bluuebunny/crossref_metadata_2025 huggingface dataset:
Case Report: Evaluating Biomechanical Risk Factors in Carotid Stenosis by Patient-Specific Fluid-Structural Interaction Biomechanical Analysis
Authors: Wang Jiaqiu , Mendieta Jessica Benitez , Paritala Phani Kumari , Xiang Yuqiao , Raffel Owen Christopher , McGahan Tim , Lloyd Thomas , Li Zhiyong
Published: March 2021

Background: Carotid atherosclerosis is one of the main underlying inducements of stroke, which is a leading cause of disability. The morphological feature and biomechanical environment have been found to play important roles in atherosclerotic plaque progression. However, the biomechanics in each patient’s blood vessel is complicated and unique. Method: To analyse the biomechanical risk of the patient-specific carotid stenosis, this study used the fluid-structure interaction (FSI) computational biomechanical model. This model coupled both structural and hemodynamic analysis. Two patients with carotid stenosis planned for carotid endarterectomy were included in this study. The 3D models of carotid bifurcation were reconstructed using our in-house-developed protocol based on multisequence magnetic resonance imaging (MRI) data. Patient-specific flow and pressure waveforms were used in the computational analysis. Multiple biomechanical risk factors including structural and hemodynamic stresses were employed in post-processing to assess the plaque vulnerability. Results: Significant difference in morphological and biomechanical conditions between 2 patients was observed. Patient I had a large lipid core and serve stenosis at carotid bulb. The stenosis changed the cross-sectional shape of the lumen. The blood flow pattern changed consequently and led to a complex biomechanical environment. The FSI results suggested a potential plaque progression may lead to a high-risk plaque, if no proper treatment was performed. The patient II had significant tandem stenosis at both common and internal carotid artery (CCA and ICA). From the results of biomechanical factors, both stenoses had a high potential of plaque progression. Especially for the plaque at ICA branch, the current 2 small plaques might further enlarge and merge as a large vulnerable plaque. The risk of plaque rupture would also increase. Conclusions: Computational biomechanical analysis is a useful tool to provide the biomechanical risk factors to help clinicians assess and predict the patient-specific plaque vulnerability. The FSI computational model coupling the structural and hemodynamic computational analysis, better replicates the in vivo biomechanical condition, which can provide multiple structural and flow-based risk factors to assess plaque vulnerability.
The Role of Amyloid PET in Diagnosing Possible Transmissible Cerebral Amyloid Angiopathy in Young Adults with a History of Neurosurgery: A Case Series
Authors: Michiels Laura , Van Weehaeghe Donatienne , Vandenberghe Rik , Demeestere Jelle , Van Laere Koen , Lemmens Robin
Published: March 2021

Background: Cerebral amyloid angiopathy (CAA) is a common cause of cerebrovascular disease in the elderly. There is accumulating evidence suggestive of transmissibility of β-amyloid resulting in amyloid pathology at younger age. According to the Boston criteria, defining CAA in patients <55 years requires histological evidence which may hamper diagnosis. We explored the role of amyloid PET in the diagnosis of possible transmissible CAA in young adults. Cases: We report 4 young adults (<55 years) presenting with clinical and neuroimaging features suggestive of CAA but without genetic evidence of hereditary CAA explaining the young onset. A common factor in all cases was a medical history of neurosurgery during childhood. All patients underwent amyloid PET to support the diagnosis of an amyloid-related pathology and the result was positive in all 4. Conclusion: Combining the clinical presentation and imaging findings of the 4 cases, we postulate transmissible CAA as the possible diagnosis. Further epidemiological studies are required to gain more insight in the prevalence of this novel entity. Amyloid PET may be a useful, non-invasive tool in these analyses especially since pathological evidence will be lacking in most of these studies.
Robustness of In-Laboratory and Daily-Life Gait Speed Measures over One Year in High Functioning 61- to 70-Year-Old Adults
Authors: Rojer Anna G.M. , Coni Alice , Mellone Sabato , Van Ancum Jeanine M. , Vereijken Beatrix , Helbostad Jorunn L. , Taraldsen Kristin , Mikolaizak Stefanie , Becker Clemens , Aminian Kamiar , Trappenburg Marijke C. , Meskers Carel G.M. , Maier Andrea B. , Pijnappels Mirjam
Published: March 2021

Introduction: Gait speed is a simple and safe measure with strong predictive value for negative health outcomes in clinical practice, yet in-laboratory gait speed seems not representative for daily-life gait speed. This study aimed to investigate the interrelation between and robustness of in-laboratory and daily-life gait speed measures over 12 months in 61- to 70-year-old adults. Methods: Gait speed was assessed in laboratory through standardized stopwatch tests and in daily life by 7 days of trunk accelerometry in the PreventIT cohort, at baseline, and after 6 and 12 months. The interrelation was investigated using Pearson’s correlations between gait speed measures at each time point. For robustness, changes over time and variance components were assessed by ANOVA and measurement agreement over time by Bland-Altman analyses. Results: Included were 189 participants (median age 67 years [interquartile range: 64–68], 52.2% females). In-laboratory and daily-life gait speed measures showed low correlations (Pearson’s r = 0.045–0.455) at each time point. Moreover, both in-laboratory and daily-life gait speed measures appeared robust over time, with comparable and smaller within-subject than between-subject variance (range 0.001–0.095 m/s and 0.032–0.397 m/s, respectively) and minimal differences between measurements over time (Bland-Altman) with wide limits of agreement (standard deviation of mean difference range: 0.12–0.34 m/s). Discussion/Conclusion: In-laboratory and daily-life gait speed measures show robust assessments of gait speed over 12 months and are distinct constructs in this population of high-functioning adults. This suggests that (a combination of) both measures may have added value in predicting health outcomes.
Physiological and Cognitive Determinants of Dual-Task Costs for Gait Parameters: The Yishun Study
Authors: Lau Lay Khoon , Mallya Jagadish Ullal , Pang Wei Jun Benedict , Chen Kexun Kenneth , Abdul Jabbar Khalid bin , Seah Wei Ting , Yap Philip Lin Kiat , Ng Tze Pin , Wee Shiou Liang
Published: March 2021

