Overexpression of Alpha-1 Antitrypsin Increases the Proliferation of Mesenchymal Stem Cells by Upregulation of Cyclin D1.

Alpha-1 antitrypsin-overexpressing mesenchymal stromal/stem cells (AAT-MSCs) showed improved innate properties with a faster proliferation rate when studied for their protective effects in mouse models of diseases. Here, we investigated the potential mechanism(s) by which AAT gene insertion increases MSC proliferation. Human bone marrow-derived primary or immortalized MSCs (iMSCs) or AAT-MSCs (iAAT-MSCs) were used in the study. Cell proliferation was measured by cell counting and cell cycle analysis. Possible pathways involved in the pro-proliferation effect of AAT were investigated by measuring mRNA and protein expression of key cell cycle genes. Interval cell counting showed increased proliferation in AAT-MSCs or iAAT-MSCs compared to their corresponding MSC controls. Cell cycle analysis revealed more cells progressing into the S and G2/M phases in iAAT-MSCs, with a notable increase in the cell cycle protein, Cyclin D1. Moreover, treatment with Cyclin D1 inhibitors showed that the increase in proliferation is due to Cyclin D1 and that the AAT protein is upstream and a positive regulator of Cyclin D1. Furthermore, AAT's effect on Cyclin D1 is independent of the Wnt signaling pathway as there were no differences in the expression of regulatory proteins, including GSK3ß and ß-Catenin in iMSC and iAAT-MSCs. In summary, our results indicate that AAT gene insertion in an immortalized MSC cell line increases cell proliferation and growth by increasing Cyclin D1 expression and consequently causing cells to progress through the cell cycle at a significantly faster rate.

Training Characteristics, Academic Accomplishments, and Motivation of Current Program Directors in Physical Medicine and Rehabilitation.

ABSTRACT: This study aimed to report the training characteristics, academic accomplishments, and motivation of current US academic physical medicine and rehabilitation program directors.A 22-question survey was developed and disseminated via email in May 2020 to 91 current residency program directors who are members of the Association of Academic Physiatrists Residency Fellowship Program Director Committee. Follow-up emails were sent 2 and 4 wks after initial distribution, and the survey was closed after 6 wks in June 2020. Data collected were deidentified. Descriptive analysis was performed.Response rate was 49.5% (45/91); 64.4% of program directors were men, and 35.6% were women. Of the respondents, 75.4% were White/Caucasian, 6.7% were Hispanic/Latinx, 15.6% were Asian, and 2.2% were Black/African American. Moreover, 56% (9/16) of female program directors vs. 0% (0/29) of male program directors reported experiencing sex discrimination in the workplace.Four percent of program directors were full professors in physical medicine and rehabilitation when first appointed, 17% were associate professors, and 72% were assistant professors. Thirty-four percent of program directors had at least six peer-reviewed publications when first appointed.This survey provides insight to the training characteristics, accomplishments, and motivation of current program directors for physiatrists aspiring to enter these ranks and highlights the underrepresentation of women/minorities among leadership positions in physical medicine and rehabilitation.

CellSeg: a robust, pre-trained nucleus segmentation and pixel quantification software for highly multiplexed fluorescence images.

BACKGROUND: Algorithmic cellular segmentation is an essential step for the quantitative analysis of highly multiplexed tissue images. Current segmentation pipelines often require manual dataset annotation and additional training, significant parameter tuning, or a sophisticated understanding of programming to adapt the software to the researcher's need. Here, we present CellSeg, an open-source, pre-trained nucleus segmentation and signal quantification software based on the Mask region-convolutional neural network (R-CNN) architecture. CellSeg is accessible to users with a wide range of programming skills. RESULTS: CellSeg performs at the level of top segmentation algorithms in the 2018 Kaggle Data Challenge both qualitatively and quantitatively and generalizes well to a diverse set of multiplexed imaged cancer tissues compared to established state-of-the-art segmentation algorithms. Automated segmentation post-processing steps in the CellSeg pipeline improve the resolution of immune cell populations for downstream single-cell analysis. Finally, an application of CellSeg to a highly multiplexed colorectal cancer dataset acquired on the CO-Detection by indEXing (CODEX) platform demonstrates that CellSeg can be integrated into a multiplexed tissue imaging pipeline and lead to accurate identification of validated cell populations. CONCLUSION: CellSeg is a robust cell segmentation software for analyzing highly multiplexed tissue images, accessible to biology researchers of any programming skill level.

