Factors affecting management decisions in rectal cancer in clinical practice: results from a national survey

Management of rectal cancer has become increasingly complex and a multidisciplinary approach is considered of key importance for improving outcomes. A national survey among specialists involved in this multidisciplinary setting was performed. A web-based survey containing 11 questions regarding rectal cancer management was sent to surgeons and medical oncologists registered by their corresponding societies as members. Statistical analysis was performed using the chi-square and Fisher`s exact tests for all categorical variables according to response to individual questions. Multivariate analysis was performed using Cox`s logistic regression. Overall, 418 email recipients responded the survey. Local staging was performed without either magnetic resonance imaging or endorectal ultrasound by 64% of responders. Seventy-two percent considered that final management decision should be made after neoadjuvant chemoradiation therapy. Additionally, 46% considered that an alternative procedure (local excision or observation) was appropriate in a patient with a complete clinical response. Colorectal surgeons were more frequently in favor of longer intervals after completion of chemoradiation therapy (P = 0.001) and of alternative management procedures after a complete clinical response (P = 0.02). After multivariate analysis, the choice of a watch and wait approach after a complete clinical response following neoadjuvant chemoradiation therapy was significantly more frequent among surgeons (OR 3.5, 95% CI 1.8-7.1). Surgeons seem to be more in favor of tailoring management of rectal cancer according to tumor response after neoadjuvant chemoradiation therapy, with longer intervals after chemoradiation therapy, decisions about treatment strategy being made after chemoradiation therapy instead of before, and the use of alternative surgical procedures after a complete clinical response following neoadjuvant therapy.

New body fat prediction equations for severely obese patients

Background & aims: Severe obesity imposes physical limitations to body composition assessment. Our aim was to compare body fat (BF) estimations of severely obese patients obtained by bioelectrical impedance (BIA) and air displacement plethysmography (ADP) for development of new equations for BF prediction. Methods: Severely obese subjects (83 female/36 mate, mean age = 41.6 +/- 11.6 years) had BF estimated by BIA and ADP. The agreement of the data was evaluated using Bland-Altman`s graphic and concordance correlation coefficient (CCC). A multivariate regression analysis was performed to develop and validate new predictive equations. Results: BF estimations from BIA (64.8 +/- 15 kg) and ADP (65.6 +/- 16.4 kg) did not differ (p > 0.05, with good accuracy, precision, and CCC), but the Bland- Altman graphic showed a wide Limit of agreement (- 10.4; 8.8). The standard BIA equation overestimated BF in women (-1.3 kg) and underestimated BF in men (5.6 kg; p < 0.05). Two BF new predictive equations were generated after BIA measurement, which predicted BF with higher accuracy, precision, CCC, and limits of agreement than the standard BIA equation. Conclusions: Standard BIA equations were inadequate for estimating BF in severely obese patients. Equations developed especially for this population provide more accurate BF assessment. (C) 2008 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Ampicillin/sulbactam compared with polymyxins for the treatment of infections caused by carbapenem-resistant Acinetobacter spp.

Background: There has been an increase in worldwide infections caused by carbapenem-resistant Acinetobacter. This poses a therapeutic challenge as few treatment options are available. Objectives: The aim of this study was to evaluate the efficacy and safety of polymyxins and ampicillin/sulbactam for treating infections caused by carbapenem-resistant Acinetobacter spp. and to evaluate prognostic factors. Methods: This was a retrospective review of patients from two teaching hospitals who had nosocomial infections caused by carbapenem-resistant Acinetobacter spp. from 1996 to 2004. Diagnosis of infection was based on CDC criteria plus the isolation of Acinetobacter from a usually sterile site or from bronchoalveolar lavage. Urinary tract infections were not included. Data on demographic and clinical features and treatment were collected from medical records. Prognostic factors associated with two outcomes (mortality during treatment and in-hospital mortality) were evaluated. Results: Eighty-two patients received polymyxins and 85 were treated with ampicillin/sulbactam. Multiple logistic regression analysis revealed that independent predictors of mortality during treatment were treatment with polymyxins, higher Acute Physiological and Chronic Health Evaluation II (APACHE II) score, septic shock, delay in starting treatment and renal failure. On multivariate analysis, prognostic factors for in-hospital mortality were older age, septic shock and higher APACHE II score. Conclusions: This is the first study comparing current therapeutic options for infections due to carbapenem-resistant Acinetobacter. The most important finding of the present study is that ampicillin/sulbactam appears to be more efficacious than polymyxins, which was an independent factor associated with mortality during treatment.

