Characteristics of "do not resuscitate" orders among elderly patients receiving mechanical ventilation in the intensive care unit in Taiwan.

Objective: As patient life expectancy has increased and people are living longer than before, the rate of mechanical ventilation among elderly patients in the intensive care unit has increased. Older patients who receive mechanical ventilation and have multiple comorbidities are more likely to have a do not resuscitate order than are younger patients with fewer comorbidities. The aim of our study was to describe the patient characteristics and predictive factors of do not resuscitate orders during hospitalization among elderly patients who received ventilation in the intensive care unit. Methods: This was a retrospective review of the electronic medical records of patients in the intensive care unit of a teaching hospital in southern Taiwan. We enrolled patients admitted to the general intensive care unit from January 1, 2018, to September 31, 2020, and patients older than 80 years who experienced respiratory failure, were intubated and received mechanical ventilation. We analyzed patient demographics, disease severity during hospitalization and comorbidities. If a patient had multiple admissions to the intensive care unit, only the first admission was recorded. Results: Of the 305 patients over 80 years of age with respiratory failure who were intubated and placed on a ventilator, 66 were excluded because of incomplete data, and 13 were excluded because they had already signed a do not resuscitate order prior to admission to the hospital. Ultimately, 226 patients were included in this study. A higher acute physiology and chronic health evaluation II score (>30) was also associated with an increased likelihood of a do not resuscitate order (odds ratio (OR) = 3.85, 95% CI = 1.09-13.62, p = 0.0362). Patients who had acute kidney injury or cerebrovascular accident were more likely to have a do not resuscitate order (OR = 2.74, 95% CI = 1.03-7.28, p = 0.0428 and OR = 7.32, 95% CI = 2.02-26.49, p = 0.0024, respectively). Conclusion: Our study showed that older age, greater disease severity, and certain critical interventions were associated with a greater propensity for do not resuscitate orders, which is crucial for understanding patient preferences and guiding end-of-life care discussions. These findings highlight the importance of clinical severity and specific health events in predicting end-of-life care preferences in older patient groups.

The association between COVID-19 vaccination and confirmed patients with hospitalization in Omicron era: A retrospective study.

With the emergence of Omicron variant of severe acute respiratory syndrome coronavirus 2, Taiwan has encountered the greatest coronavirus disease 2019 (COVID-19) pandemic since 2022 spring. We analyzed the characteristics, vaccinations, and outcomes of hospitalized COVID-19 patients quarantined in a dedicated ward. This retrospective study enrolled hospitalized COVID-19 patients in the dedicated wards of a district hospital in southern Taiwan from May 2022 to July 2022. We assessed in-hospital mortality, hospital length of stay (LOS), and dedicated ward LOS. Among 209 COVID-19 patients, the in-hospital mortality rates were 20.7% and 29.7% (P = .145) in patients with and without vaccination. A shorter dedicated ward LOS was noted in the vaccination group, with marginal statistical significance. Age, Charlson Comorbidity Index, and quick Sequential Organ Failure Assessment score were recognized as strong prognostic indicators for mortality in multivariable analysis. Vaccination demonstrated significant lower odds of death among relatively young populations in subgroup analysis. COVID-19 vaccination had significant efficacy in hospitalized COVID-19 patients in the relatively young group, and the effect may decline among individuals with advanced age and multiple comorbidities.

Analysis of non-small cell lung cancer with miliary lung metastasis in patients harboring epidermal growth factor receptor mutations.

Miliary lung metastasis is a unique feature of lung metastasis in non-small cell lung cancer (NSCLC), indicating hematogenous dissemination. Some studies reported more frequency of epidermal growth factor receptor (EGFR) mutation and worse prognosis in these patients. Cases were identified from Chi-Mei medical center cancer registry for the period 2015-2019. Inclusion criteria were NSCLC with contra-lateral lung metastasis harboring EGFR mutation, under tyrosine kinase inhibitor (TKI) prescription. Patients with miliary or non-miliary lung metastasis were enrolled for survival analysis. 182 NSCLC patients were enrolled for assessing time to discontinuation of TKI (TD-TKI), progression-free survival (PFS) and overall survival (OS). 54 patients with miliary lung metastasis had average 13.2 months [95% confidence interval (CI) 10.7-15.6] of TD-TKI, 11.4 months (95% CI 9.3-13.6) of PFS, and 21.3 months (95% CI 16.8-25.8) of OS, which were shorter than non-miliary group with marginally statistical significance. In multivariate analysis, miliary lung metastasis had no statistical significance, and other strong prognostic indicators were found including performance status, liver metastasis, EGFR type, and generation of TKI. In NSCLC patients harboring EGRF mutation under TKI prescription, miliary lung metastasis was not a dominant indicator for outcomes evaluation.

