Sleep and diabetes-specific psycho-behavioral outcomes of a new automated insulin delivery system in young children with type 1 diabetes and their parents.

BACKGROUND: Data on the use of Control-IQ, the latest FDA-approved automated insulin delivery (AID) system for people with T1D 6 years of age or older is still scarce, particularly regarding nonglycemic outcomes. Children with T1D and their parents are at higher risk for sleep disturbances. This study assesses sleep, psycho-behavioral and glycemic outcomes of AID compared to sensor-augmented pump therapy (SAP) therapy in young children with T1D and their parents. METHODS: Thirteen parents and their young children (ages 7-10) on insulin pump therapy were enrolled. Children completed an initial 4-week study with SAP using their own pump and a study CGM followed by a 4-week phase of AID. Sleep outcomes for parents and children were evaluated through actigraphy watches. Several questionnaires were administered at baseline and at the end of each study phase. CGM data were used to assess glycemic outcomes. RESULTS: Actigraphy data did not show any significant change from SAP to AID, except a reduction of number of parental awakenings during the night (p = 0.036). Parents reported statistically significant improvements in Pittsburgh Sleep Quality Index total score (p = 0.009), Hypoglycemia Fear Survey total score (p = 0.011), diabetes-related distress (p = 0.032), and depression (p = 0.023). While on AID, time in range (70-180 mg/dL) significantly increased compared to SAP (p < 0.001), accompanied by a reduction in hyperglycemia (p = 0.001). CONCLUSIONS: These results suggest that use of AID has a positive impact on glycemic outcomes in young children as well as sleep and diabetes-specific quality of life outcomes in their parents.

Heart rate informed artificial pancreas system enhances glycemic control during exercise in adolescents with T1D.

OBJECTIVE: To evaluate the safety and performance of using a heart rate (HR) monitor to inform an artificial pancreas (AP) system during exercise among adolescents with type 1 diabetes (T1D). MATERIALS AND METHODS: In a randomized, cross-over trial, adolescents with T1D age 13 - 18 years were enrolled to receive on separate days either the unmodified UVa AP (stdAP) or an AP system connected to a portable HR monitor (AP-HR) that triggered an exercise algorithm for blood glucose (BG) control. During admissions participants underwent a structured exercise regimen. Hypoglycemic events and CGM tracings were compared between the two admissions, during exercise and for the full 24-hour period. RESULTS: Eighteen participants completed the trial. While number of hypoglycemic events during exercise and rest was not different between visits (0.39 AP-HR vs 0.50 stdAP), time below 70 mg dL -1 was lower on AP-HR compared to stdAP, 0.5±2.1% vs 7.4±12.5% (P = 0.028). Time with BG within 70-180 mg dL -1 was higher for the AP-HR admission vs stdAP during the exercise portion and overall (96% vs 87%, and 77% vs 74%), but these did not reach statistical significance (P = 0.075 and P = 0.366). CONCLUSIONS: Heart rate signals can safely and efficaciously be integrated in a wireless AP system to inform of physical activity. While exercise contributes to hypoglycemia among adolescents, even when using an AP system, informing the system of exercise via a HR monitor improved time <70 mg dL -1 . Nonetheless, it did not significantly reduce the total number of hypoglycemic events, which were low in both groups.

Use of an artificial pancreas among adolescents for a missed snack bolus and an underestimated meal bolus.

OBJECTIVE: The objective of this study was to evaluate the safety and performance of the artificial pancreas (AP) in adolescents with type 1 diabetes (T1D) following insulin omission for food. RESEARCH DESIGN AND METHODS: In a randomized, cross-over trial, adolescents with T1D aged 13-18 yr were enrolled in a randomized, cross-over trial. On separate days, received either usual care (UC) through their home insulin pump or used an AP system (Diabetes Assistant platform, continuous glucose monitor, and insulin pump). Approximately 1 h after admission, participants in both groups received an unannounced snack of 30 g carbohydrate, and 4 h later they received an 80 g lunch, for which both groups only received 75% of the calculated insulin dose to cover carbohydrates. On the UC day (but not the AP day), they received their full high blood glucose (BG) correction factor at lunch. Each admission lasted approximately 8 h. RESULTS: A total of 16 participants completed the trial. On the AP day (compared to UC), mean BG was lower (197 ± 10 vs. 235 ± 14 mg/dL) and time in range 70-180 mg/dL was higher (43% ± 7 vs. 19% ± 7) (both p < 0.05) overall; these results held in the time following the snack and meal (also p < 0.05). During the trial, there were no differences between groups in the rate of hypoglycemia <70 mg/dL. CONCLUSIONS: The AP provided improvements in short-term glycemic control without increases in hypoglycemia following missed insulin for food in adolescents. Thus, the AP partly compensates for missed insulin boluses for food, a common occurrence in adolescent diabetes care. Further testing is needed in longer-term settings.

