Citations

OBJECTIVE Intensive treatment (INT) of type 1 diabetes reduces the incidence of cardiovascular disease (CVD) events compared with conventional treatment (CONV), but it also results in more weight gain. Our objective was to examine whether excessive weight gain from INT of type 1 diabetes is independently associated with subsequent CVD events. RESEARCH DESIGN AND METHODS Quartiles (Q) of weight gain in 1,213 participants aged 18 years and older at enrollment in the Diabetes Control and Complications Trial (DCCT) were determined within randomized treatment groups (INT vs. CONV) using change in BMI from baseline to the closeout DCCT visits. Effects of this weight gain on CVD risk factors and outcomes during an additional 20 years of observational follow-up were then determined. RESULTS The Q4 INT group experienced greater proportional weight gain (median change in BMI, 6.08 kg/m2), increases in CVD risk factors, and need for medications for hypertension and lipids compared with the Q1–3 INT and comparable CONV groups. Over a mean of 26 years of follow-up, the numbers of major and total CVD events were not statistically different in Q4 compared with Q1–3 of either the INT or CONV group. By year 14, however, the incident CVD event curve became significantly higher in the Q4 INT group than in the Q1–3 INT groups (P = 0.024) and was similar to that for the CONV group. CONCLUSIONS For the first 13 years after DCCT, INT for type 1 diabetes reduced macrovascular events compared with CONV, even when excessive weight gain occurred. After this, total CVD events significantly increased in the Q4 INT group, becoming equivalent to those in the CONV group. Longer follow-up is needed to determine whether this trend continues and results in more major CVD events.

101 Background: Socioeconomic status (SES) influences healthcare outcomes, but the influence of SES on cancer cachexia is unknown. We identify components of SES associated with pre-treatment cachexia in patients with non-small cell lung cancer (NSCLC) and assess their prognostic significance on survival. Methods: A prospectively maintained institutional tumor registry identified 1,365 patients with NSCLC consecutively treated at a tertiary care health system from 1/1/06 to 12/31/13. Insurance status was abstracted from the registry. Educational attainment and household income were estimated from census data using location of primary residence. Cancer cachexia was defined retrospectively using the international consensus definition. Multivariable regression analysis was used to identify prognostic factors of pre-treatment cancer cachexia and survival. Results: Cachexia was present at the time of NSCLC diagnosis in 30% of all patients including 17% of patients with stage I disease. Patients with Medicaid or no insurance were more likely to have pre-treatment cachexia compared to those with private insurance (Odds Ratio [OR] 1.9, 95% Confidence Interval [CI] 1.2-3.1; OR 2.1, 95% CI 1.2-3.4, respectively). Attainment of a high school diploma was inversely associated with pre-treatment cachexia (OR: 0.1, 95% CI 0.02-0.2). On multivariable analysis, comorbidity, histology, tumor grade, and disease stage were prognostic of survival among cachectic patients; however, insurance status, educational attainment, and household income were not. Conclusions: Lower SES is associated with pre-treatment cachexia in patients with NSCLC, but pre-treatment cachexia is detrimental to survival regardless of SES. Together, these findings suggest early intervention for patients with cancer cachexia may improve outcomes.

Background: Glucose variability (GV) has been increasingly (or more extensively) studied in patients with type 1 diabetes (T1D) in the ambulatory setting; limited data exist on GV in hospitalized patients with T1D. Materials and Methods: Retrospective single center cohort study, we analyzed in-hospital glucose measurements to assess GV in 736 hospitalized patients in different units over a consecutive 5-year period of time. GV was assessed by mean blood glucose (BG), Average daily risk range (ADRR), high BG index, and low BG index. To place our findings in context, we conducted a systematic review using Cochrane collaboration methodology to critically analyze current published literature on GV in hospitalized T1D patients. Results: Overall, glycemic control was suboptimal with mean BG 183 ± 51.5 mg/dL and mean ADRR 35 with only 16% patients being categorized as low risk (ADRR <20) for hypo or hyperglycemia. Patients admitted in medical units had mean BG of 194.4 ± 42.8 mg/dL (95% CI = 101.2–346.6) and ADRR of 39.4 ± 16 (95% CI = 1.3–118.7), which were higher than the patients admitted in the surgical units (mean BG 168.1 ± 35.7 (95% CI = 74.8–301.8) and mean ADRR (28.8 ± 13.1 [95% CI = 0.3–93.1]). For the systematic review, initial search yielded 2336 studies for screening, however, none of them had data specific for T1D. Conclusion: GV is high in hospitalized T1D patients admitted at our tertiary care center. Review of the literature shows paucity of data regarding GV in hospitalized patients with T1D.

