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Objective: In the ENGOT-EN6-NSGO/GOG3031/RUBY trial, dostarlimab+carboplatin-paclitaxel demonstrated significant improvement in progression free survival and a positive trend in overall survival compared with placebo+carboplatin-paclitaxel, with manageable toxicity, in patients with primary advanced or recurrent endometrial cancer. Here we report on patient-reported outcomes in the mismatch repair-deficient/microsatellite instability-high population, a secondary endpoint in the trial., Methods: Patients were randomized 1:1 to dostarlimab+carboplatin-paclitaxel or placebo+carboplatin-paclitaxel every 3 weeks for 6 cycles followed by dostarlimab or placebo monotherapy every 6 weeks for ≤3 years or until disease progression. Patient-reported outcomes, assessed with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and Endometrial Cancer Module, were prespecified secondary endpoints. A mixed model for repeated measures analysis, a prespecified exploratory analysis, was conducted to generate least-squares means to compare between-treatment differences while adjusting for correlations across multiple time points within a patient and controlling for the baseline value. Results are provided with 2-sided, nominal p values., Results: Of 494 patients enrolled, 118 were mismatch repair-deficient/microsatellite instability-high. In this population, mean change from baseline to end of treatment showed visual improvements in global quality of life (QoL), emotional and social function, pain, and back/pelvis pain for dostarlimab+carboplatin-paclitaxel. Meaningful differences (least-squares mean [standard error]) favoring the dostarlimab arm were reported for change from baseline to end of treatment for QoL (14.7 [5.45]; p=0.01), role function (12.7 [5.92]); p=0.03), emotional function (14.3 [4.92]; p<0.01), social function (13.5 [5.43]; p=0.01), and fatigue (-13.3 [5.84]; p=0.03)., Conclusions: Patients with mismatch repair-deficient/microsatellite instability-high primary advanced or recurrent endometrial cancer receiving dostarlimab+carboplatin-paclitaxel demonstrated improvements in several QoL domains over patients receiving placebo+carboplatin-paclitaxel. The observed improvements in progression free survival and overall survival while improving or maintaining QoL further supports dostarlimab+carboplatin-paclitaxel as a standard of care in this setting., Trial Registration: ClinicalTrials.gov NCT03981796., Competing Interests: Competing interests: GV reports consulting fees from GSK; honoraria from AstraZeneca, GSK, and MSD; travel support from AstraZeneca and PharmaMar; participation in advisory boards for AstraZeneca, Eisai, GSK, and MSD. MAP reports consulting fees from GSK, Tesaro, Merck, Eisai, SeaGen, Clovis Oncology, and AstraZeneca. SH reports consulting fees from AstraZeneca, Eisai, GSK, and MSD and honoraria from AstraZeneca and GSK. EMM reports advisory board meeting fees from AstraZeneca, GSK, and Tempus; honoraria from OncLive and Opinions in Gyn Malignancies; and support for attending meetings from Opinions in Gyn Malignancies and OncLive. ZN reports honoraria from Sofmedica, AstraZeneca, and MSD; support for attending meetings from Sofmedica and Preglem; participation on a data safety monitoring board or advisory board for AstraZeneca and Richter Gedeon; stock options from Richter Gedeon; and receipt of equipment, materials, drugs, medical writing, gifts, or other services from AstraZeneca. RH reports honoraria from GSK, AstraZeneca, Clovis Oncology, Eisai, and Merck. DD reports receiving consulting fees from AstraZeneca, GSK/Tesaro, Roche, Eisai Germany, and MSD Oncology; honoraria for advisory roles from Roche, AstraZeneca, GSK/Tesaro, Intuitive Surgical, KLS Martin, MSD, PharmaMar, and Seagen; and travel support from AstraZeneca. TM reports honoraria from Immunogen. LG reports institutional grants from Alkermes, AstraZeneca, Clovis Oncology, Esperas, IMV, ImmunoGen, Karyopharm, MSD, Mersana, Novocure, OncoQuest Pharmaceuticals, Pfizer, Roche, and Tesaro; consulting fees from Merck; honoraria from Alkermes, AstraZeneca, Eisai, Eisai-Merck, and GSK. BA reports honoraria from AstraZeneca, Eisai, GSK, MSD, Norartis, and Roche; support for attending meetings from AstraZeneca, GSK, and Roche; participation on a data safety monitoring board or advisory board for Eisai, GSK, MSD, Roche, and Sanofi Aventis. RG reports participation on a data safety monitoring board or advisory board for Pionyr Pharmaceuticals and receipt of equipment, materials, drugs, medical writing, gifts, or other services from Bausch+Lomb. NC reports advisory board fees for Aadii, GSK, Kartos, Novita Pharmaceuticals, Tarveda Therapeutics, Toray, Umoja, and Zentalis. BJM reports consulting fees from Agenus, Akeso Biopharma, Amgen, Aravive, Bayer, Elevar, EMD Merck, Genmab/Seagen, GOG Foundation, Gradalis, ImmunoGen, Iovance, Karyopharm, Macrogenics, Mersana, Myriad, Novartis, Novocure, Pfizer, Puma, Regeneron, Sorrento, US Oncology Research, and VBL and speakers’ bureau honoraria from AstraZeneca, Clovis Oncology, Eisai, Merck, Roche/Genentech, and Tesaro/GSK. TJH reports personal consulting fees from Aadi, AstraZeneca, Caris, Clovis Oncology, Eisai, Epsilogen, Genentech, GSK, Immunogen, J&J, Merck, Mersana, and Seagen; participation on a data safety monitoring board or advisory board for Corcept; and leadership role on the GOG Foundation Board and President of GOG Partners. AS reports royalties as an UptoDate reviewer. BP reports institutional grant support from AstraZeneca, Celsion, Clovis Oncology, Eisai, Genentech/Roche, Karyopharm, Merck, Mersana, SeaGen, Sutro Biopharma, Takeda Pharmaceuticals, Tesaro/GSK, Toray, and VBL Therapeutics; consulting fees from AstraZeneca, Atossa, Clovis Oncology, Deciphera, Elevar Therapeutics, I-Mab Biopharma, Merck, Mersana, Sutro Biopharma, Tesaro/GSK, and Toray; support for attending meetings from GOG Foundation; advisory board fees from Arquer Diagnostics, AstraZeneca, Atossa, Clovis Oncology, Deciphera, Eisai, Elevar Therapeutics, GOG Foundation, I-Mab Biopharma, Lilly, Merck, Mersana, Seagen, Sutro Biopharma, Tesaro/GSK, Toray, and VBL Therapeutics; and noncompensated leadership fees from NYOB Society Secretary, SGO Clinical Practice Committee Chair, and SGO COVID-19 Taskforce Co-Chair. AAS reports support paid to her institution from GSK for the present IGCS abstract; institutional grant support from AbbVie, Aravive, AstraZeneca, Clovis Oncology, Eisai, Ellipses, I-Mab Biopharma, Immunogen, Merck, Oncoquest/Canaria Bio, Roche/Genentech, Seagen, TapImmune, Tesaro/GSK, and VBL Therapeutics; honoraria from @Point of Care Clinical Care Options Curio Science, Peerview, Bio ASCEND, RTP, GOG Foundation (Highlight reel), and GOG Foundation Symposium; patent issued for 'blood based biomarkers in ovarian cancer'; noncompensated participation on a data safety monitoring board/advisory board from AstraZeneca, Clovis Oncology, Gilead, Immunogen, Imvax, Merck, Mersana, Natera, Onconova, and OncoQuest; uncompensated leadership roles with SGO, AAOGF, and NRG and compensated role from GOG; receipt of medical writing support from AstraZeneca; and uncompensated Clinical Trial Steering Committees for the AXLerate trial (Aravive), AtTEnd trial (Hoffman-LaRoche), Oval Trial (VBL Therapeutics), FLORA-5 trial (CanariaBio), and QPT-ORE-004 (CanariaBio). DC reports consultant fees from AstraZeneca and GSK and honoraria from AstraZeneca, GSK, Seagen/Genmab, and Immunogen. MRM reports consulting fees from AstraZeneca, Biocad, GSK, Karyopharm, Merck, Roche, and Zai Lab; speakers’ bureau fees from AstraZeneca and GSK; research funding (to institution) from Apexigen, AstraZeneca, Deciphera (trial chair), GSK, and Ultimovacs; and personal financial interest in Karyopharm (stocks/shares, member of board of directors). DB reports institutional grant fees from GSK; fees for being a member of GOG Partners Investigational Council; and medical director/owner of Trials365. AMT, KPP, EF, OZ, LML, IP, and SS have nothing to disclose. OM, VV, and JG are employees of GSK., (© IGCS and ESGO 2024. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Atomically precise graphene nanoribbons (GNRs) synthesized from the bottom-up exhibit promising electronic properties for high-performance field-effect transistors (FETs). The feasibility of fabricating FETs with GNRs (GNRFETs) has been demonstrated, with ongoing efforts aimed at further improving their performance. However, their long-term stability and reliability remain unexplored, which is as important as their performance for practical applications. In this work, we fabricated short-channel FETs with nine-atom-wide armchair GNRs (9-AGNRFETs). We revealed that the on-state ( I ON ) current performance of the 9-AGNRFETs deteriorates significantly over consecutive full transistor on and off logic cycles, which has neither been demonstrated nor previously considered. To address this issue, we deposited a thin ∼10 nm thick atomic layer deposition (ALD) layer of aluminum oxide (Al 2 O 3 ) directly on these devices. The integrity, compatibility, electrical performance, stability, and reliability, of the GNRFETs before and/or after Al 2 O 3 deposition were comprehensively studied. The results indicate that the observed decline in electrical device performance is most likely due to the degradation of contact resistance over multiple measurement cycles. We successfully demonstrated that the devices with the Al 2 O 3 layer operate well up to several thousand continuous full cycles without any degradation. Our study offers valuable insights into the stability and reliability of GNR transistors, which could facilitate their large-scale integration into practical applications.

