bluuebunny/crossref_metadata_2025 huggingface dataset:
Age- and Sex-Specific Reference Values of Estimated Glomerular Filtration Rate in Chinese Population
Authors: Yue Lili , Fan Li , Du Xin
Published: March 2021

Background: Due to an aging population, prevalence and mortality of CKD continue to increase. Current CKD definition has been challenged recently. Age- and sex-specific reference values of estimated glomerular filtration rate (eGFR) in China are still lacking. Methods: Age- and sex-stratified, randomly selected inhabitants received a health examination and an inquest into medical history. The GFR was estimated using CKD-EPI equation. We calculated means with ±1.96 times of standard deviation and 2.5th, 97.5th percentiles of eGFR per 5-year age-group. Some of their GFRs were measured by the Gates method (99mTc-DTPA renal scintigraphy) and estimated by cystatin C-based equation. Results: The cohort study included 17,037 male and 9,304 female Chinese persons aged 18–99 years. A reference population of apparently healthy subjects was selected by excluding persons with known hypertension, diabetes, cardiovascular, or renal diseases. This healthy cohort study included 12,231 male subjects and 6,463 female subjects. The mean eGFR was higher in the female than that in the male who were younger than 40-year (122 mL/min/1.73 m2 vs. 111 mL/min/1.73 m2). In these apparently healthy persons, GFR declined approximately 0.8 mL/min/year. The lower limit of eGFR (2.5th percentile or mean minus 1.96 times of standard deviation) was <60 or 45 mL/min/1.73 m2 at the age of ≥40 or 65 years old, respectively. Conclusion: The mean eGFR was higher in young females. GFR declined approximately 0.8 mL/min/year. The lower bound of eGFR was <60 mL/min/1.73 m2 or 45 mL/min/1.73 m2 at the age of ≥40 or ≥65 years, respectively. Our study provides age- and sex-specific reference values of GFR in a Chinese population.
Metabolic Effects of Growth Hormone Treatment in Short Prepubertal Children: A Double-Blinded Randomized Clinical Trial
Authors: Tidblad Anders , Gustafsson Jan , Marcus Claude , Ritzén Martin , Ekström Klas
Published: March 2021

Introduction: Growth hormone (GH) is a central hormone for regulating linear growth during childhood and also highly involved in the metabolism of lipids, carbohydrates, and protein. However, few studies report on how treatment with GH during childhood influences metabolic parameters. Our aim was to investigate metabolic effects of different doses of GH in short children with GH peak levels in the low to normal range. Design: Thirty-five prepubertal short children (<−2.5 SDS), aged 7–10 years, with peak levels of GH between 7 and 14 μg/L during an arginine-insulin tolerance test, were randomized to 3 different doses (11/33/100 μg/kg/day) of GH treatment for 2 years. Auxological and metabolic investigations were performed. These included metabolites in blood and interstitial microdialysis fluid, dual-energy X-ray absorptiometry, frequently sampled intravenous glucose tolerance test (FSIVGTT), and stable isotope examinations of rates of glucose production and lipolysis. Results: At 24 months, the high-dose group (HD) had higher fasting insulin compared with the standard-dose (SD) and low-dose (LD) groups (HD: 111.7 vs. SD: 61.2 and LD: 46.0 pmol/L [p < 0.001]) and showed signs of insulin resistance (HOMA-IR, HD: 4.20 vs. SD: 2.17 and LD: 1.71 (LD) [p < 0.001]). The FSIVGTT also demonstrated higher acute insulin response (p < 0.05). Few other metabolic differences were found at 24 months, but a decreased insulin sensitivity index (Si) could already be seen at 12 months for both SD and HD compared with the LD group (p < 0.05). Conclusion: Treatment with GH resulted in a dose-dependent decrease in insulin sensitivity, demonstrated by higher levels of fasting insulin and signs of insulin resistance in both HOMA indices and FSIVGTT examinations.
The Evolution of the Neonatal QRS Axis during the First Four Weeks of Life
Authors: Pærregaard Maria Munk , Kock Jesper , Pihl Christian , Pietersen Adrian , Iversen Kasper Karmark , Bundgaard Henning , Christensen Alex Hørby
Published: March 2021

Background: The QRS axis represents the sum and orientation of the ventricular depolarization. Accurate interpretation of abnormalities in the QRS axis may facilitate early diagnosis of heart disease in newborns. We aimed at describing the evolution of the QRS axis during the first 4 weeks of life and provide reference values from healthy newborns. Methods: The Copenhagen Baby Heart Study is a prospective general population study that offered cardiac evaluation during the first month of life to all newborns delivered in the Copenhagen area. Results: Electrocardiograms from 12,317 newborns (52% boys; mean age 12 days) with normal echocardiograms were included. The median QRS axis was 119° at the ages 0–7 days and shifted leftward to 102° at the ages 22–28 days (p < 0.001). We found that girls had a significantly less pronounced right-shifted axis than boys (p < 0.001) and that increasing gestational age (GA) was associated with a more pronounced right-shifted axis (p < 0.05). Infant size did not affect the axis (p > 0.05). Only 0.5% had an axis within the interval 0 to −90° and 1.1% in the interval +240 to +30°. Conclusions: The QRS axis showed a gradual leftward-shift during the first 4 weeks of life and was affected by sex and GA but unaffected by infant size. Less than 1% of the newborns had a QRS axis between 0 and −90°. This study represents updated reference values, which may facilitate the clinical handling of newborns.
Radical versus Functional Endoscopic Sinus Surgery for Osteitis in Chronic Rhinosinusitis
Authors: Wang Mingjie , Zhou Bing , Li Yunchuan , Cui Shunjiu , Huang Qian
Published: March 2021

