Citations

Management of ruptured breast implants is scarcely discussed in the literature, especially in the setting of previous breast cancer and radiation. The authors present an uncommon presentation of late breast implant rupture with seroma and history of prior radiation. It is important to acknowledge the increased risk of wound healing complications in patients who are several years’ postradiation therapy for breast cancer and should be an important factor when discussing treatment options with the patient.

Congenital disorders of glycosylation (CDG) are a group of genetic disorders that affect protein and lipid glycosylation and glycosylphosphatidylinositol synthesis. More than 100 different disorders have been reported and the number is rapidly increasing. Since glycosylation is an essential post-translational process, patients present a large range of symptoms and variable phenotypes, from very mild to extremely severe. Only for few CDG, potentially curative therapies are being used, including dietary supplementation (e.g., galactose for PGM1-CDG, fucose for SLC35C1-CDG, Mn2+ for TMEM165-CDG or mannose for MPI-CDG) and organ transplantation (e.g., liver for MPI-CDG and heart for DOLK-CDG). However, for the majority of patients, only symptomatic and preventive treatments are in use. This constitutes a burden for patients, care-givers and ultimately the healthcare system. Innovative diagnostic approaches, in vitro and in vivo models and novel biomarkers have been developed that can lead to novel therapeutic avenues aiming to ameliorate the patients’ symptoms and lives. This review summarizes the advances in therapeutic approaches for CDG.

Background and Purpose: Management of carotid stenosis remains controversial despite several trials evaluating carotid endarterectomy (CEA) and carotid angioplasty/stenting (CAS). We compared attitudes in the management of carotid stenosis between selected experts within Europe and North America. Methods: A 3-phase Delphi survey was e-mailed to select stroke experts from Europe (n = 390) and North America (n = 289). Those completing the initial survey were shown all responses after each survey round. Consensus was defined as ≥80% agreement. Results: For phases 1, 2, and 3, response rates were 32%, 62%, and 73%, respectively. Overall, 100 (15%) of 679 participated in all 3 phases, 19% Europeans versus 9% North Americans ( P = .0007). The European group reached consensus in 6 of 15 statements; The North American group reached consensus in 4 of 15. Ninety percentage of Europeans versus 70% of North Americans ( P = .017) stated CEA is superior to CAS for symptomatic carotid stenosis. This difference was not significant in the final model (adjusted odds ratio: 3.72 [95% confidence interval: 0.95-14.5]). Sixty-nine percentage of North Americans agreed there is a stronger indication for CAS over CEA in patients younger than 65 years for symptomatic carotid stenosis, whereas 55% of Europeans ( P = .023) disagreed. For asymptomatic carotid stenosis, when asked how likely they would recommend CAS, 62% North Americans said “sometimes” versus 60% of Europeans said “never” ( P = .06). Conclusion: The majority of North American and European respondents did not consider the 2 procedures equivalent and seemed to indicate that CEA was preferred for the management of carotid stenosis. These findings need to be further explored to help establish evidence-based guidelines.

Key Points Rd continuous significantly extended OS compared with MPT and resulted in comparable OS to that with Rd18 in patients with multiple myeloma. Patients achieving complete or very good partial response with Rd benefited greatly from continuous vs fixed treatment in terms of PFS.

INTRODUCTION: Postpartum hemorrhage is the leading cause of maternal mortality worldwide. There are multiple known risk factors, including induction of labor. METHODS: A retrospective cohort study was completed with review of nulliparous women undergoing labor induction at term, from July 2006 to May 2011. Baseline maternal variables and risk factors for postpartum hemorrhage were assessed. All combinations of methods of induction were sequential rather than concurrent. The need for additional uterotonics (beyond routine oxytocin) was used as a surrogate for postpartum hemorrhage. Variables were evaluated for an association with additional uterotonic use based on fitting logistic regression models. RESULTS: A total of 785 women were included in the study. Additional uterotonics were required for 84/785 (11%) of women. Based on univariate analysis, only birth weight and presence of meconium were significantly (p < 0.05) associated with additional uterotonic use, while method of induction approached statistical significance (p=0.06). The mean (SD) birth weight was 3668 (584) vs. 3463 (500) grams in those with and without additional uterotonic use. Multivariate analysis showed an increased risk of additional uterotonics with higher birth weight (adjusted odds ratio (aOR) 1.44 per 500 gram increase in birth weight; 95% CI 1.15, 1.82) and use of Foley plus oxytocin (aOR 4.40; 95% CI 1.36, 14.23). CONCLUSION: In our model, higher birth weight and induction method of Foley followed by oxytocin were associated with increased need for additional uterotonics. This data adds detail to previous studies that have broadly identified induction of labor as a risk factor for postpartum hemorrhage.

