The Association Between Low Body-Mass Index and Serious Post-endoscopic Adverse Events.

BACKGROUND: Low body mass index (LBMI) was associated with longer colonoscopy procedure time and procedural failure, and commonly considered to be a risk factor for post-endoscopic adverse events, but evidence is lacking. AIM: We aimed to assess the association between serious adverse events (SAE) and LBMI. METHODS: A single center retrospective cohort of patients with LBMI (BMI ≤ 18.5) undergoing an endoscopic procedure was matched (1:2 ratio) to a comparator group (19 ≤ BMI ≤ 30). Matching was performed according to age, gender, inflammatory bowel disease or malignancy diagnoses, previous abdomino-pelvic surgery, anticoagulation therapy and type of endoscopic procedure. The primary outcome was SAE, defined as bleeding, perforation, aspiration or infection, following the procedure. The attribution between each SAE and the endoscopic procedure was determined. Secondary outcomes included each complication alone and endoscopy-attributed SAEs. Univariate and multivariate analyses were applied. RESULTS: 1986 patients were included (662 in the LBMI group). Baseline characteristics were mostly similar between the groups. The primary outcome occurred in 31/662 (4.7%) patients in the LBMI group and in 41/1324 (3.1%) patients in the comparator group (p = 0.098). Among the secondary outcomes, infections (2.1% vs. 0.8%, p = 0.016) occurred more frequently in the LBMI group. Multivariate analysis revealed an association between SAE and LBMI (OR 1.76, 95% CI 1.07-2.87), male gender, diagnosis of malignancy, high-risk endoscopic procedure, age > 40 years, and ambulatory setting. CONCLUSION: Low BMI was associated with higher post-endoscopic serious adverse events. Special attention is required when performing endoscopy in this fragile patient population.

Third BNT162b2 Vaccine Booster Dose against SARS-CoV-2-Induced Antibody Response among Healthcare Workers.

This study assessed humoral response to the third BNT162b2 dose among healthcare workers (HCW). This prospective cohort study of HCW tested for anti-spike antibodies (LIAISON SARS-CoV-2 S1/S2 IgG assay) at 1, 3, 6, 9, and 12 months after receiving the second BNT162b2 vaccine dose (tests 1, 2, 3, 4, and 5, respectively). A third (booster) vaccination dose was introduced before test 4. Linear regression model was used to determine the humoral response following vaccine doses. For each serology test, changes in log-transformed antibody concentrations over time, adjusted for age, sex, underlying diseases, steroid treatment, and smoking were described using the general linear mix model. Serology tests were performed at 3, 6, 9, and 12 months after the second vaccine dose in 1113, 1058, 986, and 939 participants, respectively. The third dose was received by 964 participants before the 9-month tests, 797 of whom participated in the 9- and 12-month serology tests. A significant inverse correlation was noted between time from third dose and antibody concentrations (Spearman correlation −0.395; p < 0.001). Age (p < 0.0001; CI 95% −0.005−−0.004), heart disease (p < 0.0001; CI 95% −0.177−−0.052), immunodeficiency (p < 0.0001; CI 95% 0.251−−0.106), and smoking (p < 0.0001; CI 95% −0.122−−0.040) were significantly associated with decreased antibody concentrations. Female sex (p = 0.03; CI 95% 0.013−0.066) was associated with increased antibody concentrations. The third booster dose had a better effect on immunogenicity, with higher antibody concentrations among tested HCW. Heart disease, smoking, and other known risk factors were associated with decreased antibody concentrations.

