Mitochondrial DNA as a biomarker for acute central serous chorioretinopathy: A case-control study

The literature suggests that stress may play a pivotal role in the precipitation of acute central serous chorioretinopathy (CSC) because chorioretinal integrity can be affected by the psychosocial state of the patient, indicating the need for a biomarker. Not only physical stress but also psychological stress causes many types of physical disorders. However, little is known about the pathophysiology of stress-induced disease. The objective of this study was to investigate whether serum factors might be involved in the development of stress-induced ocular diseases. Methods: This observational case series included 33 eyes of 33 consecutive patients with treatment-naïve acute CSC. Fifty eyes of 50 age-matched healthy volunteers were included in this study as non-CSC controls. Serum samples were collected from all participants, and the levels of mitochondrial DNA (mtDNA) were measured by quantitative real-time (RT)-PCR. Serum levels of high-mobility group box (HMGB) 1 and 8-hydroxy-2′-deoxyguanosine (8-OHdG), biological markers of acute/chronic inflammation and oxidative stress, were also measured. The relationships between serum mtDNA, 8-OHdG, and HMGB1 concentrations were investigated by multivariate regression analysis, alongside an assessment of clinical data. Results: In the treatment-naïve acute CSC group, the serum mtDNA levels (36.5 ± 32.4 ng/mL) were significantly higher than the levels in the control group (7.4 ± 5.9 ng/mL; p < 0.001). Serum levels of 8-OHdG and HMGB1 in treatment-naïve acute CSC patients measured 0.12 ± 0.08 ng/mL and 18.1 ± 35.0 ng/mL, respectively, indicating that HMGB1 levels were elevated in CSC compared with the control group. Multivariable regression analysis demonstrated that increased serum mtDNA levels were significantly associated with the height of serous retinal detachment. Conclusion: We showed serum mtDNA and HMGB1 level elevation and its relation to the clinical activities of CSC, indicating that serum mtDNA and HMGB1 could serve as biomarkers for the acute phase of the disease. The use of these biomarkers makes it possible to predict disease onset and determine disease severity

A Multifunctional Hybrid Nanocarrier for Non-Invasive siRNA Delivery to the Retina

Drug therapy for retinal diseases (e.g., age-related macular degeneration, the leading cause of blindness) is generally performed by invasive intravitreal injection because of poor drug delivery caused by the blood–retinal barrier (BRB). This study aimed to develop a nanocarrier for the non-invasive delivery of small interfering RNA (siRNA) to the posterior segment of the eye (i.e., the retina) by eyedrops. To this end, we prepared a hybrid nanocarrier based on a multifunctional peptide and liposomes, and the composition was optimized. A cytoplasm-responsive stearylated peptide (STR-CH2R4H2C) was used as the multifunctional peptide because of its superior ability to enhance the complexation, cell permeation, and intracellular dynamics of siRNA. By adding STR-CH2R4H2C to the surface of liposomes, intracellular uptake increased regardless of the liposome surface charge. The STR-CH2R4H2C-modified cationic nanocarrier demonstrated significant siRNA transfection efficiency with no cytotoxicity, enhanced siRNA release from endosomes, and effectively suppressed vascular endothelial growth factor expression in rat retinal pigment epithelium cells. The 2.0 mol% STR-CH2R4H2C-modified cationic nanocarrier enhanced intraocular migration into the retina after instillation into rat eyes

Data from: Outcomes in patients with infections and augmented renal clearance: a multicenter retrospective study

Recently, augmented renal clearance (ARC), which accelerates glomerular filtration of renally eliminated drugs thereby reducing the systemic exposure to these drugs, has started to receive attention. However, the clinical features associated with ARC are still not well understood, especially in the Japanese population. This study aimed to evaluate the clinical characteristics and outcomes of ARC patients with infections in Japanese intensive care unit (ICU) settings. We conducted a retrospective observational study from April 2013 to May 2017 at two tertiary level ICUs in Japan, which included 280 patients with infections (median age 74 years; interquartile range, 64–83 years). We evaluated the estimated glomerular filtration rate (eGFR) at ICU admission using the Japanese equation, and ARC was defined as eGFR >130 mL/min/1.73 m2. Multivariable logistic regression analysis was performed to identify the independent risk factors for ARC and to determine if it was a predictor of ICU mortality. In addition, a receiver operating curve (ROC) analysis was performed, and the area under the ROC (AUROC) was determined to examine the significant variables that predict ARC. In total, 19 patients (6.8%) manifested ARC. Multivariable logistic regression analysis identified younger age as an independent risk factor for ARC (odds ratio [OR], 0.94; 95% confidence interval [CI], 0.91–0.96). However, ARC was not found to be a predictor of ICU mortality (OR, 0.57; 95% CI, 0.11–2.92). In addition, the AUROC of age was 0.79 (95% CI, 0.68–0.91), and the optimal cut off age for ARC was ≤63 years (sensitivity, 68.4%; specificity, 78.9%). The incidence of ARC was, therefore, low among patients with infections in the Japanese ICUs. Although younger age was associated with the incidence of ARC, it was not an independent predictor of ICU mortality

