Epidemiology of heart failure in rural Chhattisgarh, India.

Background Cardiovascular diseases, including heart failure (HF), are leading causes of death and disability in India. However, most studies in India only include urban populations or rural regions with improved access and may not represent the poorest patients or regions. We studied the epidemiology of HF patients admitted to a secondary care hospital in rural Chhattisgarh, India. Methods We did a retrospective chart review of patients hospitalized with HF in 2018 to obtain their demographic data and risk factors for developing HF. We reviewed echocardio-grams to assign patients to their most probable HF category. Results We studied 88 HF patients with a mean age of 42 years including 55 (62.5%) women. The most common categories of HF were cardiomyopathy (36.8%), rheumatic heart disease (RHD; 25.3%) and right heart failure (RHF; 18.4%). Prior tuberculosis was more prevalent in patients with RHF compared with other types of HF (43.8% v. 13.9%). Conclusions HF patients in this study from rural central India were young and predominantly women. Cardiomyopathy, RHD and RHF due to past tuberculosis were common causes of HF in this population. Further studies are needed to expand upon these single centre findings to better understand the risk factors and outcomes of HF among the rural poor.

Lessons learned from academic medical centers' response to the COVID-19 pandemic in partnership with the Navajo Nation.

INTRODUCTION: Structural forces that drive health inequalities are magnified in crises. This was especially true during the COVID-19 pandemic, and minority communities were particularly affected. The University of California San Francisco and Health, Equity, Action, Leadership Initiative jointly sent volunteer teams of nurses and doctors to work in the Navajo Nation during the COVID-19 pandemic. This presented an opportunity to explore how academic medical centers (AMCs) could effectively partner with vulnerable communities to provide support during healthcare crises. Therefore, the aims of this study were to describe volunteers' perspectives of academic-community partnerships by exploring their personal, professional and societal insights and lessons learned based on their time in the Navajo Nation during COVID-19. METHODS: We recruited key informants using purposeful sampling of physicians and nurses who volunteered to go to the Navajo Nation during the spring 2020 COVID-19 surge, as well as hospital administrators and leaders involved in organizing the COVID-19 efforts. We used in-depth qualitative interviews to explore key informants' experiences pre-departure, during their stay, and after their return, as well as perspectives of the partnership between an AMC and the Navajo Nation. We used thematic analysis to systematically identify, analyze and report patterns (themes) within the data. RESULTS: In total, 37 clinicians and hospital administrators were interviewed including 14 physicians, 16 nurses, and 7 health system leaders. Overall, we found 4 main themes each with several subthemes that defined the partnership between the AMC and the Navajo Nation. Mission and values incorporated civic duty, community engagement, leadership commitment and employee dedication. Solidarity, trust and humility encompassed pre-existing trust, workforce sustainability, humility and erasure of 'savior narratives.' Coordination included logistical coordination, flexibility, selectivity of who and what traveled to the response and coordination around media response. Workforce preparation and support encompassed understanding of historical context and providing healthcare in limited settings, dangers of inadequate preparation and the need for emotional support. CONCLUSION: This study provides guidelines which AMCs might use to develop and improve partnerships they have or would like to develop with vulnerable communities. These guidelines may even be broadly applied to partnerships outside of a pandemic response. Importantly, such partnerships need to be built with trust and with an eye towards sustainability and long-term relationships as opposed to 'medical missions'.

A new mechanism of oxidation in ultrahigh molecular weight polyethylene caused by squalene absorption.

Although synovial fluid lipids were found to absorb in ultrahigh molecular weight polyethylene (UHMWPE) total joint implants in vivo, their effect on the oxidation of the polymer was not known. Current understanding of the oxidation and oxidative stability of UHMWPE joint implants is focused on the presence or elimination of radiation-induced free radicals, which are long-lived and can react with oxygen over the long term. Recently, we found unexplained oxidation in irradiated and melted UHMWPE components that were exposed to bodily fluids then stored on the shelf despite being free of detectable free radicals at the time of implantation. Thus, we hypothesized that lipids absorbed from the synovial fluid in vivo could initiate and accelerate oxidation of UHMWPE even in the absence of detectable residual free radicals. We found that squalene, a precursor in cholesterol synthesis and a synovial fluid lipid with unsaturated bonds, accelerated oxidation in irradiated and melted UHMWPE under in vitro accelerated aging conditions. This result represents a paradigm shift in our understanding of oxidative stability of UHMWPE and prompts further investigation of in vivo oxidation mechanisms as well as the development of relevant in vitro aging models.

The elimination of free radicals in irradiated UHMWPEs with and without vitamin E stabilization by annealing under pressure.