Individual risk prediction of nodal and distant metastasis for patients with typical bronchial carcinoid tumors

Objective: Bronchial typical carcinoid tumors are tow-grade malignancies. However, metastases are diagnosed in some patients. Predicting the individual risk of these metastases to determine patients eligible for a radical lymphadenectomy and patients to be followed-up because of distant metastasis risk is relevant. Our objective was to screen for predictive criteria of bronchial typical carcinoid tumor aggressiveness based on a logistic regression model using clinical, pathological and biomolecular data. Methods: A multicenter retrospective cohort study, including 330 consecutive patients operated on for bronchial typical carcinoid tumors and followed-up during a period more than 10 years in two university hospitals was performed. Selected data to predict the individual risk for both nodal and distant metastasis were: age, gender, TNM staging, tumor diameter and location (central/peripheral), tumor immunostaining index of p53 and Ki67, Bcl2 and the extracellular density of neoformed microvessels and of collagen/elastic extracellular fibers. Results: Nodal and distant metastasis incidence was 11% and 5%, respectively. Univariate analysis identified all the studied biomarkers as related to nodal metastasis. Multivariate analysis identified a predictive variable for nodal metastasis: neo angiogenesis, quantified by the neoformed pathological microvessels density. Distant metastasis was related to mate gender. Discussion: Predictive models based on clinical and biomolecular data could be used to predict individual risk for metastasis. Patients under a high individual risk for lymph node metastasis should be considered as candidates to mediastinal lymphadenectomy. Those under a high risk of distant metastasis should be followed-up as having an aggressive disease. Conclusion: Individual risk prediction of bronchial typical carcinoid tumor metastasis for patients operated on can be calculated in function of biomolecular data. Prediction models can detect high-risk patients and help surgeons to identify patients requiring radical lymphadenectomy and help oncologists to identify those as having an aggressive disease requiring prolonged follow-up. (C) 2008 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

In situ apoptosis of adaptive immune cells and the cellular escape of rabies virus in CNS from patients with human rabies transmitted by Desmodus rotundus

The aim of the current study was to investigate the apoptosis of neurons, astrocytes and immune cells from human patients that were infected with rabies virus by vampire bats bite. Apoptotic neurons were identified by their morphology and immune cells were identified using double immunostaining. There were very few apoptotic neurons present in infected tissue samples, but there was an increase of apoptotic infiltrating CD4+ and TCD8+ adaptive immune cells in the rabies infected tissue. No apoptosis was present in NK, macrophage and astrocytes. The dissemination of the human rabies virus within an infected host may be mediated by viral escape of the virus from an infected cell and may involve an anti-apoptotic mechanism, which does not kill the neuron or pro-apoptosis of TCD4+ and TCD8+ lymphocytes and which allows for increased proliferation of the virus within the CNS by attenuation of the adaptive immune response. (C) 2011 Elsevier B.V. All rights reserved.

