bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of the potential of Pap test fluid and cervical swabs to serve as clinical diagnostic biospecimens for the detection of ovarian cancer by mass spectrometry-based proteomics
Authors: Boylan Kristin L. M. , Afiuni-Zadeh Somaieh , Geller Melissa A. , Argenta Peter A. , Griffin Timothy J. , Skubitz Amy P. N.
Published: January 2021

Background

The purpose of this study was to determine whether the residual fixative from a liquid-based Pap test or a swab of the cervix contained proteins that were also found in the primary tumor of a woman with high grade serous ovarian cancer. This study is the first step in determining the feasibility of using the liquid-based Pap test or a cervical swab for the detection of ovarian cancer protein biomarkers.

Methods

Proteins were concentrated by acetone precipitation from the cell-free supernatant of the liquid-based Pap test fixative or eluted from the cervical swab. Protein was also extracted from the patient’s tumor tissue. The protein samples were digested into peptides with trypsin, then the peptides were run on 2D-liquid chromatography mass spectrometry (2D-LCMS). The data was searched against a human protein database for the identification of peptides and proteins in each biospecimen. The proteins that were identified were classified for cellular localization and molecular function by bioinformatics integration.

Results

We identified almost 5000 proteins total in the three matched biospecimens. More than 2000 proteins were expressed in each of the three biospecimens, including several known ovarian cancer biomarkers such as CA125, HE4, and mesothelin. By Scaffold analysis of the protein Gene Ontology categories and functional analysis using PANTHER, the proteins were classified by cellular localization and molecular function, demonstrating that the Pap test fluid and cervical swab proteins are similar to each other, and also to the tumor extract.

Conclusions

Our results suggest that Pap test fixatives and cervical swabs are a rich source of tumor-specific biomarkers for ovarian cancer, which could be developed as a test for ovarian cancer detection.
Early childhood screen time as a predictor of emotional and behavioral problems in children at 4 years: a birth cohort study in China
Authors: Liu Wenwen , Wu Xiaoyan , Huang Kun , Yan Shuangqin , Ma Liya , Cao Hui , Gan Hong , Tao Fangbiao
Published: January 2021

Background

Previous studies have suggested that screen time (ST) has a negative effect on children’s emotional and behavioral health, but there are few longitudinal studies that have been conducted with infants and toddlers. This study sought to examine the effect of ST in early childhood on emotional and behavioral problems in children aged 4 years, based on a birth cohort study in China.

Methods

A total of 2492 children aged 4 years were enrolled in this study. The parents and guardians of each child completed a questionnaire that included items eliciting information on children’s birth information, socio-demographic information at baseline, and ST at each follow-up. Emotional and behavioral problems were assessed using the Strengths and Difficulties Questionnaire (SDQ) at 4 years of age. Multivariate logistic analysis was used to explore the effects of ST on emotional and behavioral problems.

Results

The percentages of children with ST > 0 h/day at age 0.5 years, ST > 2 h/day at age 2.5 years, and ST > 2 h/day at age 4 years were 45.7, 55.5, and 34.5% respectively. The prevalence of emotional and behavioral problems was 10.8%. ST at 6 months was a risk factor for emotional symptoms and hyperactivity at the age of 4 years. ST at age 2.5 years was a risk factor for hyperactivity at the age of 4 years. However, ST at age 4 years was a risk factor for total difficulties, conduct problems, peer problems, hyperactivity, and prosocial behavior.

Conclusions

Higher ST exposure at early childhood is associated with later emotional and behavioral problems. In particular, sustained high ST exposure is a risk factor for behavioral problems. These findings suggested the importance of controlling ST to prevent the occurrence of emotional and behavioral problems in the early years.
Histology of variants of urothelial carcinoma of the bladder: a Moroccan series of 39 cases
Authors: Saouli Amine , Karmouni Tarik , El Khader Khalid , Koutani Abdellatif , Andaloussi Ahmed Iben Attya
Published: January 2021

Background

The variant of urothelial carcinoma (UCV) is a rare and aggressive histological entity; its therapeutic management remains debated.

Methods

Between January 2017 and October 2019, 39 patients were diagnosed retrospectively with urothelial carcinoma with a histological variant. The aim of this study was to analyze the clinico-pathological and therapeutic aspects of these variants to better understand this invasive disease.

Results

In 39 cases, 36 (92%) were men and 3 (8%) were women; the average age was 62 years; 54% of patients had a ≥ cT3 stage with clinical lymph node involvement in 28% and 23% had distant metastases, 36% of patients were treated with RC and 54% by other therapeutic and 10% refused RC. No patient received neoadjuvant chemotherapy. Lymph node involvement was 28.5%. The two predominant histological types were squamous and micropapillary differentiation between the operating piece and bladder biopsy 28.5%, 30% and 21.5% and 13%, respectively. The overall survival at 20 months was 70 and 40% for RC and the other therapeutic (TURB alone or a TURB with an adjuvant), respectively. There was no significant difference in survival between the two groups (p = 0.27).

Conclusion

UCVs are heterogeneous groups of tumors which are increasingly identified due to their distinct morphological characteristics with variable clinical prognosis. Therapeutic management is not in favor of cystectomy in our study. However, a prospective study using a larger cohort is still necessary to validate our results.
A Novel PCR Method for Detecting ACE Gene Insertion/Deletion Polymorphisms and its Clinical Application
Authors: Yang Xue-min , Liang Jian-ping , Huang Xiao-juan , Wang Xiang-rong , Sun Yang , Dong Chen , Cui Ya-li , Hui Wen-li
Published: January 2021

Background

Angiotensin-converting enzyme (ACE) plays a major role in blood pressure regulation and cardiovascular homeostasis. The wide distribution and multifunctional properties of ACE suggest it’s involvement in various pathophysiological conditions.

