Liver Fibrosis is Associated with Ischemic Stroke Risk in Women but not Men: The REGARDS Study

BackgroundNonalcoholic fatty liver disease is inconsistently associated with ischemic stroke, with one study suggesting an association in women and not men. The relative importance of liver fibrosis, as opposed to fatty liver, for cardiovascular risk is increasingly appreciated. We hypothesized that advanced liver fibrosis is associated with incident ischemic stroke risk, and especially in women.MethodsWe performed a case-cohort study in the REasons for Geographic and Racial Differences in Stroke cohort. Black and white individuals aged 45 and older were recruited between 2003 and 2007 and followed for ischemic stroke. The Fibrosis-4 (FIB-4) score and Nonalcoholic Fatty Liver Disease Fibrosis Score (NFS) were calculated using baseline data for stroke cases and a cohort random sample; advanced liver fibrosis was classified using validated cutoffs. Cox proportional hazards models were used to estimate hazard ratios (HR) of stroke after adjusting for potential confounders. Sex differences were assessed.ResultsThere were 572 incident ischemic strokes (285 in women) over 5.4 (SD, 2.2) years. Advanced liver fibrosis was not significantly associated with ischemic stroke overall using the FIB-4 (HR 1.44; 95% CI 0.49–4.28) or NFS (HR 1.76; 95% CI 0.67–4.61). However, liver fibrosis was associated with stroke in women (HR 3.51; 95% CI 1.00–12.34) but not men (HR 0.70, 95% CI 0.16–3.16) (P = 0.098 for interaction) when using FIB-4. A similar but non-significant sex difference was seen for NFS.ConclusionAdvanced liver fibrosis may be associated with a higher risk of ischemic stroke in women but not men.     

Vitamin D and Clinical Outcomes in Dialysis

Most dialysis patients are vitamin D deficient, including deficiencies in both activated vitamin D (1, 25‐dihydroxyvitamin D) and the less active 25‐hydroxyvitamin D. These and other abnormalities associated with chronic kidney disease (CKD), if they remain untreated, lead to secondary hyperparathyroidism and bone changes, such as osteitis fibrosa cystica. Activated vitamin D has been proven to decrease parathyroid hormone (PTH) levels in dialysis patients and is currently used for this indication. There are multiple other potential “pleotrophic” effects associated with vitamin D therapy. These include associations with lower all‐cause and cardiovascular mortality, lower rates of infections and improved glycemic indexes. Meta‐analyses of multiple observational studies have shown activated vitamin D therapy to be associated with improved survival. Observational data also suggest fewer infections and better glucose control. There have been no randomized clinical trials powered to evaluate mortality or other clinical outcomes. Small trials of nutritional vitamin D (ergocalciferol and cholecalciferol) showed increases in 25‐hydroxyvitamin D levels without hypercalcemia or hyperphosphatemia, even when given in addition to activated vitamin D therapy. While activated vitamin D therapy is associated with improved outcomes, it also leads to higher fibroblast growth factor 23 (FGF‐23) levels, which may be detrimental in dialysis patients. Further research is needed to evaluate whether activated or nutritional vitamin D therapy are beneficial in dialysis patients for outcomes other than secondary hyperparathyroidism.     

Gene transfer to primary normal and malignant human hemopoietic progenitors using recombinant retroviruses

To study the feasibility of using retroviruses for gene transfer into human hemopoietic cells, various cell types were exposed to virus carrying the gene for neomycin resistance (neor). In preliminary studies using K562 cells as targets, we found that high viral titer and co-cultivation with viral producer cells rather than incubation in medium exposed to viral producer cells were important variables for achieving high frequencies of G418 resistant (G418r) colonies. The maximum frequency of G418r K562 colonies after co-cultivation with cells producing a neor virus titer of 4 X 10(6) cfu/mL was 60%. When primary human progenitors from normal marrow, fetal liver, or chronic myelogenous leukemia blood were exposed to high titer viral stocks, both with and without helper virus, under conditions optimized for K562 cells, maximum frequencies of G418r colonies were 3% to 16% for granulocyte macrophage progenitors and 2% to 6% for primitive erythroid progenitors. The presence of the neor gene in both G418r K562 and primary hemopoietic colonies was verified by Southern blot. Expression of the neor gene was shown by RNA spot blot. These data demonstrate efficient transfer and expression of the neor gene in both K562 cells and primary human hemopoietic cells from normal and leukemic individuals.     

Insurance Coverage Predicts Mortality in Patients Transferred Between Hospitals: a Cross-Sectional Study

Background

Patients transferred between hospitals are at high risk of adverse events and mortality. The relationship between insurance status, transfer practices, and outcomes has not been definitively characterized.

Objective

To identify the association between insurance coverage and mortality of patients transferred between hospitals.

Design

We conducted a single-institution observational study, and validated results using a national administrative database of inter-hospital transfers.

Setting

Three ICUs at an academic tertiary care center validated by a nationally representative sample of inter-hospital transfers.

Patients

The single-institution analysis included 652 consecutive patients transferred from 57 hospitals between 2011 and 2012. The administrative database included 353,018 patients transferred between 437 hospitals.

Measurements

Adjusted inpatient mortality and 24-h mortality, stratified by insurance status.

Results

Of 652 consecutive transfers to three ICUs, we observed that uninsured patients had higher adjusted inpatient mortality (OR 2.67, p?=?0.021) when controlling for age, race, gender, Apache-II, and whether the patient was transferred from an ED. Uninsured were more likely to be transferred from ED (OR 2.3, p?=?0.026), and earlier in their hospital course (3.9 vs 2.0 days, p?=?0.002). Using an administrative dataset, we validated these observations, finding that the uninsured had higher adjusted inpatient mortality (OR 1.24, 95% CI 1.13–1.36, p?<?0.001) and higher mortality within 24 h (OR 1.33 95% CI 1.11–1.60, p?<?0.002). The increase in mortality was independent of patient demographics, referral patterns, or diagnoses.

Limitations

This is an observational study where transfer appropriateness cannot be directly assessed.

Conclusions

Uninsured patients are more likely to be transferred from an ED and have higher mortality. These data suggest factors that drive inter-hospital transfer of uninsured patients have the potential to exacerbate outcome disparities.

     

The metabolic syndrome: what to treat, how to treat, what are the goals?

Metabolic syndrome is a cluster of risk factors for cardiovascular disease that include obesity, atherogenic dyslipidemia, raised blood pressure, and insulin resistance. The growing trend of obesity is associated with increased prevalence of metabolic syndrome. Optimizing diet and exercise are still the leading therapy for controlling the metabolic syndrome. Based on the current evidence, further emphasis should be placed on aggressive management of other metabolic risk factors such as high blood pressure and dyslipidemia.