bluuebunny/crossref_metadata_2025_split huggingface dataset:
Midazolam Sedation Induces Upper Limb Coordination Deficits That Are Reversed by Flumazenil in Patients with Eloquent Area Gliomas
Authors: Lin Nan , Han Ruquan , Hui Xuan , Zhang Kaiying , Gelb Adrian W. 
Published: May 2019

Abstract

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Background
Midazolam has been found to exacerbate or unmask limb motor dysfunction in patients with brain tumors. This study aimed to determine whether the exacerbated upper limb motor-sensory deficits are mediated through benzodiazepine sites by demonstrating reversibility by flumazenil in patients with gliomas in eloquent areas.

Methods
This was an interventional, parallel assignment, nonrandomized trial. Study subjects were admitted in the operating room. Patients with supratentorial eloquent area gliomas and volunteers of similar age without neurologic disease were sedated with midazolam, but still responsive and cooperative. Motor and sensory functions for upper extremities were evaluated by the Nine-Hole Peg Test before and after midazolam, as well as after flumazenil reversal.

Results
Thirty-two cases were included: 15 in the glioma group and 17 in the control group. The total dose of midazolam and flumazenil were comparable between the groups. In the glioma group, the times to task completion after midazolam in the contralateral hand (P = 0.001) and ipsilateral hand (P = 0.002) were 26.5 (95% CI, 11.3 to 41.7) and 13.7 (95% CI, 5.0 to 22.4) seconds slower than baseline, respectively. After flumazenil reversal, the contralateral hand (P = 0.99) and ipsilateral hand (P = 0.187) performed 1.2 (95% CI, −3.3 to 5.8) and 1.5 (95% CI, −0.5 to 3.5) seconds slower than baseline, respectively. In the control group, the dominant (P < 0.001) and nondominant hand (P = 0.006) were 2.9 (95% CI, 1.4 to 4.3) and 1.7 (95% CI, 0.5 to 2.9) seconds slower than baseline, respectively. After flumazenil, the dominant hand (P = 0.99) and nondominant hand (P = 0.019) performed 0.2 (95% CI, −0.7 to 1.0) and 1.3 (95% CI, −0.2 to 2.4) seconds faster than baseline, respectively.

Conclusions
In patients with eloquent area gliomas, mild sedation with midazolam induced motor coordination deficits in upper limbs. This deficit was almost completely reversed by the benzodiazepine antagonist flumazenil, suggesting that this is a reversible abnormality linked to occupation of the receptor by midazolam.
Dextromethorphan Analgesia in a Human Experimental Model of Hyperalgesia
Authors: Martin E. , Narjoz C. , Decleves X. , Labat L. , Lambert C. , Loriot M.-A. , Ducheix G. , Dualé C. , Pereira B. , Pickering G. 
Published: May 2019

Abstract

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What This Article Tells Us That Is New

Background
Central pain sensitization is often refractory to drug treatment. Dextromethorphan, an N-methyl-d-aspartate receptor antagonist, is antihyperalgesic in preclinical pain models. The hypothesis is that dextromethorphan is also antihyperalgesic in humans.

Methods
This randomized, double-blind, placebo-controlled, crossover study explores the antihyperalgesic effect of single and repeated 30-mg dose of oral dextromethorphan in 20 volunteers, using the freeze-injury pain model. This model leads to development of primary and secondary hyperalgesia, which develops away from the site of injury and is associated with central sensitization and activation of N-methyl-d-aspartate receptor in the spinal cord. The primary outcome was antihyperalgesia calculated with the area under the curve of the percentage change in mechanical pain threshold (electronic von Frey) on the area of secondary hyperalgesia. The secondary outcomes were mechanical pain threshold on the area of primary hyperalgesia and cognitive (reaction time) effect.

Results
Single 30-mg results are reported. Antihyperalgesia (% · min) is significantly higher on the area of secondary hyperalgesia with dextromethorphan than placebo (median [interquartile range]: 3,029 [746; 6,195] vs. 710 [–3,248; 4,439], P = 0.009, Hedge’s g = 0.8, 95% CI [0.1; 1.4]). On primary hyperalgesia area, mechanical pain threshold 2 h after drug intake is significantly higher with dextromethorphan (P = 0.011, Hedge’s g = 0.63, 95% CI [0.01; 1.25]). No difference in antinociception is observed after thermal painful stimuli on healthy skin between groups. Reaction time (ms) is shorter with placebo than with dextromethorphan (median [interquartile range]: 21.6 [–37.4; 0.1] vs. –1.2 [–24.3; 15.4], P = 0.015, Hedge’s g = 0.75, 95% CI [0.12; 1.39]). Nonserious adverse events occurrence (15%, 3 of 20 volunteers) was similar in both groups.