Results

In this study, a novel visual detection method for ACE I/D polymorphisms was designed by integrating direct PCR without the need for DNA extraction using gold magnetic nanoparticles (GMNPs)-based lateral flow assay (LFA) biosensor. The entire detection procedure could enable the genotyping of clinical samples in about 80 min. The detection limit was 0.75 ng and results could be obtained in 5 min using the LFA device. Three hundred peripheral blood samples were analyzed using the direct PCR-LFA system and then verified by sequencing to determine accuracy and repeatability. A clinical preliminary study was then performed to analyze a total of 633 clinical samples.

Conclusions

After grouping based on age, we found a significant difference between the genotypes and the age of patients in the CHD group. The introduction of this method into clinical practice may be helpful for the diagnosis of diseases caused by large fragment gene insertions/deletions.
Temporal changes in DNA methylation and RNA expression in a small song bird: within- and between-tissue comparisons
Authors: Lindner Melanie , Verhagen Irene , Viitaniemi Heidi M. , Laine Veronika N. , Visser Marcel E. , Husby Arild , van Oers Kees
Published: January 2021

Background

DNA methylation is likely a key mechanism regulating changes in gene transcription in traits that show temporal fluctuations in response to environmental conditions. To understand the transcriptional role of DNA methylation we need simultaneous within-individual assessment of methylation changes and gene expression changes over time. Within-individual repeated sampling of tissues, which are essential for trait expression is, however, unfeasible (e.g. specific brain regions, liver and ovary for reproductive timing). Here, we explore to what extend between-individual changes in DNA methylation in a tissue accessible for repeated sampling (red blood cells (RBCs)) reflect such patterns in a tissue unavailable for repeated sampling (liver) and how these DNA methylation patterns are associated with gene expression in such inaccessible tissues (hypothalamus, ovary and liver). For this, 18 great tit (Parus major) females were sacrificed at three time points (n = 6 per time point) throughout the pre-laying and egg-laying period and their blood, hypothalamus, ovary and liver were sampled.

Results

We simultaneously assessed DNA methylation changes (via reduced representation bisulfite sequencing) and changes in gene expression (via RNA-seq and qPCR) over time. In general, we found a positive correlation between changes in CpG site methylation in RBCs and liver across timepoints. For CpG sites in close proximity to the transcription start site, an increase in RBC methylation over time was associated with a decrease in the expression of the associated gene in the ovary. In contrast, no such association with gene expression was found for CpG site methylation within the gene body or the 10 kb up- and downstream regions adjacent to the gene body.

Conclusion

Temporal changes in DNA methylation are largely tissue-general, indicating that changes in RBC methylation can reflect changes in DNA methylation in other, often less accessible, tissues such as the liver in our case. However, associations between temporal changes in DNA methylation with changes in gene expression are mostly tissue- and genomic location-dependent. The observation that temporal changes in DNA methylation within RBCs can relate to changes in gene expression in less accessible tissues is important for a better understanding of how environmental conditions shape traits that temporally change in expression in wild populations.
Genome-wide association mapping reveals potential novel loci controlling stripe rust resistance in a Chinese wheat landrace diversity panel from the southern autumn-sown spring wheat zone
Authors: Wang Yuqi , Yu Can , Cheng Yukun , Yao Fangjie , Long Li , Wu Yu , Li Jing , Li Hao , Wang Jirui , Jiang Qiantao , Li Wei , Pu Zhien , Qi Pengfei , Ma Jian , Deng Mei , Wei Yuming , Chen Xianming , Chen Guoyue , Kang Houyang , Jiang Yunfeng , Zheng Youliang
Published: January 2021

Background

Stripe rust, caused by the fungal pathogenPuccinia striiformisf. sp.tritici(Pst), is a serious foliar disease of wheat. Identification of novel stripe rust resistance genes and cultivation of resistant cultivars are considered to be the most effective approaches to control this disease. In this study, we evaluated the infection type (IT), disease severity (DS) and area under the disease progress curve (AUDPC) of 143 Chinese wheat landrace accessions for stripe rust resistance. Assessments were undertaken in five environments at the adult-plant stage withPstmixture races under field conditions. In addition, IT was assessed at the seedling stage with two prevalentPstraces (CYR32 and CYR34) under a controlled greenhouse environment.

Results

Seventeen accessions showed stable high-level resistance to stripe rust across all environments in the field tests. Four accessions showed resistance to thePstraces CYR32 and CYR34 at the seedling stage. Combining phenotypic data from the field and greenhouse trials with 6404 markers that covered the entire genome, we detected 17 quantitative trait loci (QTL) on 11 chromosomes for IT associated with seedling resistance and 15 QTL on seven chromosomes for IT, final disease severity (FDS) or AUDPC associated with adult-plant resistance. Four stable QTL detected on four chromosomes, which explained 9.99–23.30% of the phenotypic variation, were simultaneously associated with seedling and adult-plant resistance. Integrating a linkage map of stripe rust resistance in wheat, 27 QTL overlapped with previously reported genes or QTL, whereas four and one QTL conferring seedling and adult-plant resistance, respectively, were mapped distantly from previously reported stripe rust resistance genes or QTL and thus may be novel resistance loci.

