Ultrasound elastography of back muscle biomechanical properties: a systematic review and meta-analysis of current methods.

OBJECTIVES: To report the current elastography methods used to quantify back muscles' biomechanical characteristics in patients with musculoskeletal disorders (MSKd) and inform on their reliability, validity, and responsiveness. METHODS: MEDLINE, Embase, CINAHL, Cochrane library and grey literature were consulted. Predefined criteria allowed for study selection and data extraction. The quality of evidence was rated using the COSMIN tool. Data were meta-analyzed in terms of pooled intraclass correlation coefficient (pICC) for reliability and pooled standardized mean difference (pSMD) for validity and responsiveness. Heterogeneity was assessed. RESULTS: Seventy-nine studies were included in the meta-analysis (total number of participants N = 3178). Three elastography methods were identified: strain imaging (SI; number of cohorts M = 26), shear wave imaging (SWI; M = 50), and vibration sonoelastography (VSE; M = 3). Strain imaging and SWI studies reported good reliability measurement properties (pICC > 0.70) and a medium pSMD (0.58 for SI and 0.60 for SWI; p ≤ 0.020) in discriminating MSKd from controls' condition (validity). Strain imaging studies reported a medium pSMD (0.64; p = 0.005) in detecting within-group changes over time, whereas SWI pSMD was very high (1.24; p = 0.005). Only SWI reported significant but small pSMD (0.30; p = 0.003) in detecting between-group changes over time. The small number of VSE studies could not be meta-analyzed. Heterogeneity was high (I-squared > 90%; p < 0.001). CONCLUSIONS: Elastography presents good reliability results and a medium pSMD in discriminating MSKd from control conditions. Responsiveness data suggest detectable changes within groups over time using SI and SWI, calling for long-term longitudinal studies. Assessing changes between groups over time using elastography still needs to be proven. Highly significant heterogeneity limits meta-analytic results. CRITICAL RELEVANCE STATEMENT: While still in its early-stage exploration phase, musculoskeletal ultrasound elastography may reliably quantify back muscles' biomechanics in asymptomatic individuals, moderately discriminate back musculoskeletal disorders and detect biomechanical changes over time in these conditions, calling for long-term longitudinal studies. KEY POINTS: Ultrasound elastography is reviewed for back pain and related musculoskeletal disorder assessments. Growing literature supports good reproducibility, some validity and responsiveness. Back muscle elastography considers assumptions calling for standardized protocols.

Hypokalemia, hypomagnesemia, and hyponatremia are associated with acute kidney injury in patients treated with cisplatin.

INTRODUCTION: Cisplatin-associated acute kidney injury (C-AKI) is common. Predictive factors include age >60 years, hypertension, cisplatin dose, diabetes, and serum albumin < 3.5 g/L. The association between C-AKI and hypokalemia, hypomagnesemia or hyponatremia has not been well characterized. METHODS: Data from a previous retrospective observational study was obtained. Patients were separated into three groups with similar cisplatin doses and schedules. Group A received cisplatin 60-100 mg/m2 every three weeks with laboratory assessments before treatment, group B received cisplatin 60-75 mg/m2 every three weeks with laboratory assessments before days 1 and 8 and group C had weekly cisplatin 40 mg/m2 with weekly laboratories assessments. The association between hypomagnesemia, hypokalemia, hyponatremia, and risk of AKI was determined using a counting process specification of Cox's regression models. RESULTS: A total of 1301 patients were separated into groups A (n = 713), B (n = 204), and C (n = 384). The proportion of patients with at least one event of hypokalemia, hypomagnesemia, or hyponatremia was lower in group A (29.2%, 57.6%, 36.2%) compared to groups B (43.6%, 67.2%, 59.8%) and C (49.0%, 78.7%, 51.0%). The incidence of all grade C-AKI was 35.6% (group A), 46.6% (group B), and 18.2% (group C). In group A, the risk of AKI doubled with hyponatremia or hypomagnesemia and tripled with hypokalemia. This association was not seen with other groups. CONCLUSION: Among patients with the highest doses of cisplatin, the presence of one electrolyte disorder was associated with an increased risk of C-AKI. Other studies are needed to characterize the presence of an electrolyte disorder as a predictive risk factor of C-AKI in this subpopulation.

Effect of fecal immunochemical test cut-off levels on adenoma detection rate: a systematic review and meta-analysis.

