Liberal or Restrictive Transfusion Strategy in Patients with Traumatic Brain Injury.

BACKGROUND: The effect of a liberal transfusion strategy as compared with a restrictive strategy on outcomes in critically ill patients with traumatic brain injury is unclear. METHODS: We randomly assigned adults with moderate or severe traumatic brain injury and anemia to receive transfusion of red cells according to a liberal strategy (transfusions initiated at a hemoglobin level of ≤10 g per deciliter) or a restrictive strategy (transfusions initiated at ≤7 g per deciliter). The primary outcome was an unfavorable outcome as assessed by the score on the Glasgow Outcome Scale-Extended at 6 months, which we categorized with the use of a sliding dichotomy that was based on the prognosis of each patient at baseline. Secondary outcomes included mortality, functional independence, quality of life, and depression at 6 months. RESULTS: A total of 742 patients underwent randomization, with 371 assigned to each group. The analysis of the primary outcome included 722 patients. The median hemoglobin level in the intensive care unit was 10.8 g per deciliter in the group assigned to the liberal strategy and 8.8 g per deciliter in the group assigned to the restrictive strategy. An unfavorable outcome occurred in 249 of 364 patients (68.4%) in the liberal-strategy group and in 263 of 358 (73.5%) in the restrictive-strategy group (adjusted absolute difference, restrictive strategy vs. liberal strategy, 5.4 percentage points; 95% confidence interval, -2.9 to 13.7). Among survivors, a liberal strategy was associated with higher scores on some but not all the scales assessing functional independence and quality of life. No association was observed between the transfusion strategy and mortality or depression. Venous thromboembolic events occurred in 8.4% of the patients in each group, and acute respiratory distress syndrome occurred in 3.3% and 0.8% of patients in the liberal-strategy and restrictive-strategy groups, respectively. CONCLUSIONS: In critically ill patients with traumatic brain injury and anemia, a liberal transfusion strategy did not reduce the risk of an unfavorable neurologic outcome at 6 months. (Funded by the Canadian Institutes of Health Research and others; HEMOTION ClinicalTrials.gov number, NCT03260478.).

Subclinical Primary Aldosteronism and Cardiovascular Health: A Population-Based Cohort Study.

BACKGROUND: Primary aldosteronism, characterized by overt renin-independent aldosterone production, is a common but underrecognized form of hypertension and cardiovascular disease. Growing evidence suggests that milder and subclinical forms of primary aldosteronism are highly prevalent, yet their contribution to cardiovascular disease is not well characterized. METHODS: This prospective study included 1284 participants between the ages of 40 and 69 years from the randomly sampled population-based CARTaGENE cohort (Québec, Canada). Regression models were used to analyze associations of aldosterone, renin, and the aldosterone-to-renin ratio with the following measures of cardiovascular health: arterial stiffness, assessed by central blood pressure (BP) and pulse wave velocity; adverse cardiac remodeling, captured by cardiac magnetic resonance imaging, including indexed maximum left atrial volume, left ventricular mass index, left ventricular remodeling index, and left ventricular hypertrophy; and incident hypertension. RESULTS: The mean (SD) age of participants was 54 (8) years and 51% were men. The mean (SD) systolic and diastolic BP were 123 (15) and 72 (10) mm Hg, respectively. At baseline, 736 participants (57%) had normal BP and 548 (43%) had hypertension. Higher aldosterone-to-renin ratio, indicative of renin-independent aldosteronism (ie, subclinical primary aldosteronism), was associated with increased arterial stiffness, including increased central BP and pulse wave velocity, along with adverse cardiac remodeling, including increased indexed maximum left atrial volume, left ventricular mass index, and left ventricular remodeling index (all P<0.05). Higher aldosterone-to-renin ratio was also associated with higher odds of left ventricular hypertrophy (odds ratio, 1.32 [95% CI, 1.002-1.73]) and higher odds of developing incident hypertension (odds ratio, 1.29 [95% CI, 1.03-1.62]). All the associations were consistent when assessing participants with normal BP in isolation and were independent of brachial BP. CONCLUSIONS: Independent of brachial BP, a biochemical phenotype of subclinical primary aldosteronism is negatively associated with cardiovascular health, including greater arterial stiffness, adverse cardiac remodeling, and incident hypertension.

Resumption of Cardiac Activity after Withdrawal of Life-Sustaining Measures.

