- Patient-Centered Outcomes after Laparoscopic Paraesophageal Hernia Repair. [Journal Article]
- JAJ Am Coll Surg 2018 Feb 14
- CONCLUSIONS: Laparoscopic paraesophageal hernia repair results in significantly improved QOL as measured by SF-36 at both short and long-term intervals. Additionally, RSI and GERD-HRQL scores improved at all postoperative time points.
- A phase II trial of riluzole, an antagonist of metabotropic glutamate receptor 1 (GRM1) signaling, in patients with advanced melanoma. [Journal Article]
- PCPigment Cell Melanoma Res 2018 Feb 17
- Studies demonstrate that GRM, expressed by >60% of human melanomas, may be a therapeutic target. We performed a phase II trial of 100 mg po bid of riluzole, an inhibitor of GRM1 signaling, in patient...
Studies demonstrate that GRM, expressed by >60% of human melanomas, may be a therapeutic target. We performed a phase II trial of 100 mg po bid of riluzole, an inhibitor of GRM1 signaling, in patients with advanced melanoma with the primary endpoint of response rate. Thirteen patients with GRM1-positive tumors were enrolled. No objective responses were observed and accrual was stopped. Stable disease was noted in 6 (46%) patients, with 1 patient on study for 42 weeks. Riluzole was well-tolerated, with fatigue (62%) as the most common adverse event. MAPK and PI3K/AKT downregulation was noted in 33% of paired tumor biopsies. Hypothesis generating correlative studies suggested that downregulation of angiogenic markers and increased leuckocytes at the active edge of tumor correlate with clinical benefit. Pharmacokinetic analysis showed inter-patient variability consistent with prior riluzole studies. Future investigations should interrogate mechanisms of biologic activity and advance development of agents with improved bioavailability. This article is protected by copyright. All rights reserved.
- Investigating the Effectiveness, Acceptability and Impact on Healthcare Usage of Providing a Cognitive-Behavioural Based Psychological Therapy Service for Patients with Primary Antibody Deficiency. [Journal Article]
- JCJ Clin Immunol 2018 Feb 17
- CONCLUSIONS: Psychological therapy based on the cognitive-behavioral model of treatment appears to be a valuable treatment for patients with primary antibody deficiency and comorbid mental health difficulties.
- Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study. [Journal Article]
- INInvest New Drugs 2018 Feb 17
- Background CD37 is expressed on B-cell lymphoid malignancies, thus making it an attractive candidate for targeted therapy in non-Hodgkin lymphoma (NHL). IMGN529 is an antibody-drug conjugate comprisi...
Background CD37 is expressed on B-cell lymphoid malignancies, thus making it an attractive candidate for targeted therapy in non-Hodgkin lymphoma (NHL). IMGN529 is an antibody-drug conjugate comprising a CD37-binding antibody linked to the maytansinoid DM1, a potent anti-mitotic agent. Methods This first-in-human, phase 1 trial recruited adult patients with relapsed or refractory B-cell NHL. The primary objective was to determine the maximum tolerated dose (MTD) and recommended phase 2 dose. Secondary objectives were to evaluate safety, pharmacokinetics, and preliminary clinical activity. IMGN529 was administered intravenously once every 3 weeks, and dosed using a conventional 3 + 3 dose-escalation design. Results Forty-nine patients were treated at doses escalating from 0.1 to 1.8 mg/kg. Dose limiting toxicities occurred in eight patients and included peripheral neuropathy, febrile neutropenia, neutropenia, and thrombocytopenia. The most frequent treatment-emergent adverse events were fatigue (39%), neutropenia, pyrexia, and thrombocytopenia (each 37%). Adverse events led to treatment discontinuation in 10 patients (20%). Eight patients (16%) had treatment-related serious adverse events, the most common being grade 3 febrile neutropenia. The MTD (with growth factor support) was 1.4 mg/kg every 3 weeks. IMGN529 plasma exposure increased monotonically with dose and was consistent with target-mediated drug disposition. Five (13%) of 39 response-evaluable patients achieved an objective response (one complete response and four partial responses), four of which occurred in the subgroup of patients with diffuse large B-cell lymphoma. Conclusions The manageable safety profile of IMGN529 and preliminary evidence of activity, particularly in DLBCL patients, support the continued development of this novel CD37-targeting agent.