Background: Studies indicate that physiological and cognitive aging are causally related and functionally interdependent. However, the relative contribution of physiological factors and cognition to dual-task costs (DTC) of gait parameters has not been well studied. In this cross-sectional study, we examined the trajectory of DTC of gait parameters across the adult age spectrum for both sexes and identified the contributions of physical and cognitive performance to DTC of gait. Methods: A total of 492 community-dwelling adults, aged 21–90 years, were randomly recruited into the study. Participants were divided into 7 age groups, with 10-year age range for each group. Demographic data, height, body mass, education level, and information on comorbidities were recorded. Cognition was measured using the Repeatable Battery for the Assessment of Neuropsychological Status. Physical performance included visual contrast sensitivity, postural sway, hand reaction time, handgrip strength, knee extensor strength, and single-task and dual-task gait assessments. Stepwise multivariable regression was used to examine the association between physical and cognitive performance with DTC of gait parameters. Results: Women were found to have significantly higher DTC of gait speed (p = 0.01), cadence (p < 0.01), and double support time (p < 0.01) than men. However, significant aging effect on DTC of gait speed (p = 0.01), step length (p = 0.01), and double support time (p = 0.01) was observed in men but not in women. Immediate memory was the primary determinant for the DTC of gait speed (β = −0.25, p < 0.01), step length (β = −0.22, p < 0.01), and cadence (β = −0.15, p = 0.03) in men. Besides immediate memory, postural sway (β = −0.13, p = 0.03) and hand reaction (β = 0.14, p = 0.02) were also significantly associated with DTC of step length and cadence, respectively, in women. Conclusion: There were sex differences in the amplitude and trajectories of DTC of gait parameters. The DTC increased with age in men but not in women. Immediate memory was the primary determinant of DTC of gait parameters in men while immediate memory, postural sway, and reaction time were associated with DTC of gait in women. Future studies should investigate the clinical implications of the sex differences in the DTC with fall risks.
Microsurgical Management of the Middle Cerebral Artery Bifurcation Aneurysms: An Anatomic Feasibility Study
Authors: Karadag Ali , Bozkurt Baran , Yagmurlu Kaan , Ozcan Ada Irmak , Moen Sean , Grande Andrew W.
Published: March 2021

Background: The proper head positioning decreases the surgical complications by enabling a better surgical maneuverability. Middle cerebral artery (MCA) bifurcation aneurysms have been classified by Dashti et al. [Surg Neurol. 2007 May;67(5):441–56] as the intertruncal, inferior, lateral, insular, and complex types based on dome projection. Our aim was to identify the optimum head positions and to explain the anatomic variables, which may affect the surgical strategy of MCA bifurcation aneurysms. Methods: The lateral supraorbital approach bilaterally was performed in the 4 cadaveric heads. All steps of the dissection were recorded using digital camera. Results: The distal Sylvian fissure (SF) dissection may be preferred for insular type and the proximal SF dissection may be preferred for all other types. Fifteen degrees head rotation was found as the most suitable position for the intertruncal, lateral type and subtype of complex aneurysms related with superior trunk. Thirty degrees head rotation was found the most suitable position for the inferior type, insular type, and subtype of complex aneurysms related with inferior trunk. Conclusions: The head positioning in middle cerebral bifurcation aneurysms surgery is a critical step. It should be tailored according to the projection and its relationship with the parent vessels of the middle cerebral bifurcation.
Kidney Biopsy in Type 2 Diabetes: A Multicenter Cross-Sectional Study
Authors: Chemouny Jonathan M. , Bobot Mickaël , Sannier Aurélie , Maisons Valentin , Jourde-Chiche Noémie , Ferriere Elsa , Joly Dominique , Vigneau Cécile , Rioux-Leclercq Nathalie , Barba Christophe , Daniel Laurent , Halimi Jean-Michel , Vrtovsnik Francois
Published: March 2021

Introduction: Kidney biopsies (KBs) are performed in patients with type 2 diabetes (T2D) to diagnose non-diabetic or hypertensive kidney disease (NDHKD) potentially requiring specific management compared to diabetic and or hypertensive nephropathy (absence of NDHKD). Indications for KB are based on the presence of atypical features compared to the typical course of diabetic nephropathy. In this study, we assessed the association of different patterns of atypical features, or KB indications, with NDHKD. Methods: Native KBs performed in patients with T2D were analyzed. Data were collected from the patients’ records. KB indications were determined according to the presence of different atypical features considered sequentially: (1) presence of any feature suggesting NDHKD which is not among the following ones, (2) recent onset of nephrotic syndrome, (3) low or rapidly declining estimated glomerular filtration rate (eGFR), (4) rapid increase in proteinuria, (5) short duration of diabetes, (6) presence of hematuria, or (7) normal retinal examination. Results: Among the 463 KBs analyzed, NDHKD was diagnosed in 40% of the total population and 54, 40, 24, and 7% of the KBs performed for indications 1–4 respectively. Conversely, no patient who underwent KB for indications 5–7 displayed NDHKD. Logistic regression analyses identified eGFRCKD-EPI >15 mL/min/1.73 m2, urinary protein-to-Cr ratio <0.3 g/mmol, hematuria, HbA1c <7%, and diabetes duration <5 years as predictors of NDHKD, independently from the indication group. Conclusion: NDHKD is frequent in T2D. Despite the association of hematuria with NDHKD, our results suggest that presence of hematuria and absence of DR are insufficient to indicate KB in the absence of concurrent atypical features. Conversely, rapid progression of proteinuria and rapid deterioration of eGFR are major signals of NDHKD.
Gelatin-Containing Vaccines for Varicella, Zoster, Measles, Mumps, and Rubella Induce Basophil Activation in Patients with Alpha-Gal Syndrome
Authors: Schmidle Paul , Mehlich Jana , Brockow Knut , Darsow Ulf , Biedermann Tilo , Eberlein Bernadette
Published: March 2021

