bluuebunny/crossref_metadata_2025 huggingface dataset:
Radial head excision and Achilles allograft interposition arthroplasty for the treatment of chronic pediatric radiocapitellar pathologies: A report of four cases
Authors: Factor Shai , Rotman Dani , Pritsch Tamir , Allon Raviv , Tordjman Daniel , Atlan Franck , Rosenblatt Yishai
Published: January 2020

Background

Severe radiocapitellar pathologies represent a unique problem in the pediatric population, as radial head excision can lead to substantial long-term complications. We present a case series of four pediatric patients treated by a novel technique—radial head excision followed by Achilles allograft interposition arthroplasty.

Methods

Four children (ages 12–15 years) are described. Their clinical and radiographic outcomes were assessed by a visual analog scale, the Mayo Elbow Performance Score, the Disabilities of the Arm, Shoulder and Hand questionnaire, grip strength, and range of motion.

Results

At a mean follow-up of two years, the average flexion-extension arc of motion improved from 107° to 131°, and the rotation arc improved from 100° to 154°. The average visual analog scale, Mayo Elbow Performance Score, and Disabilities of the Arm, Shoulder and Hand scores were 2, 92.5, and 11.5, respectively. Two patients required subsequent additional procedures—manipulation under anesthesia and ulnar shortening osteotomy. Proximal migration of the radius was observed in three out of the four patients.

Discussion

Combined radial head excision and Achilles allograft interposition arthroplasty represents a viable option for the treatment of chronic pediatric radiocapitellar pathologies, with good results in terms of clinical and functional outcomes as well as patient satisfaction in the short-medium term.
Novel reliability criteria for controlled attenuation parameter assessments for non‐invasive evaluation of hepatic steatosis
Authors: Semmler Georg , Wöran Katharina , Scheiner Bernhard , Unger Lukas Walter , Paternostro Rafael , Stift Judith , Schwabl Philipp , Bucsics Theresa , Bauer David , Simbrunner Benedikt , Stättermayer Albert Friedrich , Pinter Matthias , Trauner Michael , Reiberger Thomas , Mandorfer Mattias
Published: January 2020

Background

There is conflicting evidence regarding reliability criteria for the controlled attenuation parameter (CAP; a marker for hepatic steatosis [HS]). Thus, we assessed the diagnostic performance of CAP according to different reliability criteria based on real‐world data from an academic centre.

Methods

Patients undergoing measurement of CAP and liver biopsy (±6 months) at the Medical University of Vienna were included. HS was assessed according to SAF score.

Results

In total 319 patients were included. The main aetiologies were non‐alcoholic fatty liver disease (NAFLD, n  = 177, 55.5%), viral hepatitis (n  = 49, 15.4%), and alcoholic liver disease (ALD, n  = 29, 9.1%). Histological steatosis and fibrosis stages were: S0: 93 (29.2%), S1: 100 (31.3%), S2: 67 (21.0%), and S3: 59 (18.5%); F0/F1: 150 (47.0%), F2: 47 (14.7%), and F3/F4: 122 (48.3%). In the overall cohort, the area under the receiver operating characteristic curve (AUC) of CAP was 0.843 (95% confidence interval [CI]: 0.798–0.887) for diagnosing HS ≥ S1), 0.789 (95%CI: 0.740–0.839) for ≥S2, and 0.767 (95%CI: 0.712–0.823) for S3. CAP corrections as suggested by Karlas et al. did not improve the diagnostic performance. Importantly, the AUC of CAP for HS ≥ S1 was numerically highest in patients with CAP‐IQR/median<0.10 or <0.20 (obtained in 37.9% and 74.9%), in whom CAP also had better diagnostic performance, as compared with patients not meeting these criteria. Moreover, it was substantially higher in 288 (90.3%) patients with CAP‐IQR/median<0.3: 0.856 (95%CI: 0.809–0.903) vs. patients not meeting this criterion (0.530 [95%CI: 0.309–0.751]). In contrast, the previously suggested reliability criterion of CAP‐IQR<40 dB/m was not associated with an improved diagnostic performance for HS≥S1 (0.866 [95%CI: 0.812–0.920] vs. 0.799 [95%CI: 0.717–0.881]) and was only obtained in 199 (62.4%) patients.

Conclusion

CAP‐IQR/median<0.1, <0.2, and <0.3 identify reliable measurements for diagnosing any hepatic steatosis (≥S1). Importantly, CAP‐IQR/median<0.3 has a considerably higher applicability in clinical practice, as compared with the previously suggested CAP‐IQR<40 dB/m criterion.
Pancreatic tuberculosis: A systematic review of symptoms, diagnosis and treatment
Authors: Panic Nikola , Maetzel Hartwig , Bulajic Milutin , Radovanovic Mihailo , Löhr J‐Matthias
Published: January 2020

Introduction

Although pancreatic tuberculosis (TB) is traditionally considered to be a rare clinical entity, in recent times, an increase in the number of reports of pancreatic TB has been noted. We conducted a systematic review in order to summarise currently available data on pancreatic TB.

Methods

A comprehensive literature search of Medline, Scopus and ISI Web of Science databases was conducted in order to identify papers reporting cases of pancreatic TB. The eligibility criteria for inclusion in the review required that the studies reported patient(s) affected by pancreatic TB and that individual data on age, sex, clinical presentation and outcome were available.

