Racial and ethnic inequities in the early distribution of U.S. COVID-19 testing sites and mortality.

BACKGROUND: In 2020, early U.S. COVID-19 testing sites offered diagnostic capacity to patients and were important sources of epidemiological data about the spread of the novel pandemic disease. However, little research has comprehensively described American testing sites' distribution by race/ethnicity and sought to identify any relation to known disparities in COVID-19 outcomes. METHODS: Locations of U.S. COVID-19 testing sites were gathered from 16 April to 28 May 2020. Geographic testing disparities were evaluated with comparisons of the demographic makeup of zip codes around each testing site versus Monte Carlo simulations, aggregated to statewide and nationwide levels. State testing disparities were compared with statewide disparities in mortality observed one to 3 weeks later using multivariable regression, controlling for confounding disparities and characteristics. RESULTS: Nationwide, COVID-19 testing sites geographically overrepresented White residents on 7 May, underrepresented Hispanic residents on 16 April, 7 May and 28 May and overrepresented Black residents on 28 May compared with random distribution within counties, with new sites added over time exhibiting inconsistent disparities for Black and Hispanic populations. For every 1 percentage point increase in underrepresentation of Hispanic populations in zip codes with testing, mortality among the state's Hispanic population was 1.04 percentage points more over-representative (SE = 0.415, p = .01). CONCLUSIONS: American testing sites were not distributed equitably by race during this analysis, often underrepresenting minority populations who bear a disproportionate burden of COVID-19 cases and deaths. With an easy-to-implement measure of geographic disparity, these results provide empirical support for the consideration of access when distributing preventive resources.

Racial disparities in knowledge, attitudes and practices related to COVID-19 in the USA.

BACKGROUND: Recent reports indicate racial disparities in the rates of infection and mortality from the 2019 novel coronavirus (coronavirus disease 2019 [COVID-19]). The aim of this study was to determine whether disparities exist in the levels of knowledge, attitudes and practices (KAPs) related to COVID-19. METHODS: We analyzed data from 1216 adults in the March 2020 Kaiser Family Foundation 'Coronavirus Poll', to determine levels of KAPs across different groups. Univariate and multivariate regression analysis was used to identify predictors of KAPs. RESULTS: In contrast to White respondents, Non-White respondents were more likely to have low knowledge (58% versus 30%; P < 0.001) and low attitude scores (52% versus 27%; P < 0.001), but high practice scores (81% versus 59%; P < 0.001). By multivariate regression, White race (odds ratio [OR] 3.06; 95% confidence interval [CI]: 1.70-5.50), higher level of education (OR 1.80; 95% CI: 1.46-2.23) and higher income (OR 2.06; 95% CI: 1.58-2.70) were associated with high knowledge of COVID-19. Race, sex, education, income, health insurance status and political views were all associated with KAPs. CONCLUSIONS: Racial and socioeconomic disparity exists in the levels of KAPs related to COVID-19. More work is needed to identify educational tools that tailor to specific racial and socioeconomic groups.

Racial disparities in the utilization of parathyroidectomy among patients with primary hyperparathyroidism: Evidence from a nationwide analysis of Medicare claims.

BACKGROUND: Among patients with primary hyperparathyroidism, parathyroidectomy offers a chance of cure and mitigation of disease-related complications. The impact of race/ethnicity on referral and utilization of parathyroidectomy has not been fully explored. METHODS: Population-based, retrospective cohort study using 100% Medicare claims from beneficiaries with primary hyperparathyroidism from 2006 to 2016. Associations of race/ethnicity with disease severity, surgeon evaluation, and subsequent parathyroidectomy were analyzed using adjusted multivariable logistic regression models. RESULTS: Among 210,206 beneficiaries with primary hyperparathyroidism, 63,136 (30.0%) underwent parathyroidectomy within 1 year of diagnosis. Black patients were more likely than other races/ethnicities to have stage 3 chronic kidney disease (10.8%) but had lower prevalence of osteoporosis and nephrolithiasis compared to White patients, Black and Hispanic patients were more likely to have been hospitalized for primary hyperparathyroidism-associated conditions (White 4.8%, Black 8.1%, Hispanic 5.8%; P < .001). Patients who were White and met operative criteria were more likely to undergo parathyroidectomy than Black, Hispanic, or Asian patients (White 30.5%, Black 23.0%, Hispanic 21.4%, Asian 18.7%; P < .001). Black and Hispanic patients had lower adjusted odds of being evaluated by a surgeon (odds ratios 0.71 [95% confidence interval 0.69-0.74], 0.68 [95% confidence interval 0.61-0.74], respectively) and undergoing parathyroidectomy if evaluated by a surgeon (odds ratios 0.72 [95% confidence interval 0.68-0.77], 0.82 [95% confidence interval 0.67-0.99]). Asian race was associated with lower adjusted odds of being evaluated by a surgeon (odds ratio 0.64 [95% confidence interval 0.57-0.71]), but no difference in odds of parathyroidectomy. CONCLUSION: Racial/ethnic disparities exist in the management of primary hyperparathyroidism among older adults. Determining the factors that account for this disparity require urgent attention to achieve parity in the management of primary hyperparathyroidism.

