bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radiation-Induced Painful Neurogenic Hypertrophy Treated With Botulinum Toxin A
Authors: Filippakis Alexandra , Ho Doreen T. , Small Juan E. , Small Kirstin M. , Ensrud Erik R. 
Published: February 2018

Abstract
Painful neurogenic hypertrophy is a rare complication of radiation therapy. We report a 27-year-old woman with a history of adenoid cystic carcinoma of the submandibular gland presented with painful twitching of her left shoulder. Electrodiagnostic studies were consistent with a diagnosis of radiation-induced spinal accessory nerve hyperactivity. The patient failed conventional medical therapy. She was treated with an injection of botulinum toxin A, and within 1 month experienced significant relief of symptoms. We thus conclude that Botulinum toxin is a therapeutic option for the pain associated with radiation-induced peripheral nerve hyperactivity.
COL6A and LAMA2 Mutation Congenital Muscular Dystrophy: A Clinical and Electrophysiological Study
Authors: Verma Sumit , Goyal Parul , Guglani Lokesh , Peinhardt Charlotte , Pelzek Diane , Barkhaus Paul E. 
Published: February 2018

Abstract

Objectives:
COL6A and LAMA2 are subtypes of congenital muscular dystrophy.

Methods:
Retrospective chart review of clinical findings, spirometry, muscle histology, muscle ultrasound, neuroimaging, and Electromyography (EMG)/Nerve Conduction Study data in genetically confirmed COL6A and LAMA2 subjects.

Results:
We identified 8 COL6A and 6 LAMA2 subjects: the female-to-male ratio was 1.3:1 and the mean age was 11.9 ± 3.6 years. Gross motor delays since birth, proximal muscle weakness, and contractures were noted in both groups. Joint hyperlaxity and skin changes (follicular hyperkeratosis and muscle biopsy scar thinning) were unique to COL6A. Severe scoliosis, macrocephaly, and nonambulatory status were common in LAMA2. Increasing age was associated with poor respiratory function in COL6A. There was central “cloud appearance” on rectus femoris muscle ultrasound in COL6A and white matter T2 hyperintensity on brain magnetic resonance imaging in LAMA2. LAMA2 also showed demyelinating polyneuropathy. Neurogenic changes on EMG and muscle histology were noted in 37% and 33% of COL6A cases, respectively.

Conclusions:
COL6A has unique skin changes, central cloud appearance on muscle ultrasound. LAMA2 has demyelinating polyneuropathy and white matter changes on brain imaging. The presence of neurogenic changes on EMG and muscle histology in COL6A suggests motor axonal neuropathy. Genetic testing remains the gold standard in confirming COL6A congenital muscular dystrophy.
Amiodarone Rifampicin Drug–Drug Interaction Management With Therapeutic Drug Monitoring
Authors: Oude Munnink Thijs H. , Demmer Anna , Slenter Roel H. J. , Movig Kris L. L. 
Published: February 2018

Abstract:
The authors present a case of a 69-year-old man with arrhythmogenic right ventricular cardiomyopathy controlled with amiodarone and an infected orthopedic prosthesis requiring treatment with rifampicin. This combination involves a pharmacokinetic drug–drug interaction leading to subtherapeutic drug concentrations of amiodarone and its active metabolite. The long half-life of amiodarone and its active metabolite in combination with the late onset and offset of cytochrome P4503A (CYP3A4) induction by rifampicin makes this a challenging drug–drug interaction to cope with in clinical practice. Before, during, and after rifampicin treatment, the serum concentrations of amiodarone and its active metabolite were measured and the amiodarone dose was adjusted accordingly. The amiodarone dose required to maintain effective concentrations was 450% of the initial dose. The drug–drug interaction between amiodarone and rifampicin is relevant, both clinically and pharmacokinetically, and can be managed by dose adjustments of amiodarone based on serum concentrations.
A CASE OF INTRARETINAL PERIPAPILLARY NEOVASCULARIZATION IN ABCA4-RELATED RETINOPATHY
Authors: Essilfie Juliet O. , Huynh An , Gorin Michael B. , Sadda SriniVas R. 
Published: February 2018

Purpose:
To report a case of ABCA4-related retinopathy and potential complications.

Methods:
The authors describe a case report of intraretinal neovascularization in a patient with ABCA4-related retinopathy and describe the multimodal retinal imaging findings.

