Ending "domestic helicopter research".

"Helicopter research" refers to a practice where researchers from wealthier countries conduct studies in lower-income countries with little involvement of local researchers or community members. This practice also occurs domestically. In this Commentary, we outline strategies to curb domestic helicopter research and to foster equity-centered collaborations.

Effect of F11 Receptor/Junctional Adhesion Molecule-A-derived Peptide on Neointimal Hyperplasia in a Murine Model.

PURPOSE: To determine whether inhibition of the F11 receptor/JAM-A (F11R) using F11R-specific antagonist peptide 4D results in inhibition of smooth muscle cell (SMC) proliferation and migration in vivo, known as neointimal hyperplasia (NIH), using a mouse focal carotid artery stenosis model (FCASM). MATERIALS AND METHODS: The mouse FCASM was chosen to test the hypothesis because the dominant cell type at the site of stenosis is SMC, similar to that in vascular access stenosis. Fourteen C57BL/6 mice underwent left carotid artery (LCA) partial ligation to induce stenosis, followed by daily injection of peptide 4D in 7 mice and saline in the remaining 7 mice, and these mice were observed for 21 days and then euthanized. Bilateral carotid arteries were excised for histologic analysis of the intima and media areas. RESULTS: The mean intimal area was significantly larger in control mice compared with peptide 4D-treated mice (0.031 mm2 [SD ± 0.024] vs 0.0082 mm2 [SD ± 0.0103]; P = .011). The mean intima-to-intima + media area ratio was significantly larger in control mice compared with peptide 4D-treated mice (0.27 [SD ± 0.13] vs 0.089 [SD ± 0.081]; P = .0079). NIH was not observed in the right carotid arteries in both groups. CONCLUSIONS: Peptide 4D, an F11R antagonist, significantly inhibited NIH in C57BL/6 mice in a FCASM.

Promoting Anti-Racism in Clinical Practice: Lessons Learned in the Process of Removing the Race Coefficient from the Estimated Glomerular Filtration Rate Algorithm.

Background: Promoting anti-racism in medicine entails naming racism as a contributor to health inequities and being intentional about changing race-based practices in health care. Unscientific assumptions about race have led to the proliferation of race-based coefficients in clinical algorithms. Identifying and eliminating this practice is a critical step to promoting anti-racism in health care. The New York City Department of Health and Mental Hygiene (NYC-DOHMH) formed the Coalition to End Racism in Clinical Algorithms (CERCA), a health system consortium charged with eliminating clinical practices and policies that perpetuate racism. Objective: This article describes the process by which an academic medical center guided by the NYC-DOHMH tackled race-based clinical algorithms. Methods: Multiple key interested parties representing department chairs, hospital leaders, researchers, legal experts, and clinical pathologists were convened. A series of steps ensued, including selecting a specific clinical algorithm to address, conducting key informant interviews, reviewing relevant literature, reviewing clinical data, and identifying alternative and valid algorithms. Key Outcomes: Given the disproportionately higher rates of chronic kidney disease risk factors, estimated glomerular filtration rate (eGFR) was prioritized for change. Key informant interviews revealed concerns about the clinical impact that removing race from the equation would have on patients, potential legal implications, challenges of integrating revised algorithms in practice, and aligning this change in clinical practice with medical education. This collaborative process enabled us to tackle these concerns and successfully eliminate race as a coefficient in the eGFR algorithm. Conclusions: CERCA serves as a model for developing academic and public health department partnerships that advance health equity and promote anti-racism in practice. Lessons learned can be adapted to identify, review, and remove the use of race as a coefficient from other clinical guidelines.

Triple negative breast cancer metastasis is hindered by a peptide antagonist of F11R/JAM­A protein.

