Citations

Objective: To evaluate glycemic outcomes in the Wireless Innovation for Seniors with Diabetes Mellitus (WISDM) randomized clinical trial (RCT) participants during an observational extension phase. Research Design and Methods: WISDM RCT was a 26-week RCT comparing continuous glucose monitoring (CGM) with blood glucose monitoring (BGM) in 203 adults aged ≥60 years with type 1 diabetes. Of the 198 participants who completed the RCT, 100 (98%) CGM group participants continued CGM (CGM-CGM cohort) and 94 (98%) BGM group participants initiated CGM (BGM-CGM cohort) for an additional 26 weeks. Results: CGM was used a median of >90% of the time at 52 weeks in both cohorts. In the CGM-CGM cohort, median time <70 mg/dL decreased from 5.0% at baseline to 2.6% at 26 weeks and remained stable with a median of 2.8% at 52 weeks ( P < 0.001 baseline to 52 weeks). Participants spent more time in range 70–180 mg/dL (TIR) (mean 56% vs. 64%; P < 0.001) and had lower hemoglobin A1c (HbA1c) (mean 7.6% [59 mmol/mol] vs. 7.4% [57 mmol/mol]; P = 0.01) from baseline to 52 weeks. In BGM-CGM, from 26 to 52 weeks median time <70 mg/dL decreased from 3.9% to 1.9% ( P < 0.001), TIR increased from 56% to 60% ( P = 0.006) and HbA1c decreased from 7.5% (58 mmol/mol) to 7.3% (57 mmol/mol) ( P = 0.025). In BGM-CGM, a severe hypoglycemic event was reported for nine participants while using BGM during the RCT and for two participants during the extension phase with CGM ( P = 0.02). Conclusions: CGM use reduced hypoglycemia without increasing hyperglycemia in older adults with type 1 diabetes. These data provide further evidence for fully integrating CGM into clinical practice. Clinicaltrials.gov (NCT03240432)

Objective: Evaluating the feasibility of closed-loop insulin delivery with a zone model predictive control (zone-MPC) algorithm designed for pregnancy complicated by type 1 diabetes (T1D). Research Design and Methods: Pregnant women with T1D from 14 to 32 weeks gestation already using continuous glucose monitor (CGM) augmented pump therapy were enrolled in a 2-day multicenter supervised outpatient study evaluating pregnancy-specific zone-MPC based closed-loop control (CLC) with the interoperable artificial pancreas system (iAPS) running on an unlocked smartphone. Meals and activities were unrestricted. The primary outcome was the CGM percentage of time between 63 and 140 mg/dL compared with participants' 1-week run-in period. Early (2-h) postprandial glucose control was also evaluated. Results: Eleven participants completed the study (age: 30.6 ± 4.1 years; gestational age: 20.7 ± 3.5 weeks; weight: 76.5 ± 15.3 kg; hemoglobin A1c: 5.6% ± 0.5% at enrollment). No serious adverse events occurred. Compared with the 1-week run-in, there was an increased percentage of time in 63–140 mg/dL during supervised CLC (CLC: 81.5%, run-in: 64%, P = 0.007) with less time >140 mg/dL (CLC: 16.5%, run-in: 30.8%, P = 0.029) and time <63 mg/dL (CLC: 2.0%, run-in:5.2%, P = 0.039). There was also less time <54 mg/dL (CLC: 0.7%, run-in:1.6%, P = 0.030) and >180 mg/dL (CLC: 4.9%, run-in: 13.1%, P = 0.032). Overnight glucose control was comparable, except for less time >250 mg/dL (CLC: 0%, run-in:3.9%, P = 0.030) and lower glucose standard deviation (CLC: 23.8 mg/dL, run-in:42.8 mg/dL, P = 0.007) during CLC. Conclusion: In this pilot study, use of the pregnancy-specific zone-MPC was feasible in pregnant women with T1D. Although the duration of our study was short and the number of participants was small, our findings add to the limited data available on the use of CLC systems during pregnancy (NCT04492566).