BACKGROUND: The minimum duration of pulselessness required before organ donation after circulatory determination of death has not been well studied. METHODS: We conducted a prospective observational study of the incidence and timing of resumption of cardiac electrical and pulsatile activity in adults who died after planned withdrawal of life-sustaining measures in 20 intensive care units in three countries. Patients were intended to be monitored for 30 minutes after determination of death. Clinicians at the bedside reported resumption of cardiac activity prospectively. Continuous blood-pressure and electrocardiographic (ECG) waveforms were recorded and reviewed retrospectively to confirm bedside observations and to determine whether there were additional instances of resumption of cardiac activity. RESULTS: A total of 1999 patients were screened, and 631 were included in the study. Clinically reported resumption of cardiac activity, respiratory movement, or both that was confirmed by waveform analysis occurred in 5 patients (1%). Retrospective analysis of ECG and blood-pressure waveforms from 480 patients identified 67 instances (14%) with resumption of cardiac activity after a period of pulselessness, including the 5 reported by bedside clinicians. The longest duration after pulselessness before resumption of cardiac activity was 4 minutes 20 seconds. The last QRS complex coincided with the last arterial pulse in 19% of the patients. CONCLUSIONS: After withdrawal of life-sustaining measures, transient resumption of at least one cycle of cardiac activity after pulselessness occurred in 14% of patients according to retrospective analysis of waveforms; only 1% of such resumptions were identified at the bedside. These events occurred within 4 minutes 20 seconds after a period of pulselessness. (Funded by the Canadian Institutes for Health Research and others.).

Development of an MRI-Based Prediction Model for Anti-TNF Treatment Failure in Perianal Crohn's Disease: A Multicenter Study.

BACKGROUND & AIMS: Clinical and radiologic variables associated with perianal fistula (PAF) outcomes are poorly understood. We developed prediction models for anti-tumor necrosis factor (TNF) treatment failure in patients with Crohn's disease-related PAF. METHODS: In a multicenter retrospective study between 2005 and 2022 we included biologic-naive adults (>17 years) who initiated their first anti-TNF therapy for PAF after pelvic magnetic resonance imaging (MRI). Pretreatment MRI studies were prospectively reread centrally by blinded radiologists. We developed and internally validated a prediction model based on clinical and radiologic parameters to predict the likelihood of anti-TNF treatment failure, clinically, at 6 months. We compared our model and a simplified version of MRI parameters alone with existing imaging-based PAF activity indices (MAGNIFI-CD and modified Van Assche MRI scores) by De Long statistical test. RESULTS: We included 221 patients: 32 ± 14 years, 60% males, 76% complex fistulas; 68% treated with infliximab and 32% treated with adalimumab. Treatment failure occurred in 102 (46%) patients. Our prediction model included age at PAF diagnosis, time to initiate anti-TNF treatment, and smoking and 8 MRI characteristics (supra/extrasphincteric anatomy, fistula length >4.3 cm, primary tracts >1, secondary tracts >1, external openings >1, tract hyperintensity on T1-weighted imaging, horseshoe anatomy, and collections >1.3 cm). Our full and simplified MRI models had fair discriminatory capacity for anti-TNF treatment failure (concordance statistic, 0.67 and 0.65, respectively) and outperformed MAGNIFI-CD (P = .002 and < .0005) and modified Van Assche MRI scores (P < .0001 and < .0001), respectively. CONCLUSIONS: Our risk prediction models consisting of clinical and/or radiologic variables accurately predict treatment failure in patients with PAF.

Comparison of Positive Predictive Values of Biparametric MRI and Multiparametric MRI-directed Transrectal US-guided Targeted Prostate Biopsy.

Background Biparametric MRI (bpMRI) of the prostate is an alternative to multiparametric MRI (mpMRI), with lower cost and increased accessibility. Studies investigating the positive predictive value (PPV) of bpMRI-directed compared with mpMRI-directed targeted biopsy are lacking in the literature. Purpose To compare the PPVs of bpMRI-directed and mpMRI-directed targeted prostate biopsies. Materials and Methods This retrospective cross-sectional study evaluated men who underwent bpMRI-directed or mpMRI-directed transrectal US (TRUS)-guided targeted prostate biopsy at a single institution from January 2015 to December 2022. The PPVs for any prostate cancer (PCa) and clinically significant PCa (International Society of Urological Pathology grade ≥2) were calculated for bpMRI and mpMRI using mixed-effects logistic regression modeling. Results A total of 1538 patients (mean age, 67 years ± 8 [SD]) with 1860 lesions underwent bpMRI-directed (55%, 849 of 1538) or mpMRI-directed (45%, 689 of 1538) prostate biopsy. When adjusted for the number of lesions and Prostate Imaging Reporting and Data System (PI-RADS) score, there was no difference in PPVs for any PCa or clinically significant PCa (P = .61 and .97, respectively) with bpMRI-directed (55% [95% CI: 51, 59] and 34% [95% CI: 30, 38], respectively) or mpMRI-directed (56% [95% CI: 52, 61] and 34% [95% CI: 30, 39], respectively) TRUS-guided targeted biopsy. PPVs for any PCa and clinically significant PCa stratified according to clinical indication were as follows: biopsy-naive men, 64% (95% CI: 59, 69) and 43% (95% CI: 39, 48) for bpMRI, 67% (95% CI: 59, 75) and 51% (95% CI: 43, 59) for mpMRI (P = .65 and .26, respectively); and active surveillance, 59% (95% CI: 49, 69) and 30% (95% CI: 22, 39) for bpMRI, 73% (95% CI: 65, 89) and 38% (95% CI: 31, 47) for mpMRI (P = .04 and .23, respectively). Conclusion There was no evidence of a difference in PPV for clinically significant PCa between bpMRI- and mpMRI-directed TRUS-guided targeted biopsy. © RSNA, 2024 Supplemental material is available for this article.