BACKGROUND: Adenoma detection rate (ADR) is higher after a positive fecal immunochemical test (FIT) compared to direct screening colonoscopy. OBJECTIVE: This meta-analysis evaluated how ADR, the rates of advanced adenoma detection (AADR), colorectal cancer detection (CDR), and sessile serrated lesion detection (SSLDR) are affected by different FIT positivity thresholds. METHODS: We searched MEDLINE, EMBASE, CINAHL, and EBM Reviews databases for studies reporting ADR, AADR, CDR, and SSLDR according to different FIT cut-off values in asymptomatic average-risk individuals aged 50-74 years old. Data were stratified according to sex, age, time to colonoscopy, publication year, continent, and FIT kit type. Study quality, heterogeneity, and publication bias were assessed. RESULTS: Overall, 4280 articles were retrieved and fifty-eight studies were included (277,661 FIT-positive colonoscopies; mean cecal intubation 96.3%; mean age 60.8 years; male 52.1%). Mean ADR was 56.1% (95% CI 53.4 - 58.7%), while mean AADR, CDR, and SSLDR were 27.2% (95% CI 24.4 - 30.1%), 5.3% (95% CI 4.7 - 6.0%), and 3.0% (95% CI 1.7 - 4.6%), respectively. For each 20 µg Hb/g increase in FIT cut-off level, ADR increased by 1.54% (95% CI 0.52 - 2.56%, p < 0.01), AADR by 3.90% (95% CI 2.76 - 5.05%, p < 0.01) and CDR by 1.46% (95% CI 0.66 - 2.24%, p < 0.01). Many detection rates were greater amongst males and Europeans. CONCLUSIONS: ADRs in FIT-positive colonoscopies are influenced by the adopted FIT positivity threshold, and identified targets, importantly, proved to be higher than most current societal recommendations.

The use and abuse of survival analysis and Kaplan-Meier curves in surgical trials.

BACKGROUND: Survival analysis based on Cox regression and Kaplan-Meier curves, initially devised for oncology trials, have frequently been used in other contexts where fundamental statistical assumptions (such as a constant hazard ratio) are not satisfied. This is almost always the case in trials that compare surgery with medical management. METHODS: We review a trial that compared extracranial-intracranial bypass surgery (EC-IC bypass) with medical management (MM) of patients with symptomatic occlusion of the carotid or middle cerebral artery, where it was claimed that surgery was of no benefit. We discuss a hypothetical study and review other neurovascular trials which have also used survival analysis to compare results. RESULTS: The trial comparing EC-IC bypass and MM did not satisfy the fundamental proportional hazard assumption necessary for valid analyses. This was also the case for two prior EC-IC bypass trials, as well as for other landmark neurovascular studies, such as the trials comparing endarterectomy with MM for carotid stenoses, or for the trial that compared intervention and MM for unruptured brain arteriovenous malformations. While minor deviations may have little effect on large trials, it may be impossible to show the benefits of surgery when trial size is small and deviations large. CONCLUSION: Survival analyses are inappropriate in RCTs comparing surgery with conservative management, unless survival is calculated after the postoperative period. Alternative ways to compare final clinical outcomes, using for example a fixed follow-up period, should be planned for preventive surgical trials that compare intervention with conservative management.

Promotion of Physical Activity by Québec Primary Care Physicians: What Has Changed in the Last Decade?

OBJECTIVE: This study aimed to assess the changes in the frequency of physical activity (PA) counseling and in the predictors of primary care PA promotion in Québec primary care physicians (PCPs) between 2010 and 2020. METHODS: In 2010, we conducted a survey among Québec PCPs. Questions included: frequency of promoting PA to patients, perceived barriers, needs to improve PA promotion practice, frequency of PCPs' PA practice, and sociodemographic information. In 2020, we took over the 2010 questionnaire to document the evolution of the PA promotion practice. RESULTS: The proportion of PCPs discussing PA with their patients significantly increased (P < .05) in 2020 for the following health conditions: depression, low back pain, chronic obstructive pulmonary disease, and cancer; it declined (P < .05) for overweight patients, those with metabolic syndrome, and in primary prevention. Collaboration with PA professionals was the major need identified, and it increased in 2020. PCPs' own practice of PA was a predictor of PA promotion in 2010 (odds ratio = 6.679; P < .001) and in 2020 (odds ratio = 6.679; P < .001). In both 2010 and in 2020, older or more experienced PCPs were more likely to discuss PA with their patients without diagnosed diseases than younger ones or those with less experience. CONCLUSIONS: Over the last 10 years, there has been a significant increase in PCPs promoting PA in Québec; however, it has been mainly oriented toward secondary prevention. It is concerning that PA counseling in primary prevention has declined, notably among younger PCPs. The stronger claim for closer collaboration with kinesiologists suggests that PCPs are in favor of an interprofessional strategy, namely collaboration with PA specialists.

