Tag: pubmed

Bratisl Lek Listy. 2022;123(7):475-48. doi: 10.4149/BLL_2022_075.

ABSTRACT

BACKGROUND: Risk for developing papillary thyroid carcinoma (PTC), the most common endocrine malignancy, is thought to be mediated by lifestyle, environmental exposures and genetic factors. Recent progress in the genome-wide association studies of thyroid cancer leads to the identification of several genetic variants conferring risk to this malignancy across different ethnicities.

METHODS AND RESULTS: We set out to elucidate the impact of selected single nucleotide polymorphisms (SNPs) on papillary thyroid carcinoma risk and to evaluate the interactions of these genetic variants with associated diseases for the first time in the Slovak population. Six SNPs (rs966423, rs2439302, rs965513, rs116909374, rs1537424 and rs944289) were genotyped in 86 patients with PTC and 99 healthy control subjects. The association analysis and multivariable modelling of PTC risk by the genetic factors, supplemented with a rigorous statistical validation, were performed. One of the six SNPs rs966423 (DIRC3, OR=1.51, p=0.03) was significantly associated with PTC. Next two SNPs rs965513 (PTCSC2, OR=1.34) and rs116909374 (MBIP, OR=0.44) showed a suggestive association. Haplotype TTC (SNPs located on chromosome 14q13) showed a suggestive association with PTC (p=0.07, OR=1.55). In the PTC group, significant associations were observed between rs966423 (DIRC3) and ischemic heart diseases (p=0.009), rs965513 (PTCSC2) and diabetes mellitus (p=0.04) and haplotype 14q13 and musculoskeletal diseases. Next three associations rs966423 (DIRC3) and arterial hypertension; rs116909374 (MBIP) and other benign diseases; rs1537424 (MBIP) and disorder lipid metabolism, rs965513 (PTCSC2) and anti-Tg (thyroglobulin antibody) showed suggestive associations.

CONCLUSION: These results indicate that germline variants not only predispose to PTC, but may also be related to other risk factors, including associated diseases. However, these associations were only moderate, and further multi-ethnic studies are required to evaluate the usefulness of these germline variants in the clinical stratification of PTC patients (Tab. 8, Ref. 37).

PMID:35907052 | DOI:10.4149/BLL_2022_075

J Assist Reprod Genet. 2022 Jul 30. doi: 10.1007/s10815-022-02582-1. Online ahead of print.

ABSTRACT

PURPOSE: The latest treatments do not sufficiently prevent miscarriage and fetal growth restriction (FGR) in pregnant women. Here, we assessed the effects of a human protein, CTRP6, that specifically inhibits the activation of the alternative complement pathway on miscarriage, fetal and placental development.

METHODS: Pregnant CBA/J mice mated with DBA/2 male mice as a model of spontaneous abortion and FGR were randomly divided into the control and CTRP6 groups. In the CTRP6 group, the mice were intravenously administered CTRP6 on days 4.5 and 6.5 post-conception (dpc). The abortion rate and fetal and placental weights on 14.5 dpc were examined. Remodeling of the spiral artery was also assessed.

RESULTS: The abortion rate in the CTRP6 group (13%) was reduced compared to the control group (21%), but there was no statistical difference. The placental and fetal weights in the CTRP6 group were also heavier than those in the control (P < 0.05). Moreover, the thickness of the blood vessel wall in the CTRP6 group was significantly thinner than that in the control (P < 0.05) and comparable to that in the non-abortion model (CBA/J x BALB). The ratio of the inner-per-the-outer diameter of the spiral artery increased more in the CTRP6 group than that in the control (P < 0.05). As well, the Th1/Th2 cytokine ratio was significantly reduced by CTRP6 treatment.

CONCLUSIONS: Taken together, the supplementation with a protein that regulates the alternative complement pathway in vivo improves FGR and promotes spiral artery remodeling in a mouse model of miscarriage and FGR.

PMID:35907048 | DOI:10.1007/s10815-022-02582-1

J Neurol. 2022 Jul 30. doi: 10.1007/s00415-022-11304-7. Online ahead of print.

ABSTRACT

BACKGROUND: Hyperammonaemia is a recognised complication of antiseizure treatment but risk factors leading to individual patient susceptibility and outcome remain unclear.

OBJECTIVE: To identify risk factors for hyperammonaemia and investigate the impact of its management on clinical outcomes.

METHODS: We carried out a retrospective observational study of adults with epilepsy who had ammonia tested over a 3-year period. Hyperammonaemia was defined as ammonia level > 35 μmol/L. Patients were classified into two groups: hyperammonaemic and non-hyperammonaemic. Association analyses and linear regression analysis were used to identify risk factors for hyperammonaemia.

