Immune Reconstitution Inflammatory Syndrome Reaction in Patient on Long-Term Prednisone.

Immune reconstitution inflammatory syndrome (IRIS) can be triggered in many ways. IRIS has been recognized during tuberculosis (TB) therapy, especially in patients newly initiated on antiretroviral therapy for HIV or those taken off immunosuppressives such as tumor necrosis factor-alpha inhibitors. However, there are still many triggers of IRIS that are less understood. This case report describes a patient with scrofula that was concerning for TB reactivation, who then had subsequent IRIS. The patient had been consistently using low-dose long-term prednisone for suppression of his polymyalgia rheumatica. It is suspected that the IRIS reaction could be due to an interaction between rifampin and prednisone causing decreased efficacy of its immunosuppressive effects.

The Impact of Language on Hospital Outcomes for COVID-19 Patients: A Study of Non-English Speaking Hispanic Patients.

BACKGROUND: The COVID-19 pandemic has highlighted and exacerbated health inequities, as demonstrated by the disproportionate rates of infection, hospitalization, and death in marginalized racial and ethnic communities. Although non-English speaking (NES) patients have substantially higher rates of COVID-19 positivity than other groups, research has not yet examined primary language, as determined by the use of interpreter services, and hospital outcomes for patients with COVID-19. METHODS: Data were collected from 1,770 patients with COVID-19 admitted to an urban academic health medical center in the Chicago, Illinois area from March 2020 to April 2021. Patients were categorized as non-Hispanic White, non-Hispanic Black, NES Hispanic, and English-speaking (ES) Hispanic using NES as a proxy for English language proficiency. Multivariable logistic regression was used to compare the predicted probability for each outcome (i.e., ICU admission, intubation, and in-hospital death) by race/ethnicity. RESULTS: After adjusting for possible confounders, NES Hispanic patients had the highest predicted probability of ICU admission (p-value < 0.05). Regarding intubation and in-hospital death, NES Hispanic patients had the highest probability, although statistical significance was inconclusive, compared to White, Black, and ES Hispanic patients. CONCLUSIONS: Race and ethnicity, socioeconomic status, and language have demonstrated disparities in health outcomes. This study provides evidence for heterogeneity within the Hispanic population based on language proficiency that may potentially further contribute to disparities in COVID-19-related health outcomes within marginalized communities.

Adiponectin negatively regulates pigmentation, Wnt/ß-catenin and HGF/c-Met signalling within human scalp hair follicles ex vivo.

Adiponectin reportedly stimulates proliferation and elongation of human scalp hair follicles (HFs) ex vivo. In the current study, we investigated how adiponectin oligomers produced by perifollicular dermal white adipose tissue (dWAT), a potent source of adiponectin isoforms, influence human HF proliferation and pigmentation. To do so, we treated microdissected, organ-cultured HFs in the presence or absence of dWAT with a recombinant human adiponectin oligomer mix, or inhibited dWAT-derived adiponectin using a neutralizing antibody. Multiplex qPCR (Fluidigm) revealed that adiponectin oligomers downregulated pigmentation genes KITLG, PMEL and TYRP1 and Wnt genes AXIN2, LEF1 and WNT10B. In situ hybridization showed that adiponectin downregulated AXIN2 and LEF1, and up-regulated DKK1 within the dermal papilla (DP), a highly unusual transcriptional profile for a putative hair growth-promoting agent. Adiponectin oligomers also downregulated protein expression of the HGF receptor c-Met within the matrix and DP. However, adiponectin did not alter hair matrix keratinocyte proliferation within 48 h ex vivo, irrespective of the presence/absence of dWAT; HF pigmentation (Masson-Fontana histochemistry, tyrosinase activity) was also unchanged. In contrast, neutralizing adiponectin isoforms within HF + dWAT increased proliferation, melanin content and tyrosinase activity but resulted in fewer melanocytes and melanocytic dendrites, as assessed by gp100 immunostaining. These seemingly contradictory effects suggest that adiponectin exerts complex effects upon human HF biology, likely in parallel with the pro-pigmentation effects of dWAT- and DP-derived HGF. Our data suggest that dWAT-derived ratios of adiponectin isoforms and the cleaved, globular version of adiponectin may in fact determine how adiponectin impacts upon follicular pigmentation and growth.

