bluuebunny/crossref_metadata_2025 huggingface dataset:
Friberg Equation to Predict Pediatric Distal Forearm Fracture Remodeling
Authors: Pearce Stephanie S. , Honeycutt Michael W. , Cutchen William A. , Tillman Mark D. , Nimityongskul Prasit
Published: January 2019

Background:

This study is the first to test Friberg’s equation’s (Vt
=V
0[e
(−ßt)]) accuracy in predicting the residual angular deformity in pediatric distal forearm fractures.

Methods:

Angular deformities from distal forearm fractures in 50 children (mean age, 9 y) were retrospectively measured on follow-up radiographs once healed and compared to extrapolated angles at respective follow-up intervals from 2013 to 2015.

Results:

The predicted and actual angulations from 120 radiographs (mean follow-up, 3mo) showed that the mean predicted angle was similar to the measured angle in the radioulnar plane and only 2 degrees greater than the measured angle in the dorsovolar plane. A strong correlation was observed between predicted and measured angles in both planes.

Conclusions:

Friberg’s equation is a valid tool for predicting remodeling potential in pediatric distal 25% forearm fractures.

Level of Evidence:

Prognostic Study—Level II.
Intensivists in U.S. Acute Care Hospitals*
Authors: Halpern Neil A. , Tan Kay See , DeWitt Meghan , Pastores Stephen M.
Published: January 2019

Objectives:

To determine the total numbers of privileged and full-time equivalent intensivists in acute care hospitals with intensivists and compare the characteristics of hospitals with and without intensivists.

Design:

Retrospective analysis of the American Hospital Association Annual Survey Database (Fiscal Year 2015).

Setting:

Two-thousand eight-hundred fourteen acute care hospitals with ICU beds.

Patients:

None.

Interventions:

None.

Measurements and Main Results:

Of the 2,814 acute care hospitals studied, 1,469 (52%) had intensivists and 1,345 (48%) had no intensivists. There were 28,808 privileged and 19,996 full-time equivalent intensivists in the 1,469 hospitals with intensivists. In these hospitals, the median (25–75th percentile) numbers of privileged and full-time equivalent intensivists were 11 (5–24) and 7 (2–17), respectively. Compared with hospitals without intensivists, hospitals with privileged intensivists were primarily located in metropolitan areas (91% vs 50%; p < 0.001) and at the aggregate level had nearly thrice the number of hospital beds (403,522 [75%] vs 137,146 [25%]), 3.6 times the number of ICU beds (74,222 [78%] vs 20,615 [22%]), and almost twice as many ICUs (3,383 [65%] vs 1,846 [35%]). At the hospital level, hospitals with privileged intensivists had significantly more hospital beds (median, 213 vs 68; p < 0.0001), ICU beds (median, 32 vs 8; p < 0.0001), a higher ratio of ICU to hospital beds (15.6% vs 12.6%; p < 0.0001), and a higher number of ICUs per hospital (2 vs 1; p < 0.0001) than hospitals without intensivists.

Conclusions:

Analyzing the intensivist section of the American Hospital Association Annual Survey database is a novel approach to estimating the numbers of privileged and full-time equivalent intensivists in acute care hospitals with ICU beds in the United States. This methodology opens the door to an enhanced understanding of the current supply and distribution of intensivists as well as future research into the intensivist workforce.
New perspectives in Merkel cell carcinoma
Authors: del Marmol Véronique , Lebbé Celeste
Published: January 2019

Purpose of review

Merkel cell carcinoma (MCC), a rapidly progressing skin cancer, has poor prognosis. We reviewed the epidemiology, pathogenesis, diagnosis and treatment of MCC, with a focus on recent therapeutic advancements.

Recent findings

Risk factors for MCC, such as old age, immunosuppression, polyomavirus infection and exposure to UV radiation have already been identified, but the underlying mechanisms leading to carcinogenesis still need clarification. On the basis of recent advances, immunotherapy – in particular, inhibition targeting the programmed cell death protein 1/programmed death-ligand 1 (PD1)/PDL1) immune checkpoint blockade – is currently being investigated in the treatment of metastatic MCC. Avelumab, an anti-PDL1 antibody, was the first drug to be approved internationally as second-line monotherapy for patients with advanced MCC, based on results from the JAVELIN Merkel 200 clinical trial. Avelumab has also recently been approved as first-line treatment for advanced MCC in Europe. Pembrolizumab (anti-PD1) in first-line and nivolumab (anti-PD1) in first-line and second-line treatments are two other checkpoint inhibitors that are under investigation, and showing promising results. New innovative therapies are also in development.

New insights concerning advances in MCC diagnosis and treatment have been highlighted. Immunotherapy for metastatic MCC constitutes a recent breakthrough in an unmet medical need, but alternative therapies should continue to be investigated.
Changes in Pharmacists' Perceptions After a Training in Opioid Misuse and Accidental Overdose Prevention
Authors: Eukel Heidi N. , Skoy Elizabeth , Werremeyer Amy , Burck Siri , Strand Mark
Published: January 2019

Introduction:

Continuing education is needed for health professionals to take an active role in reversing the opioid crisis. This report describes the results of training to promote behavioral change by altering pharmacists' perceptions toward opioid misuse through the provision of content-related education.

Methods:

A free 3-hour opioid misuse and overdose prevention training program was developed and delivered to 43 community pharmacists. The training consisted of five modules addressing the disease of addiction, risks associated with opioids and accidental overdose, the role of naloxone, opioid dispensing and consultation pearls, and effective ways to communicate with patients about opioids. A paired analysis was performed from a 12-item survey delivered before and after the training program to assess changes in pharmacists' perception.