Objective: To evaluate the predictors of remnant tumor regrowth and need for salvage therapy after less than gross total resection (GTR) of vestibular schwannoma (VS). Study Design: Retrospective chart review. Setting: Tertiary neurotologic referral center. Patients: Patients who underwent VS resection between 2008 and 2019 either with GTR, near total resection (NTR), and subtotal resection (STR). Interventions: Microsurgical resection, salvage radiosurgery. Main Outcome Measures: Regrowth free interval, salvage free interval, tumor doubling rate. Results: Three hundred eighty five cases (GTR = 236, NTR = 77, and STR = 71) from 2008 to 2019 were included. STR cohort had much larger and complex tumors with significant differences in tumor volume, ventral extension and brainstem compression (p < 0.001). On single predictor analysis, tumor volume, ventral extension, brainstem compression as well as STR strategy was associated with significant increased risk of regrowth and need for salvage therapy. Multivariate analysis revealed STR strategy as significant predictor of regrowth (hazard ratio 3.79, p < 0.0005). Absolute remnant volume and extent of resection (EOR) did not predict regrowth. A small proportion of cases (NTR = 4%, STR = 15%) eventually needed salvage radiosurgery with excellent ultimate local tumor control with no known recurrence to date. Conclusions: Conservative surgical strategy employing NTR or STR can be employed safely in large and complex VS. While there is increased risk of regrowth in the STR cohort, excellent local control can be achieved with appropriate use of salvage radiosurgery. No disceret radiologic or operative predictors of regrowth were identified.

Objective: To analyze insulin delivery and glycemic metrics throughout the menstrual cycle for women with type 1 diabetes using closed loop control (CLC) insulin delivery. Methods: Menstruating women using a CLC system in a clinical trial were invited to record their menstrual cycles through a cycle-tracking application. Sixteen participants provided data for this secondary analysis over three or more complete cycles. Insulin delivery and continuous glucose monitoring (CGM) data were analyzed in relation to reported cycle phases. Results: Insulin delivery and CGM metrics remained consistent during cycle phases. Intraparticipant variability of CGM metrics and weight-based insulin delivery did not change through cycle phases. Conclusions: For this sample of menstruating women with type 1 diabetes using a CLC system, insulin delivery and glycemic metrics remained stable throughout menstrual cycle phases. Additional studies in this population are needed, particularly among women who report variable glycemic control during their cycles. Trial Registration: NCT03591354.

PURPOSE Definitive or postoperative chemoradiation (CRT) is curative for human papillomavirus–associated (HPV+) oropharynx cancer (OPC) but induces significant toxicity. As a deintensification strategy, we studied primary transoral surgery (TOS) and reduced postoperative radiation therapy (RT) in intermediate-risk HPV+ OPC. METHODS E3311 is a phase II randomized trial of reduced- or standard-dose postoperative RT for resected stage III-IVa (American Joint Committee on Cancer-seventh edition) HPV+ OPC, determined by pathologic parameters. Primary goals were feasibility of prospective multi-institutional study of TOS for HPV+ OPC, and oncologic efficacy (2-year progression-free survival) of TOS and adjuvant therapy in intermediate-risk patients after resection. TOS plus 50 Gy was considered promising if the lower limit of the exact 90% binomial confidence intervals exceeded 85%. Quality of life and swallowing were measured by functional assessment of cancer therapy-head and neck and MD Anderson Dysphagia Index. RESULTS Credentialed surgeons performed TOS for 495 patients. Eligible and treated patients were assigned as follows: arm A (low risk, n = 38) enrolled 11%, intermediate risk arms B (50 Gy, n = 100) or C (60 Gy, n = 108) randomly allocated 58%, and arm D (high risk, n = 113) enrolled 31%. With a median 35.2-month follow-up for 359 evaluable (eligible and treated) patients, 2-year progression-free survival Kaplan-Meier estimate is 96.9% (90% CI, 91.9 to 100) for arm A (observation), 94.9% (90% CI, 91.3 to 98.6]) for arm B (50 Gy), 96.0% (90% CI, 92.8 to 99.3) for arm C (60 Gy), and 90.7% (90% CI, 86.2 to 95.4) for arm D (66 Gy plus weekly cisplatin). Treatment arm distribution and oncologic outcome for ineligible or step 2 untreated patients (n = 136) mirrored the 359 evaluable patients. Exploratory comparison of functional assessment of cancer therapy-head and neck total scores between arms B and C is presented. CONCLUSION Primary TOS and reduced postoperative RT result in outstanding oncologic outcome and favorable functional outcomes in intermediate-risk HPV+ OPC.

