ObjectiveThe COVID-19 pandemic has been associated with significant occupational stressors and challenges for front-line healthcare workers (HCWs), including COVID-19 exposure risk. Our study sought to assess factors contributing to HCW infection and psychological distress during the COVID-19 pandemic in the USA.DesignWe conducted a cross sectional survey of HCWs (physicians, nurses, emergency medical technicians (EMTs), non-clinical staff) during May 2020. Participants completed a 42-item survey assessing disease transmission risk (clinical role, work environment, availability of personal protective equipment) and mental health (anxiety, depression and burn-out).SettingThe questionnaire was disseminated over various social media platforms. 3083 respondents from 48 states, the District of Columbia and US territories accessed the survey.ParticipantsUsing a convenience sample of HCWs who worked during the pandemic, 3083 respondents accessed the survey and 2040 participants completed at least 80% of the survey.Primary outcomePrevalence of self-reported COVID-19 infection, in addition to burn-out, depression and anxiety symptoms.ResultsParticipants were largely from the Northeast and Southern USA, with attending physicians (31.12%), nurses (26.80%), EMTs (13.04%) with emergency medicine department (38.30%) being the most common department and specialty represented. Twenty-nine per cent of respondents met the criteria for being a probable case due to reported COVID-19 symptoms or a positive test. HCWs in the emergency department (31.64%) were more likely to contract COVID-19 compared with HCWs in the ICU (23.17%) and inpatient settings (25.53%). HCWs that contracted COVID-19 also reported higher levels of depressive symptoms (mean diff.=0.31; 95% CI 0.16 to 0.47), anxiety symptoms (mean diff.=0.34; 95% CI 0.17 to 0.52) and burn-out (mean diff.=0.54; 95% CI 0.36 to 0.71).ConclusionHCWs have experienced significant physical and psychological risk while working during the COVID-19 pandemic. These findings highlight the urgent need for increased support for provider physical and mental health well-being.

PURPOSE Five percent to 9% of pancreatic ductal adenocarcinomas (PDACs) develop in patients with a germline BRCA1/2 or PALB2 (g BRCA/PALB2+) mutation. Phase IB data from a trial that used cisplatin, gemcitabine, and veliparib treatment demonstrated a high response rate (RR), disease control rate (DCR), and overall survival (OS) in this population. We designed an open-label, randomized, multicenter, two-arm phase II trial to investigate cisplatin and gemcitabine with or without veliparib in g BRCA/PALB2+ PDAC. PATIENTS AND METHODS Eligible patients had untreated g BRCA/PALB2+ PDAC with measurable stage III to IV disease and Eastern Cooperative Oncology Group performance status of 0 to 1. Treatment for patients in arm A consisted of cisplatin 25 mg/m2 and gemcitabine 600 mg/m2 intravenously on days 3 and 10; treatment for patients in arm B was the same as that for patients in arm A, and arm A also received veliparib 80 mg orally twice per day on days 1 to 12 cycled every 3 weeks. The primary end point was RRs of arm A and arm B evaluated separately using a Simon two-stage design. Secondary end points were progression-free survival, DCR, OS, safety, and correlative analyses. RESULTS Fifty patients were evaluated by modified intention-to-treat analysis. The RR for arm A was 74.1% and 65.2% for arm B ( P = .55); both arms exceeded the prespecified activity threshold. DCR was 100% for arm A and 78.3% for arm B ( P = .02). Median progression-free survival was 10.1 months for arm A (95% CI, 6.7 to 11.5 months) and 9.7 months for arm B (95% CI, 4.2 to 13.6 months; P = .73). Median OS for arm A was 15.5 months (95% CI, 12.2 to 24.3 months) and 16.4 months for arm B (95% CI, 11.7 to 23.4 months; P = .6). Two-year OS rate for the entire cohort was 30.6% (95% CI, 17.8% to 44.4%), and 3-year OS rate was 17.8% (95% CI, 8.1% to 30.7%). Grade 3 to 4 hematologic toxicities for arm A versus arm B were 13 (48%) versus seven (30%) for neutropenia, 15 (55%) versus two (9%) for thrombocytopenia, and 14 (52%) versus eight (35%) for anemia. CONCLUSION Cisplatin and gemcitabine is an effective regimen in advanced g BRCA/PALB2+ PDAC. Concurrent veliparib did not improve RR. These data establish cisplatin and gemcitabine as a standard approach in g BRCA/ PALB2+ PDAC.

PGAs frequently occur in pancreas exocrine neoplasms and involve multiple genes beyond those previously associated with hereditary pancreatic cancer. These PGAs are therapeutically actionable in about 5% to 10% of patients. These data support routinely offering GT in all pancreatic ductal adenocarcimona patients with a broad panel of known hereditary cancer predisposition genes.

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Comparisons are made among Molecular Dynamics (MD), Classical Density Functional Theory (c-DFT), and Poisson–Boltzmann (PB) modeling of the electric double layer (EDL) for the nonprimitive three component model (3CM) in which the two ion species and solvent molecules are all of finite size. Unlike previous comparisons between c-DFT and Monte Carlo (MC), the present 3CM incorporates Lennard-Jones interactions rather than hard-sphere and hard-wall repulsions. c-DFT and MD results are compared over normalized surface charges ranging from 0.2 to 1.75 and bulk ion concentrations from 10 mM to 1 M. Agreement between the two, assessed by electric surface potential and ion density profiles, is found to be quite good. Wall potentials predicted by PB begin to depart significantly from c-DFT and MD for charge densities exceeding 0.3. Successive layers are observed to charge in a sequential manner such that the solvent becomes fully excluded from each layer before the onset of the next layer. Ultimately, this layer filling phenomenon results in fluid structures, Debye lengths, and electric surface potentials vastly different from the classical PB predictions.

Veliparib was well tolerated, but no confirmed response was observed although four (25%) patients remained on study with SD for ≥ 4 months. Additional strategies in this population are needed, and ongoing trials are evaluating PARPis combined with chemotherapy (NCT01585805) and as a maintenance strategy (NCT02184195).

The RP2D of veliparib was 80 mg by mouth twice daily on days 1 to 12 in combination with cisplatin and gemcitabine; the DLT was myelosuppression. Substantial antitumor activity was seen in BRCA+ PDAC. A randomized phase 2 trial is currently evaluating cisplatin and gemcitabine with and without veliparib for BRCA+ PDAC (NCT01585805). Cancer 2018;124:1374-82. © 2018 American Cancer Society.

The meniscal enthesis is a complex structure that is essential to mechanical stability of the meniscus and the knee joint. Several studies document the development of anatomically shaped tissue engineered meniscus constructs, but none have focused on how to integrate such tissues with underlying bone. This study establishes a simplified construct to model the meniscal enthesis composed of a collagen gel seeded with meniscal fibrochondrocytes integrated with decellularized cancellous bone. Mechanical fixation at the bony ends induced tissue integration of fibers into the bony tissue, which is critical for mechanical performance and has yet to be shown in enthesis literature. Our test platform is amenable to targeted experiments investigating mineralization gradients, collagen fiber alignment, cell population phenotype, and media conditioning with experimental impact on enthesis studies for meniscus, tendon, and ligament.