Introduction: Osteitis in chronic rhinosinusitis (CRS) is a predictive factor of disease severity and an important potential reason for disease recalcitrance. Other than medical treatment, transnasal endoscopic surgery could be another choice to deal with osteitis in CRS. Objective: In this study, 2 different surgical outcomes and influence in patients with osteitis in CRS were discussed. Methods: A retrospective analysis of 51 cases was carried out. Osteitis in CRS was confirmed by sinus computed tomography (CT). According to surgical management, patients were divided into the radical endoscopic sinus surgery (RESS) group (n = 24) and functional endoscopic sinus surgery (FESS) group (n = 27). Baseline measures and postoperative outcomes were evaluated by symptom visual analog scale (VAS), peripheral blood eosinophil percentage, serum total IgE, skin prick test, endoscopy Lund-Kennedy score, CT scan Lund-Mackay score, and global osteitis scoring scale (GOSS) in 2 groups. Results and Conclusions: There was no significant difference between the 2 groups in age, gender, and complicated with allergic rhinitis and asthma. The preoperative symptom VAS score and endoscopy Lund-Kennedy score were higher in the RESS group than in the FESS group, and the Lund-Mackay score and GOSS score were similar in the 2 groups. One year after surgery, symptom VAS scores, endoscopy Lund-Kennedy score, and Lund-Mackay score were significantly lower in the 2 groups. The endoscopy Lund-Kennedy score and Lund-Mackay score were lower in the RESS group than in the FESS group 1 year after surgery. RESS was more effective in reducing inflammatory load of sinuses in patients with osteitis in CRS.
Early Outcomes and Complications of Endovascular Treatment of Cerebral Arteriovenous Malformations in Pediatric Patients
Authors: Rodriguez-Calienes Aaron , Bustamante-Paytan Diego , Camacho Kiara , Mayoria-Vargas Angie , Saal-Zapata Giancarlo , Rodriguez-Varela Rodolfo
Published: March 2021

Introduction: Arteriovenous malformations (AVMs) are the commonest cause of hemorrhagic stroke in children. Endovascular embolization is a feasible treatment modality, but cure rates are heterogenous from one series to another. We aimed to describe the immediate obliteration rates and periprocedural complications of embolization of pediatric AVMs. Methods: Between 2011 and 2019, participants below 18 years of age with AVMs treated by the same neurosurgeon at a single center were included. The clinical features, immediate angiographic results, and periprocedural complications were retrospectively collected from the clinical records. Results: Thirty-four embolization sessions were performed on 20 children (12 females with a mean age of 13). Intracranial hemorrhage was the most common presentation (75%), and the majority were frontal (30%) and basal ganglia (30%) lesions. An immediate complete angiographic obliteration was achieved in 9 patients (45%) with low-grade lesions (Spetzler-Martin grade I and II). NBCA was the most common embolic agent used (52.9%). Complications were reported in 3 (8.8%) out of 34 sessions. Two of them were intraoperative perforations with clinical consequences. A slight cortical hemorrhage during the procedure was observed in 1 patient without clinical repercussions. Discussion: This single-surgeon single-center experience suggests that endovascular treatment is a safe and efficient treatment for pediatric AVMs. Pediatric prognostic scores for a suitable selection of candidates are needed. Further studies are required to validate these results.
Gait Parameters of Older Adults according to Their Fall History and Functional Capacity While Walking at Different Speeds
Authors: Pophal da Silva Letícia , Boneti Moreira Natália , Barbosa de Freitas Paulo , Pereira Gleber , Rodacki André Luiz Felix
Published: March 2021

Introduction: It is believed that functional capacity and fall history are factors capable of influencing the gait parameters of older adults. Thus, the objective of this study was to verify whether gait parameters of community-dwelling older adults differ according to their functional capacity and fall history when walking at self-selected walking speed (SSWS) and fast walking speed (FWS) using principal component analysis (PCA). Methods: Two hundred ninety-five participants (82.3% women and 17.7% men) were allocated in four groups according to their fall history and functional capacity: non-fallers with higher functional capacity (NFHFC, n = 94; 69.3 ± 5.5 years), non-fallers with lower functional capacity (NFLFC, n = 114; 72.0 ± 8.1 years), fallers with higher functional capacity (FHFC, n = 29; 70.0 ± 6.0 years), and fallers with lower functional capacity (FLFC, n = 58; 72.5 ± 8.2 years). Fall history, anthropometric data, functional capacity by short physical performance battery and mobility by Timed Up and Go (TUG), and spatiotemporal gait parameters were evaluated. Results: Data analysis indicated that FLFC presented the lowest scores, especially in the Five Times Sit-to-Stand Test and TUG. The PCA showed that the first principal component (PC1) explained the most substantial amount of the data variability in both walking speeds (SSWS and FWS), predominantly including temporal parameters. PC2 composed by spatial outcomes (stride and step length and walking speed) showed the highest effect size. PC1 and PC2 were able to differentiate functional status, regardless of fall history. Conclusions: Functional capacity showed great importance when analyzing gait parameters at different walking speeds (SSWS and FWS), regardless of fall history. Older adults with high functional capacity demonstrate better performance during gait. Besides, spatiotemporal parameters are the main factors explaining gait variability, both in SSWS and FWS.
Asymptomatic Bacteriuria among Pregnant Women Attending Tertiary Care Hospital in Lucknow, India
Authors: Sonkar Naimshree , Banerjee Malay , Gupta Suman , Ahmad Absar
Published: March 2021