Conclusions

Our results provided an integrated overview of stripe rust resistance resources in a wheat landrace diversity panel from the southern autumn-sown spring wheat zone of China. The identified resistant accessions and resistance loci will be useful in the ongoing effort to develop new wheat cultivars with strong resistance to stripe rust.
Phylogenomic and evolutionary dynamics of inverted repeats across Angelica plastomes
Authors: Wang Mengli , Wang Xin , Sun Jiahui , Wang Yiheng , Ge Yang , Dong Wenpan , Yuan Qingjun , Huang Luqi
Published: January 2021

Background

AngelicaL. (family Apiaceae) is an economically important genus comprising ca. One hundred ten species.Angelicaspecies are found on all continents of the Northern Hemisphere, and East Asia hosts the highest number of species. Morphological characters such as fruit anatomy, leaf morphology and subterranean structures ofAngelicaspecies show extreme diversity. Consequently, the taxonomic classification ofAngelicaspecies is complex and remains controversial, as the classifications proposed by previous studies based on morphological data and molecular data are highly discordant. In addition, the phylogenetic relationships of major clades in theAngelicagroup, particularly in theAngelicas. s. clade, remain unclear. Chloroplast (cp) genome sequences have been widely used in phylogenetic studies and for evaluating genetic diversity.

Results

In this study, we sequenced and assembled 28 complete cp genomes from 22 species, two varieties and two cultivars ofAngelica. Combined with 36 available cp genomes in GenBank from representative clades of the subfamily Apioideae, the characteristics and evolutionary patterns ofAngelicacp genomes were studied, and the phylogenetic relationships ofAngelicaspecies were resolved. TheAngelicacp genomes had the typical quadripartite structure including a pair of inverted repeats (IRs: 5836–34,706 bp) separated by a large single-copy region (LSC: 76,657–103,161 bp) and a small single-copy region (SSC: 17,433–21,794 bp). Extensive expansion and contraction of the IR region were observed among cp genomes ofAngelicaspecies, and the pattern of the diversification of cp genomes showed high consistency with the phylogenetic placement ofAngelicaspecies. Species ofAngelicawere grouped into two major clades, with most species grouped in theAngelicagroup andA. omeiensisandA. sinensisgrouped in theSinodielsiawithLigusticum tenuissimum.

Conclusions

Our results further demonstrate the power of plastid phylogenomics in enhancing the phylogenetic reconstructions of complex genera and provide new insights into plastome evolution acrossAngelicaL.
Cardiovascular risk factors and mortality in hospitalized patients with COVID-19: systematic review and meta-analysis of 45 studies and 18,300 patients
Authors: Silverio Angelo , Di Maio Marco , Citro Rodolfo , Esposito Luca , Iuliano Giuseppe , Bellino Michele , Baldi Cesare , De Luca Giuseppe , Ciccarelli Michele , Vecchione Carmine , Galasso Gennaro
Published: January 2021

Background

A high prevalence of cardiovascular risk factors including age, male sex, hypertension, diabetes, and tobacco use, has been reported in patients with Coronavirus disease 2019 (COVID-19) who experienced adverse outcome. The aim of this study was to investigate the relationship between cardiovascular risk factors and in-hospital mortality in patients with COVID-19.

Methods

MEDLINE, Cochrane, Web of Sciences, and SCOPUS were searched for retrospective or prospective observational studies reporting data on cardiovascular risk factors and in-hospital mortality in patients with COVID-19.

Univariable and multivariable age-adjusted analyses were conducted to evaluate the association between cardiovascular risk factors and the occurrence of in-hospital death.

Results

The analysis included 45 studies enrolling 18,300 patients. The pooled estimate of in-hospital mortality was 12% (95% CI 9–15%). The univariable meta-regression analysis showed a significant association between age (coefficient: 1.06; 95% CI 1.04–1.09; p < 0.001), diabetes (coefficient: 1.04; 95% CI 1.02–1.07; p < 0.001) and hypertension (coefficient: 1.01; 95% CI 1.01–1.03; p = 0.013) with in-hospital death. Male sex and smoking did not significantly affect mortality. At multivariable age-adjusted meta-regression analysis, diabetes was significantly associated with in-hospital mortality (coefficient: 1.02; 95% CI 1.01–1.05; p = 0.043); conversely, hypertension was no longer significant after adjustment for age (coefficient: 1.00; 95% CI 0.99–1.01; p = 0.820). A significant association between age and in-hospital mortality was confirmed in all multivariable models.

Conclusions

This meta-analysis suggests that older age and diabetes are associated with higher risk of in-hospital mortality in patients infected by SARS-CoV-2. Conversely, male sex, hypertension, and smoking did not independently correlate with fatal outcome.
The M310T mutation in the GATA4 gene is a novel pathogenic target of the familial atrial septal defect
Authors: Bu Haisong , Sun Guowen , Zhu Yun , Yang Yifeng , Tan Zhiping , Zhao Tianli , Hu Shijun
Published: January 2021

Background

Although most cases of atrial septal defect (ASD) are sporadic, familial cases have been reported, which may be caused by mutation of transcription factor GATA binding protein 4 (GATA4). Herein we combined whole-exome sequencing and bioinformatics strategies to identify a novel mutation inGATA4accounting for the etiology in a Chinese family with ASD.

Methods

We identified kindred spanning 3 generations in which 3 of 12 (25.0%) individuals had ASD. Punctilious records for the subjects included complete physical examination, transthoracic echocardiography, electrocardiograph and surgical confirming. Whole-exome capture and high-throughput sequencing were performed on the proband III.1. Sanger sequencing was used to validate the candidate variants, and segregation analyses were performed in the family members.

