[THE EFFECTS OF HORMONAL REPLACEMENT THERAPY (HRT) ON MAMMOGRAPHIC BREAST DENSITY AND ABNORMAL MAMMOGRAMS PROMPTING FURTHER INVESTIGATION].

AIMS: The purpose of this study was to portray and analyze the inter-relationship between the use of HRT, mammographic breast density and the finding of any mammographic abnormality that prompted further investigation such as core needle biopsy or additional imaging testing, while controlling for obstetric and relevant demographic data. BACKGROUND: Mammographic breast density has been associated with higher risk of breast cancer and decrease in its sensitivity, while hormonal replacement therapy (HRT) in turn, has been implicated in increasing mammographic density and is considered a risk factor for breast cancer by itself. The inter-relationship between HRT, breast density and any mammographic or sonographic finding requiring further investigation has not been fully investigated. METHODS: A total of 2,758 consecutive, screening mammograms performed during one year in a single academic medical center in Israel were analyzed. Each mammogram was supplemented by high resolution ultrasound. Density was measured by a visual, semi-quantitative, 5-grade scale, based on Boyd's classification and grouped into low density mammograms (LDM) (1-3) and high density mammograms (HDM) (4-5). Demographic and obstetric data, personal and family history of breast cancer, and the use of HRT were entered into the database. These parameters were correlated with breast density and any detected abnormality that prompted further investigation. Univariate and multivariate analyses as well as multivariate logistic regression were performed using SAS 9.2. RESULTS: A significant difference in density was observed between pre- and post-menopausal women (p = 0.0001). However, the use of HRT in post-menopausal women was not associated with higher incidence of HDM (18.6%, n=110/592) compared to post-menopausal women without HRT (15.4%, n=211/1370) (p=n.s). Mammographic abnormality was more likely to occur in post-menopausal women without HRT (52%, n=711/1370) compared with women on HRT (38.7% n=229/592) (p = 0.0001). This held true for solid lump (p=0.0001), tissue irregularity (p=0.016) and calcifications (p=0.0005). Menopause was associated with higher likelihood (48%) of any mammographic finding compared with 41.6% in pre-menopausal women (p = 0.0017). A total of 266 women with mammographic findings prompting histological assessment were identified, revealing 105 malignant lesions. HRT in post-menopausal women was associated with lower incidence (28%) of malignancy compared to post-menopausal women without HRT (50%). CONCLUSIONS: The present study, portraying the inter-relationship between mammographic breast density, any abnormal finding in screening mammograms, and the use of HRT has not found such treatment to be associated neither with increased density, nor with higher probability of finding malignancy. Furthermore, a lower incidence of mammographic abnormality was noted in HRT users. Albeit, further and larger studies are required to substantiate these findings. The results of this study do not support the notion that HRT increases the likelihood of malignancy or affects breast density.

Diverticulitis: does age matter?

OBJECTIVE: Acute diverticulitis has been traditionally associated with worse outcome in young patients, indicating a more aggressive surgical approach is required for them. The aim of this study was to assess whether acute diverticulitis was more virulent in young patients. METHODS: A retrospective, cross-sectional study included all patients who were admitted for a first episode of acute diverticulitis between January 2004 and December 2013. The patients were divided into two groups (≤50 years and >50 years) based on their age. Patients' characteristics, clinical and surgical data were recorded and analyzed. RESULTS: Overall, 636 patients were included in the database, including 177 (27.8%) in the younger group and 459 in the elder group. There were no significant differences between the groups in disease complexity, peritonitis, laboratory work-up, vital signs on presentation, bowel obstruction or the presence of fistula and abscess in need of drainage. Younger patients had more free extra-luminal air on computed tomography (CT) scan (P = 0.03). Surgical data, including the intra-operative modified Hinchey score and the need for emergency and additional surgery did not significantly differ between the two groups. Young patients had more readmissions (P = 0.01) due to acute diverticulitis, diverticular complications and elective surgery. Length of hospital stay (P = 0.0001) was longer and postoperative complications were more common in the elder patients. CONCLUSIONS: The clinical presentation of acute diverticulitis does not seem to be worse in the young population. Younger patients tend to have a more severe presentation on CT scan and more readmissions, but this did not translate to a more severe disease course.

