bluuebunny/crossref_metadata_2025 huggingface dataset:
Adequate versus deep response to ursodeoxycholic acid in primary biliary cholangitis: To what extent and under what conditions is normal alkaline phosphatase level associated with complication-free survival gain?
Authors: Corpechot Christophe , Lemoinne Sara , Soret Pierre-Antoine , Hansen Bettina , Hirschfield Gideon , Gulamhusein Aliya , Montano-Loza Aldo J. , Lytvyak Ellina , Pares Albert , Olivas Ignasi , Eaton John E. , Osman Karim T. , Schramm Christoph , Sebode Marcial , Lohse Ansgar W. , Dalekos George , Gatselis Nikolaos , Nevens Frederik , Cazzagon Nora , Zago Alessandra , Russo Francesco Paolo , Floreani Annarosa , Abbas Nadir , Trivedi Palak , Thorburn Douglas , Saffioti Francesca , Barkai Laszlo , Roccarina Davide , Calvaruso Vicenza , Fichera Anna , Delamarre Adèle , Sobenko Natalia , Villamil Alejandra Maria , Medina-Morales Esli , Bonder Alan , Patwardhan Vilas , Rigamonti Cristina , Carbone Marco , Invernizzi Pietro , Cristoferi Laura , van der Meer Adriaan , de Veer Rozanne , Zigmond Ehud , Yehezkel Eyal , Kremer Andreas E. , Deibel Ansgar , Bruns Tony , Große Karsten , Wetten Aaron , Dyson Jessica Katharine , Jones David , Dumortier Jérôme , Pageaux Georges-Philippe , de Lédinghen Victor , Chazouillères Olivier , Carrat Fabrice ,   the Global & ERN Rare-Liver PBC Study Groups
Published: September 2023

Background and Aims:

Normal alkaline phosphatase (ALP) levels in ursodeoxycholic acid (UDCA)-treated patients with primary biliary cholangitis (PBC) are associated with better long-term outcome. However, second-line therapies are currently recommended only when ALP levels remain above 1.5 times the upper limit of normal (×ULN) after 12-month UDCA. We assessed whether, in patients considered good responders to UDCA, normal ALP levels were associated with significant survival gains.

Approach and Results:

We performed a retrospective cohort study of 1047 patients with PBC who attained an adequate response to UDCA according to Paris-2 criteria. Time to liver-related complications, liver transplantation, or death was assessed using adjusted restricted mean survival time (RMST) analysis. The overall incidence rate of events was 17.0 (95% CI: 13.7–21.1) per 1000 out of 4763.2 patient-years. On the whole population, normal serum ALP values (but not normal gamma-glutamyl transpeptidase (GGT), alanine aminotransferase (ALT), or aspartate aminotransferase (AST); or total bilirubin < 0.6 ×ULN) were associated with a significant absolute complication-free survival gain at 10 years (mean 7.6 months, 95% CI: 2.7 - 12.6 mo.; p = 0.003). In subgroup analysis, this association was significant in patients with a liver stiffness measurement ≥ 10 kPa and/or age ≤ 62 years, with a 10-year absolute complication-free survival gain of 52.8 months (95% CI: 45.7–59.9, p < 0.001) when these 2 conditions were met.

Conclusions:

PBC patients with an adequate response to UDCA and persistent ALP elevation between 1.1 and 1.5 ×ULN, particularly those with advanced fibrosis and/or who are sufficiently young, remain at risk of poor outcome. Further therapeutic efforts should be considered for these patients.
Canonical Wnt signaling promotes HSC glycolysis and liver fibrosis through an LDH-A/HIF-1α transcriptional complex
Authors: Wang Feixia , Chen Li , Kong Desong , Zhang Xiaojin , Xia Siwei , Liang Baoyu , Li Yang , Zhou Ya , Zhang Zili , Shao Jiangjuan , Zheng Shizhong , Zhang Feng
Published: September 2023

Background and Aims:

Aerobic glycolysis reprogramming occurs during HSC activation, but how it is initiated and sustained remains unknown. We investigated the mechanisms by which canonical Wnt signaling regulated HSC glycolysis and the therapeutic implication for liver fibrosis.

Approach and Results:

Glycolysis was examined in HSC-LX2 cells upon manipulation of Wnt/β-catenin signaling. Nuclear translocation of lactate dehydrogenase A (LDH-A) and its interaction with hypoxia-inducible factor-1α (HIF-1α) were investigated using molecular simulation and site-directed mutation assays. The pharmacological relevance of molecular discoveries was intensified in primary cultures, rodent models, and human samples. HSC glycolysis was enhanced by Wnt3a but reduced by β-catenin inhibitor or small interfering RNA (siRNA). Wnt3a-induced rapid transactivation and high expression of LDH-A dependent on TCF4. Wnt/β-catenin signaling also stimulated LDH-A nuclear translocation through importin β2 interplay with a noncanonical nuclear location signal of LDH-A. Mechanically, LDH-A bound to HIF-1α and enhanced its stability by obstructing hydroxylation-mediated proteasome degradation, leading to increased transactivation of glycolytic genes. The Gly28 residue of LDH-A was identified to be responsible for the formation of the LDH-A/HIF-1α transcription complex and stabilization of HIF-1α. Furthermore, LDH-A-mediated glycolysis was required for HSC activation in the presence of Wnt3a. Results in vivo showed that HSC activation and liver fibrosis were alleviated by HSC-specific knockdown of LDH-A in mice. β-catenin inhibitor XAV-939 mitigated HSC activation and liver fibrosis, which were abrogated by HSC-specific LDH-A overexpression in mice with fibrosis.

