Prospective evaluation of rapid antimicrobial susceptibility testing by disk diffusion on Mueller-Hinton rapid-SIR directly on blood cultures

Background

With the worldwide spread of antibiotic resistance, delivering antibiotic susceptibility test (AST) results in a timely manner represents a major challenge. In cases of sepsis, rapid AST may facilitate early optimization of empiric antibiotic therapy. Disc diffusion is a well-standardized AST method, however 16 to 24?h are required to achieve an overall AST profile according to antimicrobial societies.

Validity of injury self-reports by novice runners: comparison with reports by sports medicine physicians

This study examined the criterion validity of self-reported running-related injuries (RRI) by novice runners. Fifty-eight participants (41 females; age 46 ± 11 yrs) of the “Start-to-Run” program provided self-reports on their RRIs using an online questionnaire. Subsequently, they attended injury consultations with sports medicine physicians who provided physician-reports (blinded for the self-reports) as a reference standard. Self-reports and physician-reports included information on injury location (i.e., hip/groin, upper leg, knee, lower leg, and ankle/foot) and injury type (i.e., muscle-tendon unit, joint, ligament, or bone). Sensitivity, specificity, and positive predictive values were 100% for all five injury locations. For injury type, sensitivity was low (66% for muscle-tendon unit, 50% for ligament, and 40% for bone) and lowest for joint injuries (17%). In conclusion, the validity of self-reported RRIs by novice runners is good for injury locations but not for injury types. In particular for joint injuries, the validity of novice runners’ self-reports is low.

Abbreviations: RRI: Running Related Injury; SMC: Sports Medicine Centre; MTU: Muscle Tendon Unit; PPV: Positive Predictive Value     

Inspiratory muscle training for intensive care patients: A multidisciplinary practical guide for clinicians

ObjectivesTo describe a multidisciplinary approach to inspiratory muscle training (IMT) for patients in the intensive care unit (ICU).BackgroundInspiratory muscle weakness is a known consequence of prolonged mechanical ventilation, and there is emerging evidence that specific IMT can ameliorate this weakness. However, IMT is not yet standard practice in many ICUs, possibly because of the wide variety of methods reported and a lack of published practical guidelines. While the optimal parameters for IMT are yet to be established, we share our detailed methodology which has been shown to be safe in selected ventilator-dependent patients and is the only approach which has been shown to increase quality of life in ICU patients.MethodsPatients who have experienced invasive mechanical ventilation for at least 7 days can commence IMT in either the ventilator-dependent phase or when weaned from mechanical ventilation. Intensity should be prescribed based on maximum inspiratory pressure, which is measurable through the tracheostomy or endotracheal tube via the ventilator or a respiratory pressure meter. Using a removable threshold device, we recommend high-intensity training (5 sets of 6 breaths at a minimum of 50% of maximum inspiratory pressure) performed once per day, supervised by the physiotherapist, with intensity increased daily such that patients can only just complete the 6th breath in each set.ResultsUsing this high-intensity approach, IMT is likely to improve not only inspiratory muscle strength but also quality of life in patients recently weaned from mechanical ventilation of 7 days' duration or longer. Effective IMT requires a multidisciplinary approach to maximise feasibility, with doctors, nurses, and therapists working closely to optimise conditions for successful IMT.ConclusionsThis multidisciplinary approach to implement IMT in ICU patients should assist clinicians in translating best-available evidence into practice, with the potential to enhance patient recovery.     