Valproic acid for agitation in the intensive care unit: an observational study of psychiatric consults.

BACKGROUND: Agitation is a common clinical problem encountered in the intensive care unit (ICU). Treatment options are based on clinical experience and sparse quality literature. AIM: The aim of this study was to describe the effect of valproic acid (VPA) as adjuvant treatment for agitation in the ICU, identify predictors of response to VPA and evaluate the independent effect of VPA on agitation compared to standard of care (SOC). METHOD: This retrospective single center observational study evaluated adult patients admitted to the ICU for whom a psychiatric consultation was requested for agitation management, with agitation defined as a Richmond Agitation Sedation Score of 2 or greater. A descriptive analysis of the proportion of agitation-free patients per day of follow-up, the incidence of agitation-related-events, as well as the evolution of co-medications use over time are presented. A logistic regression model was used to assess predictors of VPA response, defined as being agitation-free on Day 7 and generalized estimating equations were used to evaluate the independent effect of VPA as adjuvant therapy for agitation in the critically ill. RESULTS: One hundred seventy-five patients were included in the study with 78 receiving VPA. The percentage of agitation-free patients on VPA was 6.5% (5/77) on Day 1, 14.1% (11/78) on Day 3 and 39.5% (30/76) on Day 7. Multivariate regression model for clinical and demographic variables identified female gender as predictor of response on Day 7 (OR 6.10 [1.18-31.64], p = 0.03). The independent effect of VPA was non-significant when compared to SOC. CONCLUSION: Although VPA used as adjuvant treatment was associated with a decrease in agitation, its effect when compared to SOC did not yield significant results.

The small trial problem.

BACKGROUND: Many randomized trials that aim to assess new or commonly used medical or surgical interventions have been so small that the validity of conclusions becomes questionable. METHODS: We illustrate the small trial problem using the power calculation of five Cochrane-reviewed studies that compared vertebroplasty versus placebo interventions. We discuss some of the reasons why the statistical admonition not to dichotomize continuous variables may not apply to the calculation of the number of patients required for trials to be meaningful. RESULTS: Placebo-controlled vertebroplasty trials planned to recruit between 23 and 71 patients per group. Four of five studies used the standardized mean difference of a continuous pain variable (centimeters on the visual analog scale (VAS)) to plan implausibly small trials. What is needed is not a mean effect at the population level but a measure of efficacy at the patient level. Clinical practice concerns the care of individual patients that vary in many more respects than the variation around the mean of a single selected variable. The inference from trial to practice concerns the frequency of success of the experimental intervention performed one patient at a time. A comparison of the proportions of patients reaching a certain threshold is a more meaningful method that appropriately requires larger trials. CONCLUSION: Most placebo-controlled vertebroplasty trials used comparisons of means of a continuous variable and were consequently very small. Randomized trials should instead be large enough to account for the diversity of future patients and practices. They should offer an evaluation of a clinically meaningful number of interventions performed in various contexts. Implications of this principle are not specific to placebo-controlled surgical trials. Trials designed to inform practice require a per-patient comparison of outcomes and the size of the trial should be planned accordingly.

Self-perceived role and knowledge of community pharmacists in organ donation.

BACKGROUND: Although a majority of North Americans is in favor of organ donation, registration remains challenging. Community pharmacists are highly accessible frontline health care professionals that could contribute to a new common registration donation consent system. AIM: The objective of the study was to assess self-perceived professional role and organ donation knowledge of community pharmacists in Quebec. METHOD: We designed a telephone interview survey using a three round modified Delphi process. Following questionnaires testing, we randomly sampled 329 community pharmacists in Quebec. Following administration, we validated the questionnaire by conducting an exploratory factorial analysis using principal component followed by a varimax rotation and rearranging domains and items accordingly. RESULTS: A total of 443 pharmacists were contacted, 329 provided answers to the self-perception role and 216 of them completed the knowledge questionnaire. Overall, community pharmacists of Quebec had a positive view on organ donation and demonstrated interest in acquiring knowledge. Respondents have identified lack of time and high pharmacy attendance as non-limiting barriers to implementing the intervention. The average score on the knowledge questionnaire was 61.2%. CONCLUSION: With the implementation of an appropriate education program to address this knowledge gap, we believe that community pharmacists could be key players in registered organ donation consent.

