A Palliative Prognostic Score for Terminally Ill Children and Adolescents With Cancer

Background. The loss of a child is considered the hardest moment in a parent`s life. Studies addressing length of survival under pediatric palliative care are rare. The aim of this study was to improve a survival prediction model for children in palliative care, as accurate information positively impacts parent and child preparation for palliative care. Procedure. Sixty-five children referred to a pediatric palliative care team were followed from August 2003 until December 2006. Variables investigated (also included in previous studies) were: diagnosis, home care provider, presence of anemia, and performance status score given by the home care provider. Clinical variables such as symptom number were also used to test the score`s ability to pre-validated using the above variables. The number of symptoms at transition to palliative care does not improve the score`s predictive ability. The sum of the single scores gives an overall score for each patient, dividing the population into three groups by probability of 60-day survival: Group A 80.0%, Group B 38.0%, and Group C 28.5% (P < 0.001). Conclusion. A pediatric palliative care score based on easily accessible variables is statistically significant in multivariate analysis. Factors that increase accuracy of life expectancy prediction enable adequate information to be given to patients and families, contributing to therapeutic decision-making issues. Pediatr Blood Cancer. 2010;55:1167-1171. (C) 2010 Wiley-Liss, Inc.

Evaluation of subclinical atherosclerosis by computed tomography coronary angiography and its association with risk factors in familial hypercholesterolemia

Background: Increasing age and cholesterol levels, male gender, and family history of early coronary heart disease (CHD) are associated with early onset of CHD in familial hypercholesterolemia (FH). Objective: Assess subclinical atherosclerosis by computed tomography coronary angiography (CTCA) and its association with clinical and laboratorial parameters in asymptomatic FH subjects. Methods: 102 FH subjects (36% male, 45 +/- 13 years, LDL-c 280 +/- 54 mg/dL) and 35 controls (40% male, 46 +/- 12 years, LDL-c 103 +/- 18 mg/dL) were submitted to CTCA. Plaques were divided into calcified, mixed and non-calcified; luminal stenosis was characterized as >50% obstruction. Results: FH had a greater atherosclerotic burden represented by higher number of patients with: plaques (48% vs. 14%, p = 0.0005), stenosis (19% vs. 3%, p = 0.015), segments with plaques (2.05 +/- 2.85 vs. 0.43 +/- 1.33, p = 0.0016) and calcium scores (55 perpendicular to 129 vs. 38 perpendicular to 140, p = 0.0028). After multivariate analysis, determinants of plaque presence were increasing age (OR = 2.06, for age change of 10 years, CI95%: 1.38-3.07, p < 0.001) and total cholesterol (OR = 1.86, for cholesterol change by 1 standard deviation, CI95%: 1.09-3.15, p = 0.027). Coronary calcium score was associated with the presence of stenosis (OR = 1.54; CI95%: 1.27-1.86, p < 0.001, for doubling the calcium score). Male gender was directly associated with the presence of non-calcified plaques (OR: 15.45, CI95% 1.72-138.23, p = 0.014) and inversely with calcified plaques (OR = 0.21, CI95%: 0.05-0.84, p = 0.027). Family history of early CHD was associated with the presence of mixed plaques (OR = 4.90, CI95%: 1.32-18.21, p = 0.018). Conclusions: Patients with FH had an increased burden of coronary atherosclerosis by CTCA. The burden of atherosclerosis and individual plaque subtypes differed with the presence of other associated risk factors, with age and cholesterol being most important. A coronary calcium score of zero ruled out obstructive disease in this higher risk population. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

APOE polymorphism is associated with lipid profile, but not with arterial stiffness in the general population