RESULTS: We reviewed 1002 ammonia requests in total and identified 76 people with epilepsy who had ammonia concentration measured, including 26 with repeated measurements. 59/76 (78%) were found to have hyperammonaemia. There was borderline statistical significance of hyperammonaemia being less common in patients with an established monogenic/metabolic condition than in those with structural or cryptogenic epilepsy (P = 0.05). Drug resistance, exposure to stiripentol and oxcarbazepine were identified as risk factors for hyperammonaemia. We found a dose-dependent association between valproate and hyperammonaemia (P = 0.033). Clinical symptoms were reported in 22/59 (37%) of the hyperammonaemic group. Improved clinical outcomes with concurrent decrease in ammonia concentration were seen in 60% of patients following treatment adjustment.

CONCLUSIONS: Drug resistance and exposure to stiripentol, oxcarbazepine or high-dose valproate are associated with an increased risk of hyperammonaemia. Clinicians should consider symptoms related to hyperammonaemia in patients on high-dose valproate or multiple antiseizure treatments. Prompt identification of hyperammonaemia and subsequent treatment adjustments can lead to improved clinical outcomes.

PMID:35907043 | DOI:10.1007/s00415-022-11304-7

J Exp Orthop. 2022 Jul 30;9(1):74. doi: 10.1186/s40634-022-00507-6.

ABSTRACT

PURPOSE: Certain types of repetitive sub-maximal knee loading cause microfatigue damage in the human anterior cruciate ligament (ACL) that can accumulate to produce macroscopic tissue failure. However, monitoring the progression of that ACL microfatigue damage as a function of loading cycles has not been reported. To explore the fatigue process, a confocal laser endomicroscope (CLEM) was employed to capture sub-micron resolution fluorescence images of the tissue in situ. The goal of this study was to quantify the in situ changes in ACL autofluorescence (AF) signal intensity and collagen microstructure as a function of the number of loading cycles.

METHODS: Three paired and four single cadaveric knees were subjected to a repeated 4 times bodyweight landing maneuver known to strain the ACL. The paired knees were used to compare the development of ACL microfatigue damage on the loaded knee after 100 consecutive loading cycles, relative to the contralateral unloaded control knee, through second harmonic generation (SHG) and AF imaging using confocal microscopy (CM). The four single knees were used for monitoring progressive ACL microfatigue damage development by AF imaging using CLEM.

RESULTS: The loaded knees from each pair exhibited a statistically significant increase in AF signal intensity and decrease in SHG signal intensity as compared to the contralateral control knees. Additionally, the anisotropy of the collagen fibers in the loaded knees increased as indicated by the reduced coherency coefficient. Two out of the four single knee ACLs failed during fatigue loading, and they exhibited an order of magnitude higher increase in autofluorescence intensity per loading cycle as compared to the intact knees. Of the three regions of the ACL – proximal, midsubstance and distal – the proximal region of ACL fibers exhibited the highest AF intensity change and anisotropy of fibers.

CONCLUSIONS: CLEM can capture changes in ACL AF and collagen microstructures in situ during and after microfatigue damage development. Results suggest a large increase in AF may occur in the final few cycles immediately prior to or at failure, representing a greater plastic deformation of the tissue. This reinforces the argument that existing microfatigue damage can accumulate to induce bulk mechanical failure in ACL injuries. The variation in fiber organization changes in the ACL regions with application of load is consistent with the known differences in loading distribution at the ACL femoral enthesis.

PMID:35907038 | DOI:10.1186/s40634-022-00507-6

Environ Manage. 2022 Jul 30. doi: 10.1007/s00267-022-01675-y. Online ahead of print.

ABSTRACT

Hazardous waste pollutes the air, soil, and water and adversely affects human health if not disposed of safely. Analysis of the efficiency of hazardous waste disposal is essential to sustainable development. This paper uses the three-stage super-efficiency Data Envelopment Analysis model to measure the efficiency of 28 EU countries from 2004 to 2016. To ensure the reliability of the results, the article utilizes a one-way ANOVA statistical test to verify whether DEA results vary significantly across various EU countries. This article discusses “how inputs and outputs can be adjusted to eliminate inefficiencies” to suggest a targeted improvement. The third stage supper efficiency DEA results shows that the efficiency varies significantly across different EU countries. The main reasons for the low efficiency are high generated hazardous waste, management expenditure, greenhouse gas emissions, and inadequate waste disposal volume. Targeted proposals from three aspects are given for policymakers in EU countries: Build a resource recycling system to reduce hazardous waste. Establish a sound fee management system to reduce expenses. Optimization of disposal technology to improve incineration efficiency.

PMID:35907030 | DOI:10.1007/s00267-022-01675-y

J Cancer Res Clin Oncol. 2022 Jul 30. doi: 10.1007/s00432-022-04173-0. Online ahead of print.

