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ObjectiveThis study describes the patterns of end of life (EOL) discussions and their impact on the use of aggressive measures in women with terminal gynecologic malignancies at a single institution.MethodsAn IRB-approved retrospective chart review identified 136 patients who died of gynecologic cancer between 2010 and 2012 with at least one interaction with their oncologists in the last 6 months of life. Aggressive measures were defined as chemotherapy within the last 14 days of life, emergency department (ED) visits, hospital and intensive care unit (ICU) admissions within the last 30 days of life, and inpatient deaths. The frequency and timing of EOL conversations were recorded. Utilization of hospice care was also described.ResultsIn the last 30 days of life, 54 (40%) patients were evaluated in the ED, 67 (49%) were admitted into hospital, and 16 (12%) were admitted to the ICU. Thirteen patients (10%) had chemotherapy in the last 14 days of life. Ninety-seven (71%) patients had a documented EOL conversation, eighteen (19%) as outpatients, and 79 (81%) as inpatients. Thirty (22%) patients died in the hospital. At the time of death, 55 (40%) patients were enrolled in outpatient hospice care. The mean amount of time in hospice was 28 days.ConclusionsEnd of life care discussions rarely occurred in the outpatient setting or >30 days before death. Inpatient encounters led to discussions about hospice and code status. Evaluation in the ED frequently resulted in escalation of care. Earlier EOL care discussions resulted in less aggressive measures.

Third sound is studied for superfluid films of 4He adsorbed on multiwall carbon nanotubes packed into an annular resonator. The third sound is generated with mechanical oscillation of the cell, and detected with carbon bolometers. A filling curve at temperatures near 250 mK shows oscillations in the third sound velocity, with maxima at the completion of the 4th and 5th atomic layers. Sharp changes in the Q factor of the third sound are found at partial layer fillings. Temperature sweeps at a number of fill points show strong broadening effects on the Kosterlitz-Thouless (KT) transition, and rapidly increasing dissipation, in qualitative agreement with the predictions of Machta and Guyer. At the 4th layer completion there is a sudden reduction of the transition temperature TKT, and then a recovery back to linear variation with temperature, although the slope is considerably smaller than the KT prediction.

ImportanceBRCA mutation carriers are at increased risk of developing breast cancer. However, the incidence of breast cancer after a diagnosis of epithelial ovarian cancer (EOC), one of the tubal/peritoneal cancers collectively referred to as pelvic serous carcinomas, is not well known. Optimal breast cancer surveillance and detection for these patients have also not been well characterized.ObjectivesTo determine the incidence of breast cancer after a diagnosis of EOC and to evaluate the need for breast cancer surveillance for these patients.Design, setting, and participantsA retrospective database review of 364 patients who underwent BRCA mutation testing for EOC (stages I-IV) between 1998 and 2012 at an academic medical center with gynecologic and breast cancer centers.Main outcomes and measuresIncidence of breast cancer and methods of surveillance.ResultsOf 364 patients, 135 (37.1%) were found to carry a germline BRCA1 or BRCA2 mutation. The mean age of patients at diagnosis of EOC was 49.5 years (range, 28-89 years). Of the 135 patients, 12 (8.9%) developed breast cancer. The median time from diagnosis of EOC to diagnosis of breast cancer was 50.5 months. Annual mammography was performed for 80 patients (59.3%), with annual magnetic resonance imaging of the breasts performed for 60 patients (44.4%). Thirteen patients (9.6%) underwent a bilateral prophylactic mastectomy at a median of 23 months following EOC diagnosis. Breast cancer was most commonly diagnosed by mammography for 7 of the 12 patients (58.3%), 3 (25.0%) of whom had a palpable mass and 2 (16.7%) of whom had incidental breast cancer detected during a prophylactic mastectomy. Seven patients with breast cancer (58.3%) underwent a bilateral mastectomy. All patients had early-stage breast cancer (stages 0-II). Four patients (33.3%) received adjuvant chemotherapy. At a median follow-up of 6.3 years, 4 of the 12 patients (33.3%) died of recurrent EOC after a diagnosis of breast cancer. The overall 10-year survival rate for the entire cohort of 135 patients was 17.0%.Conclusions and relevanceThe risk of metachronous breast cancer is low in patients with known BRCA mutations and EOC. A majority of these cases of breast cancer at an early stage are detected by use of mammography. Despite the small number of patients in our study, these results suggest that optimal breast cancer surveillance for patients with BRCA-associated EOC needs to be reevaluated given the low incidence of breast cancer among these high-risk patients. Confirmation of our findings from larger studies seems to be indicated.

Peripheral nerve injuries can result in lifelong disability. Primary coaptation is the treatment of choice when the gap between transected nerve ends is short. Long nerve gaps seen in more complex injuries often require autologous nerve grafts or nerve conduits implemented into the repair. Nerve grafts, however, cause morbidity and functional loss at donor sites, which are limited in number. Nerve conduits, in turn, lack an internal scaffold to support and guide axonal regeneration, resulting in decreased efficacy over longer nerve gap lengths. By comparison, peptide amphiphiles (PAs) are molecules that can self-assemble into nanofibers, which can be aligned to mimic the native architecture of peripheral nerve. As such, they represent a potential substrate for use in a bioengineered nerve graft substitute. To examine this, we cultured Schwann cells with bioactive PAs (RGDS-PA, IKVAV-PA) to determine their ability to attach to and proliferate within the biomaterial. Next, we devised a PA construct for use in a peripheral nerve critical sized defect model. Rat sciatic nerve defects were created and reconstructed with autologous nerve, PLGA conduits filled with various forms of aligned PAs, or left unrepaired. Motor and sensory recovery were determined and compared among groups. Our results demonstrate that Schwann cells are able to adhere to and proliferate in aligned PA gels, with greater efficacy in bioactive PAs compared to the backbone-PA alone. In vivo testing revealed recovery of motor and sensory function in animals treated with conduit/PA constructs comparable to animals treated with autologous nerve grafts. Functional recovery in conduit/PA and autologous graft groups was significantly faster than in animals treated with empty PLGA conduits. Histological examinations also demonstrated increased axonal and Schwann cell regeneration within the reconstructed nerve gap in animals treated with conduit/PA constructs. These results indicate that PA nanofibers may represent a promising biomaterial for use in bioengineered peripheral nerve repair.