Conclusions
This study shows that low-dose (30-mg) dextromethorphan is antihyperalgesic in humans on the areas of primary and secondary hyperalgesia and reverses peripheral and central neuronal sensitization. Because dextromethorphan had no intrinsic antinociceptive effect in acute pain on healthy skin, N-methyl-d-aspartate receptor may need to be sensitized by pain for dextromethorphan to be effective.
Lung Pharmacokinetics of Tobramycin by Intravenous and Nebulized Dosing in a Mechanically Ventilated Healthy Ovine Model
Authors: Dhanani Jayesh A. , Diab Sara , Chaudhary Jivesh , Cohen Jeremy , Parker Suzanne L. , Wallis Steven C. , Boidin Clément , Barnett Adrian , Chew Michelle , Roberts Jason A. , Fraser John F. 
Published: May 2019

Abstract

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New

Background
Nebulized antibiotics may be used to treat ventilator-associated pneumonia. In previous pharmacokinetic studies, lung interstitial space fluid concentrations have never been reported. The aim of the study was to compare intravenous and nebulized tobramycin concentrations in the lung interstitial space fluid, epithelial lining fluid, and plasma in mechanically ventilated sheep with healthy lungs.

Methods
Ten anesthetized and mechanically ventilated healthy ewes underwent surgical insertion of microdialysis catheters in upper and lower lobes of both lungs and the jugular vein. Five ewes were given intravenous tobramycin 400 mg, and five were given nebulized tobramycin 400 mg. Microdialysis samples were collected every 20 min for 8 h. Bronchoalveolar lavage was performed at 1 and 6 h.

Results
The peak lung interstitial space fluid concentrations were lower with intravenous tobramycin 20.2 mg/l (interquartile range, 12 mg/l, 26.2 mg/l) versus the nebulized route 48.3 mg/l (interquartile range, 8.7 mg/l, 513 mg/l), P = 0.002. For nebulized tobramycin, the median epithelial lining fluid concentrations were higher than the interstitial space fluid concentrations at 1 h (1,637; interquartile range, 650, 1,781, vs. 16 mg/l, interquartile range, 7, 86, P < 0.001) and 6 h (48, interquartile range, 17, 93, vs. 4 mg/l, interquartile range, 2, 9, P < 0.001). For intravenous tobramycin, the median epithelial lining fluid concentrations were lower than the interstitial space fluid concentrations at 1 h (0.19, interquartile range, 0.11, 0.31, vs. 18.5 mg/l, interquartile range, 9.8, 23.4, P < 0.001) and 6 h (0.34, interquartile range, 0.2, 0.48, vs. 3.2 mg/l, interquartile range, 0.9, 4.4, P < 0.001).

Conclusions
Compared with intravenous tobramycin, nebulized tobramycin achieved higher lung interstitial fluid and epithelial lining fluid concentrations without increasing systemic concentrations.
Geriatric olecranon fractures treated with plate fixation have low complication rates
Authors: Campbell Sean T. , DeBaun Malcolm R. , Goodnough L. Henry , Bishop Julius A. , Gardner Michael J. 
Published: May 2019

Background:
A recent randomized controlled trial compared operative with nonoperative treatment of olecranon fractures in patients 75 yr and older. The study was notable for high complication rates, and operative treatment was cautioned against. The purpose of this study was to determine the complication rate among geriatric patients with an olecranon fracture treated surgically with plate fixation.

Methods:
The records of patients 75 yr and older treated with plate fixation for an olecranon fracture at a single level I trauma center were reviewed. Variables recorded included basic demographic data, complications, need for reoperation, and union at final follow-up.

Results:
Thirty-six patients met inclusion criteria, with a mean follow-up of 10 mo. Thirty-four of the 36 patients went on to union successfully prior to any subsequent surgery (94%). The overall reoperation rate was 11% (4 of 36 patients).