Introduction: Asymptomatic bacteriuria (ASB) is the presence of actively multiplying bacteria within the urinary tract with absence of any symptoms, resulting in adverse pregnancy outcomes. This research study was done in order to review prevalence, antimicrobial susceptibility profile, and factors associated with ASB occurring in female patients who are pregnant and being treated at a tertiary care hospital in Lucknow, India. Method and Materials: This is a cross-sectional study done among 216 pregnant women attending a hospital for antenatal check-ups. Clean catch midstream urine samples were collected and examined microscopically, and semi-quantitative culture was done on blood agar and MacConkey agar. Isolates were identified by colony morphology and biochemical tests, and antimicrobial susceptibility testing was done by using the Kirby-Bauer method. Results: Of the 216 pregnant women, 36 (16.7%) tested positive for ASB. The female gestational period, haemoglobin level, and BMI were significantly associated with ASB. Logistic regression also showed that higher haemoglobin level was less likely to ASB (AOR = 0.42, 95% confidence interval: 0.202–0.88, p = 0.021). The predominant and usual isolates were E. coli (n = 22, 61.1%), followed by Cons (n = 6, 16.7%), and S. aureus (3, 8.3%). All Gram-negative isolates were mostly sensitive to most of the drugs like piperacillin-tazobactam, cefepime, nitrofurantoin, and meropenem but were 100% resistant to ampicillin. Similarly, Gram-positive isolates were sensitive to ampicillin, vancomycin, linezolid, and nitrofurantoin but 100% resistant to co-trimoxazole. Conclusion: The present study shows the existence of ASB was 16.7% among women who are pregnant. Pregnancy duration, haemoglobin level, and BMI were significantly associated with ASB. The isolates identified more frequently were E. coli (61.16%), Cons (16.7%), and S. aureus (8.3%). All isolates which were Gram-negative were mostly sensitive to most of the drugs but were 100% resistant to ampicillin. Similarly, Gram-positive isolates were sensitive to most of the drugs but 100% resistant to co-trimoxazole.
Nasal Cytology in Radiofrequency Turbinate Volume Reduction
Authors: Pecorari Giancarlo , Riva Giuseppe , Bartoli Claudia , Ravera Mattia , Dell’Era Valeria , Barbero Emanuela , Aluffi Valletti Paolo , Garzaro Massimiliano
Published: March 2021

Introduction: Radiofrequency turbinate volume reduction (RFTVR) is an effective treatment of inferior turbinate hypertrophy. RFTVR can reduce epithelial cell alterations in nasal mucosa. The aim of this observational study was to evaluate the effects of RFTVR on nasal obstruction and cytology, stratifying for different types of rhinitis. Methods: Nasal cytology and subjective nasal obstruction were evaluated on 113 patients before RFTVR (T0) and after 3 months (T1). The patients were divided into groups on the basis of the underlying disease: allergic rhinitis, nonallergic rhinitis, rhinitis medicamentosa, and other diseases (e.g., hormonal-based turbinate hypertrophy). Results: Nasal cytology at T0 identified 42 patients with allergic rhinitis, 40 with nonallergic rhinitis, 19 with rhinitis medicamentosa, and 12 with other diseases. An improvement of nasal cytology at T1 was observed in 29.2% of cases. They mainly consisted of patients with nonallergic rhinitis with neutrophils, whose neutrophil infiltrate decreased. Only 2 cases (1.7%) showed a worsening of nasal cytology at T1. A statistically significant decrease in subjective nasal obstruction was observed for every group (p < 0.05). Higher differences of nasal obstruction between T0 and T1 were found in patients with rhinitis medicamentosa or other diseases. Conclusion: RFTVR represents a safe and effective treatment for turbinate hypertrophy of various etiology. It is not responsible for a worsening of inflammatory infiltrate of the nasal mucosa.
An Important Form of Diabetes for Clinicians: Ketosis-Prone Diabetes
Authors: Ekiz Esra , Celepkolu Tahsin , Karahan Yavuz
Published: March 2021

Ketosis-prone diabetes (KPD) is defined as a hybrid form of diabetes mellitus, which is predominantly seen in overweight-to-obese men. Although the diagnosis is based on diabetic ketoacidosis (DKA) as a presenting feature, which also is characteristic of type 1 diabetes, the course of the disease differs from type 1. Recognition of this form by the clinicians is important as these patients are negative for autoantibodies and share the characteristics of type 2 diabetes during follow-up. Here we report 2 cases of KPD presenting with DKA and maintaining normoglycemia without insulin after receiving short-term intensive insulin treatment.
Maternal and Fetal Outcome in Intrahepatic Cholestasis of Pregnancy in a Multicultural Society Conducted at a Tertiary Care Hospital in Dubai
Authors: Aftab Nighat , Faraz Saima , Hazari Komal , Mahgoub Faiza Badawi
Published: March 2021