Background: Cardiovascular diseases (CVD) are the main cause of death and disability in developed countries. In most cases, the progress of CVD is influenced by environmental factors and multifactorial inheritance. The purpose of this study was to investigate the association between APOE genotypes, cardiovascular risk factors, and a noninvasive measure of arterial stiffness in the Brazilian population. Methods: A total of 1493 urban Brazilian individuals were randomly selected from the general population of the Vitoria City Metropolitan area. Genetic analysis of the APOE polymorphism was conducted by PCR-RFLP and pulse wave velocity analyzed with a noninvasive automatic device. Results: Age, gender, body mass index, triglycerides, creatinine, uric acid, blood glucose, blood pressure phenotypes were no different between epsilon 2, epsilon 3 and epsilon 4 alleles. The epsilon 4 allele was associated with higher total-cholesterol (p < 0.001), LDL-C (p < 0.001), total-cholesterol/HDL-C ratio (p < 0.001), LDL/HDL-C ratio (p < 0.001), lower HDL-C values (p < 0.001) and higher risk to obesity (OR = 1.358, 95% CI = 1.019-1.811) and hyperuricemia (OR = 1.748, 95% CI = 1.170-2.611). Nevertheless, pulse wave velocity (p = 0.66) measures were no different between genotypes. The significant association between APOE genotypes and lipid levels persisted after a 5-year follow-up interval, but no interaction between time and genotype was observed for lipids longitudinal behavior. Conclusion: The epsilon 4 allele of the APOE gene is associated with a worse lipid profile in the Brazilian urban population. In our relatively young sample, the observed effect of APOE genotype on lipid levels was not translated into significant effects in arterial wall stiffness.

AGE DOES NOT AFFECT EXERCISE INTENSITY PROGRESSION AMONG WOMEN

Ciolac, EG, Brech, GC, and Greve, JMD. Age does not affect exercise intensity progression among women. J Strength Cond Res 24(11): 3023-3031, 2010-It has been recommended that the intensity of exercise training (ET) should progress slowly with lower increments in older than in young people. However, scientific evidence supporting this recommendation is lacking. Our aim was to examine possible influences of age on exercise intensity progression in healthy women. Seventeen young (29.1 +/- 5.7 years) and 16 older women (64.5 +/- 4.5 years) underwent 13 weeks of ET consisting of cycle ergometry (CE, 65-75% of reserve heart rate), whole-body resistance exercise (RE, 60% of 1 repetition maximum [1RM]), and stretching. Muscle strength was assessed before and after ET by the 1RM. Cycle ergometry and RE workloads were recorded for each exercise session, and increases of 5-10% were made whenever adaptation occurred. Absolute muscle strength after ET improved (p < 0.001) in both groups, and there were no significant differences between groups. Relative exercise intensity progression was not significantly different between groups for RE (Pearson`s correlation = 0.98 +/- 0.01), but it was greater in older women for CE (p = 0.047). The ET was safe because no injuries or major muscle pain was observed in either group. These results suggest that healthy older women are capable of exercising and increasing exercise intensity in the same way as young women.

The Relationship between Intraocular Pressure Reduction and Rates of Progressive Visual Field Loss in Eyes with Optic Disc Hemorrhage

Purpose: To evaluate rates of visual field progression in eyes with optic disc hemorrhages and the effect of intraocular pressure (IOP) reduction on these rates. Design: Observational cohort study. Participants: The study included 510 eyes of 348 patients with glaucoma who were recruited from the Diagnostic Innovations in Glaucoma Study (DIGS) and followed for an average of 8.2 years. Methods: Eyes were followed annually with clinical examination, standard automated perimetry visual fields, and optic disc stereophotographs. The presence of optic disc hemorrhages was determined on the basis of masked evaluation of optic disc stereophotographs. Evaluation of rates of visual field change during follow-up was performed using the visual field index (VFI). Main Outcome Measures: The evaluation of the effect of optic disc hemorrhages on rates of visual field progression was performed using random coefficient models. Estimates of rates of change for individual eyes were obtained by best linear unbiased prediction (BLUP). Results: During follow-up, 97 (19%) of the eyes had at least 1 episode of disc hemorrhage. The overall rate of VFI change in eyes with hemorrhages was significantly faster than in eyes without hemorrhages (-0.88%/year vs. -0.38%/year, respectively, P < 0.001). The difference in rates of visual field loss pre- and post-hemorrhage was significantly related to the reduction of IOP in the post-hemorrhage period compared with the pre-hemorrhage period (r = -0.61; P < 0.001). Each 1 mmHg of IOP reduction was associated with a difference of 0.31%/year in the rate of VFI change. Conclusions: There was a beneficial effect of treatment in slowing rates of progressive visual field loss in eyes with optic disc hemorrhage. Further research should elucidate the reasons why some patients with hemorrhages respond well to IOP reduction and others seem to continue to progress despite a significant reduction in IOP levels. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2010; 117: 2061-2066 (C) 2010 by the American Academy of Ophthalmology.

