Qi Wang

Pediatric pedicle screws: Comparative effectiveness and safety - A systematic literature review from the Scoliosis Research Society and the Pediatric Orthopaedic Society of North America task force

BACKGROUND Pedicle screws are widely used in spinal surgery. There is extensive published literature concerning the use of pedicle screw instrumentation for spinal surgery in adults. Now there is a trend to use pedicle screws in pediatric patients, including the very young. A systematic review of the current English-language literature on the use of pedicle screw instrumentation in the pediatric age group was performed to specifically determine (1) the pedicle screw placement accuracy in patients with spine deformity and (2) the effect size of all-pedicle screw constructs compared with other methods of spinal instrumentation in terms of the percentage of scoliosis correction. METHODS English-language studies of pedicle screw use in pediatric patients (defined as those younger than eighteen years of age) were included. Descriptive statistics synthesized the accuracy of pedicle screw placement. Accuracy rates were compared between pediatric and adult patients. The effect of pedicle screw instrumentation on scoliosis correction was calculated with use of Cobb angle measurements. RESULTS On the basis of the literature search, 1181 articles were screened, 320 abstracts were examined, and ninety full-text articles representing 5761 patients were reviewed in detail. Seventeen studies met the inclusion criteria for the analysis of pedicle screw placement accuracy. A total of 13,536 pedicle screws were placed in 1353 pediatric patients. The overall placement accuracy rate in pediatric patients was 94.9%, which was higher than the rate of 91.5% reported for adults. The weighted, geometric, and 5% trimmed mean accuracy rates of pedicle screw placement were 91.9%, 88.5%, and 89.1%, respectively (standard deviation = 10%; interquartile range = 10%). Sixteen comparative studies met the inclusion criteria for the analysis of the effect of pedicle screw instrumentation on scoliosis correction. Pedicle screw constructs had a significantly larger percentage of Cobb angle correction compared with hooks (Cohens d = 1.14) and hybrid constructs (Cohens d = 0.49). CONCLUSIONS The accuracy of pedicle screw placement in the pediatric spine exceeds the accuracy rate reported in adults. Pedicle screw instrumentation constructs are significantly more effective for scoliosis correction, as determined on the basis of Cobb angle measurements, than are hook constructs and hybrid constructs.

Pediatric pedicle screws

BACKGROUND Pedicle screws are widely used in spinal surgery. There is extensive published literature concerning the use of pedicle screw instrumentation for spinal surgery in adults. Now there is a trend to use pedicle screws in pediatric patients, including the very young. A systematic review of the current English-language literature on the use of pedicle screw instrumentation in the pediatric age group was performed to specifically determine (1) the pedicle screw placement accuracy in patients with spine deformity and (2) the effect size of all-pedicle screw constructs compared with other methods of spinal instrumentation in terms of the percentage of scoliosis correction. METHODS English-language studies of pedicle screw use in pediatric patients (defined as those younger than eighteen years of age) were included. Descriptive statistics synthesized the accuracy of pedicle screw placement. Accuracy rates were compared between pediatric and adult patients. The effect of pedicle screw instrumentation on scoliosis correction was calculated with use of Cobb angle measurements. RESULTS On the basis of the literature search, 1181 articles were screened, 320 abstracts were examined, and ninety full-text articles representing 5761 patients were reviewed in detail. Seventeen studies met the inclusion criteria for the analysis of pedicle screw placement accuracy. A total of 13,536 pedicle screws were placed in 1353 pediatric patients. The overall placement accuracy rate in pediatric patients was 94.9%, which was higher than the rate of 91.5% reported for adults. The weighted, geometric, and 5% trimmed mean accuracy rates of pedicle screw placement were 91.9%, 88.5%, and 89.1%, respectively (standard deviation = 10%; interquartile range = 10%). Sixteen comparative studies met the inclusion criteria for the analysis of the effect of pedicle screw instrumentation on scoliosis correction. Pedicle screw constructs had a significantly larger percentage of Cobb angle correction compared with hooks (Cohens d = 1.14) and hybrid constructs (Cohens d = 0.49). CONCLUSIONS The accuracy of pedicle screw placement in the pediatric spine exceeds the accuracy rate reported in adults. Pedicle screw instrumentation constructs are significantly more effective for scoliosis correction, as determined on the basis of Cobb angle measurements, than are hook constructs and hybrid constructs.