Continuous glucose monitoring for inpatient diabetes management: an update on current evidence and practice.

Over the last few years, several exciting changes in continuous glucose monitoring (CGM) technology have expanded its use and made CGM the standard of care for patients with type 1 and type 2 diabetes using insulin therapy. Consequently, hospitals started to notice increased use of these devices in their hospitalized patients. Furthermore during the coronavirus disease 2019 (COVID) pandemic, there was a critical need for innovative approaches to glycemic monitoring, and several hospitals started to implement CGM protocols in their daily practice. Subsequently, a plethora of studies have demonstrated the efficacy and safety of CGM use in the hospital, leading to clinical practice guideline recommendations. Several studies have also suggested that CGM has the potential to become the standard of care for some hospitalized patients, overcoming the limitations of current capillary glucose testing. Albeit, there is a need for more studies and particularly regulatory approval. In this review, we provide a historical overview of the evolution of glycemic monitoring in the hospital and review the current evidence, implementation protocols, and guidance for the use of CGM in hospitalized patients.

Effect of an Automated Advice Algorithm (CloudConnect) on Adolescent-Parent Diabetes-Specific Communication and Glycemic Management: A Randomized Trial.

INTRODUCTION: Because adolescence is a time of difficult management of Type 1 diabetes (T1D) in part from adolescent-parent shared responsibility of T1D management, our objective was to assess the effects of a decision support system (DSS) CloudConnect on T1D-related communication between adolescents and their parents and on glycemic management. METHODS: We followed 86 participants including 43 adolescents with T1D (not on automated insulin delivery systems, AID) and their parents/care-giver for a 12-week intervention of UsualCare + CGM or CloudConnect, which included a Weekly Report of automated T1D advice, including insulin dose adjustments, based on data from continuous glucose monitors (CGM), Fitbit and insulin use. Primary outcome was T1D-specific communication and secondary outcomes were hemoglobin A1c, time-in-target range (TIR) 70-180 mg/dl, and additional psychosocial scales. RESULTS: Adolescents and parents reported a similar amount of T1D-related communication in both the UsualCare + CGM or CloudConnect groups and had similar levels of final HbA1c. Overall blood glucose time in range 70-180 mg/dl and time below 70 mg/dl were not different between groups. Parents but not children in the CloudConnect group reported less T1D-related conflict; however, compared to the UsualCare + CGM group, adolescents and parents in the CloudConnect reported a more negative tone of T1D-related communication. Adolescent-parent pairs in the CloudConnect group reported more frequent changes in insulin dose. There were no differences in T1D quality of life between groups. CONCLUSIONS: While feasible, the CloudConnect DSS system did not increase T1D communication or provide improvements in glycemic management. Further efforts are needed to improve T1D management in adolescents with T1D not on AID systems.

Predictors of Time-in-Range (70-180 mg/dL) Achieved Using a Closed-Loop Control System.