Competing Interests: Competing interests: None declared.

Background: Traditional health economic evaluations of antimicrobials currently underestimate their value to wider society. They can be supplemented by additional value elements including insurance value, which captures the value of an antimicrobial in preventing or mitigating impacts of adverse risk events. Despite being commonplace in other sectors, constituents of the impacts and approaches for estimating insurance value have not been investigated. Objectives: This study assessed the insurance value of a novel gram-negative antimicrobial from operational healthcare, wider population health, productivity, and informal care perspectives. Methods: A novel mixed-methods approach was used to model insurance value in the United Kingdom: (1) literature review and multidisciplinary expert workshops to identify risk events for 4 relevant scenarios: ward closures, unavoidable shortage of conventional antimicrobials, viral respiratory pandemics, and catastrophic antimicrobial resistance (AMR); (2) parameterizing mitigable costs and frequencies of risk events across perspectives and scenarios; (3) estimating insurance value through a Monte Carlo simulation model for extreme events and a dynamic disease transmission model. Results: The mean insurance value across all scenarios and perspectives over 10 years in the UK was £718 million, should AMR remain unchanged, where only £134 million related to operational healthcare costs. It would be 50%-70% higher if AMR steadily increased or if a more risk-averse view (1-in-10 year downside) of future events is taken. Discussion: The overall insurance value if AMR remains at current levels (a conservative projection), is over 5 times greater than insurance value from just the operational healthcare costs perspective, traditionally the sole perspective used in health budgeting. Insurance value was generally larger for nationwide or universal (catastrophic AMR, pandemic, and conventional antimicrobial shortages) rather than localized (ward closure) scenarios, across perspectives. Components of this insurance value match previously published estimates of operational costs and mortality impacts. Conclusions: Insurance value of novel antimicrobials can be systematically modeled and substantially augments their traditional health economic value in normal circumstances. These approaches are generalizable to similar health interventions and form a framework for health systems and governments to capture broader value in health technology assessments, improve healthcare access, and increase resilience by planning for adverse scenarios.

The nearly complete cranium DAN5/P1 was found at Gona (Afar, Ethiopia), dated to 1.5-1.6 Ma, and assigned to the species Homo erectus. Its size is, nonetheless, particularly small for the known range of variation of this taxon, and the cranial capacity has been estimated as 598 cc. In this study, we analyzed a reconstruction of its endocranial cast, to investigate its paleoneurological features. The main anatomical traits of the endocast were described, and its morphology was compared with other fossil and modern human samples. The endocast shows most of the traits associated with less encephalized human taxa, like narrow frontal lobes and a simple meningeal vascular network with posterior parietal branches. The parietal region is relatively tall and rounded, although not especially large. Based on our set of measures, the general endocranial proportions are within the range of fossils included in the species Homo habilis or in the genus Australopithecus. Similarities with the genus Homo include a more posterior position of the frontal lobe relative to the cranial bones, and the general endocranial length and width when size is taken into account. This new specimen extends the known brain size variability of Homo ergaster/erectus, while suggesting that differences in gross brain proportions among early human species, or even between early humans and australopiths, were absent or subtle., (© 2023 Wiley Periodicals LLC.)

Objective: Advanced clear cell gynecologic malignancies remain among the most challenging diseases to manage. We evaluated ovarian and endometrial clear cell carcinoma (OCCC and ECCC) specimens using comprehensive sequencing technology to identify mutational targets and compared their molecular profiles to histologically similar clear cell renal cell carcinoma (ccRCC)., Methods: Using next-generation sequencing (NGS), fragment analysis (FA), and in situ hybridization (ISH), 164 OCCC, 75 ECCC and 234 ccRCC specimens from 2015 to 2018 were evaluated and compared., Results: The highest mutation rates in ECCC and OCCC were noted in: ARID1A (75.0%, 87.5%), TP53 (34.8%, 11.1%), PIK3CA (25.0%, 46.8%), PPP2R1A (8.7%, 16.7%), MSI-high (8.8%, 6.4%) and PTEN (8.3%, 7.1%). Among these mutations, there was no significant difference between OCCC and ECCC mutation prevalence except in TP53, with higher mutation rates in ECCC versus OCCC (34.8 vs. 11.1%, respectively, p < 0.05). ccRCC demonstrated different mutation profiles with higher mutation rates in VHL (80.3%), PBRM1 (43.9%), SETD2 (31.1%), and KDM5C (29.2%). By contrast, VHL, PBRM1, and SETD2 mutations were not found in ECCC and OCCC (0.0%). Compared to ccRCC and ECCC, OCCC was found to have a significantly higher tumor mutation burden (TMB) (19.1%)., Conclusion: Gynecologic and renal CCC demonstrate separate and disparate somatic profiles. However, OCCC and ECCC are diseases with similar profiles. TMB and MSI analyses indicate that a subset of OCCC may benefit from immunotherapy. Prospective clinical trials are needed and are underway to examine targeted therapies in these gynecologic disease subtypes., Competing Interests: Declaration of Competing Interest David Arguello and Pilar Ramos are employees of Caris Life Sciences., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: Medicare Shared Savings Program (MSSP) was implemented in 2012, but the impact of the MSSP on institutional post-acute care (PAC) use, and by race/ethnicity and payer status is less studied. We studied the impact of hospital participation in the MSSP on institutional PAC use and variations by race/ethnicity and payer status among 3 Medicare patient groups: ischemic stroke, hip fracture, and elective total joint arthroplasty (TJA)., Design: A retrospective analysis of 2010-2016 Medicare Provider Analysis and Review files., Setting and Participants: Medicare fee-for-service patients originally admitted for ischemic stroke, hip fracture, or elective TJA in MSSP-participating hospitals or nonparticipating hospitals., Methods: Patient-level linear probability models with difference-in-differences approach were used to compare the changes in institutional PAC use in MSSP-participating hospitals with nonparticipating hospitals as well as to compare the changes in differences by race/ethnicity and payer status in institutional PAC use over time., Results: Hospital participation in MSSP was significantly associated with increased institutional PAC use for the ischemic stroke cohort by 1.5 percentage points [95% confidence interval (CI) 0.00-0.3, P < .05] compared with non-MSSP participating hospitals. Regarding variations by race/ethnicity and payer status, for the elective TJA patients, racial minority patients in MSSP-participating hospitals had 3.8 percentage points greater (95% CI 0.01-0.06, P < .01) in institutional PAC use than white patients. Also, for ischemic stroke cohort, dual-eligible patients in MSSP-participating hospitals had 2.0 percentage points greater (95% CI 0.00-0.04, P < .10) in institutional PAC use than Medicare-only patients., Conclusions and Implications: This study found that hospital participation in the MSSP was associated with slightly increased institutional PAC use for ischemic stroke Medicare patients. Also, compared to non-MSSP participating hospitals, MSSP-participating hospitals were more likely to discharge racial minority patients for elective TJA and dual-eligible patients for ischemic stroke to institutional PAC., (Copyright © 2022 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Objectives: Low grade serous ovarian cancer (LGSOC) differs from high grade serous in terms of pathogenesis, molecular, genetic, and clinical features. Molecular studies have been hampered by small sample sizes, heterogenous histology, and lack of comprehensive testing. We sought to molecularly profile LGSOC in a homogenously tested, histologically confirmed cohort., Methods: Using hot-spot and whole exome next generation sequencing (NGS), fusion gene analysis interrogating RNA, fragment analysis, in situ hybridization and/or immunohistochemistry, 179 specimens were evaluated by Caris Life Sciences (Phoenix, AZ). A second independent histologic review confirmed histology in 153 specimens., Results: Most frequently mutated genes (5% or greater) were members of the mitogen-activated protein kinase (MAPK) pathway: KRAS (23.7%, n = 36), NRAS (11.2%, n = 19), NF1 (7.9%, n = 5), and BRAF (6.6%, n = 10). Class III mutations were seen in 3 of 10 BRAF mutations while 7 were Class I V600E. Overall, estrogen and progesterone receptor expression was 80.2% (n = 130) and 27.8% (n = 45), respectively. Of those that were hormone negative, nearly 50% contained KRAS or NF1 mutations. None were NRAS mutated. Markers of response to immunotherapy were low to absent., Conclusion: BRAF mutations were seen to be lower than those traditionally reported. With increased MAPK activation resulting in ligand independent activation of ERα, a role of combination therapy with hormonal and targeted therapy should be considered as 49.2% of hormone negative specimens were KRAS or NF1 mutated. Absence of immunotherapy biomarkers suggest limited benefit to immunotherapeutic agents., Competing Interests: Declaration of Competing Interest David Arguello and Yasmin Baca are employees of Caris Life Sciences., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Ultrasound measurements of the aorta are typically taken in the axial plane, with the transducer perpendicular to the aorta, and diameter measurements are obtained by placing the callipers from the anterior to the posterior wall and the transverse right to the left side of the aorta. While the 'conventional' anteroposterior walls in both sagittal and transverse plains may be suitable for aneurysms with less complicated geometry, there is controversy regarding the suitability of this approach for complicated, particularly tortuous aneurysms, as they may offer a more challenging situation. Previous work undertaken within our research group found that when training inexperienced users of ultrasound, they demonstrated more optimal calliper placement to the abdominal aorta when approached from a decubitus window to obtain a coronal image compared to the traditional ultrasound approach., Purpose: To observe the level of agreement in real-world reporting between computed tomography (CT) and ultrasound measurements in three standard planes; transverse AP, sagittal AP and coronal (left to right) infra-renal abdominal aortic aneurysm (AAA) diameter., Methodology: This is a retrospective review of the Otago Vascular Diagnostics database for AAA, where ultrasound and CT diameter data, available within 90 days of each other, were compared. In addition to patient demographics, the infrarenal aorta ultrasound diameter measurements in transverse AP and sagittal AP, along with a coronal decubitus image of the aorta was collected. No transverse measurement was performed from the left to the right of the aorta., Results: Three hundred twenty-five participants (238 males, mean age 76.4 ± 7.5) were included. Mean ultrasound outer to the outer wall, transverse AP and sagittal AP diameters were 48.7 ± 10.5 mm and 48.9 ± 9.9 mm, respectively. The coronal diameter measurement of the aorta from left to right was 53.9 ± 12.8 mm in the left decubitus window. The mean ultrasound max was 54.3 ± 12.6 mm. The mean CT diameter measurement was 55.6 ± 12.7 mm. Correlation between the CT max and ultrasound max was r 2  = 0.90, and CT with the coronal measurement r 2  = 0.90, CT and AP transverse was r2=0.80, and CT with AP sagittal measurement was r 2  = 0.77., Conclusion: The decubitus ultrasound window of the abdominal aorta, with measurement of the coronal plane, is highly correlated and in agreement with CT scanning. This window may offer an alternative approach to measuring the infrarenal abdominal aortic aneurysm and should be considered when performing surveillance of all infra-renal AAA., Competing Interests: The authors have no disclosures to declare or conflicts of interest., (© 2022 The Authors. Australasian Journal of Ultrasound in Medicine published by John Wiley & Sons Australia, Ltd on behalf of Australasian Society for Ultrasound in Medicine.)

