bluuebunny/crossref_metadata_2025_split huggingface dataset:
Frozen section diagnosis of borderline ovarian tumors with suspicious features of invasive cancer is a devil’s dilemma for the surgeon: A systematic review and meta‐analysis
Authors: De Decker Koen , Jaroch Karina H. , Edens Mireille A. , Bart Joost , Kooreman Loes F. S. , Kruitwagen Roy F. P. M. , Nijman Hans W. , Kruse Arnold‐Jan 
Published: February 2021

AbstractIntroductionFrozen section diagnoses of borderline ovarian tumors are not always straightforward and a borderline frozen section diagnosis with suspicious features of invasive carcinoma (reported as “at least borderline” or synonymous descriptions) presents us with the dilemma of whether or not to perform a full surgical staging procedure. By performing a systematic review and meta‐analysis, the prevalence of straightforward borderline and “at least borderline” frozen section diagnoses, as well as proportion of patients with a final diagnosis of invasive carcinoma in these cases, were assessed and compared, as quantification of this dilemma may help us with the issue of this clinical decision.Material and methodsPubMed, EMBASE and Cochrane library databases were searched and studies discussing “at least borderline” frozen section diagnoses were included in the review. Numbers of specific frozen section diagnoses and subsequent final histological diagnoses were extracted and pooled analysis was performed to compare the proportion of patients diagnosed with invasive carcinoma following borderline and “at least borderline” frozen section diagnoses, presented as risk ratio and risk difference with 95% confidence intervals (95% CI).ResultsOf 4940 screened records, eight studies were considered eligible for quantitative analysis. A total of 921 women was identified and 230 (25.0%) of these women were diagnosed with “at least borderline” ovarian tumor at the time of frozen section. Final histological diagnoses were reported in five studies, including 61 women with an “at least borderline” diagnosis and 290 women with a straightforward borderline frozen section diagnosis. Twenty‐five of 61 women (41.0%) of the “at least borderline” group had invasive cancer at final diagnosis, compared with 28 of 290 women (9.7%) of the straightforward borderline frozen section group (risk difference −0.34, 95% CI −0.53 to −0.15; relative risk 0.25, 95% CI 0.13–0.50).ConclusionsWomen diagnosed with “at least borderline” frozen section diagnoses were found to have a higher chance of carcinoma upon final diagnosis when compared with women with a straightforward borderline frozen section diagnosis (41.0% vs 9.7%). Especially in the serous subtype, and after preoperative consent, full staging during initial surgery might be considered in these cases to prevent a second surgical procedure.
Long‐term effectiveness of an online decision aid for female cancer patients regarding fertility preservation: Knowledge, attitude, and decisional regret
Authors: Ehrbar Verena , Germeyer Ariane , Nawroth Frank , Dangel Astrid , Findeklee Sebastian , Urech Corinne , Rochlitz Christoph , Stiller Ruth , Tschudin Sibil 
Published: February 2021

AbstractIntroductionThe decision, whether to undergo fertility preservation or not is highly demanding for cancer patients. Decision aids may act as an additional source of support. So far, only a limited number of decision aids regarding fertility preservation for female cancer patients exist and have been evaluated systematically. This paper presents the results of secondary analyses of the first randomized controlled trial evaluating an online decision aid for female cancer patients affected by different types of cancer. It focuses on fertility‐related knowledge, attitude toward fertility preservation, and long‐term effectiveness regarding decisional regret.Material and methodsYoung female cancer patients between 18 and 40 years of age were recruited after fertility counseling with a reproductive specialist. They were assigned to either the control group (counseling only) or the intervention group (counseling followed by the additional use of the decision aid). Both groups had to complete a questionnaire after counseling as well as 1 and 12 months later, covering topics such as fertility‐related knowledge, attitude towards fertility preservation, decisional conflict and regret. Recruitment was ongoing during 18 months in eight fertility centers located in Switzerland and Germany.ResultsMean age of participating women was 29.31 years (SD 4.57). Of the entire sample (n = 51) 53% were affected with breast cancer, 27.4% with lymphoma, and 19.6% with various other types of cancer. Knowledge regarding the most common fertility preservation methods was high and comparable in both groups. Positive attitude significantly exceeded negative attitude among all participants (p = 0.001). Although the altogether low scores for decisional regret were on a higher level in the control group (T2: mean = 19.00, SD = 13.24; T3: mean = 22.0, SD = 20.67) than in the intervention group (T2: mean = 14.12, SD = 11.07; T3: mean = 12.94, SD = 13.24), there were no statistically significant differences between and within both groups. There was a positive association between decisional conflict and decisional regret at T3 (p = 0.001, r = 0.510).ConclusionsThis decision aid was suitable as an additional source of knowledge and may positively impact decisional regret in the long term. Results suggest that the provision of an online decision aid as a complement to fertility counseling may facilitate decision‐making.
Extracorporeal membrane oxygenation survival: External validation of current predictive scoring systems focusing on influenza A etiology
Authors: Maca Jan , Matousek Vojtech , Bursa Filip , Klementova Olga , Hanak Roman , Burda Michal , Sevcik Pavel , Rulisek Jan 
Published: February 2021