Conclusions:

Inhibition of HSC glycolysis by targeting Wnt/β-catenin signaling and LDH-A had therapeutic promise for liver fibrosis.
Spatial proteomics of immune microenvironment in nonalcoholic steatohepatitis-associated hepatocellular carcinoma
Authors: Li Meiyi , Wang Lina , Cong Liang , Wong Chi Chun , Zhang Xiang , Chen Huarong , Zeng Tao , Li Bin , Jia Xian , Huo Jihui , Huang Yuhua , Ren Xiaoxue , Peng Sui , Fu Guo , Xu Lixia , Sung Joseph J.Y. , Kuang Ming , Li Xiaoxing , Yu Jun
Published: September 2023

Background and Aims:

NASH-HCC is inherently resistant to immune checkpoint blockade, but its tumor immune microenvironment is largely unknown.

Approach and Results:

We applied the imaging mass cytometry to construct a spatially resolved single-cell atlas from the formalin-fixed and paraffin-embedded tissue sections from patients with NASH-HCC, virus-HCC (HBV-HCC and HCV-HCC), and healthy donors. Based on 35 biomarkers, over 750,000 individual cells were categorized into 13 distinct cell types, together with the expression of key immune functional markers. Higher infiltration of T cells, myeloid-derived suppressor cell (MDSCs), and tumor-associated macrophages (TAMs) in HCC compared to controls. The distribution of immune cells in NASH-HCC is spatially heterogeneous, enriched at adjacent normal tissues and declined toward tumors. Cell-cell connections analysis revealed the interplay of MDSCs and TAMs with CD8+ T cells in NASH-HCC. In particular, exhausted programmed cell death 1 (PD-1+)CD8+ T cells connected with programmed cell death-ligand 1 (PD-L1+)/inducible T cell costimulator (ICOS+) MDSCs and TAMs in NASH-HCC, but not in viral HCC. In contrast, CD4+/CD8+ T cells with granzyme B positivity were reduced in NASH-HCC. Tumor cells expressed low PD-L1 and showed few connections with immune cells.

Conclusions:

Our work provides the first detailed spatial map of single-cell phenotypes and multicellular connections in NASH-HCC. We demonstrate that interactions between MDSCs and TAMs with effector T cells underlie immunosuppression in NASH-HCC and are an actionable target.
National prevalence estimates for steatotic liver disease and subclassifications using consensus nomenclature
Authors: Lee Brian P. , Dodge Jennifer L. , Terrault Norah A.
Published: September 2023

Background and Aims:

The multisociety consensus nomenclature has renamed NAFLD to steatotic liver disease (SLD) with various subclassifications. There is a paucity of data regarding how the new nomenclature modifies our understanding of disease prevalence and patient phenotypes.

Approach and Results:

Using the National Health and Nutrition Examination Survey from January 2017 to March 2020, we included all participants aged 18 years or above with complete vibration-controlled transient elastography measures. SLD and its subclassifications [metabolic dysfunction-associated SLD (MASLD), MASLD + increased alcohol intake (MetALD), alcohol-associated liver disease (ALD), etiology-specific/cryptogenic] were defined according to consensus nomenclature. National SLD prevalence and subclassifications were estimated, and among key subgroups [age, sex, race/ethnicity, advanced liver fibrosis (liver stiffness measurement [LSM] ≥11.7 kPa)]. Among 7367 participants, 2549 had SLD (mean age 51 y, 57.7% male, 63.2% non-Hispanic White). The estimated prevalence of SLD was 34.2% (95% CI 31.9%–36.5%): MASLD 31.3% (29.2%–33.4%), MetALD 2% (1.6%–2.9%), ALD 0.7% (0.5–0.9%), etiology-specific/cryptogenic 0.03% (0.01%–0.08%). In exploratory analyses, participants classified as non-SLD with (vs. without) advanced fibrosis had a higher mean number of metabolic risk factors [2.7 (2.3–3.1) vs. 2.0 (1.9–2.0)] and a higher proportion with average alcohol use ≥20 g/d (women)/≥30 g/d (men) [20.9% (6.2%–51.3%) vs. 7.2% (6.1%–8.4%)]. In another exploratory analysis, increasing quantities of alcohol use remaining below the threshold for MASLD + increased alcohol intake were associated with advanced liver fibrosis in men, but not women. There was 99% overlap in cases of NAFLD and MASLD.

Conclusions:

Our findings highlight the utility of the new consensus nomenclature to address deficiencies present with the old nomenclature, and identify areas that require research to further refine classifications of SLD.
Physiologic changes in the hepatopulmonary syndrome before and after liver transplant: A longitudinal and predictor analysis
Authors: Zhao Xun , Kotha Sreelakshmi , Nayyar Dhruv , Ma Xiayi , Lilly Leslie , Castel Hélène , Gupta Samir
Published: September 2023

Background and Aims:

Hepatopulmonary syndrome (HPS) is a common complication of liver disease defined by abnormal oxygenation and intrapulmonary vascular dilatation, treated with liver transplantation. Little is known about changes in HPS physiological parameters over time. We sought to describe baseline clinical and physiological characteristics in HPS and their relationships, temporal changes in physiological parameters before and after transplant, and predictors of changes in oxygenation.