Results:

Five items showed a statistically significant (P < .05) change in perceptions after the training. Significant changes were reported for opioid addiction being outside the control of the affected person, the role of family history in prescription drug abuse, the value of counseling to support patients at risk of prescription opioid abuse, the value of screening tools, and the importance of viewing things from the patient's perspective. Correlation analysis identified that pharmacists' views on their role in the fight against the opioid epidemic and their agreement in the value to screen for opioid misuse were most closely related to the desire for behavioral change.

Discussion:

A training program influenced pharmacists' attitudes and perceptions about targeted behaviors and associated with the value of screening for opioid misuse or overdose risk and counseling patients about the benefits and risks of opioids.
Frequent TLE1 Expression in Cutaneous Neoplasms
Authors: Xiong Yiqin , Dresser Karen , Cornejo Kristine M.
Published: January 2019

TLE1 immunohistochemistry is widely used as a biomarker for synovial sarcoma. Recently, we identified TLE1 expression in a subset of melanomas and noted staining in sebaceous glands and follicular epithelium. TLE1 immunohistochemistry has not been well studied in cutaneous tumors. The aim was to investigate TLE1 expression in sebaceous neoplasms, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC) to determine whether the staining patterns may aid in the diagnosis or classification of these neoplasms. TLE1 immunohistochemistry was performed on sebaceous adenoma (n = 26), sebaceoma (n = 10), sebaceous carcinoma (n = 19), BCC (n = 20), and SCC (n = 19). Positivity was defined as dark-brown nuclear staining and graded as 3+ (strong staining of >50% of cells at 4×), 2+ (moderate staining of 10–50% of cells at 4× or >50% of cells staining at 10×), and 1+ (weak staining of <50% of cells at 10×). No staining was scored as 0. A score of 2–3+ was considered positive and 0–1+ negative. Nuclear TLE1 expression was identified in 25/26 (96%) sebaceous adenomas, 8/10 (80%) sebaceomas, and 17/19 (90%) sebaceous carcinomas. TLE1 also labeled 19/20 (95%) BCCs and 12/19 (63%) SCCs. TLE1 immunohistochemistry frequently highlights sebaceous neoplasms, BCC, and SCC with a fairly high sensitivity (63%–96%). Therefore, TLE1 is not a specific biomarker for synovial sarcoma and should be evaluated with caution, particularly in cases in which the differential diagnosis may include other cutaneous tumors. In addition, TLE1 does not seem to be useful in the diagnosis or classification of these neoplasms.
Serotonin 2A receptors are a stress response system: implications for post-traumatic stress disorder
Authors: Murnane Kevin Sean
Published: January 2019

Serotonin, one of the first neurotransmitters to be identified, is an evolutionarily old molecule that is highly conserved across the animal kingdom, and widely used throughout the brain. Despite this, ascribing a specific set of functions to brain serotonin and its receptors has been difficult and controversial. The 2A subtype of serotonin receptors (5-HT2A receptor) is the major excitatory serotonin receptor in the brain and has been linked to the effects of drugs that produce profound sensory and cognitive changes. Numerous studies have shown that this receptor is upregulated by a broad variety of stressors, and have related 5-HT2A receptor function to associative learning. This review proposes that stress, particularly stress related to danger and existential threats, increases the expression and function of 5-HT2A receptors. It is argued that this is a neurobiological adaptation to promote learning and avoidance of danger in the future. Upregulation of 5-HT2A receptors during stressful events forms associations that tune the brain to environmental cues that signal danger. It is speculated that life-threatening situations may activate this system and contribute to the symptoms associated with post-traumatic stress disorder (PTSD). 3,4-Methylenedioxymethamphetamine, which activates 5-HT2A receptors, has been successful in the treatment of PTSD and has recently achieved status as a breakthrough therapy. An argument is presented that 3,4-methylenedioxymethamphetamine may paradoxically act through these same 5-HT2A receptors to ameliorate the symptoms of PTSD. The central thematic contention is that a key role of serotonin may be to function as a stress detection and response system.
Effects of the α2/α3-subtype-selective GABAA receptor positive allosteric modulator KRM-II-81 on pain-depressed behavior in rats: comparison with ketorolac and diazepam
Authors: Moerke Megan J. , Li Guanguan , Golani Lalit K. , Cook James , Negus S. Stevens
Published: January 2019

This study examined effects of the α2/α3-subtype-selective GABAA receptor positive allosteric modulator KRM-II-81 in an assay of pain-related behavioral depression. Adult, male Sprague-Dawley rats responded for electrical brain stimulation in a frequency-rate intracranial self-stimulation (ICSS) procedure. Intraperitoneal injection of 1.8% lactic acid served as an acute noxious stimulus to depress ICSS. Effects of KRM-II-81 were evaluated in the absence and presence of the acid noxious stimulus. The NSAID ketorolac and the benzodiazepine diazepam were tested as comparators. Neither ketorolac nor KRM-II-81 altered ICSS in the absence of the acid noxious stimulus; however, diazepam produced facilitation consistent with its abuse liability. Ketorolac blocked acid-induced depression of ICSS, and effects of 1.0 mg/kg ketorolac lasted for at least 5 h. KRM-II-81 (1.0 mg/kg) produced significant antinociception after 30 min that dissipated by 60 min. Diazepam also attenuated acid-depressed ICSS, but only at doses that facilitated ICSS when administered alone. The lack of ketorolac or KRM-II-81 effects on ICSS in the absence of the acid noxious stimulus suggests low abuse liability for both compounds. The effectiveness of ketorolac to block acid-induced ICSS depression agrees with clinical analgesic efficacy of ketorolac. KRM-II-81 produced significant but less consistent and shorter-acting antinociception than ketorolac.
Pharmacokinetic Variability and Clinical Use of Lacosamide in Children and Adolescents in Denmark and Norway
Authors: Larsen Burns Margrete , Nikanorova Marina , Baftiu Arton , Borg Rasmussen Jan , Johannessen Svein I. , Johannessen Landmark Cecilie
Published: January 2019