Introduction: Intrahepatic cholestasis of pregnancy (ICP) has been sparsely studied especially in the Middle East. The incidence and outcome of ICP varies worldwide. Its incidence in the Middle East and primary maternal and fetal outcome must be evaluated to ascertain the burden so that appropriate preventive and intervention measures can be formulated and implemented. Objective: To assess the incidence, associations, and maternal-fetal outcomes in ICP. Design: Case-control study. Settings: tertiary care hospital settings affiliated with the academic center in the UAE. Patients and methods: a total of 150 patients were included from October 2016 to September 2018 in the study with 75 cases of ICP and 75 controls matched according to age and date of delivery. The maternal risk factors attributable to ICP were recorded. Biochemical profile of mothers was monitored. Maternal and fetal outcomes were compared in 2 groups. Main outcomes measured: incidence and associations of ICP were evaluated. Maternal and fetal outcomes were compared in cases and controls. Sample size: 150. Result: The incidence of ICP in our study in the UAE was 1.0%. ICP has significant association with past obstetric cholestasis history (p value <0.01, odds ratio [OR] 9.3, 95% CI: 2.1–41.8), gestational diabetes (p value <0.05, OR 2.0, 95% CI: 1.0–3.8), pre-eclampsia (p value <0.05, OR 7.2, 95% CI: 1.6–33.1), and undergoing induction of labor (p value <0.01, OR 8.1, 95% CI: 3.7–17.8). The maternal bile acid level above 40 μmol/L is ­associated with higher chances of preterm delivery (p value <0.01, OR 8.2, 95% CI: 3.0–22.5), intrauterine fetal demise (p value <0.01), low birth weight (p value <0.01, OR 13.6, 95% CI: 4.2–43.5), respiratory distress (p value <0.05, OR 15.5, 95% CI: 1.8–132.7), poor Apgar score (p value <0.05, OR 12.720, 95% CI: 1.5–111.4), and NICU admissions (p value <0.01, OR 9.0, 95% CI: 1.8–45.9). Conclusion: ICP mothers have low incidence in the UAE and significant association with gestational diabetes and pre-eclampsia. High maternal bile acids above 40 μmol/L have poor fetal outcomes.
Hip Fracture in Patients with Parkinson’s Disease and Related Mortality: A Population-Based Study in Korea
Authors: Nam Je Shik , Kim Yong Wook , Shin Jaeyong , Chang Jee Suk , Yoon Seo Yeon
Published: March 2021

Introduction: Patients with Parkinson’s disease (PD) are prone to falls, thereby increasing the risk of fractures and mortality. This population-based study investigated the risk of hip fractures and their effect on mortality in patients with PD in Korea. Methods: National Health Insurance Service-National Sample Cohort data were used. Patients newly diagnosed with PD between 2006 and 2015 and age- and sex-matched individuals were classified into the PD group and the comparison group, respectively, with a 1:9 ratio. The Cox proportional hazards model was used to calculate hazard ratios (HRs), and the Kaplan-Meier method to identify survivorship. Results: In total, 26,570 individuals were enrolled in the study: 2,657 in the PD cohort and 23,913 in the matched comparison cohort. The PD group had about a 2 times higher risk of hip fracture than the comparison group (3.95 vs. 1.94%, p < 0.001). According to sex, the difference between the PD and comparison groups for the risk of hip fracture was greater in males than in females. The highest difference in HR for hip fracture between the PD and comparison groups was found in individuals aged between 60 and 69 years. Regarding post-fracture mortality in patients with PD, the mortality risk was twice as high in the patients with hip fracture than in those without. The effect of hip fracture on mortality between these 2 groups was also the highest in individuals aged between 60 and 69 years. Conclusion: The PD group showed an approximately 2 times higher risk of hip fracture compared with the comparison group, and the post-fracture mortality rate was 2 times higher in the patients with PD with hip fracture than in those without. Those aged 60–69 years were associated with the highest risk of hip fracture and post-hip fracture mortality among patients with PD.
Opioid and Other Medication Use and General Health Status in a Cohort of Older Adults
Authors: Pinsky Paul F. , Durham Danielle , Strassels Scott
Published: March 2021

Objective: The aim of this study was to determine whether the use of opioids and other medications in a cohort of older adults was associated with self-reported health status. Methods: Among participants in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Screening Trial linked to Medicare Part D claims data and answering a quality-of-life questionnaire, we examined the relationship between medication use over a 5-year period and various self-reported health status variables assessed several years later, including overall health status (STATUS) and trouble with activities of daily living (TADL). Multivariable logistic regression was used to estimate odds ratios (ORs) for the health status variables and metrics of medication use, including >60-day use, and for opiates, chronic use, with models controlling for demographics (model I), additionally for chronic conditions (model II), and additionally for other medication use (model III). Results: The study cohort included 22,844 PLCO participants (56% women, 90% non-Hispanic whites); 4.2% had chronic opioid use and 12.5% used for >60 days. Fair-poor STATUS was reported in 37.9% of participants with chronic opioid use versus 15.0% of participants without (p < 0.001). ORs for chronic opioid use for fair-poor STATUS (compared to good-excellent) were significantly elevated in all models but decreased from model I (OR = 3.6; 95% CI :3.1–4.1) to model II (OR = 2.7; 95% CI :2.3–3.1) to model III (OR = 2.1; 95% CI :1.8–2.5). ORs for TADL were generally similar to those for STATUS. Other drug classes also had significantly elevated model III ORs for fair-poor versus good-excellent STATUS (range 1.1–1.6). Conclusion: Frequent use of various medication classes correlated with measures of future health status in an elderly population, with opioids having the strongest association. The magnitude of the association decreased after controlling for concurrent chronic conditions but remained elevated. Future research should consider how the use of opioids and other medications impact measures of health-related quality of life.
The COVID-Kidney Controversy: Can SARS-CoV-2 Cause Direct Renal Infection?
Authors: Lau Wei Ling , Zuckerman Jonathan E. , Gupta Ajay , Kalantar-Zadeh Kamyar
Published: March 2021

