Spontaneous echo contrast mimicking aortic root thrombus in a patient supported with extracorporeal membrane oxygenation

Aortic root spontaneous echo contrast is a rare but significant finding. We report a 31‐year‐old female who was placed on venoarterial extracorporeal membrane oxygenation emergently for acute mitral regurgitation secondary to papillary muscle rupture. Following stabilization, subsequent transesophageal echocardiography suggested aortic root thrombus and prompted emergent surgery. However, further inspection with intraoperative transesophageal echocardiography revealed a spontaneous echo contrast which aided us in the intraoperative decision making.     

Efficacy and safety of pembrolizumab for the treatment of advanced biliary cancer: Results from the KEYNOTE-158 and KEYNOTE-028 studies

We present data from patients with advanced biliary tract cancer (BTC) receiving pembrolizumab in the KEYNOTE-158 (NCT02628067; phase 2) and KEYNOTE-028 (NCT02054806; phase 1b) studies. Eligible patients aged ≥18 years from both studies had histologically/cytologically confirmed incurable BTC that progressed after standard treatment regimen(s), measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, Eastern Cooperative Oncology Group performance status 0/1, and no prior immunotherapy. Programmed death ligand 1 (PD-L1)-positive tumors were required for eligibility in KEYNOTE-028 only. Patients received pembrolizumab 200 mg every three weeks (KEYNOTE-158) or 10 mg/kg every two weeks (KEYNOTE-028) for ≤2 years. Primary efficacy endpoint was objective response rate (ORR) by RECIST v1.1. Response assessed by independent central review is reported. KEYNOTE-158 enrolled 104 patients and KEYNOTE-028 enrolled 24 patients. Median (range) follow-up was 7.5 months (0.6-34.3) in KEYNOTE-158 and 5.7 months (0.6-55.4) in KEYNOTE-028. In KEYNOTE-158, ORR was 5.8% (6/104; 95% CI, 2.1%-12.1%); median duration of response (DOR) was not reached (NR) (range, 6.2-26.6+ months). Median (95% CI) OS and PFS were 7.4 (5.5-9.6) and 2.0 (1.9-2.1) months. Among PD-L1-expressers (n = 61) and PD-L1-nonexpressers (n = 34), respectively, ORR was 6.6% (4/61) and 2.9% (1/34). In KEYNOTE-028, ORR was 13.0% (3/23; 95% CI, 2.8%-33.6%); median DOR was NR (range, 21.5-53.2+ months). Median (95% CI) OS and PFS were 5.7 (3.1-9.8) and 1.8 (1.4-3.1) months. Grade 3 to 5 treatment-related adverse events occurred in 13.5% of patients in KEYNOTE-158 (no grade 4; grade 5 renal failure, n = 1) and 16.7% in KEYNOTE-028 (no grade 4/5). In summary, pembrolizumab provides durable antitumor activity in 6% to 13% of patients with advanced BTC, regardless of PD-L1 expression, and has manageable toxicity.     

Identification of a compound heterozygous inactivating ABCC8 gene mutation responsible for young‐onset diabetes with exome sequencing

Activating mutations in the ABCC8 gene cause diabetes and inactivating mutations usually cause hyperinsulinemic hypoglycemia in infancy. Patients with hypoglycemia in infancy due to a heterozygous inactivating mutation have been reported to occasionally progress to diabetes later in life. We explored the gene responsible for diabetes in two brothers, who were suspected to have diabetes at 15 and 18 years‐of‐age, respectively, with whole exome sequencing, and identified a compound heterozygous ABCC8 gene mutation (p.Arg168Cys and p.Arg1421Cys). Although their father and mother were heterozygous carriers of the p.Arg168Cys and the p.Arg1421Cys mutation, respectively, neither parent had diabetes. These mutations have been reported to be responsible for hypoglycemia in infancy and function as an inactivating mutation. Our results suggest that the inactivating ABCC8 gene mutation is also important in the etiology of diabetes.     

Wound,pressure ulcer and burn guidelines – 4: Guidelines for the management of connective tissue disease/vasculitis-associated skin ulcers

The Japanese Dermatological Association prepared guidelines focused on the treatment of skin ulcers associated with connective tissue disease/vasculitis practical in clinical settings of dermatological care. Skin ulcers associated with connective tissue diseases or vasculitis occur on the background of a wide variety of diseases including, typically, systemic sclerosis but also systemic lupus erythematosus (SLE), dermatomyositis, rheumatoid arthritis (RA), various vasculitides and antiphospholipid antibody syndrome (APS). Therefore, in preparing the present guidelines, we considered diagnostic/therapeutic approaches appropriate for each of these disorders to be necessary and developed algorithms and clinical questions for systemic sclerosis, SLE, dermatomyositis, RA, vasculitis and APS.     