Results:
A 49-year-old woman presents with cystoid macular edema and diffuse intraretinal and perivascular hyperpigmentation in both eyes. Genetic testing confirmed ABCA4-related retinopathy. Fluorescein angiography revealed peripapillary intraretinal neovascularization in the absence of any other identifiable retinal pathology.

Conclusion:
To the authors' knowledge, this is the first reported case of intraretinal neovascularization–associated ABCA4-related retinopathy. Ancillary testing of ABCA4-related retinopathy with fluorescein angiography or optical coherence tomography angiography may be helpful in identifying this rare complication.
Soft Tissue Metrics in Thyroid Eye Disease: An International Thyroid Eye Disease Society Reliability Study
Authors: Mawn Louise A. , Dolman Peter J. , Kazim Michael , Strianese Diego , Genol Ignacio , Chong Kelvin K. L. , Sullivan Timothy J. , Korn Bobby S. , Naik Milind , Dutton Jonathan , Velasco e Cruz Augusto , Li Chun 
Published: February 2018

Purpose:
To determine the reliability of 3 scales for assessing soft tissue inflammatory and congestive signs associated with thyroid eye disease.

Methods:
This was a multicentered prospective observational study, recruiting 55 adults with thyroid eye disease from 9 international centers. Six thyroid eye disease soft tissue features were measured; each sign graded using 3 scales (presence/absence [0–1], 3-point scale [0–2], and percentage [0–100]). Each eye was graded twice by 2 independent raters. Accuracy (fraction of agreement) was calculated between the 2 trials for each rater (intrarater reliability) and between raters for all trials (interrater reliability) to determine the most sensitive scale for each feature that maintained a threshold of agreement greater than 0.70. Trial, intrarater reliability, and interrater reliability were determined by accuracy measurement of agreement for each inflammatory/congestive feature.

Results:
Fifty-five patients had 218 assessments for 6 thyroid eye disease metrics. The intrarater reliability for each feature was consistently better than the interrater reliabilities. Using an agreement of 0.70 or better, for the interrater tests, conjunctival and eyelid edema could be reliably measured using the 0–1 or 0–2 scale while conjunctival and eyelid redness could only be reliably measured with the binary 0–1 scale. Caruncular edema and superior conjunctival redness could not be measured reliably between 2 raters with any scale. The percentage scale had poor agreement unless slippage intervals of >20% were allowed on either side of the measurements.

Conclusions:
Of the specific periocular soft tissue inflammatory features measured between raters in the Clinical Activity Score and Vision, Inflammation, Strabismus, Appearance scales, edema of the eyelids and conjunctiva could reliably be measured by both 0–1 and 0–2 scales, erythema of the eyelid and bulbar conjunctiva could reliably be measured only by the 0–1 scale, and the other parameters of superior bulbar erythema and caruncular edema were not reliably measured by any scale.
Noninflammatory Thyroid Eye Disease
Authors: Ugradar Shoaib , Rootman Daniel B. 
Published: February 2018

Purpose:
Patients presenting with thyroid eye disease (TED) usually follow a well-defined self-remitting course characterized by an active inflammatory phase followed by an inactive fibrotic phase. We present 3 cases where patients presented primarily with signs of progressive fibrosis and no signs of prior active inflammation.

Methods:
We reviewed the clinical notes and investigations of 3 patients who presented to our center between January 2015 and August 2017.

Results:
All patients included in the study presented primarily with severe, progressive fibrosis without evidence of a previous active inflammatory condition. Although there were no signs of inflammation, each case was progressive, with 2 of the cases developing dysthyroid optic neuropathy that was relatively recalcitrant. We found that these patients were older than the general population of TED patients and that their disease course represents a departure from the common narrative.