Mammographic Breast Density as a Predictor of Radiological Findings Requiring Further Investigation.

BACKGROUND: High density breast mammography has been associated with a greater risk for breast cancer and an increased likelihood of false negative results. OBJECTIVES: To assess whether the degree of mammographic breast density correlates with increased risk for the presence of radiographic findings requiring further histological investigation. METHODS: Included in the study were 2760 consecutive screening mammograms performed in a large volume, early detection mammography unit. All mammograms were complemented by high resolution ultrasound and interpreted by a single expert radiologist. Breast density (BD) was evaluated using a semi-quantitative 5 grade scale and grouped into low breast density (LBD) and high breast density (HBD) mammograms. Demographic and all relevant obstetric, personal and family history of breast cancer data were recorded. RESULTS: Of the 2760 mammograms 2096 (76%) were LBD and 664 (24%) were HBD. Mean age of the LBD and HBD groups was 59 ± 10.5 and 50.9 ± 9.3 years respectively (P = 0001). Breast density significantly correlated with presence of mammographic findings requiring further histological assessment (8.7% and 12.3% for LBD and HBD respectively, P < 0.01). In women younger than 60 years in whom histological assessment was required due to these findings, malignant pathology was significantly more prevalent in the HBD group (2.3% and 4.1% respectively, P = 0.03). Age, parity, patient history and HBD were identified as independent risk factors for any pathological mammographic finding. CONCLUSIONS: Highly dense mammography, aside from being an indicator of higher risk for breast cancer, appears to be associated with a significantly higher incidence of findings that will prompt further investigation to achieve a definite diagnosis.

Israeli Dying Patient Act: physician knowledge and attitudes.

OBJECTIVES: The recently enacted Israeli Dying Patient Act was designed to strike balance between enhancing patient autonomy in end-of-life decision making and cultural/religious norms that are in opposition to active euthanasia and physician-assisted suicide (PAS). The current study evaluated physician attitudes regarding active and passive euthanasia, and their knowledge of specific aspects of the law. METHODS: A survey was administered to a convenience sample of hospital-based physicians treating terminal patients. Physicians were queried about their attitudes regarding euthanasia and PAS. Physicians were also queried about specific aspects of the law and whether they had sufficient resources to uphold the law. RESULTS: Surveys were distributed to 270 physicians and 100 were returned and evaluated (37%). Nearly all physicians supported passive euthanasia (withholding treatment), whereas over 40% maintained that active forms of euthanasia should be allowed for terminal patients in severe physical pain. Multivariate analysis showed a negative relationship between support for more active forms of euthanasia and physicians' self-reported religiosity. Physicians cited lack of time as a reason for not complying with the new law. Physicians had a familiarity with the general aspects of the new legislation, but a large proportion was not aware of the specifics of the law. CONCLUSIONS: Compared with previous surveys, a larger number of physicians support passive euthanasia. A sizable percentage of physicians would be willing to participate in active euthanasia and even PAS. Attitudes toward euthanasia are influenced by religious factors.

Correlation between visual acuity and cognitive functions.

A possible association between visual acuity (VA) and dementia was investigated in 2716 subjects who were aged between 53 and 102 at first visit and had varying degrees of dementia. Better VA was found to be significantly correlated with a lower dementia level (person coefficient range 0.146-0.261 over 10 years of follow-up, all correlations are significant, p<0.0001) as well as with a higher global cognitive score (person coefficient range -0.254 to -0.318 over 10 years of follow-up, all correlations are significant, p<0.0001), a grade encompassing 19 different cognitive tests. This correlation remained significant after adjustment for age, years of education, gender, use of ophthalmic drugs and years of follow-up.

Erythropoietin treatment is associated with an augmented immune response to the influenza vaccine in hematologic patients.