Should Clinicians Be Activists?

Physicians are ethically bound to respond to undocumented, underinsured, and uninsured patients' health needs, even those demanding complex, expensive interventions, such as organ transplantation. A social medicine skill set of structural competency, allyship, accompaniment, and activism is required to best serve patients and communities and should be widely regarded as core competencies for all health professionals. This commentary on a case considers the nature and scope of the skill of activism, specifically.

En términos éticos, los médicos están obligados a responder a las necesidades de salud de los pacientes indocumentados, subasegurados y no asegurados, incluso de aquellos que exigen intervenciones complejas y costosas, como el trasplante de órganos. Se requiere un conjunto de habilidades de medicina social que incluya la competencia estructural, las alianzas, el acompañamiento y el activismo para servir mejor a los pacientes y a las comunidades y se deberían considerar ampliamente como competencias básicas para todos los profesionales de la salud. En concreto, este comentario sobre un caso analiza la naturaleza y el alcance de la habilidad del activismo.

Racial and Ethnic Differences in Hospital Admissions of Emergency Department COVID-19 Patients.

BACKGROUND: Several studies have found that among patients testing positive for COVID-19 within a health care system, non-Hispanic Black and Hispanic patients are more likely than non-Hispanic White patients to be hospitalized. However, previous studies have looked at odds of being admitted using all positive tests in the system and not only those seeking care in the emergency department (ED). OBJECTIVE: This study examined racial/ethnic differences in COVID-19 hospitalizations and intensive care unit (ICU) admissions among patients seeking care for COVID-19 in the ED. RESEARCH DESIGN: Electronic health records (n=7549) were collected from COVID-19 confirmed patients that visited an ED of an urban health care system in the Chicago area between March 2020 and February 2021. RESULTS: After adjusting for possible confounders, White patients had 2.2 times the odds of being admitted to the hospital and 1.5 times the odds of being admitted to the ICU than Black patients. There were no observed differences between White and Hispanic patients. CONCLUSIONS: White patients were more likely than Black patients to be hospitalized after presenting to the ED with COVID-19 and more likely to be admitted directly to the ICU. This finding may be due to racial/ethnic differences in severity of disease upon ED presentation, racial and ethnic differences in access to COVID-19 primary care and/or implicit bias impacting clinical decision-making.

An Epidermal-Specific Role for Arginase1 during Cutaneous Wound Repair.

Nonhealing wounds are a major area of unmet clinical need remaining problematic to treat. Improved understanding of prohealing mechanisms is invaluable. The enzyme arginase1 (ARG1) is involved in prohealing responses, with its role in macrophages best characterized. ARG1 is also expressed by keratinocytes; however, ARG1 function in these critical wound repair cells is not understood. We characterized ARG1 expression in keratinocytes during normal cutaneous repair and reveal de novo temporal and spatial expression at the epidermal wound edge. Interestingly, epidermal ARG1 expression was decreased in both human and murine delayed healing wounds. We therefore generated a keratinocyte-specific ARG1-null mouse model (K14-cre;Arg1fl/fl) to explore arginase function. Wound repair, linked to changes in keratinocyte proliferation, migration, and differentiation, was significantly delayed in K14-cre;Arg1fl/fl mice. Similarly, using the arginase inhibitor N(omega)-hydroxy-nor-L-arginine, human in vitro and ex vivo models further confirmed this finding, revealing the importance of the downstream polyamine pathway in repair. Indeed, restoring the balance in ARG1 activity through the addition of putrescine proved beneficial in wound closure. In summary, we show that epidermal ARG1 plays, to our knowledge, a previously unreported intrinsic role in cutaneous healing, highlighting epidermal ARG1 and the downstream mediators as potential targets for the therapeutic modulation of wound repair.

End Stage Kidney Disease in Non-citizen Patients: Epidemiology, Treatment, and an Update to Policy in Illinois.

