Small cell variant of chromophobe renal cell carcinoma: Clinicopathologic and molecular-genetic analysis of 10 cases.

The morphologic diversity of chromophobe renal cell carcinoma (ChRCC) is well-known. Aside from typical morphology, pigmented adenomatoid, multicystic and papillary patterns have been described. Ten cases of CHRCC composed of small cell population in various percentages were analysed, using morphologic parameters, immunohistochemistry and next-generation sequencing (NGS) testing. Patients were five males and five females, with age ranging from 40 to 78years. The size of tumors ranged from 2.2 cm to 11 cm (mean 5.17 cm). Small cell component comprised 10 to 80% of the tumor volume, while the remaining was formed by cells with classic ChRCC morphology. The immunohistochemical profile of the small cell component was consistent with typical ChRCC immunophenotype, with CD117 and CK7 positivity. Neuroendocrine markers were negative. Mutations of 13 genes were found: DCIER1, FGFR3, JAK3, SUFO, FAM46C, FANCG, MET, PLCG2, APC, POLE, EPICAM, MUTYH and AR. However, only the PLCG2 mutation is considered pathogenic.The small cell variant of ChRCC further highlights and expand upon existing morphologic heterogeneity spectrum. Recognition of small cell variant of CHRCC is not problematic in tumors, where the “classic” CHRCC component is present. However, in limited material (i.e., core biopsy), this may present a diagnostic challenge. Based on the limited follow-up data available, it appears that the small cell tumor component had no impact on prognosis, since there was no aggressive behavior documented.   Awareness of this unusual pattern and applying additional sections to find classic morphology of ChRCC, as well as excluding neuroendocrine nature by immunohistochemistry, may help resolve difficult cases

Untangling the relationship between hemoglobin, peak troponin level, and mortality in patients with myocardial infarction

Patients with a history of myocardial infarction (MI) and lower admission hemoglobin (aHb) levels have a worse outcome than patients with higher aHb, but lower or similar peaks in enzymatic infarct size. Hemoglobin levels are positively correlated with body surface area (BSA), which is positively correlated with cardiac mass. We hypothesized that patients with lower aHb suffer comparatively greater myocardial injury. We examined the relationships between aHb, and troponin (Tn) normalized to BSA (Tn/BSA) and its association with 30-day mortality. Data from 6055 patients, who were divided into seven groups based on their aHb at 10g/L intervals, were analyzed, and the groups were compared. The relationships between aHb and Tn/BSA and between Tn/BSA and 30-day mortality were assessed. Patients with higher aHb levels had greater BSA (p<0.0001). A negative relationship between aHb and log10Tn/BSA was observed in the entire group, and in men and women separately (p<0.0001, p<0.0001, and p=0.013, respectively). The log10Tn/BSA value was associated with 30-day mortality in the entire group, and in men and women separately (p<0.0001, p=0.014, and p<0.0001, respectively). Our finding suggests that a similar peak Tn value in patients with lower aHb means comparatively greater myocardial injury relative to cardiac mass. This hypothesis helps to explain the worse outcomes in patients with lower aHb. According to our findings, troponin should be indexed to BSA to provide comparable information on cardiac injury relative to cardiac mass. Whether this relationship is causal remains to be clarified

Perineural spread in head and neck malignancies: imaging findings - an updated literature review

Perineural spread (PNS) represents the tumor’s ability to disseminate along nerves. The aim of this article is to review the relevant literature about the PNS in head and neck tumors (HN). The important information for imaging analysis is summarized in a diagnostic flow-chart. The pathogenesis, clinical signs, prognostic importance, and technical considerations for computer tomography and magnetic resonance imaging are briefly discussed. The anatomical pathways of the cranial nerves (CNs) and the main check-points are synthesized. Most commonly affected nerves are the trigeminal and facial, although any of the CNs may be involved. The described imaging features represent important clues for an optimal differential diagnosis. PNS worsens the prognosis and significantly changes the treatment, thus radiologists should be aware of this entity and be able to find it on imaging in the appropriate clinical context

Long noncoding RNA FAM225B facilitates proliferation and metastasis of nasopharyngeal carcinoma cells by regulating miR-613/CCND2 axis

