Postoperative nomogram for disease-specific survival after an R0 resection for gastric carcinoma.

PURPOSE: Few published studies have addressed individual patient risk after R0 resection for gastric cancer. We developed and internally validated a nomogram that combines these factors to predict the probability of 5-year gastric cancer-specific survival on the basis of 1,039 patients treated at a single institution. METHODS: Nomogram predictor variables included age, sex, primary site (distal one-third, middle one-third, gastroesophageal junction, and proximal one-third), Lauren histotype (diffuse, intestinal, mixed), number of positive lymph nodes resected, number of negative lymph nodes resected, and depth of invasion. Death as a result of gastric cancer was the predicted end point. The concordance index was used as an accuracy measure, with bootstrapping to correct for optimistic bias. Calibration plots were constructed. RESULTS: Gastric cancer-specific survival at 5 years was 50%. A nomogram was constructed on the basis of a Cox regression model. The bootstrap-corrected concordance index was 0.80. When compared with the predictive ability of American Joint Committee on Cancer stage, the nomogram discrimination was superior (P <.001). Nomogram calibration appeared to be excellent. CONCLUSION: A nomogram was developed to predict 5-year disease-specific survival after R0 resection for gastric cancer. This tool should be useful for patient counseling, follow-up scheduling, and clinical trial eligibility determination.     

The newer unconventional indications of permanent pacemakers

In recent years, the indications for permanent pacemakers have expanded. The interest has focussed on hypertrophic cardiomyopathy, dilated cardiomyopathy and a new entity called hypertensive hypertrophy with cavity obliteration (HHCO). Pacemaker therapy is establishing itself for the prevention of atrial fibrillation. Pacing for neurocardiogenic syncope with newer pacing mode has encouraging datas. Pacemaker for long QT syndrome, after cardiac transplant and for haemodynamic improvement in occasional cases of first degree atrio-ventricular block is getting attention. The AHA and ACC guidelines updated in 1998 for implantation of cardiac pacemakers, now include several of these newer indications.     

Leishmania promastigote membrane antigen-based enzyme-linked immunosorbent assay and immunoblotting for differential diagnosis of Indian post-kala-azar dermal leishmaniasis

Diagnosis of post-kala-azar dermal leishmaniasis (PKDL), caused by Leishmania donovani, is difficult, as the dermal lesions are of several types and resemble those caused by other skin diseases, especially leprosy. Since the disease generally appears very late after the clinical cure of kala-azar in India, it is also difficult to correlate PKDL with a previous exposure to L. donovani. Very few attempts have been made so far to diagnose PKDL serologically, and the diagnostic methods vary in their sensitivities and specificities. Diagnosis of PKDL through sophisticated PCR methods, although highly sensitive, has limited practical use. We have developed a serodiagnostic method using an enzyme-linked immunosorbent assay to detect specific immunoglobulin (Ig) isotypes and IgG subclass antibodies in the sera of Indian PKDL patients. Our assay, which uses L. donovani promastigote membrane antigens, was 100% sensitive for the detection of IgG and 96.7% specific for the detection of IgG and IgG1. Optical density values for individual patients, however, demonstrated wide variations. Western blot analysis based on IgG reactivity could differentiate patients with PKDL from control subjects, which included patients with leprosy, patients from areas where kala-azar is endemic, and healthy subjects, by the detection of polypeptides of 67, 72, and 120 kDa. The recognition patterns of the majority of serum samples from patients with PKDL were also distinct from those of the serum samples from patients with visceral leishmaniasis (VL), at least for a 31-kDa polypeptide. To further differentiate patients with PKDL from those with active and cured VL, we analyzed the specific titers of the Ig isotypes and IgG subclasses. High levels of IgG, IgG1, IgG2, and IgG3 antibodies significantly differentiated patients with PKDL from patients cured of VL. The absence of antileishmanial IgE and IgG4 in patients with PKDL differentiated these patients from those with active VL. These results imply intrinsic differences in the antibodies generated in the sera from patients with PKDL and VL.     

Derivation and validation of a novel comorbidity‐based delirium risk index to predict postoperative delirium using national administrative healthcare database

ObjectiveTo derive and validate a comorbidity‐based delirium risk index (DRI) to predict postoperative delirium.Data Source/Study SettingData of 506 438 hip fracture repair surgeries from 2006 to 2016 were collected to derive DRI and perform internal validation from the Premier Healthcare Database, which provided billing information on 20‐25 percent of hospitalizations in the USA. Additionally, data of 1 130 569 knee arthroplasty surgeries were retrieved for external validation.Study DesignThirty‐six commonly seen comorbidities were evaluated by logistic regression with the outcome of postoperative delirium. The hip fracture repair surgery cohort was separated into a training dataset (60 percent) and an internal validation (40 percent) dataset. The least absolute shrinkage and selection operator (LASSO) procedure was applied for variable selection, and weights were assigned to selected comorbidities to quantify corresponding risks. The newly developed DRI was then compared to the Charlson‐Deyo Index for goodness‐of‐fit and predictive ability, using the Akaike information criterion (AIC), Bayesian information criterion (BIC), area under the ROC curve (AUC) for goodness‐of‐fit, and odds ratios for predictive performance. Additional internal validation was performed by splitting the data by four regions and in 4 randomly selected hospitals. External validation was conducted in patients with knee arthroplasty surgeries.Data CollectionHip fracture repair surgeries, knee arthroplasty surgeries, and comorbidities were identified by using ICD‐9 codes. Postoperative delirium was defined by using ICD‐9 codes and analyzing billing information for antipsychotics (specifically haloperidol, olanzapine, and quetiapine) typically recommended to treat delirium.Principal FindingsThe derived DRI includes 14 comorbidities and assigns comorbidities weights ranging from 1 to 6. The DRI outperformed the Charlson‐Deyo Comorbidity Index with better goodness‐of‐fit and predictive performance.ConclusionsDelirium risk index is a valid comorbidity index for covariate adjustment and risk prediction in the context of postoperative delirium. Future work is needed to test its performance in different patient populations and varying definitions of delirium.     