Aim: There is increasing evidence that delayed loop ileostomy closure is associated with an increase in postoperative morbidity. In the context of a publicly funded health service with constrained theatre access, we review the impact of delay in loop ileostomy closure., Method: A retrospective cohort study of patients undergoing loop ileostomy closure at the Dunedin Public Hospital between 2000-2017 was performed. Cases and complications were identified from the prospectively maintained Otago Clinical Audit database. Patient demographics, ASA score, indications for ileostomy, reasons for delay in closure, length of stay (LOS) after ileostomy closure and complications were collected. LOS and overall complication rate were assessed using univariable and multivariable analyses., Results: A total of 292 patients were included in the study, of whom 74 (25.3%) were waiting for longer than 12 months for ileostomy closure. The overall complication rate was 21.5%. This was 8% up to 90 days, 20% between 90-360 days, 28% between 360-720 days and 54% after 720 days. Delay was associated with an increased risk of any complication (RR 1.06 for every 30 days with stoma, p < 0.001), including Ileus (OR [95% CI] 1.06 [1.00-1.11], p = 0.024). Overall mean LOS was 5.9 days (range 1-63), being 4.6 days up to 180 days, 5.6 between 180-720 days and 8.7 after 720 days. LOS significantly increased with increasing stoma duration (p = 0.04)., Conclusion: Increasing time with loop ileostomy is detrimental for patients, being associated with an increase in complication rates, and is detrimental for hospitals due to increased length of stay. Resources should be allocated for timely closure of loop ileostomies., (© 2022 The Authors. Colorectal Disease published by John Wiley & Sons Ltd on behalf of Association of Coloproctology of Great Britain and Ireland.)

Background and Objectives: The distinct illness trajectory after acute ischemic stroke demands a better understanding of the utilization of palliative care consultations (PCC) for this patient cohort. This study sought to determine the prevalence, predictors, and outcomes associated with PCC for patients hospitalized with severe ischemic stroke., Methods: This multicenter cohort study was conducted at four hospitals (2 comprehensive and 2 primary stroke centers) between January, 2016 and December, 2019. We included all patients with a discharge diagnosis of ischemic stroke and an initial National Institutes of Health Stroke Scale (NIHSS) of 10 or greater. We compared patient sociodemographic, clinical and care characteristics as well as hospital outcomes between patients who did and did not receive PCC., Results: The study included 1297 patients hospitalized with severe ischemic stroke. PCC occurred for 20% of all patients and this proportion varied across institutions from 11.9% to 43%. Less than half (43%) of patients who died in the hospital. In multivaraible analysis, PCC was less likely in female patients (OR .76, 95% CI .59, .99, P=0.04) but more likely in patients with higher NIHSS (OR1.95, 95% CI 1,13, 3.37, P=0.02). Patients with PCC had higher rates of moving to a plan focused on comfort measures (CMO) (P<0.01) and removal of artificial nutrition as part of a move to CMO (P<0.01). In a sub analysis of patients who died in the hospital and received PCC, patients who died on or before hospital day 3 were less likely to receive PCC than patients who died on or after hospital day 4 (24% v. 51%) (P=<0.01)., Conclusions: Most patients with severe stroke do not receive PCC, even among those who experience in-hospital death. The results of this study indicate there are missed opportunities for PCC to help reduce suffering after severe stroke., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim: Infection prevention and control (IPC) within residential settings is a central focus of the coronavirus disease 2019 (COVID-19) pandemic. Youth residential summer camps are an excellent model for such environments and have thus far had mixed results. The aim of this report was to describe the successful implementation of a seven-week overnight summer camp with rapid return to normal activities from June to August 2020., Subjects and Methods: This retrospective study included 427 individuals who traveled from 24 US states. All staff and campers were tested by serial nasopharyngeal PCR tests in the context of strict infection prevention and control (IPC) measures, including cohorts and masking. The entire camp population was isolated from non-camp personnel with special measures for food, supply, and mail delivery., Results: During the two-week staff session, one staff member tested positive for SARS-CoV-2, was isolated, and sent safely off premises. All other campers and staff had three negative PCR tests: 1-8 days before arrival, upon arrival, and 5-6 days after arrival. After these three negative tests, 6 days into camp, most IPCs, including masking, were successfully lifted and a normal camp experience was possible., Conclusions: These findings indicate that serial PCR-based testing and strict adherence to IPC measures among cohorts can allow for successful assumption of near normal group activities in a residential setting during the COVID-19 pandemic. This result at an overnight summer camp has broad implications for similar residential communities such as boarding schools, other youth education and development programs, as well as nursing homes and military installations., Supplementary Information: The online version contains supplementary material available at 10.1007/s10389-021-01597-9., (© The Author(s) 2021.)