Background: The alpha-gal syndrome (AGS) describes a new type I allergy entity to the carbohydrate epitope galactose-α-1,3-galactose (alpha-gal), which is mainly found in mammalian food products (e.g., beef, pork, and venison). Apart from meat products, alpha-gal can also be found in products containing gelatin of bovine or porcine origin. Recent case reports pointed to severe anaphylaxis in patients suffering from AGS after vaccination with vaccines containing hydrolyzed gelatin. It was the objective of this study to evaluate if basophil activation tests (BATs) performed with such vaccines were positive in patients with AGS. Methods: BAT was performed with different dilutions of a gelatin-containing measles, mumps, and rubella (MMR) live vaccine; an attenuated varicella (V) vaccine; an attenuated V-zoster (VZ) vaccine; a MMR live vaccine not containing gelatin (non-gelatin MMR vaccine) in 2 patients with confirmed AGS, 2 patients highly suspicious for AGS, and 2 healthy individuals without any previous medical history for allergies. Results: All patients showed strongly positive results for all gelatin-containing vaccines (MMR vaccine, V vaccine, and VZ vaccine). Non-gelatin MMR vaccine was negative. The 2 healthy controls did not show any basophil activation. Conclusions: Gelatin-containing vaccines should be administered with caution or avoided in patients with AGS because of their high potential to activate basophils indicating a risk for anaphylaxis. Also, BAT is a useful additional tool when it comes to screening for potentially high-risk alpha-gal-containing drugs.
Demoralization and Quality of Life of Patients with Parkinson Disease
Authors: Zhu Boheng , Kohn Robert , Patel Amar , Koo Brian B. , Louis Elan D. , de Figueiredo John M.
Published: March 2021

Introduction: Demoralization is quite prevalent in patients with Parkinson disease (PD). Unrecognized or untreated, demoralization may progress, at times, to demands for euthanasia and the desire for suicide. Typically, patients with PD do not complain of being “demoralized”; rather, they report disruptions in the quality of their lives. Hence, early identification of disruptions in health-related quality of life (HRQoL) specifically associated with demoralization may prompt earlier recognition and treatment. Published data on such associations, however, could not be found. Alleviation of demoralization in PD is likely to improve treatment outcomes. Objective: This research aimed at identifying the disruptions of HRQoL specifically associated with the demoralization of patients with PD. Methods: Consecutive general hospital outpatients with PD (n = 95) were assessed for: demoralization, with the Diagnostic Criteria for Psychosomatic Research Demoralization Scale (DCPR-D) and the Demoralization Scale (DS); depression, with the Patient Health Questionnaire-9 (PHQ-9); HRQoL, with the Parkinson Disease Questionnaire-Short Form (PDQ-8); sociodemographic variables; medical comorbidities; PD severity; and types of treatment. Results: The prevalence of demoralization was 19%. Regression analyses showed that demoralization was significantly more likely to be experienced by participants who had difficulty with mobility and felt embarrassed in public due to having PD. Demoralization explained HRQoL over and above depression. Conclusions: Stigma and perceived difficulty with mobility are associated with demoralization of PD patients, and they may signal the need for psychotherapeutic and behavioral interventions to prevent the progression to helplessness, hopelessness, demands for euthanasia, and desire for suicide.
Potassium Trajectories prior to Dialysis and Mortality following Dialysis Initiation in Patients with Advanced CKD
Authors: Dashputre Ankur A. , Sumida Keiichi , Potukuchi Praveen K. , Kar Suryatapa , Obi Yoshitsugu , Thomas Fridtjof , Molnar Miklos Z. , Streja Elani , Kalantar-Zadeh Kamyar , Kovesdy Csaba P.
Published: March 2021

