Use of Faropenem as an Indicator of Carbapenemase Activity in the Enterobacteriaceae

The aim of this study was to determine the ability of a disc susceptibility test using faropenem (10 μg) to predict carbapenemase activity in Enterobacteriaceae. A collection of 166 isolates of carbapenemase-producing Enterobacteriaceae (CPE) and 82 isolates of Enterobacteriaceae that produced other β-lactamases was compiled from diverse sources. Disc susceptibility testing was performed using the CLSI/EUCAST methodology with discs of faropenem (10 μg), temocillin (30 μg), and four carbapenems (each 10 μg). A further prospective evaluation of the faropenem disc susceptibility test was performed using 205 consecutive isolates referred to a United Kingdom reference laboratory in parallel with molecular methods for carbapenemase detection. Of 166 isolates of CPE, 99% showed growth up to the edge of a 10-μg faropenem disc compared with only 6% of other β-lactamase producers (sensitivity, 99%; specificity, 94%). A “double zone” around 10-μg faropenem discs was frequently associated with OXA-48 producers. Of the carbapenems, the most useful agent was imipenem, where a zone diameter of ≤23 mm as a predictor of carbapenemase activity had a sensitivity of 99% and a specificity of 85%. The presence of no zone of inhibition around a 30-μg temocillin disc was a consistent feature of strains producing OXA-48 carbapenemase. For 205 isolates of Enterobacteriaceae referred to a United Kingdom reference laboratory, growth up to a 10-μg faropenem disc correctly identified 84 of 86 carbapenemase producers (98% sensitivity), with a specificity of 87%. Disc susceptibility testing using faropenem (10 μg) is a simple, convenient, and highly predictive screening test for carbapenemase-producing Enterobacteriaceae.     

Changes in exertion-related symptoms in adults and youth who have sustained a sport-related concussion

ObjectivesTo identify the symptoms responsible for cessation of exercise testing and evaluate changes in post-concussion symptom scores on the Post-Concussion Symptom Scale (PCSS) from the Sport-Concussion Assessment Tool (SCAT5) immediately, 1–4 h, and 6–12 h following completion of the Buffalo Concussion Treadmill Test (BCTT) in youth and adults who have sustained a sport-related concussion.DesignProspective case-series.MethodsIndividuals who were diagnosed with a sport-related concussion and self-reported difficulties with exertion were referred to perform an exertional treadmill test. Individuals were recruited from a university sports medicine clinic. Change in PCSS symptom severity scores were operationally defined as a change ≥4 points.ResultsForty-five individuals aged 13–57 years consented to participate. A total of 14/24 (58.3%) female and 13/21 (61.9%) male participants reported an increase in symptom severity scores immediately following the BCTT. At 1–4 h, 5/10 (50.0%) males and 5/14 (35.7%) females who completed the PCSS had elevated symptom severity scores compared to pre-exertion. Only 24.2% (3/17 males and 5/16 females) of participants completing the PCSS at 6–12 h reported increased symptom severity scores.ConclusionExertional testing is an important component of a multifaceted assessment following concussion; however, previous research evaluating symptom responses to exertion is limited. This study provides evidence to suggest individuals who experience an exacerbation of concussion-associated symptoms after exertion are likely to return to pre-exertion levels within the same day. Future research monitoring symptoms following exertion and throughout recovery should be performed in tandem with physiological measures to better understand the source of symptoms.     

