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The Routine Assessment of Patient Index Data 3 (RAPID3) is a patient-reported outcome tool recommended for the assessment of disease activity in patients with rheumatoid arthritis (RA) in clinical practice. This analysis evaluated the long-term effect of upadacitinib vs. comparators on RAPID3 scores in patients with RA in the phase 3 SELECT clinical trial program.This post hoc analysis included data from five randomized controlled trials (RCTs) in patients receiving upadacitinib 15 mg or 30 mg once daily (QD) as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). The proportions of patients reporting RAPID3 remission (scores ≤ 3) were assessed at week 60. Correlations between absolute scores for RAPID3 and Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), and 28-joint Disease Activity Score with C-reactive protein (DAS28[CRP]) at week 60 were assessed using Spearman correlation coefficients.A total of 3117 patients were included from the SELECT-NEXT, -BEYOND, -MONOTHERAPY, -COMPARE, and -EARLY trials. By week 60, 32-52% of methotrexate-naïve and csDMARD inadequate responder (IR) patients treated with either upadacitinib 15 mg QD or upadacitinib 30 mg QD reported RAPID3 scores consistent with remission. The proportions were slightly lower in the biologic DMARD-IR SELECT-BEYOND population (19-28%). RAPID3 scores highly correlated (Spearman correlation values ≥ 0.58) with CDAI, SDAI, and DAS28(CRP) scores through week 60 (all p 0.001).Upadacitinib, as monotherapy or in combination with csDMARDs, was associated with patient-reported remission assessed by RAPID3 over 60 weeks across the SELECT RCTs in patients with RA.SELECT-BEYOND (NCT02706847); SELECT-NEXT (NCT02675426); SELECT-MONOTHERAPY (NCT02706951); SELECT-EARLY (NCT02706873); SELECT-COMPARE (NCT02629159).Rheumatoid arthritis (RA) is a disease that causes inflammation of the joints. Doctors have several ways of assessing how bad a patient’s disease is, and these often use a combination of signs and symptoms to develop a ‘score’. One method is called RAPID3, which is a score based on an overall assessment of the disease by the patient, the level of pain, and the amount of physical disability. An advantage of RAPID3 is that it is quick and easy to use, and since it uses only patient-reported symptoms, it can be measured easily via telemedicine, without the need for an in-person consultation. In this study, we decided to look into the effect of upadacitinib, a drug used for the treatment of RA, on RAPID3 score in patients with RA. We also investigated whether RAPID3 correlates with other ways of measuring RA severity, including scores that use physician-measured factors such as number of affected joints, as this can help show whether RAPID3 is a valid and useful tool. We found that upadacitinib led to long-term improvements in RAPID3 score, and that results were the same in different studies and patient groups, including patients who had not responded well to other treatments. We also found that RAPID3 correlated well with other measures, i.e., improvements in RAPID3 happened in parallel with improvements in other scores. Overall, these results suggest that RAPID3 can be a useful tool in patients with RA.

Guillain–Barré syndrome (GBS) is an acute inflammatory polyradiculoneuropathy; a disease involving the peripheral nervous system which is the most common cause of acute flaccid paralysis worldwide. So far, it is still lack of a comprehensive overview and understanding of the national epidemiological, clinical characteristics, and the risk factors of GBS in China, as well as differences between China and other countries and regions in these respects. With the global outbreak of the coronavirus disease 2019 (COVID-19), an epidemiological or phenotypic association between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and GBS has attracted great attention. In this review, we outlined the current clinical data of GBS in China by retrieving literature, extracting and synthesizing the data of GBS in China from 2010 to 2021. Besides, we compared the characteristics of epidemiology, preceding events and clinical profiles of GBS between China and other countries and regions. Furthermore, in addition to conventional intravenous immunoglobulin (IVIG) and plasma exchange (PE) therapy, the potential therapeutic effects with novel medications in GBS, such as complement inhibitors, etc., have become the research focus in treatments. We found that epidemiological and clinical findings of GBS in China are approximately consistent with those in the International GBS Outcome Study (IGOS) cohort. We provided an overall picture of the present clinical status of GBS in China and summarized the global research progress of GBS, aiming to further understand the characteristics of GBS and improve the future work of GBS worldwide, especially in countries with the middle and low incomes.

Background/Aims For patients with RA who are refractory to biologic disease-modifying antirheumatic drugs (bDMARDs), such as tumor necrosis factor inhibitors (TNFis), optimal disease control is less likely to be achieved with subsequent therapy. In line with recommendations from EULAR and ACR, switching to a treatment with a different mechanism of action is appropriate for these patients. Objectives To describe the efficacy and safety of upadacitinib (UPA) 15 mg once daily in patients with RA and an inadequate response or intolerance to TNFis (TNFi-IR). Methods A post hoc subgroup analysis was conducted in TNFi-IR patients who were treated with UPA 15 mg once daily in three Phase 3 clinical trials: SELECT-BEYOND, -CHOICE, and -COMPARE. For COMPARE, only patients treated with adalimumab and switched to UPA as rescue therapy were included. ≥20/50/70% improvement in ACR criteria, DAS28-CRP, Clinical Disease Activity Index, and Simple Disease Activity Index, as well as change from baseline in HAQ-DI and other patient-reported outcomes (PROs) were reported through 24 weeks. Non-responder imputation was used for all missing categorical outcomes; as observed (COMPARE) or multiple imputation (CHOICE, BEYOND) were used for missing continuous outcomes. Pooled safety results were presented as exposure-adjusted event rates (EAERs) with a cut-off of June 30, 2021. Results 568 TNFi-IR patients were included: 146 from BEYOND, 263 from CHOICE, and 159 from COMPARE. Mean duration since RA diagnosis was longer for BEYOND and CHOICE versus COMPARE; CV risk factors were common among this refractory population. ACR20/50/70 and disease activity outcomes observed in the TNFi-IR population were generally consistent with the overall BEYOND and CHOICE bDMARD-IR populations, and consistent across the three studies in the TNFi-IR subgroups. Improvements in PROs including HAQ-DI, fatigue, pain, and morning stiffness over 24 weeks were observed (data not shown). Pooled safety results reporting 1574.8 PY of exposure in the TNFi-IR subgroup showed similar results to the overall BEYOND and CHOICE bDMARD-IR study populations, with EAERs of 3.1 events/100 PY for herpes zoster and 0.8 events/100 PY for adjudicated major adverse CV events and venous thromboembolism, and malignancy excluding non-melanoma skin cancer. The EAER of any AE leading to death was 1.4 events/100 PY. Conclusion In this post hoc subgroup analysis, TNFi-IR patients treated with UPA 15 mg achieved clinically meaningful efficacy responses over 24 weeks, with safety consistent with the overall bDMARD-IR patient population in the Phase 3 program. Disclosure R. Fleischmann: Consultancies; Consultant for AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Galvani, Gilead, GSK, Janssen, Novartis, Pfizer Inc, and UCB. Grants/research support; Grant/research support from AbbVie, Amgen, Biosplice, Bristol-Myers Squibb, Flexion, Gilead, Horizon, Eli Lilly, Galvani, Janssen, Novartis, Pfizer Inc, Sanofi-Aventis, Selecta, Teva, UCB, Viela, and. L. Bessette: Consultancies; AbbVie, Amgen, Bristol-Meyers Squibb, Celgene, Eli Lilly, Fresenius Kabi, Gilead, Janssen, Merck, Novartis, and Pfizer, Roche, Sanofi-Aventis, Teva, and UCB. Member of speakers’ bureau; AbbVie, Amgen, Bristol-Meyers Squibb, Celgene, Eli Lilly, Fresenius Kabi, Gilead, Janssen, Merck, Novartis, and Pfizer, Roche, Sanofi-Aventis, Teva, and UCB. Grants/research support; AbbVie, Amgen, Bristol-Meyers Squibb, Celgene, Eli Lilly, Fresenius Kabi, Gilead, Janssen, Merck, Novartis, and Pfizer, Roche, Sanofi-Aventis, Teva, and UCB. S. Hall: Consultancies; AbbVie, Amgen, Bristol-Meyers Sqibb, Eli Lilly, Gilead, Janssen, Merck, Novartis, and UCB. Grants/research support; AbbVie, Amgen, Bristol-Meyers Sqibb, Eli Lilly, Gilead, Janssen, Merck, Novartis, and UCB. J. Sparks: Consultancies; Consulted for AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Inova Diagnostics, Janssen, Optum, and Pfizer. M. Jain: Consultancies; Amgen, Abbvie, Eli Lilly, Pfizer, and Novartis. Grants/research support; Amgen, Abbvie, Eli Lilly, Pfizer, and Novartis. A. Kakehasi: Consultancies; Amgen, Janssen, UCB, AbbVie, Pfizer, Eli Lilly, Novartis, Sandoz, Fresenius Kabi. Member of speakers’ bureau; Amgen, Janssen, UCB, AbbVie, Pfizer, Eli Lilly, Novartis, Sandoz, Fresenius Kabi. Grants/research support; Amgen, Janssen, UCB, AbbVie, Pfizer, Eli Lilly, Novartis, Sandoz, Fresenius Kabi. Y. Song: Shareholder/stock ownership; full-time employees of AbbVie and may own stock or options. S. Meerwein: Shareholder/stock ownership; full-time employees of AbbVie and may own stock or options. R. DeMasi: Shareholder/stock ownership; full-time employees of AbbVie and may own stock or options. J. Suboticki: Shareholder/stock ownership; full-time employees of AbbVie and may own stock or options. A. Rubbert-Roth: Consultancies; AbbVie, AbbVie Deutschland, Amgen, Bristol-Myers Squibb, Chugai Pharmaceuticals, Eli Lilly, F. Hoffman-La Roche, Gilead Sciences, Janssen Global Services, Novartis, and Sanofi Pasteur.

