Multicenter phase II study of docetaxel plus oxaliplatin combination chemotherapy in patients with advanced gastric cancer: Daegu Gyeongbuk Oncology Group

The present study was conducted to evaluate the efficacy and safety of a combination regimen of docetaxel plus oxaliplatin in patients with advanced gastric cancer. Patients with previously untreated metastatic or recurrent, measurable gastric cancer received intravenous docetaxel 65 mg m(-2) plus oxaliplatin 120 mg m(-2) on day 1 based on a 3-week cycle. Forty-two patients were enrolled in the current study, among whom 39 were assessable for efficacy and all assessable for toxicity. One complete response and 18 partial responses were confirmed, giving an overall response rate of 45.2% (95% confidence interval (CI); 31.7-59.7%). At a median follow-up of 7.7 months, the median time to progression and median overall survival was 5.7 (95% CI; 4.3-7.2) months and 9.9 (95% CI; 7.8-12.0) months, respectively. Grade 3/4 neutropenia occurred in 11 patients (26.1%) and febrile neutropenia was observed in four patients (9.5%). The common non-haematologic toxicity was fatigue (grade 1/2, 61.9%) and nausea (grade 1/2, 47.7%). The combination of docetaxel and oxaliplatin was found to be well tolerated and effective in patients with advanced gastric cancer.     

Cost of moderate to severe plaque psoriasis in Germany: a multicenter cost-of-illness study

BACKGROUND: There is little information concerning the costs of psoriasis and patients' quality of life (QoL) in Germany. OBJECTIVE: To obtain data on the annual costs and QoL(to follow in a further publication) of patients with moderate to severe plaque psoriasis. METHODS: Between October 2003 and February 2004, six office-based dermatologists and eight dermatology outpatient departments retrospectively documented cost-of-illness data from a societal cost perspective in 184 patients over a 12-month period. Patients were stratified into three subgroups according to their treatment scheme. RESULTS: Mean total costs amounted to euro 6,709 per patient and year. The mean PASI score was 18.2 and PBSA 28.9%. Annual costs were highest with euro 8,831 in high-need patients. They also showed the highest PASI score (22.2). CONCLUSION: Moderate to severe plaque psoriasis is associated with tremendous costs, particularly in patients not adequately controlled by conventional therapies, while the outcomes of patients were unsatisfactory.     

COVID-19 and Risk Factors of Anxiety and Depression in South Korea

ObjectiveThe aims of this study were to explore the prevalence of and identify predictors of anxiety and depression related to coronavirus disease of 2019 (COVID-19) in South Korea. MethodsThe analysis is based on a quota survey design and a sampling frame that permitted recruitment of a national sample of 1,014 individuals between March 17–31, 2020. Several standardized measurements were used, including GAD-7, PHQ-9, COVID-19 related fear, restrictions in deaily life, as well as sociodemographic information and physical and psychosocial needs during the pandemic. Multiple logistic regression was conducted to analyze the influence of sociodemographic factors, fear, and physical/psychosocial needs on anxiety and depression. ResultsSignificant numbers of the respondents were identifiable anxiety (19.0%) and depression group (17.5%), respectively. This indicates that the depression and anxiety prevalence rate after the COVID-19 is substantially high compared to the depression rate of 2.6% in 2020 and 2.8% in 2018 both reported in the Korea Community Health Survey and the anxiety rate of 5.7% reported in 2016 Survey of Mental Disorders in Korea. Multiple logistic regression results showed age, COVID-19 related fear, and the level of restrictions in daily as significant factors in understanding and predicting the anxiety group. Likfewise, the COVID-19 related fear, restrictions in daily life, and need for economic support were important predictors in predicting the depression group. ConclusionFindings on predictors for greater vulnerability to anxiety and depression has important implications for public mental health in the context of the COVID-19 pandemic.     

Mitral annulus velocity in the evaluation of left ventricular diastolic function in atrial fibrillation.

This study assessed the clinical utility of mitral annulus velocity in the evaluation of left ventricular diastolic function in patients with atrial fibrillation. Atrial fibrillation is the most common sustained arrhythmia encountered in clinical practice. The clinical usefulness of conventional Doppler indexes is limited in atrial fibrillation because of the altered left atrial pressure and loss of synchronized atrial contraction. Mitral inflow and mitral annulus velocities were measured simultaneously with tau in 27 patients with nonrheumatic atrial fibrillation at the cardiac catheterization laboratory. Among deceleration time of mitral inflow, peak mitral inflow velocity (E), and peak diastolic mitral annulus velocity (E), only E correlated with tau (r = 0.51, P =.007). Prolonged tau (>/=50 ms) could be predicted by E <8 cm/s with a sensitivity of 73% (16 of 22) and a specificity of 100% (5 of 5). The E/E ratio correlated with left ventricular filling pressure (r = 0.79, P <.001). The E/E ratio of >/=11 could predict elevated left ventricular filling pressure (>/=15 mm Hg) with a sensitivity of 75% (9 of 12) and a specificity of 93% (14 of 15). Mitral annulus velocity is useful in the detection of impaired left ventricular relaxation and estimation of filling pressure even in patients with atrial fibrillation.     

