Rate of prophylactic anti-Xa achievement and impact on venous thromboembolism following oncologic hepato-pancreatico-biliary surgery: A prospective cohort study.

BACKGROUND: Hepato-pancreatico-biliary (HPB) patients experience competing risk of venous thromboembolism (VTE) and bleeding. We sought to evaluate the effect of anti-Xa levels on VTE and bleeding, and to characterize factors associated with subprophylaxis. METHODS: This prospective cohort study evaluated adult HPB surgical patients; cohorts were described by anti-Xa levels as subprophylactic (<0.2 IU/mL), prophylactic (0.2-0.5 IU/mL), and supraprophylactic (>0.5 IU/mL). Primary outcome evaluated bleeding and VTE complications. Secondary outcomes evaluated factors associated with subprophylaxis. RESULTS: We included 157 patients: 68 (43.6%) attained prophylactic anti-Xa and 89 (56.7%) were subprophylactic. Subprophylactic patients experienced more VTE compared to prophylactic patients (6.9% vs 0%; p = 0.028) without differences in bleeding complications (14.6% vs 5.9%; p = 0.081). Factors associated with subprophylactic anti-Xa included female sex (OR 2.90, p = 0.008), and Caprini score (OR 1.30, p = 0.035). Enoxaparin was protective against subprophylaxis compared to tinzaparin (OR 0.43, p = 0.029). CONCLUSIONS: Many HPB patients have subprophylactic anti-Xa levels, placing them at risk of VTE. Enoxaparin may be preferential, however, studies evaluating optimized prophylaxis are needed.

Relationship between anti-Xa level achieved with prophylactic low-molecular weight heparin and venous thromboembolism in trauma patients: A systematic review and meta-analysis.

BACKGROUND: Trauma patients have simultaneously high venous thromboembolism (VTE) and bleeding risk. Optimal chemoprophylaxis regimens remain unclear. This study aims to answer three questions for trauma patients. Is there any association between anti-Xa and VTE? Does dose adjustment improve prophylactic anti-Xa rates? Does dose adjustment improve anti-Xa adequacy and VTE compared with standard dosing? METHODS: Systematic search of MEDLINE, Embase, Scopus, and Web of Science occurred in May 2021. Two author reviews included trauma studies that evaluated low molecular weight heparin chemoprophylaxis, reported anti-Xa level, and evaluated more than one outcome. Data were dually extracted and estimated effects were calculated using RevMan 5.4 applying the Mantel-Haenszel method. Analysis 1 compared patients with peak anti-Xa of 0.2 IU/mL or greater or trough 0.1 IU/mL or greater to those with lower anti-Xa using VTE as the primary outcome. Analysis 2 reported the effect of dose adjustment on anti-Xa. Analysis 3 compared standard dosing to dose adjustment with the primary outcome being anti-Xa adequacy; secondary outcomes were VTE, pulmonary embolism, and bleeding complications. RESULTS: There were 3,401 studies evaluated with 24 being included (19 retrospective studies, 5 prospective studies). In analysis 1, achieving adequate anti-Xa was associated with reduced odds of VTE (4.0% to 3.1%; odds ratio [OR], 0.52; p = 0.03). Analysis 2 demonstrated that 768 (75.3%) patients achieved prophylactic anti-Xa with adjustment protocols. Analysis 3 suggested that dose-adjusted chemoprophylaxis achieves prophylactic anti-Xa more frequently (OR, 4.05; p = 0.007) but without VTE (OR, 0.72; p = 0.15) or pulmonary embolism (OR, 0.48; p = 0.10) differences. In subgroup analysis, anti-Xa dose adjustment also suggested no VTE reduction (OR, 0.68; p = 0.08). CONCLUSION: Patients with higher anti-Xa levels are less likely to experience VTE, and anti-Xa guided chemoprophylaxis increases anti-Xa adequacy. However, dose adjustment, including anti-Xa guided dosing, may not reduce VTE. LEVEL OF EVIDENCE: Systematic Review Meta-Analysis, Level IV.

Undertriage Despite Use of Geriatric-Specific Trauma Team Activation Guidelines : Who Are We Missing?