Background:

The indication for the antiepileptic drug lacosamide (LCM) was recently extended to include children from the age of 4 years. Real-life data on the use and serum concentrations of LCM in children and adolescents are limited. The purpose of this study was to investigate the use of LCM in this patient group in relation to age, comedication, dose, serum concentrations and duration of treatment, and to examine pharmacokinetic variability.

Methods:

Children and adolescents (<18 years) who had serum concentrations of LCM measured from January 2012 to June 2018 were retrospectively identified from the therapeutic drug monitoring databases at 2 national epilepsy centers in Norway and Denmark. Clinical data were collected from request forms and medical records.

Results:

Data from 124 patients were included, 61 girls/63 boys. Weight was available for 76 patients. Median age was 15 years (range 2–17 years), dose of LCM 300 mg/d (76–600 mg/d), and serum concentration 18 µmol/L (5–138 µmol/L) [4.5 mg/L (1.3–34.5 mg/L)]. Pharmacokinetic variability was demonstrated as the concentration/(dose/kg) ratio ranged from 1.3 to 9.4 (µmol/L)/(mg/kg) and was affected by age. Polytherapy with 1–3 other antiepileptic drugs was noted in 107 patients (86%). Treatment was continued beyond 1 year in 71% (n = 45) of the 63 patients where such information was available, and all of these 45 patients had serum concentrations within the defined reference range. The 1-year retention rate was higher in patients not concomitantly using other sodium channel–blocking drugs (82% versus 56%).

Conclusions:

The study demonstrates pharmacokinetic variability in and between age groups, which indicates usefulness of therapeutic drug monitoring. More than two-thirds of patients continued treatment beyond 1 year, suggesting reasonable effectiveness.
LC-MS/MS-Based Quantification of 9 Antiepileptic Drugs From a Dried Sample Spot Device
Authors: D'Urso Annachiara , Cangemi Giuliana , Barco Sebastiano , Striano Pasquale , D'Avolio Antonio , de Grazia Ugo
Published: January 2019

Background:

Therapeutic drug monitoring (TDM) of antiepileptic drugs (AEDs) is commonly performed on plasma or serum. The use of dried plasma spots (DPSs) could represent a useful tool to facilitate sample shipment to reference laboratories. In this article, the authors describe the application of a commercially available UHPLC-MS/MS method for the determination of 9 commonly prescribed AEDs (levetiracetam, lacosamide, topiramate, ethosuximide, lamotrigine, rufinamide, zonisamide, primidone, and oxcarbazepine and its active metabolite 10-OH-monohydroxycarbazepine) to DPS collected on dried sample spot devices (DSSDs).

Method:

Fifty microliters of plasma were spotted on DSSD. After being air-dried at room temperature, they were extracted using an organic extraction solution containing the appropriate deuterated internal standards. The chromatographic separation was performed on a UHPLC reversed-phase C-18 column, and the analytes were quantified using a triple quadrupole mass spectrometer (LC-MS/MS).

Results:

The assay was linear over the concentration ranges tested with a total runtime of 10.3 minutes. Recovery ranged from 93.7% to 106.8%. Intraday and interday precision for all quality control levels, including lower limit of quantification, ranged from 2.1% to 18.4% and 2.1% to 13.2%. Intraday and interday accuracy biases ranged from −11.7% to 14.3% and −9.2% to 8.0%. The absence of matrix effects was also tested and confirmed. Real samples derived from patients under therapy were also analyzed, and the comparison of results obtained from DSSD with those obtained from plasma showed that the 2 matrices were interchangeable. Stability tests performed on both quality controls, and real samples demonstrated that DSSDs can be easily stored and shipped at room temperature for 15 days.

Conclusions:

The application of the LC-MS/MS method allowed the authors to obtain a very specific, sensitive, and rapid (total runtime = 10.3 minutes) quantification of 9 AEDs starting from very low volumes of plasma samples. The main advantage of DPS over wet samples is room temperature storage and shipment, which lowers shipment costs and makes it suitable for routine TDM. Moreover, in comparison with other alternative matrices, DPS allows for the use of the same therapeutic ranges on which routine TDM is based. DPS on DSSD can thus be considered as a useful and cheap tool for the broader application of TDM.
Myeloid‐Derived Suppressor Cells in Hematologic Diseases: Promising Biomarkers and Treatment Targets
Authors: Bizymi Nikoleta , Bjelica Sunčica , Kittang Astrid Olsnes , Mojsilovic Slavko , Velegraki Maria , Pontikoglou Charalampos , Roussel Mikael , Ersvær Elisabeth , Santibañez Juan Francisco , Lipoldová Marie , Papadaki Helen A.
Published: January 2019

