Intensity modulated radiotherapy for elderly bladder cancer patients

<p>Abstract</p> <p>Background</p> <p>To review our experience and evaluate treatment planning using intensity-modulated radiotherapy (IMRT) and helical tomotherapy (HT) for the treatment of elderly patients with bladder cancer.</p> <p>Methods</p> <p>From November 2006 through November 2009, we enrolled 19 elderly patients with histologically confirmed bladder cancer, 9 in the IMRT and 10 in the HT group. The patients received 64.8 Gy to the bladder with or without concurrent chemotherapy. Conventional 4-field "box" pelvic radiation therapy (2DRT) plans were generated for comparison.</p> <p>Results</p> <p>The median patient age was 80 years old (range, 65-90 years old). The median survival was 21 months (5 to 26 months). The actuarial 2-year overall survival (OS) for the IMRT vs. the HT group was 26.3% <it>vs </it>.37.5%, respectively; the corresponding values for disease-free survival were 58.3% <it>vs</it>. 83.3%, respectively; for locoregional progression-free survival (LRPFS), the values were 87.5% <it>vs</it>. 83.3%, respectively; and for metastases-free survival, the values were 66.7% <it>vs</it>. 60.0%, respectively. The 2-year OS rates for T1, 2 <it>vs</it>. T3, 4 were 66.7% <it>vs</it>. 35.4%, respectively (<it>p </it>= 0.046). The 2-year OS rate was poor for those whose RT completion time greater than 8 weeks when compared with the RT completed within 8 wks (37.9% vs. 0%, <it>p </it>= 0.004).</p> <p>Conclusion</p> <p>IMRT and HT provide good LRPFS with tolerable toxicity for elderly patients with invasive bladder cancer. IMRT and HT dosimetry and organ sparing capability were superior to that of 2DRT, and HT provides better sparing ability than IMRT. The T category and the RT completion time influence OS rate.</p

Lipid Anti-Lipid Antibody Responses Correlate with Disease Activity in Systemic Lupus Erythematosus

10.1371/journal.pone.0055639PLoS ONE82

Gestalt for shock and mortality in the emergency department: A prospective study

Objective The diagnosis of shock in patients presenting to the emergency department (ED) is often challenging. We aimed to compare the accuracy of experienced emergency physician gestalt against Li's pragmatic shock (LiPS) tool for predicting the likelihood of shock in the emergency department, using 30-day mortality as an objective standard. Method In a prospective observational study conducted in an urban, academic ED in Hong Kong, adult patients aged 18 years or older admitted to the resuscitation room or high dependency unit were recruited. Eligible patients had a standard ED workup for shock. The emergency physician treating the patient was asked whether he or she considered shock to be probable, and this was compared with LiPS. The proxy ‘gold’ or reference standard was 30-day mortality. The area under the receiver operating curve (AUROC) was used to predict prognosis. The primary outcome measure was 30-day mortality. Results A total of 220 patients fulfilled the inclusion criteria and were included in the analysis. The AUROC for LiPS (0.722; sensitivity = 0.733, specificity = 0.711, P < 0.0001) was greater than emergency physician gestalt (0.620, sensitivity = 0.467, specificity = 0.774, P = 0.0137) for diagnosing shock using 30-day mortality as a proxy (difference P = 0.0229). LiPS shock patients were 6.750 times (95%CI = 2.834–16.076, P < 0.0001) more likely to die within 30-days compared with non-shock patients. Patients diagnosed by emergency physicians were 2.991 times (95%CI = 1.353–6.615, P = 0.007) more likely to die compared with the same reference. Conclusions LiPS has a higher diagnostic accuracy than emergency physician gestalt for shock when compared against an outcome of 30-day mortality

Comparative epidemiology of gestational diabetes in ethnic Chinese from Shanghai birth cohort and growing up in Singapore towards healthy outcomes cohort

Background Gestational diabetes mellitus (GDM) has been associated with adverse health outcomes for mothers and offspring. Prevalence of GDM differs by country/region due to ethnicity, lifestyle and diagnostic criteria. We compared GDM rates and risk factors in two Asian cohorts using the 1999 WHO and the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria. Methods The Shanghai Birth Cohort (SBC) and the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort are prospective birth cohorts. Information on sociodemographic characteristics and medical history were collected from interviewer-administered questionnaires. Participants underwent a 2-h 75-g oral glucose tolerance test at 24-28 weeks gestation. Logistic regressions were performed. Results Using the 1999 WHO criteria, the prevalence of GDM was higher in GUSTO (20.8%) compared to SBC (16.6%) (p = 0.046). Family history of hypertension and alcohol consumption were associated with higher odds of GDM in SBC than in GUSTO cohort while obesity was associated with higher odds of GDM in GUSTO. Using the IADPSG criteria, the prevalence of GDM was 14.3% in SBC versus 12.0% in GUSTO. A history of GDM was associated with higher odds of GDM in GUSTO than in SBC, while being overweight, alcohol consumption and family history of diabetes were associated with higher odds of GDM in SBC. Conclusions We observed several differential risk factors of GDM among ethnic Chinese women living in Shanghai and Singapore. These findings might be due to heterogeneity of GDM reflected in diagnostic criteria as well as in unmeasured genetic, lifestyle and environmental factors.Peer reviewe