BACKGROUND: Elderly trauma patients are at risk for undertriage, resulting in substantial morbidity and mortality. The objective of this study was to determine whether implementation of geriatric-specific trauma team activation (TTA) protocols appropriately identified severely-injured elderly patients. METHODS: This single-center retrospective study evaluated all severely injured (injury severity score [ISS] >15), geriatric (≥65 years) patients admitted to our Level 1 tertiary-care hospital between January 2014 and September 2017. Undertriage was defined as the lack of TTA despite presence of severe injuries. The primary outcome was all-cause in-hospital mortality; secondary outcomes were mortality within 48 hours of admission and urgent hemorrhage control. A multivariable logistic regression analysis was performed to identify predictors of appropriate triage in this study. RESULTS: Out of 1039 severely injured geriatric patients, 628 (61%) did not undergo TTA. Undertriaged patients were significantly older and had more comorbidities. In-hospital mortality was 5% and 31% in the undertriaged and appropriately triaged groups, respectively (P < .0001). One percent of undertriaged patients needed urgent hemorrhage control, compared to 6% of the appropriately triaged group (P < .0001). One percent of undertriaged patients died within 48 hours compared to 19% in the appropriately triaged group (P < .0001). Predictors of appropriate triage include GCS, heart rate, systolic blood pressure, lactic acid, ISS, shock, and absence of dementia, stroke, or alcoholism. DISCUSSION: Geriatric-specific TTA guidelines continue to undertriage elderly trauma patients when using ISS as a metric to measure undertriage. However, undertriaged patients have much lower morbidity and mortality, suggesting the geriatric-specific TTA guidelines identify those patients at highest risk for poor outcomes.

Evaluation of trauma resources in rural northern Alberta identifies opportunities for improvement.

Background: The care of rural trauma patients in northern Alberta can be extremely challenging because of the vast geographic area, the limited access to health care facilities and the lack of adequate resources to manage severe injuries. Identifying gaps in equipment and personnel in rural centres can provide opportunities for improving the care of injured patients in these environments. We conducted a survey based on Canadian Accreditation Council quality indicators to evaluate trauma infrastructure and human resources in rural centres across northern Alberta. Methods: A standardized survey was developed to assess the availability of trauma-specific equipment and personnel across the prehospital and emergency department (ED) settings. The survey was distributed to 50 peripheral hospitals biannually from January 2017 to September 2018. Two-tailed paired t tests were used to evaluate changes in survey responses; a p value of less than 0.05 was considered statistically significant. Results: The survey response rate was 100%. By the end of the study period, there were significant improvements in the number of providers (p = 0.04), nurses (p = 0.01) and dedicated trauma resuscitation bays (p = 0.04) in the ED for managing injured patients. There were also significant increases in the availability of equipment, including advanced airway management tools (p = 0.02), rapid infusion devices (p = 0.02) and warmers (p = 0.04). Access to x-ray equipment (p = 0.03) and computed tomography (CT) scanners (p = 0.04) as well as equipment to support telehealth and teleconferencing (p = 0.04) increased during the study period. Access to, and supply of, blood products also increased significantly (p = 0.02) during the study period. Conclusion: Our study demonstrates that the trauma resources of rural health care centres may be evaluated in a standardized fashion centres, and the results point to opportunities to remedy gaps in equipment and personnel. Our methods may be applied to any trauma network that serves geographically large areas with a sparse distribution of health care facilities, to provide critical information for the optimization of resources in rural trauma.

Contexte: Les soins aux patients victimes de traumatismes en région rurale dans le nord de l'Alberta peuvent être très difficiles en raison de la superficie de la région, de l'accès limité aux établissements de santé et du manque de ressources pour soigner adéquatement les blessures graves. En repérant les lacunes en équipement et en personnel dans les établissements en région rurale, on peut créer des occasions d'améliorer les soins aux patients blessés dans ces milieux. Nous avons mené un sondage fondé sur les indicateurs de qualité du Conseil d'accréditation canadien pour évaluer les infrastructures et les ressources humaines en traumatologie dans les établissements des régions rurales du nord de l'Alberta. Méthodes: Un sondage standardisé a été créé pour évaluer la disponibilité des équipements et des ressources humaines en traumatologie en contexte préhospitalier et aux services d'urgence. Le sondage a été distribué 2 fois par année à 50 hôpitaux entre janvier 2017 et septembre 2018. Des tests t appariés ayant une hypothèse non nulle ont été utilisés pour évaluer les changements dans les réponses au sondage; les résultats ayant une valeur p < 0,05 étaient considérés comme statistiquement significatifs. Résultats: Le taux de participation au sondage était de 100 %. À la fin de la période étudiée, il y avait une amélioration significative du nombre de fournisseurs (p = 0,04), de personnel infirmier (p = 0,01) et d'espaces de réanimation réservés à la traumatologie (p = 0,04) dans les services d'urgence. Il y avait aussi une augmentation significative de la disponibilité de l'équipement, notamment des outils de prise en charge avancée des voies respiratoires (p = 0,02), des appareils de perfusion rapide (p = 0,02) et d'armoires chauffantes (p = 0,04). Les équipements de radiographie (p = 0,03) et de tomographie par ordinateur (p = 0,04) ainsi que les équipements facilitant la télémédecine et les téléconférences (p = 0,04) sont devenus plus accessibles pendant la période étudiée. Les réserves de produits sanguins et l'accès à ces produits a aussi augmenté de manière significative (p = 0,02). Conclusion: Notre étude montre que les ressources en traumatologie dans les établissements de santé en région rurale peuvent être évaluées de manière standardisée, et les résultats indiquent qu'il y a des occasions de combler les lacunes en équipement et en personnel. Notres méthodes peuvent être reproduites dans tout réseau de traumatologie couvrant un grand territoire où les établissements de santé sont dispersés, pour fournir des données critiques sur l'organisation des ressources de traumatologie en région rurale.

