Positive p53 Expression Is Associated with Primary Endocrine Therapy Resistance in Locally Advanced Stage Luminal B HER2-Negative Breast Cancer Patients: A Cross-Sectional Study in Indonesia.

Luminal B HER2-negative breast cancer (BC) is the most common type in Indonesian BC patients, and frequently manifests with locally advanced staging. Recurrence often occurs within two years of the endocrine therapy course (primary endocrine therapy (ET) resistance). p53 mutation often exists in luminal B HER2-negative BC, but its application as an ET resistance predictor in those populations is still limited. The primary purpose of this research is to evaluate p53 expression and its association with primary ET resistance in luminal B HER2-negative BC. This cross-sectional study compiled 67 luminal B HER2-negative patients' clinical data during their pre-treatment period until they completed a two-year course of endocrine therapy. They were divided into two groups: 29 patients with primary ET resistance and 38 without primary ET resistance. Pre-treatment paraffin blocks from each patient were retrieved, and the p53 expression difference between the two groups was analyzed. Positive p53 expression was significantly higher in patients with primary ET resistance [odds ratio (OR) of 11.78 (95% CI: 3.72-37.37, p-value < 0.0001)]. We conclude that p53 expression could be a beneficial marker for primary ET resistance in locally advanced luminal B HER2-negative BC.

Hydrocephalus is an independent factor affecting morbidity and mortality of ICH patients: Systematic review and meta-analysis.

Background: Despite advances in our knowledge of the causes, preventions, and treatments of stroke, it continues to be a leading cause of death and disability. The most common type of stroke-related morbidity and mortality is intracerebral haemorrhage (ICH). Many prognostication scores include an intraventricular extension (IVH) after ICH because it affects mortality independently. Although it is a direct result of IVH and results in significant damage, hydrocephalus (HC) has never been taken into account when calculating prognostication scores. This study aimed to evaluate the significance of hydrocephalus on the outcomes of ICH patients by meta-analysis. Methods: Studies that compared the rates of mortality and/or morbidity in patients with ICH, ICH with IVH (ICH â€‹+ â€‹IVH), and ICH with IVH and HC (ICH â€‹+ â€‹IVH â€‹+ â€‹HC) were identified. A meta-analysis was performed by using Mantel-Haezel Risk Ratio at 95% significance. Results: This meta-analysis included thirteen studies. The findings indicate that ICH â€‹+ â€‹IVH â€‹+ â€‹HC has higher long-term (90-day) and short-term (30-day) mortality risks than ICH (4.26 and 2.30 higher risks, respectively) and ICH â€‹+ â€‹IVH (1.96 and 1.54 higher risks). Patients with ICH â€‹+ â€‹IVH â€‹+ â€‹HC have lower rates of short-term (3 months) and long-term (6 months) good functional outcomes than those with ICH (0.66 and 0.38 times) or ICH â€‹+ â€‹IVH (0.76 and 0.54 times). Confounding variables included vascular comorbidities, haemorrhage volume, midline shift, and an initial GCS score below 8. Conclusion: Hydrocephalus causes a poorer prognosis in ICH patients. Thus, it is reasonable to suggest the inclusion of hydrocephalus in ICH prognostication scoring systems.

High concentration of γ­H2AX correlates with a marker of apoptotic suppression and PI3K/Akt pathway upregulation in glioblastoma multiforme.

Glioblastoma multiforme (GBM) is a very aggressive type of primary brain tumor in adults with a poor prognosis. DNA double-strand breaks are known to be associated with the development of numerous cancer types due to their ability to generate genomic instabilities. In GBM, the phosphatidylinositol 3-kinase (PI3K)/Akt pathway is a common pathway that can be activated by exogenous and endogenous factors. Genomic instability may be an endogenous stimulating factor for activation of the PI3K/Akt pathway, which may inhibit the apoptosis of GBM cells. Spontaneous DNA double-strand breaks play an essential role in the survival of GBM cells, and apoptosis levels may reflect survival ability. However, no study has yet been conducted to analyse the association between spontaneous DNA double-strand breaks and apoptosis in patients with GBM prior to treatment. Therefore, the present study examined the concentrations of γ-histone 2AX (γ-H2AX), a sensitive marker of spontaneous DNA double-strand breaks, and cleaved caspase-3, a marker of apoptosis, in patients with GBM. The correlation of γ-H2AX with cleaved caspase-3, PI3K and Akt was also investigated. A total of 26 pre-treatment tumor tissue specimens from patient with GBM were analyzed to determine the concentrations of γ-H2AX, PI3K, Akt and cleaved caspase-3 using sandwich enzyme-linked immunosorbent assays. The results showed a moderate positive correlation between γ-H2AX and PI3K (r=0.52; P=0.007), a moderate positive correlation between γ-H2AX and Akt (r=0.4; P=0.041) and a strong negative correlation between γ-H2AX and cleaved caspase-3 (r=-0.61; P=0.0009). These analyses were also performed in seven tumor tissue specimens from patients with grade I glioma as controls, but no significant correlations were detected. The findings of the present study suggest that a high level of γ-H2AX may affect GBM cell apoptosis via the PI3K/Akt pathway.

