bluuebunny/crossref_metadata_2025_split huggingface dataset:
Age-dependent Reliability of Semmes-Weinstein and 2-Point Discrimination Tests in Children
Authors: Dua Karan , Lancaster Timothy P. , Abzug Joshua M. 
Published: October 2016

Background:
Objective sensory testing is a critical component of the physical examination in children as they may be unable to communicate whether or not numbness is present. The purpose of this study was to determine at what age objective sensory tests could reliably be performed.

Methods:
Normal, uninjured participants aged 2 to 17 years were enrolled in the study. Monofilament and static/moving 2-point discrimination tests were performed bilaterally assessing the median, ulnar, and radial nerves. Performance scores were recorded using the monofilament size and 2-point discrimination distance. Statistical analysis was performed utilizing univariable linear regression, 1-way ANOVA, and Welch t test.

Results:
A total of 396 hands were tested utilizing the Semmes-Weinstein monofilament and static/moving 2-point discrimination tests. For the monofilament test, 27% of 3-year-olds, 83% of 4-year-olds, and all participants 5 years of age and older were capable of performing the monofilament test. The average monofilament scores were 2.874, 2.868, and 3.043 for the ulnar, median, and radial nerves, respectively, with no correlation with advancing age present. The ulnar and median nerve distributions were more sensitive than the radial nerve distribution (P<0.001).
For 2-point discrimination tests, 33% of 4-year-olds, 61% of 5-year-olds, 88% of 6-year-olds, 95% of 7- and 8-year-olds, and all participants 9 years and older were capable of performing the static/moving 2-point discrimination tests. The average static 2-point discrimination scores were 3.348, 2.806, and 9.637 mm for the ulnar, median, and radial nerves, respectively. The average moving 2-point discrimination scores were 2.977, 2.483, and 8.506 mm for the ulnar, median, and radial nerves, respectively. There was no correlation between advancing age and performance scores. Children are the most sensitive in the median, then ulnar, and then radial nerve distribution (P<0.001). Better discrimination is present between 2 moving points than static points (P<0.001).

Conclusions
Objective threshold testing utilizing a monofilament can reliably be performed in the vast majority of children aged 4 years and above, whereas density testing utilizing 2-point discrimination can reliably be performed in the vast majority of children aged 6 years and above.

Level of Evidence:
Level II.
The Effect of the Pucker Sign on Outcomes of Type III Extension Supracondylar Fractures in Children
Authors: Smuin Dallas M. , Hennrikus William L. 
Published: October 2016

Background:
The pucker sign, also called skin tenting, indicates significant displacement of the supracondylar fracture and can be a cause for alarm. The purpose of this study is to compare a cohort of patients with type III supracondylar fractures presenting with a pucker sign to a group without a pucker sign by evaluating neurovascular injury at presentation, need for open reduction, persistent neurovascular injury, range of motion, and carrying angle at final follow-up.

Methods:
A retrospective review was performed for Gartland type III extension type supracondylar fractures. Those with a pucker sign were identified and evaluated. Type III supracondylar fractures with a pucker sign were compared with a similar cohort without a pucker sign.

Results:
In total, 12 patients with a pucker sign at an average age of 5.2 years were evaluated. A total of 11 patients (92%) had diminished or absent pulses, and 2 (17%) had weakness in the median nerve distribution. Nine (75%) patients in this group were transferred to the university hospital. Average time to surgery was 8.9 hours with an average operating time of 25.1 minutes. Open reduction was not needed in any case. At an average follow-up of 4.7 months no patients had persistent neurovascular compromise. Two patients lacked <5 degrees of extension and 1 lacked 10 degrees of extension. One patient lacked 10 degrees of flexion. No patients had a change in carrying angle difference compared with the contralateral side. No statistical differences were observed between the 2 groups.

Conclusions:
Pucker sign, in the context of a supracondylar fracture of the humerus, is a soft tissue defect with potential entrapment of median nerve and brachial artery. At a maximum time of 16 hours from injury to surgery we report excellent outcomes and no long-term complications. Using the techniques of gradual traction, and milking the soft tissue, the pucker sign can be eliminated. Closed reduction and percutaneous pinning were performed in all the cases.