Myeloid‐derived suppressor cells (MDSC) are a heterogeneous group of immature myeloid cells that exist at very low numbers in healthy subjects but can expand significantly in malignant, infectious, and chronic inflammatory diseases. These cells are characterized as early‐MDSCs, monocytic‐MDSCs, and polymorphonuclear‐MDSCs and can be studied on the basis of their immunophenotypic characteristics and their functional properties to suppress T‐cell activation and proliferation. MDSCs have emerged as important contributors to tumor expansion and chronic inflammation progression by inducing immunosuppressive mechanisms, angiogenesis and drug resistance. Most experimental and clinical studies concerning MDSCs have been mainly focused on solid tumors. In recent years, however, the implication of MDSCs in the immune dysregulation associated with hematologic malignancies, immune‐mediated cytopenias and allogeneic hemopoietic stem cell transplantation has been documented and the potential role of these cells as biomarkers and therapeutic targets has started to attract a particular interest in hematology. The elucidation of the molecular and signaling pathways associated with the generation, expansion and function of MDSCs in malignant and immune‐mediated hematologic diseases and the clarification of mechanisms related to the circulation and the crosstalk of MDSCs with malignant cells and other components of the immune system are anticipated to lead to novel therapeutic strategies. This review summarizes all available evidence on the implication of MDSCs in hematologic diseases highlighting the challenges and perspectives arising from this novel field of research.
Surgical Corneal Anatomy in Deep Anterior Lamellar Keratoplasty: Suggestion of New Acronyms
Authors: Sarnicola Enrica , Sarnicola Caterina , Cheung Albert Y. , Holland Edward J. , Sarnicola Vincenzo
Published: January 2019

Deep anterior lamellar keratoplasty (DALK) is the ideal surgery for corneal stromal diseases with a healthy endothelium. This technique offers substantial advantages compared with penetrating keratoplasty, primarily the avoidance of endothelial rejection and longer graft survival. Several DALK techniques have been described and classified into 2 categories, descemetic DALK (dDALK) and predescemetic DALK (pdDALK) depending on whether Descemet membrane-endothelium was thought to be exposed or minimal residual stroma was left behind. This classification was crucial to identify the conditions to achieve good visual outcomes with pdDALK techniques. The recent description of Dua's layer, also known as the pre-Descemet layer, has demonstrated that a very thin layer of stroma exists in some instances where Descemet membrane was thought to be completely exposed. This concept has generated a discrepancy between the previous and current applications of the terms “dDALK” and “pdDALK.” We offer a summary of the published literature and a proposal for a new and more appropriate DALK nomenclature. We suggest adding the terms subtotal anterior lamellar keratoplasty (STALK) and total anterior lamellar keratoplasty (TALK).
Evaluation of the Ocular Surface in Different Contact Lens Replacement Schedules
Authors: Muhafiz Ersin , Bayhan Hasan Ali , Şahin Sevinç , Göçmen Ayşe Yeşim , Aslan Bayhan Seray , Gürdal Canan
Published: January 2019

Purpose:

To evaluate the effects of different contact lens (CL) replacement schedules and different CL materials on the ocular surface and tear function.

Methods:

Daily disposable hydrogel CLs were given to group 1 (n = 22), daily disposable silicone hydrogel CLs were given to group 2 (n = 25), and reusable silicone hydrogel CLs were given to group 3 (n = 24). Tear function tests and inflammatory cytokine [interleukin (IL)-6, IL-8, IL-17A, and matrix metalloproteinase (MMP)-9] levels were evaluated before and at 1 and 3 months after CL usage. Impression cytology was evaluated before and at 3 months after CL usage.

Results:

At the first and third months of CL usage, a statistically significant difference was determined between the groups in the levels of IL-6, IL-8, and IL-17A in tears, with the lowest levels in group 1 and the highest levels in group 3 (all P < 0.05). At the third month of CL usage, the levels of these cytokines (in picograms/milliliter) were 6.06 ± 0.83, 78.18 ± 12.42, 61.69 ± 13.95, and 37.71 ± 5.95 in group 1 and 8.04 ± 0.89, 107.34 ± 14.40, 68.63 ± 13.72, and 46.26 ± 6.50 in group 3, respectively. A statistically significant decrease was determined over time in the Schirmer test in group 1, in only the tear breakup time in group 2, and in the tear breakup time and Schirmer test in group 3 (all P < 0.05). A statistically significant increase was determined over time in the levels of IL-6, IL-8, IL-17A, and MMP-9 in all groups. In the third month, a significant progression was observed in the Nelson grade (P < 0.05) in all groups.

Conclusions:

The wear of daily disposable CLs can be considered to cause less damage to the ocular surface and less increase in proinflammatory cytokine levels.
Measurement of Corneal Biomechanical Properties in Diabetes Mellitus Using the Ocular Response Analyzer and the Corvis ST
Authors: Ramm Lisa , Herber Robert , Spoerl Eberhard , Pillunat Lutz E. , Terai Naim
Published: January 2019

Purpose:

Hyperglycemia in diabetes mellitus (DM) might induce changes in corneal biomechanics. Therefore, biomechanical properties of the cornea were measured using the ocular response analyzer and the Corvis ST.

Methods:

In the study, 35 eyes of 35 diabetic patients were included. After an ophthalmological examination, measurements with the ocular response analyzer and the Corvis ST were taken. Additionally, biometry and corneal topography were performed and HbA1c values were collected. Results were compared to an age-, pachymetry- and intraocular pressure-matched group of 35 healthy subjects.