CD1d- and MR1-Restricted T Cells in Sepsis.

Dysregulated immune responses to infection, such as those encountered in sepsis, can be catastrophic. Sepsis is typically triggered by an overwhelming systemic response to an infectious agent(s) and is associated with high morbidity and mortality even under optimal critical care. Recent studies have implicated unconventional, innate-like T lymphocytes, including CD1d- and MR1-restricted T cells as effectors and/or regulators of inflammatory responses during sepsis. These cell types are typified by invariant natural killer T (iNKT) cells, variant NKT (vNKT) cells, and mucosa-associated invariant T (MAIT) cells. iNKT and vNKT cells are CD1d-restricted, lipid-reactive cells with remarkable immunoregulatory properties. MAIT cells participate in antimicrobial defense, and are restricted by major histocompatibility complex-related protein 1 (MR1), which displays microbe-derived vitamin B metabolites. Importantly, NKT and MAIT cells are rapid and potent producers of immunomodulatory cytokines. Therefore, they may be considered attractive targets during the early hyperinflammatory phase of sepsis when immediate interventions are urgently needed, and also in later phases when adjuvant immunotherapies could potentially reverse the dangerous state of immunosuppression. We will highlight recent findings that point to the significance or the therapeutic potentials of NKT and MAIT cells in sepsis and will also discuss what lies ahead in research in this area.

Recalcitrant prosthetic valve endocarditis requiring repeated reconstruction: running out of options.

In this report we describe a previously healthy 36-year-old man who presented with septic shock secondary to bacterial endocarditis with multiple cerebral, mesenteric, and peripheral embolic phenomena. He underwent emergent porcine prosthetic valve replacement with aortic annular reconstruction. Subsequently, he developed recalcitrant Candida parapsilosis endocarditis requiring treatment with multiple antifungal agents and 4 repeated complex reconstructions of the aortic root and fibrous trigones over 3 years, before the infection was successfully controlled. This case underscores the significant morbidity associated with fungal endocarditis and importance of an early combined medical and surgical approach.

A robust scoring system to evaluate sepsis severity in an animal model.

BACKGROUND: The lack of a reliable scoring system that predicts the development of septic shock and death precludes comparison of disease and/or treatment outcomes in animal models of sepsis. We developed a murine sepsis score (MSS) that evaluates seven clinical variables, and sought to assess its validity and reliability in an experimental mouse model of polymicrobial sepsis. METHODS: Stool collected from the cecum of C57BL/6 (B6) mice was dissolved in 0.9% normal saline (NS) and filtered, resulting in a fecal solution (FS) which was injected intraperitoneally into B6 mice. Disease severity was monitored by MSS during the experimental timeline. Blood and tissue samples were harvested for the evaluation of inflammatory changes after sepsis induction. The correlation between pro-inflammatory markers and MSS was assessed by the Spearman rank correlation coefficient. RESULTS: Mice injected with FS at a concentration of 90 mg/mL developed polymicrobial sepsis with a 75% mortality rate at 24 hours. The MSS was highly predictive of sepsis progression and mortality, with excellent discriminatory power, high internal consistency (Cronbach alpha coefficient = 0.92), and excellent inter-rater reliability (intra-class coefficient = 0.96). An MSS of 3 had a specificity of 100% for predicting onset of septic shock and death within 24 hours. Hepatic dysfunction and systemic pro-inflammatory responses were confirmed by biochemical and cytokine analyses where the latter correlated well with the MSS. Significant bacterial dissemination was noted in multiple organs. Furthermore, the liver, spleen, and intestine demonstrated histopathological evidence of injury. CONCLUSIONS: The MSS reliably predicts disease progression and mortality in an animal model of polymicrobial sepsis. More importantly, it may be used to assess and compare outcomes among various experimental models of sepsis, and serve as an ethically acceptable alternative to death as an endpoint.

