Predictor Of Better Survival Research Articles

Sex differences in mortality in patients with COPD

Little is known about survival and clinical prognostic factors in females with chronic obstructive pulmonary disease (COPD). The aim of the present study was to determine the survival difference between males and females with COPD and to compare the value of the different prognostic factors for the disease. In total, 265 females and 272 males with COPD matched at baseline by BODE (body mass index, airflow obstruction, dyspnoea, exercise capacity) and American Thoracic Society/European Respiratory Society/Global Initiative of Chronic Obstructive Lung Disease criteria were prospectively followed. Demographics, lung function, St George's Respiratory Questionnaire, BODE index, the components of the BODE index and comorbidity were determined. Survival was documented and sex differences were determined using Kaplan-Meier analysis. The strength of the association of the studied variables with mortality was determined using multivariate and receiver operating curves analysis. All-cause (40 versus 18%) and respiratory mortality (24 versus 10%) were higher in males than females. Multivariate analysis identified the BODE index in females and the BODE index and Charlson comorbidity score in males as the best predictors of mortality. The area under the curve of the BODE index was a better predictor of mortality than the forced expiratory volume in one second for both sexes. At similar chronic obstructive pulmonary disease severity by BODE index and forced expiratory volume in one second, females have significantly better survival than males. For both sexes the BODE index is a better predictor of survival than the forced expiratory volume in one second.

The Comparison Between Matched Related Donor and Alternative Donor for Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Acquired Aplastic Anemia: KSBMT2007-02 Study

Backgound; Although allogeneic hematopoietic stem cell transplantation (alloSCT) from matched related donor (MRD) is a standard therapy for severe acquired aplastic anemia (AA), alternative donor (AD) alloSCT is increasing and the survival of alloSCT from AD improves nowadays.Aims: We planned this study to review the recent result of alloSCT survival and to compare AD with MRD.Methods: A retrospective study comparing MRD and AD for alloSCT in patients with AA was conducted by Korean Society of Blood and Marrow Transplantation (KSBMT2007-02 study).Results: The patient population was AA, pure red cell aplasia, paroxysmal nocturnal hemoglobinuria, and they underwent alloHSCT from 1997 and 2007. Total 336 patients were enrolled in 24 Korean alloSCT centers. Survival analysis was done in 331 patients because data were not available in 5 patients. Two hundred five adult patients with AA were also analyzed to define the characteristics of adult AA patients. AA was 97.3% and median age at alloSCT was 20.4 (1–62) years old. Median time from diagnosis to alloSCT was 6.2 (0.2–248.4) months. Male was 48.9%. Seventy nine percent patients received bone marrow (BM) as a stem cell source. AD had longer time from diagnosis to alloSCT (p=0.049) and received more peripheral blood (PB) or cord blood (CB) as a stem cell source (16.3% vs. 31.7%, p=0.004). Univeriate analysis showed MSD (p<0.001), age less than 15 years (p=0.010), BM as stem cell source (p=0.036) and disease duration less than 12 months (p=0.007) were significant predictor for better survival. However, multivariate analysis revealed that donor type was not significant factor (p=0.087) whereas age and BM was predictors for better survival. When 205 adult AA patients were analyzed, AD had more graft failure (p=0.005), delayed neutrophil engraftment (p=0.035), more acute graft versus host disease (GvHD; p=0.009). However, there were no different between AD and MRD in terms of platelet engraftment (p=0.618), incidence of SOS (p=0.735) and relapse rate (p=0.360). MRD (p=0.011), age less than 30Y (p=0.001), disease duration less than 12M (p=0.003), no prior immune suppression therapy, (p=0.007) and platelet transfusion less than 90U (p=0.010) significantly affected survival. Only age and platelet transfusion were significant factor for better survival in multivariate analysis.Summary: In conclusion, our study showed that donor type was not a significant factor for survival. Therefore, AD should be considered earlier when there is no MRD in patients with AA.

