They do their utmost: promise and limits of palliative care in two refugee camps in Rwanda, a qualitative study.

After often gruelling journeys, some refugees arrive at secure locations with severe injury or illness. Others find themselves shortly thereafter facing a life-limiting health condition. Palliative care has been the focus of recent research, and of academic and aid sector dialogue. In this study, we ask: What are experiences and needs of patients and care providers? What opportunities and obstacles exist to enhance or introduce means of reducing suffering for patients facing serious illness and injury in crisis settings? We present findings of a qualitative sub-study within a larger programme of research exploring moral and practical dimensions of palliative care in humanitarian crisis contexts. This paper presents vignettes about palliative care from refugees and care providers in two refugee camps in Rwanda, and is among the first to provide empirical evidence on first-hand experiences of individuals who have fled protracted conflict and face dying far from home. Along with narratives of their experiences, participants provided a range of recommendations from small (micro) interventions that are low cost, but high impact, through to larger (macro) changes at the systems and societal levels of benefit to policy developers and decision-makers.

Unraveling attrition and retention: A qualitative study with rehabilitation professionals.

BACKGROUND: Health human resources are scarce worldwide. In occupational therapy (OT), physical therapy (PT), and speech-language pathology (S-LP), attrition and retention issues amplify this situation and contribute to the precarity of health systems. OBJECTIVE: To investigate the phenomena of attrition and retention with OTs, PTs and S-LPs who stayed in, or left their profession. METHODS: Cultural-historical activity theory provided the theoretical scaffolding for this interpretive description study. We used purposeful sampling (maximum variation approach) to recruit OTs, PTs, and S-LPs from Quebec, Canada. Individual interviews were conducted with 51 OTs, PTs, and S-LPs from Quebec, Canada, in English or French (2019-2020). Inductive and deductive approaches, and constant comparative techniques were used for data analysis. RESULTS: Six themes were developed: 1) characteristics of work that made it meaningful; 2) aspects of work that practitioners appreciate; 3) factors of daily work that weigh on a practitioner; 4) factors that contribute to managing work; 5) relationships with different stakeholders that shape daily work; and 6) perceptions of the profession. Meaningfulness was tied to participants' sense that their values were reflected in their work. Factors outside work shaped participants' work experiences. Recurrent negative experiences led some to leave their profession. CONCLUSION: Findings underscore a critical need to address contributing factors to attrition and retention which are essential to ensuring the availability of OTs, PTs and SLPs for present and future rehabilitation needs.

Role of the mitochondrial protein cyclophilin D in skin wound healing and collagen secretion.

Central for wound healing is the formation of granulation tissue, which largely consists of collagen and whose importance stretches past wound healing, including being implicated in both fibrosis and skin aging. Cyclophilin D (CyD) is a mitochondrial protein that regulates the permeability transition pore, known for its role in apoptosis and ischemia-reperfusion. To date, the role of CyD in human wound healing and collagen generation has been largely unexplored. Here, we show that CyD was upregulated in normal wounds and venous ulcers, likely adaptive as CyD inhibition impaired reepithelialization, granulation tissue formation, and wound closure in both human and pig models. Overexpression of CyD increased keratinocyte migration and fibroblast proliferation, while its inhibition reduced migration. Independent of wound healing, CyD inhibition in fibroblasts reduced collagen secretion and caused endoplasmic reticulum collagen accumulation, while its overexpression increased collagen secretion. This was confirmed in a Ppif-KO mouse model, which showed a reduction in skin collagen. Overall, this study revealed previously unreported roles of CyD in skin, with implications for wound healing and beyond.

Refinement of intrathecal catheter design to enhance neuraxial distribution.

