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Aims Conditional survival is defined as the probability of surviving an additional number of years beyond that already survived. The aim of this study was to estimate conditional survival in heart failure patients after coronary artery bypass grafting (CABG). Methods Heart failure patients with multivessel coronary artery disease undergoing first-time, isolated CABG between 1992 and 2011 were included in this study. Conditional survival estimates were computed for 1, 5, and 10 years after already surviving 0.5, 1, 2, 3, 4, and 5 years. Results Compared with traditional survival estimates, conditional survival was consistently higher at all time periods. The overall 2-year adjusted survival estimate was 84% compared with the 1-year conditional survival rate of 95% for 1-year survivors. Similarly, the overall 10-year adjusted survival rate was 36% from the time of surgery compared with the 5-year conditional survival of 54% for patients who had survived 5 years. Conclusion Conditional survival provides a more accurate estimate of long-term survival in heart failure patients who have already survived for a certain amount of time after CABG. This information is useful for patients and physicians who manage their long-term care.

Background: The effect of race on long-term survival of patients undergoing elective and nonelective coronary artery bypass grafting (CABG) is currently unknown. The purpose of this study was to compare long-term survival between black and white CABG patients by operative status.Methods: Long-term survival of black versus white patients undergoing elective and nonelective CABG procedures between 1992 and 2011 was compared. Survival probabilities were computed using the Kaplan-Meier product-limit method and stratified by race. Hazard ratios (HR) and 95% confidence intervals (CI) were computed using a Cox regression model.Results: A total of 13,774 patients were included in this study. The median follow-up time for study participants was 8.2 years. Black patients undergoing elective CABG died sooner than whites (adjusted HR = 1.4, 95% CI = 1.2�1.5). Survival was similar between blacks and whites in the nonelective population (adjusted HR = 1.0, 95% CI = 0.96�1.1).Conclusions: Black race was a statistically significant predictor of long-term survival after elective but not nonelective CABG.

The two most commonly performed procedures for bariatric surgery include Roux-en-Y gastric bypass (RYGB) and adjustable gastric banding (AGB). While many studies have commented on short-term, postoperative outcomes of these procedures, few have reported long-term data. The purpose of this study was to compare long-term, postoperative outcomes between RYGB and AGB.This was a retrospective, cohort comparing all patients undergoing RYGB or AGB at our institution, from 01/1998 to 08/2012. Patients were followed at 1-, 3-, and 5-year intervals. Adjusted, Cox proportional hazard regression and mixed effects repeated measures modeling were performed to generate cure ratios (CR) and 95 % confidence intervals (CI).Two thousand four hundred twenty bariatric surgery patients (380 AGB, 2,040 RYGB) were identified by CPT code. Median (range) follow-up for patients was 3 (1-5) years. Preoperatively, RYGB patients were significantly younger, more obese, had higher hemoglobin A1c, and less often suffered from hypertension (HTN), dyslipidemia, and asthma as compared to AGB patients. Postoperatively, RYGB patients experienced significantly longer operating room times, higher incidences of intensive care unit admissions, longer hospital lengths of stay, and increased incidence of small bowel obstruction compared to AGB patients. After adjusting for statistically significant and clinically relevant factors [e.g., age, gender, body mass index, degenerative joint disease (DJD), diabetes, HTN, dyslipidemia, heart disease, apnea, and asthma], RYGB was independently associated with a significantly greater percentage of total body weight loss (p = 0.0065) and greater CR (95 % CI) regarding gastroesophageal reflux disease [2.1(1.4-3.0)], DJD [3.4(2.0-5.6)], diabetes [3.4(2.2-5.4)], apnea [3.1(1.9-5.3)], HTN [5.5(3.4-8.8)], and dyslipidemia [6.3(3.5-11)] compared to AGB.Our results support previous studies that have observed a greater weight loss associated with RYGB as compared to AGB and provide further evidence toward the long-term sustainability of this weight loss. Additionally, RYGB appears to result in a greater reduction of medical comorbidity.

Objective Improved pathophysiologic insight and prognostic information regarding in-hospital risk of mortality among stroke patients admitted to an intensive care unit. Design Retrospective analysis. Setting Neurology/neurosurgery intensive care unit in a tertiary care university medical center. Patients A total of 63 consecutive ischemic stroke patients. Interventions Patients were classified according to in-hospital mortality. Charts were reviewed to retrospectively generate an admitting Acute Physiology and Chronic Health Evaluation (APACHE) II score. The APACHE II score and its individual components were assessed for predicting subsequent death. Measurements and main results Of 63 patients, 13 died and 50 survived to either discharge or surgical intervention. The mean admitting APACHE II score of survivors (6.9) was lower than that of patients who died (17.2; p or =9. A score > or =18 was uniformly associated with fatal outcome (n = 8). Univariate analysis identified APACHE II total score, Glasgow Coma Scale score, temperature, pH, and white blood cell count as significant predictors of death. Among multivariate logistic regression models examining the components of the APACHE II score, the model containing white blood cells, temperature, and creatinine best predicted death. Conclusions Several features of the APACHE II score are associated with risk of death in this patient population. The findings suggest particular physiologic derangements that are associated with, and may contribute to, increased mortality in critically ill patients with acute ischemic stroke.

To examine prognostic indicators in aggressive fibromatoses that may be used to optimize case-specific management strategy.One hundred and seven fibromatoses presenting between 1971 and 1992 were analyzed. The following treatment modalities were utilized: (a) surgery alone for 51 tumors; (b) radiation alone for 15 tumors; and (c) radiation and surgery (combined modality) for 41 tumors. Outcome analysis was based on 5-year actuarial local control rates.Control rates among surgery, radiation therapy, and combined modality groups were 69%, 93%, and 72%. Multivariate analysis identified age18 years, recurrent disease, positive surgical margins, and treatment with surgery alone as predictors for failure. Patients treated with surgery alone had control rates of 50% (3 of 6) for gross residual, 56% for microscopically positive margins, and 77% for negative margins. Radiation and surgery resulted in rates of 59% for gross residual, 78% for microscopically positive margins, and 100% (6 of 6) for negative margins. For recurrent vs. primary tumors, control was achieved in 48% vs. 77%, 90% vs. 100% (5 of 5), and 67% vs. 79% in the Surgery, Radiation, and Combined modality Groups, respectively. Patients presenting with multiple disease sites tended to have aggressive disease. A radiation dose-control relation to60 Gy was seen in patients with unresected or gross residual disease. Of the patients, 23 with disease involving the plantar region had a control rate of 62%, with significantly worse outcomes in children.These results are consistent with those found in the relevant literature. They support primary resection with negative margins when feasible. Radiation is a highly effective alternative in situations where surgery would result in major functional or cosmetic defects. When negative surgical margins are not achieved in recurrent tumors, radiation is recommended. Perioperative radiation should be considered in other high-risk groups (recurrent disease, positive margins, and plantar tumors in young patients). Doses of 60-65 Gy for gross disease and 50-60 Gy for microscopic residual are recommended. Observation may be considered for primary tumors with disease remaining in situ when they are located such that progression would not cause significant morbidity. Although plantar lesions in children may represent a group at high risk for recurrence or aggressive behavior, the greater potential for radiation-induced morbidity in this group must also temper its use. Given the inconsistent nature and treatment response of this tumor, it is fundamental that treatment recommendations should be made based on the risk:benefit analysis for the individual patient, dependent on tumor characteristics and location, as well as patient characteristics and preferences.