Results

In total, 116 studies reporting data on 166 patients were included in the analysis. The majority of patients were males (62.1%) diagnosed at a mean age of 41.61 ± 13.95 years. Most cases were diagnosed in Asia (50.0%), followed by North America (22.9%), Europe (20.5%), Africa (4.2%) and South America (2.4%). Human immunodeficiency virus (HIV) infection was diagnosed in 25.3% of those affected. Pancreatic TB most frequently presented itself in the form of a pancreatic mass (79.5%) localised mainly in the head (59.0%) and less frequently in the body (18.2%) and tail (13.4%). Extrapancreatic TB involvement most frequently affected the peripancreatic lymph nodes (47.3%). More than half of patients (55.2%) were subjected to laparotomy, while 21.08% underwent endoscopic ultrasound fine‐needle aspiration biopsy. The presence of TB was identified most frequently through histological analysis (59.6%), followed by culture (28.9%), staining (27.7%) and, in a smaller number, by polymerase chain reaction (9.6%) and cytology (6.6%). Almost all patients received anti‐tubercular pharmacological therapy (98.2%), while 24.1% underwent surgery. Despite treatment, 8.7% of patients died.

Conclusion

Increased awareness of pancreatic TB is needed, not only in endemic areas but especially in relation to HIV infection and other clinical conditions associated with immunoincompetence.
Traditional Dietary Habits and Interprovincial Migration in College Choice: Evidence From Ningxia in China
Authors: Kang Le , Ye Xiaoyang , Ding Yanqing
Published: January 2020

Purpose:

Every September, millions of students—elite human resources—enter higher education in China. This large-scale college-induced migration has substantial impacts on China’s national and local labor markets. This study examines the migration pattern in college choice and admission among the Hui students in China. In doing so, we extend the existing interprovincial migration model by identifying and measuring the role of traditional dietary habits in college migration decisions.

Design/Approach/Methods:

This study uses college entrance examination ( Gaokao) admission data for 10 high school graduation cohorts from 2001 to 2010 in the Ningxia Hui Autonomous Region. These data are used to study the interprovincial migration of the Hui students following their college entrance examination. Ordinary least squares and logit regressions are used to control for other confounding factors, while the method of instrumental variables and placebo group comparison were used to rule out other explanations.

Findings:

Results demonstrate that traditional dietary habits produce geographic inequalities in terms of college opportunities for Hui and other minority group students. First, after controlling for variables such as college entrance examination scores and personal characteristics, results show that the Hui students are more likely to choose an institution closer to their hometown and preferred institutions located in Ningxia and the northwestern provinces rather than the Yangtze/Pearl River Delta regions and coastal provinces. Second, this migration pattern is shaped by the dietary habits of the Hui. Third, the Hui students were more likely to choose institutions in underdeveloped areas, resulting in corresponding welfare losses.

Originality/Value:

This study supplements classic college choice literature by documenting a special impact factor of geography previously overlooked by researchers, demonstrating the need to examine the underlying mechanisms of proximity and its significance in college choice. Moreover, the provision of dietary information may have important policy impacts for improved college choice, as well as for human capital investment and poverty alleviation measures in Northwest China.
Plasma neurofilament light as a longitudinal biomarker of neurodegeneration in Alzheimer’s disease
Authors: Ou Ya-Nan , Hu Hao , Wang Zuo-Teng , Xu Wei , Tan Lan , Yu Jin-Tai ,   Alzheimer’s Disease Neuroimaging Initiative
Published: January 2020

Objective:

To examine whether plasma neurofilament light (NFL) might be a potential longitudinal biomarker for Alzheimer’s disease (AD).

Methods:

A total of 835 individuals from the Alzheimer’s Disease Neuroimaging Initiative were involved. Correlations of the rate of change in plasma NFL with cerebrospinal fluid biomarkers, cognition, and brain structure were investigated. Cox proportional hazards models were used to assess the associations between quartiles of plasma NFL and the risk of AD conversion.

Results:

Participants were further divided into β amyloid-positive (Aβ+) versus β amyloid-negative (Aβ−), resulting in five biomarker group combinations, which are CN Aβ−, CN Aβ+, MCI Aβ−, MCI Aβ+ and AD Aβ+. Plasma NFL concentration markedly increased in the five groups longitudinally ( p < 0.001) with the greatest rate of change in AD Aβ+ group. The rate of change in plasma NFL was associated with cognitive deficits and neuroimaging hallmarks of AD over time ( p < 0.005). Compared with the bottom quartile, the top quartile of change rate was associated with a 5.41-fold increased risk of AD (95% CI = 1.83−16.01) in the multivariate model.

Conclusion:

Our finding implies the potential of plasma NFL as a longitudinal noninvasive biomarker in AD.
Visualizing the neuroanatomical changes in Han Chinese adulthood: A pseudo-longitudinal study based on age-related large-scale statistical Chinese brain atlases
Authors: Shi Lin , Liang Peipeng , Li Andy , Wong Raymond , Luo Yishan , Liu Kai , Li Lening , Li Kuncheng
Published: January 2020

Objective:

Understanding how brain changes over lifetime provides the basis for new insights into neurophysiology and neuropathology. In this study, we carried out a pseudo-longitudinal study based on age-related Chinese brain atlases (i.e., Chinese2020) constructed from large-scale volumetric brain MRI data collected in normal Han Chinese adults at varying ages.

Methods:

In order to quantify the deformation and displacement of brains for each voxel as age increases, optical flow algorithm was employed to compute motion vectors between every two consecutive brain templates of the age-related brain atlas, i.e., Chinese2020.