The objective of this study was to examine whether treatment with recombinant human erythropoietin (rHuEPO), previously found to be associated with a positive effect on cell-mediated immunity and humoral immunity (hepatitis B vaccine), is associated with an improved response to the seasonal influenza (flu) vaccine. Three groups received flu vaccine: healthy controls, hematologic patients not treated with rHuEPO ("No EPO" group), and hematologic patients receiving rHuEPO for their anemia ("EPO" group). Anti-flu Ab titer was measured (complement fixation test) from blood samples drawn before and approximately 3-4 weeks, 7-8 weeks and 4 months after vaccination. Nineteen healthy subjects were compared with 17 No EPO and 17 EPO patients. Mean ages were 59.5, 61.3, and 73.1 years, respectively (EPO patients were older; p = 0.005). In the healthy group, the percentage of those sustaining only a partial (twofold) response, a strong (fourfold or greater) response, and an overall response (combined partial and strong responses) were 31.6%, 57.9%, and 89.5%, respectively. In the No EPO group, values were 35.3%, 17.6%, and 52.9%, respectively. EPO group results were similar to those of the healthy controls: 23.5%, 58.8%, and 82.4% (p = 0.016, EPO vs. No EPO). In conclusion, hematologic patients (NoEPO group) respond poorly to the flu vaccine, compared with healthy subjects, and rHuEPO treatment is associated with an improved immune response to the flu vaccine in hematologic patients, with titers similar to those of healthy subjects.

Freezability and semen parameters in candidates of sperm bank donors: 1992-2010.

There has been considerable concern worldwide about possible semen quality deterioration over the last 2 decades. The aim of this study was to evaluate freezability and semen quality of healthy young males during the years 1992-2010. A total of 1211 young (20-32 years old) candidates for sperm bank donation were recruited into the study with no exclusion criteria. They were instructed to observe 2 to 3 days of abstinence from sexual activity, and most of them supplied 2 specimens each. Average values of the various semen parameters, including freezing survival, were calculated for each participant. The change in different semen parameters over years, according to yearly and monthly average temperatures, was evaluated by SAS PROC SURVEYREG analysis. During that period, there were significant increases in motility and vitality percentages, as well as in the percentage of thawed sperm motility. The parameters of volume, concentration, normal morphology, total count, and total motile count showed a significant decrease with years (P < .01). The significant increase in average yearly temperature (P < .004) had limited, nonsignificant association with any of the semen variables. However, average monthly temperature contributed significantly to the trend of semen quality parameters (ie, specimen volume, concentration, percentage of normal morphology, and thawed motility). To the best of our knowledge, this is the first demonstration of the occurrence of an improvement in percent thawed motility over the years, and its significance lies in enabling a higher proportion of sperm bank candidates to be suitable for donation. It is suggested that the global warming phenomenon might have only partial contribution to semen variable changes over the years.

Identification of children's gender and age by listeners.

OBJECTIVES: Voice carries abundant information about the speaker. This acoustic information changes throughout life. Although the ability of identifying audible cues on a speaker's gender and age is considered an intuitive task, little is known about the ability to identify and decipher this perceptual information. Most studies in the field have examined the ability to identify adults' gender and age, thus the purpose of the present study was to evaluate listeners' ability to identify gender and age of children and adolescents. METHODS: A total of 120 children in six age groups, 8, 10, 12, 14, 16, and 18 years, were recorded while producing isolated vowels and fixed sentences. The recordings were evaluated by a group of 38 untrained naive listeners, who were asked to identify the speakers' gender and age. RESULTS: Listeners were able to identify children's gender at an overall rate of 81.81%. This task was performed more successfully based on recordings of sentences (85.39%) than on isolated vowels (78.22%). Listeners were able to identify the children's age group at an overall rate of 37.16%. This task was also performed more successfully based on recordings of sentences (39.58%) than on isolated vowels (34.71%). Furthermore, when an error of ±1 age group was allowed, correct responses for age identification exceeded 80%. CONCLUSIONS: Listeners have the ability to identify children's gender and age, based on short audio recordings, even before puberty. The success rates in these perceptual tasks are dependent on the child's age and gender.

