Mixed hemodiafiltration reduces erythropoiesis stimulating agents requirement in dialysis patients: a prospective randomized study.

BACKGROUND: Improved responsiveness to erythropoiesis stimulating agents (ESAs) in patients on on-line post-dilution hemodiafiltration (Post-HDF) compared with conventional hemodialysis (HD) was reported by some authors but challenged by others. This prospective, cross-over randomized study tested the hypothesis that an alternative infusion modality of HDF, mixed-dilution HDF (Mixed HDF), could further reduce ESAs requirement in dialysis patients compared to the traditional Post-HDF. METHODS: One-hundred-twenty prevalent patients from 6 Dialysis Centers were randomly assigned to two six-months treatment sequences: A-B and B-A (A, Mixed HDF; B, Post-HDF). Primary outcome was comparative evaluation of ESA (darbepoetin alfa) requirement and ESA resistance. Treatments efficiency, iron and vitamins status, inflammation and nutrition parameters were monitored. RESULTS: In sequence A, darbepoetin requirement decreased during Mixed HDF from 29.5 to 23.7 µg/month and increased significantly during Post-HDF (32.3 µg/month at 6th month) while, in sequence B, it increased during Post-HDF from 38.2 to 43.7 µg/month and decreased during Mixed HDF (23.9 µg/month at 6th month). Overall, EPO doses at 6 months on Mixed and Post-HDF were 23.8 and 38.4 µg/month, respectively, P < 0.01. A multiple linear model confirmed that Mixed HDF vs Post-HDF reduced significantly ESA requirement and ESA resistance (P < 0.0001), by a mean of 29% (CI 23-35%) in the last three months of the observation periods. CONCLUSIONS: Mixed HDF decreased darbepoetin-alfa requirement in dialysis patients. This might help preventing the untoward side effects of high ESA doses, besides having a remarkable economic impact. Additional evidence is needed to confirm this potential benefit of Mixed-HDF.

The Prognosis of Patients with Liver Metastases from Colorectal Cancer still Depends on Anatomical Presentation more than on Treatments.

BACKGROUND: The best management of liver metastases from colorectal cancer is still debated and little is known about the true impact of treatments on survival. MATERIALS AND METHODS: The study involved 122 patients (77 males), aged 64.0 ± 11.0 years (range: 27.8-86.1) at diagnosis of liver metastatization (synchronous in 59). All underwent chemotherapy and at least one procedure of radiofrequency ablation; 53 also had partial hepatic resections. Demographics, tumor characteristics and survival outcomes from liver metastatization were analyzed with univariate and multivariate techniques. This analysis was performed also taking into account relative survival as the best estimate of specific survival. RESULTS: The analysis with observed survival selected the categorized number of involved lymph nodes in the colorectal specimens as the only statistically significant predictor, while the analysis with relative survival also showed site of the primary tumor (above the sigmoid colon or otherwise) and number of liver metastases as significant factors. The standardized mortality ratio was 9.673 (95% CI: 7.668-11.663) and a total of 201.85 years of life were lost in comparison with the survival of the reference population. CONCLUSIONS: The computation of relative survival ­ better than observed survival ­ selected a more adequate number of predictors, making investigation of even limited series of patients with confounding factors reliable. The finding that prognosis was mainly dependent on the anatomical presentation of the primary tumor and of liver metastases ­ instead of treatments ­ could explain the still contrasting opinions on the role of the available therapies in this field.

Quantitative measurement of evolution of postparetic ocular synkinesis treated with botulinum toxin type A.

BACKGROUND: The Sunnybrook Facial Grading System is considered one of the best scales available to grade facial motility and postparetic synkinesis. To measure facial landmarks and movement excursion, a new software, the Facial Assessment by Computer Evaluation, has been proposed. The aim of this study was to quantify eye synkinesis improvement after botulinum toxin type A injections using the new software and to compare this method with the Sunnybrook grading system. METHODS: The study included 40 injection sessions on 29 Caucasian outpatients with facial synkinesis. Before and 2 weeks after the injection, patients were evaluated using the Italian version of the Sunnybrook system. Eyelid fissure size at rest, during lip puckering, and while smiling was measured with the new software. RESULTS: After botulinum infiltration, the Sunnybrook grading system showed a global facial improvement with reduction of synkinesis and increase of static and dynamic symmetry. The Facial Assessment software detected an increase of ocular fissure measure at rest, during lip puckering, and especially during smiling, and the improvement was positively correlated with initial asymmetry. A single point of the Sunnybrook system synkinesis score corresponded to a mean difference of 0.77 mm during smiling and 1.0 mm during lip puckering. CONCLUSIONS: The Facial Assessment by Computer Evaluation measure allowed the authors to quantify the improvement of eye synkinesis after botulinum toxin type A injection. The Sunnybrook Facial Grading System provided an immediate instrument with which to monitor treatment in routine clinical practice, whereas the Facial Assessment system gave a more accurate quantitative assessment. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, II.