Results:

Dynamic age-related neuroanatomical changes in a standardized brain space were shown. Overall, our results demonstrate that brain inward deformation (mainly due to atrophy) can appear in adulthood and this trend generally accelerates as age increases, affecting multiple regions including frontal cortex, temporal cortex, parietal cortex, and cerebellum, whereas occipital cortex is least affected by aging, and even showed some degree of outward deformation in the midlife.

Conclusion:

Our findings indicated more complicated age-related changes instead of a simple trend of brain volume decrease, which may be in line with the recently increasing interests in the age-related cortical complexity with other morphometry measures.
The development of a comprehensive multidisciplinary endometriosis and chronic pelvic pain center
Authors: Opoku-Anane Jessica , Orlando Megan S , Lager Jeannette , Lester Felicia , Cuneo Judith , Pasch Lauri , Poder Liina , Peterson Brooke , Hullender Rubin Lee , Giudice Linda C
Published: January 2020

Endometriosis affects 2%–10% of reproductive-aged women and is one of the leading causes of chronic pelvic pain. Given the extensive diagnostic challenges, multi-system nature of the disease, and significant impacts on quality of life, there has been a long-standing recognition of the need for integrated and specialty care for women living with endometriosis. We present our experience with the development of a multidisciplinary center for endometriosis and chronic pelvic pain at the University of California San Francisco. We describe the core components of this treatment model, including (1) methods for clinical collaboration across diagnostic, medical, and surgical subspecialties; (2) promotion of surgical excision of endometriosis; (3) establishment of a patient navigator; (4) utilization of psychological interventions and integrative medicine; and (5) health care provider and community training. Since the introduction of the endometriosis center in November 2016, outpatient encounters for patients with a primary diagnosis of endometriosis increased from 2761 in 2016 to 3905 in 2018, demonstrating high demand for these services. We also highlight opportunities for collaborative research through de-identified patient surveys, clinical data, and biospecimen collection.
DNA–dependent protein kinase in telomere maintenance and protection
Authors: Sui Jiangdong , Zhang Shichuan , Chen Benjamin P. C.
Published: January 2020

This review focuses on DNA–dependent protein kinase (DNA–PK), which is the key regulator of canonical non–homologous end–joining (NHEJ), the predominant mechanism of DNA double–strand break (DSB) repair in mammals. DNA–PK consists of the DNA–binding Ku70/80 heterodimer and the catalytic subunit DNA–PKcs. They assemble at DNA ends, forming the active DNA–PK complex, which initiates NHEJ–mediated DSB repair. Paradoxically, both Ku and DNA–PKcs are associated with telomeres, and they play crucial roles in protecting the telomere against fusions. Herein, we discuss possible mechanisms and contributions of Ku and DNA–PKcs in telomere regulation.
ShinyOmics: collaborative exploration of omics-data
Authors: Surujon Defne , van Opijnen Tim
Published: January 2020

Background

Omics-profiling is a collection of increasingly prominent approaches that result in large-scale biological datasets, for instance capturing an organism’s behavior and response in an environment. It can be daunting to manually analyze and interpret such large datasets without some programming experience. Additionally, with increasing amounts of data; management, storage and sharing challenges arise.

Results

Here, we present ShinyOmics, a web-based application that allows rapid collaborative exploration of omics-data. By using Tn-Seq, RNA-Seq, microarray and proteomics datasets from two human pathogens, we exemplify several conclusions that can be drawn from a rich dataset. We identify a protease and several chaperone proteins upregulated under aminoglycoside stress, show that antibiotics with the same mechanism of action trigger similar transcriptomic responses, point out the dissimilarity in different omics-profiles, and overlay the transcriptional response on a metabolic network.

Conclusions

ShinyOmics is easy to set up and customize, and can utilize user supplied metadata. It offers several visualization and comparison options that are designed to assist in novel hypothesis generation, as well as data management, online sharing and exploration. Moreover, ShinyOmics can be used as an interactive supplement accompanying research articles or presentations.
Integrated proteomic and metabolomic analysis to study the effects of spaceflight on Candida albicans
Authors: Wang Jiaping , Liu Yu , Zhao Guangxian , Gao Jianyi , Liu Junlian , Wu Xiaorui , Xu Chong , Li Yongzhi
Published: January 2020

Background

Candida albicans is an opportunistic pathogenic yeast, which could become pathogenic in various stressful environmental factors including the spaceflight environment. In this study, we aim to explore the phenotypic changes and possible mechanisms of C. albicans after exposure to spaceflight conditions.

Results

The effect of C. albicans after carried on the “SJ-10” satellite for 12 days was evaluated by proliferation, morphology, environmental resistance and virulence experiment. The result showed that the proliferation rate, biofilm formation, antioxidant capacity, cytotoxicity and filamentous morphology of C. albicans were increased in the spaceflight group compared to the control group. Proteomics and metabolomics technologies were used to analyze the profiles of proteins and metabolites in C. albicans under spaceflight conditions. Proteomic analysis identified 548 up-regulated proteins involved in the ribosome, DNA replication, base excision repair and sulfur metabolism in the spaceflight group. Moreover, 332 down-regulated proteins related to metabolic processes were observed. The metabolomic analysis found five differentially expressed metabolites. The combined analysis of proteomic and metabolomic revealed the accumulation of cysteine and methionine in C. albicans after spaceflight.