Five-Year Serial Brain MRI Analysis of Military Members Exposed to Chronic Sub-Concussive Overpressures.

BACKGROUND: The Canadian Special Operations Forces Command conducts explosives operations and training which exposes members to explosive charges at close proximity. This 5-year longitudinal trial was conducted in follow-up to our initial trial which examined military breachers with MRI and EEG pre and post blast exposure. PURPOSE: To examine brain MRI findings in military personnel exposed to multiple repeated blast exposures. STUDY TYPE: Five-year longitudinal prospective trial. POPULATION: Ninety-two males aged 23-42 with an average of 9.4 years of blast exposure. FIELD STRENGTH/SEQUENCE: 3 T brain MRI/T1-weighted 3D with reconstruction in three planes, T2-weighted, T2-weighted fluid attenuated inversion recovery (FLAIR) 3D with reconstruction in three planes, T2-weighted gradient spin echo (GRE), saturation weighted images, DWI and ADC maps, diffusion tensor imaging. ASSESSMENT: All MRI scans were interpreted by the two neuroradiologists and one neuroradiology Fellow in a blinded fashion using a customized neuroradiology reporting form. STATISTICAL TESTS: Matching parametric statistics represented the number of participants whose brain parameters improved or deteriorated over time. Odds ratio (OR) and 95% confidence intervals (CI) were computed using log regression modeling to determine volume loss, white matter lesions, hemosiderosis, gliosis, cystic changes and enlarged Virchow Robin (VR) spaces. A Kappa (κ) statistic with a 95% CI was calculated to determine rater variability between readers. RESULTS: A significant deterioration was observed in volume loss (OR = 1.083, 95% CI 0.678-1.731, permutation test), white matter changes (OR: 0.754, 95% CI 0.442-1.284, permutation test), and enlargement of VR spaces (OR: 0.775, 95% CI 0.513-1.171). Interrater reliability was low: κ = 0.283, 0.156, and 0.557 for volume loss, white matter changes, and enlargement of VR spaces, respectively. DATA CONCLUSION: There were significant changes in brain volume, white matter lesions, and enlargement of VR spaces. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Population-wide eGFR percentiles in younger adults and clinical outcomes.

BACKGROUND AND HYPOTHESIS: Identifying meaningful estimated glomerular filtration rate (eGFR) reductions in younger adults (<65 years) could guide prevention efforts. To aid in interpretation and identification of young adults at risk, we examined the association of population-level eGFR percentiles relative to the median by age and clinical outcomes. METHODS: We conducted a retrospective cohort study of 8.7 million adults from Ontario, Canada from age 18 to 65 from 2008 to 2021 with an eGFR measure (both single outpatient value and repeat measures). We calculated median eGFR values by age and examined the association of reduced eGFR percentiles (≤10th, 5th, 2.5th and 1st) with outcomes using time to event models. Outcomes were a composite of all-cause mortality, major adverse cardiac outcomes (MACE) with/without heart failure (MACE+) and kidney failure as well as each component individually. RESULTS: From age 18 to 65, the median eGFR declined with age (range 128 to 90) and across percentiles [eGFR ranges 102 to 68 for ≤10th, 96 to 63 for ≤5th, 90 to 58 for ≤2.5th and 83 to 54 for 1st]. The adjusted rate for any adverse outcome was elevated at ≤ 10th percentile (HR 1.14 95%CI 1.10-1.18) and was consistent for all-cause mortality, MACE, MACE+ and predominant for kidney failure (HR 5.57 95%CI 3.79-8.19) compared to the median eGFR for age. Young adults with an eGFR in the lower percentiles were less likely to be referred to a specialist, have a repeat eGFR or albumin to creatinine ratio measure. CONCLUSIONS: eGFR values at the 10th percentile or lower based on a population-level distribution are associated with adverse clinical outcomes and in younger adults (18 to 39) this corresponds to a higher level of eGFR that may be underrecognized. Application of population-based eGFR percentiles may aid interpretation and improve identification of younger adults at risk.

Associations of preoperative anaemia with healthcare resource use and outcomes after colorectal surgery: a population-based cohort study.

BACKGROUND: Preoperative anaemia is common in patient undergoing colorectal surgery. Understanding the population-level costs of preoperative anaemia will inform development and evaluation of anaemia management at health system levels. METHODS: This was a population-based cohort study using linked, routinely collected data, including residents from Ontario, Canada, aged ≥18 yr who underwent an elective colorectal resection between 2012 and 2022. Primary exposure was preoperative anaemia (haemoglobin <130 g L-1 in males; <120 g L-1 in females). Primary outcome was 30-day costs in 2022 Canadian dollars (CAD), from the perspective of a publicly funded healthcare system. Secondary outcomes included red blood cell transfusion, major adverse events (MAEs), length of stay (LOS), days alive at home (DAH), and readmissions. RESULTS: We included 54,286 patients, with mean 65.3 (range 18-102) years of age and 49.0% females, among which 21 264 (39.2%) had preoperative anaemia. There was an absolute adjusted cost increase of $2671 per person at 30 days after surgery attributable to preoperative anaemia (ratio of means [RoM] 1.05, 95% confidence interval [CI] 1.04-1.06). Compared with the control group, 30-day risks of transfusion (odds ratio [OR] 4.34, 95% CI 4.04-4.66), MAEs (OR 1.14, 95% CI 1.03-1.27), LOS (RoM 1.08, 95% CI 1.07-1.10), and readmissions (OR 1.16, 95% CI 1.08-1.24) were higher in the anaemia group, with reduced DAH (RoM 0.95, 95% CI 0.95-0.96). CONCLUSIONS: Approximately $2671 CAD per person in 30-day health system costs are attributable to preoperative anaemia after colorectal surgery in Ontario, Canada.

