bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a Sensitive and High-Throughput Assay for Simultaneous Quantification of 5 Tyrosine Kinase Inhibitors and 2 Active Metabolites in Human Plasma Using Ultra-high Performance Liquid Chromatography Coupled to Tandem Mass Spectrometry
Authors: Sumimoto Takahiro , Nakahara Ryosuke , Suzuki Yosuke , Tanaka Ryota , Yoshida Natsumi , Ogata Masao , Itoh Hiroki 
Published: September 2021

Background:
Breakpoint cluster region-Abelson (BCR-ABL) tyrosine kinase inhibitors (TKIs) demonstrate improved therapeutic efficacy in chronic myeloid leukemia (CML). However, drug–drug interactions, nonadherence, and host-related factors may influence plasma concentrations. Therefore, therapeutic drug monitoring may be necessary for patients presenting inadequate treatment responses or adverse events. Herein, the authors aimed to develop a more sensitive and high-throughput method than those previously reported to simultaneously quantify 5 TKIs (imatinib, nilotinib, dasatinib, bosutinib, and ponatinib) and 2 active metabolites (N-desmethyl imatinib and N-desmethyl ponatinib) using ultra-performance liquid chromatography coupled with tandem mass spectrometry.

Methods:
Plasma samples were prepared according to a solid-phase extraction protocol using an Oasis MCX µElution plate. The assay fulfilled the requirements of the US Food and Drug Administration for assay validation, with a lower limit of quantification of 0.2 ng/mL for dasatinib, 0.3 ng/mL for N-desmethyl ponatinib, 0.5 ng/mL for N-desmethyl imatinib, bosutinib, and ponatinib, and 2.5 ng/mL for imatinib and nilotinib.

Results:
Within-batch and batch-to-batch precision at the lower limit of quantification and quality control levels were within 14.3% and 10.9%, respectively. Within-batch and batch-to-batch accuracies ranged from 15.5% to 13.0% and 5.70% to 7.03%, respectively. A positive electrospray ionization mode was used with a run time of 6.0 minutes. The assay applicability was verified by the successful measurement of 78 clinical samples from patients undergoing CML therapy.

Conclusions:
The method allows assessment of trough concentrations of TKIs and active metabolites in patients with CML, and hence can be used to assess blood samples in routine clinical settings.
Impact of sleep disturbances on employment and work productivity among midlife women in the US SWAN database: a brief report
Authors: Kagan Risa , Shiozawa Aki , Epstein Andrew J. , Espinosa Robert 
Published: September 2021

Abstract

Objective:
Menopause is associated with an increased prevalence of sleep difficulties. We evaluated the economic burden of sleep disturbances among working midlife women.

Methods:
This retrospective, longitudinal cohort study collected data from the US Study of Women's Health Across the Nation (SWAN) database of women age 42-52 years at enrollment. We assessed the association between sleep disturbances (trouble falling asleep, waking early, or nocturnal awakenings) and workplace productivity (employment [yes/no] and work hours/wk) for women who were employed at the baseline visit and had ≥1 follow-up visit. We estimated overall economic burden by multiplying changes in productivity by median age-specific hourly US wages. Each woman's data were compared from visit to visit and were excluded after the first observed unemployment. Regression analysis was used to estimate associations between changes in sleep and changes in workplace productivity while controlling for relevant characteristics that varied over time.

Results:
The analysis included 2,489 working women (19,707 visits); 31% became unemployed during follow-up. Risk of unemployment was 31% higher for women with versus without new-onset sleep disturbances (P
= 0.0474). Onset of sleep disturbances was associated with a 0.44-0.57 hours/wk reduction in work time (not significant). Using the more conservative reduction (0.44 h), sleep problems were associated with an annual loss of $517 to $524 per woman and $2.2 billion/yr in lost productivity among women age 42-64 nationwide.

Conclusions:
New-onset sleep problems in midlife women are associated with significant increases in risk of unemployment and ∼$2 billion/yr in lost productivity nationwide.

Video Summary:
http://links.lww.com/MENO/A798.
Self-care agency and associated factors in postmenopausal women
Authors: Bastos-Silva Yasmin , Aguiar Luiza Borges , Pacello Poliana , Baccaro Luiz Francisco , Orcesi Pedro Adriana , Costa-Paiva Lúcia 
Published: September 2021

Abstract

Objective:
The aging process in women is marked by several changes, including the transition to menopause. The evaluation of self-care management is essential and has great relevance for public health. The aim of the present study was to evaluate self-care management and associated factors in postmenopausal women.

