Predicting the Severity and Prognosis of Trismus after Intensity-Modulated Radiation Therapy for Oral Cancer Patients by Magnetic Resonance Imaging

To develop magnetic resonance imaging (MRI) indicators to predict trismus outcome for post-operative oral cavity cancer patients who received adjuvant intensity-modulated radiation therapy (IMRT), 22 patients with oral cancer treated with IMRT were studied over a two-year period. Signal abnormality scores (SA scores) were computed from Likert-type ratings of the abnormalities of nine masticator structures and compared with the Mann-Whitney U-test and Kruskal–Wallis one-way ANOVA test between groups. Seventeen patients (77.3%) experienced different degrees of trismus during the two-year follow-up period. The SA score correlated with the trismus grade (r = 0.52, p<0.005). Patients having progressive trismus had higher mean doses of radiation to multiple structures, including the masticator and lateral pterygoid muscles, and the parotid gland (p<0.05). In addition, this group also had higher SA-masticator muscle dose product at 6 months and SA scores at 12 months (p<0.05). At the optimum cut-off points of 0.38 for the propensity score, the sensitivity was 100% and the specificity was 93% for predicting the prognosis of the trismus patients. The SA score, as determined using MRI, can reflect the radiation injury and correlate to trismus severity. Together with the radiation dose, it could serve as a useful biomarker to predict the outcome and guide the management of trismus following radiation therapy

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

A scoping review of medical professionalism research published in the Chinese language

Abstract Background The Chinese Medical Doctors Association (CMDA) adopted the Charter of Medical Professionalism in the New Millennium (Charter) and published the Chinese Medical Doctor Declaration (Declaration). This is an important step to re-building medical professionalism in China at a time when the commercialization of health care has led to a decline in physician accountability and public trust in the profession. In response, authors have begun to examine and promote medical professionalism in China. This study aims to present the key research themes, identify research gaps and offer recommendations from reviewing the increasing pool of Chinese-language literature on medical professionalism. Methods A scoping review of Chinese language papers was conducted using the China National Knowledge Infrastructure (including China Academic Journals Full-text Database, China Doctoral Dissertations Full-text Database, Masters’ Theses Full-text Database, China Core Newspapers Full-text Database, and China Yearbooks Full-text Database) (CNKI) database. Results Four major research themes were identified in Chinese discourse: (1) teaching professionalism, (2) practicing professionalism, (3) conceptualizing professionalism and (4) assessing professionalism. Overall, authors were concerned with the cultivation of humanism in physicians and emphasized the importance of communication skills to improve the physician-patient relationship in China. They explored the role of traditional Chinese values, such as Confucian and Taoist values, as well as the Communist Party’s political values, in promoting professional behaviour. Conclusions Authors demonstrate increasing interest in medical professionalism in China. The literature is of variable quality and further empirical studies are required in order to evaluate teaching interventions and guide professionalism assessment. A common professionalism framework is absent and could be developed with consideration to China’s socio-cultural context

Role of pH Value in Clinically Relevant Diagnosis

As a highly influential physiological factor, pH may be leveraged as a tool to diagnose physiological state. It may be especially suitable for diagnosing and assessing skin structure and wound status. Multiple innovative and elegant smart wound dressings combined with either pH sensors or drug control-released carriers have been extensively studied. Increasing our understanding of the role of pH value in clinically relevant diagnostics should assist clinicians and improve personal health management in the home. In this review, we summarized a number of articles and discussed the role of pH on the skin surface as well as the factors that influence skin pH and pH-relevant skin diseases, but also the relationship of skin pH to the wound healing process, including its influence on the activity of proteases, bacterial enterotoxin, and some antibacterial agents. A great number of papers discussing physiological pH value have been published in recent decades, far too many to be included in this review. Here, we have focused on the impact of pH on wounds and skin with an emphasis on clinically relevant diagnosis toward effective treatment. We have also summarized the differences in skin structure and wound care between adults and infants, noting that infants have fragile skin and poor skin barriers, which makes them more vulnerable to skin damage and compels particular care, especially for wounds

Comparison of Indexes to Measure Comorbidity Burden and Predict All-Cause Mortality in Rheumatoid Arthritis

