Papillary Thyroid Carcinoma (PTC) accounts for approximately 85% of patients with thyroid cancer. Despite its indolent nature, progression to higher stages is expected in a subgroup of patients. ...Hence, genomic characterization of the early stages of PTC may help to identify this subgroup, leading to better clinical management.
Here, we conducted a comprehensive mutational and somatic copy number alteration (SCNA) investigation on 277 stage one PTC from TCGA.
SCNA analysis revealed amplification and deletion of several cancer related genes. We found amplification of 60 oncogenes (Oncs), from which 15 were recurrently observed. Deletion of 58 tumor suppressors (TSs) was also detected. MAPK, PI3K-Akt, Rap1 and Ras were the signaling pathways with large numbers of amplified Oncs. On the other hand, deleted TSs belonged mostly to cell cycle, PI3K-Akt, mTOR and cellular senescence pathways. This suggests that despite heterogeneity in SCNA events, the final results would be the activation/deactivation of a few cancer signaling pathways. Of note, despite large amounts of heterogeneity in stage one PTC, recurrent broad deletion on Chr22 was detected in 21 individuals, leading to deletion of several tumor suppressors.
In parallel, the oncogenic/pathogenic mutations in the RTK-RAS and PI3k-Akt pathways were detected. However, no pathogenic mutation was identified in known tumor suppressor genes. In order to identify a potential subgroup of BRAF (V600E) positive patients, who might progress to higher stages, low frequency mutations accompanying BRAF (V600E) were also identified.
In conclusion, our findings imply that SCNA have a substantial contribution to early stages of PTC. Experimental validation of the observed genomic alterations could help to stratify patients at the time of diagnosis, and to move toward precision medicine in PTC.
Aim
To explore the association of visceral adipose tissue (VAT) area and non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM).
Methods
This was a cross-sectional ...study comprising 100 patients with T2DM and 100 non-T2DM individuals, matched for age, sex, and body mass index (BMI). Transient elastography was used to assess hepatic steatosis and liver stiffness measurements (LSM). Controlled attenuation parameter (CAP) was used to quantify hepatic steatosis. To distinguish grades of hepatic steatosis, cutoff values were as follows:
S
1 ≥ 302,
S
2 ≥ 331, and
S
3 ≥ 337 dB/m. Moreover, VAT area was measured by dual-energy X-ray absorptiometry in accordance with validated protocols.
Results
CAP score was significantly higher in participants with T2DM (294.61 ± 3.82 vs. 269.86 ± 3.86 dB/ m;
P
< 0.001). Furthermore, 42% of participants with T2DM had hepatic steatosis (
S
>
S
1: 302 dB/m), while this figure was 26% in non-T2DM group (
P
< 0.003). The mean liver stiffness measuremen
t
was also significantly higher in patients with T2DM (5.53 vs. 4.79 kPa;
P
< 0.001). VAT area was greater in patients with T2DM compared to non-T2DM individuals: 163.79 ± 47.98 cm
2
versus 147.49 ± 39.09 cm
2
,
P
= 0.009. However, total and truncal fat mass were not different between the two groups. Age, BMI, waist circumference, ALT, CAP, and LSM were significantly associated with VAT area. BMI and VAT area were the important determinants of steatosis in both groups of participants with and without T2DM. Moreover, the VAT area was associated with the severity of hepatic steatosis and liver stiffness, independent of anthropometric measures of obesity.
Conclusion
VAT area is a major determinant of the severity of hepatic steatosis and liver stiffness in patient with T2DM.
It remains unclear whether a specific chest CT characteristic is associated with the clinical severity of COVID-19. This meta-analysis was performed to assess the relationship between different chest ...CT features and severity of clinical presentation in COVID-19.
PubMed, Embase, Scopus, web of science databases (WOS), Cochrane library, and Google scholar were searched up to May 19, 2020 for observational studies that assessed the relationship of different chest CT manifestations and the severity of clinical presentation in COVID-19 infection. Risk of bias assessment was evaluated applying the Newcastle-Ottawa Scale. A random-effects model or fixed-effects model, as appropriately, were used to pool results. Heterogeneity was assessed using Forest plot, Cochran's Q test, and I2. Publication bias was assessed applying Egger's test.
A total of 18 studies involving 3323 patients were included. Bronchial wall thickening (OR 11.64, 95% CI 1.81–74.66) was more likely to be associated with severe cases of COVID-19 infection, followed by crazy paving (OR 7.60, 95% CI 3.82–15.14), linear opacity (OR 3.27, 95% CI 1.10–9.70), and GGO (OR 1.37, 95% CI 1.08–1.73). However, there was no significant association between the presence of consolidation and severity of clinical presentation (OR 2.33, 95% CI 0.85–6.36). Considering the lesion distribution bilateral lung involvement was more frequently associated with severe clinical presentation (OR 3.44, 95% CI 1.74–6.79).