Background/Aims A greater proportion of patients with RA and inadequate response to methotrexate (MTX) receiving upadacitinib (UPA), achieved REM/LDA compared with adalimumab (ADA), both with background MTX, through 26 weeks in the phase 3, SELECT-COMPARE trial. Here we assessed sustainability of response over 3 years. Methods SELECT-COMPARE included a 26-week, double-blind, placebo (PBO)-controlled period, a 48-week, double-blind active comparator-controlled period, and an ongoing long-term extension for up to 10 years. Patients on background MTX received UPA 15 mg once daily, PBO, or ADA 40 mg every other week. Patients not achieving at least 20% improvements in tender/swollen joint counts (Weeks 14-22) or LDA (CDAI ≤10 at Week 26) were rescued from UPA to ADA or PBO/ADA to UPA. This post hoc analysis evaluated clinical REM (CDAI ≤2.8; SDAI ≤3.3), LDA (CDAI ≤10; SDAI ≤11), and DAS28(CRP) Results Through 3 years, a significantly higher proportion of patients receiving UPA + MTX vs ADA + MTX achieved CDAI REM (47% vs 35%, P = 0.001) as well as CDAI LDA (70% vs 60%, P = 0.001). At 30 months after first occurrence of response, CDAI REM/LDA was sustained in 19%/42% of patients randomized to UPA and 10%/30% of patients randomized to ADA. Time to initial clinical response did not appear to be predictive of sustained disease control. C-index for CDAI REM/LDA was 0.50/0.60 on UPA vs 0.49/0.56 on ADA. Through last follow-up visit, 37%/58% of patients receiving UPA and 27%/48% on ADA remained in CDAI REM/LDA, respectively. Of patients who lost CDAI REM, 68% on UPA and 55% on ADA remained in LDA. Roughly similar proportions on UPA and ADA recaptured CDAI REM/LDA (UPA, 40%/17%; ADA, 48%/19%). Similar results were observed for REM/LDA based on SDAI and for DAS28(CRP) Conclusion Among patients with inadequate response to MTX, a higher proportion receiving UPA + MTX achieved remission or LDA across disease activity measures vs ADA + MTX. UPA-treated patients demonstrated a consistently higher sustained response rate over 3 years compared to those receiving ADA. Furthermore, significant proportions of patients who lost response on either UPA or ADA were able to recapture remission or LDA. Disclosure M.H. Buch: Consultancies; M.H.B. has received consulting fees/meeting support from AbbVie, Boehringer Ingleheim, Eli Lilly, Merck-Serono, and Sanofi. Grants/research support; M.H.B. has received research grants from Pfizer, Gilead, and UCB. P. Nash: Honoraria; P.N. has received honoraria for lectures and advice from AbbVie, BMS, Pfizer, Gilead/Galapagos, Sanofi, Celgene, Novartis, Lilly, Janssen, UCB, Samsung, MSD, Roche. Grants/research support; P.N. has received research funding for clinical trials. A. Kavanaugh: Consultancies; A.K. has provided expert advice to AbbVie Inc., Amgen, Astra-Zeneca, BMS, Celgene, Centocor-Janssen, Pfizer, Roche, and UCB. Grants/research support; A.K. has has received grants/research support. B. Combe: Consultancies; B.C. has received consulting fees from AbbVie, BMS, Celltrion, Gilead, Galapagos, Janssen, Eli Lilly, MSD, Pfizer, Roche Chugai. L. Bessette: Consultancies; L.B. has received consulting fees from Amgen, BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Merck, Celgene, Sanofi, Eli Lilly, Novartis. Sandoz, Gilead, Fresenius Kabi, and Teva. Member of speakers’ bureau; L.B. has served as a speaker for Amgen, BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Merck, Celgene, Sanofi, Eli Lilly, Novartis. Sandoz, Gilead, Fresenius Kabi, and Teva. Grants/research support; L.B. has received grants/research support from Amgen, BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Merck, Celgene, Sanofi, Eli Lilly, Novartis. Sandoz, Gilead, Fresenius Kabi, and Teva. I. Song: Shareholder/stock ownership; IH.S. is an employee of AbbVie and may hold stock or options. T. Shaw: Shareholder/stock ownership; T.S. is an employee of AbbVie and may hold stock or options. Y. Song: Shareholder/stock ownership; Y.S. is an employee of AbbVie and may hold stock or options. J.L. Suboticki: Shareholder/stock ownership; J.L.S is an employee of AbbVie and may hold stock or options. R. Fleischmann: Consultancies; R.F. is a consultant for AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, GSK, Janssen, Novartis, Pfizer Inc, Sanofi-Aventis, and UCB. Grants/research support; R.F. has received grant/research support from AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Genentech, Janssen, Novartis, Pfizer, UCB, Regeneron, Roche,Sanofi-Aventis.

