bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toileting Resistance Among Preschool-Age Children with and Without Autism Spectrum Disorder
Authors: Wiggins Lisa D. , Nadler Cy , Hepburn Susan , Rosenberg Steven , Reynolds Ann , Zubler Jennifer 
Published: February 2022

ABSTRACT:

Objective:
Children with autism spectrum disorder (ASD) may achieve continence later than other children. Little is known about factors associated with toileting resistance in children with ASD and other developmental delays/disabilities (DD). We sought to describe toileting resistance in children with ASD and DD and those from the general population (POP) and identify factors associated with toileting resistance in children with ASD and DD.

Method:
Families and children aged 24 to 68 months were enrolled in the Study to Explore Early Development, a multisite case-control study on ASD. Children with ASD (N = 743) and DD (N = 766) and those from the POP (N = 693) who were 48 months or older were included in this study. Parents reported toileting resistance, gastrointestinal issues, behavior problems, and ASD symptoms in their children. Children completed an in-person evaluation to determine ASD status and developmental level.

Results:
Toileting resistance was more common among children with ASD (49.1%) than children with DD (23.6%) and those from the POP (8.0%). Diarrhea and deficits in social awareness were significantly associated with toileting resistance in children with ASD and DD. Constipation, expressive language delays, and low social motivation were significantly associated with toileting resistance only in children with ASD; very low visual reception skills and oppositional behaviors were significantly associated with toileting resistance in only children with DD (all p ≤ 0.05).

Conclusion:
Evaluating gastrointestinal issues, developmental delays, and social deficits before toileting training may help identify children with atypical development who are likely to present with toileting resistance. These evaluations can be incorporated into health supervision visits.
The Adenylate Cyclase Activator Forskolin Potentiates the Positive Inotropic Effect of the Phosphodiesterase Inhibitor Milrinone But Not of the Calcium Sensitizer Levosimendan nor of Its Hemodynamically Active Metabolites: An Apparent Conundrum
Authors: Levijoki Jouko , Pollesello Piero , Grossini Elena , Papp Zoltán 
Published: February 2022

Abstract:
OR-1855 and OR-1896 are 2 hemodynamically active metabolites of the inodilator levosimendan, with calcium sensitizing activity, but their mechanism of action is still not fully understood. It has been previously reported that the positive inotropic effect of levosimendan is not potentiated by the adenylate cyclase activator forskolin, whereas forskolin does potentiate the effects of the phosphodiesterase (PDE) inhibitor milrinone. To ascertain whether the active metabolites follow the same pattern of levosimendan, the positive inotropic effects of OR- 1855 and OR-1896 were studied in guinea-pig-isolated papillary muscle in the presence and absence of forskolin. OR-1855 and OR-1896 were also tested as inhibitors of PDE-III and PDE-IV. Our results show that 0.1 µM forskolin did not potentiate the positive inotropic effect of OR-1855 or OR-1896, as in the case of the parent compound levosimendan. As in previous studies, the positive inotropic effect of milrinone was markedly potentiated in the presence of forskolin. From these data, we propose an explanation for the divergent behavior of the calcium sensitizing drugs and PDE inhibitors.
Microdebridement of Intranasal Cysts Associated With Congenital Dacryocystoceles
Authors: Magoon Katie , Landau Prat Daphna , Guo Michelle , Revere Karen , Katowitz William R. 
Published: February 2022

Purpose:
The surgical management of congenital dacryocystoceles has evolved in recent decades. The aim of this study was to explore the effectiveness of endoscopic examination and powered microdebridement in the management of nasal cysts associated with congenital dacryocystoceles.

Methods:
In this retrospective case series, all patients with congenital dacryocystoceles who underwent surgical intervention under general anesthesia at a single institution over a 12-year period (2009–2020) were included.

Results:
Thirty-seven lacrimal drainage systems from 29 patients were included, 8 patients (28%) had bilateral dacryocystoceles. Twenty-two (76%) were females, and 5 (17%) patients had a history of prematurity. Mean (±SD) age at diagnosis was 15 ± 28 days, and 1.4 ± 1.7 months at surgical intervention. Mean follow-up was 7.5 months. The right side was more commonly involved (20 [69%] OD vs. 17 [59%] OS). Dacryocystitis was diagnosed at presentation in 23 lacrimal drainage systems (62%). Intraoperatively, intranasal cysts were observed in 32 lacrimal drainage systems (86%), and a powered microdebrider was used to excise each cyst. In 6 of the 21 supposed unilateral cases (29%), a contralateral cyst was identified and treated. The average birth age of patients with intranasal cysts was 39 weeks versus 36 weeks of patients without (p = 0.03). Surgical success was found in 36 of 37 sides treated (97%); one case (3%) underwent unilateral endoscopic dacryocystorhinostomy during the follow-up period due to persistent symptoms.

