An MDS-specific frailty index based on cumulative deficits adds independent prognostic information to clinical prognostic scoring.

The frailty index (FI) is based on the principle that the more deficits an individual has, the greater their risk of adverse outcomes. It is expressed as a ratio of the number of deficits present to the total number of deficits considered. We developed an MDS-specific FI using a prospective MDS registry and assessed its ability to add prognostic power to conventional prognostic scores in MDS. The 42 deficits included in this FI included measurements of physical performance, comorbidities, laboratory values, instrumental activities of daily living, quality of life and performance status. Of 644 patients, 440 were eligible for FI calculation. The median FI score was 0.25 (range 0.05-0.67), correlated with age and IPSS/IPSS-R risk scores and discriminated overall survival. With a follow-up of 20 months, survival was 27 months (95% CI 24-30.4). By multivariate analysis, age >70, FI, transfusion dependence, and IPSS were significant covariates associated with OS. The incremental discrimination improvement of the frailty index was 37%. We derived a prognostic score with five risk groups and distinct survivals ranging from 7.4 months to not yet reached. If externally validated, the MDS-FI could be used as a tool to refine the risk stratification of current clinical prognostication models.

Influence of comorbidities on transplant outcomes in patients aged 50 years or more after myeloablative conditioning incorporating fludarabine, BU and ATG.

Non-myeloablative (MA) and reduced intensity allo-SCT regimens are offered to older patients and/or those with comorbidities because the morbidity and mortality attributable to fully MA conditioning is thought to be unacceptably high. A total of 207 patients aged 50-66 years were treated between 1999 and 2008 with SCT after MA conditioning with fludarabine 50 mg/m(2) daily × 5 and i.v. BU 3.2 mg/kg daily × 4.90 (43%) had additional TBI 200 cGy × 2. GVHD prophylaxis was CsA, MTX and thymoglobulin (4.5 mg/kg total dose). As defined by the hematopoietic cell transplantation co-morbidity index (HCT-CI) scoring system 117 (57%) pts scored 0 and 90 (43%) 1. At 5 years OS was 39 vs 54% (P=0.008), disease-free survival 38 vs 49% (P=0.03), TRM 39 vs 19% (P=0.003) and relapse 36 vs 39% (P=ns) in those with scores of 0 and 1, respectively. Multivariate analysis confirmed the influence of HCT-CI scores on TRM (subhazard ratios=2.29; 95% confidence interval=1.29-4.08; P=0.005). We conclude that comorbidities as assessed by the HCT-CI do influence TRM with this regimen but that age alone should not be an indication to prefer a less intense protocol.

High incidence of post transplant lymphoproliferative disorder after antithymocyte globulin-based conditioning and ineffective prediction by day 28 EBV-specific T lymphocyte counts.

The largest study on post-allogeneic hematopoietic cell transplant lymphoproliferative disorder (PTLD) epidemiology showed a cumulative incidence of 1.7% in patients receiving antithymocyte globulin (ATG). We had noted an apparently higher incidence in our transplant recipients whose conditioning included ATG. Therefore, we formally determined the incidence of PTLD through chart review. We also evaluated whether counts of EBV-specific T lymphocytes measured by cytokine flow cytometry could identify patients at risk of developing PTLD. Among 307 allogeneic transplant recipients, 25 (8.1%) developed PTLD. This was biopsy proven in 11 patients, and was fatal in seven patients. Patient age, EBV serostatus, donor type/match or GVHD did not influence PTLD risk significantly. Median onset of PTLD was 55 (range, 28-770) days post transplant. Day 28 EBV-specific T lymphocyte counts were not significantly different in 11 patients who developed PTLD and 31 non-PTLD patients matched for published risk factors for PTLD. In summary, when using conditioning with thymoglobulin 4.5 mg/kg, the incidence of PTLD is relatively high and cannot be predicted by day 28 cytokine flow cytometry-determined EBV-specific T lymphocyte counts. Thus, in this scenario PTLD prevention may be warranted, for example, using EBV DNAemia monitoring with preemptive therapy.

Hematopoietic cell transplantation for Crohn's disease; is it time?