Training Characteristics, Academic Accomplishments, and Motivation of Current Chairs in Physical Medicine and Rehabilitation.

OBJECTIVE: The aim of the study was to report the training characteristics, academic accomplishments, and motivation of current United States academic physical medicine and rehabilitation chairs. DESIGN: The authors developed a 23-question survey that was disseminated via e-mail to 86 current chairs who were members of the Chairs Council from the Association of Academic Physiatrists in May 2020. Follow-up e-mails were sent 2 and 4 wks after the initial distribution, and the survey closed after 6 wks in June 2020. The data collected were deidentified. Descriptive analysis was performed. RESULTS: Forty-nine chair responses were received, which had a response rate of 60%. A total of 69.4% of the chairs (32 of 49) were men and 30.6% (17 of 49) were women. A total of 75.5% (37 of 49) were White/Caucasian, 12.2% (6 of 49) Hispanic/Latinx, 10.2% (5 of 49) Asian, and 2% (1 of 49) were Black/African American. A total of 8.2% of the chairs (4 of 49) reported having a disability. Sixty-seven percent of the female chairs (10 of 15) reported experiencing gender discrimination in the workplace versus 3% of male chairs (1 of 34). Twenty-nine percent of the chairs were full professors in physical medicine and rehabilitation when first appointed, 57.1% associate professors, and 6% assistant professors. A total of 73.5% of the chairs had served as a reviewer for a peer-reviewed publication. Fifty-two percent of the chairs had a leadership role in a national physical medicine and rehabilitation organization. Fifty-eight percent of the chairs had at least 16 peer-reviewed publications when first appointed. CONCLUSIONS: This survey provides insight to the training characteristics, accomplishments, and motivation of current chairs for physiatrists aspiring to enter these ranks. It also highlights the underrepresentation of women and minorities among leadership positions in physical medicine and rehabilitation.

Therapeutic efficacy of low-dose steroid combined with hyaluronidase in ultrasonography-guided intra-articular injections into the shoulder for adhesive capsulitis.

PURPOSE: The purpose of this study was to compare the efficacy of low-dose steroid, highdose steroid, and low-dose steroid combined with hyaluronidase with respect to intra-articular injection therapy for adhesive capsulitis (AC) of the shoulder. METHODS: Thirty patients with primary AC in the initial stage were randomly assigned into three groups to receive ultrasound-guided intra-articular injections with 20 mg of triamcinolone acetonide (group A, n=10), 40 mg of triamcinolone acetonide (group B, n=10) and 20 mg of triamcinolone acetonide combined with hyaluronidase (group C, n=10). The outcome measures included a visual analogue scale (VAS), the Shoulder Disability Questionnaire (SDQ), abduction and external rotation range of motion, and intra-sheath fluid (ISF) before treatment and at 2, 4, 8, and 16 weeks after treatment. RESULTS: Among the 30 patients, one participant in group B dropped out; therefore, a total of 29 patients completed this study and were successfully injected. After the injection, the VAS, SDQ, range of flexion and external rotation, and ISF improved in all groups compared with the preinjection status, regardless of treatment or time point. In the comparison between groups, the SDQ and ISF showed significantly greater improvements in groups B and C than in group A. CONCLUSION: The therapeutic efficacy of combined low-dose corticosteroid and hyaluronidase is superior to that of low-dose corticosteroid and equivalent to that of high-dose corticosteroid in early AC.