Results:

Mean age (67.6 ± 10.3; 64.1 ± 8.3 years), intraocular pressure (13.4 ± 2.9; 12.8 ± 2.8 mm Hg), and central corneal thickness (556.4 ± 31.7; 548.6 ± 32.9 μm) were not significantly different between the groups (P > 0.05). In DM, the corneal hysteresis (CH) and the corneal resistance factor (CRF) were increased (CH: 10.8 ± 2 vs. 9.4 ± 1.6, P = 0.002; CRF: 10.6 ± 2.1 vs. 9.6 ± 1.5, P = 0.022). Also, most dynamic corneal response parameters showed significant differences. Beside others, A1 and A2 deflection amplitudes were increased (P < 0.001) and highest concavity and A2 time were extended (P < 0.001 and 0.007) in DM. According to current HbA1c value, DM was classified as controlled (≤7%) and poorly controlled (>7%) and significant biomechanical differences were measured between both groups.

Conclusions:

In DM, significant changes in corneal biomechanical properties were detectable. In patients, CH and CRF were increased and most dynamic corneal response parameters were different compared to healthy subjects.
Lucia and Beyond: Development of an Affordable Keratoprosthesis
Authors: Bakshi Shaunak K. , Paschalis Eleftherios I. , Graney John , Chodosh James
Published: January 2019

Purpose:

Severe corneal disease contributes significantly to the global burden of blindness. Corneal allograft surgery remains the most commonly used treatment, but does not succeed long term in every patient, and the odds of success fall with each repeated graft. The Boston keratoprosthesis type I has emerged as an alternative to repeat corneal allograft. However, cost limits its use in resource-poor settings, where most corneal blind individuals reside.

Methods:

All aspects of the Boston keratoprosthesis design process were examined to determine areas of potential modification and simplification, with dual goals to reduce cost and improve the cosmetic appearance of the device in situ.

Results:

Minor modifications in component design simplified keratoprosthesis manufacturing. Proportional machinist time could be further reduced by adopting a single axial length for aphakic eyes, and a single back plate diameter. The cosmetic appearance was improved by changing the shape of the back plate holes from round to radial, with a petaloid appearance, and by anodization of back plate titanium to impute a more natural color.

Conclusions:

We have developed a modified Boston keratoprosthesis type I, which we call the “Lucia.” The Lucia retains the 2 piece design and ease of assembly of the predicate device, but would allow for manufacturing at a reduced cost. Its appearance should prove more acceptable to implanted patients. Successful keratoprosthesis outcomes require daily medications for the life of the patient and rigorous, frequent, postoperative care. Effective implementation of the device in resource-poor settings will require further innovations in eye care delivery.
Deep Trephination Allows High Rates of Successful Pneumatic Dissection for DALK Independent of Surgical Experience
Authors: Myerscough James , Bovone Cristina , Scorcia Vincenzo , Ricci-Filipovic Benedetta , Leon Pia , Mimouni Michael , Nahum Yoav , Busin Massimo
Published: January 2019

Purpose:

To evaluate the relationship between surgical experience and the success rate of pneumatic dissection for deep anterior lamellar keratoplasty (DALK) using deep trephination.

Methods:

A noncomparative case series evaluating the first 10 consecutive keratoconic eyes without deep stromal scarring, operated by 8 surgeons of 3 different experience levels, was conducted; there were a total of 80 patients. Standardized DALK was performed, including deep trephination 450 to 550 μm in depth and 9 mm in diameter, pneumatic dissection, removal of the stroma, and transplantation of a 9-mm partial-thickness anterior lamellar graft. The success rate of pneumatic dissection correlated with surgical experience.

Results:

Pneumatic dissection succeeded in 7, 7, 8, and 9 cases of 10 cases in the first group of 4 inexperienced surgeons (under 10 previous keratoplasties of any kind); in 9 and 10 of 10 cases in the second group of 2 relatively experienced surgeons (under 100 keratoplasties); and in 10 and 8 of 10 cases in the third group of 2 very experienced surgeons (more than 1000 previous keratoplasties). No difference between the groups was found to be statistically significant with the χ2 test (P > 0.05).

Conclusions:

The standardized DALK technique using a deep trephination allows high success rates of pneumatic dissection even for surgeons inexperienced in keratoplasty.
Screening Glaucoma With Red-free Fundus Photography Using Deep Learning Classifier and Polar Transformation
Authors: Lee Jinho , Kim Youngwoo , Kim Jong Hyo , Park Ki Ho
Published: January 2019

Précis:

The novel proposed algorithm using deep learning classifier and polar transformation technique can be an economical as well as an effective tool for early detection of glaucomatous RNFL defect.

Purpose:

The main purpose of this study was to develop novel software to determine whether there is a retinal nerve fiber layer (RNFL) defect in a given fundus image using deep learning classifier and, if there is, where it presents.

Materials and Methods:

In the deep learning classifier, the bottleneck features were extracted, followed by application of the softmax classifier, which outputted the glaucoma probability. For localization of RNFL defect, an image processing algorithm was implemented as follows: (1) the given image was normalized to enhance the contrast; (2) the region of interest (ROI) was set as the circumferential area surrounding the optic disc (internal diameter: 2 disc diameters, external diameter: 3 disc diameter), and converted to a polar image; (3) blood vessels were removed and the average curvatures were calculated. If the local maximum curvature was greater than the cut-off value, the sector was considered to be an RNFL defect.

The images of 100 normal healthy controls and 100 open-angle glaucoma patients were enrolled. Maximum curvatures and area under receiver operating characteristic curve were compared to determine the diagnostic validity.

Results:

There were no significant differences in age or sex (P=0.275, P=0.479, respectively) between the 2 groups. In the glaucoma group, the mean deviation was −4.9±5.4 dB. There was a significant difference of maximum curvature (14.37±5.13 in control group, 20.67±10.56 in glaucoma group, P<0.001). Area under receiver operating characteristic curve was 0.939 in deep learning classifier and 0.711 in maximum curvature.