Associations Between Maternal Distress During Early Life Periods and Offspring Respiratory Infections and Allergic Outcomes

DOI does not function. It has been reported to the journal 28.12.2022BackgroundIncreasing evidence suggests that maternal distress is a risk factor for development of respiratory infections and allergic diseases in the offspring. We aim to evaluate the link between maternal distress during critical periods in early life, namely the preconception, pregnancy and postnatal periods, and development of respiratory infections and allergic diseases in the offspring from the Singapore PREconception Study of long Term maternal and child Outcomes (S-PRESTO) cohort. MethodsMaternal perceived distress was evaluated using validated questionnaires including Beck Depression Inventory-II (BDI-II) administered during three time periods: preconception (three months apart at four timepoints), pregnancy (during each trimester) and postnatal (3 and 6 months post-delivery). Child eczema, rhinitis and wheeze outcomes were evaluated using a modified ISAAC questionnaire at ages 3, 6, 12, and 18 months. Child allergic sensitization was determined by skin prick testing at 18 months. ResultsAmong 332 mother-child pairs studied, higher maternal distress during preconception and pregnancy increased the risks of wheeze development in the first 18 months; for example, preconception and pregnancy BDI-II scores >= 20 were associated with increased risks of wheeze by 18 months [adjusted risk ratios 3.2 (95%CI 1.1-9.4) and 2.5 (1.0-5.9), respectively]. Emotional and practical support from family during preconception decreased the risks of offspring wheeze. No associations were observed between maternal distress and offspring eczema, rhinitis and allergic sensitization. ConclusionMaternal distress during critical early life periods was associated with offspring wheeze in the first 18 months of life. Supporting maternal mental health even before pregnancy could reduce the risk of offspring wheeze.Peer reviewe

Blood lipid profiles and peripheral blood mononuclear cell cholesterol metabolism gene expression in patients with and without methotrexate treatment

<p>Abstract</p> <p>Background</p> <p>Methotrexate (MTX) is the most commonly prescribed disease-modifying antirheumatic drug (DMARD) in rheumatoid arthritis. ATP-binding cassette transporter-A1 (ABCA1) and 27-Hydroxylase (HY27) are known antiatherogenic proteins that promote cellular cholesterol efflux. In THP-1 macrophages, MTX can promote the reversal of cholesterol transport, limit foam cell formation and also reverse COX-2 inhibitor-mediated downregulation of ABCA1. Despite its antiatherogenic potential <it>in vitro</it>, the impact of clinical use of low-dose MTX on cholesterol metabolism in humans is unknown. Objective of the study was to examine whether clinical MTX use is associated with altered blood lipids and/or <it>ABCA1/HY27 </it>expressions.</p> <p>Methods</p> <p>In all, 100 rheumatoid arthritis subjects were recruited from a medical center in central Taiwan. Plasma lipid profiles and peripheral blood mononuclear cell <it>HY27 </it>and <it>ABCA1 </it>expressions were compared between subjects taking MTX (MTX+) and other disease-modifying antirheumatic drugs (DMARDs) (MTX-). Dietary intake was assessed by a registered dietician.</p> <p>Results</p> <p>Though no difference observed in the blood lipids between MTX+ and MTX- subjects, the expressions of <it>ABCA1 </it>and <it>HY27 </it>were significantly elevated in MTX+ subjects (n = 67) compared to MTX- subjects (n = 32, p < 0.05). ABCA expression correlated with MTX doses (r = 0.205, p = 0.042), and MTX+ subjects are more likely to have increased <it>HY27 </it>compared to MTX- subjects (OR = 2.5, p = 0.038). Prevalence of dyslipidemia and overweight, and dietary fat/cholesterol intake were lower than that of the age-matched population. Although no differences were observed in the blood lipids, the potential impacts of MTX on cholesterol metabolism should not be overlooked and the atheroprotective effects from MTX induced <it>HY27 </it>and <it>ABCA1 </it>expressions may still be present in those persons with pre-existing dyslipidemia.</p> <p>Conclusions</p> <p>We demonstrated novel findings on the increased gene expressions of atheroprotective protein <it>HY27 </it>and <it>ABCA1 </it>in human peripheral blood mononuclear cells (PBMCs) with clinical use of low-dose MTX. Whether MTX induced <it>HY27 </it>and <it>ABCA1 </it>expressions can protect against cardiovascular disease in patients with chronic inflammation through the facilitation of cholesterol export remains to be established. Further studies on the impacts of low-dose MTX on hypercholesterolemic patients are underway.</p