Objective: Immuno-oncology (IO) has rapidly evolved, with many IO therapies either approved or under investigation for multiple malignancies. Biomarkers exist that can predict response to IO therapies including PD-L1 expression, microsatellite instability (MSI), and total mutation burden (TMB). This paper serves to analyze the presence of these biomarkers across gynecologic cancers., Methods: A total of 16,300 gynecologic cancer specimens submitted for molecular profiling to Caris Life Sciences were reviewed. Immunohistochemistry was performed using the SP142 anti-PD-L1 clone and assessed for intensity. Next-generation sequencing, immunohistochemistry, and fragment analysis were used to determine MSI status. TMB was measured by counting all non-synonymous missense mutations found per tumor not previously described as germline alterations. Chi-Square, Fisher Exact, and the Kruskal-Wallis test were used to compare cohorts., Results: Of 16,300 specimens, 54.1% were ovarian, 37.2% uterine, 7.2% cervical, 0.3% vulvar, 1.2% vaginal, with 0.1% unspecified. MSI-H was most frequent in uterine cancer (17.7%) and only 1% of ovarian cancers. PD-L1 expression was present in 38.3% of cervical and 62.5% of vulvar cancers, but less than 8% of ovarian and uterine cancers. TMB-H was present in 21.1% cervical, 19.7% uterine, and 5% ovarian cancers. Few specimens exhibited a "triple positive" phenotype - 0.3% ovarian, 1.5% uterine, and 1.5% cervical. Associations were seen between MSI, TMB, and PD-L1 across all cancer types., Conclusions: The frequency of individual biomarkers pertinent to IO therapy varies by cancer type. HPV-driven genital tract cancers have higher frequencies of PD-L1 expression, MSI-H, and TMBH. Endometrial cancers are characterized by MSI-H and TMB, whereas ovarian cancers have a low frequency of MSI-H and modest PD-L1 or TMBH. The incidence of 'triple positive" cases was less than 2%., Competing Interests: Declaration of competing interest W.M. Korn is both an employee and stockholder of Caris Life Sciences and acts as a consultant for Merck. T. Herzog receives consulting fees from AZ, Caris, Clovis, Eisai, Genentech, GSK, J&J, and Merck; additionally, he participates on the Corcept data safety monitoring board and acts as treasurer for the GOG foundation. N. Jones receives consulting fees from Seagan. All other authors have no conflicts of interest to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: Readmissions for Medicare patients initially admitted for stroke are common and costly. Rehabilitation in an institutional postacute care (PAC) setting is an evidence-based component of recovery for stroke. Under current Medicare payment reforms, care coordination across hospitals and PAC providers is key to improving quality and efficiency of care. We examined the causal impact of institutional PAC use on 30-day readmission rates for Medicare fee-for-service patients initially admitted for ischemic stroke., Data Sources: The 2010-2016 Medicare Provider Analysis and Review files., Research Design: We used the method of instrumental variable (IV) analysis to control for unobserved differences in the types of patients admitted to each PAC facility. We chose the distance from the patient's residence to the closest institutional PAC provider and the number of PAC providers of each type within a county where the patient resides as IVs., Principal Findings: In the naive model, an increase in institutional PAC use was significantly associated with an increase in 30-day readmission by 0.03 percentage points. However, using IV analysis to control for endogeneity bias, an increase in institutional PAC use was associated with a decrease in 30-day readmission rate by 0.19 percentage points. Our findings indicate that reducing institutional PAC use among patients typically requiring rehabilitation in institutional settings for recovery may potentially lead to adverse postdischarge outcomes that require rehospitalization. Thus, payment incentives to reduce institutional PAC use should be balanced with postdischarge outcomes among ischemic stroke patients., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Dysphagia is a common problem affecting all ages. It is increasing in frequency particularly among the younger population due to the rising incidence of eosinophilic oesophagitis, a condition which often leads to acute presentation to hospital for the first time with food bolus obstruction requiring endoscopic removal. Careful history taking remains the first and most important step in evaluating dysphagia, and it is especially important to distinguish an oropharyngeal versus oesophageal origin, which helps to guide further investigation and therapy. The three main investigations for dysphagia remain endoscopy, barium study and manometry, with endoscopy also offering therapeutic potential. Management is largely determined by the eventual diagnosis, often in a multi-disciplinary setting., (© 2021 Royal Australasian College of Physicians.)

Objectives: To assess associations between treatment and recurrence-free survival (RFS) among patients with isolated tumor cells (ITCs) in sentinel lymph nodes (SLN) and otherwise stage I/II endometrioid endometrial cancer (EC)., Methods: A multi-institutional retrospective study of patients with SLN ITCs (<200 cells and < 0.2 mm) was performed. Only patients with otherwise stage I/II EC, endometrioid histology, and no evidence of micro-or macrometastases were included. Univariate and multivariable Cox proportional hazard models were used to evaluate associations between treatment, tumor characteristics, and RFS., Results: 175 patients were included. Median follow up time was 31 months. 39% stage IB and 12% stage II disease. 76 (43%) received no adjuvant therapy or vaginal brachytherapy only (NAT/VBT), 21 (12%) had external beam radiation (EBRT), and 78 (45%) received chemotherapy +/- radiation. Patients who received chemotherapy more often had tumors with deep myoinvasion, lymphovascular space invasion (LVSI), and higher grade. Nine (5.1%) patients recurred; 5 distant, 3 retroperitoneal, and 1 vaginal. Extra-vaginal recurrences were similar in patients with or without chemotherapy (5.2% vs 3.8%, p = 0.68). After controlling for stage, LVSI and grade, chemotherapy and EBRT were not associated with RFS (HR = 0.63, 95%CI 0.11-3.52, and HR = 0.90, 95%CI 0.22-3.61, respectively). Type of lymph node dissection and ITC detection method were not associated with RFS., Conclusions: Risk of retroperitoneal and/or distant recurrence is low (4.6%) for patients with stage I/II endometrioid EC and ITCs in SLNs regardless of treatment. Our preliminary data suggests that adjuvant therapy may not be significantly associated with RFS. However, longer follow-up time and a larger sample size are needed before definitive recommendations regarding adjuvant therapy for patients with EC and only ITCs in SLN can be made., Competing Interests: Declaration of Competing Interest Dr. Leitao reports personal fees from JnJ/Ethicon, outside the submitted work; and Dr. Leitao is an ad hoc speaker for Intuitive Surgical, Inc. Dr. Abu-Rustum reports grants from GRAIL, grants from Stryker, outside the submitted work. Dr. Backes reports grants and personal fees from Eisai, grants and personal fees from Merck, grants from Immunogen, grants and personal fees from Clovis, personal fees from Agenus, personal fees from AstraZeneca, personal fees from Genentech, personal fees from GlaxoSmithKline, all outside the submitted work. None of the other authors have a significant conflict of interest related to the current study. Some of the investigators (Felix, Abu-Rustum, Leitao) receive grants for other projects that fund part of their time., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: Accountable care organizations in the Medicare Shared Savings Program (MSSP) in the United States attempt to reduce cost and improve quality for their patients by improving care coordination across care settings. We examined the impact of hospital participation in the MSSP on 30-day readmissions for several groups of Medicare inpatients, and by race/ethnicity and payer status., Main Data Source: A 2010-2016 Medicare Provider Analysis and Review files., Research Design: With propensity score matched sample of MSSP and non-MSSP-participating hospitals, patient-level linear probability models with difference-in-differences approach were used to compare the changes in readmission rates for Medicare fee-for-service patients initially admitted for ischemic stroke, hip fracture, or total joint arthroplasty in MSSP-participating hospitals with non-MSSP-participating hospitals as well as to compare the changes in disparities in readmission rates over time., Principal Findings: Hospital participation in MSSP was associated with further reduced readmission rate by 1.1 percentage points (95% confidence interval: -0.02 to 0.00, P<0.05) and 1.5 percentage points (95% confidence interval: -0.03 to 0.00, P=0.08) for ischemic stroke and hip fracture cohorts, respectively, compared with non-MSSP-participating hospitals, after the third year of hospital participation in the MSSP. There was no evidence that MSSP had an impact on racial/ethnic disparities, but increased disparity by payer status (dual vs. Medicare-only) was observed. These findings together suggest that MSSP accountable care organizations may take at least 3 years to achieve reduced readmissions and may increase disparities by payer status., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The objective of this study was to assess the rate of discordance between clinical and pathologic tumor size for women with stage IB1 cervical cancer (FIGO 2009 criteria), assess risk factors for discordance, and determine the impact of discordance on oncologic outcomes., Methods: This was a secondary analysis of a prior multi-institutional retrospective review of patients diagnosed with stage IB1 (FIGO 2009 staging) cervical cancer undergoing radical hysterectomy between 2010 and 2017. Demographic, clinicopathologic, and oncologic data were collected. Pathologic upstaging was defined as having a preoperative diagnosis of stage IB1 cervical cancer with pathology demonstrating a tumor size >4 cm. Demographic and clinicopathologic data was compared using chi-square, fisher exact or 2-sided t-test. Survival was estimated using the Kaplan-Meier method., Results: Of the 630 patients, 77 (12%) were upstaged. Patients who were upstaged had lower rates of preoperative conization (p < .001) or preoperative tumor sizes ≤2 cm (p < .001). Upstaged patients had increased odds of deep stromal invasion, lymphovascular space invasion, positive margins and positive lymph nodes. Almost 88% of upstaged patients received adjuvant therapy compared to 29% of patients with tumors ≤4 cm (odds 18.49, 95% CI 8.99-37.94). Finally, pathologic upstaging was associated with an increased hazard of recurrence (hazard ratio [HR] 1.95, 95% CI 1.03-3.67) and all-cause death (HR 2.31, 95% CI 1.04-5.11)., Conclusions: Pathologic upstaging in stage IB1 cervical cancer is relatively common. Upstaging is associated with an 18-fold increased risk of receipt of adjuvant therapy. Patients undergoing preoperative conization and those with tumors <2 cm had lower risks of upstaging. Improvement in preoperative assessment of tumor size may better inform primary treatment decisions., Competing Interests: Declaration of Competing Interest The authors of this manuscript have no conflicts of interest to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Night-time gastroesophageal reflux (nGER) symptoms are commonly associated with interrupted sleep. Most studies attempting to understand the relationship between sleep, arousal, and nGER events have been performed so using accelerometry; however, this technology is limited in its ability to precisely determine the temporal association between sleep and reflux events. We aimed to examine the temporal relationships between nGER events and arousal/awakening from sleep using high resolution, in-laboratory polysomnography (PSG)., Methods: Individuals between 18 and 70 years who had undergone a gastroscopy within 12 months underwent simultaneous 24-hour pH/impedance monitoring and in-laboratory PSG. The temporal relationship between each nGER event and sleep/arousals/awakenings was determined for each participant. Analyses were limited to the sleep period (between "lights out" and time of final waking)., Results: Analyses were conducted on the data from 25 individuals, 64% of whom had nGER episodes (5 ± 5 events per person, range 1-18) and 64% of whom had obstructive sleep apnea (OSA, mean apnea-hypopnea index 20 ± 11 events/hr, range 6-44). There were no differences in PSG-determined sleep duration, sleep efficiency, sleep architecture, arousals/awakenings, or sleep apnea severity between those with nGER and those without. Most nGER events (82%) occurred during a PSG epoch that had been classified as wake. Arousals/awakenings preceded almost all events (73/76), whereas fewer had an arousal/awakening after the event (15/76)., Discussion: As opposed to what is typically assumed, nGER does not seem to cause arousal from sleep, but rather arousal from sleep predisposes to nGER.