BACKGROUND: The F11R/JAM-A cell adhesion protein was examined as the therapeutic target in triple negative breast cancer (TNBC) with the use of the peptide antagonist to F11R/JAM-A, that previously inhibited the early stages of breast cancer metastasis in vitro. METHODS: The online in silico analysis was performed by TNMPlot, UALCAN, and KM plotter. The in vitro experiments were performed to verify the effect of peptide 4D (P4D) on human endothelial cell lines EA.hy926 and HMEC-1 as well as on human TNBC cell line MDA-MB-231. The cell morphology upon P4D treatment was verified by light microscopy, while the cell functions were assessed by colony forming assay, MTT cell viability assay, BrdU cell proliferation assay, and Transepithelial/Endothelial Electrical Resistance measurements. The in vivo experiments on 4T1 murine breast cancer model were followed by histopathological analysis and a series of quantitative analyses of murine tissues. RESULTS: By in silico analysis we have found the elevated gene expression in breast cancer with particular emphasis on TNBC. The elevated F11R expression in TNBC was related with poorer survival prognosis. Peptide 4D has altered the morphology and increased the permeability of endothelial monolayers. The colony formation, viability, and proliferation of MDA-MB-231 cells were decreased. P4D inhibited the metastasis in 4T1 breast cancer murine model in a statistically significant manner that was demonstrated by the resampling bootstrap technique. CONCLUSIONS: The P4D peptide antagonist to F11R/JAM-A is able to hinder the metastasis in TNBC. This assumption needs to be confirmed by additional 4T1 mouse model study performed on larger group size, before making the decision on human clinical trials.

Impact of diabetes on COVID-19 patient health outcomes in a vulnerable racial minority community.

BACKGROUND: Diabetes is a growing health concern in the United States and especially New York City. New York City subsequently became an epicenter for the coronavirus pandemic in the Spring of 2020. Previous studies suggest that diabetes is a risk factor for adverse outcomes in COVID-19. OBJECTIVE: To investigate the association between diabetes and COVID-19 outcomes as well as assess other covariates that may impact health outcomes. DESIGN: Retrospective cohort study of COVID-19 hospitalized patients from March to May, 2020. PARTICIPANTS: In total, 1805 patients were tested for COVID-19 and 778 tested positive for COVID-19. Patients were categorized into 2 groups: diabetes (measured by an Hba1c >6.5 or had a history of diabetes) and those without diabetes. RESULTS: After controlling for other comorbidities, diabetes was associated with increased risk of mortality (aRR = 1.28, 95% CI 1.03-1.57, p = 0.0231) and discharge to tertiary care centers (aRR = 1.69, 95% CI 1.04-2.77, p = 0.036). compared to non-diabetes. Age and coronary artery disease (CAD) increased the risk of mortality among diabetic patients compared to patients with diabetes alone without CAD or advanced age. The diabetes cohort had more patients with resolving acute respiratory failure (62.2%), acute kidney injury secondary to COVID-19 (49.0%) and sepsis secondary to COVID-19 (30.1%). CONCLUSION: This investigation found that COVID-19 patients with diabetes had increased mortality, multiple complications at discharge, and increased rates of admission to a tertiary care center than those without diabetes suggesting a more severe and complicated disease course that required additional services at time of discharge.

A Case of Acute Colonic Pseudo-Obstruction (Ogilvie's Syndrome) in a Nonsurgical Patient with Plasma Cell Leukemia.

Ogilvie's syndrome, also known as acute colonic pseudo-obstruction (ACPO), is a rare, nonobstructive dilation of the colon of unclear etiology. We present the case of a patient who presented with Ogilvie's syndrome and significant hypokalemia due to colonic loss despite repletion. This case report demonstrates the difficulty in diagnosis, treatment, and outcome.

