Fatal Ifosfamide-Induced Metabolic Encephalopathy in Patients with Recurrent Epithelial Ovarian Cancer: Report of Two Cases

Central nervous system (CNS) toxicity has been reported in approximately 10-30% of patients receiving intravenous infusions of ifosfamide. Encephalopathy is a rare but serious CNS adverse reaction in these patients, and although usually transient and reversible, may cause persistent neurological dysfunction or death. Clinical features range from fatigue and confusion to coma and death. Although methylene blue can be used to treat ifosfamide-induced neurotoxicity, including encephalopathy, its mechanism of action remains poorly defined. We describe here two patients with recurrent epithelial ovarian cancer who experienced fatal encephalopathy following ifosfamide/mesna treatment

Different degree of cytokinemia and T-cell activation according to serum IL-6 levels in critical COVID-19

IntroductionTocilizumab, a humanized anti-interleukin-6 receptor (IL-6R) antibody, is recommended for the treatment of severe to critical coronavirus diseases 2019 (COVID-19). However, there were conflicting results on the efficacy of tocilizumab. Therefore, we hypothesized that the differences in tocilizumab efficacy may stem from the different immune responses of critical COVID-19 patients. In this study, we described two groups of immunologically distinct COVID-19 patients, based on their IL-6 response.MethodsWe prospectively enrolled critical COVID-19 patients, requiring oxygen support with a high flow nasal cannula or a mechanical ventilator, and analyzed their serial samples. An enzyme-linked immunosorbent assay and flow cytometry were used to evaluate the cytokine kinetics and cellular immune responses, respectively.ResultsA total of nine patients with critical COVID-19 were included. The high (n = 5) and low IL-6 (n = 4) groups were distinguished by their peak serum IL-6 levels, using 400 pg/mL as the cut-off value. Although the difference of flow cytometric data did not reach the level of statistical significance, the levels of pro-inflammatory cytokines and the frequencies of intermediate monocytes (CD14+CD16+), IFN-γ+ CD4+ or CD8+ T cells, and HLA-DR+PD-1+ CD4+ T cells were higher in the high IL-6 group than in the low IL-6 group.ConclusionThere were distinctive two groups of critical COVID-19 according to serum IL-6 levels having different degrees of cytokinemia and T-cell responses. Our results indicate that the use of immune modulators should be more tailored in patients with critical COVID-19

A Controlled Fermented Samjunghwan Herbal Formula Ameliorates Non-alcoholic Hepatosteatosis in HepG2 Cells and OLETF Rats

Hepatosteatosis (HS), a clinical feature of fatty liver with the excessive intracellular accumulation of triglyceride in hepatocytes, is manifested by perturbation of the maintenance of liver lipid homeostasis. Samjunghwan (SJH) is an herbal formula used mostly in Korean traditional medicine that is effective against a number of metabolic diseases, including obesity. Herbal drugs, enriched with numerous bioactive substances, possess health-protective benefits. Meanwhile, fermented herbal products enriched with probiotics are known to improve metabolic processes. Additionally, current lines of evidence indicate that probiotics-derived metabolites, termed as postbiotics, produce the same beneficial effects as their precursors. Herein, the anti-HS effects of 5-weeks naturally fermented SJH (FSJH) was investigated with FSJH-mixed chow diet in vivo using Otsuka Long-Evans Tokushima Fatty (OLETF) and Long-Evans Tokushima Otsuka (LETO) rats as animal models of HS and controls, respectively. In parallel, the anti-HS effects of postbiotic-metabolites of three bacterial strains [Lactobacillus brevis (LBB), Lactococcus lactis (LCL) and Lactobacillus plantarum (LBP)] isolated from FSJH were also evaluated in vitro using the FFAs-induced HepG2 cells. Feeding OLETF rats with FSJH-diet effectively reduced body, liver, and visceral adipose tissue (VAT) weights, produced marked hypolipidemic effects on serum and hepatic lipid parameters, decreased serum AST and ALT levels, and upregulated the HMGCOR, SREBP, and ACC, and downregulated the AMPK and LDLR gene expressions levels. Additionally, exposure of FFAs-induced HepG2 cells to postbiotic metabolic media (PMM) of bacterial strains also produced marked hypolipidemic effects on intracellular lipid contents and significantly unregulated the HMGCOR, SREBP, and ACC, and downregulated the AMPK and LDLR genes expressions levels. Overall, our results indicate that FSJH enriched with fermented metabolites could be an effective anti-HS formulation