Background: Studies of closed-loop control (CLC) in patients with type 1 diabetes (T1D) consistently demonstrate improvements in glycemic control as measured by increased time-in-range (TIR) 70-180 mg/dL. However, clinical predictors of TIR in users of CLC systems are needed. Materials and Methods: We analyzed data from 100 children aged 6-13 years with T1D using the Tandem Control-IQ CLC system during a randomized trial or subsequent extension phase. Continuous glucose monitor data were collected at baseline and during 12-16 weeks of CLC use. Participants were stratified into quartiles of TIR on CLC to compare clinical characteristics. Results: TIR for those in the first, second, third, and fourth quartiles was 54%, 65%, 71%, and 78%, respectively. Lower baseline TIR was associated with lower TIR on CLC (r = 0.69, P < 0.001). However, lower baseline TIR was also associated with greater improvement in TIR on CLC (r = -0.81, P < 0.001). During CLC, participants in the highest versus lowest TIR-quartile administered more user-initiated boluses daily (8.5 ± 2.8 vs. 5.8 ± 2.6, P < 0.001) and received fewer automated boluses (3.5 ± 1.0 vs. 6.0 ± 1.6, P < 0.001). Participants in the lowest (vs. the highest) TIR-quartile received more insulin per body weight (1.13 ± 0.27 vs. 0.87 ± 0.20 U/kg/d, P = 0.008). However, in a multivariate model adjusting for baseline TIR, user-initiated boluses and insulin-per-body-weight were no longer significant. Conclusions: Higher baseline TIR is the strongest predictor of TIR on CLC in children with T1D. However, lower baseline TIR is associated with the greatest improvement in TIR. As with open-loop systems, user engagement is important for optimal glycemic control.

The Use of a Smart Bolus Calculator Informed by Real-time Insulin Sensitivity Assessments Reduces Postprandial Hypoglycemia Following an Aerobic Exercise Session in Individuals With Type 1 Diabetes.

OBJECTIVE: Insulin dosing in type 1 diabetes (T1D) is oftentimes complicated by fluctuating insulin requirements driven by metabolic and psychobehavioral factors impacting individuals' insulin sensitivity (IS). In this context, smart bolus calculators that automatically tailor prandial insulin dosing to the metabolic state of a person can improve glucose management in T1D. RESEARCH DESIGN AND METHODS: Fifteen adults with T1D using continuous glucose monitors (CGMs) and insulin pumps completed two 24-h admissions in a hotel setting. During the admissions, participants engaged in an early afternoon 45-min aerobic exercise session, after which they received a standardized dinner meal. The dinner bolus was computed using a standard bolus calculator or smart bolus calculator informed by real-time IS estimates. Glucose control was assessed in the 4 h following dinner using CGMs and was compared between the two admissions. RESULTS: The IS-informed bolus calculator allowed for a reduction in postprandial hypoglycemia as quantified by the low blood glucose index (2.02 vs. 3.31, P = 0.006) and percent time <70 mg/dL (8.48% vs. 15.18%, P = 0.049), without increasing hyperglycemia (high blood glucose index: 3.13 vs. 2.09, P = 0.075; percent time >180 mg/dL: 13.24% vs. 10.42%, P = 0.5; percent time >250 mg/dL: 2.08% vs. 1.19%, P = 0.317). In addition, the number of hypoglycemia rescue treatments was reduced from 12 to 7 with the use of the system. CONCLUSIONS: The study shows that the proposed IS-informed bolus calculator is safe and feasible in adults with T1D, appropriately reducing postprandial hypoglycemia following an exercise-induced IS increase.

Safety and Efficacy of Initializing the Control-IQ Artificial Pancreas System Based on Total Daily Insulin in Adolescents with Type 1 Diabetes.

Objective: To assess the safety and efficacy of a simplified initialization for the Tandem t:slim X2 Control-IQ hybrid closed-loop system, using parameters based on total daily insulin ("MyTDI") in adolescents with type 1 diabetes under usual activity and during periods of increased exercise. Research Design and Methods: Adolescents with type 1 diabetes 12-18 years of age used Control-IQ for 5 days at home using their usual parameters. Upon arrival at a 60-h ski camp, participants were randomized to either continue Control-IQ using their home settings or to reinitialize Control-IQ with MyTDI parameters. Control-IQ use continued for 5 days following camp. The effect of MyTDI on continuous glucose monitoring outcomes were analyzed using repeated measures analysis of variance (ANOVA): baseline, camp, and at home. Results: Twenty participants were enrolled and completed the study; two participants were excluded from the analysis due to absence from ski camp (1) and illness (1). Time in range was similar between both groups at home and camp. A tendency to higher time <70 mg/dL in the MyTDI group was present but only during camp (median 3.8% vs. 1.4%, P = 0.057). MyTDI users with bolus/TDI ratios >40% tended to show greater time in the euglycemic range improvements between baseline and home than users with ratios <40% (+16.3% vs. -9.0%, P = 0.012). All participants maintained an average of 95% time in closed loop (84.1%-100%). Conclusions: MyTDI is a safe, effective, and easy way to determine insulin parameters for use in the Control-IQ artificial pancreas. Future modifications to account for the influence of carbohydrate intake on MyTDI calculations might further improve time in range.