Relationship between the Soluble F11 Receptor and Annexin A5 in African Americans Patients with Type-2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is characterized by endothelial dysfunction, increased thrombogenicity, and inflammation. The soluble human F11 receptor (sF11R) and annexin A5 (ANXA5) play crucial roles in inflammatory thrombosis and atherosclerosis. We examined the relationship between circulating sF11R and ANXA5 and their impact on endothelial function. The study included 125 patients with T2DM. Plasma levels of sF11R and ANXA5 were quantified by ELISA. Microvascular function was assessed using the vascular reactivity index (VRI). Large artery stiffness was assessed by carotid-femoral pulse wave velocity (PWV). Carotid intima-media thickness (CIMT) was assessed by B-mode ultrasound imaging. The mean age of patients in the study was 59.7 ± 7.8 years, 78% had hypertension, 76% had dyslipidemia, and 12% had CKD. sF11R correlated positively with ANXA5 levels (ß = 0.250, p = 0.005), and correlated inversely with VRI and total nitic oxide (NO), (ß = −0.201, p = 0.024; ß = −0.357, p = 0.0001, respectively). Multivariate regression analysis revealed that sF11R was independently associated with ANXA5 in the total population and in patients with HbA1c > 6.5% (ß = 0.366, p = 0.007; ß = 0.425, p = 0.0001, respectively). sF11R and ANXA5 were not associated with vascular outcome, suggesting that they may not be reliable markers of vascular dysfunction in diabetes. The clinical significance of sF11R/ANXA5 association in diabetes warrants further investigation in a larger population.

Determination of unacceptable antigens by summation of anti-HLA eplet antibody strength (MFI) based on single antigen bead assays: Excellent correlation with negative cell based cross matches.

The reliability of single antigen bead (SAB) assays and their use in predicting a negative cell based cross match (CBXM) is essential in the era of expanded organ sharing. A wide range of accuracy (80-95%) in predicting negative CBXM has been reported. We hypothesized that in SAB assays an antibody against an HLA eplet that was common among a number of different HLA alleles would be distributed among all of the shared eplet positive SABs. This would reduce binding to the donor specific SAB resulting in an under-estimate of antibody strength. We tested this proposal in adsorption studies using, instead of lymphocytes, a novel reagent, single-SAB (sSAB). Properties of SAB assays were examined that provided a basis for conducting adsorption - elution experiments with the sSABs. We found that incubation of sera with sA*02:01 or sB*42:01 not only depleted reactivity to these alleles but also depleted reactivity to beads that shared the reactive eplet. Anti-eplet strength from SAB data (sum of the MFI of eplet positive SABs (MFI-s) was compared with CBXM out comes in two case studies and with 99 proficiency testing sera. In these validation studies, an MFI-s above 11,000 was associated with a positive FCXM. This approach was placed into clinical practice for listing unacceptable antigens that shared a common eplet. CDCXMs (n = 3261) and FCXMs (n = 1012) were performed on patients listed in UNOS for deceased donor kidneys. All CDCXMs were negative and all FCXMs except one were negative. We conclude that summation of eplet strength provides a highly reliable method of predicting prospective negative CBXMs resulting in substantial savings of time and effort. Based on shared eplet summation data, CMS/NYSDOH has accepted our bead based XM (BBXM) method (aka, virtual XM) performed prior to transplant as fulfilling the regulation that XM results be available before kidney transplantation.

Genes modulating intestinal permeability and microbial community are dysregulated in sickle cell disease.

Based on previous studies showing abnormalities in the intestinal pathophysiology characterized by disruption in the gut barrier functions, and alteration in the intestinal microbial load and composition, we set out in the study to examine the expression of genes that might be involved in mediating these changes in Townes sickle cell disease (SCD) mice at 6 months old compared to non-SCD control mice. Using qPCR on total RNA isolated from the intestine, we found downregulation of the TJ genes JAM-A, Occludin, and ZO-1 in both the small intestine and colon. E-Cadherin and MUC2 were also downregulated. In contrast, gene encoding claudin-2 that mediates increase permeability to water and ions was upregulated in the small intestine. Claudin-2 upregulation is usually also associated with ongoing inflammation. Intestinal epithelium also includes Paneth cells that produce antimicrobial peptides (AMPs) that regulate intestinal microbial community. We also found that the expression of the genes encoding the AMPs defensin-α4 was reduced in the small intestine and colon and defensin-α1 in the colon in the SCD mice. Our findings are novel and provide direction for further studies into the characteristics and mechanisms of the intestinal pathophysiologic changes observed in SCD.

