Osteoarthritic human chondrocytes proliferate in 3D co‐culture with mesenchymal stem cells in suspension bioreactors

Osteoarthritis (OA) is a painful disease, characterized by progressive surface erosion of articular cartilage. The use of human articular chondrocytes (hACs) sourced from OA patients has been proposed as a potential therapy for cartilage repair, but this approach is limited by the lack of scalable methods to produce clinically relevant quantities of cartilage‐generating cells. Previous studies in static culture have shown that hACs co‐cultured with human mesenchymal stem cells (hMSCs) as 3D pellets can upregulate proliferation and generate neocartilage with enhanced functional matrix formation relative to that produced from either cell type alone. However, because static culture flasks are not readily amenable to scale up, scalable suspension bioreactors were investigated to determine if they could support the co‐culture of hMSCs and OA hACs under serum‐free conditions to facilitate clinical translation of this approach. When hACs and hMSCs (1:3 ratio) were inoculated at 20,000 cells/ml into 125‐ml suspension bioreactors and fed weekly, they spontaneously formed 3D aggregates and proliferated, resulting in a 4.75‐fold increase over 16 days. Whereas the apparent growth rate was lower than that achieved during co‐culture as a 2D monolayer in static culture flasks, bioreactor co‐culture as 3D aggregates resulted in a significantly lower collagen I to II mRNA expression ratio and more than double the glycosaminoglycan/DNA content (5.8 vs. 2.5 μg/μg). The proliferation of hMSCs and hACs as 3D aggregates in serum‐free suspension culture demonstrates that scalable bioreactors represent an accessible platform capable of supporting the generation of clinical quantities of cells for use in cell‐based cartilage repair.     

Practice-Based Research Priorities for Palliative Care: Results From a Research-to-Practice Consensus Workshop

We employed the research-to-practice consensus workshop (RTP; workshops held in New York City and Tompkins County, New York, in 2013) model to merge researcher and practitioner views of translational research priorities in palliative care. In the RTP approach, a diverse group of frontline providers generates a research agenda for palliative care in collaboration with researchers. We have presented the major workshop recommendations and contrasted the practice-based research priorities with those of previous consensus efforts. We uncovered notable differences and found that the RTP model can produce unique insights into research priorities. Integrating practitioner-identified needs into research priorities for palliative care can contribute to addressing palliative care more effectively as a public health issue.Over the past 2 decades, palliative care has become established as a promising approach for addressing the needs of individuals with life-threatening illnesses from a holistic, interdisciplinary perspective. For this project, we defined palliative care as an approach that improves the quality of life of patients and families facing the problems encountered in life-threatening illness by preventing and relieving suffering. Core components of palliative care include providing relief from pain and other distressing symptoms, affirming dying as a normal process, integrating psychological and spiritual aspects of care, enhancing the quality of life of patients, and offering support systems to patients and their families to help them live as fully as possible until death occurs.Research suggests that palliative care results in positive patient outcomes, greater patient and family satisfaction, and significant cost savings.1,2 The American Public Health Association, the World Health Organization, and the Institute of Medicine3–6 have identified the development of a robust palliative care delivery system as a key public health issue because of the documented ability of palliative care to deliver effective and efficient patient- and symptom-focused care to a growing population in need.In its 2013 report the American Public Health Association specifically detailed the public health implications of palliative care, acknowledged the growing burden of advanced chronic illness and disease in older adults, and recommended key steps to address the problem. This policy statement called for federal, state, and local efforts to promote effective symptom management in populations with serious illness or at the end of life. Other recommended initiatives included the development of a palliative care workforce, educational programs to improve uptake and use of palliative and hospice care, and research funding to support the expansion of palliative care initiatives. Achieving these goals will require moving beyond traditional medical practices to include both policies and initiatives at the public health level.Despite the potential of palliative care to address the mental and physical health needs of individuals with advanced illness, significant knowledge gaps impede its reach and effectiveness. Reports from scientific bodies and consensus workshops have highlighted weaknesses in the literature and called for more research on palliative care and improved research methods.7–10 Thus, although both interest in and demand for palliative care are increasing, reviews of the knowledge base continue to lament the lack of research on many key issues.11,12Especially urgent is a research agenda that fits most closely with the needs of providers who deliver palliative care. The systematic engagement of community practitioners in a consensus process can lead to particularly useful and actionable recommendations for research,13–15 which are greatly needed at this stage in the development of the field. Therefore, to shed new light on research priorities in palliative care, we used a structured, participatory method designed to solicit practitioner input on research priorities: the research-to-practice consensus workshop (RTP) model.16We employed the RTP approach to identify knowledge gaps and types of studies that should be conducted to improve providers’ ability to deliver palliative care most effectively. This model harnesses practice wisdom by engaging clinicians, agency staff, and other practitioners with researchers in a process of articulating and refining research questions and research priorities that honors scientific expertise and practice wisdom.     