Results

Direct sequencing ofGATA4from the genomic DNA of family members identified a T-to-C transition at nucleotide 929 in exon 5 that predicted a methionine to threonine substitution at codon 310 (M310T) in the nuclear localization signal (NLS) region. Two affected members (II.2 and III.3) and the proband (III.1) who was recognized as a carrier exhibited this mutation, whereas the other unaffected family members or control individuals did not. More importantly, the mutationGATA4(c.T929C: p.M310T) has not been reported previously in either familial or sporadic cases of congenital heart defects (CHD).

Conclusions

We identified for the first time a novel M310T mutation in theGATA4gene that is located in the NLS region and leads to family ASD with arrhythmias. However, the mechanism by which this pathogenic mutation contributes to the development of heart defect and tachyarrhythmias remains to be ascertained.
Effect of PCSK9 inhibitor on lipoprotein particles in patients with acute coronary syndromes
Authors: Li Tingting , Zhang Yingyi , Cong Hongliang
Published: January 2021

Background

To assess the effects of proprotein convertase subtilisin/kexin type 9 inhibitor (evolocumab) on lipoprotein particles subfractions with Nuclear Magnetic Resonance spectroscopy in patients with acute coronary syndromes.

Methods

A total of 99 consecutive patients with ACS were enrolled and assigned to either the experimental group (n = 54) or the control group (n = 45). The combination therapy of PCSK9 inhibitor (Repatha®, 140 mg, q2w) and moderate statin (Rosuvastatin, 10 mg, qn) was administered in the experimental group, with statin monotherapy (Rosuvastatin, 10 mg, qn) in the control group. The therapeutic effects on lipoprotein particle subfractions were assessed with NMR spectroscopy after 8 weeks treatment, and the achievement of LDL-C therapeutic target in both groups were analyzed.

Results

In the experimental group, after 8 weeks of evolocumab combination treatment, the concentrations of blood lipids (TC, LDL-C and its subfractions [LDL-1 to 6], VLDL-C and its subfractions [VLDL-1 to 5], IDL-C, and HDL-C), lipoprotein particles, and their subfractions [VLDL-P, IDL-P, LDL-P, and its subfractions [LDL-P1 to 6], apoB, and LP(a)] demonstrated therapeutic benefits with statistical significance (P < 0.05). The decrease in total LDL-P concentrations was mainly due to a decreased concentration of small-sized LDL particles (LDL-P 5 + 6), which was significantly more prominent than the decrease in medium-sized LDL-P (LDL-P3 + 4) and large-sized LDL-P (LDL-P1 + 2) (P < 0.001). According to lipid control target recommended by the latest China Cholesterol Education Program Expert Consensus in 2019, after 8 weeks treatment, 96.3% patients in the experimental group and 13.3% in the control group had achieved the LDL-C therapeutic target (P < 0.01).

Conclusions

Evolocumab combination treatment for 8 weeks significantly improves the plasma lipid profiles in ACS patients, and significantly decrease the concentration of lipoprotein particles which might contribute to the pathonesis of atherosclerosis.
The utility of the rapid emergency medicine score (REMS) compared with SIRS, qSOFA and NEWS for Predicting in-hospital Mortality among Patients with suspicion of Sepsis in an emergency department
Authors: Ruangsomboon Onlak , Boonmee Phetsinee , Limsuwat Chok , Chakorn Tipa , Monsomboon Apichaya
Published: January 2021

Background

Many early warning scores (EWSs) have been validated to prognosticate adverse outcomes secondary to sepsis in the Emergency Department (ED). These EWSs include the Systemic Inflammatory Response Syndrome criteria (SIRS), the quick Sequential Organ Failure Assessment (qSOFA) and the National Early Warning Score (NEWS). However, the Rapid Emergency Medicine Score (REMS) has never been validated for this purpose. We aimed to assess and compare the prognostic utility of REMS with that of SIRS, qSOFA and NEWS for predicting mortality in patients with suspicion of sepsis in the ED.

Methods

We conducted a retrospective study at the ED of Siriraj Hospital Mahidol University, Thailand. Adult patients suspected of having sepsis in the ED between August 2018 and July 2019 were included. Their EWSs were calculated. The primary outcome was all-cause in-hospital mortality. The secondary outcome was 7-day mortality.

Results

A total of 1622 patients were included in the study; 457 (28.2%) died at hospital discharge. REMS yielded the highest discrimination capacity for in-hospital mortality (the area under the receiver operator characteristics curves (AUROC) 0.62 (95% confidence interval (CI) 0.59, 0.65)), which was significantly higher than qSOFA (AUROC 0.58 (95%CI 0.55, 0.60); p = 0.005) and SIRS (AUROC 0.52 (95%CI 0.49, 0.55); p < 0.001) but not significantly superior to NEWS (AUROC 0.61 (95%CI 0.58, 0.64); p = 0.27). REMS was the best EWS in terms of calibration and association with the outcome. It could also provide the highest net benefit from the decision curve analysis. Comparison of EWSs plus baseline risk model showed similar results. REMS also performed better than other EWSs for 7-day mortality.