BACKGROUND: Delivery of therapeutics via indwelling intrathecal catheters is highly efficacious for targeting of pain, spasticity, neuraxial cancer and neurodegenerative disorders. However, current catheter designs have some major limitations. Given limited CSF flow, fixed intrathecal volume and the large distance of the rostro-caudal spinal axis, current intrathecal delivery routes fail to achieve adequate drug distribution. Additionally open catheter systems are plagued with cellular ingrowth and debris accumulation if used intermittently. NEW METHOD: RESULTS/COMPARISON WITH EXISTING METHOD(S): High speed imaging showed micro-valve catheters greatly increase fluid exit velocities compared to typical open-ended catheters, which prevents pooling of injectate proximal to the opening. When implanted intrathecally in rats, small injection volumes (7.5 µL) of dye or AAV9-RFP, resulted in an even rostro-caudal distribution along the spinal axis and robust transfection of neurons from cervical to lumbar dorsal root ganglia. In contrast, such injections with an open-ended catheter resulted in localized distribution and transfection proximal to the delivery site. Our poly micro-valve catheter design resulted in equivalent transfection rates of cervical DRG neurons using 100x lower titer of AAV9-RFP. Unlike open port catheters, no debris accumulation was observed in the lumen of implanted catheters, showing potential for long-term intermittent use. CONCLUSIONS: This catheter platform, suitable for small animal models is easily scalable for human use and addresses many of the problems observed with common catheter systems.

CD163+ macrophages monitor enhanced permeability at the blood-dorsal root ganglion barrier.

In dorsal root ganglia (DRG), macrophages reside close to sensory neurons and have largely been explored in the context of pain, nerve injury, and repair. However, we discovered that most DRG macrophages interact with and monitor the vasculature by sampling macromolecules from the blood. Characterization of the DRG vasculature revealed a specialized endothelial bed that transformed in molecular, structural, and permeability properties along the arteriovenous axis and was covered by macrophage-interacting pericytes and fibroblasts. Macrophage phagocytosis spatially aligned with peak endothelial permeability, a process regulated by enhanced caveolar transcytosis in endothelial cells. Profiling the DRG immune landscape revealed two subsets of perivascular macrophages with distinct transcriptome, turnover, and function. CD163+ macrophages self-maintained locally, specifically participated in vasculature monitoring, displayed distinct responses during peripheral inflammation, and were conserved in mouse and man. Our work provides a molecular explanation for the permeability of the blood-DRG barrier and identifies an unappreciated role of macrophages as integral components of the DRG-neurovascular unit.

Multifaceted roles of mitochondria in wound healing and chronic wound pathogenesis.

Mitochondria are intracellular organelles that play a critical role in numerous cellular processes including the regulation of metabolism, cellular stress response, and cell fate. Mitochondria themselves are subject to well-orchestrated regulation in order to maintain organelle and cellular homeostasis. Wound healing is a multifactorial process that involves the stringent regulation of several cell types and cellular processes. In the event of dysregulated wound healing, hard-to-heal chronic wounds form and can place a significant burden on healthcare systems. Importantly, treatment options remain limited owing to the multifactorial nature of chronic wound pathogenesis. One area that has received more attention in recent years is the role of mitochondria in wound healing. With regards to this, current literature has demonstrated an important role for mitochondria in several areas of wound healing and chronic wound pathogenesis including metabolism, apoptosis, and redox signalling. Additionally, the influence of mitochondrial dynamics and mitophagy has also been investigated. However, few studies have utilised patient tissue when studying mitochondria in wound healing, instead using various animal models. In this review we dissect the current knowledge of the role of mitochondria in wound healing and discuss how future research can potentially aid in the progression of wound healing research.

Anti-satellite glia cell IgG antibodies in fibromyalgia patients are related to symptom severity and to metabolite concentrations in thalamus and rostral anterior cingulate cortex.

Recent translational work has shown that fibromyalgia might be an autoimmune condition with pathogenic mechanisms mediated by a peripheral, pain-inducing action of immunoglobulin G (IgG) antibodies binding to satellite glia cells (SGC) in the dorsal root ganglia. A first clinical assessment of the postulated autoimmunity showed that fibromyalgia subjects (FMS) had elevated levels of antibodies against SGC (termed anti-SGC IgG) compared to healthy controls and that anti-SGC IgG were associated with a more severe disease status. The overarching aim of the current study was to determine whether the role of anti-SGC IgG in driving pain is exclusively through peripheral mechanisms, as indirectly shown so far, or could be attributed also to central mechanisms. To this end, we wanted to first confirm, in a larger cohort of FMS, the relation between anti-SGC IgG and pain-related clinical measures. Secondly, we explored the associations of these autoantibodies with brain metabolite concentrations (assessed via magnetic resonance spectroscopy, MRS) and pressure-evoked cerebral pain processing (assessed via functional magnetic resonance imaging, fMRI) in FMS. Proton MRS was performed in the thalamus and rostral anterior cingulate cortex (rACC) of FMS and concentrations of a wide spectrum of metabolites were assessed. During fMRI, FMS received individually calibrated painful pressure stimuli corresponding to low and high pain intensities. Our results confirmed a positive correlation between anti-SGC IgG and clinical measures assessing condition severity. Additionally, FMS with high anti-SGC IgG levels had higher pain intensity and a worse disease status than FMS with low anti-SGC IgG levels. Further, anti-SGC IgG levels negatively correlated with metabolites such as scyllo-inositol in thalamus and rACC as well as with total choline and macromolecule 12 in thalamus, thus linking anti-SGC IgG levels to the concentration of metabolites in the brain of FMS. However, anti-SGC IgG levels in FMS were not associated with the sensitivity to pressure pain or the cerebral processing of evoked pressure pain. Taken together, our results suggest that anti-SGC IgG might be clinically relevant for spontaneous, non-evoked pain. Our current and previous translational and clinical findings could provide a rationale to try new antibody-related treatments in FMS.