The Skin Antiseptic agents at Vaginal dElivery (SAVE) trial: study protocol for a randomized controlled trial

Background Cleansing of the vulva and perineum is recommended during preparation for vaginal delivery, and special attention is paid to cleansing before episiotomy because episiotomy is known to increase the risk of perineal wound infection and/or dehiscence. However, the optimal method of perineal cleansing has not been established, including the choice of antiseptic agent. To address this issue, we designed a randomized controlled trial to examine whether skin preparation with chlorhexidine-alcohol is superior to povidone-iodine for the prevention of perineal wound infection after vaginal delivery. Methods In this multicenter randomized controlled trial, term pregnant women who plan to deliver vaginally after episiotomy will be enrolled. The participants will be randomly assigned to use antiseptic agents for perineal cleansing (povidone-iodine or chlorhexidine-alcohol). The primary outcome is superficial or deep perineal wound infection within 30 days after vaginal delivery. The secondary outcomes are the length of hospital stay, physician office visits, or hospital readmission for infection-related complications, endometritis, skin irritations, and allergic reactions. Discussion This study will be the first randomized controlled trial aiming to determine the optimal antiseptic agent for the prevention of perineal wound infections after vaginal delivery. Trial registration ClinicalTrials.gov NCT05122169. First submitted date on 8 November 2021. First posted date on 16 November 202

Electrocardiographic Left Ventricular Hypertrophy and Outcome in Hemodialysis Patients

BACKGROUND AND AIMS: Electrocardiography (ECG) is the most widely used initial screening test for the assessment of left ventricular hypertrophy (LVH), an independent predictor of cardiovascular mortality in patients with end-stage renal disease (ESRD). However, traditional ECG criteria based only on voltage to detect LVH have limited clinical utility for the detection of LVH because of their poor sensitivity. METHODS: This prospective observational study was undertaken to compare the prognostic significance of commonly used ECG criteria for LVH, namely Sokolow-Lyon voltage (SV) or voltage-duration product (SP) and Cornell voltage (CV) or voltage-duration product (CP) criteria, and to investigate the association between echocardiographic LV mass index (LVMI) and ECG-LVH criteria in ESRD patients, who consecutively started maintenance hemodialysis (HD) between January 2006 and December 2008. RESULTS: A total of 317 patients, who underwent both ECG and echocardiography, were included. Compared to SV and CV criteria, SP and CP criteria, respectively, correlated more closely with LVMI. In addition, CP criteria provided the highest positive predictive value for echocardiographic LVH. The 5-year cardiovascular survival rates were significantly lower in patients with ECG-LVH by each criterion. In multivariate analyses, echocardiographic LVH [adjusted hazard ratio (HR): 11.71; 95% confidence interval (CI): 1.57-87.18; P = 0.016] and ECG-LVH by SP (HR: 3.43; 95% CI: 1.32-8.92; P = 0.011) and CP (HR: 3.07; 95% CI: 1.16-8.11; P = 0.024) criteria, but not SV and CV criteria, were significantly associated with cardiovascular mortality. CONCLUSIONS: The product of QRS voltage and duration is helpful in identifying the presence of LVH and predicting cardiovascular mortality in incident HD patients

Endothelial Nitric Oxide Synthase Glu298Asp Gene Polymorphism is Associated with Hypertensive Response to Exercise in Well-Controlled Hypertensive Patients

PURPOSE: Hypertensive response to exercise (HRE) is known to be an adverse prognostic factor for future cardiovascular events and may be associated to endothelial dysfunction. Previous studies regarding endothelial nitric oxide synthase (eNOS) Glu298Asp polymorphism focused upon its relation to hypertension. In this study, we hypothesize that the polymorphism may be associated with inherent difference in endothelial response to exercise. PATIENTS AND METHODS: Two hundred sixty nine patients who underwent treadmill test were enrolled in this study; 77 patients (mean age 55.8 +/- 9.4 years) had hypertensive response (peak systolic BP of > or = 210 mmHg in men and > or = 190 mmHg in women). Pulse wave velocity (PWV) was measured on 153 patients of them. The Glu298Asp exchange in exon 7 was determined by the methods of single base extension with amplifying primers and probes for TaqMan. RESULTS: The percentages of the GG, GT and TT genotypes were 81.0, 18.6 and 0.4 %, respectively. The presence of GT or TT genotype was independently associated with prevention of HRE when controlled for age, sex, baseline systolic BP and homeostatic model assessment (HOMA) index (OR=0.35, p=0.016). Subgroup analysis showed that preventive effect for HRE of T allele was significant in females (p < 0.001) and patients without insulin resistance (p=0.009). CONCLUSION: In our study, eNOS Glu298Asp polymorphism was significantly associated with HRE. This result suggests that the presence of T allele of the Glu298Asp polymorphism may be a favorable factor to in preventing HRE, especially in female and patients without insulin resistance.ope