End-stage kidney disease (ESKD) is common in the U.S. There is no cure, and survival requires either dialysis or kidney transplant. Medicare provides coverage for most ESKD patients in the U.S., though non-citizens are excluded from most current policies providing standard ESKD care, especially regarding kidney transplants. Despite being eligible to be organ donors, non-citizens often have few avenues to be organ recipients-a major equity problem. Overall, transplants are cost-saving compared to dialysis, and non-citizens have comparable outcomes to the general population. We reviewed the literature regarding the vastly different policies across the U.S., with a focus on current Illinois policy, including updates regarding Illinois legislation which passed in 2014 providing non-citizens to receive coverage for transplants. Unfortunately, despite legislation providing avenues for transplants, funds were not allocated, and the bill has not had the impact that was expected when initially passed. We outline opportunities for improving current policies.

Interhospital Transfer Outcomes for Critically Ill Patients With Coronavirus Disease 2019 Requiring Mechanical Ventilation.

Studying interhospital transfer of critically ill patients with coronavirus disease 2019 pneumonia in the spring 2020 surge may help inform future pandemic management. OBJECTIVES: To compare outcomes for mechanically ventilated patients with coronavirus disease 2019 transferred to a tertiary referral center with increased surge capacity with patients admitted from the emergency department. DESIGN SETTING PARTICIPANTS: Observational cohort study of single center urban academic medical center ICUs. All patients admitted and discharged with coronavirus disease 2019 pneumonia who received invasive ventilation between March 17, 2020, and October 14, 2020. MAIN OUTCOME AND MEASURES: Demographic and clinical variables were obtained from the electronic medical record. Patients were classified as emergency department admits or interhospital transfers. Regression models tested the association between transfer status and survival, adjusting for demographics and presentation severity. RESULTS: In total, 298 patients with coronavirus disease 2019 pneumonia were admitted to the ICU and received mechanical ventilation. Of these, 117 were transferred from another facility and 181 were admitted through the emergency department. Patients were primarily male (64%) and Black (38%) or Hispanic (45%). Transfer patients differed from emergency department admits in having English as a preferred language (71% vs 56%; p = 0.008) and younger age (median 57 vs 61 yr; p < 0.001). There were no differences in race/ethnicity or primary payor. Transfers were more likely to receive extracorporeal membrane oxygenation (12% vs 3%; p = 0.004). Overall, 50 (43%) transferred patients and 78 (43%) emergency department admits died prior to discharge. There was no significant difference in hospital mortality or days from intubation to discharge between the two groups. CONCLUSIONS AND RELEVANCE: In a single-center retrospective cohort, no significant differences in hospital mortality or length of stay between interhospital transfers and emergency department admits were found. While more study is needed, this suggests that interhospital transfer of critically ill patients with coronavirus disease 2019 can be done safely and effectively.

The Financial Impact of a Partnership Between an Academic Medical Center and a Free Clinic.

PURPOSE: The objective of this study is to examine the association between an academic medical center and free clinic referral partnership and subsequent hospital utilization and costs for uninsured patients discharged from the academic medical center's emergency department (ED) or inpatient hospital. METHODS: This retrospective, cross-sectional study included 6014 uninsured patients age 18 and older who were discharged from the academic medical center's ED or inpatient hospital between July 2016 and June 2017 and were followed for 90 days in the organization's electronic medical record to identify the occurrence and cost of subsequent same-hospital ED visits and hospital admissions. The occurrence of any subsequent ED visits or hospital admissions and the cost of subsequent hospital care were compared by free clinic referral status after inverse probability of treatment weighting. RESULTS: Overall, 330 (5.5%) of uninsured patients were referred to the free clinic. Compared with patients referred to the free clinic, patients not referred had greater odds of any subsequent ED visits or hospital admissions within 90 days (odds ratio, 1.8; 95% confidence interval: 1.7-2.0). For patients with any subsequent ED visits or hospital admissions, the mean cost of care for those who were not referred to the free clinic was 2.3 times higher (95% confidence interval: 2.0-2.7) compared to referred patients. CONCLUSION: An academic medical center-free clinic partnership for follow-up care after discharge from the ED or hospital admission is a promising approach for improving access to care for uninsured patients.

Dermal Adipose Tissue Secretes HGF to Promote Human Hair Growth and Pigmentation.