Evidence for atypical auditory brainstem responses in young children with suspected autism spectrum disorders.

AIM: The aim of this study was to characterize the auditory brainstem responses (ABRs) of young children with suspected autism spectrum disorders (ASDs) and compare them with the ABRs of children with language delay and with clinical norms. METHOD: The ABRs of 26 children with suspected ASDs (21 males, five females; mean age 32.5 mo) and an age- and sex-matched group of 26 children with language delay (22 males, four females) were analysed. All children had normal hearing. The absolute latencies of waves I, III, and V, and interpeak latencies (IPLs) I to III, I to V, and III to V of the group with ASDs and the group with language delay were compared. Data from both groups were further compared with clinical norms. RESULTS: All absolute latencies and IPLs were significantly prolonged in the group with suspected ASDs compared with the group with language delay, excluding IPL III-V (all p-values <0.05) and with clinical norms (all p-values <0.001; IPL III-V, p<0.05). Significant prolongation of absolute and IPLs was also evident in the group with language delay compared with clinical norms, excluding IPL III to V (all p-values <0.001). The prevalence of abnormal findings in two or more absolute latencies was found to be significantly higher in the group with ASDs (50%) than in the group with language delay (8%; p=0.002). INTERPRETATION: The results provide first-time evidence for a neurodevelopmental brainstem abnormality that is already apparent in young children with suspected ASD and language delay. The overlap in ABR findings supports the assertion that an auditory processing deficit may be at the core of these two disorders.

Tissue expression of squamous cellular carcinoma antigen and Ki67 in hepatocellular carcinoma-correlation with prognosis: a historical prospective study.

BACKGROUND: Squamous cellular carcinoma antigen (SCCA) is overexpressed in hepatocellular carcinoma (HCC) tissue and in sera of HCC patients. Our aim was to assess hepatic SCCA immunostaining in a series of HCCs and to correlate its presence with cell proliferation, apoptosis and clinical outcome. METHODS: Sixty-one HCC patients were included. Liver specimens were obtained either by biopsy (n = 17) or surgically (resection 27, transplantation 17). Immunostaining for AFP, Ki-67, SCCA and TUNEL assay were performed. RESULTS: SCCA staining was detected in 83.6% of specimens. A statistical significant correlation was found between negative SCCA staining and mortality (p = 0.026) and a higher immunostaining score for Ki67 (p = 0.017). Positive SCCA staining was associated with well and moderate differentiated tumors (p = 0.022). Using multiple logistic regression analysis, Ki67 and TUNEL assay were found to be significant independent predictors of negative SCCA immunostaining. The area under the receiver operator characteristic curve was 0.87. Kaplan-Meier survival analysis revealed a significant difference between the patient group with positive versus negative SCCA immunostaining relating to survival time (p = 0.0106). Cox proportional hazard regression analysis demonstrated that Ki67 immunostaining and liver transplantation or resection were independently associated with mortality. CONCLUSIONS: SCCA is overexpressed in HCC. SCCA status is associated with cell proliferation, apoptosis and survival. SCCA and Ki67 staining can predict survival. Our study results support a potential association of negative SCCA expression with other markers of poor outcome in HCC. More studies are needed to clarify the role of SCCA in HCC and expand the knowledge of the SCCA antigen in HCC patients.

The effects of group 1 versus group 2 carbapenems on imipenem-resistant Pseudomonas aeruginosa: an ecological study.