In airway smooth muscle (ASM) cells, excitation-contraction coupling is accomplished via a cascade of events that connect an elevation of cytosolic Ca2+concentration ([Ca2+]cyt) with cross-bridge attachment and ATP-consuming mechanical work. Excitation-energy coupling is mediated by linkage of the elevation of [Ca2+]cytto an increase in mitochondrial Ca2+concentration, which in turn stimulates ATP production. Proximity of mitochondria to the sarcoplasmic reticulum (SR) and plasma membrane is thought to be an important mechanism to facilitate mitochondrial Ca2+uptake. In this regard, mitochondrial movement in ASM cells may be key in establishing proximity. Mitochondria also move where ATP or Ca2+buffering is needed. Mitochondrial movement is mediated through interactions with the Miro-Milton molecular complex, which couples mitochondria to kinesin motors at microtubules. We examined mitochondrial movement in human ASM cells and hypothesized that, at basal [Ca2+]cytlevels, mitochondrial movement is necessary to establish proximity of mitochondria to the SR and that, during the transient increase in [Ca2+]cytinduced by agonist stimulation, mitochondrial movement is reduced, thereby promoting transient mitochondrial Ca2+uptake. We further hypothesized that airway inflammation disrupts basal mitochondrial movement via a reduction in Miro and Milton expression, thereby disrupting the ability of mitochondria to establish proximity to the SR and, thus, reducing transient mitochondrial Ca2+uptake during agonist activation. The reduced proximity of mitochondria to the SR may affect establishment of transient “hot spots” of higher [Ca2+]cytat the sites of SR Ca2+release that are necessary for mitochondrial Ca2+uptake via the mitochondrial Ca2+uniporter.

359 Background: GA, FOLFIRINOX and FOLFIRI are standard chemotherapy (CTX) regimens for mPC.The optimal introduction of these regimens following GA is not known. This phase II study evaluated 2 different approaches to this question. Methods: Eligibility criteria included 1) untreated mPC, 2) ECOG PS 0/1, 3) organ function adequate for Rx. Patients (pts) were treated according to one of 2 methods following GA given per standard dose/schedule: FOLFIRINOX (bolus 5-FU omitted) for up to 12 cycles at 24 weeks or at time of disease progression (S); or GA alternating with FOLFIRI q8 weeks up to 48 weeks total Rx (A). Results: 54 evaluable pts (28S, 26A) were enrolled . Pt characteristics included median age 65, M/F 48/52% , liver involvement 89%. 17/53 pts (31%) did not achieve disease control at 8 weeks (8 toxicity/complications , 6 disease progression, 3 declined further protocol therapy). Of the remaining 37 pts, 24/13 were treated with S/A regimens, respectively. Grade ≥ 3 treatment toxicities reported while on study with frequency ≥ 10% included anemia 21%, neutropenia 43%, thrombocytopenia 15%, and fatigue 22%. Grade ≥ 3 neuropathy occurred in 8% of pts. For all 54 pts using RECIST 1.0, CR/PR/SD/DC was 2 (4%)/20 (37%)/19 (35%)/41(76%). Ca19.9 response ≥ 90% was seen in 20/37 (54%). For all pts, median OS was 12.3 months ( 95% CI 8.6-14.5 mo); 12 and 24 mo OS was 51% and 11%, respectively. For the 37 pts with DC on GA at 8 weeks (calculated from start Rx) median OS was 13.5 mo (95% CI 10.7-15.4 mo); 12 and 24 mo OS was 55% and 16% , respectively. No statistically significant differences were seen between S and A with respect to toxicity, response or survival. Conclusions: 1) As opposed to introduction of 5FU-based CTX at the time of disease progression/prohibitive toxicity, introduction prior to that time may be at least comparable regarding both toxicity and OS. 2) This approach may further enhance OS in pts who achieve DC on GA at 8 weeks. 3) Neither S nor A method of 5FU-based CTX introduction following GA was clearly superior in this study. 4) How best to combine 5FU-based combination CTX following GA in mPC merits further study. Supported by the Seena Magowitz Foundation.