Gamma Knife surgery for adrenocorticotropic hormone-producing pituitary adenomas after bilateral adrenalectomy.

OBJECT: Patients with adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas may require a bilateral adrenalectomy to treat their Cushing's disease. Approximately one third of these patients, however, will experience progressive enlargement of the residual pituitary adenoma, develop hyperpigmentation, and have an elevated level of serum ACTH. These patients with Nelson's syndrome can be treated with Gamma Knife surgery (GKS). METHODS: The prospectively collected University of Virginia Gamma Knife database of patients with pituitary adenomas was reviewed to identify all individuals with Nelson's syndrome who were treated with GKS. Twenty-three patients with a minimum of 6 months of follow up were identified in the database. These patients were assessed for tumor control (that is, lack of tumor growth over time) with neuroimaging studies (median follow-up duration 22 months) and for biochemical normalization of their ACTH levels (median follow-up duration 50 months). Neuroimaging follow-up studies were available for 22 patients, and endocrine follow up was available for 15 patients in whom elevation of ACTH levels was documented prior to GKS. In the 22 patients in whom neuroimaging follow-up studies were available, 12 had a decrease in tumor size, eight had no tumor growth, and two had an increase in tumor volume. Ten of 15 patients with elevated ACTH levels prior to GKS showed a decrease in their ACTH levels at last follow up; three of these 10 patients achieved normal ACTH levels (< 50 pg/ml) and the other five patients with initially elevated values had an increase in ACTH levels. Ten patients were thoroughly evaluated for post-GKS pituitary function; four were found to have new pituitary hormone deficiency and six did not have hypopituitarism after GKS. One patient suffered a permanent third cranial nerve palsy and four patients are now deceased. CONCLUSIONS: Gamma Knife surgery may control the residual pituitary adenoma and decrease ACTH levels in patients with Nelson's syndrome. Delayed hypopituitarism or cranial nerve palsies can occur after GKS. Patients with Nelson's syndrome require continued multidisciplinary follow-up care. Given the difficulties associated with management of Nelson's syndrome, even the modest results of GKS may be helpful for a number of patients.

Improving the Safety and Functionality of an Artificial Pancreas System for Use in Younger Children: Input from Parents and Physicians.

BACKGROUND: Artificial pancreas (AP) systems have initially been designed for and tested in teens and adults, but there is evidence that an AP system with additional support and safety systems could greatly benefit younger children with type 1 diabetes (T1D). SUBJECTS AND METHODS: Five pediatric endocrinologists and 15 parents of children aged 5-8 years with T1D participated in a total of four focus groups. Focus groups investigated current diabetes technology use and acceptance, as well as possible modifications to the current adult AP system, which would allow for safe and successful use in younger children. Modifications discussed include child-specific functionality for input tasks, safety features, and monitoring capabilities. RESULTS: Participant suggestions included the following: passcodes for differential access to AP features by parents, ancillary caregivers, and the child; preset early, intermediate, and advanced child access categories; maximal customization for general and alarm settings; simplified meal screens utilizing the AP' corrective blood glucose (BG) ability; automated exercise mode; spoken and dictated messaging capabilities; emergency contacts; treatment instructions for the child and caregiver; remote monitoring website and application; animated continuous glucose monitor BG trace; gamification, such as rewarding diabetes-friendly behaviors; and comprehensive training of all individuals involved in the child's diabetes care. CONCLUSION: Parents and physicians were eager for AP applications to be available for younger children, but stressed that a modified system could better serve this group's needs for safety and improved diabetes-related communication. The diverse and emerging needs of 5-8-year olds require flexible and customizable systems for T1D management.

The Impact of Frequency and Tone of Parent-Youth Communication on Type 1 Diabetes Management.