Psychosocial perspectives among cancer patients during the coronavirus disease 2019 (COVID-19) crisis: An observational longitudinal study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) crisis and consequent changes in medical practice have engendered feelings of distress in diverse populations, potentially adversely affecting the psychological well-being of cancer patients. AIM: The purpose of this observational longitudinal study was to evaluate psychosocial perspectives among patients with cancer on intravenous treatment during the COVID-19 pandemic. METHODS AND RESULTS: The study recruited 164 cancer patients undergoing intravenous anti-neoplastic therapy in a tertiary cancer center. Psychosocial indices were assessed at two points in time, corresponding with the beginning of the first wave of COVID-19 pandemic in Israel (March 2020) and the time of easing of restrictions implemented to curtail spread of infection (May 2020). At Time 1 (T1), elevated COVID-19 distress levels (score 1 and 2 on 5-point scale) were observed in 44% of patients, and associated with pre-existing hypertension and lung disease in multivariate analyses but no demographic or cancer related factors. At Time 2 (T2), 10% had elevated anxiety and 24% depression as indicated by Hospital Anxiety and Depression Scale (HADS-A/D). COVID-19 distress at T1 was related to higher levels of HADS-A at T2 (Spearman 0.33 p < .01), but not HADS-D. Patients with breast cancer expressed greater COVID-19 distress compared with other cancer types (p < .01), while both HADS-A and HADS-D were highest for patients with GI cancer. Patient report of loneliness and decreased support from relatives were factors associated with HADS-A (p = .03 and p < .01, respectively), while HADS-D was not similarly related to the factors evaluated. CONCLUSION: Patients with cancer undergoing intravenous treatment may be vulnerable to acute adverse psychological ramifications of COVID-19, specifically exhibiting high levels of anxiety. These appear unrelated to patient age or disease stage. Those with underlying comorbidities, breast cancer or reduced social support may be at higher risk.

Secukinumab real world drug retention compared to TNF-alpha inhibitors in psoriatic arthritis.

OBJECTIVES: To prospectively study real-world efficacy and safety of secukinumab in psoriatic arthritis (PsA) patients from the Israeli registry of inflammatory diseases. METHODS: PsA patients fulfilling the CASPAR criteria were included in the analysis from 2010 to 2019. The primary endpoint was secukinumab drug retention compared to other TNF-α inhibitors (TNFi). Bivariate and multivariate analyses were made by Cox regression analysis. Drug retention according to treatment line was examined with Kaplan-Meier curves. RESULTS: Included were 404 PsA patients who had 709 treatment courses during the study period. Ninety patients had been treated with secukinumab (22%). The secukinumab-treated patients were significantly older and their disease duration was longer. Secukinumab was less likely to be the first line of treatment compared to TNFi. Secukinumab had a drug retention comparable to TNFi, and a better drug retention than TNFi among biologic-experienced patients. Neither methotrexate combination nor body mass index affected the inefficacy event rate. Secukinumab had a similar rate of adverse events as TNFi. CONCLUSIONS: This multicentre real-world study demonstrated that secukinumab had a drug retention comparable to TNFi. Secukinumab had a better drug retention than TNFi among biologic-experienced patients. IL-17 inhibition is an effective mechanism of action to treat PsA in real life.

Six-Month Efficacy and Toxicity Profile of BNT162b2 Vaccine in Cancer Patients with Solid Tumors.

We had previously reported short-term efficacy, immunogenicity, and safety of the BNT162b2 vaccine among cancer patients with solid tumors. We aimed to evaluate these outcomes at six months postvaccination. The study cohort comprised patients who were on treatment during vaccination and throughout six months postvaccination. Serologic tests were performed after second vaccination and six months afterward. An age-matched cohort of health care workers served as controls. Documentation of COVID-19 infection, blood tests, and imaging studies during the study period was reviewed. Participants included 154 patients and 135 controls. Six months postvaccination, 122 (79%) patients were seropositive compared with 114 (84%) controls (P = 0.32). Serology titer dramatically decreased in a similar manner in both cohorts. No COVID-19 cases were documented in controls, and one case occurred in patient cohort. All previously reported adverse effects resolved. Taken together, the pattern of immunogenicity, efficacy, and safety of BNT162b2 in patients with cancer with solid tumors at six months postvaccination resembles that of the general population. SIGNIFICANCE: Evidence regarding efficacy and safety of COVID-19 vaccines in patients with cancer indicate a favorable short-term profile. Immunomodulation due to anticancer treatments may affect immunity and immunogenicity of patients with cancer to the BNT162b2 vaccine over time. Our study sheds light on these long-term outcomes and portrays a trend that resembles the general population.This article is highlighted in the In This Issue feature, p. 2355.