Clotting of Hemodialysis Access in Patients with COVID-19 in an Inner-City Hospital.

BACKGROUND: An increased incidence of thrombotic complications in patients with coronavirus disease 2019 (COVID-19) has been reported. Severe acute kidney injury (AKI) is one of the major clinical manifestations of COVID-19 with the need for renal replacement therapy. It was observed that hemodialysis (HD) accesses tended to thrombose more often in the COVID-19 population than in non-COVID-19 patients. We hypothesize that the hypercoagulable state of COVID-19 is associated with higher incidence of access clotting. METHOD: In this retrospective single-centered study at Kings County Hospital in New York City, 1,075 patients with COVID-19 were screened, and 174 patients who received HD from January 3, 2021 to May 15, 2020 were enrolled to examine the risk factors of dialysis access clotting in patients with COVID-19. RESULTS: Of the 174 patients, 109 (63%) were COVID-19 positive. 39 (22.6%) patients had dialysis access clotting at least once during their hospitalization, and they had significantly higher body mass index (BMI) (p = 0.001), higher rates of COVID-19 (p = 0.015), AKI (p < 0.001), higher platelet counts (p = 0.029), higher lactate dehydrogenase levels (p = 0.009), and lower albumin levels (p = 0.001) than those without access malfunctions. Low albumin levels (p = 0.008), AKI (p = 0.008), and high BMI (p = 0.018) were risk factors associated with HD access clotting among COVID-19 patients. CONCLUSION: Patients with COVID-19 who receive HD for AKI with high BMI are at a higher risk of clotting their HD access.

Intestinal pathophysiological abnormalities in steady state and after vaso-occlusive crisis in murine sickle cell disease.

We showed in the present study that, not unlike in adult patients with sickle cell disease (SCD), Townes mice exhibit increases in serum intestinal fatty acid binding proteins and lipopolysaccharides (LPS), together with a breach in the intestinal barrier. These abnormalities increased rapidly after the induction of vaso-occlusive crisis (VOC). We also confirmed higher intestinal microbial density in SCD. These findings support the concept that SCD and/or its complications, and not hospitalisation or medications, are responsible for the intestinal pathophysiological changes. The present results provide the basis for use of Townes mice to further elucidate the mechanistic relationship between intestinal pathophysiology and VOC.

The Implication of Dropping Race from the MDRD Equation to Estimate GFR in an African American-Only Cohort.