Background: Suboptimal glycemic control is associated with maternal and neonatal morbidity and mortality in pregnancy complicated by type 1 diabetes (T1D). Prospective analysis of continuous glucose monitoring (CGM) metrics, insulin pump settings, and insulin delivery can better characterize the changes in glycemic levels and insulin use throughout pregnancy with T1D. Materials and Methods: Prescribed parameters, insulin delivery, carbohydrate intake, and CGM data for 25 pregnant women with T1D from three U.S. sites were collected. Participants enrolled before 17 weeks gestation and used personal insulin pumps and study CGM. Mean daily total, basal, and bolus insulin doses (units/kg), CGM time in range (TIR: 63–140 mg/dL), and pump-entered carbohydrates were analyzed for every 2-week gestational interval. Linear mixed-effects regression models were used to evaluate changes across gestational ages compared to 12–14 weeks. Results: Basal insulin was higher during weeks 6–12 and 24–40. Daily bolus and total insulin were higher during weeks 20–40. Pump parameters were adjusted to intensify insulin therapy from 22 weeks onward. Average TIR across pregnancy was 59% ± 14%. Between 18 and 30 weeks, TIR was significantly lower, and time above range was significantly higher compared to the reference biweek. Time below target was lower between 22 and 34 weeks. Seven participants achieved >70% recommended TIR for pregnancy. Participants with maternal complications or infant neonatal intensive care unit admissions had lower TIR. Conclusion: While insulin dosing changed significantly with advancing gestation, most participants did not achieve >70% TIR. Customized anticipatory pump setting adjustments and automated systems aimed toward the designated TIR are needed to improve outcomes for this population. NCT03761615

BACKGROUND Increased activation of Group III/IV skeletal muscle afferents is suggested to play a role in exercise intolerance in heart failure (HF). PURPOSE The purpose of this study was to examine if skeletal muscle afferent feedback inhibition improves exercise tolerance in HF. METHODS 8 HF patients [59±8 yr, mean±SD] participated in two randomized incremental recumbent cycling exercise sessions to peak capacity (peak oxygen consumption, VO 2 ). Session 1: The synthetic opioid fentanyl (50 mcg), known to block afferent feedback, was injected intrathecally (INJ) in the lumbar spine (L3‐L4 intervertebral space) prior to exercise. Session 2: Participants were prepared similarly with a sham injection (placebo, PLA). Gas exchange, dyspnea and RPE were measured. RESULTS HF patients exercised for a longer duration (Δ3±3 min, p=0.02) and reached a higher power output (PLA:109±30 vs. INJ:128±34 W, p=0.02) with locomotor afferent inhibition. Additionally, peak VO 2 was non‐significantly greater (PLA:18.7±3.3 vs. INJ:21.8±4.4 ml/kg/min, p=0.10). With INJ workload matched to peak PLA workload, RPE was reduced (PLA:18±2 vs. INJ:15±2, respectively, p=0.005) and dyspnea was lower (PLA:7.5±2 vs. INJ:4.2±1, p=0.003) with no difference in VO 2 (p>0.05). CONCLUSION Inhibition of group III/IV locomotor muscle afferent feedback contributes to improved exercise tolerance and exertional symptoms in HF patients.