Computational Methods for the Discovery of Metabolic Markers of Complex Traits.

Metabolomics uses quantitative analyses of metabolites from tissues or bodily fluids to acquire a functional readout of the physiological state. Complex diseases arise from the influence of multiple factors, such as genetics, environment and lifestyle. Since genes, RNAs and proteins converge onto the terminal downstream metabolome, metabolomics datasets offer a rich source of information in a complex and convoluted presentation. Thus, powerful computational methods capable of deciphering the effects of many upstream influences have become increasingly necessary. In this review, the workflow of metabolic marker discovery is outlined from metabolite extraction to model interpretation and validation. Additionally, current metabolomics research in various complex disease areas is examined to identify gaps and trends in the use of several statistical and computational algorithms. Then, we highlight and discuss three advanced machine-learning algorithms, specifically ensemble learning, artificial neural networks, and genetic programming, that are currently less visible, but are budding with high potential for utility in metabolomics research. With an upward trend in the use of highly-accurate, multivariate models in the metabolomics literature, diagnostic biomarker panels of complex diseases are more recently achieving accuracies approaching or exceeding traditional diagnostic procedures. This review aims to provide an overview of computational methods in metabolomics and promote the use of up-to-date machine-learning and computational methods by metabolomics researchers.

Early Intra-articular Corticosteroid Injection Improves Pain and Function in Adhesive Capsulitis of the Shoulder: 1-Year Retrospective Longitudinal Study.

BACKGROUND: Intra-articular corticosteroid injection is a commonly used therapy for adhesive capsulitis, but not enough studies exist on the optimal timing of the injection. OBJECTIVE: To determine whether intra-articular corticosteroid injection has better outcomes in patients with earlier stage than later stage of adhesive capsulitis. STUDY DESIGN: Retrospective longitudinal study SETTING: University-affiliated tertiary care hospital. PARTICIPANTS: Primary adhesive capsulitis patients (n=339) who were unresponsive to at least 1 month of conservative treatment and who had ultrasound-guided corticosteroid injection. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASUREMENTS: Visual analogue scale, Shoulder Pain and Disability Index, and passive range of motion (flexion, abduction, external rotation, and internal rotation and extension) were evaluated at pretreatment, month 1 and 12 after the first injection. RESULTS: The result of the multiple regressions, which considered the main and the interaction effect of confounding variables, showed that the differences of all outcomes in both short-term effect at month 1 and long-term effect at month 12 are greater when the duration of pain prior to injection is shorter. Among the confounders, the injection number in the difference of internal rotation and extension between month 0 and 12 (IRE Δ(0-12)) was statistically significant. IRE Δ(0-12) was also greater when the pain duration was shorter, though the decrease in IRE Δ(0-12) differed depending on the number of injections. CONCLUSIONS: Early injection improves outcomes of adhesive capsulitis at both short- and long-term follow-ups. If pain persists despite non-invasive and conservative treatments, early injection may be considered to shorten its natural history. LEVEL OF EVIDENCE: III.

Preventive effect of a vapocoolant spray on propofol-induced pain: a prospective, double-blind, randomized study.

