Alex Han

The cranberry flavonoids PAC DP-9 and quercetin aglycone induce cytotoxicity and cell cycle arrest and increase cisplatin sensitivity in ovarian cancer cells

Cranberry flavonoids (flavonols and flavan-3-ols), in addition to their antioxidant properties, have been shown to possess potential in vitro activity against several cancers. However, the difficulty of isolating cranberry compounds has largely limited anticancer research to crude fractions without well-defined compound composition. In this study, individual cranberry flavonoids were isolated to the highest purity achieved so far using gravity and high performance column chromatography and LC-MS characterization. MTS assay indicated differential cell viability reduction of SKOV-3 and OVCAR-8 ovarian cancer cells treated with individual cranberry flavonoids. Treatment with quercetin aglycone and PAC DP-9, which exhibited the strongest activity, induced apoptosis, led to caspase-3 activation and PARP deactivation, and increased sensitivity to cisplatin. Furthermore, immunofluorescence microscopy and western blot study revealed reduced expression and activation of epidermal growth factor receptor (EGFR) in PAC DP-9 treated SKOV-3 cells. In addition, quercetin aglycone and PAC DP-9 deactivated MAPK-ERK pathway, induced downregulation of cyclin D1, DNA-PK, phosphohistone H3 and upregulation of p21, and arrested cell cycle progression. Overall, this study demonstrates promising in vitro cytotoxic and anti-proliferative properties of two newly characterized cranberry flavonoids, quercetin aglycone and PAC DP-9, against ovarian cancer cells.

Effect of Sarcopenia on Postoperative Morbidity and Mortality After Thoracolumbar Spine Surgery.

Sarcopenia is the loss of muscle mass associated with aging and advanced disease. This study retrospectively examined patients older than 55 years (N=46) who underwent thoracolumbar spine surgery between 2003 and 2015. Each patients comorbidity burden was determined using the Charlson Comorbidity Index, and the Mirza Surgical Invasiveness Index was used to measure procedural complexity. Sarcopenia was diagnosed by measuring the total cross-sectional area of the psoas muscle at the L4 vertebrae using perioperative computed tomography scans. Of the 46 patients assessed, 16 were in the lowest third for L4 total psoas area (sarcopenic). Average follow-up time was 5.2 years (range, 6 days to 12.7 years). The cohort of patients with sarcopenia was significantly older than the cohort without sarcopenia (mean age, 76.4 vs 69.9 years; P=.01) but did not have a significantly different mean Charlson Comorbidity Index (3.3 vs 2.0; P=.32) or mean Mirza Surgical Invasiveness Index (7.1 vs 7.0; P=.49). Patients with sarcopenia had a hospital length of stay 1.7-fold longer than those without sarcopenia (8.1 vs 4.7 days; P=.02) and a 3-fold increase in postoperative in-hospital complications (1.2 vs 0.4; P=.02), and they were more likely to require discharge to a rehabilitation or nursing facility (81.2% vs 43.3%; P=.006). Patients with sarcopenia had a significantly lower cumulative survival (log rank=0.007). All 4 deaths occurred among patients with sarcopenia. Patients with sarcopenia have a significantly increased risk of in-hospital complications, longer length of stay, increased rates of discharge to rehabilitation facilities, and increased mortality following thoracolumbar spinal surgery, making sarcopenia a useful perioperative risk stratification tool. [Orthopedics. 2016; 39(6):e1159-e1164.].

HE4 expression is associated with hormonal elements and mediated by importin-dependent nuclear translocation

Antiestrogens including tamoxifen and fulvestrant have been evaluated as chemotherapeutics for ovarian cancer, particularly in cases of platinum resistant disease. Human epididymis protein 4 (HE4) is highly overexpressed in women with ovarian cancer and overexpression of HE4 has been found to correlate with platinum resistance. However, the role of HE4 in modulating responses to hormones and hormonal therapy has not been characterized in ovarian cancer. Here we demonstrate that 17β-estradiol, tamoxifen, and fulvestrant induce nuclear and nucleolar translocation of HE4 and that HE4 overexpression induces resistance to antiestrogens. HE4 was found to interact with estrogen receptor-α (ER-α), and HE4 overexpression resulted in ER-α downregulation in vitro and in human ovarian cancers. We identified a novel role for importin-4 in governing the nuclear transport of HE4. Treatment with ivermectin, an importin inhibitor, blocked HE4/importin-4 nuclear accumulation and sensitized HE4-overexpressing ovarian cancer cells to fulvestrant and tamoxifen.