Conclusion

REMS was an early warning score with higher accuracy than sepsis-related scores (qSOFA and SIRS), similar to NEWS, and had the highest utility in terms of net benefit compared to SIRS, qSOFA and NEWS in predicting in-hospital mortality in patients presenting to the ED with suspected sepsis.
Pattern-mixture model in network meta-analysis of binary missing outcome data: one-stage or two-stage approach?
Authors: Spineli Loukia M. , Papadimitropoulou Katerina , Kalyvas Chrysostomos
Published: January 2021

Background

Trials with binary outcomes can be synthesised using within-trial exact likelihood or approximate normal likelihood in one-stage or two-stage approaches, respectively. The performance of the one-stage and the two-stage approaches has been documented extensively in the literature. However, little is known about how these approaches behave in the presence of missing outcome data (MOD), which are ubiquitous in clinical trials. In this work, we compare the one-stage versus two-stage approach via a pattern-mixture model in the network meta-analysis using Bayesian methods to handle MOD appropriately.

Methods

We used 29 published networks to empirically compare the two approaches concerning the relative treatment effects of several competing interventions and the between-trial variance (τ2), while considering the extent and level of balance of MOD in the included trials. We additionally conducted a simulation study to compare the competing approaches regarding the bias and width of the 95% credible interval of the (summary) log odds ratios (OR) andτ2in the presence of moderate and large MOD.

Results

The empirical study did not reveal any systematic bias between the compared approaches regarding the log OR, but showed systematically larger uncertainty around the log OR under the one-stage approach for networks with at least one small trial or low event risk and moderate MOD. For these networks, the simulation study revealed that the bias in log OR for comparisons with the reference intervention in the network was relatively higher in the two-stage approach. Contrariwise, the bias in log OR for the remaining comparisons was relatively higher in the one-stage approach. Overall, bias increased for large MOD. For these networks, the empirical results revealed slightly higherτ2estimates under the one-stage approach irrespective of the extent of MOD. The one-stage approach also led to less precise log OR andτ2when compared with the two-stage approach for large MOD.

Conclusions

Due to considerable bias in the log ORs overall, especially for large MOD, none of the competing approaches was superior. Until a more competent model is developed, the researchers may prefer the one-stage approach to handle MOD, while acknowledging its limitations.
Perspectives of family physicians towards access to lung cancer screening for individuals living with low income – a qualitative study
Authors: Sayani Ambreen , Vahabi Mandana , O’Brien Mary Ann , Liu Geoffrey , Hwang Stephen W. , Selby Peter , Nicholson Erika , Lofters Aisha
Published: January 2021

Background

Individuals living with low income are less likely to participate in lung cancer screening (LCS) with low-dose computed tomography. Family physicians (FPs) are typically responsible for referring eligible patients to LCS; therefore, we sought to understand their perspectives on access to lung cancer screening for individuals living with low income in order to improve equity in access to LCS.

Methods

A theory-informed thematic analysis was conducted using data collected from 11 semi-structured interviews with FPs recruited from three primary care sites in downtown Toronto. Data was coded using the Systems Model of Clinical Preventative Care as a framework and interpretation was guided by the synergies of oppression analytical lens.

Results

Four overarching themes describe FP perspectives on access to LCS for individuals living with low income: the degree of social disadvantage that influences lung cancer risk and opportunities to access care; the clinical encounter, where there is often a mismatch between the complex health needs of low income individuals and structure of health care appointments; the need for equity-oriented health care, illustrated by the neglect of structural origins of health risk and the benefits of a trauma-informed approach; and finally, the multiprong strategies that will be needed in order to improve equity in health outcomes.

Conclusion

An equity-oriented and interdisciplinary team based approach to care will be needed in order to improve access to LCS, and attention must be given to the upstream determinants of lung cancer in order to reduce lung cancer risk.
Design and rationale of a routine clinical care pathway and prospective cohort study in older patients needing intensive treatment
Authors: van Holstein Yara , van Deudekom Floor J. , Trompet Stella , Postmus Iris , Uit den Boogaard Anna , van der Elst Marjan J. T. , de Glas Nienke A. , van Heemst Diana , Labots Geert , Altena Mariëtte , Slingerland Marije , Liefers Gerrit Jan , van den Bos Frederiek , van der Bol Jessica M. , Blauw Gerard J. , Portielje Johanneke E. A. , Mooijaart Simon P.
Published: January 2021

Background

Treatment decisions concerning older patients can be very challenging and individualised treatment plans are often required in this very heterogeneous group. In 2015 we have implemented a routine clinical care pathway for older patients in need of intensive treatment, including a comprehensive geriatric assessment (CGA) that was used to support clinical decision making. An ongoing prospective cohort study, the Triaging Elderly Needing Treatment (TENT) study, has also been initiated in 2016 for participants in this clinical care pathway, to study associations between geriatric characteristics and outcomes of treatment that are relevant to older patients. The aim of this paper is to describe the implementation and rationale of the routine clinical care pathway and design of the TENT study.

Methods

A routine clinical care pathway has been designed and implemented in multiple hospitals in the Netherlands. Patients aged ≥70 years who are candidates for intensive treatments, such as chemotherapy, (chemo-)radiation therapy or major surgery, undergo frailty screening based on the Geriatric 8 (G-8) questionnaire and the Six-Item Cognitive Impairment Test (6CIT). If screening reveals potential frailty, a CGA is performed. All patients are invited to participate in the TENT study. Clinical data and blood samples for biomarker studies are collected at baseline. During follow-up, information about treatment complications, hospitalisations, functional decline, quality of life and mortality is collected. The primary outcome is the composite endpoint of functional decline or mortality at 1 year.