PURPOSE: Propofol causes injection pain. Although lidocaine pre-treatment via venous occlusion is known to be the most effective way, it still has some inconvenience. We implemented this study to compare the effect of a vapocoolant spray with lidocaine pre-treatment. METHODS: Participants (n = 90) were randomized to one of three groups. Group V: after placebo injection and tourniquet, the vapocoolant spray was applied; group L: after lidocaine injection and tourniquet, the placebo spray was applied; group C: after placebo injection and tourniquet, the placebo spray was applied. The intensity of propofol-induced pain, the incidence of metallic taste, and the satisfaction were assessed. RESULTS: Propofol-induced pain was significantly lower in groups V and L than in group C [0.5 (0-2.25), 0.5 (0-1), and 5 (1-7), median (interquartile range), respectively, p < 0.001]. There was no significant difference in pain intensity between groups V and L. Group L showed a significantly higher incidence of metallic taste than groups V and C (23, 0, and 0%, respectively; p = 0.001). Groups V and L showed higher satisfaction scores than group C [5 (4-5), 4 (3.75-5), and 2 (2-3), respectively; p < 0.001], and there was a significant difference between groups V and L (p = 0.012). CONCLUSION: Vapocoolant spray showed a similar effect to lidocaine in analgesia and lowered the incidence of a metallic taste. These resulted in greater satisfaction with the vapocoolant spray compared with lidocaine. Vapocoolant spray is an effective and convenient way to prevent propofol-induced pain.

Effect of adductor canal block on medial compartment knee pain in patients with knee osteoarthritis: Retrospective comparative study.

Knee osteoarthritis (KOA) is a common disease in middle-aged and elderly people. Pain is the chief complaint of symptomatic KOA and a leading cause of chronic disability, which is most often found in medial knees. The aim of this study is to evaluate the efficacy of pain relief and functional improvement in KOA patients treated with ultrasound-guided adductor canal block (ACB).This is a 3-month retrospective case-controlled comparative study. Two hundred patients with anteromedial knee pain owing to KOA that was unresponsive to 3-month long conservative treatments. Ninety-two patients received ACB with 9 mL of 1% of lidocaine and 1 mL of 10 mg triamcinolone acetonide (ACB group), and 108 continued conservative treatments (control group). The main outcome measure was visual analog scale (VAS) of the average knee pain level for the past one week. Secondary outcomes were the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the timed up and go test, numbers of analgesic ingestion per day, and opioid consumption per day.During the 3-month follow-up, 86 patients in ACB group and 92 in control group were analyzed. There was no significant difference, with the exception of the duration of symptoms, between the 2 groups in age, sex, body mass index, and Kellgren-Lawrence grade. Repeated-measures analysis of variance and post hoc tests showed improvement of VAS (at month 1), WOMAC (at month 1), and opioid consumption per day (at month 1 and 2) in ACB group. No adverse events were reported.To our knowledge, this is the first study to assess the efficacy of ACB for patients with KOA. ACB is an effective and safe treatment and can be an option for patients who are either unresponsive or unable to take analgesics.

Capsule-Preserving Hydrodilatation With Corticosteroid Versus Corticosteroid Injection Alone in Refractory Adhesive Capsulitis of Shoulder: A Randomized Controlled Trial.

OBJECTIVE: To determine whether capsule-preserved hydrodilatation with corticosteroid improves pain and function in patients with refractory adhesive capsulitis (AC) better than intra-articular corticosteroid injection (IACI) alone. DESIGN: Prospective randomized controlled study. SETTING: University-affiliated tertiary care hospital. PARTICIPANTS: Subjects with primary AC (N=64) with shoulder pain level of visual analog scale (VAS) score ≥5, even after the initial administration of IACI alone. INTERVENTIONS: Participants randomly received ultrasound-guided IACI alone with 1mL of 40mg/mL triamcinolone acetonide and 3mL of 1% lidocaine (n=32) or ultrasound-guided capsule-preserved hydrodilatation with corticosteroid with a mixture of 1mL of 40mg/mL triamcinolone acetonide, 6mL of 1% lidocaine, and normative saline (n=32). MAIN OUTCOME MEASURES: The primary outcome measure was the Shoulder Pain and Disability Index score. Secondary outcomes were the VAS of shoulder pain level and angles of shoulder passive range of motion, including flexion, abduction, extension, external rotation, and internal rotation at pretreatment and weeks 3, 6, and 12 of posttreatment. RESULTS: There were no significant differences between the 2 groups in terms of demographic characteristics (age, sex, duration of symptoms, shoulder affected, and body mass index) at baseline. Repeated-measures analysis of variance showed significant effect of time in all outcome measurements in both groups. However, group-by-time interactions were not significantly different for any of the outcomes between groups. CONCLUSIONS: This study shows that compared with pretreatment, all outcome measures improved significantly in both groups by time; however, there was no significant difference between the 2 groups. Therefore, we recommend IACI alone over capsule-preserved hydrodilatation with corticosteroid when considering the corticosteroid injection as a secondary option after the initial IACI fails to improve symptoms for patients with refractory AC.