Method:
This study was a cross-sectional study performed with 260 postmenopausal women who attended routine consultations at the Menopause Outpatient Clinic of the Hospital of the State University of Campinas-SP. Women aged 50 years or older with amenorrhea for at least 12 months were included. The women were interviewed by a researcher during the routine consultation, and the self-care agency assessment was performed using the Appraisal of Self-Care Agency Scale-Revised questionnaire.

Results:
The average total self-care score for the women in this study was 62.27 (± 9.64). Higher Appraisal of Self-Care Agency Scale-Revised scores were associated with performing outdoor activities, better self-perceived health, and a higher score on knowledge about vitamin D. Active smoking was associated with a lower self-care score.

Conclusion:
We observed that the self-care management of postmenopausal women was satisfactory and was associated with lifestyle, self-perceived health, and knowledge about vitamin D.
LONG-TERM VISUAL OUTCOMES AND THE TIMING OF SURGICAL REPAIR OF FOVEA-SPLITTING RHEGMATOGENOUS RETINAL DETACHMENTS
Authors: Lee Ramon , Shields Ryan A. , Maywood Michael J. , Nemeth Cire , Wa Christianne A. , Williams George A. , Hassan Tarek S. , Garretson Bruce R. , Capone Antonio , Ruby Alan J. , Drenser Kimberly A. , Faia Lisa J. , Randhawa Sandeep , Mahmoud Tamer H. , Wolfe Jeremy D. 
Published: September 2021

Purpose:
To evaluate the visual outcomes and the affect of timing of surgical repair of fovea-splitting rhegmatogenous retinal detachments.

Method:
A retrospective, consecutive cohort from multiple surgeons at a single center. Fovea status (fovea-on, fovea-splitting, or fovea-off) was classified by preoperative optical coherence tomography. The primary outcome measure was the visual acuity at the last follow-up that was further correlated with the timing of surgical repair.

Results:
One hundred and ninety-five eyes were included with 62 fovea-on, 65 fovea-splitting, and 68 fovea-off detachments. The mean preoperative logarithm of the minimum angle of resolution visual acuity for fovea-on, fovea-splitting, and fovea-off groups was 0.16 ± 0.21, 0.70 ± 0.56, and 1.67 ± 0.87, respectively (P = <0.001). Mean postoperative logarithm of the minimum angle of resolution visual acuity for fovea-on, fovea-splitting, and fovea-off groups were 0.07 ± 0.13, 0.10 ± 0.15, and 0.20 ± 0.22, respectively (P = <0.001). A statistically significant difference in mean postoperative logMAR visual acuity was found between fovea-off and fovea-on groups (P = 0.003) and between fovea-off and fovea-splitting groups (P = 0.013), however not between fovea-on and fovea-splitting groups (P = 0.827). Visual acuity improved when repair was performed earlier after presentation for fovea-on (R = 0.378, P = 0.002) and fovea-off groups (R = 0.277, P = 0.022), but not for the fovea-splitting group (R = 0.089, P = 0.481).

Conclusion:
We described the favorable visual outcomes of surgery for fovea-splitting rhegmatogenous retinal detachment and correlated these with the timing of surgical repair, which may help guide the management of this urgent, vision-threatening condition.
STEP-WISE APPROACH TO THE MANAGEMENT OF SUBMACULAR HEMORRHAGE USING PNEUMATIC DISPLACEMENT AND VITRECTOMY
Authors: Chew Grace W. M. , Ivanova Tsveta , Patton Niall , Dhawahir-Scala Felipe , Jasani Kirti M. , Turner George , Charles Stephen , Jalil Assad 
Published: September 2021

Purpose:
To evaluate a sequential approach of pneumatic displacement followed by vitrectomy (pars plana vitrectomy) in failed cases to deal with submacular hemorrhage (SMH) of various etiologies.

Methods:
Retrospective, nonrandomized interventional case series of consecutive patients with SMH of up to 2 weeks’ duration, who were treated with a stepwise approach. Step 1 involved intravitreal injection of 0.3 mL 100% C3F8 and recombinant tissue plasminogen activator 50 μg/0.1 mL. If unsuccessful, a prompt pars plana vitrectomy with subretinal recombinant tissue plasminogen activator 50 μg/0.1 mL and 20% SF6 gas tamponade was performed as a second attempt to displace the SMH.

