Photosensitizing and radiosensitizing effects of mitoxantrone: combined chemo-, photo-, and radiotherapy of DFW human melanoma cells

This study evaluated the effects of mitoxantrone (MX), an antitumor agent, as a sensitizer to both photodynamic and radiation therapy in DFW human melanoma cells. Cells were incubated with MX at different concentrations for 90 min and then exposed to non-coherent light at different fluence rates and/or X-ray ionizing radiation at different dose rates. Combinatorial effects of this chemo-, photo-, and radiotherapy were also evaluated. MX had no significant effects on viability at moderate doses but had a strong cytotoxic effect on cancer cells when used as a photosensitizer. MX also acted as a potent radiosensitizer. We observed a dose-dependent effect on cell viability in cells exposed to MX in combination with phototherapy and radiotherapy. Strong synergistic effects were observed for combinations of two or more treatment methods, which, in some cases, induced complete cell death. Thus, a combination of ionizing radiation with MX-mediated photodynamic therapy could serve as a new method for cancer therapy with fewer adverse side effects.     

Rituximab induced cytokine release syndrome in an MS patient: A case report

Cytokine release syndrome with rituximab has been reported in certain diseases, however, it is rarely reported in MS patients treated with rituximab. The treating physician should suspect the syndrome when typical signs and symptoms appear.     

Dual-energy CT evaluation of gastrointestinal bleeding

Abdominal Radiology - Gastrointestinal bleeding is a common cause for hospital admissions and is an important cause of morbidity and mortality. Although endoscopy is accepted as the standard...     

The Correlation Between Prolonged Corrected QT Interval with the Frequency of Respiratory Arrest,Endotracheal Intubation,and Mortality in Acute Methadone Overdose

Corrected QT interval (QTc) prolongation is long considered as a predisposing factor for the occurrence of torsade de pointes (TdP) and sudden cardiac arrest in methadone maintenance treatment. We aimed to elucidate the correlation between QTc prolongation and in-hospital death, respiratory arrest, and endotracheal intubation in acute methadone-intoxicated patients presenting to the emergency department and to assess the value of QTc in predicting these outcomes. A prospective cross-sectional study with a convenience sample of patients with acute methadone overdose was done. Participants were 152 patients aged 15–65 with negative urinary dipstick test for cyclic antidepressants, no history of other QTc-prolonging conditions and co-ingestions, no severe comorbidities affecting the outcomes, and positive urinary dipstick results for methadone. QTc intervals were measured and calculated in triage-time electrocardiogram (ECG). Death was correlated with QTc (P = 0.014) and length of ICU admission (P < 0.001). In multivariable analysis, death was independently associated only with length of ICU admission [odds ratio (OR) 95 % confidence intervals (95 % CI) 1.36 (1.14–1.61)]. Intubation and respiratory arrest were independently associated with QTc interval [OR (95 % CI) 1.03 (1.02–1.04) and 1.02 (1.01–1.03), respectively]. The receiver operating characteristics curves drawn to show the ability of QTc to predict death, intubation, and respiratory arrest showed thresholds of 470, 447.5, and 450 ms with sensitivity (95 % CI) and specificity (95 % CI) of 87.5 (47.3–99.7), 86.8 (74.7–94.5), and 77.3 (62.2–88.5), respectively. Our study showed that QTc is a potential predictor for adverse outcomes related to acute methadone intoxication. The correlations shown in this study between triage-time QTc and in-hospital respiratory arrest or intubation in methadone overdose may be of clinical value, whether these outcomes are hypothesized to be a reflection of background TdP or intoxication severity.     

Predictors of Left Ventricular Ejection Fraction Improvement after Radiofrequency Catheter Ablation in Patients with PVC-Induced Cardiomyopathy: A Systematic Review

