First Real-World Experience With Bigfoot Unity: A 6-Month Retrospective Analysis.

The Bigfoot Unity Diabetes Management System, a smart pen cap system cleared by the U.S. Food and Drug Administration in May 2021, incorporates continuous glucose monitoring data, real-time glycemic alerts, and clinician-directed dose recommendations. This study analyzed real-world clinical outcomes data for an initial cohort (n = 58, from 13 clinics) managing multiple daily injection insulin therapy using the pen cap system for 6 months. We examined glycemic control, including hypoglycemia events and interaction with and use of the pen cap system. In a cohort mainly consisting of adults with type 2 diabetes and an average age of 62 years, the results demonstrate close adherence to established glycemic targets, including a relatively short amount of time spent in the hypoglycemic range.

Balloon kyphoplasty versus non-surgical fracture management for treatment of painful vertebral body compression fractures in patients with cancer: a multicentre, randomised controlled trial.

BACKGROUND: Non-randomised trials have reported benefits of kyphoplasty in patients with cancer and vertebral compression fractures (VCFs). We aimed to assess the efficacy and safety of balloon kyphoplasty compared with non-surgical management for patients with cancer who have painful VCFs. METHODS: The Cancer Patient Fracture Evaluation (CAFE) study was a randomised controlled trial at 22 sites in Europe, the USA, Canada, and Australia. We enrolled patients aged at least 21 years who had cancer and one to three painful VCFs. Patients were randomly assigned by a computer-generated minimisation randomisation algorithm to kyphoplasty or non-surgical management (control group). Investigators and patients were not masked to treatment allocation. The primary endpoint was back-specific functional status measured by the Roland-Morris disability questionnaire (RDQ) score at 1 month. Outcomes at 1 month were analysed by modified intention to treat, including all patients with data available at baseline and at 1 month follow-up. Patients in the control group were allowed to crossover to receive kyphoplasty after 1 month. This study is registered with ClinicalTrials.gov, NCT00211237. FINDINGS: Between May 16, 2005, and March 11, 2008, 134 patients were enrolled and randomly assigned to kyphoplasty (n=70) or non-surgical management (n=64). 65 patients in the kyphoplasty group and 52 in the control group had data available at 1 month. The mean RDQ score in the kyphoplasty group changed from 17·6 at baseline to 9·1 at 1 month (mean change -8·3 points, 95% CI -6·4 to -10·2; p<0·0001). The mean score in the control group changed from 18·2 to 18·0 (mean change 0·1 points; 95% CI -0·8 to 1·0; p=0·83). At 1 month, the kyphoplasty treatment effect for RDQ was -8·4 points (95% CI -7·6 to -9·2; p<0·0001). The most common adverse events within the first month were back pain (four of 70 in the kyphoplasty group and five of 64 in the control group) and symptomatic vertebral fracture (two and three, respectively). One patient in the kyphoplasty group had an intraoperative non-Q-wave myocardial infarction, which resolved and was attributed to anaesthesia. Another patient in this group had a new VCF, which was thought to be device related. INTERPRETATION: For painful VCFs in patients with cancer, kyphoplasty is an effective and safe treatment that rapidly reduces pain and improves function. FUNDING: Medtronic Spine LLC.

Efficacy and safety of balloon kyphoplasty compared with non-surgical care for vertebral compression fracture (FREE): a randomised controlled trial.

