Relationship between the cAMP levels in leukocytes and the cytokine balance in patients surviving gram negative bacterial pneumonia

Lipopolysaccharide-stimulated leukocytes secrete proinflammatory cytokines including tumor necrosis factor-α and interleukin-12. Over-activation of host defense systems may result in severe tissue damage and requires regulation. Granulocyte colony-stimulating factor and interleukin-10 are candidate cytokines for inducing tolerance to lipopolysaccharide re-stimulation. We compared cytokines secreted by lipopolysaccharide-stimulated blood cells from patients who had survived gram negative bacterial pneumonia (Pseudomonas aeruginosa, Escherichia coli or Proteus mirabilis, n = 26) and age-matched healthy volunteers (n = 18). Interleukin-12p70 and tumor necrosis factor-α expression was significantly lower in patients (p = 0.0039 and p<0.001) compared to healthy controls, while granulocyte colony-stimulating factor production was markedly higher in patients (p<0.001). Levels of interleukin-10 were comparable. Granulocyte colony-stimulating factor expression was inversely correlated with interleukin-12p70 (R = −0.71, p<0.001) and tumor necrosis factor-α (R = −0.64, p<0.001) expression; interleukin-10 showed no significant correlation. In unstimulated leukocytes from patients, cAMP levels were significantly raised (p = 0.020) and were correlated inversely with interleukin-12p70 levels (R = −0.81, p<0.001) and directly with granulocyte colony-stimulating factor (R = 0.72, p = 0.0020), matrix metalloproteinase-9 (R = 0.67, p = 0.0067) and interleukin-10 (R = 0.54, p = 0.039) levels. Our results demonstrate that granulocyte colony-stimulating factor production by lipopolysaccharide-stimulated leukocytes is a useful indicator of tolerance induction in surviving pneumonia patients and that measuring cAMP in freshly isolated leukocytes may also be clinically significant

Fast and Slow Oscillation Electrooculography in Harada Disease

We assessed clinical utility of fast and slow oscillations (FO and SO) of the electrooculogram (EOG) in Harada disease. In 12 eyes of 4 female and 2 male subject patients aged 18 to 77 years (average: 41.8 years), FO and SO were recorded using an automated electrooculograph, the Nidek EOG-2, in the acute period before treatment and in the remission period under corticosteroid therapy. FO parameters, namely the RfFO [the average ratio in percentage of the maximum amplitude in the dark period (AD)/the minimum amplitude in the light period (AL) during FO measurement] and the dfFO (the average difference in ?V between AD and AL) were evaluated. The L/DSO (the light peak/dark trough ratio of the SO) was calculated as an SO parameter. The RfFO, dfFO and L/DSO showed low values in 7 (58.3%), 10 (83.3%) and 8 (66.7%) out of all 12 eyes in the acute period, respectively. In the remission period, values in the normal range were obtained in 12 (100%), 11 (91.7%) and 8 (66.7%) out of 12 eyes in the RfFO, dfFO and L/DSO, respectively. In mutual relation to each RfFO, dfFO and L/DSO in the acute and remission periods, all 12 eyes showed recovery values both in the RfFO and dfFO in the remission stage after systemic administration of corticosteroids, but 4 out of 12 eyes (33.3%) showed no recovery in the L/DSO. The FO may therefore well reflect the affected or ameliorated conditions in the outer layers of the retina and the choroid in Harada disease, in contrast to the SO. However, further observations are requested in more Harada disease patients

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Intestinal endometriosis combined with colorectal cancer: a case series

Abstract Background Intestinal endometriosis is a common benign disease among menstruating women that affects the intestinal tract. Case presentation This case report presents seven Japanese cases of intestinal endometriosis with colorectal cancer treated by laparoscopic surgery. Five of the seven cases reported here are women presenting with bowel obstruction due to colorectal endometriosis with colorectal cancer. It can be confused with serious lesions such as advanced colorectal cancer with peritoneal involvement or invasion of adjacent organs (T4). Conclusions Therefore, we should consider the probability that the cause of bowel obstruction is not T4 but intestinal endometriosis. For surgical treatment, we recommend laparoscopic surgery for colorectal resection because of its benefits of differential diagnosis of T4, preserving fertility, and preventing excessive surgical stress. We performed laparoscopic resection in seven patients with intestinal endometriosis and colorectal cancer. These cases demonstrate the difficulty of establishing a differential diagnosis of intestinal endometriosis with colorectal cancer from T4