Context: Determining whether SARS-CoV-2 causes direct infection of the kidneys is challenging due to limitations in imaging and molecular tools. Subject of Review: A growing number of conflicting kidney biopsy and autopsy reports highlight this controversial issue. Second Opinion: Based on the collective evidence, therapies that improve hemodynamic stability and oxygenation, or dampen complement activation, are likely to ameliorate acute kidney injury in COVID-19. At this time, whether inhibition of viral infection and replication directly modulates kidney damage is inconclusive.
Fatal Disseminated Multiple Intracranial Juvenile Xanthogranuloma without Cutaneous and Other Organ Involvement: A Rare Case Report
Authors: Bilgin Emre , Ökten Ali Ihsan
Published: March 2021

Introduction: Juvenile xanthogranuloma (JXG) is a disorder of histiocytic proliferation that affects young children and usually presents as spontaneously regressing cutaneous lesions. JXG with systemic involvement is a rare entity associated with significant morbidity and mortality. Intracranial solitary lesions are uncommon, and when comorbid with multiple lesions of the central nervous system in young children, it has an extremely worse prognosis. Case Presentation: We have reported here an unusual case of a 6-year-old boy who initially presented with the complaints of headache, vomiting, seizure, and speech disorder without cutaneous and other organ involvement and a neurological tendency to sleep. Acute hydrocephalus was detected in his brain CT. As an emergency intervention, ventriculo-peritoneal shunt operation was performed on the patient. His postoperative MRI revealed a disseminated intracranial disease involving the extensive dural, sellar-suprasellar region, the orbit, and the brain parenchyma. The patient accordingly underwent a pterional approach for open biopsy and for the mass tissue diagnosis. Histopathology reports were consistent with JXG. Unfortunately, the patient succumbed to the disseminated disease within 2 months of the JXG diagnosis. Conclusion: JXG is a disorder that usually affects the skin. Intracranial lesion can be simple or have multiple involvement. This is a rare case of fatal disseminated multiple intracranial JXG without cutaneous and other organ manifestations. The presentation as a sellar-suprasellar, extensive dural, orbit, and parenchymal involvement at the time of diagnosis is unusual and rarely described in the literature.
Evaluation of Clinical Properties and Diagnostic Test Results of Cephalosporin Allergy in Children
Authors: Yilmaz Topal Ozge , Kulhas Celik Ilknur , Turgay Yagmur Irem , Toyran Muge , Civelek Ersoy , Karaatmaca Betul , Dibek Misirlioglu Emine
Published: March 2021

Introduction: Beta-lactams (BLs) are one of the most frequent causes of drug hypersensitivity reactions (HRs), and cephalosporins are a widely used subclass of BLs, especially in children. The aim of this study was to evaluate the clinical features and diagnostic test results of pediatric patients evaluated for suspected cephalosporin allergy. Methods: This study included patients who presented to our pediatric allergy clinic with a history of reactions attributed to cephalosporins between January 1, 2011, and December 31, 2019, and whose diagnostic tests were completed for the diagnosis. Results: This study included 120 pediatric patients and 69 (57.5%) of them were girls. The median age was 38.63 (interquartile range 10.5–85.7) months. Reactions occurring within 1 h of drug intake were reported in 33 patients (27.5%). Reactions were maculopapular rash in 55 (45.8%) patients, urticaria and/or angioedema in 49 (40.8%), anaphylaxis in 11 (9.2%), severe cutaneous drug reaction in 4 (3.3%), and fixed drug reaction in 1 patient (0.83%). The most frequently suspected agent was cefixime in 41 patients (34.2%). In total, 30 (25%) patients were diagnosed as having cephalosporin hypersensitivity. Confirmation of HRs was also significantly more frequent among patients who were older (p: 0.000), who had taken the drug parenterally (p: 0.000) and with immediate reactions (p: 0.000). Conclusion: Cephalosporin allergy has been confirmed in approximately one-fourth of the patients evaluated for suspected cephalosporin allergy. Confirmation of HRs was significantly more common among patients who were older, had immediate reactions, and had taken the drug parenterally.
Choosing Antifungals for the Midostaurin-Treated Patient: Does CYP3A4 Outweigh Recommendations? A Brief Insight from Real Life
Authors: Menna Pierantonio , Salvatorelli Emanuela , Del Principe Maria Ilaria , Perrone Salvatore , Pagano Livio , Marchesi Francesco , Minotti Giorgio
Published: March 2021

Introduction: Patients treated with midostaurin and chemotherapy are at risk of invasive fungal disease. Prophylactic posaconazole is recommended for these patients, but posaconazole strongly inhibits the CYP3A4 isozyme that metabolizes midostaurin. Posaconazole therefore introduces a risk of patient’s overexposure to midostaurin. Methods: Blood samples were obtained from 4 patients treated with midostaurin for newly diagnosed FLT3-mutAML. Patients had received a concomitant treatment with posaconazole, isavuconazole, or micafungin, respectively. All blood samples were drawn before daily dose administration of midostaurin. Results: Posaconazole caused a ≥8-fold increase of midostaurin plasma levels at through, which was accompanied by a decreased plasma exposure to O-demethylated or hydroxylated midostaurin metabolites. We also show that hematologists react to risk perception by replacing posaco­nazole with antifungals like micafungin or isavuconazole, which lack a strong inhibition of CYP3A4 and fail to modify midostaurin pharmacokinetics but are not formally recommended in these settings. Discussion: In real-life scenarios, concerns about CYP3A4 inhibition may outweigh compliance with recommendations. Large studies are needed to survey the risk:benefit of hematologist’s decision to replace posaconazole with other antifungals.
Cytogenetic Analysis of Panaqolus tankei Cramer & Sousa, 2016 (Siluriformes, Loricariidae), an Ornamental Fish Endemic to Xingu River, Brazil
Authors: Ferreira Alex M.V. , Viana Patrik F. , Zuanon Jansen , Ezaz Tariq , Cioffi Marcelo B. , Takagui Fábio H. , Feldberg Eliana
Published: March 2021