Hair follicles (HFs) are immersed within dermal white adipose tissue (dWAT), yet human adipocyte‒HF communication remains unexplored. Therefore, we investigated how perifollicular adipocytes affect the physiology of human anagen scalp HFs. Quantitative immunohistomorphometry, X-ray microcomputed tomography, and transmission electron microscopy showed that the number and size of perifollicular adipocytes declined during anagen‒catagen transition, whereas fluorescence-lifetime imaging revealed increased lipid oxidation in adipocytes surrounding the bulge and/or sub-bulge region. Ex vivo, dWAT tendentially promoted hair shaft production, and significantly stimulated hair matrix keratinocyte proliferation and HF pigmentation. Both dWAT pericytes and PREF1/DLK1+ adipocyte progenitors secreted HGF during human HF‒dWAT co-culture, for which the c-Met receptor was expressed in the hair matrix and dermal papilla. These effects were reproduced using recombinant HGF and abrogated by an HGF-neutralizing antibody. Laser-capture microdissection‒based microarray analysis of the hair matrix showed that dWAT-derived HGF upregulated keratin (K) genes (K27, K73, K75, K84, K86) and TCHH. Mechanistically, HGF stimulated Wnt/ß-catenin activity in the human hair matrix (increased AXIN2, LEF1) by upregulating WNT6 and WNT10B, and inhibiting SFRP1 in the dermal papilla. Our study demonstrates that dWAT regulates human hair growth and pigmentation through HGF secretion, and thus identifies dWAT and HGF as important novel molecular and cellular targets for therapeutic intervention in human hair growth and pigmentation disorders.

Treatment pathway analysis of newly diagnosed dementia patients in four electronic health record databases in Europe.

PURPOSE: Real-world studies to describe the use of first, second and third line therapies for the management and symptomatic treatment of dementia are lacking. This retrospective cohort study describes the first-, second- and third-line therapies used for the management and symptomatic treatment of dementia, and in particular Alzheimer's Disease. METHODS: Medical records of patients with newly diagnosed dementia between 1997 and 2017 were collected using four databases from the UK, Denmark, Italy and the Netherlands. RESULTS: We identified 191,933 newly diagnosed dementia patients in the four databases between 1997 and 2017 with 39,836 (IPCI (NL): 3281, HSD (IT): 1601, AUH (DK): 4474, THIN (UK): 30,480) fulfilling the inclusion criteria, and of these, 21,131 had received a specific diagnosis of Alzheimer's disease. The most common first line therapy initiated within a year (± 365 days) of diagnosis were Acetylcholinesterase inhibitors, namely rivastigmine in IPCI, donepezil in HSD and the THIN and the N-methyl-D-aspartate blocker memantine in AUH. CONCLUSION: We provide a real-world insight into the heterogeneous management and treatment pathways of newly diagnosed dementia patients and a subset of Alzheimer's Disease patients from across Europe.

COVID-19 Among African Americans: An Action Plan for Mitigating Disparities.

As the COVID-19 pandemic has unfolded across the United States, troubling disparities in mortality have emerged between different racial groups, particularly African Americans and Whites. Media reports, a growing body of COVID-19-related literature, and long-standing knowledge of structural racism and its myriad effects on the African American community provide important lenses for understanding and addressing these disparities.However, troubling gaps in knowledge remain, as does a need to act. Using the best available evidence, we present risk- and place-based recommendations for how to effectively address these disparities in the areas of data collection, COVID-19 exposure and testing, health systems collaboration, human capital repurposing, and scarce resource allocation.Our recommendations are supported by an analysis of relevant bioethical principles and public health practices. Additionally, we provide information on the efforts of Chicago, Illinois' mayoral Racial Equity Rapid Response Team to reduce these disparities in a major urban US setting.

Vascular and metabolic risk factor differences prior to dementia diagnosis: a multidatabase case-control study using European electronic health records.