BACKGROUND: The purpose of this study is to assess the impact of frequency and tone of parent-youth communication on glycemic control as measured by the Family Communication Inventory (FCI). Adolescence provides a unique set of diabetes management challenges, including suboptimal glycemic control. Continued parental involvement in diabetes management is associated with improved HbA1c outcomes; however, diabetes-related conflict within the family can have adverse effects. Although it is clear that communication plays an important role in diabetes outcomes, the specific impact of frequency and tone of such communication is largely understudied. METHODS: A total of 110 youths with type 1 diabetes and their parents completed questionnaires assessing diabetes-related adherence, family conflict, and family communication (i.e., frequency and tone) during a routine clinic visit. Routine testing of HbA1c was performed. RESULTS: Youth- and parent-reported frequency of communication were unrelated to HbA1c. Instead, greater discrepancies between parents and children on reported frequency of communication (most commonly parents reporting frequent and youth reporting less frequent communication) corresponded with poorer glycemic control and increased family conflict. More positive tone of communication as rated by youth was associated with lower HbA1c. CONCLUSIONS: Diabetes-related communication is more complex than conveyed simply by how often children and their parents communicate. Tone of communication and discrepancies in a family's perception of the frequency of communication were better than frequency as predictors of glycemic control. The FCI appears to capture the frequency and tone of diabetes-related communication, though larger-scale studies are warranted to inform future use of this scale.

Closed-Loop Control During Intense Prolonged Outdoor Exercise in Adolescents With Type 1 Diabetes: The Artificial Pancreas Ski Study.

OBJECTIVE: Intense exercise is a major challenge to the management of type 1 diabetes (T1D). Closed-loop control (CLC) systems (artificial pancreas) improve glycemic control during limited intensity and short duration of physical activity (PA). However, CLC has not been tested during extended vigorous outdoor exercise common among adolescents. RESEARCH DESIGN AND METHODS: Skiing presents unique metabolic challenges: intense prolonged PA, cold, altitude, and stress/fear/excitement. In a randomized controlled trial, 32 adolescents with T1D (ages 10-16 years) participated in a 5-day ski camp (∼5 h skiing/day) at two sites: Wintergreen, VA, and Breckenridge, CO. Participants were randomized to the University of Virginia CLC system or remotely monitored sensor-augmented pump (RM-SAP). The CLC and RM-SAP groups were coarsely paired by age and hemoglobin A1c (HbA1c). All subjects were remotely monitored 24 h per day by the study physicians and clinical team. RESULTS: Compared with physician-monitored open loop, percent time in range (70-180 mg/dL) improved using CLC: 71.3 vs. 64.7% (+6.6% [95% CI 1-12]; P = 0.005), with maximum effect late at night. Hypoglycemia exposure and carbohydrate treatments were improved overall (P = 0.001 and P = 0.007) and during the daytime with strong ski level effects (P = 0.0001 and P = 0.006); ski/snowboard proficiency was balanced between groups but with a very strong site effect: naive in Virginia and experienced in Colorado. There was no adverse event associated with CLC; the participants' feedback was overwhelmingly positive. CONCLUSIONS: CLC in adolescents with T1D improved glycemic control and reduced exposure to hypoglycemia during prolonged intensive winter sport activities, despite the added challenges of cold and altitude.

Performance of an Artificial Pancreas System for Young Children with Type 1 Diabetes.

BACKGROUND: Young children 5-8 years old with type 1 diabetes (T1D) exhibit clear needs for improved glycemic control but may be limited in their ability to safely interact with an artificial pancreas system. Our goal was to evaluate the safety and performance of an artificial pancreas (AP) system among young children with T1D. RESEARCH DESIGN AND METHODS: In a randomized, crossover trial, children with T1D age 5-8 years were enrolled to receive on separate study periods (in random order) either the UVa AP using the DiAs Control Platform software with child-resistant lock-out screens (followed as an out-patient admission) or their usual insulin pump+continuous glucose monitor (CGM) care at home. Hypoglycemic events and CGM tracings were compared between the two 68-h study periods. All analyses were adjusted for level of physical activity as tracked using Fitbit devices. RESULTS: Twelve participants (median age 7 years, n = 6 males) completed the trial. Compared to home care, the AP admission resulted in increased time with blood glucose (BG) 70-180 mg/dL (73% vs. 47%) and lower mean BG (152 mg/dL vs. 190 mg/dL), both P < 0.001 after adjustment for activity. Occurrence of hypoglycemia was similar between sessions without differences in time <70 mg/dL (AP 1.1% ± 1.1%; home 1.6% ± 1.2%). There were no adverse events during the AP or home study periods. CONCLUSIONS: Use of an AP in young children was safe and resulted in improved mean BG without increased hypoglycemia. This suggests that AP use in young children is safe and improves overall diabetes control. ClinicalTrials.gov registration number: NCT02750267.

