bluuebunny/crossref_metadata_2025 huggingface dataset:
Hepatitis E virus infection in pregnant women, Argentina
Authors: Tissera Gabriela , Lardizabal María Cecilia , Torres Sofía Belén , Fantilli Anabella Clara , Martínez Wassaf Maribel G. , Venezuela Fernando , Capra Raúl , Balderramo Domingo C. , Travella Claudia , Ré Viviana E. , Pisano María Belén
Published: May 2020

Background

Hepatitis E virus (HEV) infection is an important cause of acute hepatitis worldwide. In pregnant women, HEV can cause more severe symptoms, with high rates of fatal hepatic failure in endemic countries. However, HEV prevalence and circulation among pregnant women from South America is almost unknown. We aimed to investigate HEV infection in pregnant women for the first time in Argentina.

Methods

IgG and IgM anti-HEV antibodies and RNA-HEV were investigated (by ELISA assays and RT-Nested-PCR, respectively) in 202 serum samples from pregnant women collected in the central region of Argentina between 2015 and 2017. A control group of 155 non-pregnant women was included (year 2018).

Results

The IgG anti-HEV positivity rate was 8.4% (17/202), higher than the 2.6% (4/155) obtained for the non-pregnant women control group, and showing association between pregnancy and HEV infection (p = 0.023, OR = 3.5, CI95% = 1.1–10.5). Women younger than 25 years old presented higher levels of antibodies, and there were no differences in the prevalences between trimesters of pregnancy. Two samples were reactive for IgM anti-HEV, showing recent infections, although no symptoms were registered in these patients. All samples were negative for RNA-HEV amplification.

Conclusions

HEV produces infections in pregnant women from Argentina, alerting health teams to consider it as a possible cause of liver disease.
Live poultry market closure and avian influenza A (H7N9) infection in cities of China, 2013–2017: an ecological study
Authors: Chen Ying , Cheng Jian , Xu Zhiwei , Hu Wenbiao , Lu Jiahai
Published: May 2020

Background

Previous studies have proven that the closure of live poultry markets (LPMs) was an effective intervention to reduce human risk of avian influenza A (H7N9) infection, but evidence is limited on the impact of scale and duration of LPMs closure on the transmission of H7N9.

Method

Five cities (i.e., Shanghai, Suzhou, Shenzhen, Guangzhou and Hangzhou) with the largest number of H7N9 cases in mainland China from 2013 to 2017 were selected in this study. Data on laboratory-confirmed H7N9 human cases in those five cities were obtained from the Chinese National Influenza Centre. The detailed information of LPMs closure (i.e., area and duration) was obtained from the Ministry of Agriculture. We used a generalized linear model with a Poisson link to estimate the effect of LPMs closure, reported as relative risk reduction (RRR). We used classification and regression trees (CARTs) model to select and quantify the dominant factor of H7N9 infection.

Results

All five cities implemented the LPMs closure, and the risk of H7N9 infection decreased significantly after LPMs closure with RRR ranging from 0.80 to 0.93. Respectively, a long-term LPMs closure for 10–13 weeks elicited a sustained and highly significant risk reduction of H7N9 infection (RRR = 0.98). Short-time LPMs closure with 2 weeks in every epidemic did not reduce the risk of H7N9 infection (p > 0.05). Partially closed LPMs in some suburbs contributed only 35% for reduction rate (RRR = 0.35). Shenzhen implemented partial closure for first 3 epidemics (p > 0.05) and all closure in the latest 2 epidemic waves (RRR = 0.64).

Conclusion

Our findings suggest that LPMs all closure in whole city can be a highly effective measure comparing with partial closure (i.e. only urban closure, suburb and rural remain open). Extend the duration of closure and consider permanently closing the LPMs will help improve the control effect. The effect of LPMs closure seems greater than that of meteorology on H7N9 transmission.
Precision diagnosis and therapy of a case of brain abscesses associated with asymptomatic pulmonary arteriovenous fistulas
Authors: Gao Lu-Yao , Xu Guang-Run , Dai Ting-Jun
Published: May 2020

Background

Brain abscesses, a severe infectious disease of the CNS, are usually caused by a variety of different pathogens, which include Streptococcus intermedius (S. intermedius). Pulmonary arteriovenous fistulas (PAVFs), characterized by abnormal direct communication between pulmonary artery and vein, are a rare underlying cause of brain abscesses.

Case presentation

The patient was a previous healthy 55-year-old man who presented with 5 days of headache and fever. Cerebral magnetic resonance imaging (MRI) suggested a brain abscess. Thoracic CT scan and angiography demonstrated PAVFs. Aiding by metagenomic next-generation sequencing (mNGS) of the cerebrospinal fluid (CSF) sample which identified S. intermedius as the causative pathogen, the patient was switched to the single therapy of large dose of penicillin G and was cured precisely and economically.

Conclusions

It is an alternative way to perform mNGS to identify causative pathogens in patients with brain abscesses especially when the results of traditional bacterial culture were negative. Further thoracic CT or pulmonary angiography should also be undertaken to rule out PAVFs as the potential cause of brain abscess if the patient without any known premorbid history.
Zika virus in southeastern Senegal: survival of the vectors and the virus during the dry season
Authors: Diouf Babacar , Gaye Alioune , Diagne Cheikh Tidiane , Diallo Mawlouth , Diallo Diawo
Published: May 2020

Background

Zika virus (ZIKV, genus Flavivirus, family Flaviviridae) is transmitted mainly by Aedes mosquitoes. This virus has become an emerging concern of global public health with recent epidemics associated to neurological complications in the pacific and America. ZIKV is the most frequently amplified arbovirus in southeastern Senegal. However, this virus and its adult vectors are undetectable during the dry season. The aim of this study was to investigate how ZIKV and its vectors are maintained locally during the dry season.