Despite conservation of the diploid number, a huge diversity in karyotype formulae is found in the Ancistrini tribe (Loricariidae, Hypostominae). However, the lack of cytogenetic data for many groups impairs a comprehensive understanding of the chromosomal relationships and the impact of chromosomal changes on their evolutionary history. Here, we present for the first time the karyotype of Panaqolus tankei Cramer & Sousa, 2016. We focused on the chromosomal characterization, using conventional and molecular cytogenetic techniques to unravel the evolutionary trends of this tribe. P. tankei, as most species of its sister group Pterygoplichthini, also possessess a conserved diploid number of 52 chromosomes. We observed heterochromatin regions in the centromeres of many chromosomes; pairs 5 and 6 presented interstitial heterochromatin regions, whereas pairs 23 and 24 showed extensive heterochromatin regions in their q arms. In situ localization of 18S rDNA showed hybridization signals correlating with the nucleolus organizer regions, which are located in the q arms of pair 5. However, the 5S rDNA was detected in the centromeric and terminal regions of the q arms of pair 8. (TTAGGG)n hybridized only in the terminal regions of all chromosomes. Microsatellite in situ localization showed divergent patterns, (GA)15 repeated sequences were restricted to the terminal regions of some chromosomes, whereas (AC)15 and (GT)15 showed a scattered hybridization pattern throughout the genome. Intraspecific comparative genomic hybridization was performed on the chromosomes of P. tankei to verify the existence of sex-specific regions. The results revealed only a limited number of overlapping hybridization signals, coinciding with the heterochromatin in centromeric regions without any sex-specific signals in both males and females. Our study provides a karyotype description of P. tankei, highlighting extensive differences in the karyotype formula, the heterochromatin regions, and sites of 5S and 18S rDNA, as compared with data available for the genus.
The Brain Connectome after Gamma Knife Radiosurgery of the Ventro-Intermediate Nucleus for Tremor: Marseille-Lausanne Radiobiology Study Protocol
Authors: Tuleasca Constantin , Witjas Tatiana , Levivier Marc , Girard Nadine , Cretol Axelle , Levy Nicolas , Thiran Jean-Philippe , Guedj Eric , Van de Ville Dimitri , Régis Jean
Published: March 2021

Essential tremor (ET) is the most common movement disorder. Deep brain stimulation is the current gold standard for drug-resistant tremor, followed by radiofrequency lesioning. Stereotactic radiosurgery by Gamma Knife (GK) is considered as a minimally invasive alternative. The majority of procedures aim at the same target, thalamic ventro-intermediate nucleus (Vim). The primary aim is to assess the clinical response in relationship to neuroimaging changes, both at structural and functional level. All GK treatments are uniformly performed in our center using Guiot’s targeting and a radiation dose of 130 Gy. MR neuroimaging protocol includes structural imaging (T1-weighted and diffusion-weighted imaging [DWI]), resting-state functional MRI, and 18F-fluorodeoxyglucose-positron emission tomography. Neuroimaging changes are studied both at the level of the cerebello-thalamo-cortical tract (using the prior hypothesis based upon Vim’s circuitry: motor cortex, ipsilateral Vim, and contralateral cerebellar dentate nucleus) and also at global brain level (no prior hypothesis). This protocol aims at using modern neuroimaging techniques for studying Vim GK radiobiology for tremor, in relationship to clinical effects, particularly in ET patients. In perspective, using such an approach, patient selection could be based upon a specific brain connectome profile.
Serum Vitamins and Homocysteine Levels in Obsessive-Compulsive Disorder: A Systematic Review and Meta-Analysis
Authors: Balandeh Ebrahim , Karimian Mohammad , Behjati Mohaddeseh , Mohammadi Amir Hossein
Published: March 2021

Vitamin and homocysteine (Hcy) alternations have been associated with psychiatric disorders. The aim of this meta-analysis was to assess the association of serum vitamin and Hcy levels with obsessive-compulsive disorder (OCD). Following PRISMA protocol, we used the databases including Scopus, PubMed, Google Scholar, and Web of Science with no time restriction. Data were pooled using a random-effects model and/or fixed-effects model to estimate the standard mean difference (SMD) for evaluation of the strength of association analyses. Our data showed a significant reduction in vitamin B12 (SMD = −0.58, 95% CI = −1.08 to −0.08, p = 0.02, I2 = 65%; pheterogeneity = 0.06), vitamin E (SMD = −0.89, 95% CI = −1.23 to −0.56, p < 0.00001, I2 = 23%; pheterogeneity = 0.26), and vitamin C (SMD = −1.40, 95% CI = −2.44 to −0.36, p = 0.008, I2 = 92%; pheterogeneity < 0.0001) in OCD patients. In addition, the findings showed significantly higher levels of Hcy (SMD = 1.11, 95% CI = [0.48, 1.75], p = 0.0006, I2 = 73%; ph = 0.02) in patients compared to controls. Also, our data showed that vitamin B9 and D levels are not associated with OCD (vitamin B9: SMD = −0.23, 95% CI = −1.01 to 0.55, p = 0.56, I2 = 88%; pheterogeneity < 0.0001; vitamin D: SMD = −0.63, 95% CI = −1.41 to 0.15, p = 0.11, I2 = 88%; pheterogeneity = 0.0002). Our findings support significant impacts of Hcy and vitamin B12, E, and C levels in OCD pathogenesis. This will be important for prevention and treatment of OCD. However, further studies are recommended to elucidate more accurate conclusions.
Irritable Mood and Subthreshold Hypomanic Episodes Correlate with More Severe Major Depression
Authors: Serretti Alessandro , De Ronchi Diana , Olgiati Paolo
Published: March 2021