AbstractDespite increasing clinical experience with extracorporeal membrane oxygenation (ECMO), its optimal indications remain unclear. Here, we externally evaluated all currently available ECMO survival‐predicting scoring systems and the APACHE II score in subjects undergoing veno‐venous ECMO (VV ECMO) support due to acute respiratory distress syndrome (ARDS) with influenza (IVA) and non‐influenza (n‐IVA) etiologies. Our aim was to find the best scoring system for influenza A ARDS ECMO success prediction. Retrospective data were analyzed to assess the abilities of the PRESERVE, RESP, PRESET, ECMOnet, Roch, and APACHE II scores to predict patient outcome. Patients treated with veno‐venous ECMO support for ARDS were divided into two groups: IVA and n‐IVA etiologies. Parameters collected within 24 hours before ECMO initiation were used to calculate PRESERVE, RESP, PRESET, ECMOnet, Roch, and APACHE II scores. Compared to the IVA group, the n‐IVA group exhibited significantly higher ICU, 28‐day, and 6‐month mortality (P = .043, .034, and .047, respectively). Regarding ECMO support success predictions, the area under the receiver operating characteristic curve (AUC) was 0.62 for PRESERVE, 0.44 for RESP, 0.57 for PRESET, and 0.67 for ECMOnet, and 0.62 for Roch calculated for all subjects according to the original papers. In the IVA group, APACHE II had the best predictive value for ICU, hospital, 28‐day, and 6‐month mortality (AUC values of 0.73, 0.73, 0.70, and 0.73, respectively). In the n‐IVA group, APACHE II was the best predictor of survival in the ICU and hospital (AUC 0.54 and 0.57, respectively). From all possible ECMO survival scoring systems, the APACHE II score had the best predictive value for VV ECMO subjects with ARDS caused by influenza A‐related pneumonia with a cut‐off value of about 32 points.
The COVID‐19 pandemic dramatically reduced admissions of children with and without chronic conditions to general paediatric wards
Authors: Gavish Rachel , Levinsky Yoel , Dizitzer Yotam , Bilavsky Efraim , Livni Gilat , Pirogovsky Avinoam , Scheuerman Oded , Krause Irit 
Published: February 2021

AbstractAimWe examined the impact of the COVID‐19 pandemic on how many children were admitted to Israel's largest tertiary paediatric hospital and why they were admitted.MethodsIsrael declared COVID‐19 a national emergency on 19 March 2020. This study examined daily hospital admissions to our three general paediatric wards during the COVID‐19 lockdown period from 20 March to 18 April 2020. These 258 admissions were compared with the 4217 admissions from the period immediately before this, 1 February to 19 March 2020, plus 1 February to 18 April in 2018 and 2019. We also compared why patients were admitted during the study period, and any pre‐existing conditions, with 638 children hospitalised during the same period in 2019.ResultsThe mean number of daily hospitalisations during the COVID‐19 lockdown period was 8.6, which was 59% lower than the 20.9 recorded during the other three periods before COVID‐19. There was a significant decrease in the number of patients admitted with infectious (74%) and non‐infectious (44%) aetiologies from 2019 to 2020, and these occurred among patients with (58%), and without (55%), pre‐existing medical conditions.ConclusionThe Israeli COVID‐19 lockdown had a dramatic effect on admissions to the paediatric wards of a tertiary hospital.
Formulation of a recombinant HIV‐1 polytope candidate vaccine with naloxone/alum mixture: induction of multi‐cytokine responses with a higher regulatory mechanism
Authors: Fathi Meimanat , Nezamzadeh Reza , Abdollahpour‐Alitappeh Meghdad , Yazdi Mohammad Hossein , Khoramabadi Nima , Mahdavi Mehdi 
Published: February 2021