Results:
Thirty-one patients with SMH underwent pneumatic displacement; 24 (77.4%) had a successful outcome without further intervention. The mean presenting visual acuity of the “successful cohort” was 1.34 logMAR (20/440 Snellen), improving to 0.83 logMAR (20/135 Snellen) 1 month after treatment. Five of the seven patients with failed pneumatic displacement underwent pars plana vitrectomy with subretinal recombinant tissue plasminogen activator at an average of 5 days poststep 1, with successful SMH displacement in 3 patients, giving an overall success of 87.1% for this treatment protocol.

Conclusion:
A sequential approach of expansile gas injection followed by prompt pars plana vitrectomy, aided by recombinant tissue plasminogen activator at both steps, is a coherent, logical pathway to treat SMH with high anatomical and functional success.
Corneal Nerve Fiber and Sensitivity Loss After Repeated Intravitreal Anti-VEGF Injections: An In Vivo Confocal Microscopy Study
Authors: Polat Osman Ahmet , Şener Hidayet , Erkiliç Kuddusi 
Published: September 2021

Purpose:
The purpose of this study was to investigate corneal sensation, subbasal nerve plexus (SBNP), and ocular surface symptoms in patients who underwent multiple intravitreal antivascular endothelial growth factor (anti-VEGF) injections for age-related macular degeneration (AMD) and diabetic macular edema (DME).

Methods:
Forty patients with previous anti-VEGF intravitreal injections (20 AMD and 20 DME) and 30 healthy controls were included in this study. In vivo corneal confocal microscopy (IVCM) of the SBNP, corneal sensitivity measurement with a Cochet–Bonnet esthesiometer, noninvasive tear break-up times, and ocular surface disease score index (OSDI) calculation were performed for each participant. Corneal nerve fiber density, corneal nerve branch density, total length of all nerve fibers, corneal total branch density, corneal nerve fiber area, corneal nerve fiber width, and corneal nerve fiber fractal dimension parameters were obtained by automatic digital analysis.

Results:
Corneal nerve fiber density, corneal nerve branch density, total length of all nerve fibers, and corneal nerve fiber fractal dimension in IVCM imaging and corneal sensitivity were significantly decreased in both AMD and DME groups compared with the control group. Corneal nerve fiber width and OSDI scores were significantly increased in AMD and DME groups compared with the control group. None of the IVCM parameters were significantly different between AMD and DME groups. Corneal sensitivity was decreased in patients with DME compared with patients with AMD. Tear break-up time was not different among the groups.

Conclusions:
Corneal SBNP parameters were affected, corneal sensitivity was decreased, and OSDI scores were increased in patients with multiple intravitreal anti-VEGF injections. IVCM parameters were not significantly different between AMD and DME groups.
Thermokeratoplasty for Keratoconus: A More Than 30-Year Follow-Up Study
Authors: Itoi Motohiro , Higashihara Hisayo , Yamagishi Keiko , Hyakutake Yoko , Okahisa Takashi , Matui Futoshi , Nakayama Toshio , Sotozono Chie 
Published: September 2021

Purpose:
The aim of this study was to investigate the long-term outcomes of thermokeratoplasty (TKP) surgery in patients with keratoconus (KC).

Methods:
We retrospectively reviewed our clinical database of 2949 patients with KC seen at the Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan, between April 1979 and December 1991. Patients with KC who underwent TKP with a greater-than 30-year postoperative follow-up were included. The occurrence of adverse events including infectious keratitis, corneal perforation, corneal melting, bullous keratopathy, consistency of contact lenses (CL) wear at the final visit, and a history of corneal transplantation post-TKP was assessed.

Results:
Forty-two patients (29 male and 13 female patients) with a mean age at initial visit of 23.4 years (range: 13.9–39.5 yrs) were included, and TKP was performed unilaterally in all cases. The mean follow-up period was 35.2 years (range: 30.1–41.6 yrs). As for adverse events/complications, no cases of infectious keratitis, corneal perforation, corneal melting, and/or BK were observed. However, 11 eyes received corneal transplants at an average of 24.9 years postoperatively because of the inability to wear CL continuously. At the last visit, 31 eyes were able to continue wearing CL without corneal transplantation, and the remaining 11 eyes were able to continue wearing contact lenses in all cases after corneal transplantation.

