John H. Shin

Insulin Pump Therapy With Automated Insulin Suspension in Response to Hypoglycemia: Reduction in nocturnal hypoglycemia in those at greatest risk

OBJECTIVE To evaluate a sensor-augmented insulin pump with a low glucose suspend (LGS) feature that automatically suspends basal insulin delivery for up to 2 h in response to sensor-detected hypoglycemia. RESEARCH DESIGN AND METHODS The LGS feature of the Paradigm Veo insulin pump (Medtronic, Inc., Northridge, CA) was tested for 3 weeks in 31 adults with type 1 diabetes. RESULTS There were 166 episodes of LGS: 66% of daytime LGS episodes were terminated within 10 min, and 20 episodes lasted the maximum 2 h. LGS use was associated with reduced nocturnal duration ≤2.2 mmol/L in those in the highest quartile of nocturnal hypoglycemia at baseline (median 46.2 vs. 1.8 min/day, P = 0.02 [LGS-OFF vs. LGS-ON]). Median sensor glucose was 3.9 mmol/L after 2-h LGS and 8.2 mmol/L at 2 h after basal restart. CONCLUSIONS Use of an insulin pump with LGS was associated with reduced nocturnal hypoglycemia in those at greatest risk and was well accepted by patients.

The Accuracy and Efficacy of Real-Time Continuous Glucose Monitoring Sensor in Patients with Type 1 Diabetes

BACKGROUND The accuracy and efficacy of the Medtronic Diabetes (Northridge, CA) Real-Time (RT)-Continuous Glucose Monitoring (CGM) sensor were analyzed in 72 subjects with type 1 diabetes. METHODS This was a retrospective analysis of 60,050 temporally paired data points (sensor and glucose meter values) obtained during the course of an outpatient ambulatory study evaluating the efficacy of a sensor-augmented pump system in adults and adolescents. Subjects uploaded sensor values and self-monitoring blood glucose data to the CareLink Clinical Application (Medtronic Diabetes) via the Internet, every 2 weeks during the course of the study. RESULTS The overall percentage of sensor readings within +/-20% or +/-30% agreement of reference glucose readings was 75.6% and 86.8%, respectively. The highest rate of agreement occurred in the 240-400 mg/dL range, where 79.9% of sensor readings were within +/-20% of meter values and 91.5% of sensor readings were within 30% of meter values. The mean absolute relative difference for all subjects was 15.8%, and the median absolute relative difference was 10.9%. The bias was -2.13 mg/dL. Paired glucose measurements from the RT-CGM and meter demonstrated that 95.9% of paired points in the overall subject population fell in zones A and B of the Clarke Error Grid. Consensus Error Grid Analysis established that 99.2% of paired data points were in zones A and B. CONCLUSIONS This study reports the accuracy of a continuous glucose sensor with a large number of paired data points (60,050). RT-CGM is safe and well tolerated and provides readings that are in close agreement with glucose meter values.

Reduction in Duration of Hypoglycemia by Automatic Suspension of Insulin Delivery: The In-Clinic ASPIRE Study

BACKGROUND The efficacy of automatic suspension of insulin delivery in induced hypoglycemia among subjects with type 1 diabetes was evaluated. SUBJECTS AND METHODS In this randomized crossover study, subjects used a sensor-augmented insulin pump system with a low glucose suspend (LGS) feature that automatically stops insulin delivery for 2 h following a sensor glucose (SG) value ≤70 mg/dL. Subjects fasted overnight and exercised until their plasma glucose (measured with the YSI 2300 STAT Plus™ glucose and lactate analyzer [YSI Life Sciences, Yellow Springs, OH]) value reached ≤85 mg/dL on different occasions separated by washout periods lasting 3-10 days. Exercise sessions were done with the LGS feature turned on (LGS-On) or with continued insulin delivery regardless of SG value (LGS-Off). The order of LGS-On and LGS-Off sessions was randomly assigned. YSI glucose data were used to compare the duration and severity of hypoglycemia from successful LGS-On and LGS-Off sessions and to estimate the risk of rebound hyperglycemia after pump suspension. RESULTS Fifty subjects attempted 134 sessions, 98 of which were successful. The mean±SD hypoglycemia duration was less during LGS-On than during LGS-Off sessions (138.5±76.68 vs. 170.7±75.91 min, P=0.006). During LGS-On compared with LGS-Off sessions, mean nadir YSI glucose was higher (59.5±5.72 vs. 57.6±5.69 mg/dL, P=0.015), as was mean end-observation YSI glucose (91.4±41.84 vs. 66.2±13.48 mg/dL, P<0.001). Most (53.2%) end-observation YSI glucose values in LGS-On sessions were in the 70-180 mg/dL range, and none was >250 mg/dL. CONCLUSIONS Automatic suspension of insulin delivery significantly reduced the duration and severity of induced hypoglycemia without causing rebound hyperglycemia.