Methods

Soil, sand, and detritus contained in 1339 potential breeding sites (tree holes, rock holes, fruit husks, discarded containers, used tires) were collected in forest, savannah, barren and village land covers and flooded for eggs hatching. The emerging larvae were reared to adult, identified, and blood fed for F1 production. The F0 and F1 adults were identified and tested for ZIKV by Reverse Transcriptase-Real time Polymerase Chain Reaction.

Results

A total of 1016 specimens, including 13 Aedes species, emerged in samples collected in the land covers and breeding sites investigated. Ae. aegypti was the dominant species representing 56.6% of this fauna with a high plasticity. Ae. furcifer and Ae. luteocephalus were found in forest tree holes, Ae. taylori in forest and village tree holes, Ae. vittatus in rock holes. ZIKV was detected from 4 out of the 82 mosquito pools tested. Positive pools included Ae. bromeliae (2 pools), Ae. unilineatus (1 pool), and Ae. vittatus (1 pool), indicating that the virus is maintained in these Aedes eggs during the dry season.

Conclusion

Our investigation identified breeding sites types and land cover classes where several ZIKV vectors are maintained, and their maintenance rates during the dry season in southeastern Senegal. The maintenance of the virus in these vectors in nature could explain its early amplification at the start of the rainy season in this area.
Fetal magnetic resonance imaging contributes to the diagnosis and treatment of meconium peritonitis
Authors: Lu Yuanting , Ai Bin , Zhang Weijuan , Liu Hongsheng
Published: May 2020

Background

Meconium peritonitis (MP) is a rare fetal disease that needs to be urgently identified for surgical intervention. We report a series of 35 patients diagnosed prenatally with MP by magnetic resonance imaging (MRI), illustrate the imaging findings and investigate the predictive value of these findings for postpartum management.

Method

A consecutive cohort of patients diagnosed with MP who were born at our institution from 2013 to 2018 was enrolled retrospectively. The prenatal ultrasound and MRI findings were analyzed. Fisher’s exact probability test was used to evaluate the predictive value of MRI for surgical intervention between the operative group and the nonoperative group.

Results

Ascites (30/35) and distended bowel loops (27/35) were two of the most common prenatal MP-related findings on fetal MRI. Of the 35 infants, 26 received surgical intervention. All fetuses with MRI scans showing bowel dilatation (14/26,p = 0.048) and micro-colorectum (13/26,p = 0.013) required surgery. There were no significant differences in the number of fetuses with meconium pseudocysts and peritoneal calcifications between the two groups.

Conclusion

Fetuses with bowel dilatation and micro-colorectum on MRI may need postpartum surgical intervention. Infants with only a small amount of ascites and slight bowel distention were likely to receive conservative treatment.
A novel ultra-sensitive method for the detection of FGFR3 mutations in urine of bladder cancer patients – Design of the Urodiag® PCR kit for surveillance of patients with non-muscle-invasive bladder cancer (NMIBC)
Authors: Roperch Jean-Pierre , Hennion Claude
Published: May 2020

Background

We have recently developed a highly accurate urine-based test, named Urodiag®, associating FGFR3 mutation and DNA methylation assays for recurrence surveillance in patients with low-, intermediate-, and high-risk NMIBC. Previously, the detection of four FGFR3 mutations (G372C, R248C, S249C and Y375C) required amplification steps and PCR products were analyzed by capillary electrophoresis (Allele Specific-PCR, AS-PCR), which was expensive and time-consuming. Here, we present the development a novel ultra-sensitive multiplex PCR assay as called “Mutated Allele Specific Oligonucleotide-PCR (MASO-PCR)”, generating a cost-effective, simple, fast and clinically applicable assay for the detection of FGFR3 mutations in voided urine.

Methods

Comparative clinical performances of MASO-PCR and AS-PCR technologies were performed from 263 urine DNA samples (87 FGFR3 mutated and 176 FGFR3 wild-type). In the development of Urodiag® PCR Kit, we studied the stability and reproducibility of each all-in-one PCR master mix (single reaction mixture including all the necessary PCR components) for MASO-PCR and QM-MSPCR (Quantitative Multiplex Methylation-Specific PCR to co-amplify SEPTIN9, HS3ST2 and SLIT2 methylated genes) assays.

Results

Complete concordance (100%) was observed between the MASO-PCR and AS-PCR results. Each PCR master mix displayed excellent reproducibility and stability after 12 months of storage at − 20 °C, with intra-assay standard deviations lower than 0.3 Ct and coefficient of variations (CV) lower than 1%. The limit of detection (LoD) of MASO-PCR was 5% mutant detection in a 95% of wild-type background. The limit of quantification (LoQ) of QM-MSPCR was 10 pg of bisulfite-converted DNA.

Conclusions

We developed and clinically validated the MASO-PCR assay, generating cost-effective, simple, fast and clinically applicable assay for the detection of FGFR3 mutations in urine. We also designed the Urodiag® PCR Kit, which includes the MASO-PCR and QM-MSPCR assays. Adapted to routine clinical laboratory (simplicity, accuracy), the kit will be a great help to urologists for recurrence surveillance in patients at low-, intermediate- and high-risk NMIBC. Reducing the number of unnecessary cystoscopies, it will have extremely beneficial effects for patients (painless) and for the healthcare systems (low cost).
The mutational spectrum of hunter syndrome reveals correlation between biochemical and clinical profiles in Tunisian patients
Authors: Chkioua L , Grissa O , Leban N , Gribaa M , Boudabous H , Turkia H Ben , Ferchichi S , Tebib N , Laradi S
Published: May 2020

Background

Mucopolysaccharidosis type II (MPS II) or Hunter syndrome is an X-linked recessive lysosomal storage disorder resulting from deficient activity of iduronate 2-sulfatase (IDS) and the progressive lysosomal accumulation of sulfated glycosaminoglycans (GAGs).