Introduction: Irritable mood (IM) and subthreshold hypomanic symptoms are reported in half and two-fifths of major depressed subjects respectively, but their clinical and prognostic meanings remain unclear. The aim of this study was to test the clinical usefulness of 2 specifiers in DSM-IV major depressive disorder (MDD): IM occurring during an index episode (IM+) and lifetime episodes of elated mood or IM with at least 2 concurrent hypomanic symptoms (subthreshold hypomanic episodes [SHEs]). Method: We included 482 outpatients with MDD participating in the Combining Medications to Enhance Depression Outcome study (mean age 43.14 ± 12.46 years, 144 males – 30%). The main aim of the original study was to test whether 2 different medications when given in combination as the first treatment step, compared to 1 medication, would improve antidepressant response. Results: IM + subjects (N = 349; 70%) were younger and more often females, with a more severe depression, a more marked social impairment, and more psychiatric comorbidities. The IM + group was also characterized by higher levels of suicidal ideation and more cases of emotional abuse. The combination of IM+ and SHEs was associated with an even more severe clinical picture. Limitations include the post hoc method, incomplete assessment of bipolar validators (e.g., family history of bipolar illness), personality disorders and suicide attempts. Conclusions: The presence of IM and SHEs in MDD correlate with an overall more severe clinical condition.
On-Demand Mobile Health Infrastructure for Remote Rhythm Monitoring within a Wait-and-See Strategy for Recent-Onset Atrial Fibrillation: TeleWAS-AF
Authors: Pluymaekers Nikki A.H.A. , van der Velden Rachel M.J. , Hermans Astrid N.L. , Gawalko Monika , Buskes Saskia , Keijenberg Joyce J.H.M.W. , Vorstermans Bianca , Crijns Harry J.G.M. , Hendriks Jeroen M. , Linz Dominik
Published: March 2021

Recently, we introduced the TeleCheck-AF approach, an on-demand mobile health (mHealth) infrastructure using app-based heart rate and rhythm monitoring for 7 days, to support long-term atrial fibrillation (AF) management through teleconsultation. Herein, we extend the mHealth approach to patients with recent-onset AF at the emergency department (ED). In the proposed TeleWAS-AF approach, on-demand heart rate and rhythm monitoring are used to support a wait-and-see strategy at the ED. All stable patients who present to the ED with recent-onset symptomatic AF and who are able to use mHealth solutions for heart rate and rhythm monitoring are eligible for this approach. Patients will receive both education on AF and instructions on the use of the mHealth technology before discharge from the ED. A case coordinator will subsequently check whether patients are able to activate the mHealth solution and to perform heart rate and rhythm measurements. Forty hours after AF onset, the first assessment teleconsultation with the physician will take place, determining the need for delayed cardioversion. After maximal 7 days of remote monitoring, a second assessment teleconsultation may occur, in which the rhythm can be reassessed and further treatment strategy can be discussed with the patients. This on-demand mHealth prescription increases patient involvement in the care process and treatment decision-making by encouraging self-management, while avoiding excess data-load requiring work-intensive and expensive data management. Implementation of the TeleWAS-AF approach may facilitate the management of AF in the ED and reduce the burden on the ED system, which enhances the capacity for health care utilization.
Effects of Sex and Physical Activity Level on Serum Biomarker-Based Physiological Dysregulation: The Impact to Predict Frailty and Mortality in the Quebec NuAge Cohort
Authors: Ghachem Ahmed , Dufour Frédérik , Fülöp Tamas , Gaudreau Pierrette , Cohen Alan A.
Published: March 2021

Background: Age-related changes in biological processes such as physiological dysregulation (the progressive loss of homeostatic capacity) vary considerably among older adults and may influence health profiles in late life. These differences could be related, at least in part, to the impact of intrinsic and extrinsic factors such as sex and physical activity level (PAL). Objectives: The objectives of this study were (1) to assess the magnitude and rate of changes in physiologi­cal dysregulation in men and women according to PAL and (2) to determine whether/how sex and PAL mediate the apparent influence of physiological dysregulation on health outcomes (frailty and mortality). Methods: We used data on 1,754 community-dwelling older adults (age = 74.4 ± 4.2 years; women = 52.4%) of the Quebec NuAge cohort study. Physiological dysregulation was calculated based on Mahalanobis distance of 31 biomarkers regrouped into 5 systems: oxygen transport, liver/kidney function, leukopoiesis, micronutrients, and lipids. Results: As expected, mean physiological dysregulation significantly increased with age while PAL decreased. For the same age and PAL, men showed higher levels of physiological dysregulation globally in 3 systems: oxygen transport, liver/kidney function, and leukopoiesis. Men also showed faster global physiological dysregulation in the liver/kidney and leukopoiesis systems. Overall, high PAL was associated with lower level and slower rate of change of physiological dysregulation. Finally, while mortality and frailty risk significantly increased with physiological dysregulation, there was no evidence for differences in these effects between sexes and PAL. Conclusion: Our results showed that both sex and PAL have a significant effect on physiological dysregulation levels and rates of change. Also, although a higher PAL was associated with lower level and slower rate of change of physiological dysregulation, there was no evidence that PAL attenuates the effect of physiological dysregulation on subsequent declines in health at the end of life. Substantial work remains to understand how modifiable behaviors impact the relationship between physiological dysregulation, frailty, and mortality in men and women.
Quantitative Measurement of IgG to Severe Acute Respiratory Syndrome Coronavirus-2 Proteins Using ImmunoCAP
Authors: Keshavarz Behnam , Wiencek Joesph R. , Workman Lisa J. , Straesser Matthew D. , Muehling Lyndsey M. , Canderan Glenda , Drago Fabrizio , Bonham Catherine A. , Sturek Jeffrey M. , Ramani Chintan , McNamara Coleen A. , Woodfolk Judith A. , Kadl Alexandra , Platts-Mills Thomas A.E. , Wilson Jeffrey M.
Published: March 2021

