David Asuzu

Normalized Early Postoperative Cortisol and ACTH Values Predict Nonremission After Surgery for Cushing Disease

Context Perioperative increases in adrenocorticotropic hormone (ACTH) and cortisol mimic results of corticotropin-releasing hormone (CRH) stimulation testing. This phenomenon may help identify patients with residual adenoma after transsphenoidal surgery (TSS) for Cushing disease (CD). Objective To predict nonremission after TSS for CD. Design Retrospective case-control study of patients treated at a single center from December 2003 until July 2016. Early and medium-term remission were assessed at 10 days and 11 months. Patients and Setting Two hundred and ninety-one consecutive TSS cases from 257 patients with biochemical evidence of CD seen at a clinical center. Interventions Normalized early postoperative values (NEPVs) for cortisol and ACTH were calculated as immediate postoperative cortisol or ACTH levels minus preoperative post-CRH-stimulation test levels. Main Outcome Measures Prediction of early nonremission was evaluated using logistic regression. Prediction of medium-term remission was assessed using Cox regression. Predictive ability was quantified by area under the receiver operating characteristic curve (AUROC). Results NEPVs for cortisol and ACTH predicted early nonremission [adjusted odds ratio (OR): 1.1; 95% confidence interval (CI): 1.0, 1.1; P = 0.016 and adjusted OR: 1.0; 95% CI: 1.0, 1.0; P = 0.048, respectively]. AUROC for NEPV of cortisol was 0.78 (95% CI: 0.61, 0.95); for NEPV of ACTH, it was 0.80 (95% CI: 0.61, 0.98). NEPVs for cortisol and ACTH predicted medium-term nonremission [hazard ratio (HR): 1.1; 95% CI: 1.0, 1.1; P = 0.023 and HR: 1.0; 95% CI: 1.0, 1.0; P = 0.025, respectively]. Conclusions NEPVs for cortisol and ACTH predicted nonremission after TSS for CD.

Earlier post-operative hypocortisolemia may predict durable remission from Cushing's Disease

CONTEXT Achievement of hypocortisolemia following transsphenoidal surgery (TSS) for Cushings disease (CD) is associated with successful adenoma resection. However, up to one-third of these patients recur. OBJECTIVE We assessed whether delay in reaching post-operative cortisol nadir may delineate patients at risk of recurrence for CD following TSS. METHODS A retrospective review of 257 patients who received 291 TSS procedures for CD at NIH, between 2003 and 2016. Early biochemical remission (serum cortisol nadir <5 μg/dL) was confirmed with endocrinological and clinical follow-up. Recurrence was detected by laboratory testing, clinical stigmata or medication dependence during a median follow-up of 11 months. RESULTS Of the 268 unique admissions, remission was recorded in 241 instances. Recurrence was observed in 9% of these cases with cortisol nadir ≤5 μg/dL and 6% of cases with cortisol nadir ≤2 μg/dL. The timing of hypocortisolemia was critical in detecting late recurrences. Morning POD-1 cortisol <3.3 μg/dL was 100% sensitive in predicting durable remission and morning POD-3 cortisol ≥18.5 μg/dL was 98.6% specific in predicting remote recurrence. AUROC analysis revealed that hypocortisolemia ≤5 µg/dL before 15 h (post-operative) had 95% sensitivity and an NPV of 0.98 for durable remission. Serum cortisol level ≤2 µg/dL, when achieved before 21 h, improved sensitivity to 100%. CONCLUSIONS In our cohort, early, profound hypocortisolemia could be used as a clinical prediction tool for durable remission. Achievement of hypocortisolemia ≤2 µg/dL before 21 post-operative hours appeared to accurately predict durable remission in the intermediate term.

On- versus Off-Hour Patient Cohorts at a Primary Stroke Center: Onset-to-Treatment Duration and Clinical Outcomes after IV Thrombolysis.

BACKGROUND The symptom onset-to-treatment (OTT) duration predicts symptomatic intracerebral hemorrhage (sICH) and adverse outcomes after ischemic stroke. Previous studies found disparities in OTT durations and clinical outcomes between stroke patients with symptom onset during on-hours versus off-hours, which led to the initiation of nationwide efforts to provide consistent 24-hour stroke care. GOAL Our objective is to compare OTT durations and clinical outcomes in ischemic stroke patients whose symptoms originated during on- versus off-hours at a primary stroke center. METHODS We analyzed clinical data from 210 consecutive patients receiving intravenous recombinant tissue plasminogen activator therapy between January 2009 and December 2013 at Yale-New Haven Stroke Center, a primary stroke center. Stroke severity was assessed by baseline National Institutes of Health Stroke Scale (NIHSS) scores. Clinical outcomes were assessed by presence of sICH and by stroke-related fatalities. OTT durations and clinical outcomes were compared using Mann-Whitney tests, 2-sample tests of proportions, and 2-sample t-tests after testing for equal variance. FINDINGS We found no significant differences in OTT durations between on-hour and off-hour patient cohorts (137 minutes versus 145 minutes, P = .53). There were also no differences in stroke severity (mean NIHSS score 12.4 versus 11.3, P = .27), sICH rates (4.6% versus 6.5%, P = .56), or stroke fatality rates (9.2% versus 9.8%, P = .89) between the 2 cohorts. CONCLUSIONS Our results represent progress in emergency response and acute stroke care, and reinforce ongoing nationwide efforts to increase stroke awareness and provide consistent quality care for patients with acute stroke.