ABSTRACT

PURPOSE: Immune-based (IO)-combinations are the backbone in the systemic therapy of metastatic renal cell carcinoma (mRCC). Despite phase III clinical trial data, real world data are of special importance to reflect clinical practice.

METHODS: This retrospective study included 201 mRCC patients receiving first-line systemic therapy from January 2006. Clinicopathological and treatment-related data were recorded. Progression-free (PFS) and overall survival (OS) were analyzed using descriptive statistics and Kaplan-Meier analysis.

RESULTS: Over the years, IO-based therapies have increased significantly. The collective comprises 76 patients with first-line IO-based therapy (IO-IO:55, TKI-IO:21) and 125 patients with TKI-monotherapy. PFS was significantly improved with TKI-IO combinations if compared to both TKI-monotherapy (23.9 vs. 10.3 months, HR 0.48, p = 0.034) and IO-IO combination (23.9 vs. 6.1 months, HR 0.37, p = 0.012). OS for TKI-IO treated patients was longer compared to TKI-monotherapy (HR 0.37, p = 0.050) at median follow-up of 24.1 versus 29.9 months. In a subanalysis of nivolumab treated patients, starting from second-line (n = 40), PFS was 5.5 months. The addition of nivolumab either in second-or later lines improved OS compared to repeated TKI- or mTOR-therapies alone (6.13 vs. 2.61 years, HR 0.46, p = 0.003).

CONCLUSION: Both first-line IO-based combinations and nivolumab after first-line TKI-monotherapy prolong OS in a real-world setting.

PMID:35907009 | DOI:10.1007/s00432-022-04173-0

Skeletal Radiol. 2022 Jul 30. doi: 10.1007/s00256-022-04108-3. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess the validity and reliability of the calf injury classification system proposed by the Olympic Park group which focuses on connective tissue structure integrity on MRI.

MATERIALS AND METHODS: A retrospective study analysing calf muscle group injuries in an English Premiership professional rugby union club using the MRI classification proposed by the Olympic Park group. Classification on MRI examinations of 28 calf injuries sustained over a 6-year period was performed by three independent musculoskeletal radiologists to determine the inter-observer variability and correlation of the grade of injury with return-to-full-training (RTFT) time.

RESULTS: RTFT time ranged from 5 to 110 days (mean = 40.1, SD = 26.4) following calf muscle injury. The Olympic Park classification injury grade demonstrated moderate to strong correlation with RTFT time (Spearman’s rank correlation coefficient, 0.661-0.715, p < 0.01). RTFT time was statistically different between different injury grades (one-way ANOVA, p < 0.01). Inter-observer agreement of the overall grade between radiologist pairs was fair to moderate (weighted kappa 0.406-0.583).

CONCLUSION: The Olympic Park classification system demonstrates moderate to strong correlation with time to RTFT following calf injury. Inter-observer reliability is fair to moderate.

PMID:35907017 | DOI:10.1007/s00256-022-04108-3

Eur Arch Otorhinolaryngol. 2022 Jul 30. doi: 10.1007/s00405-022-07571-9. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to evaluate the efficacy and safety of programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) inhibitor plus chemotherapy vs standard of care (SoC) treatment in the first-line treatment for recurrent or metastatic head and neck squamous cell carcinoma (R/M-SCCHN).

METHODS: Randomized controlled trials (RCTs) that investigated PD-1/PD-L1 inhibitor plus chemotherapy vs SoC as first-line treatment for R/M-SCCHN were searched from electronic databases (PubMed, Embase and Cochrane Library). The primary outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs).

RESULTS: In total, three phase 3 RCTs (KEYNOTE-048, CAPTAIN-1st, and JUPITER-02; n = 1120) with three PD-1 inhibitors (pembrolizumab, camrelizumab and toripalimab) were included in the analysis. Compared with SoC, PD-1 inhibitor plus chemotherapy significantly prolonged PFS (hazard ratio [HR] 0.66, 95% CI 0.40-0.93, p < 0.001) and OS (HR 0.73, 95% CI 0.60-0.86, p < 0.001) of patients. There was no statistical differences in ORR (odds ratio [OR] 1.26; 95% CI 0.97-1.64, p = 0.086), grade 3 or higher AEs (OR 0.77, 95% CI 0.50-1.17, p = 0.221), and treatment-related deaths (OR 1.34, 95% CI 0.60-2.98, p = 0.470) between the two groups.

CONCLUSION: PD-1 inhibitor plus chemotherapy showed more survival benefit than SoC in the first-line treatment for R/M-SCCHN, with a similar safety profile.

PMID:35907001 | DOI:10.1007/s00405-022-07571-9

J Clin Endocrinol Metab. 2022 Jul 30:dgac458. doi: 10.1210/clinem/dgac458. Online ahead of print.