- A phase I and pharmacokinetic study of taladegib, a Smoothened inhibitor, in Japanese patients with advanced solid tumors. [Journal Article]
- INInvest New Drugs 2018 Feb 17
- Background This phase I dose-escalation study investigated the safety of the Smoothened inhibitor taladegib in Japanese patients with advanced solid tumors. Methods Patients received taladegib orally...
Background This phase I dose-escalation study investigated the safety of the Smoothened inhibitor taladegib in Japanese patients with advanced solid tumors. Methods Patients received taladegib orally once daily for 28-day cycles, using a 3 + 3 dose-escalation method. The primary objective was the safety and tolerability of taladegib at doses up to the global recommended dose (400 mg). Secondary objectives included pharmacokinetics, changes in skin glioma-associated oncogene homolog 1 (Gli1) transcript levels, and antitumor activity. Results Nineteen patients received treatment (100 mg: 3; 200 mg: 3; 400 mg: 13). No dose-limiting toxicities (DLTs) were observed at doses of 100 mg or 200 mg; 3 of the 9 patients evaluable for DLTs at the 400 mg dose level experienced DLTs (thrombocytopenia: 1; decreased appetite: 2). The most commonly reported treatment-related adverse events were dysgeusia (13/19, 68.4%), decreased appetite (12/19, 63.2%), nausea (9/19, 47.4%), fatigue (9/19, 47.4%), and vomiting (6/19, 31.6%). The pharmacokinetic profile suggested that exposure to taladegib was higher in Japanese than non-Japanese patients, possibly related to differences in body weight and/or drug formulation. At all dose levels, a high level of inhibition of skin Gli1 transcript levels was observed after 15 and 30 days of exposure to taladegib. Partial response was achieved by 1 patient (basal cell carcinoma of the skin) and stable disease by 4 patients. Conclusions Taladegib doses of 100 mg and 200 mg, but not the global recommended dose of 400 mg, were well tolerated in this population of Japanese patients with advanced solid tumors.
- Pulmonary sarcoidosis with and without extrapulmonary involvement: a cross-sectional and observational study in China. [Journal Article]
- BOBMJ Open 2018 Feb 16; 8(2):e018865
- CONCLUSIONS: Extrapulmonary involvement is common in patients with pulmonary sarcoidosis, with the most common sites being extrathoracic lymph nodes and skin. Patients with sarcoidosis with extrapulmonary involvement are more symptomatic (fatigue), have higher SACE levels and more deteriorating HRCT findings, to which clinicians should pay attention.
- Calcar screw position in proximal humerus fracture fixation: Don't miss high! [Journal Article]
- IInjury 2018 Feb 11
- CONCLUSIONS: The distal and neutral groups had similar mechanical properties in many cadaveric comparisons while the proximal group trended towards decreased construct stiffness.Successful proximal humerus fracture reconstruction is inherent upon anatomic fracture reduction coupled with medial column support. Results from this experiment suggest that missing the calcar proximally is deleterious to fixation strength, while it is safe, and perhaps even desirable, to aim slightly distal to the intended target.
- Primary sclerosing cholangitis. [Review]
- LctLancet 2018 Feb 13
- Primary sclerosing cholangitis is a rare, chronic cholestatic liver disease characterised by intrahepatic or extrahepatic stricturing, or both, with bile duct fibrosis. Inflammation and fibrosis of b...