Purpose: To determine the temporal lobe (TL) damage rate in 96 patients treated with high-dose proton and photon irradiation for chordomas and chondrosarcomas of the base of the skull. Methods and Materials: The records of 96 consecutive patients treated at Massachusetts General Hospital (MGH) and Harvard Cyclotron Laboratory (HCL) between June 1984 and 1993, for chordomas and chondrosarcomas of the base of the skull were reviewed. All the patients had undergone some degree of resection of the tumor prior to radiation therapy. Seventy-five patients were classified as "primary tumors" and 21 as recurrent or regrowing tumors after one or more surgical procedures. All the patients were randomized to receive 66.6 or 72 cobalt Gray equivalent (CGE) on a prospective dose-searching study by proton and photon irradiation (Radiation Therapy Oncology Group #85-26) with conventional fractionation (1.8 CGE/day, 5 fractions/week). All treatments were planned using the three-dimensional (3D) planning system developed at the Massachusetts General Hospital, and the dose was delivered using opposed lateral fields for the photon component and a noncoplanar isocentric technique for the proton component. Clinical symptoms of TL damage were classified into 4 grades. Computerized tomography (CT) and magnetic resonance imaging (MRI) scans were evaluated for white matter changes. Abnormalities associated with persistent or recurrent tumor were distinguished from radiation-induced changes. TLs were delineated on the original scans of the 10 patients with damage and those of a group of 33 patients with no clinical or MRI evidence of injury. Dose distributions were calculated and dose–volume histograms were obtained for these patients. Results: Of the patients, 10 developed TL damage, with bilateral injury in 2 and unilateral injury in 8. The cumulative TL damage incidence at 2 and 5 years was 7.6 and 13.2%, respectively. The MRI areas suggestive of TL damage were always separated from the tumor bed. Symptoms were severe to moderate in 8 patients. Several baseline factors, tumor- or host-related, were analyzed to evaluate their predictivity for TL damage: age, gender, tumor site, histology, type of presentation, type and number of surgical procedures, primary tumor volume, prescribed dose, normal tissue involvement, and volume of TL receiving doses ranging between 10 and 50 CGE or more. Only gender, in a univariate analysis (log rank) was a significant predictor of damage (0.0155), with male patients being at significantly higher risk of TL injury. In a stepwise Cox regression that included gender as a variable, no other baseline variable improved the prediction of damage. Conclusions: The 2- and 5-year cumulative TL damage rates were 7.6 and 13.2%, respectively. Despite the different TL damage rates related to age, tumor volume, number of surgical procedures prior to radiation therapy, and prescribed doses to the tumor, only gender was a significant predictor of damage ( p = 0.0155) using a univariate (log rank) test. Chordomas and chondrosarcomas of the base of the skull may represent an interesting model to evaluate the TL damage rates because of their extradural origin, displacing the white matter instead of infiltrating it as gliomas do, because of their longer local recurrence-free survival other than gliomas and other brain tumors and because of the high doses of irradiation delivered to the target volume to obtain local control.

Background Onset of postoperative atrial fibrillation ( POAF ) is a common and costly complication of heart surgery despite major improvements in surgical technique and quality of patient care. The etiology of POAF , and the ability of clinicians to identify and therapeutically target high‐risk patients, remains elusive. Methods and Results Myocardial tissue dissected from right atrial appendage ( RAA ) was obtained from 244 patients undergoing cardiac surgery. Reactive oxygen species ( ROS ) generation from multiple sources was assessed in this tissue, along with total glutathione ( GSH t) and its related enzymes GSH ‐peroxidase ( GP x) and GSH ‐reductase ( GR ). Monoamine oxidase ( MAO ) and NADPH oxidase were observed to generate ROS at rates 10‐fold greater than intact, coupled mitochondria. POAF risk was significantly associated with MAO activity (Quartile 1 [Q1]: adjusted relative risk [ ARR ]=1.0; Q2: ARR =1.8, 95% confidence interval [ CI ]=0.84 to 4.0; Q3: ARR =2.1, 95% CI =0.99 to 4.3; Q4: ARR =3.8, 95% CI =1.9 to 7.5; adjusted P trend =0.009). In contrast, myocardial GSH t was inversely associated with POAF (Quartile 1 [Q1]: adjusted relative risk [ ARR ]=1.0; Q2: ARR =0.93, 95% confidence interval [ CI ]=0.60 to 1.4; Q3: ARR =0.62, 95% CI =0.36 to 1.1; Q4: ARR =0.56, 95% CI =0.34 to 0.93; adjusted P trend =0.014). GP x also was significantly associated with POAF ; however, a linear trend for risk was not observed across increasing levels of the enzyme. GR was not associated with POAF risk. Conclusions Our results show that MAO is an important determinant of redox balance in human atrial myocardium, and that this enzyme, in addition to GSH t and GP x, is associated with an increased risk for POAF . Further investigation is needed to validate MAO as a predictive biomarker for POAF , and to explore this enzyme's potential role in arrhythmogenesis.

Animal viruses and bacteria are ubiquitous in the environment. However, little is known about their mode of transmission and etiologic role in human cancers, especially among high-risk groups (e.g., farmers, veterinarians, poultry plant workers, pet owners, and infants). Many factors may affect the survival, transmissibility, and carcinogenicity of these agents, depending on the animal-host environment, hygiene practices, climate, travel, herd immunity, and cultural differences in food consumption and preparation. Seasonal variations in immune function also may increase host susceptibility at certain times of the year. The lack of objective measures, inconsistent study designs, and sources of epidemiologic bias (e.g., residual confounding, recall bias, and non-randomized patient selection) are some of the factors that complicate a clear understanding of this subject.

The purpose of this study was to determine whether African-American lung cancer patients are diagnosed at a later stage than white patients, regardless of insurance type. The relationship between race and stage at diagnosis by insurance type was assessed using a Poisson regression model, with relative risk as the measure of association. The setting of the study was a large tertiary care cancer center located in the southeastern United States. Patients who were diagnosed with lung cancer between 2001 and 2010 were included in the study. A total of 717 (31%) African-American and 1,634 (69%) white lung cancer patients were treated at our facility during the study period. Adjusting for age, sex, and smoking-related histology, African-American patients were diagnosed at a statistically significant later stage (III/IV versus I/II) than whites for all insurance types, with the exception of Medicaid. Our results suggest that equivalent insurance coverage may not ensure equal presentation of stage between African-American and white lung cancer patients. Future research is needed to determine whether other factors such as treatment delays, suboptimal preventive care, inappropriate specialist referral, community segregation, and a lack of patient trust in health care providers may explain the continuing racial disparities observed in the current study.