Reproducibility and agreement in evaluating retinal nerve fibre layer thickness between Stratus and Spectralis OCT

PurposeTo evaluate intra-device reproducibility of retinal nerve fibre layer (RNFL) measurements obtained using Stratus and Spectralis optical coherence tomography, and to analyze inter-device correlation and agreement for these measurements.DesignProspective observational study.MethodsA total of 30 normal individuals participated in the study. One eye of each participant was scanned three times during one session by the same operator using Spectralis and Stratus. Intra-class correlation coefficients (ICCs), correlation coefficients (R), and Bland–Altman plots (BAPs) were used to assess reproducibility, correlation, and agreement between the two devices, respectively.ResultsA significant difference in mean RNFL thickness was seen between Stratus and Spectralis (106.2±6.9 μm vs100.0±7.3 μm, P=0.0001). ICCs of RNFL thickness measurements ranged from 0.69 (clock hour 2; 95% confidence interval (95% CI): 0.54, 0.85) to 0.91 (inferior quadrant; 95% CI: 0.86, 0.96) for Stratus and were higher for Spectralis, ranging from 0.87 (temporal-superior sector; 95% CI: 0.79, 0.94) to 0.96 (global and nasal-inferior sector; 95% CI: 0.94, 0.99). Rs of RNFL thickness measurements between the two instruments ranged from 0.61 (temporal quadrant) to 0.87 (superior quadrant). BAPs demonstrated a systematic difference in RNFL values between the two devices, with Spectralis producing thinner RNFL values than Stratus.ConclusionsSpectralis demonstrated higher ICCs and thinner RNFL measurements than Stratus. Although the inter-device correlation was good, differences in RNFL measurements obtained by the two devices indicate that these measurements would not be interchangeable in clinical evaluations.

Durability of Addition of Roux-en-Y Gastric Bypass to Lifestyle Intervention and Medical Management in Achieving Primary Treatment Goals for Uncontrolled Type 2 Diabetes in Mild-to-Moderate Obesity: A Randomized Control Trial

OBJECTIVE We compared 3-year achievement of an American Diabetes Association composite treatment goal (HbA1c <7.0%, LDL cholesterol <100 mg/dL, and systolic blood pressure <130 mmHg) after 2 years of intensive lifestyle-medical management intervention, with and without Roux-en-Y gastric bypass, with one additional year of usual care. RESEARCH DESIGN AND METHODS A total of 120 adult participants, with BMI 30.0–39.9 kg/m2 and HbA1c ≥8.0%, were randomized 1:1 to two treatment arms at three clinical sites in the U.S. and one in Taiwan. All patients received the lifestyle-medical management intervention for 24 months; half were randomized to also receive gastric bypass. RESULTS At 36 months, the triple end point goal was met in 9% of lifestyle-medical management patients and 28% of gastric bypass patients (P = 0.01): 10% and 19% lower than at 12 months. Mean (SD) HbA1c values at 3 years were 8.6% (3.5) and 6.7% (2.0) (P < 0.001). No lifestyle-medical management patient had remission of diabetes at 36 months, whereas 17% of gastric bypass patients had full remission and 19% had partial remission. Lifestyle-medical management patients used more medications than gastric bypass patients: mean (SD) 3.8 (3.3) vs. 1.8 (2.4). Percent weight loss was mean (SD) 6.3% (16.1) in lifestyle-medical management vs. 21.0% (14.5) in gastric bypass (P < 0.001). Over 3 years, 24 serious or clinically significant adverse events were observed in lifestyle-medical management vs. 51 with gastric bypass. CONCLUSIONS Gastric bypass is more effective than lifestyle-medical management intervention in achieving diabetes treatment goals, mainly by improved glycemic control. However, the effect of surgery diminishes with time and is associated with more adverse events.

Rapid Induction of Cerebral Organoids From Human Induced Pluripotent Stem Cells Using a Chemically Defined Hydrogel and Defined Cell Culture Medium

Tissue organoids are a promising technology that may accelerate development of the societal and NIH mandate for precision medicine. Here we describe a robust and simple method for generating cerebral organoids (cOrgs) from human pluripotent stem cells by using a chemically defined hydrogel material and chemically defined culture medium. By using no additional neural induction components, cOrgs appeared on the hydrogel surface within 10–14 days, and under static culture conditions, they attained sizes up to 3 mm in greatest dimension by day 28. Histologically, the organoids showed neural rosette and neural tube‐like structures and evidence of early corticogenesis. Immunostaining and quantitative reverse‐transcription polymerase chain reaction demonstrated protein and gene expression representative of forebrain, midbrain, and hindbrain development. Physiologic studies showed responses to glutamate and depolarization in many cells, consistent with neural behavior. The method of cerebral organoid generation described here facilitates access to this technology, enables scalable applications, and provides a potential pathway to translational applications where defined components are desirable.

