Tag: pubmed

Blood. 2021 Mar 18:blood.2020006005. doi: 10.1182/blood.2020006005. Online ahead of print.

ABSTRACT

Sustained expression of therapeutic factor IX (FIX) levels has been achieved after adeno-associated viral (AAV) vector-based gene therapy in patients with hemophilia B. Nevertheless, patients are still at risk of vector dose-limiting toxicity, particularly liver inflammation justifying the need for more efficient vectors and a lower dosing regimen. A novel increased potency FIX (designated as CB 2679d-GT), containing three amino acid substitutions (R318Y, R338E, T343R), significantly outperformed the R338L-Padua variant after gene therapy. CB 2679d-GT demonstrated a statistically significant ~3-fold improvement in clotting activity when compared to R338L-Padua after AAV-based gene therapy in hemophilic mice. Moreover, CB 2679d-GT gene therapy showed a significantly reduced bleeding time (~5 to 8-fold) and total blood loss volume (~4-fold) compared with mice treated with the R338L-Padua, thus achieving a more rapid and robust hemostatic correction. FIX expression was sustained for at least 20 weeks with both CB 2679d-GT and R338L-Padua while immunogenicity was not significantly increased. This is a novel gene therapy study demonstrating the superiority of CB 2679d-GT highlighting its potential to obtain higher FIX activity levels and superior hemostatic efficacy following AAV directed gene therapy in hemophilia B patients than what is currently achievable with the R338L-Padua variant.

PMID:33735915 | DOI:10.1182/blood.2020006005

J Perinat Med. 2021 Mar 18. doi: 10.1515/jpm-2020-0352. Online ahead of print.

ABSTRACT

OBJECTIVES: To determine the causes of fetal death among the stillbirths using two classification systems from 22 weeks of gestation in a period of three years in high-risk pregnancies. This is a retrospective observational study.

METHODS: The National Institute of Perinatal Health in Mexico City is a Level 3 care referral center attending high-risk pregnancies from throughout the country. The population consisted of patients with fetal death during a three-year period. Between January 2016 and December 2018, all stillbirths were examined in the Pathology Department by a pathologist and a medical geneticist. Stillbirth was defined as a fetal death occurring after 22 weeks of gestation.

RESULTS: Main outcome measures: Causal analysis of fetal death using the International Statistical Classification of Disease and Related Health Problems-Perinatal Mortality (ICD-PM) and initial causes of fetal death (INCODE) classification systems. A total of 297 stillborn neonates were studied. The distribution of gestational age in antepartum stillbirths (55.2%) showed a bimodal curve, 36% occurred between 24 and 27 weeks and 32% between 32 and 36 weeks. In comparison, the majority (86%) of intrapartum deaths (44.8%) were less than 28 weeks of gestation. Of the 273 women enrolled, 93 (34%) consented to a complete fetal autopsy. The INCODE system showed a present cause in 42%, a possible cause in 54% and a probable cause in 93% of patients.

CONCLUSIONS: The principal causes of antepartum death were fetal abnormalities and pathologic placental conditions and the principal causes of intrapartum death were complications of pregnancy which caused a premature labor and infections.

PMID:33735952 | DOI:10.1515/jpm-2020-0352

ORL J Otorhinolaryngol Relat Spec. 2021 Mar 18:1-6. doi: 10.1159/000513529. Online ahead of print.

ABSTRACT

PURPOSE: The aim of the study was to investigate the role of the exoscope as an assisting tool in endoscopic dacryocystorhinostomy (e-DCR).

MATERIALS AND METHODS: In this observational retrospective study, the application of the VITOM® exoscope was studied in a group of 21 patients undergoing mono- or bilateral DCR. The primary endpoint was to evaluate resolution of symptoms (epiphora/dacryocystitis) at the 6-month follow-up and time for surgery. Qualitative features of the exoscope (intraoperative view of the surgical field) and comparison with the typical setting for DCR were analyzed as secondary endpoints. A questionnaire was administered to surgical team members (ENT surgeon, ophthalmologist, and scrub nurse) to evaluate the perceived quality of this new technology (12 items valued as “good” = 2, “acceptable” = 1, and “not acceptable” = 0). A questionnaire score of 24 out of 24 was valued as “completely approved,” score 20-23 as “moderately approved,” and score ≤19 as “weakly approved.” Patients were divided into 3 consecutive groups, and questionnaire scores by each team member were analyzed for tendencies. Statistical analysis was performed to test significance at p < 0.05. Local Ethical Committee approval was obtained.