OBJECTIVE Artificial pancreas (AP) systems are best positioned for optimal treatment of type 1 diabetes (T1D) and are currently being tested in outpatient clinical trials. Our consortium developed and tested a novel adaptive AP in an outpatient, single-arm, uncontrolled multicenter clinical trial lasting 12 weeks. RESEARCH DESIGN AND METHODS Thirty adults with T1D completed a continuous glucose monitor (CGM)-augmented 1-week sensor-augmented pump (SAP) period. After the AP was started, basal insulin delivery settings used by the AP for initialization were adapted weekly, and carbohydrate ratios were adapted every 4 weeks by an algorithm running on a cloud-based server, with automatic data upload from devices. Adaptations were reviewed by expert study clinicians and patients. The primary end point was change in hemoglobin A1c (HbA1c). Outcomes are reported adhering to consensus recommendations on reporting of AP trials. RESULTS Twenty-nine patients completed the trial. HbA1c, 7.0 ± 0.8% at the start of AP use, improved to 6.7 ± 0.6% after 12 weeks (−0.3, 95% CI −0.5 to −0.2, P &lt; 0.001). Compared with the SAP run-in, CGM time spent in the hypoglycemic range improved during the day from 5.0 to 1.9% (−3.1, 95% CI −4.1 to −2.1, P &lt; 0.001) and overnight from 4.1 to 1.1% (−3.1, 95% CI −4.2 to −1.9, P &lt; 0.001). Whereas carbohydrate ratios were adapted to a larger extent initially with minimal changes thereafter, basal insulin was adapted throughout. Approximately 10% of adaptation recommendations were manually overridden. There were no protocol-related serious adverse events. CONCLUSIONS Use of our novel adaptive AP yielded significant reductions in HbA1c and hypoglycemia.

Purpose Using common datasets, to estimate and compare the diagnostic performance of image‐based denoising techniques or iterative reconstruction algorithms for the task of detecting hepatic metastases. Methods Datasets from contrast‐enhanced CT scans of the liver were provided to participants in an NIH ‐, AAPM ‐ and Mayo Clinic‐sponsored Low Dose CT Grand Challenge. Training data included full‐dose and quarter‐dose scans of the ACR CT accreditation phantom and 10 patient examinations; both images and projections were provided in the training data. Projection data were supplied in a vendor‐neutral standardized format ( DICOM ‐ CT ‐ PD ). Twenty quarter‐dose patient datasets were provided to each participant for testing the performance of their technique. Images were provided to sites intending to perform denoising in the image domain. Fully preprocessed projection data and statistical noise maps were provided to sites intending to perform iterative reconstruction. Upon return of the denoised or iteratively reconstructed quarter‐dose images, randomized, blinded evaluation of the cases was performed using a Latin Square study design by 11 senior radiology residents or fellows, who marked the locations of identified hepatic metastases. Markings were scored against reference locations of clinically or pathologically demonstrated metastases to determine a per‐lesion normalized score and a per‐case normalized score (a faculty abdominal radiologist established the reference location using clinical and pathological information). Scores increased for correct detections; scores decreased for missed or incorrect detections. The winner for the competition was the entry that produced the highest total score (mean of the per‐lesion and per‐case normalized score). Reader confidence was used to compute a Jackknife alternative free‐response receiver operating characteristic ( JAFROC ) figure of merit, which was used for breaking ties. Results 103 participants from 90 sites and 26 countries registered to participate. Training data were shared with 77 sites that completed the data sharing agreements. Subsequently, 41 sites downloaded the 20 test cases, which included only the 25% dose data ( CTDI vol = 3.0 ± 1.8 mG y, SSDE = 3.5 ± 1.3 mG y). 22 sites submitted results for evaluation. One site provided binary images and one site provided images with severe artifacts; cases from these sites were excluded from review and the participants removed from the challenge. The mean (range) per‐lesion and per‐case normalized scores were −24.2% (−75.8%, 3%) and 47% (10%, 70%), respectively. Compared to reader results for commercially reconstructed quarter‐dose images with no noise reduction, 11 of the 20 sites showed a numeric improvement in the mean JAFROC figure of merit. Notably two sites performed comparably to the reader results for full‐dose commercial images. The study was not designed for these comparisons, so wide confidence intervals surrounded these figures of merit and the results should be used only to motivate future testing. Conclusion Infrastructure and methodology were developed to rapidly estimate observer performance for liver metastasis detection in low‐dose CT examinations of the liver after either image‐based denoising or iterative reconstruction. The results demonstrated large differences in detection and classification performance between noise reduction methods, although the majority of methods provided some improvement in performance relative to the commercial quarter‐dose images with no noise reduction applied.

