Patient-reported distress as an early warning sign of unmet palliative care needs and increased healthcare utilization in patients with advanced cancer.

INTRODUCTION: Cancer patients' sources of distress are often unaddressed, and patient-reported distress data could be utilized to identify those with unmet and impending care needs. We explored the association between moderate/severe distress and healthcare utilization in a large sample of non-small cell lung cancer (NSCLC) and non-colorectal gastrointestinal cancer patients. METHODS AND MATERIALS: Adult patients treated between July 2013 and March 2019. Data from the NCCN Distress Thermometer (DT) and the accompanying "Problem List" were extracted from the EHR. A DT score of ≥ 4 indicates "actionable distress." Statistical analysis was performed using descriptive analysis for patient characteristics, clinical outcomes, and sources of distress. Generalized linear mixed models were fit to determine the relationship between distress and healthcare utilization (hospitalization, emergency department (ED) visit, or both). RESULTS: The ten most frequently reported problems were from the Physical and Emotional domains of the Problem List. Distress was mostly related to physical symptoms (pain, fatigue) and emotional issues (worry, fears, sadness, nervousness). Patients with actionable distress generally reported more problems across all their visits. Actionable distress was associated with higher odds of the composite outcome measure of hospitalization or visiting the ED, within both the next 3 months (OR = 1.37; 95% CI = 1.19, 1.58; p < 0.001) and 6 months (OR = 1.19; 95% CI = 1.03, 1.37; p = 0.019). CONCLUSION: Patients with significant distress had marked utilization of ED and inpatient services. DT scores are a source of untapped data in the EHR that can highlight patients in need of intervention, including palliative care and cancer support services.

Telomere length and somatic mutations in correlation with response to immunosuppressive treatment in aplastic anaemia.

We investigated the frequencies of cytogenetic aberrations and somatic mutations of prognostic relevance in 393 patients with aplastic anaemia (AA). Clonality was determined by G-banding/fluorescence in situ hybridization (FISH) (n = 245), and targeted capture sequencing was performed for 88 haematopoiesis-related genes (n = 70). The telomere length (TL) of bone marrow nucleated cells was measured at the single cell level by FISH (n = 135). Eighteen (4·6%) patients showed disease progression, and monosomy 7 (50·0%) was the most predominant cytogenetic evolution at disease transformation. One third of patients (32·9%) presented at least 1 mutation; the most frequently mutated genes were NOTCH1, NF1, SCRIB, BCOR and DNMT3A. The patient group with clonal changes (30·7%) showed an adverse response to immunosuppressive treatment (IST), compared to the non-clonal group, but this finding did not show statistical significance. The TL of AA patients was significantly shorter than normal control and patients with clonal changes showed significantly shorter TLs. Patients with TL>5·9 showed a higher response rate to IST (P = 0·048). In conclusion, the patients with clonal changes or TL attrition showed a poor response to IST. Shorter TL can be used not only as a biomarker, but also as a predictive marker for treatment response to IST.

Preparation of nanocrystalline TiN coated cubic boron nitride powders by a sol-gel process.

Cubic boron nitride (cBN) particles coated with 20 wt% nanocrystalline TiN were prepared by coating the surface of cBN particles with TiO2, followed by nitridation with NH3 gas at 900 degrees C. Coating of TiO2 on cBN powders was accomplished by a sol-gel process from a solution of titanium (IV) isopropoxide and anhydrous ethanol. An amorphous TiO(x) layer of 50 nm thickness was homogenously formed on the surface of the cBN particles by the sol-gel process. The amorphous layer was then crystallized to an anatase TiO2 phase through calcination in air at 400 degrees C. The crystallized TiO2 layer was 50 nm in thickness, and the size of TiO2 particles comprising the layer was nearly 10 nm. The TiO2 on cBN surfaces was completely converted into nanocrystalline TiN of uniform particles 20 nm in size on cBN particles by nitridation under flowing NH3 gas.

Cysteinyl leukotriene receptor antagonist regulates vascular permeability by reducing vascular endothelial growth factor expression.

BACKGROUND: Inflammation of the asthmatic airway is usually accompanied by increased vascular permeability and plasma exudation. Cysteinyl leukotrienes (cysLTs) potently elicit increased vascular permeability in airways, leading to airway edema. Vascular endothelial growth factor (VEGF) is 1 of the most potent proangiogenic cytokines and also increases vascular permeability so that plasma proteins can leak into the extravascular space. However, the mechanisms by which cysLTs induce increased vascular permeability are not clearly understood. OBJECTIVE: An aim of the current study was to determine the role of the cysLTs, more specifically in the increase of vascular permeability. METHODS: We used a BALB/c mouse model of allergic asthma to examine effects of cysLT receptor antagonists on bronchial inflammation and airway hyperresponsiveness, more specifically on the increase of vascular permeability. RESULTS: These mice develop the following typical pathophysiological features of asthma in the lungs: increased numbers of inflammatory cells of the airways, airway hyperresponsiveness, increased vascular permeability, and increased levels of VEGF. Administration of cysLT receptor antagonists markedly reduced plasma extravasation and VEGF levels in allergen-induced asthmatic lungs. CONCLUSION: These results indicate that cysLT receptor antagonists modulate vascular permeability by reducing VEGF expression and suggest that cysLT receptor may regulate the VEGF expression.

Phase II study of docetaxel and cisplatin combination chemotherapy in metastatic or unresectable localized non-small-cell lung cancer.

BACKGROUND: Docetaxel is highly active in the second-line treatment of patients with metastatic or unresectable locally advanced nonsmall-cell lung cancer (NSCLC). As there is a need for first-line chemotherapy that is more effective than standard platinum-based chemotherapy, this study was undertaken to evaluate the efficacy and tolerability of a docetaxel/cisplatin combination as first-line chemotherapy in advanced NSCLC. METHODS: Newly diagnosed, chemotherapy-naive patients with histologically confirmed NSCLC (measurable stage IIIB/IV NSCLC; Karnofsky performance status, 70-100; adequate bone marrow, renal, hepatic, and cardiac function) were eligible for the study. Docetaxel 75 mg/m2 was administered IV over 1 h, followed immediately by cisplatin 75 mg/m2, given IV over 30 min, with cycles repeated every 3 weeks, for up to six or nine cycles. RESULTS: Thirty-nine patients were enrolled and treated. Their median age was 59 years (range, 32-71 years) and median performance status, 90 (range, 70-100). Histologically, 23 patients (59%) had adenocarcinoma, 12 (30.8%) had squamous cell carcinoma, and 16 patients (41%) had stage IV disease. Thirty-seven patients were eligible for inclusion. In the 39 patients evaluable for safety, significant grade 3/4 toxicities included neutropenia (82%), nausea (10.3%), fatigue (10.3%), and diarrhea (7.7%). Of the 33 patients evaluable for response, 16 patients (48.5%) achieved a partial response and 7 showed progressive disease. Median overall survival time in all eligible patients was 10.5 months. CONCLUSION: Docetaxel/cisplatin produced promising response rates that compare favorably with those of current standard platinum combinations, with manageable toxicity. Further investigations of this first-line combination in NSCLC are warranted.