Conclusions:
TKP for KC resulted in relatively favorable surgical outcomes over the long-term postoperative period.
Posterior Polymorphous Corneal Dystrophy in a Pediatric Population
Authors: Elhusseiny Abdelrahman M. , Saeed Hajirah N. 
Published: September 2021

Purpose:
The aim of this study was to evaluate the clinical and topographic features of posterior polymorphous corneal dystrophy (PPCD) in children aged 15 years or younger with a long-term follow-up. Retrospective case series.

Methods:
A retrospective chart review of patients who were diagnosed with PPCD at Boston Children's Hospital from 1999 to 2020 was performed. Data collected included age at the time of diagnosis, slit lamp findings, cycloplegic refraction, best-corrected visual acuity, central corneal thickness, specular microscopy, and corneal topography findings whenever available.

Results:
Twenty-seven eyes of 19 patients were included (11 unilateral and 8 bilateral cases). Ten patients were girls (52.6%). Left eye was affected in 14 eyes. The mean age at the time of diagnosis was 8.5 ± 3.3 years, with a mean follow-up of 5.3 years. In unilateral cases, there was a statistically significant difference in the endothelial cell density (P = 0.01), coefficient variation (P = 0.03), and hexagonality (P = 0.01) between the affected and the contralateral unaffected eyes. The mean best-corrected visual acuity at initial presentation was 0.8 ± 0.2 compared with 0.9 ± 0.08 in unaffected eyes (P = 0.04). The mean astigmatism was higher in the affected eye (+1.7 diopters) compared with (+1.00) the unaffected eye (P = 0.07). At initial presentation, 7 of 27 eyes had amblyopia, which resolved, either partially or completely, in 5 eyes after treatment.

Conclusions:
PPCD can present early in children with astigmatism and anisometropic amblyopia. A careful slit lamp examination for children presenting with anisoastigmatism is necessary to diagnose PPCD. Contrary to adults, presentation is often unilateral. Such patients should be followed up regularly with cycloplegic retinoscopy to prevent and treat refractive amblyopia if present.
Epithelial ingrowth after LASIK September consultation #1
Authors: Nuijts Rudy M.M.A. , Kartal Serdar 
Published: September 2021

A 62-year-old woman presented to our clinic in April 2021 with a painful right eye and increased light sensitivity for 1 week, 30 years after laser in situ keratomileusis (LASIK) in both eyes for myopia of −2.5 diopters. There were no complaints of the left eye. There were no abnormalities in her medical history. The uncorrected distance visual acuity (UDVA) of the right eye at presentation was 20/20.
Slitlamp biomicroscopy revealed epithelial ingrowth on the right eye with stromal edema and inflammation and fine keratic precipitates on the endothelium (Figures 1 and 2

JOURNAL/jcrs/04.03/02158034-202109000-00024/figure1/v/2023-08-19T002615Z/r/image-tiff

JOURNAL/jcrs/04.03/02158034-202109000-00024/figure2/v/2023-08-19T002615Z/r/image-tiff

). The cornea of the left eye was unremarkable. The anterior chamber of the right eye showed 1 + cells (SUN grading). There were no abnormalities in the posterior segment. Figure 3

JOURNAL/jcrs/04.03/02158034-202109000-00024/figure3/v/2023-08-19T002615Z/r/image-tiff

shows the corneal epithelial ingrowth with a swept-source optical coherence tomography (OCT) and Figure 4

JOURNAL/jcrs/04.03/02158034-202109000-00024/figure4/v/2023-08-19T002615Z/r/image-tiff

an axial corneal Scheimpflug tomography map.
What is your treatment advice for this patient from a short- and long-term perspective?
Anorectal malignant melanoma with multiple organ metastases
Authors: Zheng Honghong , Song Jia , Li Jianjun , Zheng Shuai , Zhao Enhong 
Published: September 2021

Abstract

Introduction:
Anal malignant melanoma (ARMM) is a fatal malignancy with high malignant potential and poor patient prognosis. The ARMM incidence account for 0.4% to 1.6% of all malignant melanomas (MM), and 37% of patients already have distant or local metastases during the initial diagnosis. However, the low ARMM incidence and the lack of definitive studies have led to a very high rate of misdiagnosis and missed diagnosis. This case report describes brain metastasis and liver metastasis in ARMM patient.

Patient Concerns:
The patient, a 49-year-old Chinese male, was admitted to the hospital because of altered defecation habits for four years, hematochezia, and difficult defecation for 2 months.

Diagnoses:
Rectal palpation found a mass 2 cm from the anus. Colonoscopy revealed an infiltrative growing mass 2 cm from the anus. Pathological results confirmed MM. The diagnosis was Rectal MM with incomplete intestinal obstruction.