Conclusions:
Congenital dacryocystoceles are associated with intranasal cysts in most cases. Surgical intervention with microdebrider is associated with a favorable outcome. Bilateral endonasal examination is ideal in all cases.
Blink Reflex in Neurotrophic Keratopathy: An Electrophysiological Evaluation
Authors: Syed Sara Fatima , Marshall Andrew , Hossain Parwez , Sadiq Saghir Ahmed 
Published: February 2022

Purpose:
Neurotrophic keratitis (NK) is a rare condition which may result in visual loss. This case review investigates if there may be an association between NK and the blink reflex in the absence of facial nerve palsy and lagophthalmos.

Methods:
This is a retrospective case review of 5 patients with trigeminal nerve damage referred to the oculoplastic department with suspected anesthetic corneae. Information on etiology, symptoms, duration, associated medical conditions, medications, examination findings including Mackie stage of keratopathy, management of keratopathy, and blink electrophysiology results was obtained.

Results:
All 5 patients demonstrated absence of corneal sensation. All patients had preserved facial nerve function with no evidence of lagophthalmos. Keratopathy ranged from Mackie stage 0–2. Management ranged from ocular lubricants to Botulinum-toxin-induced ptosis. Blink studies demonstrated reduction in amplitude as well as increased latency in 2 patients, conferring reduced blink strength. Two patients demonstrated an absent blink reflex on the affected side. One patient had blink latency within the normative range; this patient recovered corneal sensation and was discharged.

Conclusions:
Our finding of reduced amplitude in blink studies offers both a factor in pathogenesis of NK and a potential therapeutic target. Additionally, blink studies may provide prognostic information for recovery and therefore guide management. We suggest performing blink electrophysiology in patients with trigeminal nerve damage to assess nerve function.
Clinical and refractive outcomes after topography-guided refractive surgery planned using Phorcides surgery planning software
Authors: Stulting R. Doyle , Lobanoff Mark , Mann Paul M. , Wexler Stephen , Stonecipher Karl , Potvin Richard 
Published: February 2022

Purpose:
To evaluate prospectively the clinical outcomes of topography-guided laser in situ keratomileusis (LASIK) surgery performed with Contoura Vision using the Wavelight excimer laser and planned with the Phorcides Analytical Engine.

Setting:
Four clinical practices in the U.S.

Design:
Prospective single-arm interventional study.

Methods:
130 eyes of 65 patients with myopia or myopic astigmatism were enrolled in a prospective study of visual and refractive outcomes after treatment with Contoura Vision using the Wavelight EX500 excimer laser to achieve optimal distance vision. At 3 months postoperatively, uncorrected distance visual acuity (UDVA), manifest refraction, and corrected distance visual acuity (CDVA) were measured and compared with previously published studies.

Results:
At 3 months postoperatively, 100%, 89%, and 28% of eyes achieved UDVA of 20/20, 20/15, and 20/12.5 or better, respectively. 92% of eyes had postoperative UDVA equal to or better than their preoperative CDVA. Postoperative CDVA was equal to, 1 line better, or 2 lines better than the preoperative CDVA in 53%, 40%, and 6% of eyes, respectively. Only 1 eye lost 1 line of CDVA, and no eyes lost more than 1 line of CDVA. A statistically significant decrease was noted in subjective visual complaints, including glare, halos, difficulty driving at night, reading difficulty, starbursts, fluctuation in vision, and light sensitivity.

Conclusions:
The Phorcides Analytical Engine can be used to optimize visual outcomes for the correction of myopia and myopic astigmatism.
Long-term results in patients with iris-fixated foldable phakic intraocular lenses for myopia and astigmatism
Authors: Marta Ana , Leite João , Abreu Ana Carolina , Monteiro Sílvia , Pinto Céu 
Published: February 2022

Purpose:
To evaluate the long-term results of iris-fixated foldable phakic intraocular lens (pIOL) implantation for the management of myopia and astigmatism.

Setting:
Centro Hospitalar Universitário do Porto, Oporto, Portugal.

Design:
Prospective clinical study.