In clinical studies, it is common to have binary outcomes collected over time as repeated measures. This manuscript reviews and evaluates two popular classes of statistical methods for analyzing binary response data with repeated measures: likelihood-based Generalized Linear Mixed Model (GLMM), and semiparametric Generalized Estimating Equation (GEE). Recommendations for choice of analysis model and points to consider for implementation in clinical studies in the presence of missing data are provided based on a comprehensive literature review, as well as, a simulation study evaluating the performance of both GLMM and GEE under scenarios representative of typical clinical trial settings. Under Missing at Random (MAR) assumption, GLMM is preferred over GEE, and the SAS PROC GLIMMIX marginal model is recommended for implementing GLMM in analyzing clinical trial data. When there is an underlying continuous variable used to define the binary response, and the missing proportion is high and/or unbalanced between treatment groups, a two-step approach combining Multiple Imputation (MI) and GEE (MI-GEE) is recommended.

Introduction The efficacy of pharmacotherapy and deep brain stimulation of the subthalamic nucleus in treating Parkinson's disease motor symptoms is highly variable and may be influenced by patient genotype. The relatively common (prevalence about one in three) and protein-altering rs6265 single nucleotide polymorphism (C > T) in the gene BDNF has been associated with different clinical outcomes with levodopa. Objective We sought to replicate this reported association in early-stage Parkinson's disease subjects and to examine whether a difference in clinical outcomes was present with subthalamic nucleus deep brain stimulation. Materials and methods Fifteen deep brain stimulation and 13 medical therapy subjects were followed for 24 months as part of the Vanderbilt DBS in Early Stage PD clinical trial (NCT00282152, FDA IDE #G050016). Primary outcome measures were the Unified Parkinson's Disease Rating Scale (UPDRS) and Parkinson's Disease Questionnaire-39. Results Outcomes with drug therapy in subjects carrying the rs6265 T allele were significantly worse following 12 months of treatment compared to C/C subjects (UPDRS: +20 points, p = 0.019; PDQ-39: +16 points, p = 0.018). In contrast, rs6265 genotype had no effect on overall motor response to subthalamic nucleus deep brain stimulation at any time point; further, rs6265 C/C subjects treated with stimulation were associated with worse UPDRS part II scores at 24 months compared to medical therapy. Conclusions Genotyping for the rs6265 polymorphism may be useful for predicting long-term response to drug therapy and counseling Parkinson's disease patients regarding whether to consider earlier subthalamic nucleus deep brain stimulation. Validation in a larger cohort of early-stage Parkinson's disease subjects is warranted.

ObjectivesLong-term safety and efficacy of adalimumab among patients with juvenile idiopathic arthritis (JIA) was evaluated through 6 years of treatment.MethodsChildren aged 4–17 years with polyarticular JIA were enrolled in a phase III, randomised-withdrawal, double-blind, placebo-controlled trial consisting of a 16-week open-label lead-in period, 32-week randomised double-blind period and 360-week long-term extension. Patients were stratified by baseline methotrexate use. Adverse events (AEs) were monitored, and efficacy assessments included JIA American College of Rheumatology (JIA ACR) 30%, 50%, 70% or 90% responses and the proportions of patients achieving 27-joint Juvenile Arthritis Disease Activity Score (JADAS27) low disease activity (LDA, ≤3.8) and inactive disease (ID, ≤1).ResultsOf 171 patients enrolled, 62 (36%) completed the long-term extension. Twelve serious infections in 11 patients were reported through 592.8 patient-years of exposure. No cases of congestive heart failure-related AEs, demyelinating disease, lupus-like syndrome, malignancies, tuberculosis or deaths were reported. JIA ACR 30/50/70/90 responses and JADAS27 LDA were achieved in 66% to 96% of patients at week 104, and 63 (37%) patients achieved clinical remission (JADAS27 ID sustained for ≥6 continuous months) during the study. Attainment of JIA ACR 50 or higher and JADAS27 LDA or ID in the initial weeks were the best predictors of clinical remission. Mean JADAS27 decreased from baseline, 22.5 (n=170), to 2.5 (n=30) at week 312 (observed analysis).ConclusionsThrough 6 years of exposure, adalimumab was well tolerated with significant clinical response (up to clinical remission) and a relatively low retention rate.

Neuromyelitis optica spectrum disorder (NMOSD) is a common neuroinflammatory demyelinating disease associated with aquaporin-4 (AQP4) antibody in the central nervous system. Neurosyphilis is a neurological disease caused by Treponema pallidum infection. NMOSD commonly occurs concurrently with autoimmune diseases. However, they have rarely been associated with infectious diseases. In this report we describe a rare case of concurrent AQP4-positive NMOSD and neurosyphilis. A 60-year-old man was admitted to our hospital with a complaint of progressive weakness in his legs for one month. T2-weighted magnetic resonance images of the spinal cord showed longitudinal extensive lesions at C7–T7. The rapid plasma reagin test and T. pallidum particle agglutination assay performed using patient serum and cerebrospinal fluid (CSF) were positive. Additionally, the AQP4-immunoglobulin (Ig) G was detected in the serum and CSF. The patient's symptom gradually improved after penicillin and methylprednisolone treatment. This case report highlights the possibility of the presence of an infectious disease in patients with NMOSD.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a rare inflammatory disorder, mainly involving the brainstem. Posterior reversible encephalopathy syndrome (PRES) is a syndrome that affects the bilateral parietal-occipital region. Here, we describe a rare case of CLIPPERS with PRES. A 47-year-old woman presented with subacute, progressive ataxia symptoms, and radiological and pathological findings were consistent with CLIPPERS. In addition, she had acute convulsions and was unconscious, and brain magnetic resonance imaging fluid-attenuated inversion recovery showed patchy high-intensity posterior cerebral white matter signals, with imaging lesions showing vasogenic oedema, a typical manifestation of PRES. The imaging lesions showed vasogenic oedema in bilateral parietal and occipital lobes and typical ‘pepper-like’ punctate gadolinium enhancement in pons and bilateral cerebellar hemispheres, which were considered to be caused by merger of CLIPPERS and PRES. Clinical manifestations and imaging lesions disappeared after two months of steroids and symptomatic treatment, supporting the diagnosis of CLIPPERS with PRES. When patients with CLIPPERS show unusual symptoms or atypical vasogenic oedema lesions in the posterior cerebral white matter, the coexistence of PRES should be considered.

Psychogenic nonepileptic seizures (PNES) are a common cause of refractory seizures. Video-electroencephalographic (EEG) monitoring has allowed PNES to be effectively distinguished from epileptic seizures. Once the diagnosis of PNES is established, neurologists face the challenge of explaining it to patients. Patients may not always receive the diagnosis well. The aim of this study is to evaluate how effectively patients receive and perceive the diagnosis of PNES. This prospective study was conducted in an eight-bed epilepsy monitoring unit (EMU). Adult patients with newly confirmed PNES were included. After receiving written consent, a self-administered questionnaire was given to patients after the attending physician had communicated the diagnosis of PNES. A total of 75 patients were recruited. All patients had their typical seizures recorded on video-EEG (range 1-12, mean 2.18). Seventy patients were satisfied with the diagnosis of PNES. Nine patients did not agree that PNES has a psychological cause. Nineteen patients thought that the EMU doctors had no clue as to the cause of their seizures and 20 thought that there was no hope for a cure of their seizures. A significant number of patients with PNES feel that there is no hope for cure of their seizures. Thorough education about PNES, properly preparing patients before discussing the diagnosis of PNES, and preferably earlier diagnosis may prevent this miscommunication and result in better outcomes. A comprehensive approach including psychological counseling and psychiatric input, evaluation and treatment, in order to bring the illness from the subconscious to the conscious level, and effective follow-up may be helpful.