Background: This randomized phase II study tested the hypothesis that schedule dependent chemo-immunotherapy with oregovomab improves progression free survival (PFS) and overall survival (OS) in optimally resected, Stage III/IV ovarian cancer., Methods: Patients from both academic centers and private practice in the US and Italy with Stage III/IV optimally cytoreduced ovarian cancer were randomized to standard six cycle IV carboplatin-paclitaxel chemotherapy (CP) versus CP plus four immunizations with oregovomab (CPO). A translational assessment of a cellular immune response was the primary endpoint; PFS and OS were measured as secondary endpoints., Findings: 97 patients at thirteen centers were accrued to the protocol, 47 to CPO and 50 to CP. Technical issues led to inconsistent performance of the primary CA125 ELISPOT leading to unevaluable results. At a median follow up of 42 months, PFS and OS outcomes revealed an unexpectedly large treatment effect for CPO relative to CP alone, with median PFS of 41.8 months (95% C.I.: 21.8 - N.E.) for CPO and 12.2 months (10.4-18.6) for CP (p = 0.0027, HR 0.46, CI 0.28-0.7). For OS, the median for CPO has not yet been reached (NE) (45.2-NE) and for CP was 43.2 months (31.8-NE) (p = 0.043, HR 0.35, CI 0.16-0.74). The oregovomab treatment resulted in no change in toxicity profile from CP., Interpretation: The previously identified potential clinical benefit of IV CP when administered with oregovomab was further refined in this randomized phase II study. Increases of PFS and OS of statistically and clinically significant magnitude were evident in this study of a front line chemo-immunotherapy treatment of ovarian cancer., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Importance: Patients with recurrent ovarian carcinoma frequently develop resistance to platinum-based chemotherapy, at which time treatment options become limited., Objective: To evaluate the poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor niraparib combined with pembrolizumab in patients with recurrent ovarian carcinoma., Design, Setting, and Participants: The TOPACIO/KEYNOTE-162 (Niraparib in Combination With Pembrolizumab in Patients With Triple-Negative Breast Cancer or Ovarian Cancer) trial, an open-label, single-arm phases 1 and 2 study enrolled women with advanced or metastatic triple-negative breast cancer (TNBC) or recurrent ovarian carcinoma, irrespective of BRCA mutation status. Median follow-up was 12.4 months (range, 1.2 to ≥23.0 months). Data were collected from April 15, 2016, through September 4, 2018, with September 4, 2018, as a data cutoff, and analyzed from September 4, 2018, through January 30, 2019., Interventions: The recommended phase 2 dose (RP2D) was 200 mg of oral niraparib once daily and 200 mg of intravenous pembrolizumab on day 1 of each 21-day cycle., Main Outcomes and Measures: The primary objectives of phase 1 were to evaluate dose-limiting toxic effects and establish the RP2D and dosing schedule. The primary objective of phase 2 was to assess objective response rate (ORR; complete plus partial responses). Results from the phase 1 ovarian carcinoma and TNBC cohorts and phase 2 ovarian carcinoma cohort are reported. Because of the similarity in the phase 1 and 2 ovarian carcinoma populations, the data were pooled to perform an integrated efficacy analysis., Results: Fourteen patients (9 with ovarian carcinoma and 5 with TNBC) in phase 1 and 53 patients with ovarian carcinoma in phase 2 were enrolled, for a pooled ovarian carcinoma cohort of 62 patients (median age, 60 years [range, 46-83 years]). In the integrated efficacy phases 1 and 2 ovarian carcinoma population (60 of 62 evaluable patients), ORR was 18% (90% CI, 11%-29%), with a disease control rate of 65% (90% CI, 54%-75%), including 3 (5%) with confirmed complete responses, 8 (13%) with confirmed partial responses, 28 (47%) with stable disease, and 20 (33%) with progressive disease. The ORRs were consistent across subgroups based on platinum-based chemotherapy sensitivity, previous bevacizumab treatment, or tumor BRCA or homologous recombination deficiency (HRD) biomarker status. Median duration of response was not reached (range, 4.2 to ≥14.5 months). At data cutoff, 2 patients with a response and 1 patient with stable disease continued to receive treatment., Conclusions and Relevance: Niraparib in combination with pembrolizumab is tolerable, with promising antitumor activity for patients with ovarian carcinoma who have limited treatment options regardless of platinum status, biomarker status, or prior treatment with bevacizumab. Responses in patients without tumor BRCA mutations or non-HRD cancers were higher than expected with either agent as monotherapy., Trial Registration: ClinicalTrials.gov identifier: NCT02657889.

Background: Treatment options for achalasia include endoscopic and surgical techniques that carry the risk of esophageal bleeding and perforation. The rare coexistence of esophageal varices has only been anecdotally described and treatment is presumed to carry additional risk., Methods: Experience from physicians/surgeons treating this rare combination of disorders was sought through the International Manometry Working Group., Results: Fourteen patients with achalasia and varices from seven international centers were collected (mean age 61 ± 9 years). Five patients were treated with botulinum toxin injections (BTI), four had dilation, three received peroral endoscopic myotomy (POEM), one had POEM then dilation, and one patient underwent BTI followed by Heller's myotomy. Variceal eradication preceded achalasia treatment in three patients. All patients experienced a significant symptomatic improvement (median Eckardt score 7 vs 1; p  < 0.0001) at 6 months follow-up, with treatment outcomes resembling those of 20 non-cirrhotic achalasia patients who underwent similar therapy. No patients had recorded complications of bleeding or perforation., Conclusion: This study shows an excellent short-term symptomatic response in patients with esophageal achalasia and varices and demonstrates that the therapeutic outcomes and complications, other than transient encephalopathy in both patients who had a portosystemic shunt, did not differ to disease-matched patients without varices.

Objective: To compare the efficacy of mental health professional versus primary care nurse-delivered telehealth cognitive-behavioral therapy (CBT) and supportive care (SC) treatments for chronic low back pain, using data from 2 separate randomized controlled trials. Both trials were completed in the same hospital and used the same study design, research team, and outcome measures., Materials and Methods: Participants from Study 1 (Mental Health Professional Study) (N=66; 2007 to 2011) and Study 2 (Nursing Study) (N=61; 2012 to 2016) were patients with chronic low back pain (≥4/10 intensity) randomized to either an 8-week CBT or an SC telehealth condition matched for contact frequency, format, and time. Participants completed validated measures of improvement in back pain disability (Roland Morris Disability Questionnaire [RMDQ]), pain intensity (Numeric Rating Scale [NRS]), depressive symptoms (Beck Depression Inventory 2 [BDI-2]), pain catastrophizing (Pain Catastrophizing Scale [PCS]), and overall improvement (Global Clinical Impressions [GCI])., Results: Intent-to-treat analyses at posttreatment showed that scores on the RMDQ (Cohen d=0.33 to 0.55), NRS (d=0.45 to 0.90), PCS (d=0.21 to 0.41), and GCI (18.5% to 39.1%) improved significantly in both studies and in both treatments from pretreatment to posttreatment. Changes in BDI scores were inconsistent (d=-0.06 to 0.51). The analyses revealed no significant differences in treatment efficacy between the trained nurse versus the mental health professionals on the RMDQ, NRS, PCS, or GCI measures (P>0.20)., Discussion: Results from these clinical trials suggest that the benefits of home-based, telehealth-delivered CBT and SC treatments for chronic back pain were comparable when delivered by a primary care nurse or mental health professional.

This study evaluated a nurse-delivered, telehealth intervention of cognitive-behavioral therapy (CBT) versus supportive psychotherapy for chronic back pain. Participants (N = 61) had chronic back pain (pain "daily" ≥6 months at an intensity of ≥4 of 10 scale) and were randomized to an 8-week, 12-session, CBT or to supportive care (SC) matched for frequency, format, and time, with each treatment delivered by a primary care nurse. The primary outcome was the Roland Morris Disability Questionnaire (RMDQ). Secondary outcomes included the numeric rating scale (NRS) and the Patient Global Impressions Scale (CGI). CBT participants (n = 30) showed significant improvements on the RMDQ (mean = 11.4 [SD = 5.9] vs 9.4 [SD = 6.1] at baseline and post-treatment, respectively, P < .05; d = .33), NRS (mean = 4.9 [SD = 2.1] vs 4.0 [SD = 1.9], respectively, P < .05; d = .45), and on the CGI (39.1% reporting "much improved" or "very much improved"). SC participants (n = 31) also showed significant improvements on the RMDQ (mean = 11.1 [SD = 5.4] vs 9.1 [SD = 5.2], respectively, P < .05; d = .38), the NRS, (mean = 5.0 [SD = 1.9] vs 3.8 [SD = 2.1], respectively, P < .05; d = .60), and 26.7% reporting "much improved" or "very much improved" on the CGI. Between groups comparisons of CBT and SC showed no differences on the study outcomes (Ps > .10). The results suggest that telehealth, nurse-delivered CBT, and SC treatments for chronic back pain can offer significant and relatively comparable benefits., Perspective: This article describes the benefits of training primary care nurses to deliver evidence-based behavioral therapies for low back pain. Because of the high prevalence of chronic pain and the growing emphasis on nonopioid therapies, training nurses to provide behavior therapies could be a cost-effective way to improve pain management., (Published by Elsevier Inc.)