ABSTRACT

CONTEXT: Our previous study showed that paternal subclinical hypothyroidism (SCH) had a detrimental effect on the clinical outcomes of assisted reproductive technologies. However, it remains to be determined whether paternal SCH affects sperm DNA integrity.

OBJECTIVE: To investigate the association between SCH and sperm DNA fragmentation in men seeking infertility care.

METHODS: This cross-sectional study included 4,983 men with euthyroidism and 418 men with SCH seeking infertility treatment in a tertiary care academic medical center between January 2017 and December 2021. The outcome measures were the absolute DNA fragmentation index (DFI) and the risk of abnormal DFI (defined as a DFI of ≥25% or ≥30%).

RESULTS: The mean (standard deviation) age of men with euthyroidism and men with SCH was 34.20 (5.97) and 35.35 (6.48) years, respectively (p < 0.001). The difference in DFI was not statistically significant [adjusted mean: 19.7% vs. 18.9% in the SCH and euthyroidism groups, respectively, p = 0.07] after confounder adjustment. A DFI of ≥25% was significantly more frequent in men with SCH (20.57%) than in men with euthyroidism (14.49%) after confounder adjustment [odds ratio (OR) (95% CI): 1.43 (1.09-1.88)]. A DFI of ≥30% was also significantly more common in men with SCH (11.72%) than in men with euthyroidism (6.74%) [OR (95%CI): 1.84 (1.34-2.52)]. In addition, thyroid-stimulating hormone (TSH) concentration was significantly associated with an increased risk of having a DFI of ≥25% (p < 0.001) or ≥30% (p = 0.011).

CONCLUSIONS: SCH was significantly associated with an increased risk of an abnormal DFI.

PMID:35906991 | DOI:10.1210/clinem/dgac458

Eur J Clin Invest. 2022 Jul 29:e13849. doi: 10.1111/eci.13849. Online ahead of print.

ABSTRACT

BACKGROUND: Ischemic Stroke (IS) is associated with various modifiable risk factors but the association of these risk factors based on TOAST classification, which characterizes IS into five subtypes, large artery atherosclerosis (LAA), small vessel occlusion (SVO), cardioembolic disease (CE), other determined etiology (ODE), and undetermined etiology (UDE), is unknown. We aimed to summarize the published evidence for the association of modifiable risk factors with IS subtypes based on TOAST classification, specifically focussing on the Asian versus Caucasian population.

METHOD: A comprehensive search for all the published articles was performed in electronic databases including PubMed, EMBASE, Cochrane Library, and Google Scholar from 01^st January 1950 to 10^th April 2022 based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Odds ratio (OR) with 95% Confidence interval (CIs) along with random effect models were used to calculate summary estimates.

RESULTS: In our meta-analysis, 32 studies with a total of 23404 IS (14364 in Asian vs. 9040 in Caucasian population), 7121 LAA (5219 in Asian vs. 1902 in Caucasian), 5532 SVO (3604 in Asian vs. 1928 in Caucasian), 3498 CE (1634 in Asian vs. 1864 in Caucasian), 1131 ODE (546 in Asian vs. 585 in Caucasian) and 4519 UDE (2076 in Asian vs. 2443 in Caucasian) were included. Our findings suggest a significant association between LAA and hypertension (OR=1.07, 95% CI=1.02-1.12), smoking (OR=1.11, 95% CI=1.04-1.17), dyslipidemia (OR=1.13, 95% CI=1.06-1.21), diabetes mellitus (OR=1.18, 95% CI=1.11-1.25) and atrial fibrillation (OR=0.55, 95% CI=0.40-0.75). Significantly strong association of hypertension, smoking, dyslipidemia, diabetes mellitus, and atrial fibrilation was observed with SVO and CE stroke subtypes. Subgroup analysis based on ethnicity revealed a significant association for dyslipidemia, diabetes mellitus, and atrial fibrilation in LAA for both Asians and Caucasians. Hypertension was significantly associated with SVO and ODE subtypes in both Asians and Caucasians; however, only Asian population showed significant association of hypertension in LAA and CE subtypes. The other risk factors did not show any statistical difference between the ethnic groups for the different stroke subtypes. The majority of the risk factors depicted positive association with LAA and SVO, negative with CE and neutral with ODE and UDE.

CONCLUSION: Our findings suggest strong association of smoking, dyslipidemia, and diabetes mellitus with LAA and SVO subtypes in the Caucasian population. However, only diabetes mellitus showed significant association with both LAA and SVO subtypes in Asian population as well. Thus, a majority of the traditional modifiable risk factors had a positive association in LAA and SVO, while a negative protective association was observed in CE subtype, among both the Asian and Caucasian subgroups.

PMID:35906805 | DOI:10.1111/eci.13849