Background and Purpose Lowering of blood pressure can adversely affect ischemic symptoms in acute stroke. The aim of our study was to determine whether induced hypertension in stroke is safe and to examine its effects on neurological deficits in patients presenting with acute cerebral ischemia. Methods We retrospectively reviewed all patients admitted to our neurological intensive care unit with the diagnosis of ischemic stroke over a 2.5-year period. Thirty-three patients were not given a pressor agent (Ph− group), while 30 were treated with phenylephrine (Ph+ group) in an attempt to improve cerebral perfusion. Results Baseline characteristics showed few differences between the Ph+ and Ph− groups. Intracerebral hemorrhage, brain edema, cardiac morbidity, and mortality were not increased in the Ph+ group. In 10 of 30 Ph+ patients, a systolic blood pressure threshold was identified below which ischemic deficits worsened and above which deficits improved. The mean threshold was 156 mm Hg (range, 120 to 190 mm Hg). The mean number of stenotic/occluded cerebral arteries was greater in those Ph+ patients with an identified clinical blood pressure threshold (mean, 2.1 per patient) than in Ph+ patients without a threshold (mean, 1.2 per patient; P Conclusions The results suggest that careful use of phenylephrine-induced hypertension is not associated with an increase in morbidity or mortality in acute stroke. Although based on a retrospective analysis of clinical practice, this report suggests that a subset of patients, particularly those with multiple stenosis of cerebral arteries, may improve neurologically upon elevation of the blood pressure.

The grading of glial tumors has traditionally relied on histological assessment, but the distinction between grade II and grade III gliomas is still a subject of debate. We examined the value of the monoclonal antibody MIB-1 (Ki-67) labeling index (LI) in the differentiation between grade II and grade III gliomas by either the 1993 WHO grading scheme or the St. Anne-Mayo grading scale. The MIB-1 Li in the most densely labeled areas from 80 diffuse cerebral hemispheric gliomas was determined. The tumors included 16 grade II, 31 grade III and 33 grade IV gliomas by the WHO scale. The mean LIs (%) were 0.88 +/- 0.29 for grade II, 8.75 +/- 1.71 for grade III, and 9.12 +/- 1.55 for grade IV gliomas. Analysis of variance indicated a significant difference in mean LIs between grades II and III and grades II and IV (por = 0.0001), but not between grades III and IV. Seven tumors were classified differently by the 2 systems (grade III by WHO, but grade 2 by St. Anne-Mayo), and all had MIB-1 LI over 3%. Univariate analysis showed that MIB-1 LI with a cut-off point at 1.5% was a significant prognostic factor (por = 0.0005). High tumor grade (WHO, por = 0.0002; St. Anne-Mayo, por = 0.0006) and patient age50 (por = 0.0001) were also significant factors for shorter survival. Using Cox Regression Multivariate Analysis, MIB-1 LI1.5% was a significant independent predictor of shorter disease survival when paired with tumor grade (por = 0.032), patient age (por = 0.0065), or gender (por = 0.0007). We conclude that the MIB-1 immunoreactivity is useful in distinguishing grade II from grade III gliomas, and maybe more sensitive in assigning aggressive gliomas to grade III than the St. Anne-Mayo grading system.

Hintergrund Vorliegender Beitrag wertet die Erfahrungen des Massachusetts General Hospital in Boston mit der Behandlung von Weichteilsarkomen des Kopf-Hals-Bereichs beim Erwachsenen aus. Sie sind bereits in ausfuhrlicher Form dargestellt worden [17].

Bitter Melon (Momordica charantia) is a widely used traditional remedy for hyperglycemia. While the medicinal properties of this plant have been studied extensively using in vitro and animal models, the clinical efficacy and safety in humans is largely unknown. This review discusses the benefits and limitations of bitter melon supplementation in the context of epidemic levels of insulin resistance and pre-diabetes throughout the world.

Author(s): Sharma, Rachna; Efird, Jimmy T; Chein, Aung; Holly, Elizabeth A; Krajden, Mel; Berry, J Michael; Darragh, Teresa M; Jay, Naomi; Palefsky, Joel M | Abstract: ObjectiveHuman papillomavirus (HPV) vaccination is routinely recommended in HIV-positive men who have sex with men (MSM) aged ≤ 26 years. Levels of previous HPV exposure in older HIV-positive MSM are assumed to be too high to warrant routine HPV vaccination. However, little is known about the prevalence of and risk factors for neutralizing antibody seropositivity to HPV-16 or HPV-18, a key measure of previous exposure to these types.MethodsCross-sectional analysis of baseline visit for 296 HIV-positive MSM participating in a prospective cohort study of anal squamous intraepithelial lesions at a university-based research clinic. Participants completed a questionnaire detailing behaviors and medical history. Phlebotomy, anal cytology, HPV DNA testing with quantitation, and high-resolution anoscopy with biopsy were performed. A pseudovirion-based neutralizing antibody assay was used to measure HPV-16 and HPV-18 neutralizing antibodies.ResultsOne hundred thirty-two of 296 (45%) men were HPV-16 seropositive and 141 of 296 (48%) were HPV-18 seropositive. One hundred seventy-five of 296 (59%) of the men were positive for HPV-16 antibodies or DNA and 167 of 296 (56%) were positive for HPV-18 antibodies or DNA. In multivariable analysis, HPV-16 seropositivity did not correlate with age, years of HIV positivity, CD4 level, or HIV viral load. Significant risk factors included HPV-16 DNA positivity with higher DNA levels (ptrend l 0.001) and higher number of receptive sexual partners in the last year (ptrend = 0.012).ConclusionsA high proportion of HIV-positive MSM aged g26 years are DNA negative and seronegative to HPV-16 and HPV-18 even when using a sensitive pseudovirion-based neutralizing antibody assay. Prospective studies are needed to determine the clinical- and cost-effectiveness of HPV vaccination in HIV-positive MSM aged g26 years.

It is known that lung cancer incidence and mortality rate are higher in African Americans (AA) than whites. In Eastern North Carolina, there is a higher percentage of AA population than the national average (30.2% vs. 12.4%) and a higher incidence of lung cancer in this region. We investigated demography and survival of lung cancer patients diagnosed and treated in a single institution.The study includes 2351 patients diagnosed with lung cancer between 2001 and 2010 at East Carolina University. AA and whites were compared by age, sex, race, stage, histology, smoking history and insurance information using chi-square analyses. Patient survival was modeled using Cox proportional hazards regression (SAS version 9.2).The distribution of lung cancer was 70% in whites and 30% in AA. The proportion of AA and whites differed significantly for age, sex, histology, stage, and insurance. Patients aged70 (p0.0001) and 51-70 (p = 0.0064) died sooner than those ≤ 50 years old. Compared with squamous cell, SCLC had inferior survival (HR = 2.0, 95% CI = 1.7-2.3). Privately insured patients survived longer than those with medicare (p0.0001), medicaid (p = 0.0009), or no insurance (p0.0001). The survival disadvantage for medicaid (p = 0.0076) and no insurance (p = 0.0033) persisted on multivariable analysis. Race was not a significant predictor of survival on multivariable analysis (p = 0.66).This is one of the largest lung cancer patient populations from a single institution showing demographic differences between the two races with similar survival outcome. Age, histology and type of insurance were strong predictors of survival outcome. Older age, small cell histology and medicaid and no insurance had significantly shorter overall survival.