Hypothermic Perfusion Modifies the Association Between Anti-LG3 Antibodies and Delayed Graft Function in Kidney Recipients.

We previously reported associations between autoantibodies to the LG3 fragment of perlecan, anti-LG3, and a higher risk of delayed graft function (DGF) in kidney transplant recipients. Here, we aimed to determine whether some factors that modulate ischemia-reperfusion injury (IRI) can modify this association. We performed a retrospective cohort study in kidney transplant recipients in 2 university-affiliated centers. In 687 patients, we show that high pre-transplant anti-LG3 are associated with DGF when the kidney is transported on ice (odds ratio (OR): 1.75, 95% confidence interval 1.02-3.00), but not when placed on hypothermic perfusion pump (OR: 0.78, 95% CI 0.43-1.37). In patients with DGF, high pre-transplant anti-LG3 are associated with a higher risk of graft failure (subdistribution hazard ratio (SHR): 4.07, 95% CI: 1.80, 9.22), while this was not the case in patients with immediate graft function (SHR: 0.50, 95% CI 0.19, 1.29). High anti-LG3 levels are associated with a higher risk of DGF in kidneys exposed to cold storage, but not when hypothermic pump perfusion is used. High anti-LG3 are also associated with a higher risk of graft failure in patients who experience DGF, a clinical manifestation of severe IRI.

Pharmacologic Interventions to Minimize Fluid Absorption at the Time of Hysteroscopy: A Systematic Review and Meta-analysis.

OBJECTIVE: To assess which interventions are effective in reducing fluid absorption at the time of hysteroscopy. DATA SOURCE: Ovid MEDLINE, Ovid EMBASE, PubMed (non-MEDLINE records only), EBM Reviews-Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov , and Web of Science were searched from inception to February 2022 without restriction on language or geographic origin. METHODS OF STUDY SELECTION: Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, all English-language, full-text articles reporting fluid balance, with an intervention and comparator arm, were included. Title and abstract screening and full-text review were completed independently by two authors. Conflicts were resolved through discussion and consensus. Studies' risk of bias was assessed using the Cochrane Risk of Bias Tool for RCTs and the Newcastle-Ottawa Scale for observational studies. TABULATION, INTEGRATION, AND RESULTS: The search identified 906 studies, 28 of which were eligible for inclusion, examining the following interventions: gonadotropin-releasing hormone (GnRH) agonist; ulipristal acetate; vasopressin; danazol; oxytocin; and local, general, and regional anesthesia. A significant reduction in mean fluid absorption was seen in patients preoperatively treated with danazol (-175.7 mL, 95% CI -325.4 to -26.0) and a GnRH agonist (-139.68 mL, 95% CI -203.2, -76.2) compared with patients in a control group. Ulipristal acetate and type of anesthesia showed no difference. Data on type of anesthesia and vasopressin use were not amenable to meta-analysis; however, four studies favored vasopressin over control regarding fluid absorption. Mean operative time was reduced after preoperative treatment with ulipristal acetate (-7.1 min, 95% CI -11.31 to -2.9), danazol (-7.5 min, 95% CI -8.7 to -6.3), and a GnRH agonist (-3.3 min, 95% CI -5.6 to -0.98). CONCLUSION: Preoperative treatment with a GnRH agonist and danazol were both found to be effective in reducing fluid absorption and operative time across a range of hysteroscopic procedures. High-quality research aimed at evaluating other interventions, such as combined hormonal contraception, progestin therapy, and vasopressin, are still lacking in the literature. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42021233804.

Impact of Implementing a Bendamustine-Based Conditioning Regimen on Outcomes of Autologous Stem Cell Transplantation in Lymphoma while Novel Cellular Therapies Emerge.

