Deployment of an Interdisciplinary Predictive Analytics Task Force to Inform Hospital Operational Decision-Making During the COVID-19 Pandemic

In March 2020, our institution developed an interdisciplinary predictive analytics task force to provide coronavirus disease 2019 (COVID-19) hospital census forecasting to help clinical leaders understand the potential impacts on hospital operations. As the situation unfolded into a pandemic, our task force provided predictive insights through a structured set of visualizations and key messages that have helped the practice to anticipate and react to changing operational needs and opportunities. The framework shared here for the deployment of a COVID-19 predictive analytics task force could be adapted for effective implementation at other institutions to provide evidence-based messaging for operational decision-making. For hospitals without such a structure, immediate consideration may be warranted in light of the devastating COVID-19 third-wave which has arrived for winter 2020–2021.     

A novel low-molecular weight inhibitor of focal adhesion kinase, TAE226, inhibits glioma growth

Glioblastomas are highly lethal cancers that resist current therapies. Novel therapies under development target molecular mechanisms that promote glioblastoma growth. In glioblastoma patient specimens, the non-receptor tyrosine kinase focal adhesion kinase (FAK) is overexpressed. Upon growth factor receptor stimulation or integrin engagement, FAK is activated by phosphorylation on critical tyrosine residues. Activated FAK initiates a signal transduction cascade which promotes glioma growth and invasion by increasing cellular adhesion, migration, invasion, and proliferation. We find that human glioma cell lines express different levels of total FAK protein and activating phosphorylation of tyrosine residues Tyr397, Tyr861, and Tyr925. As all glioma cell lines examined expressed phosphorylated FAK, we examined the efficacy of a novel low-molecular weight inhibitor of FAK, TAE226, against human glioma cell lines. TAE226 inhibited the phosphorylation of FAK as well as the downstream effectors AKT, extracellular signal-related kinase, and S6 ribosomal protein in multiple glioma cell lines. TAE226 induced a concentration-dependent decrease in cellular proliferation with an associated G(2) cell cycle arrest in every cell line and an increase in apoptosis in a cell-line-specific manner. TAE226 also decreased glioma cell adhesion, migration, and invasion through an artificial extracellular matrix. Together, these data demonstrate the potential benefit of TAE226 for glioma therapy.     

Efficacy of systematic lymphadenectomy and adjuvant radiotherapy in node-positive endometrial cancer patients

OBJECTIVE: To assess the efficacy of systematic lymphadenectomy and adjuvant radiotherapy in minimizing pelvic sidewall and para-aortic failures. METHODS: Between January 1984 and December 2001, a total of 146 patients with stage III and IV endometrial cancer and lymph node metastases were treated at our institution. Adequate pelvic lymphadenectomy was defined as the removal of more than 10 pelvic lymph nodes, and adequate para-aortic lymphadenectomy was defined as removal of 5 or more para-aortic lymph nodes. The 24 patients who received adjuvant chemotherapy were excluded. We assessed the ability of adequate pelvic and para-aortic lymphadenectomy, together with radiotherapy, to prevent pelvic and para-aortic recurrences. RESULTS: Of the 122 patients studied, 94 (77%) had adequate pelvic lymphadenectomy and 47 (39%) had adequate para-aortic lymphadenectomy. Pelvic radiotherapy was administered to 78% and para-aortic radiotherapy to 29% of patients. Median follow-up of censored patients was 56 months. Twenty-five percent of patients had pelvic sidewall failure at 5 years. Pelvic sidewall failures at 5 years occurred in 57% of patients who had inadequate node dissection and/or no radiotherapy, compared with 10% for those having both adequate lymphadenectomy and radiotherapy (P < 0.001). After risk factor assessment in a regression model, only treatment with adequate lymphadenectomy and radiotherapy was a significant independent predictor of pelvic control (P = 0.03). The performance of definitive pelvic lymphadenectomy may have increased treatment-related morbidity in the subgroup of patients who had postoperative radiotherapy. For the 41 patients with positive para-aortic lymph nodes, the 5-year para-aortic failure rate was 34% after adequate lymphadenectomy but without adjuvant para-aortic radiotherapy. Likewise, 69% failed in the para-aortic area when adjuvant para-aortic radiotherapy was administered to patients not having adequate para-aortic lymphadenectomy; however, none of the 11 patients failed in the para-aortic area after adequate lymphadenectomy and para-aortic radiotherapy (P = 0.08). CONCLUSIONS: Adequate (pelvic and para-aortic) lymphadenectomy and adjuvant radiotherapy appear complementary in reducing failures in both the pelvis and para-aortic areas in patients with node-positive endometrial cancer.     