A description of adaptive and maladaptive behaviour in children and adolescents with Cri-du-chat syndrome

Background Psychological tests can be useful to record adaptive and maladaptive behaviours of children with intellectual disability. The objective of this study was to describe the adaptive and maladaptive behaviour of children and adolescents with Cri-du-chat syndrome. Methods The sample consisted of 10 children and adolescents with Cri-du-chat syndrome (mean chronological age = 11.3 years, mean mental age = 18 months). The developmental quotient was calculated through the Psychoeducational Profile - Revised. An observational protocol was used to record adaptive and maladaptive behaviours. Results The number of maladaptive behaviours observed was different among participants. However, all of them had high rates of adaptive behaviours, such as rule-following. Conclusions These results, though preliminary, justify that we continue to think about the need for psychoeducational interventions aimed at stimulating the repertoire of adaptive behaviours, in people with Cri-du-chat syndrome.

Hormonal Contraceptives and the Length of Their Use Are Not Independent Risk Factors for High-Risk HPV Infections or High-Grade CIN

Aims: To evaluate the role of hormonal contraceptives as a risk factor of high-risk human papillomavirus (HR-HPV), cervical intraepithelial lesions (CIN) and cervical cancer in our multi-center population-based LAMS (Latin American Screening) study. Methods: A cohort study with >12,000 women from Brazil and Argentina using logistic regression to analyze the covariates of hormonal contraception (HOC - oral, injections, patches, implants, vaginal ring and progesterone intrauterine system) use followed by multivariate modeling for predictors of HR-HPV and CIN2+. Results: HR-HPV infection was a consistent risk factor of high-grade CIN in all three groups of women. The length of HOC use was not significantly related to high-grade squamous intraepithelial lesions (HSIL)+ Pap (p = 0.069), LSIL+ Pap (p = 0.781) or ASCUS+ (p = 0.231). The same was true with the length of HOC use and histology CIN3+ (p = 0.115) and CIN2+ (p = 0.515). Frequently, HOC users have previously shown more HPV-related lesions, as well as lower HPV prevalence if they were current smokers. But HOC use and time of usage were not independent risk factors of either HR-HPV infection or high-grade CIN using multiple logistic regressions. Conclusions: No evidence was found for an association between the use of HOC with an increased risk for HR-HPV infection or high-grade CIN in this cohort. Copyright (C) 2010 S. Karger AG, Basel

GB virus type C infection modulates T-cell activation independently of HIV-1 viral load

Background: Many clinical studies have suggested a beneficial effect of GB virus type C (GBV-C) on the course of HIV-1 infection, but the mechanisms involved in such amelioration are not clear. As recent evidence has implicated cellular activation in HIV-1 pathogenesis, we investigated the effect of GBV-C viremia on T-cell activation in early HIV-1 infection. Methods: Forty-eight recently infected HIV-1 patients (23 GBV-C viremic) were evaluated for T-cell counts, expanded immunophenotyping GBV-C RNA detection, and HIV-1 viral load. Nonparametric univariate and multivariate analyses were carried out to identify variables associated with cellular activation, including GBV-C status, HIV-1 viral load, T lymphocyte counts, and CD38 and chemokine (C-C motif) receptor 5 (CCR5) surface expression. Finding: We not only confirmed the positive correlation between HIV-1 viral load and the percentage of T cells positive for CD38(+)CD8(+) but also observed that GBV-C viremic patients had a lower percentage of T cells positive for CD38(+)CD4(+), CD38(+)CD8(+), CCR5(+)CD4(+), and CCR5(+)CD8(+) compared with HIV-1-infected patients who were not GBV-C viremic. In regression models, GBV-C RNA(+) status was associated with a reduction in the CD38 on CD4(+) or CD8(+) T cells and CCR5(+) on CD8(+) T cells, independent of the HIV-1 viral load or CD4(+) and CD8(+) T-cell counts. These results were also supported by the lower expression of CD69 and CD25 in GBV-C viremic patients. Interpretation: The association between GBV-C replication and lower T-cell activation may be a key mechanism involved in the protection conferred by this virus against HIV-1 disease progression to immunodeficiency in HIV-1-infected patients. (C) 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins

Prevalence and correlates of alcoholism in community-dwelling elderly living in Sao Paulo, Brazil