A systematic review of 30-day readmission after cranial neurosurgery.

OBJECTIVE The 30-day readmission rate has emerged as an important marker of the quality of in-hospital care in several fields of medicine. This review aims to summarize available research reporting readmission rates after cranial procedures and to establish an association with demographic, clinical, and system-related factors and clinical outcomes. METHODS The authors conducted a systematic review of several databases; a manual search of the Journal of Neurosurgery, Neurosurgery, Acta Neurochirurgica, Canadian Journal of Neurological Sciences; and the cited references of the selected articles. Quality review was performed using the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) criteria. Findings are reported according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. RESULTS A total of 1344 articles published between 1947 and 2015 were identified; 25 were considered potentially eligible, of which 12 met inclusion criteria. The 30-day readmission rates varied from 6.9% to 23.89%. Complications arising during or after neurosurgical procedures were a prime reason for readmission. Race, comorbidities, and longer hospital stay put patients at risk for readmission. CONCLUSIONS Although readmission may be an important indicator for good care for the subset of acutely declining patients, neurosurgery should aim to reduce 30-day readmission rates with improved quality of care through systemic changes in the care of neurosurgical patients that promote preventive measures.

Systematic Literature Review of AbobotulinumtoxinA in Clinical Trials for Lower Limb Spasticity.

To elucidate clinical trial efficacy, safety, and dosing practices of AbobotulinumtoxinA (ABO) treatment in adult patients with lower limb spasticity.A systematic literature review was performed to identify randomized controlled trials of ABO in the treatment of adult lower limb spasticity.Of the 295 records identified, 6 primary publications evaluated ABO for the management of lower limb spasticity of various etiologies and were evaluated. Total ABO doses ranged between 500 and 2000 U for lower limb spasticity, depending on the muscles injected. All studies in lower limb spasticity showed statistically significant reduction in muscle tone based on Modified Ashworth Scale of ABO versus placebo. Significant effects on active movement and pain were demonstrated albeit less consistently. ABO was generally well tolerated across the individual studies; most adverse events reported were considered unrelated to treatment. Treatment-related adverse events included but not limited to fatigue, local pain at injection site, hypertonia, dry mouth, weakness of the noninjected muscle, abnormal gait, and urinary tract infection.These data from 6 randomized clinical studies provide the beginnings of an evidence base for the use of ABO to reduce lower limb spasticity. Ongoing studies in this area will add to this evidence base.

Causes of 30-day readmission after neurosurgery of the spine.

OBJECT Thirty-day readmission has been cited as an important indicator of the quality of care in several fields of medicine. The aim of this systematic review was to examine rate of readmission and factors relevant to readmission after neurosurgery of the spine. METHODS The authors carried out a systematic review using several databases, searches of cited reference lists, and a manual search of the JNS Publishing Group journals (Journal of Neurosurgery; Journal of Neurosurgery: Spine; Journal of Neurosurgery: Pediatrics; and Neurosurgical Focus), Neurosurgery, Acta Neurochirurgica, and Canadian Journal of Neurological Sciences. A quality review was performed using STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) criteria and reported according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. RESULTS A systematic review of 1136 records published between 1947 and 2014 revealed 31 potentially eligible studies, and 5 studies met inclusion criteria for content and quality. Readmission rates varied from 2.54% to 14.7%. Sequelae that could be traced back to complications that arose during neurosurgery of the spine were a prime reason for readmission after discharge. Increasing age, poor physical status, and comorbid illnesses were also important risk factors for 30-day readmission. CONCLUSIONS Readmission rates have predictable factors that can be addressed. Strategies to reduce readmission that relate to patient-centered factors, complication avoidance during neurosurgery, standardization with system-wide protocols, and moving toward a culture of nonpunitive system-wide error and "near miss" investigations and quality improvement are discussed.