RESULTS: No significant differences were found between exoscope-set DCR and classic setting for concerned patient outcomes (failure rate: 3.2 vs. 3.8%, respectively, p = 0.896) and mean time for surgery (20′ vs. 23′, respectively, p = 0.091). The exoscope was valued by surgical team members as “completely approved” in 55.5% of cases, “moderately approved” in 39.7%, and “weakly approved” in 4.8%. Questionnaire scores by the ENT, ophthalmologist, and scrub nurse showed an average increase in the 3 consecutive groups (p = 0.119, p = 0.024, and p < 0.001, respectively).

CONCLUSIONS: The exoscope is a new tool that may support e-DCR. It has no effects on symptom outcomes (epiphora/dacryocystitis) and time for surgery compared to classic DCR. Based on self-perception, this new technology was accepted by all team members.

PMID:33735886 | DOI:10.1159/000513529

Chemotherapy. 2021 Mar 18:1-5. doi: 10.1159/000515340. Online ahead of print.

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originated in Wuhan, China, in early December 2019 has rapidly widespread worldwide, becoming one of the major global public health issues of the last centuries. Key Messages: Over the course of the pandemic, due to the advanced whole-genome sequencing technologies, an unprecedented amount of genomes have been generated, providing invaluable insights into the ongoing evolution and epidemiology of the virus during the pandemic. Therefore, this large amount of data played an important role in the SARS-CoV-2 mitigation and control strategies. Key Messages: The active monitoring and characterization of the SARS-CoV-2 lineages circulating worldwide is useful for a more specific diagnosis, better care, and timely treatment. In this review, a concise characterization of all the lineages and sub-lineages circulating and co-circulating across the world has been presented in order to determine the magnitude of the SARS-CoV-2 threat and to better understand the virus genetic diversity and its dispersion dynamics.

PMID:33735881 | DOI:10.1159/000515340

Digestion. 2021 Mar 18:1-6. doi: 10.1159/000513715. Online ahead of print.

ABSTRACT

INTRODUCTION: For over 30 years, ascites has been postulated to facilitate fibrinolysis in patients with liver cirrhosis. In contrast to previous research employing conventional coagulation tests, this study aimed to characterize hemostatic interactions between blood and ascites using the rotational thromboelastometry (ROTEM).

METHODS: Blood samples – pure or mixed with ascites in a ratio of 1:1 – from cirrhotic patients (n = 10) were subjected to ROTEM analysis. In addition, a negative control group was built with cirrhotic patients (n = 10) whose blood was mixed with physiologic sodium chloride (0.9% NaCl) solution in a ratio of 1:1. Subsequently, ROTEM measurements were subjected to statistical analysis.

RESULTS: During ascites challenge, clotting time (CT, measured in seconds) was significantly prolonged in EXTEM (blood: 70.40 ± 20.40 vs. ascites/blood: 109.8 ± 47.7) and APTEM (blood: 66.50 ± 14.55 vs. ascites/blood: 138.7 ± 105.8), likely reflecting a dilution effect. However, CT in INTEM remained unchanged, suggesting a sustained intrinsic pathway function. Maximal clot firmness (measured in millimeters) in FIBTEM decreased significantly (blood: 14.70 ± 9.55 vs. ascites/blood: 6.00 ± 5.66), thus indicating depletion of fibrinogen in ascites. Strikingly, maximum lysis (measured in %) significantly decreased in EXTEM (blood: 9.30 ± 2.79 vs. ascites/blood: 5.50 ± 2.84), APTEM (blood: 8.50 ± 3.10 vs. ascites/blood: 5.60 ± 2.88), and INTEM (blood: 7.50 ± 2.27 vs. ascites/blood: 5.10 ± 3.48).

CONCLUSIONS: ROTEM provided new evidence that ascites may not primarily induce fibrinolysis in cirrhotic patients. This finding seems to be of significant importance for the clinical management of cirrhotic patients experiencing complications, for example, abdominal hemorrhage after liver biopsy or paracentesis; here, replacement of prothrombin complex concentrates and/or fibrinogen concentrates may prove more beneficial than the use of fresh frozen plasma or antifibrinolytic drugs.