Statins withdrawal, vascular complications, rebound effect and similitude

Hahnemann considered the secondary action of medicines to be a law of nature and reviewed the conditions under which it occurs. It is closely related to the rebound effects observed with many modern drugs. I review the evidence of the rebound effect of statins that support the similitude principle. In view of their indications in primary and secondary prevention of cardiovascular diseases, statins are widely prescribed. Besides reducing cholesterol biosynthesis, they provide vasculoprotective effects (pleiotropic effects), including improvement of endothelial function, increased nitric oxide bioavailability, antioxidant properties, inhibition of inflammatory and thrombogenic responses, stabilisation of atherosclerotic plaques, and others. Recent studies suggest that suspension of statin treatment leads to a rebound imparing of vascular function, and increasing morbidity and mortality in patients with vascular diseases. Similarly to other classes of modern palliative drugs, this rebound effect is the same as a secondary action or vital reaction described by Samuel Hahnemann, and used in homeopathy in a therapeutic sense. Homeopathy (2010) 99, 255-262.

Complete Clinical Response after Neoadjuvant Chemoradiation for Distal Rectal Cancer

Multimodality treatment of rectal cancer, with the combination of radiation therapy, chemotherapy, and surgery has become the preferred approach to locally advanced rectal cancer The use of neoadjuvant chemoradiation therapy (CRT) has resulted in reduced toxicity rates, significant tumor down-sizing and downstaging, better chance of sphincter preservation, and improved functional results A proportion of patients treated with neoadjuvant CRT may ultimately develop complete clinical response Management of these patients with complete clinical response remains controversial and approaches including radical resection, transanal local excision, and observation alone without immediate surgery have been proposed The use of strict selection criteria of patients after neoadjuvant CRT has resulted in excellent long-term results with no oncological compromise after observation alone in patients with complete clinical response Recurrences are detectable by clinical assessment and frequently amenable to salvage procedures

Influence of the Fibroblast Growth Factor Receptor 4 Expression and the G388R Functional Polymorphism on Cushing`s Disease Outcome

Context: Abnormal FGFR4 expression has been detected in pituitary tumors, especially in larger and invasive adenomas. In addition, the FGFR4 functional polymorphism G388R has been associated with poor outcome in several human malignancies. Then, we hypothesized that FGFR4 expression and genotype could be markers of adverse outcome of Cushing`s disease after transsphenoidal surgery. Objectives: The objective was to investigate whether there is an association between the postoperative outcome of Cushing`s disease (remission/recurrence) and the FGFR4 G388R genotype or the FGFR4 expression in corticotrophinomas. Design and Patients: Clinical, hormonal, and pathological data of 76 patients who underwent the first transsphenoidal surgery were retrospectively reviewed. All patients were genotyped for G388R polymorphism. FGFR4 expression was assessed by real-time PCR in 18 corticotrophinomas. Main Outcome Measures: The outcome measures included the FGFR4 G388R genotype and FGFR4 expression in postoperative remission and recurrence of Cushing`s disease. Results: Homozygosis for FGFR4 glycine (Gly(388)) allele was associated with reduced disease-free survival, in the univariate analysis (hazard ratio of 6.91; 95% confidence interval of 1.14-11.26; P = 0.028). Male gender (P = 0.036), lack of pathology confirmation (P = 0.009), and cortisol levels more than 2 mu g/dl in the early postoperative period (P < 0.001) were also significant predictors of Cushing`s disease recurrence in the univariate analysis. FGFR4 overexpression was found in 44% of the corticotrophinomas, and it was associated with lower postoperative remission rate (P = 0.009). Conclusions: Our data suggest that homozygosis for FGFR4 Gly(388) allele and FGFR4 overexpression are associated with higher frequency of postoperative recurrence and persistence of Cushing`s disease, respectively. (J Clin Endocrinol Metab 95: E271-E279, 2010)