Methods

A diagnosis of MPS II or Hunter syndrome was performed based on the following approach after a clinical and paraclinical suspicion. Two biochemical and molecular tests were carried out separately and according to the availability of the biological material.

Results

All patients in this cohort presented the most common MPS II clinical features. Electrophoresis of GAGs on a cellulose acetate plate in the presence of a high concentration of heparane sulfate showed an abnormal dermatan sulfate band in the patients compared with that in a control case. Furthermore, leukocyte IDS activity ranged from 0.00 to 0.75 nmol/h/mg of leukocyte protein in patients.

Five previously reported mutations were identified in this study patients: one splice site mutation, c.240 + 1G > A; two missense mutations, p.R88P and p.G94D; a large deletion of exon 1 to exon 7; and one nonsense mutation, p.Q396*. In addition, two novel alterations were identified in the MPS II patients: one frame shift mutation, p.D450Nfs*95 and one nonsense mutation, p.Q204*.

Additionally, five known IDS polymorphisms were identified in the patients: c.419–16 delT, c.641C > T (p.T214M), c.438 C > T (p.T146T), c.709-87G > A, and c.1006 + 38 T > C.

Conclusions

The high level of urine GAGs and the deficiency of iduronate 2-sulfatase activity was associated with the phenotype expression of Hunter syndrome. Molecular testing was useful for the patients’ phenotypic classification and the detection of carriers.
Aspiration-sclerotherapy versus laparoscopic de-roofing in the treatment of renal cysts: which is better?
Authors: Zhang Xueling , Cao Dehong , Han Peizhen , Ren Zhengju , Wang Jia , Wei Qiang
Published: May 2020

Background

To compare the clinical efficiency between aspiration-sclerotherapy (AS) and laparoscopic de-roofing (LD) in the management of renal cysts through meta-analysis of comparative studies.

Method

A comprehensive literature search was performed by PubMed, MEDLINE, Ovid and Web of Science for relevant studies published up to January 2020. The statistical analyses were conducted with Review Manager 5.3.0 and Stata 15.1. The sensitivity analysis was also carried out to confirm the reliability of this Meta-analysis.

Results

Our searches of literature generated 6 studies (1547 patients incorporated) comparing AS with LD in the impacts of renal cyst therapy. Of these, 6 studies contained 1106 and 441 patients who were treated with AS and LD, respectively. The outcome of this meta-analysis indicated that LD group was superior in symptomatic successful rate [Odds Ratio (OR): 0.28; 95%Confidence Interval (CI): 0.09 to 0.86;P = 0.03), radiological successful rate (OR: 0.06; 95%CI: 0.02 to 0.15;P < 0.01) and recurrence rate (OR: 6.08; 95%CI: 2.81 to 13.15;p < 0.01). Nevertheless, AS group had shorter treatment time [Mean Difference (MD):-51.10; 95% CI:-73.01 to − 29.20;p < 0.01]. No statistically significant difference was showed in the rate of complications (OR: 3.19; 95% CI: 0.39 to 25.88;P = 0.28).

Conclusions

In our meta-analysis, LD had higher symptomatic successful rate, radiological successful rate as well as lower recurrence rate than AS, while the treatment time was longer.
Primary antiphospholipid syndrome associated with anti-phospholipase A2 receptor antibody-positive membranous nephropathy
Authors: Teisseyre Maxime , Perrochia Hélène , Reboul Pascal , Cariou Sylvain , Renaud Sophie , Aglae Cédric , Moranne Olivier
Published: May 2020

Background

The kidney is a major target in primary antiphospholipid syndrome. Several types of nephropathy have been reported, the most frequent being acute or chronic specific vascular nephropathies and membranous nephropathy.

Case presentation

A 59-year-old male presented in our unit with nephrotic syndrome. He had a history of primary antiphospholipid syndrome with lupus anticoagulant treated with vitamin K antagonist therapy. On admission, antiphospholipid (lupus anticoagulant) and anti-PLA2R antibodies were positive. Screening for secondary etiologies was negative. In the context of primary antiphospholipid syndrome treated with vitamin K antagonist therapy, we did not perform a biopsy and we treated the patient with angiotensin-converting-enzyme inhibitor. No remission was observed at 6 months with persistent anti-PLA2R antibodies while antiphospholipid antibody level became negative. Consequently, kidney biopsy was performed showing both membranous nephropathy with PLA2R in deposits on immunohistochemistry with IgG4 dominance and antiphospholipid syndrome chronic vascular nephropathy. Following that, treatment with rituximab was started with secondarily a decrease in serum PLA2R antibody levels and partial remission.