The widely used Modification of Diet in Renal Disease (MDRD) formula adapts a 1.212 multiplier for individuals who are identified as African Americans (AAs) or Blacks, which leads to a higher GFR estimation. As it stands, AAs have a lower prevalence of chronic kidney disease (CKD) but higher incidence of end-stage renal disease (ESRD) compared with Whites. Many hypotheses have been postulated to explain this paradox, but the imprecision of the GFR estimation with race-adaptation could be contributory. We performed a single-center, longitudinal, retrospective study on a cohort of outpatient AA patients using the MDRD and MDRDrace removed and CKD-EPI and CKD-EPIrace removed and their progression to CKD G5 (eGFR <15 ml/min/1.73 m2). 327 patients were analyzed. Median follow-up was 88.1 months (interquartile range, 34.4-129.1). When race was removed from MDRD, 39.9% of patients in CKD G1/2 were reclassified to CKD G3a, 72.6% of patients in CKD G3a would be reclassified to CKD G3b, and 54.1% and 36.4% of patients would be reclassified from CKD 3b to CKD G4 and CKD G4 to CKD G5, respectively (p < 0.0001). Comparing the CKD-EPI formula against the MDRD in our cohort, we found that 8.2%, 18.8%, and 11.4% of patients were reclassified from CKD G1/2 to CKD G3a, CKD G3a to G3b, and CKD G3b to CKD G4 respectively. Overall median time to progression to CKD G5 was 137.4 (131.9-142.8) months in patients who were not reclassified and 133.6 (127.6-139.6) months for patients who were reclassified by MDRDrace removed(p < 0.288). Concerns of inequitable access to healthcare have elicited calls to review race-corrected eGFR equations. A substantial number of individuals would have their CKD stage reclassified should have the MDRDrace removed equation be adopted en masse on an AA-only population. The discrepancy is highest at the 45-59 and >60 ml/min/1.72 min2 ranges. This will have tremendous impact on our center's approach to pharmacological dosing, referral system, best practices, and outcome surveillance. Comprehensive review of the current "race-corrected" eGFR will require a multifaceted approach and adjunctive use of noncreatinine-based approach.

Hematopoietic Stem Cell Transplant for Sickle Cell Disease: PATIENT SELEction and Timing Based on Sickle Cell-Related Multiple Chronic Conditions.

Hematopoietic stem cell transplant (HSCT) is the only cure for patients with sickle cell disease (SCD). Although most SCD patients experience progressive end-organ damage and shortened lifespans, not all patients follow the same disease course, tempo, or outcome. Therefore, the dilemma facing physicians is weighing the selection of patients and timing for the procedure against donor type and transplant-related mortality and morbidity that go up with increasing age. On the other hand, the dilemma facing the patients and families is how acceptable HSCT that carries some mortality risks to them. We have analyzed the chronic conditions due to SCD in 449 patients to determine whether SCD-related multiple chronic conditions (MCC) can be risk-stratified to identify the group of patients predicted to not only have shortened lifespans but also functional limitation and poor quality of life so that these at-risk patients can be offered HSCT early and before MCC develops. We identified that the age of onset of the first SCD-related chronic conditions strongly predicted for the risks for disease-related MCC. SCD patients who suffered their first disease-related chronic condition before age 30 years developed MCC at a rate of 19.1 times faster than those at a later age. These patients are therefore high-risk patients and should be offered HSCT early in the course of their disease before multiple organ damage intervenes, even if matched-related donors are not available. This patient selection and timing approach provides a forum for an easy-to-understand and real-time discussion, including the choice of donor type, with SCD patients and families when considering HSCT.

Obesity and diabetes mellitus in patients with sickle cell disease.

Obesity and diabetes mellitus are prevalent among the African-American/Black population. They result in multiple chronic conditions that impact the quality and lifespan of the patients. Their occurrence in patients with sickle cell disease (SCD) will increase the risks for multimorbidity in these patients. We have carried out a chart survey of a cohort of 449 patients with SCD to determine the prevalence rates of obesity and diabetes mellitus in these patients. SCD patients were less likely to develop obesity and diabetes mellitus, compared to their peers of the same race/ethnicity. The lower prevalence rates were observed in those over the age of 6 years, irrespective of the gender of the patients. Their life-time probabilities for obesity and diabetes mellitus were also low. Within this group of SCD patients, obesity was associated with significantly higher prevalence of diabetes mellitus. The underlying reasons for our observed results of low prevalence rate of obesity in SCD remain speculative but may be related to reduced calorie intake, increased calorie use due to hypermetabolism, reduced intestinal absorption, or intestinal dysbiosis.

Opioids and Acute Kidney Injury.

Opioid use and misuse in the United States has been at epidemic proportions and is predicted to increase further in the setting of the Coronavirus disease 19 pandemic. Acute kidney injury is a condition associated with significant morbidity and increased mortality. We review the literature on the effect of opioids on kidney function and critically examine the association between opioid use and acute kidney injury and identify at-risk populations in whom opioids should be used with caution. We also discuss the role of biomarkers in elucidating this condition and propose preventive measures, novel therapeutic options, and research directions.