Day and Night Closed-Loop Control Using the Integrated Medtronic Hybrid Closed-Loop System in Type 1 Diabetes at Diabetes Camp

OBJECTIVE To evaluate the feasibility and efficacy of a fully integrated hybrid closed-loop (HCL) system (Medtronic MiniMed Inc., Northridge, CA), in day and night closed-loop control in subjects with type 1 diabetes, both in an inpatient setting and during 6 days at diabetes camp. RESEARCH DESIGN AND METHODS The Medtronic MiniMed HCL system consists of a fourth generation (4S) glucose sensor, a sensor transmitter, and an insulin pump using a modified proportional-integral-derivative (PID) insulin feedback algorithm with safety constraints. Eight subjects were studied over 48 h in an inpatient setting. This was followed by a study of 21 subjects for 6 days at diabetes camp, randomized to either the closed-loop control group using the HCL system or to the group using the Medtronic MiniMed 530G with threshold suspend (control group). RESULTS The overall mean sensor glucose percent time in range 70–180 mg/dL was similar between the groups (73.1% vs. 69.9%, control vs. HCL, respectively) (P = 0.580). Meter glucose values between 70 and 180 mg/dL were also similar between the groups (73.6% vs. 63.2%, control vs. HCL, respectively) (P = 0.086). The mean absolute relative difference of the 4S sensor was 10.8 ± 10.2%, when compared with plasma glucose values in the inpatient setting, and 12.6 ± 11.0% compared with capillary Bayer CONTOUR NEXT LINK glucose meter values during 6 days at camp. CONCLUSIONS In the first clinical study of this fully integrated system using an investigational PID algorithm, the system did not demonstrate improved glucose control compared with sensor-augmented pump therapy alone. The system demonstrated good connectivity and improved sensor performance.

Safety and efficacy of stereotactic body radiotherapy as primary treatment for vertebral metastases: a multi-institutional analysis

PurposeTo evaluate patient selection criteria, methodology, safety and clinical outcomes of stereotactic body radiotherapy (SBRT) for treatment of vertebral metastases.Materials and methodsEight centers from the United States (n = 5), Canada (n = 2) and Germany (n = 1) participated in the retrospective study and analyzed 301 patients with 387 vertebral metastases. No patient had been exposed to prior radiation at the treatment site. All patients were treated with linac-based SBRT using cone-beam CT image-guidance and online correction of set-up errors in six degrees of freedom.Results387 spinal metastases were treated and the median follow-up was 11.8 months. The median number of consecutive vertebrae treated in a single volume was one (range, 1-6), and the median total dose was 24 Gy (range 8-60 Gy) in 3 fractions (range 1-20). The median EQD210 was 38 Gy (range 12-81 Gy). Median overall survival (OS) was 19.5 months and local tumor control (LC) at two years was 83.9%. On multivariate analysis for OS, male sex (p < 0.001; HR = 0.44), performance status <90 (p < 0.001; HR = 0.46), presence of visceral metastases (p = 0.007; HR = 0.50), uncontrolled systemic disease (p = 0.007; HR = 0.45), >1 vertebra treated with SBRT (p = 0.04; HR = 0.62) were correlated with worse outcomes. For LC, an interval between primary diagnosis of cancer and SBRT of ≤30 months (p = 0.01; HR = 0.27) and histology of primary disease (NSCLC, renal cell cancer, melanoma, other) (p = 0.01; HR = 0.21) were correlated with worse LC. Vertebral compression fractures progressed and developed de novo in 4.1% and 3.6%, respectively. Other adverse events were rare and no radiation induced myelopathy reported.ConclusionsThis multi-institutional cohort study reports high rates of efficacy with spine SBRT. At this time the optimal fractionation within high dose practice is unknown.