Approach and Results:

This was a retrospective cohort study in the Canadian HPS Program (n = 132). Rates of change after diagnosis were: −3.7 (−6.4, −0.96) mm Hg/year for partial pressure of arterial oxygen (PaO2); −26 (−96, 44) m/year for 6-minute walk distance, and 3.3% (−6.6, −0.011) predicted/year for diffusion capacity. Noninvasive shunt of ≥ 20% predicted a slower PaO2 decline by 0.88 (0.36, 1.4) mm Hg/month. We identified 2 PaO2 deterioration classes—“very severe disease, slow decliners” (PaO2 45.0 mm Hg; −1.0 mm Hg/year); and “moderate disease, steady decliners” (PaO2 65.5 mm Hg; −2.5 mm Hg/year). PaO2 increased by 6.5 (5.3, 7.7) mm Hg/month in the first year after transplant. The median time to normalization was 149 (116, 184) days. Posttransplant improvement in PaO2 was 2.5 (0.1, 4.9) mm Hg/month faster for every 10 mm Hg greater pretransplant orthodeoxia.

Conclusions:

We present a large and long longitudinal data analysis in HPS. In addition to rates of physiological decline and improvement before and after liver transplantation, we present novel predictors of PaO2 decline and improvement rates. Our findings enhance our understanding of the natural history of HPS and provide pathophysiologic clues. Importantly, they may assist providers in prognostication and prioritization before and after transplant.
Botryosphaeria dothidea Mycotic Keratitis: A Novel Phytopathogen Causing Human Infection
Authors: Xie Hua-Tao , Cheng Shi-Ming , Wang Jia-Song , Xiao Yu-Ting , Zhang Ming-Chang
Published: September 2023

Purpose:

The aim of this study was to report the first case of mycotic keratitis caused by Botryosphaeria dothidea.

Methods:

A 29-year-old man developed a fungal infection after being hit with chestnut thorns in the left eye. In vivo confocal microscopy, microbial culture, and next-generation sequencing (NGS) were used in the diagnosis of mycotic keratitis.

Results:

The patient was provisionally diagnosed with mycotic keratitis based on IVCM and promptly received local and systemic antifungal treatment with voriconazole and amphotericin B. Although microbial culture failed to identify the pathogen, NGS revealed B. dothidea as the causative agent. Although the infection was quickly contained, corneal perforation still occurred. Owing to the lack of fresh donor corneas, the patient underwent multilayer amniotic membrane and conjunctival pedicle graft surgery. The infection was successfully controlled, and during the 6-month follow-up, the cornea remained clear in the inferotemporal optical zone.

Conclusions:

We report a novel phytopathogen—B. dothidea—causing mycotic keratitis. Our case indicates that B. dothidea responds well to voriconazole and amphotericin therapy. This case broadens the spectrum of fungal keratitis and highlights the application of NGS in identifying molds.
Case of Progressive Keratoconus With Newly Diagnosed Pellucid Marginal Degeneration After Corneal Cross-Linking
Authors: Wileman Justin M. , Price Marianne O. , Price Francis W.
Published: September 2023

Purpose:

The purpose of this study was to document, to our knowledge, the first reported case of keratoconus progression accompanied with newly diagnosed pellucid marginal degeneration after corneal cross-linking (CXL).

Methods:

A novel case of further keratoconus progression plus development of pellucid marginal degeneration in the same eye after CXL was documented with supporting evidence from Scheimpflug and optical coherence tomography imaging.

Results:

A male patient was diagnosed with progressive keratoconus in the left eye and treated with CXL when aged 25 years. Although strongly cautioned not to rub his eyes, he admitted that he continued eye rubbing in association with atopic disease. At a follow-up examination 3.5 years after CXL, progressive keratoconus was detected and pellucid marginal degeneration was newly diagnosed in the left eye. The eye was retreated with CXL.

Conclusions:

This case illustrates that progressive keratoconus and pellucid marginal degeneration can occur in the same eye after CXL and demonstrates the deleterious effects that can develop with continued eye rubbing.
A cognitive–behavioral digital health intervention for sickle cell disease pain in adolescents: a randomized, controlled, multicenter trial
Authors: Palermo Tonya M. , Lalloo Chitra , Zhou Chuan , Dampier Carlton , Zempsky William , Badawy Sherif M. , Bakshi Nitya , Ko Yeon Joo , Nishat Fareha , Stinson Jennifer N.
Published: September 2023

Severe acute and chronic pain are the most common complications of sickle cell disease (SCD). Pain results in disability, psychosocial distress, repeated clinic visits/hospitalizations, and significant healthcare costs. Psychosocial pain interventions that teach cognitive and behavioral strategies for managing pain have been effective in other adolescent populations when delivered in person or through digital technologies. Our aim was to conduct a multisite, randomized, controlled trial to improve pain and coping in youth aged 12 to 18 years with SCD using a digital cognitive–behavioral therapy program (iCanCope with Sickle Cell Disease; iCC-SCD) vs Education control. We enrolled 137 participants (ages 12-18 years, 59% female) and analyzed 111 adolescents (107 caregivers), 54 randomized to Education control and 57 randomized to iCC-SCD. Ninety-two percent of youth completed posttreatment assessments and 88% completed 6-month follow-up. There was a significant effect of treatment group (iCC-SCD vs Education) on reduction in average pain intensity from baseline to 6-month follow-up (b = −1.32, P = 0.009, 95% CI [−2.29, −0.34], d = 0.50), and for the number of days with pain, adolescents in the iCC-SCD group demonstrated fewer pain days compared with the Education group at 6-month follow-up (incident rate ratio = 0.63, P = 0.006, 95% CI [0.30, 0.95], d = 0.53). Treatment effects were also found for coping attempts, momentary mood, and fatigue. Several secondary outcomes did not change with intervention, including anxiety, depression, pain interference, and global impression of change. Future studies are needed to identify effective implementation strategies to bring evidence-based cognitive–behavioral therapy for sickle cell pain to SCD clinics and communities.
Communication and activation in pain to enhance relationships and treat pain with equity (COOPERATE): a randomized clinical trial
Authors: Matthias Marianne S. , Daggy Joanne K. , Perkins Anthony J. , Adams Jasma , Bair Matthew J. , Burgess Diana J. , Eliacin Johanne , Flores Perla , Myers Laura J. , Menen Tetla , Procento Philip , Rand Kevin L. , Salyers Michelle P. , Shanahan Mackenzie L. , Hirsh Adam T.
Published: September 2023