Methods:
Patients who underwent Artiflex Myopia or Artiflex Toric iris-fixed pIOL implantation for the treatment of myopia or astigmatism between 2003 and 2011 were included. Refractive stability, refractive predictability, safety, efficacy, and cumulative probability of success were evaluated at 5 years, 10 years, and 15 years of follow-up.

Results:
5-year, 10-year, and 15-year follow-ups were completed by 199 of 217 (91.7%), 187 of 217 (86.2%), and 43 of 45 (95.6%) eyes implanted with pIOLs, respectively. The mean spherical equivalent was −8.36 ± 2.75 diopters (D), −0.11 ± 0.31 D, −0.33 ± 0.62 D, and −0.80 ± 1.32 D preoperatively and after 5 years, 10 years, and 15 years after surgery. At 5 years, 10 years, and 15 years after surgery, 100%, 95.6%, and 81.6% were within ±1.00 D. The safety and efficacy indexes were 1.07 and 1.06 at 5 years, 1.04 and 0.99 at 10 years, and 1.05 and 1.00 at 15 years of follow-up, respectively. Kaplan-Meier analysis showed survival rates of 97% at 5 years, 73% at 10 years, and 43% at 15 years of follow-up.

Conclusions:
Long-term results demonstrated that the implantation of Artiflex pIOLs was a stable, predictable, and effective procedure at 5 years, 10 years, and 15 years of follow-up. Annual follow-up visits to evaluate endothelial cell density and anterior chamber depth decrease, to alert patients to this need in the preoperative evaluation, is recommended.
Assessing the Prognostic Value of the ChOLE Classification in Predicting the Severity of Acquired Cholesteatoma
Authors: Eggink Maura C. , de Wolf Maarten J. F. , Ebbens Fenna A. , Dikkers Frederik G. , van Spronsen Erik 
Published: February 2022

Objective:
To assess the prognostic value of the ChOLE classification in predicting the severity of acquired cholesteatoma.

Method:
A retrospective chart review of patients undergoing primary cholesteatoma surgery in our tertiary referral center. The primary outcome measures were analyzed in three groups of follow up (FU): residual cholesteatoma in group A, FU > 52 weeks after last-look surgery or MRI-DWI; recurrent cholesteatoma in group B, FU > 52 weeks after last outpatient visit; and adverse events (AE) in group C, FU > 12 weeks after surgery. Cholesteatomata were staged according to the ChOLE classification. Kaplan–Meier curves were used to determine the prognostic value of the classification in predicting cholesteatoma severity, while correcting for FU.

Results:
No significant differences were observed between the various stages of the ChOLE classification and residual or recurrent cholesteatoma rate, nor the occurrence of AE. Cholesteatoma extension to the sinus tympani or widespread in the mastoid, as well as absence of the stapes superstructure were predictive of residual disease. Sclerotic mastoids had a lower risk of residual disease than mastoids with good or poor pneumatization and ventilation. Poorly ventilated and poorly pneumatized mastoids were associated with increased risk of recurrence. Widespread cholesteatoma in the mastoid as well as presence of preoperative extracranial complications were correlated with an increased risk of AE.

Conclusion:
The ChOLE classification does not predict residual nor recurrent disease, nor the occurrence of AE, in our study population. Risk factors for severe cholesteatoma were identified, potentially useful for the development of future classifications.
Detection of Extracochlear Electrodes Using Stimulation-Current- Induced Non-Stimulating Electrode Voltage Recordings With Different Electrode Designs
Authors: de Rijk Simone R. , Hammond-Kenny Amy , Tam Yu C. , Eitutis Susan T. , Garcia Charlotte , Carlyon Robert P. , Bance Manohar 
Published: February 2022

Hypothesis:
Stimulation-Current-Induced Non-Stimulating Electrode Voltage Recordings (SCINSEVs) can help detect extracochlear electrodes for a variety of Cochlear Implant (CI) devices.

Background:
Extracochlear electrodes (EEs) occur in 9 to 13% of cochlear implantations and commonly go unnoticed without imaging. Electrodes on the electrode array located extracochlearly are associated with non-auditory stimulation and a decrease in speech outcomes. We have previously shown that SCINSEVs, with hardware and software from one manufacturer, could detect EEs. Here, we test the generalizability to other manufacturers.

