Postoperative development of sarcopenia is a strong predictor of a poor prognosis in patients with adenocarcinoma of the esophagogastric junction and upper gastric cancer

Background

There were few studies assessed the postoperative sarcopenia in patients with cancers. The objective of present study was to assess whether postoperative development of sarcopenia could predict a poor prognosis in patients with adenocarcinoma of esophagogastric junction, (AEG) and upper gastric cancer (UGC).

A multicenter,open‐label,phase II study of tirabrutinib (ONO/GS‐4059) in patients with Waldenström’s macroglobulinemia

Tirabrutinib is a second‐generation Bruton’s tyrosine kinase inhibitor with greater selectivity than ibrutinib. Here, we conducted a multicenter, phase II study of tirabrutinib in patients with treatment‐naïve (Cohort A) or with relapsed/refractory (Cohort B) Waldenström’s macroglobulinemia (WM). Patients were treated with tirabrutinib 480 mg once daily. The primary endpoint was major response rate (MRR; ≥ partial response). Secondary endpoints included overall response rate (ORR; ≥ minor response), time to major response (TTMR), progression‐free survival (PFS), overall survival (OS), and safety. In total, 27 patients (18 in Cohort A; 9 in Cohort B) were enrolled. The median age was 71 y, and the median serum immunoglobulin M level was 3600 mg/dL. Among the patients, 96.2% had the MYD88^L265P mutation. MRR and ORR were 88.9% and 96.3%, respectively (Cohort A: MRR, 88.9%; ORR, 94.4%; Cohort B: MRR, 88.9%; ORR, 100%). Median TTMR was 1.87 mo. PFS and OS were not reached with a median follow‐up of 6.5 and 8.3 mo for Cohorts A and B, respectively. The most common adverse events (AEs) were rash (44.4%), neutropenia (25.9%), and leukopenia (22.2%), with most AEs classified as grade 1 or 2. Grade ≥ 3 AEs included neutropenia (11.1%), lymphopenia (11.1%), and leukopenia (7.4%). No grade 5 AEs were noted. All bleeding events were grade 1; none were associated with drug‐related atrial fibrillation or hypertension. Although the follow‐up duration was relatively short, the study met the primary endpoint. Therefore, tirabrutinib monotherapy is considered to be highly effective for both untreated and relapsed/refractory WM with a manageable safety profile. (JapicCTI‐173646).     

Validity of Extended-Field-of-View Ultrasound Imaging to Evaluate Quantity and Quality of Trunk Skeletal Muscles

This study examined the validity of extended-field-of-view (EFOV) ultrasound imaging for evaluating the quantity (cross-sectional area [CSA]) and quality (accumulation of intramuscular fat) of trunk skeletal muscles (rectus abdominis, abdominal oblique and erector spinae) using magnetic resonance imaging (MRI) as a reference. Thirty healthy young men participated in this study. Cross-sectional images of the trunk at the height of the third lumbar vertebra were acquired and compared by EFOV ultrasound imaging and MRI. No significant differences were observed in CSAs between the two methods (0.74 ≤ R² ≤ 0.85). Echo intensities significantly correlated with MRI-derived accumulation of intramuscular fat in each skeletal muscle group. However, the correlation coefficients were relatively low (0.37 ≤ r ≤0.47; p < 0.05). These results indicate that EFOV ultrasound imaging is a reliable method for assessing trunk skeletal muscle CSA. Further research is warranted to find the optimal ultrasound setting for evaluating muscle quality.     

Trends in pediatric nephrotic syndrome

Nephrotic syndrome (NS) is relatively common in children, with most of its histological types being minimal changed disease. Its etiology has long been attributed to lymphocyte (especially T-cell) dysfunction, while T-cell-mediated vascular hyperpermeability increases protein permeability in glomerular capillaries, leading to proteinuria and hypoproteinemia. Based on this etiology, steroids and immunosuppressive drugs that are effective against this disease have also been considered to correct T-cell dysfunction. However, in recent years, this has been questioned. The primary cause of NS has been considered damage to glomerular epithelial cells and podocyte-related proteins. Therefore, we first describe the changes in expression of molecules involved in NS etiology, and then describe the mechanism by which abnormal expression of these molecules induces proteinuria. Finally, we consider the mechanism by which infection causes the recurrence of NS.     

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.     

Human plasma metabolic profiles of benzydamine,a flavin-containing monooxygenase probe substrate,simulated with pharmacokinetic data from control and humanized-liver mice

1.?Benzydamine is used clinically as a nonsteroidal anti-inflammatory drug in oral rinses and is employed in preclinical research as a flavin-containing monooxygenase (FMO) probe substrate. In this study, plasma concentrations of benzydamine and its primary N-oxide and N-demethylated metabolites were investigated in control TK-NOG mice, in humanized-liver mice, and in mice whose liver cells had been ablated with ganciclovir.

2.?Following oral administration of benzydamine (10?mg/kg) in humanized-liver TK-NOG mice, plasma concentrations of benzydamine N-oxide were slightly higher than those of demethyl benzydamine. In contrast, in control and ganciclovir-treated TK-NOG mice, concentrations of demethyl benzydamine were slightly higher than those of benzydamine N-oxide.

3.?Simulations of human plasma concentrations of benzydamine and its N-oxide were achieved using simplified physiologically based pharmacokinetic models based on data from control TK-NOG mice and from reported benzydamine concentrations after low-dose administration in humans. Estimated clearance rates based on data from humanized-liver and ganciclovir-treated TK-NOG mice were two orders magnitude high.

4.?The pharmacokinetic profiles of benzydamine were different for control and humanized-liver TK-NOG mice. Humanized-liver mice are generally accepted human models; however, drug oxidation in mouse kidney might need to be considered when probe substrates undergo FMO-dependent drug oxidation in mouse liver and kidney.     

Effect of <Emphasis Type="Italic">Kaempferia parviflora</Emphasis> extract on knee osteoarthritis

Knee osteoarthritis (OA) is becoming more prevalent worldwide due to increases in the numbers of elderly and obese patients. Currently, pharmaceutical medicines used for the treatment of OA are for symptomatic therapy and therefore new therapeutic agents are needed. Kaempferia parviflora (KP) is a plant growing naturally in Southeast Asia and has various pharmacological effects including an anti-inflammatory effect, but no effect on OA has yet been reported. We therefore conducted a search for the effects KP and the active components of KP extract (KPE) exert on OA as well as its mechanism of action. Results from a study of KPE using the monoiodoacetic acid rat OA model revealed that KPE reduced the pain threshold and severity of osteoarthritic cartilage lesions. The mechanism of action and active components were then investigated using IL-1β-treated human knee-derived chondrocytes. KPE, as well as 5,7-dimethoxyflavone and 5,7,4′-trimethoxyflavone, which are key constituents of KPE and highly absorbable into the body, reduced the expression of matrix metalloproteinases (MMPs), which are the main extracellular matrix enzymes that degrade collagen within cartilage. As mentioned above, KPE acted to suppress OA and 5,7-dimethoxyflavone and 5,7,4′-trimethoxyflavone were shown to be involved as part of KPE’s mechanism that inhibits MMPs.