With the advent of new cellular and targeted therapies, treatment options for relapsed and refractory (r/R) lymphomas have multiplied, and the optimal approach offering the best outcomes remains a matter of passionate debate. High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is still considered a treatment option for patients with chemosensitive lymphoma when cure is the expected goal. The myeloablative conditioning regimen preceding the stem cell infusion is considered the effective component of this approach. Carmustine (BCNU)-based preparative regimens, such as BEAM and BEAC, are considered the standard of care and have shown efficacy and low nonrelapse mortality (NRM). Comparative studies between conditioning regimens have failed to identify a better option. After a BCNU drug shortage in Canada followed by a steep increase in price, we elected to substitute BCNU for bendamustine (benda) in the preparative regimen. The purpose of this substitution was to improve response while preserving safety and controlling costs. From May 2015 to May 2018, a total of 131 consecutive lymphoma patients received benda-EAM conditioning. These patients were compared with 96 consecutive patients who received BCNU-based conditioning from January 2012 to May 2015. Apart from conditioning, supportive care measures were the same in the 2 groups. Patients receiving benda were older (55.7 years versus 51.1 years; P = .002). The development of grade ≥3 mucositis was more frequent with benda conditioning (39.5% versus 7.8%; P < .001) leading to a greater requirement for parenteral nutrition (48.9% versus 21.9%; P < .001). A transient creatinine increase >1.5 times the upper limit of normal (15.3% versus 4.2%; P < .008) and intensive care unit admission (6.9% versus 1.1%; P < .029) were more frequent with benda; however, there were no between-group differences in cardiac, pulmonary, or liver toxicity and NRM. With a median follow-up of 48 months for the benda group and 60 months for the BCNU group, benda was associated with significantly better progression-free survival (71% versus 61%; P = .040; hazard ratio [HR], 1.6; 95% confidence interval [CI], 1.0 to 2.7) and overall survival (86% vs 71%; P = .0066; HR, 2.6; 95% CI, 1.3 to 5.4) compared with BCNU-based conditioning regimens. While novel therapies emerge, our study demonstrates that benda-EAM is safe and effective and should be considered a valid alternative to BCNU conditioning to improve outcomes of patients with chemosensitive r/R lymphomas undergoing ASCT.

Differentiation of focal nodular hyperplasia and hepatocellular adenoma using qualitative and quantitative imaging features and classification and regression tree analysis.

PURPOSE: To assess qualitative and quantitative analysis of gadoxetate disodium-enhanced hepatobiliary phase MR imaging (MRI) and assess the performance of classification and regression tree analysis for the differentiation of focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA). MATERIALS AND METHODS: This retrospective study was approved by our local ethics committee. One hundred seventy patients suspected of having FNH or HCA underwent gadoxetate disodium-enhanced MRI. The reference standard was either pathology or follow-up imaging. Two readers reviewed images to identify qualitative imaging features and measure signal intensity on unenhanced, dynamic, and hepatobiliary phase images. For quantitative analysis, contrast enhancement ratio (CER), lesion-to-liver contrast (LLC), signal intensity ratio (SIR), and relative signal enhancement ratio (RSER) were calculated. A classification and regression tree (CART) analysis was developed. RESULTS: Eighty-five patients met the inclusion criteria, with a total of 97 FNHs and 43 HCAs. For qualitative analysis, the T1 signal intensity on the hepatobiliary phase provided the highest overall classification performance (91.9% sensitivity, 90.1% specificity, and 90.9% accuracy). For quantitative analysis, RSER in the hepatobiliary phase with a threshold of 0.723 provided the highest classification performance (92.6% sensitivity and 89.4% specificity) to differentiate FNHs from HCAs. A CART model based on five qualitative imaging features provided an accuracy of 94.4% (95% confidence interval 90.0-98.9%). CONCLUSION: Gadoxetate disodium-enhanced hepatobiliary phase provides high diagnostic performance as demonstrated in quantitative and qualitative analysis in differentiation of FNH and HCA, supported by a CART decision model.

Validation of the Augmented Renal Clearance in Trauma Intensive Care scoring system for augmented renal clearance prediction in a trauma subgroup of a mixed ICU population.