Assessment of IGRT variability for lung SBRT

PurposeThe purpose of this project was to assess factors that may influence variability in the pre-treatment kilovoltage cone beam computed tomography (kV CBCT) image matching process for lung stereotactic body radiation therapy (SBRT).Methods and materialsPre-treatment CBCT and planning CT data sets of previously-treated lung SBRT patients were gathered and anonymized from four radiotherapy centers in Alberta. Eight radiation therapists (RTTs) and four radiation oncologists (ROs) were recruited from the same four cancer centers for image matching. Identical data sets were provided to each user, but the order of image sets was randomized independently for each user to remove any learning bias. Inter-user variabilities were then investigated as functions of various factors, including image origin (source institution/machine), user's institution (local matching protocol), profession (RTT vs. RO), years of experience and image quality (presence/absence of added noise).ResultsVery little variation in image matching between different users was observed. The mean differences from the consensus means for different image sets were less than 1 mm in all directions, and cases that exceeded 3 mm (i.e. clinically significant differences) were extremely rare. Image origin, user's institution, and profession (RTT vs. RO) didn't lead to any meaningful clinical differences, while image quality didn't introduce any statistically significant differences. In addition, no discernible trend was seen between user's experience and deviation from the user mean. Overall, no meaningful differences in inter-user variabilities for the different factors investigated were found in this study.ConclusionsThere appears to be an adequate standardization across the province of Alberta in terms of CBCT image matching process. No clinically significant differences were observed as functions of various factors investigated in this study. Consistency in matching between RTTs and ROs in this study suggests that RTTs do not need systematic RO approval of their lung CBCT match. It should be noted that RTTs at the centers in this study receive comprehensive training in CBCT-based image matching.     

A posterior ring apophyseal fracture and disc herniation in a 21-year-old competitive basketball player: a case report

Objective:

To describe the diagnosis and management of a competitive male basketball player with discogenic low back pain and presence of an old posterior ring apophyseal fracture (PRAF). This case will highlight the importance of early recognition and considerations regarding patient management for this differential of radiating low back pain.

Clinical Features:

A 21-year-old provincial basketball player presented with recurrent radiating low back pain into the left groin and lower limb. After several weeks of persistent symptoms including pain, muscle weakness, and changes in the Achilles deep tendon reflex, imaging was obtained that revealed a large disc extrusion with an old posterior ring apophyseal fracture. In collaboration with a spine surgeon and family physician, the patient was treated using a conservative, multimodal approach. Treatment consisted of graded mobilizations, spinal manipulative therapy, interferential current, and soft tissue therapy to the lumbar spine. Rehabilitation exercises focused on centralizing symptoms and improving strength, proprioception and function of the lower limb. After a period of 8 weeks, the patient was able to complete all activities of daily living without pain in addition to returning to basketball practice.

Summary:

PRAF is a unique condition in the immature spine and recent evidence suggests that those involved in sports requiring repetitive motion of the lumbar spine may be at increased risk. The astute clinician must consider this differential in young populations presenting with discogenic low back pain, as a timely diagnosis and necessary referral may allow for effective conservative management to reduce symptoms. Equally as important, one must be aware of the complications from PRAF as a contributing source of low back pain and dysfunction into adulthood. Knowing when to refer for advanced imaging and/or a surgical consult given the variable clinical presentation and prognosis is an essential component to care.     

Inhibition of autophagy increases apoptosis during re‐warming after cold storage in renal tubular epithelial cells

Prolonged cold storage and re‐warming (CS/REW) of kidneys are risk factors for delayed graft function (DGF). Studies in renal tubular epithelial cells (RTECs) have determined apoptosis and autophagy in models of either cold storage (CS) or re‐warming alone. The effect of both cold storage and re‐warming on apoptosis and autophagy, in RTECS is not known and is relevant to DGF as the kidney is subjected to both CS and re‐warming. We hypothesized that CS/REW of RTECs would induce autophagy that protects against apoptosis. In CS/REW, there was increased autophagic flux of RTECs. Autophagy inhibition using an Atg5 siRNA resulted in increased cleaved caspase‐3 and increased apoptotic cells (on both morphology and annexin V staining) during CS/REW. The effect of autophagy inhibition on necrosis in RTECs is unknown. There were increased necrosis and caspase‐1, a mediator of necrosis, during CS/REW, and the Atg5 siRNA had no effect on necrosis and caspase‐1. In a kidney transplant model, there was an increase in LC3 II, a marker of autophagy, in kidneys transplanted after cold storage. In summary, autophagic flux is increased during CS/REW. Autophagy inhibition resulted in increased cleaved caspase‐3 and increased apoptosis during CS/REW without an effect on necrosis or caspase‐1. In conclusion, autophagy inhibition in RTECs after CS/REW induces apoptotic cell death and may be deleterious as a therapy to decrease DGF.