ObjectivesA growing body of evidence supports a role for thrombocytosis in the promotion of epithelial ovarian cancer biology. However, studies have only linked preoperative platelet count at time of initial cytoreductive surgery to clinical outcome. Here, we sought to determine the impact of elevated platelet count at time of secondary cytoreductive surgery (SCS) for recurrent disease.MethodsUnder an IRB-approved protocol, we identified 107 women with invasive epithelial ovarian cancer who underwent SCS between January 1997 and June 2012. We reviewed clinical, laboratory, and pathologic records from this retrospective cohort. The data was analyzed using the chi-squared, Fisher's exact, Cox proportional hazards, and Kaplan-Meier tests. We defined thrombocytosis as a platelet count ≥ 350 × 10(9)/L and optimal resection at SCS as microscopic residual disease.ResultsThirteen of 107 women (12%) with recurrent ovarian cancer had thrombocytosis prior to SCS. Preoperative thrombocytosis at SCS was associated with failure to undergo optimal resection (p=0.0001). Women with preoperative thrombocytosis at time of SCS demonstrated shorter overall survival (33 months) compared to those with normal platelet counts (46 months, p=0.004). On multivariate analysis, only preoperative platelet count retained significance as an independent prognostic factor (p=0.025) after controlling for age at SCS (p=0.90), disease free interval from primary treatment (0.06), and initial stage of disease (0.66).ConclusionsElevated platelet count at time of SCS is associated with suboptimal resection and shortened overall survival. These data provide further evidence supporting a plausible role for thrombocytosis in aggressive ovarian tumor biology.

The external incentives model (EIM) proved highly compelling in explaining Europeanization and rule adoption in countries from Central, Eastern and Southeast Europe. Building on the EIM, the present article seeks to contribute along three key objectives. First, it proposes to re‐evaluate the EIM for the Eastern European Neighbourhood Policy (ENP) region: Armenia, Azerbaijan, Georgia, Moldova and Ukraine. Second, the paper introduces a conceptual distinction between domestic transformation costs and regulatory costs. Third, it integrates and evaluates the EIM in a broader framework, incorporating domestic and alternative international conditions. The paper combines theory‐guided case comparisons and panel data analysis, based on a dataset with evidence collected from the Eastern ENP countries. The study corroborates the EIM and finds that higher domestic transformation costs lead to lower levels of democratic development and a positive cost–benefit balance of transformation, on the other hand, tends to encourage democratic consolidation in the Eastern ENP region. [ABSTRACT FROM AUTHOR]

ObjectiveThere are few studies analyzing surveillance for Type II endometrial cancer recurrence. Our objective was to determine the types of post treatment surveillance tests performed in our institution and the efficacy of these tests in detecting recurrence in type II endometrial cancer patients.MethodsOne hundred and thirty six cases of type II endometrial cancers at Cedars-Sinai Medical Center from January of 2000 to August of 2011 were identified and 106 patients met inclusion criteria. Medical charts were reviewed for surveillance methods and number of follow up visits. For patients who underwent a recurrence of disease, the surveillance method utilized for detection was documented.ResultsForty-seven of the 106 (44%) patients developed recurrence with a mean progression free interval of 11 months. All patients had a history and physical at each surveillance visit, 78% had Pap testing, 57% had CA-125 levels drawn, 59% had CT (computed tomography) scans done, 6% had PET (positron emission tomography) scans done for surveillance. In our cohort, recurrence was detected by symptoms in 16, by CA-125 in 11, by physical exam in 7, by CT scan in 12, and by PET scan in one patient. No patients had recurrence detected by vaginal cytology.ConclusionsAlthough performed in the majority of patients, Pap testing did not detect any recurrences within this cohort. History and physical exam detected the most recurrences. These findings suggest that educating patients about relevant symptoms and performing thorough follow-up exams may be the most important aspects of detecting type II endometrial cancer recurrence.

Inflammation and macrophage foam cells are characteristic features of atherosclerotic lesions, but the mechanisms linking cholesterol accumulation to inflammation and LXR-dependent response pathways are poorly understood. To investigate this relationship, we utilized lipidomic and transcriptomic methods to evaluate the effect of diet and LDL receptor genotype on macrophage foam cell formation within the peritoneal cavities of mice. Foam cell formation was associated with significant changes in hundreds of lipid species and unexpected suppression, rather than activation, of inflammatory gene expression. We provide evidence that regulated accumulation of desmosterol underlies many of the homeostatic responses, including activation of LXR target genes, inhibition of SREBP target genes, selective reprogramming of fatty acid metabolism, and suppression of inflammatory-response genes, observed in macrophage foam cells. These observations suggest that macrophage activation in atherosclerotic lesions results from extrinsic, proinflammatory signals generated within the artery wall that suppress homeostatic and anti-inflammatory functions of desmosterol.

Complex early and late neuropathies resulting from direct and conductive electrical patterns of injury are disabling and extremely challenging to manage. We report a patient who suffered acute onset of right-hand weakness and decreased sensation following a radar equipment-related electrical injury. He received a carpal and Guyon tunnel release, regaining sensation and strength to his right hand by the first postoperative day.