Familial syndromes associated with intracranial tumours: a review.

BACKGROUND: Most cancers of the central nervous system (CNS) occur sporadically in the absence of any known underlying familial disorder or multi-systemic syndrome. Several syndromes are associated with CNS malignancies, however, and their recognition has significant implications for patient management and prognosis. Patients with syndrome-associated CNS malignancies often have multiple tumours (either confined to one region or distributed throughout the body), with similar or different histology. OBJECTIVE: This review examines syndromes that are strongly associated with CNS cancers: the phakomatosis syndromes, familial syndromes such as Li-Fraumeni and familial polyposis syndromes and dyschondroplasia.

Analgesia in the management of paediatric and adolescent trauma during the resuscitative phase: the role of the pediatric trauma centre.

BACKGROUND: The objective of this study was to evaluate the use of analgesia in the resuscitative phase of severely injured children and adolescents. METHODS: A retrospective cohort of paediatric (age<18 years), severely injured (ISS≥12) patients were identified from the London Health Sciences Centre's Trauma Registry from 2007 to 2010. Variables were compared between Analgesia and Non-analgesia groups with Pearson Chi-square and Mann-Whitney U tests. Resuscitative analgesia use was assessed through multivariable logistic regression controlling for age, gender, mechanism, arrival and Trauma Team Activation (TTA). RESULTS: Analgesia was used in 32% of cases. Univariate analysis did not reveal any differences in gender, age, injury type, injury profile and arrival patterns. Significant differences were found with analgesia used more frequently in patients injured in a motor vehicle collision (58% vs. 42%, p=0.026) and having parents in the resuscitation room (17% vs. 6%, p=0.01). Analgesia patients were more injured (median ISS 22 vs. 17, p=0.027) and had 2.25 times more TTA (39% vs. 17%). Logistic regression revealed patients arriving directly to a trauma centre had a higher incidence of receiving analgesia (OR 2.01, 95% CI: 1.03-3.93), as did TTA (OR 2.18, 95% CI: 1.01-4.73) and having parents in resuscitation room (3.56, 95% CI: 1.23-10.33). Narcotics were most commonly used (85%), followed by benzodiazepines (16%), with 66% given during the primary survey. CONCLUSION: Use of analgesia is important in the acute management of paediatric trauma. Direct presentation to a level I trauma centre, TTA and the presence of parents lead to higher appropriate use of analgesia in paediatric trauma resuscitation.

Fournier's gangrene of the penis caused by Streptococcus dysgalactiae subspecies equisimilis: case report and incidence study in a tertiary-care hospital.

BACKGROUND: Fournier's gangrene is a rare necrotizing soft tissue infection of the scrotum and penis. We report, to our knowledge, the first case of Fournier's gangrene caused by Streptococcus dysgalactiae subsp. equisimilis (SDSE), a strain of pyogenic ß-hemolytic streptococci that is increasingly being recognized as an important human pathogen. CASE PRESENTATION: We describe a healthy 59 year-old Caucasian male who presented to the emergency department with Fournier's gangrene of the penis and scrotum, with extension to the anterior abdominal wall. He underwent urgent surgical debridement of his scrotum, penis, and anterior abdomen. Swabs from the scrotum grew Gram-positive cocci, which were initially identified as Streptococcus anginosus group by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). However, polymerase chain reaction (PCR) amplification and sequencing of the 16S rRNA gene identified the isolate as Streptococcus dysgalatiae subspecies equisimilis (SDSE). The incidences of invasive S. anginosus group and SDSE infections at the London Health Sciences Centre, a tertiary-care institution in southwestern Ontario, were determined between August 1, 2011 and August 31, 2012, revealing a slightly lower rate of SDSE (3.2 cases per 100,000 population) than other studies. CONCLUSIONS: This case highlights a unique disease manifestation of the emerging human pathogen Streptococcus dysgalatiae subspecies equisimilis that has not been previously reported. This case also underscores the limitations of MALDI-TOF MS in differentiating between closely-related streptococcal species which may have different pathogenic profiles.