bluuebunny/crossref_metadata_2025 huggingface dataset:
NORMAL ELECTROOCULOGRAPHY IN BEST DISEASE AND AUTOSOMAL RECESSIVE BESTROPHINOPATHY
Authors: Khan Kamron N. , Islam Farrah , Holder Graham E. , Robson Anthony , Webster Andrew R. , Moore Anthony T. , Michaelides Michel
Published: February 2017

Purpose:

To evaluate the electrooculogram (EOG) in a large series of patients with Best disease and autosomal recessive bestrophinopathy.

Methods:

A retrospective review of consecutive cases at Moorfields Eye Hospital, London, United Kingdom. Patients with Best disease or autosomal recessive bestrophinopathy who, after electrophysiologic testing, had a normal or atypical EOG light rise were identified. Main outcome measure was EOG amplitude, clinical phenotype and genotype.

Results:

One hundred thirteen patients were identified with likely disease-causing sequence variants in BEST1 (99 Best disease and 14 autosomal recessive bestrophinopathy). Electrooculograms had been performed in 75 patients. Twenty patients (27%) had no detectable light rise (Arden ratio of 100%) and 49 (65%) had Arden ratios of between 100% to 165%. Six patients (8%) were found to have an EOG light rise of >165%. No cases demonstrated significant interocular asymmetry in EOG amplitude.

Conclusion:

The current work provides significant clinical evidence that the EOG phenotype in Best disease and autosomal recessive bestrophinopathy is more variable than currently appreciated. As a normal EOG may occur in the presence of a classical fundus appearance, the consequences of BEST1 mutation may be independently expressed, possibly mediated through differential effects on intracellular calcium homeostasis.
THICKNESS OF THE MACULA, RETINAL NERVE FIBER LAYER, AND GANGLION CELL–INNER PLEXIFORM LAYER IN THE AGE-RELATED MACULAR DEGENERATION
Authors: Shin Il-Hwan , Lee Woo-Hyuk , Lee Jong-Joo , Jo Young-Joon , Kim Jung-Yeul
Published: February 2017

Purpose:

To determine the repeatability of measuring the thickness of the central macula, retinal nerve fiber layer, and ganglion cell–inner plexiform layer (GC-IPL) using spectral domain optical coherence tomography (Cirrus HD-OCT) in eyes with age-related macular degeneration.

Methods:

One hundred and thirty-four eyes were included. The measurement repeatability was assessed by an experienced examiner who performed two consecutive measurements using a 512 × 128 macular cube scan and a 200 × 200 optic disk cube scan. To assess changes in macular morphology in patients with age-related macular degeneration, the patients were divided into the following three groups according to the central macular thickness (CMT): A group, CMT < 200 μm; B group, 200 μm ≤ CMT < 300 μm; and C group, CMT > 300 μm.

Results:

Measurement repeatability was assessed using test–retest variability, a coefficient of variation, and an intraclass correlation coefficient. The mean measurement repeatability for the central macular, retinal nerve fiber layer, and GC-IPL thickness was high in the B group. The mean measurement repeatability for both the central macula and retinal nerve fiber layer thickness was high in the A and C groups, but was lower for the GC-IPL thickness. The measurement repeatability for GC-IPL thickness was high in the B group, but low in the A group and in the C group.

Conclusion:

The automated measurement repeatability for GC-IPL thickness was significantly lower in patients with age-related macular degeneration with out of normal CMT range. The effect of changes in macular morphology should be considered when analyzing GC-IPL thicknesses in a variety of ocular diseases.
QUANTIFICATION OF INTRARETINAL HARD EXUDATES IN EYES WITH DIABETIC RETINOPATHY BY OPTICAL COHERENCE TOMOGRAPHY
Authors: Srinivas Sowmya , Nittala Muneeswar G. , Hariri Amirhossein , Pfau Maximilian , Gasperini Julie , Ip Michael , Sadda SriniVas R.
Published: February 2017

Purpose:

To evaluate the reproducibility of intraretinal hard exudate (HE) quantification from spectral domain optical coherence tomography (SD-OCT) images of eyes with diabetic retinopathy (DR).

Methods:

Cases with diabetic macular edema were enrolled. The area of HE obtained by B-scan segmentation was compared with the area obtained by en face segmentation.

Results:

The mean ± SD for the HE area was 1.78 ± 1.37 mm2 with B-scan segmentation and 0.72 ± 0.82 mm2 with the automated en face analysis tool; the absolute difference was 1.01 ± 0.64 mm2. There was excellent correlation in total HE area between the two methods (r = 0.95, P < 0.0001). The HE volume was 0.06 ± 0.07 mm2. The correlation between HE volume and en face HE area was high (r = 0.95, P < 0.001). Intergrader reproducibility yielded excellent agreement with an intraclass correlation coefficient value of 0.99 (95% CI 0.994–0.999) for the en face approach and 0.99 (95% CI 0.977–0.997) for manual segmentation.

Conclusion:

Quantification of HE in eyes with diabetic retinopathy can be performed reliably using en face segmentation and, though the en face results are consistently lower, correlates well with HE measurements obtained by exhaustive segmentation of all B-scans in dense volume optical coherence tomography (OCT).
EFFECT OF AN INTRAVITREAL DEXAMETHASONE IMPLANT ON DIABETIC MACULAR EDEMA AFTER CATARACT SURGERY
Authors: Calvo Pilar , Ferreras Antonio , Al Adel Fadwa , Dangboon Wantanee , Brent Michael H.
Published: February 2017

Purpose:

To analyze the effects of a dexamethasone intravitreal implant (DEX; Ozurdex 700 μg; Allergan) administered immediately after cataract surgery in diabetic patients.