Abstract Background Recurrent Clostridium difficile infections (rCDI) are associated with decreased diversity and altered intestinal microbiome compared with healthy patients. RBX2660, a standardized microbiota-based drug, is designed to restore microbiome diversity and composition in patients’. The effect of RBX2660 on rCDI patient microbiomes was evaluated by comparing pre- and post-treatment samples from PUNCH CD 2—a randomized, double-blind, placebo-controlled study. Methods rCDIsubjects were randomized to receive blinded treatments of 2 doses of RBX2660 (Group A), 2 doses of placebo (Group B), or 1 dose each of RBX2660 and placebo (Group C), by enema 7 days apart. Subjects submitted stool samples at baseline, day 7, 30, and 60 after treatment. Stool samples from responders to RBX2660 treatment per protocol defined as the absence of CDI for 8 weeks after treatment were compared with non-responders. Relative taxonomic abundances at the class level were determined using 16s rRNA sequencing analysis for 94 stool samples from 45 patients in Groups A and C. Relative abundance data were grouped longitudinally using Bray-Curtis dissimilarity index. Analyses were performed based on the Dirichlet-Multinomial distribution to compare group mean relative taxonomic abundances; Simpson and Shannon diversity indices were compared among groups longitudinally. Results Baseline patient microbiomes were similar across response groups. RBX2660 treatment shifted the relative microbiome densities with taxa-specific increase in Bacteroidia, Clostridia, and decrease in Gamma-proteobacteria abundance. A larger shift from baseline microbiome was seen in responders to RBX2600 compared with non-responders (Figure 1). Microbiome changes in responders were durable to 60 days. RBX2660 treatment increased Shannon and Simpson diversity at 7 days post-treatment in responders but not in non-responders (P &lt; 0.05). Conclusion RBX2660 treatment shifts patient intestinal microbiomes with greater alterations seen in those with a successful clinical outcome. Funded by Rebiotix Inc., Roseville, MN. Disclosures S. Khanna, Rebiotix, Inc.: Scientific Advisor, Consulting fee; K. Blount, Rebiotix, Inc.: Employee, Salary; C. Jones, Rebiotix, Inc.: Employee, Salary; B. Shannon, Rebiotix, Inc.: Research Contractor, Consulting fee; S. Carter, Rebiotix, Inc.: Research Contractor, Consulting fee

Aim To describe the impact of steps towards reduction of procedural doses of radiation during neuroendovascular procedures. Methods Phantom exposures under controlled circumstances were performed using a Rando-Alderson adult-sized head phantom. Customized imaging protocols were devised for pediatric and adult imaging and implemented in clinical use. Outcome data for estimated skin doses (ESD) and dose–area product (DAP) following pediatric and adult diagnostic and interventional procedures over 4.5 years were analyzed retrospectively. Results Dose estimates were reduced by 50% or more after introduction of customized imaging protocols in association with modification of personnel behavior compared with doses recorded with previously used vendor-recommended protocols. Discussion Substantial reductions in radiation use during neuroendovascular procedures can be achieved through a combination of equipment modification and operator behavior.