The ubiquitin ligase RNF5 determines acute myeloid leukemia growth and susceptibility to histone deacetylase inhibitors.

Acute myeloid leukemia (AML) remains incurable, largely due to its resistance to conventional treatments. Here, we find that increased abundance of the ubiquitin ligase RNF5 contributes to AML development and survival. High RNF5 expression in AML patient specimens correlates with poor prognosis. RNF5 inhibition decreases AML cell growth in culture, in patient-derived xenograft (PDX) samples and in vivo, and delays development of MLL-AF9-driven leukemogenesis in mice, prolonging their survival. RNF5 inhibition causes transcriptional changes that overlap with those seen upon histone deacetylase (HDAC)1 inhibition. RNF5 induces the formation of K29 ubiquitin chains on the histone-binding protein RBBP4, promoting its recruitment to and subsequent epigenetic regulation of genes involved in AML maintenance. Correspondingly, RNF5 or RBBP4 knockdown enhances AML cell sensitivity to HDAC inhibitors. Notably, low expression of both RNF5 and HDAC coincides with a favorable prognosis. Our studies identify an ERAD-independent role for RNF5, demonstrating that its control of RBBP4 constitutes an epigenetic pathway that drives AML, and highlight RNF5/RBBP4 as markers useful to stratify patients for treatment with HDAC inhibitors.

High Body Mass Index is Associated with Shorter Retention of Tumor Necrosis Factor-Alpha Blocker Treatment in Rheumatoid Arthritis.

PURPOSE: To evaluate the association between body mass index (BMI) and tumor necrosis factor α (TNF-α) blockers retention in patients with rheumatoid arthritis (RA). PATIENTS AND METHODS: This prospective cohort study analyzed data about patients with RA who initiated TNF blockers from the Israeli registry of inflammatory diseases from 2011 to 2019. Patients were grouped by BMI: normal (BMI <24.9 kg/m2), overweight (BMI 25-29.9 kg/m2), obese (BMI 30-34.9 kg/m2) and morbid obese (BMI ≥35 kg/m2). Treatment cessation due to inefficacy was defined as an "event" and therapy with a drug above 3 months was defined as a "course." Kaplan-Meier survival curve was used to describe drug survival. Event-free survival was calculated using Cox regression with a hazard ratio and confidence interval of 95%. RESULTS: The final analysis included 521 RA patients (80% females) treated with etanercept, infliximab, adalimumab or golimumab. Eight hundred and eighteen treatment initiations were included in the final analysis, 334 (41%) in the normal weight group, 261 (32%) in the overweight, 144 (17%) in the obese and 79 (10%) in the morbid obesity group. Three hundred and twenty-six (40%) treatment initiations were with etanercept, 215 (26%) with adalimumab 197 (24%) with infliximab, and 80 (10%) with golimumab. BMI was inversely associated with drug survival. Morbid obese patients were more likely to discontinue treatment compared with normal weight patients HR 2.28 (95% CI 1.67-3.10, p<0.01). This association remained significant for each drug type (except for golimumab) in a subgroup analysis. Adalimumab switch rate was higher compared to etanercept with HR =1.51 (95% CI 1.20-1.91, p<0.01), no other significant differences were noted between the other drugs. CONCLUSION: Morbid obese RA patients have lower TNF-α blocker retention compared to normal weight patients.

Serologic Status and Toxic Effects of the SARS-CoV-2 BNT162b2 Vaccine in Patients Undergoing Treatment for Cancer.

