Calcineurin Inhibition in Deceased Organ Donors: A Systematic Review and Meta-analysis of Preclinical Studies.

Background: Preconditioning deceased organ donors with calcineurin inhibitors (CNIs) may reduce ischemia-reperfusion injury to improve transplant outcomes. Methods: We searched MEDLINE, EMBASE, Cochrane Library, and conference proceedings for animal models of organ donation and transplantation, comparing donor treatment with CNIs with either placebo or no intervention, and evaluating outcomes for organ transplantation. Reviewers independently screened and selected studies, abstracted data, and assessed the risk of bias and clinical relevance of included studies. Where possible, we pooled results using meta-analysis; otherwise, we summarized findings descriptively. Results: Eighteen studies used various animals and a range of CNI agents and doses and evaluated their effects on a variety of transplant outcomes. The risk of bias and clinical applicability were poorly reported. Pooled analyses suggested benefit of CNI treatment on early graft function in renal transplants (3 studies; serum creatinine: ratio of means [RoM] 0.54; 95% confidence interval [CI], 0.34-0.86) but not for liver transplants (2 studies; serum alanine transaminase: RoM 0.61; 95% CI, 0.30-1.26; and serum aspartate aminotransferase: RoM 0.58; 95% CI, 0.26-1.31). We found no reduction in graft loss at 7 d (2 studies; risk ratio 0.54; 95% CI, 0.08-3.42). CNI treatment was associated with reduced transplant recipient levels of interleukin-6 (4 studies; RoM 0.36; 95% CI, 0.19-0.70), tumor necrosis factor-alpha (5 studies; RoM 0.36; 95% CI, 0.12-1.03), and cellular apoptosis (4 studies; RoM 0.30; 95% CI, 0.19-0.47). Conclusions: Although this compendium of animal experiments suggests that donor preconditioning with CNIs may improve early kidney graft function, the limited ability to reproduce a true clinical environment in animal experiments and to assess for risk of bias in these experiments is a serious weakness that precludes current clinical application.

The reticular activating system: a narrative review of discovery, evolving understanding, and relevance to current formulations of brain death.

A series of landmark experiments conducted throughout the 20th century progressively localized the regions involved in consciousness to the reticular activating system (RAS) and its ascending projections. The first description of the RAS emerged in 1949 through seminal experiments performed by Moruzzi and Magoun in feline brainstems; additional experiments in the 1950s revealed connections between the RAS and the thalamus and neocortical structures. This knowledge has allowed for the explanation of disorders of consciousness with exquisite anatomic precision. The clinical relevance of the RAS is further apparent in modern definitions of brain death/death by neurologic criteria (BD/DNC), which require demonstration of the complete and permanent loss of capacity for consciousness as one of their core criteria. BD/DNC is currently understood across jurisdictions in terms of "whole brain" and "brainstem" formulations. Although their clinical examination between formulations is indistinguishable, policies for BD/DNC declaration may differ in the rare scenario of patients with isolated infratentorial brain injuries, in which ancillary testing is advised in the whole brain formulation but not the brainstem formulation. Canadian guidelines acknowledge that the distinction between whole brain and brainstem formulations is unclear with respect to clinical implications for patients with isolated infratentorial injuries. This has led to variability in Canadian clinicians' use of ancillary testing when the mechanism of BD/DNC is suspected to be an isolated infratentorial injury. The present narrative review highlights these concepts and explores implications for determination of BD/DNC in Canada, with specific emphasis on the RAS and its relevance to both formulations.