Readability of Patient Education Materials on the American Orthopaedic Society for Sports Medicine Website

Abstract Background: The recommended readability of patient education materials by the American Medical Association (AMA) and National Institutes of Health (NIH) should be no greater than a sixth-grade reading level. However, online resources may be too complex for some patients to understand, and poor health literacy predicts inferior health–related quality of life outcomes. Aim: This study evaluated whether the American Orthopaedic Society for Sports Medicine (AOSSM) websites patient education materials meet recommended readability guidelines for medical information. We hypothesized that the readability of these online materials would have a Flesch-Kincaid formula grade above the sixth grade. Methods: All 65 patient education entries of the AOSSM website were analyzed for grade level readability using the Flesch-Kincaid formula, a widely used and validated tool to evaluate the text reading level. Results: The average (standard deviation) readability of all 65 articles was grade level 10.03 (1.44); 64 articles had a readability score above the sixth-grade level, which is the maximum level recommended by the AMA and NIH. Mean readability of the articles exceeded this level by 4.03 grade levels (95% CI, 3.7–4.4; P < 0.0001). We found post-hoc that only 7 articles had a readability score ≤ an eighth-grade level, the average reading level of US adults. Mean readability of the articles exceeded this level by 2.03 grade levels (95% CI, 1.7–2.4; P < 0.0001). Conclusion: The readability of online AOSSM patient education materials exceeds the readability level recommended by the AMA and NIH, and is above the average reading level of the majority of US adults. This online information may be of limited utility to most patients due to a lack of comprehension. Our study provides a clear example of the need to improve the readability of specific education material in order to maximize the efficacy of multimedia sources.

The Use of Dehydrated Human Amnion/Chorion Membrane Allograft Injection for the Treatment of Tendinopathy or Arthritis: A Case Series Involving 40 Patients

Degenerative joint and tendon injuries remain difficult to treat, with few effective conservative treatment options available. Regenerative approaches aim to promote the inherent healing capacity of injured tissues. Micronized dehydrated human amnion/chorion membrane (dHACM) injection is an emerging regenerative option with promising preclinical results.

Tetrathiomolybdate mediates cisplatin-induced p38 signaling and EGFR degradation and enhances response to cisplatin therapy in gynecologic cancers

Cisplatin and its analogs are among the most widely used chemotherapeutic agents against various types of cancer. It is known that cisplatin can activate epidermal growth factor receptor (EGFR), which may provide a survival benefit in cancers. Tetrathiomolybdate (TM) is a potent anti-cancer and anti-angiogenic agent and has been investigated in a number of clinical trials for cancer. In this study, we explore the therapeutic potential of TM on cisplatin-mediated EGFR regulation. Our study shows that TM is not cytotoxic, but exerts an anti-proliferative effect in ECC-1 cells. However, TM treatment prior to cisplatin markedly improves cisplatin-induced cytotoxicity. TM suppressed cisplatin-induced activation of EGFR while potentiating activation of p38; the activation of p38 signaling appeared to promote cisplatin-induced EGFR degradation. These results are in contrast to what we saw when cells were co-treated with cisplatin plus an EGFR tyrosine kinase inhibitor, where receptor activation was inhibited but receptor degradation was also blocked. Our current study is in agreement with previous findings that TM may have a therapeutic benefit by inhibiting EGFR activation. We furthermore provide evidence that TM may provide an additional benefit by potentiating p38 activation following cisplatin treatment, which may in turn promote receptor degradation by cisplatin.

Inpatient costs and blood transfusion rates of sarcopenic patients following thoracolumbar spine surgery

OBJECTIVE Sarcopenia, the muscle atrophy associated with aging and disease progression, accounts for nearly

Diagnostic Criteria and Clinical Outcomes in Sarcopenia Research: A Literature Review

18.5 billion in health care expenditures annually. Given the high prevalence of sarcopenia in patients undergoing orthopedic surgery, the goal of this study was to assess the impact of sarcopenia on inpatient costs following thoracolumbar spine surgery. METHODS Patients older than 55 years undergoing thoracolumbar spine surgery from 2003 to 2015 were retrospectively analyzed. Sarcopenia was measured using total psoas area at the L-4 vertebra on perioperative CT scans. Hospital billing data were used to compare inpatient costs, transfusion rate, and rate of advanced imaging utilization. RESULTS Of the 50 patients assessed, 16 were sarcopenic. Mean total hospital costs were 1.75-fold greater for sarcopenic patients compared with nonsarcopenic patients (

Developments in trapezium replacements

53,128 vs

Current trends in the management of trapeziometacarpal arthritis

30,292, p = 0.04). Sarcopenic patients were 2.1 times as likely to require a blood transfusion (43.8% vs 20.6%, p = 0.04). Sarcopenic patients had a 2.6-fold greater usage of advanced imaging (68.8% vs 26.5%, p = 0.002) with associated higher diagnostic imaging costs (