Postoperative atrial fibrillation (POAF) is a known predictor of in-hospital morbidity and short-term survival after coronary artery bypass grafting (CABG). The impact of race and long-term survival has not been examined in this population. We aimed to examine the influence of these factors on long-term survival in patients undergoing CABG.Patients undergoing first-time, isolated CABG between 1992 and 2011 were included in this study. Long-term survival was compared in patients with and without POAF and stratified by race. Hazard ratios (HR) and 95% confidence intervals (CI) were computed using a Cox regression model.A total of 2,907 (22%) patients developed POAF (black n=370; white n=2,537) following CABG (N=13,165). Median follow-up for study participants was 8.2 years. Long-term survival after CABG differed by POAF status and race (no POAF: HR=1.0; white POAF: adjusted HR=1.1, 95% CI=1.06-1.2; black POAF: adjusted HR=1.4, 95% CI=1.2-1.6; pTrend=0.0002). lack POAF patients also died sooner after surgery than their white counterparts (adjusted HR=1.2, 95% CI=1.02-1.4).Black race was a statistically significant predictor of decreased survival among POAF patients after CABG. This finding provides useful outcome information for surgeons and their patients.

Author(s): Hessol, Nancy A; Holly, Elizabeth A; Efird, Jimmy T; Minkoff, Howard; Weber, Kathleen M; Darragh, Teresa M; Burk, Robert D; Strickler, Howard D; Greenblatt, Ruth M; Palefsky, Joel M | Abstract: ObjectiveTo assess factors associated with concomitant anal and cervical human papillomavirus (HPV) infections in HIV-infected and at-risk women.DesignA study nested within the Women's Interagency HIV Study (WIHS), a multicenter longitudinal study of HIV-1 infection in women conducted in six centers within the United States.MethodsFour hundred and seventy HIV-infected and 185 HIV-uninfected WIHS participants were interviewed and examined with anal and cervical cytology testing. Exfoliated cervical and anal specimens were assessed for HPV using PCR and type-specific HPV testing. Women with abnormal cytologic results had colposcopy or anoscopy-guided biopsy of visible lesions. Logistic regression analyses were performed and odds ratios (ORs) measured the association for concomitant anal and cervical HPV infection.ResultsOne hundred and sixty-three (42%) HIV-infected women had detectable anal and cervical HPV infection compared with 12 (8%) of the HIV-uninfected women (P l 0.001). HIV-infected women were more likely to have the same human papillomavirus (HPV) genotype in the anus and cervix than HIV-uninfected women (18 vs. 3%, P l 0.001). This was true for both oncogenic (9 vs. 2%, P = 0.003) and nononcogenic (12 vs. 1%, P l 0.001) HPV types. In multivariable analysis, the strongest factor associated with both oncogenic and nononcogenic concomitant HPV infection was being HIV-infected (OR = 4.6 and OR = 16.9, respectively). In multivariable analysis of HIV-infected women, CD4 cell count of less than 200 was the strongest factor associated with concomitant oncogenic (OR = 4.2) and nononcogenic (OR = 16.5) HPV infection.ConclusionHIV-infected women, particularly those women with low CD4 cell counts, may be good candidates for HPV screening and monitoring for both cervical and anal disease.

Cardiovascular disease is the leading cause of morbidity and mortality in patients on hemodialysis. To our knowledge, no studies have examined long-term outcomes of hemodialysis patients following coronary artery bypass grafting (CABG) in a predominately rural, low-income, and racially dichotomous population.Long-term survival of hemodialysis patients undergoing non-emergent, isolated CABG was compared with non-hemodialysis patients. Survival probabilities were computed using the Kaplan-Meier product limit method and stratified by hemodialysis. Hazard ratios (HR) and 95% confidence intervals (95%CI) were computed using a Cox regression model.Hemodialysis patients (n=220) had shorter long-term survival than non-hemodialysis patients (median survival=3.3 versus 14 years, p0.0001). The survival difference remained statistically significant after adjusting for clinically relevant variables (HR=5.2, 95%CI=4.4-6.2).Hemodialysis patients had significantly shorter long-term survival compared with non-hemodialysis patients after CABG. Further research is needed to address the cost and policy implications of our findings, especially among priority populations.

Several randomized control trials have reported conflicting results concerning mortality between CABG and PCI. The purpose of this study was to conduct a meta-analysis of recent retrospective studies examining the long-term mortality of patients with multi-vessel coronary artery disease undergoing

Article abstract-Chronic lymphocytic leukemia is the most common human leukemia but infrequently causes neurologic symptoms. We have reviewed all previously reported cases of chronic lymphocytic leukemia in the CNS along with three new cases; one patient was diagnosed antemortem and treated with immediate improvement and 4-year survival. In addition, we reviewed all autopsy cases since 1972 and available lumbar puncture data on patients with chronic lymphocytic leukemia admitted to the Massachusetts General Hospital. Invasion of the CNS by chronic lymphocytic leukemia often leads to confusional state, meningitis with cranial nerve abnormalities, optic neuropathy, or cerebellar dysfunction. Lumbar puncture shows a lymphocytosis consisting of monoclonal B cells, but CSF cytology studies are of limited value in establishing the diagnosis. Long-term survival may be related to the stage of chronic lymphocytic leukemia at the time of CNS disease and may be associated with intrathecal chemotherapy. A mild, asymptomatic infiltration of the brain, frequently noted in late-stage chronic lymphocytic leukemia in autopsy series, may explain the CSF lymphocytosis in some patients with late-stage chronic lymphocytic leukemia.NEUROLOGY 1996;46: 19-25

Background: Previous studies examining the influence of prior percutaneous coronary intervention (PCI) on longterm survival after coronary artery bypass grafting (CABG) have reported conflicting results. The purpose of this study was to further examine the influence of prior PCI on long-term survival after CABG at a large tertiary referral heart institute. Methods: Long-term survival between 1992 and 2011 was compared in non-emergent CABG cases with and without prior PCI. Hazard ratios (HR) and 95% confidence intervals (CI) were computed using a Cox regression model. Results: A total of 2532 (19%) patients had prior PCI before CABG (n = 13,354). The median follow-up for study participants was 8.1 years. The median survival for patients with and without prior PCI was 15 years and 14 years, respectively (p < 0.0001). Long-term survival was similar between patients with and without prior PCI after adjusting for age, sex, race, hypertension, coronary artery disease severity, congestive heart failure, and prior stroke (adjusted HR = 0.99, 95%CI = 0.91–1.06). Conclusion: Findings from outcomes research are important in the planning of appropriate postoperative patient care. Our study provides additional evidence that prior PCI is not a significant predictor of long-term survival after CABG.