Conclusions:

The proposed software can be an effective tool for automated detection of RNFL defect.
Meta-analysis of the psychometric properties of the Pain Catastrophizing Scale and associations with participant characteristics
Authors: Wheeler Claire H.B. , Williams Amanda C de C. , Morley Stephen J.
Published: January 2019

The aims of this study were to review the psychometric properties of the widely used Pain Catastrophizing Scale (PCS) using meta-analytic methods and to investigate the relationship between PCS scores and participant characteristics. A systematic search from 1995 found 229 experimental, quasi-experimental, and correlational studies that report PCS scores. Multivariate regression explored variables related to pain catastrophizing and participant demographics. Across studies, good internal reliability (α = 0.92, 95% confidence interval 0.91-0.93) and test–retest reliability scores (Spearman ρ = 0.88, 95% confidence interval 0.83-0.93) were found for PCS total scores but not for subscales. Pain Catastrophizing Scale scores were unrelated to age or sex, but strongly related to participants' pain type, highest in those with generalized pain. Language of the PCS also affected PCS scores, with further research necessary to determine linguistic, cultural, or methodological (eg, sampling strategy) influences. Study type influenced PCS scores with nonrandomized controlled trials reporting higher PCS scores than other study types, but results were confounded with pain diagnosis, as controlled trials were more likely than quasi-experimental studies to recruit clinical samples. The meta-analytic results provide insights into demographic influences on pain catastrophizing scores and highlight areas for further research. The advantages of systematic review and meta-analytic methods to achieve greater understanding and precision of psychometric properties—in this case, of the PCS—are applicable to other widely used outcome tools.
Peripheral oxytocin restores light touch and nociceptor sensory afferents towards normal after nerve injury
Authors: Boada M. Danilo , Gutierrez Silvia , Eisenach James C.
Published: January 2019

Oxytocin reduces primary sensory afferent excitability and produces analgesia in part through a peripheral mechanism, yet its actions on physiologically characterized, mechanically sensitive afferents in normal and neuropathic conditions are unknown. We recorded intracellularly from L4 dorsal root ganglion neurons characterized as low-threshold mechanoreceptors (LTMRs) or high-threshold mechanoreceptors (HTMRs) in female rats 1 week after L5 partial spinal nerve injury or sham control (n = 24 rats/group) before, during, and after ganglionic perfusion with oxytocin, 1 nM. Nerve injury desensitized and hyperpolarized LTMRs (membrane potential [Em] was −63 ± 1.8 mV in sham vs −76 ± 1.4 mV in nerve injury; P < 0.001), and sensitized HTMRs without affecting Em. In nerve-injured rats, oxytocin depolarized LTMRs towards normal (Em = −69 ± 1.9 mV) and, in 6 of 21 neurons, resulted in spontaneous action potentials. By contrast, oxytocin hyperpolarized HTMRs (Em = −68 ± 2.7 mV before vs −80 ± 3.2 mV during oxytocin exposure; P < 0.01). These effects were reversed after removal of oxytocin, and oxytocin had minimal effects in neurons from sham surgery animals. Sensory afferent neurons immunopositive for the vasopressin 1a receptor were larger (34 ± 6.3 μm, range 16-57 μm) than immunonegative neurons (26 ± 3.4 μm, range 15-43 μm; P < 0.005). These data replicate findings that neuropathic injury desensitizes LTMRs while sensitizing HTMRs and show rapid and divergent oxytocin effects on these afferent subtypes towards normal, potentially rebalancing input to the central nervous system. Vasopressin 1a receptors are present on medium to large diameter afferent neurons and could represent oxytocin's target.
Comfort or Care: Why Do We Have to Choose? Implementing a Geriatric Trauma Palliative Care Program
Authors: Brown Kristie L. , Ashcraft Alyce S.
Published: January 2019

The geriatric (≥65 years of age) population is one of the fastest growing age groups in the United States. As this number increases, so does the number of geriatric trauma patients. Because this group has higher mortality rates and requires more resources, a Geriatric Trauma Palliative Care Program was created at a Level 1 Trauma Center in Dallas, TX, to provide concurrent lifesaving therapies and primary palliative care to older adults. The trauma program implemented the American College of Surgeons (ACS) Trauma Quality Improvement Program Palliative Care Best Practices Guidelines (ACS, 2017) to better care for acute traumatic injuries as well as the specific spiritual, emotional, and psychiatric needs of the geriatric trauma palliative care patient and family. Using the guidelines, the team performed a gap analysis, carried out program development, created a palliative care pathway to guide our evidence-based practice implementation, and performed retrospective chart reviews for 3-month pre- and postimplementation analysis. Using Person's χ2 test and Fisher's exact test, our initial evaluation of the program showed statistically significant (p < .001) improvements in the measures related to the implementation of primary palliative care, pain and symptom management, and end-of-life care. The guidelines gave the team a consistent framework for implementing the basic competencies required to deliver primary palliative care, pain and symptom management, and end-of-life care to trauma patients.
Three things every nurse practitioner can do to integrate genetics into practice
Authors: Reed E. Kate , Ingram Therese , Edelman Emily A.
Published: January 2019

Genetic and genomic information has the potential to improve patient care and outcomes by improving clinicians' ability to identify patients at increased risk of disease and, in some cases, personalize treatment and management. However, many clinicians report that they feel unprepared and lack confidence in talking about genomics with their patients. By focusing on family history information and knowing when and how to refer to genetic experts, clinicians can take meaningful steps to improve integration of genetics into patient care.
Observed Colposcopy Practice in US Community-Based Clinics: The Retrospective Control Arm of the IMPROVE-COLPO Study
Authors: Huh Warner K. , Papagiannakis Emmanouil , Gold Michael A.
Published: January 2019

Objective

The aim of the study was to characterize colposcopy practice and management of women with cervical abnormalities in US community-based clinics.

