Royal Columbian Hospital

Objectives:We described the clinical outcomes and estimated cost savings from switching patients to early oral therapy from intravenous (IV) therapy for prosthetic joint infections (PJI) based on predefined criteria.Methods:Retrospective observational study in a large health authority consisting of 12 acute care hospitals in Canada. Patient demographics, microbiological and treatment data were collected for all patients with first episode of knee or hip PJI in 2022. Treatment failure rates, allergic or adverse reactions to IV or oral treatment, and hospital readmission rates were reported for those who met criteria for early switch to oral therapy.Results:Fifty-one patients were included. Thirty-seven patients (73%) had knee PJI, with debridement, antibiotics, and implant retention being the most common procedure. Sixteen patients (31%) had IV therapy for the entire duration of treatment, and the mean duration was 44 days. Twenty-three patients (45%) could have been switched to oral therapy. In practice however, only 3 patients (6%) were switched to oral therapy by day 7 following surgical source control. Five patients (22%) had clinical and/or microbiological failure 2 years postsurgery. Four patients (17%) and 6 patients (26%) developed an allergic or adverse reaction to IV and oral therapy, respectively. Five patients (22%) developed line complications. We estimated potential cost savings of almost $70,000 Canadian dollars with early oral therapy.Conclusion:Almost half of our PJI patients could have been switched to oral therapy within 7 days post-surgical source control. This study highlights a great opportunity for antimicrobial stewardship.

IntroductionTremelimumab in combination with Durvalumab has recently been approved for the treatment of unresectable hepatocellular carcinoma (HCC). While immune checkpoint inhibitors (ICIs) have transformed cancer therapy, they are associated with rare but potentially fatal immune-related adverse events, including myocarditis.Case reportWe report a case of fulminant myocarditis in a 66-year-old female with advanced HCC, 38 days after initiating the Tremelimumab/Durvalumab STRIDE protocol. She presented with cardiogenic shock requiring V-A ECMO support. High-dose corticosteroid therapy resulted in full recovery of cardiac function.DiscussionICI-associated myocarditis has a reported prevalence of 1.14%, with a high rate of major adverse cardiac events. We reported a case of Tremelimumab/Durvalumab-associated myocarditis requiring mechanical circulatory support. Prompt recognition and immunosuppression were critical for recovery.ConclusionClinicians should maintain a high index of suspicion for myocarditis in patients on ICI therapy, as early intervention can be lifesaving.

Many survivors of traumatic injuries are affected by mental disorders, which has recently led to the publication of clinical practice guidelines (CPGs). However, there is no comprehensive synthesis of guideline recommendations to inform clinicians on those that should be prioritized for implementation and thus promote adherence to them. To identify guideline recommendations for the prevention and management of mental disorders in patients with traumatic injuries, appraise their quality, and synthesize the quality of evidence and the strength of included recommendations. MEDLINE, Embase, CINAHL, PsycINFO, Cochrane Central, Web of Science, and 61 websites of professional associations and guideline repositories were searched between January 2008 and September 2024. We included CPGs pertinent to the acute and early recovery phases (<3 months) of adult patients (≥18 years) with traumatic injuries with at least 1 recommendation on mental health. Pairs of reviewers independently extracted data and assessed guideline quality using the Appraisal of Guidelines Research and Evaluation (AGREE) II tool. The quality of evidence on recommendations was synthesized using a matrix based on the categories of the Grading of Recommendations, Assessment, Development and Evaluation (GRADE). Mental health recommendations had to target prevention, screening, evaluation, intervention, referral for follow-up or specialized services, and a patient- and family-centered care approach. Forty-three CPGs were included, 25 of which (58%) were high quality. Rigor of development, applicability, lack of involvement from all interested parties, and editorial independence were the most common methodological weaknesses. High-quality CPGs included 200 recommendations; of these, 50 (25%) were supported by moderate- to high-quality evidence and 30 (60%) targeted patients with traumatic brain injury. They covered mainly nonpharmacological and pharmacological interventions to treat acute stress disorder, substance use disorders, posttraumatic stress disorder, depression, or aggression. Fewer recommendations related to prevention, screening, evaluation, and referral were identified as having high empirical support. Fifty recommendations were identified that may be considered for implementation in clinical settings in patients with traumatic brain injury and other trauma populations. Our review underlines important areas for future research, including training for clinicians, a patient- and family-centered care approach, and health care equity.