Introduction: Patients with advanced non-dialysis-dependent CKD (NDD-CKD) have a reduced ability for maintaining plasma potassium (K) in normal range. Deviation from normal plasma K ranges is associated with increased mortality; however, the average trajectory of plasma K over time in patients with advanced NDD-CKD and the outcomes associated with plasma K trajectory are unknown. Methods: We identified 34,167 US veterans with advanced NDD-CKD transitioning to dialysis between October 2007 and March 2015 with at least 1 K measurement each year over a 3-year period prior to dialysis transition (3-year prelude). The K trajectory defined as the change in K (slope) per year over the entire 3-year prelude was estimated using linear mixed-effects models. The association between unadjusted (crude) K slope (categorized as stable [−0.09 to 0.09 mEq/L/year], decreasing [≤−0.10 mEq/L/year], and increasing [≥0.10 mEq/L/year]) and time to all-cause and cardiovascular mortality during the 6 months following dialysis initiation was assessed using multivariable-adjusted survival models. Results: The crude and multivariable-adjusted K slopes (mean, 95% CI) over the 3-year prelude were 0.008 (0.0059, 0.0110) and −0.15 mEq/L/year (−0.19, −0.11), respectively. Decreasing K slope was associated with higher multivariable-adjusted risk of all-cause mortality (adjusted hazard ratio [95% CI] vs. stable K slope: 1.08 [1.00–1.17]). No association was observed between K slope and cardiovascular mortality. Discussion/Conclusion: The average intraindividual plasma K trajectory is remarkably stable in patients with advanced NDD-CKD. A decreasing K slope is associated with higher all-cause mortality risk.
Development and Evaluation of the Psychosocial Adaptation Questionnaire among Patients with Chronic Skin Disease
Authors: Zhang Xiu-jie , Xu Hui , Wang Ai-ping
Published: March 2021

Background/Objective: Chronic skin disease (CSD) often has physiological, psychological, and social impacts, which requires the patient to adjust to achieve psychosocial adaptation (PSA). As a standardized assessment instrument was lacking, we developed a PSA questionnaire for patients with CSD (PSAQ-CSD). Methods: According to the steps of questionnaire development, a systematic process of scoping review, qualitative research, content validity expert review, testing in a sample of 321 adults, item analysis, and classical test theory methods were applied. Results: Following item analysis and exploratory factor analyses, 18 items were eventually entered into the model of confirmatory factor analyses, with a cumulative contribution of 65.435%. Three subscales were developed: emotional, self-cognitive, and social dimensions. Item analysis, exploratory factor analyses, and content validity expert review narrowed the subscales to 8, 6, and 4 items, respectively. Conclusions: The 18-item PSAQ-CSD has been confirmed to have good internal consistency reliability and convergent and discriminant validity. It may be a useful tool to evaluate the PSA among patients with CSD and provide a basis for further research.
Comparison of the Clinical Outcome of Ramucirumab for Unresectable Hepatocellular Carcinoma with That of Prior Tyrosine Kinase Inhibitor Therapy
Authors: Amioka Kei , Kawaoka Tomokazu , Ogawa Yutaro , Kikukawa Chihiro , Naruto Kensuke , Yoshikawa Yuki , Ando Yuwa , Kosaka Yumi , Uchikawa Shinsuke , Morio Kei , Fujino Hatsue , Nakahara Takashi , Murakami Eisuke , Yamauchi Masami , Tsuge Masataka , Hiramatsu Akira , Imamura Michio , Fukuhara Takayuki , Mori Nami , Takaki Shintaro , Tsuji Keiji , Masaki Keiichi , Honda Yoji , Kouno Hirotaka , Kohno Hiroshi , Chayama Kazuaki , Aikata Hiroshi
Published: March 2021

Introduction: The clinical outcome of ramucirumab in multi-molecular targeted agent (MTA) sequential therapy for unresectable hepatocellular carcinoma (u-HCC) was assessed in comparison with that of prior tyrosine kinase inhibitor (TKI) therapy. Methods: Sixteen patients who received ramucirumab as part of multi-MTA sequential therapy for u-HCC were enrolled in a retrospective, cohort study. Ramucirumab was started as 2nd line in 7 patients, 3rd line in 5 patients, and 4th line in 4 patients. Results: The overall response rate was 6.3%, the disease control rate (DCR) was 50.0%, median progression-free survival was 2.0 months (evaluated by mRECIST), median overall survival (OS) with ramucirumab was 7.9 months, and the median OS from 1st-line therapy was 28.1 months. One month after the start of ramucirumab, α-fetoprotein (AFP) decreased in 6 of 12 cases (50.0%), and the DCR in AFP-decreased cases was 83.3%. The DCR of ramucirumab was 66.7% in cases in which disease control was obtained by prior TKI therapy, whereas it was 0.0% in the cases in which disease control was not obtained by prior TKI therapy. Examining the adverse events, no new safety concerns were confirmed. Conclusion: The AFP response to ramucirumab and the treatment response to prior TKI therapy are associated with treatment response to ramucirumab.
Identifying Responders and Exploring Mechanisms of Action of the Endobronchial Coil Treatment for Emphysema
Authors: Hartman Jorine E. , Klooster Karin , Augustijn Sonja W.S. , van Geffen Wouter H. , Garner Justin L. , Shah Pallav L. , Ten Hacken Nick H.T. , Slebos Dirk-Jan
Published: March 2021

Background: So far, 3 randomized controlled trials have shown that the endobronchial treatment using coils is safe and effective. However, the more exact underlying mechanism of the treatment and best predictors of response are unknown. Objectives: The aim of the study was to gain more knowledge about the underlying physiological mechanism of the lung volume reduction coil treatment and to identify potential predictors of response to this treatment. Methods: This was a prospective nonrandomized single-center study which included patients who were bilaterally treated with coils. Patients underwent an extensive number of physical tests at baseline and 3 months after treatment. Results: Twenty-four patients (29% male, mean age 62 years, forced expiratory volume in 1 s [FEV1] 26% pred, residual volume (RV) 231% pred) were included. Three months after treatment, significant improvements were found in spirometry, static hyperinflation, air trapping, airway resistance, treated lobe RV and treated lobes air trapping measured on CT scan, exercise capacity, and quality of life. The change in RV and airway resistance was significantly associated with a change in FEV1, forced vital capacity, air trapping, maximal expiratory pressure, dynamic compliance, and dynamic hyperinflation. Predictors of treatment response at baseline were a higher RV, larger air trapping, higher emphysema score in the treated lobes, and a lower physical activity level. Conclusions: Our results confirm that emphysema patients benefit from endobronchial coil treatment. The primary mechanism of action is decreasing static hyperinflation with improvement of airway resistance which consequently changes dynamic lung mechanics. However, the right patient population needs to be selected for the treatment to be beneficial which should include patients with severe lung hyperinflation, severe air trapping, and significant emphysema in target lobes.
Muscle Tone Assessment under General Anesthesia for Sjögren-Larsson Syndrome and Spasticity
Authors: Georgoulis George , Dinopoulos Argyrios , Gkliatis Emmanouil
Published: March 2021