How Did Governments Address the Needs of People With Disabilities During the COVID-19 Pandemic? An Analysis of 14 Countries' Policies Based on the UN Convention on the Rights of Persons With Disabilities.

BACKGROUND: People with disabilities have experienced heightened social risks in the context of the pandemic, resulting in higher rates of infection and mortality. They have also borne elevated burdens associated with public health measures. The United Nations Convention on the Rights of Persons with Disabilities (UNCRPD) obliges its 184 state parties to eliminate discrimination and ensure equality and inclusion for persons with disabilities, including protection and safety in situations of emergency. It remains unclear to what extent national COVID-19 policies have aligned with these commitments under the UNCRPD. Our objective in this exploratory study was to assess alignment between the UNCRPD indicators and COVID-19 policies from 14 countries with the goal of informing policy development that is inclusive of persons with disabilities and responsive to rights under the UNCRPD. METHODS: We identified COVID-19 policy documents from 14 purposively selected countries. Country selection considered diversity based on geographic regions and national income levels, with restriction to those countries that had ratified the UNCRPD and had English or French as an official language. We used a computational text mining approach and developed a complex multilevel dictionary or categorization model based on the UNCRPD Bridging the Gap indicators proposed by the Office of the High Commissioner on Human Rights (OHCHR). This dictionary was used to assess the extent to which indicators across the entirety of the UNCRPD were represented in the selected policies. We analyzed frequency of associations with UNCRPD, as well as conducting 'key word in context' analyses to identify themes. RESULTS: We identified 764 COVID-19 national policy documents from the period of January 2020 to June 2021. When analyzed in relation to the Articles of the UNCRPD, the most frequently identified were Articles 11 (risk and humanitarian emergencies), 23 (home and family), 24 (education), and 19 (community living). Six countries produced 27 policies that were specifically focused on disability. Common themes within these documents included continuation of services, intersectionality and equity, and disability considerations in regulations and public health measures. CONCLUSION: Analyzing country policies in light of the UNCRPD offers important insights about how these policies do and do not align with states' commitments. As new policies are developed and existing ones revised, more comprehensive approaches to addressing the rights of persons with disabilities are urgently needed.

Insights into FcγR involvement in pain-like behavior induced by an RA-derived anti-modified protein autoantibody.

Joint pain is one of the most debilitating symptoms of rheumatoid arthritis (RA) and patients frequently rate improvements in pain management as their priority. RA is hallmarked by the presence of anti-modified protein autoantibodies (AMPA) against post-translationally modified citrullinated, carbamylated and acetylated proteins. It has been suggested that autoantibody-mediated processes represent distinct mechanisms contributing to pain in RA. In this study, we investigated the pronociceptive properties of monoclonal AMPA 1325:01B09 (B09 mAb) derived from the plasma cell of an RA patient. We found that B09 mAb induces pain-like behavior in mice that is not associated with any visual, histological or transcriptional signs of inflammation in the joints, and not alleviated by non-steroidal anti-inflammatory drugs (NSAIDs). Instead, we found that B09 mAb is retained in dorsal root ganglia (DRG) and alters the expression of several satellite glia cell (SGC), neuron and macrophage-related factors in DRGs. Using mice that lack activating FcγRs, we uncovered that FcγRs are critical for the development of B09-induced pain-like behavior, and partially drive the transcriptional changes in the DRGs. Finally, we observed that B09 mAb binds SGC in vitro and in combination with external stimuli like ATP enhances transcriptional changes and protein release of pronociceptive factors from SGCs. We propose that certain RA antibodies bind epitopes in the DRG, here on SGCs, form immune complexes and activate resident macrophages via FcγR cross-linking. Our work supports the growing notion that autoantibodies can alter nociceptor signaling via mechanisms that are at large independent of local inflammatory processes in the joint.