Damage-associated molecular pattern (DAMP) activation in melanoma: investigation of the immunogenic activity of 15-deoxy, Δ12,14 prostamide J2

Metastatic melanoma is the most deadly skin neoplasm in the United States. Outcomes for this lethal disease have improved dramatically due to the use of both targeted and immunostimulatory drugs. Immunogenic cell death (ICD) has emerged as another approach for initiating antitumor immunity. ICD is triggered by tumor cells that display damage-associated molecular patterns (DAMPs). These DAMP molecules recruit and activate dendritic cells (DCs) that present tumor-specific antigens to T cells which eliminate neoplastic cells. Interestingly, the expression of DAMP molecules occurs in an endoplasmic reticulum (ER) stress-dependent manner. We have previously shown that ER stress was required for the cytotoxic activity of the endocannabinoid metabolite, 15-deoxy, Δ^12,14 prostamide J₂ (15dPMJ₂). As such, the current study investigates whether 15dPMJ₂ induces DAMP signaling in melanoma. In B16F10 cells, 15dPMJ₂ caused a significant increase in the cell surface expression of calreticulin (CRT), the release of ATP and the secretion of high-mobility group box 1 (HMGB1), three molecules that serve as surrogate markers of ICD. 15dPMJ₂ also stimulated the cell surface expression of the DAMP molecules, heat shock protein 70 (Hsp70) and Hsp90. In addition, the display of CRT and ATP was increased by 15dPMJ₂ to a greater extent in tumorigenic compared to non-tumorigenic melanocytes. Consistent with this finding, the activation of bone marrow-derived DCs was upregulated in co-cultures with 15dPMJ₂-treated tumor compared to non-tumor melanocytes. Moreover, 15dPMJ₂-mediated DAMP exposure and DC activation required the electrophilic cyclopentenone double bond within the structure of 15dPMJ₂ and the ER stress pathway. These results demonstrate that 15dPMJ₂ is a tumor-selective inducer of DAMP signaling in melanoma.     

EAU-EANM-ESTRO-ESUR-SIOG Guidelines on Prostate Cancer—2020 Update. Part 1: Screening,Diagnosis, and Local Treatment with Curative Intent

ObjectiveTo present a summary of the 2020 version of the European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy and Oncology (ESTRO)-European Society of Urogenital Radiology (ESUR)-International Society of Geriatric Oncology (SIOG) guidelines on screening, diagnosis, and local treatment of clinically localised prostate cancer (PCa).Evidence acquisitionThe panel performed a literature review of new data, covering the time frame between 2016 and 2020. The guidelines were updated and a strength rating for each recommendation was added based on a systematic review of the evidence.Evidence synthesisA risk-adapted strategy for identifying men who may develop PCa is advised, generally commencing at 50 yr of age and based on individualised life expectancy. Risk-adapted screening should be offered to men at increased risk from the age of 45 yr and to breast cancer susceptibility gene (BRCA) mutation carriers, who have been confirmed to be at risk of early and aggressive disease (mainly BRAC2), from around 40 yr of age. The use of multiparametric magnetic resonance imaging in order to avoid unnecessary biopsies is recommended. When a biopsy is performed, a combination of targeted and systematic biopsies must be offered. There is currently no place for the routine use of tissue-based biomarkers. Whilst prostate-specific membrane antigen positron emission tomography computed tomography is the most sensitive staging procedure, the lack of outcome benefit remains a major limitation. Active surveillance (AS) should always be discussed with low-risk patients, as well as with selected intermediate-risk patients with favourable International Society of Urological Pathology (ISUP) 2 lesions. Local therapies are addressed, as well as the AS journey and the management of persistent prostate-specific antigen after surgery. A strong recommendation to consider moderate hypofractionation in intermediate-risk patients is provided. Patients with cN1 PCa should be offered a local treatment combined with long-term hormonal treatment.ConclusionsThe evidence in the field of diagnosis, staging, and treatment of localised PCa is evolving rapidly. The 2020 EAU-EANM-ESTRO-ESUR-SIOG guidelines on PCa summarise the most recent findings and advice for their use in clinical practice. These PCa guidelines reflect the multidisciplinary nature of PCa management.Patient summaryUpdated prostate cancer guidelines are presented, addressing screening, diagnosis, and local treatment with curative intent. These guidelines rely on the available scientific evidence, and new insights will need to be considered and included on a regular basis. In some cases, the supporting evidence for new treatment options is not yet strong enough to provide a recommendation, which is why continuous updating is important. Patients must be fully informed of all relevant options and, together with their treating physicians, decide on the most optimal management for them.