Background: Detailed understanding of the immune response to severe acute respiratory syndrome coronavirus (SARS-CoV)-2, the cause of coronavirus disease 2019 (CO­VID-19) has been hampered by a lack of quantitative antibody assays. Objective: The objective was to develop a quantitative assay for IgG to SARS-CoV-2 proteins that could be implemented in clinical and research laboratories. Methods: The biotin-streptavidin technique was used to conjugate SARS-CoV-2 spike receptor-binding domain (RBD) or nucleocapsid protein to the solid phase of the ImmunoCAP. Plasma and serum samples from patients hospitalized with COVID-19 (n = 60) and samples from donors banked before the emergence of COVID-19 (n = 109) were used in the assay. SARS-CoV-2 IgG levels were followed longitudinally in a subset of samples and were related to total IgG and IgG to reference antigens using an ImmunoCAP 250 platform. Results: At a cutoff of 2.5 μg/mL, the assay demonstrated sensitivity and specificity exceeding 95% for IgG to both SARS-CoV-2 proteins. Among 36 patients evaluated in a post-hospital follow-up clinic, median levels of IgG to spike-RBD and nucleocapsid were 34.7 μg/mL (IQR 18–52) and 24.5 μg/mL (IQR 9–59), respectively. Among 17 patients with longitudinal samples, there was a wide variation in the magnitude of IgG responses, but generally the response to spike-RBD and to nucleocapsid occurred in parallel, with peak levels approaching 100 μg/mL, or 1% of total IgG. Conclusions: We have described a quantitative assay to measure IgG to SARS-CoV-2 that could be used in clinical and research laboratories and implemented at scale. The assay can easily be adapted to measure IgG to mutated COVID-19 proteins, has good performance characteristics, and has a readout in standardized units.
The Relationship between Adult Height and Blood Pressure
Authors: Cochran John Michael , Siebert Vincent R. , Bates Jeffrey , Butulija Djenita , Kolpakchi Anna , Kadiyala Himabindu , Taylor Addison , Jneid Hani
Published: March 2021

Background: Identification and modification of cardiovascular risk factors is paramount to reducing cardiovascular disease morbidity and mortality. Hypertension is a major risk factor for cardiovascular disease, but its association with height remains largely underrecognized. Objectives: The objective of this manuscript is to review the evidence examining the association between blood pressure and human stature and to summarize the plausible pathophysiological mechanisms behind such an association. Methods: A systematic review of adult human height and its association with hypertension and coronary artery disease was undertaken. The literature evidence is summarized and tabulated, and an overview of the pathophysiological basis for this association is presented. Results: Shorter arterial lengths found in shorter individuals may predispose to hypertension in a complex hemodynamic interplay, which is explained predominantly by summated arterial wave reflections and an elevated augmentation index. Our systemic review suggests that an inverse relationship between adult height and blood pressure exists. However, differences in the studied populations and heterogeneity in the methods applied across the various studies limit the generalizability of these findings and their clinical application. Conclusion: Physiological studies and epidemiological data suggest a potential inverse association between adult height and blood pressure. Further research is required to define the relationship more clearly between adult height and blood pressure and to assess whether antihypertensive therapeutic approaches and goals should be modified according to patients’ heights.
Hemodynamic Changes in an Actively Rupturing Abdominal Aortic Aneurysm
Authors: McClarty Davis B. , Kuhn David C.S. , Boyd April J.
Published: March 2021

Computational fluid dynamics were used to assess hemodynamic changes in an actively rupturing abdominal aortic aneurysm (AAA) over a 9-day period. Active migration of contrast from the lumen into the thickest region of intraluminal thrombus (ILT) was demonstrated until it ultimately breached the adventitial layer. Four days after symptom onset, there was a discrete disruption of adventitial calcium with bleb formation at the site of future rupture. Rupture occurred in a region of low wall shear stress and was associated with a marked increase in AAA diameter from 6.6 to 8.4 cm. The cross-sectional area of the flow lumen increased across all time points from 6.28 to 12.08 cm2. The increase in luminal area preceded the increase in AAA diameter and was characterized by an overall deceleration in recirculation flow velocity with a coinciding increase in flow velocity penetrating the ILT. We show that there are significant hemodynamic and structural changes in the AAA flow lumen in advance of any appreciable increase in aortic diameter or rupture. The significant increase in AAA diameter with rupture suggests that AAA may actually rupture at smaller sizes than those measured on day of rupture. These findings have implications for algorithms the predict AAA rupture risk.