Prediction Models for Forecasting Risk of Development of Surgical Site Infection after Lower Limb Revascularization Surgery: A Systematic Review.

BACKGROUND: Surgical site infections (SSIs) are a common and potentially preventable complication of lower limb revascularization surgery associated with increased healthcare resource utilization and patient morbidity. We conducted a systematic review to evaluate multivariable prediction models designed to forecast risk of SSI development after these procedures. METHODS: After protocol registration (CRD42022331292), we searched MEDLINE, EMBASE, CENTRAL, and Evidence-Based Medicine Reviews (inception to April 4th, 2023) for studies describing multivariable prediction models designed to forecast risk of SSI in adults after lower limb revascularization surgery. Two investigators independently screened abstracts and full-text articles, extracted data, and assessed risk of bias. A narrative synthesis was performed to summarize predictors included in the models and their calibration and discrimination, validation status, and clinical applicability. RESULTS: Among the 6,671 citations identified, we included 5 studies (n = 23,063 patients). The included studies described 5 unique multivariable prediction models generated through forward selection, backward selection, or Akaike Information Criterion-based methods. Two models were designed to predict any SSI and 3 Szyilagyi grade II (extending into subcutaneous tissue) SSI. Across the 5 models, 18 adjusted predictors (10 of which were preoperative, 3 intraoperative, and 5 postoperative) significantly predicted any SSI and 14 adjusted predictors significantly predict Szilagyi grade II SSI. Female sex, obesity, and chronic obstructive pulmonary disease significantly predicted SSI in more than one model. All models had a "good fit" according to the Hosmer-Lemeshow test (P > 0.05). Model discrimination was quantified using the area under the curve, which ranged from 0.66 to 0.75 across models. Two models were internally validated using non-exhaustive twofold cross-validation and bootstrap resampling. No model was externally validated. Three studies had a high overall risk of bias according to the Prediction model Risk Of Bias ASsessment Tool (PROBAST). CONCLUSIONS: Five multivariable prediction models with moderate discrimination have been developed to forecast risk of SSI development after lower limb revascularization surgery. Given the frequency and consequences of SSI after these procedures, development and external validation of novel prediction models and comparison of these models to the existing models evaluated in this systematic review is warranted.

Knowledge, protective behaviours, and perception of Lyme disease in an area of emerging risk: results from a cross-sectional survey of adults in Ottawa, Ontario.

BACKGROUND: The number of Lyme disease risk areas in Canada is growing. In regions with emerging tick populations, it is important to emphasize peridomestic risk and the importance of protective behaviours in local public health communication. This study aims to identify characteristics associated with high levels of Lyme disease knowledge and adoption of protective behaviours among residents in the Ottawa, Ontario region. METHODS: A geographically stratified web survey was conducted in November 2020 (n = 2018) to determine knowledge, attitudes, and practices regarding Lyme disease among adult residents. Responses were used to calculate: (i) composite scores for knowledge and adoption of protective practices; and (ii) an exposure risk index based on reported activity in woodlands during the spring-to-fall tick exposure risk period. RESULTS: 60% of respondents had a high knowledge of Lyme disease, yet only 14% indicated they often use five or more measures to protect themselves. Factors strongly associated with a high level of Lyme disease knowledge included being 55 or older (Odds Ratio (OR) = 2.04), living on a property with a yard (OR = 3.22), having a high exposure index (OR = 1.59), and knowing someone previously infected with Lyme disease (OR = 2.05). Strong associations with the adoption of a high number of protective behaviours were observed with membership in a non-Indigenous racialized group (OR = 1.70), living on a property with a yard (OR = 2.37), previous infection with Lyme disease (OR = 2.13), prior tick bite exposure (OR = 1.62), and primarily occupational activity in wooded areas (OR = 2.31). CONCLUSIONS: This study highlights the dynamics between Lyme disease knowledge, patterns of exposure risk awareness, and vigilance of personal protection in a Canadian region with emerging Lyme disease risk. Notably, this study identified gaps between perceived local risk and protective behaviours, presenting opportunities for targeted enhanced communication efforts in areas of Lyme disease emergence.

Blood Pressure Management in Early Aneurysmal Subarachnoid Hemorrhage: A National Cross-Sectional Survey of Canadian Intensivists and Cerebrovascular Neurosurgeons.