Objectives: To examine the comorbidity burden in patients with rheumatoid arthritis (RA) patients using a nationwide population-based cohort by assessing the Charlson Comorbidity Index (CCI), Elixhauser Comorbidity Index (ECI), Multimorbidity Index (MMI), and Rheumatic Disease Comorbidity Index (RDCI) scores and to investigate their predictive ability for all-cause mortality. Methods: We identified 24,767 RA patients diagnosed from 1998 to 2008 in Taiwan and followed up until 31 December 2013. The incidence of comorbidities was estimated in three periods (before, during, and after the diagnostic period). The incidence rate ratios were calculated by comparing during vs. before and after vs. before the diagnostic period. One- and 5-year mortality rates were calculated and discriminated by low and high-score groups and modified models for each index. Results: The mean score at diagnosis was 0.8 in CCI, 2.8 in ECI, 0.7 in MMI, and 1.3 in RDCI, and annual percentage changes are 11.0%, 11.3%, 9.7%, and 6.8%, respectively. The incidence of any increase in the comorbidity index was significantly higher in the periods of &ldquo;during&rdquo; and &ldquo;after&rdquo; the RA diagnosis (incidence rate ratios for different indexes: 1.33&ndash;2.77). The mortality rate significantly differed between the high and low-score groups measured by each index (adjusted hazard ratios: 2.5&ndash;4.3 for different indexes). CCI was slightly better in the prediction of 1- and 5-year mortality rates. Conclusions: Comorbidities are common before and after RA diagnosis, and the rate of accumulation accelerates after RA diagnosis. All four comorbidity indexes are useful to measure the temporal changes and to predict mortality

Adaptor proteins NUMB and NUMBL promote cell cycle withdrawal by targeting ERBB2 for degradation

Failure of trabecular myocytes to undergo appropriate cell cycle withdrawal leads to ventricular noncompaction and heart failure. Signaling of growth factor receptor ERBB2 is critical for myocyte proliferation and trabeculation. However, the mechanisms underlying appropriate downregulation of trabecular ERBB2 signaling are little understood. Here, we have found that the endocytic adaptor proteins NUMB and NUMBL were required for downregulation of ERBB2 signaling in maturing trabeculae. Loss of NUMB and NUMBL resulted in a partial block of late endosome formation, resulting in sustained ERBB2 signaling and STAT5 activation. Unexpectedly, activated STAT5 overrode Hippo-mediated inhibition and drove YAP1 to the nucleus. Consequent aberrant cardiomyocyte proliferation resulted in ventricular noncompaction that was markedly rescued by heterozygous loss of function of either ERBB2 or YAP1. Further investigations revealed that NUMB and NUMBL interacted with small GTPase Rab7 to transition ERBB2 from early to late endosome for degradation. Our studies provide insight into mechanisms by which NUMB and NUMBL promote cardiomyocyte cell cycle withdrawal and highlight previously unsuspected connections between pathways that are important for cardiomyocyte cell cycle reentry, with relevance to ventricular noncompaction cardiomyopathy and regenerative medicine

Factors related to the time to cryptorchidism surgery—A nationwide, population-based study in Taiwan

Current guidelines recommend that the optimal timing for cryptorchidism surgery is by the age of 12 months. This study investigated the trend of surgical timing and examined the factors associated with time to surgery for cryptorchidism in Taiwan by using a nationwide, population-based database. Methods: The present study utilized the Longitudinal Health Insurance Database 2005, a subset of the National Health Insurance Research Database, which contains data on all paid medical benefit claims over the period 1997–2007 for a subset of 1 million beneficiaries randomly drawn from 22.72 million individuals enrolled in the National Health Insurance program in 2005. We analyzed the timing of surgery in boys younger than 18 years with diagnosis of cryptorchidism. Results: We identified 547 boys who underwent surgery under 18 years of age. Approximately 79.2% of study participants received surgery after the age of 12 months. A multivariate analysis showed that several factors were significantly associated with time to surgery: age of the physician making the diagnosis, age of the surgeon performing the surgery, age of the patient at the first diagnosis of cryptorchidism, and number of previous clinic visits with the diagnosis of cryptorchidism and urbanization level of the patient’s residence. Conclusion: A surprisingly high rate (79.2%) of all study participants underwent surgery beyond the optimal timing. Certain doctor and patient factors were associated with time to cryptorchidism surgery. Improving the alertness and education of parents and specialists may lead to earlier surgeries

Can mesenchymal stem cell lysate reverse aging?

Recent findings regarding uses of adipose-derived mesenchymal stem cell (MSC)-lysate on weight loss and improved glucose tolerance in mice on a high-fat diet suggest an encouraging possibility of using MSC lysate for an anti-aging intervention in humans. However, weight loss and lipopenia during late life can be as life-threatening as hyperglycemia during early adulthood. For this 3-year lifelong experiment, a total of 92 rats were randomized into the vehicle-injected group (F=22; M=24) and the MSC lysate injected group (F=22, M=24). We examined longevity, spontaneous locomotor activity, and body composition in rats maintained on a normal diet and received an intermittent treatment of human adipose-derived MSC lysate (3 times a week, 11 times a month given every second month), starting at 12 months of age until natural death. In substantiating previous knowledge regarding the effects of long-term MSC lysate treatments on fat loss and insulin resistance, the present findings also highlighted a shortened average lifespan, a longer inactive time, and a greater bone loss with a relative increase of lean mass in MSC lysate rats with respect to controls. Conclusion: Our data suggest that MSC lysate treatments stimulate disparity in tissue development and produce a cachexia-like effect to decrease longevity