Methods:
Fresh-frozen human cadaveric heads were implanted with Cochlear Ltd. CI522 (CI-A) and MED-EL's FLEX24 (CI-B) electrodes. Contact impedances and SCIN- SEVs were measured, with Cochlear Ltd. research Custom Sound software (Transimpedance Matrix) and MED-EL's clinical MAESTRO (Impedance Field Telemetry), for full insertion and EEs in air, saline and soft tissue. An automated detection tool was optimized and tested for these implants. Intra-operative SCINSEVs with EEs were collected for clinical purposes for six patients.

Results:
The pattern of SCINSEVs changed in the transition zone from intracochlear to extracochlear electrodes, even with low contact impedances on EEs. Automated detection in the cadaveric specimens, with two or more EEs in saline or soft tissue, showed a mean 91% sensitivity and specificity for CI-A and 100% sensitivity and specificity for CI-B. Quantification of EEs showed significant correlations of r
= 0.69 between estimated and actual EEs for CI-A and r = 0.76 for CI-B.

Conclusion:
The applicability of SCINSEVs to detect extra- cochlear electrodes could be expanded to other cochlear implant companies despite differences in electrode array design and measurement software.
Spironolactone Ameliorates Cochlear Implant Induced Endolymphatic Hydrops
Authors: Creber Nathan J. , Eastwood Hayden T. , Hampson Amy J. , Lo Jonathon , Zhang Dongcheng , Chambers Scott A. , Bester Christo W. , Thorne Peter R. , O’Leary Stephen J. 
Published: February 2022

Background
Endolymphatic hydrops (EH) has been observed in both animal and human cochleae following cochlear implant (CI) surgery. We tested whether EH could be eliminated by administration of mineralocorticoid steroid antagonist spironolactone and explored the electrophysiological consequences of this.

Methods
Sixty-four adult guinea pigs underwent cochlear implantation with a dummy electrode. Animals then survived either 2, 7, or 28 days. Auditory function was monitored by recording electrocochleography from the round window membrane preimplantation, and on the last day of the experiment. Spironolactone or control solution was added to animals’ feed for 7 days (if they survived that long) beginning immediately prior to surgery. The presence of EH was determined using thin-sheet laser imaging microscopy.

Results
Treatment with spironolactone resulted in significant reduction in EH in the second cochlear turn 7 days postimplantation. In all animals, the compound action potential (CAP) threshold was elevated 2 days postimplantation, but for most frequencies had recovered substantially by 28 days. There was no treatment effect on CAP thresholds. SP/AP ratios were elevated at day 2. The amplitude growth of the CAP did not differ between test and control groups at any time after implantation.

Conclusions
EH can be suppressed by antagonism of mineralocorticoid receptors in the week after cochlear implantation. Reduction in EH did not lead to any change in hearing, and there was no indication of synaptopathy signalled by reduced CAP amplitude at high sound intensities. We found no electrophysiological evidence that EH early after implantation impacts negatively upon preservation of residual hearing.
Chlamydia trachomatis Variants Escaping Detection in the Aptima Combo 2 Assay in the United States
Authors: Katz Samantha S. , Danavall Damien C. , Morris Monica R. , Herrod Bridgett P. , Dale Suzanne E. , Nye Melinda B. , Kersh Ellen N. , Kirkcaldy Robert D. , Raphael Brian H. 
Published: February 2022

Background
The Aptima Combo 2 (AC2) assay manufactured by Hologic, Inc., detects Neisseria gonorrhoeae and/or Chlamydia trachomatis (CT) in urogenital and extragenital specimens by targeting either a 16S rRNA (N. gonorrhoeae) or 23S rRNA (CT) region. In 2019, a mutation (C1515T) in the 23S rRNA region was reported to cause false-negative/equivocal results in specimens collected in Finland. Specimens containing this variant (Fl-nvCT) were also discovered internationally. Working with specimens submitted to a large commercial laboratory, we sought to determine if this variant was also present in the United States.

Methods
A subset (n = 401) of specimens tested with the AC2 assay collected during a 5-week period in late 2019/early 2020 were evaluated using an updated AC2 assay.

Results
Although the FI-nvCT variant was not detected within this specimen panel, 2 CT variants containing 23S rRNA mutations (A1518G, G1526A) were identified. The updated AC2 assay targeting an additional region of the 23S rRNA detected both of these variants. A retrospective study of >18 million AC2 results tested between 2018 and 2019 did not display a decrease in CT positivity.