Level of Evidence:
Level III—retrospective comparative study.
Peripheral neuropathic changes in pachyonychia congenita
Authors: Pan Baohan , Byrnes Kelly , Schwartz Mary , Hansen C. David , Campbell Claudia M. , Krupiczojc Malvina , Caterina Michael J. , Polydefkis Michael 
Published: October 2016

AbstractWe compared patterns of intraepidermal nerve fibers and mechanoreceptors from affected and unaffected plantar skin from patients with pachyonychia congenita (PC) and control subjects. Plantar biopsies from 10 genetically confirmed patients with PC (with a mutation inKRT6A) were performed at the ball of the foot (affected skin) and the arch (unaffected) and were compared to biopsies from corresponding locations in 10 control subjects. Tissue was processed to visualize intraepidermal nerve fibers (IENF) (PGP9.5), subsets of IENF (CGRP, substance P, tyrosine hydroxylase), myelinated nerve fiber (neurofilament H, NFH), blood vessels (CD31), Meissner corpuscles, and Merkel cells (MCs). Structures were quantified using stereology or validated quantification methods. We observed that PC-affected plantar skin had significantly lower sweat gland innervation (sweat gland nerve fiber density) and reduced numbers of Meissner corpuscles compared to PC-unaffected or anatomically matched control skin. In contrast, Merkel cell densities and blood vessel counts were higher in PC-affected skin compared to either control or PC-unaffected skin. There were no differences in myelinated nerve fiber densities, SP, or CGRP between the groups. Pressure pain thresholds in PC-affected skin were lower compared to PC-unaffected and anatomically matched control skin. Additionally, MC densities in callused plantar skin from healthy runners with callus and one subject with a nonpainful palmoplantar keratoderma (AQP5mutation) were similar to PC-unaffected and control skin consistent with callus alone not being sufficient to increase MC number. These findings suggest that alterations in PC extend beyond keratinocytes and may provide strategies to study neuropathic pain in PC.
Manipulating the extracellular matrix: an animal model of the bladder pain syndrome
Authors: Offiah Ifeoma , Didangelos Athanasios , O'Reilly Barry A. , McMahon Stephen B. 
Published: October 2016

AbstractBladder pain syndrome (BPS) is associated with breakdown of the protective uroepithelial barrier of the urinary bladder allowing urinary constituents access to bladder sensory neurons. Although there are several animal models of cystitis, none specifically relates to BPS. Here, we aimed to create such a model using enzymatic digestion of the barrier proteoglycans (PGs) in the rat. Twenty female Wistar rats were anaesthetized and transurethrally catheterized. Ten animals were treated with 0.25IU of intravesical chondroitinase ABC and heparanase III to digest chondroitin sulphate and heparin sulphate PGs, respectively. Ten animals received saline. Following PG deglycosylation, bladders showed irregular loss of the apical uroplakin and a significant increase in neutrophils, not evident in the control group. Spinal cord sections were also collected for c-fos analysis. A large and significant increase in fos immunoreactivity in the L6/S1 segments in the treatment vs control bladders was observed. Cystometry was performed on 5 treatment and 5 control animals. Analysis revealed a significant increase in micturition reflex excitability postdeglycosylation. On a further group of 10 animals, von Frey mechanical withdrawal thresholds were tested on abdominal skin before and after PG digestions. There was a significant decrease in abdominal mechanical withdrawal threshold postdeglycosylation compared with controls. The results of this animal study suggest that many of the clinical features of BPS are seen after PG digestion from the bladder lumen. This model can be used to further understand mechanisms of pain in patients with BPS and to test new therapeutic strategies.
Ex vivo nonviral gene delivery of μ-opioid receptor to attenuate cancer-induced pain
Authors: Yamano Seiichi , Viet Chi T. , Dang Dongmin , Dai Jisen , Hanatani Shigeru , Takayama Tadahiro , Kasai Hironori , Imamura Kentaro , Campbell Ron , Ye Yi , Dolan John C. , Kwon William Myung , Schneider Stefan D. , Schmidt Brian L. 
Published: October 2016