Lipid anti-lipid antibody responses correlate with disease activity in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by broad clinical manifestations including cardiovascular and renal complications with periodic disease flares and significant morbidity and mortality. One of the main contributing factors to the pathology of SLE is the accumulation and impaired clearance of immune complexes of which the principle components are host auto-antigens and antibodies. The contribution of host lipids to the formation of these autoimmune complexes remains poorly defined. The aim of the present study was to identify and analyze candidate lipid autoantigens and their corresponding anti-lipid antibody responses in a well-defined SLE patient cohort using a combination of immunological and biophysical techniques. Disease monitoring in the SLE cohort was undertaken with serial British Isles Lupus Assessment Group (BILAG) scoring. Correlations between specific lipid/anti-lipid responses were investigated as disease activity developed from active flares to quiescent during a follow up period. We report a significant negative correlation between anti-lipid antibodies for 24S-hydroxycholesterol, cardiolipin and phosphatidylserine with SLE disease activity. Taken together, these data suggest that lipid autoantigens represent a new family of biomarkers that can be employed to monitor disease activity plus the efficacy of therapeutic intervention in SLE

Comparison of coplanar and noncoplanar intensity-modulated radiation therapy and helical tomotherapy for hepatocellular carcinoma

<p>Abstract</p> <p>Background</p> <p>To compare the differences in dose-volume data among coplanar intensity modulated radiotherapy (IMRT), noncoplanar IMRT, and helical tomotherapy (HT) among patients with hepatocellular carcinoma (HCC) and portal vein thrombosis (PVT).</p> <p>Methods</p> <p>Nine patients with unresectable HCC and PVT underwent step and shoot coplanar IMRT with intent to deliver 46 - 54 Gy to the tumor and portal vein. The volume of liver received 30Gy was set to keep less than 30% of whole normal liver (V30 < 30%). The mean dose to at least one side of kidney was kept below 23 Gy, and 50 Gy as for stomach. The maximum dose was kept below 47 Gy for spinal cord. Several parameters including mean hepatic dose, percent volume of normal liver with radiation dose at X Gy (Vx), uniformity index, conformal index, and doses to organs at risk were evaluated from the dose-volume histogram.</p> <p>Results</p> <p>HT provided better uniformity for the planning-target volume dose coverage than both IMRT techniques. The noncoplanar IMRT technique reduces the V10 to normal liver with a statistically significant level as compared to HT. The constraints for the liver in the V30 for coplanar IMRT vs. noncoplanar IMRT vs. HT could be reconsidered as 21% vs. 17% vs. 17%, respectively. When delivering 50 Gy and 60-66 Gy to the tumor bed, the constraints of mean dose to the normal liver could be less than 20 Gy and 25 Gy, respectively.</p> <p>Conclusion</p> <p>Noncoplanar IMRT and HT are potential techniques of radiation therapy for HCC patients with PVT. Constraints for the liver in IMRT and HT could be stricter than for 3DCRT.</p

Allergic sensitization trajectories to age 8 years in the Singapore GUSTO cohort

Background: Allergic sensitization is linked to allergy development, with early sensitization often associated with worse outcomes. We aimed to identify if distinct allergic sensitization trajectories existed within a diverse and multi-ethnic Asian cohort.Methods: We administered modified ISAAC questionnaires in the first 8 years and conducted skin prick testing at ages 18 months, 3, 5 and 8 years in the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort. We used latent class analysis to derive allergic sensitization trajectories, and adjusted odds ratios (AOR) to evaluate predictive risk factors and associations with allergic comorbidities.Results: Among 997 children, three trajectories were identified: early food and mite sensitization (16.2%), late mite sensitization (24.2%) and no/low sensitization (59.6%). Early food and mite sensitization was associated with early eczema by 6 months [AOR (95%CI) 4.67 (1.78-12.28)], increased risk of wheeze by 3-8 years (ARR 1.72-1.99) and eczema in the first 8 years of life (ARR 1.87-2.41). Late mite sensitization was associated with female sex [AOR 0.58 (0.35-0.96)], cesar-ean section [AOR 0.54 (0.30-0.98)], early eczema by 6 months [AOR 3.40 (1.38-8.42)], and increased risk of eczema by 18 months [ARR 1.47 (1.03-2.08)] and 8 years [ARR 1.35 (1.05-1.73)].Conclusion: Early onset of eczema and early allergic sensitization were strongly associated. Early sensitization, especially to house dust mites, was associated with increased risks of developing wheeze and eczema, pointing to the importance of developing preventive perinatal interventions and effective therapeutics for sensitized toddlers.Peer reviewe