The potency of a vaccine highly depends upon the nature of the adjuvant used. There are a variety of ineffective vaccines, such as HIV‐1 vaccine candidates, that need to be optimized with new adjuvant formulations to improve vaccine potency and efficacy. Studies show the potency of naloxone (NLX)/alum mixture in the induction of Th1/Th2 response for vaccine. However, other immunologic patterns inducing by this adjuvant and its immunoregulatory effect is unclear. In this regard, the aim of the present study was to investigate the effect of the NLX/alum mixture, as an adjuvant, on cytokine networks and immunoregulatory activity for an HIV‐1 polytope vaccine. BALB/c mice were divided into six groups (n = 6) and immunized subcutaneously with 10 μg of the vaccine formulated with NLX/alum, NLX, alum, and Freund's adjuvants. At the same time, the mice in the control groups received an equal volume of PBS or NLX. The lymphocyte proliferation assay was carried out using the BrdU method. ELISA was used to measure the levels of IFN‐γ, IL‐2, IL‐4, IL‐10, IL‐12, and IL‐17 cytokines, total IgG, as well as IgG1 and IgG2a subtypes in serum samples. Our findings showed that mice receiving the NLX/alum‐adjuvanted vaccine exhibited increased antibody levels compared with other groups. In addition, there was a considerable difference in the levels of IgG1, IgG2a, IFN‐γ, IL‐2, IL‐10, IL‐12, and IL‐17 in mice receiving the NLX/alum‐adjuvanted vaccine as compared with other groups. The NLX/alum mixture, as an adjuvant, may have a positive effect on the induction of multi‐cytokine responses, as well as the increased level of IL‐10, showing its higher immunogenicity with a higher immunoregulatory mechanism.
Phase I evaluation of pharmacokinetics and tolerability of the HIV‐1 maturation inhibitor GSK3640254 and dolutegravir in healthy adults
Authors: Pene Dumitrescu Teodora , Joshi Samit R. , Xu Jianfeng , Greene Thomas J. , Johnson Mark , Butcher Laurie , Zimmerman Eric , Webster Lindsey , Pham Theresa T. , Lataillade Max , Min Sherene 
Published: February 2021

AimsGSK3640254, a novel, next‐generation maturation inhibitor effective against a range of HIV polymorphisms with no cross‐resistance to current antiretroviral therapy, could potentially be coadministered with dolutegravir as a 2‐drug regimen. In this phase I study, pharmacokinetics and tolerability of GSK3640254 plus dolutegravir were assessed.MethodsHealthy participants received dolutegravir 50 mg once daily (QD) on Days 1–5 in period 1, GSK3640254 200 mg QD on Days 1–7 in period 2, and dolutegravir 50 mg plus GSK3640254 200 mg QD on Days 1–7 in period 3. All treatments were administered with a moderate‐fat meal 30 minutes prior to dosing. Pharmacokinetics parameters were derived by noncompartmental methods, and geometric mean ratios (GMRs) and 90% confidence intervals (CIs) were derived using linear mixed effects models. Adverse events, laboratory measurements, electrocardiography and vital signs were monitored.ResultsSixteen participants completed the study. GMRs (90% CIs) for dolutegravir area under the plasma concentration–time curve from time 0 to the end of the dosing interval at steady state, maximum observed concentration and plasma concentration at the end of the dosing interval were 1.17 (1.118–1.233), 1.09 (1.044–1.138) and 1.24 (1.160–1.315), respectively. The GMRs (90% CIs) for GSK3640254 were 1.04 (0.992–1.094), 0.99 (0.923–1.065) and 0.10 (0.939–1.056), respectively. Dolutegravir plus GSK3640254 coadministration did not meaningfully alter steady‐state exposure to dolutegravir or GSK3640254. No clinically significant trends in tolerability or safety were observed.ConclusionCoadministration of GSK3640254 with dolutegravir did not result in clinically significant drug interaction and was well tolerated.
A pharmacovigilance study of pharmacokinetic drug interactions using a translational informatics discovery approach
Authors: Wang Lei , Shendre Aditi , Chiang Chien‐Wei , Cao Weidan , Ning Xia , Zhang Ping , Zhang Pengyue , Li Lang 
Published: February 2021