Achalasia is a relatively rare primary motor esophageal disorder, characterized by absence of relaxations of the lower esophageal sphincter and of peristalsis along the esophageal body. As a result, patients typically present with dysphagia, regurgitation and occasionally chest pain, pulmonary complication and malnutrition. New diagnostic methodologies and therapeutic techniques have been recently added to the armamentarium for treating achalasia. With the aim to offer clinicians and patients an up-to-date framework for making informed decisions on the management of this disease, the International Society for Diseases of the Esophagus Guidelines proposed and endorsed the Esophageal Achalasia Guidelines (I-GOAL). The guidelines were prepared according the Appraisal of Guidelines for Research and Evaluation (AGREE-REX) tool, accredited for guideline production by NICE UK. A systematic literature search was performed and the quality of evidence and the strength of recommendations were graded according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Given the relative rarity of this disease and the paucity of high-level evidence in the literature, this process was integrated with a three-step process of anonymous voting on each statement (DELPHI). Only statements with an approval rate >80% were accepted in the guidelines. Fifty-one experts from 11 countries and 3 representatives from patient support associations participated to the preparations of the guidelines. These guidelines deal specifically with the following achalasia issues: Diagnostic workup, Definition of the disease, Severity of presentation, Medical treatment, Botulinum Toxin injection, Pneumatic dilatation, POEM, Other endoscopic treatments, Laparoscopic myotomy, Definition of recurrence, Follow up and risk of cancer, Management of end stage achalasia, Treatment options for failure, Achalasia in children, Achalasia secondary to Chagas' disease.

Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) is a self-limited idiopathic inflammatory ophthalmologic condition with characteristic funduscopic and fluorescein angiography findings. It is typically characterized by a flu-like prodrome followed by monocular or binocular vision loss. Often, prognosis is excellent with complete or near-complete recovery of vision. Rarely, however, APMPPE is associated with neurologic complications, including meningitis, cerebral vasculitis, and stroke. Treatment in patients with central nervous system (CNS) involvement involves steroids and ultimately other immunosuppressive therapy, as there can be significant resulting morbidity and mortality otherwise. Evidence or guidelines regarding duration of treatment are lacking. We present 4 patients diagnosed with APMPPE who demonstrate the spectrum of neurologic sequelae associated with APMPPE. The first 2 cases highlight cerebrospinal fluid lymphocytic pleocytosis as an indicator of active CNS inflammation and the potential utility of serial lumbar punctures (LPs) to guide treatment duration. Cases 3 and 4 demonstrate the neurovascular complications seen in CNS vasculitis. Case 4 also highlights the potential use of magnetic resonance vessel wall imaging (VWI) as a noninvasive means for disease surveillance and treatment guidance. This case series emphasizes the importance of recognition by neurologists of APMPPE as an entity associated with strokes and cerebral vasculitis in order to provide appropriate and timely treatment. Active CNS inflammation warrants continued aggressive immunosuppressant treatment, and we propose that serial LPs and/or magnetic resonance VWIs may be effective tools to guide disease surveillance and subsequent treatment duration., Competing Interests: Declaration of Conflicting Interests: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr Scagnelli serves as a consultant for Teva Pharmaceutics, Novartis Pharmaceuticals, Biogen IDEC, and Sanofi-Genzyme. Dr Holloway serves as a consultant for Milliman Inc in reviewing practice guidelines.

Background: Indonesia's progress on reducing maternal and newborn mortality rates has slowed in recent years, predominantly in rural areas. To reduce maternal and newborn mortality, access to quality and skilled care, particularly at the facility level, is crucial. Yet, accessing such care is often delayed when maternal and newborn complications arise. Using the "Three Delays" model originated by Thaddeus and Maine (1994), investigation into reasons for delaying the decision to seek care, delaying arrival at a health facility, and delaying the receiving of adequate care, may help in establishing more focused interventions to improve maternal and newborn health in this region., Methods: This qualitative study focused on identifying, analyzing, and describing illness recognition and care-seeking patterns related to maternal and newborn complications in the Jayawijaya district of Papua province, Indonesia. Group interviews were conducted with families and other caregivers from within 15 villages of Jayawijaya who had either experienced a maternal or newborn illness or maternal or newborn death., Results: For maternal cases, excessive bleeding after delivery was recognized as a danger sign, and the process to decide to seek care was relatively quick. The decision-making process was mostly dominated by the husband. Most care was started at home by birth attendants, but the majority sought care outside of the home within the public health system. For newborn cases, most of the caregivers could not easily recognize newborn danger signs. Parents acted as the main decision-makers for seeking care. Decisions to seek care from a facility, such as the clinic or hospital, were only made when healthcare workers could not handle the case within the home. All newborn deaths were associated with delays in seeking care due to caretaker limitations in danger sign identification, whereas all maternal deaths were associated with delays in receiving appropriate care at facility level., Conclusions: For maternal health, emphasis needs to be placed on supply side solutions, and for newborn health, emphasis needs to be placed on demand and supply side solutions, probably including community-based interventions. Contextualized information for the design of programs aimed to affect maternal and newborn health is a prerequisite.

Background: Infective endocarditis has been reported post Melody percutaneous pulmonary valve implant; the incidence and risk factors, however, remain poorly defined. We identified four cases of endocarditis from our first 25 Melody implants. Our aim was to examine these cases in the context of postulated risk factors and directly compare endocarditis rates with local surgical valves., Methods: We conducted a retrospective review of patients post Melody percutaneous pulmonary valve implant in New Zealand (October, 2009-May, 2015) and also reviewed the incidence of endocarditis in New Zealand among patients who have undergone surgical pulmonary valve implants., Results: In total, 25 patients underwent Melody implantation at a median age of 18 years. At a median follow-up of 2.9 years, most were well with low valve gradient (median 27 mmHg) and only mild regurgitation. Two patients presented with life-threatening endocarditis and obstructive vegetations at 14 and 26 months post implant, respectively. Two additional patients presented with subacute endocarditis at 5.5 years post implant. From 2009 to May, 2015, 178 surgical pulmonic bioprostheses, largely Hancock valves and homografts, were used at our institution. At a median follow-up of 2.9 years, four patients (2%) had developed endocarditis in this group compared with 4/25 (16%) in the Melody group (p=0.0089). Three surgical valves have been replaced., Conclusions: The Melody valve offers a good alternative to surgical conduit replacement in selected patients. Many patients have excellent outcomes in the medium term. Endocarditis, however, can occur and if associated with obstruction can be life threatening. The risk for endocarditis in the Melody group was higher in comparison with that in a contemporaneous surgical pulmonary implant cohort.

Background: Criteria for transient lower esophageal sphincter relaxations (TLESRs) are well-defined for Dentsleeve manometry. As high-resolution manometry (HRM) is now the gold standard to assess esophageal motility, our aim was to propose a consensus definition of TLESRs using HRM., Methods: Postprandial esophageal HRM combined with impedance was performed in 10 patients with gastroesophageal reflux disease. Transient lower esophageal sphincter relaxations identification was performed by 17 experts using a Delphi process. Four investigators then characterized TLESR candidates that achieved 100% agreement (TLESR events) and those that achieved less than 25% agreement (non-events) after the third round. Logistic regression and decision tree analysis were used to define optimal diagnostic criteria., Key Results: All diagnostic criteria were more frequently encountered in the 57 TLESR events than in the 52 non-events. Crural diaphragm (CD) inhibition and LES relaxation duration >10 seconds had the highest predictive value to identify TLESR. Based on decision tree analysis, reflux on impedance, esophageal shortening, common cavity, upper esophageal sphincter relaxation without swallow and secondary peristalsis were alternate diagnostic criteria., Conclusion & Inferences: Using HRM, TLESR might be defined as LES relaxation occurring in absence of swallowing, lasting more than 10 seconds and associated with CD inhibition., (© 2016 John Wiley & Sons Ltd.)

Objective: Gamma Knife ®  (GK) (Elekta Instruments, Stockholm, Sweden) radiosurgery is well established for treatment of brain metastases. There are limited data on patients treated with GK from gynecological cancers. The authors sought to determine the effectiveness of the GK in patients with brain metastases from gynecological cancers., Methods: An IRB-approved database was queried for patients with gynecologic cancers treated with GK between June 1996 and May 2016. Imaging studies were reviewed post-SRS (stereotactic radiosurgery) to evaluate local control (LC) and distant brain control (DC). Overall survival (OS), local control, and distant brain control were calculated using the Kaplan-Meier (KM) method and log-rank test.  Results: Thirty-three patients underwent SRS for 73 separate cranial lesions. The median age was -58.5 years, and 17 (52%) also had extracranial metastases. Ten (30%) patients had previously received whole brain radiotherapy (WBRT), and 11 (33%) underwent concurrent WBRT. The median tumor volume was 0.96 cm 3 . Median radiographic follow-up was 11 months. At the time of treatment, 39% of patients were categorized as recursive partitioning analysis (RPA) Class I, 55% as RPA Class II, and 6% as RPA Class III. The local failure rate was 8%. Five patients (15%) developed new brain lesions outside the radiation field with a median progression-free survival (PFS) of seven (range: 3-9) months. Median OS was 15 months from GK treatment. One-year OS was 72.9% from GK treatment. Primary cancer histology was a significant predictor of OS, favoring ovarian and endometrial cancer (p = 0.03)., Conclusions: Gamma Knife stereotactic radiosurgery for gynecologic brain metastases leads to excellent control rates of treated lesions. Primary histology may have a significant impact on OS following GK, with improved survival seen with ovarian and cervical cancer following Gamma Knife radiosurgery (p = 0.03)., Competing Interests: The authors have declared that no competing interests exist.