Abstract
Virus-mediated gene delivery shows promise for the treatment of chronic pain. However, viral vectors have cytotoxicity. To avoid toxicities and limitations of virus-mediated gene delivery, we developed a novel nonviral hybrid vector: HIV-1 Tat peptide sequence modified with histidine and cysteine residues combined with a cationic lipid. The vector has high transfection efficiency with little cytotoxicity in cancer cell lines including HSC-3 (human tongue squamous cell carcinoma) and exhibits differential expression in HSC-3 (∼45-fold) relative to HGF-1 (human gingival fibroblasts) cells. We used the nonviral vector to transfect cancer with OPRM1, the μ-opioid receptor gene, as a novel method for treating cancer-induced pain. After HSC-3 cells were transfected with OPRM1, a cancer mouse model was created by inoculating the transfected HSC-3 cells into the hind paw or tongue of athymic mice to determine the analgesic potential of OPRM1 transfection. Mice with HSC-3 tumors expressing OPRM1 demonstrated significant antinociception compared with control mice. The effect was reversible with local naloxone administration. We quantified β-endorphin secretion from HSC-3 cells and showed that HSC-3 cells transfected with OPRM1 secreted significantly more β-endorphin than control HSC-3 cells. These findings indicate that nonviral delivery of the OPRM1 gene targeted to the cancer microenvironment has an analgesic effect in a preclinical cancer model, and nonviral gene delivery is a potential treatment for cancer pain.
X-linked Malformation and Cochlear Implantation
Authors: Smeds Henrik , Wales Jeremy , Asp Filip , Löfkvist Ulrika , Falahat Babak , Anderlid Britt-Marie , Anmyr Lena , Karltorp Eva 
Published: October 2016

Objective:
To evaluate if cochlear implantation is safe and constitutes an option for hearing rehabilitation of children with x-linked inner ear malformation.

Study Design:
Retrospective patient review in combination with a multidisciplinary follow-up.

Setting:
Tertiary referral hospital and cochlear implant program.

Patients:
Ten children with severe-profound mixed hearing loss and radiological findings consistent with Incomplete Partition type 3 cochlear malformation received cochlear implants during the years 2007 to 2015. Nine of the children had a mutation affecting the gene POU3F4 on Xq21.

Intervention:
Cochlear implantation.

Main Outcome Measures:
Surgical events, intraoperative measures and electrical stimulation levels, hearing and spoken language abilities.

Results:
In all, 15 cochlear implantations were performed. In three cases the electrode was found to be in the internal auditory canal on intraoperative x-ray and repositioned successfully. One child had a postoperative rhinorrhea confirmed to be cerebrospinal fluid but this resolved on conservative treatment. No severe complications occurred. Postoperative electrical stimulation levels were higher in 9 of 10 children, as compared with typically reported average levels in patients with a normal cochlea. Eight patients developed spoken language to various degrees while two were still at precommunication level. However, speech recognition scores were lower than average pediatric cases.

Conclusion:
Cochlear implantation is a safe procedure for children with severe-profound mixed hearing loss related to POU3F4 mutation inner ear malformation. The children develop hearing and spoken language but outcome is below average for pediatric CI recipients.
Hearing Changes After Intratympanically Applied Steroids for Primary Therapy of Sudden Hearing Loss: A Meta-analysis Using Mathematical Simulations of Drug Delivery Protocols
Authors: Liebau Arne , Pogorzelski Olivia , Salt Alec N. , Plontke Stefan K. 
Published: October 2016

Objective:
Controlled and uncontrolled studies with primary intratympanic or combined intratympanic and systemic application of glucocorticosteroids for idiopathic sudden hearing loss were analyzed by means of a meta-analysis in an attempt to establish optimal local drug delivery protocols.

Study Design:
A total of 25 studies with 28 treatment groups between January 2000 and June 2014 were selected that adequately described drug delivery protocols. Cochlear drug levels were calculated by a validated computer model of drug dispersion in the inner ear fluids based on the concentration and volume of glucocorticoids applied, the time the drug remained in the middle ear, and the specific timing of injections. Various factors were compared with hearing outcome, including baseline data, individual parameters of the application protocols, calculated peak concentration (C
max), and total dose (area under the curve).

Results:
There was no dependence of hearing outcome on individual parameters of the application protocol, C
max, or area under the curve. Final hearing threshold was notably independent of delay of treatment.

Conclusion:
During primary intratympanic or combined steroid therapy of idiopathic sudden hearing loss, the tendency toward early treatment having a positive effect on hearing improvement is thought to be a “sham effect,” likely related to spontaneous recovery. Change in pure-tone average may not be an adequate outcome parameter to assess effectiveness of the intervention, as it depends on the degree of initial hearing loss. Final pure-tone average provides a better alternative.
Nystagmus at the Onset of Vertiginous Attack in Ménière's Disease
Authors: Hirai Chiaki , Yamamoto Yukiko , Takeda Takamori , Tasaki Akihisa , Inaba Yuichiro , Kiyokawa Yusuke , Suzuki Yasuhiro , Tsutsumi Takeshi 
Published: October 2016

Objective:
To clarify the direction and characteristics of nystagmus at the onset of a vertiginous attack in Ménière's disease.