Conclusions
Although we did not detect the Fl-nvCT variant among US specimens, we show evidence that the low occurrence of similar diagnostic-escape mutants can be detected with an updated AC2 assay using multiple 23S rRNA targets.
Cerebral Blood Flow of the Frontal Lobe in Untreated Children with Trigonocephaly versus Healthy Controls: An Arterial Spin Labeling Study
Authors: de Planque Catherine A. , Petr Jan , Gaillard Linda , Mutsaerts Henk J. M. M. , van Veelen Marie-Lise C. , Versnel Sarah L. , Dremmen Marjolein H. G. , Mathijssen Irene M. J. 
Published: February 2022

Background:
Craniofacial surgery is the standard treatment for children with moderate to severe trigonocephaly. The added value of surgery to release restriction of the frontal lobes is unproven, however. In this study, the authors aim to address the hypothesis that the frontal lobe perfusion is not restricted in trigonocephaly patients by investigating cerebral blood flow.

Methods:
Between 2018 and 2020, trigonocephaly patients for whom a surgical correction was considered underwent magnetic resonance imaging brain studies with arterial spin labeling to measure cerebral perfusion. The mean value of cerebral blood flow in the frontal lobe was calculated for each subject and compared to that of healthy controls.

Results:
Magnetic resonance imaging scans of 36 trigonocephaly patients (median age, 0.5 years; interquartile range, 0.3; 11 female patients) were included and compared to those of 16 controls (median age, 0.83 years; interquartile range, 0.56; 10 female patients). The mean cerebral blood flow values in the frontal lobe of the trigonocephaly patients (73.0 ml/100 g/min; SE, 2.97 ml/100 g/min) were not significantly different in comparison to control values (70.5 ml/100 g/min; SE, 4.45 ml/100 g/min; p = 0.65). The superior, middle, and inferior gyri of the frontal lobe showed no significant differences either.

Conclusions:
The authors’ findings suggest that the frontal lobes of trigonocephaly patients aged less than 18 months have a normal cerebral blood flow before surgery. In addition to the very low prevalence of papilledema or impaired skull growth previously reported, this finding further supports the authors’ hypothesis that craniofacial surgery for trigonocephaly is rarely indicated for signs of raised intracranial pressure or restricted perfusion for patients younger than 18 months.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Risk, II.
Traumatic brain injury provokes low fibrinolytic activity in severely injured patients
Authors: Meizoso Jonathan P. , Moore Hunter B. , Moore Ernest E. , Gilna Gareth P. , Ghasabyan Arsen , Chandler James , Pieracci Fredric M. , Sauaia Angela 
Published: February 2022

Background
Traumatic brain injury (TBI) in combination with shock has been associated with hypocoagulability. However, recent data suggest that TBI itself can promote a systemic procoagulant state via the release of brain-derived extracellular vesicles. The objective of our study was to identify if TBI was associated with differences in thrombelastography indices when controlling for other variables associated with coagulopathy following trauma. We hypothesized that TBI is independently associated with a less coagulopathic state.

Methods
Prospective study includes all highest-level trauma activations at an urban Level I trauma center, from 2014 to 2020. Traumatic brain injury was defined as Abbreviated Injury Scale head score greater than 3. Blood samples were drawn at emergency department admission. Linear regression was used to assess the role of independent predictors on trauma induced coagulopathy. Models adjusted for Injury Severity Score (ISS), shock (defined as ED SBP<70, or ED SBP<90 and ED HR>108, or first hospital base deficit >10), and prehospital Glasgow Coma Scale score.

Results
Of the 1,023 patients included, 291 (28%) suffered a TBI. Traumatic brain injury patients more often were female (26% vs. 19%, p = 0.01), had blunt trauma (83% vs. 43%, p < 0.0001), shock (33% vs. 25%, p = 0.009), and higher median ISS (29 vs. 10, p < 0.0001). Fibrinolysis shutdown (25% vs. 18%) was more common in the TBI group (p < 0.0001). When controlled for the confounding effects of ISS and shock, the presence of TBI independently decreases lysis at 30 minutes (LY30) (beta estimate: −0.16 ± 0.06, p = 0.004). This effect of TBI on LY30 persisted when controlling for sex and mechanism of injury in addition to ISS and shock (beta estimate: −0.13 ± 0.06, p = 0.022).

Conclusion
Traumatic brain injury is associated with lower LY30 independent of shock, tissue injury, sex, and mechanism of injury. These findings suggest a propensity toward a hypercoagulable state in patients with TBI, possibly due to fibrinolysis shutdown.

LEVEL OF EVIDENCE
Prognostic and Epidemiologic; Level III.