Therapeutic Effect of Extracorporeal Shock Wave Therapy According to Treatment Session on Gastrocnemius Muscle Spasticity in Children With Spastic Cerebral Palsy: A Pilot Study.

OBJECTIVE: To investigate the therapeutic effect of extracorporeal shockwave therapy (ESWT) according to treatment session on gastrocnemius muscle spasticity in children with spastic cerebral palsy (CP). METHODS: Twelve children with spastic CP underwent 1 ESWT and 2 sham ESWT sessions for gastrocnemius (group 1) or 3 ESWT sessions (group 2) once per week for 3 weeks. Modified Ashworth Scale (MAS) score, passive range of motion (PROM) of the ankle plantar-flexor muscles with knee extension, and median red pixel intensity (RPI) of color histogram of medial gastrocnemius on real-time sonoelastography (RTS) were measured before ESWT, immediately after the first and third ESWT, and at 4 weeks after the third ESWT. RESULTS: Mean ankle PROM was significantly increased whereas as mean ankle MAS and median gastrocnemius RPI were significantly decreased in both groups after the first ESWT. Clinical and RTS parameters before ESWT were not significantly different from those immediately after the third ESWT or at 4 weeks after the third ESWT in group 1. However, they were significantly different from those immediately after the third ESWT or at 4 weeks after the third ESWT in group 2. Mean ankle PROM, mean ankle MAS, and median gastrocnemius RPI in group 2 were significantly different from that in group 1 at 4 weeks or immediately after the third ESWT. CONCLUSION: The therapeutic effect of ESWT on spastic medial gastrocnemius in children with spastic CP is dependent on the number of ESWT sessions.

Systematic literature review of abobotulinumtoxinA in clinical trials for adult upper limb spasticity.

OBJECTIVE: The aim of this study was to elucidate clinical trial efficacy, safety, and dosing practices of abobotulinumtoxinA (ABO) treatment in adult patients with upper limb spasticity (ULS). METHODS: A systematic literature review was performed to identify randomized controlled trials and other comparative clinical studies of ABO in the treatment of adult ULS published in English between January 1991 and January 2013. Medical literature databases (PubMed, Cochrane Library, and EMBASE) were searched, and a total of 295 records were identified. Of these, 12 primary publications that evaluated ABO for the management of ULS were included in the final data report. SYNTHESIS: Total ABO doses ranged between 500 and 1500 U for ULS. Most of the studies in ULS showed statistically significant benefits (reduction in muscle tone based on Ashworth score) of ABO vs. placebo. Statistical significance was reached for most evaluations of spasticity using the Modified Ashworth Scale. Statistically significant effects on active movement and pain were demonstrated, albeit less consistently. ABO was generally well tolerated across the individual studies; most adverse events reported were considered unrelated to treatment. Adverse events considered associated with ABO treatment included fatigue, tiredness, arm pain, skin rashes, flu-like symptoms, worsening of spasm, and weakness. CONCLUSIONS: On the basis of data extracted from 12 randomized clinical studies, a strong evidence base (9/12 studies) exists for the use of ABO to reduce ULS caused by stroke.

Botulinum toxin injection techniques for the management of adult spasticity.