OBJECTIVE: The objective of the study is to compare body mass index (BMI), systolic/diastolic blood pressure (SBP/DBP) and serum total cholesterol levels between dementia cases and controls at multiple time intervals prior to dementia onset, and to test time interval as a modifying factor for these associations. DESIGN: Case-control study. SETTING: Six European electronic health records databases. PARTICIPANTS: 291 780 cases at the date of first-recorded dementia diagnosis, compared with 29 170 549 controls randomly selected from the same databases, age matched and sex matched at this index date. EXPOSURE: The following measures were extracted whenever recorded within each dataset: BMI (kg/m2), SBP and DBP (mm Hg) and serum total cholesterol (mmol/L). Levels for each of these variables were defined within six 2-year time intervals over the 12 years prior to the index date. MAIN OUTCOMES: Case-control differences in exposures of interest were modelled for each time period and adjusted for demographic and clinical factors (ischaemic/unspecified stroke, type 2 diabetes mellitus, acute myocardial infarction, hypertension diagnosis, antihypertensive medication, cholesterol-lowering medication). Coefficients and interactions with time period were meta-analysed across the six databases. RESULTS: Mean BMI (coefficient -1.16 kg/m2; 95% CI -1.38 to 0.93) and SBP (-2.83 mm Hg; 95% CI -4.49 to -1.16) were lower in cases at diagnosis, and case-control differences were greater in more recent time periods, as indicated by significant case-x-time interaction and case-x-time-squared interaction terms. Time variations in coefficients for cholesterol levels were less consistent between databases and those for DBP were largely not significant. CONCLUSION: Routine clinical data show emerging divergence in levels of BMI and SBP prior to the diagnosis of dementia but less evidence for DBP or total cholesterol levels. These divergences should receive at least some consideration in routine dementia risk screening, although underlying mechanisms still require further investigation.

Methotrexate and relative risk of dementia amongst patients with rheumatoid arthritis: a multi-national multi-database case-control study.

BACKGROUND: Inflammatory processes have been shown to play a role in dementia. To understand this role, we selected two anti-inflammatory drugs (methotrexate and sulfasalazine) to study their association with dementia risk. METHODS: A retrospective matched case-control study of patients over 50 with rheumatoid arthritis (486 dementia cases and 641 controls) who were identified from electronic health records in the UK, Spain, Denmark and the Netherlands. Conditional logistic regression models were fitted to estimate the risk of dementia. RESULTS: Prior methotrexate use was associated with a lower risk of dementia (OR 0.71, 95% CI 0.52-0.98). Furthermore, methotrexate use with therapy longer than 4 years had the lowest risk of dementia (odds ratio 0.37, 95% CI 0.17-0.79). Sulfasalazine use was not associated with dementia (odds ratio 0.88, 95% CI 0.57-1.37). CONCLUSIONS: Further studies are still required to clarify the relationship between prior methotrexate use and duration as well as biological treatments with dementia risk.

Neuroendocrinology and neurobiology of sebaceous glands.

The nervous system communicates with peripheral tissues through nerve fibres and the systemic release of hypothalamic and pituitary neurohormones. Communication between the nervous system and the largest human organ, skin, has traditionally received little attention. In particular, the neuro-regulation of sebaceous glands (SGs), a major skin appendage, is rarely considered. Yet, it is clear that the SG is under stringent pituitary control, and forms a fascinating, clinically relevant peripheral target organ in which to study the neuroendocrine and neural regulation of epithelia. Sebum, the major secretory product of the SG, is composed of a complex mixture of lipids resulting from the holocrine secretion of specialised epithelial cells (sebocytes). It is indicative of a role of the neuroendocrine system in SG function that excess circulating levels of growth hormone, thyroxine or prolactin result in increased sebum production (seborrhoea). Conversely, growth hormone deficiency, hypothyroidism, and adrenal insufficiency result in reduced sebum production and dry skin. Furthermore, the androgen sensitivity of SGs appears to be under neuroendocrine control, as hypophysectomy (removal of the pituitary) renders SGs largely insensitive to stimulation by testosterone, which is crucial for maintaining SG homeostasis. However, several neurohormones, such as adrenocorticotropic hormone and α-melanocyte-stimulating hormone, can stimulate sebum production independently of either the testes or the adrenal glands, further underscoring the importance of neuroendocrine control in SG biology. Moreover, sebocytes synthesise several neurohormones and express their receptors, suggestive of the presence of neuro-autocrine mechanisms of sebocyte modulation. Aside from the neuroendocrine system, it is conceivable that secretion of neuropeptides and neurotransmitters from cutaneous nerve endings may also act on sebocytes or their progenitors, given that the skin is richly innervated. However, to date, the neural controls of SG development and function remain poorly investigated and incompletely understood. Botulinum toxin-mediated or facial paresis-associated reduction of human sebum secretion suggests that cutaneous nerve-derived substances modulate lipid and inflammatory cytokine synthesis by sebocytes, possibly implicating the nervous system in acne pathogenesis. Additionally, evidence suggests that cutaneous denervation in mice alters the expression of key regulators of SG homeostasis. In this review, we examine the current evidence regarding neuroendocrine and neurobiological regulation of human SG function in physiology and pathology. We further call attention to this line of research as an instructive model for probing and therapeutically manipulating the mechanistic links between the nervous system and mammalian skin.