Methods:

This prospective, single-arm, open label study (NCT01748487 at ClinicalTrials.gov) involved Type 2 diabetic patients with at least mild diabetic retinopathy (DR) who underwent cataract surgery and DEX insertion after phacoemulsification, and intraocular lens implantation were enrolled. Best-corrected visual acuity and central retinal thickness (CRT) measured by spectral-domain optical coherence tomography were recorded at 1 week preoperatively, and 1 week, 1 month, and 3 months after surgery. Adverse events were also recorded.

Results:

Twenty-four eyes of 24 patients (17 [70.8%] men; mean age 63.7 ± 8.7 years) with mild nonproliferative DR (41.7%), moderate nonproliferative DR (33.3%), severe nonproliferative DR (16.7%), or treated proliferative DR (8.3%) were selected. After DEX treatment, mean CRT changed from 241.1 μm (95% confidence interval, 227.5–254.6 μm) at baseline to 236.9 μm (95% confidence interval, 223.9–249.9 μm) at 1 week (P = 0.09), 238.9 μm (95% confidence interval, 225.5–252.3 μm) at 1 month (P = 0.44), and 248 μm (95% confidence interval, 232.4–260.8 μm) at 3 months (P = 0.15). No eyes showed a postoperative increase >50 μm in the CRT at any visit. A 10% increase in CRT was found in 8.3% of eyes. Mean best-corrected visual acuity significantly improved from 0.37 (20/50) at baseline to 0.19 (20/30) at 1 week, 0.12 (20/25) at 1 month, and 0.12 (20/25) at 3 months (P < 0.001 for each comparison). Mean intraocular pressure before surgery was 13.8 mmHg, and none of the patients developed an intraocular pressure ≥22 mmHg at any visit. None of the patients developed any serious adverse events during the follow-up.

Conclusion:

These short-term results suggest that a single DEX injection intraoperatively after phacoemulsification could avoid an increase in CRT after cataract surgery in diabetic patients.
ANGIOPOIETIN-LIKE 4 CORRELATES WITH RESPONSE TO INTRAVITREAL RANIBIZUMAB INJECTIONS IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION
Authors: Kim Jong Ho , Shin Jae Pil , Kim In Taek , Park Dong Ho
Published: February 2017

Purpose:

To investigate whether the aqueous angiopoietin-like 4 (ANGPTL4) level correlates with clinical features in neovascular age-related macular degeneration (AMD).

Methods:

The control and study groups consisted of all consecutive patients who received senile cataract surgery or intravitreal ranibizumab injection for treatment-naïve neovascular AMD, respectively. The AMD group received 3 monthly ranibizumab injections followed by monthly pro re nata for at least 12 months. Aqueous ANGPTL4 and vascular endothelial growth factor (VEGF) were measured at baseline and 4 weeks after the first injection. In the AMD group, best-corrected visual acuity, lesion area by fluorescein angiography, and central subfield thickness were measured at baseline and at 12 months.

Results:

The AMD group (30 eyes) had higher baseline aqueous ANGPTL4 and VEGF levels than those of the control group (32 eyes) (both P < 0.001). Four weeks after the first injection, VEGF in the patients with AMD had dropped significantly (P < 0.001). Baseline ANGPTL4 correlated with the lesion area at baseline and at 12 months (P < 0.05, respectively), and also correlated with the frequency of anti-VEGF injections during 12 months (P = 0.008).

Conclusion:

Aqueous ANGPTL4 levels correlated with the lesion area and anti-VEGF treatment frequency. Angiopoietin-like 4 may be a potential diagnostic and/or therapeutic biomarker in the neovascular AMD.
ANGIOGRAPHIC SUBTYPES OF POLYPOIDAL CHOROIDAL VASCULOPATHY IN TAIWAN
Authors: Yeung Ling , Kuo Chien-Neng , Chao An-Ning , Chen Kuan-Jen , Wu Wei-Chi , Lai Chien-Hsiung , Wang Nan-Kai , Hwang Yih-Shiou , Chen Ching-Lung , Lai Chi-Chun
Published: February 2017

Purpose:

To determine the incidence and clinical characteristics of angiographic subtypes of polypoidal choroidal vasculopathy (PCV).

Methods:

It is a prospective, multicenter, cross-sectional study. Patients with newly diagnosed exudative macular degeneration are classified into PCV, age-related macular degeneration (AMD), and retinal angiomatous proliferation. Polypoidal choroidal vasculopathy is further classified into two subtypes depending on the presence (Type 1: polypoidal choroidal neovascularization) or absence (Type 2: typical PCV) of feeder vessels on indocyanine green angiography.

Results:

We enrolled 169 patients: 76 (45%) with PCV, 75 (44.4%) with AMD, and 14 (8.3%) with retinal angiomatous proliferation. Of the patients with PCV, 20 (26%) were classified as Type 1 PCV and 56 (74%) were classified as Type 2 PCV. The Type 1 PCV had a similar mean age compared to the AMD group (73.1 ± 9.6 vs. 75.6 ± 8.8 years, P = 0.281) and the Type 2 PCV (68.8 ± 9.6 years) was younger than the AMD group (P < 0.001). Type 1 PCV presented with worse visual acuity compared with the AMD. Both PCV subtypes had a higher incidence of hemorrhagic complications (85% and 75% respectively).