Introduction: Study of muscle tone in individuals with severe spasticity (Modified Asworth Scale – MAS:3) under general anesthesia can confirm or rule out the eventual necessity of the impending spasticity relieving ablative neurosurgery by observing the hypertonia reduction and passive range of motion expansion. Therefore, what we measure under muscle relaxants is practically a fixed deformity. Case Presentation: The study was performed on a girl with Sjögren-Larsson syndrome, presenting with icthyosis and spastic diplegia. Proposed intervention was Dorsal Rhizotomy. Under general anesthesia, with and without muscle relaxants, hypertonia was significantly reduced (MAS:1), but the angle of motion did not increase much. Conclusion: We decided not to perform such a neurosurgical procedure. In ambiguous situations, the proposed study can help in decision-making for spasticity treatment.
Lhermitte-Duclos Disease in Pediatric Population: Report of 2 Cases
Authors: Pregúntegui-Loayza Ivethe , Apaza-Tintaya Alejandro , Ramírez-Espinoza Alberto , Mayo-Simón Nancy , Toledo-Aguirre Mauro
Published: March 2021

Introduction: Lhermitte-Duclos disease (LDD), also known as dysplastic cerebellar gangliocytoma, is an uncommon disorder in children, characterized by being a slow-growing lesion of the posterior fossa, which mainly affects the granular cell layer of the cerebellar parenchyma and may be associated with other multiple hereditary hamartomas and neoplasms. Case Presentation: We report 2 cases of LDD in pediatric patients and describe clinical symptoms and radiological and histopathological characteristics. In addition, we analyzed the relation to Cowden Syndrome based on the International Cowden Syndrome Consortium Operational Criteria and the most updated guidelines by the National Comprehensive Cancer Network (NCCN Guidelines Version 1.2020). Conclusion: LDD is a very rare disease in childhood but should be considered in the differential diagnosis of posterior fossa lesions. LDD can mimic low-grade glial tumors or infectious diseases. Patients develop late clinical manifestations due to the slow-growing pattern, and conservative treatment with outpatient follow-up may be an option in asymptomatic children.
Uncommon Nail Involvement during Bullous Pemphigoid
Authors: Zaouak Anissa , Gara Soumaya , Fenniche Samy , Hammami Houda
Published: March 2021

Bullous pemphigoid (BP) is the most frequent autoimmune blistering disorder. The immune reaction targets BP180 and BP230 antigens, 2 components of junctional adhesion complexes at the basement membrane zone. Clinical aspect includes multiple tense bullae on urticarial plaques of the skin. Although the nail apparatus may be affected by the immune process, nail changes have been rarely reported during BP. We report a case of a 72-year-old woman diagnosed with BP who subsequently developed a secondary nail loss of the 2 thumbs and the left middle finger. Also, she presented onycholysis of the fourth left finger with the aspect of roller-coaster of the proximal border at dermoscopy. Steroid therapy at high doses was ineffective and the nail atrophy was permanent.
An Accidental Repetitive 10-Fold Overdose of Sildenafil in a Young Infant with Pulmonary Hypertension
Authors: Peeters Laura E.J. , Cochius-den Otter Suzan C.M. , Witjes Bregje C.M. , Gischler Saskia J. , Flint Robert B.
Published: March 2021

Sildenafil is a selective phosphodiesterase type-5 inhibitor that is increasingly used to treat pulmonary hypertension (PH) in neonates. Only little is known about the relation between the dose of sildenafil, plasma concentrations, and the degree of toxicity. Here, we present a young infant with congenital diaphragmatic hernia and PH who received an unintentional 10-fold overdose of oral sildenafil for 6 consecutive days. This overdose, compared to the therapeutic dose, resulted in increased plasma concentrations of sildenafil from 42 to 521 mcg/L and desmethylsildenafil from 81 to 393 mcg/L. However, the high exposure only led to diarrhea, without any other serious adverse events. This case describes the mild symptoms upon an overdose with the role of therapeutic drug monitoring to monitor exposure in relation to symptoms and therewith support clinical decision-making.
Use of Composite Outcomes in Neonatal Trials: An Analysis of the Cochrane Reviews
Authors: Lai Nai Ming , Yap Amanda Qiao Ying , Ong Hwee Chin , Wai Sheng Xuan , Yeo Julie Hsiao Hui , Koo Charis Yen Ee , Lah Wen Chin , Lim Yin Sear , Ovelman Colleen , Soll Roger F.
Published: March 2021