The prognostic impact of NF-κB p105, vimentin, E-cadherin and Par6 expression in epithelial and stromal compartment in non-small-cell lung cancer

Vimentin, nuclear factor-κB (NF-κB) p105, fascin, E-cadherin, TGF-β, Par6 and atypical PKC are molecular markers that play an important role in cell differentiation. Herein, we investigate their prognostic impact in primary non-small-cell carcinoma (NSCLC). Tumour tissue samples from 335 resected patients with stage I–IIIA were used. Tissue microarrays were constructed from duplicate cores of both neoplastic cells and stromal cells and were immunohistochemically evaluated. In univariate analyses, high tumour epithelial cell expressions of NF-κB p105 (P=0.02) and E-cadherin (P=0.03) were positive prognostic indicators for disease-specific survival (DSS), whereas high tumour epithelial cell expression of vimentin (P=0.001) was a negative prognostic indicator. High expression of NF-κB p105 (P=0.001) and Par6 (P=0.0001) in the stromal compartment correlated with a good prognosis. In multivariate analyses, the tumour epithelial cell expression of NF-κB p105 (P=0.0001) and vimentin (P=0.005) and the stromal cell expression of NF-κB p105 (P=0.007) and Par6 (P=0.0001) were independent prognostic factors for DSS. High expression of NF-κB p105 and low expression of vimentin in tumour epithelial cells are independent predictors of better survival in primary NSCLC. In stromal cells, high expressions of NF-κB p105 and Par6 are both favourable independent prognostic indicators.

Long-Term Survival and Prognostic Indicators in Small (≤2 cm) Pancreatic Cancer

Objectives: In a matched analysis, we investigated clinical, histopathological, and survival characteristics of small (≤2 cm) pancreatic cancer (PaC) as compared to large PaC. Methods: From the Mayo pathology database, we identified 41 consecutive patients with small PaC and 94 matched controls with margin-negative PaC >2 cm. Two experienced pathologists, who were blinded to survival data, independently reviewed tumor stage and differentiation. Kaplan-Meier survival analysis and Cox proportional hazards models were applied for data analyses. Results: In patients with localized disease (stages I and II), survival was similar in small and large PaC but survival was significantly better in small PaC with regional nodal metastasis (stage III) as compared to similar stage large PaC (5-year survival 44 vs. 7%, median survival 58 vs.18 months, p < 0.001). Well-differentiated small and large PaC had similar median survival (76 vs. 74 months, p = NS). In multivariate analysis, tumor differentiation, not tumor size, was the only independent factor predicting survival in PaC (risk ratio, RR, for moderate vs. well- differentiated: 2.6,95% confidence interval, CI, 1.5-4.5, and RR for poorly differentiated vs. well-differentiated: 5.0, 95% CI 2.4–10.1). Conclusion: Tumor differentiation may be a better predictor of survival in resectable PaC than tumor stage.

Sequential Organ Failure Assessment Score and Comorbidity: Valuable Prognostic Indicators in Chronically Critically Ill Patients

Chronically critically ill patients are defined as those who survive initial life-threatening, possibly reversible organ failure(s) but are unable to recover rapidly to a point at which they are fully independent of life support. Accordingly, these patients require mechanical ventilation and medical resources for a long time in an intensive care unit (ICU). The present study analysed demographic, clinical and survival data of chronically critically ill patients, to identify condition(s) related to poor prognosis. A total of 141 chronically critically ill patients were studied retrospectively over a two-year period (July 1, 2003 to June 30, 2005). Their mean lengths of stay in the ICU and in the hospital were 42.9+/-36.4 and 83.9+/-100.5 days respectively. ICU and six-month cumulative mortality rates were 42.6% and 75.9% respectively. Non-survivors had a significantly higher Sequential Organ Failure Assessment (SOFA) score than survivors on day 21 of ICU admission, as well as having significantly lower changes of SOFA scores between days three and 21. Multivariate analysis demonstrated that the SOFA score on day 21 and the Charlson Comorbidity Index were the best predictor of survival for six months after hospital discharge. The SOFA score on day 21 and comorbidity in the ICU appears to be a valuable prognostic indicators in chronically critically ill patients.