Conclusion:

Type 2 PCV is more common than Type 1 PCV in Taiwan. Our results support the hypothesis that polypoidal choroidal neovascularization and typical PCV may be distinct entities.
VISUALIZATION OF THE MACULA IN GAS-FILLED EYES
Authors: Ahn Seong Joon , Park Seung Hoon , Lee Byung Ro
Published: February 2017

Purpose:

To compare the visualization of the macula between spectral domain optical coherence tomography (SD-OCT) and swept-source OCT (SS-OCT) in gas-filled eyes.

Methods:

Sixty-one patients with common indications of gas tamponade, including 27 with macular holes and 34 with rhegmatogenous retinal detachment, who were treated with vitrectomy and gas tamponade were imaged using both SD-OCT (3D-OCT 2000, Topcon, Tokyo, Japan) and SS-OCT (DRI-OCT, Topcon) at 1, 3, and 7 days after the surgery. Good visualization of the macular area was defined as 1) visible foveal contour and discriminable status of hole (open or closed) for macular hole and 2) visible macular contour and distinguishable status for the presence of subretinal fluid for rhegmatogenous retinal detachment. The frequencies of good visualization were compared between SD-OCT and SS-OCT in each case.

Results:

Among 27 eyes with macular hole, good visualization at Day 1 was observed in 16 (59.3%) with SD-OCT and 24 (88.9%) with SS-OCT using a line scan protocol. For the cases with rhegmatogenous retinal detachment, good visualization at the day was noted in 12 (35.3%) and 25 (73.5%) eyes with SD-OCT and SS-OCT, respectively. For each scan protocol, the differences in good visualization of the macula between SD-OCT and SS-OCT were statistically significant for macular hole and rhegmatogenous retinal detachment (all P < 0.05). There were no significant differences between line and volume scan protocols, although good visualization was more frequently noted using the line scan protocol.

Conclusion:

In gas-filled eyes, SS-OCT performed significantly better than SD-OCT to visualize the macula. Using SS-OCT may lead to better decisions on further treatment during the early postoperative period, especially about postoperative positioning.
ENDOGENOUS NOCARDIA ENDOPHTHALMITIS PRESENTING AS A MASS LESION IN A PATIENT WITH METATSTATIC NONSMALL CELL CARCINOMA OF THE LUNG
Authors: Lee Brian , Drayna Paul , Maltry Amanda C. , Mason Craig M. , Montezuma Sandra R. , Koozekanani Dara
Published: February 2017

Purpose:

To report a case of Nocardia cyriacigeorgica endophthalmitis.

Methods:

Case report.

Results:

A 71-year-old man on long-term steroid therapy for poor respiratory function from lung carcinoma and presumed recent liver metastases presented with a four week history of blurry vision in the left eye. Ophthalmic examination revealed a white elevated mass in the macula with hemorrhage, concerning for metastasis. The patient was treated for presumed ocular metastases but had poor response to radiotherapy and was diagnosed four weeks later with N. cyriacigeorgica by retinal biopsy. Despite intravitreal and systemic antibiotics, the patient had progression of disease and died of respiratory involvement.

Conclusion:

Nocardia endogenous endophthalmitis can present as a mass retinal lesion in immunosuppressed patients with metastatic disease. Early vitreous and retinal biopsy may be required for definitive diagnosis and treatment. A pulmonary source of infection should be suspected and monitored closely.
RELENTLESS PLACOID CHORIORETINITIS: SUCCESSFUL LONG-TERM TREATMENT WITH INTRAVITREAL TRIAMCINOLONE
Authors: Roth Daniel B. , Ballintine Sheila , Mantopoulos Dimosthenis , Prenner Jonathan , Fine Howard F.
Published: February 2017

Purpose:

To report a case of relentless placoid chorioretinitis (ampiginous choroiditis) treated with intravitreal triamcinolone acetonide (IVTA).

Methods:

Interventional case report.

Results:

A 34-year-old pregnant woman with a history of poor visual acuity in her left eye, secondary to an undetermined cause, developed an acute painless central scotoma and blurred vision in the right eye. The examination revealed decreased visual acuity, active inflammatory placoid choroidal lesions in the posterior pole, and mid-periphery with sharp disk margins and normal-appearing vasculature. A diagnosis of relentless placoid chorioretinitis was made, and the patient was treated biannually with 4 mg IVTA for 3 years with visual improvement to 20/25. Although she experienced a relapse at 12 months, the episode was adequately controlled with repeat IVTA. After the sixth IVTA treatment occurring at 30 months, the decision was made to stop IVTA, ultimately facilitating the preservation of 20/25 in the right eye at 63-month follow-up. The disease course was complicated by cataract progression that was successfully treated with a cataract extraction and episodic increases in intraocular pressure which were successfully treated with timolol ophthalmic solution.

Conclusion:

Intravitreal triamcinolone acetonide therapy represents an important alternative in the treatment of relentless placoid chorioretinitis. By avoiding the potentially significant side effects of long-term systemic corticosteroid and immunosuppressive therapies, IVTA can be an important alternative in the long-term management of this uncommon and complicated entity.
IDENTIFICATION OF INCREASED BLUE LIGHT REFLECTIVITY IN MACULAR TELANGIECTASIA TYPE 2 USING SCANNING LASER OPHTHALMOSCOPY VERSUS RED-FREE FUNDUS PHOTOGRAPHY
Authors: Soorma Talha , Heeren Tjebo , Florea Daniela , Leung Irene , Peto Tunde
Published: February 2017

Purpose:

To compare two modalities used for detection of the characteristic parafoveal hyperreflective area seen in macular telangiectasia Type 2.

Methods:

Scanning laser ophthalmoscope blue light reflectance was compared with red-free fundus photography imaging. Images were obtained as part of the international Natural History Study of Macular Telangiectasia (MacTel Study).