Modest Association between the Discharge Modified Rankin Scale Score and Symptomatic Intracerebral Hemorrhage after Intravenous Thrombolysis

BACKGROUND Thirty- and 90-day modified Rankin Scale (mRS) scores are used to monitor adverse outcome or symptomatic intracerebral hemorrhage (sICH) in ischemic stroke patients after intravenous (IV) thrombolytic therapy. Discharge mRS scores are more readily available and could serve as a proxy for 30- or 90-day mRS data. Our goal was to evaluate agreement between the discharge mRS score and sICH. Additionally, we tested for correlations between the discharge mRS score and 8 clinical scores developed to predict sICH or adverse outcomes based on 90-day mRS data. METHODS Clinical data were analyzed from 210 patients receiving IV thrombolysis from January 2009 till December 2013 at the Yale New Haven Hospital. Agreement between sICH and the discharge mRS score was assessed using linear kappa. Eight clinical scores were calculated for each patient and compared with the discharge mRS score by univariate logistic regression. Goodness of fit was tested by receiver operating characteristic (ROC) analysis and by Hosmer-Lemeshow statistics. RESULTS We found only modest agreement between sICH and unfavorable discharge mRS scores (mRS ≥ 5), with kappa .22, P = .0001. All 8 clinical scores tested showed good agreement with discharge mRS score of 5 or more (ROC area >.7). CONCLUSIONS The discharge mRS score shows only modest agreement with sICH and therefore cannot be recommended as a proxy for 30- or 90-day mRS data. However, the discharge mRS score correlates strongly with clinical scores predicting long-term adverse outcome; therefore, assessment of discharge mRS scores may be of some clinical benefit.

Revised cardiac risk index poorly predicts cardiovascular complications after adhesiolysis for small bowel obstruction

Background: The number of patients undergoing preoperative risk stratification in the United States is expected to increase as the population ages. A large percentage of patients undergo some form of preoperative testing, and society guidelines suggest that up to 50% of the testing in lower risk surgical subgroups is unnecessary. The Revised Cardiac Risk Index and the risk calculator of the American College of Surgeons National Surgical Quality Improvement Program are widely used tools as the first step of preoperative cardiac evaluation. The Revised Cardiac Risk Index was developed to fill a need for objective perioperative cardiac risk evaluation. Despite the ease of use of Revised Cardiac Risk Index, it is uncertain if the stratification is accurate for surgical patients because its accuracy in large surgical samples has not been tested. With the National Surgical Quality Improvement Program risk calculator having excellent accuracy in estimating cardiac complications (area under the receiver operating characteristic 0.895), a unique opportunity to test the predictive accuracy of postsurgical cardiac events became available. The purpose of this study is to determine the accuracy of the Revised Cardiac Risk Index for predicting cardiovascular complications after adhesiolysis for small bowel obstruction. Methods: From 2005 to 2015, 34,032 cases of open or laparoscopic adhesiolysis (Current Procedural Terminology codes 44005 and 44180) for small bowel obstruction (International Classification of Diseases, 10th edition [ICD‐10]) were analyzed using the National Surgical Quality Improvement Program dataset. Revised Cardiac Risk Index estimates were calculated for each case and compared to reported cardiovascular complications (myocardial infarction or cardiac arrest) using univariable logistic regression. Overall predictive accuracy was assessed by measuring model discrimination (area under the receiver operating characteristic) and model calibration (Hosmer‐Lemeshow chi‐squared statistics). Results: Although the Revised Cardiac Risk Index predicted cardiovascular complications with an odds ratio of 2.3 and a 95% confidence interval of 1.9 to 2.8 (P < .001) and the Hosmer‐Lemeshow chi‐square was significant (0.22, P = 0.64), the area under the receiver operating characteristic was poor (0.63, 95% confidence interval 0.59–0.67). Conclusion: Despite its relative simplicity, the Revised Cardiac Risk Index performed poorly as a predictor of cardiovascular complications after adhesiolysis for small bowel obstruction. These findings question the utility of the Revised Cardiac Risk Index in this patient population. Future studies should aim to develop models that are computationally simple while retaining predictive accuracy.