Conclusions:
This subgroup of TED patients do not conform to the typical inflammatory natural history of TED. We propose that the heterogeneity of the orbital fibroblast pool and their function may be different in this subgroup. Further work will be required to reveal the pathophysiology of this atypical TED process, potentially revealing links between aging and the inflammatory mediators in TED.
Heterozygous mutations in GTP-cyclohydrolase-1 reduce BH4 biosynthesis but not pain sensitivity
Authors: Nasser Arafat , Møller Anette Torvin , Hellmund Vibe , Thorborg Sidsel Salling , Jespersgaard Cathrine , Bjerrum Ole J. , Dupont Erik , Nachman Gösta , Lykkesfeldt Jens , Jensen Troels Staehelin , Møller Lisbeth Birk 
Published: February 2018

Abstract
Human studies have demonstrated a correlation between noncoding polymorphisms of “the pain protective” haplotype in the GCH1 gene that encodes for GTP cyclohydrolase I (GTPCH1)—which leads to reduced tetrahydrobiopterin (BH4) production in cell systems—and a diminished perception of experimental and clinical pain. Here, we investigate whether heterozygous mutations in the GCH1 gene which lead to a profound BH4 reduction in patients with dopa-responsive dystonia (DRD) have any effect on pain sensitivity. The study includes an investigation of GCH1-associated biomarkers and pain sensitivity in a cohort of 22 patients with DRD and 36 controls. The patients with DRD had, when compared with controls, significantly reduced levels of BH4, neopterin, biopterin, and GTPCH1 in their urine, blood, or cytokine-stimulated fibroblasts, but their pain response with respect to non-painful stimulation, (acute) stimulus-evoked pain, or pain response after capsaicin-induced sensitization was not significantly different. A family-specific cohort of 11 patients with DRD and 11 controls were included in this study. The patients with DRD were heterozygous for the pain protective haplotype in cis with the GCH1 disease-causing mutation, c.899T>C. No effect on pain perception was observed for this combined haplotype. In conclusion, a reduced concentration of BH4 is not sufficient to alter ongoing pain sensitivity or evoked pain responses.
The prevalence of unexplained falls and syncope in older adults presenting to an Irish urban emergency department
Authors: Bhangu Jaspreet , Hall Patricia , Devaney Naomi , Bennett Kathleen , Carroll Laura , Kenny Rose-Anne , McMahon C. Geraldine 
Published: February 2018

Aim
There is growing evidence of an overlap between unexplained falls and syncope in older adults. Our aim was to examine the prevalence and associated resource utilization of these conditions in an urban emergency department (ED).

Patients and methods
A single-centre, prospective, observational study was carried out over a 6-month period. Consecutive patients older than 50 years who presented to the ED because of a fall, collapse or syncope were included. Univariate analysis of demographic data is presented as percentages, mean (SD), 95% confidence intervals (CIs) and medians (interquartile range). Logistic regression modelling was used to examine the association between falls and resource utilization.

Results
A total of 561 patients fulfilled the inclusion criteria during the study period. Unexplained fallers accounted for 14.3% (n=80; 95% CI: 13.3–15.3) and syncope for 12.7% (n=71; 95% CI: 11.7–13.6) of all fall presentations. Overall, 50% (n=282; 95% CI: 48.20–52.34) of patients required admission to hospital. Patients with syncope [odds ratio (OR)=2.48, 95% CI: 1.45–4.23], and unexplained falls (OR=2.36, 95% CI: 1.37–4.08) were more likely to require admission than those with an explained falls. Unexplained fallers were nearly five times more likely to suffer recurrent falls (OR=4.97, 95% CI: 2.89–8.56).

Conclusion
One in four older fallers presenting to ED have symptoms suggestive of syncope or an unexplained fall. There are significant biological consequences of recurrent falls including greater rates of cognitive decline, gait and mobility disturbances, depression and frailty. Recognition that syncope can present as an unexplained fall in older adults is important to ensure that appropriate early modifiable interventions are initiated.
Hypofibrinogenemia Is Associated With Poor Outcome and Secondary Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome in Pediatric Severe Sepsis*
Authors: Signoff Jessica K. , Fitzgerald Julie C. , Teachey David T. , Balamuth Fran , Weiss Scott L. 
Published: February 2018

Objectives:
Some children with sepsis exhibit a sustained hyperinflammatory response that can trigger secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome. Although hypofibrinogenemia is a shared feature of sepsis and hemophagocytic lymphohistiocytosis, there are no data about fibrinogen as a biomarker to identify children with sepsis/secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome overlap. We hypothesized that hypofibrinogenemia is associated with poor outcomes and secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome and has utility as a screening biomarker for this sepsis phenotype.

Design:
A retrospective cohort study of patients less than or equal to 21 years treated for severe sepsis from January 2012 to December 2014.

Setting:
Emergency department and PICU at a single academic children’s hospital.