WHAT IS KNOWN AND OBJECTIVE: Augmented renal clearance is prevalent in trauma patients and leads to subtherapeutic levels of renally eliminated medications with potentially unfavourable clinical outcomes. The Augmented Renal Clearance of Trauma in Intensive Care (ARCTIC) score has been developed to predict augmented renal clearance in critically ill trauma patients. Our primary objective was to validate this score among the trauma subgroup of a mixed intensive care patient cohort. METHODS: This single-centre, retrospective, observational cohort study assessed augmented renal clearance using a timed 24-h urine collection performed weekly. ARC was defined as a measured creatinine clearance of ≥130 ml/min/1.73 m2 . ARCTIC score performance was evaluated through a receiver operator characteristic curves and analysis of sensitivities and specificities for the trauma subgroup, the medical/surgical subgroup and the pooled cohort. RESULTS AND DISCUSSION: Augmented renal clearance was observed in 33.9% (n = 58) of trauma patients (n = 171) and 15.7% (n = 24) of medical/surgical patients (n = 153). Examination of different cutoffs for the ARCTIC score in our trauma population confirmed that the optimal cutoff score was ≥6. Comparison between ROC curves for ARCTIC score and for regression model based upon our data in trauma patients indicated validation of the score in this subgroup. Comparison of sensitivities and specificities for ARCTIC score between trauma (93.1% and 41.6%, respectively) and medical/surgical subjects (87.5% and 49.6%, respectively) showed no clinical nor statistical difference, suggesting validation for the medical/surgical subgroup as well. WHAT IS NEW AND CONCLUSION: In our mixed ICU population, the ARCTIC score was validated in the trauma subgroup. We also found that the score performed well in the medical/surgical population. Future studies should assess the performance of the ARCTIC score prospectively.

Clinical Uncertainty and Equipoise in the Management of Recurrent Glioblastoma.

BACKGROUND: A significant proportion of glioblastoma (GBM) patients are considered for repeat resection, but evidence regarding best management remains elusive. Our aim was to measure the degree of clinical uncertainty regarding reoperation for patients with recurrent GBM. METHODS: We first performed a systematic review of agreement studies examining the question of repeat resection for recurrent GBM. An electronic portfolio of 37 pathologically confirmed recurrent GBM patients including pertinent magnetic resonance images and clinical information was assembled. To measure clinical uncertainty, 26 neurosurgeons from various countries, training backgrounds, and years' experience were asked to select best management (repeat surgery, other nonsurgical management, or conservative), confidence in recommended management, and whether they would include the patient in a randomized trial comparing surgery with nonsurgical options. Agreement was evaluated using κ statistics. RESULTS: The literature review did not reveal previous agreement studies examining the question. In our study, agreement regarding best management of recurrent GBM was slight, even when management options were dichotomized (repeat surgery vs. other options; κ=0.198 [95% confidence interval: 0.133-0.276]). Country of practice, years' experience, and training background did not change results. Disagreement and clinical uncertainty were more pronounced within clinicians with (κ=0.167 [0.055-0.314]) than clinicians without neuro-oncology fellowship training (κ=0.601 [0.556-0.646]). A majority (51%) of responders were willing to include the patient in a randomized trial comparing repeat surgery with nonsurgical alternatives in 26/37 (69%) of cases. CONCLUSION: There is sufficient uncertainty and equipoise regarding the question of reoperation for patients with recurrent glioblastoma to support the need for a randomized controlled trial.

Surgical or Endovascular Management of Middle Cerebral Artery Aneurysms: A Randomized Comparison.

OBJECTIVE: There are few randomized data comparing clipping and coiling for middle cerebral artery (MCA) aneurysms. We analyzed results from patients with MCA aneurysms enrolled in the CURES (Collaborative UnRuptured Endovascular vs. Surgery) and ISAT-2 (International Subarachnoid Aneurysm Trial II) randomized trials. METHODS: Both trials are investigator-led parallel-group 1:1 randomized studies. CURES includes patients with 3-mm to 25-mm unruptured intracranial aneurysms (UIAs), and ISAT-2 includes patients with ruptured aneurysms (RA) for whom uncertainty remains after ISAT. The primary outcome measure of CURES is treatment failure: 1) failure to treat the aneurysm, 2) intracranial hemorrhage during follow-up, or 3) residual aneurysm at 1 year. The primary outcome of ISAT-2 is death or dependency (modified Rankin Scale score >2) at 1 year. One-year angiographic outcomes are systematically recorded. RESULTS: There were 100 unruptured and 71 ruptured MCA aneurysms. In CURES, 90 patients with UIA have been treated and 10 await treatment. Surgical and endovascular management of unruptured MCA aneurysms led to treatment failure in 3/42 (7%; 95% confidence interval [CI], 0.02-0.19) for clipping and 13/48 (27%; 95% CI, 0.17-0.41) for coiling (P = 0.025). All 71 patients with RA have been treated. In ISAT-2, patients with ruptured MCA aneurysms managed surgically had died or were dependent (modified Rankin Scale score >2) in 7/38 (18%; 95% CI, 0.09-0.33) cases, and 8/33 (24%; 95% CI, 0.13-0.41) for endovascular. One-year imaging results were available in 80 patients with UIA and 62 with RA. Complete aneurysm occlusion was found in 30/40 (75%; 95% CI, 0.60-0.86) patients with UIA allocated clipping, and 14/40 (35%; 95% CI, 0.22-0.50) patients with UIA allocated coiling. Complete aneurysm occlusion was found in 24/34 (71%; 95% CI, 0.54-0.83) patients with RA allocated clipping, and 15/28 (54%; 95% CI, 0.36-0.70) patients with RA allocated coiling. CONCLUSIONS: Randomized data from 2 trials show that better efficacy may be obtained with surgical management of patients with MCA aneurysms.