Results:

The hyperreflective area can more frequently be seen with scanning laser ophthalmoscope blue light reflectance than with red-free imaging.

Conclusion:

Detection of the hyperreflective area might help to identify macular telangiectasia in earlier disease stages. Scanning laser ophthalmoscope blue light reflectance should be preferred as a diagnostic tool when the suspicion of macular telangiectasia arises. However, red-free imaging offers a viable option to scanning laser ophthalmoscope blue light reflectance when good quality is achieved.
A Review of Techniques to Measure Protein Sorption to Soft Contact Lenses
Authors: Hall Brad , Forrest James A. , Jones Lyndon
Published: February 2017

Purpose:

To compare and critically evaluate a variety of techniques to measure the quantity and biological activity of protein sorption to contact lenses over short time periods.

Methods:

A literature review was undertaken investigating the major techniques to measure protein sorption to soft contact lens materials, with specific reference to measuring protein directly on lenses using in situ, ex situ, protein structural, and biological activity techniques.

Results:

The use of in situ techniques to measure protein quantity provides excellent sensitivity, but many are not directly applicable to contact lenses. Many ex situ techniques struggle to measure all sorbed proteins, and these measurements can have significant signal interference from the lens materials themselves. Techniques measuring the secondary and tertiary structures of sorbed proteins have exhibited only limited success.

Conclusions:

There are a wide variety of techniques to measure both the amount of protein and the biological activity of protein sorbed to soft contact lens materials. To measure the mass of protein sorbed to soft contact lenses (not just thin films) over short time periods, the method of choice should be I125 radiolabeling. This technique is sensitive enough to measure small amounts of deposited protein, provided steps are taken to limit and measure any interaction of the iodine tracer with the materials. To measure the protein activity over short time periods, the method of choice should be to measure the biological function of sorbed proteins. This may require new methods or adaptations of existing ones.
Conjunctival Impression Cytology and Dry Eye in Patients With Ulcerative Colitis: A Pilot Study
Authors: Oltulu Pembe , Oltulu Refik , Asil Mehmet , Satirtav Gunhal , Mirza Enver
Published: February 2017

Purpose:

The aim of this study was to compare signs of dry eye between ulcerative colitis (UC) patients and healthy subjects.

Methods:

Fifteen patients with UC (group 1) and 15 healthy subjects (group 2) were enrolled in this study. Tear volume measurement, Schirmer-I test with no anesthetic, tear break-up time, and conjunctival impression cytology (CIC) were evaluated in both groups.

Results:

Patients with UC showed lower tear volumes when compared with healthy subjects (P<0.05). There was a statistically significant difference in distribution of CIC grades between groups 1 and 2 (P<0.05). Tear break-up time and Schirmer-I measurements were significantly lower in group 1 compared with group 2 (P<0.05).

Conclusions:

The results of this study indicate that UC is associated with demonstrable disturbances in tear function and conjunctival cytology.
Child Growth According to Maternal and Child HIV Status in Zimbabwe
Authors: Omoni Adetayo O. , Ntozini Robert , Evans Ceri , Prendergast Andrew J. , Moulton Lawrence H. , Christian Parul S. , Humphrey Jean H.
Published: February 2017

Background:

Growth failure is common among HIV-infected infants, but there are limited data on the effects of HIV exposure or timing of HIV acquisition on growth.

Methods:

Fourteen thousand one hundred ten infants were enrolled in the Zimbabwe Vitamin A for Mothers and Babies trial in Zimbabwe before the availability of antiretroviral therapy or co-trimoxazole. Anthropometric measurements were taken from birth through 12–24 months of age. Growth outcomes were compared between 5 groups of children: HIV-infected in utero (IU), intrapartum (IP) or postnatally (PN); HIV-exposed uninfected (HEU); and HIV unexposed.

Results:

Growth failure was common across all groups of children. Compared with HIV-unexposed children, IU-, IP- and PN-infected children had significantly lower length-for-age and weight-for-length Z scores throughout the first 2 years of life. At 12 months, odds ratios for stunting were higher in IU [6.25, 95% confidence interval (CI): 4.20–9.31] and IP infants (4.76, 95% CI: 3.58–6.33) than in PN infants (1.70, 95% CI: 1.16–2.47). Compared with HIV-unexposed infants, HEU infants at 12 months had odds ratios for stunting of 1.23 (95% CI: 1.08–1.39) and wasting of 1.56 (95% CI: 1.22–2.00).

Conclusions:

HIV-infected infants had very high rates of growth failure during the first 2 years of life, particularly if IU or IP infected, highlighting the importance of early infant diagnosis and antiretroviral therapy. HEU infants had poorer growth than HIV-unexposed infants in the first 12 months of life.
Development and Validation of the Cochlear Implant Surgical Competency Assessment Instrument
Authors: Balkany Thomas , Lo Kaming , Francis Howard , Angeli Simon , Novak Michael , Luxford William , Lusk Rodney , Strader Heather
Published: February 2017

Objective:

We present a new instrument for evaluation of cochlear implant (CI) surgical skills and review its validation process.

Methods:

An instrument to assess CI surgical competency incorporated results of structured surveys of comprehensiveness sent to 30 international CI experts and US trainees. One-hundred evaluations of 28 residents, fellows, and practicing CI surgeons were completed. Surgical skills were evaluated by four experienced neurotologists (two raters per subject) using two temporal bones per subject. A training session was completed by 24 subjects between the first and second procedure. Comparison of two blinded rater's scores per subject provided information on interrater reliability. Correlation of competency scores with degree of training and with improvement after a training session provided information on construct validity.