The prognostic role of time to diagnosis and presenting symptoms in patients with pancreatic cancer.

BACKGROUND: The aim of this study was to investigate the prognostic role of diagnostic delay and clinical presentation (regarding pain, jaundice, and weight loss) in pancreatic carcinoma. METHODS: One hundred and seventy patients with pancreatic cancer were diagnosed and treated in the decade 2001-2010 (100 males and 70 females, with a mean age of 65.8 years [range, 36-91]). Patients were staged with spiral computed tomography and 75% were found to have advanced disease (28 stage III, 99 stage IV disease). Ductal adenocarcinoma was diagnosed in 147 cases, other subtypes of carcinoma in the remaining 23. Fifty patients were operated with radical intent, 19 had palliative surgery, 101 were considered inoperable because of advanced disease or heavy anesthesiologic risk; 31 of these inoperable patients underwent biliary decompression by insertion of an endoluminal or percutaneous stent. Gemcitabine-containing regimens were administered to 143 patients and radiotherapy was combined in 19. Overall and relative survival were the parameters studied. Multivariate analysis was performed by multiple regressions applied to proportional-hazards model. RESULTS: From all the clinical, pathological and therapeutical factors evaluated the statistically significant ones were time to diagnosis and surgery. Among symptoms pain was related to the shortest mean time to diagnosis, weight loss to the longest, with corresponding differences in survival. These differences of observed survival were substantially confirmed in terms of relative survival. CONCLUSIONS: The poor prognosis of pancreatic carcinoma seems to depend, in part, on diagnostic delay and this, in turn, is influenced by the type of presenting symptoms.

[An update on several indicators of the quality of data flow in a cancer registry in Vercelli (Piedmont, Italy)]. / L'incidenza oncologica nell'ASL VC di Vercelli dal 2002 al 2009: aggiornamento indicatori di qualità del flusso informativo.

The first estimates of cancer incidence in the city of Vercelli in Piedmont (Italy) are now available for the years 2002 to 2005 and preliminary data are also available up to 2009. With respect to previously published results, the cancer database has been integrated with information from additional data sources to ensure that it will become, in the near future, a sound basis of information upon which to build an accredited cancer registry. An evaluation was therefore performed of two indicators of the quality of data flow: the proportion of cases with histological confirmation of diagnosis and cancer mortality to incidence (M/I) ratios. Both show an improvement with respect to 2005 but need to be significantly improved to reach the levels of excellence and accuracy that a registry must necessarily possess. Local health authorities will need to ensure staff availability and facilitate access to key data sources to fully evaluate cancer epidemiology in the area.

A long diagnostic delay in patients with Hereditary Haemorrhagic Telangiectasia: a questionnaire-based retrospective study.

BACKGROUND: The difficulty in establishing a timely correct diagnosis is a relevant matter of concern for several rare diseases. Many rare-disease-affected patients suffer from considerable diagnostic delay, mainly due to their poor knowledge among healthcare professionals, insufficient disease awareness among patients' families, and lack of promptly available diagnostic tools. Hereditary Haemorrhagic Telangiectasia (HHT) is an autosomal-dominantly inherited vascular dysplasia, affecting 1:5,000-10,000 patients. HHT is characterized by high variability of clinical manifestations, which show remarkable overlapping with several common diseases. AIM: To perform a detailed analysis concerning the diagnostic time lag occurring in patients with HHT, defined as the time period spanning from the first clinical manifestation to the attainment of a definite, correct diagnosis. METHODS: A questionnaire was administered to the HHT patients previously recruited from 2000 and 2009. Clinical onset, first referral to a physician for disease manifestations, and first correct diagnosis of definite HHT were collected. Eventual misdiagnosis at first referral and serious complications occurring throughout the time elapsing between disease onset and definite diagnosis were also addressed. RESULTS: In the 233 respondents, the clinical onset of disease occurred at an age of 14.1 yrs, while the age of first referral and the age of first definite diagnosis of HHT were 29.2 yrs and 40.1 yrs, respectively. Only 88/233 patients received a correct diagnosis at first counseling. Thus, the diagnostic time lag, represented by the time elapsing from disease onset and first definite diagnosis of HHT, proved to be 25.7 yrs. Twenty-two patients suffered from severe complications during this time interval. The diagnostic delay was significantly longer (p < 0.001) in index patients (first patients who attained definite HHT diagnosis in a given family) than in non-index patients (relative of index patients). The diagnostic time lag was also significantly associated with education grade (p < 0.001). CONCLUSIONS: Our data report for the first time a systematic inquiry of diagnostic delay in HHT showing that patients receive a definite diagnosis only after nearly three decades from disease onset. Concerted efforts are still to be made to increase awareness of this disease among both families and physicians.

