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Αλέξανδρος Γ. Σφακιανάκης

Sunday, January 2, 2022

Place des biopsies liquides dans le diagnostic et la caractérisation moléculaire des cancers du sein: Role of liquid biopsies in the diagnosis and molecular characterization of breast cancer

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Bull Cancer. 2021 Dec;108(11S):11S46-11S54. doi: 10.1016/S0007-4551(21)00636-6.

ABSTRACT

The tumor biopsy remains essential for breast cancer diagnosis and characterization. Indeed, the treatment is decided according to histological subtype, and according to the presence of targetable molecular alterations. Notably, the presence of hormone receptors, ERBB2 hyperexpression or the existence of PIK3CA or ESR1 mutations are among the alterations commonly investigated. But these biological characteristics are determined only partially by tumor biopsy, due to tumor heterogeneity or tumor plasticity that happens spontaneously or under treatment. Liquid biopsy, and in particular circulating tumor DNA and circulating tumor cells, is a non-invasive method to identify and characterize the presence of cancer in the blood. The aim of this review is to determine the value of liquid biopsy to enhance or replace the data provided by a tumor biopsy.

PMID:34969515 | DOI:10.1016/S0007-4551(21)00636-6

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Cytomorphological study of thyroid carcinoma

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Exp Ther Med. 2022 Feb;23(2):117. doi: 10.3892/etm.2021.11040. Epub 2021 Dec 6.

ABSTRACT

The most common neoplasm of the endocrine system is found in the thyroid gland with a significant increase in recent decades largely due to modern diagnostic methods. Thyroid tumors generally have a favorable evolution, but there are also aggressive variants with a poor prognosis. In these aggressive tumors, the most reliable method of detecting and making a differential diagnosis is represented by ultrasound-guided fine-needle cytopuncture, confirmed by histopathological examination. Although fine-needle aspiration puncture and cytological examination are considered to have a high sensitivity and specificity, diagnostic certainty is established later only by histopathological examination. Fine-needle aspiration cytopuncture of the thyroid gland correlated with histopathological examination has played a crucial role in recognizing and identifying v ariants of papillary carcinoma known to have aggressive biological behavior, especially in cases of poorly differentiated carcinoma. Recognition of aggressive variants of papillary carcinoma is of major importance in the prognosis and clinical management of patients. The aim of this study was to present the correlations found in a series of thyroid tumors from patients treated in surgery and oncology departments, as well as tumors accidentally detected during autopsies in the department of forensics. All the cases selected in the study benefited from a complex histopathological diagnosis adapted to each case in order to ensure maximum efficiency.

PMID:34970340 | PMC:PMC8713177 | DOI:10.3892/etm.2021.11040

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Treatment of patients with Covid-19 with a high dose of ulinastatin

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Exp Ther Med. 2022 Feb;23(2):121. doi: 10.3892/etm.2021.11044. Epub 2021 Dec 7.

ABSTRACT

Currently, there are no specific therapeutic agents available for the treatment of coronavirus disease 2019 (Covid-19). The present study aimed to assess the efficacy of high-dose ulinastatin for the treatment of patients with Covid-19. A total of 12 patients hospitalized with confirmed severe acute respiratory syndrome coronavirus 2 infection were treated with a high dose of ulinastatin alongside standard care. Changes in clinical manifestations, laboratory examinations and chest images were retrospectively analyzed. A total of 10 patients with severe Covid-19 and two patients with moderate Covid-19 received ulinastatin treatment. The average age of the patients was 68.0±11.9 years (age range, 48-87 years). In total, nine of the 12 patients (75.0%) had one or more comorbidities. The most common symptoms on admission were fever (8/12, 66.7%), coug h (5/12, 41.7%) and dyspnea (5/12, 41.7%). The percentage of lymphocytes was decreased in 41.7% of patients (5/12) and 58.3% of patients (7/12) had elevated hypersensitive C-reactive protein (CRP) levels (mean, 49.70±77.70 mg/l). The white blood cell levels and the percentage of lymphocytes returned to normal in all of the patients, and CRP was significantly decreased and returned to normal in 83.3% of patients (10/12; mean, 6.87±6.63 mg/l) on day 7 after ulinastatin treatment. Clinical symptoms were relieved synchronously. The peripheral oxygen saturation improved and 66.7% of the patients (8/12) did not require further oxygen therapy 7 days after ulinastatin treatment. No patients required intensive care unit admission or mechanical ventilation. All patients revealed different degrees of absorption of pulmonary lesions after treatment. Compared with the standard care group, ulinastatin treatment significantly prevented illness deterioration. In conclusion, these preliminary data revealed that high-dose ulinastatin treatment was safe and exhibited a potential beneficial effect for patients with Covid-19.