BACKGROUND: Balloon kyphoplasty is a minimally invasive procedure for the treatment of painful vertebral fractures, which is intended to reduce pain and improve quality of life. We assessed the efficacy and safety of the procedure. METHODS: Adults with one to three acute vertebral fractures were eligible for enrolment in this randomised controlled trial at 21 sites in eight countries. We randomly assigned 300 patients by a computer-generated sequence to receive kyphoplasty treatment (n=149) or non-surgical care (n=151). The primary outcome was the difference in change from baseline to 1 month in the short-form (SF)-36 physical component summary (PCS) score (scale 0-100) between the kyphoplasty and control groups. Quality of life and other efficacy measurements and safety were assessed up to 12 months. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00211211. FINDINGS: 138 participants in the kyphoplasty group and 128 controls completed follow-up at 1 month. By use of repeated measures mixed effects modelling, all 300 randomised participants were included in the analysis. Mean SF-36 PCS score improved by 7.2 points (95% CI 5.7-8.8), from 26.0 at baseline to 33.4 at 1 month, in the kyphoplasty group, and by 2.0 points (0.4-3.6), from 25.5 to 27.4, in the non-surgical group (difference between groups 5.2 points, 2.9-7.4; p<0.0001). The frequency of adverse events did not differ between groups. There were two serious adverse events related to kyphoplasty (haematoma and urinary tract infection); other serious adverse events (such as myocardial infarction and pulmonary embolism) did not occur perioperatively and were not related to procedure. INTERPRETATION: Our findings suggest that balloon kyphoplasty is an effective and safe procedure for patients with acute vertebral fractures and will help to inform decisions regarding its use as an early treatment option.

Prospective and Multicenter Evaluation of Outcomes for Quality of Life and Activities of Daily Living for Balloon Kyphoplasty in the Treatment of Vertebral Compression Fractures: The EVOLVE Trial.

BACKGROUND: Osteoporotic and neoplastic vertebral compression fractures (VCF) are common and painful, threatening quality of life and increasing risk of morbidity and mortality. Balloon kyphoplasty is a percutaneous option for treating painful cancer- and osteoporosis-related VCFs, supported by 2 randomized trials demonstrating efficacy benefits of BKP over nonsurgical care. OBJECTIVE: To investigate 12-mo disability, quality of life, and safety outcomes specifically in a Medicare-eligible population, representing characteristic patients seen in routine clinical practice. METHODS: A total of 354 patients with painful VCFs were enrolled at 24 US sites with 350 undergoing kyphoplasty. Four coprimary endpoints-Numerical Rating Scale (NRS) back pain, Oswestry Disability Index (ODI), Short Form-36 Questionnaire Physical Component Summary (SF-36v2 PCS), EuroQol-5-Domain (EQ-5D)-were evaluated for statistically significant improvement 3 mo after kyphoplasty. Data were collected at baseline, 7 d, and 1, 3, 6, and 12 mo (www.clinicaltrials.gov registration NCT01871519). RESULTS: At the 3-mo primary endpoint, NRS improved from 8.7 to 2.7 and ODI improved from 63.4 to 27.1; SF-36 PCS was 24.2 at baseline improving to 36.6, and EQ-5D improved from 0.383 to 0.746 (P < .001 for each). These outcomes were statistically significant at every follow-up time point. Five device-/procedure-related adverse events, intraoperative asymptomatic balloon rupture, rib pain, and aspiration pneumonia, and a new VCF 25 d postprocedure, and myocardial infarction 105 d postprocedure were reported and each resolved with proper treatment. CONCLUSION: This large, prospective, clinical study demonstrates that kyphoplasty is a safe, effective, and durable procedure for treating patients with painful VCF due to osteoporosis or cancer.

A randomized trial of balloon kyphoplasty and nonsurgical management for treating acute vertebral compression fractures: vertebral body kyphosis correction and surgical parameters.