RéSUMé: Une série d'expériences marquantes menées tout au long du 20e siècle a progressivement permis de localiser les régions impliquées dans la conscience dans le système d'activation réticulaire (SAR) et ses projections ascendantes. La première description du SAR a vu le jour en 1949 grâce à des expériences fondatrices réalisées par Moruzzi et Magoun dans des troncs cérébraux félins; d'autres expériences menées au cours des années 1950 ont révélé des liens entre le SAR et le thalamus et les structures néocorticales. Ces connaissances ont permis d'expliquer les troubles de la conscience avec une précision anatomique extraordinaire. La pertinence clinique du SAR est encore plus évidente dans les définitions modernes de la mort cérébrale / du décès déterminé par des critères neurologiques (MC/DCN), qui exigent la démonstration de la perte complète et permanente de la capacité de conscience comme l'un de ses critères de base. La mort cérébrale est actuellement comprise partout en termes de formulations de « cerveau entier ¼ et de « tronc cérébral ¼. Bien que l'examen clinique ne fasse pas de distinction entre ces formulations, les politiques de déclaration de MC/DCN peuvent différer dans le rare cas de patients présentant des lésions cérébrales infratentorielles isolées, pour lesquels des examens auxiliaires sont conseillés lorsqu'on parle de cerveau entier mais pas lorsqu'on utilise la formulation de tronc cérébral. Les lignes directrices canadiennes reconnaissent que la distinction entre les termes de cerveau entier et de tronc cérébral n'est pas claire en ce qui concerne leurs implications cliniques pour les patients présentant des lésions infratentorielles isolées. Cela a entraîné une variabilité dans l'utilisation des examens auxiliaires par les cliniciens canadiens lorsqu'ils soupçonnent que le mécanisme de MC/DCN consiste en une lésion infratentorielle isolée. Ce compte rendu narratif met en lumière ces concepts et explore les implications pour la détermination de la MC/DCN au Canada, en mettant une emphase spécifique sur le SAR et sa pertinence pour les deux formulations.

Recommendations for the Management of Incidental Musculoskeletal Findings on MRI and CT.

The Canadian Association of Radiologists (CAR) Incidental Findings Working Group consists of both academic subspeciality and general radiologists tasked with either adapting American College of Radiology (ACR) guidelines to meet the needs of Canadian radiologists or authoring new guidelines where appropriate. In this case, entirely new guidelines to deal with incidental musculoskeletal findings that may be encountered on thoracoabdominal computed tomography or magnetic resonance imaging were drafted, focussing on which findings should prompt recommendations for further workup. These recommendations discuss how to deal with incidental marrow changes, focal bone lesions, abnormalities of the pubic symphysis and sacroiliac joints, fatty soft tissue masses, manifestations of renal osteodystrophy and finally discuss opportunistic osteoporosis evaluation.

The frailty, outcomes, recovery and care steps of critically ill patients (FORECAST) study: pilot study results.

INTRODUCTION: Frailty is common in critically ill patients and is associated with increased morbidity and mortality. There remains uncertainty as to the optimal method/timing of frailty assessment and the impact of care processes and adverse events on outcomes is unknown. We conducted a pilot study to inform on the conduct, design and feasibility of a multicenter study measuring frailty longitudinally during critical illness, care processes, occurrence of adverse events, and resultant outcomes. METHODS: Single-center pilot study enrolling patients over the age of 55 admitted to an Intensive Care Unit (ICU) for life-support interventions including mechanical ventilation, vasopressor therapy and/or renal replacement therapy. Frailty was measured on ICU admission and hospital discharge with the Clinical Frailty Scale (CFS), the Frailty Index (FI) and CFS at 6-month follow-up. Frailty was defined as CFS ≥ 5 and a FI ≥ 0.20. Processes of care and adverse events were measured during their ICU and hospital stay including nutritional support, mobility, nosocomial infections and delirium. ICU, hospital and 6 months were determined. RESULTS: In 49 patients enrolled, the mean (SD) age was 68.7 ± 7.9 with a 6-month mortality of 29%. Enrollment was 1 patient/per week. Frailty was successfully measured at different time points during the patients stay/follow-up and varied by method/timing of assessment; by CFS and FI, respectively, in 17/49 (36%), 23/49 (47%) on admission, 22/33 (67%), 21/33 (63%) on hospital discharge and 11/30 (37%) had a CFS ≥ 5 at 6 months. Processes of care and adverse events were readily captured during the ICU and ward stay with the exception of ward nutritional data. ICU, hospital outcomes and follow-up outcomes were worse in those who were frail irrespective of ascertainment method. Pre-existing frailty remained static in survivors, but progressed in non-frail survivors. DISCUSSION: In this pilot study, we demonstrate that frailty measurement in critically ill patients over the course and recovery of their illness is feasible, that processes of care and adverse events are readily captured, have developed the tools and obtained data necessary for the planning and conduct of a large multicenter trial studying the interaction between frailty and critical illness.

Poor Sensitivity of Magnetic Resonance Arthrography to Detect Hip Chondral Delamination: A Retrospective Follow-Up of 227 FAI-Operated Patients.