Data from: Outcomes in patients with infections and augmented renal clearance: a multicenter retrospective study

Recently, augmented renal clearance (ARC), which accelerates glomerular filtration of renally eliminated drugs thereby reducing the systemic exposure to these drugs, has started to receive attention. However, the clinical features associated with ARC are still not well understood, especially in the Japanese population. This study aimed to evaluate the clinical characteristics and outcomes of ARC patients with infections in Japanese intensive care unit (ICU) settings. We conducted a retrospective observational study from April 2013 to May 2017 at two tertiary level ICUs in Japan, which included 280 patients with infections (median age 74 years; interquartile range, 64–83 years). We evaluated the estimated glomerular filtration rate (eGFR) at ICU admission using the Japanese equation, and ARC was defined as eGFR >130 mL/min/1.73 m2. Multivariable logistic regression analysis was performed to identify the independent risk factors for ARC and to determine if it was a predictor of ICU mortality. In addition, a receiver operating curve (ROC) analysis was performed, and the area under the ROC (AUROC) was determined to examine the significant variables that predict ARC. In total, 19 patients (6.8%) manifested ARC. Multivariable logistic regression analysis identified younger age as an independent risk factor for ARC (odds ratio [OR], 0.94; 95% confidence interval [CI], 0.91–0.96). However, ARC was not found to be a predictor of ICU mortality (OR, 0.57; 95% CI, 0.11–2.92). In addition, the AUROC of age was 0.79 (95% CI, 0.68–0.91), and the optimal cut off age for ARC was ≤63 years (sensitivity, 68.4%; specificity, 78.9%). The incidence of ARC was, therefore, low among patients with infections in the Japanese ICUs. Although younger age was associated with the incidence of ARC, it was not an independent predictor of ICU mortality

Carbon Monoxide-Loaded Red Blood Cell Prevents the Onset of Cisplatin-Induced Acute Kidney Injury

Cisplatin-induced acute kidney injury (AKI) is an important factor that limits the clinical use of this drug for the treatment of malignancies. Oxidative stress and inflammation are considered to be the main causes of not only cisplatin-induced death of cancer cells but also cisplatin-induced AKI. Therefore, developing agents that exert antioxidant and anti-inflammatory effects without weakening the anti-tumor effects of cisplatin is highly desirable. Carbon monoxide (CO) has recently attracted interest due to its antioxidant, anti-inflammatory, and anti-tumor properties. Herein, we report that CO-loaded red blood cell (CO-RBC) exerts renoprotective effects on cisplatin-induced AKI. Cisplatin treatment was found to reduce cell viability in proximal tubular cells via oxidative stress and inflammation. Cisplatin-induced cytotoxicity, however, was suppressed by the CO-RBC treatment. The intraperitoneal administration of cisplatin caused an elevation in the blood urea nitrogen and serum creatinine levels. The administration of CO-RBC significantly suppressed these elevations. Furthermore, the administration of CO-RBC also reduced the deterioration of renal histology and tubular cell injury through its antioxidant and anti-inflammatory effects in cisplatin-induced AKI mice. Thus, our data suggest that CO-RBC has the potential to substantially prevent the onset of cisplatin-induced AKI, which, in turn, may improve the usefulness of cisplatin-based chemotherapy

Vesicocutaneous fistula formation during treatment with sunitinib malate: Case report

<p>Abstract</p> <p>Background</p> <p>The oral multi-kinase inhibitor sunitinib malate improves the survival of patients with gastrointestinal stromal tumors (GIST) after the disease progresses or intolerance to imatinib mesylate develops. Urinary fistulae arising during treatment with sunitinib for GIST have not been described.</p> <p>Case presentation</p> <p>We describe a 62-year-old female patient diagnosed with unresectable GIST that involved the abdominal wall, urinary bladder wall, bowel, mesentery and peritoneum in the pelvic cavity. Intestinocutaneous fistulae developed on a surgical lesion after orally administered imatinib was supplemented by an arterial infusion of 5-flurouracil. Sunitinib was started after the patient developed resistance to imatinib. On day 4 of the fourth course of sunitinib, a widely dilated cutaneous fistula discharged large amounts of fluid accompanied by severe abdominal pain. Urinary communication was indicated based on the results of an intravenous injection of indigo carmine. Computed tomography findings suggested a small opening on the anterior urinary bladder wall and fistulous communication between the bladder and abdominal walls bridged by a subcutaneous cavity. The fistula closed and the amount of discharge decreased when sunitinib was discontinued. Therefore, sunitinib might have been associated with the development of the vesicocutaneous fistula in our patient.</p> <p>Conclusion</p> <p>This is the first description of a vesicocutaneous fistula forming while under sunitinib treatment. Clinicians should be aware of the possible complication of vesicocutaneous fistula formation during treatment with molecular targeting agents in patients with extravesical invasion and peritoneal dissemination of GIST.</p