Use of Subjective Global Assessment and Clinical Outcomes in Critically Ill Geriatric Patients Receiving Nutrition Support

The objective of this study is to examine the prevalence of malnutrition and evaluate the nutrition status and clinical outcome in hospitalized patients aged 65 years and older receiving enteral-parenteral nutrition. This retrospective study was carried out at Başkent University Hospital, Adana, Turkey. A total of 119 patients older than 65 years were recruited. Patients were classified into 3 groups: protein-energy malnutrition (PEM), moderate PEM, and well nourished according to subjective global assessment (SGA) at admission. All patients were fed by enteral or parenteral route. Acute physiological and chronic health evaluation (APACHE-2) and simplified acute physiology (SAPS 2) scores were recorded in patients followed in the intensive care unit (ICU). Nutrition status was assessed with biochemical (serum albumin, serum prealbumin) parameters. These results were compared with mortality rate and length of hospital stay (LOS). The subjects' mean (+/-SD) age was 73.1 +/- 5.4 years. Using SGA, 5.9% (n = 7) of the patients were classified as severely PEM, 27.7% (n = 33) were classified as moderately PEM, and 66.4% (n = 79) were classified as well nourished. Some 73.1% (n = 87) of the patients were followed in the ICU. Among all patients, 42.9% (n = 51) were fed by a combined enteral-parenteral route, 31.1% (n = 37) by an enteral route, 18.5% (n = 22) by a parenteral route, and 7.6% (n = 9) by an oral route. The average length of stay for the patients was 18.9 +/- 13.7 days. The mortality rate was 44.5% (n = 53). The mortality rate was 43% (n = 34) in well-nourished patients (n = 79), 48.5% (n = 16) in moderately PEM patients (n = 33), and 42.9% (n = 3) in severely PEM patients (n = 7) (P = .86). The authors observed no difference between well-nourished and malnourished patients with regard to the serum protein values on admission, LOS, and mortality rate. In this study, malnutrition as defined by SGA did not influence the mortality rate of critically ill geriatric patients receiving enteral or parenteral nutrition. Furthermore, no factor was found to be a good predictor of survival.

Role of Immunohistochemistry in Staging Diffuse Large B-cell Lymphoma (DLBCL)

The use of immunohistochemistry (IHC) in staging bone marrow in non-Hodgkin's lymphoma (NHL) is largely limited to ambiguous cases, particularly those with lymphoid aggregates. Its role in routine clinical practice remains unestablished. This study aimed to determine whether the routine use of IHC in diffuse large B-cell lymphoma (DLBCL) would improve the detection of lymphomatous involvement in the bone marrow. It also sought to determine the impact of IHC on predicting survival compared with routine histological diagnosis using hematoxylin and eosin (H&E), Giemsa, and reticulin staining. The bone marrow trephines of 156 histologically proven DLBCL cases were assessed on routine histology, and IHC using two T-cell markers (CD45RO and CD3), two B-cell markers (CD20 and CD79a), and kappa and lambda light chains. IHC detected lymphomatous involvement on an additional 11% cases compared with histology alone. Although both routine histology and IHC were good predictors of survival, IHC was better at predicting survival on stepwise multivariate Cox regression analysis. IHC performed routinely on bone marrow trephines has the ability to improve detection of occult lymphoma in experienced hands. Furthermore, it is a better predictor of survival compared with routine histological examination alone.