OBJECTIVE: The purpose of this study was to retrospectively assess the frequency and characteristics of acetabular cartilage delamination (CD) in femoroacetabular impingement (FAI) patients and to assess the sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of magnetic resonance arthrography (MRA) in detecting CD based on the radiologist report. DESIGN: This is a single-center retrospective review of consecutive patients operated for symptomatic FAI. All of the patients had a 1.5-T MR-arthrogram within 12 months preoperatively. MRA reports of these patients were compared with operation notes and surgical videos of all patients by two trained assessors. RESULTS: At surgery, CD of the acetabulum was present in 169 patients out of a total of 229 patients (74%). Only 6.5% (11 patients) of CD was described on the MRA reports preoperatively. The mean age of the patients was 37.6 ± 13.3 years. The average extent of delamination was 3.12 ± 1.5 cm2 with a mean coronal × sagittal extent of 0.68 × 4.33 cm. There was a significant difference regarding age (P = 0.002), alpha angle from frog view (P = 0.002), and alpha angle from anteroposterior view (P = 0.012) between the patients with delamination and without delamination. The majority of labral tears and cartilage damage were located in the anterosuperior quadrant. MRA sensitivity was 6%, specificity 98%, NPV 27%, and PPV 91% based on the radiologist report. CONCLUSION: The CD in patients with FAI can be severely underdiagnosed with MRA. There is a need for better standard diagnostic criteria to detect CD in patients with FAI.

Preliminary Experience With SPECT/CT to Evaluate Periarticular Arthritis Progression and the Relationship With Clinical Outcome Following Ankle Arthrodesis.

BACKGROUND: Single photon emission computed tomography combined with computed tomography (SPECT/CT) could potentially aid in diagnosing periarticular arthritis/activity and progression, facilitate effective treatment options, and evaluate the effect surgery has on the clinical outcome of patients with ankle arthritis. The goal of our study was to assess SPECT/CT activity in the ankle and periarticular joints before and after ankle fusion surgery and determine whether it was associated with clinical pain and function scores. METHODS: Thirty-four patients recruited into this study underwent either arthroscopic or open ankle fusion. X-ray (XR) and SPECT/CT imaging was obtained as well as completion of patient Ankle Osteoarthritis Scale (AOS) and 36-item Short Form Survey (SF-36) questionnaires preoperatively and at 6 months postoperatively. Ankle, subtalar, and talonavicular joint arthritis grading on XR and CT, along with SPECT/CT activity, was evaluated by 2 nuclear medicine radiologists. Data were assessed for normality and analyzed with the appropriate comparative test. P value was set at <.05. Thirty patients (31 ankles) completed follow-up and were analyzed. RESULTS: SPECT/CT activity showed no significant difference in the ankle joint at 6 months postoperatively while periarticular joint activity significantly increased (P < .05). Six months postoperatively, patients had significant improvements in their AOS and SF-36 scores (P < .05). SPECT/CT grading of all joints analyzed, however, was not associated with AOS or SF-36 scores preoperatively or at 6 months postoperatively. CONCLUSION: In this study, intensity of activity as evaluated by SPECT/CT in periarticular hindfoot joints in patients who had ankle arthrodesis was not associated with clinical/functional scores at 6 months postoperatively. LEVEL OF EVIDENCE: Level IV, diagnostic study.

Radiographic Analysis of Glenoid Size and Shape After Arthroscopic Coracoid Autograft Versus Distal Tibial Allograft in the Treatment of Anterior Shoulder Instability.