Correlation between Transient Hypotension and Exclusively Exercise-induced Symptoms of Two-to-One Atrioventricular Block

A 62-year-old woman with activity-dependent two-to-one atrioventricular block (2:1AVB) and a normal left ventricular ejection fraction was referred to our department for the evaluation of exclusively exercise-induced marked symptoms. The treadmill test helped establish a clear correlation between 2:1AVB and symptoms. The test results demonstrated that exercise-induced marked symptoms were attributed to abrupt transient hypotension combined with relative bradycardia, probably due to increased diastolic mitral and tricuspid regurgitation because of 2:1AVB during moderate-to-heavy exercise. After pacemaker implantation for 2:1AVB, the symptoms and transient hypotension disappeared, and her exercise capacity improved.     

N-terminal pro-brain natriuretic peptide predicts hospitalization for ischemic stroke in Japanese hemodialysis patients

Clinical and Experimental Nephrology - The association between N-terminal pro-brain natriuretic peptide (NT-proBNP) and stroke in Japanese hemodialysis (HD) outpatients is unclear. Therefore, in...     

Cognitive Frailty is Associated with Fall-Related Fracture among Older People

Objective

Cognitive frailty refers to cognitive impairment and physical frailty. Both cognitive impairment and physical frailty include risks of falling. The purpose of the study is to examine cognitive frailty and falling with/without a fracture.

Design

Cross-sectional observation study.

Setting

General communities in Japan.

Participants

Data of 10,202 older adults aged ≥ 65 years were collected.

Measurements

Physical frailty was characterized as slow walking speed and/or muscle weakness. Assessment of cognitive function included word lists memory, attention, executive function, and processing speed. Cognitive impairment refers to one or more cognitive decline indicated by at least 1.5 standard deviations below the threshold after adjusting for age and education. We operationally defined cognitive frailty as having both cognitive impairment and physical frailty. Participants were interviewed about their falling, history of fall-related fractures, and several potentially confounding factors such as demographic characteristics.

Results

Multinomial logistic regression analysis revealed that functional decline in all groups, as compared to the robust group, was significantly associated with falling without fractures, after adjusting for the covariates; cognitive impairment group (P =.017), physical frailty group (P =.002), and cognitive frailty group (P <.001). Only the cognitive frailty group had a significant association with fall-related fracture after adjusting for the covariates (OR 1.92, 95% CI: 1.20–3.08, P =.007).

Conclusion

Cognitive frailty is associated with not only falling but also fall-related fractures. Cognitive frailty may have a greater risk for fall-related fractures than cognitive impairment or physical frailty alone. Future research should examine causal the relationship between fall-related fractures and cognitive frailty.

     

Effects of Combined Physical and Cognitive Exercises on Cognition and Mobility in Patients With Mild Cognitive Impairment: A Randomized Clinical Trial

Importance

Although participation in physical and cognitive activities is encouraged to reduce the risk of dementia, the preventive efficacy of these activities for patients with mild cognitive impairment is unestablished.

Social Frailty Has a Stronger Impact on the Onset of Depressive Symptoms than Physical Frailty or Cognitive Impairment: A 4-Year Follow-up Longitudinal Cohort Study

Objectives

To examine the association between each type of frailty status and the incidence rate of depressive symptoms among community-dwelling older adults.

Deformation properties of Ti-6A1-7Nb alloy castings for removable partial denture frameworks

Ti-6Al-7Nb alloy was cast into three differently designed, removable partial denture frameworks: Palatal strap (PS), Anterior-posterior bar (AP), and Horseshoe-shaped bar (HS). The vertical displacement and local strain of Ti-6Al-7Nb alloy frameworks were investigated to compare against those of Co-Cr alloy frameworks. Vertical loading force of 19.6 N was applied at two locations, 10 and 20 mm, from the distal end of the framework. Although higher vertical displacement and local strain were observed for Ti-6Al-7Nb alloy frameworks than those for Co-Cr alloy frameworks, the PS framework appeared to show the least deformation. In addition, the strain at 10-mm location was higher than that at 20-mm location for AP and HS frameworks. This study thus proved that design had a significant influence on the deformation properties of denture frameworks. The PS design was evaluated to be a suitable design for the removable denture framework with Ti-6Al-7Nb alloy.