PMID:34970344 | PMC:PMC8713169 | DOI:10.3892/etm.2021.11044

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Role of heparinase in the gastrointestinal dysfunction of sepsis (Review)

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Exp Ther Med. 2022 Feb;23(2):119. doi: 10.3892/etm.2021.11042. Epub 2021 Dec 6.

ABSTRACT

Heparinase (HPA) is a β-D glucuronidase that belongs to the endoglycosidase enzyme family, and plays an important role in numerous pathological and physiological processes, including inflammation, angiogenesis and tumor metastasis. When the expression of HPA is abnormally high, the side chain of heparin sulfate proteoglycans degrades, destroying the cell barrier and leading to the occurrence and development of inflammation, with systemic inflammation occurring in severe cases. Sepsis is a major cause of mortality in critically ill patients. In sepsis, the gastrointestinal tract is the first and most frequently involved target organ, which often leads to gastrointestinal dysfunction. HPA overexpression has been determined to accelerate sepsis progression and gastrointestinal dysfunction; thus, it was hypothesized that HPA may play an important role and may serve as an index for the diagnosis of gastrointestinal dysfunction in sepsis. HPA inhibitors may therefore become applicable as targeted drugs for the treatment of gastrointestinal dysfunction in patients with sepsis. The present review mainly discussed the role of HPA in gastrointestinal dysfunction of sepsis.

PMID:34970342 | PMC:PMC8713170 | DOI:10.3892/e tm.2021.11042

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Serous otitis media: Clinical and therapeutic considerations, including dexamethasone (C22H29FO5) intratympanic injection

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Exp Ther Med. 2022 Feb;23(2):125. doi: 10.3892/etm.2021.11048. Epub 2021 Dec 7.

ABSTRACT

Serous otitis media (SOM) occurs in children and constitutes one of the most significant causes of hearing loss in young age, posing as an important risk factor for long-term hearing loss. SOM is underdiagnosed, most frequently in infants, or the appointment to the ENT doctor is delayed due to non-acute symptomatology. The aim of the present study was to assess 285 patients with SOM diagnosed within a two-year span. The etiology and pathology of hearing loss in patients with different age groups were examined. The importance of a clinical examination and tympanometry was emphasized as absolutely necessary for a correct diagnosis. Treatment targeted Eustachian Tube permeabilization for satisfactory long-term middle ear aeration. Nasal drops with vasoconstrictor drugs (phenylephrine) and disinfectant (colloidal silver 1%) were commonly used, but some patients also benefitted from dexamethasone intratympanic injection. Patients were evaluated at the end of the treatment and follow-up occurred at one month, one year and three years later.

PMID:34970348 | PMC:PMC8713185 | DOI:10.3892/etm.2021.11048

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VEGF mitigates bisphosphonate-induced apoptosis and differentiation inhibition of MC3T3-E1 cells

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Exp Ther Med. 2022 Feb;23(2):130. doi: 10.3892/etm.2021.11053. Epub 2021 Dec 10.