Effect of mannitol on acute kidney injury induced by cisplatin.

PURPOSE: Acute kidney injury (AKI) is a frequent dose-limiting toxicity induced by cisplatin. Mannitol has been used in hydration protocols to mitigate this adverse event but its role remains controversial. The aim of this study is to define the impact of mannitol on AKI in patients receiving cisplatin. METHODS: This retrospective observational study was conducted in cancer patients who received at least one dose of cisplatin between September 2010 and December 2016 at the Centre hospitalier de l'Université de Montréal. The primary outcome of this study was the comparison of all grade cisplatin-associated AKI between hydration protocols with or without mannitol. RESULTS: A total of 1821 patients were included of which 658 received mannitol whilst 1163 received hydration alone. The risk of all grade cisplatin-associated AKI was significantly lower for the mannitol group (Hazard Ratio (HR) = 0.62; 95% CI [0.42, 0.89]). This result was mainly driven by gynecologic (HR = 0.50), upper gastrointestinal (HR = 0.32), urinary tract malignancies (HR = 0.29) and lymphoma (HR = 0.33). No significant difference was seen for head and neck (HN), lung, germ cells and other cancers. However, HN cancers patients receiving mannitol had fewer grade 2 and 3 AKI. Significantly fewer AKI events were observed in HN, lung, upper gastrointestinal and urinary tract cancer when mannitol was added for cisplatin dose <75 mg/m2. CONCLUSION: Although the results were generally driven by a decrease of grade 1 AKI for most cancers, the greatest benefit of mannitol was seen with cisplatin doses lower than 75 mg/m2 and should probably be reinstated in this setting.

Abnormal glucose tolerance in a pediatric cystic fibrosis cohort: Trends in clinical outcomes and associated factors in the preceding years.

BACKGROUND AND AIMS: Deterioration of anthropometric and lung function parameters was shown to precede the onset of cystic fibrosis-related diabetes (CFRD) in adults. In children, studies have been conducted in small cohorts with relatively short observation period. Study objectives were to document the longitudinal trends of anthropometric, pulmonary, nutritional and metabolic parameters from cystic fibrosis (CF) diagnosis to the ascertainment of abnormal glucose tolerance and identify parameters associated with the incidence of such abnormalities in a pediatric CF cohort. METHODS AND RESULTS: Retrospective cohort study of 281 children with CF. Longitudinal trends of anthropometric, lung function, nutritional and metabolic data were generated from CF diagnosis to the ascertainment of abnormal glucose tolerance defined as the presence of either impaired glucose tolerance (IGT), unconfirmed CFRD or CFRD. Cox models and Kaplan-Meier curves were used to identify factors associated with developing abnormal glucose tolerance. Forty-five percent of cohort had normal glucose tolerance (NGT), 27% IGT, 10% unconfirmed CFRD and 18% CFRD. Children who developed CFRD displayed lower height z-scores from a very early age. Conversely, HbA1c levels began to rise closer to CFRD ascertainment. Height z-scores (HR: 0.45; CI 95% [0.29-0.69]) and HbA1c (HR: 2.43; CI 95% [1.86-3.18]) in years preceding ascertainment were associated with the risk of developing CFRD. CONCLUSION: Children who developed CFRD display distinctive trends for height z-scores from a very early age, whereas HbA1c appears as a marker of established glucose metabolism derangements.

Systemic Inflammatory Markers Are Predictive of the Response to Brachytherapy in the Prostate.