Results:

High levels of interrater reliability were confirmed by using the intraclass correlation coefficient. Construct validity was demonstrated by correlation of higher performance scores with increasing years of training, board certification, and fellowship training. Construct validity is also supported by improvement in scores after a CI training session as well as by acceptability surveys.

Discussion:

Data indicate that this instrument is an objective, accurate, and dependable procedure-specific instrument for evaluating CI surgical competency.

Conclusion:

The cochlear implant surgical competency assessment (CI-SCA) can be used to establish CI surgical competency, identify surgical skills that require remediation and demonstrate progress during training.
Population Statistics Approach for Safety Assessment in Robotic Cochlear Implantation
Authors: Williamson Tom , Gavaghan Kate , Gerber Nicolas , Weder Stefan , Anschuetz Lukas , Wagner Franca , Weisstanner Christian , Mantokoudis Georgios , Caversaccio Marco , Weber Stefan
Published: February 2017

Hypothesis:

Descriptive statistics with respect to patient anatomy and image guidance accuracy can be used to assess the effectiveness of any system for minimally invasive cochlear implantation, on both an individual patient and wider population level.

Background:

Minimally invasive cochlear implantation involves the drilling of a tunnel from the surface of the mastoid to cochlea, with the trajectory passing through the facial recess. The facial recess anatomy constrains the drilling path and places prohibitive accuracy requirements on the used system. Existing single thresholds are insufficient for assessing the effectiveness of these systems.

Methods:

A statistical model of the anatomical situation encountered during minimally invasive drilling of the mastoid for cochlear implantation was developed. A literature review was performed to determine the statistical distribution of facial recess width; these values were confirmed through facial recess measurements on computed tomography (CT) data. Based on the accuracy of a robotic system developed by the authors, the effect of variation of system accuracy, precision, and tunnel diameter examined with respect to the potential treatable portion of the population.

Results:

A facial recess diameter of 2.54 ± 0.51 mm (n = 74) was determined from a review of existing literature; subsequent measurements on CT data revealed a facial recess diameter of 2.54 ± 0.5 mm (n = 23). The developed model demonstrated the effects of varying accuracy on the treatable portion of the population.

Conclusions:

The presented model allows the assessment of the applicability of a system on a wider population scale beyond examining only the system's ability to reach an arbitrary threshold accuracy.
Interventional Treatment of LVAD Outflow Graft Stenosis by Introduction of Bare Metal Stents
Authors: Wiedemann Dominik , Schlöglhofer Thomas , Haberl Thomas , Riebandt Julia , Dimitrov Kamen , Schima Heinrich , Kastner Johannes , Matzek Wolfgang , Laufer Günther , Zimpfer Daniel
Published: February 2017

Left ventricular assist device outflow graft stenosis is a rare but life-threatening complication of mechanical cirulatory support therapy. Current treatment modalities (pump exchange or systemic thrombolytic therapy) are associated with significant mortality and morbidity. Implantation of bare metal stents within the stenosed outflow graft is an alternative. Herein, we describe a series of three cases with successful stent placement. This seems to be safe and successful; however, correct and early diagnosis of outflow stenosis can be challenging. Information provided by the HeartWare ventricular assist device (HVAD) logfiles is extremely helpful for diagnosis.
High-frequency oscillatory ventilation: still a role?
Authors: Ng Jensen , Ferguson Niall D.
Published: February 2017

Purpose of review

In light of emerging data from clinical trials, the place of high-frequency oscillatory ventilation (HFOV) in the management of acute respiratory distress syndrome (ARDS) is uncertain. This review provides an overview of these new clinical data and also explores new areas of investigation for HFOV in adults.

Recent findings

While prior meta-analyses suggested benefit for HFOV, updated systematic reviews published this year, which include two large recent clinical trials, now show no statistically significant impact of HFOV on mortality in adults with ARDS. It is possible that HFOV would be safer and more effective with a more individualized approach to setting mean airway pressure (mPaw). Possible techniques to achieve this include titrating mPaw in response to oxygenation or hemodynamic changes after HFOV initiation, by measuring respiratory system impedance, or by following echocardiographic changes.

Although not first-line, HFOV remains a tool in the armamentarium of the intensivist managing the patient with severe ARDS and refractory hypoxemia. A refinement in the approach to delivering HFOV is warranted, with more attention paid to its adverse hemodynamic consequences.
Spreading depolarization monitoring in neurocritical care of acute brain injury
Authors: Hartings Jed A.
Published: February 2017

Purpose of review

Spreading depolarizations are unique in being discrete pathologic entities that are well characterized experimentally and also occur commonly in patients with substantial acute brain injury. Here, we review essential concepts in depolarization monitoring, highlighting its clinical significance, interpretation, and future potential.

Recent findings

Cortical lesion development in diverse animal models is mediated by tissue waves of mass spreading depolarization that cause the toxic loss of ion homeostasis and limit energy substrate supply through associated vasoconstriction. The signatures of such deterioration are observed in electrocorticographic recordings from perilesional cortex of patients with acute stroke or brain trauma. Experimental work suggests that depolarizations are triggered by energy supply–demand mismatch in focal hotspots of the injury penumbra, and depolarizations are usually observed clinically when other monitoring variables are within recommended ranges. These results suggest that depolarizations are a sensitive measure of relative ischemia and ongoing secondary injury, and may serve as a clinical guide for personalized, mechanistically targeted therapy. Both existing and future candidate therapies offer hope to limit depolarization recurrence.