Ultrasound education continues to be integrated into gross anatomy courses in the United States. The team based design of the anatomy course at Mayo Clinic School of Medicine incorporates team‐based ultrasound oriented activities that are formalized through defined course objectives and assessed in the final examination. Providing personal handheld ultrasound devices to first‐year medical students during the gross anatomy course has been the mainstay of ultrasound education for the past three years. Handheld ultrasound devices have been provided to students for limited periods in some medical schools within the United States, but unique to this curriculum, students are assigned devices that can be utilized outside formal class time. This provides unlimited opportunity to apply their understanding of three‐dimensional, living anatomy, while simultaneously promoting student comfort and engagement with advancing ultrasound technology. Student perception related to the use of ultrasound outside of formal curricular time was evaluated on a five point Likert scale. Both quantitative and qualitative analyses were used to interpret the data obtained from this study. A total of three surveys were sent to medical students over a period of twelve months with an average response rate of 58.9%. Students indicated that (1) ultrasound devices at personal disposal during the anatomy course improved understanding of anatomical structures imaged ( mean 3.9, SD=+/− 1.01 ), (2) the handheld ultrasound device was easy to use ( mean 3.9, SD = +/− 0.8), and (3) it would be beneficial if ultrasound was implemented as part of the longitudinal learning experience in medical school ( mean 4.1, SD = +/ − 0.7 ). Students were not convinced that (1) having a personal ultrasound device influenced future choice of medical specialty ( mean 2.8, SD = +/− 1.0 ) and (2) the opportunity augmented coursework in the past three months of medical school at time of taking the survey ( mean 2.7, SD =+/ − 1.25 ). Results of the study indicated that access to personal handheld devices motivated students to use ultrasound devices and that they did so with increasing frequency outside of class time. In addition, students were able to apply and reinforce anatomical concepts by using landmarks to first locate and orientate the anatomic field and then interpret images of underlying structures. The fact that students did not see the value of ultrasound in determining future career choices or relate their learning of ultrasound to subsequent courses should not deter prospective opportunity for use of ultrasound in clinical practice. Basic ultrasound proficiency and an ability to effectively interpret scans are skills that in the long term will significantly decrease the learning curve in the use of technology as a diagnostic tool in future clinical settings. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .

Background Heart failure (HF) is associated with impaired exercise pulmonary gas exchange (PGX) that is likely related to the development and severity of pulmonary hypertension (PH). Purpose To determine whether PGX measures differentiate HF patients with reactive PH from patients with passive PH or no PH. Methods/Results Pulmonary arterial pressure (P AP ), pulmonary wedge pressure (P WP ), transpulmonary pressure gradient (TPG) and PGX indices [end‐tidal CO 2 (P ET CO 2 ), ventilatory efficiency (V E /VCO 2 ), O 2 pulse, estimated pulmonary arterial capacitance (GX CAP )] were assessed simultaneously at rest and during cycle exercise in 38 HF patients undergoing right heart catheterization. Post hemodynamic evaluation, patients were classified as having no PH ( n = 12), passive PH ( n = 10) or reactive PH ( n = 16). TPG increased during exercise in all groups but was greater at end exercise in the reactive PH vs. the passive PH and no PH patients (21±9 vs. 14±7 vs. 12±7 mmHg). At an equivalent VO 2 , P ET CO 2 , O 2 pulse and GX CAP were higher and V E /VCO 2 ratio lower in the no PH and, to a lesser extent, in the passive PH vs. the reactive PH subjects (Figure 1). Conclusion Noninvasive measures of PGX during exercise appear to differentiate HF patients with reactive PH from patients with passive PH or no PH and may be a useful adjunct to invasive catheterization in assessing PH type and severity. HL71478, AHA12POST12070084, Gilead Science