Discussion

Implementation of a routine clinical care pathway for older patients in need of intensive treatment provides the opportunity to study associations between determinants of frailty and outcomes of treatment. Results of the TENT study will support individualised treatment for future patients.

Trial registration

The study is retrospectively registered at the Netherlands Trial Register (NTR), trial number NL8107. Date of registration: 22-10-2019.
Continuous elevation of procalcitonin in cirrhosis combined with hepatic carcinoma: a case report
Authors: Lu Juan , Chen Chun-lei , Jin Jian-di , Chen Jun , Yu Cheng-bo
Published: January 2021

Background

Serum levels of procalcitonin (PCT) are considered a useful biomarker for the diagnosis of bacterial infection or inflammation. There are few reports of high PCT levels in end-stage liver disease regardless of bacterial infection. Here, we present a case of extremely high PCT levels (> 100 ng/mL) in a patient with severe cirrhosis combined with hepatic carcinoma.

Case presentation

A 65-year-old man developed end-stage cirrhosis with hepatic carcinoma. Radiographic imaging showed a massive hepatocellular carcinoma with multiple loci lack of indications of resection. Hence, transcatheter hepatic arterial chemoembolization was performed three times over a period of 4 months. Before and after interventional therapies, the biochemistry laboratory results were only slightly abnormal except for persistently high PCT concentrations (> 100 ng/mL), irrespective of the evidence for bacterial infection or sepsis.

Conclusions

This case suggests that continuously high levels of PCT (> 100 ng/mL) may be present in advanced liver disease, particularly in complex situations such as decompensated cirrhosis and liver cancer, in the absence of severe infection or sepsis. This knowledge could expand the significance of PCT in liver disease.
Antimicrobial resistance awareness and antibiotic prescribing behavior among healthcare workers in Nigeria: a national survey
Authors: Chukwu Emelda E. , Oladele David A. , Enwuru Christian A. , Gogwan Peter L. , Abuh Dennis , Audu Rosemary A. , Ogunsola Folasade T.
Published: January 2021

Background

Antimicrobial resistance (AMR) is a global problem compromising the effective treatment of infectious diseases. The World Health Organization (WHO) is encouraging and promoting awareness creation among health workers as one of its strategies to reduce the rate of emergence and transmission of AMR. Available data on the prescribing behavior of healthcare workers (HCWs) in Nigeria remains incomplete. This study was designed to provide an up-to-date estimate of the knowledge, attitude and antibiotic prescribing behavior of HCWs in Nigeria.

Methods

This is a cross-sectional study. Self-administered questionnaires were distributed to healthcare workers selected from six states, one each from the 6 geopolitical zones in Nigeria. A multi-stage sampling technique was used to reflect the three tiers of healthcare: primary, secondary and tertiary levels. Quantitative data was summarized using descriptive statistics. All data analysis was done using the Statistical package for social sciences version 26.0.

Results

Of the 420 questionnaires distributed, 358 (85.2%) responded. The mean year of practice of the respondents was 9.32 ± 7.8 years. About a half (50.3%) agreed that their prescribing behavior could promote antimicrobial resistance. 49.2% had a good knowledge of AMR and physicians had significantly better knowledge than other HCWs (X2 = 69.59, P < 0.001). Several participants prescribed antibiotics for common viral infections such as sore throats (75.7%), measles (37.7%), common cold and flu (21.2%). Over 60.3% admitted prescribing antibiotics just to be on the safe side. In general, 70.9% of the respondents frequently or moderately use practice guidelines while 25.7% often apply the delayed antibiotic prescription (DAP) strategy to reduce antimicrobial prescription.

Conclusion

This study reveals an overall moderate level of knowledge of AMR and attitude towards minimizing the emergence of antimicrobial resistance though this did not translate significantly to practice. Further efforts must be made in order to improve rational prescription of antimicrobials among HCWs in Nigeria.
Cryptococcal fungemia and Mycobacterium haemophilum cellulitis in a patient receiving ruxolitinib: a case report and literature review
Authors: Sayabovorn Naruemit , Chongtrakool Piriyaporn , Chayakulkeeree Methee
Published: January 2021

Background

Ruxolitinib is a novel oral Janus kinase inhibitor that is used for treatment of myeloproliferative diseases. It exhibits potent anti-inflammatory and immunosuppressive effects, and may increase the risk of opportunistic infections. Here, we report a rare case of Cryptococcus neoformans and Mycobacterium haemophilum coinfection in a myelofibrosis patient who was receiving ruxolitinib.

Case presentation

A 70-year-old Thai man who was diagnosed with JAK2V617F-mutation-positive primary myelofibrosis had been treated with ruxolitinib for 4 years. He presented with cellulitis at his left leg for 1 week. Physical examination revealed fever, dyspnea, desaturation, and sign of inflammation on the left leg and ulcers on the right foot. Blood cultures showed positive for C. neoformans. He was prescribed intravenous amphotericin B deoxycholate with a subsequent switch to liposomal amphotericin B due to the development of acute kidney injury. He developed new onset of fever after 1 month of antifungal treatment, and the lesion on his left leg had worsened. Biopsy of that skin lesion was sent for mycobacterial culture, and the result showed M. haemophilum. He was treated with levofloxacin, ethambutol, and rifampicin; however, the patient eventually developed septic shock and expired.