ABSTRACT Introduction Diaphragm neurostimulation is a muscle stimulation technique that, through electrodes placed directly on or at the vicinity of the phrenic nerves, induces diaphragm contractions independently of the patient’s cooperation. Recently, the technical development of temporary diaphragm neurostimulation devices has paved the way for a new era in the management of critically ill patients. Areas covered In this review, we describe the latest technical developments in diaphragm neurostimulation and its physiological effects. We searched MEDLINE of experimental and clinical studies in English language published from database inception until 31 October 2024. We also discuss the advances in terms of patients centered outcomes and the key areas for improvement. Lastly, we introduce possible future directions and the novel improvements in patient care. Expert opinion The research on diaphragm neurostimulation promise as an emerging intervention which addresses common complications associated with mechanical ventilation. Large-scale clinical trials are necessary to validate diaphragm neurostimulation efficacy and safety in humans, establish treatment protocols, and determine cost-effectiveness, all of which are essential for diaphragm neurostimulation to be widely accepted in clinical practice.

Abstract INTRODUCTION: Mechanical ventilation (MV) is associated with a greater risk of acute kidney injury (VIKI). Neutrophil gelatinase-associated lipocalin (NAGL) is one of the most studied markers of kidney injury. Lung-protective ventilation with low tidal volumes and high positive end-expiratory pressure have been shown to mitigate kidney injury during MV. However, it is challenging to identify the optimal ventilatory settings to mitigate VIKI. Phrenic nerve stimulation resulted in lung-protective ventilation with better ventilation distribution compared to standard MV. This study investigated whether applying phrenic nerve stimulation to pigs with induced acute respiratory distress syndrome (ARDS) would result in VIKI mitigation. METHODS: Eighteen deeply sedated, human-size pigs were ventilated using volume-control: 8 ml/kg, PEEP 5 cmH2O, with rate and FiO2 set to achieve normal arterial blood gases. Injured-lung series: ARDS was induced using oleic acid via the pulmonary artery until PaO2/FiO2 was lower than 200 mmHg. Pigs were then ventilated for 12 hours post-injury. The study had three groups, two groups receiving temporary transvascular diaphragm neurostimulation (TTDN) synchronized to inspiration, one group on every breath (MV+TTDN100%) and the second on every second breath (MV+TTDN50%), targeting a reduction in ventilator pressure-time product of 15-20% and a third group on volume-control MV only (Control group). At the study end, kidney biopsies were assessed for IL-1a, IL-1ra, IL-1b, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-18, TNFa, NAGL, and VEGFa. Cytokine concentrations were measured in homogenized tissue using porcine-specific ELISA discovery assays via an external, blinded laboratory and normalized by weight. Statistical analysis used a non-parametric ranked test (Kruskal Wallis test). P-values &amp;lt;0.05 were considered statistically significant. RESULTS: Animals that received respectively TTDN 100% and 50% showed statistically significant lower kidney concentrations normalized by weight in percentage of NAGL than control, 18 vs 17 vs 29, p=0.012) and TNFa (26 vs 10 vs 52, p&amp;lt;0.0001) (Figure). The TTDN 100% group also showed greater IL-10 tissue concentrations normalized by weight in percentage compared to the other groups, 42 vs 9 vs 12, p=0.03. There was no statistically significant difference for the other tissue cytokines concentrations analyzed. CONCLUSIONS: In deeply sedated MV moderate ARDS pigs, diaphragm neurostimulation reduced tissue concentration of a biomarker for kidney injury, NAGL, and TNFa kidney concentration along with increased IL-10 tissue concentration, an anti-inflammatory cytokine, compared to the control group. These results are promising and grant further investigation in the clinical scenario for kidney protection due to diaphragm neurostimulation.

IntroductionNeuroendocrine neoplasm (NENs) make up approximately 2–3 % of gallbladder malignancies, while only 0.5 % of all NENs develop in the gallbladder. Most Gallbladder neuroendocrine neoplasms (GB-NENs) are discovered incidentally during pathological examinations post-cholecystectomy. Case presentation70-year-old male presents with an incidentally discovered 2.2 cm enhancing intraluminal soft tissue mass on abdominal CT scan. The mass demonstrates restricted diffusion on MR imaging, concerning for gallbladder malignancy. Radical cholecystectomy, confirms primary gallbladder neuroendocrine tumor (GB-NET). No adjuvant therapy was recommended at multidisciplinary cancer conference review. The patient is currently disease free at 18 months follow up. DiscussionThe management of GB-NEN remains challenging, due to the lack of specific clinical manifestations and typical imaging features preoperatively. GB-NENs are usually asymptomatic, and the paucity of reported imaging characteristics makes prospective diagnosis of GB-NENs challenging. GB-NEN tend to be larger in size, demonstrating well defined, intact mucosa, with a thick rim of hyperintensity on diffusion weighted images (DWI). Distinguishing between gallbladder neuroendocrine carcinoma (GB-NEC) and gallbladder neuroendocrine tumor (GB-NET) on pathologic evaluation is essential in developing a treatment plan. GB-NETs have superior survival compared to GB-NECs. GB-NETs can be managed utilizing a cholecystectomy with portal lymphadenectomy +/− segment 4b/5 liver resection. ConclusionGB-NETs may achieve curative resection, if identified at an early disease stage.