Electrocorticographic monitoring of spreading depolarizations in patients with acute brain injury provides a sensitive measure of relative energy shortage in focal, vulnerable brains regions and indicates ongoing secondary damage. Depolarization monitoring holds potential for targeted clinical trial design and implementation of precision medicine approaches to acute brain injury therapy.
Lessons learned in applying the International Society for Pharmacoeconomics and Outcomes Research methodology to translating Canadian Emergency Department Information System Presenting Complaints List into German
Authors: Brammen Dominik , Greiner Felix , Dormann Harald , Mach Carsten , Wrede Christian , Ballaschk Anne , Stewart Declan , Walker Steven , Oesterling Christine , Kulla Martin
Published: February 2017

Objectives

The patient’s presenting complaint guides diagnosis and treatment in the emergency department, but there is no classification system available in German. The Canadian Emergency Department Information System (CEDIS) Presenting Complaint List (PCL) is available only in English and French. As translation risks the altering of meaning, the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) has set guidelines to ensure translational accuracy. The aim of this paper is to describe our experiences of using the ISPOR guidelines to translate the CEDIS PCL into German.

Materials and methods

The CEDIS PCL (version 3.0) was forward-translated and back-translated in accordance with the ISPOR guidelines using bilingual clinicians/translators and an occupationally mixed evaluation group that completed a self-developed questionnaire.

Results

The CEDIS PCL was forward-translated (four emergency physicians) and back-translated (three mixed translators). Back-translation uncovered eight PCL items requiring amendment. In total, 156 comments were received from 32 evaluators, six of which resulted in amendments.

Conclusion

The ISPOR guidelines facilitated adaptation of a PCL into German, but the process required time, language skills and clinical knowledge. The current methodology may be applicable to translating the CEDIS PCL into other languages, with the aim of developing a harmonized, multilingual PCL.
Complexity of mechanisms among human proprotein convertase subtilisin–kexin type 9 variants
Authors: Dron Jacqueline S. , Hegele Robert A.
Published: February 2017

Purpose of review

There are many reports of human variants in proprotein convertase subtilisin–kexin type 9 (PCSK9) that are either gain-of-function (GOF) or loss-of-function (LOF), with downstream effects on LDL cholesterol and cardiovascular disease (CVD) risk. However, data on particular mechanisms have only been minimally curated.

Recent findings

GOF variants are individually ultrarare, affect all domains of the protein, act to reduce LDL receptor expression through several mechanisms, are a minor cause of familial hypercholesterolemia, have been reported mainly within families, have variable LDL cholesterol–raising effects, and are associated with increased CVD risk mainly through observational studies in families and small cohorts. In contrast, LOF variants can be either ultrarare mutations or relatively more common polymorphisms seen in populations, affect all domains of the protein, act to increase LDL receptor expression through several mechanisms, have variable LDL cholesterol–lowering effects, and have been associated with decreased CVD risk mainly through Mendelian randomization studies in epidemiologic populations.

There is considerable complexity underlying the clinical concept of both LOF and GOF variants of PCSK9. But despite the underlying mechanistic heterogeneity, altered PCSK9 secretion or function is ultimately correlated with plasma LDL cholesterol level, which is also the driver of CVD outcomes.
Low-density lipoprotein receptor mutational analysis in diagnosis of familial hypercholesterolemia
Authors: Bourbon Mafalda , Alves Ana C. , Sijbrands Eric J.
Published: February 2017

Purpose of review

To present up to date evidence on the pathogenicity of low-density lipoprotein receptor (LDLR) variants and to propose a strategy that is suitable for implementation in the clinical work-up of familial hypercholesterolaemia.

Recent findings

More than 1800 variants have been described in theLDLRgene of patients with a clinical diagnosis of familial hypercholesterolaemia; however, less than 15% have functional evidence of pathogenicity.

The spectrum of variants in theLDLRidentified in patients with clinical familial hypercholesterolaemia is increasing as novel variants are still being reported. However, over 50% of allLDLRvariants need further evidence before they can be confirmed as mutations causing disease. Even with applying the recent American College of Medical Genetics variant classification, a large number of variants are still considered variants of unknown significance. Before obtaining an undisputable confirmation of the effect on the expression and activity of the LDLR, reporting these variants as part of a clinical diagnosis to the patient holds the risk that it might need to be withdrawn in a later stage. An investment should be made to develop functional assays to characterizeLDLRvariants of unknown significance for a better patient diagnosis and to prevent confusion in the physician's office.
Supratracheal partial laryngectomy: indications, oncologic and functional results
Authors: Succo Giovanni , Fantini Marco , Rizzotto Giuseppe
Published: February 2017

Purpose of review

To describe current evidence about supratracheal laryngectomies, focusing on indications, contraindications, oncologic results, functional outcomes and side-effects of this ‘extreme’ function-sparing surgical approach to laryngeal cancer.

Recent findings

In the latest years, some studies have analyzed oncologic and functional results of open partial supratracheal laryngectomy, a surgical approach whose modern technique was recently described. In selected patients, supratracheal partial laryngectomies show promising long-term oncologic and functional outcomes, similar to those of supracricoid partial laryngectomies.

The application of supratracheal laryngectomy in the context of a surgical modular approach can be considered a valid and effective therapeutic choice for selected patients with glottic or transglottic laryngeal cancer with subglottic extension, not only in terms of oncologic results, but also in regard of functional outcomes.
Hypoparathyroidism after thyroidectomy: prevention, assessment and management
Authors: Dedivitis Rogerio A. , Aires Felipe T. , Cernea Claudio R.
Published: February 2017

Purpose of review

Permanent hypoparathyroidism is the most common long-term complication after total thyroidectomy and it can cause significant morbidity and increased costs. Its incidence varies from 30% to 60%.