Our meta-analysis of observational studies indicates some specific chest CT features are associated with clinical severity of COVID-19.
•Chest CT can be considered a key tool to evaluate the progression of COVID-19.•There is an association between chest CT findings and clinical severity.•Bronchial wall thickening is the highest chest CT predictor of poor outcome.
The objective of this study was to compare the histomorphological changes of placenta and umbilical cord (UC), between gestational diabetes mellitus (GDM) and non- GDM pregnancies.
In this ...prospective study, 222 parturients were recruited (117 GDM and 105 non-GDM). GDM was confirmed at 24–28 weeks of gestation, using one-step strategy. A full record of demographic, laboratory, histologic and gross morphology data of placenta and UC was extracted and analyzed.
Overall, 222 placentas/UCs met inclusion criteria. The mean (SD) of gestational age of GDM diagnosis was 20.68 (10.02) and the GDM duration was 16.76 (8.98) weeks. The mean HbA1C was 6.03 (0.41) % in the GDM group. The gross morphology findings including UC diameter and thick edematous UC differed significantly between two groups and more presented in GDM group, 1.41 (0.03) vs. 1.28 (0.03) centimeters; p-value = 0.006 and 34.19% vs. 16.19%; p-value = 0.002, respectively. The umbilical coiling index (UCI) was similar in two groups (p-value = 0.61). In the histological evaluation, persistence of central vessels differed significantly between two groups, more detected in non-GDM (47.62% vs. 32.97%; p-value = 0.04). No other significant histomorphological changes were detected between two groups.
This study showed that gross morphologic features such as UC diameter increment and thick edematous UC happened more frequently, among the GDM parturients. Due to early diagnosis, diagnosis strategy, and optimal glycemic control, the histomorphological changes were less in GDM comparing of non-GDM group.
•GDM could induce the histomorphological changes of placenta and umbilical cord.•The histomorphological changes depends on GDM duration and its glycemic control.•The histomorphological changes in GDM are inconsistent and somewhat controversial.•This longitudinal study allowed us to follow the prenatal and postnatal period.•The study population comprised GDM and normal pregnancy, providing valid comparison.
Introduction
Pharmacogenetics studies suggest that genetic variants have a possible influence on the inter-individual differences in therapeutic response to glucagon-like peptide 1 receptor agonists ...(GLP-1 RAs). We aimed to examine the potential role of genetic variability of glucagon-like peptide 1 receptor (GLP-1R) on glycemic response to GLP-1 RAs in a population of Iranian people with type 2 diabetes mellitus (T2DM).
Methods
In this study, we analyzed the data from participants in a non-inferiority randomized clinical trial between 2019 and 2020. Patients received liraglutide 1.8 mg/day subcutaneously for 24 weeks. They were stratified by the baseline hemoglobin A1c (HbA1c) into four categories: 7–7.99, 8–8.99, 9–9.99, and ≥ 10%. In each category, subjects with HbA1c reduction greater than the median ΔHbA1c value for that group were defined as optimal responders. The pooled number of optimal/suboptimal responders in the four groups was used for the comparison. We evaluated two genetic variants of GLP-1R, rs6923761 and rs10305420, using Sanger sequencing. Logistic regression analyses were performed to examine the associations of the GLP-1R variants with the glycemic response in different genetic models.
Results
Out of 233 participants, 120 individuals were optimal responders. Median HbA1c reduction was − 2.5% in the optimal responder group compared with − 1.0% in the suboptimal responder group (
P
< 0.001). In genetic models, rs10305420 T allele homozygosity was associated with optimal glycemic response to liraglutide compared with heterozygous and wild-type homozygous states (recessive model: OR 3.28, 95% CI 1.41–7.65,
P
= 0.006; codominant model: OR 2.52, 95% CI 1.03–6.13,
P
= 0.04). No significant association was found between rs6923761 variant and HbA1c reduction.
Conclusion
GLP-1R rs10305420 polymorphism can explain some of the inter-individual differences in glycemic response to liraglutide in a population of Iranian people with T2DM.
Advanced maternal age, family history of diabetes, pre-gestational obesity, increased level of HbA1c, history of gestational diabetes mellitus (GDM), and poor pregnancy consequences are considered ...risk factors for antenatal insulin requirement in women with GDM. However, the role of assisted reproductive technology (ART) in increasing the risk of insulin therapy in pregnancies complicated with GDM remained elusive. The current study aimed to determine the role of ART in predicting insulin therapy in GDM women and investigate the clinical and biochemical factors predicting the need for insulin therapy in pregnancies complicated with GDM.
In this prospective cohort study, 236 Iranian women with GDM were diagnosed by one-step oral glucose tolerance test (OGTT) between October 2014 and June 2017. They were mainly assigned to two groups; the first group (n = 100) was designated as ART which was further subdivided into two subgroups as follows: 60 participants who received medical nutrition therapy (MNT) and 40 participants who received MNT plus insulin therapy (MNT-IT). The second group (n = 136) was labeled as the spontaneous conception (SC), consisting of 102 participants receiving MNT and 34 participants receiving MNT in combination with IT (MNT-IT). The demographic, clinical, and biochemical data were compared between groups. Multivariate logistic regression was performed to estimate prognostic factors for insulin therapy.