Background: Achalasia can be subdivided into manometric subtypes according to the Chicago classification. These subtypes are proposed to predict outcome after treatment. This hypothesis was tested using a database of patients who underwent laparoscopic Heller's cardiomyotomy with anterior fundoplication., Methods: All patients who underwent Heller's cardiomyotomy for achalasia between June 1993 and March 2015 were identified from an institutional database. Manometry tracings were retrieved and re-reported according the Chicago classification. Outcome was assessed by a postal questionnaire, and designated a success if the modified Eckardt score was 3 or less, and the patient had not undergone subsequent surgery or pneumatic dilatation. Difference in outcome after cardiomyotomy was analysed with a mixed-effects logistic regression model., Results: Sixty, 111 and 24 patients had type I, II and II achalasia respectively. Patients with type III achalasia were more likely to be older than those with type I or II (mean age 63 versus 50 and 49 years respectively; P = 0·001). Some 176 of 195 patients returned questionnaires after surgery. Type III achalasia was less likely to have a successful outcome than type II (odds ratio (OR) 0·38, 95 per cent c.i. 0·15 to 0·94; P = 0·035). There was no significant difference in outcome between types I and II achalasia (II versus I: OR 0·87, 0·47 to 1·60; P 0·663). The success rate at 3-year follow-up was 69 per cent (22 of 32) for type I, 66 per cent (33 of 50) for type II and 31 per cent (4 of 13) for type III., Conclusion: Type III achalasia is a predictor of poor outcome after cardiomyotomy. There was no difference in outcome between types I and II achalasia., (© 2016 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Trans-sphincteric pressure gradient (TSPG) seems to play a relevant role in eliciting refluxes during transient lower esophageal sphincter relaxations (TLESRs). Intra-bolus pressure (IBP) is considered to be correlated to esophageal wall tone. We aimed to evaluate the relationship between IBP, TSPG during TLESRs and the dynamic properties of refluxate in gastroesophageal reflux disease. Sixteen non-erosive reflux disease (NERD), 10 erosive disease (ERD) patients and 12 healthy volunteers (HVs), underwent 24-hour impedance-pH monitoring and combined high-resolution manometry-impedance before and 60 minutes. After a meal, ERD patients presented a significantly lower mean IBP (4.7 ± 1.6 mmHg) respect to NERD patients (8.9 ± 2.8 mmHg) and HVs (9.2 ± 3.2 mmHg). NERD patients with physiological abnormal acid exposure time showed a mean IBP (10.4 ± 3.1 mmHg) significantly higher than that in NERD with pathological abnormal acid exposure time (5.1 ± 1.5 mmHg). The TSPG value was significantly higher during TLESRs accompanied by reflux than during TLESRs not associated with reflux, both in patients and in HVs. A significant direct correlation was found between IBP, TSPG and proximal spread of refluxes in patients and in HVs. Gastroesophageal reflux disease patients display different degrees of esophageal distension. An increased compliance of the distal esophagus may accommodate larger volumes of refluxate and likely facilitates the injuries development. Higher TSPG values appear to facilitate the occurrence of refluxes during TLESRs. In patients with NERD, higher TSPG and IBP values favor proximal spread of refluxate and hence may play a relevant role in symptom generation., (© 2015 International Society for Diseases of the Esophagus.)

Labial striations on the anterior teeth have been documented in numerous European pre-Neandertal and Neandertal fossils and serve as evidence for handedness. OH-65, dated at 1.8 mya, shows a concentration of oblique striations on, especially, the left I 1 and right I 1 , I 2 and C 1 , which signal that it was right-handed. From these patterns we contend that OH-65 was habitually using the right hand, over the left, in manipulating objects during some kind of oral processing. In living humans right-handedness is generally correlated with brain lateralization, although the strength of the association is questioned by some. We propose that as more specimens are found, right-handedness, as seen in living Homo, will most probably be typical of these early hominins., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

This article discusses the care of a 62-year-old man with non-small-cell lung cancer and associated cancer anorexia-cachexia syndrome (CACS), and demonstrates common challenges faced by such patients and their family caregivers. The case description illustrates the fragmented approach of various disciplines to the patient's CACS care, resulting in undertreatment, delayed and burdensome visits, and patient and caregiver frustration and emotional distress. The mounting problems that arise for the patient over time exemplify the absence of a shared mental model among the various providers, patient, and caregiver for the care of CACS. Shared knowledge among providers regarding the tasks to be performed, the other clinicians' functions, and optimal processes for CACS care was limited. Each provider was responsive to individual symptoms, rather than conceptualizing the constellation of symptoms as a syndrome that warrants coordinated care among clinicians. This resulted in the patient and the family caregiver being at odds with their various providers instead of working in partnership with a shared understanding toward common goals. Team mental models have the potential to enhance development and implementation of care plans and improve patient care and satisfaction by helping clinical care teams establish team membership, identify shared tasks, and facilitate interactions. To help inform ongoing clinical practice and research, this article demonstrates how clinicians at one cancer center are leveraging a team mental model to form and support an interdisciplinary CACS team that provides coordinated patient-centered care.

The mission of the American Heart Association/American Stroke Association includes increasing access to high-quality, evidence-based care that improves patient outcomes such as health-related quality of life and is consistent with the patients' values, preferences, and goals. Awareness of and access to palliative care interventions align with the American Heart Association/American Stroke Association mission. The purposes of this policy statement are to provide background on the importance of palliative care as it pertains to patients with advanced cardiovascular disease and stroke and their families and to make recommendations for policy decisions. Palliative care, defined as patient- and family-centered care that optimizes health-related quality of life by anticipating, preventing, and treating suffering, should be integrated into the care of all patients with advanced cardiovascular disease and stroke early in the disease trajectory. Palliative care focuses on communication, shared decision making about treatment options, advance care planning, and attention to physical, emotional, spiritual, and psychological distress with inclusion of the patient's family and care system. Our policy recommendations address the following: reimbursement for comprehensive delivery of palliative care services for patients with advanced cardiovascular disease and stroke; strong payer-provider relationships that involve data sharing to identify patients in need of palliative care, identification of better care and payment models, and establishment of quality standards and outcome measurements; healthcare system policies for the provision of comprehensive palliative care services during hospitalization, including goals of care, treatment decisions, needs of family caregivers, and transition to other care settings; and health professional education in palliative care as part of licensure requirements., (© 2016 American Heart Association, Inc.)

Background: Cardiac arrest is a devastating complication of acute ischemic stroke, but little is known about its incidence and characteristics. We studied a large ischemic stroke inpatient population and compared patients with and without cardiac arrest., Methods: We studied consecutive patients from the Ontario Stroke Registry who had an ischemic stroke between July 2003 and June 2008 at 11 tertiary care stroke centers in Ontario. Multivariable analyses were used to determine independent predictors of cardiac arrest and associated outcomes. Adjusted survival curves were computed, and hazard ratios for mortality at 30 days and 1 year were determined for cardiac arrest and other major outcomes., Results: Among the 9019 patients with acute ischemic stroke, 352 had cardiac arrest, for an overall incidence of 3.9%. In a sensitivity analysis with palliative patients removed, the incidence of cardiac arrest was 2.5%. Independent predictors of cardiac arrest were as follows: older age, greater stroke severity, preadmission dependence, and a history of diabetes, myocardial infarction, congestive heart failure, and atrial fibrillation. Systemic complications associated with cardiac arrest were as follows: myocardial infarction, pulmonary embolism, sepsis, gastrointestinal hemorrhage, and pneumonia. Patients with cardiac arrest had higher disability at discharge, and a markedly increased 30-day mortality of 82.1% compared with 9.3% without cardiac arrest., Conclusions: Cardiac arrest had a high incidence and was associated with poor outcomes after ischemic stroke, including multiple medical complications and very high mortality. Predictors of cardiac arrest identified in this study could help risk stratify ischemic stroke patients for cardiac investigations and prolonged cardiac monitoring., (Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Introduction: Janus kinases (JAKs) regulate inflammatory gene expression through phosphorylation of signal transducer and activator of transcription (STAT) proteins. Expression of STAT proteins is increased in chronic obstructive pulmonary disease (COPD), and may be involved in driving chronic inflammation. Oral JAK inhibitors are effective as anti-inflammatory therapy but exhibit dose-limiting adverse effects. Development of inhaled compounds would be enhanced by robust biomarkers that directly reflect the anti-inflammatory and pharmacological activity in the lung., Methods: A novel flow cytometry assay was developed to measure STAT1 phosphorylation in sputum inflammatory cells. The standard sputum processing method was refined to improve sputum cell viability. The flow cytometric assay was used to assess the reproducibility of the measurement of STAT1 phosphorylation and the in vitro activity of a pan JAK-inhibitor on three separate visits in patients with COPD., Results: Upregulation of STAT1 phosphorylation was measured following in vitro IFNγ stimulation of sputum macrophages (stimulated/unstimulated ratio 1.57; p<0.00001). Upregulation was inhibited following in vitro preincubation with a pan JAK-inhibitor (inhibited+stimulated/unstimulated ratio 0.97). STAT1 phosphorylation activity could only be measured in macrophages., Conclusions: Sputum from patients with COPD can be used to reproducibly measure phospho-STAT expression in sputum macrophages. The flow cytometry-based method can be used to evaluate kinase inhibitors in vitro and subsequently in ex vivo studies. The assay is particularly useful for the assessment of inhaled compounds where whole blood assays may not be relevant.