(18)F-FDG PET After 2 Cycles of ABVD Predicts Event-Free Survival in Early and Advanced Hodgkin Lymphoma

Our objective was to assess the prognostic value of (18)F-FDG PET after 2 cycles of chemotherapy using doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in Hodgkin lymphoma (HL) patients overall and in subgroups of patients with early and advanced stages and with low and high risks according to the International Prognostic Score (IPS). Methods: One hundred fifteen patients with newly diagnosed HL were prospectively included in the study. All underwent standard ABVD therapy followed by consolidation radiotherapy in cases of bulky disease. After 2 cycles of ABVD, the patients were evaluated with PET (PET2). Prognostic analysis compared the 3-y event-free survival (EFS) rate to the PET2 results, clinical data, and IPS. Results: Of the 104 evaluated patients, 93 achieved complete remission after first-line therapy. During a median follow-up of 36 mo, relapse or disease progression was seen in 22 patients. Treatment failure was seen in 16 of the 30 PET2-positive patients and in only 6 of the 74 PET2-negative patients. PET2 was the only significant prognostic factor. The 3-y EFS was 53.4% for PET2-positive patients and 90.5% for PET2-negative ones (P < 0.001). When patients were categorized according to low or high IPS risk and according to early or advanced stage of disease, PET2 was also significantly associated with treatment outcome. Conclusion: PET2 is an accurate and independent predictor of EFS in HL. A negative interim (18)F-FDG PET result is highly predictive of treatment success in overall HL patients, as well as in subgroups with early or advanced-stage disease and with low or high IPS risk.

Effects of anti-TNF therapy on glucose metabolism in patients with ankylosing spondylitis, psoriatic arthritis or juvenile idiopathic arthritis

The objective of this study was to evaluate the influence of anti-tumor necrosis factor (anti-TNF) in juvenile idiopathic arthritis (DA), ankylosing spondylitis (AS) or psoriatic arthritis (PsA). Sixty-two patients were investigated: 7 DA; 37 AS; and 18 PsA. Caucasian race accounted for 79% and 29% were female. Mean age was 40.4 +/- 12.6years. None of the patients had a history of diabetes, and none had used oral hypoglycemic agents or insulin. Treatment was with adalimumab, infliximab and etanercept. Glucose, inflammatory markers and prednisone dose were assessed at baseline, as well as after three and six months of treatment. The mean erythrocyte sedimentation rate was significantly lower at three months and six months than at baseline (13.7 +/- 18.0 and 18 +/- 22.5 vs. 27.9 +/- 23.4 mm; p = 0.001). At baseline, three months and six months, we found the following: mean C-reactive protein levels were comparable (22.1 +/- 22.7, 14.5 +/- 30.7 and 16.0 +/- 23.8 mg/L, respectively; p = 0.26); mean glucose levels remained unchanged (90.8 +/- 22.2 mg/dl, 89.5 +/- 14.6 mg/dl and 89.8 +/- 13.6 mg/dl, respectively; p = 0.91); and mean prednisone doses were low and stable (3.9 +/- 4.9 mg/day, 3.7 +/- 4.8 mg/day and 2.6 +/- 4.0 mg/day, respectively; p = 0.23). During the first six months of treatment, anti-TNF therapy does not seem to influence glucose metabolism in JIA, AS or PsA. (C) 2010 The International Association for Biologicals. Published by Elsevier Ltd. All rights reserved.