Use of the group 2 carbapenems, imipenem and meropenem, may lead to emergence of Pseudomonas aeruginosa resistance. The group 1 carbapenem ertapenem has limited activity against P. aeruginosa and is not associated with imipenem-resistant P. aeruginosa (IMP-R PA) in vitro. This retrospective, group-level, longitudinal study collected patient, antibiotic use, and resistance data from 2001 to 2005 using a hospital database containing information on 9 medical wards. A longitudinal data time series analysis was done to evaluate the association between carbapenem use (defined daily doses, or DDDs) and IMP-R PA. A total of 139 185 patient admissions were included, with 541 150 antibiotics DDDs prescribed: 4637 DDDs of group 2 carbapenems and 2130 DDDs of ertapenem. A total of 779 IMP-R PA were isolated (5.6 cases/1000 admissions). Univariate analysis found a higher incidence of IMP-R PA with group 2 carbapenems (P < 0.001), aminoglycosides (P = 0.034), and penicillins (P = 0.05), but not with ertapenem. Multivariate analysis showed a yearly increase in incidence of IMP-R-PA (3.8%, P < 0.001). Group 2 carbapenem use was highly associated with IMP-R PA, with a 20% increase in incidence (P = 0.0014) for each 100 DDDs. Group 2 carbapenem use tended to be associated with an increased proportion of IMP-R PA (P = 0.0625) in multivariate analysis. Ertapenem was not associated with IMP-R PA. These data would support preferentially prescribing ertapenem rather than group 2 carbapenems where clinically appropriate.

Inflammatory mediators in breast cancer: coordinated expression of TNFα & IL-1ß with CCL2 & CCL5 and effects on epithelial-to-mesenchymal transition.

BACKGROUND: The inflammatory chemokines CCL2 (MCP-1) & CCL5 (RANTES) and the inflammatory cytokines TNFα & IL-1ß were shown to contribute to breast cancer development and metastasis. In this study, we wished to determine whether there are associations between these factors along stages of breast cancer progression, and to identify the possible implications of these factors to disease course. METHODS: The expression of CCL2, CCL5, TNFα and IL-1ß was determined by immunohistochemistry in patients diagnosed with: (1) Benign breast disorders (=healthy individuals); (2) Ductal Carcinoma In Situ (DCIS); (3) Invasive Ducal Carcinoma without relapse (IDC-no-relapse); (4) IDC-with-relapse. Based on the results obtained, breast tumor cells were stimulated by the inflammatory cytokines, and epithelial-to-mesenchymal transition (EMT) was determined by flow cytometry, confocal analyses and adhesion, migration and invasion experiments. RESULTS: CCL2, CCL5, TNFα and IL-1ß were expressed at very low incidence in normal breast epithelial cells, but their incidence was significantly elevated in tumor cells of the three groups of cancer patients. Significant associations were found between CCL2 & CCL5 and TNFα & IL-1ß in the tumor cells in DCIS and IDC-no-relapse patients. In the IDC-with-relapse group, the expression of CCL2 & CCL5 was accompanied by further elevated incidence of TNFα & IL-1ß expression. These results suggest progression-related roles for TNFα and IL-1ß in breast cancer, as indeed indicated by the following: (1) Tumors of the IDC-with-relapse group had significantly higher persistence of TNFα and IL-1ß compared to tumors of DCIS or IDC-no-relapse; (2) Continuous stimulation of the tumor cells by TNFα (and to some extent IL-1ß) has led to EMT in the tumor cells; (3) Combined analyses with relevant clinical parameters suggested that IL-1ß acts jointly with other pro-malignancy factors to promote disease relapse. CONCLUSIONS: Our findings suggest that the coordinated expression of CCL2 & CCL5 and TNFα & IL-1ß may be important for disease course, and that TNFα & IL-1ß may promote disease relapse. Further in vitro and in vivo studies are needed for determination of the joint powers of the four factors in breast cancer, as well as analyses of their combined targeting in breast cancer.

Do oncologists engage in bereavement practices? A survey of the Israeli Society of Clinical Oncology and Radiation Therapy (ISCORT).

