Application of Global Lung Function Initiative Global Spirometry Reference Equations across a Large, Multicenter Pulmonary Function Lab Population.

Rationale: Global Lung Function Initiative (GLI) Global spirometry reference equations were recently derived to offer a "race-neutral" interpretation option. The impact of transitioning from the race-specific GLI-2012 to the GLI Global reference equations is unknown. Objectives: Describe the direction and magnitude of changes in predicted lung function measurements in a population of diverse race and ethnicity using GLI Global in place of GLI-2012 reference equations. Methods: In this multicenter cross-sectional study using a large pulmonary function laboratory database, 109,447 spirometry tests were reanalyzed using GLI Global reference equations and compared with the existing GLI-2012 standard, stratified by self-reported race and ethnicity. Measurements and Main Results: Mean FEV1 and FVC percent predicted increased in the White and Northeast Asian groups and decreased in the Black, Southeast Asian, and mixed/other race groups. The prevalence of obstruction increased by 9.7% in the White group, and prevalences of possible restriction increased by 51.1% and 37.1% in the Black and Southeast Asian groups, respectively. Using GLI Global in a population with equal representation of all five race and ethnicity groups altered the interpretation category for 10.2% of spirometry tests. Subjects who self-identified as Black were the only group with a relative increase in the frequency of abnormal spirometry test results (32.9%). Conclusions: The use of GLI Global reference equations will significantly impact spirometry interpretation. Although GLI Global offers an innovative approach to transition from race-specific reference equations, it is important to recognize the continued need to place these data within an appropriate clinical context.

The Resident Learning Journey in the Medical Intensive Care Unit.

Background: The medical intensive care unit (MICU) offers rich resident learning opportunities, but traditional teaching strategies can be difficult to employ in this fast-paced, high-acuity environment. Resident perspectives of learning within this environment may improve our understanding of the common challenges residents face and inform novel approaches to transform the MICU educational experience. Objective: We conducted a qualitative study of internal medicine residents to better understand their approach to learning the critical care activities that they are entrusted to perform in the MICU. Methods: Using a thematic analysis approach, we conducted six focus group interviews with 15 internal medicine residents, separated by postgraduate year. A trained investigator led each interview, which was audio-recorded and transcribed verbatim for analysis. Our diverse research team, representing different career stages across the continuum of learning to minimize interpretive bias, identified codes and subsequent themes inductively. We refined these themes through group discussion and sensitizing social learning theory concepts using Wenger's community of practice and organized them to create learner archetypes and a conceptual framework of resident learning in the MICU. Results: We identified three thematic resident learning categories: learning goals and motivation, clinical engagement, and interprofessional collaboration. We distinguished three learner archetypes, the novice, experiential learner, and practicing member, to describe progressive resident development within the interprofessional MICU team, the challenges they frequently encounter, and potential teaching strategies to facilitate learning. Conclusion: We developed a conceptual framework that describes the resident's journey to becoming a trusted, collaborating member of the interprofessional MICU team. We identified common developmental challenges residents face and offer educational strategies that may support their progress. These findings should inform future efforts to develop novel teaching strategies to promote resident learning in the MICU.

Surgery for Refractory Coccygodynia: Operative Versus Nonoperative Treatment.

STUDY DESIGN: This is a retrospective cohort study. OBJECTIVE: To evaluate the long-term outcomes for patients with refractory coccygodynia treated with coccygectomy compared to a nonsurgical regimen of sitting aids, physical therapy, medications, and injections. SUMMARY OF BACKGROUND DATA: The surgical treatment of coccygodynia remains controversial. To date, there has only been one small comparative study of surgical versus nonsurgical treatment. METHODS: From 2004 to 2014, 109 patients presenting with coccygodynia were treated with either total coccygectomy or a nonsurgical course of sitting aids, physical therapy, anti-inflammatory medications, and injections. All had at least 2 years of symptoms before surgery. The patient principally made the treatment decision, counseled by the treating physician. Before surgery, all subjects underwent at least 2 years of conservative treatment and three-dimensional imaging (computed tomography and/or magnetic resonance imaging). Subjects completed visual analog pain scales, EuroQol five-dimension, components of the PROMIS measure, and a novel Coccygodynia Disability Index evaluation. Work status, complications, and satisfaction were recorded. RESULTS: A total of 61 patients received nonsurgical care; eight declined participation and five could not be located. Forty-eight patients underwent total coccygectomy; three declined participation and five could not be located. At an average 4.8 years of follow-up (range: 2-9), the nonsurgical visual analog pain scales was 5 and the surgical 2 (P = 0.001); 79% of surgically treated patients were improved at 2 years versus 43% for the nonsurgical group. EuroQol five-dimension (P = 0.002), Coccygodynia Disability Index (0.01), and PROMIS Pain interference scores (0.02) were also significantly improved in the surgical group. Eleven surgical patients (26%) had complications, all wound related with successful resolution; seven treated with dressing changes and four with surgical debridement. CONCLUSION: Total coccygectomy is a safe and effective surgical treatment of coccygodynia refractory to nonoperative care. Patient-reported outcome measures were improved after surgery compared with nonsurgical management. Postoperative wound care remains a concern. LEVEL OF EVIDENCE: 4.