HIV Testing Correlates: U.S. and Foreign Born High-Risk Black Heterosexual Men.

In the U.S., Black men are disproportionately affected by HIV, with some of the highest HIV incidence rates and lowest rates of HIV testing. We examined correlates of HIV testing and knowledge among participants of the Barbershop Talk with Brothers (BTWB) project, an HIV prevention program targeting high-risk sexual behaviors among Black heterosexual men in Brooklyn, New York. Specifically, we examined differences between U.S. vs. foreign-born status and HIV testing rates, HIV knowledge, and socio-demographic factors. Of the 855 men included, the mean age was 33 years and 35.0% were foreign-born. Lifetime HIV testing was reported at 84%, with greater proportion of U.S. vs foreign-born men reporting lifetime (88.6% vs. 75.0%) and recent testing (68.6% vs. 51.0%), p < 0.001. Among foreign-born men, recent HIV testing was associated with lower stigma and greater HIV transmission knowledge than those un-tested. The authors recommend tailored approaches to increasing HIV testing in Black communities, based on nativity and social factors.

Association between nitrated lipoproteins and vascular function in type 2 diabetes.

Higher levels of nitrated lipoproteins (NT-HDL and NT-LDL) were found in blood and atherosclerotic plaques of patients with coronary artery disease. We aimed to examine the relationship between plasma NT-HDL and NT-LDL and diabetic vascular dysfunction. The study included 125 African-American patients with T2DM. NT-HDL and NT-LDL were quantified by ELISA. Microvascular function was assessed by vascular reactivity index (VRI). Large artery stiffness was assessed by carotid-femoral pulse wave velocity (PWV). Carotid intima-media thickness (CIMT) was assessed by B-mode ultrasound imaging. In univariate analysis, NT-HDL was associated with VRI in total population and in patients with HbA1c more than or equal to 7.0 percent (beta= -0.178, p= 0.034; beta = -0.265, p= 0.042; respectively). In contrast, NT-LDL was associated with CIMT in total population and in patients with HbA1c more than 7.0 percent (beta = -0.205, p= 0.022; beta = -0.244, p= 0.042; respectively). Multivariable-adjusted regression analysis demonstrated that NT-HDL independently predicted VRI outcome in total population and in well-controlled patients (beta = -0.282, p= 0.014; beta = -0.400, p= 0.035, respectively). These results suggest that NT-HDL could be used as marker to identify diabetic patients at risk of developing early microvascular complications.

Association of Physical Function and Survival in Older-Adult Renal Transplant Recipients.

There is an increase in older-adult renal transplant recipients in United States. The objective of this study was to assess the association between physical function (PF) and patient survival in renal transplant recipients who are aged 65 years or older. Using United Network for Organ Sharing (UNOS) data from 2007 to 2016, renal transplant recipients aged 65 years or older were included. Multivariable Cox regression was used to assess associations between survival and functional status adjusted for age, sex, race, donor quality, diabetes, and dialysis vintage. The study identified 26,721 patients. Patient survival was significantly higher in recipients who needed no assistance and lowest in patients in need of total assistance (P < .0001). In deceased donor (DD) transplants, the relative risk for mortality was 2.06 (1.74-2.43) for total assistance and 1.17 (1.08-1.28) for moderate assistance compared to no assistance (P < .0001). In living donor (LD) transplants, the relative risk of mortality was 1.38 (0.78-2.42) for patients needing total assistance and 1.37 (1.14-1.65) for patients needing moderate assistance compared to patients who did not need assistance (0.003). PF is an independent predictor of post-transplant mortality. Assessment of older potential renal transplant recipients should include assessment and standardization of functional status to counsel about post-transplant survival.