Racial/ethnic minority segregation and low birth weight in five North American cities.

Comparisons of communities across cities are rare in social epidemiology. Our prior work exploring racial/ethnic segregation and the prevalence of low birth weight (LBW) in communities from two large urban cities showed a strong relationship in Chicago and a very weak relationship in Toronto. This study extends that work by examining the association between racial/ethnic minority segregation and LBW in total of 307 communities in five North American cities: Baltimore, Boston, Chicago, Philadelphia, and Toronto. We used Pearson correlation coefficients and OLS regression models to examine potential variability in the association between racial/ethnic minority segregation and LBW, controlling for community-level unemployment. In a combined model with community-level data from all cities, a 10% increase in minority composition is associated with a 0.7% increase in LBW. While racial/ethnic minority segregation and unemployment are not associated with LBW in Toronto, these social determinants have strong and significant associations with LBW across communities in the four US cities in the analysis. Subsequent models revealed opposite effects for percentage non-Hispanic Black and percentage Hispanic. Across communities in the US cities in this analysis, there is considerable similarity in the strength of the effect of racial/ethnic segregation on LBW. Future work should incorporate communities from additional cities, looking to identify community assets and public policies that allow some minority communities to thrive, while other minority communities suffer from a high prevalence of LBW. More work is also needed on the generalizability of these patterns to other health outcomes.

Non-alcoholic fatty liver disease and risk of incident acute myocardial infarction and stroke: findings from matched cohort study of 18 million European adults.

OBJECTIVE: To estimate the risk of acute myocardial infarction (AMI) or stroke in adults with non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH). DESIGN: Matched cohort study. SETTING: Population based, electronic primary healthcare databases before 31 December 2015 from four European countries: Italy (n=1 542 672), Netherlands (n=2 225 925), Spain (n=5 488 397), and UK (n=12 695 046). PARTICIPANTS: 120 795 adults with a recorded diagnosis of NAFLD or NASH and no other liver diseases, matched at time of NAFLD diagnosis (index date) by age, sex, practice site, and visit, recorded at six months before or after the date of diagnosis, with up to 100 patients without NAFLD or NASH in the same database. MAIN OUTCOME MEASURES: Primary outcome was incident fatal or non-fatal AMI and ischaemic or unspecified stroke. Hazard ratios were estimated using Cox models and pooled across databases by random effect meta-analyses. RESULTS: 120 795 patients with recorded NAFLD or NASH diagnoses were identified with mean follow-up 2.1-5.5 years. After adjustment for age and smoking the pooled hazard ratio for AMI was 1.17 (95% confidence interval 1.05 to 1.30; 1035 events in participants with NAFLD or NASH, 67 823 in matched controls). In a group with more complete data on risk factors (86 098 NAFLD and 4 664 988 matched controls), the hazard ratio for AMI after adjustment for systolic blood pressure, type 2 diabetes, total cholesterol level, statin use, and hypertension was 1.01 (0.91 to 1.12; 747 events in participants with NAFLD or NASH, 37 462 in matched controls). After adjustment for age and smoking status the pooled hazard ratio for stroke was 1.18 (1.11 to 1.24; 2187 events in participants with NAFLD or NASH, 134 001 in matched controls). In the group with more complete data on risk factors, the hazard ratio for stroke was 1.04 (0.99 to 1.09; 1666 events in participants with NAFLD, 83 882 in matched controls) after further adjustment for type 2 diabetes, systolic blood pressure, total cholesterol level, statin use, and hypertension. CONCLUSIONS: The diagnosis of NAFLD in current routine care of 17.7 million patient appears not to be associated with AMI or stroke risk after adjustment for established cardiovascular risk factors. Cardiovascular risk assessment in adults with a diagnosis of NAFLD is important but should be done in the same way as for the general population.