BackgroundWhile the pharmacokinetic (PK) mechanisms for many drug interactions (DDIs) have been established, pharmacovigilance studies related to these PK DDIs are limited. Using a large surveillance database, a translational informatics approach can systematically screen adverse drug events (ADEs) for many DDIs with known PK mechanisms.MethodsWe collected a set of substrates and inhibitors related to the cytochrome P450 (CYP) isoforms, as recommended by the United States Food and Drug Administration (FDA) and Drug Interactions Flockhart table™. The FDA's Adverse Events Reporting System (FAERS) was used to obtain ADE reports from 2004 to 2018. The substrate and inhibitor information were used to form PK DDI pairs for each of the CYP isoforms and Medical Dictionary for Regulatory Activities (MedDRA) preferred terms used for ADEs in FAERS. A shrinkage observed‐to‐expected ratio (Ω) analysis was performed to screen for potential PK DDI and ADE associations.ResultsWe identified 149 CYP substrates and 62 CYP inhibitors from the FDA and Flockhart tables. Using FAERS data, only those DDI‐ADE associations were considered that met the disproportionality threshold of Ω > 0 for a CYP substrate when paired with at least two inhibitors. In total, 590 ADEs were associated with 2085 PK DDI pairs and 38 individual substrates, with ADEs overlapping across different CYP substrates. More importantly, we were able to find clinical and experimental evidence for the paclitaxel‐clopidogrel interaction associated with peripheral neuropathy in our study.ConclusionIn this study, we utilized a translational informatics approach to discover potentially novel CYP‐related substrate‐inhibitor and ADE associations using FAERS. Future clinical, population‐based and experimental studies are needed to confirm our findings.
MCRT, a multifunctional ligand of opioid and neuropeptide FF receptors, attenuates neuropathic pain in spared nerve injury model
Authors: He Chunbo , Wang Xiaoli , Zhang Jing , Wang Hao , Zhao Yaofeng , Shah Jagat Narayan , Ma Chan , Li Hailan , Su Wenting , Zhang Zhe , Chen Shasha , Zhou Lanxia , Dong Shouliang 
Published: February 2021

AbstractChimeric peptide MCRT (YPFPFRTic‐NH2) was a multifunctional ligand of opioid and neuropeptide FF (NPFF) receptors and reported to be potentially antalgic in acute tail‐flick test. Here, we developed spared nerve injury (SNI) model to explore its efficacy in chronic neuropathic pain. Analgesic tolerance, opioid‐induced hyperalgesia and gastrointestinal transit were measured for safety evaluation. Intracerebroventricular (i.c.v.) and intraplantar (i.pl.) injections were conducted as central and peripheral routes, respectively. Results demonstrated that MCRT alleviated neuropathic pain effectively and efficiently, with the ED50 values of 4.93 nmol/kg at the central level and 3.11 nmol/kg at the peripheral level. The antagonist blocking study verified the involvement of mu‐, delta‐opioid and NPFF receptors in MCRT produced anti‐allodynia. Moreover, the separation of analgesia from unwanted effects was preliminarily achieved and that MCRT caused neither analgesic tolerance nor hyperalgesia after chronic i.c.v. administration, nor constipation after i.pl. administration. Notably, the local efficacy of MCRT in SNI mice was about one thousandfold higher than morphine and ten thousandfold higher than pregabalin, indicating a great promise in the future treatment of neuropathic pain.
Proarrhythmic potential of metoclopramide in a sensitive whole‐heart model
Authors: Wolfes Julian , Ellermann Christian , Burde Sophie , Fehr Michael , Eckardt Lars , Frommeyer Gerrit 
Published: February 2021

AbstractBackgroundMetoclopramide (MCP) is a dopamine D2‐receptor antagonist, mainly used to treat post‐operative or chemotherapy‐induced nausea. While it is very effective in the cure of gastric symptoms, MCP can cause severe neurologic side effects. Furthermore, there is growing evidence for severe arrhythmic side effects resulting from inhibitory effects on cardiac sodium and potassium channels.Methods and ResultsThirteen hearts of New Zealand white rabbits were retrogradely perfused, and electrophysiology studies were performed to obtain action potential duration (APD90) and effective refractory period (ERP). After generating baseline data, the hearts were perfused with increasing concentrations of metoclopramide (MCP 10 µM, MCP 50 µM, MCP 100 µM) and the standardized protocol was repeated for each concentration. Perfusion with MCP resulted in a significant prolongation of APD90 and QT interval. In parallel, the incidence of ventricular tachycardias was significantly increased by high doses of MCP.ConclusionThis is the first experimental study that investigated the effect of increasing doses of metoclopramide on a sensitive whole‐heart model of proarrhythmia. MCP led to a significant increase in action potential duration and QT interval; meanwhile, the number of ventricular tachycardias was significantly increased.
Nomograms for predicting adverse obstetric outcome in IVF pregnancy: A preliminary study
Authors: Portal Alice , Sunyach Claire , Loundou Anderson , Lacroix‐Paulmye Odile , Perrin Jeanne , Courbiere Blandline 
Published: February 2021