Endonuclease G mediates endothelial cell death induced by carbamylated LDL.

End-stage kidney disease is a terminal stage of chronic kidney disease, which is associated with a high incidence of cardiovascular disease. Cardiovascular disease frequently results from endothelial injury caused by carbamylated LDL (cLDL), the product of LDL modification by urea-derived cyanate. Our previous data suggested that cLDL induces mitogen-activated protein kinase-dependent mitotic DNA fragmentation and cell death. However, the mechanism of this pathway is unknown. The current study demonstrated that cLDL-induced endothelial mitotic cell death is independent of caspase-3. The expression of endonuclease G (EndoG), the nuclease implicated in caspase-independent DNA fragmentation, was significantly increased in response to cLDL exposure to the cells. The inhibition of EndoG by RNAi protected cLDL-induced DNA fragmentation, whereas the overexpression of EndoG induced more DNA fragmentation in endothelial cells. Ex vivo experiments with primary endothelial cells isolated from wild-type (WT) and EndoG knockout (KO) mice demonstrated that EndoG KO cells are partially protected against cLDL toxicity compared with WT cells. To determine cLDL toxicity in vivo, we administered cLDL or native LDL (nLDL) intravenously to the WT and EndoG KO mice and then measured floating endothelial cells in blood using flow cytometry. The results showed an increased number of floating endothelial cells after cLDL versus nLDL injection in WT mice but not in EndoG KO mice. Finally, the inhibitors of MEK-ERK1/2 and JNK-c-jun pathways decreased cLDL-induced EndoG overexpression and DNA fragmentation. In summary, our data suggest that cLDL-induced endothelial toxicity is caspase independent and results from EndoG-dependent DNA fragmentation.

Probability of positive genetic testing in patients diagnosed with pheochromocytoma and paraganglioma: Criteria beyond a family history.

BACKGROUND: Genetic testing for germline pheochromocytoma and paraganglioma susceptibility genes is associated with improved patient management. However, data are currently sparse on the probability of a positive testing result based on an individual's clinical presentation. This study evaluates clinical characteristics for association with testing positive for known pheochromocytoma and paraganglioma susceptibility genes. METHODS: This retrospective analysis examined 111 patients with a diagnosis of pheochromocytoma and paraganglioma who underwent genetic testing. Logistic regression and receiver operating characteristic analyses were performed to identify factors associated with a positive genetic testing result. Probabilities were then calculated for combinations of significant factors to determine the likelihood of a positive test result in each group. RESULTS: Of 32 patients with a family history of pheochromocytoma and paraganglioma, 31 (97%) had a germline mutation detected. Of 79 patients without a family history, 24 (30%) had a pathogenic germline mutation detected. In multivariate analysis, a positive family history, aged ≤47 years, and tumor size ≤2.9 cm were independent factors associated with a positive genetic testing result. Patients meeting all 3 criteria had a 100% probability compared with 13% in those without any of the criteria. In addition to a positive family history, having either aged ≤47 years or tumor size ≤2.9 cm resulted in a 90% and 100% probability of a positive result, respectively. In the absence of a family history, the probability in patients who were aged ≤47 years and had a tumor size ≤2.9 cm was 60%. CONCLUSION: In addition to a family history of pheochromocytoma and paraganglioma, aged ≤47 years, and tumor size ≤2.9 cm are associated with a higher probability of testing positive for a pheochromocytoma and paraganglioma susceptibility gene mutation. Patients meeting all 3 criteria have a 100% probability of a positive genetic testing result.

An update on familial nonmedullary thyroid cancer.