Vertebral compression fractures after stereotactic body radiation therapy: a large, multi-institutional, multinational evaluation

OBJECTIVE The purpose of this study was to identify factors contributing to an increased risk for vertebral compression fracture (VCF) following stereotactic body radiation therapy (SBRT) for spinal tumors. METHODS A total of 594 tumors were treated with spinal SBRT as primary treatment or re-irradiation at 8 different institutions as part of a multi-institutional research consortium. Patients underwent LINAC-based, image-guided SBRT to a median dose of 20 Gy (range 8-40 Gy) in a median of 1 fraction (range 1-5 fractions). Median patient age was 62 years. Seventy-one percent of tumors were osteolytic, and a preexisting vertebral compression fracture (VCF) was present in 24% of cases. Toxicity was assessed following treatment. Univariate and multivariate analyses were performed using a logistic regression method to determine parameters predictive for post-SBRT VCF. RESULTS At a median follow-up of 10.1 months (range 0.03-57 months), 80% of patients had local tumor control. At the time of last imaging follow-up, at a median of 8.8 months after SBRT, 3% had a new VCF, and 2.7% had a progressive VCF. For development of any (new or progressive) VCF following SBRT, the following factors were predictive for VCF on univariate analysis: short interval from primary diagnosis to SBRT (less than 36.8 days), solitary metastasis, no additional bone metastases, no prior chemotherapy, preexisting VCF, no MRI used for target delineation, tumor volume of 37.3 cm(3) or larger, equivalent 2-Gy-dose (EQD2) tumor of 41.8 Gy or more, and EQD2 spinal cord Dmax of 46.1 Gy or more. Preexisting VCF, solitary metastasis, and prescription dose of 38.4 Gy or more were predictive on multivariate analysis. The following factors were predictive of a new VCF on univariate analysis: solitary metastasis, no additional bone metastases, and no MRI used for target delineation. Presence of a solitary metastasis and lack of MRI for target delineation remained significant on multivariate analysis. CONCLUSIONS A VCF following SBRT is more likely to occur following treatment for a solitary spinal metastasis, reflecting a more aggressive treatment approach in patients with adequately controlled systemic disease. Higher prescription dose and a preexisting VCF also put patients at increased risk for post-SBRT VCF. In these patients, pre-SBRT cement augmentation could be considered to decrease the risk of subsequent VCF.

Subconcussive Impact in Sports: A New Era of Awareness

ional athletes vanced degenaradigm shift tion experts. only an all-orso result from al detrimental nto the media veteran footer of the ball were heavier, after a 5-year tensive degenCTE were disted as cause of y” was docuA concussive episode refers to inertially induced duced traumatic alteration of function of the cere associated imaging abnormalities. Appreciation f of gravity linear acceleration, angular velocity, and eration during dynamic motion of the head a emerged recently in the neurosurgical community literature details potential detrimental effects of r cussive episodes in contact sports such as boxin American football (4, 8, 13-15, 25, 32, 35-37), rug 42), hockey (9, 49, 50), and soccer (18, 23, 24, repeat concussive episode before resolution of init symptoms has been associated with fatal cerebral hypothesized “second impact syndrome” (5, 6, 27 prevention efforts in sports have focused on minim lete’s concussive episode risk, and although the e tive subconcussive trauma in contact sports ha creased attention recently, it has yet to be fully add The term dementia pugilistica (22) describes a syndro sive neurodegeneration, first described in retired box repetitive subconcussive head impacts, that shares logic features with Alzheimer disease (1, 2, 11, 31, 3 term replacing dementia pugilistica, chronic traumati pact-inwithout ad center lar accelrain has luminous itive con, 17, 26), 9, 20, 29, 46-48). A ncussion a via the ain injury g an athof repetieived ined. f progresxposed to icopatho. The new phalopathy which is recognized to result from a variety of minor CTE is associated with personality changes, memor parkinsonism, and speech and gait abnormalities. P marks include gross cerebral andmedial temporal lo extensive tau-immunoreactive neurofibrillary tangle 30, 45). Spurred by highly publicized cases of profess who died at a young age and were found to have ad erative brain changes at autopsy, there has been a p among sports medicine and head injury preven An increasing realization is that brain injury is not nothing phenomenon (eg, concussion) but may al accumulated subconcussive impacts. The potenti effect of repetitive heading in soccer was thrust i limelight in 2002 following the death of English baller Jeffrey Astle. Astle had been a prolific head during an era in which the leather balls employed especially in wet conditions. Astle died at age 59 history of rapidly deterioratingmental capacity. Ex erative brain disease and taupathy consistent with covered at autopsy;minor repetitive traumawas sta death, and a verdict of “death by industrial injur ic entity, mented (28). This ruling of cause of death was especially striking

The impact of diabetes mellitus on patients undergoing degenerative cervical spine surgery.