PMID:33735883 | DOI:10.1159/000513715

Am J Nephrol. 2021 Mar 18:1-11. doi: 10.1159/000514302. Online ahead of print.

ABSTRACT

INTRODUCTION: Prorenin, a precursor of renin, and renin play an important role in regulation of the renin-angiotensin system. More recently, receptor-bound prorenin has been shown to activate intracellular signaling pathways that mediate fibrosis, independent of angiotensin II. Prorenin and renin may thus be of physiologic significance in CKD, but their plasma concentrations have not been well characterized in CKD.

METHODS: We evaluated distribution and longitudinal changes of prorenin and renin concentrations in the plasma samples collected at follow-up years 1, 2, 3, and 5 of the Chronic Renal Insufficiency Cohort (CRIC) study, an ongoing longitudinal observational study of 3,939 adults with CKD. Descriptive statistics and multivariable regression of log-transformed values were used to describe cross-sectional and longitudinal variation and associations with participant characteristics.

RESULTS: A total of 3,361 CRIC participants had plasma available for analysis at year 1. The mean age (±standard deviation, SD) was 59 ± 11 years, and the mean estimated glomerular filtration rate (eGFR, ± SD) was 43 ± 17 mL/min per 1.73 m2. Median (interquartile range) values of plasma prorenin and renin at study entry were 4.4 (2.1, 8.8) ng/mL and 2.0 (0.8, 5.9) ng/dL, respectively. Prorenin and renin were positively correlated (Spearman correlation 0.51, p < 0.001) with each other. Women and non-Hispanic blacks had lower prorenin and renin values at year 1. Diabetes, lower eGFR, and use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, statins, and diuretics were associated with higher levels. Prorenin and renin decreased by a mean of 2 and 5% per year, respectively. Non-Hispanic black race and eGFR <30 mL/min/1.73 m2 at year 1 predicted a steeper decrease in prorenin and renin over time. In addition, each increase in urinary sodium excretion by 2 SDs at year 1 increased prorenin and renin levels by 4 and 5% per year, respectively.

DISCUSSION/CONCLUSIONS: The cross-sectional clinical factors associated with prorenin and renin values were similar. Overall, both plasma prorenin and renin concentrations decreased over the years, particularly in those with severe CKD at study entry.

PMID:33735863 | DOI:10.1159/000514302

Caries Res. 2021 Mar 18:1-9. doi: 10.1159/000514667. Online ahead of print.

ABSTRACT

INTRODUCTION: Genetic biomarkers have the potential to be used in personalised dentistry for improved prevention and decision-making in caries management. The amylase alpha 1 gene (AMY1) encodes salivary α-amylase and may be one such biomarker. We examined the association between AMY1 copy number variation (CNV) and dental caries experience in adults.

MATERIALS AND METHODS: A stratified random sample of 193 participants from the Lithuanian National Oral Health Survey (LNOHS) agreed to provide saliva samples and were included in this analysis (age 35-44 years; participation rate 43%). Information on socio-demographic and behavioural characteristics was taken from the LNHOS, which used the self-administered World Health Organisation (WHO) questionnaire. Data on fluoride levels in drinking water at the recruitment areas was recorded based on information provided by water suppliers. Dental caries experience was recorded at a surface level (smooth-surface and occlusal-surface decayed, missing, filled surfaces [D3MFS] score) by one trained and calibrated examiner using WHO criteria, and subsequently dichotomised for the statistical analyses. DNA extracted from saliva samples was used to investigate AMY1 CNV using the QX200 droplet digital PCR system. Bivariate and multivariable statistical analyses were employed.

RESULTS: When compared to participants with an AMY1 copy number (CN) of 2-3, higher odds of smooth-surface D3MFS >14 was observed for participants with a CN of 4-5 (OR 13.3, 95% CI 2.1-86.3), 6-9 (OR 7.0, 95% CI 1.4-34.1), and 10-16 (OR 5.8, 95% CI 1.2-32.2). Female sex was independently associated with a smooth-surface D3MFS >14 (OR 5.7, 95% CI 1.9-17.2).

CONCLUSIONS: Our study demonstrated an association between AMY1 CNV and high smooth-surface caries experience. Studies with larger sample sizes are needed to validate this association.

PMID:33735865 | DOI:10.1159/000514667

Chemotherapy. 2021 Mar 18:1-5. doi: 10.1159/000515342. Online ahead of print.

