Clinical Utility of Folic Acid Testing for Patients with Anemia or Dementia

Background  Serum folic acid tests are routinely ordered by physicians for evaluating anemia and sometimes ordered for evaluating dementia and altered mental status. Objective  To determine the utility of routine folic acid testing for patients with anemia or dementia/altered mental status in the era of folic acid fortification. Design  Retrospective analysis of consecutive folic acid tests performed on adults over a 4-month period; chart review of patients without anemia. Measurements and Main Results  Serum folic acid level, mean corpuscular volume (MCV), and hematocrit. We reviewed 1,007 folic acid tests performed on 980 patients. The average age was 63.8 years, and 62% of the tests were from outpatient facilities. Only 4 (0.4%) patients had folic acid levels <3 ng/mL, while 10 (1%) patients had levels of 3–4 ng/mL (borderline). Thirty-five percent of the folic acid tests were performed on patients who were not anemic; most of these were ordered to evaluate dementia or altered mental status and folic acid level was normal in all these patients. Only 7% of the patients tested had a macrocytic anemia; these patients were more likely than those without macrocytic anemia to have low folic acid levels (2.8% vs 0.4%, p < .03). Conclusion  Low serum folic acid levels were rarely detected in a series of patients being evaluated for anemia, dementia, or altered mental status. The test should be reserved for patients with macrocytic anemia and those at high risk for folic acid deficiency.     

Comparison of Clinical and Radiographic Periodontal Status Between Habitual Water‐Pipe Smokers and Cigarette Smokers

Background: There is a dearth of studies that have compared clinical and radiologic markers of periodontal inflammation between water‐pipe smokers (WPs) and cigarette smokers (CSs). The aim of the present study is to compare the clinical and radiographic periodontal status between habitual WPs and CSs. Methods: In total, 200 males (50 WPs, 50 CSs, and 100 controls) with comparable mean age and education were included. Demographic information was recorded using a questionnaire. Periodontal parameters (plaque index [PI], bleeding on probing [BOP], probing depth [PD], clinical attachment loss [AL], and marginal bone loss [MBL]) and numbers of missing teeth (MT) were recorded. Results: The duration of each smoking session for WPs and CSs was 50.2 ± 6.7 and 15.3 ± 0.4 minutes, respectively. Number of MT [P <0.0001], PI [P <0.0001], AL [P <0.0001], PD ≥4 mm [P <0.0001], and MBL [P <0.0001]) was significantly higher among WPs and CSs than controls. BOP was significantly higher among controls than WPs (P <0.0001) and CSs (P <0.0001). There was no statistically significant difference in the aforementioned parameters between WPs and CSs. Conclusions: Males in a Saudi Arabian community who were CSs or WPs had more MT and poorer periodontal condition than never smokers. The periodontal condition of WPs was equally as poor as CSs. Additional clinical observational studies with emphasis on sex and sociodemographic characteristics are needed.     

Relationship between heart failure treatment and development of worsening renal function among hospitalized patients

Background

Among patients who are hospitalized with heart failure (HF), worsening renal function (WRF) is associated with worse outcomes. Whether treatment for HF contributes to WRF is unknown. In this study, we sought to assess whether acute treatment for patients who were hospitalized with HF contributes to WRF.

Methods

Data were collected in a nested case-control study on 382 subjects who were hospitalized with HF (191 patients with WRF, defined as a rise in serum creatinine level >26.5 μmol/L [0.3 mg/dL], and 191 control subjects). The association of medications, fluid intake/output, and weight with WRF was assessed.

Results

Calcium channel blocker (CCB) use and loop diuretic doses were higher in patients on the day before WRF (25% vs 10% for CCB; 199 ± 195 mg vs 143 ± 119 mg for loop diuretics; both P <.05). There were no significant differences in the fluid intake/output or weight changes in the 2 groups. Angiotensin-converting enzyme (ACE) inhibitor use was not associated with WRF. Other predictors of WRF included elevated creatinine level at admission, uncontrolled hypertension, and history of HF or diabetes mellitus. Higher hematocrit levels were associated with a lower risk. Vasodilator use was higher among patients on the day before WRF (46% vs 35%, P <.05), but was not an independent predictor in the multivariable analysis.

Conclusions

Several medical strategies, including the use of CCBs and a higher dose of loop diuretics, but not ACE inhibitors, were associated with a higher risk of WRF. Although assessment of inhospital diuresis was limited, WRF could not be explained by greater fluid loss in these patients. Determining whether these interventions are responsible for WRF or are markers of higher risk requires further investigation.     

Concentration‐dependent induction of reactive oxygen species,cell cycle arrest and apoptosis in human liver cells after nickel nanoparticles exposure

Due to advent of nanotechnology, nickel nanoparticles (Ni NPs) are increasingly recognized for their utility in various applications including catalysts, sensors and electronics. However, the environmental and human health effects of Ni NPs have not been fully investigated. In this study, we examined toxic effects of Ni NPs in human liver (HepG2) cells. Ni NPs were prepared and characterized by X‐ray diffraction, transmission electron microscopy and dynamic light scattering. We observed that Ni NPs (size, ～28 nm; concentration range, 25–100 μg/mL) induced cytotoxicity in HepG2 cells and degree of induction was concentration‐dependent. Ni NPs were also found to induce oxidative stress in dose‐dependent manner evident by induction of reactive oxygen species and depletion of glutathione. Cell cycle analysis of cells treated with Ni NPs exhibited significant increase of apoptotic cell population in subG1 phase. Ni NPs also induced caspase‐3 enzyme activity and apoptotic DNA fragmentation. Upregulation of cell cycle checkpoint gene p53 and bax/bcl‐2 ratio with a concomitant loss in mitochondrial membrane potential suggested that Ni NPs induced apoptosis in HepG2 cells was mediated through mitochondrial pathway. This study warrants that applications of Ni NPs should be carefully assessed as to their toxicity to human health. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 137–148, 2015.     