AIM: To review all studies in the literature that have assessed Hematopoietic cell transplantation (HCT) and Crohn's disease (CD) with the ultimate aims of determining if this is a viable treatment option for those with CD. A secondary aim was to review the above literature and determine if the studies shed further light on the mechanisms involved in the pathogenesis of CD. METHODS: An extensive Medline search was performed on all articles from 1970 to 2005 using the keywords; bone marrow transplant, stem cell, hematopoietic cell, Crohn's disease and inflammatory bowel disease. RESULTS: We identified one case in which a patient developed CD following an allogeneic HCT from a sibling suffering with CD. Evidence for transfer of the genetic predisposition to develop CD was also identified with report of a patient that developed severe CD following an allogeneic HCT. Following HCT it was found that the donor (that had no signs or symptoms of CD) and the recipient had several haplotype mismatches in HLA class III genes in the IBD3 locus including a polymorphism of NOD2/CARD15 that has been associated with CD. Thirty three published cases of patients with CD who underwent either autologous or allogeneic HCT were identified. At the time of publication 29 of these 33 patients were considered to be in remission. The median follow-up time was seven years, and twenty months for allogeneic and autologous HCT respectively. For patients who underwent HCT primarily for treatment of their CD there have been no mortalities related to transplant complications. CONCLUSION: Overall these preliminary data suggest that both allogeneic and autologous HCT may be effective in inducing remission in refractory CD. This supports the hypothesis that the hematolymphatic cells play a key role in CD and that resetting of the immune system may be a critical approach in the management or cure of CD.

Comparative sensitivity of a simulated driving task to self-report, physiological, and other performance measures during prolonged wakefulness.

OBJECTIVES: The objectives of this study were to compare (1) the sensitivity of simulated driving to self-report measures, nocturnal sleep latency tests (SLTs), and an auditory vigilance task and (2) urban and motorway driving. METHODS: Healthy males 18 to 35 years maintained wakefulness for one night and were tested at 2400, 0230, 0500 and 0730 h. In Study 1 (n=11), the SLTs were followed by auditory vigilance and simulated driving tasks; in Study 2 (n=18), the SLTs were preceded and followed by simulated driving on motorway and urban routes. RESULTS: In Study 1, speed variability, tracking variability, and driving off the road on the driving simulator had comparable sensitivity to d' on the auditory vigilance task. In Study 2, driving performance was consistently worse on the motorway route. CONCLUSION: The driving simulator was equally sensitive to another performance measure during prolonged wakefulness and impairments were greater with motorway driving.

Effect of medroxyprogesterone pretreatment on pentagastrin-induced panic symptoms in females with panic disorder.

Clinical observation, as well as epidemiological and research data, suggest that female gonadal hormones influence the course of panic disorder (PD). Panicogenic agents such as pentagastrin are useful tools with which to study the pathophysiology of panic attacks. Nine women with PD were randomly assigned to receive, in a crossover design, a 3-day pretreatment with medroxyprogesterone acetate (MP) prior to an injection of pentagastrin, and a 3-day pretreatment with a placebo prior to another injection of pentagastrin. The panic response and the anxiety response to pentagastrin were decreased after MP pretreatment. These preliminary results support the use of laboratory models for investigations of the interactions between progestins and anxiety.

The use of complementary therapies by breast cancer patients attending conventional treatment.

The aim of this study was to measure the proportion and characteristics of complementary therapy (CT) users among female breast cancer patients receiving conventional treatment. 473 women who had received surgical intervention for breast cancer in the year of diagnosis were sent a questionnaire for completion, and 242 responded. CT had been used by 16.5% after cancer diagnosis, only 8.7% before. The most commonly used CTs were homeopathy, manual healing method, herbalism and acupuncture. The main reason for using CTs was physical distress. Only a minority was searching for psychological support. 24 users were satisfied with these treatments, and two-thirds would suggest them. Users were significantly younger, more educated, and previous users of CTs than non-users. Adjusting each variable for the effect of the others, only previous use had an independent effect on increasing the probability of being users after cancer diagnosis.

Malignant melanoma in Europe: changes in mortality rates (1970-90) in European Community countries.