Introduction: Composite outcomes are used to increase the power of a study by combining event rates. Many composite outcomes in adult clinical trials have components that differ substantially in patient importance, event rate, and effect size, making interpretation challenging. Little is known about the use of composite outcomes in neonatal randomized controlled trials (RCTs). Methods: We assessed the use of composite outcomes in neonatal RCTs included in Cochrane Neonatal reviews published till November 2017. Two authors reviewed the components of the composite outcomes to compare their patient importance and computed the ratios of effect sizes and event rates between the components, with an a priori threshold of 1.5, indicating a substantial difference. Descriptive statistics were presented. Results: We extracted 7,766 outcomes in 2,134 RCTs in 312 systematic reviews. Among them, 55 composite outcomes (0.7%) were identified in 46 RCTs. The vast majority (92.7%) of composite outcomes had 2 components, with death being the most common component (included 51 times [92.7%]). The components in nearly three-quarters of the composite outcomes (n = 40 [72.7%]) had different patient importance, while the effect sizes and event rates differed substantially between the components in 27 (49.1%) and 35 (63.6%) outcomes, respectively, with up to 43-fold difference in the event rates observed. Conclusions: The majority of composite outcomes in neonatal RCTs had different patient importance with contrasting effect sizes and event rates between the components. In patient communication, clinicians should highlight individual components, rather than the composites, with explanation on the relationship between the components, to avoid misleading impression on the effect of the intervention. Future trials should report the estimates of all individual components alongside the composite outcomes presented.
Diffusion-Weighted Imaging of Different Breast Cancer Molecular Subtypes: A Systematic Review and Meta-Analysis
Authors: Meyer Hans-Jonas , Wienke Andreas , Surov Alexey
Published: March 2021

Background: Magnetic resonance imaging can be used to diagnose breast cancer (BC).Diffusion-weighted imaging (DWI) and the apparent diffusion coefficient (ADC) can be used to reflect tumor microstructure. Objectives: This analysis aimed to compare ADC values between molecular subtypes of BC based on a large sample of patients. Method: The MEDLINE library and Scopus database were screened for the associations between ADC and molecular subtypes of BC up to April 2020. The primary end point of the systematic review was the ADC value in different BC subtypes. Overall, 28 studies were included. Results: The included studies comprised a total of 2,990 tumors. Luminal A type was diagnosed in 865 cases (28.9%), luminal B in 899 (30.1%), human epidermal growth factor receptor (Her2)-enriched in 597 (20.0%), and triple-negative in 629 (21.0%). The mean ADC values of the subtypes were as follows: luminal A: 0.99 × 10–3 mm2/s (95% CI 0.94–1.04), luminal B: 0.97 × 10–3 mm2/s (95% CI 0.89–1.05), Her2-enriched: 1.02 × 10–3 mm2/s (95% CI 0.95–1.08), and triple-negative: 0.99 × 10–3 mm2/s (95% CI 0.91–1.07). Conclusions: ADC values cannot be used to discriminate between molecular subtypes of BC.
Intralateral and Perilateral Ventricular Arteries on Original Axial Magnetic Resonance Angiography in Adult Moyamoya Disease
Authors: Ishikawa Mami , Terao Satoshi , Kagami Hiroshi , Inaba Makoto , Naritaka Heiji
Published: March 2021

Background: Patients with moyamoya disease often develop cerebral infarction and hemorrhage, but the ischemic and hemorrhagic subtypes are difficult to diagnose prior to disease onset. We aimed to differentiate the ischemic and hemorrhagic subtypes of moyamoya disease by analyzing the intralateral and perilateral ventricular arteries on the original axial magnetic resonance angiography (MRA) images. Methods: We retrospectively analyzed the intralateral and perilateral ventricular arteries on the original axial time-of-flight (TOF)-MRA images of 18 patients with hemorrhagic moyamoya disease, 25 patients with ischemic moyamoya disease, and 22 control patients with unruptured aneurysms. Results: There were significantly more intralateral and perilateral ventricular arteries on the original axial MRA images in the patients with hemorrhagic moyamoya disease (6.3 ± 2.7) than in those with ischemic moyamoya disease (0.8 ± 0.9) and those with unruptured aneurysms (0.4 ± 0.8). Conclusion: The intralateral and perilateral ventricular arteries on the original axial TOF-MRA images might suggest the hemorrhagic type of moyamoya disease prior to onset.
The Potential Preventive Effect of Pregnancy and Breastfeeding on Multiple Sclerosis
Authors: Alhomoud Mohsen Ali , Khan Abdul Sattar , Alhomoud Iftetah
Published: March 2021

Background: Multiple sclerosis (MS) is an inflammatory demyelinating chronic neurological disease that affects the central nervous system of young adults and their quality of life. Several studies have investigated the effects of pregnancy and breastfeeding on MS. However, the evidence regarding the influence of pregnancy and breastfeeding on MS is still accumulating. This review aimed to summarize the current evidence regarding the effects of pregnancy and breastfeeding on MS. Summary: A systematic electronic literature search of the PubMed and Embase databases was conducted to determine relevant published articles. The eligible studies were summarized and evaluated in tables. Key Messages: The majority of the studies indicated that pregnancy appears to lower the rate of MS relapses, particularly in the third trimester. The evidence regarding the effect of breastfeeding on MS remains inconsistent. Despite reports of negative obstetric outcomes in some pregnant women with MS, pregnancies in women with MS should not be categorized as high-risk pregnancies.
Is Anti-Müllerian Hormone a Marker of Ovarian Reserve in Young Breast Cancer Patients Receiving a GnRH Analog during Chemotherapy?
Authors: Torrisi Rosalba , Basilico Vera , Giordano Laura , Caruso Michele , Musolino Antonino , Monari Marta Noemi , Carnaghi Carlo , Santoro Armando
Published: March 2021