AbstractBackgroundIn a previous study, we showed that the obstetric complication rate after in vitro fertilization (IVF) pregnancy was 40%. The main objective of our study was to determine maternal prognosis factors that influence the IVF pregnancy outcome.MethodsWe conducted an observational retrospective monocentric study between January 2014 and January 2018. Pregnancy over 22 gestational weeks (GW) obtained after IVF in our infertility clinic was included. Maternal characteristics and pregnancy outcome were collected.ResultsData from 498 IVF pregnancies were analyzed. The most significant maternal prognosis factors for obstetric complications were maternal age above 40 years (OR 3,0 [95% IC 1,30‐7,09], P = 0,010), twin pregnancies (3.8 [95% IC 1.49‐9.99], P = .005), daily maternal smoking above 10 cigarettes (7.1 [95% IC 1.22‐41.74], P = .029), maternal obesity (2.2 [95% IC 1.19‐4.07], P = .012), endometriosis stages III and IV (6.4 [95% IC 1.52‐27.04], P = .011), and history of ovarian hyperstimulation syndrome (OHSS) in early pregnancy (5.7 [95% IC 1.29‐24.74], P = .021). Risk increase was independent of pregnancy type (singleton or twin) and allowed the elaboration of 2 nomograms.ConclusionsOur study showed a link between some maternal factors and increase in obstetric complications after IVF. Screening of these factors during preconceptional visit is essential to identify at high‐risk pregnancies and adapt their monitoring.
Women’s childbirth experiences: A content analysis from the Listening to Mothers in California survey
Authors: Edmonds Joyce K. , Declercq Eugene , Sakala Carol 
Published: February 2021

AbstractBackgroundThe World Health Organization's recent recommendations on intrapartum care regard women's experience of care as an essential aspect of high‐quality maternity care. A better understanding of women's perspectives on their childbirth experiences in the United States is needed to place women in the center of care and optimize their experience of childbirth.MethodsThis study analyzed data from the Listening to Mothers in California survey completed by a representative sample of women who gave birth in 2016 in California hospitals. Responses to one or both open‐ended questions about the best and worst part of respondent's hospital stay for childbirth were subject to a content analysis.ResultsFindings from 2539 participants included 2336 best and 1410 worst part responses. References to the attitudes and behaviors of health care practitioners were the most commonly reported (47% best and 29.1% worst part). Nurses were the most frequently mentioned practitioner type. Additional best part categories in rank order included the quality of physical care of the mom and feelings about the care experience. Additional worst part categories in rank order included the quality of the facility and food, delays in care, infant feeding, the quality of physical care of the mom, and lack of privacy.DiscussionWomen's hospital experiences during childbirth, while multidimensional in nature, are primarily shaped by their relationships with health care practitioners, the care provided, and the facility in which childbirth occurs. Women's feedback provides actionable information to promote a positive birth experience.
Patients with haemophilia A with inhibitors in China: a national real‐world analysis and follow‐up
Authors: Dou Xueqing , Liu Wei , Poon Man‐Chiu , Zhang Xinsheng , Wu Jingsheng , Zeng Xiaojing , Wu Runhui , Hu Qun , Li Chengping , Wang Xiaomin , Song Xuewen , Chen Lingling , Zhang Lei , Xue Feng , Yang Renchi 
Published: February 2021

SummaryThe development of alloantibodies (inhibitors) against coagulation factor VIII (FVIII) is the most serious complication of FVIII replacement therapy in patients with haemophilia A (HA). We carried out a nationwide study focussing on patients with HA with inhibitors in China to evaluate the condition and management of this population. The study retrospectively analysed patient characteristics, clinical history, manifestation, treatment strategy as well as individual haemophilia care of 493 patients with inhibitors (466 with severe HA and 27 with non‐severe HA) registered all over China. The median (interquartile range) age at diagnosis of FVIII inhibitors was 13 (5–28) years in patients with severe HA and 24 (10·5–39·5) years in patients with non‐severe HA. Most patients (85%) had high‐titre inhibitors. Prothrombin complex concentrate and recombinant activated coagulation factor VII were used respectively in 76·2% and 29·2% of patients for acute bleeding. Only 22·3% of patients underwent immune tolerance induction (ITI) treatment, of whom 64·9% achieved negative inhibitor titre. In patients who did not undergo ITI, the inhibitors turned negative in 17·7%, and patients with low peak inhibitor titre were more likely to acquire negative titre spontaneously (odds ratio 11·524, 95% confidence interval 5·222–25·432; P = 0·000). We recorded that 3·2% of the patients died from haemophilia‐related life‐threatening bleeding.