Racialized disparities in chronic pain care are well-documented and persist despite national priorities focused on health equity. Similar disparities have been observed in patient activation (ie, having the knowledge, confidence, and skills to manage one's health). As such, interventions targeting patient activation represent a novel approach to addressing and reducing disparities in pain care. Communication and Activation in Pain to Enhance Relationships and Treat Pain with Equity is a randomized controlled trial of a 6-session telephone-delivered intervention to increase patient activation for Black patients with chronic pain. Two hundred fifty Black patients from a Midwestern Veterans Affairs medical center were randomized to the intervention or attention control. The primary outcome was patient activation; secondary outcomes included communication self-efficacy, pain, and psychological functioning. Outcomes were assessed at baseline and at 3 (primary endpoint), 6, and 9 months (sustained effects). Analyses used an intent-to-treat approach. Compared with baseline, patient activation increased 4.6 points at 3 months (versus +0.13 in control group, 95% CI: 0.48, 7.34; P = 0.03). These improvements in the intervention group were sustained, with +7 from baseline at 6 months and +5.77 at 9 months, and remained statistically significant from the control group. Communication self-efficacy increased significantly relative to the control group from baseline to 3 months. Pain intensity and interference improved at 3 months, but differences were not significant after adjusting for multiple comparisons. Most other secondary outcomes improved, but group differences were not statistically significant after controlling for multiple comparisons. Results suggest that increasing patient activation is a potentially fruitful path toward improving pain management and achieving health equity.
Fibroblasts Derived From Vestibular Schwannoma Express Protumorogenic Markers
Authors: Baruah Paramita , Marshall Jennifer , Jones Philip N. , Major Triin , Pucino Valentina , O'Neil John D. , Nefla Meriam , McGettrick Helen , Monksfield Peter , Irving Richard , Buckley Christopher D.
Published: September 2023

Background and aim

Vestibular schwannomas (VSs), despite being histologically benign, cause significant morbidity because of their challenging intracranial location and the propensity for growth. The role of the stroma and particularly fibroblasts, in the progression of VS, is not completely understood. This study examines the profile of fibroblasts in VS.

Methods

Seventeen patients undergoing surgical excision of VS were recruited into the study. Reverse transcription with quantitative polymerase chain reaction (RT-qPCR) was performed on VS tissue samples and fibroblast-associated molecules examined. Immunofluorescence and immunohistochemistry in VS tissue were used to study the expression of fibroblast markers CD90 and podoplanin in situ. Fibroblast cultures were established from VS, and RT-qPCR analysis was performed on a panel of fibroblast markers on VS and control tissue fibroblasts.

Results

Several fibroblast-associated molecules including members of galectin family and matrix metalloproteinases were found to be expressed in VS tissue on RT-qPCR analysis. In situ, expression of CD90 and podoplanin was observed in VS tissue both on immunohistochemistry and immunofluorescence. RT-qPCR analysis of fibroblasts from VS and control vestibular neuroepithelium (NE) showed a higher expression of several molecules of the galectin and matrix metalloproteinases family on VS fibroblasts compared with NE fibroblasts.

Conclusion

This work examines fibroblasts from VS and shows qualitative differences from NE fibroblasts on RT-qPCR. Further understanding of the fibroblast function in the progression of VS will potentially unveil new targets to manage VS growth.
Diagnostic Efficacy of High-Resolution Computed Tomography Densitometry for Diagnosing Otosclerosis
Authors: Puiggrós Ignacio Viza , Moreno Esther Granell , Dotu César Orús , Agustí Miquel Quer i , Díaz Francesc Larrosa
Published: September 2023

Objectives

The purpose of this study is to evaluate the reliability of temporal bone density measurements for diagnosing otosclerosis.

Materials and methods

A retrospective case-control study is presented. Bone density was measured in Hounsfield units (HUs) by using high-resolution computed tomography in eight regions of interest (ROI) where otosclerotic foci are usually localized. The density of 113 otosclerotic ears was compared with that of 33 nonotosclerotic ears to determine sensitivity and specificity. Furthermore, the binormal receiver operating characteristic curve of each ROI's density was calculated to estimate the diagnostic value for osteosclerosis. In addition, the radiological density of seven cases—where radiological visual examination exhibited no findings but surgery confirmed stapes fixation—was compared with nonotosclerotic controls.

Results

ROI densities were significantly lower in otosclerotic patients compared with nonotosclerotic controls. The area under the curve of the fissula ante fenestram (FAF) presented the highest diagnostic performance: 1,871 HU cut-off value (area under the curve = 0.986), 96.64% sensitivity, and 100% specificity. Significantly lower densities in the FAF area were observed in the seven cases with negative radiology but intraoperatively confirmed otosclerosis.

Conclusion

The high-resolution computed tomography density of the FAF is a reliable measurement for diagnosing otosclerosis. A value less than 1,871 HU exhibited the highest sensitivity and specificity in a European Caucasian population.
Factors Affecting Performance in Adults With Cochlear Implants: A Role for Cognition and Residual Cochlear Function
Authors: Walia Amit , Shew Matthew A. , Lefler Shannon M. , Ortmann Amanda J. , Durakovic Nedim , Wick Cameron C. , Herzog Jacques A. , Buchman Craig A.
Published: September 2023

Objective

To evaluate the impact of preoperative and perioperative factors on postlinguistic adult cochlear implant (CI) performance and design a multivariate prediction model.