Abnormal platelet reactivity is associated with recurrent ischemia and bleeding following percutaneous coronary intervention (PCI). Protease-activated receptor-1 (PAR1), encoded by F2R, is a high affinity thrombin receptor on platelets and the target of the antiplatelet drug vorapaxar. The intronic single nucleotide polymorphism F2R IVS-14 A/T affects PAR1 receptor density and function. We hypothesized that carriers of the T allele, who have been shown to have decreased platelet reactivity, would be at lower risk for thrombotic events, but higher risk for bleeding following PCI. Using BioVU, the Vanderbilt DNA repository linked to the electronic medical record, we studied 660 patients who underwent PCI for unstable or stable coronary artery disease. Primary outcome measures were major adverse cardiovascular events (MACE, composite of revascularization, MI, stroke, death) and bleeding (assessed by Bleeding Academic Research Consortium scale) over 24 months. The minor allele (T) frequency was 14.8 %. There were no genotypic differences in the frequency of MACE (33.7, 28.8, and 31.6 % for A/A, A/T, and T/T respectively, P = 0.50) or bleeding (15.7, 14.7, and 18.8 % for A/A, A/T, and T/T respectively, P = 0.90). In a Cox regression model, fully adjusted for age, race, sex, BMI, and smoking status, carrying a T allele was not associated with MACE (HR 1.19, 95 % CI 0.89-1.59, P = 0.23) or bleeding (HR 0.73, 95 % CI 0.37-1.4, P = 0.34). In conclusion, in our population, F2R IVS-14 PAR1 variability does not affect risk of MACE or bleeding following PCI.

To determine the long-term clinical effectiveness and safety of maxillomandibular advancement (MMA) for the treatment of moderate to severe obstructive sleep apnea (OSA).A prospective two-center cohort study design was used to evaluate OSA patients who underwent MMA2 years ago. The primary outcome measure was the apnea-hypopnea index (AHI). Secondary outcome measures included blood pressure (BP), sleepiness (Epworth Sleepiness Scale [ESS]), and quality of life (Functional Outcomes of Sleep Questionnaire [FOSQ]).30 adult patients (80% men, age 50.5 ± 9.6 years [mean ± SD]) participated in the study. The AHI decreased from a mean of 49 to 10.9 events/h (p0.0001) at the time of long-term evaluation (6.6 ± 2.8 years after MMA), with 46.7% of patients obtaining an AHI5 and 83.4% of patients attaining an AHI ≤ 15 events/h. The mean diastolic BP decreased from 83.7 to 79.0 mm Hg (p0.05). ESS decreased from a mean of 12.1 to 6.0 (p0.01). FOSQ increased from a mean of 12.6 to 17.3 (p0.05). Few long-term treatment-related adverse events occurred, which had minimal impact on quality of life (QOL).MMA is a clinically effective and safe long-term treatment for most patients with moderate-to-severe OSA as demonstrated by significant decreases in AHI, diastolic BP, and subjective sleepiness, with concomitant significant improvements in QOL. The results of this small cohort study suggest that MMA should be considered as the alternative treatment of choice for patients with severe OSA who cannot fully adhere to CPAP therapy.

Accurate identification of atrial fibrillation episodes from polysomnograms is important for research purposes but requires manual review of a large number of long electrocardiographic tracings. As automated assessment of these tracings for atrial fibrillation may improve efficiency, this study aimed to evaluate this approach in polysomnogram-derived electrocardiographic data. A previously described algorithm to detect atrial fibrillation from single-lead electrocardiograms was applied to polysomnograms from a large epidemiologic study of obstructive sleep apnea in older men (Osteoporotic Fractures in Men [MrOS] Sleep Study). Atrial fibrillation status during each participant’s PSG was determined by independent manual review. Models to predict atrial fibrillation status from a combination of algorithm output and clinical/polysomnographic characteristics were developed, and their accuracy was evaluated using standard statistical techniques. Derivation and validation cohorts each consisted of 1395 individuals; 5 % of each group had atrial fibrillation. Model parameters were optimized for the derivation cohort using the Akaike information criterion. Application to the validation cohort of these optimized models revealed high sensitivity (85–90 %) and specificity (90–95 %) as well as good predictive ability, as assessed by the C statistic (>0.9) and generalized R 2 values (∼0.6). Addition of cardiovascular or polysomnogram data to the models did not improve their performance. In a research setting, automated detection of atrial fibrillation from polysomnogram-derived electrocardiographic signals appears feasible and agrees well with manual identification. Future studies can evaluate the utility of this technique as applied to clinical polysomnograms and ambulatory electrocardiographic monitoring.

Background Deep brain stimulation (DBS) is an effective treatment for patients with advanced Parkinson's disease (PD) and motor symptom complications. Recently, attention has been focused on whether offering DBS earlier in the course of PD is beneficial. Objective The purpose of this study was to determine the effects of DBS on neuropsychological functioning in subjects with early stage PD. Methods Thirty subjects with early PD (Hoehn & Yahr Stage II off medication) were randomized to optimal drug therapy (ODT) (n = 15) or bilateral subthalamic nucleus (STN) DBS+ODT (n = 15) after completing an expanded informed consent process specially designed for the study and administered by a medical ethicist and the study team. Comprehensive neuropsychological testing was completed in the treatment-withdrawn state at baseline and at 12 month and 24 month follow-ups. Results Two serious adverse events occurred in the DBS+ODT group. One subject experienced a stroke and another developed infected hardware that contributed to specific declines in cognitive functioning. However, compared to the ODT group, the remaining subjects in the DBS+ODT group exhibited modest reductions on a few measures of attention, executive function, and word fluency at 12 months. These differences were largely diminished at 24 months, especially when those with the adverse events were excluded. Conclusions The results of this trial provide novel data regarding the effects of DBS on cognitive function in early PD. We believe that the findings and insights from this trial can help guide the safety analysis and risk-benefit evaluations in future discussions of DBS in early stage PD.

Background— Despite increased secondary cardiovascular events in patients with ischemic cardiomyopathy (ICM), the expression of innate cardiac protective molecules in the hearts of patients with ICM is incompletely characterized. Therefore, we used a nonbiased RNAseq approach to determine whether differences in cardiac protective molecules occur with ICM. Methods and Results— RNAseq analysis of human control and ICM left ventricular samples demonstrated a significant decrease in KCNJ11 expression with ICM. KCNJ11 encodes the Kir6.2 subunit of the cardioprotective K ATP channel. Using wild-type mice and kcnj11 -deficient ( kcnj11 -null) mice, we examined the effect of kcnj11 expression on cardiac function during ischemia-reperfusion injury. Reactive oxygen species generation increased in kcnj11 -null hearts above that found in wild-type mice hearts after ischemia-reperfusion injury. Continuous left ventricular pressure measurement during ischemia and reperfusion demonstrated a more compromised diastolic function in kcnj11 -null compared with wild-type mice during reperfusion. Analysis of key calcium-regulating proteins revealed significant differences in kcnj11 -null mice. Despite impaired relaxation, kcnj11 -null hearts increased phospholamban Ser16 phosphorylation, a modification that results in the dissociation of phospholamban from sarcoendoplasmic reticulum Ca 2+ , thereby increasing sarcoendoplasmic reticulum Ca 2+ –mediated calcium reuptake. However, kcnj11 -null mice also had increased 3-nitrotyrosine modification of the sarcoendoplasmic reticulum Ca 2+ -ATPase, a modification that irreversibly impairs sarcoendoplasmic reticulum Ca 2+ function, thereby contributing to diastolic dysfunction. Conclusions— KCNJ11 expression is decreased in human ICM. Lack of kcnj11 expression increases peroxynitrite-mediated modification of the key calcium-handling protein sarcoendoplasmic reticulum Ca 2+ -ATPase after myocardial ischemia-reperfusion injury, contributing to impaired diastolic function. These data suggest a mechanism for ischemia-induced diastolic dysfunction in patients with ICM.