Objectives To assess the prevalence of alcoholism in elderly living in the city of Sao Paulo (Brazil) and investigate associated risk factors. Methods A total of 1,563 individuals aged 60 years or older, of both genders of three districts of different socioeconomic classes (high, medium and low) in the city of Sao Paulo (Brazil) were interviewed. The CAGE screening test for alcoholism was applied and a structured interview was used to assess associated sociodemographic and clinical factors. The tests Mini Mental State Examination, Fuld Object Memory Evaluation, The Informant Questionnaire on Cognitive Decline in the Elderly and Bayer-Activities of Daily Living Scale were used for cognitive and functional assessment. Results Prevalence of alcoholism was 9.1%. Multivariate regression analysis showed that alcoholism was associated with male gender, `mulatto` ethnicity, smoking, and cognitive and functional impairment. In addition, the younger the individual and the lower the schooling level, the higher the risk for alcoholism. Conclusions The results obtained in this study show that alcoholism is highly frequent in the community-dwelling elderly living in Sao Paulo, and that it is associated with socio-demographic and clinical risk factors similar to those reported in the literature. This suggests that alcoholism in the elderly of a developing country shares the same basic characteristics seen in developed countries. These findings suggest that it is essential for health services and professional to be prepared to meet this demand that will significantly grow in the next years, especially in developing countries, where the rates of population aging are higher than those of developed countries. Copyright (C) 2009 John Wiley & Sons, Ltd.

Survival and Recurrence in Nonmycosis Fungoides Primary Cutaneous Lymphoma

Purpose: To evaluate overall and relapse-free survival (RFS) in patients with nonmycosis fungoides (non-MF) primary cutaneous lymphoma (PCL). Methods: Thirty-eight patients with PCL excluding cases of MF treated between 1993 and 2006 were analyzed retrospectively. Survival statistics were estimated by the methods of Kaplan and Meier, and univariate and multivariate significance testing were performed by Cox regression analysis. Results: The median follow-up was 34.6 months (range, 2-138.3 months). The overall survival for the entire study population, at 5 and 10 years, was 97% and 78%, respectively. The RFS for the entire study population, at 5 and 10 years, was 30% and 22%, respectively. For those who received radiotherapy (RT) as a component of their initial therapy, the RFS at 5 and 10 years was 48% and 36%, respectively. Among those receiving RT who relapsed, the site of relapse was out-of-field in 82% of the cases. In our multivariate analysis, only RT as a component of the initial therapy and the absence of bulky disease had a statistically significant improvement in RFS (P = 0.01 and < 0.01, respectively). Conclusion: RT improves the local control and RFS of patients with non-MF PCL.

Factors determining normal adult height in girls with gonadotropin-dependent precocious puberty treated with depot gonadotropin-releasing hormone analogs

Context: Several factors can affect adult height (AH) of patients with gonadotropin-dependent precocious puberty (GDPP) treated with depot GnRH analogs. Objective: Our objective was to determine factors influencing AH in patients with GDPP treated with depot GnRH analogs. Patients: A total of 54 patients (45 girls) with GDPP treated with depot GnRH analog who reached AH was included in the study. Design: Univariate and multivariate analyses of the factors potentially associated with AH were performed in all girls with GDPP. In addition, clinical features of the girls who attained target height (TH) range were compared with those who did not. Predicted height using Bayley and Pinneau tables was compared with attained AH. Results: In girls the mean AH was 155.3 +/- 6.9 cm (-1.2 +/- 1 SD) with TH range achieved by 81% of this group. Multiple regression analysis revealed that the interval between chronological age at onset of puberty and at the start of GnRH analog therapy, height SD scores (SDSs) at the start and end of therapy, and TH explained 74% of AH variance. The predicted height at interruption of GnRH therapy, obtained from Bayley and Pinneau tables for average bone age, was more accurate than for advanced bone age in both sexes. In boys the mean AH was 170.6 +/- 9.2 cm (-1 +/- 1.3 SDS), whereas TH was achieved by 89% of this group. Conclusions: The major factors determining normal AH in girls with GDPP treated with depot GnRH analogs were shorter interval between the onset of puberty and start of therapy, higher height SDS at the start and end of therapy, and TH. Therefore, prompt depot GnRH analog therapy in properly selected patients with GDPP is critical to obtain normal AH.