Acid and NaCl Limits to Growth of Listeria monocytogenes and Influence of Sequence of Inimical Acid and NaCl Levels on Inactivation Kinetics

Variability in growth limits of Listeria monocytogenes in response to low pH (adjusted with HCl) or high salinity (NaCl) was evaluated for 127 strains in brain heart infusion broth at 25°C. Over 95% of strains habituated at pH 5.0 grew subsequently at pH 4.2, while 25% were able to grow at pH 4.1. More than 85% of strains preadapted to growth at 8.5% NaCl (wt/vol) subsequently grew in the presence of 11.3% NaCl, while 25% were able to grow at 13% NaCl, and 4.7% grew in the presence of 13.9% NaCl. The results extend the generally accepted growth limits for L. monocytogenes in response to these hurdles. Two strains, one of which was relatively tolerant of both hurdles, and another that was less tolerant of both hurdles, were subjected to different sequences of lethal acid (pH 3.5) and NaCl (14%, wt/vol) stresses to determine whether survival was affected by growth limits, or by sequence of application of treatment. There was no significant difference in the inactivation kinetics of the two strains, but inactivation rates were affected by different treatments. For both strains, the inactivation rates, from fastest to slowest, resulted from: (i) lethal pH and then by lethal water activity, or lethal water activity and then by lethal pH; (ii) lethal pH and water activity applied simultaneously; (iii) lethal pH; and (iv) lethal water activity. The results demonstrated that the sequence of lethal stress application strongly influences L. monocytogenes inactivation, and that L. monocytogenes growth limits are not good predictors of survival in inimical environments.

Adult testicular lymphoma in the United States (1985–2004): Analysis of 3,669 cases from the National Cancer Data Base (NCDB)

19503 Background: Because patients with testicular lymphoma are rare and generally excluded from clinical trials, data on clinical features,treatment and survival are limited. Methods: We retrospectively reviewed all cases of adult (age ≥18 years) testicular lymphoma registered with the NCDB from 1985–2004. Survival data were available only for patients diagnosed before 2001. The NCDB, a project of the American College of Surgeons Commission on Cancer, serves as a comprehensive clinical surveillance resource for all forms of cancer and captures approximately 75% of all cancer cases in the US. Results: We identified3669 cases of testicular lymphoma. This comprised 0.6% of all non-Hodgkin lymphoma. Major histological groups included diffuse large B-cell (DLBCL) (77.8%), other B-cell (21.1%), and T/NK/null cell (1.1%). Median age at diagnosis was 70 years (range, 20–101), with 34.9% under age 65. The right testis was as frequently involved as the left (46.4% v 44.2%). Bilateral testicular involvement occurred in 6.1%. Among those with complete staging work-up, the stage distribution was: I (59.1%), II (15.3%), III (6.0%), and IV (19.6%). Majority were cared for in the community(62.4%) and either had surgery plus additional treatment (59.9%) or surgery alone (23.8%). Median overall survival improved over time, 35.5, 37.6, and 49.5 months for those diagnosed in 1985–1989, 1990–1994, and 1995–2000, respectively (P= 0.01). Other significant predictors of better survival were age <65 years, non-black race, stages I/II at diagnosis, multi-modality treatment, and treatment at a non- Veterans Affairs facility. After multivariate analysis, only age, stage, race, and treatment modality remained independent predictors of survival. Conclusions: This is the largest reported clinical series of testicular lymphoma. Testicular lymphoma is rare and usually presents as early stage disease. Even prior to the introduction of rituximab, the prognosis of testicular lymphoma improved over time, perhaps due to the more frequent use of multimodality therapy. Notably, black race predicted for a worse outcome while DLBCL histology unexpectedly did not. No significant financial relationships to disclose.

Ultraviolet‐blue reflectance of some nestling plumage patches mediates parental favouritism in great tits Parus major

The colouration exhibited by nestling birds is generally cryptic, but in some species it has a conspicuous appearance. The adaptive function of these nestling displays is poorly known, especially in altricial species. We performed an experimental study in which the ultraviolet‐blue reflectance of the carotenoid‐based plumage of great tit Parus major nestlings was reduced in order to find possible evidence of parental favouritism. Tarsus length increment in a three‐day period was significantly lower in manipulated nestlings than in their control siblings. As tarsus length may be a good predictor of survival, the parents may increase their fitness return by investing more in those nestlings reflecting more in the UV‐blue spectral region. Interestingly, this effect was only found in a yellow patch located at the nape of nestlings that has been previously overlooked, as all the studies on plumage colouration in this species have focused on the breast plumage. Some quality indicators are proposed for the colour of nestling plumage, though the possibility exists that selection may operate through aspects of signal efficacy instead of aspects of signal content.