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped virus initially detected in Wuhan in December 2019, responsible for coronavirus disease 2019 (COVID-19), a respiratory syndrome currently affecting >220 countries around the world, with >80 million cases registered and >1.8 million deaths.

OBJECTIVE: As several vaccines are still being developed and 2 have been approved, it is particularly important to perform evolutionary surveillance to identify mutations potentially affecting vaccine efficacy.

METHODS: DynaMut server has been used to evaluate the impact of the mutation found on SARS-CoV-2 isolates available on GISAID.

RESULTS: In this article, we analyze whole genomes sequenced from Italian patients, and we report the characterization of 3 mutations, one of which presents in the spike protein.

CONCLUSION: The mutations analyzed in this article can be useful to evaluate the evolution of SARS-CoV-2.

PMID:33735872 | DOI:10.1159/000515342

Complement Med Res. 2021 Mar 18:1-10. doi: 10.1159/000515003. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: The present systematic review and meta-analysis of randomized controlled trials aimed to determine the effects of saffron supplementation on liver function tests among adults.

METHODS: Electronic databases including PubMed, ISI Web of Science, and Scopus were searched up to January 2021. The risk of bias in individual studies was assessed using the Cochrane Collaboration tool. The overall estimates and their 95% CIs were calculated using random-effects models. Egger’s test and Begg’s rank-correlation were run to assess the presence of publication bias. p < 0.05 was considered statistically significant.

RESULTS: A total of 12 trials involving 608 participants were included in this systematic review and meta-analysis. Saffron supplementation had no significant effect on liver function tests including aspartate transaminase (AST) (weighted mean difference [WMD] = 0.23 U/L; 95% CI -2.22 to 2.69; p = 0.851; I2 = 74.0%), alanine aminotransferase (ALT) (WMD = -1.49 U/L; 95% CI -3.84 to 0.86; p = 0.213; I2 = 60.2%), and alkaline phosphatase (ALP) (WMD = -0.70 U/L; 95% CI -11.35 to 9.95; p = 0.898; I2 = 40.8%) compared to placebo.

CONCLUSION: Based on what was discussed, it seems that saffron supplementation could not improve liver function tests including AST, ALT, and ALP among the adult population. Further clinical trials with larger sample size, longer duration, and higher doses of saffron should be conducted exclusively among patients with liver dysfunction to elucidate the beneficial role of saffron consumption on liver function.

PMID:33735877 | DOI:10.1159/000515003

Physiol Meas. 2021 Mar 18. doi: 10.1088/1361-6579/abf01e. Online ahead of print.

ABSTRACT

OBJECTIVE: Clinical assessment of upper limb hemiparesis in acute stroke involves repeated manual examination of hand movements during instructed tasks. This process is labour-intensive and prone to human errors while also being strenuous for the patient. Wearable motion sensors can automate the process by measuring characteristics of hand activity. Existing work in this direction either use multiple sensors or complex instructed movements, or analyze only the quantity of upper limb motion. These methods are obtrusive and strenuous for acute stroke patients and also sensitive to noise. In this work, we propose to use only two wrist-worn accelerometer sensors to study the quality of completely spontaneous upper limb motion and investigate correlation with clinical scores for acute stroke care.

APPROACH: Velocity time series estimated from acquired acceleration data during spontaneous motion is decomposed into smaller movement elements. Measures of density, duration and smoothness of these component elements are extracted and their disparity is studied across the two hands.

MAIN RESULTS: Spontaneous upper limb motion in acute stroke can be decomposed into movement elements that resemble point-to-point reaching tasks. These elements are smoother and sparser in the normal hand than the hemiparetic hand, and the amount of smoothness correlates with hemiparetic severity. Features characterizing the disparity of these movement elements between two hands show statistical significance in differentiating mild-to-moderate and severe hemiparesis. Using data from 67 acute stroke patients, the proposed method can classify the two levels of hemiparetic severity with 85% accuracy. Additionally, compared to activity based features, the proposed method is robust to the presence of noise in acquired data.

SIGNIFICANCE: This work demonstrates that the quality of upper limb motion can characterize and identify hemiparesis in stroke survivors. This is clinically significant towards continuous automated assessment of hemiparesis in acute stroke using minimally intrusive wearable sensors.

PMID:33735840 | DOI:10.1088/1361-6579/abf01e