Study Design

Prospective cohort study.

Setting

Tertiary referral center.

Patients and Interventions

Two hundred thirty-nine postlinguistic adult CI recipients.

Main Outcome Measure(s)

Speech-perception testing (consonant-nucleus-consonant [CNC], AzBio in noise +10-dB signal-to-noise ratio) at 3, 6, and 12 months postoperatively; electrocochleography–total response (ECochG-TR) at the round window before electrode insertion.

Results

ECochG-TR strongly correlated with CNC word score at 6 months (r = 0.71, p < 0.0001). A multivariable linear regression model including age, duration of hearing loss, angular insertion depth, and ECochG-TR did not perform significantly better than ECochG-TR alone in explaining the variability in CNC. AzBio in noise at 6 months had moderate linear correlations with Montreal Cognitive Assessment (MoCA; r = 0.38, p < 0.0001) and ECochG-TR (r = 0.42, p < 0.0001). ECochG-TR and MoCA and their interaction explained 45.1% of the variability in AzBio in noise scores.

Conclusions

This study uses the most comprehensive data set to date to validate ECochG-TR as a measure of cochlear health as it relates to suitability for CI stimulation, and it further underlies the importance of the cochlear neural substrate as the main driver in speech perception performance. Performance in noise is more complex and requires both good residual cochlear function (ECochG-TR) and cognition (MoCA). Other demographic, audiologic, and surgical variables are poorly correlated with CI performance suggesting that these are poor surrogates for the integrity of the auditory substrate.
Emerging Mechanisms in the Pathogenesis of Menière’s Disease: Evidence for the Involvement of Ion Homeostatic or Blood–Labyrinthine Barrier Dysfunction in Human Temporal Bones
Authors: Johns J. Dixon , Olszewski Rafal , Strepay Dillon , Lopez Ivan A. , Ishiyama Akira , Hoa Michael
Published: September 2023

Hypothesis

Analysis of human temporal bone specimens of patients with Menière’s disease (MD) may demonstrate altered expression of gene products related to barrier formation and ionic homeostasis within cochlear structures compared with control specimens

Background

MD represents a challenging otologic disorder for investigation. Despite attempts to define the pathogenesis of MD, there remain many gaps in our understanding, including differences in protein expression within the inner ear. Understanding these changes may facilitate the identification of more targeted therapies for MD.

Methods

Human temporal bones from patients with MD (n = 8) and age-matched control patients (n = 8) were processed with immunohistochemistry stains to detect known protein expression related to ionic homeostasis and barrier function in the cochlea, including CLDN11, CLU, KCNJ10, and SLC12A2. Immunofluorescence intensity analysis was performed to quantify protein expression in the stria vascularis, organ of Corti, and spiral ganglion neuron (SGN).

Results

Expression of KCNJ10 was significantly reduced in all cochlear regions, including the stria vascularis (9.23 vs 17.52,p= 0.011), OC (14.93 vs 29.16,p= 0.014), and SGN (7.69 vs 18.85,p= 0.0048) in human temporal bone specimens from patients with MD compared with control, respectively. CLDN11 (7.40 vs 10.88,p= 0.049) and CLU (7.80 vs 17.51,p= 0.0051) expression was significantly reduced in the SGN.

Conclusion

The results of this study support that there may be differences in the expression of proteins related to ionic homeostasis and barrier function within the cochlea, potentially supporting the role of targeted therapies to treat MD.
Assisted reproductive technology outcomes and management considerations for people with epilepsy
Authors: Lemley Regan J. , Voinescu Paula Emanuela
Published: September 2023

Purpose of review

Epilepsy is a common neurologic condition amongst people with reproductive capacity, and assisted reproductive technology (ART) is being increasingly utilized. A recent population-based study described favorable outcomes of ART in this population, but other work shows how fluctuating sex hormones may influence medication concentrations and seizures.

Recent findings

This review discusses hormonal influences on epilepsy and catamenial epilepsy, considerations regarding fertility in women with epilepsy, emerging ART outcomes, and management considerations for people with epilepsy undergoing ART.

Utilizing ART is an effective treatment for people with epilepsy desiring pregnancy, but closer monitoring and antiseizure medication adjustments may be needed to ensure the best outcomes. More research is needed to better guide epilepsy care during ART.
Patient-reported Primary Care Video and Telephone Telemedicine Preference Shifts During the COVID-19 Pandemic
Authors: Millman Andrea , Huang Jie , Graetz Ilana , Lee Catherine , Shan Judy , Hsueh Loretta , Muelly Emilie , Gopalan Anjali , Reed Mary
Published: September 2023

Background:

Patient perceptions of primary care telephone and video telemedicine and whether COVID-19 pandemic-related telemedicine exposure shifted patients’ visit preference is unknown.

Objectives:

We examined patient surveys to understand the health care experience of patients seeking primary care through telemedicine and how patients expected their preferences to shift as a result of the COVID-19 pandemic.

Research Design/Subjects:

In an integrated delivery system that shifted to a “telemedicine-first” health care model during the COVID-19 pandemic, we sampled monthly and collected 1000 surveys from adults with primary care telemedicine visits scheduled through the online patient portal between 3/16/2020 and 10/31/2020.

Measures:

Participants reported their preferred primary care visit modality (telephone, video, or in-person visits) across 3 time points: before, during and (hypothetically) after the COVID-19 pandemic, and reported their general assessment of primary care visits during the pandemic.