Radiation crosslinking of ultrahigh molecular weight polyethylene (UHMWPE) has been used to decrease the wear of joint implant bearing surfaces. While radiation crosslinking has been successful in decreasing femoral head penetration into UHMWPE acetabular liners in vivo, postirradiation thermal treatment of the polymer is required to ensure the oxidative stability of joint implants in the long term. Two types of thermal treatment have been used: (i) annealing below the melting point preserves the mechanical properties but the residual free radicals trapped in the crystalline regions are not completely eliminated, leading to oxidation in the long-term and (ii) annealing above the melting point (melting) eliminates the free radicals but leads to a decrease in mechanical properties through loss of crystallinity during the melting process. In this study, we hypothesized that free radicals could be reduced by annealing below the melting point under pressure effectively without melting due to the elevation of the melting point. By avoiding the complete melting of UHMWPE, mechanical properties would be preserved. Our hypothesis tested positive in that we found the radiation-induced free radicals to be markedly reduced (below the detection limit of state-of-the-art electron spin resonance) by thermal annealing under pressure in radiation crosslinked virgin UHMWPE and UHMWPE/vitamin-E blends without loss of mechanical properties.

A surface crosslinked UHMWPE stabilized by vitamin E with low wear and high fatigue strength.

Wear particle-induced periprosthetic osteolysis has been a clinical problem driving the development of wear resistant ultrahigh molecular weight polyethylene (UHMWPE) for total joint replacement. Radiation crosslinking has been used to decrease wear through decreased plastic deformation; but crosslinking also reduces mechanical properties including fatigue resistance, a major factor limiting the longevity of joint implants. Reducing UHMWPE wear with minimal detriment to mechanical properties is an unaddressed need for articular bearing surface development. Here we report a novel approach to achieve this by limiting crosslinking to the articular surface. The antioxidant vitamin E reduces crosslinking efficiency in UHMWPE during irradiation with increasing concentration, thus we propose to spatially control the crosslink density distribution by controlling the vitamin E concentration profile. Surface crosslinking UHMWPE prepared using this approach had high wear resistance and decreased crosslinking in the bulk resulting in high fatigue crack propagation resistance. The interface region did not represent a weakness in the material due to the gradual change in the crosslink density. Such an implant has the potential of decreasing risk of fatigue fracture of total joint implants as well as expanding the use of UHMWPE to younger and more active patients.

Transient overexpression of sonic hedgehog alters the architecture and mechanical properties of trabecular bone.

Bone formation and remodeling involve coordinated interactions between osteoblasts and osteoclasts through signaling networks involving a variety of molecular pathways. We hypothesized that overexpression of Sonic hedgehog (Shh), a morphogen with a crucial role in skeletal development, would stimulate osteoblastogenesis and bone formation in adult animals in vivo. Systemic administration of adenovirus expressing the N-terminal form of Shh into adult mice resulted in a primary increase in osteoblasts and their precursors. Surprisingly, however, this was associated with altered trabecular morphology, decreased bone volume, and decreased compressive strength in the vertebrae. Whereas no change was detected in the number of osteoclast precursors, bone marrow stromal cells from Shh-treated mice showed enhanced osteoclastogenic potential in vitro. These effects were mediated by the PTH/PTH-related protein (PTHrP) pathway as evidenced by increased sensitivity to PTH stimulation and upregulation of the PTH/PTHrP receptor (PPR). Together, these data show that Shh has stimulatory effects on osteoprogenitors and osteoblasts in adult animals in vivo, which results in bone remodeling and reduced bone strength because of a secondary increase in osteoclastogenesis.

Effect of cross-link density on the high pressure crystallization of UHMWPE.

Ultrahigh molecular weight polyethylene (UHMWPE) is a bearing surface material for total joint implants. It is radiation cross-linked for high wear resistance and is melted or treated with vitamin E for oxidative stability. We investigated high pressure crystallization (HPC) of irradiated UHMWPE as an alternative method to improve the mechanical strength while stabilizing the residual free radicals from radiation cross-linking. HPC of uncross-linked UHMWPE has resulted in the formation of extended chain crystals and increased crystallinity, leading to improved strength. We hypothesized that increased cross-link density would hinder crystallization during HPC due to decreased chain mobility. Therefore, we investigated the crystalline structure and tensile mechanical properties of high pressure crystallized 25-, 65- and 100-kGy irradiated UHMWPE. We also determined free radical content and wear. The strength of 25- and 65-kGy irradiated UHMWPEs was improved by HPC with increased crystallinity and crystal size. 100-kGy irradiated UHMWPE did not show improved strength, supporting our hypothesis that decreased chain mobility would hinder crystal formation and strength improvement. None of the HPC irradiated UHMWPEs contained detectable free radicals and their wear properties were maintained, suggesting oxidative and mechanical stability in the long term. Therefore, HPC can be used effectively for imparting oxidative stability while strength improvement can be achieved for irradiated UHMWPE with low to moderate cross-link density.