Study Design. Retrospective administrative database analysis. Objective. To determine the impact of glycemic control on perioperative complications and outcomes in patients undergoing degenerative cervical spine surgery. Summary of Background Data. Diabetes mellitus (DM) is a highly prevalent systemic disease that has been shown to increase morbidity and mortality after spine surgery. Few studies have demonstrated negative effects on patients with DM who undergo cervical spine procedures; however, whether glycemic control influences surgical outcome is still unknown. Methods. The Nationwide Inpatient Sample was queried from 2002 to 2011. Patients who underwent cervical spine surgery for degenerative conditions were identified using the International Classification of Diseases Ninth Revision, Clinical Modification, codes. Three surgical cohorts were chosen: controlled diabetic, uncontrolled diabetic, and patients without diabetes. Patient demographics, surgical procedures, perioperative complications and postoperative outcomes were assessed. Results. The prevalence of controlled and uncontrolled diabetic patients undergoing degenerative cervical spine surgery had been increasing significantly from 2002 to 2011. Compared with patients without diabetes, uncontrolled diabetic patients had significantly increased odds of respiratory, cardiac, and genitourinary complications. Uncontrolled diabetic patients also had significantly increased risk of pulmonary embolism and postoperative infection. Uncontrolled diabetic patients had increased risk of inpatient mortality (odds ratio = 6.39, 95% confidence interval = 4.09–10.00, P < 0.0001) and increased mean length of stay (almost 5 d) compared with nondiabetic patients. Similarly, controlled diabetic patients increased the odds of perioperative complications; however not nearly to the same degree. Controlled diabetic patients extended the mean length of stay by almost a day (P < 0.0001) and significantly increased costs compared with nondiabetic patients. Conclusion. Poor glycemic control increases the odds of inpatient mortality and perioperative complications in patients undergoing degenerative cervical spine surgery. Controlling DM before degenerative cervical spine surgery may lead to better outcomes and decreased costs. Level of Evidence: Therapeutic Level 3

Flow-assisted surgical cerebral revascularization

Extracranial-intracranial bypass surgery has advanced from a mere technical feat to a procedure requiring careful patient selection and a justifiable decision-making paradigm. Currently available technologies for flow measurement in the perioperative and intraoperative setting allow a more structured and analytical approach to decision making. The purpose of this report is to review the use of flow measurement in cerebral revascularization, presenting algorithms for flow-assisted surgical planning, technique, and surveillance.

Effects of sensor-augmented pump therapy on glycemic variability in well-controlled type 1 diabetes in the STAR 3 study.

BACKGROUND Compared with multiple daily injections (MDI), sensor-augmented pump (SAP) insulin therapy may reduce glycemic variability and oxidative stress in type 1 diabetes in a glycosylated hemoglobin (A1C)-independent manner. SUBJECTS AND METHODS The STAR 3 study compared SAP with MDI therapy for 1 year. Week-long continuous glucose monitoring studies were conducted at baseline and 1 year for assessment of glycemic variability in both groups. Soluble CD40 ligand (CD40L), a biomarker of inflammation and thrombocyte function, was measured at baseline and 1 year. Subjects were classified according to treatment group and 1-year A1C levels (<6.5%, 6.5-6.9%, 7-7.9%, ≥8%). Glycemic parameters were compared between SAP and MDI subjects in each A1C cohort. RESULTS At 1 year, sensor glucose values at A1C levels ≥6.5% were similar in the SAP and MDI groups. However, sensor glucose SD and coefficient of variation (CV) values were lower at A1C levels <8% among SAP than among MDI subjects; the overall between-group difference was significant for both SD (P<0.01) and CV (P=0.01). The overall mean amplitude of glycemic excursion was similar in MDI and SAP groups (P=0.23). CD40L levels fell over the course of the study in both groups, but the between-group difference was not significant (P=0.18). CD40L concentrations were unrelated to A1C, change in A1C from baseline, or glycemic variability. CONCLUSIONS At comparable A1C levels of <8%, SAP reduced glycemic variability as measured by SD and CV compared with MDI. SAP may provide beneficial reductions in the number and severity of glycemic excursions.