IN BRIEF Postpartum follow-up for patients with gestational diabetes mellitus (GDM) is essential to manage future disease risk. In a diverse, urban population of GDM patients at a major medical center, high fasting glucose, high BMI at diagnosis, and low education level were associated with not following up in the endocrinology clinic after delivery; patients least likely to follow up are, therefore, also at greatest risk of GDM complications. Although race/ethnicity was not a significant predictor of follow-up, Hispanic/Latina and African-American patients were more likely to have risk factors for postpartum clinical attrition.

Background and Objectives In 2002, with the advent of better classification techniques, the World Health Organization declassified malignant fibrous histiocytoma (MFH) as a distinct histological entity in favor of the reclassified entity high-grade undifferentiated pleomorphic sarcoma (HGUPS). To date, no study has evaluated comparative outcomes between patients designated historically in the MFH group and those classified in the new HGUPS classification. Our goal was to determine the presence of clinical prognostic implications that have evolved with this new nomenclature. Methods Sixty-eight patients were retrospectively evaluated between January 1998 and December 2007. Forty-five patients diagnosed with MFH between 1998 and 2003 were compared to 23 patients in the HGUPS group, from 2004 to 2007. Primary prognostic outcomes assessed included overall survival, metastatic-free, and local recurrence-free survival. Results Five-year survivorship between MFH and HGUPS populations, using Kaplan–Meier or competing risk methods, did not show statistical difference for overall survival (60% vs. 74%, P = 0.36), 5-year metastasis-free survival (31% vs. 26%, P = 0.67), or local recurrence-free survival (13% vs. 16%, P = 0.62). Conclusion Despite new classification nomenclature, there appears to be no identifiable prognostic implications for sarcomas that remain in the unclassifiable HGUPS group, as compared to the previously accepted MFH group. J. Surg. Oncol. 2015 111:173–177. © 2014 Wiley Periodicals, Inc.

BACKGROUND Spousal support has been hypothesized as providing important psychosocial support for patients and as such has been noted to provide a survival advantage in a number of chronic diseases and cancers. However, the specific effect of marital status on survival in soft tissue sarcomas (STSs) of the extremity has not been explored in detail. PATIENTS AND METHODS A total of 7384 patients were evaluated for this study using a Surveillance, Epidemiology, and End Results (SEER) registry query for patients over 20 years old with extremity STS diagnosed between 2004 and 2009. Survival outcomes were analyzed using Gray's test after patients were stratified by marital status. The Fine and Gray model, a multivariable regression model, was used to assess whether marital status was an independent predictor of sarcoma specific death. Statistical significance was maintained at P < 0.05. RESULTS Analysis of the SEER database showed that single patients were more likely to die of their STS and at a faster rate than married patients. No differences were noted in tumor size and tumor site on presentation between married and single patients. However, single patients presented with higher grade tumors more frequently (P = 0.013), received less radiotherapy (P < 0.001), and had less surgery carried out (P < 0.001), compared with their married peers. Regression analysis showed that after accounting for tumor size, grade, site, histology, use of radiotherapy, age, gender, region where the patients were from, and income, being single continued to serve as an independent predictor of sarcoma-specific death; P < 0.0001. CONCLUSION Overall survival is worse for single patients, when compared with married patients, with STS. Single patients do not undergo surgical resection or receive radiation therapy as frequently as their married counterparts. Social support systems and barriers to care should be evaluated at time of diagnosis and addressed in single patients to potentially improve survival outcomes.

Background Children with autism spectrum disorder (ASD) are impaired in social communication and interaction with peers, which may reflect diminished social motivation. Many children with ASD show enhanced stress when playing with other children. This study investigated social and stress profiles of children with ASD during play. Methods We utilized a peer interaction paradigm in a natural playground setting with 66 unmedicated, prepubertal, children aged 8–12 years [38 with ASD, 28 with typical development (TD)]. Salivary cortisol was collected before and after a 20-min playground interaction that was divided into periods of free and solicited play facilitated by a confederate child. Statistical analyses included Wilcoxon rank-sum tests, mixed effects models, and Spearman correlations to assess the between-group differences in social and stress functioning, identify stress responders, and explore associations between variables, respectively. Results There were no differences between the groups during unsolicited free play; however, during solicited play by the confederate, significant differences emerged such that children with ASD engaged in fewer verbal interactions and more self-play than the TD group. Regarding physiological arousal, children with ASD as a group showed relatively higher cortisol in response to social play; however, there was a broad range of responses. Moreover, those with the highest cortisol levels engaged in less social communication. Conclusions The social interaction of children with ASD can be facilitated by peer solicitation; however, it may be accompanied by increased stress. The children with ASD that have the highest level of cortisol show less social motivation; yet, it is unclear if it reflects an underlying state of heightened arousal or enhanced reactivity to social engagement, or both.

Background and Objectives Prior studies have demonstrated postoperative infection may confer a survival benefit after osteosarcoma resection. Our aim was to determine whether infection after soft tissue sarcoma resection has similar effects on metastasis, recurrence and survival. Methods A retrospective review was conducted; 396 patients treated surgically for a soft tissue sarcoma between 2000 and 2008 were identified. Relevant oncologic data were collected. Fifty-six patients with a postoperative infection were compared with 340 patients without infection. Hazard ratios and overall cumulative risk were evaluated. Results There was no difference in survival, local recurrence or metastasis between patients with or without a postoperative infection. Patients were evenly matched for age at diagnosis, gender, smoking status, and diabetes status. Tumor characteristics did not differ between groups in tumor size, location, depth, grade, margin status, stage, and histologic subtype. There was no difference in utilization of chemotherapy or radiation therapy between groups. From our competing risk model, only positive margin status significantly impacted the risk of local recurrence. An increase in tumor size corresponded to an increased risk of metastasis and death. Conclusions Postoperative infection neither conferred a protective effect, nor increased the risk of adverse oncologic outcomes after soft tissue sarcoma resection. J. Surg. Oncol. 2014 109:415–420. © 2013 Wiley Periodicals, Inc.

Social Emotional NeuroScience Endocrinology Theatre is a novel intervention program aimed at improving reciprocal social interaction in youth with autism spectrum disorder (ASD) using behavioral strategies and theatrical techniques in a peer-mediated model. Previous research using a 3-month model showed improvement in face perception, social interaction, and reductions in stress. The current study assessed a 2-week summer camp model. Typically developing peers were trained and paired with ASD youth (8-17 years). Social perception and interaction skills were measured before and after treatment using neuropsychological and parental measures. Behavioral coding by reliable, independent raters was conducted within the treatment context (theatre) and outside the setting (playground). Salivary cortisol levels to assess physiological arousal were measured across contexts (home, theatre, and playground). A pretest-posttest design for within-group comparisons was used, and prespecified pairwise comparisons were achieved using a nonparametric Wilcoxon signed-rank test. Significant differences were observed in face processing, social awareness, and social cognition (P < 0.05). Duration of interaction with familiar peers increased significantly over the course of treatment (P < 0.05), while engagement with novel peers outside the treatment setting remained stable. Cortisol levels rose on the first day of camp compared with home values yet declined by the end of treatment and further reduced during posttreatment play with peers. Results corroborate previous findings that the peer-mediated theatre program contributes to improvement in core social deficits in ASD using a short-term, summer camp treatment model. Future studies will explore treatment length and peer familiarity to optimize and generalize gains.