PURPOSE: We sought to determine the level of involvement of oncologists in bereavement rituals after a patient dies. SUBJECTS AND METHODS: Members of the Israeli Society for Clinical Oncology and Radiation Therapy (ISCORT) were surveyed. The survey instrument consisted of questions regarding participation in bereavement rituals for patients in general and those with whom the oncologist had a special bond. Oncologists were queried as to the reasons for nonparticipation in bereavement rituals. RESULTS: Nearly 70% of the ISCORT membership (126 of 182) completed the survey tool. Respondents included radiation, surgical, and medical oncologists. In general, oncologists rarely participated in bereavement rituals that involved direct contact with families such as funerals and visitations. Twenty-eight percent of physicians at least occasionally participated in rituals involving direct contact whereas 45% had indirect contact (e.g., letter of condolence) with the family on an occasional basis. There was significantly greater involvement in bereavement rituals when oncologists developed a special bond with the patient. In a stepwise linear regression model, the only factor significantly associated with greater participation in bereavement rituals was self-perceived spirituality in those claiming not to be religious. The major reasons offered for nonparticipation were time constraints, need to maintain appropriate boundaries between physicians and patients, and fear of burnout. CONCLUSION: Although many oncologists participate at least occasionally in some sort of bereavement ritual, a significant proportion of oncologists are not involved in these practices at all.

Long-term cryostorage of sperm in a human sperm bank does not damage progressive motility concentration.

BACKGROUND: The use of quarantined cryopreserved semen is mandatory in donor insemination programs. Whether sperm cells can survive and retain their ability to fertilize after long-term storage remains a controversial issue. The objective of this study was to determine the effect of the duration of cryostorage in liquid nitrogen on the sperm cells' progressive motility concentration (PMC) in a large study group. METHODS: A total of 2525 thawed sperm specimens, packed in straws and donated by 72 sperm bank donors for intrauterine insemination (IUI), were evaluated in an assisted reproduction institute. PMC was recorded after 0.5-14.4 years of cryostorage. RESULTS: The mean (+/-SD) value of PMC of all study samples was 10.8 +/- 3.3 x 10(6)/ml after freezing/thawing and before cryostorage (T0), and 12.3 +/- 2.9 x 10(6)/ml after storage and before using the specimen for IUI (T1, P < 0.0001). Specimen storage for different lengths of time revealed that storage duration had no significant influence on the PMC of the specimens (r = -0.03, P = 0.08). The PMC of partially filled straws was lower than in full straws. Cryostorage duration made no difference in the PMC of raw and washed sperm specimens. CONCLUSION: Prolonged storage of donated sperm in liquid nitrogen had no influence on the PMC of the specimens and therefore should not alter the fertilization potency of donated sperm. The high post-storage values of the PMC compared with the pre-storage PMC values was probably an artifact of the small volume of the pre-storage sample.

[Laparoscopic colon and rectal surgery--after ten years and 350 operations].

BACKGROUND: Within a decade since laparoscopy was used in cholecystectomy it has become the preferred approach in many abdominal procedures. Laparoscopic colon and rectal surgery has not yet been adopted by the majority of surgeons, due to technical complexity and reservation regarding its oncological safety. As data and experience accumulate, this attitude is gradually changing. We present our experience with laparoscopic surgery of the large bowel over the last ten years. AIM: To assess the short and intermediate term results after laparoscopic colon and rectal surgery, and to summarize the long term results after curative colectomy for malignancy. METHODS: Data regarding all patients undergoing laparoscopic colon and rectal surgery was prospectively entered into a computerized database, including demographics, surgical technique and perioperative course. Follow-up information was gathered at outpatient clinic visits, and using telephone interviews in selected cases. Data analysis was performed using a statistical software package. RESULTS: Over a period of ten years, 350 various laparoscopic colon and rectal procedures were performed, for both benign and malignant conditions. Sixty percent of the operations were for treatment of colorectal cancer. In 14.5% of cases conversion to open laparotomy was required. Post-operative complications included surgical site infection in 17.4%, anastomotic leak in 6.9%, and a mortality rate of 2.8%. Long term follow-up revealed cancer recurrence locally in 2.3% and systemically in 8.2%. Five year survival was 56% after resection of colorectal cancer regardless of the stage, and 63% after resection with curative intent. CONCLUSIONS: The laparoscopic approach to large bowel surgery enables short and long term results comparable with those achieved by open technique, regarding perioperative complication rate and long term oncologic outcome. The advantages of laparoscopy, related to reduced abdominal wall trauma, justify the adoption of this technique as a legitimate alternative to the open approach.

