Journal of investigative medicine : the official publication of the American Federation for Clinical Research
-
Breast cancer (BC) is the most common cancer affecting women worldwide. In 2021, the estimated number of new breast cancer cases was 281 550 and about 43 500 women died from metastatic breast cancer (mBC). For women aged 20-59 years, mBC remains the leading cause of cancer death and is, therefore, an important public health concern. ⋯ Even with the major progress that has been made in understanding the biology of BC, challenges such as resistance frequency to therapies, unknown efficacy, concerns for safety of drug combination and toxicities still remain high. Therefore, a new targeted and more selective treatment approaches are the need of the hour. In this review, we aim to outline the most recently approved medications in treatment of Her2-positive and triple-negative breast cancers.
-
Since the outbreak of COVID-19, research has been focused on establishing effective treatments, especially for patients with severe pneumonia and hyperinflammation. The role and dose of corticosteroids remain obscure. We evaluated 58 patients with severe COVID-19 during two periods. 24 patients who received methylprednisolone pulses (250 mg/day intravenously for 3 days) were compared with 34 patients treated according to the standard dexamethasone protocol of 6 mg/day. ⋯ Treatment with methylprednisolone pulses significantly reduced hospitalization time. Although there was no statistically significant influence on the necessity for intubation, methylprednisolone pulses revealed a tendency to delay intubation and hospital discharges. This treatment could benefit patients in the hyperinflammatory phase of the disease.
-
The intact telomere structure is essential for the prevention of the chromosome end-to-end fusions and maintaining genomic integrity. The maintenance of telomere length is critical for cellular homeostasis. The shortening of telomeres has been reported in patients with chronic liver diseases. ⋯ In this brief report, we observed evidence of telomere shortening without changes in the telomerase activity in the liver of patients with alcoholic hepatitis and alcoholic cirrhosis when compared with controls. The alterations in the genes associated with telomere binding proteins were only observed in patients with alcoholic cirrhosis. Future studies are required to determine the mechanism of how alcohol affects the length of the telomere and if the shortening impacts the disease progression in ALD.
-
Randomized Controlled Trial
Methotrexate effects on adenosine receptor expression in peripheral monocytes of persons with type 2 diabetes and cardiovascular disease.
The Cardiovascular Inflammation Reduction Trial (CIRT) was designed to assess whether low-dose methotrexate (LD-MTX) would reduce future cardiac events in patients with metabolic syndrome or type 2 diabetes (T2DM) who are post-myocardial infarction (MI) or have multivessel disease. Our previous work indicates that MTX confers atheroprotection via adenosine A2A receptor (A2AR) activation. In order for A2AR ligation to reduce cardiovascular events, A2AR levels would need to be preserved during MTX treatment. ⋯ Compared with placebo, the LD-MTX group exhibited a trend toward an increase in A2AR (p=0.06), while A3R expression was significantly decreased (p=0.01) after 6 weeks. Cholesterol efflux gene expression did not change significantly. Persistence of A2AR combined with A3R downregulation indicates that failure of MTX to be atheroprotective in CIRT was not due to loss of adenosine receptors on PBMC (ClinicalTrials.gov identifier: NCT01594333).
-
Dysglycemia is a common complication in hospitalized patients and has been suggested to play a significant role in the pathology and virulence of patients with bacteremia. The literature evaluating this relationship in critically ill patients, however, is limited. This retrospective, single-center cohort study aimed to investigate the relationship of glycemic control with 28-day intensive care unit (ICU)-free days in critically ill patients with bacteremia. ⋯ Of the survivors, no difference was seen with TIR status and the number of ICU-free days (p=0.780). These findings demonstrate that glycemic control may increase the likelihood of being liberated from the ICU within a 28-day period, which the authors attributed to increased survival. However, of the patients who left the ICU, glycemic control was not associated with a significant difference in the number of ICU-free days.