Paradoxical preexcitation during cryoablation of a concealed parahisian accessory pathway

A 16‐year‐old male presented with an orthodromic atrioventricular reentrant tachycardia over a concealed parahisian accessory pathway (AP). Cryoablation of the AP resulted in transient manifestation of a fully preexcited sinus rhythm of parahisian AP morphology. Potential causes for the paradoxical preexcitation include inadvertent atrioventricular nodal block, sourse‐sink mismatch, as well as the activation of a dormant AP capable of anterograde conduction.     

Drainage of the inferior vena cava to the left atrium

Drainage of the inferior vena cava to the left atrium is an extremely unusual congenital heart disease. We describe a 54-year-old woman, in whom the diagnosis was suggested by transthoracic echocardiography, and then confirmed by a transesophageal exam and magnetic resonance imaging, which also revealed an associated secundum atrial septal defect. Surgical management involved reconstruction of the interatrial septum to include the inferior vena cava in the right atrium. The few previously reported cases in the literature are reviewed.     

3p21, 5q21, 9p21 and 17p13.1 allelic deletions are potential markers of individuals with a high risk of developing adenocarcinoma in Barrett's epithelium without dysplasia

BACKGROUND/AIMS: A common genetic abnormality detected in Barrett's adenocarcinoma is LOH (loss of heterozygosity) at the sites of known or putative tumor suppressor genes. Thus, some deletions have also been determined in peritumoral Barrett's epithelium. These findings suggest that a tissue field of somatic genetic alterations precede the histopathological phenotypic changes of carcinoma. We investigated 32 cases of Barrett's esophagus with no evidence of dysplasia for LOH at 5q21 (APC), 3p21, 9p21 (p16) and 17p13.1 (p53) chromosomal regions. METHODOLOGY: Two groups were randomly selected and compared: 16 cases of Barrett's epithelium adjacent to adenocarcinoma and 16 cases of Barrett's epithelium with no evidence of malignant transformation in a 5-10 years follow-up period. In three adenocarcinomas cases several previous endoscopic biopsies of Barrett's esophagus were available. RESULTS: We determined frequent allelic losses in adenocarcinomas at p53 (54%), p16 (50%), 3p21 (40%) and 5q21 (33%). Identical LOH was present in most cases in the Barrett's epithelium adjacent to adenocarcinoma. LOH at these loci was unusual in Barrett's epithelium with no evidence of malignant transformation. However, in cases where sequential endoscopic biopsies were performed in advance to the adenocarcinoma diagnosis LOH was already present in the Barrett's epithelium. CONCLUSIONS: We suggest that LOH at these loci may be present before the onset of the malignant growth and LOH studies may supplement the histopathological evaluation of Barrett's epithelium. LOH at 3p21, 5q21, 9p21 and 17p13 chromosomal regions in cells of Barrett's epithelium without dysplasia may have a role as a potential marker for individuals with a high risk of developing adenocarcinoma.