Birth control pills and nonprofessional voice: acoustic analyses.

PURPOSE: Two studies are presented here. Study 1 was aimed at evaluating whether the voice characteristics of women who use birth control pills that contain different progestins differ from the voice characteristics of a control group. Study 2 presents a meta-analysis that combined the results of Study 1 with those from 3 recent studies that compared voices of women who use and do not use birth control pills. METHOD: In Study 1, voice samples from 30 women with no history of voice training, who use pills with different progestins (drospirenone, desogestrel, gestodene), and 10 women who do not use the pill were recorded at specific time points across the menstrual cycle and were analyzed acoustically. In Study 2, results from Study 1 were analyzed jointly with results from three recent studies, which used similar methodologies. RESULTS: Results of Study 1 did not reveal acoustic differences in sustained phonation of vowels across the pill groups and controls. Results of the meta-analysis performed in Study 2 indicated that pill users exhibited lower jitter and shimmer values on sustained vowels, whereas no difference of fundamental frequency was observed among women who use the pill. CONCLUSIONS: These results support findings from previous studies, which suggested that no adverse effect on voice was detected among nonprofessional speakers who use new-generation monophasic birth control pills, for the measures studied. Furthermore, results of the meta-analysis suggested that some acoustic properties of the voice, which are reflected in perturbation measures in sustained vowels, may be improved among women who use the pill.

Is the model of end-stage liver disease (MELD) valid in Israel? A critical analysis of liver transplant waiting list mortality.

BACKGROUND: The model for end-stage liver disease is the best available predictor of waiting list mortality among liver transplant candidates. OBJECTIVES: To validate the applicability of MELD in Israel. METHODS: All candidates awaiting liver transplantation in our institution were followed prospectively since 2002. We measured the concordance (c-statistic) equivalent to the area under the receiver operating characteristic curve in order to assess the predictive power of MELD. Other independent mortality risk factors were identified by a separate multivariate analysis. Mortality rates within different MELD and Child-Pugh-Turcotte scores were compared to the original (United States) MELD data. RESULTS: Of 86 patients listed for transplantation, 40 were transplanted (36 in Israel and 4 abroad). Of the other 46 patients, 24 are alive and still listed, and 22 died (25%, approximately 7%/year). The area under the ROC curve for MELD score was 0.79 (0.83 USA) compared to a CPT score of 0.71 (0.76 USA). High MELD scores, occurrence of spontaneous bacterial peritonitis, and diagnosis of hepatocellular carcinoma were independent risk factors of mortality. Death rates per mid-MELD score (20-29) were significantly higher than the USA results. CONCLUSIONS: MELD is valid in Israel and superior to CPT in predicting waiting list mortality. Although longer waiting time due to organ scarcity is a key factor, death rates in the mid-range (10-29) MELD groups indicate further audit of the care of patients with end-stage liver disease.

The chemokine CCL5 as a potential prognostic factor predicting disease progression in stage II breast cancer patients.