We analyzed the influence of the neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) on the biochemical recurrence (BCR) in low-intermediate risk prostate cancer (PCa). A total of 604 patients treated with exclusive brachytherapy for low- and intermediate-risk cancers were included in this study. No patient received either androgen deprivation or brachytherapy as a boost. BCR was defined according to the Phoenix definition (nadir prostatic specific antigen (PSA) +2). The median follow-up was 60 months (IQR 44-48 months). An NLR > 3 was more frequent in statin users (p = 0.025), but not in diabetics (p = 0.079). In univariate analysis (UVA) and multivariate analysis (MVA), a NLR > 3 (MVA p = 0.03), as well as Cancer of the Prostate Risk Assessment (CAPRA) low- vs. intermediate-risk (MVA p = 0.04), were predictive of BCR. When combining the NLR score with the CAPRA risk group, CAPRA intermediate risk patients with an NLR ≤ 3 (n = 157) had the worst (p = 0.0276) BCR rates, with a 5-year recurrence-free survival (p = 0.004, Bonferroni correction for six comparisons p = 0.024). We were able to identify a subgroup of PCa patients with CAPRA intermediate-risk and an NLR ≤ 3 who had worse BCR. This is in contrast to most other cancers, which have a worse prognosis when the NLR is high.

Measuring clinical uncertainty and equipoise by applying the agreement study methodology to patient management decisions.

BACKGROUND: Clinical uncertainty and equipoise are vague notions that play important roles in contemporary problems of medical care and research, including the design and conduct of pragmatic trials. Our goal was to show how the reliability study methods normally used to assess diagnostic tests can be applied to particular management decisions to measure the degree of uncertainty and equipoise regarding the use of rival management options. METHODS: We first use thrombectomy in acute stroke as an illustrative example of the method we propose. We then review, item by item, how the various design elements of diagnostic reliability studies can be modified in order to measure clinical uncertainty. RESULTS: The thrombectomy example shows sufficient disagreement and uncertainty to warrant the conduct of additional randomized trials. The general method we propose is that a sufficient number of diverse individual cases sharing a similar clinical problem and covering a wide spectrum of clinical presentations be assembled into a portfolio that is submitted to a variety of clinicians who routinely manage patients with the clinical problem. DISCUSSION: Clinicians are asked to independently choose one of the predefined management options, which are selected from those that would be compared within a randomized trial that would address the clinical dilemma. Intra-rater agreement can be assessed at a later time with a second evaluation. Various professional judgments concerning individual patients can then be compared and analyzed using kappa statistics or similar methods. Interpretation of results can be facilitated by providing examples or by translating the results into clinically meaningful summary sentences. CONCLUSIONS: Measuring the uncertainty regarding management options for clinical problems may reveal substantial disagreement, provide an empirical foundation for the notion of equipoise, and inform or facilitate the design/conduct of clinical trials to address the clinical dilemma.

Adrenal vein sampling: External validation of multinomial regression modelling and left adrenal vein-to-peripheral vein ratio to predict lateralization index without right adrenal vein sampling.

BACKGROUND: Adrenal vein sampling (AVS) failure is mainly due to right adrenal vein unavailability. Multinomial regression modelling (MRM) and left adrenal vein-to-peripheral vein ratio (LAV/PV) were proposed to predict the lateralization index without the right AVS. OBJECTIVE: To assess external validity of MRM and LAV/PV to predict lateralization index when right adrenal vein sampling is missing. DESIGN: Diagnostic retrospective study. PATIENTS: Development and validation cohorts included AVS of 174 and 122 patients, respectively, from 2 different centres. MEASUREMENTS: Development and validation cohort data were used, respectively, for calibration and for validation of MRM and LAV/PV to predict the lateralization index without the right adrenal vein sampling. Sensitivity and specificity of MRM and LAV/PV were compared between both centres at different pre-established specificity thresholds based on receiver operating characteristic curves generated from the development cohort data. RESULTS: At a specificity threshold of 95% set in the development cohort, specificity values exceeded 90% (range, 90.6%-98.8%) for all verified MRM and LAV/PV models in the validation cohort. Corresponding sensitivities for MRM and LAV/PV, respectively, range from 54.1% to 83.7% and 32.8% to 88.4% for the development cohort compared to 33.3%-87.5% and 2.8%-79.2% for the validation cohort. Overall, diagnostic accuracy of both methods was higher to detect right (82.8%-93.5%) than left (70.2%-80.6%) lateralization index status in both centres. CONCLUSIONS: Minimal changes in specificity from development to validation cohorts validate the use of MRM and LAV/PV to predict the lateralization index when the right AVS is missing. Both methods had better accuracy for right than left lateralization detection.