Conclusions

This is the first case of C. neoformans and M. haemophilum coinfection in a patient receiving ruxolitinib treatment. Although uncommon, clinicians should be aware of the potential for multiple opportunistic infections that may be caused by atypical pathogens in patients receiving ruxolitinib.
Legionnaire’s disease presenting as bilateral central scotomata: a case report
Authors: Yamada Sho , Kitajima Takamasa , Marumo Satoshi , Fukui Motonari
Published: January 2021

Background

Legionnaire’s disease is one of the major causes of community-acquired pneumonia and is occasionally complicated by neurological symptoms. However, reports of ocular lesions due to Legionnaire’s disease are limited.

Case presentation

We report the case of a patient with Legionnaire’s disease presenting as bilateral central scotomata due to retinal lesions. The patient consulted due to fever and bilateral central scotomata, as well as other extrapulmonary symptoms. Optical coherence tomography (OCT) showed bilateral accumulations of fluid under the retina, and the patient was diagnosed with bilateral exudative retinal detachment. Later, Legionnaire’s disease was confirmed by pulmonary infiltrates on chest imaging and positive urinary antigen for Legionella pneumophila. After administration of antibiotics, the bilateral central scotomata and bilateral subretinal fluid accumulations completely resolved, as did the other extrapulmonary symptoms and the pulmonary infiltrates. Thus, the bilateral central scotomata due to exudative retinal detachment were thought to be caused by Legionnaire’s disease.

Conclusions

This case demonstrates that Legionnaire’s disease can present as bilateral central scotomata. We may consider the possibility of extrapulmonary involvement complicating Legionnaire’s disease when we encounter bilateral ocular lesions in patients with fever and pneumonia.
Performance of case definitions and clinical predictors for influenza surveillance among patients followed in a rural cohort in Senegal
Authors: Barry Mamadou Aliou , Arinal Florent , Talla Cheikh , Hedible Boris Gildas , Sarr Fatoumata Diene , Ba Ibrahim Oumar , Diop Boly , Dia Ndongo , Vray Muriel
Published: January 2021

Background

Influenza is a major cause of morbidity and mortality in Africa. However, a lack of epidemiological data remains for this pathology, and the performances of the influenza-like illness (ILI) case definitions used for sentinel surveillance have never been evaluated in Senegal. This study aimed to i) assess the performance of three different ILI case definitions, adopted by the WHO, USA-CDC (CDC) and European-CDC (ECDC) and ii) identify clinical factors associated with a positive diagnosis for Influenza in order to develop an algorithm fitted for the Senegalese context.

Methods

All 657 patients with a febrile pathological episode (FPE) between January 2013 and December 2016 were followed in a cohort study in two rural villages in Senegal, accounting for 1653 FPE observations with nasopharyngeal sampling and influenza virus screening by rRT-PCR. For each FPE, general characteristics and clinical signs presented by patients were collected. Sensitivity, Specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV) for the three ILI case definitions were assessed using PCR result as the reference test. Associations between clinical signs and influenza infection were analyzed using logistic regression with generalized estimating equations. Sore throat, arthralgia or myalgia were missing for children under 5 years.

Results

WHO, CDC and ECDC case definitions had similar sensitivity (81.0%; 95%CI: 77.0–85.0) and NPV (91.0%; 95%CI: 89.0–93.1) while the WHO and CDC ILI case definitions had the highest specificity (52.0%; 95%CI: 49.1–54.5) and PPV (32.0%; 95%CI: 30.0–35.0). These performances varied by age groups. In children < 5 years, the significant predictors of influenza virus infection were cough and nasal discharge. In patients from 5 years, cough, nasal discharge, sore throat and asthenia grade 3 best predicted influenza infection. The addition of “nasal discharge” as a symptom to the WHO case definition decreased sensitivity but increased specificity, particularly in the pediatric population.

Conclusion

In summary, all three definitions studies (WHO, ECDC & CDC) have similar performance, even by age group. The revised WHO ILI definition could be chosen for surveillance purposes for its simplicity. Symptomatic predictors of influenza virus infection vary according the age group.
Increased mRNA expression of key cytokines among suspected cases of Pneumocystis jirovecii infection
Authors: Alshahrani Mohammad Y. , Alfaifi Mohammed , Al Shahrani Mesfer , Alshahrani Abdulaziz S. , Alkhathami Ali G. , Dera Ayed A. , Ahmad Irfan , Wahab Shadma , Beg Mirza M. A. , Hakamy Ali , Hamid Mohamed E.
Published: January 2021

Background

Pneumocystis pneumonia (PCP) is a fatal infectious disease caused by Pneumocystis jirovecii (PJP). The major factor relevant to morbidity and mortality seems to be the host inflammatory reaction. The objective of this study was to evaluate the role of IL-2, IL-4, IL-10, and IL-13 cytokine mRNA expression among suspected P. jirovecii infection.

Methods

This was a cross-sectional analytical study undertaken in Aseer region, Saudi Arabia. One hundred suspected PCP cases and 100 healthy controls were included in the study. Basic clinical manifestations, radiological findings, microbiological and immunological findings were extracted from the hospital records from January 2019 to August 2019, Pneumocystis detection was done by immune-fluorescent staining (IFAT, Gomorimethanamine silver staining (GMSS), Giemsa staining, Toluidine blue O (TBO), and Pneumocystis RT-PCR.