Preserved Insulin Secretory Capacity and Weight Loss Are the Predominant Predictors of Glycemic Control in Patients With Type 2 Diabetes Randomized to Roux-en-Y Gastric Bypass

Improvement in type 2 diabetes after Roux-en-Y gastric bypass (RYGB) has been attributed partly to weight loss, but mechanisms beyond weight loss remain unclear. We performed an ancillary study to the Diabetes Surgery Study to assess changes in incretins, insulin sensitivity, and secretion 1 year after randomization to lifestyle modification and intensive medical management (LS/IMM) alone (n = 34) or in conjunction with RYGB (n = 34). The RYGB group lost more weight and had greater improvement in HbA1c. Fasting glucose was lower after RYGB than after LS/IMM, although the glucose area under the curve decreased comparably for both groups. Insulin sensitivity increased in both groups. Insulin secretion was unchanged after LS/IMM but decreased after RYGB, except for a rapid increase during the first 30 min after meal ingestion. Glucagon-like peptide 1 (GLP-1) was substantially increased after RYGB, while gastric inhibitory polypeptide and glucagon decreased. Lower HbA1c was most strongly correlated with the percentage of weight loss for both groups. At baseline, a greater C-peptide index and 90-min postprandial C-peptide level were predictive of lower HbA1c at 1 year after RYGB. β-Cell glucose sensitivity, which improved only after RYGB, and improved disposition index were associated with lower HbA1c in both groups, independent of weight loss. Weight loss and preserved β-cell function both predominantly determine the greatest glycemic benefit after RYGB.

Post-Gastric Bypass Hyperinsulinemic Hypoglycemia: Fructose is a Carbohydrate Which Can Be Safely Consumed

CONTEXT Postprandial hypoglycemia after gastric bypass surgery is a serious problem. Available treatments are often ineffective. OBJECTIVE The objective was to test the hypotheses that injection of rapid-acting insulin before a high-carbohydrate meal or replacement of other carbohydrates with fructose in the meal would prevent hypoglycemia. DESIGN This was a randomized, crossover trial comparing a high-carbohydrate meal with premeal saline injection (control), a high-carbohydrate meal with premeal insulin injection, and a high-fructose meal with total carbohydrate content similar to the control meal. SETTING The setting was an academic medical center. PATIENTS Ten patients with post-gastric bypass hyperinsulinemic hypoglycemia participated. INTERVENTIONS Interventions included lispro insulin injected before test meals and replacement of other carbohydrates with fructose in test meals. MAIN OUTCOME MEASURE The main outcome measure was plasma glucose < 60 mg/dL after test meals. RESULTS After the control meal, mean peak glucose and insulin were 173 ± 47 mg/dL and 134 ± 55 mU/L, respectively; mean glucose nadir was 44 ± 15 mg/dL; and eight of 10 subjects demonstrated glucose < 60 mg/dL. Five subjects demonstrated a glucose nadir < 40 mg/dL. There were no significant differences in the corresponding values after premeal insulin treatment, except that the mean glucose nadir of 34 ± 10 mg/dL was lower (P < .05). After the fructose meal, mean peak postprandial glucose and insulin were 117 ± 20 mg/dL and 45 ± 31 mU/L, respectively (both P < .001 for comparison with control), mean glucose nadir was 67 ± 10 mg/dL (P < .001), and two of 10 subjects demonstrated glucose < 60 mg/dL (P < .05). CONCLUSIONS People with post-gastric bypass hypoglycemia can consume a meal sweetened with fructose with little risk of hypoglycemia. Treatment with rapid-acting insulin before a carbohydrate-containing meal did not prevent hypoglycemia.