Safety of outpatient closed-loop control: first randomized crossover trials of a wearable artificial pancreas.

OBJECTIVE: We estimate the effect size of hypoglycemia risk reduction on closed-loop control (CLC) versus open-loop (OL) sensor-augmented insulin pump therapy in supervised outpatient setting. RESEARCH DESIGN AND METHODS: Twenty patients with type 1 diabetes initiated the study at the Universities of Virginia, Padova, and Montpellier and Sansum Diabetes Research Institute; 18 completed the entire protocol. Each patient participated in two 40-h outpatient sessions, CLC versus OL, in randomized order. Sensor (Dexcom G4) and insulin pump (Tandem t:slim) were connected to Diabetes Assistant (DiAs)-a smartphone artificial pancreas platform. The patient operated the system through the DiAs user interface during both CLC and OL; study personnel supervised on site and monitored DiAs remotely. There were no dietary restrictions; 45-min walks in town and restaurant dinners were included in both CLC and OL; alcohol was permitted. RESULTS: The primary outcome-reduction in risk for hypoglycemia as measured by the low blood glucose (BG) index (LGBI)-resulted in an effect size of 0.64, P = 0.003, with a twofold reduction of hypoglycemia requiring carbohydrate treatment: 1.2 vs. 2.4 episodes/session on CLC versus OL (P = 0.02). This was accompanied by a slight decrease in percentage of time in the target range of 3.9-10 mmol/L (66.1 vs. 70.7%) and increase in mean BG (8.9 vs. 8.4 mmol/L; P = 0.04) on CLC versus OL. CONCLUSIONS: CLC running on a smartphone (DiAs) in outpatient conditions reduced hypoglycemia and hypoglycemia treatments when compared with sensor-augmented pump therapy. This was accompanied by marginal increase in average glycemia resulting from a possible overemphasis on hypoglycemia safety.

Feasibility of outpatient fully integrated closed-loop control: first studies of wearable artificial pancreas.

OBJECTIVE: To evaluate the feasibility of a wearable artificial pancreas system, the Diabetes Assistant (DiAs), which uses a smart phone as a closed-loop control platform. RESEARCH DESIGN AND METHODS: Twenty patients with type 1 diabetes were enrolled at the Universities of Padova, Montpellier, and Virginia and at Sansum Diabetes Research Institute. Each trial continued for 42 h. The United States studies were conducted entirely in outpatient setting (e.g., hotel or guest house); studies in Italy and France were hybrid hospital-hotel admissions. A continuous glucose monitoring/pump system (Dexcom Seven Plus/Omnipod) was placed on the subject and was connected to DiAs. The patient operated the system via the DiAs user interface in open-loop mode (first 14 h of study), switching to closed-loop for the remaining 28 h. Study personnel monitored remotely via 3G or WiFi connection to DiAs and were available on site for assistance. RESULTS: The total duration of proper system communication functioning was 807.5 h (274 h in open-loop and 533.5 h in closed-loop), which represented 97.7% of the total possible time from admission to discharge. This exceeded the predetermined primary end point of 80% system functionality. CONCLUSIONS: This study demonstrated that a contemporary smart phone is capable of running outpatient closed-loop control and introduced a prototype system (DiAs) for further investigation. Following this proof of concept, future steps should include equipping insulin pumps and sensors with wireless capabilities, as well as studies focusing on control efficacy and patient-oriented clinical outcomes.

Prevalence, severity, and impact of foraminal and canal stenosis among adults with degenerative scoliosis.

