Efficacy of istradefylline for gait disorders with freezing of gait in Parkinson’s disease: A single-arm,open-label,prospective, multicenter study

Background: Gait disorders are common in Parkinson’s disease patients who respond poorly to dopaminergic treatment. Blockade of adenosine A_2A receptors is expected to improve gait disorders. Istradefylline is a first-in-class selective adenosine A_2A receptor antagonist with benefits for motor complications associated with Parkinson’s disease.

Research design and methods: This multicenter, open-label, single-group, prospective interventional study evaluated changes in total gait-related scores of the Part II/III Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and Freezing of Gait Questionnaire (FOG-Q) in 31 Parkinson’s disease patients treated with istradefylline. Gait analysis by portable gait rhythmogram was performed.

Results: MDS-UPDRS Part III gait-related total scores significantly decreased at Weeks 4–12 from baseline with significant improvements in gait, freezing of gait, and postural stability. Significant decreases in MDS-UPDRS Part II total scores and individual item scores at Week 12 indicated improved daily living activities. At Week 12, there were significant improvements in FOG-Q, new FOG-Q, and overall movement per 48 h measured by portable gait rhythmogram. Adverse events occurred in 7/31 patients.

Conclusions: Istradefylline improved gait disorders in Parkinson’s disease patients complicated with freezing of gait, improving their quality of life. No unexpected adverse drug reactions were identified.

Trial registration: UMIN-CTR (UMIN000020288).     

Contemporary Use of Venoarterial Extracorporeal Membrane Oxygenation: Insights from the Multicenter RESCUE Registry

BackgroundVenoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used as a life-saving therapy for patients with cardiovascular collapse, but identifying patients unlikely to benefit remains a challenge.Methods and ResultsWe created the RESCUE registry, a retrospective, observational registry of adult patients treated with VA-ECMO between January 2007 and June 2017 at 3 high-volume centers (Columbia University, Duke University, and Washington University) to describe short-term patient outcomes. In 723 patients treated with VA-ECMO, the most common indications for deployment were postcardiotomy shock (31%), cardiomyopathy (including acute heart failure) (26%), and myocardial infarction (17%). Patients frequently suffered in-hospital complications, including acute renal dysfunction (45%), major bleeding (41%), and infection (33%). Only 40% of patients (n = 290) survived to discharge, with a minority receiving durable cardiac support (left ventricular assist device [n = 48] or heart transplantation [n = 7]). Multivariable regression analysis identified risk factors for mortality on ECMO as older age (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.12–1.42) and female sex (OR, 1.44; 95% CI, 1.02–2.02) and risk factors for mortality after decannulation as higher body mass index (OR 1.17; 95% CI, 1.01-1.35) and major bleeding while on ECMO support (OR, 1.92; 95% CI, 1.23–2.99).ConclusionsDespite contemporary care at high-volume centers, patients treated with VA-ECMO continue to have significant in-hospital morbidity and mortality. The optimization of outcomes will require refinements in patient selection and improvement of care delivery.     

Gastric volvulus and giant Bochdalek hernia in an adult patient that were safely repaired by endoscopic reduction and elective laparoscopic surgery

A Bochdalek hernia (BH) is a congenital abnormality with incomplete closure of the diaphragm. It is usually manifested in infants but rarely in adults. Here, we report an adult patient with gastric volvulus and giant BH that were safely repaired by endoscopic reduction and elective laparoscopic surgery, respectively. A 79-year-old woman presented with left upper abdominal pain but no history of trauma. CT revealed a giant BH with gastric volvulus. After emergency endoscopic reduction of the volvulus, elective laparoscopic repair of the BH was performed. The 8 × 8-cm defect was repaired with interrupted nonabsorbable sutures and a mesh. The patient's postoperative course was uneventful, and no complications or recurrence were observed in the 6 months that followed.     

Dermoscopic features of hidroacanthoma simplex: Usefulness in distinguishing it from Bowen's disease and seborrheic keratosis

Hidroacanthoma simplex (HAS) is a rare benign eccrine adnexal tumor. HAS is sometimes clinically or pathologically misdiagnosed as squamous cell carcinoma in situ (Bowen's disease; BD), seborrheic keratosis (SK) or other adnexal tumor. To date, there has never been a report focusing on dermoscopic features to distinguish HAS from BD and SK. We found the following dermoscopic findings to be characteristic of HAS: fine black dots/globules (75% of cases) and fine scales arranged annularly (100% of cases). In contrast, glomerular vessels, which are typically observed in BD, were not seen in any of the four cases. Cerebriform appearance and milia‐like cysts, which are typically observed in SK, were also not seen in any of the four cases. The existence of “scattered fine black dots/globules” and “fine scales arranged annularly”, and the absence of the glomerular vessels, may contribute to precise diagnosis of HAS. Even though HAS resembles BD or SK clinically, it can be distinguished from these by the characteristic dermoscopic features.     

Contrast-enhanced intraoperative ultrasonography of small hepatocellular carcinomas

Nine patients with small hepatocellular carcinomas, ranging up to 2 cm in size (phi: 1.7 +/- 0.2 cm, mean +/- SD), have been encountered, and in two of these patients the cancer was not identifiable by intraoperative ultrasonography. Thus to achieve a better detection of such small hepatic cancers, enhanced intraoperative ultrasonography was tested. Detection by enhanced intraoperative ultrasonography proved successful in all cases. These preliminary results indicate the potential of carbon dioxide as a contrast agent to enhance intraoperative visualization of small liver cancers.     

Tumor markers in human breast cancer

We described tumor markers which are considered to be useful for the detection of recurrence, index of the efficacy of treatment and assessment for the prognosis of the patients with breast cancer. CEA and CA 15-3 are relatively useful markers among various serological ones. However, although accuracy of the diagnosis with CA 15-3 and CEA is generally thought to be not superior to those of imaging method, CA 15-3 and CEA seems to be clinically useful tools for making diagnosis because of its simplicity and less cost. Estrogen and progesterone receptors shows good responses to endocrine therapy. Response rate was 70 to 80% in both receptor-positive patients. Presence of ER shows higher rate of recurrence and shorter survival of the patients than those with absence of ER. Recent attention has been focused on EGF and proto-oncogene, suggesting relationship of those to prognosis.     

Effects of tension on local blood flow in experimental intestinal anastomoses

In intestinal anastomoses, local blood flow is one of the most important factors contributing to the success of the healing process. While submucosal local blood flow is maintained better in the colon than in the small intestine, the incidence of anastomotic leakage is higher in the former than in the latter. To resolve this conflict, we have examined differences in the reactivity of the intestinal segments toward the application of tension. Anastomosis was performed with a stapler on the jejunum, ileum, and colon of experimental dogs. The anastomotic sites were subjected to tensile loads applied in incremental steps to measure and compare local blood flow, measured by the hydrogen clearance method, in the submucosal layers of the anastomoses in these intestinal segments. The results of these comparative evaluations indicate that, at a tensile stress level of more than 4 g/mm2, local blood flow in the colon is significantly smaller than that in the jejunum and ileum. These findings were corroborated by microangiographical observations carried out during stress application. The microangiographical data suggest that the rate of filling of the contrast medium is lower with colonic anastomosis than with jejunal and ileal anastomoses. In addition, the intraluminal pressure of the colon was higher than that of the small intestine during the induced peristalsis. The different sensitivity of the local microcirculation systems of the intestinal segments to tension may thus be considered one of the factors accounting for the higher incidence of clinical suture failure in colonic than in small intestinal anastomoses.