Introduction: Anti-Müllerian hormone (AMH) is the most reliable biomarker of ovarian reserve; however, its role in predicting ovarian recovery after chemotherapy is unclear. Administration of a GnRH analog (GnRHa) during chemotherapy significantly reduces the ovarian failure rate and increases the pregnancy rate. The available data on the behavior of AMH during concurrent administration of chemotherapy and GnRHa are inconsistent. We investigated whether concurrent administration of triptorelin and adjuvant chemotherapy might reduce the expected drop of AMH. Methods: Eligible patients were premenopausal women aged <40 years, with a diagnosis of early breast cancer, and candidates to 4–8 cycles of adjuvant chemotherapy. Triptorelin (3.75 mg i.m.) was started before chemotherapy and administered every 4 weeks thereafter. The principal endpoint was the proportion of patients with an AMH percent change ≤50% between 12 months after chemotherapy and basal levels. The secondary endpoint was the proportion of patients achieving postchemotherapy AMH levels above the threshold of 0.2 ng/mL. Results: Fifty patients were enrolled, 31 of whom had blood samples available at baseline and 1 year after the end of chemotherapy. AMH decreased to nearly undetectable levels after chemotherapy and recovered after 12 months, but they did not exceed 1 tenth of the pretreatment levels. As for the secondary endpoint, 15 of the 31 patients recovered AMH levels above the threshold. Conclusions: This study did not reach its principal endpoint; however, the rate of 48% of patients who recovered AMH above threshold levels favorably compared with those in studies without concurrent GnRHa, supporting a better recovery of AMH with triptorelin.
Uric Acid-to-Albumin Ratio: A Novel Marker for the Extent of Coronary Artery Disease in Patients with Non-ST-Elevated Myocardial Infarction
Authors: Çakmak Ender Özgün , Bayam Emrah , Çelik Mehmet , Kahyaoğlu Muzaffer , Eren Kıvanç , Imanov Elmin , Karagöz Ali , İzgi İbrahim Akın
Published: March 2021

Objective: This research aimed to investigate the predictive value of the uric acid-to-serum albumin ratio (UAR) in establishing the severity and extent of coronary artery disease (CAD) with non-ST segment elevation myocardial infarction (NSTEMI) patients. Methods: A total of 402 patients (mean age 63.5 ± 11.6 years) were included in this retrospectively designed study. We compared Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery Scores (SS) between low (≤22) and intermediate-high (>22) groups. The UAR, the neutrophil-to-lymphocyte ratio (NLR), and the C-reactive protein-to-albumin ratio (CAR) were evaluated and compared. Results: SS >22 were observed in 30.8% (n = 124) of the patients, and their UAR, NLR, and CAR were significantly higher. Three separate multivariate analysis models performed as the outcome of a reliable correlation between UAR, NLR, CAR, and consequently UAR (OR = 2.08; 95% CI 1.21–3.58; p = 0.008) and CAR (OR = 3.33; 95% CI 1.85–5.9; p < 0.001) reached significance but NLR (OR = 1.26; 95% CI 0.86–1.84; p = 0.20) clinically trended significance (not statistically). Model performance comparisons demonstrated that UAR is a better predictor regarding likelihood ratios (UAR, 60.95; NLR, 57.8; and CAR, 59.0). Conclusion: As a novel inflammatory marker, UAR independently predicted better outcomes than CAR and might be used reliably in prediction of the extent of CAD in NSTEMI patients.
Exploring the Conceptual Frameworks Guiding Developmental Research and Practice in Higher Education: Some Challenges for Transdisciplinary Work
Authors: Budwig Nancy , Alexander Achu Johnson
Published: March 2021

This article examines questions initially raised at a meeting that took place 50 years ago on the topic of the development of knowledge in higher education where Jean Piaget coined the term “transdisciplinarity” and distinguished it from interdisciplinarity. We consider the question of why transdisciplinary scholarship has been so challenging for the field of developmental science. We argue that shifts in the guiding metatheoretical framework of theory and research, away from split-mechanistic paradigms and towards process-relational ones, do not always align with the conceptual frameworks used in educational practice. Using the example considered by Piaget and others at the original conference on higher education and the development of knowledge and also examining the domain of identity development, we find support for ways developmental scholarship has embraced the shift to a relational-developmental metatheory. In contrast, we argue that the relational-developmental paradigm has not been fully adopted by practitioners, with evidence of some using the Cartesian-split-mechanistic paradigm and others using some aspects of the relational-developmental paradigm. We highlight the importance of examining the conceptual frameworks guiding developmental scholarship and practice, suggesting that alignment of conceptual frameworks is an essential ingredient for progress in transdisciplinary scholarship and practice to take place. Conceptualizations at the metatheoretical level condition each and every aspect of theory, research, and practice, giving meaning to both theoretical and empirical activities and guiding practice-based work. Debates often occur at the metatheoretical level, and thus are not open to empirical adjudication. We conclude that metatheoretical alignment between scholars and practitioners is critically important to transdisciplinary efforts in developmental science and therefore more attention to the metatheoretical assumptions of the process-relational paradigm is critical for work with practitioners to succeed.
Treatment of Luminal Metastatic Breast Cancer beyond CDK4/6 Inhibition: Is There a Standard of Care in Clinical Practice?
Authors: Mavratzas Athanasios , Marmé Frederik
Published: March 2021