Survival paradoxes are commonly observed in the literature. This phenomenon describes the association of certain risk factors with negative outcomes in the general population and the opposite effect in certain subpopu-lations and vice versa. Overall, the field is poorly understood. The counter-intuitive findings reported in the literature have contributed to confusion among clinicians regarding the appropriate treatment of conventional risk factors in patients with chronic diseases. Below we review two such paradoxes in kidney and cardiovascular disease epidemiology and discuss possible explanations of these findings.

Background Although peripheral arterial disease (PAD) is more prevalent among blacks, the effect of race on long-term survival after coronary artery bypass grafting (CABG) has not been examined in this population. Methods A retrospective cohort study was conducted of CABG patients between 1992 and 2011. Long-term survival was compared in patients with and without PAD and stratified by race. Hazard ratios (HR) and 95% confidence intervals were computed using a Cox regression model. Results Of 13,053 patients who underwent CABG, 1,501 (11%) had PAD, comprising 311 blacks and 1,190 whites. Median follow-up was 8.3 years. Long-term survival differed by race (no PAD: HR, 1.0; white PAD: adjusted HR, 1.5, 95% confidence interval, 1.4 to 1.6; black PAD: adjusted HR, 2.1, 95% confidence interval, 1.8 to 2.5; p Conclusions Risk of death after CABG was comparatively higher among black PAD patients. This finding provides useful outcome information for surgeons and their patients.

Maintaining the Benefit of Cardiovascular Disease Prevention Programs: The Challenge for Future Generations Cardiovascular diseases (CVD) account for 1 in every 3 deaths in the United States at an annual cost of $149 billion dollars or 17% of total medical expenditure. Over the next 20 years, the prevalence of CVD will increase by 10% with a 3-fold increase in cost. CVD has emerged as a leading cause for mortality in both males and females in the United States.

Pulmonary Hypertension in Patients Undergoing Kidney Transplant - A Single Center Experience Pulmonary hypertension (PH) is a fatal disease with a high mortality rate. It has also been found to increase perioperative complications including persistent post-operative hypoxia, right ventricular failure and coronary ischemia. Reich and colleagues observed that a mean pulmonary artery pressure >30 mm Hg was a significant independent predictor of post-operative mortality in over 2000 patients undergoing cardiopulmonary bypass.

Acute Right Ventricular Failure and Pulmonary Hypertension Secondary to Acute on Chronic Pulmonary Thromboembolic Disease Pulmonary embolism is a potentially correctable cause of Pulmonary Hypertension (PH). The right ventricle is susceptible to failure with acute elevations in afterload. Without intervention, the rate of survival is low and proportional to the degree of PH. Pulmonary thromboendarterectomy is considered in symptomatic patients who have hemodynamic or ventilatory impairment at rest or with exercise.

The introduction of the information age has created new opportunities for data collection, processing, and representation in the field of cancer research. Advances in bioinformatics, automated data retrieval systems, and data storage have improved data accessibility and the ability to make critical decisions based on the analyses of often complex and multivariable data. The challenge remains to condense and filter this data in such a fashion that it is readily interpretable to trained scientists, clinicians, the general public, and funding agencies (i.e., individuals with the most to gain from the information but with the least amount of time to interpret the data). These points are especially important if one’s results are to be translated into practical application and the solicitation of future research support. The ultimate goal is to display information as simply as possible without losing the significant meaning and interpretation of the results.

Women in Cardiovascular Clinical Trials Between 1980 and 2000, the age-adjusted death rate due to coronary heart disease (CHD) decreased by 48%. The optimization of medical therapies (OMT) and revascularization procedures such as percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) has accounted for 50% of the decline. While mortality rates for CHD have not declined equally for men and women, recent randomized clinical trials have not addressed gender differences regarding the efficacy of therapeutic interventions. Historically, women have been underrepresented in clinical trials of cardiovascular disease.

Purpose: To determine the patterns of failure and outcome following relapse of chordomas of the base of skull and cervical spine. Methods and Materials: Between November 1975 and October 1993, 204 patients were treated for chordoma of the base of skull or cervical spine, of which 63 have developed relapse. These 63 patients constitute the main focus of this study. Forty-five patients presented with base of skull and 18 with cervical spine tumors. All patients received combined proton and photon beam radiation. The median prescribed dose was 70.1 cobalt-Gray equivalent (CGE) (range 66.6–77.4). There were 25 males and 38 females, with a median age of 41 years (range 7–66). Median follow-up was 54 months (range 8–158). Results: Sixty-three of the 204 patients treated (31%) had treatment failure. Among the 63 patients who relapsed, 60 (95%) experienced local recurrence, and in 49 patients (78%), this was the only site of failure. Two of 63 patients (3%) developed regional lymph node relapse and 3 of 63 (5%) developed surgical pathway recurrence (1 left neck, 1 palate and 1 nasal cavity). Thirteen of 204 patients relapsed in distant sites, accounting for 20% (13 of 63) of all patients with recurrence in this series. The most common metastic sites were lungs and bones presenting in 7 of 13 and 6 of 13 patients, respectively. Only 2 of 13 patients failed with isolated distant metastasis. The actuarial 3- and 5-year survival rates after local relapse (60 patients) were 44 and 5%, respectively. Following distant failure (13 patients), the 3- and 5-year survival rates were 25 and 12%, respectively. After any relapse (63 patients) the corresponding survival rates were 43 and 7%. Following local relapse, 49 of 60 patients underwent salvage therapy consisting of subtotal resection in most patients (46 of 49). The remaining 11 of 60 patients received supportive care only. Salvage therapy resulted in stable or improved status without subsequent disease progression in 7 of 49 (14%), stable or improved status with subsequent disease progression in 26 of 49 (53%), and progressive disease in 16 of 49 patients (33%). The actuarial 2- and 5-year overall survival rates following relapse for the 49 patients who underwent salvage treatment were 63 and 6%, which favorably compared to the 2-year survival rate of 21% for those who received supportive care only ( p = 0.001). Conclusions: Local relapse is the predominant type of treatment failure for chordomas of the base of skull and cervical spine. Salvage treatment may relieve symptoms; however, most patients will ultimately succumb to their disease. Poor long-term survival rates following relapse emphasize the importance of a combined treatment approach with experienced surgeons and radiation oncologists at the time of primary treatment. For most patients, only permanent local tumor control will offer a chance of cure.