OBJECTIVEThe subspecialization of neurosurgical practice is an ongoing trend in modern neurosurgery. However, it remains unclear whether the degree of surgeon specialization is associated with improved patient outcomes. The authors hypothesized that a trend toward increased neurosurgeon specialization was associated with improved patient morbidity and mortality rates.METHODSThe Nationwide Inpatient Sample (NIS) was used (1998–2009). Patients were included in a spinal analysis cohort for instrumented spine surgery involving the cervical spine (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] codes 81.31–81.33, 81.01–81.03, 84.61–84.62, and 84.66) or lumbar spine (codes 81.04–81.08, 81.34–81.38, 84.64–84.65, and 84.68). A cranial analysis cohort consisted of patients receiving a parenchymal excision or lobectomy operation (codes 01.53 and 01.59). Surgeon specialization was measured using unique surgeon identifiers in the NIS and defined as the proportion of a surgeon’s total practice dedicated to cranial or spinal cases.RESULTSA total of 46,029 and 231,875 patients were identified in the cranial and spinal analysis cohorts, respectively. On multivariate analysis in the cranial analysis cohort (after controlling for overall surgeon volume, patient demographic data/comorbidities, hospital characteristics, and admitting source), each percentage-point increase in a surgeon’s cranial specialization (that is, the proportion of cranial cases) was associated with a 0.0060 reduction in the log odds of patient mortality (95% CI 0.0034–0.0086) and a 0.0042 reduction in the log odds of morbidity (95% CI 0.0032–0.0052). This resulted in a 15% difference in the predicted probability of mortality for neurosurgeons at the 75th versus the 25th percentile of cranial specialization. In the spinal analysis cohort, each percentage-point increase in a surgeon’s spinal specialization was associated with a 0.0122 reduction in the log odds of mortality (95% CI 0.0074–0.0170) and a 0.0058 reduction in the log odds of morbidity (95% CI 0.0049–0.0067). This resulted in a 26.8% difference in the predicted probability of mortality for neurosurgeons at the 75th versus the 25th percentile of spinal specialization.CONCLUSIONSFor both spinal and cranial surgery patient cohorts derived from the NIS database, increased surgeon specialization was significantly and independently associated with improved mortality and morbidity rates, even after controlling for overall case volume.

PurposeTo investigate the use of magnetic resonance elastography (MRE) in the quantitative assessment of pulmonary fibrosis by comparing quantitative shear stiffness measurements of lung parenchyma in patients diagnosed with fibrotic interstitial lung disease (ILD) and healthy controls.Materials and MethodsA 1.5T spin‐echo, echo planar imaging MRE (SE‐EPI MRE) pulse sequence was utilized to assess absolute lung shear stiffness in 15 patients with diagnosed ILD and in 11 healthy controls. Data were collected at residual volume (RV) and total lung capacity (TLC). Spirometry data were obtained immediately prior to scanning. To test for statistical significance between RV and TLC shear stiffness estimates a two‐sample t‐test was performed. To assess variability within individual subject shear stiffness estimates, the intraclass correlation coefficient (ICC) and Krippendorff's alpha were calculated.ResultsPatients with ILD exhibited an average (±1 standard deviation) shear stiffness of 2.74 (±0.896) kPa at TLC and 1.32 (±0.300) kPa at RV. The corresponding values for healthy individuals were 1.33 (±0.195) kPa and 0.849 (±0.250) kPa, respectively. The difference in shear stiffness between RV and TLC was statistically significant (P < 0.001). At TLC, the ICC and alpha values were 0.909 and 0.887, respectively. At RV, the ICC and alpha values were 0.852 and 0.862, respectively.ConclusionIn subjects with known fibrotic interstitial lung disease, parenchymal shear stiffness is increased when compared to normal controls at both RV and TLC, with TLC demonstrating the most significant difference. MRE‐derived parenchymal shear stiffness is a promising new noninvasive imaging‐based biomarker of interstitial lung disease.Level of Evidence:1J. MAGN. RESON. IMAGING 2017;46:1–1