Results:

The majority of participants preferred in-person visits before (69%) and after the COVID-19 pandemic (57%). However, most participants reported a preference for telemedicine visits during the pandemic and continue to prefer telemedicine visits at a 12% higher rate post-pandemic. Many participants (63%) expressed interest in using telemedicine at least some of the time. Among participants reporting a recent telemedicine visit, 85% agreed that the visit addressed their health needs.

Conclusion:

As primary care visit modality preferences continue to evolve, patients anticipate that they will continue to prefer telemedicine visits, both video and telephone, at an increased rate than before the COVID-19 pandemic.
An Integrative Review of Response Rates in Nursing Research Utilizing Online Surveys
Authors: L’Ecuyer Kristine M. , Subramaniam Divya S. , Swope Clarissa , Lach Helen W.
Published: September 2023

Background

Online surveys in nursing research have both advantages and disadvantages. Reaching a sample and attaining an appropriate response rate is an ongoing challenge and necessitates careful consideration when designing a nursing research study using an online survey approach.

Objective

In this study, we aimed to explore response rates and survey characteristics of studies by nurse researchers that used online methodologies to survey nurses, nursing students, and nursing faculty.

Methods

We conducted an integrative review of research studies that used online surveys for data collection published from 2011–2021. We examined response rates and survey characteristics such as recruitment method, use of incentives, question type, length of survey, time to complete the survey, and use of reminders.

Results

Our review included 51 studies published by nurses with target samples of nurses, nursing students, or nursing faculty. Study sample sizes ranged from 48–29,283, the number of respondents ranged from 29–3,607, and the response rates ranged from 3.4%–98%, with an average of 42.46%. Few patterns emerged regarding recruitment or other factors to enhance response rates; only five studies used incentives.

Conclusion

Response rates to online surveys are unlikely to reach the rates seen in older mailed surveys. Researchers need to design online survey studies to be easily accessible, concise, and appealing to participants.
Chlamydia trachomatis–Specific Antibody Responses in Women in Cameroon With Secondary Infertility
Authors: D'Amico Madison , Mbah J. Clarisse Engowei , Gupta Kanupriya , Dionne Jodie A. , Akoachere Jane Francis , Nguedia Jules Clement Assob , Van Der Pol Barbara , Geisler William M.
Published: September 2023

The contribution of chlamydia to secondary infertility in women is poorly understood. Among 404 female participants enrolled in a previous study in Cameroon, 142 had secondary infertility (cases) and 262 were pregnant with no history of infertility (controls), Chlamydia trachomatis seropositivity was 92%. Seropositivity did not significantly differ by case/control status.
Viral Detection by Reverse Transcriptase Polymerase Chain Reaction in Upper Respiratory Tract and Metagenomic RNA Sequencing in Lower Respiratory Tract in Critically Ill Children With Suspected Lower Respiratory Tract Infection
Authors: Osborne Christina M. , Langelier Charles , Kamm Jack , Williamson Kayla , Ambroggio Lilliam , Reeder Ron W. , Locandro Christopher , Kirk Harris J. , Wagner Brandie D. , Maddux Aline B. , Caldera Saharai , Lyden Amy , Soesanto Victoria , Simões Eric A.F. , Leroue Matthew K. , Carpenter Todd C. , Hall Mark W. , Zuppa Athena F. , Carcillo Joseph A. , Meert Kathleen L. , Pollack Murray M. , McQuillen Patrick S. , Notterman Daniel A. , DeRisi Joseph , Mourani Peter M. ,   National Institute for Child Health and Human Development Collaborative Pediatric Critical Care Research Network
Published: September 2023

OBJECTIVES:

Viral lower respiratory tract infection (vLRTI) contributes to substantial morbidity and mortality in children. Diagnosis is typically confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) of nasopharyngeal specimens in hospitalized patients; however, it is unknown whether nasopharyngeal detection accurately reflects presence of virus in the lower respiratory tract (LRT). This study evaluates agreement between viral detection from nasopharyngeal specimens by RT-PCR compared with metagenomic next-generation RNA sequencing (RNA-Seq) from tracheal aspirates (TAs).

DESIGN:

This is an analysis of of a seven-center prospective cohort study.

SETTING:

Seven PICUs within academic children’s hospitals in the United States.

PATIENTS:

Critically ill children (from 1 mo to 18 yr) who required mechanical ventilation via endotracheal tube for greater than or equal to 72 hours.

INTERVENTIONS:

We evaluated agreement in viral detection between paired upper and LRT samples. Results of clinical nasopharyngeal RT-PCR were compared with TA RNA-Seq. Positive and negative predictive agreement and Cohen’s Kappa were used to assess agreement.

MEASUREMENTS AND MAIN RESULTS:

Of 295 subjects with paired testing available, 200 (68%) and 210 (71%) had positive viral testing by RT-PCR from nasopharyngeal and RNA-Seq from TA samples, respectively; 184 (62%) were positive by both nasopharyngeal RT-PCR and TA RNA-Seq for a virus, and 69 (23%) were negative by both methods. Nasopharyngeal RT-PCR detected the most abundant virus identified by RNA-Seq in 92.4% of subjects. Among the most frequent viruses detected, respiratory syncytial virus demonstrated the highest degree of concordance (κ = 0.89; 95% CI, 0.83–0.94), whereas rhinovirus/enterovirus demonstrated lower concordance (κ = 0.55; 95% CI, 0.44–0.66). Nasopharyngeal PCR was more likely to detect multiple viruses than TA RNA-Seq (54 [18.3%] vs 24 [8.1%], p ≤ 0.001).