Atypical retinal microvasculopathy after bone marrow transplantation

Objective : Typical early ischaemic retinal microvascular changes with cotton wool spots after allogeneic bone marrow transplantation (BMT) are well recognised. In this study an atypical non‐ischaemic late retinopathy is described. Methods : Sequential cases of late retinal microvasculopathy following allogeneic BMT were reviewed. Demographic features and clinical and angiographic data were collected. Results : Of 399 patients undergoing allogeneic BMT between 1992 and 1999, eight eyes of four patients developed atypical retinopathy. All patients were male and the age range was 27–50 (mean 37.5) years. The indications for BMT were acute lymphoblastic leukaemia (two patients), chronic myeloid leukaemia (one patient) and chronic lymphocytic leukaemia (one patient). Two patients had conditioning regimens including irradiation. All had cyclosporine and methotrexate as graft‐versus‐host disease prophylaxis. All but one had cyclophosphamide and busulphan as conditioning treatment. One had interferon. No patients had sustained hypertension or diabetes mellitus. Atypical retinopathy was identified 13–62 (mean 50) months after BMT and clinical features consisted of microaneurysms (MA; 4/4), hard exudates (1/4) and macular oedema (1/4). No patient had cotton wool spots. The median acuity was 6/5. Angiographic features were MA (4/4), late leak (2/4) and peripheral (1/4) or central (1/4) ischaemia. One patient underwent focal photocoagulation for macular oedema. Conclusion : Retinal microvascular incompetence (without cotton wool spots) with good vision may occur in a small number of patients as a late complication of allogeneic BMT.     

Differential effects of CYP2E1 status on the metabolic activation of the colon carcinogens azoxymethane and methylazoxymethanol.

Methylazoxymethanol (MAM) and its chemical and metabolic precursor, azoxymethane (AOM), both strong colon carcinogens in rodents, can be metabolically activated by CYP2E1 in vitro. Using CYP2E1-null mice, we found that CYP2E1 deficiency differentially affects the activation of AOM and MAM, as reflected in DNA guanine alkylation in the colon and in the formation of colonic aberrant crypt foci (ACF). Male and female inbred 129/SV wild-type (WT) and CYP2E1-null (null) mice were treated with 189 micromol/kg of either AOM or methylazoxymethyl acetate (MAMAc), and 7-methylguanine (7-MeG) and O(6)-methylguanine (O(6)-MeG) were measured in the DNAs of various organs. The levels of O(6)-MeG (as pmol/nmol guanine) in the liver, colon, kidney, and lung of male null mice treated with AOM were 87, 48, 70, and 43% lower, respectively, than in AOM-treated WT mice. In null mice treated with MAMAc, the DNA O(6)-MeG levels were lower by 38% in the liver but were higher by 368, 146, and 194% in the colon, kidney, and lung, respectively, compared with the same organs of WT mice treated in the same way. Determination of ACF revealed that although AOM-induced ACF formation was significantly lower in the null group than in the WT group, MAMAc-induced ACF formation was significantly higher in the null group than in the WT group. These results demonstrate an important role for CYP2E1 in the in vivo activation of AOM and MAM and suggest that agents that modify CYP2E1 activity at the tumor initiation stage might either enhance or inhibit colon carcinogenesis, depending on whether AOM or MAMAc is used as the carcinogen. The mechanism of this effect is discussed.     

Aloe emodin-induced apoptosis in t-HSC/Cl-6 cells involves a mitochondria-mediated pathway

The aim of our study was to clarify the apoptosis pathway induced by aloe emodin, an hydroxyanthraquinone present in aloe vera leaves, in rat hepatic stellate cells transformed by simian virus 40 (t-HSC/Cl-6), which retain the features of activated rat stellate cells. Apoptosis was determined by DNA fragmentation, caspase activity assay and western blotting analysis. Treatment of t-HSC/Cl-6 cells with 12.5, 25, or 50 microM aloe emodin inhibited t-HSC/Cl-6 cell viability in a dose- and time-dependent manner. The induction of apoptosis by aloe emodin was confirmed by typical DNA ladder formation and annexin v-propidium iodide flow-cytometric analysis. Aloe emodin treatment of t-HSC/Cl-6 cells caused activation of caspase-3 and caspase-9, detected with a caspase activity assay, although no change was observed in caspase-8 activity. Western blotting showed caspase-3 and caspase-9 active forms and the subsequent proteolytic cleavage of poly(ADP-ribose) polymerase. Aloe emodin induced mitochondrial membrane depolarization. Our data also show that cytochrome c increased in the cytosol but decreased in the mitochondria in a time-dependent manner. Increased Bax and unchanged Bcl-2 levels resulted in an increased Bax/Bcl-2 ratio. Thus, our research provides evidence that aloe emodin-induced apoptosis involves a mitochondria-associated apoptosis pathway.