Idiopathic Spinal Epidural Lipomatosis in the Lumbar Spine.

Overgrowth of epidural fat, known as spinal epidural lipomatosis (SEL), can cause symptomatic compression of the spinal cord, conus medullaris, or cauda equina. Suggested predisposing factors such as obesity, steroid use, and diabetes mellitus have been based on a few reported cases, many of which were not surgically confirmed. There is a paucity of epidemiological data in surgically confirmed cases for this disorder. The purpose of this independently reviewed, retrospective, matched cohort analysis was to compare the demographics and incidence of comorbidities of patients who underwent lumbar decompression for SEL vs degenerative stenosis without SEL. Two surgeons' databases were reviewed to identify patients older than 18 years who underwent decompression surgery for magnetic resonance imaging-verified, symptomatic lumbar SEL. A matched control group comprised an equal number of patients with degenerative stenosis (n=14). Demographic data, body mass index, symptom type/duration, comorbidities, complications, treatment history, and associated pathology were collected from medical records. Previously suggested risk factors, such as obesity, endocrinopathy, and epidural steroid injections, were not significantly different between the SEL and control groups. Furthermore, there were no differences in operative times, complications, or blood loss. The only noted difference between the 2 groups was the preoperative duration of symptoms, on average double in patients with SEL. This series represents the largest of its kind reported to date. Because symptom duration was the only difference noted, it is postulated to be the result of lack of awareness of SEL. Future prospective study in a larger group of patients is warranted. [Orthopedics. 2016; 39(3):163-168.].

The influence of adjacent level disc disease on discectomy outcomes.

PURPOSE: The state of adjacent level discs and its impact on surgical outcomes following single-level lumbar discectomy have not been previously investigated. The purpose of the present study was to determine if a significant relationship exists between the degree of preoperative adjacent level disc degeneration and post-operative clinical outcomes following lumbar discectomy. METHODS: This study retrospectively used preoperative magnetic resonance imaging (MRI) and prospectively collected data from a randomized clinical trial at two tertiary-care academic hospitals. Patients who underwent a primary, single-level lumbar discectomy were included. Exclusion criteria included prior lumbar surgery. Outcome measures were the Modified Oswestry Disability Index (ODI) score and Visual Analog Scale (VAS) scores for back and leg pain. These were recorded at baseline and at 3 months, 1, and 2 years postoperatively. An independent reviewer graded adjacent level disc degeneration on all preoperative MRIs using the Pfirrmann grading scale. These data were then analyzed for correlation with each outcome measure. RESULTS: Forty-seven patients were included in the study. No statistically significant correlations were found when comparing preoperative 3-month or 1-year postoperative scores or change from baseline of any outcome measure between Pfirrmann grades. Only about half the patients had 2-year follow-up, but at that time point a statistically significant difference in back VAS scores was observed between Pfirrmann groups. No other significant differences were observed at that point. CONCLUSIONS: The degree of preoperative adjacent level degeneration does not significantly affect functional or pain relief outcomes following lumbar discectomy up to 1 year after surgery.

How Does the Level of Sacral Resection for Primary Malignant Bone Tumors Affect Physical and Mental Health, Pain, Mobility, Incontinence, and Sexual Function?

BACKGROUND: En bloc resection for treatment of sacral tumors is the approach of choice for patients with resectable tumors who are well enough to undergo surgery, and studies describe patient survival, postoperative complications, and recurrence rates associated with this treatment. However, most of these studies do not provide patient-reported functional outcomes other than binary metrics for bowel and bladder function postresection. QUESTIONS/PURPOSES: The purpose of this study was to use validated patient-reported outcomes tools to compare quality of life based on level of sacral resection in terms of (1) physical and mental health; (2) pain; (3) mobility; and (4) incontinence and sexual function. METHODS: Our analysis included 33 patients (19 men, 14 women) who had a mean age of 53 years (range, 22-72 years) with a quality-of-life survey administered at a mean postoperative followup of 41 months (range, 6-123 months). The majority of patient-reported quality-of-life outcome surveys for this study were taken from the National Institute of Health's Patient Reported Outcome Measurement Information System (PROMIS) system. To assess physical and mental health, the PROMIS Global Items Survey with physical and mental subscores, Anxiety, and Depression scores were used. Pain outcomes were assessed using PROMIS Pain Intensity and Pain Interference surveys. Patient-reported lower extremity function was assessed using the PROMIS Mobility Survey. Patient-reported quality of life for sexual function was assessed using the PROMIS Sex Interest and Orgasm survey, whereas incontinence was measured using the International Continence Society Voiding and Incontinence scores and the Modified Obstruction and Defecation Score. Surveys were collected prospectively during clinic visits in the postoperative period. Patients were grouped by the level of osteotomy as determined by review of postoperative MRI or CT and half levels were grouped with the more cephalad level. This resulted in the inclusion of total sacrectomy (N = 6), S1 (N = 8), S2 (N = 10), S3 (N = 5), and S4 (N = 4). One-way analysis of variance tests on means or ranks were used to conduct statistical analysis between levels. RESULTS: Patients with more caudal resections had higher physical health (95% confidence interval [CI] total sacrectomy 36-42 versus S4 50-64, p < 0.001), less intense pain (95% CI total sacrectomy 47-60 versus S4 28-37, p < 0.001), less interference resulting from pain (95% CI total sacrectomy 58-69 versus S4 36-51, p = 0.004), higher mobility (95% CI total sacrectomy 24-46 versus S4 59-59, p = 0.002), and were more functionally able to achieve orgasm (95% CI S1 1-1 versus S4 2.2-5.3, p = 0.043). No difference was found for PROMIS Global Item Mental Health Subscore, Sex Interest, Sex Satisfaction, modified obstruction and defecation score, and International Continence Society Voiding and Incontinence although this could be the result of an inadequate sample size. CONCLUSIONS: Our analysis on patient-reported quality of life based on the level of bony resection in patients who underwent resection for primary sacral tumor indicates that patients with higher resections have more pain and loss of physical function in comparison to patients with lower resections. Additionally, use of the PROMIS outcomes allows for comparisons to normative data. LEVEL OF EVIDENCE: Level III, therapeutic study.