Conclusion

We report the first association between primary antiphospholipid syndrome and membranous nephropathy with anti-PLA2R antibodies. Our observations could suggest a causal link between primary antiphospholipid syndrome and PLA2R-related membranous nephropathy. Consequently, it would be interesting to screen for anti-PLA2R antibodies for further cases of nephrotic syndrome in patients with primary antiphospholipid syndrome and to search antiphospholipid antibodies in all membranous nephropathies.
Implementation of a new program of gestational diabetes screening and management in Morocco: a qualitative exploration of health workers’ perceptions
Authors: Utz Bettina , Assarag Bouchra , Lekhal Touria , Van Damme Wim , De Brouwere Vincent
Published: May 2020

Background

Gestational diabetes mellitus (GDM) is associated with an increased risk for a future type 2 diabetes mellitus in women and their children. As linkage between maternal health and non-communicable diseases, antenatal care plays a key role in the primary and secondary prevention of GDM associated adverse outcomes. While implementing a locally adapted GDM screening and management approach through antenatal care services at the primary level of care, we assessed its acceptability by the implementing health care providers.

Methods

As part of a larger implementation effectiveness study assessing a decentralized gestational diabetes screening and management approach in the prefecture of Marrakech and the rural district of Al Haouz in Morocco, we conducted four focus group discussions with 29 primary health care providers and seven in-depth interviews with national and regional key informants. After transcription of data, we thematically analyzed the data using a combined deductive and inductive approach.

Results

The intervention of screening and managing women with gestational diabetes added value to existing antenatal care services but presented an additional workload for first line health care providers. An existing lack of knowledge about gestational diabetes in the community and among private health care physicians required of public providers to spend more time on counselling women. Nurses had to adapt recommendations on diet to the socio-economic context of patients. Despite the additional task, especially nurses and midwives felt motivated by their gained capacity to detect and manage gestational diabetes, and to take decisions on treatment and follow-up.

Conclusions

Detection and initial management of gestational diabetes is an acceptable strategy to extend the antenatal care service offer in Morocco and to facilitate service access for affected pregnant women. Despite its additional workload, gestational diabetes management can contribute to the professional motivation of primary level health care providers.

Trial registration

clinicaltrials.gov; NCT02979756.
Interventions to improve adherence to antenatal and postnatal care regimens among pregnant women in sub-Saharan Africa: a systematic review
Authors: Esopo Kristina , Derby Lilly , Haushofer Johannes
Published: May 2020

Background

Pregnant women in sub-Saharan Africa tend to have low adherence to antenatal and postnatal care regimens, contributing to high infant and child mortality rates. Despite low adherence figures and the high returns from attending antenatal and postnatal care visits, research on interventions to improve adherence is in its infancy. Our aim was to determine the effectiveness of existing interventions to improve adherence to antenatal and postnatal care regimens among pregnant women in sub-Saharan Africa.

Methods

Full text, peer-reviewed articles, published in English and listed in PubMed or PsycINFO through January 2018 were identified in a systematic review. Studies were restricted to randomized controlled trials only and had to assess intervention impact on antenatal and postnatal care adherence, operationalized as the frequency of visits attended. Two reviewers independently screened papers for inclusion and evaluated the risk of systematic error in each study using the Cochrane risk of bias tool. Any discrepancies were reconciled by a third independent reviewer.

Results

The initial search generated 186 articles, of which, five met our inclusion criteria. Due to the small sample size and methodological variation across studies, a pooled effect size estimate could not be obtained. Therefore, effects on antenatal and postnatal care adherence were examined and reported at the individual study level. None of the interventions were directly aimed at improving adherence, but two of the five, both behavioral interventions, demonstrated effectiveness in increasing antenatal care (rate ratio 5.86, 95% CI 2.6-13.0, p<0.0001) and postnatal care adherence (31.3%, 95% CI 15.4-47.2, p=0.0009), respectively. Three home visit interventions had no effect on antenatal care adherence. Although the risk of bias was unclear or high in some cases, it remained low in most categories across studies.

Conclusions

Results point to a large gap in the literature on interventions to address antenatal and postnatal care adherence in sub-Saharan Africa. Interventions drawing upon the executive function literature and the promising results of the behavioral interventions reviewed here are urgently needed to address these gaps.

Trial registration

The review was prospectively registered with PROSPERO, id numberhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=88152, on February 7, 2018.
The burden of adolescent motherhood and health consequences in Nepal
Authors: Gurung Rejina , Målqvist Mats , Hong Zhou , Poudel Pragya Gautam , Sunny Avinash K. , Sharma Srijana , Mishra Sangeeta , Nurova Nisso , KC Ashish
Published: May 2020

Background

Annually, 18 million babies are born to mothers 18 years or less. Two thirds of these births take place in South Asia and Sub-Saharan Africa. Due to social and biological factors, adolescent mothers have a higher risk of adverse birth outcomes. We conducted this study to assess the incidence, risk factors, maternal and neonatal health consequences among adolescent mothers.

Methods

We conducted an observational study in 12 hospitals of Nepal for a period of 12 months. Patient medical record and semi-structured interviews were used to collect demographic information of mothers, intrapartum care and outcomes. The risks of adverse birth outcomes among adolescent compared to adult mothers were assessed using multivariate logistic regression.

Results

During the study period, among the total 60,742 deliveries, 7.8% were adolescent mothers. Two third of the adolescent mothers were from disadvantaged ethnic groups, compared to half of adult mothers (66.1% vs 47.8%, p-value< 0.001). One third of the adolescent mothers did not have formal education, while one in nine adult mothers did not have formal education (32.6% vs 14.2%, p-value< 0.001). Compared to adult mothers, adolescent mothers had higher odds of experiencing prolonged labour (aOR-1.56, 95% CI, 1.17–2.10, p-0.003), preterm birth (aOR-1.40, 95% CI, 1.26–1.55, p < 0.001) and of having a baby being small for gestational age (aOR-1.38, 95% CI 1.25–1.52, p < 0.001). The odds of major malformation increased by more than two-fold in adolescent mothers compared to adult mothers (aOR-2.66, 95% CI 1.12–6.33, p-0.027).