Conclusions:
The complication and reoperation rates after plate fixation of geriatric olecranon fractures were low. Loss of reduction was uncommon, and most patients went on to uneventful fracture union. These results support plate fixation of olecranon fractures in geriatric patients as a viable alternative to nonoperative management.
A systematic review of treatment of frozen shoulder by hydrodistension with or without steroid or intraarticular steroid injection
Authors: Raghavan Roshan , Dwyer Amitabh J. 
Published: May 2019

Background:
Hydrodistension is a popular mode of treatment for frozen shoulder. Hydrodistension of the shoulder joint capsule is either performed with or without use of a steroid. A simple intraarticular corticosteroid injection into the shoulder joint is also used in treatment of frozen shoulder. This article reviews randomized controlled studies that have shown and compared evidence on efficacy of these two treatment methods.

Methods:
A systematic review of the literature was done using online database EMBASE, Pubmed, Cochrane database, Medline, and CINAHL. Only randomized studies that compared hydrodistension with or without steroid to intraarticular steroid injection alone were included.

Results:
Of the five studies identified, three showed no difference between steroid injections alone when compared to distension with steroids. One showed better results with distension with steroid and with intraarticular steroid alone when compared with distension alone. One showed better results with distension with steroids than with intraarticular steroid alone at short-term follow-up of 3 mo.

Conclusions:
Our systematic review demonstrated that patients treated by any of the three modalities improved with no significant difference among them over a period of 6 to 12 mo. However, at 3 mo distension with steroids and steroid injection alone were superior to distension alone.
Effect of a Dynamic Fixation Construct on Syndesmosis Reduction: A Cadaveric Study
Authors: Honeycutt M. Wesley , Riehl John T. 
Published: May 2019

Objectives:
To explore what effect a dynamic fixation construct would have on the final reduction of the syndesmosis.

Methods:
Syndesmotic ligaments were sectioned in 10 cadaveric specimens. The syndesmosis was intentionally malreduced with a clamp, and the distance from the anterior edge of the fibula to the anterior incisura of the tibia was measured to quantify the sagittal syndesmotic displacement (SSD). A 3.5-mm quadricortical screw was then placed, the clamp was removed, and the SSD measured. The clamp was then replaced, and a suture-button construct (Knotless Tightrope; Arthrex Inc, Naples, FL) was then placed through the bone tunnel, the clamp was again removed, and the SSD was measured.

Results:
In all cases, the fibula reduced to within 1 mm of its native anatomical position with the dynamic construct. The static screw construct, however, maintained an identical SSD measurement as the clamped malreduction. The dynamic suture-button construct reliably improved the SSD (P < 0.0001).

Conclusions:
Our study demonstrates that dynamic fixation constructs can help restore anatomical alignment in the case of syndesmotic malreduction. The size difference between the suture diameter and drill hole effectively allows the fibula to be pulled and seated into the tibial incisura fibularis. These findings should not be viewed as a justification to ignore the syndesmotic reduction; however, they do validate an important benefit of dynamic fixation that has been found in the recent clinical literature.

Level of Evidence:
Therapeutic Level III.
Long-term Results of Matrix-assisted Autologous Chondrocyte Transplantation Combined With Autologous Bone Grafting for the Treatment of Juvenile Osteochondritis Dissecans
Authors: Roffi Alice , Andriolo Luca , Di Martino Alessandro , Balboni Federica , Papio Tiziana , Zaffagnini Stefano , Filardo Giuseppe 
Published: May 2019

Background:
Osteochondritis dissecans is a pathology affecting young patients that involves the entire osteochondral unit. In the case of unfixable fragments, regenerative cartilage treatments are a viable solution, but little is known about the use of these procedures for the treatment of juvenile osteochondritis dissecans (JOCD). The aim of this study was to evaluate the long-term results offered by matrix-assisted autologous chondrocyte transplantation combined with autologous bone grafting for the treatment of JOCD.

Methods:
Nineteen patients have been enrolled. The mean age at the time of treatment was 16.8±1.5 years, with a mean body mass index of 22.9±2.7. The average size of the defects was 2.8±1.2 cm2. All patients were evaluated prospectively before surgery and at 12, 24, 60, and at a final follow-up of 120 months with International Knee Documentation Committee scores, EuroQol-Visual Analogue Scale, and the Tegner Score.