Familial nonmedullary thyroid cancer (FNMTC) constitutes 3-9% of all thyroid cancer cases. FNMTC is divided into two groups: syndromic and nonsyndromic. Nonsyndromic FNMTC is more common as compared with syndromic FNMTC. In syndromic FNMTC, patients are at risk of nonmedullary thyroid cancer (NMTC) and other tumors, and the susceptibility genes are known. In nonsyndromic FNMTC, NMTC is the major feature of the disease and occurs in isolation with an autosomal dominant pattern of inheritance and variable penetrance. New data have emerged on the genetics, clinical characteristics, and outcomes of patients with FNMTC that may have clinical relevance in the management of patients. In this review, we focus on newly characterized syndromic FNMTC entities, criteria for screening and surveillance of nonsyndromic FNMTC, and the classification of nonsyndromic FNMTC as well as the genetic background and heterogeneity of nonsyndromic FNMTC.

Surgery for adrenocortical carcinoma: When and how?

Adrenocortical carcinoma (ACC) is a rare malignancy that is frequently asymptomatic at presentation, yet has a high rate of metastatic disease at the time of diagnosis. Prognosis is overall poor, particularly with cortisol-producing tumors. While the treatment of ACC is guided by stage of disease, complete surgical resection is the most important step in the management of patients with primary, recurrent, or metastatic ACC. Triphasic chest, abdomen, and pelvis computer tomography (CT) scans and 18F flourodeoxyglucose positron emission tomography CT scanning are essential for accurate staging; moreover, MRI may be helpful to identify liver metastasis and evaluate the involvement of adjacent organs for operative planning. Surgical resection with negative margins is the single most important prognostic factor for survival in patients with ACC. To achieve the highest rate of R0 resection, open adrenalectomy is the gold standard surgical approach for confirmed or highly suspected ACC. It is extremely important that the tumor capsule is not ruptured, regardless of the surgical approach used. The best post-operative outcomes (complications and oncologic) are achieved by high-volume surgeons practicing at high-volume centers.

Splenectomy for benign and malignant hematologic pathology: Modern morbidity, mortality, and long-term outcomes.

BACKGROUND: The role of splenectomy to diagnose and treat hematologic disease continues to evolve. In this single-center retrospective review, we describe modern morbidity, mortality, and long-term outcomes associated with splenectomy for benign and malignant hematologic disorders. METHODS: We analyzed all nontrauma splenectomies performed for benign or malignant hematologic disorders from January 2009 to September 2018. Variables collected included demographics, preexisting comorbidities, laboratory results, intra- and postoperative features, and long-term follow-up. Outcomes of interest included postoperative complications, 30-day mortality, and overall mortality. RESULTS: We identified 161 patients who underwent splenectomy for hematologic disorders. Median age was 54 years (range 19-94), and 83 (52%) were female. Splenectomy was performed for 95 (59%) patients with benign hematologic disorders and for 66 (41%) with malignant conditions. Most splenectomies were laparoscopic (76%), followed by laparoscopic hand assisted (11%), open (8%), and laparoscopic converted to open (6%). Median follow-up was 761 days (interquartile range: 179-2025 days). Major complications occurred in 21 (13%) patients. Three (2%) patients died within 30 days; 16 (9%) died more than 30 days after operation, none from surgical complications, with median time to death of 438 days (interquartile range: 231-1497 days). Among malignant cases, only preoperative thrombocytopenia predicted death (odds ratio = 5.8, 95% confidence interval = 1.1-31.8, P = .04). For benign cases, increasing age was associated with inferior survival (odds ratio = 2.3, 95% confidence interval = 1.0-5.1, P = .05). CONCLUSION: Splenectomy remains an important diagnostic and therapeutic option for patients with benign and malignant hematologic disorders and can be performed with a low complication rate. Despite considerable burden of comorbid disease in these patients, early postoperative mortality was uncommon.

Incidence of metastasis and prostate-specific antigen levels at diagnosis in Gleason 3+4 versus 4+3 prostate cancer.