Interventions:
The patient underwent laparoscopic assisted combined abdominal perineal resection under general anesthesia.

Outcomes:
On the second day after surgery, the patient developed sensory impairment and motor dysfunction in the right upper extremity. Cranial computed tomography and magnetic resonance imaging suggested multiple occupying lesions in the brain. On the eighth postoperative day, the patient's condition deteriorated. The patient died after a one-month follow-up.

Conclusions:
This study describes a ARMM patient with brain and liver metastases that was diagnosed late. Pathology combined with immunohistochemistry is important to diagnose ARMM and proper auxiliary examinations can help in early diagnosis.
Traumatic Brain Injury in Children
Authors: Ryan Emer , Kelly Lynne , Stacey Catherine , Duff Eimear , Huggard Dean , Leonard Ann , Boran Gerard , McCollum Danielle , Doherty Dermot , Bolger Turlough , Molloy Eleanor J. 
Published: September 2021

ObjectivesGlial fibrillary acidic protein (GFAP) is a neuronal protein released after traumatic brain injury (TBI) and detectable in serum samples. GFAP correlates with symptom severity in adults and may be a marker of brain injury in children with milder symptoms or preverbal children.MethodsGFAP was examined in children with severe TBI (initial Glasgow Coma Scale score <8), with mild TBI (Glasgow Coma Scale score 14/15), and at 0 to 4 and at 10 to 14 days after TBI and was compared with healthy age-matched controls. Mechanism, time points from injury, and symptoms were recorded.ResultsThe study enrolled 208 children including 110 with TBI (n = 104 mild, 6 severe) and controls (n = 98). GFAP was higher in mild TBI than in controls and highest in the severe TBI cohort, with a maximum value at 6 hours from injury. Vomiting was significantly associated with higher GFAP levels, but no association was found with amnesia, loss of consciousness, and the Sports Concussion Assessment Tool. Children reporting >1-point changes from their preinjury functioning on the Post-Concussive Symptom Inventory had higher initial GFAP but not total Post-Concussive Symptom Inventory score changes.ConclusionsGFAP identifies children with TBI, even at the milder end of the spectrum, and is strongly associated with postinjury vomiting. It may be a useful marker of pediatric TBI; however, sampling is time critical.
Personalized Chest Computed Tomography
Authors: May Matthias , Heiss Rafael , Koehnen Julia , Wetzl Matthias , Wiesmueller Marco , Treutlein Christoph , Braeuer Lars , Uder Michael , Kopp Markus 
Published: September 2021

Objectives
The purpose of this study was to evaluate the minimum diagnostic radiation dose level for the detection of high-resolution (HR) lung structures, pulmonary nodules (PNs), and infectious diseases (IDs).

Materials and Methods
A preclinical chest computed tomography (CT) trial was performed with a human cadaver without known lung disease with incremental radiation dose using tin filter-based spectral shaping protocols. A subset of protocols for full diagnostic evaluation of HR, PN, and ID structures was translated to clinical routine. Also, a minimum diagnostic radiation dose protocol was defined (MIN). These protocols were prospectively applied over 5 months in the clinical routine under consideration of the individual clinical indication. We compared radiation dose parameters, objective and subjective image quality (IQ).

Results
The HR protocol was performed in 38 patients (43%), PN in 21 patients (24%), ID in 20 patients (23%), and MIN in 9 patients (10%). Radiation dose differed significantly among HR, PN, and ID (5.4, 1.2, and 0.6 mGy, respectively; P < 0.001). Differences between ID and MIN (0.2 mGy) were not significant (P = 0.262). Dose-normalized contrast-to-noise ratio was comparable among all groups (P = 0.087). Overall IQ was perfect for the HR protocol (median, 5.0) and decreased for PN (4.5), ID-CT (4.3), and MIN-CT (2.5). The delineation of disease-specific findings was high in all dedicated protocols (HR, 5.0; PN, 5.0; ID, 4.5). The MIN protocol had borderline IQ for PN and ID lesions but was insufficient for HR structures. The dose reductions were 78% (PN), 89% (ID), and 97% (MIN) compared with the HR protocols.

Conclusions
Personalized chest CT tailored to the clinical indications leads to substantial dose reduction without reducing interpretability. More than 50% of patients can benefit from such individual adaptation in a clinical routine setting. Personalized radiation dose adjustments with validated diagnostic IQ are especially preferable for evaluating ID and PN lesions.