BACKGROUND: The Latarjet procedure for autograft transposition of the coracoid to the anterior rim of the glenoid remains the most common procedure for reconstruction of the glenoid after shoulder instability. The anatomic glenoid reconstruction using distal tibial allograft has gained popularity and is suggested to better match the normal glenoid size and shape. However, concerns about decreased healing and increased resorption arise when an allograft bone is used. PURPOSE: To use radiological findings to evaluate the arthroscopic reconstruction of the glenoid with respect to the size, shape, healing, and resorption of coracoid autograft versus distal tibial allograft. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A retrospective review was performed of 48 consecutive patients who had an arthroscopic bony reconstruction of the glenoid (12 coracoid autograft, 36 distal tibial allograft), diagnosed anterior shoulder instability, and computed tomography (CT)-confirmed glenoid bone loss more than 20%. Coracoid autograft was performed only when tibial allograft was not accessible from a bone bank. Two fellowship-trained musculoskeletal radiologists reviewed pre- and postoperative CT scans at a minimum follow-up of 6 months for the following: graft position, glenoid concavity, cross-sectional area, width, version, total area, osseous union, and graft resorption. Clinical outcome was noted in terms of instability, subluxation, and dislocation at a minimum follow-up of 2 years. Simple logistic regression, 2-tailed independent-sample t tests, paired t tests, and Fisher exact tests were performed. RESULTS: Graft union was seen in 9 of the 12 patients (75%) who had coracoid autograft and 34 of the 36 patients (94%) who had tibial allograft (odds ratio, 5.66; 95% CI, 0.81-39.20; P = .08). The odds ratio comparing allograft to coracoid for overall resorption was 7.00 (95% CI, 1.65-29.66; P = .008). Graft resorption ≥50% was seen in 3 (8%) of the patients who had tibial allograft and none of the patients who had coracoid autograft. Graft resorption less than 50% was seen in the majority of patients in both groups: 27 (73%) patients with tibial allograft and 5 (42%) patients with coracoid autograft. No statistically significant difference was found between the 2 procedures regarding anteroposterior diameter of graft ( P = .81) or graft cross-sectional area ( P = .93). However, a significant difference was observed in step formation between the 2 procedures ( P < .001). Two patients experienced subluxations in the coracoid group (16%) as well as 2 patients in the tibial allograft group (6%) with a P value of .25. CONCLUSION: Arthroscopic anatomic glenoid reconstruction via distal tibial allograft showed similar bony union but higher resorption compared with coracoid autograft. Even so, no statistically significant difference was found between the 2 procedures regarding final graft surface area, the size of grafts, and the anteroposterior dimensions of the reconstructed glenoids. These short-term results suggest that distal tibial allografts can be used as an alternative to coracoid autograft in the recreation of glenoid bony morphologic features.

Canada-DONATE study protocol: a prospective national observational study of the medical management of deceased organ donors.

INTRODUCTION: Research on the management of deceased organ donors aims to improve the number and quality of transplants and recipient outcomes. In Canada, this research is challenged by regionalisation of donation services within provinces and the geographical, clinical and administrative separation of donation from transplantation services. This study aims to build a national platform for future clinical trials in donor management. Objectives are to engage collaborators at donation hospitals and organ donation organisations (ODOs) across Canada, describe current practices, evaluate the effectiveness of donation-specific interventions and assess the feasibility of future clinical trials. METHODS AND ANALYSIS: This ongoing prospective observational study of the medical management of deceased organ donors will enrol more than 650 consented potential donors from adult intensive care units at 33 hospital sites across Canada, each participating for 12 months. ODOs ensure enrolment of consecutive eligible participants. Research staff record detailed data about participants, therapies, organ assessments, death declaration procedures and adverse clinical exposures from the time of donation consent to organ recovery. ODOs provide reasons that organs are declined, dates and places of transplantation, and recipient age and sex.Descriptive analyses will summarise current practices. Effectiveness analyses will examine donation-specific interventions with respect to the number of transplants, using multilevel regression models to account for clustering by donor, hospitals and ODOs. Feasibility analyses will focus on acceptance of the research consent model; participation of academic and community hospitals as well as ODOs; and accessibility of recipient data. ETHICS AND DISSEMINATION: This study uses a waiver of research consent. Hospitals will receive reports on local practices benchmarked to (1) national practices and (2) national donor management guidelines. We will report findings to donation and transplant collaborators (ie, clinicians, researchers, ODOs) and publish in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03114436.

Proximal opening wedge osteotomy with wedge-plate fixation compared with proximal chevron osteotomy for the treatment of hallux valgus: a prospective, randomized study.

BACKGROUND: Hallux valgus with an increased intermetatarsal angle is usually treated with a proximal metatarsal osteotomy. The proximal chevron osteotomy is commonly used but is technically difficult. This study compares the proximal opening wedge osteotomy of the first metatarsal with the proximal chevron osteotomy for the treatment of hallux valgus with an increased intermetatarsal angle. METHODS: This prospective, randomized multicenter (three-center) study was based on the clinical outcome scores of the Short Form-36, the American Orthopaedic Foot & Ankle Society forefoot questionnaire, and the visual analog scale for pain, activity, and patient satisfaction. Subjects were assessed prior to surgery and at three, six, and twelve months postoperatively. Surgeon preference was evaluated based on questionnaires and the operative times required for each procedure. RESULTS: No significant differences were found for any of the patients' clinical outcome measurements between the two procedures. The proximal opening wedge osteotomy was found to lengthen, and the proximal chevron osteotomy was found to shorten, the first metatarsal. The intermetatarsal angles improved (decreased) significantly, from 14.8° ± 3.2° to 9.1° ± 2.9 (mean and standard deviation) after a proximal opening wedge osteotomy and from 14.6° ± 3.9° to 11.3° ± 4.0° after a proximal chevron osteotomy (p < 0.05 for both). Operative time required for performing a proximal opening wedge osteotomy is similar to that required for performing a proximal chevron osteotomy (mean and standard deviation, 67.1 ± 16.5 minutes compared with 69.9 ± 18.6 minutes; p = 0.510). CONCLUSIONS: Opening wedge and proximal chevron osteotomies have comparable radiographic outcomes and comparable clinical outcomes for pain, satisfaction, and function. The proximal opening wedge osteotomy lengthens, and the proximal chevron osteotomy shortens, the first metatarsal. The proximal opening wedge osteotomy was subjectively less technically demanding and was preferred by the orthopaedic surgeons in this study. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Cost-effectiveness of the two-compound formulation calcipotriol and betamethasone dipropionate compared with commonly used topical treatments in the management of moderately severe plaque psoriasis in Scotland.