STUDY DESIGN: Multicenter randomized controlled trial. OBJECTIVE: To compare the efficacy and safety of balloon kyphoplasty (BKP) with nonsurgical management (NSM) during 24 months in patients with painful vertebral compression fractures (VCFs). SUMMARY OF BACKGROUND DATA: Recently, several large randomized controlled trials have been conducted and reported how vertebral augmentation compares with NSM for patients with acute VCFs. Few of these trials report on the surgical aspects and radiographical vertebral deformity results. METHODS: Adults with 1 to 3 VCFs were randomized within 3 months of pain to undergo bilateral BKP (n = 149) or NSM (n = 151). Surgical parameters, subjective quality of life assessments and objective functional (timed up and go) and radiographical assessments were collected. RESULTS: Compared with NSM, the BKP group had greater improvements in SF-36 physical component summary (PCS) scores at 1 month (5.35 points; 95% CI, 3.41-7.30; P < 0.0001) and when averaged across the 24 months (overall treatment effect 2.71 points; 95% CI, 1.34-4.09; P = 0.0001). The kyphoplasty group also had greater functionality by assessing timed up and go (overall treatment effect -2.49 s; 95% CI, -0.82 to -4.15; P = 0.0036). At 24 months, the change in index fracture kyphotic angulation was statistically significantly improved in the kyphoplasty group (average 3.13° of correction for kyphoplasty compared with 0.82° in the control, P = 0.003). Number of baseline prevalent fractures (P = 0.0003) and treatment assignment (P = 0.004) are the most predictive variables for PCS improvement; however, in patients who underwent BKP, there may also be a link with kyphotic angulation. In BKP, the highest quart for kyphotic angulation correction had higher PCS improvement (13.4 points) than the quart having lowest correction of angulation (7.40 points, P = 0.0146 for difference). The most common adverse events temporally related to surgery (i.e., within 30 d) were back pain (20 BKP, 11 NSM) new VCF (11 BKP, 7 NSM), nausea/vomiting (12 BKP, 4 NSM), and urinary tract infection (10 BKP, 3 NSM). Several other adverse events were possibly related to patient positioning in the operating room. CONCLUSION: Compared with NSM, BKP improves patient quality of life and pain averaged during 24 months and results in better improvement of index vertebral body kyphotic angulation. Perioperative complications may be reduced with more care in patient positioning. LEVEL OF EVIDENCE: 2.

Balloon kyphoplasty for the treatment of acute vertebral compression fractures: 2-year results from a randomized trial.

Vertebral fractures are often painful and lead to reduced quality of life and disability. We compared the efficacy and safety of balloon kyphoplasty to nonsurgical therapy over 24 months in patients with acute painful fractures. Adults with one to three vertebral fractures were randomized within 3 months from onset of pain to undergo kyphoplasty (n = 149) or nonsurgical therapy (n = 151). Quality of life, function, disability, and pain were assessed over 24 months. Kyphoplasty was associated with greater improvements in Short-Form 36 (SF-36) Physical Component Summary (PCS) scores when averaged across the 24-month follow-up period compared with nonsurgical therapy [overall treatment effect 3.24 points, 95% confidence interval (CI) 1.47-5.01, p = .0004]; the treatment difference remained statistically significant at 6 months (3.39 points, 95% CI 1.13-5.64, p = .003) but not at 12 months (1.70 points, 95% CI -0.59 to 3.98, p = .15) or 24 months (1.68 points, 95% CI -0.63 to 3.99, p = .15). Greater improvement in back pain was observed over 24 months for kyphoplasty (overall treatment effect -1.49 points, 95% CI -1.88 to -1.10, p < .0001); the difference between groups remained statistically significant at 24 months (-0.80 points, 95% CI -1.39 to -0.20, p = .009). There were two device-related serious adverse events in the second year that occurred at index vertebrae (a spondylitis and an anterior cement migration). There was no statistically significant difference between groups in the number of patients (47.5% for kyphoplasty, 44.1% for control) with new radiographic vertebral fractures; fewer fractures occurred (~18%) within the second year. Compared with nonsurgical management, kyphoplasty rapidly reduces pain and improves function, disability, and quality of life without increasing the risk of additional vertebral fractures. The differences from nonsurgical management are statistically significant when averaged across 24 months. Most outcomes are not statistically different at 24 months, but the reduction in back pain remains statistically significant at all time points.

Lumbar intersegmental spacing and angulation in the modified lateral decubitus position versus variants of prone positioning.