Materials and Methods

IMPROVE-COLPO was a 2-arm study of colposcopy patients with an abnormal screening result. The prospective arm recruited women to undergo examination with a commercial digital colposcope. The retrospective-control arm collected data (chart review) from previous colposcopies performed using standard equipment and methods. From the retrospective arm, we analyzed referral trends, colposcopy and biopsy practice, and management patterns.

Results

We collected data of 3,602 eligible women (median age = 34 years) that had been examined from 2012 to 2017 by 154 colposcopists at 44 clinics across 12 states. Most patients were premenopausal (87.9%), privately insured (88.2%), and had a low-grade (low-grade squamous intraepithelial lesion/atypical squamous cells of undetermined significance/human papillomavirus positive) indication (87.2%). Most colposcopists performed less than 3 colposcopies monthly and their biopsy rate was 1.47 biopsies/patient for high-grade referrals and 0.97 for low-grade referrals (p < .001). Random biopsy was rare (0.4% of biopsies). Most women (74.9%) underwent endocervical sampling, including 62.5% of women aged 21 to 24 years. Colposcopic impression was frequently not reported (58.8%), and its sensitivity to predict histology-confirmed cervical intraepithelial neoplasia (CIN) 2+ as “high-grade” was 56.5% for high-grade referrals and 23.2% for low-grade referrals. Excisions often (44.5%) returned <CIN 2, including patients aged 21–40 years (37.4%).

Conclusions

In this analysis, most colposcopists performed few colposcopies and took less than 2 biopsies per patient. Colposcopic impression had a poor sensitivity to predict histology-confirmed CIN 2+. Although recent research indicates that taking multiple biopsies improves sensitivity and detection of CIN 2+, this is not being practiced in the US.
Increased Risk of Benign Paroxysmal Positional Vertigo in Patients With a History of Sudden Sensory Neural Hearing Loss: A Longitudinal Follow-up Study Using a National Sample Cohort
Authors: Lee Sang-Yeon , Kong Il Gyu , Oh Dong Jun , Choi Hyo Geun
Published: January 2019

Objective:

To evaluate the association between benign paroxysmal positional vertigo (BPPV) and sudden sensorineural hearing loss (SSNHL) using a national sample cohort from Korea.

Methods:

Data from the years 2002 through 2013 were collected for individuals aged more than or equal to 20 years from the Korean National Health Insurance Service-National Sample Cohort. SSNHL was classified based on the International Classification of Disease-10 (ICD-10) code H91.2. We included only participants who received an audiometry examination and steroid treatment. After exclusion of participants diagnosed with Menière's disease (H81.0), we extracted data for SSNHL patients (n = 4,109) and 1:4-matched controls (n = 16,436). Matching was performed based on age, sex, income, region of residence, and medical history. BPPV was diagnosed with the ICD-10 code H81.1. Among them, we only included the participants who visit more than or equal to two times for BPPV that does not mean recurrent BPPV. The crude and adjusted hazard ratios (HRs) were calculated using Cox proportional hazard models, and the 95% confidence intervals (CIs) were determined. Subgroup analyses were also performed according to age and sex.

Results:

The rate of BPPV in the SSNHL group (3.8% [157/4,109]) was higher than that in the control group (1.9% [220/16,436], p < 0.001). The adjusted HR of BPPV was 2.90 (95% CI = 2.36–3.56, p < 0.05). After experiencing SSNHL, the rate of BPPV in the SSNHL group was significantly higher for patients with two, three to four, and more than or equal to five visits for BPPV. In the subgroup analyses, a significant association between SSNHL and BPPV was observed regardless of age and sex.

Conclusion:

The risk of BPPV is greater in patients with SSNHL.
Long-term Vertigo Control and Vestibular Function After Low-dose On-demand Transtympanic Gentamicin for Refractory Menière's Disease
Authors: Nicolas Sarah , Kmeid Michel , Mansour Charles , Fraysse Bernard , Deguine Olivier , Marx Mathieu , Fraysse Marie-José Esteve
Published: January 2019

Objective:

To describe the long-term clinical vertigo control along with measured lateral canal vestibular function in patients with unilateral refractory Menière's disease (MD) treated with gentamicin transtympanic injections (TTI).

Study Design:

Retrospective analytic study.

Setting:

Tertiary referral center.

Patients:

Thirty-eight patients treated by TTI for medically refractory unilateral MD, defined by the 1995 AAO-HNS criteria, between May 2006 and December 2012.

Intervention(s):

One-year course of treatment with gentamicin TTI following a low dose on-demand protocol. TTI were repeated in new courses of treatment when MD recurrence occurred.

Main Outcome Measure(s):

AAO-HNS class of control, caloric tests (CalT), recurrence rate.