Candesartan as a tentative treatment for COVID-19: A prospective non-randomized open-label study.

BACKGROUND: This study aimed to investigate whether the addition of candesartan to the standard care regimen improved the outcome in patients with coronavirus 2019 (COVID-19). METHODS: A prospective non-randomized open-label study was undertaken from May to August 2020 on 75 subjects (aged 18-70 years) hospitalized in Siloam Kelapa Dua Hospital. Uni- and multi-variable Cox regression analyses were performed to obtain hazard ratios (HRs). The primary outcomes were: (1) length of hospital stay; (2) time to negative swab; and (3) radiological outcome (time to improvement on chest X ray). RESULTS: None of the 75 patients with COVID-19 required intensive care. All patients were angiotensin-receptor-blocker naïve. In comparison with the control group, the candesartan group had a significantly shorter hospital stay [adjusted HR 2.47, 95% confidence interval (CI) 1.16-5.29] after adjusting for a wide range of confounders, and no increased risk of intensive care. In the non-obese subgroup, the candesartan group had a shorter time to negative swab (unadjusted HR 2.11, 95% CI 1.02-4.36; adjusted HR 2.40, 95% CI 1.08-5.09) and shorter time to improvement in chest x ray (adjusted HR 2.82, 95% CI 1.13-7.03) compared with the control group. CONCLUSION: Candesartan significantly reduces the length of hospital stay after adjustment for covariates. All primary outcomes improved significantly in the non-obese subgroup receiving candesartan.

Impact of cerebrovascular and cardiovascular diseases on mortality and severity of COVID-19-systematic review, meta-analysis, and meta-regression.

BACKGROUND: We conducted a systematic review and meta-analysis to evaluate the latest evidence on the association between cerebrovascular, and cardiovascular diseases and poor outcome in patients with Coronavirus Disease 2019 (COVID-19) pneumonia. METHODS: A comprehensive systematic literature search was performed using PubMed, SCOPUS, EuropePMC, and Cochrane Central Database. The outcome of interest was composite poor outcome that comprised of mortality and severe COVID-19. RESULTS: A total of 4448 patients were obtained from 16 studies. Cerebrovascular disease was associated with an increased composite poor outcome (RR 2.04 [1.43,2.91], p<0.001; I2: 77%). Subgroup analysis revealed that cerebrovascular disease was associated with mortality (RR 2.38 [1.92,2.96], p<0.001; I2: 0%) and showed borderline significance for severe COVID-19 (RR 1.88 [1.00,3.51], p = 0.05; I2: 87%). Cardiovascular disease was associated with increased composite poor outcome (RR 2.23 [1.71,2.91], p<0.001; I2: 60%), mortality (RR 2.25 [1.53,3.29], p<0.001; I2: 33%) and severe COVID-19 (RR 2.25 [1.51,3.36], p<0.001; I2: 76%). Meta-regression demonstrate that the association was not influenced by gender, age, hypertension, diabetes, and respiratory comorbidities. Furthermore, the association between cerebrovascular disease and poor outcome was not affected by cardiovascular diseases and vice versa. CONCLUSION: Cerebrovascular and cardiovascular diseases were associated with an increased risk for poor outcome in patients with COVID-19.

Impact of cerebrovascular and cardiovascular diseases on mortality and severity of COVID-19-systematic review, meta-analysis, and meta-regression.

BACKGROUND: We conducted a systematic review and meta-analysis to evaluate the latest evidence on the association between cerebrovascular, and cardiovascular diseases and poor outcome in patients with Coronavirus Disease 2019 (COVID-19) pneumonia. METHODS: A comprehensive systematic literature search was performed using PubMed, SCOPUS, EuropePMC, and Cochrane Central Database. The outcome of interest was composite poor outcome that comprised of mortality and severe COVID-19. RESULTS: A total of 4448 patients were obtained from 16 studies. Cerebrovascular disease was associated with an increased composite poor outcome (RR 2.04 [1.43,2.91], p<0.001; I2: 77%). Subgroup analysis revealed that cerebrovascular disease was associated with mortality (RR 2.38 [1.92,2.96], p<0.001; I2: 0%) and showed borderline significance for severe COVID-19 (RR 1.88 [1.00,3.51], p = 0.05; I2: 87%). Cardiovascular disease was associated with increased composite poor outcome (RR 2.23 [1.71,2.91], p<0.001; I2: 60%), mortality (RR 2.25 [1.53,3.29], p<0.001; I2: 33%) and severe COVID-19 (RR 2.25 [1.51,3.36], p<0.001; I2: 76%). Meta-regression demonstrate that the association was not influenced by gender, age, hypertension, diabetes, and respiratory comorbidities. Furthermore, the association between cerebrovascular disease and poor outcome was not affected by cardiovascular diseases and vice versa. CONCLUSION: Cerebrovascular and cardiovascular diseases were associated with an increased risk for poor outcome in patients with COVID-19.