Predicting 90 day acute heart failure readmission and death using machine learning‐supported decision analysis

Readmission or death soon after heart failure (HF) admission is a significant problem. Traditional analyses for predicting such events often fail to consider the gamut of characteristics that may contribute– tending to focus on 30‐day outcomes even though the window of increased vulnerability may last up to 90 days. Risk assessments incorporating machine learning (ML) methods may be better suited than traditional statistical analyses alone to sort through multitude of data in the electronic health record (EHR) and identify patients at higher risk.HypothesisML‐based decision analysis may better identify patients at increased risk for 90‐day acute HF readmission or death after incident HF admission.Methods and ResultsAmong 3189 patients who underwent index HF hospitalization, 15.2% experienced primary or acute HF readmission and 11.5% died within 90 days. For risk assessment models, 98 variables were considered across nine data categories. ML techniques were used to help select variables for a final logistic regression (LR) model. The final model''s AUC was 0.760 (95% CI 0.752 to 0.767), with sensitivity of 83%. This proved superior to an LR model alone [AUC 0.744 (95% CI 0.732 to 0.755)]. Eighteen variables were identified as risk factors including dilated inferior vena cava, elevated blood pressure, elevated BUN, reduced albumin, abnormal sodium or bicarbonate, and NT pro‐BNP elevation. A risk prediction ML‐based model developed from comprehensive characteristics within the EHR can efficiently identify patients at elevated risk of 90‐day acute HF readmission or death for whom closer follow‐up or further interventions may be considered.     

Caffeine inhibition of ionotropic glycine receptors

We found that caffeine is a structural analogue of strychnine and a competitive antagonist at ionotropic glycine receptors (GlyRs). Docking simulations indicate that caffeine and strychnine may bind to similar sites at the GlyR. The R131A GlyR mutation, which reduces strychnine antagonism without suppressing activation by glycine, also reduces caffeine antagonism. GlyR subtypes have differing caffeine sensitivity. Tested against the EC₅₀ of each GlyR subtype, the order of caffeine potency (IC₅₀) is: α2β (248 ± 32 μ m ) ≈α3β (255 ± 16 μ m ) > α4β (517 ± 50 μ m ) > α1β(837 ± 132 μ m ). However, because the α3β GlyR is more than 3-fold less sensitive to glycine than any of the other GlyR subtypes, this receptor is most effectively blocked by caffeine. The glycine dose–response curves and the effects of caffeine indicate that amphibian retinal ganglion cells do not express a plethora of GlyR subtypes and are dominated by the α1β GlyR. Comparing the effects of caffeine on glycinergic spontaneous and evoked IPSCs indicates that evoked release elevates the glycine concentration at some synapses whereas summation elicits evoked IPSCs at other synapses. Caffeine serves to identify the pharmacophore of strychnine and produces near-complete inhibition of glycine receptors at concentrations commonly employed to stimulate ryanodine receptors.     

Cellular proliferative effect of dexamethasone in immortalized trabecular meshwork cell (TM5) line

Dexamethasone (DEX), one of the corticosteroid hormones, is one of the most common therapeutic strategies in ophthalmological treatment. Despite its widespread use and clinical efficiency, little is known regarding the specific effects of DEX on cell growth, differentiation and cell death in human trabecular meshwork cells. The presence of the glucocorticoid receptor (GR, dexamethasone receptor) in TM-5 cell line, which was derived from the primary human trabecular meshwork cells, was verified by RT-PCR and western blot analysis. The effects of DEX on the cellular proliferation of TM5 cells were measured by a BrdU incorporation assay. Western blot analysis were used to examine the effects of DEX on the Ras/MEK/ERK signaling pathway. The total Ras, MEK1/2 and ERK1/2 protein levels as well as the levels of activated (phosphorylated) form were both significantly increased by the DEX treatment for 5 days. Both MEK1/2 and ERK1/2 were significantly activated by phosphorylation after 10 minutes. The dependence of this increased cell proliferation on GR activation by DEX and the sustained activation of ERK was examined using RU486 (a GR inhibitor) and U0126 (a MEK inhibitor). Both RU486 and U0126 prevented the induction of cell proliferation by the DEX treatment in the TM5 cells. In conclusion this study demonstrated that GR is expressed in TM5 cells. Secondly, DEX treatment for 5 days stimulates cell proliferation in TM5 cells, and that this increased proliferation effect is mediated by the Ras/MEK/ERK pathway.     

Photodynamic Therapy with Ablative Carbon Dioxide Fractional Laser in Treatment of Actinic Keratosis

Background

Recently, photodynamic therapy (PDT) has been shown to be an effective first-line treatment for actinic keratosis (AK). However, a major limitation of PDT is the long incubation time required to allow penetration of the photosensitizer.

Objective

The aim of this study was to assess if pretreatment with an ablative carbon dioxide (CO₂) fractional laser can reduce the incubation time of the photosensitizer.

