Search

ECMO is becoming widely used as a life-saving measure for critically ill patients. However, there is limited data on pharmacokinetics and the dosing of beta-lactam antibiotics in ECMO. In this study, we evaluated the serum concentrations of cefepime in patients on ECMO to determine the impact of ECMO circuitry and to guide therapeutic dosing. Methods: Patients 19 years or older admitted to the ICU, treated with ECMO and beta-lactam antibiotics for presumed or documented infection, were enrolled. Three blood samples (peak, midpoint, trough) were obtained before ECMO (pre-ECMO) and during ECMO (intra-ECMO) at a steady state. Results: Eight patients met inclusion criteria; six received cefepime. All patients were male. Average ± SD age was 45.8 ± 14.7. Four patients received ECMO for severe SARS-CoV-2 infection, and one each for Pneumocystis pneumonia and influenza A infection. Mean ± SD APACHE II and SOFA scores prior to ECMO were 24.6 ± 7.1 and 11.0 ± 3.9, respectively. All but one of the patients received venovenous (VV) ECMO. Cefepime 1 g every 6 h intravenously over 2 min was administered to all patients before and during ECMO. Cefepime concentrations were fit to non-compartment analysis (NCA) and area under the serum concentration–time curve averaged ± SE 211.9 ± 29.6 pre-ECMO and 329.6 ± 32.3 mg*h/L intra-ECMO, p = 0.023. No patients displayed signs of cefepime neurotoxicity. Patients received ECMO for 43.1± 30 days. All patients expired. Cefepime dosed at 1 g every 6 h intravenously appears to achieve therapeutic levels for critically ill patients on ECMO. [ABSTRACT FROM AUTHOR]

A new technique has been devised for measuring the in situ tension in small ligaments. It is based on measuring the tension in an axially loaded flexible cable with pinned endpoints by deflecting the cable laterally and measuring its lateral load and deformation. Studies were performed in which nylon line and bone ligament bone preparations were placed in a materials tester and loaded in axial tension. Axial load as measured by lateral load and deformation was found to agree with the known load to within 8 percent. The method was sensitive to error in determination of ligament length, nonperpendicularity of the laterally applied load to the long axis of the ligament, and when used in situ, impingement of the ligament on a third bone causing bending. A device, consisting of an LVDT mounted to a rigid frame with its core rod connected to a load cell, was developed. The position of the core rod was controlled by a manual screw drive, and a hook on the other end of the core rod was used to deflect the ligament laterally. This device was applied to the study of tensions in five ligaments of the palmar wrist carpus, in seven cadaver specimens. Results showed that the radioscaphocapitate (RSC) and radiolunate (RL) ligaments had significantly greater tensions than the lunotriquetral (LT), the triquetrocapitate (TC), and scaphocapitate (SC) ligaments. For the four positions of the hand tested, neutral, 14 deg radial and 14 deg ulnar deviation, and 28 deg of extension, ligament tensions were found to be unaffected by position. In all positions tested, all ligaments had measurable tension, demonstrating the importance of ligaments in maintaining the integrity of the wrist carpus.

Striped bass (Morone saxatilis) are anadromous fish that support an important fishery along the east coast of North America. In Chesapeake Bay, strong juvenile recruitment of striped bass can occur when larvae overlap with high concentrations of their zooplankton prey, but the mechanisms fostering the temporal overlap are unknown. Here, the influence of winter temperature on the peak abundances of a key prey, Eurytemora carolleeae , was estimated with a temperature-dependent developmental model. The role of these peaks in regulating striped bass recruitment was explored in three nursery areas: upper Chesapeake Bay, Choptank River, and Patuxent River. Model results indicated that cold winters delay the timing and increase the size of peak E. carolleeae spring abundance. When the model output was used in regression relationships with striped bass juvenile recruitment and freshwater discharge, the regression models explained up to 78% of annual recruitment variability. Results suggests that cold, wet winters could increase the chance of a match between striped bass larvae and high concentrations of their prey. This mechanistic link between winter temperatures and striped bass production, acting through prey dynamics, could further understanding of fish recruitment variability and indicates that warmer winters could negatively affect some striped bass populations. [ABSTRACT FROM AUTHOR]

Background Pleurodesis is the standard of care for non‐small cell lung cancer (NSCLC) patients with symptomatic malignant pleural effusion (MPE). However, there is no standard management for MPE uncontrolled by pleurodesis. Most patients with unsuccessful MPE control are unable to receive effective chemotherapy. Vascular endothelial growth factor (VEGF) plays an important role in the pathogenesis of MPE. This multicenter, phase II study investigated the effects of bevacizumab plus chemotherapy in nonsquamous NSCLC patients with unsuccessful management of MPE. Methods Nonsquamous NSCLC patients with MPE following unsuccessful tube drainage or pleurodesis received bevacizumab (15 mg/kg) plus chemotherapy every three weeks. The primary endpoint was pleural effusion control rate (PECR), defined as the percentage of patients without reaccumulation of MPE at eight weeks. Secondary endpoints included pleural progression‐free survival (PPFS), safety, and quality of life (QoL). Results A total of 20 patients (median age: 69 years; 14 males; 20 adenocarcinomas; six epidermal growth factor receptor mutations) were enrolled in nine centers. The PECR was 80% and the primary end point was met. The PPFS and the overall survival (OS) were 16.6 months and 19.6 months, respectively. Patients with high levels of VEGF in the MPE had shorter PPFS (P = 0.010) and OS (P = 0.002). Toxicities of grade ≥ 3 included neutropenia (50%), thrombocytopenia (10%), proteinuria (10%), and hypertension (2%). The cognitive QoL score improved after treatment. Conclusions Bevacizumab plus chemotherapy is highly effective with acceptable toxicities in nonsquamous NSCLC patients with uncontrolled MPE, and should be considered as a standard therapy in this setting. Key points Significant findings of the study Bevacizumab plus chemotherapy is highly effective with acceptable toxicities in nonsquamous NSCLC patients with uncontrolled MPE. What this study adds Bevacizumab plus chemotherapy should be considered as a standard treatment option for patients with uncontrolled MPE. Clinical trial registration UMIN000006868 was a phase II study of efficacy of bevacizumab plus chemotherapy for the management of malignant pleural effusion (MPE) in nonsquamous non‐small cell lung cancer patients with MPE unsuccessfully controlled by tube drainage or pleurodesis (North East Japan Study Group Trial NEJ‐013B) (http://umin.sc.jp/ctr/).