A higher rate of insulin therapy was observed in the ART group as compared with the SC group (40% vs. 25%; P < 0.001). Multivariate logistic regression demonstrated that maternal age ≥ 35 years OR: 2.91, 95% CI: (1.28-6.62), high serum FBS 1.10: (1.04-1.16), HbA1c 1.91 (1.09-3.34), and ART treatment 2.94: (1.24-6.96) were independent risk factors for insulin therapy in GDM women.
Apart from risk factors mentioned earlier, ART may be a possible prognostic factor for insulin therapy in pregnancies complicated with GDM.
Introduction
Type 2 diabetes mellitus (T2DM) is a significant risk factor for the development of critical limb ischemia (CLI), the most advanced stage of peripheral arterial disease. The concurrent ...existence of T2DM and CLI often leads to adverse outcomes, namely limb amputation.
Objective
To identify biomarkers for improving the screening of CLI in high-risk people with T2DM.
Methods
We investigated metabolome profiles in serum samples of 113 T2DM people with CLI (n = 23, G2) and without CLI (n = 45, G0: no lower limb stenosis (LLS) and n = 45, G1: LLS < 50%), using hydrogen nuclear magnetic resonance (
1
H NMR) approach. Principle component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were used to analyze
1
H NMR data.
Results
Twenty potential metabolites that could discriminate people with T2DM and CLI (G2) from non-CLI patients without LLS (G0) were determined in serum samples. The correct percent of classification for the PLS-DA model for the test set samples was 85% (n = 20) and 100% (n = 5) for G0 and G2 groups, respectively. Non-CLI patients with LLS < 50% (G1) were projected on the PCA abstract space built using 20 discriminatory metabolites. Eleven people with T2DM and LLS < 50% were prospectively followed, and their ankle-brachial index (ABI) was measured after 4 years. A promising agreement existed between the PCA model's predictions and those obtained by ABI values.
Conclusion
The findings suggest that confirmation of blood potential metabolic biomarkers as a complement to ABI for screening of CLI in a large group of high-risk people with T2DM is needed.
Body composition is related to cardiometabolic disorders and is a major driver of the growing incidence of type 2 diabetes mellitus (T2DM). Altered fat distribution and decreased muscle mass are ...related to dysglycemia and impose adverse health-related outcomes in people with T2DM. Hence, improving body composition and maintaining muscle mass is crucial in T2DM. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are novel glucose-lowering medications gaining popularity because of their cardiorenal-protective effects and weight-lowering characteristics. However, reports on myopathy secondary to SGLT2 inhibitor treatment raised a safety concern. The importance of maintaining muscle mass in people with T2DM necessitates further investigation to explore the impact of novel medications on body composition. In this review, we discussed current evidence on the impact of SGLT2 inhibitors on body composition in people with T2DM.
Purpose
Thyroid eye disease (TED) is the foremost extrathyroidal manifestation of Graves’ disease (GD). Currently, available treatments do not entirely prevent the long-term consequences of TED and ...have distinct disadvantages. Therefore, this systematic review explored available evidence regarding the efficacy of statins in preventing and treating TED.
Methods
Relevant studies investigating statin usage in patients with GD or TED were identified by searching Medline (Pubmed and Ovid), Scopus, Web of Science, ProQuest, and Cochrane Library databases (from the database inception to
September 2023
). The review was done according to the PRISMA statement. Web searching was done independently by two investigators. Two researchers independently extracted the data, and any disagreement was adjudicated by consensus. Based on the study design, the studies’ quality appraisal was done using the Newcastle-Ottawa Scale (NOS) and Version 2 of the Cochrane risk-of-bias tool (RoB2).
Results
The literature search identified 145 publications, of which four met the inclusion criteria (Three retrospective cohort studies and one randomized clinical trial) and were reviewed in full text. The two retrospective cohort studies demonstrated the beneficial effects of statins on TED in newly diagnosed GD Stein et al. showed that statins, regardless of the type, prevent or delay TED (HR: 0.74 (0.65–0.84)), especially in men or treatment duration of more than one year. Nilsson et al. fascinatingly revealed that at least 60 days of statin usage in the preceding year could decrease the risk of TED development by around 40%. One RCT showed a higher treatment response for active moderate-to-severe TED in patients with hypercholesterolemia who took atorvastatin 20 mg in addition to ivGC for 24 weeks without any increase in serious side effects. The retrospective study revealed that the need for reconstructive surgery was reduced in patients with severe TED who received statin therapy.
Conclusion
Statin therapy could be a potential adjunctive modality for preventing and treating TED.
Trial registration
PROSPERO registration number: CRD42022315522.
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