Background: CDK4/6 inhibitors have become the standard for first-line treatment of metastatic luminal breast cancer based on consistent data from several phase 3 trials demonstrating clinically meaningful improvement of progression-free as well as overall survival. In addition, they are about to become a part of adjuvant treatment for patients with high-risk luminal disease based on positive results from the first randomized phase 3 trial on abemaciclib. Nevertheless, the majority of patients with advanced or metastatic luminal breast cancer and prospectively a relevant proportion of patients treated in the adjuvant setting will eventually develop resistance to this endocrine based combination within 12–36 months, depending on the line of treatment. Conclusion: Potential subsequent therapies include PI3K inhibitors, mTOR inhibitors, endocrine monotherapy, PARP inhibitors, and chemotherapy. However, these therapies have mainly been developed in the pre-CDK4/6 inhibitor era and little is known about potential cross-resistance. The concept of continuing CDK4/6 inhibition beyond progression is supported by some preclinical data, but to date there is very limited clinical evidence to support this strategy. Therefore, treatment of metastatic luminal breast cancer after progression on CDK4/6 inhibitors remains a challenge. Key Messages: Here we review current evidence from pro- and retrospective studies and give an outlook on future developments with respect to novel therapeutic agents, including oral SERD and AKT inhibitors, which have the potential to change the therapeutic landscape in the future. Furthermore, clinical treatment algorithms and current research will also be discussed.
Bidirectional Association between Psoriasis and Atopic Dermatitis: A Nationwide Population-Based Cohort Study
Authors: Dai Ying-Xiu , Tai Ying-Hsuan , Chang Yun-Ting , Chen Tzeng-Ji , Chen Mu-Hong
Published: March 2021

Background: There have been some reports on the coexistence of psoriasis and atopic dermatitis; however, the longitudinal relationship between these two diseases remains unclear. Objective: This study aimed to investigate the bidirectional association between psoriasis and atopic dermatitis. Methods: This cohort study recruited patients from the National Health Insurance Research Database in Taiwan. We included 8,206 patients with psoriasis and 32,824 matched controls to assess the risk of atopic dermatitis and 25,743 patients with atopic dermatitis and 102,972 matched controls to assess the risk of psoriasis. Cox regression model was used for the analyses. Results: After adjusting for potential confounders, patients with psoriasis had a higher risk of atopic dermatitis (adjusted hazard ratio [aHR] 13.01; 95% CI 10.23–16.56) than the controls. Patients with atopic dermatitis had a higher risk of psoriasis (aHR 10.37; 95% CI 6.85–15.69) than the controls. Stratified analyses revealed similar results in both sexes and all age groups. Conclusion: Our study demonstrated a bidirectional association between psoriasis and atopic dermatitis, suggesting that psoriasis and atopic dermatitis are not mutually exclusive and may share some biological mechanisms.
Astilbin Protects Against Carbon Tetrachloride-Induced Liver Fibrosis in Rats
Authors: Sun Xiao-Hui , Zhang He , Fan Xiao-Ping , Wang Zhao-Hui
Published: March 2021

Background: Hepatic fibrosis is an inflammatory liver disease, and there is no effective therapy at present. Astilbin is a bioactive ingredient found in many medicinal and food plants, with antioxidative, anti-inflammatory, and antitumor properties. Objectives: This study aimed to investigate the protective effect and related molecular mechanism of astilbin against carbon tetrachloride (CCl4)-induced liver fibrosis in rats. Methods: Liver fibrosis was induced by injection of CCl4 in male Sprague-Dawley rats, and those rats were then treated with astilbin at different concentrations. Pathological changes, collagen production, inflammatory cytokine, and oxidative stress were evaluated to evaluate the effects of astilbin on CCl4-induced hepatic fibrosis. Real-time PCR and western blot were performed to detect the mRNA and protein expression of indicated genes. Results: We discovered that CCl4 caused significant fibrosis damage in rat liver, and astilbin dose-dependently improved the liver functions and fibrosis degree. Astilbin treatment significantly decreased collagen production, inflammatory response, and oxidative stress in vivo. Mechanically, administration of astilbin obviously elevated the hepatic levels of Nrf2 and its downstream components, including NAD(P)H:quinone oxidoreductase 1 (Nqo1), heme oxygenase (HO-1), glutamate-cysteine ligase catalytic subunit, and glutamate cysteine ligase modifier. Conclusions: Taken together, these findings demonstrate that astilbin could protect against CCL4 induced-liver fibrosis in rats.
Abdominal Recurrence after Robotic Nephron-Sparing Surgery for Wilms Tumor in an Adult Patient
Authors: Schiavetti Amalia , Ferrara Eva , De Grazia Alessandra , Cozzi Denis A.
Published: March 2021

A 31-year-old man was referred to an adult urologist for a renal polar mass that measured 7.2 cm in maximum diameter. Robotic assisted complete tumor excision for suspicious renal cell carcinoma was carried out, preserving the rest of the left kidney. Histopathology showed a Wilms tumor (WT) with positive margins. No postoperative therapy was made, and the patient shortly presented an abdominal recurrence. The patient was referred to our pediatric oncology unit; he received preoperative chemotherapy, followed by surgery (completion nephrectomy and removal of neoplastic deposits in the omentum and parietal peritoneum), postoperative chemotherapy, and abdomen radiotherapy. He is well at the 5-year follow-up. Peritoneal dissemination after laparoscopic nephron-sparing surgery (NSS) in a child with a 10-cm WT was previously reported. We suggest open NSS for large WT may be safer than laparoscopic or robotic NSS because carbon dioxide pneumoperitoneum and traumatic handling of tumor may predispose to tumor cell migration. An abdominal WT relapse in adults can be salvaged by multimodal therapy recommended by current pediatric WT guidelines.