Conclusions

Mechanisms that could explain the results in the phenotypic experiment of C. albicans were found through proteomic and metabolomic analysis. And our data provide an important basis for the assessment of the risk that C. albicans could cause under spaceflight environment.
Dynamic accumulation of fatty acids in duck (Anas platyrhynchos) breast muscle and its correlations with gene expression
Authors: Fan Wenlei , Liu Wenjing , Liu Hehe , Meng Qingshi , Xu Yaxi , Guo Yuming , Wang Baowei , Zhou Zhengkui , Hou Shuisheng
Published: January 2020

Background

Fatty acid composition contributes greatly to the quality and nutritional value of meat. However, the molecular regulatory mechanisms underlying fatty acid accumulation in poultry have not yet been cleared. The aims of this study were to characterize the dynamics of fatty acid accumulation in duck breast muscle and investigate its correlations with gene expression.

Results

Here, we analyzed the fatty acid profile and transcriptome of breast muscle derived from Pekin ducks and mallards at the ages of 2 weeks, 4 weeks, 6 weeks and 8 weeks. Twenty fatty acids were detected in duck breast muscle, with palmitic acid (C16:0, 16.6%~ 21.1%), stearic acid (C18:0, 9.8%~ 17.7%), oleic acid (C18:1n-9, 15.7%~ 33.8%), linoleic acid (C18:2n-6, 10.8%~ 18.9%) and arachidonic acid (C20:4n-6, 11.7%~ 28.9%) as the major fatty acids. Our results showed that fatty acid composition was similar between the two breeds before 6 weeks, but the compositions diverged greatly after this point, mainly due to the stronger capacity for C16:0 and C18:1n-9 deposition in Pekin ducks. By comparing the multistage transcriptomes of Pekin ducks and mallards, we identified 2025 differentially expressed genes (DEGs). Cluster analysis of these DEGs revealed that the genes involved in oxidative phosphorylation, fatty acid degradation and the PPAR signaling pathway were upregulated in mallard at 8 weeks. Moreover, correlation analysis of the DEGs and fatty acid composition traits suggested that the DEGs involved in lipogenesis, lipolysis and fatty acid β-oxidation may interact to influence the deposition of fatty acids in duck breast muscle.

Conclusions

We reported the temporal progression of fatty acid accumulation and the dynamics of the transcriptome in breast muscle of Pekin ducks and mallards. Our results provide insights into the transcriptome regulation of fatty acid accumulation in duck breast muscle, and will facilitate improvements of fatty acid composition in duck breeding.
Prognostic value of dual-source computed tomography (DSCT) angiography characteristics in anomalous coronary artery from the opposite sinus (ACAOS) patients: a large-scale retrospective study
Authors: Diao Kai-yue , Zhao Qin , Gao Yue , Shi Ke , Ma Min , Xu Hua-yan , Guo Ying-kun , Yang Zhi-gang
Published: January 2020

Background

Most reported cases of right anomalous coronary artery from the opposite sinus (R-ACAOS) have benign clinical outcomes. However, patients with left ACAOS (L-ACAOS) and some of the patients with R-ACAOS are more at risk for arrhythmias and sudden cardiac death, which remains a major concern. Here we report the prevalence and anatomical features of ACAOS patients. Moreover, we explore the high-risk morphological signs and evaluate their mid-term prognostic value in R-ACAOS patients without surgical intervention.

Methods

Data from coronary computed tomography angiography (CTA) of 30,593 patients, pertaining to a single center over 5 consecutive years, were retrospectively analyzed. The image analysis included stenosis severity ranking and high-risk anatomy evaluation, based on the commercially available image post-processing software OsirX. Patients with R-ACAOS and without evidence of coronary atherosclerosis (CAD) were followed-up, with recording of the cardiovascular clinical events. Cox regression analysis was performed to identify the potential anatomical risk factors of cardiovascular clinical events for non-CAD R-ACAOS patients, using R project.

Results

The prevalence of ACAOS in the study population was 0.69% (211/30593). Significant differences were found between patients with mild (< 50%) and severe (> 50%) stenosis, in terms of height-to-weight ratio (HW ratio), take-off angle, and proximal stenosis length. A total of 54 cardiovascular clinical events were observed among 108 non-CAD R-ACAOS patients and an average follow-up of 27.8 ± 18.7 months. Among those patients’ anatomical features, stenosis severity was the main risk factor for cardiovascular clinical events during the mid-term follow-up, with a risk ratio of 4.14 (95% CI: 1.78 to 9.63, P < 0.001).

Conclusions

Among patients referred to coronary CTA, the overall incidence of ACAOS was 0.69%. For patients with R-ACAOS, severe stenosis was the independent risk factor of adverse clinical events in the mid-term follow-up, and positive clinical intervention might be needed to help them avoid the malignant clinical events.
Reversal of stage 5 chronic kidney disease by aortic valve replacement in kidney transplant recipient: a case report
Authors: Hryniewiecka E. , Hryniewiecki T. , Różański J. , Pilecki T. , Zagożdżon R. , Orłowski T. , Gołębiowski M. , Pączek L. , Mucha K. , Foroncewicz B.
Published: January 2020

Background

Cardiorenal syndrome (CRS) is a group of pathophysiological disorders affecting heart and kidneys.