To examine cognitive function and its relationships to demographic characteristics and social support among elders in central China.Cognitive decline is prevalent among elders. Few studies have explored the relationship between social support and cognitive function among elders.A cross-sectional, descriptive correlational study.A quasi-random, point of reference sample of 120 elders residing in central China was recruited for study. Instruments used included a: Socio-demographic Questionnaire, the Multidimensional Scale on Perceived Social Support and the Mini-Mental State Examination. Hierarchical multiple regression was performed to examine the relationships among demographic variables, social support and cognitive function.Age, education and social support accounted for 45·2% of the variance in cognitive function. Family support was the strongest predictor of cognitive function. Elders who had higher educational levels and more family support had better cognitive function. Relevance to clinical practice. Community healthcare providers should consolidate social support among elders in China and use family support interventions to reduce or delay cognitive decline, especially among those of increased age who are illiterate.Elders who had higher educational level and more family support had better cognitive function levels. Interventions that include family support are needed to improve cognitive function among elders in China.

Objective: To examine the independent contributions of prenatal methamphetamine exposure (PME) and prenatal tobacco exposure (PTE) on brain morphology among a sample of nonalcohol-exposed 3- to 5-year-old children followed prospectively since birth. Study Design: The sample included 20 children with PME (19 with PTE) and 15 comparison children (7 with PTE), matched on race, birth weight, maternal education and type of insurance. Subcortical and cortical volumes and cortical thickness measures were derived through an automated segmentation procedure from T1-weighted structural magnetic resonance images obtained on unsedated children. Attention was assessed using the computerized Conners’ Kiddie Continuous Performance Test Version 5 (K-CPT™ V.5). PME effects on subcortical and cortical brain volumes and cortical thickness were tested by general linear model with type III sum of squares, adjusting for PTE, prenatal marijuana exposure, age at time of scan, gender, handedness, pulse sequence and total intracranial volume (for volumetric outcomes). A similar analysis was done for PTE effects on subcortical and cortical brain volumes and thickness, adjusting for PME and the above covariates. Results: Children with PME had significantly reduced caudate nucleus volumes and cortical thickness increases in perisylvian and orbital-frontal cortices. In contrast, children with PTE showed cortical thinning in perisylvian and lateral occipital cortices and volumetric increases in frontal regions and decreases in anterior cingulate. PME was positively related and caudate volume was inversely related to K-CPT reaction time by inter-stimulus interval, a measure of the ability to adjust to changing task demands, suggesting that children with PME may have subtle attentional deficits mediated by caudate volume reductions. Conclusions: Our results suggest that PME and PTE may have distinct differential cortical effects on the developing central nervous system. Additionally, PME may be associated with subtle deficits in attention mediated by caudate volume reductions.

The human genome is far from random. Much like the master craftsman of fine Persian rugs, nature has injected subtle variants into the genetic sequence, giving uniqueness to every rug and reminding us of the cosmic grand scheme of life. Unraveling the complexities of this system is akin to understanding and fluently speaking an alien language, should extraterrestrials one day land in our backyard. Deciphering this code and finding discernible patterns lies at the heart of cancer informatics. Developing the tools of the modern cancer informatician will encompass merging the ways of the old with the new, integrating ideas and concepts across disciplines, and taking risks to develop cutting-edge techniques and methodology.

Background. Chordomas are uncommon primary malignant tumors of bone that typically occur in the axial skeleton including the sacrum, vertebrae, and skull base. The base of skull tumors usually are not amenable to complete surgical resection, and most require postoperative radiotherapy. The natural history of skull base chordoma is typified by slow locally invasive tumor progression and eventual death, although few parameters are known that allow stratification of patients into prognostic groups. Methods. Sixty-two patients with skull base chordomas treated at the Massachusetts General Hospital by proton beam irradiation therapy with at least 2 years of follow-up information were reviewed in an attempt to identify clinical and pathologic parameters that predicted outcome. Results. Female sex, tumor necrosis in preradiation treatment biopsy, and tumor volume in excess of 70 ml were each independent predictors of shortened overall survival after radiation therapy for skull base chordoma. Conclusions. Stratification of patients with skull base chordoma into poor and good outcome groups can be performed using the three parameters identified in our study. In addition, the striking difference in survival between the sexes suggests that further investigations of these tumors should include determination of their hormonal receptor status and consideration of hormonal manipulation in their management.

Background. Several histologic classifications of thymomas have been proposed, and attempts have been made to correlate the different histologic subtypes to clinical behavior and prognosis. Recently, Marino and Muller-Hermelink and Kirchner et al. proposed a new morphologic classification of thymomas based on the resemblance of the neoplastic cells to subtypes of the normal thymic epithelial cells. In this classification, six categories of thymic epithelial tumors are recognized, They define four categories of thymoma: medullary, mixed, organoid (predominantly cortical), and cortical, and two subgroups of thymic carcinomas: well differentiated thymic carcinoma and high grade carcinomas. Methods. The authors studied 116 patients with thymic epithelial tumors classified according to the proposals of Marino and Muller-Hermelink and Kirchner et al. to assess the effect of histologic classification and other factors (stage, size of tumor, lymphoid hyperplasia, myasthenia gravis, age, sex, and treatment) on survival, and freedom from relapse. Results. Eight cases (7%) were medullary, 32 cases (28%) mixed, 20 cases (17%) organoid (predominantly cortical), 21 cases (18%) cortical, 29 cases (25%) well differentiated carcinoma (WDTC), two cases (2%) high grade carcinoma, and four cases (3%) unclassifiable. Fifty-two patients were in stage I, 32 stage II (16 HA, 16 HB), 28 stage III, and four Stage IVA. Only stage (P = 0.0001; hazard ratio = 5.36) and histology (P = 0.0019; hazard ratio = 8.010) were significant in predicting recurrence. Histology was highly correlated with stage, but by multivariate analysis was an independent factor in predicting relapse (P = 0.0281; hazard ratio = 5.92). None of the medullary or mixed thymornas recurred, even though 30% were invasive. Patients with WDTC recurred more often and earlier than patients with organoid and cortical thymoma (log rank, P = 0.001). The actuarial freedom from relapse for patients with WDTC was 58% at 5 years and 46% at 10 years compared with 100% for other subtypes. Both advanced stage (III and IV) and the WDTC histologic subtype significantly increased the risk of death from thymoma (log rank, P = 0.0001). The actuarial survival of patients with WDTC was 80% at 5 years and 54% at 10 years, whereas that of patients with the other subtypes was 100% at 5 and 10 years. Five of seven relapses and six of seven deaths from thymoma occurred in patients with WDTC. In Stage II patients, one of 16 minimally invasive (Stage IIA) tumors recurred, compared with 3 of 16 grossly invasive (Stage IIB) tumors, indicating that microscopic assessment of invasion is important in staging. Conclusions. The bistologic classification of Marino and Muller-Hermelink has prognostic significance, independent of tumor stage. Medullary and mixed thymomas were benign tumors with no risk of recurrence, even when capsular invasion was present. Organoid and cortical thymoma showed intermediate invasiveness and a low, but significant, risk of late relapse, even with minimal invasion. WDTC were always invasive and had a significantly increased risk of relapse and death, even for Stage II patients. Adjuvant therapy appears unnecessary for medullary and mixed thymomas, even when invasive Cancer 1994; 74:606-17.