Results:

After an average clinical follow-up of 71 months, all patients entered a class of control A (78%) or B (22%), with an average of 2.3 TTI received. The mean maximal obtained deficit was 88.5%, and the mean long-term deficit was 85.5%. Ten (26%) patients had disease recurrence requiring a new course of treatment. A value of the first CalT in the 3 months following the first TTI strictly higher than 78% was significantly associated with disease control and the absence of symptom recurrence (p≤0.01). In the “recurrence” group, four patients had a significantly lower mean value of all CalT performed after the first TTI when compared with other patients (p≤0.001), indicating gentamicin resistance

Conclusion:

Achieving a sustainable vestibular deficit on caloric testing is key for MD symptom control after gentamicin TTI. Gentamicin resistance must be diagnosed early to adapt therapeutic strategies.
Increased Stroke Risk in Children and Young Adults on Extracorporeal Life Support with Carotid Cannulation
Authors: Di Gennaro Jane L. , Chan Titus , Farris Reid W. D. , Weiss Noel S. , McMullan David M.
Published: January 2019

Patients on extracorporeal life support (ECLS) are at risk for central nervous system (CNS) injury. One potentially modifiable risk factor is site of arterial cannulation in venoarterial (VA) ECLS, as in most cases one can choose the femoral or carotid artery. There is acute alteration in cerebral blood flow with carotid cannulation, potentially increasing the risk of stroke. Children may have lower risk of stroke with carotid cannulation compared with adults because of impaired cerebral circulation with aging. Our objective was to evaluate risk of stroke with carotid versus femoral cannulation and determine whether this differs between children and adults. Using the Extracorporeal Life Support Organization Registry, we evaluated patients 6–40 years old on VA ECLS during 2000–2012. We used multivariable logistic regression to estimate the relationship between location of arterial cannulation and stroke. We included an interaction term to assess whether this was modified by age. One thousand five hundred eighteen patients were included in the analysis. There was a fourfold increased odds of CNS infarct (odds ratio [OR]: 4.03; 95% CI: 2.17–7.46) with carotid cannulation. This estimate was not modified by age. There is increased likelihood of stroke with carotid cannulation in patients 6–40 years old in comparison with femoral cannulation during VA ECLS.
Efficacy and Safety of Endoscopic Ultrasound-guided Choledochoduodenostomy
Authors: Mohan Babu P. , Shakhatreh Mohammed , Garg Rajat , Ponnada Suresh , Navaneethan Udayakumar , Adler Douglas G.
Published: January 2019

Introduction:

Endoscopic retrograde cholangiopancreatography is the preferred method in biliary drainage. Endoscopic ultrasound (EUS) guidance has shown tremendous success in situations where endoscopic retrograde cholangiopancreatography fails or is contraindicated. EUS-guided choledochoduodenostomy (CDD) in particular is gathering a lot of interest due to its ease, and high rates of success. The reported adverse events with this procedure have been inconsistent among studies.

Methods:

We conducted a search of multiple electronic databases and conference proceedings from inception through June 2018. The primary outcome was to estimate the risk of adverse events, and the commonly reported subtype of adverse events in EUS-CDD. The secondary outcome was to estimate the pooled technical and clinical success rates.

Results:

Thirteen studies including 572 patients underwent biliary drainage with EUS-CDD. The pooled rate of all adverse events was 0.136 (95% confidence interval, 0.097-0.188; P=0.01) with moderate heterogeneity (I
2=56.9), and pooled rate of cholangitis was 4.2%, bleeding was 4.1%, bile leak was 3.7%, and perforation was 2.9%. On subgroup analysis, the pooled rate of adverse events with the use of lumen-apposing metal stent was 9.3% (95% confidence interval, 4.8-17.3).

Conclusions:

On the basis of our analysis EUS-CDD has an adverse event risk of 13.4%, which is lowest reported in literature so far. Reported adverse rates appeared to be lower with the use of lumen-apposing metal stent, except for perforation.
18F-FDG PET/CT for staging and response assessment of primary parotid MALT lymphoma with multiple sites involvement
Authors: Ren Yixuan , Huang Lele , Han Yuping , Cui Zhencun , Li Jicheng , Dong Chi , Liu Jiangyan
Published: January 2019

Rationale:

Mucosa-associated lymphoid tissue (MALT) lymphoma is an extranodal low-grade B cell lymphoma that generally exhibits an indolent clinical course. Currently, the application of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in MALT lymphoma is still controversial. Herein, we reported a case of using 18F-FDG PET/CT for staging and response assessment of primary parotid MALT lymphoma with multiple sites involvement. As far as we know, there are no similar case reports have been published before.

Patient concerns:

A 71-year-old woman, who received mass resection twice during the past 2 years due to the repeatedly relapse of facial painless masses and diagnosed as reactive lymphoid hyperplasia by pathologic tests. However, the pathological diagnosis was then changed to primary parotid MALT lymphoma after left parotidectomy operation because of a new mass found in her left parotid. Four months later, the right eyelid of the patient swelled with a blurred vision. Then, 18F-FDG PET/CT scan was performed for staging, and the imaging results showed an abnormal increase of 18F-FDG uptake in multiple sites including bilateral ocular adnexal, lungs, pleura, occipital subcutaneous tissue, left kidney, and lymph nodes.

Diagnoses:

The patient was diagnosed as primary parotid MALT lymphoma with Ann Arbor stage of IVA based on the 18F-FDG PET/CT findings.

Interventions:

The patient received 4 cycles of chemotherapy, followed by a partial metabolic remission (PMR), which was determined by interim 18F-FDG PET/CT, and finally additional 2 cycles of chemotherapy.

Outcomes:

The follow-up study illustrated that the patient had been alive and doing well at 12 months after chemotherapy.

Lessons:

Although MALT lymphoma normally localizes in the primary organs, the involvement of multiple organs and lymph nodes is possible. The use of PET/CT demonstrated significant clinical values in the accurate staging and response assessment of 18F-FDG-avid MALT lymphoma. It is potentially useful for indicating the progress and transformation of MALT lymphoma, and guidance in localization of pathological biopsy. It is also helpful for clinicians to choose reasonable treatment strategy and improve the prognosis of patients.