Case presentation

We present 44-year-old kidney transplant recipient with acute-on-chronic graft failure in the course of CRS due to acutely decompensated heart failure associated with severe aortic regurgitation successfully treated with aortic valve replacement. Because of graft failure progression and difficult to eradicate infections he was treated with dialysis and radical minimization of immunosuppression. After 74 days of renal replacement therapy the patient regained graft function after successful aortic valve replacement. The dialysis could be stopped and immunosuppressive therapy was reintroduced. Heart and renal function are stable and patient is doing well without dialysis for 3 years.

Conclusions

The return of kidney graft function can occur even after a long period of dialysis therapy due to improved cardiovascular function. Therefore, distinguishing an acute-on-chronic CRS subtype is mandatory to enable specific patient approach.
Myocardial injury and pericarditis after combined left atrial and coronary sinus ablation in Wolff–Parkinson–White syndrome: a case report
Authors: Zheng Mei-fang , Wang Zhen , Bao Zheng-yu
Published: January 2020

Background

Radiofrequency catheter ablation is an established procedure with a high success rate for treating Wolff–Parkinson–White (WPW) syndrome. Rare complications post-ablation may nonetheless occur particularly associated with coronary sinus. Identifying and avoiding these complications remains a challenge.

Case presentation

A 66-year-old woman with WPW syndrome was admitted to the hospital due to frequent attacks of paroxysmal tachycardia. During electrophysiological study, an accessory pathway was thought to connect the posterior wall of the left ventricle. The patient underwent Radiofrequency (RF) catheter ablation. The procedure was time-consuming because of combined left atrial and coronary sinus ablation. The total amount of radiofrequency application energy in the coronary sinus was 6800 J. After the operation, widespread concave ST-segment elevation, significantly increased value of serum troponin I and mild pericardial effusion were identified, but the patient did not show any symptoms. Therefore, the patient was suspected to have myocardial injury and pericarditis caused by ablation-related injury. The patient was uneventfully discharged five days after the procedure with a significantly decreased value of troponin I. The reexamined electrocardiogram was normal after three weeks.

Conclusions

To the best of our knowledge, this is the first study to report on myocardial injury and pericarditis after combined left atrial and coronary sinus ablation in WPW syndrome. Our findings underscore the need for detailed mapping and careful ablation with low energy, as well as the merits of identifying myocardial infarction after coronary sinus ablation.
Nocardia farcinica as a cause of chronic meningitis – case report
Authors: Moniuszko-Malinowska Anna , Czupryna Piotr , Swiecicka Izabela , Grześ Henryk , Siemieniako Agnieszka , Grygorczuk Sambor , Tarasów Eugeniusz , Pancewicz Sławomir
Published: January 2020

Background

Nocardiosis is an uncommon disease caused by aerobic gram-positive bacteria Nocardia spp. Although it is usually an opportunistic infection affecting immunocompromised patients, even one third of cases occur in immunocompetent persons. The aim of the study was to describe the course of chronic meningitis due to Nocardia infection.

Case presentation

A 52-year-old patient, chalk miner, suffered from a chronic meningitis caused by an extremely rare pathogen. The patient’s history was complicated and diagnostic process covered multiple examinations and consultations. Initially Kocuria rosea was cultured, yet after molecular examination the result was verified to Nocardia farcinica. Targeted antibiotic treatment was implemented, which resulted in gradual improvement of patients condition. A full recovery was achieved after one year antibiotic therapy.

Conclusions

Nocardia farcinica is an uncommon but possible cause of chronic meningitis.

In the case of a chronic meningitis of unknown origin multiple cerebrospinal fluid cultures should be performed as the identification of pathogen may be crucial for patient’s recovery.

In case of unusual culture, such as Kocuria spp. PCR should be performed.
The effect of therapeutic drug monitoring of beta-lactam and fluoroquinolones on clinical outcome in critically ill patients: the DOLPHIN trial protocol of a multi-centre randomised controlled trial
Authors: Abdulla A. , Ewoldt T. M. J. , Hunfeld N. G. M. , Muller A. E. , Rietdijk W. J. R. , Polinder S. , van Gelder T. , Endeman H. , Koch B. C. P.
Published: January 2020

Background

Critically ill patients undergo extensive physiological alterations that will have impact on antibiotic pharmacokinetics. Up to 60% of intensive care unit (ICU) patients meet the pharmacodynamic targets of beta-lactam antibiotics, with only 30% in fluoroquinolones. Not reaching these targets might increase the chance of therapeutic failure, resulting in increased mortality and morbidity, and antibiotic resistance. The DOLPHIN trial was designed to demonstrate the added value of therapeutic drug monitoring (TDM) of beta-lactam and fluoroquinolones in critically ill patients in the ICU.

Methods

A multi-centre, randomised controlled trial (RCT) was designed to assess the efficacy and cost-effectiveness of model-based TDM of beta-lactam and fluoroquinolones. Four hundred fifty patients will be included within 24 months after start of inclusion. Eligible patients will be randomly allocated to either study group: the intervention group (active TDM) or the control group (non-TDM). In the intervention group dose adjustment of the study antibiotics (cefotaxime, ceftazidime, ceftriaxone, cefuroxime, amoxicillin, amoxicillin with clavulanic acid, flucloxacillin, piperacillin with tazobactam, meropenem, and ciprofloxacin) on day 1, 3, and 5 is performed based upon TDM with a Bayesian model. The primary outcome will be ICU length of stay. Other outcomes amongst all survival, disease severity, safety, quality of life after ICU discharge, and cost effectiveness will be included.

Discussion

No trial has investigated the effect of early TDM of beta-lactam and fluoroquinolones on clinical outcome in critically ill patients. The findings from the DOLPHIN trial will possibly lead to new insights in clinical management of critically ill patients receiving antibiotics. In short, to TDM or not to TDM?