Reducing mortality, especially premature death, is a major goal of the fight against cancer. In this study, we have analyzed trends in malignant melanoma (MM) mortality in the European Community (EC) as a whole and for each country. The data (obtained from the World Health Organization data bank) have been analyzed for the period 1970-90, by age groups (20-44, 45-64, 65-74, 75+ years). Trends are presented as percentage change of mortality rate for each three-year period in comparison with the rate in the first one (1970-72). The mortality from MM in the EC as a whole increased for both genders (men, +89.2 percent; women, +72.6 percent), with statistically significant trends in all age classes. Northern countries experienced mortality changes about 30 to 50 percent less than the EC average increase. Greater changes were seen in southern European countries, in which recent standardized rates are near to those observed in northern European populations. Among Mediterranean people, the highest increase (more than fourfold) was observed in Spain. The significant increase found for the younger age class makes unlikely the risk of misclassification with other skin cancers. No future decrease in MM mortality in the EC is indicated from these data.

[Hospital admissions, diagnostic and therapeutic procedures of patients with colorectal cancer during 5 years after diagnosis: population-based study]. / Ricoveri ospedalieri, prestazioni diagnostiche e terapeutiche nei pazienti affetti da tumore del colonretto durante cinque anni dalla diagnosi: uno studio di popolazione.

This research evaluated basic parameters of care, also in the terms of costs. The study examined a sample of colorectal cancer cases incident in 1987 in the population of Florence's municipality, taken from the data base of Tuscany Cancer Registry (RTT). We collected, for 71 patients, all clinical records, for the five follow-up years and evaluated the diagnostic and therapeutic procedures (blood tests, histologic examination, instrumental investigation and surgical intervention) and the duration of all hospitalisations. Besides, on the basis of the diagnostic and therapeutic procedures and of the discharge diagnosis, each hospitalisation was coded following the DRG system and the economic cost of hospital care was analysed. The average number of hospitalisations and the average length of stay for patient in five follow-up years are respectively 1.9 (SD = 1.3) and 41.3 (SD = 25.8); the length of stay resulted highly correlated with the stage of disease. The mean hospital cost per patient (about ItL 18.000.000 overall) was higher in patients with more advanced disease at diagnosis. In the period of study an average 125.9 blood tests (SD = 110.7), 1.2 histologic examinations (SD = 0.9) and 10.3 instrumental investigations (SD = 9.0) were performed for each patient; 61 subjects (86%) were submitted to surgical intervention, of which 4 had a second intervention, and 1 subject was submitted to surgical intervention for liver's metastases.

Survival of classic Kaposi's sarcoma and risk of second cancer.

In order to elucidate survival rates and risk of second primary cancer, we assessed 204 patients with histologically confirmed classic Kaposi's sarcoma (KS) who were identified in 11 Italian population-based cancer registries. One hundred and thirty-nine were men (median age 70 years) and 65 were women (median age 72). One, 5 and 10 year survival rates were 0.92, 0.69 and 0.46 respectively. Median survival was 9.4 years (i.e. not different from the Italian general population of the same sex and age). Survival did not vary according to sex and tumour site (i.e. lower limbs only or other). Eleven second primary cancers, including two lung and two kidney cancers, were reported after KS diagnosis (not different from the expected number).

Colorectal, lung, and breast cancer care during the three years following the diagnosis: a population-based study.

AIMS: We evaluated a number of basic parameters of care during hospitalization that contribute to the total cost of therapy during the 3 years after the first diagnosis of cancer. METHODS: The study examined a sample of cases of cancer of the colon-rectum (164 cases), lung (160 cases) and breast (144 cases) diagnosed in 1987, taken from the data base of the Tuscany Cancer Registry. All the information collected by the Registry was examined and the sample was further validated by reviewing original clinical records. The agreement between the two sources was very high, confirming the adequacy of the Registry as a source of information. The parameters evaluated for each patient were the number of cytohistologic examinations, surgery, hospital admissions and days spent in hospital during the 3 follow-up years. RESULTS: The average number of admittances in 3 years was 1.93 for colorectal, 3.39 for lung and 2.15 for breast cancer. The mean number of days spent in hospital in the 3 follow-up years was 39.9 for colorectal, 50.1 for lung and 21.1 for breast cancer. The parameters differed among subjects still alive, those deceased and those in various stages of the illness. CONCLUSIONS: The costs of the time spent in hospital, based on the number of days during the first 3 years of the illness, were higher in cases of lung cancer than of the other sites, and more so for patients diagnosed in an advanced phase of the disease.