Background:Tibial eminence fractures occur most commonly in skeletally immature children. Several techniques using physeal-sparing fracture fixation have been described, but their structural properties have not been evaluated.Purpose:To determine the strength and resistance to displacement of physeal-sparing techniques used to fix tibial eminence fractures.Study Design:Controlled laboratory study.Methods:Skeletally immature porcine knees were randomized into 4 treatment groups: (1) ultra–high molecular weight polyethylene suture–suture button (UHMWPE/SB), (2) suture anchor, (3) polydioxanone suture–suture button (PDS/SB), and (4) screw fixation. A prospective analysis of bone mineral density using dual-energy x-ray absorptiometry was performed on all specimens. Fracture fragments were created in a standardized manner and measured for size comparison. After fracture fixation, biomechanical testing was performed with cyclical and load-to-failure protocols by loading the tibia with an anterior shear force.Results:In load-to-failure testing, screw fixation had a significantly lower median peak failure load (186.4 N; lower quartile [LQ], 158.4 N; upper quartile [UQ], 232.6 N) than did UHMWPE/SB (465.8 N; LQ, 397.8 N; UQ, 527.8 N), suture anchors (440.5 N; LQ, 323.0 N; UQ, 562.3 N), and PDS/SB (404.3 N; LQ, 385.9 N; UQ, 415.6 N). UHMWPE/SB demonstrated a significantly higher median yield load (465.8 N; LQ, 397.8 N; UQ, 527.8 N) than did PDS/SB (306.7 N; LQ, 271.4, N; UQ, 405.7 N) and screw fixation (179.0 N; LQ, 120.2 N; UQ, 232.5 N). During cyclical testing, screw fixation demonstrated significantly lower percentage survival of specimens (0%) compared with the other groups (UHMWPE/SB, 100%; suture anchor, 78%; PDS/SB, 78%). After 1000 cycles of loading, PDS/SB fixation had significantly more median creep (6.76 mm; LQ, 6.34 mm; UQ, 8.28 mm) than did UHMWPE/SB (4.43 mm; LQ, 3.80 mm; UQ, 4.73 mm) and suture anchor fixation (3.06 mm; LQ, 2.59 mm; UQ, 4.28 mm). The lowest median stiffness was observed in the PDS/SB group (48.6 N/mm; LQ, 45.3 N/mm; UQ, 54.2 N/mm). UHMWPE/SB fixation demonstrated a significantly higher median peak failure load after cyclic testing (469.0 N; LQ, 380.6 N; UQ, 507.2 N) than did PDS/SB (237.7 N; LQ, 197.3 N; UQ, 298.3 N) and screw fixation (132.4 N; LQ, 123.7 N; UQ, 180.9 N). Suture anchor fixation had significantly more variance, as demonstrated by width of interquartile range, in peak failure load, yield load, and creep than did other techniques.Conclusion:Physeal-sparing fixation of tibial eminence fractures with UHMWPE suture–suture button is biomechanically superior to both PDS suture–suture button and a single screw at the time of surgery and provides more consistent fixation than do suture anchors.Clinical Relevance:Suture anchors provide inconsistent fixation for tibial eminence fractures.

Background and Objectives Administration of preoperative radiotherapy for extremity soft tissue sarcoma improves local control, while allowing for a more conservative surgical resection. During radiation treatment tumor size typically decreases or remains constant. In a subset of patients, however, a size increase in the tumor occurs. Our goal was to investigate the prognosis of patients who had a size increase of at least 20% over the course of preoperative radiotherapy versus those who did not. Methods This retrospective study evaluated 70 patients treated for localized primary STS of the extremities between January 2000 and December 2008. Kaplan–Meier curves for disease-specific and metastasis-free survival were calculated for both groups. Results Sixty-one patients had stable or decrease local tumor size following preoperative radiotherapy and nine patients had an increase of at least 20% in tumor size. There were no statistically significant differences found in disease-specific survival and metastasis-free survival (Gray's test, P = 0.93 and P = 0.68, respectively) among the two groups. Conclusion Our results indicate that a 20% increase in tumor size following preoperative radiotherapy did not result in a worse outcome for patients when compared to those who had stable or decrease local tumor size following preoperative radiotherapy. J. Surg. Oncol. 2013;107:723–727. © 2013 Wiley Periodicals, Inc.

To determine risk factors associated with tracheostomy placement after severe traumatic brain injury (TBI) and subsequent outcomes among those who did and did not receive a tracheostomy.This retrospective cohort study compared adult trauma patients with severe TBI (n = 583) who did and did not receive tracheostomy. A multivariable logistic regression model assessed the associations between age, sex, race, insurance status, admission GCS, AIS (Head, Face, Chest) and tracheostomy placement. Ordinal logistic regression models assessed tracheostomy's influence on ventilator days and ICU LOS. To limit immortal time bias, Cox proportional hazards models assessed mortality at 1, 3 and 12-months.In this multivariable model, younger age and private insurance were associated with increased probability of tracheostomy. AIS, ISS, GCS, race and sex were not risk factors for tracheostomy placement. Age showed a non-linear relationship with tracheostomy placement; likelihood peaked in the fourth decade and declined with age. Compared to uninsured patients, privately insured patients had an increased probability of receiving a tracheostomy (OR = 1.89 [95% CI = 1.09-3.23]). Mortality was higher in those without tracheostomy placement (HR = 4.92 [95% CI = 3.49-6.93]). Abbreviated injury scale-Head was an independent factor for time to death (HR = 2.53 [95% CI = 2.00-3.19]), but age, gender and insurance were not.Age and insurance status are independently associated with tracheostomy placement, but not with mortality after severe TBI. Tracheostomy placement is associated with increased survival after severe TBI.

To determine if amputation increases survival when compared to limb salvage surgery in patients with a soft tissue sarcoma (STS) of the extremity when there is often a misconception among physicians and patients that ablative surgery eliminates local recurrence and increases overall survival. This retrospective cohort study assessed 278 patients with STS and compared 18 patients who had undergone amputations for soft tissue sarcomas of the extremities to a comparative cohort of 260 patients who underwent limb salvage surgery during the same time period. Our limb salvage surgery (LSS) rate was 94% overall for soft tissue sarcomas with a median follow-up of 3.1 years. Patients undergoing amputations either had tumors that involved a critical neurovascular bundle (in particular nerve rather than vessel resection was more responsible for a decision toward ablation), or underlying bone or had neoplasms whose large size would require such an enormous resection that a functional limb would not remain. In comparing prognostic effects, mainly death due to sarcoma, distant metastasis and local recurrence, it was found that there was no statistically significant difference between patients undergoing amputation to those undergoing limb salvage surgery (p > 0.05). While amputations do not increase overall survival in soft tissue sarcomas of the extremity as compared to LSS, they are still a valuable option in a surgeon's arsenal. In particular, amputations can provide improved local control and symptomatic treatment in patients who might not be candidates for limb salvage surgery.