OBJECTIVES: To determine the cost-effectiveness of calcipotriol/betamethasone dipropionate (Dovobet) in the initial treatment of moderate severity plaque psoriasis vulgaris in Scotland. RESEARCH DESIGN AND METHODS: An economic model was developed to simulate the costs and benefits of the most commonly used topicals in the management of plaque psoriasis. This was informed by an indirect unadjusted comparison of the effectiveness data to determine the relative efficacy of commonly used topicals. The model estimated their impact on costs and utility gain over a 1-year period. We accounted for direct medical costs from a health payer perspective. The cost-utility analysis included pharmacy costs and costs of failure of topicals in primary care in terms of secondary-care referrals for phototherapy. Extensive sensitivity analyses were undertaken to address areas of uncertainty in the parameters of the model. RESULTS: Patients treated with the two-compound formulation (TCF) of calcipotriol and betamethasone dipropionate (BDP) experienced better control of their psoriasis. In our model, this translated into reduced costs, as patients were less likely to be referred for phototherapy, and increased quality adjusted life years (QALYs) relative to other commonly used topicals. The TCF was estimated to generate annual savings ranging from 96 to 276 pounds per patient per year compared to the other commonly used alternative topicals. With reduced costs and superior outcomes, the TCF 'dominated' these other treatments since the latter were associated with higher cost and lower utility or QALY gain. The model findings were not influenced by changes to a range of model input parameters within plausible limits. CONCLUSIONS: Use of the TCF in patients with plaque psoriasis represents excellent value for money by delivering savings to the National Health Service (NHS) in Scotland. Similar findings are predicted for the management of psoriasis patients elsewhere in the UK.

Posterior tibialis tendon tears: comparison of the diagnostic efficacy of magnetic resonance imaging and ultrasonography for the detection of surgically created longitudinal tears in cadavers.

RATIONALE AND OBJECTIVES: The optimal advanced imaging method for detection and characterization of posterior tibialis tendon (PTT) tears is unclear. The purpose of this study was to investigate the utility of ultrasonography (US) and MR imaging in the detection of surgically created PTT tears in cadavers. MATERIALS AND METHODS: This was a prospective blinded study in which 16 fresh cadaveric foot and ankle specimens (3 men, 13 women; average age at death 83.9 years; age range 71-96 years) were scanned with both US and MR imaging before and after the surgical creation of 64 variable length longitudinal tears of the PTT. Ultrasonography was performed with a 12 MHz linear transducer with independent interpretations of static and dynamic studies separately by two blinded and experienced musculoskeletal radiologists. MR imaging was performed at 1.5 T with a standard transmit-receive extremity coil using axial, sagittal, coronal T1-weighted (TR 600, TE 20), and axial fast spin echo proton density and T2-weighted (TR 3000, TE 161/20, ETL 12) images. MR images were reviewed independently by two experienced musculoskeletal radiologists who were blinded to the status of the PTT. RESULTS: Sensitivity, specificity, and accuracy of MR imaging in the diagnosis of PTT tears were 73%, 69%, and 72%, respectively. Dynamic US interpretation yielded values of 69% sensitivity, 81% specificity, and 72% accuracy. Static US interpretation was less reliable than dynamic interpretation, and the only significance of static imaging was a high specificity (94%) for detection of longitudinal tears. The positive predictive value (PPV) for MR imaging and US was 88% and 92% respectively, and the negative predictive value (NPV) was 46% for both MR imaging and US. CONCLUSION: Our results suggest that US and MR imaging perform at the same level for the detection of surgically created longitudinal PTT tears in a cadaveric model. US has a higher specificity compared with MR imaging.