Children with Disabilities in Canada during the COVID-19 Pandemic: An Analysis of COVID-19 Policies through a Disability Rights Lens.

Children with disabilities were especially vulnerable during the COVID-19 pandemic, and policies designed to mitigate its effects were limited in addressing their needs. We analyzed Canadian policies related to children with disabilities and their families during the COVID-19 pandemic to identify the extent to which these policies aligned with the United Nations Convention on the Rights of Persons with Disabilities (UN CRPD) and responded to their mental health needs by conducting a systematic collection of Canadian provincial/territorial policies produced during the pandemic, building a categorization dictionary based on the UN CRPD, using text mining, and thematic analysis to identify policies' alignment with the UN CRPD and mental health supports. Mental health was addressed as a factor of importance in many policy documents, but specific interventions to promote or treat mental health were scarce. Most public health policies and recommendations are related to educational settings, demonstrating how public health for children with disabilities relies on education and community that may be out of the healthcare system and unavailable during extended periods of the pandemic. Policies often acknowledged the challenges faced by children with disabilities and their families but offered few mitigation strategies with limited considerations for human rights protection.

Metabolic Reprogramming and Reliance in Human Skin Wound Healing.

Impaired skin wound healing is a significant global health issue, especially among the elderly. Wound healing is a well-orchestrated process involving the sequential phases of inflammation, proliferation, and tissue remodeling. Although wound healing is a highly dynamic and energy-requiring process, the role of metabolism remains largely unexplored. By combining transcriptomics and metabolomics of human skin biopsy samples, we mapped the core bioenergetic and metabolic changes in normal acute as well as chronic wounds in elderly subjects. We found upregulation of glycolysis, the tricarboxylic acid cycle, glutaminolysis, and ß-oxidation in the later stages of acute wound healing and in chronic wounds. To ascertain the role of these metabolic pathways on wound healing, we targeted each pathway in a wound healing assay as well as in a human skin explant model using metabolic inhibitors and stimulants. Enhancement or inhibition of glycolysis and, to a lesser extent, glutaminolysis had a far greater impact on wound healing than similar manipulations of oxidative phosphorylation and fatty acid ß-oxidation. These findings increase the understanding of wound metabolism and identify glycolysis and glutaminolysis as potential targets for therapeutic intervention.

Attrition and Retention of Rehabilitation Professionals: A Scoping Review.

INTRODUCTION: Attrition is defined as a permanent departure from one's profession or the workforce. Existing literature on retention strategies, contributing factors to the attrition of rehabilitation professionals and how different environments influence professionals' decision-making to stay in/leave their profession, is limited in scope and specificity. The objective of our review was to map the depth and breadth of the literature on attrition and retention of rehabilitation professionals. METHODS: We used Arksey and O'Malley's methodological framework. A search was conducted on MEDLINE (Ovid), Embase (Ovid), AMED, CINAHL, Scopus, and ProQuest Dissertations and Theses from 2010 to April 2021 for concepts of attrition and retention in occupational therapy, physical therapy, and speech-language pathology. RESULTS: Of the 6031 retrieved records, 59 papers were selected for data extraction. Data were organized into three themes: (1) descriptions of attrition and retention, (2) experiences of being a professional, and (3) experiences in institutions where rehabilitation professionals work. Seven factors across three levels (individual, work, and environment) were found to influence attrition. DISCUSSION: Our review showcases a vast, yet superficial array of literature on attrition and retention of rehabilitation professionals. Differences exist between occupational therapy, physical therapy, and speech-language pathology with respect to the focus of the literature. Push , pull , and stay factors would benefit from further empirical investigation to develop targeted retention strategies. These findings may help to inform health care institutions, professional regulatory bodies, and associations, as well as professional education programs, to develop resources to support retention of rehabilitation professionals.

Aid when 'there is nothing left to offer': Experiences of palliative care and palliative care needs in humanitarian crises.