ABSTRACT

The present study aimed to investigate whether VEGF was involved in bisphosphonate (BP)-induced apoptosis and differentiation of osteoblasts. Murine MC3T3-E1 osteoblasts were stimulated with zoledronic acid (ZA) for 7 days. VEGF mRNA and protein expression levels were determined via reverse transcription-quantitative PCR and western blot analysis, respectively. Cell viability was evaluated using Cell Counting Kit-8 assay. In addition, the cell apoptotic rate and the expression levels of apoptosis-related proteins were measured using a TUNEL staining kit and western blot analysis, respectively. To evaluate mineralization, cells were stained with alizarin red, while the secretion levels of alkaline phosphatase (ALP) were measured using the corresponding assay kit. Finally, the expression levels of differentiation-related proteins and proteins of the Nod-like receptor family pyrin domain-containing 3 (NLRP3)/caspase 1/gasdermin D (GSDMD) pyroptosis pathway were measured by western blot analysis. VEGF expression level was notably decreased in ZA-stimulated MC3T3-E1 cells. However, the viability of these cells was enhanced following VEGF addition. Furthermore, VEGF attenuated apoptosis, promoted mineralization and increased ALP activity in ZA-stimulated MC3T3-E1 cells. The ZA-mediated decrease in the protein expression of the osteogenic genes osteopontin, osteocalcin and runt-related transcription factor 2 was restored after MC3T3-E1 cell treatment with 10 ng/ml VEGF. The present study demonstrated that VEGF could attenuate BP-induced apoptosis and differentiation of MC3T3 cells by regulating the NLRP3/caspase 1/GSDMD pathway.

PMID:34970353 | PMC:PMC8713161 | DOI:10.3892/etm.2021.11053

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Increased Incidence of Tapia's Syndrome Cases Since the COVID-19 Pandemic

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Ear Nose Throat J. 2021 Dec 30:1455613211068570. doi: 10.1177/01455613211068570. Online ahead of print.

NO ABSTRACT

PMID:34969313 | DOI:10.1177/01455613211068570

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Restoration of Homeostasis in the Tracheal Mucosa After Thyroid Surgery in a Rat Model

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In Vivo. 2022 Jan-Feb;36(1):161-169. doi: 10.21873/invivo.12687.

ABSTRACT

BACKGROUND/AIM: This study aimed to investigate the process of homeostatic restoration in the tracheal mucosa (TM) after thyroid surgery.

MATERIALS AND METHODS: Fifty-four rats were divided into normal controls (NC) and three experimental groups: (i) flap elevation (FE), (ii) thyroid exposure (TE), and (iii) thyroid isthmusectomy (TI). Expression of mRNA and proteins of key factors regulating homeostasis were evaluated in the TM obtained 3, 7, and 21 days after thyroid surgery.

RESULTS: Increased mRNA expression of transforming growth factor-β1 (TGF-β1), hypoxia-inducible factor-1α (HIF-1α), and matrix metalloproteinase-9 (MMP-9) were observed 21 days after thyroid surgery in all experimental groups compared to that of NC group.

CONCLUSION: Thyroid surgery leads to an actual increase of TGF-β1, HIF-1α, and MMP-9 expression in the TM. This increased expression of key regulators of homeostatic restoration in the TM lasts for a considerable period of time after surgery, especially if the extent of surgery increased.

PMID:34972711 | DOI:10.21873/invivo.12687

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Prone Positioning in Patients With COVID-19: Analysis of Multicenter Registry Data and Meta-analysis of Aggregate Data

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In Vivo. 2022 Jan-Feb;36(1):361-370. doi: 10.21873/invivo.12711.

ABSTRACT

BACKGROUND/AIM: Evidence suggests a beneficial effect of prone positioning (PP) in COVID-19.

MATERIALS AND METHODS: Meta-analysis of individual (7 investigators' groups) and aggregate data (PubMed/EMBASE) regarding the impact of PP on the ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PO2/FiO2) in patients with COVID-19.