Diospyros kaki and Citrus unshiu Mixture Improves Disorders of Lipid Metabolism in Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) has been a major cause of a chronic liver disease over recent decades and increasing worldwide in parallel with the remarkable growth of obesity. In the present study, we investigate the ameliorative effects of PCM, a combination of Diospyros kaki fruit and Citrus unshiu peel mixture, on high-fat diet- (HFD-) induced NAFLD and clarify the potential mechanisms. PCM in HFD-fed mice was orally administered at a dose of 50 or 100 mg/kg subsequently for 2 months. Thereafter, lipid metabolism parameters and fat synthesis-related genes in the mouse liver were evaluated. Subsequently, body weight changes, liver weight, serum liver function and lipid profiles, and liver pathology were examined, and the relative levels of fatty acid synthesis and β-oxidation gene expression were evaluated by western blot. Serum AST, ALT, and TG levels in the HFD control mice were significantly higher than those of normal mice. Compared with HFD control mice, PCM supplementation increased phosphorylation of AMP-activated protein kinase (AMPK). Peroxisome proliferator-activated receptor (PPAR) α was significantly increased by PCM administration. Continuously, the activation of PPARα significantly elevated carnitine palmitoyltransferase 1 (CPT-1), a key enzyme in fatty acid β-oxidation, and mitochondrial uncoupling protein 2 (UCP-2), thermogenic regulatory genes, in PCM-treated mice compared with those of HFD control mice. Moreover, PCM inhibits lipogenesis and cholesterol synthesis via suppression of sterol regulatory element binding protein-1 (SREBP-1) and SREBP-2 and its target genes such as acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), stearoyl-CoA desaturase-1 (SCD-1), and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR). Taken together, these effects were mediated through activation of AMPK. In the conclusion, PCM improved liver damage in HFD-fed mice and attenuated NAFLD by the activation of PPARα and the inhibition of SREBPs expression via AMPK-dependent pathways

The clinical characteristics and neurodevelopmental outcome of preterm infants with persistent periventricular echogenicity

Purpose: Periventricular echogenicity (PVE) presents as diffuse echo dense lesions of the periventricular white matter on cranial ultrasonography. Beyond two weeks of life, it is considered as prolonged or persistent PVE. The aim of our study was to investigate the clinical characteristics of preterm infants with persistent PVE beyond 2 weeks after birth and to determine whether these infants had an adverse neurodevelopmental outcome. Methods: The medical records of preterm infants who were born at < 34 weeks of gestation and admitted to Pusan National University Hospital between 2009 and 2014 were reviewed. A total of 28 preterm infants with persistent PVE were enrolled. Sixty compatible infants closely matched for gestational age and birth weight to infants with PVE were selected as the control group. Clinical data, including maternal, perinatal and neonatal characteristics, were analyzed. We compared the Bayley Scales of Infant Development-III at 12 months' corrected age. Results: The mean gestational age and birth weight were 31 + 3 (range, 29 + 2–33 + 6) weeks and 1523 (range, 911–2210) g, respectively, in the persistent PVE group. In the control group, the mean gestational age was 31 + 4 (range, 29 + 2–33 + 6) weeks and the mean birth weight was 1537 (range, 840–2100) g. There was no significant difference between the persistent PVE group and the control group, except for a significantly higher incidence of late sepsis in the persistent PVE group (p = 0.001). The results of Bayley test at 12 months of corrected age were available for 24 infants in the persistent PVE group and for 26 infants in the control group. A motor score of 86 (range, 78–95) versus 88 (range, 79–100), a language composite score of 88 (range, 78–97) versus 89 (range, 80–105), and a cognitive score of 90 (range, 81–100) versus 92 (range, 85–105) were observed in the persistent PVE group and the control group, respectively. No difference was detected in any scores between the two groups. Conclusion: The clinical characteristics and neurodevelopmental outcomes of preterm infants with persistent PVE were not different from those of infants with normal findings. Our study supports the concept that persistent PVE without cystic change may be a benign finding. Key Words: infant, leukomalacia, periventricular, prematur