Recent findings

The surgical technique and the extent of thyroidectomy are related to parathyroid injury and hypoparathyroidism. The glands should be identified in situ, carefully manipulated and preserved, as well as their vascularization. In case of incidental removal, routine autotransplantation is advocated. Low calcium levels, identification of fewer than two parathyroid glands at surgery, reoperation for bleeding, Graves disease and heavier thyroid specimens were considered independent predictors of permanent hypocalcemia. Intraoperative parathyroid hormone (PTH) measurements allows the early detection of hypocalcemia. Treatment is recommended for patients with symptoms of hypocalcemia or corrected serum calcium < 7.5 mg/dL. Acute hypocalcemia is treated with either oral calcium or an intravenous infusion. The goal is to preserve serum calcium in the low normal or mildly subnormal levels. Hypocalcemia symptoms should be considered a medical emergency. Treatment with PTH has been recently performed for the management of cases not adequately controlled with conventional therapy.

Hypoparathyroidism is the most common long-term complication after total thyroidectomy. Adequate recognition and management decrease its morbidity and costs.
Unique Inflammatory Bowel Disease Phenotype of Pediatric Primary Sclerosing Cholangitis
Authors: Shiau Henry , Ihekweazu Faith D. , Amin Mansi , Fofanova Tatiana , Miloh Tamir , Kellermayer Richard
Published: February 2017

Objectives:

In adults, primary sclerosing cholangitis (PSC), a cholestatic liver disease characterized by inflammation/fibrosis of intra/extrahepatic bile ducts, associates with a milder form of inflammatory bowel disease (IBD), particularly ulcerative colitis (UC). The pediatric PSC‐IBD phenotype is less well characterized.

Methods:

We performed a retrospective, single‐center study examining patients with PSC‐IBD at Texas Children's Hospital between 2000 and 2015. IBD‐phenotype (Modified Montreal Classification), medications, laboratory values, endoscopic records, and IBD‐based hospital admissions were collected. PSC‐UC phenotype was compared to UC, non‐PSC patients (n = 95) from Texas Children's Hospital. Elevated gamma‐glutamyl transpeptidase levels were compared to calprotectin levels and IBD‐flare activity, that is, gastrointestinal symptoms resulting in office/emergency department visits or hospital admission.

Results:

Of 39 patients with PSC‐IBD, 34 (87.2%) had UC (PSC‐UC) and 5 (12.8%) had Crohn disease. Pancolitis was more common in PSC‐UC than UC, non‐PSC (96.3%, 64%, P = 0.0009). Patients with PSC‐UC required less treatment with steroids (76.5%, 91.6%, P = 0.0326) or infliximab (8.8%, 37.9%, P = 0.0011), and fewer had at least 1 IBD‐related hospital admission (32.4%, 63.2%, P = 0.0025) than UC, non‐PSC. Progression to colectomy was significantly less (5.8%, 24.2%, P = 0.0223) in PSC‐UC. Median diagnosis‐to‐colectomy time tended to be longer in PSC‐UC (6.37, 2.5 years, P = 0.0792). In 2 smaller subsets, gamma‐glutamyl transpeptidase did not correlate with calprotectin in PSC‐UC (n = 11, P = 0.7922) and less strongly associated with IBD‐flares in PSC‐UC than UC, non‐PSC (n = 33, n = 67; 15.2%, 41.8%, P = 0.0120).

Conclusions:

Pediatric PSC appears to associate with milder pancolitic‐UC. PSC and IBD activity do not appear to correlate. Our findings may provide useful information toward etiology and management of pediatric PSC‐IBD.
Risk of Colectomy in Patients With Pediatric‐onset Ulcerative Colitis
Authors: Rinawi Firas , Assa Amit , Eliakim Rami , Mozer‐Glassberg Yael , Nachmias‐Friedler Vered , Niv Yaron , Rosenbach Yoram , Silbermintz Ari , Zevit Noam , Shamir Raanan
Published: February 2017

Objectives:

Data describing the incidence and risk factors for colectomy in pediatric ulcerative colitis (UC) is inconsistent. Our aim was to describe the colectomy rate and to identify risk factors associated with colectomy in a large cohort of children with UC with long‐term follow‐up.

Materials and Methods:

We performed a retrospective chart review of pediatric UC cases that were diagnosed at Schneider Children's Medical Center of Israel between 1981 and 2013. Potential predictors for colectomy including age at diagnosis, sex, disease extent, severity indices, and different therapeutic regimens during disease course were assessed.

Results:

Of 188 patients with pediatric onset UC, 34 (18%) underwent colectomy. Median follow‐up was 6.9 years (range, 1–30). Kaplan‐Meier survival estimates of the cumulative probability for colectomy were 4% at 1 year and 17% at 10 years from diagnosis. Multivariate Cox models showed that male sex (hazard ratio 4.2, P = 0.001) and severe disease at diagnosis reflected by Pediatric Ulcerative Colitis Activity Index score ≥65 (hazard ratio 8.9, P < 0.001) were associated with increased risk for colectomy. Age, disease extent, ethnicity, family history of inflammatory bowel disease, early introduction of immunomodulators, or treatment with antitumor necrosis factor α agent did not affect the risk of colectomy.

