer [ORint = 0.85 (0.78-0.92), Pint = 7.4 x 10-5) in current users of estrogen-progesterone therapy compared with non-users. This finding was supported by replication using OncoArray data of the previously reported interaction between rs13387042 (r2 = 0.93 with rs4442975) and current estrogen-progesterone therapy for overall disease (Pint = 0.004). The two other interactions suggested stronger associations between SNP rs6596100 and ER-negative breast cancer with increasing parity and younger age at first birth. CONCLUSIONS: Overall, our study does not suggest strong effect modification of common breast cancer susceptibility variants by established risk factors

Polygenic Risk Scores for Prediction of Breast Cancer and Breast Cancer Subtypes.

Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to empirically validate the PRSs in prospective studies. The development dataset comprised 94,075 case subjects and 75,017 control subjects of European ancestry from 69 studies, divided into training and validation sets. Samples were genotyped using genome-wide arrays, and single-nucleotide polymorphisms (SNPs) were selected by stepwise regression or lasso penalized regression. The best performing PRSs were validated in an independent test set comprising 11,428 case subjects and 18,323 control subjects from 10 prospective studies and 190,040 women from UK Biobank (3,215 incident breast cancers). For the best PRSs (313 SNPs), the odds ratio for overall disease per 1 standard deviation in ten prospective studies was 1.61 (95%CI: 1.57-1.65) with area under receiver-operator curve (AUC) = 0.630 (95%CI: 0.628-0.651). The lifetime risk of overall breast cancer in the top centile of the PRSs was 32.6%. Compared with women in the middle quintile, those in the highest 1% of risk had 4.37- and 2.78-fold risks, and those in the lowest 1% of risk had 0.16- and 0.27-fold risks, of developing ER-positive and ER-negative disease, respectively. Goodness-of-fit tests indicated that this PRS was well calibrated and predicts disease risk accurately in the tails of the distribution. This PRS is a powerful and reliable predictor of breast cancer risk that may improve breast cancer prevention programs

Ankle fractures in the elderly: risks and management challenges

Rishin J Kadakia,1 Briggs M Ahearn,1 Andrew M Schwartz,1 Shay Tenenbaum,2 Jason T Bariteau1 1Department of Orthopaedics, Emory University School of Medicine, Atlanta, GA, USA; 2Department of Orthopedic Surgery, Chaim Sheba Medical Center at Tel Hashomer, Affiliated to the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel Abstract: Ankle fractures are the third most common osseous injury in the elderly, behind hip and distal radius fractures. While there is a rich history of clinical advancement in the timing, technique, perioperative management, and associated risks of hip fractures, similar evaluations are only more recently being undertaken for ankle fractures. Traditionally, elderly patients were treated more conservatively; however, nonoperative management has been found to be associated with increased mortality. As such, older and less healthy patients have become operative candidates. The benefits of geriatric/orthopedic inpatient comanagement that have been well elucidated in the hip fracture literature also seem to improve outcomes in elderly patients with ankle fractures. One of the orthopedist’s roles is to recognize the complexities of osteoporotic bone fixation and optimize wound healing potential. Though the immediate cost of this surgical approach is inevitably higher, the ultimate cost of long-term care has been found to be substantially reduced. It is important to consider the mortality and morbidity benefits and cost reductions of operative intervention and proper inpatient care of geriatric ankle fractures when they present to the emergency department or the office. Keywords: ankle fractures, geriatrics, trauma, outcomes, management, surger

MRI and the Distribution of Bone Marrow Fat in Hip Osteoarthritis

$\textbf{Purpose:}$ To characterize the distribution of bone marrow fat in hip osteoarthritis (OA) using magnetic resonance imaging (MRI) and to assess its use as a potential biomarker. $\textbf{Materials and Methods:}$ In all, 67 subjects (39 female, 28 male) with either total hip replacement (THA) or different severities of radiographic OA, assessed by Kellgren-Lawrence grading (KLG), underwent 3T MRI of the pelvis using the IDEAL sequence to separate fat and water signals. Six regions of interest (ROIs) were identified within the proximal femur. Within each ROI the fractional-fat distribution, represented by pixel intensities, was described by its mean, standard deviation, skewness, kurtosis, and entropy. $\textbf{Results:}$ Hips were graded: 12 as severe symptomatic (THA), 33 had KLG0 or 1, 9 were KLG2, 11 with KLG3, and 2 with KLG4 were analyzed together. The fractional-fat content in the whole proximal femur did not vary with severity in males (mean (SD) 91.2 (6.0)%) but reduced with severity in females from 89.1 (6.7)% (KLG0,1), 91.5 (2.9)% (KLG2), 85.8 (16.7)% (KLG3,4) to 77.5 (11.9)% (THA) (analysis of variance [ANOVA] $P$=0.029). These differences were most pronounced in the femoral head, where mean values fell with OA severity in both sexes from 97.9% (2.5%) (KLG0,1) to 73.0% (25.9%) (THA, $P$ < 0.001) with the largest difference at the final stage. The standard deviation and the entropy of the distribution both increased ($P$ < 0.001). $\textbf{Conclusion:}$ Descriptors of the fractional fat distribution varied little with the severity of OA until the most severe stage, when changes appeared mainly in the femoral head, and have, therefore, limited value as biomarkers.Translational Medicine Research Collaboration, a consortium made up of the Universities of Aberdeen, Dundee, Edinburgh, and Glasgow, the four associated NHS Health Boards (Grampian, Tayside, Lothian, and Greater Glasgow & Clyde), Scottish Enterprise, and Wyeth; contract grant number: WHMSB-AU11