Results:
A statistically significant improvement in all clinical scores was observed from baseline evaluation to 120 months of final follow-up. In particular, the International Knee Documentation Committee subjective score improved from the preoperative evaluation of 38.7±17.3 to 74.0±21.8 at 12 months (P<0.0005), with scores remaining stable for up to 120 months (83.8±20.7), with all follow-ups showing a statistically significant improvement compared with the basal value (P<0.0005). Three patients failed at 12 months, for a failure rate of 16% at 10 years of follow-up. Lesions >3.5 cm2 obtained worse subjective results. In addition, lesion size and female sex were significantly associated with failures.

Conclusions:
The matrix-assisted autologous chondrocyte transplantation technique with autologous bone grafting is a valid treatment option for JOCD in case of unfixable fragments. The clinical improvement obtained is significant and stable, with good results maintained for up to 10 years of follow-up and an overall low failure rate. Lesion size and sex could influence the clinical outcome and should be considered in the treatment choice.

Level of Evidence:
Level IV—case series.
Co-occurrence of Sensory Overresponsivity with Obsessive-Compulsive Symptoms in Childhood and Early Adolescence
Authors: Van Hulle Carol A. , Esbensen Karyn , Goldsmith H. Hill 
Published: May 2019

ABSTRACT:

Objective:
Sensory overresponsivity (SOR) is characterized by challenges in integrating and responding to everyday sensory experiences. Obsessive-compulsive disorder (OCD) is characterized by intrusive thoughts, ritualistic behaviors, and sensory phenomena. There is some evidence that individuals with co-occurring symptoms of SOR and OCD experience more severe anxiety than those with symptoms of OCD alone, but most studies employed small numbers of participants (typically with an OCD diagnosis) assessed at a single time point. Our 2-fold objective was to replicate previous research showing an association between OCD symptoms and SOR symptoms concurrently and to extend these analyses longitudinally in a large, birth-register-based sample.

Method:
Twins (N = 1613) and their primary caregivers participated in a multimodal, multimethod, longitudinal study. Primary caregivers completed the SOR inventory for their offspring at the age of 8 years, and twins completed the adult sensory profile at the age of 13 years. Parents completed the OCD module of the Diagnostic Interview Schedule for Children-IV when twins were 8 years; twins completed the same module at 13 years. Linear regression models tested for the concurrent and longitudinal associations between SOR and OCD controlling for socioeconomic status.

Results:
Concurrently, participants' likelihood of exhibiting OCD symptoms increased with each symptom of tactile or auditory overresponsivity at 8 years and 13 years (odds ratio = 1.1–2.7). However, SOR measured at age 8 years was unrelated to adolescent OCD symptoms at 13 years and vice versa.

Conclusion:
SOR symptoms, although significantly related to concurrent OCD symptoms, do not appear to precede OCD symptoms, suggesting that SOR symptoms may reflect another type of OCD sensory phenomenon rather than a comorbid condition.
Unplanned Readmissions After Acute Myocardial Infarction: 1-Year Trajectory Following Discharge From a Safety Net Hospital
Authors: Shah Ishan T. , Keeley Ellen C. 
Published: May 2019

Background:
Financial penalties rendered by the Centers for Medicare and Medicaid Services have brought about new challenges for safety net hospitals that serve a vulnerable patient population with risk factors associated with high readmission rates. Our goal was to determine the 1-year trajectory of unplanned readmissions in post-myocardial infarction (MI) patients, and to identify factors associated with readmission.

Methods:
A total of 261 acute MI patients admitted from April 2015 to April 2016 were evaluated in a multidisciplinary cardiology clinic within 10 days of hospital discharge and baseline characteristics and medical comorbidities were collected. Readmission and mortality data were obtained at 1 year through chart review and telephone follow-up.

Results:
At 1 year, there were 90 (34%) unplanned readmissions of which half were for noncardiac diagnoses. Of these, 69 patients (77%) were readmitted once, 16 (18%) were readmitted twice, 2 (2%) were readmitted 3 times, and 3 (3%) were readmitted 4 times over the subsequent year. Cardiac causes of 1-year readmission included recurrent MI in 23 (9%) and decompensated heart failure in 18 (7%) patients. Depressed left ventricular systolic function (hazard ratio, 2.23; 95% confidence interval, 2.00–2.44; P = 0.0003) and diabetes mellitus (hazard ratio, 1.60; 95% confidence interval, 1.38–1.82; P = 0.029) were associated with a significantly higher risk of readmission at 1 year.

