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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CPNE3 interaction with RACK1 protects against myocardial ischemia/reperfusion injury

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Exp Ther Med. 2022 Feb;23(2):128. doi: 10.3892/etm.2021.11051. Epub 2021 Dec 10.

ABSTRACT

Copine 3 (CPNE3) and receptor for activated C kinase 1 (RACK1) have been determined to be risk factors for patients with acute myocardial ischemia/reperfusion (I/R). The present study aimed to evaluate the role of CPNE3 and its interaction with RACK1 in myocardial (I/R) injury. Reverse transcription-quantitative PCR (RT-qPCR) and western blotting were performed to detect CPNE3 and RACK1 expression levels in H9c2 cells before and after the transfection of CPNE3 overexpression plasmid or small interfering RNA-RACK1. Cell viability was detected using a Cell Counting Kit-8 assay, and immunoprecipitation assays were performed to determine the interaction between CPNE3 and RACK1. A commercial kit was used to examine lactate dehydrogenase (LDH) levels. The expression levels of inflammatory cytokines were detected via RT-qPCR and western blotting. Cell ap optosis was assessed via TUNEL staining and western blotting. The results demonstrated that the expression levels of CPNE3 and RACK1 were decreased in hypoxia/reoxygenation (H/R)-induced H9c2 cardiomyocytes, which was consistent with the expression levels observed in the myocardial I/R injury rat model. It was found that CPNE3 overexpression upregulated RACK1 expression, increased cell viability and suppressed the release of LDH in H/R-induced H9c2 cells. Furthermore, CPNE3 overexpression inhibited the release of inflammatory cytokines and decreased cell apoptosis in H/R-induced cardiomyocytes by activating RACK1 expression. The present study suggested that CPNE3 served an important role in preventing I/R injury by interacting with RACK1, providing novel insight into the prevention of myocardial I/R injury, as well as the treatment and care of patients with myocardial I/R.

PMID:34970351 | PMC:PMC8713176 | DOI:10.3892/etm.2021.11051

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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.Tapia's syndrome is an uncommon disease described in 1904 by Antonio Garcia Tapia, a Spanish otolaryngologist. It is characterized by concomitant paralysis of the hypoglossal (XIIth) and pneumogastric (Xth) nerves.

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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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Dispersed Bone Spicules as a Cause of Postoperative Headache after Retrosigmoid Vestibular Schwannoma Surgery: A Myth?

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10-1055-s-0041-1741112_210127-1.jpg

J Neurol Surg B Skull Base
DOI: 10.1055/s-0041-1741112

Objectives Dispersion of bone dust in the posterior fossa during retrosigmoid craniectomy for vestibular schwannoma (VS) resection could be a source of meningeal irritation and lead to development of persistent postoperative headaches (POH). We aim to determine risk factors, including whether the presence of bone spicules that influence POH after retrosigmoid VS resection. Design Present study is a retrospective case series. Setting The study was conducted at a tertiary skull-base referral center. Participants Adult patients undergoing VS resection via a retrosigmoid approach between November 2017 and February 2020 were included for this study. Main Outcome Measures Development of POH lasting ≥ 3 months is the primary outcome of this study. Results Of 64 patients undergoing surgery, 49 had complete data (mean age, 49 years; 53% female). Mean follow-up time was 2.4 years. At latest follow up, 16 (33%) had no headaches, 14 (29%) experienced headaches lasting <3 months, 19 (39%) reported POH lasting ≥3 months. Twenty-seven (55%) patients had posterior fossa bone spicules detectable on postoperative computed tomography (CT). Age, gender, body mass index, length of stay, tumor diameter, size of craniectomy, the presence of bone spicules, or the amount of posterior petrous temporal bone removed from drilling did not differ significantly between patients with POH and those without. On multivariate logistic regression, patients with POH were less likely to have preoperative brainstem compression by the tumor (odds ratio [OR] = 0.21, p = 0.028) and more likely to have higher opioid requirements during hospitalization (OR = 1.023, p = 0.045). Conclusion The presence of bone spicules in the posterior fossa on postoperative CT did not contribute to headaches following retrosigmoid craniectomy approach for VS resection.
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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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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Administrative delays of temporary recommendation for use: Impact on access to innovation in melanoma

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Bull Cancer. 2021 Dec 28:S0007-4551(21)00514-2. doi: 10.1016/j.bulcan.2021.11.007. Online ahead of print.

ABSTRACT

INTRODUCTION: Melanoma has benefited in recent years from therapeutic innovations, which have improved overall survival of patients. France has developed a regulatory arsenal allowing faster access to innovative drugs before marketing authorization: temporary authorization for use (ATU) and temporary recommendation for use (RTU).

METHOD: We describe here the decision-making processes that led to the non-publication of the decree on the funding of three RTU in adjuvant melanoma therapy: nivolumab, pembrolizumab and the combination of dabrafenib and trametinib, and we analyse the fate of these drugs in order to quantify the potential loss of chance.

RESULTS: On 03AUG2018, the French National Agency for Medicines and Health Product Safety (ANSM) published 3 RTU in order to give rapid access to major innovations in adjuvant melanoma therapy: nivolumab, pembrolizumab and the combination of dabrafenib and trametinib. These drugs have respectively demonstrated reductions in the risk of recurrence by 35 %, 43% and 55% for target populations of 2200, 1900 and 650 patients per year. Despite a favourable opinion on reimbursement from the French National Authority for Health (HAS), the decrees on reimbursement will never be published, prohibiting the use of these products before the marketing authorisation, and depriving many patients of a potential cure.

CONCLUSION: Despite a favourable opinion from scientists and health agencies for the rapid availability of a drug, the French public health code does not systematically imply access to a therapeutic innovation. The reform of access to innovation implemented on 01JUL2021 may help tackle this issue.

PMID:34972538 | DOI:10.1016/j.bulcan.2021.11.007

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