Cervical human papillomavirus infection and shedding of human immunodeficiency virus in cervicovaginal fluids: a cross-sectional study.

We evaluated the association between human papillomavirus cervical infection and HIV shedding in cervicovaginal lavage fluid (CVL), studying 89 HIV-infected women recruited at the Department of Infectious Diseases of Brescia (Italy). HIV shedding in CVL was found in a similar proportion of women with (30%; 21/70) and without (31.6%; 6/19) cervical human papillomavirus infection. A statistically significant correlation was found between HIV viral load in serum and CVL among the 27 women with detectable HIV in CVL (r = 0.4; P = 0.04). However, women on highly active antiretroviral therapy were more likely to have detectable HIV-RNA in CVL despite negative viremia (80% vs. 8%; P < 0.005).

Influence of lingual bracket position on microbial and periodontal parameters in vivo

OBJECTIVE: Lingual orthodontics is becoming more popular in dental practice. The purpose of the present investigation was to compare plaque formation on teeth bonded with the same bracket onto buccal or lingual surface, with non-bonded control teeth, via an in vivo growth experiment over a 30-day period. MATERIAL AND METHODS: A randomized controlled trial with split-mouth design was set up enrolling 20 dental students. Within each subject sites with buccal and lingual brackets and control sites were followed. Clinical periodontal parameters (periodontal pocket depth: PPD; bleeding on probing: BOP) were recorded at baseline and on days 1, 7 and 30. Microbiological samples were taken from the brackets and the teeth on days 1, 7 and 30 to detect colony-forming units (CFU). Total CFU, streptococci CFU and anaerobe CFU were measured. RESULTS: No significant differences (P>0.05) were found between buccal and lingual brackets in terms of clinical periodontal parameters and microbiological values. Conclusion: Bracket position does not have significant impact on bacterial load and on periodontal parameters.

[Cancer mortality in a local health district of Vercelli (Italy) 2000-2009]. / Andamento della mortalità oncologica nell'Asl Vc di Vercelli. Estensione database al 2006-2009 e analisi decennio 2000-2009.

Cancer mortality data for 2000-2009 in the local health district of Vercelli (northern Italy) were analysed. Overall, standard mortality rates show excess mortality rates in men for colon and rectal cancers, central nervous system cancers, as well as esophageal, laryngeal, renal, lung, skin (non melanoma) and skeletal system cancers. For women, excess mortality rates were found for skin (non melanoma), leukemias, nervous system cancers, lymphomas and skeletal system cancers. Mortality data for the years 2006-2009 were compared to data for 2000-2005. Results show an increased mortality risk for mesothelioma in the period 2006-2009 with respect to the period 2000-2005. On the other hand decreased mortality risks were found for nervous system tumours and leukemia, even though current standard mortality rates remain in excess. In light of these findings, it is advisable to monitor the phenomenon in the coming years and to conduct studies to identify possible risk factors.

An analysis to study trends in occupational exposure to antineoplastic drugs among health care workers.