Brain structure and symptom dimension relationships in obsessive-compulsive disorder: A voxel-based morphometry study

Background: Obsessive-compulsive disorder (OCD) is a clinically heterogenous disorder characterized by temporally stable symptom dimensions. Past inconsistent results from structural neuroimaging studies of OCD may have resulted from the effects of these specific symptom dimensions as well as other socio-demographic and clinical variables upon gray matter (GM) volume. Methods: GM volume was measured in 25 adult OCD patients and 20 adult healthy controls using voxel-based morphometry (VBM), controlling for age and total brain GM volume. Univariate and multivariate regression analyses were carried out between regions of GM difference and age, age of onset, medication load, OCD severity, depression severity, and separate symptom dimension scores. Results: Significant GM volumetric differences in OCD patients relative to controls were found in dorsal cortical regions, including bilateral BA6, BA46, BA9 and right BA8 (controls > patients), and bilateral midbrain (patients > controls). Stepwise regression analyses revealed highly significant relationships between greater total OCD symptom severity and smaller GM volumes in dorsal cortical regions and larger GM volumes in bilateral midbrain. Greater age was independently associated with smaller GM volumes in right BA6, left BA9, left BA46 and larger GM volumes in right midbrain. Greater washing symptom severity was independently associated with smaller GM volume in right BA6, while there was a trend association between greater hoarding symptom severity and lower GM volume in left BA6. Limitations: The sample was relatively small to examine the relationship between symptom scores and GM volumes. Multiple patients were taking medication and had comorbid disorders. Conclusions: These analyses suggest dorsal prefrontal cortical and bilateral midbrain GM abnormalities in OCD that appear to be primarily driven by the effects of total OCD symptom severity. The results regarding the relationship between GM volumes and symptom dimension scores require examination in larger samples. (C) 2008 Elsevier B.V. All rights reserved.

Comparison of HRT-3 glaucoma probability score and subjective stereophotograph assessment for prediction of progression in glaucoma

PURPOSE. To assess whether baseline Glaucoma Probability Score (GPS; HRT-3; Heidelberg Engineering, Dossenheim, Germany) results are predictive of progression in patients with suspected glaucoma. The GPS is a new feature of the confocal scanning laser ophthalmoscope that generates an operator-independent, three-dimensional model of the optic nerve head and gives a score for the probability that this model is consistent with glaucomatous damage. METHODS. The study included 223 patients with suspected glaucoma during an average follow-up of 63.3 months. Included subjects had a suspect optic disc appearance and/or elevated intraocular pressure, but normal visual fields. Conversion was defined as development of either repeatable abnormal visual fields or glaucomatous deterioration in the appearance of the optic disc during the study period. The association between baseline GPS and conversion was investigated by Cox regression models. RESULTS. Fifty-four (24.2%) eyes converted. In multivariate models, both higher values of GPS global and subjective stereophotograph assessment ( larger cup-disc ratio and glaucomatous grading) were predictive of conversion: adjusted hazard ratios (95% CI): 1.31 (1.15 - 1.50) per 0.1 higher global GPS, 1.34 (1.12 - 1.62) per 0.1 higher CDR, and 2.34 (1.22 - 4.47) for abnormal grading, respectively. No significant differences ( P > 0.05 for all comparisons) were found between the c-index values ( equivalent to area under ROC curve) for the multivariate models (0.732, 0.705, and 0.699, respectively). CONCLUSIONS. GPS values were predictive of conversion in our population of patients with suspected glaucoma. Further, they performed as well as subjective assessment of the optic disc. These results suggest that GPS could potentially replace stereophotograph as a tool for estimating the likelihood of conversion to glaucoma.