Trial registration

EudraCT number: 2017–004677-14. Sponsor protocol name: DOLPHIN. Registered 6 March 2018 . Protocol Version 6, Protocol date: 27 November 2019.
Methadone-induced encephalopathy: a case series and literature review
Authors: Haghighi-Morad Maryam , Naseri Zahra , Jamshidi Nazila , Hassanian-Moghaddam Hossein , Zamani Nasim , Ahmad-Molaei Leila
Published: January 2020

Background

Accidental ingestion or consumption of supra-therapeutic doses of methadone can result in neurological sequelae in humans. We aimed to determine the neurological deficits of methadone-poisoned patients admitted to a referral poisoning hospital using brain magnetic resonance (MR) and diffusion weighted (DW) imaging.

Methods

In this retrospective study, brain MRIs of the patients admitted to our referral center due to methadone intoxication were reviewed. Methadone intoxication was confirmed based on history, congruent clinical presentation, and confirmatory urine analysis. Each patient had an MRI with Echo planar T1, T2, FLAIR, and DWI and apparent deficient coefficient (ADC) sequences without contrast media. Abnormalities were recorded and categorized based on their anatomic location and sequence.

Results

Ten patients with abnormal MRI findings were identified. Eight had acute- and two had delayed-onset encephalopathy. Imaging findings included bilateral confluent or patchy T2 and FLAIR high signal intensity in cerebral white matter, cerebellar involvement, and bilateral occipito-parietal cortex diffusion restriction in DWI. Internal capsule involvement was identified in two patients while abnormality in globus pallidus and head of caudate nuclei were reported in another. Bilateral cerebral symmetrical confluent white matter signal abnormality with sparing of subcortical U-fibers on T2 and FLAIR sequences were observed in both patients with delayed-onset encephalopathy.

Conclusions

Acute- and delayed-onset encephalopathies are two rare adverse events detected in methadone-intoxicated patients. Brain MRI findings can be helpful in detection of methadone-induced encephalopathy.
Exploring issues in caregivers and parent communication of sexual and reproductive health matters with adolescents in Ebonyi state, Nigeria
Authors: Mbachu Chinyere Ojiugo , Agu Ifunanya Clara , Eze Irene , Agu Chibuike , Ezenwaka Uche , Ezumah Nkoli , Onwujekwe Obinna
Published: January 2020

Background

Parent-child communication is an effective tool for fostering healthy sexual and reproductive behaviours among adolescents. However, the topic is underexplored in Nigeria. This study examines how parents and caregivers communicate sexual and reproductive health-related matters with adolescents aged 13–18 years in Nigeria.

Method

The study was undertaken in six communities in Ebonyi state, Nigeria using quantitative and qualitative research methods. Data were collected through, i) cluster randomized survey of 1057 adolescents aged 13–18 years, ii) twelve sex-disaggregated focus group discussions with adolescents aged 13 to 18 years, and iii) eight in-depth interviews with parents and caregivers. Univariate and bivariate analysis were performed for quantitative data, while qualitative data were analysed using thematic framework approach.

Results

Less than half (47.9%) of adolescents in the survey reported ever discussing sex-related matters with anyone. Three-quarters of those who had this discussion did so with a friend/peer and this had significant correlation with sex/gender (p = 0.04). Out of 1057 adolescents who participated in the survey only 4.5% had ever discussed sex-related matters with a parent and this correlated significantly with wealth index (p = 0.003). Findings from qualitative interviews show that sex-related discussions between parents and adolescents are sporadic, mostly triggered by unpleasant occurrences, and consist of, i) information on pubertal changes, ii) warnings against intersex relationships and premarital sex, iii) promotion of abstinence, and iv) warnings against teenage pregnancy and unsafe abortion. Some parents were of the opinion that sex-related matters should not be discussed with adolescents because it could be interpreted as tolerance for sexual promiscuity. Overall, parents expressed that their capacity to discuss sex-related matters with adolescents is limited by lack of knowledge, and restrictive religious and cultural norms about adolescent sexuality.

Conclusion

Communication between parents and adolescents on sexual health and reproductive-related matters rarely occurs. However, when it does, it mostly consists of strict warnings that may not protect adolescents from making unhealthy sexual and reproductive health choices. Interventions to improve parent-adolescent communication of sexual and reproductive health (SRH) should aim at improving parents’ capacity to communicate sexual and reproductive health matters, and deconstructing sociocultural norms around adolescent sexuality.
Curricular changes: the impact on medical students knowledge of neuroanatomy
Authors: Arantes Mavilde , Andrade José Paulo , Barbosa Joselina , Ferreira Maria Amélia
Published: January 2020

Background

Although neuroanatomy is considered an essential requirement in medical curriculum, its teaching has undergone many changes in recent years, with most medical schools starting to implement an integrated approach. The current paper describes the comparative evaluation of the neuroanatomy knowledge scores of medical students who attended two different pedagogic approaches of neuroanatomy in the Faculty of Medicine of the University of Porto.

Methods

Forty fourth-year medical students who attended a traditional stand-alone approach and 42 third-year medical students who attended an integrated approach completed a written test of knowledge.

Results

Although there were some significant differences, the results globally revealed no statistically significant difference between the neuroanatomy knowledge scores of the integrated and traditional education groups, with most students obtaining a passing score in both curricula.