Results

Increased more than 5 fold, 3 fold, 4 fold, and 7 fold of IL-2, IL-4, IL-10, and IL-13 mRNA expression were observed in PCP cases compared to controls. Higher expression of IL-2 mRNA was connected with crept, wheezing and chest X-ray findings like central perihilar infiltrate, patchy infiltrate, consolidation, hilar lymphadenopathy, pneumothorax, pleural effusion which showed higher expression compared to counterpart (p< 0.0001). Higher expression of IL-4 mRNA was found to be significantly associated with weight loss (p=0.002), dyspnea (p=0.003), crept (p=0.01), and chest X-ray findings (p< 0.0001). Significantly increased expression of IL-10 mRNA was observed to be associated with weight loss, dyspnea, night sweats, wheezing, and different findings of chest X-ray compared to their counterparts, whereas, IL-13 mRNA was observed in cases with fever. Suspected cases of PCP confirmed positive by IFTA with higher IL-2, IL-4, and IL-10 mRNA expression compared to negative cases. RT-PCR confirmed PCP cases had significantly higher expression of IL-2, IL-4, and IL-10 as well as IL-13 mRNA compared to negative cases. Positive detected cases by GMSS showed higher IL-2, IL-10 mRNA expression, while Giemsa showed only higher IL-4 mRNA expression compared to negative cases.

Conclusion

Confirmed cases of P. jirovecii showed higher IL-2, IL-4, IL-10, and IL-13 mRNA expression comparatively to negative cases. Increased expression of cytokines may be indicative of infection severity and could help in patients’ management.
Chronic Candida infection, bronchiectasis, immunoglobulin abnormalities, and stunting: a case report of a natural mutation of STAT1 (c.986C>G) in an adolescent male
Authors: Yu Yali , Xu Fei , Shen Hui , Wu Jiang
Published: January 2021

Background

Chronic mucocutaneous candidiasis (CMC) is the most common clinical symptom of singer transducer and signal transducer and activator of transcription 1 (STAT1) gain-of-function (GOF) mutations. Bronchiectasis is a chronic lung disease that is characterized by permanent bronchiectasis, causing cough, expectoration, and even haemoptysis. The underlying pathogeny is not yet clear. Immunoglobulin (Ig) A is derived from memory B cells and correlates with immune-related diseases. STAT1 is closely associated with signal transmission and immune regulation.

Case presentation

We report a 17-year-old male patient carrying a GOF mutation in STAT1. The variant led to CMC, bronchiectasis, and elevated serum IgA levels, as well as stunting. Whole-exome sequencing (WES) revealed a c.986C>G (p.P329R) heterozygous mutation in the STAT1 gene.

Conclusion

Further Sanger sequencing analysis of STAT1 in the patient and his parents showed that the patient harboured a de novo mutation.
The antiphospholipid syndrome may induce non-thrombotic internal jugular vein stenosis: two cases report
Authors: Song Si-ying , Rajah Gary , Ding Yu-chuan , Ji Xun-ming , Meng Ran
Published: January 2021

Background

Antiphospholipid syndrome (APS) is associated with a high incidence of thrombotic events, either arterial thrombosis or venous thrombosis. However, APS-related non-thrombotic venous stenosis is rarely reported.

Case presentation

This study described two cases of young women with APS-related internal jugular vein stenosis (IJVS) and reviewed current literature on this issue, including clinical features, diagnosis, and treatment.

Conclusions

IJVS is a rather rare complication of APS. Two cases were reported for the first time that high titer of antiphospholipid antibodies (aPL) might mediate direct vessel wall damage and further induce venous stenosis despite long-term standardized anticoagulation to prevent thrombus formation. Therefore, dynamic monitoring of autoantibodies and concomitant use of anticoagulants and corticosteroids may be necessary to the management of APS and its complications.
Postnatal care utilisation among women in rural Ghana: analysis of 2014 Ghana demographic and health survey
Authors: Appiah Francis , Salihu Tarif , Fenteng Justice Ofosu Darko , Darteh Andrews Ohene , Kannor Patience , Ayerakwah Patience Ansomah , Ameyaw Edward Kwabena
Published: January 2021

Background

Maternal mortality is high in Ghana, averaging 310 maternal deaths per 100,000 live births in 2017. This is partly due to inadequate postnatal care especially among rural communities. Ghana can avert the high maternal deaths if women meet the World Health Organisation’s recommended early postnatal care check-up. Despite the association between geographical location and postnatal care utilisation, no study has been done on determinants of postnatal care among rural residents in Ghana. Therefore, this study determined the prevalence and correlates of postnatal care utilization among women in rural Ghana.

Methods

The study utilised women’s file of the 2014 Ghana Demographic and Health Survey (GDHS). Following descriptive computation of the prevalence, binary logistic regression was fitted to assess correlates of postnatal care at 95% confidence interval. The results were presented in adjusted odds ratio (AOR). Any AOR less than 1 was interpreted as reduced likelihood of PNC attendance whilst AOR above 1 depicted otherwise. All analyses were done using Stata version 14.0.

Results

The study revealed that 74% of the rural women had postnatal care. At the inferential level, women residing in Savanna zone had higher odds of postnatal care compared to those in the Coastal zone [AOR = 1.80, CI = 1.023–3.159], just as among the Guan women as compared to the Akan [AOR = 7.15, CI = 1.602–31.935]. Women who were working were more probable to utilise postnatal care compared to those not working [AOR = 1.45, CI = 1.015–2.060]. Those who considered distance as unproblematic were more likely to utilise postnatal care compared to those who considered distance as problematic [AOR = 1.63, CI = 1.239–2.145].

Conclusions

The study showed that ethnicity, ecological zone, occupation and distance to health facility predict postnatal care utilisation among rural residents of Ghana. The study points to the need for government to increase maternal healthcare facilities in rural settings in order to reduce the distance covered by women in seeking postnatal care.