Conclusion:
Following acute MI, patients are readmitted for cardiac and noncardiac diagnoses well beyond the 30-day mark. This is likely a function of the vulnerability of the patient population rather than a reflection of the medical care provided. More frequent surveillance may attenuate this problem.
Dynamic Scheimpflug Ocular Biomechanical Parameters in Healthy and Medically Controlled Glaucoma Eyes
Authors: Miki Atsuya , Yasukura Yuichi , Weinreb Robert N. , Yamada Tomomi , Koh Shizuka , Asai Tomoko , Ikuno Yasushi , Maeda Naoyuki , Nishida Kohji 
Published: May 2019

Purpose:To evaluate the relationship between biomechanical parameters measured with a dynamic Scheimpflug analyzer and glaucoma.Patients and Methods:Cross-sectional observational data of 47 eyes of 47 consecutive subjects with medically controlled primary open-angle glaucoma and 75 eyes of 75 healthy subjects examined with a dynamic Scheimpflug analyzer (Corvis ST) were retrospectively investigated. Eight biomechanical parameters were compared between eyes with and without glaucoma using multivariable models adjusting for intraocular pressure (IOP), central corneal thickness, age, and axial length.Results:In multivariable models, glaucoma was negatively correlated with A1 time (P<0.001, coefficient=−0.5535), A2 time (P=0.008, coefficient=−0.1509), radius (P=0.011, coefficient=−0.4034), and whole eye movement (P<0.001, coefficient=−0.0622). Negative correlation between glaucoma and 3 parameters (A1 time, A2 time, and radius) consistently indicate larger deformability of the cornea and negative correlation between glaucoma and whole eye movement indicate smaller eye movement, in glaucoma eyes. There were significant correlations of many biomechanical parameters with other baseline factors (8 parameters with IOP, 2 with central corneal thickness, 4 with age, and 7 with axial length).Conclusions:Eyes with medically controlled glaucoma were more deformable than healthy eyes, which may increase the risk of optic nerve damage through an underestimation of IOP and biomechanical vulnerability of the globe. Many parameters showed a significant correlation with baseline factors, suggesting the importance of adjustment for these confounding factors when evaluating the correlation between biomechanical parameters and ocular diseases. These results suggest the relevance of measuring biomechanical properties of glaucoma eyes for accurate IOP measurement and risk assessment.
Longitudinal translocator protein-18 kDa–positron emission tomography imaging of peripheral and central myeloid cells in a mouse model of complex regional pain syndrome
Authors: Cropper Haley C. , Johnson Emily M. , Haight Elena S. , Cordonnier Stephanie A. , Chaney Aisling M. , Forman Thomas E. , Biswal Anjali , Stevens Marc Y. , James Michelle L. , Tawfik Vivianne L. 
Published: May 2019

Abstract
Complex regional pain syndrome (CRPS) is a severely disabling disease characterized by pain, temperature changes, motor dysfunction, and edema that most often occurs as an atypical response to a minor surgery or fracture. Inflammation involving activation and recruitment of innate immune cells, including both peripheral and central myeloid cells (ie, macrophages and microglia, respectively), is a key feature of CRPS. However, the exact role and time course of these cellular processes relative to the known acute and chronic phases of the disease are not fully understood. Positron emission tomography (PET) of translocator protein-18 kDa (TSPO) is a method for noninvasively tracking these activated innate immune cells. Here, we reveal the temporal dynamics of peripheral and central inflammatory responses over 20 weeks in a tibial fracture/casting mouse model of CRPS through longitudinal TSPO-PET using [18F]GE-180. Positron emission tomography tracer uptake quantification in the tibia revealed increased peripheral inflammation as early as 2 days after fracture and lasting 7 weeks. Centralized inflammation was detected in the spinal cord and brain of fractured mice at 7 and 21 days after injury. Spinal cord tissue immunofluorescent staining revealed TSPO expression in microglia (CD11b+) at 7 days but was restricted mainly to endothelial cells (PECAM1+) at baseline and 7 weeks. Our data suggest early and persistent peripheral myeloid cell activation and transient central microglial activation are limited to the acute phase of CRPS. Moreover, we show that TSPO-PET can be used to noninvasively monitor the spatiotemporal dynamics of myeloid cell activation in CRPS progression with potential to inform disease phase–specific therapeutics.