Growing evidence has suggested that abnormally expressed long non-coding RNAs (lncRNAs) play critical regulatory roles in nasopharyngeal carcinoma (NPC) pathogenesis. Family with sequence similarity 225 member B (FAM225B) is a novel lncRNA that has been implicated in several human cancers, yet its role in the context of NPC remains largely unclear. The aim of this study was to determine the expression level of FAM225B and its clinical significance in NPC patients. We observed a remarkable increase of FAM225B in NPC tissues and cell lines compared with controls. Also, highly expressed FAM225B was closely correlated with advanced TNM stage, distant metastasis, and poor overall survival. Interestingly, loss-of-function analysis revealed that FAM225B knockdown significantly inhibited tumor growth in vitro and in vivo, and decreased the migratory and invasive capacity of NPC cells. Mechanically, FAM225B functioned as an endogenous sponge by competing for miR-613 binding to up-regulate CCND2 expression. More importantly, rescue experiments further demonstrated that the suppressive impacts of FAM225B knockdown on cell proliferation, migration and invasion were significantly reversed after CCND2 overexpression. Taken all together, these findings highlight FAM225B as an oncogene that promotes NPC proliferation and metastasis through miR-613/CCND2 axis

The prognostic value of MKL1 in predicting breast cancer immune infiltrates and chemosensitivity

Megakaryocytic leukemia 1 (MKL1) acts as a transcription factor in the regulation of the immune system and is associated with cancer biology. However, its function in the infiltrating immune cells in breast cancer has not been explored. Our study aimed to analyze the expression of MKL1 in The Cancer Genome Atlas (TCGA) breast cancer dataset. The aim of this study was to evaluate the correlations between MKL1 expression, infiltrating immune cells, and immune control genes. Enriched signaling pathways and drug sensitivity analyses were also performed. Our results indicate that high MKL1 expression could predict better survival in breast cancer patients. MKL1 expression was associated with the expression and function of different immune cells, including T cells, B cells, natural killer (NK) cells, macrophages, neutrophils and dendritic cells (DCs). The chromatin modifying enzymes, cellular senescence, epigenetic regulation of gene expression, estrogen-dependent gene expression, and chromosome maintenance were differentially enriched in MKL1 low expression phenotype. Patients in the high MKL1 expression group showed sensitivity to paclitaxel, while those in the low expression group showed potential sensitivity for cisplatin and docetaxel. In conclusion, MKL1 might act as a potential biomarker of prognostic value for immune infiltration and drug sensitivity in breast cancer

Role of dynamic contrast enhanced magnetic resonance imaging in the diagnosis and management of vascular lesions of the head and neck

Vascular anomalies comprise a wide and heterogeneous group of lesions that may be found in all parts of the body, with most of the cases of vascular malformations involving the head and neck region. Ultrasound (US) is the reliable first-line imaging technique to assess flow parameters. However, in some cases, US fails to depict the real extent of the lesions. On the other hand, magnetic resonance imaging (MRI) allows the evaluation of the full extension and anatomic relationship of the vascular anomalies with the neighboring structures and provides hemodynamic characterization using dynamic contrast enhanced MRI (DCE-MRI), avoiding unnecessary invasive catheter-based procedures. DCE-MRI angiography can make a distinction between low and high flow vascular anomalies and it is useful for selecting adequate therapy and appreciating prognosis. The aim of this paper is to review the role of DCE -MRI in the evaluation of flow characteristics and lesion extent in vascular anomalies of the head and neck region

Construction and validation of a preterm birth risk assessment model using fuzzy analytic hierarchy process

Preterm births account for almost 1 million deaths globally. The objective of this study is to develop and evaluate a model that assists clinicians in assessing the risk of preterm birth, using fuzzy multicriteria analysis. The model allows experts to incorporate their intuition and judgment into the decision-making process and takes into consideration six (6) risk dimensions reflecting the socio-economic, behavioural and medical profile of pregnant women, thus adopting a holistic approach to risk assessment. Each risk dimension is further analysed and measured in terms of risk factors associated with it. Data was collected from a selected group of 35 experts, each one with more than 20 years of obstetric experience. The model criteria were selected after a thorough literature analysis, so as to ensure a holistic approach to risk assessment. The criteria were reviewed by the experts and the model structure was finalised. The fuzzy analytic hierarchy method was applied to calculate the relative importance of each criterion and subsequent use of the model in assessing and ranking pregnant women by their preterm risk. The proposed model utilises fuzzy logic and multicriteria analysis. It addresses the multifactorial nature of decision making when assessing the preterm birth risk. It also incorporates the obstetricians’ intuitive judgement during risk assessment and it can be used to classify cases based upon their risk level. Additionally, it can be applied to evaluate the risk of individual cases in a personalised manner. The proposed model is compared and validated for its predictive value against judgments made by experts.&nbsp

Novel insights into the pathological development of dyslipidemia in patients with hypothyroidism