AIMS: The aim is to assess for a difference in the incidence of metastasis (IM) and prostate-specific antigen (PSA) levels at diagnosis in patients with Gleason score (GS) 3+4 versus 4+3 prostate cancer using a large veterans affairs database. SUBJECTS AND METHODS: A retrospective review of 1402 medical records from 5 VA hospitals was conducted. The study period was from 2009 to 2014. Primary endpoints were IM and PSA levels at diagnosis. A secondary endpoint was overall survival. STATISTICAL ANALYSIS USED: Chi-square tests for categorical variables, Student's t-test for continuous, normally distributed variables, and rank sum tests for continuous nonnormally distributed variables. RESULTS: There were 1050 patients with GS3+4 and 352 with GS4+3. There were no differences in sociodemographic and clinical characteristics of the study population. PSA at the time of diagnosis was significantly higher in the GS4+3 patients compared to GS3+4 (18.0 vs. 11.4, respectively; P < 0.001). The IM at diagnosis was higher in the GS4+3 patients (10/352) compared to GS3+4 (9/1041) (2.8% vs. 0.9%; P = 0.005). In an adjusted model, GS4+3 was associated with higher PSA, higher IM at diagnosis. There was no difference in overall survival between the 2 groups though a 23% reduction in overall survival in the GS4+3 was noted (P = 0.53). CONCLUSIONS: Our results indicate that patients with GS4+3 prostate cancers have higher PSA levels at diagnosis. GS4+3 is associated with 3-fold increased risk of IM at diagnosis than GS3+4 though the overall incidence is low. Further research is needed to assess whether GS4+3 patients need routine staging imaging investigations at the time of diagnosis similar to patients with higher Gleason scores (GS ≥8).

Knowledge, Attitude, and Practices Regarding Vector-borne Diseases in Western Jamaica.

BACKGROUND: Outbreaks of vector-borne diseases (VBDs) such as dengue and malaria can overwhelm health systems in resource-poor countries. Environmental management strategies that reduce or eliminate vector breeding sites combined with improved personal prevention strategies can help to significantly reduce transmission of these infections. OBJECTIVE: The aim of this study was to assess the knowledge, attitudes, and practices (KAPs) of residents in western Jamaica regarding control of mosquito vectors and protection from mosquito bites. METHODS: A cross-sectional study was conducted between May and August 2010 among patients or family members of patients waiting to be seen at hospitals in western Jamaica. Participants completed an interviewer-administered questionnaire on sociodemographic factors and KAPs regarding VBDs. KAP scores were calculated and categorized as high or low based on the number of correct or positive responses. Logistic regression analyses were conducted to identify predictors of KAP and linear regression analysis conducted to determine if knowledge and attitude scores predicted practice scores. FINDINGS: In all, 361 (85 men and 276 women) people participated in the study. Most participants (87%) scored low on knowledge and practice items (78%). Conversely, 78% scored high on attitude items. By multivariate logistic regression, housewives were 82% less likely than laborers to have high attitude scores; homeowners were 65% less likely than renters to have high attitude scores. Participants from households with 1 to 2 children were 3.4 times more likely to have high attitude scores compared with those from households with no children. Participants from households with at least 5 people were 65% less likely than those from households with fewer than 5 people to have high practice scores. By multivariable linear regression knowledge and attitude scores were significant predictors of practice score. CONCLUSION: The study revealed poor knowledge of VBDs and poor prevention practices among participants. It identified specific groups that can be targeted with vector control and personal protection interventions to decrease transmission of the infections.

Axon degeneration is key component of neuronal death in amyloid-ß toxicity.

Depending upon the stimulus, neuronal cell death can either be triggered from the cell body (soma) or the axon. We investigated the origin of the degeneration signal in amyloid ß (Aß) induced neuronal cell death in cultured in vitro hippocampal neurons. We discovered that Aß1-42 toxicity-induced axon degeneration precedes cell death in hippocampal neurons. Overexpression of Bcl-xl inhibited both axonal and cell body degeneration in the Aß-42 treated neurons. Nicotinamide mononucleotide adenylyltransferase 1 (Nmnat1) blocks axon degeneration in a variety of paradigms, but it cannot block neuronal cell body death. Therefore, if the neuronal death signals in Aß1-42 toxicity originate from degenerating axons, we should be able to block neuronal death by inhibiting axon degeneration. To explore this possibility we over-expressed Nmnat1 in hippocampal neurons. We found that inhibition of axon degeneration in Aß1-42 treated neurons prevented neuronal cell death. Thus, we conclude that axon degeneration is the key component of Aß1-42 induced neuronal degeneration, and therapies targeting axonal protection can be important in finding a treatment for Alzheimer's disease.