Chronic Kidney Disease Increases Cerebral Microbleeds in Mouse and Man.

Brain microbleeds are increased in chronic kidney disease (CKD) and their presence increases risk of cognitive decline and stroke. We examined the interaction between CKD and brain microhemorrhages (the neuropathological substrate of microbleeds) in mouse and cell culture models and studied progression of microbleed burden on serial brain imaging from humans. Mouse studies: Two CKD models were investigated: adenine-induced tubulointerstitial nephritis and surgical 5/6 nephrectomy. Cell culture studies: bEnd.3 mouse brain endothelial cells were grown to confluence, and monolayer integrity was measured after exposure to 5-15% human uremic serum or increasing concentrations of urea. Human studies: Progression of brain microbleeds was evaluated on serial MRI from control, pre-dialysis CKD, and dialysis patients. Microhemorrhages were increased 2-2.5-fold in mice with CKD independent of higher blood pressure in the 5/6 nephrectomy model. IgG staining was increased in CKD animals, consistent with increased blood-brain barrier permeability. Incubation of bEnd.3 cells with uremic serum or elevated urea produced a dose-dependent drop in trans-endothelial electrical resistance. Elevated urea induced actin cytoskeleton derangements and decreased claudin-5 expression. In human subjects, prevalence of microbleeds was 50% in both CKD cohorts compared with 10% in age-matched controls. More patients in the dialysis cohort had increased microbleeds on follow-up MRI after 1.5 years. CKD disrupts the blood-brain barrier and increases brain microhemorrhages in mice and microbleeds in humans. Elevated urea alters the actin cytoskeleton and tight junction proteins in cultured endothelial cells, suggesting that these mechanisms explain (at least in part) the microhemorrhages and microbleeds observed in the animal and human studies

Dietary Tetrahydrocurcumin Reduces Renal Fibrosis and Cardiac Hypertrophy in 5/6 Nephrectomized Rats

Tetrahydrocurcumin (THC) is the principal metabolite of curcumin and has antioxidant properties. In the present investigation, the effect of THC on renal and cardiovascular outcomes was studied in rats with chronic kidney disease (CKD). CKD rats were randomized following 5/6 nephrectomy to a special diet for 9 weeks which contained 1% THC (CKD+THC group). Low-dose polyenylphosphatidylcholine was used as a lipid carrier to increase bioavailability. Endpoints included tail blood pressure, normalized heart weight, plasma and urine biochemical data, and kidney tissue analyses. CKD animals demonstrated increased proteinuria, decreased creatinine clearance, hypertension, and cardiac hypertrophy. The antioxidant proteins CuZn SOD and glutathione peroxidase were decreased in the remnant kidney, while apoptosis (caspase-3) and fibrosis (alpha-SM actin) were increased. Renal fibrosis was confirmed histologically on trichrome staining. These pathologic changes were ameliorated in the CKD+THC group with significant decrease in proteinuria, hypertension, and kidney fibrosis. THC therapy restored levels of CuZn SOD and glutathione peroxidase. Consistent with prior reports, dietary THC did not improve nuclear Nrf2 levels. In summary, dietary THC therapy improved expression of antioxidant proteins in the remnant kidney, decreased renal fibrosis and proteinuria, and ameliorated hypertension in 5/6 nephrectomized rats

Use and outcomes of antihypertensive medication treatment in the US hypertensive population: A gender comparison

Background: Although effective antihypertensive medications have existed for decades, only about half of the hypertensive individuals are considered to have controlled blood pressure. Limited research studies have investigated gender disparity in the utilization and effectiveness of antihypertensive medications treatment. To examine the gender difference in antihypertensive medications’ use and the effect of using antihypertensive medication treatment on blood pressure control among the U.S. adult with hypertension. Methods: Analysis of National Health and Nutrition Examination Survey (NHANES) data from (1999-2012) including individuals≥18 years old with hypertension. Study variables included gender, age, race/ethnicity, obesity, smoking, comorbidities, treatment medication type, and continuity of care. We used multivariate logistic regression in STATA V14. The data is presented as adjusted odds ratios (ORs) and 95% confidence interval (CI). Results: Of the 15719 participants, 52% were female. 49% of the antihypertensive medication users had their blood pressure under control (95% CI). In the adjusted logistic regression analysis, use of antihypertensive medications was found to be 12% greater in females as compared to males (OR=1.12; CI=1.02-1.22; P<0.05). No association between gender and blood pressure control was found. Blood pressure control was less likely achieved among 50 years or younger individuals, Blacks and Hispanics, obese, and those taking calcium channel blocker (CCB). Conclusion: Hypertensive females are more likely than males to use antihypertensive medications. The effectiveness of treatment to control blood pressure is equal across males and females. Our findings have implications for practitioners to account gender-specific approaches when discussing adherence to hypertension medication treatment with their patients

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial

Trends and racial disparity in primary pressure ulcer hospitalizations outcomes in the US from 2005 to 2014