Influence of age and magnesium on calcium metabolism in rats

This study evaluates the effect of dietary magnesium concentration on calcium metabolism in rats of differing ages. Young (3 wk) and old (18 mo) Fischer 344 rats were fed the AIN-76A diet modified to contain either low (218 mg/kg) or adequate (419 mg/kg) Mg for 4 wk. Some rats subsequently underwent a metabolic balance study (12 d duration). Other rats were gavaged with approximately 220 KBq (6 microCi) of 47Ca; daily fecal and urine collections were made and periodic whole body radioactivity determined. Femurs were removed and analyzed. Calcium retention and balance were not affected by Mg in young rats. In old rats low Mg intake increased apparent Ca balance. Young rats retained about 3.25 times more of the original dose of 47Ca than did old rats. Young rats retained more 47Ca in the femur than did old rats; Mg intake had little effect. Aging accelerated Ca turnover rate, and whole body retention data suggest that adequate Mg does not significantly reduce Ca turnover.     

Dysgerminoma of the ovary: A retrospective study

A retrospective analysis of 22 patients with ovarian dysgerminoma who were treated between 1980 and 1987 was carried out. The median age at presentation was 24.5 years. A total of 15 patients were in stage I, one patient was in stage II and six patients were in stage III. Bilateral ovarian involvement was present in four patients. Conservative surgery was carried out in nine patients and 11 patients underwent radical surgery. Two patients had biopsy only. Fourteen patients received adjuvant radiotherapy and three patients received salvage radiation for recurrent disease. The 10-year actuarial survival rate was 81.8%. All 15 patients in stage I were alive and disease-free at a median follow-up of 125 months. Four patients (one in stage II and three in stage III) died of progressive or recurrent abdominopelvic disease. Pelvic recurrence occurred after conservative surgery in two patients in stage IA who had a tumour size greater than 10 cm, but they were salvaged with radical surgery, chemotherapy and radiotherapy. There were seven patients aged 20 years or less. All were alive and disease-free at a median follow-up of 127 months.     

Inhibition of VEGF-dependent multistage carcinogenesis by soluble EphA receptors

Elevated expression of Eph receptors has long been correlated with the growth of solid tumors. However, the functional role of this family of receptor tyrosine kinases in carcinogenesis and tumor angiogenesis has not been well characterized. Here we report that soluble EphA receptors inhibit tumor angiogenesis and tumor progression in vivo in the RIP-Tag transgenic model of vascular endothelial growth factor (VEGF)-dependent multistage pancreatic islet cell carcinoma. Soluble EphA receptors delivered either by a transgene or an osmotic minipump inhibited the formation of angiogenic islet, a premalignant lesion, and reduced tumor volume of solid islet cell carcinoma. EphA2-Fc or EphA3-Fc treatment resulted in decreased tumor volume but increased tumor and endothelial cell apoptosis in vivo. In addition, soluble EphA receptors inhibited VEGF and betaTC tumor cell-conditioned medium-induced endothelial cell migration in vitro and VEGF-induced cornea angiogenesis in vivo. A dominant negative EphA2 mutant inhibited--whereas a gain-of-function EphA2 mutant enhanced--tumor cell-induced endothelial cell migration, suggesting that EphA2 receptor activation is required for tumor cell-endothelial cell interaction. These data provide functional evidence for EphA class receptor regulation of VEGF-dependent tumor angiogenesis, suggesting that the EphA signaling pathway may represent an attractive novel target for antiangiogenic therapy in cancer.