Lifestyle Intervention and Medical Management With vs Without Roux-en-Y Gastric Bypass and Control of Hemoglobin A1c, LDL Cholesterol, and Systolic Blood Pressure at 5 Years in the Diabetes Surgery Study

Importance The Roux-en-Y gastric bypass is effective in achieving established diabetes treatment targets, but durability is unknown. Objective To compare durability of Roux-en-Y gastric bypass added to intensive lifestyle and medical management in achieving diabetes control targets. Design, Setting, and Participants Observational follow-up of a randomized clinical trial at 4 sites in the United States and Taiwan, involving 120 participants who had a hemoglobin A1c (HbA1c) level of 8.0% or higher and a body mass index between 30.0 and 39.9 (enrolled between April 2008 and December 2011) were followed up for 5 years, ending in November 2016. Interventions Lifestyle-intensive medical management intervention based on the Diabetes Prevention Program and LookAHEAD trials for 2 years, with and without (60 participants each) Roux-en-Y gastric bypass surgery followed by observation to year 5. Main Outcomes and Measures The American Diabetes Association composite triple end point of hemoglobin A1c less than 7.0%, low-density lipoprotein cholesterol less than 100 mg/dL, and systolic blood pressure less than 130 mm Hg at 5 years. Results Of 120 participants who were initially randomized (mean age, 49 years [SD, 8 years], 72 women [60%]), 98 (82%) completed 5 years of follow-up. Baseline characteristics were similar between groups: mean (SD) body mass index 34.4 (3.2) for the lifestyle–medical management group and 34.9 (3.0) for the gastric bypass group and had hemoglobin A1c levels of 9.6% (1.2) and 9.6% (1.0), respectively. At 5 years, 13 participants (23%) in the gastric bypass group and 2 (4%) in the lifestyle-intensive medical management group had achieved the composite triple end point (difference, 19%; 95% CI, 4%-34%; P = .01). In the fifth year, 31 patients (55%) in the gastric bypass group vs 8 (14%) in the lifestyle–medical management group achieved an HbA1c level of less than 7.0% (difference, 41%; 95% CI, 19%-63%; P = .002). Gastric bypass had more serious adverse events than did the lifestyle–medical management intervention, 66 events vs 38 events, most frequently gastrointestinal events and surgical complications such as strictures, small bowel obstructions, and leaks. Gastric bypass had more parathyroid hormone elevation but no difference in B12 deficiency. Conclusions and Relevance In extended follow-up of obese adults with type 2 diabetes randomized to adding gastric bypass compared with lifestyle and intensive medical management alone, there remained a significantly better composite triple end point in the surgical group at 5 years. However, because the effect size diminished over 5 years, further follow-up is needed to understand the durability of the improvement. Trial Registration clinicaltrials.gov Identifier: NCT00641251

Training alters the distribution of perilipin proteins in muscle following acute free fatty acid exposure

The lipid droplet (LD)‐associated perilipin (PLIN) proteins promote intramuscular triglyceride (IMTG) storage, although whether the abundance and association of the PLIN proteins with LDs is related to the diverse lipid storage in muscle between trained and sedentary individuals is unknown. We show that lipid infusion augments IMTG content in type I fibres of both trained and sedentary individuals. Most importantly, despite there being no change in PLIN protein content, lipid infusion did increase the number of LDs connected with PLIN proteins in trained individuals only. We conclude that trained individuals are able to redistribute the pre‐existing pool of PLIN proteins to an expanded LD pool during lipid infusion and, via this adaptation, may support the storage of fatty acids in IMTG.

The student-run free clinic: an ideal site to teach interprofessional education?

Abstract Student-run free clinics (SRFCs) often include an interprofessional group of health professions students and preceptors working together toward the common goal of caring for underserved populations. Therefore, it would seem that these clinics would be an ideal place for students to participate in an interprofessional collaborative practice and for interprofessional education to occur. This article describes a prospective, observational cohort study of interprofessional attitudes and skills including communication and teamwork skills and attitudes about interprofessional learning, relationships and interactions of student volunteers in a SRFC compared to students who applied and were not accepted to the clinic and to students who never applied to the clinic. This study showed a decrease in attitudes and skills after the first year for all groups. Over the next two years, the total score on the survey for the accepted students was higher than the not accepted students. The students who were not accepted also became more similar to students who never applied. This suggests a protective effect against declining interprofessional attitudes and skills for the student volunteers in a SRFC. These findings are likely a function of the design of the clinical and educational experience in the clinic and of the length of contact the students have with other professions.