Conclusion

Women from disadvantaged ethnic group have higher risk of being pregnant during adolescent age. Adolescent mothers were more likely to have prolonged labour, a preterm birth, small for gestational age baby and major congenital malformation. Special attention to this high-risk group during pregnancy, labour and delivery is critical.
The effect of high dietary fiber intake on gestational weight gain, fat accrual, and postpartum weight retention: a randomized clinical trial
Authors: Hull Holly R. , Herman Amy , Gibbs Heather , Gajewski Byron , Krase Kelli , Carlson Susan E. , Sullivan Debra K. , Goetz Jeannine
Published: May 2020

Background

Interventions to prevent excessive gestational weight gain (GWG) have had limited success This pilot study examined the effectiveness of a single goal (SG) high dietary fiber intervention to prevent excessive GWG.

Methods

Twelve weekly lessons focused on consuming a high fiber diet (≥30 g/day). Snacks containing 10–12 g of dietary fiber were given for the first 6 weeks only. Body composition was measured at baseline and at the end of the intervention. At one-year postpartum, body weight retention and dietary practices were assessed. Ap-value is reported for the primary analysis only. For all other comparisons, Cohen’s d is reported to indicate effect size.

Results

The SG group increased fiber intake during the study (32 g/day at 6 weeks, 27 g/day at 12 weeks), whereas the UC group did not (~ 17 g/day). No differences were found for the proportion of women classified as excessive gainers (p = 0.13). During the intervention, the SG group gained less body weight (− 4.1 kg) and less fat mass (− 2.8 kg) (d = 1.3). At 1 year postpartum, the SG group retained less weight (0.35 vs. 4.4 kg, respectively, d = 1.8), and reported trying to currently eat high fiber foods.

Conclusion

The SG intervention resulted in less weight gain, fat accrual, and weight retention at 1 year postpartum. A residual intervention effect was detected postpartum with the participants reporting continued efforts to consume a high fiber diet.

Trial registration

NCT03984630; Trial registered June 13, 2019 (retrospectively registered).
A novel risk score model based on eight genes and a nomogram for predicting overall survival of patients with osteosarcoma
Authors: Wu Guangzhi , Zhang Minglei
Published: May 2020

Background

This study aims to identify a predictive model to predict survival outcomes of osteosarcoma (OS) patients.

Methods

A RNA sequencing dataset (the training set) and a microarray dataset (the validation set) were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database, respectively. Differentially expressed genes (DEGs) between metastatic and non-metastatic OS samples were identified in training set. Prognosis-related DEGs were screened and optimized by support vector machine (SVM) recursive feature elimination. A SVM classifier was built to classify metastatic and non-metastatic OS samples. Independent prognosic genes were extracted by multivariate regression analysis to build a risk score model followed by performance evaluation in two datasets by Kaplan-Meier (KM) analysis. Independent clinical prognostic indicators were identified followed by nomogram analysis. Finally, functional analyses of survival-related genes were conducted.

Result

Totally, 345 DEGs and 45 prognosis-related genes were screened. A SVM classifier could distinguish metastatic and non-metastatic OS samples. An eight-gene signature was an independent prognostic marker and used for constructing a risk score model. The risk score model could separate OS samples into high and low risk groups in two datasets (training set: log-rank p < 0.01, C-index = 0.805; validation set: log-rank p < 0.01, C-index = 0.797). Tumor metastasis and RS model status were independent prognostic factors and nomogram model exhibited accurate survival prediction for OS. Additionally, functional analyses of survival-related genes indicated they were closely associated with immune responses and cytokine-cytokine receptor interaction pathway.

Conclusion

An eight-gene predictive model and nomogram were developed to predict OS prognosis.
Metastasis-directed therapy in castration-refractory prostate cancer (MEDCARE): a non-randomized phase 2 trial
Authors: Berghen Charlien , Joniau Steven , Rans Kato , Devos Gaëtan , Poels Kenneth , Slabbaert Koen , Dumez Herlinde , Albersen Maarten , Goffin Karolien , Haustermans Karin , De Meerleer Gert
Published: May 2020

Background

Patients diagnosed with metastatic castration-refractory prostate cancer (mCRPC) rely on a limited number of therapeutic agents resulting in a median survival of 2–3 years. A subgroup of those patients with mCRPC presents with oligoprogressive disease, with a limited number of progressive lesions while other metastases are still controlled by ongoing systemic treatment.

Methods

In this single arm prospective phase II trial, we aim to include 18 patients with oligoprogressive mCRPC (1–3 metastases and/or local recurrence) who will be treated with metastasis-directed therapy to all visible progressive lesions. Progression is based on conventional imaging, as the use of PSMA PET-CT is considered investigational. However all patients will undergo PSMA PET-CT and the images will be blinded until progression. Primary endpoint is the postponement of the start of next-line systemic treatment (NEST) and the additional clinical value of PSMA PET-CT. Recruitment of patients for this trial started in January 2020 and will be completed approximately by December 2020.

Discussion

In this phase 2 trial on oligoprogressive mCRPC, we will investigate the benefit of progression-directed therapy while continuing ongoing systemic treatment. We hypothesize that progression-directed therapy (PDT) with surgery or stereotactic body radiation therapy for these oligoprogressive lesions will postpone the start of next-line systemic treatment and therefore serve as a new or add-on therapy in the spectrum of treatments available for mCRPC. The results of this trial will serve as guidance for a later randomized phase 3 trial. All participants are given an information sheet and are required to give written informed consent. Results will be published in a peer-reviewed journal.