Background. This study reviews the experience of patients with early stage rectal cancer managed by local excision or abdominoperineal resection to clarify the relative indications and results of these two approaches. Methods. From 1962 to 1991, 125 patients with T1 and T2 rectal cancer underwent local excision (56 patients) or abdominoperineal resection (69 patients). Outcome was analyzed by stage, treatment, and pathologic features of tumor grade and vessel involvement. Results. The 5-year actuarial recurrence-free survival and local control was 87% and 96%, respectively, for 28 patients undergoing local excision with favorable histologic features (well or moderately well differentiated histologic findings without venous/lymph vessel involvement). These results were 57% and 68% for 28 patients with unfavorable histologic features (poorly differentiated histology and/or venous/lymph vessel involvement). For patients undergoing abdominoperineal resection, the 5-year actuarial recurrence-free survival and local control of 49 patients with favorable histologic features was 91% and 91%, respectively. These results were 79% and 89%, respectively, for patients with poorly differentiated histology or venous/lymph vessel involvement. Conclusions. For patients with T1 and T2 tumors having favorable histologic features, a satisfactory survival and local control was achieved for patients undergoing local excision or abdominoperineal resection. In contrast, patients with T1 and T2 tumors having poorly differentiated histologic features and/or venous/lymph vessel involvement undergoing local excision or abdominoperineal resection appeared to have decreased rates of survival and of local control. For these patients, radical resection combined with pelvic irradiation and 5-fluorouracil-based chemotherapy should be investigated. Cancer 1994; 73:2716–20.

PURPOSE This study examines the association between the pathologic response of rectal cancer after irradiation and its pretreatment proliferative state as assayed by proliferating cell nuclear antigen (PCNA) and mitotic activity. PATIENTS AND METHODS Ninety patients with clinical stage T3 and T4 rectal cancer received preoperative irradiation followed by surgery. Pretreatment tumor biopsies were scored for PCNA activity (number of tumor cells staining immunohistochemically with an anti-PCNA monoclonal antibody) and the number of mitoses per 10 high-powered fields (hpf). Postirradiation surgical specimens were examined for extent of residual disease. RESULTS The tumors of 33 of 90 patients (37%) exhibited marked pathologic downstaging (no residual tumor or cancer confined to the rectal wall) after preoperative irradiation. Two features were independently associated with the likelihood of marked pathologic regression after preoperative irradiation: lesion size and PCNA/mitotic activity. When stratified by tumor size, marked tumor regression occurred most frequently in smaller tumors with high PCNA/mitotic activity compared with larger tumors with lower PCNA/mitotic activity. Intermediate downstaging rates were seen for small or large tumors with moderate PCNA/mitotic activity. CONCLUSION Tumor PCNA/mitotic activity predicts the likelihood of response to irradiation, which may aid in formulating treatment policies for patients with rectal cancer.

OBJECTIVE: The authors investigated the combined experience of a single institution in treating bile duct carcinoma during the modern era. SUMMARY BACKGROUND DATA: Bile duct carcinomas are notoriously difficult to cure, with locoregional recurrence the rule, even after radical resection. Adjuvant efforts have included various radiation modalities, with limited success. Recently, charged-particle radiotherapy has also been used in these patients. METHODS: The authors performed a retrospective chart analysis of 129 patients with bile duct adenocarcinomas treated between 1977 and 1987 through the University of California at San Francisco, including 22 patients treated at Lawrence Berkeley Laboratory with the charged particles helium and neon. The minimum follow-up was 5 years. Survival, outcome, and complication results were analyzed. RESULTS: Sixty-two patients were treated with surgery alone (S), 45 patients received conventional adjuvant x-ray radiotherapy (S + X), and 22 were treated with charged particles (S + CP). The median survival times were 6.5, 11, and 14 months, respectively, for the entire group, and 16, 16, and 23 months in patients treated with curative intent. There was a survival difference in patients undergoing total resection compared with debulking (p = 0.05) and minor resections (p = 0.0001). Patients with microscopic residual disease had increased median survival times when they were treated with adjuvant irradiation, most markedly after CP (p = 0.0005) but also with conventional X (p = 0.0109). Patients with gross residual disease had a less marked but still statistically significant extended survival (p = 0.05 for S + X and p = 0.0423 for S + CP) after irradiatio CONCLUSIONS: The mainstay of bile duct carcinoma management was maximal surgical resection in these patients. Postoperative radiotherapy gave patients with positive microscopic margins a significant survival advantage and may be of value in selected patients with gross disease.

A dose-response analysis was undertaken in a group of patients with clinically node-negative carcinoma of the anal canal treated with a sphincter-sparing approach. Twenty-three patients underwent biopsy of the primary tumor, followed by concurrent radiation and chemotherapy. The chemotherapy regimen of 5-fluorouracil and mitomycin C and radiation technique were uniform in all patients. The total radiation dose, given in daily fractions of 180–200 cGy, was escalated over the years as an institutional policy. The total radiation dose was ≤5,200 cGy (mean 4,550 cGy) in 11 cases treated before September 1989 and >5,200 cGy (mean 5,572 cGy) in 12 cases treated subsequently. The 3-year actuarial local control rates were 53% vs. 100% for the low vs. high dose groups, respectively (P = 0.015). The 3-year actuarial overall survival rates were 82% vs. 100% in the 2 groups, respectively. No increase in late toxicity in the high dose group has been observed compared to the low dose group. These results, albeit based on limited patient numbers, suggest that total radiation dose is an important determinant of long-term tumor control in patients with localized anal canal carcinoma. A total radiation dose of approximately 5,500 cGy has led to excellent tumor control and sphincter function. © Wiley-Liss, Inc.