Patients:
Consecutive patients with greater than or equal to one episode of hypofibrinogenemia (serum fibrinogen < 150 mg/dL) within 7 days of sepsis were compared with a random sample of patients without hypofibrinogenemia using an a priori sample size target of 190. Thirty-eight patients with hypofibrinogenemia were compared with 154 without hypofibrinogenemia.

Interventions:
None.

Measurements and Main Results:
The primary outcome was “complicated course” (composite of 28-d mortality or ≥ two organ failures at 7 d). Secondary outcomes were 28-day mortality and fulfillment of diagnostic criteria for secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome. We used Wilcoxon rank-sum, Fisher exact test, and multivariable logistic regression to compare patients with versus without hypofibrinogenemia. Patients with hypofibrinogenemia were more likely to have a complicated course (73.7% vs 29.2%; p < 0.001), 28-day mortality (26.3% vs 7.1%, p = 0.002), and meet diagnostic criteria for secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome (21.1% vs 1.3%; p < 0.001). After controlling for confounders, hypofibrinogenemia remained associated with complicated course (adjusted odds ratio, 8.8; 95% CI, 3.5–22.4), mortality (adjusted odds ratio, 6.0; 95% CI, 2.0–18.1), and secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome (adjusted odds ratio, 27.6; 95% CI, 4.4–173).

Conclusions:
Hypofibrinogenemia was independently associated with poor outcome and secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome in pediatric sepsis. Measurement of fibrinogen may provide a pragmatic biomarker to identify children with possible sepsis/secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome overlap for whom further diagnostic testing and consideration of adjunctive immunomodulatory therapies should be considered.
Outcome Trends of Adult Cancer Patients Receiving Inpatient Rehabilitation
Authors: Gallegos-Kearin Vanessa , Knowlton Sasha E. , Goldstein Richard , Mix Jacqueline , Zafonte Ross , Kwan Michael , Silver Julie , Schneider Jeffrey C. 
Published: February 2018

Objective
This study describes characteristics and trends of inpatient rehabilitation among cancer patients within the United States over a 13-yr period.

Design
This was a retrospective study of data from the Uniform Data System for Medical Rehabilitation from 2002 to 2014. Patients older than 17 yrs admitted to inpatient rehabilitation facilities with a diagnosis of malignant cancer were included. Trends of rehabilitation outcomes including length of stay, Functional Independence Measure (FIM) Instrument scores, and discharge location were examined.

Results
Data from 115,570 cancer patients were evaluated. Mean age was 66 ± 14 yrs and 49% were women. Mean length of stay decreased over time (2002: 14 days to 2014: 13 days; P < 0.0005). Patient's admission total FIM scores decreased over time (2002: 68 ± 18 to 2014: 61 ± 16; P < 0.0005). The FIM change score increased over time (2002: 19 ± 16 to 2014: 25 ± 17; P < 0.0005). The greatest significant functional gains occurred in self care and transfers. Most patients (>70%) were discharged to the community.

Conclusions
Cancer patients receiving acute inpatient rehabilitation demonstrated significant improvements in functional outcomes from admission to discharge. Cancer patients became more independent in important activities of daily living, thereby potentially reducing caregiver burden and ensuring safer discharges back to the community. This study suggests potential benefit of inpatient rehabilitation for appropriate cancer patients.
Hypercholesterolemia Is Associated with the Subjective Evaluation of Postoperative Outcomes in Patients with Idiopathic Carpal Tunnel Syndrome Who Undergo Surgery: A Multivariate Analysis
Authors: Yano Koichi , Kawabata Akira , Ikeda Mikinori , Suzuki Keisuke , Kaneshiro Yasunori , Egi Takeshi 
Published: February 2018

Background:
Carpal tunnel syndrome is a compression neuropathy of the median nerve at the wrist; its symptoms include neuropathic pain and sensory and motor disturbance distributed by the median nerve. Carpal tunnel syndrome and hypercholesterolemia have similar backgrounds, but the effect of these similarities on postoperative outcomes has not been reported. Using multivariate analysis, the authors analyzed the relationship between prognostic factors, including the presence of hypercholesterolemia, and subjective postoperative outcomes of patients with idiopathic carpal tunnel syndrome.