Trial registration

This study is registered at ClinicalTrials.gov: NCT04222634 (December 18th 2019).
LRIG1 gene copy number analysis by ddPCR and correlations to clinical factors in breast cancer
Authors: Faraz Mahmood , Tellström Andreas , Ardnor Christina Edwinsdotter , Grankvist Kjell , Huminiecki Lukasz , Tavelin Björn , Henriksson Roger , Hedman Håkan , Ljuslinder Ingrid
Published: May 2020

Background

Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) copy number alterations and unbalanced gene recombination events have been reported to occur in breast cancer. Importantly, LRIG1 loss was recently shown to predict early and late relapse in stage I-II breast cancer.

Methods

We developed droplet digital PCR (ddPCR) assays for the determination of relative LRIG1 copy numbers and used these assays to analyze LRIG1 in twelve healthy individuals, 34 breast tumor samples previously analyzed by fluorescence in situ hybridization (FISH), and 423 breast tumor cytosols.

Results

Four of the LRIG1/reference gene assays were found to be precise and robust, showing copy number ratios close to 1 (mean, 0.984; standard deviation, +/− 0.031) among the healthy control population. The correlation between the ddPCR assays and previous FISH results was low, possibly because of the different normalization strategies used. One in 34 breast tumors (2.9%) showed an unbalanced LRIG1 recombination event. LRIG1 copy number ratios were associated with the breast cancer subtype, steroid receptor status, ERBB2 status, tumor grade, and nodal status. Both LRIG1 loss and gain were associated with unfavorable metastasis-free survival; however, they did not remain significant prognostic factors after adjustment for common risk factors in the Cox regression analysis. Furthermore, LRIG1 loss was not significantly associated with survival in stage I and II cases.

Conclusions

Although LRIG1 gene aberrations may be important determinants of breast cancer biology, and prognostic markers, the results of this study do not verify an important role for LRIG1 copy number analyses in predicting the risk of relapse in early-stage breast cancer.
Cancer risks in Lynch syndrome, Lynch-like syndrome, and familial colorectal cancer type X: a prospective cohort study
Authors:   on behalf of the German Consortium for Familial Intestinal Cancer, Bucksch Karolin , Zachariae Silke , Aretz Stefan , Büttner Reinhard , Holinski-Feder Elke , Holzapfel Stefanie , Hüneburg Robert , Kloor Matthias , von Knebel Doeberitz Magnus , Morak Monika , Möslein Gabriela , Nattermann Jacob , Perne Claudia , Rahner Nils , Schmiegel Wolff , Schulmann Karsten , Steinke-Lange Verena , Strassburg Christian P. , Vangala Deepak B. , Weitz Jürgen , Loeffler Markus , Engel Christoph
Published: May 2020

Background

Individuals with pathogenic germline variants in DNA mismatch repair (MMR) genes are at increased risk of developing colorectal, endometrial and other cancers (Lynch syndrome, LS). While previous studies have extensively described cancer risks in LS, cancer risks in individuals from families without detectable MMR gene defects despite MMR deficiency (Lynch-like syndrome, LLS), and in individuals from families fulfilling the Amsterdam-II criteria without any signs of MMR deficiency (familial colorectal cancer type X, FCCX) are less well studied. The aim of this prospective study was to characterise the risk for different cancer types in LS, LLS, and FCCX, and to compare these with the cancer risks in the general population.

Methods

Data was taken from the registry of the German Consortium for Familial Intestinal Cancer, where individuals were followed up prospectively within the framework of an intensified surveillance programme at recommended annual examination intervals. A total of 1120 LS, 594 LLS, and 116 FCCX individuals were analysed. From this total sample, eight different cohorts were defined, in which age-dependent cumulative risks and standardised incidence ratios were calculated regarding the first incident occurrence of any, colorectal, stomach, small bowel, urothelial, female breast, ovarian, and endometrial cancer, separately for LS, LLS, and FCCX.

Results

The number of individuals at risk for first incident cancer ranged from 322 to 1102 in LS, 120 to 586 in LLS, and 40 to 116 in FCCX, depending on the cancer type of interest. For most cancer types, higher risks were observed in LS compared to LLS, FCCX, and the general population. Risks for any, colorectal, stomach, urothelial, and endometrial cancer were significantly higher in LLS compared to the general population. No significantly increased risks could be detected in FCCX compared to LLS patients, and the general population. Colorectal and endometrial cancer risks tended to be higher in LLS than in FCCX.

Conclusions

The characterisation of cancer risks in patients with LLS and FCCX is important to develop appropriate surveillance programmes for these specific intermediate risk groups. Larger prospective studies are needed to obtain more precise risk estimates.
Could venous thromboembolism and major bleeding be indicators of lung cancer mortality? A nationwide database study
Authors: Howlett Jennifer , Benzenine Eric , Cottenet Jonathan , Foucher Pascal , Fagnoni Philippe , Quantin Catherine
Published: May 2020

Background

Venous thromboembolism (VTE) is highly prevalent in cancer patients and can cause severe morbidity. VTE treatment is essential, but anticoagulation increases the risk of major bleeding. The purpose was to evaluate the impact of VTE and major bleeding on survival and to identify significant risk factors for these events in lung cancer patients.

Methods

Data were extracted from a permanent sample of the French national health information system (including hospital and out-of-hospital care) from 2009 to 2016. All episodes of VTE and major bleeding events within one year after cancer diagnosis were identified. A Cox model was used to analyse the effect of VTE and major bleeding on the patients’ one-year survival. VTE and major bleeding risk factors were analysed with a Fine and Gray survival model.