BACKGROUND: Management approaches for adult scoliosis are primarily based on adults with idiopathic scoliosis and extrapolated to adults with degenerative scoliosis. However, the often substantially, but poorly defined, greater degenerative changes present in degenerative scoliosis impact the management of these patients. OBJECTIVE: To assess the prevalence, severity, and impact of canal and foraminal stenosis in adults with degenerative scoliosis seeking operative treatment. METHODS: A prospectively collected database of adult patients with deformity was reviewed for consecutive patients with degenerative scoliosis seeking surgical treatment, without prior corrective surgery. Patients completed the Oswestry Disability Index, SF-12, Scoliosis Research Society 22 questionnaire, and a pain numeric rating scale (0-10). Based on MRI or CT myelogram, the central canal and foraminae from T6 to S1 were graded for stenosis (normal or minimal/mild/moderate/severe). RESULTS: Thirty-six patients were included (mean age, 68.9 years; range, 51-85). The mean leg pain numeric rating scale was 6.5, and the mean Oswestry Disability Index score was 53.2. At least 1 level of severe foraminal stenosis was identified in 97% of patients; 83% had maximum foraminal stenosis in the curve concavity. All but 1 patient reported significant radicular pain, including 78% with discrete and 19% with multiple radiculopathies. Of those with discrete radiculopathies, 76% had pain corresponding to areas of the most severe foraminal stenosis, and 24% had pain corresponding to areas of moderate stenosis. CONCLUSION: Significant foraminal stenosis was prevalent in patients with degenerative scoliosis, and the distribution of leg pain corresponded to levels of moderate or severe foraminal stenosis. Failure to address symptomatic foraminal stenosis when surgically treating adult degenerative scoliosis may negatively impact clinical outcomes.

Safety, efficacy, and dosing of recombinant human bone morphogenetic protein-2 for posterior cervical and cervicothoracic instrumented fusion with a minimum 2-year follow-up.

BACKGROUND: Considerable attention has focused on concerns of increased complications with recombinant human bone morphogenetic protein-2 (rhBMP-2) use for anterior cervical fusion, but few reports have assessed its use for posterior cervical fusions. OBJECTIVE: To assess the safety, efficacy, and dosing of rhBMP-2 as an adjunct for instrumented posterior cervical arthrodesis. METHODS: All patients treated by the senior author with posterior cervical or cervicothoracic instrumented fusion using rhBMP-2 from 2003 to 2008 with a minimum of 2 years of follow-up were included. Diagnosis, levels fused, rhBMP-2 dose, complications, and fusion were assessed. RESULTS: Fifty-three patients with a mean age of 55.7 years (range, 2-89 years) and an average follow-up of 40 months (range, 25-80 months) met inclusion criteria. Surgical indications included basilar invagination (n = 6), fracture (n = 6), atlantoaxial instability (n = 16), kyphosis/kyphoscoliosis (n = 22), osteomyelitis (n = 1), spondylolisthesis (n = 1), and cyst (n = 1). Fifteen patients had confirmed rheumatoid disease. The average rhBMP-2 dose was 1.8 mg per level, with a total of 282 levels treated (average, 5.3 levels; SD, 2.8 levels). Among 53 patients, only 2 complications (3.8%) were identified: a superficial wound infection and an adjacent-level degeneration. No cases of dysphagia or neck swelling requiring treatment were identified. At the last follow-up, all patients had achieved fusion. CONCLUSION: Despite many of the patients in the present series having complex pathology and/or rheumatoid arthritis, a 100% fusion rate was achieved. Collectively, these data suggest that use of rhBMP-2 as an adjunct for posterior cervical fusion is safe and effective at an average dose of 1.8 mg per level.

The embryo makes red blood cell progenitors in every tissue simultaneously with blood vessel morphogenesis.

During embryonic life, hematopoiesis occurs first in the yolk sac, followed by the aorto-gonado-mesonephric region, the fetal liver, and the bone marrow. The possibility of hematopoiesis in other embryonic sites has been suspected for a long time. With the use of different methodologies (transgenic mice, electron microscopy, laser capture microdissection, organ culture, and cross-transplant experiments), we show that multiple regions within the embryo are capable of forming blood before and during organogenesis. This widespread phenomenon occurs by hemo-vasculogenesis, the formation of blood vessels accompanied by the simultaneous generation of red blood cells. Erythroblasts develop within aggregates of endothelial cell precursors. When the lumen forms, the erythroblasts "bud" from endothelial cells into the forming vessel. The extensive hematopoietic capacity found in the embryo helps explain why, under pathological circumstances such as severe anemia, extramedullary hematopoiesis can occur in any adult tissue. Understanding the intrinsic ability of tissues to manufacture their own blood cells and vessels has the potential to advance the fields of organogenesis, regeneration, and tissue engineering.