Natural History of Emphysema

Chronic obstructive pulmonary disease (COPD) is a progressive disease with studies of disease progression generally focusing on measures of airflow and mortality. In nonsmokers, maximal lung function is attained around age 15 to 25 years, and after a variable plateau phase, subsequently declines at approximately 20 to 25 ml/year. Smoking may reduce the maximal FEV(1) achieved, shorten or eliminate the plateau phase, and may accelerate the rate of decline in lung function in a dose-dependent manner. Some smokers are predisposed to more rapid declines in lung function than others, and recent reports suggest that females may be at higher risk of lung damage related to smoke exposure than males. Progressive deterioration in dyspnea, functional status, and health-related quality of life (HRQL) in patients with COPD is well known, but the magnitude and rate of decline and its association with severity of airflow obstruction remains poorly defined. Many studies have identified pulmonary function, in particular the FEV(1), as the single best predictor of survival. An impaired diffusing capacity and overall impairment in functional status have also been associated with impaired survival in COPD. The National Emphysema Treatment Trial has provided additional insight into these features in a large, well-characterized group of patients with severe airflow obstruction and structural emphysema.

Pediatric Invasive Aspergillosis: A Multicenter Retrospective Analysis of 139 Contemporary Cases

Invasive aspergillosis is a major cause of morbidity and mortality in immunocompromised children. Invasive aspergillosis has been well characterized in adults; however, the incidence and analysis of risk factors, diagnostic tools, treatments, and outcomes have not been well described for a large cohort of pediatric patients. We conducted the largest retrospective review of contemporary cases of proven and probable pediatric invasive aspergillosis diagnosed at 6 major medical centers (January 1, 2000, to July 1, 2005). Aspergillus fumigatus was the species most frequently recovered (52.8%) for the 139 patients analyzed. The majority of the children had a malignancy with or without hematopoietic stem cell transplant. Significant risk factors that impacted survival were immunosuppressive therapies and allogeneic stem cell transplant. The most common clinical site of invasive aspergillosis was the lungs (59%), and the most frequent diagnostic radiologic finding was nodules (34.6%). Only 2.2% of children showed the air crescent sign, 11% demonstrated the halo sign, and cavitation was seen in 24.5% of patients. Before the diagnosis of invasive aspergillosis, 43.1% of patients received fluconazole, and 39.2% received liposomal amphotericin B. After the diagnosis of invasive aspergillosis, 57% were treated with a lipid formulation of amphotericin B; however, 45.8% received > or = 3 concomitant antifungal agents. Analysis did not show superiority of any 1 antifungal related to overall mortality. A total of 52.5% (73 of 139) died during treatment for invasive aspergillosis. Of all the interventions implemented, surgery was the only independent predictor of survival. Our analyses revealed common findings between adult and pediatric invasive aspergillosis. However, one key difference is diagnostic radiologic findings. Unlike adults, children frequently do not manifest cavitation or the air crescent or halo signs, and this can significantly impact diagnosis. Immune reconstitution, rather than specific antifungal therapy, was found to be the best predictor of survival.