Conclusions

Our study is the first attempt to compare the knowledge acquired by medical students from two different pedagogical approaches to neuroanatomy. Although the integrated curricula were only implemented in the Faculty of Medicine of the University of Porto a few years ago, the students who attended these curricula obtained similar scores as those obtained by the students of the traditional curriculum. This finding suggests that an integrated curriculum can be, in light of curricular reform, an efficient approach to teaching neuroanatomy to medical students.
Functional interaction between plasma phospholipid fatty acids and insulin resistance in leucocyte telomere length maintenance
Authors: Zhao Yi , Wang Binxia , Wang Guoqi , Huang Lixia , Yin Ting , Li Xiaoxia , Liu Xiuying , Wang Qingan , Jing Jinyun , Yang Jianjun , Zhang Yuhong
Published: January 2020

Background

Previous evidence suggests that plasma phospholipid fatty acids (PPFAs) and HOMA insulin resistance (HOMA-IR) are independently related to leukocyte telomere length (LTL). However, there is limited evidence of regarding the effect of their interaction on relative LTL (RLTL). Therefore, here, we aimed to determine the effect of the interaction between PPFAs and HOMA-IR on RLTL.

Methods

We conducted a cross-sectional study, involving a total of 1246 subjects aged 25–74 years. PPFAs and RLTL were measured, and HOMA-IR was calculated. The effect of the interaction between PPFAs and HOMA-IR on RLTL was assessed by univariate analysis, adjusting for potential confounders.

Results

In age-adjusted analyses, multivariate linear regression revealed a significant association of the levels of elaidic acid, HOMA-IR, monounsaturated fatty acids (MUFA) and omega-6 (n-6) polyunsaturated fatty acid (PUFA) with RLTL. After adjustment of age and gender, race, smoking, drinking, tea, and exercise, elaidic acid, and omega-3 (n-3) PUFA were negatively associated with RLTL, and HOMA-IR and n-6 PUFA were positively associated with RLTL. These associations were not significantly altered upon further adjustment for anthropometric and biochemical indicators. Meanwhile, the effect of the interaction of elaidic acid and HOMA-IR on RLTL was significant, and remained unchanged even after adjusting for the aforementioned potential confounders. Interestingly, individuals who had the lowest HOMA-IR and the highest elaidic acid levels presented the shortest RLTL.

Conclusions

Our findings indicated that shorter RLTL was associated with lower HOMA-IR and higher elaidic acid level. These findings might open a new avenue for exploring the potential role of the interaction between elaidic acid and HOMA-IR in maintaining RLTL.
Neighbourhood drivability: environmental and individual characteristics associated with car use across Europe
Authors: den Braver Nicolette R. , Kok Julia G. , Mackenbach Joreintje D. , Rutter Harry , Oppert Jean-Michel , Compernolle Sofie , Twisk Jos W. R. , Brug Johannes , Beulens Joline W. J. , Lakerveld Jeroen
Published: January 2020

Background

Car driving is a form of passive transportation associated with higher sedentary behaviour, which is associated with morbidity. The decision to drive a car is likely to be influenced by the ‘drivability’ of the built environment, but there is lack of scientific evidence regarding the relative contribution of environmental characteristics of car driving in Europe, compared to individual characteristics. This study aimed to determine which neighbourhood- and individual-level characteristics were associated with car driving in adults of five urban areas across Europe. Second, the study aimed to determine the percentage of variance in car driving explained by individual- and neighbourhood-level characteristics.

Methods

Neighbourhood environment characteristics potentially related to car use were identified from the literature. These characteristics were subsequently assessed using a Google Street View audit and available GIS databases, in 59 administrative residential neighbourhoods in five European urban areas. Car driving (min/week) and individual level characteristics were self-reported by study participants (analytic sample n = 4258). We used linear multilevel regression analyses to assess cross-sectional associations of individual and neighbourhood-level characteristics with weekly minutes of car driving, and assessed explained variance at each level and for the total model.

Results

Higher residential density (β:-2.61, 95%CI: − 4.99; -0.22) and higher land-use mix (β:-3.73, 95%CI: − 5.61; -1.86) were significantly associated with fewer weekly minutes of car driving. At the individual level, higher age (β: 1.47, 95%CI: 0.60; 2.33), male sex (β: 43.2, 95%CI:24.7; 61.7), being employed (β:80.1, 95%CI: 53.6; 106.5) and ≥ 3 person household composition (β: 47.4, 95%CI: 20.6; 74.2) were associated with higher weekly minutes of car driving. Individual and neighbourhood characteristics contributed about equally to explained variance in minutes of weekly car driving, with 2 and 3% respectively, but total explained variance remained low.

Conclusions

Residential density and land-use mix were neighbourhood characteristics consistently associated with minutes of weekly car driving, besides age, sex, employment and household composition. Although total explained variance was low, both individual- and neighbourhood-level characteristics were similarly important in their associations with car use in five European urban areas. This study suggests that more, higher quality, and longitudinal data are needed to increase our understanding of car use and its effects on determinants of health.
The capsaicin receptor TRPV1 is the first line defense protecting from acute non damaging heat: a translational approach
Authors: Rosenberger Daniela C. , Binzen Uta , Treede Rolf-Detlef , Greffrath Wolfgang
Published: January 2020

Background

Pain is the vital sense preventing tissue damage by harmful noxious stimuli. The capsaicin receptor TRPV1 is activated by noxious temperatures, however, acute heat pain is only marginally affected in mice after TRPV1 knockout but completely eliminated in mice lacking TRPV1 positive fibers. Exploring contribution of candidate signal transduction mechanisms to heat pain in humans needs translational models.