Limb salvage surgery (LSS) has gained widespread acceptance as the current treatment for treating extremity soft tissue sarcoma (STS) and has been greatly refined since its inception. Combined with improved adjuvant treatment modalities, rates of local relapse have greatly decreased. Nonetheless, local recurrence still occurs and identifying the cause and the subsequent effects of local recurrence can provide valuable insights as LSS continues to evolve.This retrospective study evaluated 278 patients treated for STS of the extremities between 2000 and 2006. Of these, 41 patients developed a local recurrence while 247 did not. Tumor characteristics and prognostic outcomes were analyzed. Wilcoxon rank sum test and either χ(2) or Fisher's exact was used to compare variables. Kaplan Meier and Gray's test for cumulative risk were also performed.Patients who had a positive margin were 3.76 times more likely to develop local recurrence when compared to those with negative margins. This corresponds to a 38% risk of local recurrence if the margins were positive after six years vs. 12% if the margins were negative. In patients who underwent a re-excision, the presence or absence of residual disease upon re-excision did not have any bearing on local recurrence (p = 0.27). In comparing patients with and without local recurrence, there was no statistically significant difference in the rate and the proportion encountering distant metastasis and death due to sarcoma (p0.05).Despite advancements in surgery, radiation and imaging, positive margins still occur, and the presence of positive margins following definitive treatment continues to remain as a strong predictor for local recurrence. While local recurrence represents a negative outcome for a patient, its impact on future prognosis is influenced by a variety of factors such as time to local recurrence as well as the tumor's inherent biological characteristics.

The present investigation revealed how the surface morphology and hydrophobicity of polyvinylidene fluoride (PVDF) membranes, which were prepared via a vapor-induced phase separation (VIPS) method, were affected by the exposure time. The mass variation of the cast film was recorded. Membrane morphologies were observed by scanning electron microscopy (SEM) and thermal behaviors of membranes were examined by differential scanning calorimetry (DSC). Wide angle X-ray diffraction (WAXD) was employed to analyze the crystalline structures of the overall membranes and the surface layers. The results showed that different membrane morphologies and hydrophobicities could be obtained by changing the exposure time. A long exposure time facilitated the crystallization process, resulting in the formation of a porous skin and particle morphology, which increased the hydrophobicity of the surface. A short exposure time favored the formation of a digitate macrovoid and dense skin resulting from liquid–liquid phase separation in the immersion process, which reduced surface hydrophobicity. The water permeate flux in vacuum membrane distillation was greatly affected by the membrane porosity and surface hydrophobicity.

The aim of the current study was to explore the effects and possible mechanisms of tripterygium glycosides tablet (TGT) in the treatment of active ankylosing spondylitis (AS). Thirty-six patients with active AS were given a 20 mg TGT treatment three times per day for 12 weeks, and 21 unrelated healthy controls were recruited as the control group. Efficacy measures included the Bath AS disease activity index (BASDAI), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) prior and subsequent to TGT treatment. Serum dickkopf homolog 1 (DKK1) and interleukin-17 (IL-17) levels before and after TGT treatment were assessed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and ELISA assay. The levels of several serum biomarkers were determined by ELISA, including receptor activator of nuclear factor κ-B ligand (RANKL), osteoprotegerin (OPG), bone alkaline phosphatase (BAP), bone morphogenetic protein-2 (BMP-2), matrix metalloproteinase-3 (MMP-3), cross-linked telopeptide of type II collagen (CTX-II), vascular endothelial growth factor (VEGF), and prostaglandin E2 (PGE2). After 12 weeks of TGT treatment, the BASDAI score of the patients was significantly reduced (P

STUDY DESIGN A retrospective cohort study. OBJECTIVE To evaluate the clinical indications for acquiring arterial imaging in cervical trauma. SUMMARY OF BACKGROUND DATA Cervical spine injuries are very common in high-energy trauma and are frequently seen at Level I trauma centers across the country. A clinical standard of care does not exist to indicate when further evaluation of the cervical vasculature is warranted after a documented cervical spine injury. METHODS After institutional review board approval, a retrospective study combining the data from 2 Level I trauma centers was undertaken. An evaluation of every arterial imaging procedure (computed tomography and magnetic resonance angiography) of the cervical spine was collected to further delineate indications and outcomes of these imaging modalities. RESULTS From 2005 to 2009, there were a total of 159 patients who underwent cervical arterial imaging at the 2 participating institutions for the indication of cervical trauma with concern for arterial injury. Thirty-six (22.64%) were found to have an injury after arterial imaging. There was a statistically significant correlation with displaced cervical injuries (P < 0.0153), which were defined as cervical dissociations or perched and/or jumped facets. The other statistically significant correlation was the presence of a neurological deficit (P < 0.001), defined as any presenting deficit on sensory or motor examination. Level of injury defined as axial (O-C2) versus subaxial (C3-C7), age, body mass index, and history of cigarette smoking were not statistically related to vascular injury. CONCLUSION Our retrospective evaluation indicates that there should be a lower threshold for obtaining arterial imaging with cervical injury patterns historically known to compromise the vasculature, which also have concomitant displaced cervical spine injuries and/or a neurological deficit.

Study design A prospective cohort study. Objective To evaluate the effects of epidural steroid injections (ESIs) on blood glucose levels in patients with diabetes mellitus. Summary of background data ESIs are commonly used in the treatment of multiple spinal disorders. Corticosteroid injections have been evaluated in the total joints and hand literature showing systemic effects to diabetics. Methods Diabetic patients who were scheduled for an ESI were given an opportunity to enroll in our IRB-approved study. We collected the patient's most recent hemoglobin A(1c) (hA(1c)) and then asked them to track their blood glucose numbers at least twice per day for 2 weeks prior to and after their ESIs. Results We noted a statistically significant increase in blood glucose levels in diabetic patients (n = 30) after ESI. The mean blood glucose level prior to ESI was 160.18 ± 47.46, and, after ESI, it was 286.13 ± 111.11. This represents an average 125.96 ± 100.97 increase in blood glucose levels after injection. Using a nonlinear mixed effect model, the estimated half-life of this increase was 1.06 days (95% CI 0.80, 1.58), meaning that the patients were back within their normal standard deviation mean glucose levels within 2 days of injection. There was no association between observed glucose level change and preinjection hA(1c) levels or age (Spearman = 0.0326 and -0.1091 separately), indicating that there is no correlation between preinjection hA(1c) levels and systemic response to ESI. Conclusion ESIs were noted to cause a significant increase in the blood glucose levels in diabetics. There was no correlation between preinjection diabetic control, represented by hA(1c) levels, and postinjection response. Diabetics who are candidates for ESI should be counseled that a blood glucose increase may be apparent post intervention, but effects should not last longer than approximately 2 days.

Background Soft tissue sarcomas (STS) are rare and are commonly excised outside of a sarcoma center without appropriate preoperative planning. Studies have shown varying results in survival and outcome when comparing patients undergoing re-excision to patients undergoing a single, planned excision. Methods This retrospective study evaluated 278 patients treated for STS of the extremities between January 2000 and July 2006. One hundred seventy-two patients had a primary excision while 106 patients had a sarcoma re-excised. Survival curves for disease-free survival, metastasis-free survival, and local recurrence-free survival were calculated using competing risk analysis for both groups. Results After adjusting for high-risk variables, our results indicate that re-excision is a proxy for smaller, low-grade tumors which tend to have a better survival profile. Death due to sarcoma and distant metastases were correlated with high-grade and large tumors. The presence of positive microscopic margins was the strongest predictor of local recurrence (P