The use of antineoplastic agents for the treatment of cancer and other non-neoplastic diseases is an increasingly common practice in hospitals. As a result, workers involved with handling antineoplastic drugs may be accidentally exposed to these agents, placing them at potential risk for long term adverse effects. To date, the challenge of protecting workers' health is persisting and expanding, with an increasing number of publications demonstrating that contamination of antineoplastic drugs (ADs) is still present on work surfaces after cleaning procedures are concluded. In this paper, five workplaces were selected for surveillance of professional exposure to ADs. Hospital pharmacies involved in the study were set in the North (Units A1 and B2), Center (Units C3 and D4) and South (Unit E5) of Italy. Contamination levels on a number of work surfaces and trends over a 10-year period are presented. Environmental and biological levels were obtained by high performance liquid chromatography (HPLC) coupled with tandem mass spectrometry (MS/MS). A strong reduction of surface contamination was evidenced since 2003, when the recommended procedures for the safe handling of antineoplastic drugs started to be followed by health care workers. Employers' adherence to these recommendations allowed risk characterisation to achieve other important goals. The percentage of positive urine samples was found to be around 30% in the 1990s and 2% in the 2000s. Moreover, no positive samples were detected in 2006 or 2007. In conclusion, our study emphasized that one helpful strategy to reduce risk to all potentially exposed workers is also provided by a data-storage system that allows potential risks of working to be rapidly identified and controlled.

[Epidemiology of tumour mortality from 2000 to 2005 in the province of Vercelli (Italy)]. / La mortalità per tumore in provincia di Vercelli dal 2000 al 2005: considerazioni territoriali ed epidemiologiche.

The main aim of this study was to assess the burden of cancer disease in residents of Vercelli (northern Italy), by analysing mortality data and hospital discharge forms. This was done in order to verify whether, as widely suspected among the city's population, an increased risk of cancer exists in the area, due to the large number of existing agricultural and industrial activities. Tumour mortality rates were compared with mortality data from the tumour registries of the province of Biella and of the city of Turin to identify a possible excess number of cases in Vercelli.An increased mortality rate was observed with respect to reference values (mortality registry of the city of Turin) for several tumours; more specifically results revealed a significantly increased mortality rate due to colorectal tumours, leukemias and nervous system tumours in both genders. Excess mortality was detected in males but not in females for esophageal cancer, non melanoma skin cancers, pancreatic, laryngeal, prostatic, renal and bone cancers. Conversely, in females, the standard mortality ratios (SMR) were found to be statistically significant for renal and laryngeal cancers and for Hodgkin's lymphoma.

Dietary intakes in infertile women a pilot study.

BACKGROUND: The reproductive axis is closely linked to nutritional status. The purpose of this study was to compare the nutritional status in two groups of young infertile women, without clinically overt eating disorders: hypothalamic amenorrhea (HA) and polycystic ovary syndrome (PCOS). METHODS: Eighteen young infertile women (10 HA, 8 PCOS) attending an outpatient gynecological endocrinology unit, underwent evaluation of anthropometry, body composition, dietary intakes by means of a food frequency questionnaire (FFQ) and a seven-day food diary (7DD), and psychological characteristics by means of EDI2 and SCL90 tests. RESULTS: HA women had lower BMI and body fat compared to PCOS women. Habitual intake derived from FFQs showed a similar macronutrient distribution between groups (about 16% protein, 33% fat, 52% carbohydrates). The psychometric profiles of the two groups did not differ significantly. The underreporting of dietary intakes (measured as habitual energy intake by FFQs/basal metabolic rate) was found to be negatively correlated with the interpersonal sensitivity SCL-90 subscale scores (r = -0.54, p = 0.02). CONCLUSION: Our study identified differences in body composition but not in dietary habits between HA and PCOS infertile women. We documented, for the first time, a relationship between the accuracy of dietary surveys and the psychological characteristics of subjects with anovulation. This finding suggests that it may be important to be aware of the psychological terrain when planning a dietary survey in infertile women.

[Estimating the incidence of cancer in the VC Local Health Authority in Vercelli (Italy) from 2002 to 2005]. / Stime d'incidenza oncologica nell'Asl Vc di Vercelli dal 2002 al 2005.

The aim of this study was to describe the epidemiology of tumours in a geographical area in Italy devoid of a tumour registry. A descriptive study was conducted in the territory of the VC local health authority. To estimate incidence, hospital discharge forms were analysed together with data from pathology archives. The standardized incidence rate (SIR) was calculated by using age specific rates in the VC local health authority in the years 2002-2005 and the tumour incidence in the city of Turin as the standard population. As regards low mortality tumours, an excess of bladder cancers (SIR=1,2; 1,1-1,3) and melanomas (SIR=1,3; 1,1-1,6) were found in males and of thyroid cancer (SIR=1,9; 1,6-2,2) and non-Hodgkin lymphomas (SIR=1,4; 1,2-1,6) in females. In addition, an excess of rectal and colon cancers, and leukemia were observed in both genders and of central nervous system tumours in women. This preliminary study may be considered as a basis for the creation of a tumour registry which would necessarily need to integrate additional sources of information. In any case the results of this study have identified certain peculiarities regarding the epidemiology of tumours in this area, which should be further studied in terms of a Public Health problem.