Characterization of CADASIL among the Han Chinese in Taiwan: Distinct Genotypic and Phenotypic Profiles.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is originally featured with a strong clustering of mutations in NOTCH3 exons 3-6 and leukoencephalopathy with frequent anterior temporal pole involvement. The present study aims at characterizing the genotypic and phenotypic profiles of CADASIL in Taiwan. One hundred and twelve patients with CADASIL from 95 families of Chinese descents in Taiwan were identified by Sanger sequencing of exons 2 to 24 of NOTCH3. Twenty different mutations in NOTCH3 were uncovered, including 3 novel ones, and R544C in exon 11 was the most common mutation, accounting for 70.5% of the pedigrees. Haplotype analyses were conducted in 14 families harboring NOTCH3 R544C mutation and demonstrated a common haplotype linked to NOTCH3 R544C at loci D19S929 and D19S411. Comparing with CADASIL in most Caucasian populations, CADASIL in Taiwan has several distinct features, including less frequent anterior temporal involvement, older age at symptom onset, higher incidence of intracerebral hemorrhage, and rarer occurrence of migraine. Subgroup analyses revealed that the R544C mutation is associated with lower frequency of anterior temporal involvement, later age at onset and higher frequency of cognitive dysfunction. In conclusion, the present study broadens the spectrum of NOTCH3 mutations and provides additional insights for the clinical and molecular characteristics of CADASIL patients of Han-Chinese descents.

MicroRNA-765 influences arterial stiffness through modulating apelin expression.

The present study aims to discover single nucleotide polymorphisms (SNPs) at the apelin gene (APLN) in relation to arterial stiffness, and to explore its molecular mechanisms. A two-step genetic association study was conducted using 799 and 937 subjects in the screening and validation data, respectively. Four tagging SNPs of APLN were tested. SNP rs3115757 was significantly associated with stiffness parameters (ß, Ep and PWV) in women, but not in men. The function of rs3115757 was tagged by rs3115758 which is located in miR-765 binding site in the 3' untranslated region of APLN. The reporter assay confirmed that different alleles of rs3115758 interfered with miR-765 binding and then modified APLN expression. Over-expression of miR-765 in endothelial cells decreased mRNA and protein levels of APLN, which further inhibited the phosphorylation of eNOS and ERK/Akt/AMPK signaling. Collectively, our data showed that rs3115758 accounts for the susceptibility of arterial stiffening through miR-765-induced APLN repression.

Let-7g improves multiple endothelial functions through targeting transforming growth factor-beta and SIRT-1 signaling.

OBJECTIVES: The present study aimed to explore the role of microribonucleic acid (miRNA) Let-7g in regulating endothelial functions. BACKGROUND: Derangement of miRNAs is implicated in the pathogenesis of cardiovascular diseases. Because the transforming growth factor (TGF)-ß pathway plays a regulatory role in endothelial functions, miRNAs targeted at TGF-ß signal cascade might affect vascular health. METHODS: Bioinformatics software predicted that Let-7g can influence the TGF-ß pathway by targeting 3 genes. The Let-7g's effects on multiple endothelial functions were first tested in endothelial cells (ECs) and then in apolipoprotein E knockout mice. Blood samples from lacunar stroke patients were also examined to further support Let-7g's effects on human subjects. RESULTS: Let-7g was experimentally confirmed to knock down the THBS1, TGFBR1, and SMAD2 genes in the TGF-ß pathway. PAI-I, one of the downstream effectors of the TGF-ß pathway, was also down-regulated by Let-7g. Let-7g decreased EC inflammation and monocyte adhesion and increased angiogenesis via the TGF-ß pathway. Furthermore, Let-7g reduced EC senescence through increasing SIRT-1 protein. Venous injection of Let-7g inhibitor into apolipoprotein E knockout mice caused overgrowth of vascular intima-media, overexpression of PAI-1, increased macrophage infiltration, and up-regulation of TGF-ß downstream genes in the carotid arteries. Let-7g's beneficial effects on EC were reduced, whereas the TGF-ß pathway was suppressed by ribonucleic acid interference. Restoration of the TGF-ß pathway also attenuated the effects of Let-7g overexpression. Low serum levels of Let-7g were associated with increased circulating PAI-1 levels. CONCLUSIONS: Decreased Let-7g levels impair endothelial function and increase the risks of cardiovascular diseases through targeting TGF-ß and SIRT-1 signaling.

Predictive value of plasma (D)-dimer levels for cancer-related stroke: a 3-year retrospective study.

BACKGROUND: Cerebrovascular disease is the second leading cause of central nervous system pathology in cancer patients. Cancer-associated hypercoagulation plays an important role in cancer-related stroke. The present study aims to test whether plasma d-dimer levels could predict comorbid malignancy in patients with ischemic stroke. METHODS: Five hundred sixteen stroke patients with measured d-dimer levels and who were consecutively admitted to our stroke center from 2009 to 2012 were included. Cancer status was determined by medical chart, and 59 patients were identified to have active cancer. An additional 48 cancer patients with stroke were identified from the hospital database. Several d-dimer cutoff levels were used to predict cancer-related stroke. RESULTS: Stroke patients with active cancer had significantly higher d-dimer levels than those without cancer (P < .001). The average d-dimer level in stroke patients without cancer was .66 ± 1.83 mg/L, whereas the levels for active cancer patients from the stroke center and hospital database were 5.70 ± 9.63 mg/L and 10.47 ± 12.31 mg/L, respectively. When using d-dimer of .55 mg/L or more and multiple territory infarctions as criteria, the specificity and positive predictive value (PPV) for cancer-related stroke were 99.7% and 92.9%, respectively. When using d-dimer of 5.5 mg/L or more as the cutoff value, the test had a high specificity and PPV regardless the brain magnetic resonance imaging (MRI) findings. Six stroke patients fitting our criteria were confirmed to have occult malignancy after comprehensive cancer survey. CONCLUSIONS: Extraordinary high d-dimer levels or combining d-dimer and MRI findings may be used as a screening tool to detect malignancy in stroke patients.