Patients:
Two patients with Ménière's disease, whose nystagmus at the onset of a vertiginous attack was recorded using electronystagmography.

Interventions:
Diagnostic.

Main Outcome Measures:
Electronystagmographic recordings of nystagmus.

Results:
In both patients, nystagmus was directed toward the affected side over the entire course of the vertiginous attack. One patient experienced a severe sensation of vertigo and exhibited strong nystagmus from the onset of the attack. The other patient reported a mild sensation of vertigo, which was accompanied by intermittent nystagmus.

Conclusions:
Vertiginous attacks in Ménière's disease are accompanied by irritative nystagmus. The intensity and characteristics (e.g., continuous or intermittent expression) of the nystagmus may be associated with pathophysiological severity.
Implantation of Bone-Anchored Hearing Devices Through a Minimal Skin Punch Incision Versus the Epidermal Flap Technique
Authors: Dumon Thibaud , Wegner Inge , Sperling Neil , Grolman Wilko 
Published: October 2016

Objective:
To compare the minimal skin punch incision without additional skin incision or soft tissue reduction with the epidermal flap technique and soft tissue reduction, for the implantation of percutaneous bone-anchored hearing devices.

Study Design:
Prospective cohort study.

Setting:
Tertiary care referral center.

Subjects and Methods:
Two hundred seventeen patients underwent 220 implantations. Sixty five cases underwent implantation by means of a skin punch resection without soft tissue reduction (punch group) and 155 cases underwent epidermal flap and soft tissue reduction (dermatome group). Main outcome measures were duration of surgery, perioperative adverse events, skin tolerance, and revision surgery.

Results:
The duration of surgery was shorter in the punch group (p < 0.001). The percentage of normal to moderate skin reactions, by Holgers classification, was higher in the punch group (90%) than in the dermatome group (84%). No severe reactions occurred in the punch group, but did occur in 7% in the dermatome group. These differences, although clinically important, did not reach statistical significance (p = 0.071). The rate of revision surgeries was not significantly different between the two groups. The indication for revision was different: mainly for skin issues in the dermatome group, against implant dislocation in the punch group.

Conclusion:
The implantation of the currently available percutaneous bone-anchored hearing implants with a minimal skin punch resection shortened duration of surgery and improved postoperative appearance, while preserving a good skin tolerance. In the punch group, there were less skin issues leading to revision surgery, however we did observe more implant dislocations needing revision surgery.
Can Endoscopic Bleeding Control Improve the Prognosis of Advanced Gastric Cancer Patients?
Authors: Park Hyungchul , Ahn Ji Yong , Jung Hwoon-Yong , Chun Joo Hyun , Nam Kwangwoo , Lee Jeong Hoon , Jung Kee Wook , Kim Do Hoon , Choi Kee Don , Song Ho June , Lee Gin Hyug , Kim Jin-Ho 
Published: October 2016

Background:
Gastric bleeding is not rare and difficult to treat in gastric cancer patients. We investigated whether this affects survival and if successful bleeding control improves the prognosis.

Patients/Material and Methods:
We retrospectively reviewed medical records for 64 subjects who underwent endoscopic therapy for gastric cancer bleeding at Asan Medical Center from January 2012 to December 2014 (bleeding group). Each subject was matched 1:2 by age, sex, and American Joint Committee on Cancer staging with 128 randomly selected patients treated for stomach cancer during the same period (control group). Median survival, bleeding treatment methods, successful bleeding control, and rebleeding rate were investigated.

Results:
The median age was 58.5 years, the male to female ratio 4.3:1. The initial hemostasis rate was 73.4%. Most patients were treated with a single method (37 patients, 57.8%); the coagrasper (32/95 cases, 33.7%) was the most frequently used treatment. Among the 47 patients in which successful bleeding control was achieved, 17 (36.2%) experienced rebleeding after 3 days. The median survival was longer in the control than in the bleeding group (18.5 vs. 6.5 mo), and in the successful bleeding control than in the failed bleeding control group (8.5 vs. 1.8 mo). However, the successful bleeding control group had lower survival than the control group (18.5 vs. 8.5 mo). Multivariate analysis showed that the risk of bleeding was lower in Borrmann type II, IV cancer, but was higher in the patients using antiplatelet or anticoagulant.