Access to palliative care, and more specifically the alleviation of avoidable physical and psychosocial suffering is increasingly recognized as a necessary component of humanitarian response. Palliative approaches to care can meet the needs of patients for whom curative treatment may not be the aim, not just at the very end of life but alleviation of suffering more broadly. In the past several years many organizations and sectoral initiatives have taken steps to develop guidance and policies to support integration of palliative care. However, it is still regarded by many as unfeasible or aspirational in crisis contexts; particularly where care for persons with life threatening conditions or injuries is logistically, legally, and ethically challenging. This article presents a synthesis of findings from five qualitative sub-studies within a research program on palliative care provision in humanitarian crises that sought to better understand the ethical and practical dimensions of humanitarian organizations integrating palliative care into emergency responses. Our multi-disciplinary, multi-national team held 98 in-depth semi-structured interviews with people with experiences in natural disasters, refugee camps in Rwanda and Jordan, and in Ebola Treatment Centers in Guinea. Participants included patients, family members, health care workers, and other staff of humanitarian agencies. We identified four themes from descriptions of the struggles and successes of applying palliative care in humanitarian settings: justification and integration of palliative care into humanitarian response, contextualizing palliative care approaches to crisis settings, the importance of being attentive to the 'situatedness of dying', and the need for retaining a holistic approach to care. We discuss these findings in relation to the ideals embraced in palliative care and corresponding humanitarian values, concluding that palliative care in humanitarian response is essential for responding to avoidable pain and suffering in humanitarian settings.

Fibromyalgia patients with elevated levels of anti-satellite glia cell immunoglobulin G antibodies present with more severe symptoms.

ABSTRACT: Transferring fibromyalgia patient immunoglobulin G (IgG) to mice induces pain-like behaviour, and fibromyalgia IgG binds mouse and human satellite glia cells (SGCs). These findings suggest that autoantibodies could be part of fibromyalgia pathology. However, it is unknown how frequently fibromyalgia patients have anti-SGC antibodies and how anti-SGC antibodies associate with disease severity. Here, we quantified serum or plasma anti-SGC IgG levels in 2 fibromyalgia cohorts from Sweden and Canada using an indirect immunofluorescence murine cell culture assay. Fibromyalgia serum IgG binding to human SGCs in human dorsal root ganglia tissue sections was also assessed by immunofluorescence. In the cell culture assay, anti-SGC IgG levels were increased in both fibromyalgia cohorts compared with control group. Elevated anti-SGC IgG was associated with higher levels of self-reported pain in both cohorts, and higher fibromyalgia impact questionnaire scores and increased pressure sensitivity in the Swedish cohort. Anti-SGC IgG levels were not associated with fibromyalgia duration. Swedish fibromyalgia (FM) patients were clustered into FM-severe and FM-mild groups, and the FM-severe group had elevated anti-SGC IgG compared with the FM-mild group and control group. Anti-SGC IgG levels detected in culture positively correlated with increased binding to human SGCs. Moreover, the FM-severe group had elevated IgG binding to human SGCs compared with the FM-mild and control groups. These results demonstrate that a subset of fibromyalgia patients have elevated levels of anti-SGC antibodies, and the antibodies are associated with more severe fibromyalgia symptoms. Screening fibromyalgia patients for anti-SGC antibodies could provide a path to personalized treatment options that target autoantibodies and autoantibody production.

Integration of High-Throughput Imaging and Multiparametric Metabolic Profiling Reveals a Mitochondrial Mechanism of Tenofovir Toxicity.

Nephrotoxicity is a major cause of kidney disease and failure in drug development, but understanding of cellular mechanisms is limited, highlighting the need for better experimental models and methodological approaches. Most nephrotoxins damage the proximal tubule (PT), causing functional impairment of solute reabsorption and systemic metabolic complications. The antiviral drug tenofovir disoproxil fumarate (TDF) is an archetypal nephrotoxin, inducing mitochondrial abnormalities and urinary solute wasting, for reasons that were previously unclear. Here, we developed an automated, high-throughput imaging pipeline to screen the effects of TDF on solute transport and mitochondrial morphology in human-derived RPTEC/TERT1 cells, and leveraged this to generate realistic models of functional toxicity. By applying multiparametric metabolic profiling-including oxygen consumption measurements, metabolomics, and transcriptomics-we elucidated a highly robust molecular fingerprint of TDF exposure. Crucially, we identified that the active metabolite inhibits complex V (ATP synthase), and that TDF treatment causes rapid, dose-dependent loss of complex V activity and expression. Moreover, we found evidence of complex V suppression in kidney biopsies from humans with TDF toxicity. Thus, we demonstrate an effective and convenient experimental approach to screen for disease relevant functional defects in kidney cells in vitro, and reveal a new paradigm for understanding the pathogenesis of a substantial cause of nephrotoxicity.