According to the previous reports, hypothyroidism has been shown to be strongly correlated with increased circulating concentrations of total cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). Notably, thyroid hormones  are confirmed to modulate the production, clearance, and transformation process of cholesterol within circulation of mammals. Moreover, emerging evidence suggests that the thyroid-stimulating hormone could also participate in modulating serum lipid metabolism independently of thyroid hormones, which further induces the pathological development of dyslipidemia. However, the underlying mechanism is still not fully elucidated. Recently, several research studies have demonstrated that the pathogenic progression of hypothyroidism-related dyslipidemia might be correlated with the decreased serum concentrations of thyroid hormones and the increased serum concentrations of thyroid-stimulating hormones. Thus, this indicates that hypothyroidism could induce dyslipidemia and its related cardio-metabolic disorder diseases. In addition, several newly identified modulatory biomarkers, such as proprotein convertase subtilisin/kexin type 9 (PCSK9), angiopoietin-like protein (ANGPTLs), and fibroblast growth factors (FGFs), might play an important role in the regulation of dyslipidemia induced by hypothyroidism. Furthermore, under the status of hypothyroidism, significantly dysfunctional HDL particles could also be observed. In the current review, we summarized the recent knowledge of the relationship between the development of hypothyroidism with dyslipidemia. We also discussed the updated understanding of the mechanisms whereby hypothyroidism induces the risk and the development of dyslipidemia and cardio-metabolic diseases.&nbsp

Quercetin ameliorates testosterone secretion disorder by inhibiting endoplasmic reticulum stress through the miR-1306-5p/HSD17B7 axis in diabetic rats

Testicular damage and testosterone secretion disorder are associated with diabetes mellitus. Quercetin,  a common flavonoid, has antioxidant, anti-cancer,  and blood sugar lowering effects. Therefore, this study aims to investigate the effect of quercetin on the reproductive system of male rats with diabetes in vivo and in vitro and elucidate its mechanism. Streptozotocin (STZ)  induction was used to establish a diabetes model in forty male Sprague Dawley (SD) rats, which were subsequently administered with 20 or 50 mg/kg of quercetin. Leydig cells of rat testes were treated by high glucose (HG) followed by 5 or 10 μM quercetin. Two doses of quercetin increased rat body weight and testicular weight, decreased blood glucose,and inhibited oxidative stress. RT-qPCR and Western blotting revealed that quercetin alleviated STZ-induced testicular damage and promoted testosterone synthesis. Both doses of quercetin reduced ROS and MDA levels, and increased SOD level in HG-treated cells. Both, in vivo and in vitro results confirmed that a high dose of quercetin was more effective. MiR-1306-5p was upregulated in testicular tissue of diabetic rats and HG-treated cells. 17β-hydroxysteroid dehydrogenase (HSD17B7) was a target of miR-1306-5p and HSD17B7 was downregulated in STZ-induced rat tissues and HG-treated cells. HSD17B7 overexpression reversed the increase of C/EBP homologous protein (CHOP) and glucose-regulated protein 78 (Grp78) protein levels as well as eIF2α phosphorylation level and promotion of cell apoptosis caused by miR-1306-5p overexpression. Moreover, overexpression of HSD17B7 activated the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) axis in HG-treated cells. In conclusion, quercetin inhibits ER stress and improves testosterone secretion disorder through the miR-1306-5p/HSD17B7 axis in diabetic rats

Sustained seroprevalence of SARS-CoV-2 antibodies one year after infection: one of the first COVID-19 cluster cases in Bosnia and Herzegovina

SARS-CoV-2 (severe acute respiratory syndrome coronavirus type 2) is a novel virus that has been identified as a causal agent of COVID-19,  an emergent infectious disease which brought about a new pandemic in the twenty-first century. The immune responses and clinical features of individuals infected with SARS-CoV-2 have not yet been fully described. Thus, in this study, we compare the seroprevalence and define the correlation between symptoms and serological results in the first COVID-19 cluster in the city of Konjic, Bosnia and Herzegovina. Of the total number, 93% of RT-PCR positive participants had positive IgG serology and 75% of them developed symptoms of COVID-19. We found that there was no significant alteration in specific IgG (p = 0.504) antibody levels during the 1-year period after COVID-19. Our results indicate that symptomatic COVID-19 patients have a higher rate of seroconversion (p < 0.01). The IgG seroconversion was correlated with high fever (p = 0.002) and headache (p = 0.007), suggesting that these symptoms could be considered as indicators of a better immune response. This study has demonstrated persistence of sustained levels of specific SARS-CoV-2 antibodies after recovering from COVID-19 infection. However, in order to gain a better insight into the immune response to SARS-CoV-2, further systematic studies should be focused on quality and longevity analyses