Methods:
Of 168 hands with carpal tunnel syndrome that were treated surgically, 141 that were followed up and assessed 1 year postoperatively or thereafter were included. The mean postoperative follow-up period was 40.8 months. Surgery was performed through a small palmar skin incision under local anesthesia. The outcomes were postoperative symptoms, including pain and numbness, and overall Kelly assessment.

Results:
Preoperative numbness and pain resolved and alleviated in 94 of 141 hands and was diminished in 59 of 64 hands. Univariate analysis showed that postoperative numbness and Kelly assessment were significantly associated with hypercholesterolemia. Multivariate analysis showed that postoperative numbness was significantly associated with smoking and hypercholesterolemia, and Kelly assessment was significantly associated with smoking (adjusted OR, 3.3; 95 percent CI, 1.1 to 10; p = 0.04) and hypercholesterolemia (adjusted OR, 2.9; 95 percent CI, 1.4 to 6.3; p = 0.01).

Conclusion:
Hypercholesterolemia, usually a systemic condition in sites other than the hand, is associated with the subjective evaluation of postoperative symptoms in patients with idiopathic carpal tunnel syndrome.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Risk, III.
Asthmatic Exacerbation as a Cause of False-Positive Whole-Body Iodine Scan in a Patient With Treated Papillary Thyroid Carcinoma
Authors: Chaussé Guillaume , Kader Tina , Abikhzer Gad , Probst Stephan 
Published: February 2018

Abstract
A 44-year-old woman was found to have new diffuse lung uptake on a follow-up whole-body 131I scan 1 year after being treated with surgery and radioactive iodine for papillary thyroid cancer. However, subsequent CT thorax and thyroglobulin levels were both unremarkable. Shortly after, she presented with respiratory symptoms, exhibiting end-expiratory wheezing on auscultation. Metacholine challenge test confirmed asthma. Symptoms improved under inhaled corticosteroids and beta-2 agonists. Resolution of lung uptake was confirmed on a second 131I imaging 6 months later.
Improving Quality of Dynamic Airway Computed Tomography Using an Expiratory Airflow Indicator Device
Authors: Hahn Lewis D. , Sung Arthur W. , Shafiq Majid , Guo Haiwei Henry 
Published: February 2018

Purpose:
Dynamic computed tomography (CT) of the airways is increasingly used to evaluate patients with suspected expiratory central airway collapse, but current protocols are susceptible to inadequate exhalation caused by variable patient compliance with breathing instructions during the expiratory phase. We developed and tested a low-cost single-use expiratory airflow indicator device that was designed to improve study quality by providing a visual indicator to both patient and operator when adequate expiratory flow was attained.

Materials and Methods:
A total of 56 patients undergoing dynamic airway CT were evaluated, 35 of whom were scanned before introduction of the indicator device (control group), with the rest comprising the intervention group. Lung volumes and tracheal cross-sectional areas on inspiratory/expiratory phases were computed using automated lung segmentation and quantitative software analysis. Inadequate exhalation was defined as absolute volume change of <500 mL during the expiratory phase.

Results:
Fewer patients in the intervention group demonstrated inadequate exhalation. The average change in volume was higher in the intervention group (P=0.004), whereas the average minimum tracheal cross-sectional area was lower (P=0.01).

Conclusions:
The described expiratory airflow indicator device can be used to ensure adequate exhalation during the expiratory phase of dynamic airway CT. A higher frequency of adequate exhalation may improve reliability and sensitivity of dynamic airway CT for diagnosis of expiratory central airway collapse.
Opioid addiction, diversion, and abuse in chronic and cancer pain
Authors: Kata Vijay , Novitch Matthew B. , Jones Mark R. , Anyama Best O. , Helander Erik M. , Kaye Alan D. 
Published: February 2018

Purpose of review
The primary cause of overdose death in the United States is related to pharmaceutical opioids. A few particular populations that struggle with adverse outcomes related to opioid abuse are those in palliative care, those with chronic pain, and those receiving pain treatments secondary to cancer or chemotherapy.

Recent findings
There have been massive efforts to decrease the use of opioid abuse in patient care in a gestalt manner, but palliative care provides unique challenges in applying these reduction tactics used by other specialties.

Summary
We explore behavioral interventions, provider education, alternative pain management techniques, postmarketing surveillance, and abuse-deterrent formulas as emerging methods to counteract opioid abuse in these populations.