Expression of excision repair cross-complementation group 1 and class III β-tubulin predict survival after chemotherapy for completely resected non-small cell lung cancer

In this study, we examined the expression of excision repair cross-complementation group 1 (ERCC1) protein in 90 completely resected lung cancer samples from patients who received adjuvant or neo-adjuvant platinum-based chemotherapy. Epidermal growth factor receptor (EGFR) was also studied in these samples. We also examined class III beta-tubulin protein expression in 50 patients treated with a platinum-based drug plus paclitaxel. Among 90 patients treated with platinum-based chemotherapy, the loss of ERCC1 protein expression was associated with a better prognosis (p=0.0068). The effect of ERCC1 expression on survival was not seen in a separate set of 59 patients who underwent curative resection but did not receive adjuvant chemotherapy. Among 50 patients treated with a platinum-based drug plus paclitaxel, loss of class III beta-tubulin protein expression was also associated with a better prognosis (p=0.0303). When combined, patients with a tumor that was negative for both ERCC1 and class III beta-tubulin had a significantly longer overall survival than those with a tumor that expressed either ERCC1 or class III beta-tubulin (p=0.0230). There was no relationship between the presence of an EGFR mutation and the patients' survival after the platinum-based chemotherapy. In conclusion, we found that the loss of ERCC1 and class III beta-tubulin protein expression were predictors of better survival in patients who received a platinum-based plus taxane chemotherapy.

Lung function predicts survival in a cohort of asbestos cement workers

To study the predictive power of respiratory screening examinations a cohort of asbestos workers was followed from active work in an asbestos cement plant until death. From a cohort with data on individual exposure since first employment 309 workers who had a preventive medical examination in 1989/1990 were observed until death or the end of 2006. The impact of asbestos exposure (fibre years) and of smoking history on lung function was examined by linear regression, on specific causes of death and total mortality by Cox regression. The prognostic value of lung function, chest X-ray, and various clinical findings regarding total mortality was also examined by Cox regression. Lung function proved to be the best predictor of survival apart from current smoking. Depending on the lung function variable an impairment by the interquartile range resulted in a hazard ratio of 1.5-1.6 while for current smokers it was 2.3. An increase of 70 fibre years (interquartile range) led to a hazard ratio of only 1.1. Lung function was influenced by asbestos exposure, current (but not former) smoking, and by pathological X-ray findings. The risk for pleural mesothelioma was dominated by time since first exposure to crocydolite in the pipe factory while the risk for bronchial cancer increased with smoking and total fibre years. An unexpected finding was an increase of gastric cancer in asbestos cement workers. Lung function decrease predicts risk of premature death better than exposure history and regular spirometry should therefore be offered as primary screening to all former asbestos workers. In workers with a history of high cumulative exposure or rapid lung function decrease or radiological signs (diffuse pleural thickening or small irregular opacities) more sensitive techniques (high resolution computer tomography) need to be applied. All smokers with a history of asbestos exposure should be given free smoking cessation therapy to prevent premature death and lung cancer in particular.

Surgery for atrial fibrillation in patients with mitral valve disease: Results at five years from the International Registry of Atrial Fibrillation Surgery

We sought to assess the clinical and survival benefit of atrial fibrillation surgery in patients submitted to mitral valve surgery after stabilization of postoperative rhythm at 1 year. One thousand seven hundred twenty-three patients were enrolled. Patients with follow-up of longer than 1 year (n = 972) were divided into 3 groups according to surface electrocardiographic rhythm during follow-up visits: stable sinus rhythm, stable atrial fibrillation, and intermittent rhythms. Adverse cardiac event incidence and predictors of long-term outcome were compared among the 3 groups. In-hospital mortality was 2.6%. Risk factors for mortality were the cut-and-sew technique (odds ratio, 8.92; 95% confidence interval, 1.71-46.50; P = .009) and isolated left atrial procedure (odds ratio, 0.16; 95% confidence interval, 0.04-0.56; P = .004). At 1 year, 63.4% patients were in stable sinus rhythm. Stable sinus rhythm was found to be associated with early and late survival (P = .01, log-rank analysis). Multivariate binary logistic regression analysis found that left atrial dimension (odds ratio, 0.97; 95% confidence interval, 0.96-0.99; P = .005) and concomitant coronary revascularization (odds ratio, 0.48; 95% confidence interval, 0.25-0.92; P = .027) were independent predictors of stable sinus rhythm at 1 year after surgical intervention. At 48 months' follow-up, predictors for stable sinus rhythm were biatrial surgical approach and absence of preoperative permanent atrial fibrillation (odds ratio, 3.56; 95% confidence interval, 1.62-7.83; P < .002). Left atrial size (each millimeter) has a borderline statistical significance (odds ratio, 0.97; 95% confidence interval, 0.93-1.00; P = .065). Thromboembolic events were found to be associated with absence of stable sinus rhythm (P = .010, log-rank analysis). The achievement of stable sinus rhythm is a predictor of better survival and lower incidence of thromboembolic events. Predictors of stable sinus rhythm were smaller dimensions of the left atrium, biatrial approach, absence of preoperative permanent atrial fibrillation, and absence of concomitant coronary artery bypass grafting.

