Targeted therapies for the treatment of soft tissue sarcoma.

Soft tissue sarcomas are rare malignant tumors derived from mesenchymal cells that have a high morbidity and mortality related to frequent occurrence of advanced and metastatic disease. Over the past two decades there have been significant advances in the use of targeted therapies for the treatment of soft tissue sarcoma. The ability to study various cellular markers and pathways related to sarcomagenesis has led to the creation and approval of multiple novel therapies. Herein, we describe the current landscape of targeted medications used in the management of advanced or metastatic soft tissue sarcomas, excluding GIST. We distinguish three categories: targeted therapies that have current US Food and Drug Administration (FDA) approval for treatment of soft tissue sarcoma, non-FDA approved targeted therapies, and medications in development for treatment of patients with soft tissue sarcoma.

Emerging targeted and cellular therapies in the treatment of advanced and metastatic synovial sarcoma.

Synovial sarcoma is a soft tissue sarcoma accounting for approximately 1,000 cases per year in the United States. Currently, standard treatment of advanced and metastatic synovial sarcoma is anthracycline-based chemotherapy. While advanced synovial sarcoma is more responsive to chemotherapy compared to other soft tissue sarcomas, survival rates are poor, with a median survival time of less than 18 months. Enhanced understanding of tumor antigen expression and molecular mechanisms behind synovial sarcoma provide potential targets for treatment. Adoptive Cell Transfer using engineered T-cell receptors is in clinical trials for treatment of synovial sarcoma, specifically targeting New York esophageal squamous cell carcinoma-1 (NY-ESO-1), preferentially expressed antigen in melanoma (PRAME), and melanoma antigen-A4 (MAGE-A4). In this review, we explore the opportunities and challenges of these treatments. We also describe artificial adjuvant vector cells (aAVCs) and BRD9 inhibitors, two additional potential targets for treatment of advanced synovial sarcoma. This review demonstrates the progress that has been made in treatment of synovial sarcoma and highlights the future study and qualification needed to implement these technologies as standard of care.

The Ignatian Examen in Medical Practice: A Model for Clinicians.

St. Ignatius of Loyola created The Examination of Conscience (The Examen) as a daily practice for spiritual and moral formation by cultivating awareness, gratitude, and generosity. For five hundred years, people of various cultures and creeds have learned The Examen from the Jesuits and adapted it for personal reflection and spiritual growth. The practice of medicine requires dedicated time to reflect on personal and professional development, to improve oneself and advance patient care and health equity. Here we present a model for use of The Examen in medical practice.

An innovative approach to teaching cross-cultural communication among dental students.

Introduction There is a lack of concordance in demographics between dental professionals and their patients. Professional organisations have recognised the necessity of cultural competency training in dental education. This study sought to employ and evaluate a novel intervention in cultural competency training on cross-cultural communication for undergraduate dental students.Material and methods The session employed dyad training, roleplaying, Kleinman's Explanatory Model and introduced the new 'Model for Negotiating Across Cultures', applied to patients' cultures. Learners included 24 first-year and 27 third-year dental students. Evaluation compared pre- and post-intervention responses to the modified Health Belief Attitudes Survey (HBAS). Paired t-tests were conducted to determine difference in pre- and post-intervention scores.Results For first-year students, the mean difference improvement between the pre- and post-intervention surveys for each HBAS domain was statistically significant (p <0.05). For the third-year students, improvement was significant in all domains except for quality (p = 0.083).Discussion Dental students were found to have improved cultural competency scores by the HBAS. Implementation of this educational intervention demonstrates a paradigm that could be implemented for cross-cultural communication.Conclusion The intervention can be utilised as a resource for cross-cultural communication education for dental students and could be expanded for all health professional students.

Analysis of Physeal Fractures from the United States National Trauma Data Bank.

BACKGROUND: Pediatric long-bone physeal fractures can lead to growth deformities. Previous studies have reported that physeal fractures make up 18-30% of total fractures. This study aimed to characterize physeal fractures with respect to sex, age, anatomic location, and Salter-Harris (SH) classification from a current multicenter national database. METHODS: A retrospective cohort study was performed using the 2016 United States National Trauma Data Bank (NTDB). Patients ≤ 18 years of age with a fracture of the humerus, radius, ulna, femur, tibia, or fibula were included. RESULTS: The NTDB captured 132,018 patients and 58,015 total fractures. Physeal fractures made up 5.7% (3291) of all long-bone fractures, with males accounting for 71.0% (2338). Lower extremity physeal injuries comprised 58.6% (1929) of all physeal fractures. The most common site of physeal injury was the tibia comprising 31.8% (1047), 73.9% (774) of which were distal tibia fractures. Physeal fractures were greatest at 11 years of age for females and 14 years of age for males. Most fractures were SH Type II fractures. DISCUSSION AND CONCLUSIONS: Our analysis indicates that 5.7% of pediatric long-bone fractures involved the physis, with the distal tibia being the most common. These findings suggest a lower incidence of physeal fractures than previous studies and warrant further investigation.

Patient desire for spiritual assessment is unmet in urban and rural primary care settings.

