RESUMEN
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, with a continuously growing prevalence. The pathophysiology of the disease is complex and includes several mechanisms, with metabolic syndrome and insulin resistance playing a major role. It is crucial to diagnose NAFLD before it advances to nonalcoholic steatohepatitis (NASH), which can progress to cirrhosis, presented by its complications which include ascites, portal hypertension, bleeding varices and encephalopathy. Another important complication of NAFLD and cirrhosis is hepatocellular carcinoma (HCC), a cancer with increasing incidence and poor prognosis. Even with the growing prevalence of NAFLD, diagnosis via liver biopsies is unrealistic, considering the costs and complications. Noninvasive tests, including serum biomarkers and elastography, are cost-effective and convenient, thereby replacing liver biopsies in diagnosing and excluding liver fibrosis. However, currently, these noninvasive tests have several limitations, such as variability, inadequate accuracy and risk factors for error. The limitations and variability of these tests comet the investigator to propose combining them in diagnostic algorithms to produce more accurate tools. Identifying patients with significant fibrosis is important for targeted therapies to prevent disease progression. Effective screening using noninvasive tests can be crucial for patient risk stratification and early diagnosis.
RESUMEN
(1) Background/Aim: People infected with SARS-CoV-2 may develop COVID-19 in a wide range of clinical severity. Pulmonary fibrosis is characterized by several grades of chronic inflammation and collagen deposition in the interalveolar space. SARS-CoV-2 infection has been demonstrated to cause lung fibrosis without a currently elucidated mechanism. Some studies emphasize the role of proinflammatory cytokines. This research studies the correlation of the released cytokines with mortality or lung injury in COVID-19 patients. (2) Methods: Electronic medical record data from 40 patients diagnosed with COVID-19 in the COVID-19 Department, Galilee Medical Center, Nahariya, Israel, were collected. Epidemiological, clinical, laboratory, and imaging variables were analyzed. The cytokine levels were measured upon admission and discharge. A correlation between cytokine levels and severity and mortality or lung involvement was undertaken. (3) Results: IFN-gamma and IL-10 are the most powerful risk factors for mortality in the COVID-19 patient groups in a multivariate analysis. However, in a univariate analysis, TGF-ß, CXCL-10, IFN gamma, and IL-7 affected mortality in COVID-19 patients. MMP-7 was significantly correlated with a cytokine storm and a high 4-C (severity) score in COVID-19 patients. MMP-7, TGF-ß, IL-10, IL-7, TNF-α, and IL-6 were correlated with high lung involvement in COVID-19 patients. Serum concentrations of IGF-1 were significantly increased upon discharge, but MMP-7 was decreased. (4) Conclusions: Proinflammatory cytokines predict clinical severity, lung fibrosis, and mortality in COVID-19 patients. High concentrations of TGF-ß, CXCL-10, IL-10, IL-6, and TNF-α are correlated to severity and lung injury. However, certain cytokines have protective effects and higher levels of these cytokines increase survival levels and lower lung damage. High levels of INF-γ, IL-7, MMP-7, and IGF-1 have protection probabilities against lung injury and severity.
RESUMEN
Talazoparib is an oral PARP inhibitor approved for locally advanced/metastatic breast cancer. There is no consensus, however, as to whether it is better used as a first-line treatment or after other therapies in patients with gBRCA mutations. In fact, talazoparib showed its superiority compared with chemotherapy in the survival and quality of life of patients with BRCA mutations, with an acceptable toxicity profile. While its role in this indication is not debated, its cost as well as the availability of other effective new agents, particularly immune checkpoint inhibitors, may encourage the movement of this drug to later treatment lines. Until more robust data are available, the best treatment sequence for BRCA-mutated breast cancer must be personalized on a case-by-case basis.