Background Frequent premature ventricular contractions (PVC) can result in PVC-induced cardiomyopathy (PVC-iCMP), leading to reduced Left Ventricular Ejection Fraction (LVEF) that can be improved by radiofrequency catheter ablation (RFCA). We performed a systematic review to determine the variables predicting LVEF improvement after RFCA in PVC-iCMP.Methods We developed a “population, intervention, outcome and predictive factors” framework and searched MEDLINE, Embase, Cochrane Library, Cochrane Collaboration and Cochrane Database of Systematic Reviews (CDSR) for full-text, peer-reviewed publications. These publications addressing predictive factors of LVEF improvement showed ≥5% improvement only if deemed significant by the respective study, ≥10% or ≥ 50% after RFCA ablation in patients with PVC-iCMP with no type/date/language limitation until the end of 2017.Results Our initial search yielded 2226 titles, 1519 of which remained after removing the duplicates. Finally, 11 articles - 2 cohorts, 7 quasi-experimental studies, 1 case-control and 1 meta-analysis- were included. Sustained successful ablation, higher baseline PVC burden, LVEF, QRS duration, post-PVC systolic blood pressure rise and post-PVC pulse pressure change, the absence of an underlying cardiomyopathy, younger age, and variability of the frequency of PVCs during the day and lower left ventricular end-diastolic diameter (LVEDD) have been suggested as predictive factors for LVEF improvement in patients with PVC-iCMP.Conclusion The mentioned factors may all be useful to identify PVC-iCMP patients who would benefit from RFCA, although the evidence is not yet strong enough.     

The effect of PCSK9 immunization on the hepatic level of microRNAs associated with the PCSK9/LDLR pathway

IntroductionMicroRNAs (miRNAs) are a class of gene expression epigenetic regulators that play roles in regulating genes involved in cholesterol homeostasis, including low-density lipoprotein receptor (LDLR) and PCSK9; therefore, miRNAs have been suggested as potential therapeutic targets for treating cardiometabolic disorders. Thus, the present study aimed to assess the effect of immunotherapy with the PCSK9 peptide vaccine on the hepatic expression levels of microRNAs associated with the LDLR pathway, including miRNA-27a, miRNA-30c, and miRNA-191, in normal vaccinated mice.Material and methodsPCSK9 immunogenic peptide and 0.4% alum adjuvant were mixed at a 1 : 1 ratio and used as a vaccine formulation. Male albino mice were randomly assigned to the vaccine or control group. Mice in the vaccine group were injected four times at two-week intervals with a PCSK9 peptide vaccine, and mice in the control group were injected with phosphate-buffered saline (PBS). Animal livers were sampled 2 weeks after the last injection to assess miRNA expression levels. The hepatic expression levels of miRNA-27a, miRNA-30c, and miRNA-191 were evaluated by SYBR Green real-time PCR, quantified by a comparative (2^–ΔΔCT) method (fold change (FC)) and normalized to U6 small nuclear RNA (U6snRNA) expression as an internal control.ResultsThe hepatic expression level of miRNA-27a was significantly lower in mice following immunotherapy with the PCSK9 peptide vaccine compared to the control group (FC: 0.731 ±0.1, p = 0.027). Also, there was a borderline significantly lower hepatic expression level of miRNA-30c in the vaccinated group compared to the control (FC: 0.569 ±0.1, p = 0.078). However, no significant differences were found in the hepatic expression level of miRNA-191 between the two studied groups (FC: 0.852 ±0.1, p = 0.343).ConclusionsAccording to the findings, the PCSK9 peptide vaccine could effectively reduce the hepatic expression level of miRNA-27a and may be helpful in the management of LDL-C level and atherosclerosis, which may be mediated through the LDLR pathway.     

Impact of bariatric surgery on circulating PCSK9 levels as a marker of cardiovascular disease risk: a meta-analysis

IntroductionThis systematic review and meta-analysis focuses on PCSK9 changes in obese patients following bariatric surgery.MethodsA systematic literature search in four databases was performed. Comprehensive Meta-Analysis (CMA) V2 software used to conduct the meta-analysis. Studies were evaluated regarding heterogeneity in design, populations under investigation, and treatment duration using a random-effects model and the generic inverse variance weighting approach. A random-effect meta-regression approach was used to investigate the association with the estimated effect size.ResultsThe results of the meta-analysis on 4 trials including 260 individuals demonstrated a remarkable decline of PCSK9 after bariatric surgery (WMD = –57.34 ng/ml, 95% CI: –87.97, –26.71, p < 0.001; I² = 96.25%). Consistently, a significant decrease of LDL-C after bariatric surgery (WMD = –22.57 mg/dl, 95% CI: –27.5, –17.574, p < 0.001; I² = 86.35%) was observed.ConclusionsPCSK9 is reduced significantly after bariatric surgery. The decrease of PCSK9 might be utilized as an independent surrogate marker of improvement of atherosclerotic cardiovascular disease risk after bariatric surgery.