Conclusions:
Successful bleeding control is essential for improving survival in bleeding gastric cancer patients.
Optical Diagnosis of Sessile Serrated Polyps
Authors: Vleugels Jasper L.A. , IJspeert Joep E.G. , Hazewinkel Yark , van der Vlugt Manon , Fockens Paul , Koens Lianne , Dekker Evelien 
Published: October 2016

Background:Optical diagnosis of diminutive (1 to 5 mm) polyps could result in a more cost-effective colonoscopy practice. Previous optical diagnosis studies did not incorporate the differentiation of sessile serrated polyps (SSPs). This study aimed to evaluate the impact of optical diagnosis of diminutive SSPs on the overall performance of endoscopic polyp differentiation in daily colonoscopy practice.Methods:Endoscopy data were prospectively collected between 2011 and 2014 in a colonoscopy center. Each endoscopist reported a real-time optical diagnosis (SSP, adenoma or hyperplastic polyp) for all lesions in a structured colonoscopy reporting system, using narrow band imaging at their discretion. Study outcomes were accuracy of optical diagnosis, surveillance interval agreement and negative predictive value for diminutive rectosigmoid neoplastic histology based on the optical diagnosis of diminutive polyps compared to histopathology.Results:Of 2853 removed diminutive polyps, 202 (7.1%) were histologically proven SSPs. Optical diagnosis of diminutive SSPs was accurate in 24.4%. Diminutive SSPs determined 6.9% of postpolypectomy surveillance assignments. Inaccurate optical diagnosis of diminutive SSPs led to lower surveillance interval agreement (78.1% vs. 53.3%,P<0.01) and pooled negative predictive value per polyp (84.3% vs. 50.0%;P<0.01) in patients with diminutive SSPs when compared to patients without diminutive SSPs. Accurate endoscopic identification of diminutive SSPs improved from 0% in 2011 to 47% in 2014 (P=0.02).Conclusions:Endoscopic characterization of diminutive SSPs is difficult, impairing overall performance of optical diagnosis in patients with diminutive SSPs. Future optical diagnosis studies should use validated trainings and classification algorithms that include differentiation of SSPs.
Quality of Sleep and Coexistent Psychopathology Have Significant Impact on Fatigue Burden in Patients With Inflammatory Bowel Disease
Authors: Hashash Jana G. , Ramos-Rivers Claudia , Youk Ada , Chiu Wai Kan , Duff Kyle , Regueiro Miguel , Binion David G. , Koutroubakis Ioannis , Vachon Ashley , Benhayon David , Dunn Michael A. , Szigethy Eva M. 
Published: October 2016

Background:
Fatigue is common in inflammatory bowel disease (IBD) patients and is associated with factors such as psychopathology, sleep quality, and disease activity.

Goal:
To investigate the combined role of all the above factors in the burden of fatigue among IBD patients.

Study:
We conducted an observational study of adult patients enrolled in an IBD clinical research registry at a tertiary care clinic. Fatigue burden was defined by Item 1 of the Short-form IBD Questionnaire (SIBDQ), which is scored on a 7-point Likert scale. Crohn’s disease (CD) and ulcerative colitis (UC) disease activity were measured with the Harvey-Bradshaw Index or the UC Activity Index, respectively. Labs were obtained to assess anemia, vitamin deficiencies, and inflammatory markers. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Use of psychotropic medications and narcotics was used as proxy measure of psychopathology and pain.

Results:
Among 685 IBD patients enrolled in the registry, 631 (238 UC, 393 CD) had a complete SIBDQ. High fatigue burden was found in 57.5% of patients (64.4% CD, 46.2% UC). Fatigue burden was significantly associated with sleep disturbance (PSQI), SIBDQ, and disease activity. CD patients had more fatigue burden than UC patients. Multivariate regression showed that poor quality of life, sleep disturbance, and being on a psychotropic medication are significantly associated with fatigue burden for both UC and CD.

Conclusion:
Because fatigue is common in IBD patients, these findings suggest that attention to quality of sleep and psychopathology is as important as medical disease management.