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.     

Dynamic high-spatial-resolution MR imaging of invasive ductal carcinoma: influence of histological scirrhous component on MR descriptors.

PURPOSE: The purpose of this study was to assess the relationship between the amount of scirrhous component in invasive ductal carcinoma and its MR characteristics. MATERIALS AND METHODS: We retrospectively reviewed 71 consecutive patients with invasive ductal carcinoma smaller than 25 mm (average, 16.6 mm) in diameter. The scirrhous component was defined as invasive foci in small clusters of cancer cells showing desmoplasia. Invasive ductal carcinoma was subclassified into 3 groups in accordance with the amount of the scirrhous component (scirrhous component degree; SCD): SCD I (scirrhous component less than 20%), SCD II (intermediate), and SCD III (more than 80%). Dynamic magnetic resonance (MR) imaging was performed using volumetric interpolated sequence. Prior to dynamic study, T2*-weighted first-pass perfusion images were obtained before, during, and after bolus injection of 0.1 mmol Gd-DTPA/kg. RESULTS: Twenty-eight lesions were classified as SCD I, 14 as SCD II, and 29 as SCD III. Mass margin and signal intensity loss in the perfusion study were significantly different among the 3 SCD groups (P<0.001). The kinetic patterns were significantly different among the 3 SCD groups (P=0.04), and between SCD I/II and SCD III (P=0.03). The presence of enhancing internal septations was significantly different between SCD I/II and SCD III carcinomas (P=0.05). Central enhancement was only observed in SCD I carcinoma (4%; 3/71). CONCLUSION: The histological predominance of the scirrhous component in invasive ductal carcinoma may be one explanation for the differences in morphologic and kinetic patterns on MR imaging.     

Endoscopic anterior cruciate ligament reconstruction using a computer-assisted fluoroscopic navigation system

Background During anterior cruciate ligament (ACL) reconstruction, placement of the reconstructed ligament affects the clinical results. To accomplish accurate and reproducible placement of the tibial bone tunnel, we employed a fluoroscopic navigation system for endoscopic ACL reconstruction. In this study, preciseness of the tibial tunnel placement was evaluated, and the advantages and disadvantages of this navigation system for endoscopic ACL reconstruction are discussed. Methods Altogether, 16 knees of 16 patients who had undergone ACL reconstruction using this system (navi group) were evaluated regarding the positioning of the tibial tunnel against Blumensaat's line using X-p and the route of the graft by magnetic resonance imaging (MRI). Another 16 knees of 16 patients who underwent endoscopic ACL reconstruction without the navigation system were the controls (control group). Results At the 1-year follow-up, maximally extended lateral knee X-p revealed that the anterior edge of the tibial tunnel and Blumensaat's line were almost aligned and that roof impingement was avoided; the T2-weighted MR images showed that the graft was placed close to and parallel to the intercondylar roof in all the knees of the navi group. The ratio of the distance between Blumensaat's line and the anterior edge of the tibial tunnel at the level of the tibial plateau to the anteroposterior width in fully extended true lateral radiographs was 2.7% ± 3.4% in the navi group and 8.4% ± 7.4% in the control group. Conclusions The computer-assisted fluoroscopic navigation system improves accuracy and decreases dispersion of the tibial tunnel placement against Blumensaat's line in single-bundle ACL reconstruction. This innovative device renders the reconstruction procedure more reliable, eliminating the problem of skeletal variation among patients. However, the function of this navigation system for femoral tunnel placement is insufficient at present. Further refinement of the system is necessary, and the method of application requires improvement.     

Congenital quadricuspid aortic valve with tetralogy of Fallot and pulmonary atresia

We report the case of a 4-year-old girl who had quadricuspid aortic valve regurgitation with tetralogy of Fallot and pulmonary atresia. This combination is very uncommon. Aortic valve replacement was performed successfully due to aortic regurgitation which had progressed one year after the total repair. The dilated aortic annulus plus quadricuspid aortic valve may result in progressive aortic regurgitation for a short period.     

Effects of a new analog of thyrotropin-releasing hormone, N alpha-[(S)-4-oxo-2-azetidinyl) carbonyl]-L-histidyl-L-prolinamide dehydrate (YM-14673) on spinal reflex potentials and flexor reflexes in spinalized rats

Experiments were performed on spinalized rats, transected at the Cl level. The intravenous administration of TRH and its analog YM-14673 (N alpha-[(S)-4-oxo-2-azetidinyl) carbonyl]-L-histidyl-L-prolinamide dehydrate) produced marked increases in the amplitude of mono- and polysynaptic reflex potentials and those of the withdrawal flexor reflexes. The effects of YM-14673 were stronger and longer-lasting than those of TRH. The stimulant action of TRH and YM-14673 on the flexor reflexes was not antagonized by prazosin, chlorpromazine, haloperidol or cyproheptadine, suggesting no involvement of the release of catecholamines or serotonin in the stimulant effects of TRH and its analog. Therefore, YM-14673 may be beneficial for the treatment of several spinal motor neuron diseases.