BACKGROUND: In aneurysmal subarachnoid hemorrhage (aSAH), rebleeding of the culprit aneurysm is associated with significant morbidity and mortality. Blood pressure reduction to specific target levels, with the goal of preventing rebleeding, has been a mainstay of care prior to definitively securing the aneurysm. Clinical practice guidelines have recently changed and no longer recommend specific blood pressure targets. This survey aims to identify the reported practice patterns and beliefs regarding blood pressure management during the early phase of aSAH. METHODS: We conducted a self-administered, Web-based survey of critical care physicians and cerebrovascular neurosurgeons practicing in Canada. The questionnaire contained 21 items, including 3 case-based scenarios to elicit blood pressure target selection, both before and after aneurysm securing. RESULTS: In the presecured period, systolic blood pressures of 160 mm Hg (50% [144 of 287]) and 140 mm Hg (42% [120 of 287]) were the most frequently selected upper-limit targets. In the postsecured period, a systolic blood pressure of 180 mm Hg (32% [93 of 287]) was the most frequently selected upper-limit target, but there was a wide distribution of targets selected across all three cases ranging from 100 to > 200 mm Hg. A mean arterial pressure of 65 mm Hg was the most common lower-limit target in both the presecured and postsecured periods. There was little change in blood pressure targets with increasing clinical severity. Predictors of higher or lower blood pressure target selection and barriers to implementation of the desired target were identified. CONCLUSIONS: During the presecured period, nearly half of the reported upper-limit blood pressure targets are lower than previous guideline recommendations. These targets remain consistent despite increasing clinical severity and could potentially exacerbate cerebral ischemia and negatively impact clinical outcomes. In the postsecured period, there is wide variation in the reported blood pressure targets. A clinical trial is urgently needed to guide decision-making.

Short Timeframe Prediction of Kidney Failure among Patients with Advanced Chronic Kidney Disease.

BACKGROUND: Development of a short timeframe (6-12 months) kidney failure risk prediction model may serve to improve transitions from advanced chronic kidney disease (CKD) to kidney failure and reduce rates of unplanned dialysis. The optimal model for short timeframe kidney failure risk prediction remains unknown. METHODS: This retrospective study included 1757 consecutive patients with advanced CKD (mean age 66 years, estimated glomerular filtration rate 18 mL/min/1.73 m2). We compared the performance of Cox regression models using (a) baseline variables alone, (b) time-varying variables and machine learning models, (c) random survival forest, (d) random forest classifier in the prediction of kidney failure over 6/12/24 months. Performance metrics included area under the receiver operating characteristic curve (AUC-ROC) and maximum precision at 70% recall (PrRe70). Top-performing models were applied to 2 independent external cohorts. RESULTS: Compared to the baseline Cox model, the machine learning and time-varying Cox models demonstrated higher 6-month performance [Cox baseline: AUC-ROC 0.85 (95% CI 0.84-0.86), PrRe70 0.53 (95% CI 0.51-0.55); Cox time-varying: AUC-ROC 0.88 (95% CI 0.87-0.89), PrRe70 0.62 (95% CI 0.60-0.64); random survival forest: AUC-ROC 0.87 (95% CI 0.86-0.88), PrRe70 0.61 (95% CI 0.57-0.64); random forest classifier AUC-ROC 0.88 (95% CI 0.87-0.89), PrRe70 0.62 (95% CI 0.59-0.65)]. These trends persisted, but were less pronounced, at 12 months. The random forest classifier was the highest performing model at 6 and 12 months. At 24 months, all models performed similarly. Model performance did not significantly degrade upon external validation. CONCLUSIONS: When predicting kidney failure over short timeframes among patients with advanced CKD, machine learning incorporating time-updated data provides enhanced performance compared with traditional Cox models.

Resident Match During the COVID Pandemic: How Have Neurology Programs Adapted? - A Survey.

BACKGROUND: We aimed to evaluate the perceived effectiveness of interventions implemented by Canadian neurology residency programs for the 2020-2021 iteration of the Canadian Resident Matching Service (CaRMS). METHODS: A cross-sectional survey was distributed to Canadian neurology residency programs and final-year Canadian medical students who applied to at least one neurology program during the 2020-2021 match cycle. The surveys evaluated pre-interview and interview period interventions implemented by Canadian neurology residency programs and accessed by medical students. RESULTS: Thirty-five medical students and 13 out of 15 institutions in Canada with neurology residency programs responded to the survey. Multiple adaptations were implemented, including social media advertisement, web-based platforms, pre-interview information sessions, and teaching sessions, with all surveyed programs implementing at least two virtual interventions. We found that all interventions were perceived as adequate by a majority (>60%) of medical students, with pre-interview period virtual information sessions perceived as effective by the largest proportion of respondents. All Canadian neurology residency programs held virtual interviews for the 2020-2021 cycle, and most programs utilized the same interview structure as prior years. There was discordance between residency program stakeholders and medical students on the most helpful interview period modality. Medical students found the hospital tours and information sessions most valuable, whereas program stakeholders perceived the virtual socials and interviews as most helpful. CONCLUSION: The COVID-19 pandemic has led to innovative adaptations implemented by Canadian neurology residency programs, which were seen as effective by both medical students and program stakeholders.