Results

Among the 2553 included patients with lung cancer, 208 (8%) had a VTE episode in the year following diagnosis and 341 (13%) had major bleeding. Almost half of the patients died during follow-up. Fifty-six (60%) of the patients presenting with pulmonary embolism (PE) died, 48 (42%) of the patients presenting with deep vein thrombosis (DVT) alone died and 186 (55%) of those presenting with a major bleeding event died. The risk of death was significantly increased following PE and major bleeding events. VTE concomitant with cancer diagnosis was associated with an increased risk of VTE recurrence beyond 6 months after the first VTE event (sHR = 4.07 95% CI: 1.57–10.52). Most major bleeding events did not appear to be related to treatment.

Conclusion

VTE is frequent after a diagnosis of lung cancer, but so are major bleeding events. Both PE and major bleeding are associated with an increased risk of death and could be indicators of lung cancer mortality.
Text mining in a literature review of urothelial cancer using topic model
Authors: Lin Hsuan-Jen , Sheu Phillip C.-Y. , Tsai Jeffrey J. P. , Wang Charles C. N. , Chou Che-Yi
Published: May 2020

Background

Urothelial cancer (UC) includes carcinomas of the bladder, ureters, and renal pelvis. New treatments and biomarkers of UC emerged in this decade. To identify the key information in a vast amount of literature can be challenging. In this study, we use text mining to explore UC publications to identify important information that may lead to new research directions.

Method

We used topic modeling to analyze the titles and abstracts of 29,883 articles of UC from Pubmed, Web of Science, and Embase in Mar 2020. We applied latent Dirichlet allocation modeling to extract 15 topics and conducted trend analysis. Gene ontology term enrichment analysis and Kyoto encyclopedia of genes and genomes pathway analysis were performed to identify UC related pathways.

Results

There was a growing trend regarding UC treatment especially immune checkpoint therapy but not the staging of UC. The risk factors of UC carried in different countries such as cigarette smoking in the United State and aristolochic acid in Taiwan and China. GMCSF, IL-5, Syndecan-1, ErbB receptor, integrin, c-Met, and TRAIL signaling pathways are the most relevant biological pathway associated with UC.

Conclusions

The risk factors of UC may be dependent on the countries and GMCSF, IL-5, Syndecan-1, ErbB receptor, integrin, c-Met, and TRAIL signaling pathways are the most relevant biological pathway associated with UC. These findings may provide further UC research directions.
Comparison of 99mTc-MIBI scintigraphy, ultrasound, and mammography for the diagnosis of BI-RADS 4 category lesions
Authors: Liu Hongbiao , Zhan Hongwei , Sun Da
Published: May 2020

Background

We sought to determine the diagnostic efficacy of Breast-specific gamma imaging (BSGI) in Chinese women with BI-RADS 4 category lesions and to compare this efficacy to that of ultrasound/mammography.

Methods

We retrospectively analyzed data from 177 women that had undergone BSGI of BI-RADS 4 category lesions originally detected via ultrasound and/or mammography.

Results

Of these 177 cases, 117 (66.1%) were malignant lesions and 60 (33.9%) were benign. The sensitivity, specificity, positive predictive values, and negative predictive values of BSGI were 94.9% (111/117), 78.3% (47/60), 89.5% (111/124), and 88.7% (47/53), respectively. The specificity and positive predictive values for mammography were 48.3% (29/60) and 77.5% (107/138), while for ultrasound they were 53.3% (32/60) and 79.6% (109/137), respectively. The sensitivity and specificity of BSGI for the detection of lesions ≤1 cm in size were 90.9% (10/11) and 88.0% (22/25), respectively, while for breast lesions >1 cm in size these values were 94.3% (100/106) and 71.4% (25/35), respectively. In addition, BSGI sensitivity and specificity values for dense breast tissue were 94.0% (79/84) and 78.0% (39/50), respectively, whereas for non-dense breast tissue these vales were 97.0% (32/33) and 80.0% (8/10), respectively. The sensitivity of BSGI for invasive ductal carcinomas (IDC) and ductal carcinomas in situ (DCIS) was 98.9% (95/96) and 75.0% (9/12), respectively. The tumor to normal tissue ratio of BSGI for malignant lesions was significantly higher than for benign lesions (2.18 ± 1.17 vs 1.66 ± 0.40, t = 7.56, P<0.05).

Conclusions

These results indicate that BSGI is highly sensitive for the detection of such lesions, achieving good positive/negative predictive values. This suggests that for IDC in particular, BSGI is superior to ultrasound and mammography for the diagnosis of BI-RADS 4 category lesions, although this was less apparent for the diagnosis of DCIS lesions. BSGI exhibited excellent performance in dense breast tissue and for the detection of lesions ≤1 cm in size.
Combination of preoperative neutrophil-lymphocyte ratio, platelet-lymphocyte ratio and monocyte-lymphocyte ratio: a superior prognostic factor of endometrial cancer
Authors: Cong Rong , Kong Fanfei , Ma Jian , Li Qing , Wu Qijun , Ma Xiaoxin
Published: May 2020

Background

The preoperative peripheral blood neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and monocyte-lymphocyte ratio (MLR) have been reported to be associated with the prognosis of various cancers but are always discussed separately. The aim of this study is to bring the combination of NLR, PLR and MLR into the prognostic assessment system of endometrial cancer (EC) and establish a nomogram to provide an objective prediction model for clinical decisions.