RESULTS: Among 121 patients (mean age±SD 59.1±10.7 years, 55% males, 57% intubated) the mean post-versus pre- PP PO2/FiO2 difference was: (i) 50.4±64.3 mmHg, p<0.01, (ii) similar in awake (58.7±72.1 mmHg) versus intubated patients (44.1±57.5 mmHg, p=NS), (iii) inversely correlated with body mass index (r=-0.43, p<0.01). Meta-analysis of 23 studies (n=547, weighted age 58.3±4.1, 73% males, 59% intubated) showed a pooled PO2/FiO2 difference of 61.8 [95% confidence intervals=49.9-73.6] mmHg. Meta-regression analysis revealed no associations with baseline demographics, the time in PP before assessment, and the risk of bias of the studies.

CONCLUSION: PP seems to improve oxygenation of patients with COVID-19.

PMID:34972735 | DOI:10.21873/invivo.12711

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Impact of Pectoral Muscle Values on Clinical Outcomes in Patients With Severe Covid-19 Disease

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In Vivo. 2022 Jan-Feb;36(1):375-380. doi: 10.21873/invivo.12713.

ABSTRACT

BACKGROUND/AIM: The effect of sarcopenia on patients with severe Covid-19 disease is unknown. We aimed to assess the influence of baseline computed tomography (CT)-based body composition parameters (pectoralis muscle area, pectoralis muscle index, skeletal muscle gauge) on clinical variables in patients with severe Covid-19 disease.

PATIENTS AND METHODS: Chest CT scans of adult patients with confirmed Covid-19 who were hospitalized from March 2020 to May 2021 at a level-one medical center in Germany were retrospectively analyzed. Pectoralis muscle area, pectoralis muscle index and skeletal muscle gauge were measured on the first CT scan after admission. Body composition parameters were assessed for association with clinical variables and 30-day mortality.

RESULTS: A total of 46 patients were included. None of the body composition parameters was a pred ictor for 30-day mortality, duration of hospital stay, duration of intensive care unit treatment, or duration of invasive mechanical ventilation.

CONCLUSION: Pectoralis muscle composition parameters in CT chest scans did not predict outcomes in adult patients with severe Covid-19 infection.

PMID:34972737 | DOI:10.21873/invivo.12713

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Epipharyngeal Abrasive Therapy Down-regulates the Expression of SARS-CoV-2 Entry Factors ACE2 and TMPRSS2

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In Vivo. 2022 Jan-Feb;36(1):371-374. doi: 10.21873/invivo.12712.

ABSTRACT

BACKGROUND: The epipharynx, with its high expression of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) entry factors angiotensin-converting enzyme 2 (ACE2) and transmembrane protease, serine 2 (TMPRSS2), is a primary target for SARS-CoV-2 replication in the early stage of Coronavirus Disease 19 (COVID-19). Epipharyngeal abrasive therapy (EAT) is a treatment for epipharyngitis in Japan which involves applying zinc chloride to the epipharyngeal mucosa. In this study, we evaluated the expression patterns of ACE2 and TMPRSS2 in tissue samples from patients before and after EAT.

PATIENTS AND METHODS: The study subjects were seven patients that had not been treated with EAT and 11 patients that had. For immunohistochemical assessment of the epipharyngeal mucosa, the staining intensity of ACE2 and TMPRSS2 was described as an immunohistochemical score (IHC score).

RESULTS: The IHC scores for ACE2 and TEMPRSS2 in the EAT-treated group were 3.40-fold and 1.81-fold lower, respectively, than those in the non-treated group (p=0.0208 and p=0.0244, respectively).

CONCLUSION: EAT down-regulates the expression of SARS-CoV-2 entry factors ACE2 and TMPRSS2. Thus, EAT has potential as a novel COVID-19 preventative method.

PMID:34972736 | DOI:10.21873/invivo.12712

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