Impacts of the COVID-19 Pandemic: Pan-Canadian Perspectives From Parents and Caregivers of Youth With Neurodevelopmental Disabilities.

INTRODUCTION: The COVID-19 pandemic brought unprecedented challenges for youth with neurodevelopmental disabilities (NDD) and their families. Although health measures were implemented to contain the COVID-19 virus, they disrupted public service, profoundly impacting youth and their families' access to services. This study sought to better understand the perspectives and experiences of parents and caregivers of youth with NDD across Canada in accessing services and their mental health needs during the pandemic. METHOD: The study used a qualitative research design in which we interviewed 40 parents and caregivers across Canada. RESULTS: The results enabled us to understand the impact of service disruptions in significant areas of life, including health, education, employment, and risk mitigation. DISCUSSION: Policymakers must consider a disability-inclusive lens during public health emergency planning and response to reduce the disproportionate impacts faced by youth with NDD and their families.

Predictors of Long-term Ophthalmic Complications after Closed Globe Injuries Using the Intelligent Research in Sight (IRIS®) Registry.

Purpose: To identify clinical factors associated with the need for future surgical intervention following closed globe ocular trauma. Design: Retrospective cohort study. Subjects Participants and/or Controls: Patients in the American Academy of Ophthalmology Intelligent Research in Sight (IRIS®) Registry with a diagnosis of closed globe ocular trauma occurring between 2013 and 2019, identified using International Classification of Disease, 10th Revision and Systematized Nomenclature of Medicine codes. Methods: Diagnosis codes were used to identify multiple concomitant diagnoses present on the date of closed globe ocular trauma. Survival analyses were performed for each outcome of interest, and linear regression was used to identify clinical factors associated with the risk of surgical intervention. Main Outcome Measures: Outcomes included retinal break treatment, retinal detachment (RD) repair, retinal break treatment or RD repair, glaucoma surgery, and cataract surgery. Results: Of the 206 807 patients with closed globe ocular trauma, 9648 underwent surgical intervention during the follow-up period (mean, 444 days): 1697 (0.8%) had RD repair, 1658 (0.8%) had retinal break treatment, 600 (0.3%) had glaucoma surgery, and 5693 (2.8%) had cataract surgery. Traumatic cataract was the strongest risk factor for cataract surgery (hazard ratio, 13.0; 95% confidence interval, 10.8-15.6), traumatic hyphema showed highest risk for glaucoma surgery (7.24; 4.60-11.4), and vitreous hemorrhage was the strongest risk factor for retinal break treatment and detachment repair (11.01; 9.18-13.2 and 14.2; 11.5-17.6, respectively) during the first 60 days after trauma date. Vitreous hemorrhage was a risk factor for cataract surgery at > 60 days after trauma date only. Iris-angle injury was the strongest risk factor for glaucoma surgery > 60 days after trauma, while vitreous hemorrhage remained the strongest factor for retinal break treatment and detachment repair at > 60 days. Traumatic hyphema was a risk factor for all surgical outcomes during all follow-up intervals. Conclusions: Diagnosis of concomitant traumatic cataract, vitreous hemorrhage, traumatic hyphema, and other risk factors may increase the likelihood of requiring surgical intervention after closed globe ocular trauma.

Odontoid Fracture as Proximal Junctional Failure in Patients With Multilevel Spine Fusions.