High-dose enzyme replacement therapy in murine Hurler syndrome.

Mucopolysaccharidosis type I (MPS I) is an autosomal recessive disease that is systemic, including progressive neurodegeneration, mental retardation and death before the age of 10 years. MPS I results from deficiency of α-L-iduronidase (IDUA) in lysosomes and subsequent accumulation of glycosaminoglycans (GAG). Clinical enzyme replacement therapy (ERT) with intravenous laronidase reverses some aspects of MPS I disease (e.g., hepatomegaly, splenomegaly, glycosaminoglycanuria) and ameliorates others (e.g., pulmonary function, cardiac disease, arthropathy, exercise tolerance). However, neurologic benefits are thought to be negligible because the blood-brain barrier (BBB) blocks enzyme from reaching the central nervous system (CNS). We considered the possibility that a very high dose of intravenous laronidase might be able to traverse the BBB in small quantities, and provide some metabolic correction in the brain. To address this question, high-dose laronidase was administered (11.6 mg/kg, once per week, 4 weeks) to adult MPS I mice. IDUA enzyme activity in the cortex of treated mice increased to 97% of that in wild type mice (p<0.01). GAG levels in cortex were reduced by 63% of that from untreated MPS I mice (p<0.05). Further, immunohistochemical analysis showed that treatment reduced secondary GM3-ganglioside accumulation in treated MPS I mice. Water T-maze tests showed that the learning abnormality in MPS I mice was reduced (p<0.0001). In summary, repeated, high-dose ERT facilitated laronidase transit across the BBB, reduced GAG accumulation within the CNS, and rescued cognitive impairment.

Early colon screening of adult patients with cystic fibrosis reveals high incidence of adenomatous colon polyps.

BACKGROUND AND GOALS: Cystic fibrosis (CF) is associated with increased incidence of gastrointestinal cancer. Increasing overall life expectancy of CF patients predicts emergence of colon cancer as a significant clinical problem in the adult CF population. The primary aim of this study was to estimate the incidence of adenomatous colon polyps in patients with CF during systematic screening by colonoscopy. STUDY: This is a single-center series of 45 CF patients aged 40 years and above (mean age, 47 y) undergoing colonoscopic screening. A fraction of these patients (9/45) had history of organ transplantation. Results from transplant and nontransplant patients were analyzed separately. RESULTS: Adult CF patients have a high incidence of adenomatous polyps identified by colonoscopy. In addition, positive examinations are characterized by multiple polyps and common features of advanced pathology. The incidence of adenomatous colon polyps is greater in male patients, although the 1 patient in this cohort found to have colorectal cancer was female. CONCLUSIONS: CF has features of a hereditary colon cancer syndrome. Increasing life expectancy of CF patients suggests that earlier colon screening in this population may be warranted. Optimal criteria for initiation of screening and frequency of surveillance should be subject of further studies.

Standardization of α-L-iduronidase enzyme assay with Michaelis-Menten kinetics.

The lack of methodological uniformity in enzyme assays has been a long-standing difficulty, a problem for bench researchers, for the interpretation of clinical diagnostic tests, and an issue for investigational drug review. Illustrative of the problem, α-L-iduronidase enzyme catalytic activity is frequently measured with the substrate 4-methylumbelliferyl-α-L-iduronide (4MU-iduronide); however, final substrate concentrations used in different assays vary greatly, ranging from 25 µM to 1425 µM (Km ≈ 180 µM) making it difficult to compare results between laboratories. In this study, α-L-iduronidase was assayed with 15 different substrate concentrations. The resulting activity levels from the same specimens varied greatly with different substrate concentrations but, as a group, obeyed the expectations of Michaelis-Menten kinetics. Therefore, for the sake of improved comparability, it is proposed that α-L-iduronidase enzyme assays should be conducted either (1) under substrate saturating conditions; or (2) when concentrations are significantly below substrate saturation, with results standardized by arithmetic adjustment that considers Michaelis-Menten kinetics. The approach can be generalized to many other enzyme assays.