CONCLUSIONS:

Viral nucleic acid detection in the upper versus LRT reveals good overall agreement, but concordance depends on the virus. Further studies are indicated to determine the utility of LRT sampling or the use of RNA-Seq to determine LRTI etiology.
Molecular Classification of Endometrial Endometrioid Carcinoma With Microcystic Elongated and Fragmented Pattern
Authors: Ju Baohui , Wu Jianghua , Sun Lin , Yang Chunrui , Yu Hu , Hao Quan , Wang Jianmei , Zhang Huiying
Published: September 2023

The studies on the molecular classification of endometrioid carcinoma (EC) with microcystic, elongated, and fragmented (MELF) pattern invasion are limited. In this study, 77 cases of ECs with MELF patterns in Chinese women were collected. The molecular classification of the fifth edition of the World Health Organization was used to classify the molecular subtypes using immunohistochemistry staining (mismatch repair [MMR]-immunohistochemistry: MSH2, MSH6, MLH1, and PMS2; p53) and Sanger sequencing targeted POLE. The results showed that the prevalence of the 4 molecular subtypes in EC with MELF pattern was 6.5% (5/77) for POLE mutation, 20.8% (16/77) for MMR deficient, 11.7% (9/77) for p53-mutant, and 61.0% (47/77) for no specific molecular profile. The clinicopathological characteristics of each subtype were compared. The p53-mutant and no specific molecular profile subgroups were associated with higher International Federation of Gynecology and Obstetrics stage and International Federation of Gynecology and Obstetrics grade, deeper myometrial invasion, lymphovascular space invasion, lymph node metastasis, and absence of tumor-infiltrating lymphocytes, whereas the POLE mutation and MMR deficient subgroups were associated with lower aggressive features and prominent tumor-infiltrating lymphocytes. Progression-free survival showed that the p53-mutant and no specific molecular profile subgroups had a poorer prognosis than the POLE mutation and MMR deficient subgroups. However, lymph node metastasis was an independent factor associated with a higher risk of disease recurrence in multivariate analysis. In conclusion, ECs with MELF patterns can be divided into 4 molecular subtypes with discrepancies in aggressive clinicopathological characteristics and tumor-infiltrating lymphocytes. Molecular classification has clinical significance in a morpho-molecular approach for ECs with MELF patterns.
Fatigue Experiences in People With Stroke
Authors: Bhimani Rozina , Xiong Jiayue , Anderson Lisa
Published: September 2023

Purpose

Fatigue is a major symptom in patients with stroke. Because fatigue is an overarching multidimensional phenomenon, it is important to understand how the characteristics of fatigue change over time. The purpose of this study was to explore how fatigue characteristics change over time in patients with stroke.

Design

This study used a mixed-method observational design.

Methods

This study is a secondary analysis of data from a previous study, the results of which indicated fatigue to be a prominent symptom. Participants in that study were patients with stroke who met eligibility criteria and provided informed consent. This secondary analysis used data from numeric rating scale scores for fatigue, Functional Assessment of Chronic Illness Therapy–Fatigue Scale scores, fatigue descriptors, and participant comments about fatigue gleaned from transcribed interviews.

Results

Twenty-two patients participated in the study. Thirteen characteristics of fatigue were evaluated. Seven characteristics showed significant improvement (p < .05) from admission to 1 month follow-up, and six characteristics did not change significantly.

Conclusions

Fatigue experiences vary over time and have both physical and mental aspects to them.

Clinical Relevance to Rehabilitation Nursing

Nurses may consider providing a quiet environment for physical rest, which may allow the brain to not be distracted by multiple stimuli.
Voiding Trial Outcomes After Prolapse Surgery: Before Versus During the COVID-19 Pandemic
Authors: Courtepatte Alexa , Miranne Jeannine M. , Murray Tayler , Kelly Maura , Minassian Vatche A.
Published: September 2023

Importance

Coronavirus disease 2019 (COVID-19) has changed practice patterns resulting in same-day discharge after most urogynecologic surgical procedures.

Objective

We aimed to determine if COVID-19 practice patterns changed patients' voiding trial (VT) results after surgery.

Study Design

This is a retrospective cohort study of women undergoing urogynecologic surgery at an academic tertiary care center. We compared patients who had surgery between January 1, 2019, and February 28, 2020, (pre-COVID, discharged on postoperative day [POD] 1) with those who underwent surgery between January 1, 2021, and February 28, 2022, (during COVID, discharged on POD 0 or POD 1). Demographics, surgical characteristics, and VT results were compared using nonparametric tests. A logistic regression was performed to adjust for confounders. P value <0.05 was considered statistically significant.

Results

A total of 237 patients were included. Patients were mostly White, older than 65 years (interquartile range, 56–73 years), and had a median parity of 2 (interquartile range, 2–3). Approximately 31% of patients in the pre-COVID group failed their VT, whereas 38% in the during-COVID group failed (P = 0.275). Moreover, 40.5% of women discharged the day of surgery failed their VT (P = 0.172). Compared with the pre-COVID group, more patients in the during-COVID group and those discharged on POD 0 contacted their surgeons with questions postoperatively (20.5% vs 35.0% and 35.4%, P = 0.014 and 0.022, respectively). Rates of urinary tract infection were similar by period and discharge day (P > 0.05). There was no statistical association between day of discharge or the COVID-19 pandemic and VT results.

Conclusions

Neither day of discharge nor the presence of the COVID-19 pandemic had a significant effect on postoperative outcomes, including urinary retention, after urogynecologic surgery. Same-day discharge is appropriate for most patients.
Optometric Practice Patterns for Acute Central and Branch Retinal Artery Occlusion
Authors: Mileski Kelsey M. , Biousse Valérie , Newman Nancy J. , Flowers Alexis M. , Chan Wesley , Dattilo Michael
Published: September 2023

Background:

Optometrists are often the first providers to evaluate patients with acute vision loss and are often the first to diagnose a central retinal artery occlusion (CRAO). How quickly these patients present to the optometrist, are diagnosed, and referred for evaluation are major factors influencing the possibility of acute therapeutic intervention. Our aim was to survey the U.S. optometric community to determine current optometric practice patterns for management of CRAO.