Methods

Initially, 29 patients with a total of 34 AK lesions were treated with an ablative CO₂ fractional laser at Ajou University Hospital between January and December 2010. Immediately after the laser treatment, topical 20% 5-aminolevulinic acid or methyl-aminolevulinate was applied to the AK lesions and incubated for 70 to 90 minutes. Then, the treated areas were illuminated with a red light source. Improvement was clinically or histologically assessed eight weeks after the treatment.

Results

In spite of the short incubation time, 24 lesions (70.6%) showed a complete response (CR) within three sessions of PDT (10 lesions a clinical CR and 14 lesions a clinical/histological CR). There were no significant side effects associated with the combination of ablative CO₂ fractional laser and PDT.

Conclusion

Ablative CO₂ fractional laser may be considered an additional treatment option for reducing the incubation time of the photosensitizer in PDT.     

Dose–response relationship between cigarette smoking and risk of ulcerative colitis: a nationwide population-based study

Background

Former cigarette smokers are at risk of developing ulcerative colitis (UC). However, the impact of smoking behavior on the occurrence of UC according to the amount smoked remains elusive. We aimed to determine the relationship between smoking behavior and the risk of UC development.

Methods

We conducted a retrospective population-based cohort study using the National Health Insurance Service database in South Korea. From January 2009 to December 2012, 23,235,771 individuals over 18 years of age who underwent a national health examination were enrolled and followed until 2016. All study participants were divided into the following 3 groups: nonsmokers, former smokers, and current smokers. The primary endpoint was newly developed UC.

Results

Compared with nonsmokers, the risk of UC development was significantly higher in former smokers [adjusted hazard ratio (aHR) 1.83; 95% confidence interval (CI) 1.73–1.95] but significantly lower in current smokers (aHR 0.92; 95% CI 0.87–0.98). Among current smokers, individuals who stopped smoking after the baseline evaluation had a significantly higher risk of UC development than those who continued to smoke (aHR 2.42; 95% CI 2.10–2.80). The risk of UC development among former smokers was significantly associated with smoking amount and duration. Among current smokers, however, the risk of UC development was not correlated with the cumulative lifetime smoking exposure. The preventive effect of current smoking on UC development was observed only in men (aHR 0.90; 95% CI 0.84–0.96).

Conclusions

Compared with nonsmokers, former smokers have a significantly higher risk of UC development that may be proportional to the cumulative smoking exposure.

     

Effect of pedunculagin investigated by non‐invasive evaluation on atopic‐like dermatitis in NC/Nga mice

Background/purpose: Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disorder that is becoming increasingly prevalent. Experimental animal models have been an indispensable tool for studying its pathological mechanisms and for in vivo testing of novel therapeutic approaches. AD‐like lesions can be induced experimentally in NC/Nga mice. Pedunculagin, an ellagitannin purified from the Manchurian alder, Alnus hirsuta var. microphylla, Betulaceae, is a novel immunomodulator. To evaluate the effect of pedunculagin for AD‐like lesions in NC/Nga mice, using clinical and non‐invasive methods. Methods: AD‐like lesions were induced in NC/Nga mice using 2,4,6‐trinitrochlorobenzene (TNCB). A cream containing 0.1% or 0.5% pedunculagin was applied to the positive treatment group, and the base cream without pedunculagin was applied to the negative treatment group. The control group did not receive any kind of topical agents. We evaluated the therapeutic efficacy of pedunculagin for AD by statistical evaluation of the clinical severity score using non‐invasive biomedical engineering tools before treatment, and 1 day, 3 days, 1 week, 2 weeks and 4 weeks afterwards. Results: An AD‐like skin rash was successfully induced using TNCB in NC/Nga mice. The group receiving higher concentrations of pedunculagin showed faster and greater improvement. Conclusion: Our results suggest that remedies made from natural materials like pedunculagin are now showing promise for medical applications, and many new studies are expected to explore this potential.     

Morbidity of Solid Cancer in Beh?et's Disease: Analysis of 11 Cases in a Series of 506 Patients

Purpose

Behçet''s disease (BD) is rarely reported to be associated with malignancies in the literature. However, the frequency of cancer in BD patients remains unknown. This study evaluated cancer morbidity in BD patients compared with that in the general population of Korea.

Materials and Methods

A retrospective chart review was performed on 506 patients visiting our hospital from 1994 to 2011 for BD. We analyzed the standardized morbidity rate (SMR), which is the ratio of observed to expected malignancies. Furthermore, we reviewed cases of solid cancer in BD patients in the literature.

Results

Of the 506 patients with BD, 11 (2.17%) developed cancer. We found a variety of solid cancers without predominance and no hematologic malignancies. The total number of cancers observed was less than expected, which was determined from the statistical data of the National Cancer Information Center of Korea, with an SMR of 0.023 (95% confidence interval, 0.012-0.039).

Conclusion

BD may be associated with a lower cancer-related morbidity compared with the general population of Korea.