Importance: The Medical Student Performance Evaluation (MSPE)--formerly called the dean's letter--is an important tool for residency program directors to use in assessing student qualifications for both invitation to interview and construction of their rank order list. Many institutions are now allowing students to construct their own Unique Characteristics (UC) section for the MSPE. This study addresses the results of allowing students to construct their own UC., Objectives: The goal of this study was to allow students to voice their thoughts regarding their participation in the construction of the UC section of the MSPE. The survey evaluated student attitude toward, value of, and support for the UC section., Method: We conducted a cross-sectional survey of all fourth-year medical students at the Medical College of Wisconsin during the 2014-2015 academic year. Responses were received from 66% of students (133 out of 199). We developed a question bank to cover the aims of the study--to assess student perceived value, experience writing, and support for the UC section., Results: There was agreement among students that their participation will positively affect their candidacy for interview selection and success in the match. Overall significance of regression model P = .001, R2. = .60. Additionally, students believed they had an advantage over applicants at other schools without the opportunity to draft their UC. Other findings included that men found the task more challenging, psychiatry applicants were least satisfied with the character count, and emergency medicine applicants voiced the lowest value for the UC section., Conclusions: The present study supports, in general terms, the utility and value of students drafting their own UC section of the MSPE. Future investigations should focus on expanding to other schools, comparing public to private institutions, and refining the interspecialty comparisons.

Objective: To compare perioperative and clinico-pathological outcomes of patients with early-stage cervical cancer who underwent robot-assisted radical hysterectomy (RRH) and open radical hysterectomy (ORH)., Methods: This retrospective multi-center study abstracted demographic, clinico-pathological and perioperative outcomes data from medical records of 491 cervical cancer patients treated with RRH (n = 259) ORH (n = 232) between 2005 and 2011 at two American and one Norwegian University Cancer Centres., Results: Mean estimated blood loss (EBL) and transfusion rates were less for RRH than for ORH (97 vs. 49 mL, p < 0.001, and 3% vs. 7%, p = 0.018, respectively). Mean length of hospital stay (LOS) was significantly shorter in RRH versus ORH (1.8 vs. 5.1 days, p < 0.001). Mean operative time was longer for RRH than ORH (220 vs. 156 min, p < 0.001). Although overall complications were similar (p = 0.49), intra-operative complications were less common in the RRH group than ORH (4% vs. 10%, p = 0.004). In multivariate regression analyses longer operative time, less EBL and intra-operative complications, shorter LOS, and more pre-operative cone were significantly associated with RRH versus ORH. Recurrence and death rates were not statistically different for the two groups at a mean follow-up time of 39 months (p = 1.00 and p = 0.48, respectively)., Conclusions: RRH had improved clinical outcomes compared to ORH in the treatment of early-stage cervical cancer in terms of EBL, intra-operative complications, transfusion rates, LOS, and pre-operative cone. Disease recurrence and survival were comparable for the two procedures., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The complexities of planning for and responding to the emergence of novel influenza viruses emphasize the need for systematic frameworks to describe the progression of the event; weigh the risk of emergence and potential public health impact; evaluate transmissibility, antiviral resistance, and severity; and make decisions about interventions. On the basis of experience from recent influenza responses, CDC has updated its framework to describe influenza pandemic progression using six intervals (two prepandemic and four pandemic intervals) and eight domains. This updated framework can be used for influenza pandemic planning and serves as recommendations for risk assessment, decision-making, and action in the United States. The updated framework replaces the U.S. federal government stages from the 2006 implementation plan for the National Strategy for Pandemic Influenza (US Homeland Security Council. National strategy for pandemic influenza: implementation plan. Washington, DC: US Homeland Security Council; 2006. Available at http://www.flu.gov/planning-preparedness/federal/pandemic-influenza-implementation.pdf). The six intervals of the updated framework are as follows: 1) investigation of cases of novel influenza, 2) recognition of increased potential for ongoing transmission, 3) initiation of a pandemic wave, 4) acceleration of a pandemic wave, 5) deceleration of a pandemic wave, and 6) preparation for future pandemic waves. The following eight domains are used to organize response efforts within each interval: incident management, surveillance and epidemiology, laboratory, community mitigation, medical care and countermeasures, vaccine, risk communications, and state/local coordination. Compared with the previous U.S. government stages, this updated framework provides greater detail and clarity regarding the potential timing of key decisions and actions aimed at slowing the spread and mitigating the impact of an emerging pandemic. Use of this updated framework is anticipated to improve pandemic preparedness and response in the United States. Activities and decisions during a response are event-specific. These intervals serve as a reference for public health decision-making by federal, state, and local health authorities in the United States during an influenza pandemic and are not meant to be prescriptive or comprehensive. This framework incorporates information from newly developed tools for pandemic planning and response, including the Influenza Risk Assessment Tool and the Pandemic Severity Assessment Framework, and has been aligned with the pandemic phases restructured in 2013 by the World Health Organization.

The objective of this review is to summarize recent scientific and medical literature regarding chemoresponse assays or chemotherapy sensitivity and resistance assays (CSRAs), specifically as applied to epithelial ovarian cancer. A total of sixty-seven articles, identified through PubMed using the key words "in vitro chemoresponse assay," "chemo sensitivity resistance assay," "ATP," "HDRA," "EDR," "MiCK," and "ChemoFx," were reviewed. Recent publications on marker validation, including relevant clinical trial designs, were also included. Recent CSRA research and clinical studies are outlined in this review. Published findings demonstrate benefits regarding patient outcome with respect to recent CSRAs. Specifically, analytical and clinical validations, as well as clinical utility and economic benefit, of the most common clinically used CSRA in the United States support its use to aid in making effective, individualized clinical treatment selections for patients with ovarian cancer.

Health economic studies in Parkinson's disease (PD) have become increasingly common in recent years. Because several methodologies and instruments have been used to assess cost and outcomes in PD, the Movement Disorder Society (MDS) commissioned a Task Force to assess their properties and make recommendations regarding their use. A systematic literature review was conducted to explore the use of those instruments in PD and to determine which should be selected for this review. We assessed approaches to evaluate cost of illness (COI), cost effectiveness, and cost utilities, which include the use of direct (standard gamble, time trade-off. and visual analogue scales) and indirect instruments to measure health status and utilities. No validated instruments/models were identified for the evaluation of COI or cost-effectiveness in patients with PD; therefore, no instruments in this group are recommended. Among utility instruments, only a few of these outcome instruments have been used in the PD population, and only limited psychometric data are available for these instruments with respect to PD. Because psychometric data for further utility instruments in conditions other than PD already exist, the standard gamble and time trade-off methods and the EQ-5D (a European quality-of-life health states instrument) and Health Utility Index instruments met the criteria for scales that are "recommended (with limitations)," but only the EQ-5D has been assessed in detail in PD patients. The MDS Task Force recommends further study of these instruments in the PD population to establish core psychometric properties. For the assessment of COI, the Task Force considers the development of a COI instrument specifically for PD, like that available for Alzheimer's disease., (© 2013 Movement Disorder Society.)

Objective: Use of in vitro chemoresponse assays for informing effective treatment selection is a compelling clinical question and a topic of debate among oncologists. A prospective study was conducted evaluating the use of a chemoresponse assay in recurrent ovarian cancer patients., Methods: Women with persistent or recurrent ovarian cancer were enrolled under an IRB-approved protocol, and fresh tissue samples were collected for chemoresponse testing. Patients were treated with one of 15 protocol-designated treatments empirically selected by the oncologist, blinded to the assay results. Each treatment was classified by the assay as: sensitive (S), intermediate (I), or resistant (R). Patients were prospectively monitored for progression-free survival (PFS) and overall survival (OS). Associations of assay response for the physician-selected treatment with PFS and OS were analyzed., Results: A total of 262 evaluable patients were enrolled. Patients treated with an assay-sensitive regimen demonstrated significantly improved PFS and OS while there was no difference in clinical outcomes between I and R groups. Median PFS was 8.8 months for S vs. 5.9 months for I+R (hazard ratio [HR]=0.67, p=0.009). The association with assay response was consistent in both platinum-sensitive and platinum-resistant tumors (HR: 0.71 vs. 0.66) and was independent of other covariates in multivariate analysis (HR=0.66, p=0.020). A statistically significant14-month improvement in mean OS (37.5 months for S vs. 23.9 months for I+R, HR=0.61, p=0.010) was demonstrated., Conclusions: This prospective study demonstrated improved PFS and OS for patients with either platinum-sensitive or platinum-resistant recurrent ovarian cancer treated with assay-sensitive agents., (© 2013. Published by Elsevier Inc. All rights reserved.)