Spasticity is often experienced by individuals with injury or illness of the central nervous system from etiologies such as stroke, spinal cord injury, brain injury, multiple sclerosis, or other neurologic conditions. Although spasticity may provide benefits in some patients, it more often leads to complications negatively impacting the patient. Nonpharmacologic treatment options often do not provide long-term reduction of spasticity, and systemic interventions, such as oral medications, can have intolerable side effects. The use of botulinum neurotoxin injections is one option for management of focal spasticity. Several localization techniques are available to physicians that allow for identification of the selected target muscles. These methods include anatomic localization in isolation or in conjunction with electromyography guidance, electrical stimulation guidance, or ultrasound guidance. This article will focus on further description of each of these techniques in relation to the treatment of adult spasticity and will discuss the advantages and disadvantages of each technique, as well as review the literature comparing the techniques.

Comparative effects of prolonged and intermittent stimulation of the glucagon-like peptide 1 receptor on gastric emptying and glycemia.

Acute administration of glucagon-like peptide 1 (GLP-1) and its agonists slows gastric emptying, which represents the major mechanism underlying their attenuation of postprandial glycemic excursions. However, this effect may diminish during prolonged use. We compared the effects of prolonged and intermittent stimulation of the GLP-1 receptor on gastric emptying and glycemia. Ten healthy men received intravenous saline (placebo) or GLP-1 (0.8 pmol/kg ⋅ min), as a continuous 24-h infusion ("prolonged"), two 4.5-h infusions separated by 20 h ("intermittent"), and a 4.5-h infusion ("acute") in a randomized, double-blind, crossover fashion. Gastric emptying of a radiolabeled mashed potato meal was measured using scintigraphy. Acute GLP-1 markedly slowed gastric emptying. The magnitude of the slowing was attenuated with prolonged but maintained with intermittent infusions. GLP-1 potently diminished postprandial glycemia during acute and intermittent regimens. These observations suggest that short-acting GLP-1 agonists may be superior to long-acting agonists when aiming specifically to reduce postprandial glycemic excursions in the treatment of type 2 diabetes.

The effect of exogenous glucose-dependent insulinotropic polypeptide in combination with glucagon-like peptide-1 on glycemia in the critically ill.

OBJECTIVE: Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) have additive insulinotropic effects when coadministered in health. We aimed to determine whether GIP confers additional glucose lowering to that of GLP-1 in the critically ill. RESEARCH DESIGN AND METHODS: Twenty mechanically ventilated critically ill patients without known diabetes were studied in a prospective, randomized, double-blind, crossover fashion on 2 consecutive days. Between T0 and T420 minutes, GLP-1 (1.2 pmol/kg·min(-1)) was infused intravenously with either GIP (2 pmol/kg·min(-1)) or 0.9% saline. Between T60 and T420 minutes, nutrient liquid was infused into the small intestine at 1.5 kcal/min. RESULTS: Adding GIP did not alter blood glucose or insulin responses to small intestinal nutrient. GIP increased glucagon concentrations slightly before nutrient delivery (P=0.03), but not thereafter. CONCLUSIONS: The addition of GIP to GLP-1 does not result in additional glucose-lowering or insulinotropic effects in critically ill patients with acute-onset hyperglycemia.

The significance of tibial and common peroneal nerves in nerve blocks.

PURPOSE: The aim of this study was to elucidate the anatomical location of tibial nerve (TN) and common peroneal nerve (CPN) in the popliteal crease for specific nerve block. METHODS: Fifty fresh specimens from 27 adult Korean cadavers (16 males and 11 females, age 35-87 years) were investigated. Five of the 27 cadavers were used to determine the depths of nerves in cross-section. RESULTS: Tibial nerve was located 50 % from the most lateral point of the popliteal crease and 1.4-cm deep to the surface. In 20 % of the 50 specimens, the medial sural cutaneous nerve branched out below or at the popliteal crease, whereas the CPN was located at 26 % from the most lateral point of the popliteal crease and 0.7-cm deep from the surface. Furthermore, in 6 % of specimens the lateral sural cutaneous nerve branched out below or at the popliteal crease. CONCLUSION: The results concerning the location of the TN and CPN at the popliteal crease offer a good guide to optimal nerve block.