Methods

We used focused, non-damaging, short near-infrared laser heat stimuli (wavelength 1470/1475 nm) to study the involvement of TRPV1-expressing nerve fibers in the encoding of heat pain intensity. Human psychophysics (both sexes) were compared to calcium transients in native rat DRG neurons and heterologously expressing HEK293 cells.

Results

Heating of dermal and epidermal nerve fibers in humans with laser stimuli of ≥ 2.5 mJ (≥ 25 ms, 100 mW) induced pain that increased linearly as a function of stimulus intensity in double logarithmic space across two orders of magnitude and was completely abolished by desensitization using topical capsaicin. In DRG neurons and TRPV1-expressing HEK cells, heat sensitivity was restricted to capsaicin sensitive cells. Strength duration curves (2–10 ms range) and thresholds (DRGs 0.56 mJ, HEK cells 0.52 mJ) were nearly identical. Tachyphylaxis upon repetitive stimulation occurred in HEK cells (54%), DRGs (59%), and humans (25%).

Conclusion

TRPV1-expressing nociceptors encode transient non-damaging heat pain in humans, thermal gating of TRPV1 is similar in HEK cells and DRG neurons, and TRPV1 tachyphylaxis is an important modulator of heat pain sensitivity. These findings suggest that TRPV1 expressed in dermal and epidermal populations of nociceptors serves as first line defense against heat injury.
Overcoming barriers to evidence-based patient blood management: a restricted review
Authors: Delaforce Alana , Duff Jed , Munday Judy , Hardy Janet
Published: January 2020

Background

Blood transfusions are associated with a range of adverse patient outcomes, including coagulopathy, immunomodulation and haemolysis, which increase the risk of morbidity and mortality. Consideration of these risks and potential benefits are necessary when deciding to transfuse. Patient blood management (PBM) guidelines exist to assist in clinical decision-making, but they are underutilised. Exploration of barriers to the implementation and utilisation of the PBM guidelines is required. This study aimed to identify common barriers and implementation strategies used to implement PBM guidelines, with a comparison against current expert opinion.

Methods

A restricted review approach was used to identify the barriers to PBM guideline implementation as reported by health professionals and to review which implementation strategies have been used. Searches were undertaken in MEDLINE/PubMed, CINAHL, Embase, Scopus and the Cochrane library. The Consolidated Framework for Implementation Research (CFIR) was used to code barriers. The Expert Recommendations for Implementing Change (ERIC) tool was used to code implementation strategies, and subsequently, develop recommendations based on expert opinion.

Results

We identified 14 studies suitable for inclusion. There was a cluster of barriers commonly reported: access to knowledge and information (n= 7), knowledge and beliefs about the intervention ( = 7) and tension for change (n= 6). Implementation strategies used varied widely (n= 25). Only one study reported the use of an implementation theory, model or framework. Most studies (n= 11) had at least 50% agreement with the ERIC recommendations.

Conclusions

There are common barriers experienced by health professionals when trying to implement PBM guidelines. There is currently no conclusive evidence to suggest which implementation strategies are most effective. Further research using validated implementation approaches and improved reporting is required.
Finnish gelsolin amyloidosis causes significant disease burden but does not affect survival: FIN-GAR phase II study
Authors: Schmidt Eeva-Kaisa , Mustonen Tuuli , Kiuru-Enari Sari , Kivelä Tero T. , Atula Sari
Published: January 2020

Background

Hereditary gelsolin (AGel) amyloidosis is an autosomal dominantly inherited systemic amyloidosis that manifests with the characteristic triad of progressive ophthalmological, neurological and dermatological signs and symptoms. The National Finnish Gelsolin Amyloidosis Registry (FIN-GAR) was founded in 2013 to collect clinical data on patients with AGel amyloidosis, including altogether approximately one third of the Finnish patients. We aim to deepen knowledge on the disease burden and life span of the patients using data from the updated FIN-GAR registry. We sent an updated questionnaire concerning the symptoms and signs, symptomatic treatments and subjective perception on disease progression to 240 members of the Finnish Amyloidosis Association (SAMY). We analyzed the lifespan of 478 patients using the relative survival (RS) framework.

Results

The updated FIN-GAR registry includes 261 patients. Symptoms and signs corresponding to the classical triad of ophthalmological (dry eyes in 93%; corneal lattice amyloidosis in 89%), neurological (numbness, tingling and other paresthesias in 75%; facial paresis in 67%), and dermatological (drooping eyelids in 86%; cutis laxa in 84%) manifestations were highly prevalent. Cardiac arrhythmias were reported by 15% of the patients and 5% had a cardiac pacemaker installed. Proteinuria was reported by 13% and renal failure by 5% of the patients. A total of 65% of the patients had undergone a skin or soft tissue surgery, 26% carpal tunnel surgery and 24% at least unilateral cataract surgery. As regards life span, relative survival estimates exceeded 1 for males and females until the age group of 70–74 years, for which it was 0.96.

Conclusions

AGel amyloidosis causes a wide variety of ophthalmological, neurological, cutaneous, and oral symptoms that together with repeated surgeries cause a clinically significant disease burden. Severe renal and cardiac manifestations are rare as compared to other systemic amyloidoses, explaining in part the finding that AGel amyloidosis does not shorten the life span of the patients at least for the first 75 years.