Epidemiology of lung cancer.

Primary lung cancer is now the most frequent cancer in the world. Tobacco smoking still represents its predominant cause: a recent estimate attributes 80-85% of lung cancers to smoking and the epidemic of lung cancer mortality is still ongoing, with a major contribution from East European and developing countries. The study of smoking in association with lung cancer has contributed to the understanding of the carcinogenic process in humans, especially since molecular epidemiology techniques have been developed. However, the most probable carcinogenic model, still needs to be more clearly established. Presently, it can be summarised that smoking cessation is beneficial at any age, and more so when early. The contribution of passive smoking to lung cancer risk has been widely documented; its effect in terms of attributable number of cases, however, is not easily estimated at a population level. Some authors suggest that non-smoking-related lung cancer frequency is increasing over time. Exposure to environmental carcinogens with a major emphasis on those deriving from industrial processes, among which asbestos, and on air pollution due to traffic in urban areas has been advocated. Finally, a special interest has grown in the last years on possible protective factors for lung cancer, mainly diet-related (high intake of fresh fruits and vegetables), but results from the first large randomised chemoprevention trial based on alpha-tocopherol and beta-carotene treatment, dealt with "paradoxical" results.

[Gastrointestinal system tumors in Italian emigrants]. / I tumori dell'apparato gastroenterico nei migranti italiani all'estero.

In this paper we present the risk of death for stomach, colon, rectum and pancreas cancers in Italian migrants to Canada, Argentina, Australia, France and England and Wales. Estimations of relative risks (RR) in Italian migrants, in residents in Italy and in Southern Italy relative to the local born in the host country are shown. Relative risks in Italian migrants to Australia were analysed also by duration of stay in the host country. The Italian migrants' cancer profile in intermediate between the origin and the host population: a reduction of risk of death for stomach cancer and an increase of risk for colorectal cancers are the main results. The results are discussed taking into account the analysis by duration of residence and the pattern of food prevalent in the different countries considered.

[Etiological epidemiology of colorectal tumors]. / Epidemiologia eziologica dei tumori del colon-retto.

We reviewed the main results of colon cancer (CC) epidemiologic studies, according to data published in the 1973-1994 period, with a particular mention to dietary factors and to differences with Italian findings. Meat (mostly, red meat), animal fats and high energy intake not counterbalanced by sufficient physical activity seem to be the most consistent risk factors for CC. On the contrary, the vegetarian based diet seems to reduce the risk of CC. Although interestingly, the relevance to CC of other life-style and diet-related factors (alcohol intake, smoking habits, processing and cooking methods, occupation, drugs, personal medical and reproductive history) must be better defined and requests further investigations. More recently, genetic studies are clarifying the hereditary risk of CC. Several colon carcinogenesis hypotheses have been proposed, but general agreement on the most reliable is still lacking. Authors argue that in the next future, new acquirements could emerge from metabolic polymorphism studies, possibly reconciling the biological significance of individual susceptibility and environmental factors to CC incidence.

Epidemiology of classic Kaposi's sarcoma, with special reference to mediterranean population.

An excess of classic Kaposi's sarcoma (KS) in individuals of southern European ancestry has long been suspected and recently quantified in terms of age-standardized rates. In Italy and most notably in southern Italy for the period 1976-84, prior to the AIDS epidemic, KS incidence rates were two-to-three-fold higher than in the United States and Sweden and many ten-fold higher than in England and Wales and Australia. A high frequency of classic KS has also been documented in Israel and, in low-risk countries, in individuals born in southern Europe and the Middle East. Many infections have been suspected to play a role in the etiology of KS, including cytomegalovirus, malaria and, most recently, a new virus of the herpes family, identified in AIDS-associated and classic KS. The present review deals with epidemiologic data concerning KS in the Mediterranean and stresses the opportunity to combine the study of KS in AIDS as well as non-AIDS patients in order to shed light on this no longer rare disease.