Giomas constitute a broad class of neuroectodermal tumours believed to originate from sustentacular neuroglial cells (Kleihues and Cavenee 2000). Astrocytomas form the largest group of gliomas (>75%) and glioblastoma multiforme (GBM) is the most common type of astrocytoma (CBTRUS 2011). Gliomas that share histologic characteristics with ependymal or oligodendrocyte cells are named ependymomas and oligodendrogliomas, but may not necessarily originate from the aforementioned cell types (Kleihues and Cavenee 2000). Mixed gliomas include those which consist of more than one glia cell type. For example, oligodendroglial glioblastoma multiforme (as defined by some neuropathologists) are GBM tumours with an oligodendroglioma component and generally have a significantly worse clinical outcome than GBM tumours overall (Louis et al 2007). Another mixed glioma is oligoastrocytoma, which contains both oligodendrocyte and astrocyte cells. The Third Edition of the International Classification of Diseases for oncology (ICD-O-3) is widely used to categorize gliomas by histology (e.g., malignant glioma=9380, ependymoma NOS=9391, astrocytoma=9430, glioblastoma NOS=9440, oligodendroglioma NOS=9450) (Fritz et al 2000). Furthermore, tumours are grouped by site in the ICD-O-3 system using Ccodes (e.g., cerebrum=C71.0, frontal lobal=C71.1, temporal lobe=C71.2, parietal lobe=C71.3, occipital lobe=C71.4, ventricle=C71.5, cerebellum=C71.6, spinal cord=C72.0). The World Health Organization (WHO) also has developed a classification index which grades gliomas by disease prognosis (I=best to IV=worst) (Kliehues et al 1993). Recent additions to the “WHO Classification of Tumours” include Grade I angiocentric gliomas (predominantly occurring in children and young adults in the fronto-parietal cortex, temporal lobe, and hippocampal region), and Grade II – pilomyxoid astrocytoma (typically occurring in infants and children in the hypothalamic/chiasmatic region) (Louis et al 2007). Additionally, WHO has recognized a divergent pattern of gliomas named small cell glioblastoma characterized by EGFR amplification, p16INK4a homozygous deletion, PTEN mutations, and LOH 10q (Louis et al 2007).

Purpose: Dose escalation for prostate cancer by external beam irradiation is feasible by a 160 MeV perineal proton beam that reduces the volume of rectum irradiated. We correlated the total doses received to portions of the anterior rectum to study the possible relationship of the volume irradiated to the incidence of late rectal toxicity. Methods: We have randomized 191 patients with stages T3 and T4 prostatic carcinoma to one of two treatment dose arms. These were: 1) 75.6 Cobalt-Gy-equivalent (CGE), 50.4 Gy delivered by 107−25 MV photons followed by 25.2 CGE delivered perineally by protons (Arm 1) or 2) 67.2 CGE delivered by 10−25 MV photons (Arm 2). Results: With a median follow-up of 3.7 years, post-irradiation rectal bleeding (grades 1 and 2 only, none requiring surgery or hospitalization) from telangietatic rectal mucosal vessels has occurred in 34% of 99 Arm-1 patients and 16% of 92 Arm-2 patients ( p = 0.013). Dose-volume histograms (DVHs) for the anterior rectal wall, the posterior rectal wall and the total rectum in 41 patients treated on Arm 1 were calculated from the three dimensional dose distributions. Rectal bleeding has occurred in 14 or 34% of the 41 DVH-analyzed subset of Arm-1 patients. Both the fractional volume of the anterior rectum and the total dose received by fractional volumes of the anterior rectum significantly correlate with the actuarial probability of bleeding. Conclusions: Clinicians planning dose escalation to men with localized prostate cancer should approve with caution treatment plans raising more than 40% of the anterior rectum to more than 75 CGE without additional effort to protect the rectal mucosa because this late sequela data indicate that more than half of these men will otherwise have rectal bleeding.

Background. The prognostic significance of the cellular composition of the nodules of Hodgkin disease, nodular sclerosis type (HDNS), is controversial. Methods Tumors from 79 patients with HDNS, who had a median follow-up time of 9.3 years, were studied. Results. Based on British National Lymphoma Investigation criteria, 58 cases were classified as NSI (low-grade) and 21 as NSII (high-grade). The study included 24 male and 55 female patients, aged 10–57 years (mean, 27 years), who presented with Stage I (13 patients [12A, 1B]), Stage II (45 patients [40A, 5B]), or Stage III (21 patients [16A, 5B]) disease. Fifty-three patients had no relapse, 4 died of other causes, and 49 are in complete clinical remission. Twenty-six patients had progression of disease during therapy or relapsed and 17 were successfully salvaged. Overall length of survival was significantly shorter with NSII (P = 0.0001), extensive necrosis (P = 0.0034), high stage (P = 0.0058), and B symptoms (P = 0.030). Multivariate analysis showed that grade had the strongest effect on overall survival (P = 0.0042; hazard ratio = 10.19). The 5-year survival was 100% for NSI patients and 75% for NSII patients. Only B symptoms were significantly associated with risk of relapse after initial therapy (P = 0.030). For patients who relapsed, only histologic grade predicted subsequent disease-free survival (P = 0.0023; hazard ratio = 26.5). Five-year disease-free survival after first relapse was 94% for NSI patients and 11% for NSII patients. Conclusions. Patients with NSI disease who relapse have a more successful salvage and longer period of survival than do those with NSII disease. Histologic subclassification of HDNS appears clinically relevant, and consideration of histologic subtype may be important when planning therapy.

Adult onset glioma is a rare cancer which occurs more frequently in Caucasians than African Americans, and in men than women. The etiology of this disease is largely unknown. Exposure to ionizing radiation is the only well established environmental risk factor, and this factor explains only a small percentage of cases. Several recent studies have reported an association between season of birth and glioma risk. This paper reviews the plausibility of evidence focusing on the seasonal interrelation of farming, allergies, viruses, vitamin D, diet, birth weight, and handedness. To date, a convincing explanation for the occurrence of adult gliomas decades after a seasonal exposure at birth remains elusive.

Evidence of an association between survival time and date of birth would suggest an etiologic role for a seasonally variable environmental exposure occurring within a narrow perinatal time period. Risk factors that may exhibit seasonal epidemicity include diet, infectious agents, allergens, and antihistamine use. Typically data has been analyzed by simply categorizing births into months or seasons of the year and performing multiple pairwise comparisons. This paper presents a statistically robust alternative, based upon a trigonometric Cox regression model, to analyze the cyclic nature of birth dates related to patient survival. Disease birth-date results are presented using a sinusoidal plot with peak date(s) of relative risk and a single P value that indicates whether an overall statistically significant seasonal association is present. Advantages of this derivative-free method include ease of use, increased power to detect statistically significant associations, and the ability to avoid arbitrary, subjective demarcation of seasons.

Secondary brain injury due to increased intracranial pressure (ICP) contributes to post-traumatic morbidity and mortality. Although it is often taught that increased ICP begins early after traumatic brain injury, some patients develop increased ICP after the first 3 days post-injury. We examined our data to describe temporal patterns of increased ICP.This is a retrospective review of prospectively collected physiologic and demographic data.Seventy-seven patients were included. We identified four patterns of increased ICP: beginning within 72 h (early), beginning after 72 h (late), early increases with resolution, and then a second rise after 72 h (bimodal), and continuously increased ICP. Late increases in ICP occur in 17% of this cohort. Peak day of swelling was day 7 for the "late" rise group and day 4 for the other patients with increased ICP. Forty-four percent of patients showed enlargement of cerebral contusions on follow-up imaging at 24 h post-injury.Late rises in ICP were not rare in this cohort. This is clinically relevant as it may impact decisions about ICP monitor removal. Differences between groups in age, CT patterns of injury, fluid therapy, osmotic use, and fever were not statistically significant.