Diagnostic and prognostic implications of the World Health Organization classification of neuroendocrine tumors

Neuroendocrine differentiation of tumors is often difficult to establish. In the same manner, the evaluation of the prognostic role of neuroendocrine differentiation may constitute a relevant clinical problem. Although different classifications are used for neuroendocrine tumors (NET) of different origin, the last World Health Organization (WHO) classification of NET, originally proposed for gastroenteropancreatic tumors, has proved to be a practical tool to allow pathologists to uniform the diagnoses and re-classify these tumors into 3 main categories. The present study was carried out in order to evaluate diagnostic and prognostic implications of NET reclassification according to the last WHO classification of NET. Thirty-one tumors with an initial diagnosis referable to a NET achieved before 1999 were independently evaluated by 3 pathologists on the basis of the 2000 WHO classification of NET. Immunohistochemistry for panneuroendocrine markers and Ki-67 was also performed in all cases. Twelve, 14, and 4 tumors were respectively reclassified as well-differentiated NET, well-differentiated neuroendocrine carcinoma and poorly differentiated neuroendocrine carcinoma; 1 tumor was reclassified as mixed endocrine-exocrine tumor. Two or more neuroendocrine markers were expressed in all NET regardless of histotype, differentiation degree, and site of primary tumor. After revision, 10 of the 31 tumors under study (32%) changed histo-prognostic category when compared to the initial diagnosis. Ki-67 score was the best predictor of survival at the multivariate analysis. The WHO classification is suitable to accurately reclassify tumors with an initial diagnosis referable to a NET and to separate these tumors in 3 well-distinct histo-prognostic categories with relevant clinical implications. Ki-67 score seems to be a better predictor of survival than the degree of differentiation.

MGMT Promoter Methylation Status Predicts Survival in Pediatric Glioblastoma

Pediatric glioblastoma (pGBM) represents 15% of pediatric brain tumors with a 3‐year survival rate of &lt; 20%. Effective DNA repair is an important cellular mechanism for resistance to chemotherapy and radiation. The role of this mechanism in pGBM remains poorly understood. We evaluated the expression pattern of proteins (by immunohistochemistry) involved in the repair of DNA damage induced by alkylating agents, as well as, mismatch and base excision repairs including hMLH1, hMSH2 and PARP in fifteen pGBMs. MGMT promoter methylation was analyzed using methylation specific PCR and pyrosequencing. The relationship between DNA repair pathway alteration and survival was analyzed.MGMT promoter methylation was detected in 33% of tumors. Loss of hMLH1 and hMSH2 protein expression was seen in 47% and 53% of tumors, respectively. PARP expression was seen in 100% of pGBMs. hMLH1, hMSH2 and PARP expressions did not correlate with either event free survival or overall survival (p &gt; 0.05). MGMT promoter methylation correlated significantly with better overall survival (p = 0.035). We conclude that MGMT promoter methylation status is a predictor of better survival in treated pGBM.

