Hepatocellular carcinoma (HCC) remains a major health problem worldwide with a continuous increasing prevalence. Despite the introduction of targeted therapies like the multi-kinase inhibitor sorafenib, treatment outcomes are not encouraging. The prognosis of advanced HCC is still dismal, underlying the need for novel effective treatments. Apart from the various risk factors that predispose to the development of HCC, epigenetic factors also play a functional role in tumor genesis. Histone deacetylases (HDACs) are enzymes that remove acetyl groups from histone lysine residues of proteins, such as the core nucleosome histones, in this way not permitting DNA to loosen from the histone octamer and consequently preventing its transcription. Considering that HDAC activity is reported to be up-regulated in HCC, treatment strategies with HDAC inhibitors (HDACIs) showed some promising results. This review focuses on the use of HDACIs as novel anticancer agents and explains the mechanisms of their therapeutic effects in HCC.
BACKGROUND
In the context of the Coronavirus disease 2019 (COVID-19) pandemic, it has been reported that elderly patients are particularly at risk of developing severe illness and exhibiting increased mortality. While many studies on hospitalized elderly patients with COVID-19 have been published, limited information is available on the characteristics and clinical outcomes of those elderly patients admitted to intensive care unit (ICU).
AIM
To review the available evidence of the clinical data of elderly patients admitted to the ICU due to COVID-19.
METHODS
We searched for published articles available in English literature to identify those studies conducted in critically ill patients admitted to the ICU due to COVID-19, either exclusively designed for the elderly or for the whole ICU population with COVID-19, provided that analyses according to the patients’ age had been conducted.
RESULTS
Only one study exclusively focusing on critically ill elderly patients admitted to the ICU due to COVID-19 was found. Eighteen additional studies involving 17011 ICU patients and providing information for elderly patients as a subset of the whole study population have also been included in the present review article. Among the whole patient population, included in these studies, 8310 patients were older than 65 years of age and 2630 patients were older than 70 years. Clinical manifestations were similar for all patients; however, compared to younger ones, they suffered from more comorbidities and showed a varied, albeit high mortality.
CONCLUSION
In summary, at present, although elderly patients constitute a considerable proportion of critically ill patients admitted to the ICU due to severe COVID-19, studies providing specific information are limited. The evidence so far suggests that advanced age and comorbidities are associated with worse clinical outcome. Future studies exclusively designed for this vulnerable group are needed.
Recently, immunotherapy has shown promising results in solid tumors. To the best of our knowledge, this is the first systematic review of published literature synthesizing all the available data and evaluating both the efficacy and safety of pembrolizumab in endometrial cancer. The present study was performed in accordance with the PRISMA guidelines. Eligible articles were identified by searching the MEDLINE and ClinicalTrials.gov databases, using a predefined combination of the terms 'endometrial cancer' and 'pembrolizumab'. Overall, nine articles incorporating data from 712 patients were eligible. Pembrolizumab was demonstrated to be an effective and safe therapeutic option for the management of advanced/metastatic endometrial cancer. Results of ongoing trials evaluating either pembrolizumab alone or in combination with other antineoplastic regimens are expected to confirm its efficacy in this setting of patients. Pembrolizumab appears to be both durable and robust in endometrial cancer. However, there is an emerging need for novel predictive biomarkers to guide clinical practice. Contents 1. Introduction 2. Sources and study selection 3. Data on efficacy and safety 4. Discussion 5. Conclusion
Low levels of serum calcium, elevated levels of serum phosphorus and absent or abnormally low levels of serum parathyroid hormone characterize hypoparathyroidism, a rare endocrine deficiency illness. Hypoparathyroidism is caused by injury to the parathyroid gland as a result of surgery or autoimmune disease. In addition, hypoparathyroidism may develop due to genetic causes or infiltrative diseases. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is characterized by multi-organ involvement, including the dysfunction of endocrine glands. Previous studies have demonstrated that SARS-CoV-2 infection induces endocrine tissue damage via various mechanisms, including direct cell damage from viral entry to the glands by binding to the angiotensin converting enzyme 2 receptors and replication, vasculitis, arterial and venous thrombosis, hypoxic cell damage, immune response and the cytokine storm. The effects of the new coronavirus, coronavirus disease 2019 (COVID-19) on the parathyroid glands have received limited attention. Hypoparathyroidism has been observed in a small number of individuals as a result of SARS-CoV-2 infection. The present study describes the case of a patient with primary hypoparathyroidism induced by COVID-19. Clinicians should also keep in mind that, despite the fact that SARS-CoV-2 has no known tropism for the parathyroid glands, it can result in primary hypoparathyroidism and decompensation of old primary hypoparathyroidism.
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Colorectal cancer (CRC) comprises a heterogeneous group of gastrointestinal tract tumors. It is a multifactorial disease, and a plethora of distinct factors are involved in its pathogenesis and pathophysiology. The development of CRC is not limited to genetic changes, but epigenetic and environmental factors are also involved. Among the epigenetic factors, histone deacetylases (HDACs), a group of epigenetic enzymes that regulate gene expression, have been reported to be over-expressed in CRC. HDACs and their inhibitors seem to play an important role in the molecular pathophysiology of CRC. The aim of this review was to define the role of HDAC inhibitors as potential anticancer agents against CRC.
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