PURPOSE: The aim of this study was to determine the prognostic value of the chemokine CCL5, considered as a promalignancy factor in breast cancer, in predicting breast cancer progression and to evaluate its ability to strengthen the prognostic significance of other biomarkers. EXPERIMENTAL DESIGN: The expression of CCL5, alone and in conjunction with estrogen receptor (ER)-alpha, ER-beta, progesterone receptor (PR), and HER-2/neu (ErbB2), was determined in breast tumor cells by immunohistochemistry. The study included 142 breast cancer patients, including individuals in whom disease has progressed. RESULTS: Using Cox proportional hazard models, univariate analysis suggested that, in stage I breast cancer patients, CCL5 was not a significant predictor of disease progression. In contrast, in stage II patients, the expression of CCL5 (CCL5(+)), the absence of ER-alpha (ER-alpha(-)), and the lack of PR expression (PR(-)) increased significantly the risk for disease progression (P = 0.0045, 0.0041, and 0.0107, respectively). The prognostic strength of CCL5, as well as of ER-alpha(-), improved by combining them together (CCL5(+)/ER-alpha(-): P = 0.0001), being highly evident in the stage IIA subgroup [CCL5(+)/ER-alpha(-) (P = 0.0003); ER-alpha(-) (P = 0.0315)]. In the stage II group as a whole, the combinations of CCL5(-)/ER-alpha(+) and CCL5(-)/PR(+) were highly correlated with an improved prognosis. Multivariate analysis indicated that, in stage II patients, ER-alpha and CCL5 were independent predictors of disease progression. CONCLUSIONS: CCL5 could be considered as a biomarker for disease progression in stage II breast cancer patients, with the CCL5(+)/ER-alpha(-) combination providing improved prediction of disease progression, primarily in the stage IIA subgroup.

Cortical activity of children with dyslexia during natural speech processing: evidence of auditory processing deficiency.

Children with dyslexia have difficulties with phonological processing. It is assumed that deficits in auditory temporal processing underlie the phonological difficulties of dyslectic subjects (i.e. the processing of rapid acoustic changes that occur in speech). In this study we assessed behavioral and electrophysiological evoked brain responses of dyslectic and skilled reading children while performing a set of hierarchically structured auditory tasks. Stimuli consisted of auditory natural unmodified speech that was controlled for the parameter of changing rate of main acoustic cues: vowels (slowly changing speech cues: /i/ versus /u/) and consonant-vowel (CV) syllables (rapidly changing speech cues: /da/ versus /ga/). Brain auditory processing differed significantly between groups: reaction time of dyslectic readers was prolonged in identifying speech stimuli and increased with increased phonological demand. Latencies of auditory evoked responses (auditory event related potentials [AERPs]) recorded during syllable identification of the dyslectic group were prolonged relative to those of skilled readers. Moreover, N1 amplitudes during vowel processing were larger for the dyslectic children and P3 amplitudes during CV processing were smaller for the dyslectic children. From the results of this study it is evident that the latency and amplitude of AERPs are sensitive measures of the complexity of phonological processing in skilled and dyslectic readers. These results may be signs of deficient auditory processing of natural speech under normal listening conditions as a contributing factor to reading difficulties in dyslexia. Detecting a dysfunction in the central auditory processing pathway might lead to early detection of children who may benefit from phonetic-acoustic training methods.

Monitoring oral anticoagulant therapy by telephone communication.

The number of patients who need supervision during oral anticoagulant treatment is growing constantly. We have presently enrolled 156 patients who were referred to our anticoagulant clinic and who were taking sodium warfarin with target International Normalized Ratios (INR) of low (2-3), intermediate (2.5-3.5) and high (3-4) range. Patients performed the tests in laboratories situated in locations at their convenience and received further instructions from a specialist via telephone communication. A total of 8758 prothrombin times (5214, 1947 and 1597 tests for individuals in the low, intermediate and high range, respectively) were performed over the period of 3.16 +/- 2.6 years (range, 6 months-9.5 years) and reported to the specialist. It was found that in the aforementioned three groups of intensity 63.3, 57.0 and 47.7% of the INRs were within the target range, the respective percentages for the expanded (+/- 0.5) target INR being 92.8, 87.8 and 78.5%. The INTERDAY software was used to calculate the number and proportion of days within the target INR range, the respective results being 71.0, 64.0 and 51.6% and 96.2, 93.2, 86.4% for the expanded range. The number and percentage of bleeding and embolic complications' referrals to the emergency room and hospitalizations were similar to those reported for anticoagulant clinics in which patients have to actually pay a personal visit in order to receive instructions. Our study is significant in that it documents that trans-telephonic communication is feasible safe and cost-effective and that the clinical results are at least as good as those obtained by traditional consultation.