Post-operative surveillance for somatotroph, lactotroph and non-functional pituitary adenomas after curative resection: a systematic review.

CONTEXT: Pituitary tumors are the third most common brain tumor and yet there is no standardization of the surveillance schedule and assessment modalities after transsphenoidal surgery. EVIDENCE ACQUISITION: OVID, EMBASE and the Cochrane Library databases were systematically screened from database inception to March 5, 2020. Inclusion and exclusion criteria were designed to capture studies examining detection of pituitary adenoma recurrence in patients 18 years of age and older following surgical resection with curative intent. EVIDENCE SYNTHESIS: A total of 7936 abstracts were screened, with 812 articles reviewed in full text and 77 meeting inclusion criteria for data extraction. A pooled analysis demonstrated recurrence rates at 1 year, 5 years and 10 years for non-functioning pituitary adenomas (NFPA; N = 3533 participants) were 1%, 17%, and 33%, for prolactin-secreting adenomas (PSPA; N = 1295) were 6%, 21%, and 28%, and for growth-hormone pituitary adenomas (GHPA; N = 1257) were 3%, 8% and 13%, respectively. Rates of recurrence prior to 1 year were 0% for NFPA, 1-2% for PSPA and 0% for GHPA. The mean time to disease recurrence for NFPA, PSPA and GHPA were 4.25, 2.52 and 4.18 years, respectively. CONCLUSIONS: This comprehensive review of the literature quantified the recurrence rates for commonly observed pituitary adenomas after transsphenoidal surgical resection with curative intent. Our findings suggest that surveillance within 1 year may be of low yield. Further clinical trials and cohort studies investigating cost-effectiveness of surveillance schedules and impact on quality of life of patients under surveillance will provide further insight to optimize follow-up.

Risk for Recurrent Venous Thromboembolism in Patients With Subsegmental Pulmonary Embolism Managed Without Anticoagulation : A Multicenter Prospective Cohort Study.

BACKGROUND: The incidence of pulmonary embolism has been increasing, but its case-fatality rate is decreasing, suggesting a lesser severity of illness. The clinical importance of patients with pulmonary embolism isolated to the subsegmental vessels is unknown. OBJECTIVE: To determine the rate of recurrent venous thromboembolism in patients with subsegmental pulmonary embolism managed without anticoagulation. DESIGN: Multicenter prospective cohort study. (ClinicalTrials.gov: NCT01455818). SETTING: Eighteen sites between February 2011 and February 2021. PATIENTS: Patients with isolated subsegmental pulmonary embolism. INTERVENTION: At diagnosis, patients underwent bilateral lower-extremity venous ultrasonography, which was repeated 1 week later if results were negative. Patients without deep venous thrombosis did not receive anticoagulant therapy. MEASUREMENTS: The primary outcome was recurrent venous thromboembolism during the 90-day follow-up period. RESULTS: Recruitment was stopped prematurely because the predefined stopping rule was met after 292 of a projected 300 patients were enrolled. Of the 266 patients included in the primary analysis, the primary outcome occurred in 8 patients, for a cumulative incidence of 3.1% (95% CI, 1.6% to 6.1%) over the 90-day follow-up. The incidence of recurrent venous thromboembolism was 2.1% (CI, 0.8% to 5.5%) and 5.7% (CI, 2.2% to 14.4%) over the 90-day follow-up in patients with single and multiple isolated subsegmental pulmonary embolism, respectively. No patients had a fatal recurrent pulmonary embolism. LIMITATION: The study was restricted to patients with low-risk subsegmental pulmonary embolism. CONCLUSION: Overall, patients with subsegmental pulmonary embolism who did not have proximal deep venous thrombosis had a higher-than-expected rate of recurrent venous thromboembolism. PRIMARY FUNDING SOURCE: Heart and Stroke Foundation of Canada and French Ministry of Health Programme Hospitalier de Recherche Clinique.

Immunosuppressant Medication Use in Patients with Kidney Allograft Failure: A Prospective Multicenter Canadian Cohort Study.

BACKGROUND: Patients with kidney transplant failure have a high risk of hospitalization and death due to infection. The optimal use of immunosuppressants after transplant failure remains uncertain and clinical practice varies widely. METHODS: This prospective cohort study enrolled patients within 21 days of starting dialysis after transplant failure in 16 Canadian centers. Immunosuppressant medication use, death, hospitalized infection, rejection of the failed allograft, and anti-HLA panel reactive antibodies were determined at 1, 3, 6, and 12 months and and then twice yearly until death, repeat transplantation, or loss to follow-up. RESULTS: The 269 study patients were followed for a median of 558 days. There were 33 deaths, 143 patients hospitalized for infection, and 21 rejections. Most patients (65%) continued immunosuppressants, 20% continued prednisone only, and 15% discontinued all immunosuppressants. In multivariable models, patients who continued immunosuppressants had a lower risk of death (hazard ratio [HR], 0.40; 95% confidence interval [CI], 0.17 to 0.93) and were not at increased risk of hospitalized infection (HR, 1.81; 95% CI, 0.82 to 4.0) compared with patients who discontinued all immunosuppressants or continued prednisone only. The mean class I and class II panel reactive antibodies increased from 11% to 27% and from 25% to 47%, respectively, but did not differ by immunosuppressant use. Continuation of immunosuppressants was not protective of rejection of the failed allograft (HR, 0.81; 95% CI, 0.22 to 2.94). CONCLUSIONS: Prolonged use of immunosuppressants >1 year after transplant failure was not associated with a higher risk of death or hospitalized infection but was insufficient to prevent higher anti-HLA antibodies or rejection of the failed allograft.