Prognostic validation of the international classification of immunoglobulin M gammopathies: a survival advantage for patients with immunoglobulin M monoclonal gammopathy of undetermined significance?

PURPOSE: To verify the reliability of the new criteria for the diagnosis of IgM gammopathies recently proposed by an international panel of experts (Athens, 2002). EXPERIMENTAL DESIGN: A retrospective series of 698 patients with IgM gammopathy was reviewed paying attention to symptoms, serum IgM concentration, bone marrow infiltration, blood cell count and clinical course. Four clinical entities can be identified: IgM monoclonal gammopathy of undetermined significance (IgM-MGUS), asymptomatic and symptomatic Wandenstrom's macroglobulinemia (A-WM and S-WM, respectively), and IgM-related disorders, although this last was excluded from the study because of the scarcity of patients due to probable selection biases. The observed mortality was studied related to that expected in the general population of comparable age and sex and over an equivalent period of follow-up (standardized mortality ratio, SMR). RESULTS: IgM-MGUS, A-WM, and S-WM shared many clinical aspects but, with respect to the general population, patients with IgM-MGUS had a slight but definite survival advantage, those with A-WM had a mortality rate equivalent to that of the general population, whereas the SMR of patients with S-WM was 5.4. Within A-WM and S-WM the SMR values did not vary significantly in relation to marrow lymphocyte counts or serum IgM concentrations. CONCLUSIONS: Our findings represent a prognostic validation of the applied diagnostic criteria for three of the four identifiable clinical entities and highlight the importance of symptoms over serum IgM concentration and marrow infiltration.

Prognostic factors in symptomatic Waldenstrom's macroglobulinemia.

We analyze the prognostic value of the presenting features of a series of patients with symptomatic Waldenstrom's macroglobulinemia who were homogeneously treated. A total of 215 patients (119 males) with a median age of 62.6 years (range, 24.9 to 91.6) were retrospectively analyzed. The median overall follow-up was 57.6 months (range, 0.6 to 281): 58 (0.9 to 281) for living patients and 52.2 (0.6 to 261.3) for those who died. All patients were treated with alkylating agent-based chemotherapy. The overall median survival was 77.2 months, without significant differences based on the duration of the previous monoclonal gammopathy of undetermined significance (MGUS) phase. The multivariate Cox analysis performed on the whole population showed that age, hemoglobin level, and serum albumin level predicted survival. The addition of beta(2)-microglobulin, available in the subgroup of 60 patients diagnosed after 1990, in a Cox stepwise selection showed that this parameter was by far the main prognostic determinant. Application of the Dhodapkar, Morel, and Gobbi scoring systems to this population of patients showed that all three stratified the population into groups with significantly distinct prognoses. A prognostic index based on age, hemoglobin, and albumin is capable of identifying various groups of patients with different therapeutic needs.

Clinical presentation and survival of smear-positive pulmonary tuberculosis patients of a University General Hospital in a developing country

From January 1995 to August 1997 we evaluated prospectively the clinical presentation, laboratory findings and short-term survival of smear-positive pulmonary tuberculosis (TB) patients who sought care at our hospital. After providing informed, written consent, the patients were interviewed and laboratory tests were performed. Information about survivorship and death was collected through September 1998. Eighty-six smear-positive pulmonary TB patients were enrolled; 26.7 percent were HIV-seropositive. Seventeen HIV-seronegative pulmonary TB patients (19.8 percent) presented chronic diseases in addition to TB. In the multiple logistic regression analysis a CD4+ cell count <= 200 cell/mm was independently associated with HIV seropositivity. In the Cox regression model, fitted to all patients, HIV seropositivity and age > or = 50 years were independently associated with decreased survival. Among HIV-seronegative persons, the presence of an additional disease increased the risk of death of almost six-fold. Use of antiretroviral drugs was associated with a lower risk of death among HIV-seropositive smear-positive pulmonary TB patients (RH = 0.32, 95 percent CI 0.10-0.92). In our study smear-positive pulmonary TB patients had a low short-term survival rate that was strongly associated with HIV infection, age and co-morbidities. Therapy with antiretroviral drugs reduced the short-term risk of death among HIV-seropositive patients after TB diagnosis