Methods:

An anonymous seven-question survey was emailed in 2020 to the 5,101 members of the American Academy of Optometry and the 26,502 members of the American Optometric Association.

Results:

Of 31,603 optometrists who were sent the survey, 1,926 responded (6.1%). Most respondents (1,392/1,919, 72.5%) worked in an optometry-predominant outpatient clinic and were less than 30 minutes from a certified stroke center (1,481/1,923, 77.0%). Ninety-eight percent (1,884/1,922) of respondents had diagnosed less than 5 CRAOs in the previous year, and 1,000/1,922 (52.0%) had not diagnosed a CRAO in the prior year. Of the optometrists who diagnosed at least one CRAO in the previous year, 661/922 (71.7%) evaluated these patients more than 4 hours after the onset of vision loss. Optometrists who diagnosed a CRAO or branch retinal artery occlusion referred patients to an emergency department (ED) affiliated with a certified stroke center (844/1,917, 44.0%), an outpatient ophthalmology clinic (764/1,917, 39.9%), an ED without a stroke center (250/1,917, 13.0%), an outpatient neurology clinic (20/1,917, 1.0%), or other (39/1,917, 2.0%); most (22/39, 56.4%) who responded “other” would refer to a primary care physician.

Conclusions:

Optometrists are likely the first providers to evaluate patients with acute vision loss, including from a retinal artery occlusion. However, only 6.1% of optometrists responded to our survey despite 2 reminder emails, likely reflecting the lack of exposure to acute retinal artery occlusions, and a potential lack of interest of optometrists in participating in research. Of the optometrists who reported evaluating a CRAO in the previous year, less than 29% saw the patient within 4 hours of vision loss. In addition, a large portion of optometrists are referring acute CRAO patients to outpatient ophthalmology clinics, delaying appropriate acute management. Therefore, it is imperative that optometrists and ophthalmologists are educated to view acute retinal arterial ischemia as an acute stroke and urgently refer these patients to an ED affiliated with a stroke center. The delay in patient presentation and these referral patterns make future clinical trials for acute CRAO challenging.
3D fusion between SPECT myocardial perfusion imaging and invasive coronary angiography to guide the treatment for patients with stable CAD
Authors: Xu Zhihui , Malhotra Saurabh , Zhao Chen , Jiang Jingfeng , Vij Aviral , Ye Zekang , Hua Rui , Li Chunjian , Wang Cheng , Zhou Weihua
Published: September 2023

Objective

We evaluated the value of three-dimensional (3D) fusion of SPECT myocardial perfusion imaging (MPI) with invasive coronary angiography (ICA) to guide coronary revascularization for patients with stable coronary artery disease (CAD).

Methods

A retrospective observational study of 621 patients who underwent SPECT MPI and ICA was conducted. Based on the location of perfusion deficit on SPECT MPI and stenosis on ICA, patients were classified into matched, unmatched, or normal groups via the fusion or side-by-side analysis. The treatments recommended by the fusion or side-by-side analysis were compared with those that the patients actually received. The treatment was defined as concordant if there was revascularization in concordance with the recommendation by the fusion or side-by-side analysis or if patient did not require revascularization; otherwise, it is classified as discordant. Major adverse cardiac events (MACE) were defined as all-cause and cardiac death, myocardial infarction, unstable angina requiring hospitalization or ICA, or unplanned revascularization.

Results

Over a five-year follow-up, 15.9% of patients experienced MACE. The MACE rates in the fusion and side-by-side groups were 19.8% and 24.4% for matched findings, 14.4% and 14.0% for unmatched findings, and 7.2% and 8.2% for normal findings, respectively (P<0.01). Among the 366 patients with at least one vessel stenosis of >50%, those who received the treatment concordant with fusion had significantly better outcomes compared to those who did not (16.8% vs 27.0%, P<0.05), particularly in the sub-group with intermediate stenosis (stenosis: 50-80%) (10.8% vs 26.5%, P<0.01). The treatment concordant with fusion is an independent protective factor against MACE (HR:0.48, CI:0.28-0.83 P<0.01) while the treatment concordant with the side-by-side analysis is not. The concordant group showed a significantly higher lesion vessel rate in the left circumflex artery (LCX) (31.2% vs. 14.3%, P<0.01) compared to the discordant group as classified by fusion.

Conclusions

3D fusion before coronary revascularization can guide the treatment to improve outcomes among patients with known or suspected CAD, particularly those with intermediate stenosis.
Prolonged survival of rabid mice after treatment with Poly-ICLC Hiltonol®
Authors: Brandão P.E. , Agostinho W.C. , Caballero O.L. , Salazar A.M. , Gomes C.O.M.S.
Published: September 2023

Despite its 100% lethality and approximately 59,000 human deaths a year, rabies is still in want of an effective treatment. A host of trials has been described aiming at impairing the life cycle ofLyssavirus rabies(RABV), the chief worldwide lyssavirus causing rabies, but with limited success. In this study, mice intranasally inoculated with the CVS strain of RABV were serially treated with 50µg/day of the Poly ICLC Hiltonol® jn MEM showed significantly higher survival time and disease incubation period as compared to control mice that received MEM only. These very preliminary results indicate that Hiltonol® might be an effective drug against rabies that merits widerin vivoinvestigation.