Is There Evidence of P-Hacking in Imaging Research?

BACKGROUND: P-hacking, the tendency to run selective analyses until they become significant, is prevalent in many scientific disciplines. PURPOSE: This study aims to assess if p-hacking exists in imaging research. METHODS: Protocol, data, and code available here https://osf.io/xz9ku/?view_only=a9f7c2d841684cb7a3616f567db273fa. We searched imaging journals Ovid MEDLINE from 1972 to 2021. Text mining using Python script was used to collect metadata: journal, publication year, title, abstract, and P-values from abstracts. One P-value was randomly sampled per abstract. We assessed for evidence of p-hacking using a p-curve, by evaluating for a concentration of P-values just below .05. We conducted a one-tailed binomial test (α = .05 level of significance) to assess whether there were more P-values falling in the upper range (e.g., .045 < P < .05) than in the lower range (e.g., .04 < P < .045). To assess variation in results introduced by our random sampling of a single P-value per abstract, we repeated the random sampling process 1000 times and pooled results across the samples. Analysis was done (divided into 10-year periods) to determine if p-hacking practices evolved over time. RESULTS: Our search of 136 journals identified 967,981 abstracts. Text mining identified 293,687 P-values, and a total of 4105 randomly sampled P-values were included in the p-hacking analysis. The number of journals and abstracts that were included in the analysis as a fraction and percentage of the total number was, respectively, 108/136 (80%) and 4105/967,981 (.4%). P-values did not concentrate just under .05; in fact, there were more P-values falling in the lower range (e.g., .04 < P < .045) than falling just below .05 (e.g., .045 < P < .05), indicating lack of evidence for p-hacking. Time trend analysis did not identify p-hacking in any of the five 10-year periods. CONCLUSION: We did not identify evidence of p-hacking in abstracts published in over 100 imaging journals since 1972. These analyses cannot detect all forms of p-hacking, and other forms of bias may exist in imaging research such as publication bias and selective outcome reporting.

Multicenter Evaluation of Multiparametric MRI Clear Cell Likelihood Scores in Solid Indeterminate Small Renal Masses.

Background Solid small renal masses (SRMs) (≤4 cm) represent benign and malignant tumors. Among SRMs, clear cell renal cell carcinoma (ccRCC) is frequently aggressive. When compared with invasive percutaneous biopsies, the objective of the proposed clear cell likelihood score (ccLS) is to classify ccRCC noninvasively by using multiparametric MRI, but it lacks external validation. Purpose To evaluate the performance of and interobserver agreement for ccLS to diagnose ccRCC among solid SRMs. Materials and Methods This retrospective multicenter cross-sectional study included patients with consecutive solid (≥25% approximate volume enhancement) SRMs undergoing multiparametric MRI between December 2012 and December 2019 at five academic medical centers with histologic confirmation of diagnosis. Masses with macroscopic fat were excluded. After a 1.5-hour training session, two abdominal radiologists per center independently rendered a ccLS for 50 masses. The diagnostic performance for ccRCC was calculated using random-effects logistic regression modeling. The distribution of ccRCC by ccLS was tabulated. Interobserver agreement for ccLS was evaluated with the Fleiss κ statistic. Results A total of 241 patients (mean age, 60 years ± 13 [SD]; 174 men) with 250 solid SRMs were evaluated. The mean size was 25 mm ± 8 (range, 10-39 mm). Of the 250 SRMs, 119 (48%) were ccRCC. The sensitivity, specificity, and positive predictive value for the diagnosis of ccRCC when ccLS was 4 or higher were 75% (95% CI: 68, 81), 78% (72, 84), and 76% (69, 81), respectively. The negative predictive value of a ccLS of 2 or lower was 88% (95% CI: 81, 93). The percentages of ccRCC according to the ccLS were 6% (range, 0%-18%), 38% (range, 0%-100%), 32% (range, 60%-83%), 72% (range, 40%-88%), and 81% (range, 73%-100%) for ccLSs of 1-5, respectively. The mean interobserver agreement was moderate (κ = 0.58; 95% CI: 0.42, 0.75). Conclusion The clear cell likelihood score applied to multiparametric MRI had moderate interobserver agreement and differentiated clear cell renal cell carcinoma from other solid renal masses, with a negative predictive value of 88%. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Mileto and Potretzke in this issue.

Randomized trial of surveillance with abbreviated MRI in women with a personal history of breast cancer- impact on patient anxiety and cancer detection.