Primary sclerosing cholangitis is a rare, chronic cholestatic liver disease characterised by intrahepatic or extrahepatic stricturing, or both, with bile duct fibrosis. Inflammation and fibrosis of bile ducts and the liver are followed by impaired bile formation or flow and progressive liver dysfunction. Patients might be asymptomatic at presentation or might have pruritus, fatigue, right upper quadrant pain, recurrent cholangitis, or sequelae of portal hypertension. The key diagnostic elements are cholestatic liver biochemistry and bile duct stricturing on cholangiography. Genetic and environmental factors are important in the cause of the disease, with the intestinal microbiome increasingly thought to play a pathogenetic role. Approximately 70% of patients have concurrent inflammatory bowel disease and patients require colonoscopic screening and surveillance. Primary sclerosing cholangitis is associated with increased malignancy risk and surveillance strategies for early cholangiocarcinoma detection are limited. No single drug has been proven to improve transplant-free survival. Liver transplantation is effective for advanced disease but at least 25% of patients develop recurrent disease in the graft.
- A machine learning approach to detect changes in gait parameters following a fatiguing occupational task. [Journal Article]
- EErgonomics 2018 Feb 16; :1-21
- The purpose of this study is to provide a method for classifying non-fatigued versus fatigued states following manual material handling. A method of template matching pattern recognition for feature ...
The purpose of this study is to provide a method for classifying non-fatigued versus fatigued states following manual material handling. A method of template matching pattern recognition for feature extraction (1$ Recognizer) along with the support vector machine (SVM) model for classification were applied on the kinematics of gait cycles segmented by our stepwise search-based segmentation algorithm. A single inertial measurement unit (IMU) on the ankle was used, providing a minimally intrusive and inexpensive tool for monitoring. The classifier distinguished between states using distance-based scores from the recognizer and the step duration. The results of fatigue detection showed an accuracy of 90% across data from 20 recruited subjects. This method utilizes the minimum amount of data and features from only one low-cost sensor to reliably classify the state of fatigue induced by a realistic manufacturing task using a simple machine learning algorithm that can be extended to real-time fatigue monitoring as a future technology to be employed in the manufacturing facilities. Practitioner Summary We examined the use of a wearable sensor for the detection of fatigue-related changes in gait based on a simulated manual material handling task. Classification based on foot acceleration and position trajectories resulted in 90% accuracy. This method provides a practical framework for predicting realistic levels of fatigue.
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- Development of a specific index to detect malnutrition in athletes: Validity in weight class or intermittent fasted athletes. [Journal Article]
- BOBiochim Open 2017; 4:1-7
- Fasted or weight-category athletes manage their training under strict diet conditions that could impair the stress-recovery balance and result in acute or chronic fatigue. However, to date, no valida...
Fasted or weight-category athletes manage their training under strict diet conditions that could impair the stress-recovery balance and result in acute or chronic fatigue. However, to date, no validated biomarker are available to quantify this phenomena. The aim of this study was to assess the validity of a specific index combining plasma albumin and weight change to detect nutrition-related risks of fatigue increase and under-performance in athletes experiencing particular nutritional conditions. An athlete's nutrition risk index (ANRI) equation, based on data from lightweight and heavyweight rowers, was developed using relationship between plasma albumin concentrations combined to weight changes with sport performance and overtraining scores and was tested by odds ratio for failure. The accuracy and sensitivity of this former specific equation was subsequently tested on runners observing the Ramadan-fasting as well as on boxers after a short weight-loss period. Independently of training and performance, lightweight rowers presented lower nutritional parameters than heavyweight (albumin: 37.4 ± 2.7vs39.9 ± 1.8 g·L-1,P < 0.05; weight state: 94.5 ± 1.8vs99.9 ± 0.9%,P < 0.01). In lightweight, ANRI was related with overtraining score (R2 = 0.21,P < 0.01), risks for failure in competition were enhanced when ANRI increased (OR:2.5,P = 0.03). Relationship of ANRI with overtraining score tended to be also significant in runners (R2 = 0.32,P = 0.06) but not in boxers (P = 0.4). Albumin concentrations combined to weight loss appeared relevant to delineate nutrition-related risks of fatigue and/or competitive failure associated with mid-term diets (about 30 days) as observed in rowers and Ramadan-fasted runners. ANRI may benefit to athletes monitoring by delineating effects of their weight loss program.