Modeling adverse environmental impacts on the reproductive system

When priority topics are being established for the study of women's health, it is generally agreed that one important area on which to focus research is reproduction. For example, increasing attention has been directed to environmental exposures that disrupt the endocrine system and alter reproduction. These concerns also suggest the need to give greater attention to the use of animal toxicologic testing to draw inferences about human reproductive risks. Successful reproduction requires multiple simultaneous and sequential processes in both the male and female, and the effect of toxicity on reproduction-related processes is time dependent. Currently, however, the risk assessment approach does not allow for the use of multiple processes or for considering the reproductive process response as a function of time. We discuss several issues in modeling exposure effects on reproductive function for risk assessment and present an overview of approaches for reproductive risk assessment. Recommendations are provided for an effective animal study design for determining reproductive risk that addresses optimization of the duration of dosing, observation of the effects of exposure on validated biomarkers, analysis of several biomarkers for complete characterization of the exposure on the underlying biologic processes, the need for longitudinally observed exposure effects, and a procedure for estimating human reproductive risk from the animal findings. An approach to characterizing reproductive toxicity to estimate the increased fertility risks in a dibromochloropropane (DBCP)-exposed human population is illustrated, using several reproductive biomarkers simultaneously from a longitudinal rabbit inhalation study of DBCP and an interspecies extrapolation method.     

Phase II trial of bortezomib for patients with advanced renal cell carcinoma.

PURPOSE: To assess the efficacy and toxicity of bortezomib (Velcade; Milennium Pharmaceuticals Inc, Cambridge, MA; formerly PS-341) in patients with metastatic renal cell carcinoma (RCC). PATIENTS AND METHODS: Thirty-seven patients with metastatic RCC were treated with bortezomib. The first 25 patients enrolled onto the trial were treated with a dose of 1.5 mg/m2. The dose was decreased to 1.3 mg/m2 for the subsequent 12 patients, because more than 50% of the patients treated at the higher dose required dose reductions. Bortezomib was given by intravenous administration on a twice-weekly schedule for 2 weeks followed by 1 week without treatment until progression or unacceptable toxicity occurred. Twenty-three patients (62%) previously had undergone nephrectomy, and 19 patients (51%) had previously been treated with cytokine therapy. RESULTS: Of the 37 assessable patients, the best response was a partial response in four patients (11%; 95% CI, 3% to 25%) and stable disease in 14 patients (38%; 95% CI, 23% to 55%). The four patients with partial response experienced response durations of 8, 8+, 15+, and 20+ months. Grade 2 or 3 sensory neuropathy was present in 10 patients (53%) overall. One patient in the 1.5 mg/m2 group had grade 3 sensory neuropathy; no grade 3 sensory neuropathy was seen in the 1.3 mg/m2 group. CONCLUSION: The results of this trial suggest that bortezomib has an antitumor effect in individual patients with metastatic RCC. The small proportion of patients who achieved a partial response does not support routine use in metastatic RCC. Efforts to identify the molecular profile associated with clinical response or combination therapy with interferon alfa or other novel agents, may be considered.     

Magnetic,structural and magnetocaloric properties of Ni-Si and Ni-Al thermoseeds for self-controlled hyperthermia

Self-controlled hyperthermia is a non-invasive technique used to kill or destroy cancer cells while preserving normal surrounding tissues. We have explored bulk magnetic Ni-Si and Ni-Al alloys as a potential thermoseeds. The structural, magnetic and magnetocaloric properties of the samples were investigated, including saturation magnetisation, Curie temperature (T_C), and magnetic and thermal hysteresis, using room temperature X-ray diffraction and magnetometry. The annealing time, temperature and the effects of homogenising the thermoseeds were studied to determine the functional hyperthermia applications. The bulk Ni-Si and Ni-Al binary alloys have Curie temperatures in the desired range, 316?K–319?K (43?°C–46?°C), which is suitable for magnetic hyperthermia applications. We have found that T_C strictly follows a linear trend with doping concentration over a wide range of temperature. The magnetic ordering temperature and the magnetic properties can be controlled through substitution in these binary alloys.     

Encoded Exposure and Social Norms in Entertainment-Education

Entertainment-education is an effective health communication strategy that combines or embeds educational messages into entertainment programs to bring about social and behavior change. For years, scholars have considered how entertainment-education works. Some contemporary theories posit that entertainment-education does not engender behavior change directly but does so through mediating variables. This study adds to the literature on this topic by exploring the direct relationship between exposure and social norms instead of their relationship through behavior as a mediator. Novel to this study is the use of encoded exposure, a continuous and recognition-based measure of exposure that includes ever watching, recall, involvement, and dose in its operationalization. Using cross-sectional data from Kyunki … Jeena Issi Ka Naam Hai, an entertainment-education program in India, this exploratory analysis indicates a positive and significant relationship between encoded exposure and social norms. How can this finding be applied to future programs? Questions remain, and replication is needed, but if it is not essential to go through behavior in order to change social norms, then implications emerge for the theory and practice of entertainment-education.