BACKGROUND: Abbreviated breast MRI (A-MRI) substantially reduces the image acquisition and reading times and has been reported to have similar diagnostic accuracy as a full diagnostic protocol but has not been evaluated prospectively with respect to impact on psychological distress in women with a prior history of breast cancer (PHBC). This study aimed to determine if surveillance mammography (MG) plus A-MRI reduced psychological distress and if A-MRI improved cancer detection rates (CDR) as compared to MG alone. METHODS: This prospective controlled trial of parallel design was performed at a tertiary cancer center on asymptomatic women with PHBC who were randomized into two groups: routine surveillance with MG or intervention of MG plus A-MRI in a 1:1 ratio. Primary outcome was anxiety measured by four validated questionnaires at three different time-points during the study. Other parameters including CDR and positive predictive value for biopsy (PPV3) were compared between imaging modalities of MG and A-MRI. Tissue diagnoses or 1 year of follow-up were used to establish the reference standard. Linear mixed models were used to analyze anxiety measures and Fisher's exact test to compare imaging outcomes. RESULTS: One hundred ninety-eight patients were allocated to either MG alone (94) or MG plus A-MRI (104). No significant group difference emerged for improvement in trait anxiety, worry and perceived health status (all Time-by-surveillance group interaction ps > .05). There was some advantage of A-MRI in reducing state anxiety at Time 2 (p < .05). Anxiety scores in all questionnaires were similarly elevated in both groups (50.99 ± 4.6 with MG alone vs 51.73 ± 2.56 with MG plus A-MRI, p > 0.05) and did not change over time. A-MRI detected 5 invasive cancers and 1 ductal carcinoma in situ (DCIS), and MG detected 1 DCIS. A-MRI had higher incremental CDR (48/1000(5/104) vs MG 5/1000(1/198, p = 0.01)) and higher biopsy rates (19.2% (20/104) vs MG 2.1% (2/94), p < 0.00001) with no difference in PPV3 (A-MRI 28.6% (6/21) vs MG 16.7% (1/6, p > .05). CONCLUSION: There was no significant impact of A-MRI to patient anxiety or perceived health status. Compared to MG alone, A-MRI had significantly higher incremental cancer detection in PHBC. Despite a higher rate of biopsies, A-MRI had no demonstrable impact on anxiety, worry, and perceived health status. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT02244593 ). Prospectively registered on Sept. 14, 2014.

Evaluation of the T2-weighted (T2W) adrenal MRI calculator to differentiate adrenal pheochromocytoma from lipid-poor adrenal adenoma.

OBJECTIVES: To evaluate the T2-weighted (T2W) MRI calculator to differentiate adrenal pheochromocytoma from lipid-poor adrenal adenoma. METHODS: Twenty-nine consecutive pheochromocytomas resected between 2010 and 2019 were compared to 23 consecutive lipid-poor adrenal adenomas. Three blinded radiologists (R1, R2, R3) subjectively evaluated T2W signal intensity and heterogeneity and extracted T2W signal intensity ratio (SIR) and entropy. These values were imputed into a quantitative and qualitative T2W adrenal MRI calculator (logistic regression model encompassing T2W SIR + entropy and subjective SI [relative to renal cortex] and heterogeneity) using a predefined threshold to differentiate metastases from adenoma and accuracy derived by a 2 × 2 table analysis. RESULTS: Subjectively, pheochromocytomas were brighter (p < 0.001) and more heterogeneous (p < 0.001) for all three radiologists. Inter-observer agreement was fair-to-moderate for T2W signal intensity (K = 0.37-0.46) and fair for heterogeneity (K = 0.24-0.32). Pheochromocytoma had higher T2W-SI-ratio (p < 0.001) and entropy (p < 0.001) for all three readers. The quantitative calculator differentiated pheochromocytoma from adenoma with high sensitivity, specificity, and accuracy (100% [95% confidence intervals 88-100%], 87% [66-97%], and 94% [86-100%] R1; 93% [77-99%], 96% [78-100%], and 94% [88-100%] R2; 97% [82-100%], 96% [78-100%], and 96% [91-100% R3]). The qualitative calculator was specific with lower sensitivity and overall accuracy (48% [29-68%], 100% [85-100%], and 74% [65-83%] R1; 45% [26-64%], 100% [85-100%], and 72% [63-82%] R2; 59% [39-77%], 100% [85-100%], and 79% [70-88% R3]). CONCLUSIONS: T2W signal intensity and heterogeneity differ, subjectively and quantitatively, in pheochromocytoma compared to adenoma. Use of a quantitative T2W adrenal calculator which combines T2W signal intensity ratio and entropy was highly accurate to diagnose pheochromocytoma outperforming subjective analysis. KEY POINTS: • Pheochromocytomas have higher T2-weighted signal intensity and are more heterogeneous compared to lipid-poor adrenal adenomas evaluated subjectively and quantitatively. • The quantitative T2-weighted adrenal MRI calculator, a logistic regression model combining T2-weighted signal intensity ratio and entropy, is highly accurate for diagnosis of pheochromocytoma. • The qualitative T2-weighed adrenal MRI calculator had high specificity but lower sensitivity and overall accuracy compared to quantitative assessment and agreement was only fair-to-moderate.