Methods

A total of 1111 patients with EC who had accepted surgical treatment during 2013–2017 were involved in the analysis. Their NLR, PLR, and MLR levels were obtained from a routine blood examination within 2 weeks before operation. Receiver operating characteristic curve (ROC) analysis was performed to determine optimal cutoffs. Chi-square tests analysed the associations of the ratios with other clinicopathological variables. The prognostic value was indicated by overall survival (OS) via Cox proportional hazards models and Kaplan-Meier analysis. R software was used to establish the nomogram based on the combination of NLR, PLR, MLR and other clinicopathological factors.

Results

The median follow-up period was 40 months, and the median age was 56. The enrolled patients were stratified by cutoffs of 2.14 for NLR, 131.82 for PLR and 0.22 for MLR. Multivariate analyses demonstrated that high NLR over 2.14 (HR = 2.71, 95%CI = 1.83–4.02, P<0.001), high PLR over 131.82 (HR = 2.75, 95%CI = 1.90–3.97, P<0.001), and high MLR over 0.22 (HR = 1.72, 95%CI = 1.20–2.45, P = 0.003) were significantly associated with worse OS. The combined indicator, high NLR + high PLR + high MLR (HR = 4.34, 95%CI = 2.54–7.42, P<0.001), showed the highest prognostic value. The Harrell’s concordance index of the nomogram was 0.847 (95% CI = 0.804–0.890), showing good discrimination and calibration of this model.

Conclusion

The combination of NLR, PLR, and MLR is a superior prognostic factor of EC. The nomogram involving the combination of NLR, PLR, MLR and other clinicopathological factors is recommended to predict OS for EC patients clinically.
Achieving objective response in treatment of non-resectable neuroendocrine tumors does not predict longer time to progression compared to achieving stable disease
Authors: Thiis-Evensen Espen , Poole Amalie Christine , Nguyen Hong-Thien Thi , Sponheim Jon
Published: May 2020

Background

There are several treatment modalities for unresectable neuroendocrine tumors. Traditionally, the aim of these treatments has been to reduce the tumor load; referred to as objective response (OR). Less emphasis has been put on inducing the tumors to stop growing without a reduction in total tumor load; termed as stable disease (SD). We wanted to investigate whether achieving OR compared to obtaining SD predicted a longer time to progression (TTP) in patients with neuroendocrine tumors (WHO Grade 1 and 2) treated with peptide receptor radionuclide therapy, chemotherapy or molecular targeted therapy.

Methods

Patients treated with either peptide receptor radionuclide therapy (PRRT) with 177Lutetium-DOTA-octreotate, the chemotherapy combination streptozotocin/5-fluorouracil or everolimus were retrospectively assessed to evaluate the effect of the treatments on disease progression. We analyzed the TTP for patients for each treatment modality and compared the TTP between those who achieved OR and those who achieved SD.

Results

Altogether 56 patients treated with PRRT, 32 treated with streptozotocin/5-fluorouracil and 52 treated with everolimus were included in the analyses. The median TTP for those treated with PRRT and achieving OR was 31 months, the TTP for those achieving SD was 43 months (p = 0,2). For patients treated with streptozotocin/5-fluorouracil the results were: OR: 18 months, SD: 23 months (p = 0,9) and for those treated with everolimus; OR: 9 months, SD: 20 months (p = 0,5), respectively. We found no differences between patients achieving OR compared to SD regarding age, sex, stage, primary tumor location, Ki-67% or ongoing treatment with somatostatin analogues.

Conclusions

We found no treatment benefit with regard to TTP for our patients that experienced OR compared to those who achieved SD.
Prognostic impact of Dynamin related protein 1 (Drp1) in epithelial ovarian cancer
Authors: Tsuyoshi Hideaki , Orisaka Makoto , Fujita Yuko , Asare-Werehene Meshach , Tsang Benjamin K. , Yoshida Yoshio
Published: May 2020

Background

The mitochondrial fission protein, Dynamin related protein 1 (Drp1), and its upstream protein calcium/calmodulin–dependent protein kinase I (CaMKI) play a critical role in chemoresistance in ovarian cancer (OVCA). Thus, we examined the expression of Drp1, CaMKI and their phosphorylated forms and their prognostic impact in epithelial OVCA patients.

Methods

Expression analysis was performed by immunohistochemistry (IHC) of paraffin-embedded tumor samples from 49 patients with epithelial OVCA. Staining intensity and the percentage of positively stained tumor cells were used to calculate an immunoreactive score (IRS) of 0–12. The expression scores calculated were correlated with clinicopathological parameters and patient survival.

Results

High immunoreactivity of phospho-Drp1Ser637 was significantly correlated with high-grade serous carcinoma (HGSC) (p = 0.034), residual postoperative tumor of > 1 cm (p = 0.006), and non-responders to adjuvant chemotherapy (p = 0.007), whereas high expression of CaMKI was significantly correlated with stage III/IV [International Federation of Gynecologists and Obstetricians (FIGO)] (p = 0.011) and platinum-resistant recurrence (p = 0.030). ROC curve analysis showed that Drp1, phospho-Drp1Ser637 and CaMKI could significantly detect tumor progression with 0.710, 0.779, and 0.686 of area under the curve (AUC), respectively. The Kaplan-Meier survival curve showed that patients with high Drp1, phospho-Drp1Ser637 and CaMKI levels had significantly poorer progression free survival (PFS) (p = 0.003, p < 0.001 and p = 0.017, respectively). Using multivariate analyses, phospho-Drp1Ser637 was significantly associated with PFS [p = 0.043, hazard ratio (HR) 3.151, 95% confidence interval (CI) 1.039–9.561].

Conclusions

Drp1 and CaMKI are novel potential candidates for the detection and prognosis of epithelial OVCA and as such further studies should be performed to exploit their therapeutic significance.