BACKGROUND: Incorporation of patient religious and spiritual beliefs in medical care has been shown to improve the efficacy of medical interventions and health outcomes. While previous study has highlighted differences in patient desire for spiritual assessment based on patient religiosity, little is known about patient desire for spiritual assessment based on community type, particularly in urban compared to rural communities. We hypothesized that, given demographic trends which show a higher degree of religiosity in rural areas, patients in rural communities will be more likely to desire spiritual assessment. METHODS: In this cross-sectional study of 141 adult primary care patients in rural and urban Colorado at non-religiously affiliated clinics, we surveyed patient demographic information, measures of religiosity, patient desire for spiritual assessment, and frequency of spiritual assessment in practice. Univariate logistic regression analyses were used to compare the two populations. RESULTS: In both Denver County (urban) and Lincoln County (rural) over 90% of patients identified as religious, spiritual, or a combination of the two. Thirty eight percent (38.3%) of patients in Denver County and 49.1% of patients in Lincoln desired spiritual assessment. Over 97% of patients in both areas reported rarely or never being asked about their R/S within the past year. For patients who have had five or more clinic visits in the past year, more than 91% in both areas stated they have never or rarely been asked about their beliefs. CONCLUSIONS: While the majority of patients in this study identify as religious or spiritual and many patients desire spiritual assessment, the majority of patients have never or rarely been asked about their spirituality within the past year. This demonstrates a significant gap between patient preference and provider practice of spiritual assessment in the primary care setting, which was similar in both rural and urban settings. This highlights the need for interdisciplinary focus on spiritual assessment and incorporation of patient R/S beliefs in medical care to provide holistic patient care and improve health outcomes.

Counteracting Throwaway Culture in Daily Clinical Practice.

Since his election in March 2013, Pope Francis has brought significant attention to the concept of "throwaway culture." This moral paradigm-which has been defined by Francis in various speeches and the encyclical Laudato si'-characterizes a present-day culture in which food, disposable objects, and even human beings themselves are "discarded as 'unnecessary.'" As Catholic physicians, it is our duty to ensure that we are working to counteract throwaway culture in our daily clinical practice by embracing and exhibiting a culture of encounter. When throwaway culture is discussed within the context of medical practice, it is easy to think of major life and systemic issues including abortion, assistive reproductive technology, physician assisted suicide, and so on. However, rejection of throwaway culture has much broader implications for Catholic physicians. We are called to resist this perverse culture whenever we experience a situation that requires special attention to the respect of human dignity. In this article, we present two common situations encountered in clinical practice in which it is essential to counteract throwaway culture and embrace a culture of encounter: in working with patients who are isolation settings and those who require translation services. Various studies are cited which demonstrate a lack of respect for human dignity that can be seen when working with these patient populations, and recommendations are provided which illustrate how to embrace a culture of encounter in each scenario. The authors conclude that through adoption of a culture of encounter, Catholic physicians as a community can be role models for coworkers, trainees, and students, promoting a culture in which we validate human dignity and ensure the quality and just care of even our most vulnerable patients. SUMMARY: Pope Francis had defined a "throwaway culture" in which "Human life, the person, are no longer seen as a primary value to be respected and safeguarded." In this article we present two common situations encountered in clinical practice in which it is essential to counteract throwaway culture and embrace a culture of encounter: in working with patients who are isolation settings and those who require translation services. We conclude that, as Catholic physicians, it is our duty to ensure that we are working to counteract throwaway culture in our daily clinical practice by embracing and exhibiting a culture of encounter.

Rabbit Model of Physeal Injury for the Evaluation of Regenerative Medicine Approaches.

Physeal injuries can lead to bony repair tissue formation, known as a bony bar. This can result in growth arrest or angular deformity, which is devastating for children who have not yet reached their full height. Current clinical treatment involves resecting the bony bar and replacing it with a fat graft to prevent further bone formation and growth disturbance, but these treatments frequently fail to do so and require additional interventions. Novel treatments that could prevent bone formation but also regenerate the injured physeal cartilage and restore normal bone elongation are warranted. To test the efficacy of these treatments, animal models that emulate human physeal injury are necessary. The rabbit model of physeal injury quickly establishes a bony bar, which can then be resected to test new treatments. Although numerous rabbit models have been reported, they vary in terms of size and location of the injury, tools used to create the injury, and methods to assess the repair tissue, making comparisons between studies difficult. The study presented here provides a detailed method to create a rabbit model of proximal tibia physeal injury using a two-stage procedure. The first procedure involves unilateral removal of 25% of the physis in a 6-week-old New Zealand white rabbit. This consistently leads to a bony bar, significant limb length discrepancy, and angular deformity within 3 weeks. The second surgical procedure involves bony bar resection and treatment. In this study, we tested the implantation of a fat graft and a photopolymerizable hydrogel as a proof of concept that injectable materials could be delivered into this type of injury. At 8 weeks post-treatment, we measured limb length, tibial angle, and performed imaging and histology of the repair tissue. By providing a detailed, easy to reproduce methodology to perform the physeal injury and test novel treatments after bony bar resection, comparisons between studies can be made and facilitate translation of promising therapies toward clinical use. Impact Statement This study provides details to create a rabbit model of physeal injury that can facilitate comparisons between studies and test novel regenerative medicine approaches. Furthermore, this model mimics the human, clinical situation that requires a bony bar resection followed by treatment. In addition, identification of a suitable treatment can be seen in the correction of the growth deformity, allowing this model to facilitate the development of novel physeal cartilage regenerative medicine approaches.