STUDY DESIGN: Retrospective study. OBJECTIVE: Proximal junctional failure (PJF) commonly occurs as a recognized potential outcome of fusion surgery. Here we describe a unique series of patients with multilevel spine fusion including the cervical spine, who developed PJF as an odontoid fracture. METHODS: We performed a single site retrospective review of patients with prior fusion that included a cervical component, who presented with an odontoid fracture between 2012 and 2019. Radiographic measurements included C2-C7 SVA, C2-C7 lordosis, T1 slope, Occiput-C2 angle, proximal junctional kyphosis, and cervical mismatch. Associated fractures, medical comorbidities, and treatments were determined via chart review after IRB approval. RESULTS: Nine patients met inclusion criteria. 5 reported trauma with subsequent onset of pain. All patients sustained a Type II odontoid fracture. 5 with associated C1/Jefferson fractures. In all patients, pre-injury Occiput-C2 angle was outside normative range; C2-C7 SVA was greater than 4 cm in 6 patients; T1-slope minus cervical lordosis was greater than 18.5 degrees in 6 patients. 7 patients were treated operatively with extension of fusion to C1 and 2 patients declined operative treatment. CONCLUSION: In this series of 9 patients with multilevel fusion with type II odontoid fractures, all patients demonstrated abnormal pre-fracture sagittal alignment parameters and a greater than normal association of C1 fractures was noted. Further study is needed to establish the role of poor sagittal alignment with compensatory occiput-C2 angulation as a predisposing factor for odontoid fracture as a proximal junctional failure mechanism.

Association of Environmental Factors with Age-Related Macular Degeneration using the Intelligent Research in Sight Registry.

Purpose: Investigate associations of natural environmental exposures with exudative and nonexudative age-related macular degeneration (AMD) across the United States. Design: Database study. Participants: Patients aged ≥ 55 years who were active in the IRIS Registry from 2016 to 2018 were analyzed. Patients were categorized as nonexudative, inactive exudative, and active exudative AMD by International Classification of Diseases 10th Revision and Current Procedural Terminology (CPT) codes. Patients without provider-level ZIP codes matching any ZIP code tabulation area were excluded. Methods: Environmental data were obtained from public sources including the US Geological Survey, National Renewable Energy Laboratory, National Oceanic and Atmospheric Administration, and Environmental Protection Agency. Multiple variable, mixed effects logistic regression models with random intercepts per ZIP code tabulation area quantified the association of each environmental variable with any AMD versus non-AMD patients, any exudative AMD versus nonexudative AMD, and active exudative AMD versus inactive exudative and nonexudative AMD using 3 separate models, while adjusting for age, sex, race, insurance type, smoking history, and phakic status. Main Outcome Measure: Odds ratios for environmental factors. Results: A total of 9 884 527 patients were included. Elevation, latitude, solar irradiance measured in global horizontal irradiance (GHI) and direct normal irradiance (DNI), temperature and precipitation variables, and pollution variables were included in our models. Statistically significant associations with active exudative AMD were GHI (odds ratio [OR], 3.848; 95% confidence interval [CI] with Bonferroni correction, 1.316-11.250), DNI (OR, 0.581; 95% CI, 0.370-0.913), latitude (OR, 1.110; 95% CI, 1.046-1.178), ozone (OR, 1.014; 95% CI, 1.004-1.025), and nitrogen dioxide (OR, 1.005; 95% CI, 1.000-1.010). The only significant environmental associations with any AMD were inches of snow in the winter (OR, 1.005; 95% CI, 1.001-1.009) and ozone (OR, 1.011; 95% CI, 1.003-1.019). Conclusions: The strongest environmental associations differed between AMD subgroups. The solar variables GHI, DNI, and latitude were significantly associated with active exudative AMD. Two pollutant variables, ozone and nitrogen dioxide, also showed positive associations with AMD. Further studies are warranted to investigate the clinical relevance of these associations. Our curated environmental dataset has been made publicly available at https://github.com/uw-biomedical-ml/AMD_environmental_dataset.

B cell expansion hinders the stroma-epithelium regenerative cross talk during mucosal healing.

Therapeutic promotion of intestinal regeneration holds great promise, but defining the cellular mechanisms that influence tissue regeneration remains an unmet challenge. To gain insight into the process of mucosal healing, we longitudinally examined the immune cell composition during intestinal damage and regeneration. B cells were the dominant cell type in the healing colon, and single-cell RNA sequencing (scRNA-seq) revealed expansion of an IFN-induced B cell subset during experimental mucosal healing that predominantly located in damaged areas and associated with colitis severity. B cell depletion accelerated recovery upon injury, decreased epithelial ulceration, and enhanced gene expression programs associated with tissue remodeling. scRNA-seq from the epithelial and stromal compartments combined with spatial transcriptomics and multiplex immunostaining showed that B cells decreased interactions between stromal and epithelial cells during mucosal healing. Activated B cells disrupted the epithelial-stromal cross talk required for organoid survival. Thus, B cell expansion during injury impairs epithelial-stromal cell interactions required for mucosal healing, with implications for the treatment of IBD.