BACKGROUND CONTEXT: Interspinous process devices represent an emerging treatment for neurogenic intermittent claudication resulting from lumbar spinal stenosis. Most published descriptions of the operative technique involve treatment of patients in the modified lateral decubitus knee-chest position (modified lateral decubitus), and yet many surgeons have begun to perform the procedure in various prone positions. The patient's positioning on the operating room table seems likely to influence resting interspinous distance, and thus implant sizing and possibly the risk of intraoperative spinous process fracture. The intersegmental lumbar effect of variants on operative prone positioning compared with the modified lateral decubitus position has not been studied. PURPOSE: We performed this study to determine the comparative differences in interspinous distance and intersegmental angulation effected by the lateral decubitus knee-chest position and the variants on prone positioning used in practice. STUDY DESIGN/SETTING: Experimental human radiographic study. PATIENT SAMPLE: Twenty healthy male volunteers with a mean age of 43.6+/-10.8 years (range, 24-63), without chronic back pain, symptoms of neurogenic claudication, or history of lumbar surgery were enrolled. OUTCOME MEASURES: Interspinous distance, anterior and posterior disc heights, disc angulation were measured on PACS monitor. METHODS: Lateral X-rays were taken of the lower lumbar spine in each of four different surgical positions (modified lateral decubitus, Andrews frame, Wilson frame, and Jackson frame). Statistical analysis was performed on the resultant data points to assess the significance of the effect of the position of the subject on intersegmental spacing and angulation. RESULTS: The 20 enrollees had a mean age of 43.6+/-10.8 years (range, 24-63). The mean interspinous distance at the L4-L5 level was greatest on the Andrews table (23.5+/-8.3mm) followed by the modified lateral decubitus position (19.6+/-5.1mm), the Wilson frame (15.6+/-4.6mm), and then the Jackson frame (10.1+/-4.7mm; significantly less than all other positions p< or =.036). Mean segmental extension at the L4-L5 level was least in the modified lateral decubitus position (-0.1 degrees +/-2.9 degrees ); this was statistically similar to extension on the Andrews table (1.5 degrees +/-4.7 degrees , p=1.0), but significantly less than that recorded on the Wilson frame (4.6 degrees +/-3.1 degrees , p<.001), and also significantly less than that recorded on the Jackson frame (p< or =.001). Similar differences in segmental measurements were observed at L3-L4. CONCLUSIONS: Prone positioning of patients in flexion on the operating table using the Andrews table or Wilson frame resulted in similar lumbar interspinous distance compared with the modified lateral decubitus position. Prone positioning on the Jackson frame resulted in statistically less interspinous distance than all other positions. Positioning on the Andrews table resulted in similar segmental angulation to the modified lateral decubitus position. Extrapolation from these data, obtained in healthy males younger than the typical age of patients treated with interspinous distraction devices, should clearly be done with caution. However, it seems reasonable to suggest that performing these procedures in the prone position using the Andrews table (greatest interspinous distance) is unlikely to result in the placement of significantly undersized implants, or significantly increase the force required to insert an implant.

Expression of a structurally unique osteoclastic protein-tyrosine phosphatase is driven by an alternative intronic, cell type-specific promoter.

An osteoclastic protein-tyrosine phosphatase (PTP-oc), essential for osteoclast activity, shows sequence identity with the intracellular domain of GLEPP1, a renal receptor-like transmembrane PTP. PTP-oc has been assumed to be a truncated variant of GLEPP1, resulting from alternative splicing. However, the 5'-untranslated region sequence of PTP-oc mRNA contains 217 bp from an intron of GLEPP1. There are no splicing acceptor sites at the PTP-oc transcription site. The intronic sequence flanking the 5' end of the PTP-oc transcription start site contains potential promoter elements essential for transcriptional initiation. To test the hypothesis that the PTP-oc gene has an alternative, tissue-specific, intronic promoter, the promoter activity of a 1.3-kb PCR fragment covering the 5'-flanking region of the PTP-oc gene was measured. The putative PTP-oc promoter fragment showed strong promoter activity in U937 cells. Mutation of the putative TATA box within the PTP-oc promoter abolished 60-90% of its promoter activity. The PTP-oc promoter fragment showed strong promoter activity in cells that express PTP-oc (U937 cells and RAW264.7 cells) but not in cells that do not express the enzyme (skin fibroblasts, TE85 cells, and HEK293 cells). These findings strongly support the conclusion that the 1.3-kb intronic fragment contains the tissue-specific, PTP-oc proximal promoter. Deletion and functional analyses indicate that the proximal 5' sequence flanking the TATA box of the PTP-oc contains potential repressor elements. The removal of the putative repressor elements led to the apparent loss of tissue specificity. In summary, we conclude that an intronic promoter within the GLEPP1 gene drives the expression of the PTP-oc in a cell type-specific manner. This GLEPP1/PTP-oc gene system is one of the very few systems in which two important tissue-specific enzymes are derived from the same gene by the use of alternative intronic promoters.