Prothrombin complex concentrate in major bleeding associated with DOACs; an updated systematic review and meta-analysis

Background

Four-factor prothrombin complex concentrate (PCC) is frequently used as a reversal agent for major bleeding in patients on factor Xa inhibitors. Piran et al. reviewed its safety and efficacy for the first time in 2018. However, more studies have been published on the matter since then. The aim of this study is to investigate the efficacy and safety of this use and update this review.

Methods

We systematically searched in Medline, Scopus, and the Cochrane Library from 1/1/2018 to 6/19/2020. A random effects model meta-analysis of proportions was used to study the efficacy of PCC on major bleeding control, mortality and thrombosis incidence.

Results

33 studies (n?=?2568 patients), with the majority of studies being uncontrolled retrospective cohort studies, were included; atrial fibrillation was the main factor Xa inhibitors indication and approximately 62% of patients presented with intracranial hemorrhage. We estimated the pooled proportion outcomes for hemostasis (80%, CI 0.75–0.84), mortality (15%, CI 0.11–0.19) and thromboembolic adverse events (3%, CI 0.02–0.05). High versus low dose PCC did not affect hemostasis or thrombosis. Patients with ICH had higher mortality rates (22%, CI 0.13–0.32). Heterogeneity was significant (Ι²?>?50% with p?<?0.05) for all pooled proportional outcomes. The quality of evidence was low given that included studies were not randomized or controlled.

Conclusion

Our study demonstrates the efficacy and safety of the off label use of 4F PCC in major bleeding associated with factor Xa inhibitors. Our data require further validation with future randomized clinical trials.

     

Kras activation in p53-deficient myoblasts results in high-grade sarcoma formation with impaired myogenic differentiation

While genomic studies have improved our ability to classify sarcomas, the molecular mechanisms involved in the formation and progression of many sarcoma subtypes are unknown. To better understand developmental origins and genetic drivers involved in rhabdomyosarcomagenesis, we describe a novel sarcoma model system employing primary murine p53-deficient myoblasts that were isolated and lentivirally transduced with Kras^G12D. Myoblast cell lines were characterized and subjected to proliferation, anchorage-independent growth and differentiation assays to assess the effects of transgenic Kras^G12D expression. Kras^G12D overexpression transformed p53^−/− myoblasts as demonstrated by an increased anchorage-independent growth. Induction of differentiation in parental myoblasts resulted in activation of key myogenic regulators. In contrast, Kras-transduced myoblasts had impaired terminal differentiation. p53^−/− myoblasts transformed by Kras^G12D overexpression resulted in rapid, reproducible tumor formation following orthotopic injection into syngeneic host hindlimbs. Pathological analysis revealed high-grade sarcomas with myogenic differentiation based on the expression of muscle-specific markers, such as Myod1 and Myog. Gene expression patterns of murine sarcomas shared biological pathways with RMS gene sets as determined by gene set enrichment analysis (GSEA) and were 61% similar to human RMS as determined by metagene analysis. Thus, our novel model system is an effective means to model high-grade sarcomas along the RMS spectrum.     

Mutation analysis of AMP-activated protein kinase subunits in inherited cardiomyopathies: implications for kinase function and disease pathogenesis

Familial hypertrophic cardiomyopathy (HCM) has been defined as a disease of the cardiac sarcomere, although sarcomeric protein mutations are not found in one third of cases. We have recently shown that HCM associated with Wolff-Parkinson-White syndrome (WPW) and conduction disease can be caused by mutations in PRKAG2, which encodes the gamma2 subunit of AMPK, an enzyme central to cellular energy homeostasis. AMPK is a heterotrimer composed of one catalytic subunit (alpha) and two regulatory subunits (beta and gamma). Seven known genes encode the subunit isoforms (alpha1, alpha2, beta1, beta2, gamma1, gamma2, gamma3) and all are expressed in the heart.To better understand the role of AMPK mutations in HCM/WPW and other inherited cardiomyophathies, all 7 subunit genes were screened for mutations in a panel of probands: 3 with HCM/WPW, 4 with DCM/WPW, 38 with HCM alone (in whom contractile protein mutations had not been found) and 13 with DCM alone. In total, 73 amplimers were screened in the 58 probands and a number of polymorphisms, including non-conservative substitutions, were identified. However, no further disease-causing mutations were found in any AMPK subunit gene.These results indicate that HCM with WPW is a distinct, but genetically heterogeneous, condition caused by mutations in PRKAG2 and in an unknown gene or genes, not involved in the AMPK complex. Mutations in PRKAG2 appear to specifically cause HCM with WPW and conduction disease, and not other inherited cardiomyopathies. As deleterious alleles were not found in other AMPK subunit isoforms, the mutations affecting PRKAG2 are likely to confer a specific alteration of AMPK function of particular importance in the myocardium.     

A pilot randomized controlled trial comparing bismuth iodine paraffin paste external ear pack and no ear pack after middle ear surgery

European Archives of Oto-Rhino-Laryngology - To pilot a substantive randomized control trial comparing post-operative external ear canal pack with no ear pack after middle ear surgery, 32 adults...