In the United States (US), pressure ulcers affect ≤3 million people and costs exceed 26.8 billion US dollars in spending. To examine trends in primary pressure ulcer (PPU) hospitalization mortality, length of hospital stay (LOS), and inflation-adjusted charges (IAC) in the US from 2005 to 2014 by race/ethnicity. We secondarily examined the relationship between race/ethnicity with PPU mortality, LOS, and IAC with race/ethnicity. This cross-sectional study used Nationwide Inpatient Sample (NIS) data from 2005 to 2014. The study sample included all hospitalizations with the designated ICD-9-CM code of 707.20-25 (pressure ulcer). There was a notable decline in PPU hospitalization from 11.5% to 7.77 % between 2005 and 2014. The mean mortality decreased from 2.32% to 1.12% (P &lt; .001), the mean LOS declined from 9.39 days (P &lt; .001), and the mean IAC per hospitalization decreased from $30,935 to$29,432 (P &lt; .001). Positive changes observed in mortality, LOS, and IAC trends were consistent across different racial and ethnic groups. The results of multivariable logistic and linear regression analyses revealed that Black patients (β = 0.68, 95% CI 0.36-1.01, P &lt; .001) and patients belonging to the Other race/ethnic category (β = 0.93, 95% CI 0.18-1.69) had longer hospital stays compared to their White counterparts. Regarding IAC, Black patients (β = 2846, 95% CI 1254-4439, P &lt; .005), Hispanic patients (β = 6527, 95% CI 4925-8130), and patients from the Other race/ethnic category (β = 3473, 95% CI 1771-5174) had higher IAC for PPU treatment compared to their White counterparts. PPU hospitalization discharges, as well as hospitalization mortality, LOS, and IAC, decreased during the study period, however, our findings revealed disparities in PPU outcomes among different racial/ethnic groups. Implications of the findings are discussed

Racial and ethnic disparities in chronic health conditions among women with a history of gestational diabetes mellitus.

Background: This study aims to examine and determine the role of race/ethnicity in chronic conditions in women diagnosed with gestational diabetes mellitus (GDM) during any of their previous pregnancies. Methods: We used the National Health and Nutrition Examination Survey (NHANES) from2007-2016 to identify women who self-reported prior GDM and chronic disease diagnoses such as cardiovascular disease, hypertension, depression, and type 2 diabetes mellitus (T2DM).We used bivariate analysis using the chi-square test (χ²) and multiple logistic regressions to perform statistical test for associations, taking into consideration design and sample weight. Results: Among participants with prior GDM diagnoses, black women had a 74.4% prevalence of chronic disease, followed by Whites, 58.5% Hispanics, 58.0%, and Asians, 51.9% (P=0.009).Black women with prior GDM diagnoses had 2.4 odds of having chronic conditions compared to Whites (adjusted odds ratio [AOR]=2.40, 95% confidence interval [CI] = 1.28-4.50). In addition, they had higher odds of being former smokers (AOR=1.73, 95% CI=1.01-2.96),current smokers (AOR=1.96, 95% CI=1.06-3.61), having a body mass index (BMI) of 25-29.9(AOR=2.55, 95% CI=1.10-5.87), or a BMI ≥30 (AOR=4.09, 95% CI = 2.05-8.17) compared to their White counterparts. Hispanic women had lower odds of being diagnosed with GDM and associated chronic diseases. Conclusion: Black women with GDM were disproportionally affected and at higher risk to be diagnosed with chronic conditions. Smoking and obesity were strongly associated with chronic disease diagnoses. Our findings also suggest a 'Hispanic Paradox', requiring further study. These findings inform primary care clinicians and Obstetricians, and Gynecologists of at-risk patients who could benefit from lifestyle modification recommendations and counseling

Use and outcomes of antihypertensive medication treatment in the US hypertensive population: A gender comparison.

BACKGROUND: Although effective antihypertensive medications have existed for decades, only about half of the hypertensive individuals are considered to have controlled blood pressure. Limited research studies have investigated gender disparity in the utilization and effectiveness of antihypertensive medications treatment. To examine the gender difference in antihypertensive medications use and the effect of using antihypertensive medication treatment on blood pressure control among the U.S. adult with hypertension. METHODS: Analysis of National Health and Nutrition Examination Survey (NHANES) data from (1999-2012) including individuals≥18 years old with hypertension. Study variables included gender, age, race/ethnicity, obesity, smoking, comorbidities, treatment medication type, and continuity of care. We used multivariate logistic regression in STATA V14. The data is presented as adjusted odds ratios (ORs) and 95% confidence interval (CI). RESULTS: Of the 15719 participants, 52% were female. 49% of the antihypertensive medication users had their blood pressure under control (95% CI). In the adjusted logistic regression analysis, use of antihypertensive medications was found to be 12% greater in females as compared to males (OR=1.12; CI=1.02-1.22; P&lt;0.05). No association between gender and blood pressure control was found. Blood pressure control was less likely achieved among 50 years or younger individuals, Blacks and Hispanics, obese, and those taking calcium channel blocker (CCB). CONCLUSION: Hypertensive females are more likely than males to use antihypertensive medications. The effectiveness of treatment to control blood pressure is equal across males and females. Our findings have implications for practitioners to account gender-specific approaches when discussing adherence to hypertension medication treatment with their patients