Digoxin for the treatment of fetal congestive heart failure with sinus rhythm assessed by cardiovascular profile score

Objective. To evaluate the effects of digoxin on the progression of congestive heart failure (CHF), and to determine the best predictors of perinatal death in fetuses with sinus rhythm and CHF.Methods. This was a retrospective case series of fetuses with CHF treated with transplacental digoxin, evaluated at baseline (before treatment), weekly during treatment, and prior to death or delivery, using a 10-point cardiovascular profile score (CVPS) consisting of echocardiographic markers of cardiac dysfunction: cardiomegaly, valve insufficiency, hydrops, and abnormal venous and arterial Doppler flow profiles. Composite CVPS and component markers were compared before and after digoxin treatment by nonparametric testing and best predictors of perinatal survival assessed by regression analysis and receiver operating characteristics.Results. The overall mortality of the 28 subjects was 32%. First, last, and CVPS after 1 week of treatment predicted survival (odds ratio 2.34, 95% confidence interval 1.10–4.96) with a CVPS of ≥6 being the best predictor of survival (sensitivity 0.83, specificity 0.75). All fetuses that died had notching of the umbilical venous flow. CVPS increased from baseline during treatment (p = 0.003) in all subjects.Conclusions. The CVPS score is useful in assessing therapeutic effects of digoxin in the fetus with multiple etiologies for CHF. Further studies are needed to test the efficacy of digoxin in specific defects causing CHF.

Diagnosis of laryngeal carcinoma

DIAGNOSTICAL PROBLEMS OF LARYNGEAL CARCINOMA: Carcinoma of the larynx is still a prognostic serious disease associated with high mortality. Survival rates for these tumors vary and depend on the presence of early symptoms, anatomic accessibility and lymphatic supply. Despite advances in therapy and novel surgical and non-surgical approaches, early diagnosis remains the best predictor of survival. This article reviews the diagnosis for laryngeal carcinoma in an effort to heighten the clinical and endoscopic recognition of these lesions, providing also global overview of clinical conventional and recent endoscopic diagnostic tools for squamous cell type of carcinoma of the larynx. Screening of asymptomatic individuals would detect tumors at an early enough stage to patients' benefit. The progress in the elucidation of the molecular genetic changes in these tumors should soon bring novel diagnostic procedures into the clinical practise. The review higlights the important advances of endoscopic, radilogical and molecular methods in detection of the tumor which may help clinicians to diagnose tumors as early as possible. TNM staging, biopsy and histopathological grading remain the gold standard for diagnosis of laryngeal carcinoma. A great number of novel endoscopical methods are only supplementary tools to microlaryngoscopy. Some of the most significant biological markers might be integrated with the evaluation of behavioural factors, clinical and histopathological examinations for a new clinicomolecular approach to laryngeal cancer.

Parameters assessing neurological status in malignant glioma patients: prognostic value for survival and relapse-free time

Malignant gliomas are the commonest primary brain tumours in adults and harbour a dismal prognosis. So far, established parameters with predictive significance for prognosis do not include the neurological functional assessment of patients. The aim of this study was to investigate the prognostic value of parameters assessing neurological status in malignant glioma patients for outcome and survival. Evaluation of neurological status included the Sawaya Functional Grade (SFG) and the Neurological Performance Scale (NPS). Moreover, the Karnofsky Performance Status (KPS), medical risk factors, extension of resection, postoperative complications, and the predictive value of these variables for outcome and survival were studied. For this purpose, we have analysed 110 consecutive patients with malignant gliomas who were treated at our institution. As expected, age (p <0.001), KPS (p = 0.003) and extent of resection (p <0.001) were good predictors of survival. Strikingly, SFG and NPS showed the highest significant correlation with survival (both p <0.0001) and, furthermore, they were the only predictors of the relapse-free time (p = 0.035 and p = 0.004, respectively). Our data strongly suggests that SFG and NPS accurately predict both survival and relapse-free time, which may add a valuable tool for tailoring individual therapy strategies.