Conclusions:

Male sex and higher Pediatric Ulcerative Colitis Activity Index score at diagnosis are independent risk factors for colectomy.
Diagnosis and Management of Abdominal Wall Endometriosis: A Systematic Review and Clinical Recommendations
Authors: Rindos Noah B. , Mansuria Suketu
Published: February 2017

Importance

Abdominal wall endometriosis (AWE) is a rare but easily treated cause of pain in women, especially those who have undergone cesarean deliveries.

Objective

This article reviews the diagnosis and management of AWE, a condition that generally develops after surgery but may arise spontaneously. We present a systematic review of the existing literature on AWE, as well as our clinical recommendations for medical and surgical management.

Evidence Acquisition

We searched PubMed and other databases using the search criteria “abdominal wall endometriosis,” “abdominal wall endometriomas,” and “abdominal wall mass.” The references of those articles were then reviewed, and additional publications were evaluated.

Results

Many case reports and case series have been published describing AWE. The overall quality of evidence is poor due to the lack of prospective studies and heterogeneous descriptions of AWE lesions and treatment options. Based on the available literature, it appears that AWE may arise spontaneously but is generally associated with prior pelvic surgery. Abdominal wall endometriosis can be diagnosed with a careful history and physical examination. Imaging including ultrasound and magnetic resonance imaging can assist with localization of the lesions, and aid in surgical excision and management. Lesions that have been removed in their entirety are unlikely to reoccur.

Conclusions and Relevance

Although limited, the body of literature describing management of AWE suggests that it can be successfully treated in most patients with careful surgical planning.

Target Audience

Obstetricians and gynecologists, family physicians.

Learning Objectives

After completing this activity, the learner should be better able to identify risk factors for abdominal wall endometriosis, counsel their patients on management options, and understand the utility of preoperative imaging.
Mucin Balls Influence Corneal Infiltrative Events
Authors: Szczotka-Flynn Loretta B. , Jiang Ying , Stiegemeier Mary Jo , Mutti Donald O. , Walline Jeffrey , Wilson Tawnya , Debanne Sara
Published: February 2017

Purpose

To determine whether mucin ball (MB) formation is protective against corneal infiltrative events (CIEs) as previously reported.

Methods

Two hundred eighty-two eligible participants were enrolled at three sites in the USA. Participants began a 1-month continuous wear run-in period with high modulus lotrafilcon A lenses to assess their ability to form MBs (phase 1). Subsequently, they were stratified by this characteristic and randomized to balafilcon A or comfilcon A lenses for 7-day extended wear and followed for 1 year (phase 2). MB formation in each phase was defined as repeated presence of any MBs on a person level. Multivariable Cox proportional hazards regression was used to model the probability of a CIE as a function of MB formation in each phase and other covariates.

Results

Of the 282 participants who entered phase 1, 218 of them entered the phase 2 randomized trial during which 33 CIEs occurred. Overall, 74%, 61%, and 79% of participants repeatedly produced MBs in lotrafilcon A, balafilcon A, and comfilcon A lenses, respectively. Early repeated MB presence in phase 1 with lotrafilcon A lenses significantly increased the rate of CIEs in phase 2 (12-month follow-up) by 466% (HR 4.66, 95% confidence interval 1.10–19.79, P = .0372). Repeated, longer-term MB presence during wear of balafilcon A or comfilcon A in phase 2 did not significantly reduce the incidence of CIEs; however, it significantly decreased the rate of CIEs by 62% (hazard ratio (HR) 0.380, 95% confidence interval 0.145–0.998, P = .0494).

Conclusions

The overarching hypothesis that MB formation is protective against CIEs throughout extended wear was not supported. Although a protective effect of longer-term MB presence on rate of CIEs was detected, early-onset MB formation substantially increased the hazard for CIE in subsequent wear with different lens types.
Factors Associated With Mortality in Low-Risk Pediatric Critical Care Patients in The Netherlands*
Authors: Verlaat Carin W. , Visser Idse H. , Wubben Nina , Hazelzet Jan A. , Lemson Joris , van Waardenburg Dick , van der Heide Douwe , van Dam Nicolette A. , Jansen Nicolaas J. , van Heerde Mark , van der Starre Cynthia , van Asperen Roelie , Kneyber Martin , van Woensel Job B. , van den Boogaard Mark , van der Hoeven Johannes
Published: February 2017

Objective:

To determine differences between survivors and nonsurvivors and factors associated with mortality in pediatric intensive care patients with low risk of mortality.

Design:

Retrospective cohort study.

Setting:

Patients were selected from a national database including all admissions to the PICUs in The Netherlands between 2006 and 2012.

Patients:

Patients less than 18 years old admitted to the PICU with a predicted mortality risk lower than 1% according to either the recalibrated Pediatric Risk of Mortality or the Pediatric Index of Mortality 2 were included.

Interventions:

None.

Measurements and Main Results:

In total, 16,874 low-risk admissions were included of which 86 patients (0.5%) died. Nonsurvivors had more unplanned admissions (74.4% vs 38.5%; p < 0.001), had more complex chronic conditions (76.7% vs 58.8%; p = 0.001), were more often mechanically ventilated (88.1% vs 34.9%; p < 0.001), and had a longer length of stay (median, 11 [interquartile range, 5–32] d vs median, 3 [interquartile range, 2–5] d; p < 0.001) when compared with survivors. Factors significantly associated with mortality were complex chronic conditions (odds ratio, 3.29; 95% CI, 1.97–5.50), unplanned admissions (odds ratio, 5.78; 95% CI, 3.40–9.81), and admissions in spring/summer (odds ratio, 1.67; 95% CI, 1.08–2.58).

Conclusions:

Nonsurvivors in the PICU with a low predicted mortality risk have recognizable risk factors including complex chronic condition and unplanned admissions.