OBJECTIVE To investigate differences in T2 intensity of deep gray matter (dGM) structures by magnetic resonance imaging (MRI) in multiple sclerosis (MS) patients undergoing various immunomodulatory therapies. BACKGROUND In MS, dGM T2 hypointensities by MRI are hypothesized to represent iron deposition and are known to be associated with worse disease stage as assessed by brain atrophy, cognitive and physical disability. The relation between immunotherapies and T2 intensity, however, has been not been investigated in detail. METHODS A total of 255 MS patients were stratified into those on no treatment (NON, n= 45), and those on immunomodulatory treatments for ≥6 months (ie, interferon beta [IFNβ]n= 118, glatiramer acetate [GA]n= 41, natalizumab [NAT]n= 39, and mycophenolate mofetil [MMF]n= 12). T2 intensities of dentate nucleus (DN), substantia nigra (SN), red nucleus (RN), and globus pallidus (GP) were measured. Group differences in T2 intensities were assessed using a linear regression model with T2 intensities as outcome variable, treatment group as main independent variable, and clinical measures such as Expanded Disability Status Scale (EDSS) score, years of MS, and 25-feet walk time (T25-FW) as covariates. To compare T2 intensities before and after treatment in a subset of NAT-treated patients, we used the Wilcoxon signed-rank test. RESULTS When adjusted for EDSS, duration of disease and T25-FW, across all deep nuclei, NAT-treated patients had significantly higher T2 intensities than untreated patients (DN p= 1.65 × 10−5; SN p= 2.37 × 10−5; RN p= 3.90 × 10−6; GP p= 1.05 × 10−6), IFNβ-treated patients (DN p= 1.65 × 10−5; SN p= 2.37 × 10−5; RN p= 3.90 × 10−6; GP p= 1.05 × 10−6), and GA-treated patients (DN p= 1.65 × 10−5; SN p= 2.37 × 10−5; RN p= 3.90 × 10−6; GP p= 1.05 × 10−6). In a subset of MS patients receiving NAT, there was a significant increase in T2 intensities in all the dGM nuclei after 24 months of treatment (DN p= 0.00021; SN p=

Postural tachycardia syndrome (POTS) affects an estimated 500,000 people in the United States alone. POTS is defined as excessive increase in heart rate (≥ 30 beats/min) with upright posture, associated with orthostatic symptoms including palpitation, chest pain syndrome, dyspnea on standing, mental clouding, and difficulties with concentration in the absence of orthostatic hypotension. It can produce substantial disability among otherwise healthy people.1,2 The pathophysiology of POTS is poorly understood, however many patients suffer from either a primary or secondary increase in sympathetic nervous system tone.3 Patients with POTS commonly complain of symptoms including fatigue and difficulty with sleep. One study found that patients with POTS had a diminished quality of life when measured using a standard health status instrument (SF-36).4 There are no published data, however, on the quality of sleep or sleep disturbances in patients with POTS. Conversely, problems with autonomic nervous system regulation have been noted in several primary disorders of sleep. These include relatively common sleep disorders such as obstructive sleep apnea5–7 and less common disorders such as fatal familial insomnia, sleep terrors, and REM sleep behavior disorder.8–10 Recent studies have shown that subjective poor sleep is associated with reduced physical performance, greater functional limitation, increased risk for cardiovascular diseases, and may even predict all-cause mortality.11–14 Therefore poor sleep may be a core factor associated with the low quality of life reported by patients with POTS. BRIEF SUMMARY Current Knowledge/Study Rationale: Patients with POTS commonly complain of symptoms including fatigue and difficulty with sleep. Prior to this paper, there were no published data on the quality of sleep or sleep disturbances in patients with POTS. Study Impact: This study found that patients with POTS have poor sleep quality, excessive sleepiness, excessive fatigue, and a high proportion of diminished quality of life due to sleep problems. Further objective sleep assessments are needed to delineate the specific sleep problems in patients with POTS, which will be a pre-requisite to develop optimal treatments. The aim of this study was to formally assess sleep quality, fatigue, and health-related quality of life (HRQL) in patients with POTS as compared with healthy control subjects.

Sensitive biomarkers are lacking in amyotrophic lateral sclerosis (ALS). Muscle ultrasound (MUS) can quantify muscle thickness and echointensity (EI). We evaluated the rate of muscle atrophy in ALS using MUS. Ten patients had serial unilateral MUS examination of biceps, wrist flexors, and tibialis anterior over 6 months. The rates of change of muscle thickness and EI were determined. Muscle thickness declined at a mean rate of -0.663 mm/month (P = 0.0014), greatest in biceps. Muscle thickness correlated moderately with ALSFRS-R, grip dynamometry, and body weight. There was no change in EI. MUS can quantify the rate of reduction in muscle thickness in ALS patients. The lack of strong correlation between muscle thickness and standard ALS measures may reflect limited sensitivity in these conventional measures. The rate of change of muscle thickness merits further study as a potential biomarker in ALS, particularly when considering biceps brachii as a candidate.

SUMMARY Purpose: A drug holiday seems to produce seizure interval prolongation (SIP) after reinstitution of antiepileptic drugs (AEDs). This effect was demonstrated mainly with carbamazepine. We evaluated SIP with newer AEDs and tested the relationship of SIP to history of AED tolerance. Methods: We prospectively studied patients with refractory epilepsy admitted to the Vanderbilt epilepsy monitoring unit (EMU) over a period of 12 months. We included only patients on levetiracetam, lamotrigine, or oxcarbazepine who had their AEDs withdrawn on admission and reinstituted without change upon discharge. We defined SIP as the interval from EMU discharge tofirst seizure minus the interval between the last two seizures before EMU admission. Results: A total of 43 patients completed the study; 15 were on monotherapy. SIP was greater than zero in this patient group (p < 0.0001), with a mean prolongation of 19.4 ± 28.0 days. The average SIP was higher (p = 0.01) in patients on monotherapy (29.7 ± 23.8 days) than patients on polytherapy (13.9 ± 29.0 days). SIP tended to be greater in patients with a prior history of AED tolerance (25.7 ± 36.8 days) compared to patient with no prior history of AED tolerance (14.0 ± 16.3 days). Discussion: SIP does occur after brief AED withdrawal. This effect is greater in patients on monotherapy and tends to be larger in patients with a history of AED tolerance. The SIP effect may be related to the phenomenon of tolerance, clinically seen as resistance to AED therapeutic effect.

Background Selective amygdalohippocampectomy (SelAH) is increasingly performed in patients with mesial temporal lobe epilepsy and hippocampal sclerosis. To determine whether visual field defects are less pronounced after SelAH than after standard temporal lobectomy (StTL), we retrospectively analyzed postoperative quantitative visual fields after the 2 procedures. Methods Humphrey visual field analysis was obtained postoperatively in 18 patients who had undergone SelAH and in 33 patients who had undergone StTL. The SelAH was performed via a transcortical approach through the middle temporal gyrus and included the amygdala, 3 cm of the hippocampus, and the parahippocampal gyrus. The visual field pattern deviation was used for analysis. We considered a defect clinically significant if there were 3 contiguous coordinates affected at the 5% level or 2 at the 1% level. Results All but 2 of 18 patients who had undergone SelAH had homonymous superior quadrantic visual field defects contralateral to the side of the surgery. One patient had no defects by our criteria, and one had a mild defect that reached significance only in the ipsilateral eye. The averaged defect affected mostly coordinates close to the vertical meridian with relative sparing of points close to the horizontal meridian. All but 3 of the 33 patients who had undergone StTL had homonymous superior quadrantic visual field defects. One patient had no defects; 2 had defects that reached significance in only one eye. The averaged defect involved all points in the affected quadrant, but was also greater near the vertical meridian. Of 13 tested visual field coordinates, 4 were significantly less affected by SelAH in the ipsilateral eye and 3 in the contralateral eye. The coordinates close to the horizontal meridian were significantly spared by SelAH. Conclusions Visual field defects are very common after SelAH but are significantly less pronounced than after StTL. In particular, the visual field close to the horizontal meridian is relatively spared in SelAH.