Functional and Quality of Life Outcomes of a Hand Surgery Mission to Honduras

Background: The objective of this study was to assess functional, quality of life, and satisfaction outcomes of a hand surgery short-term surgical mission (STSM) to Honduras, and determine whether patient demographics and surgery characteristics during a surgical mission correlate with outcome. Methods: A total of 63 patients who received upper extremity surgery at a week-long hand surgery STSM to Honduras in March 2013 participated in the study. A before-after study design was used. Before receiving surgery, participants completed the Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) questionnaire and the Short Form 12 Health Survey version 2 (SF12v2). Four months postoperatively, participants completed the QuickDASH, SF12v2, and Satisfaction Survey. Results: The mean QuickDASH score significantly improved preoperatively to postoperatively. Demographics measures of age, sex, education, and income did not correlate with QuickDASH scores. Preoperative QuickDASH statistically significantly correlated with surgery type: Carpal tunnel patients had the highest scores (worst functioning). Postoperatively, mass excision and scar contracture/skin graft patients were correlated with the lowest scores. Carpal tunnel and tendon surgery patients showed greatest correlation with QuickDASH improvement. SF-12 scores revealed improvements in mental domains and declines in physical domains. Conclusions: Hand surgery performed during STSMs can result in significant functional improvement, regardless of socioeconomic status. Patients benefited from both simpler and more complex operations. Four months after surgery, general health-related quality of life measures showed improved mental indices. Measured physical indices declined despite improved QuickDASH scores. This may be due to the early general postoperative state. Further outcome research in STSMs in additional countries and specialties is required to expand our conclusions to other STSM contexts and guide best practices in STSMs.

A simple predictor of post-operative complications after open surgical adhesiolysis for small bowel obstruction

BACKGROUND Small bowel obstruction is common and often requires surgical management. Simple preoperative models are lacking to predict post-operative complications after surgical management of adhesive small bowel obstruction. METHODS We retrospectively analyzed data from 15,036 patients who underwent open lysis of adhesions for small bowel obstruction from 2005 to 2013 using the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database. Predictors of post-operative complications were identified using logistic regression. Predictive models were compared using areas under the receiver operating characteristic curves (AUROC). RESULTS A three-parameter model was constructed, termed FAS: Functional status, American Society of Anesthesiologists (ASA) classification, and prior Sepsis. FAS predicted post-operative complications with odds ratio (OR) 1.11, 95% CI (1.10, 1.12), P < 0.001 and AUROC of 0.69, 95% CI (0.67, 0.70). CONCLUSIONS FAS predicts post-operative complications after open lysis of adhesions using three readily available clinical parameters.

Risk rtPA: An iOS mobile application based on TURN for predicting 90-day outcome after IV thrombolysis

OBJECTIVE We recently developed Thrombolysis risk Using mRS and NIHSS (TURN), a simple score using only prestroke mRS scores and admission NIHSS scores to predict 90-day outcome after IV thrombolysis in ischemic stroke patients. Our purpose was to develop and test a mobile application for utilization of TURN at the bedside. METHODS We developed Risk rtPA, an iOS mobile application based on TURN for prediction of 90-day excellent and severe outcome after IV thrombolysis. Excellent outcome was defined as 90-day mRS≤1. Severe outcome was defined as 90-day mRS≥5. Predictors for excellent and severe outcome were calculated using the inverse logit of -TURN and TURN respectively. We retrospectively validated our mobile application using data from 303 patients who received IV rt-PA during the NINDS rt-PA trial. Sensitivity and specificity analyses were performed using receiver operating characteristic (ROC) curves. RESULTS Prediction of excellent and severe outcome using Risk rtPA followed an S-shaped curve as expected. We confirmed this finding using data from the NINDS trial. Cutoffs selected after ROC analysis predicted severe outcome with sensitivity of 94.4% and specificity of 52.2%, and excellent outcome with specificity of 83.9% and sensitivity of 61.2%. CONCLUSION The Risk rtPA mobile application predicted 90-day excellent and severe outcome in most clinically relevant cases. This mobile application brings the TURN score to the bedside for prediction of 90-day outcome in ischemic stroke patients being evaluated for IV thrombolysis.

Validation of TURN, a simple predictor of symptomatic intracerebral hemorrhage after IV thrombolysis.

OBJECTIVE We recently described TURN (Thrombolysis risk Using mRS and NIHSS), a computationally simple tool for predicting symptomatic intracerebral hemorrhage (sICH) after IV thrombolysis (rt-PA). Our objective was to compare TURN to existing scores for predicting sICH. METHODS Our internal dataset consisted of 210 ischemic stroke patients receiving IV rt-PA from January 2009 until July 2013 at Yale New Haven Hospital. Our external dataset included 303 patients who received IV rt-PA during the NINDS rt-PA trial. Predictive ability and goodness of fit were quantified by odds ratios (OR) and areas under the receiver operating characteristic curve (AUROC), and compared using unequal variance two-sample t-tests. RESULTS TURN predicted sICH with a higher OR than ASTRAL in the internal dataset (2.72 versus 1.10, P=0.05). We found no other significant differences in OR or AUROC between TURN and other scores in both datasets. CONCLUSION Despite its computational simplicity, TURN predicts sICH with accuracy comparable to existing scores.