Policy Recommendations Regarding Skilled Nursing Facility Management of Coronavirus 19 (COVID-19): Lessons from New York State

To provide policy recommendations for managing Coronavirus 19 (COVID-19) in skilled nursing facilities, a group of certified medical directors from several facilities in New York state with experience managing the disease used e-mail, phone, and video conferencing to develop consensus recommendations. The resulting document provides recommendations on screening, protection of staff, screening of residents, management of Coronavirus 19 positive and presumed positive cases, communication during an outbreak, management of admissions and readmissions, and providing emotional support for staff. These consensus guidelines have been endorsed by the Executive Board of the New York Medical Directors Association and the Board of the Metropolitan Area Geriatrics Society.     

Chemotherapy and novel therapeutics before radical prostatectomy for high-risk clinically localized prostate cancer

Although both surgery and radiation are potential curative options for men with clinically localized prostate cancer, a significant proportion of men with high-risk and locally advanced disease will demonstrate biochemical and potentially clinical progression of their disease. Neoadjuvant systemic therapy before radical prostatectomy (RP) is a logical strategy to improve treatment outcomes for men with clinically localized high-risk prostate cancer. Furthermore, delivery of chemotherapy and other systemic agents before RP affords an opportunity to explore the efficacy of these agents with pathologic end points.Neoadjuvant chemotherapy, primarily with docetaxel (with or without androgen deprivation therapy), has demonstrated feasibility and safety in men undergoing RP, but no study to date has established the efficacy of neoadjuvant chemotherapy or neoadjuvant chemohormonal therapies. Other novel agents, such as those targeting the vascular endothelial growth factor receptor, epidermal growth factor receptor, platelet-derived growth factor receptor, clusterin, and immunomodulatory therapeutics, are currently under investigation.     

老年人桡骨远端C型骨折的手术治疗与非手术治疗的疗效对比

目的：探讨老年人桡骨远端C型骨折的手术治疗与非手术治疗的疗效差异，评价两种方法的优缺点。方法回顾性分析2009-12—2011-12收治的老年桡骨远端C型骨折68例，按照治疗方法分为A组(手术组)及B组(非手术组)，统计分析两组患者的临床资料。结果 A组33例， B组35例，平均随访21.5个月。两组患者的年龄、骨折类型均无差异(P＞0.05)；术后影像学指标A组优于B组，骨折愈合时间B组优于A组，治疗成本A组大于B组(P＜0.05)；Cooney评分早期A组优于B组，1年后两组无差异，两组的并发症无差异(P＞0.05)。结论老年人桡骨远端C型骨折手术治疗较非手术治疗可获得更好的复位及早期功能，但远期功能恢复无差异。     

Magnesium modification of a calcium phosphate cement alters bone marrow stromal cell behavior via an integrin-mediated mechanism

The chemical composition, structure and surface characteristics of biomaterials/scaffold can affect the adsorption of proteins, and this in turn influences the subsequent cellular response and tissue regeneration. With magnesium/calcium phosphate cements (MCPC) as model, the effects of magnesium (Mg) on the initial adhesion and osteogenic differentiation of bone marrow stromal cells (BMSCs) as well as the underlying mechanism were investigated. A series of MCPCs with different magnesium phosphate cement (MPC) content (0∼20%) in calcium phosphate cement (CPC) were synthesized. MCPCs with moderate proportion of MPC (5% and 10%, referred to as 5MCPC and 10MCPC) were found to effectively modulate the orientation of the adsorbed fibronectin (Fn) to exhibit enhanced receptor binding affinity, and to up-regulate integrin α5β1 expression of BMSCs, especially for 5MCPC. As a result, the attachment, morphology, focal adhesion formation, actin filaments assembly and osteogenic differentiation of BMSCs on 5MCPC were strongly enhanced. Further in vivo experiments confirmed that 5MCPC induced promoted osteogenesis in comparison to ot her CPC/MCPCs. Our results also suggested that the Mg on the underlying substrates but not the dissolved Mg ions was the main contributor to the above positive effects. Based on these results, it can be inferred that the specific interaction of Fn and integrin α5β1 had predominant effect on the MCPC-induced enhanced cellular response of BMSCs. These results provide a new strategy to regulate BMSCs adhesion and osteogenic differentiation by adjusting the Mg/Ca content and distribution in CPC, guiding the development of osteoinductive scaffolds for bone tissue regeneration.     

Anomalous Origin of the Left Coronary Artery from the Pulmonary Artery: Diagnoses and Surgical Results in 12 Pediatric Patients

Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital condition. It responds well to early diagnosis and treatment, but otherwise the prognosis is poor. We present our case series of 12 patients (mean age, 2 ± 2.58 yr; age range, 2 mo–8 yr), emphasizing the diagnostic process and discussing our surgical results. The diagnosis of ALCAPA should be suspected in infants who have dilated cardiomyopathy with electrocardiographic changes that suggest ischemia, and in older children who have isolated mitral regurgitation. When clinical suspicion is high, the results of 2-dimensional echocardiography combined with color-flow Doppler studies in expert hands can establish the diagnosis, thus avoiding angiography in critically ill infants. The treatment of choice in our patients was transfer and reimplantation of the left coronary artery onto the ascending aorta. There were 2 deaths: both were infants in extremis who underwent emergency surgery. An older child with severe ventricular dysfunction was given mechanical ventricular assistance and then heart transplantation. As of this report, all 10 survivors remained well and asymptomatic.     

Validity and reliability of the Turkish version of the pressure injury knowledge assessment tool 2.0

AimThe aim of this study was to develop a Turkish version of the Pressure Ulcer Knowledge Assessment Tool 2.0 (PUKAT 2.0) and determine its validity and reliability.Materials and MethodsThis was a cross-cultural adaptation and validation study. The study sample included a total of 451 participants (232 nurses and 219 nursing students). The validity of the Turkish version of the PUKAT 2.0 was evaluated with linguistic validity, content validity, item validity (item difficulty, discriminating index), and construct validity (known-groups technique) analyses. The reliability of the tool was evaluated by conducting a test–retest analysis.ResultsContent validity index (CVI) for the items (Item-CVI) ranged from 0.83 to 1.00 and the CVI for the scale (Scale-CVI) was 0.95. The difficulty index for 21 items ranged from 0.10 to 0.63. Four items were found to be too difficult. Item discriminating index values ranged from 0.00 to 0.61. The overall intraclass correlation coefficient (ICC) was found to be 0.80.ConclusionThe Turkish version of the Pressure Injury Knowledge Assessment Tool 2.0 (PIKAT 2.0-Tr) is supported by acceptable psychometric properties and can be used to evaluate the knowledge of nurses and nursing students in Turkey about the prevention of PI.     

Proteases and their inhibitors as prognostic factors for high-grade serous ovarian cancer

Ovarian carcinoma is one of the most lethal malignancies, but only very few prognostic biomarkers are known. The degradome, comprising proteases, protease non-proteolytic homologues and inhibitors, have been involved in the prognosis of many cancer types, including ovarian carcinoma. The prognostic significance of the whole degradome family has not been specifically studied in high-grade serous ovarian cancer. A targeted DNA microarray known as the CLIP-CHIP microarray was used to identify potential prognostic factors in ten high-grade serous ovarian cancer women who had early recurrence (<1.6 years) or late/no recurrence after first line surgery and chemotherapy. In women with early recurrence, we identified seven upregulated genes (TMPRSS4, MASP1/3, SPC18, PSMB1, IGFBP2, CFI – encoding Complement Factor I – and MMP9) and one down-regulated gene (ADAM-10). Using immunohistochemistry, we evaluated the prognostic effect of these 8 candidate genes in an independent cohort of 112 high-grade serous ovarian cancer women. Outcomes were progression, defined according to CA-125 criteria, and death. Multivariate Cox proportional hazard regression models were done to estimate the associations between each protein and each outcome. High ADAM-10 expression (intensity of 2–3) was associated with a lower risk of progression (adjusted hazard ratio (HR): 0.51; 95% confidence interval (CI): 0.29-0.87). High complement factor I expression (intensity 2–3) was associated with a higher risk of progression (adjusted HR: 2.30, 95% CI: 1.17–4.53) and death (adjusted HR: 3.42; 95% CI: 1.72–6.79). Overall, we identified the prognostic value of two proteases, ADAM-10 and complement factor I, for high-grade serous ovarian cancer which could have clinical significance.     

Development of an IgG-Fc fusion COVID-19 subunit vaccine,AKS-452

AKS-452 is a biologically-engineered vaccine comprising an Fc fusion protein of the SARS-CoV-2 viral spike protein receptor binding domain antigen (Ag) and human IgG1 Fc (SP/RBD-Fc) in clinical development for the induction and augmentation of neutralizing IgG titers against SARS-CoV-2 viral infection to address the COVID-19 pandemic. The Fc moiety is designed to enhance immunogenicity by increasing uptake via Fc-receptors (FcγR) on Ag-presenting cells (APCs) and prolonging exposure due to neonatal Fc receptor (FcRn) recycling. AKS-452 induced approximately 20-fold greater neutralizing IgG titers in mice relative to those induced by SP/RBD without the Fc moiety and induced comparable long-term neutralizing titers with a single dose vs. two doses. To further enhance immunogenicity, AKS-452 was evaluated in formulations containing a panel of adjuvants in which the water-in-oil adjuvant, Montanide™ ISA 720, enhanced neutralizing IgG titers by approximately 7-fold after one and two doses in mice, including the neutralization of live SARS-CoV-2 virus infection of VERO-E6 cells. Furthermore, ISA 720-adjuvanted AKS-452 was immunogenic in rabbits and non-human primates (NHPs) and protected from infection and clinical symptoms with live SARS-CoV-2 virus in NHPs (USA-WA1/2020 viral strain) and the K18 human ACE2-trangenic (K18-huACE2-Tg) mouse (South African B.1.351 viral variant). These preclinical studies support the initiation of Phase I clinical studies with adjuvanted AKS-452 with the expectation that this room-temperature stable, Fc-fusion subunit vaccine can be rapidly and inexpensively manufactured to provide billions of doses per year especially in regions where the cold-chain is difficult to maintain.