Importance: The efficacy and safety profile of SARS-CoV-2 vaccines have been acquired from phase 3 studies; however, patients with cancer were not represented in these trials. Owing to the recommendation to prioritize high-risk populations for vaccination, further data are warranted. Objective: To evaluate the use and safety of the BNT162b2 vaccine in patients undergoing treatment for cancer. Design, Setting, and Participants: In January 2021, mass SARS-CoV-2 vaccination of high-risk populations, including patients with cancer, was initiated in Israel. This cohort study prospectively enrolled and followed up patients with cancer and healthy participants between January 15 and March 14, 2021. The study was conducted at the Division of Oncology of Rambam Health Care Campus, the major tertiary (referral) medical center of northern Israel. Participants included 232 patients with cancer who were receiving active treatment after the first and second doses of the BNT162b2 vaccine and 261 healthy, age-matched health care workers who served as controls. Exposures: Serum samples were collected after each vaccine dose and in cases of seronegativity. Questionnaires regarding sociodemographic characteristics and adverse reactions were administered at serum collection. A regulatory agencies-approved assay was used to assess IgG at all time points. Patients' electronic medical records were reviewed for documentation of COVID-19 infection and results of blood cell counts, liver enzyme levels, and imaging studies. Main Outcomes and Measures: Seroconversion rate after the first and second doses of the BNT162b2 vaccine and documented COVID-19 infection. Results: Of the 232 patients undergoing treatment for cancer, 132 were men (57%); mean (SD) age was 66 (12.09) years. After the first dose of BNT162b2 vaccine, 29% (n = 25) patients were seropositive compared with 84% (n = 220) of the controls (P < .001). After the second dose, the seropositive rate reached 86% (n = 187) in the patients. Testing rate ratios per 1000 person-days after the first dose were 12.5 (95% CI, 3.4-45.7) for the patients and 48.5 (95% CI, 37.2-63.2) for the controls. Patients undergoing chemotherapy showed reduced immunogenicity (odds ratio, 0.41; 95% CI, 0.17-0.98). In seronegative patients, the rate of documented absolute leukopenia reached 39%. No COVID-19 cases were documented throughout the study period; however, 2 cases in the patient cohort were noted immediately after the first dose. Reported adverse events were similar to data in former trials comprising mostly healthy individuals. Conclusions and Relevance: In this cohort study, the SARS-CoV-2 BNT162b2 vaccine appeared to be safe and achieve satisfactory serologic status in patients with cancer. There was a pronounced lag in antibody production compared with the rate in noncancer controls; however, seroconversion occurred in most patients after the second dose. Future real-world data are warranted to determine the long-term efficacy of the vaccine with regard to type of anticancer treatment.

Robotic inguinal hernia repair: Is it a new era in the management of inguinal hernia?

OBJECTIVE: We compared outcomes of elective inguinal hernia repair performed at one institution by three approaches: robotic-assistance, laparoscopic, and open. METHODS: Characteristics of the patients, the hernia and the procedures performed during 2014-2016 were accessed from patient electronic medical files of 137 elective inguinal hernia repairs. 24 surgeries were robotic-assisted, 16 laparoscopic and 97 open repairs. RESULTS: Distributions of age, sex and BMI did not differ between the groups. Bilateral repair was more common in the robotic (70.8%) than the laparoscopic (50.0%) and open groups (12.4%) (p < 0.001). Direct hernias were more common in the open (45.4%) than the robotic (20.8%) and laparoscopic (12.5%) groups (p < 0.001). Only 3 hernias were inguinoscrotal, all in the robotic group. The median operation times were 44.0, 79.0 and 92.5 min for the open, laparoscopic and robotic methods, respectively (p < 0.001). Among the unilateral repairs, the median operative times were the same for the robotic and laparoscopic procedures, 73 min, and less for the open procedures, 40 min. The proportion of patients hospitalized for 2-3 days was higher for open repair (13.4% vs. 6.2% and 0% for laparoscopic and robotic), but this difference was not statistically significant. The median maximal postoperative pain according to a 0-10-point visual analogue score was 5.0, 2.0 and 0 for open, laparoscopic and robotic procedures, respectively (p < 0.001). CONCLUSIONS: This report demonstrated the safety and feasibility of robotic-assisted inguinal hernia repair.

The Potential Role of Immune Alteration in the Cancer-COVID19 Equation-A Prospective Longitudinal Study.

Background: The risk of cancer patients to develop COVID19 infection is unclear. We aimed to prospectively study cancer patients and oncology healthcare workers for COVID19 serology. In IgG+ cases, immune profile was determined to portray the pattern of immune response to SARS-CoV2. Methods: Cancer patients on active treatment and healthcare workers were enrolled. During the study period (3/2020-6/2020), demographic data and blood were collected at three time points. Expression of IgG, IgM, and IgA were assessed. In SARS-CoV-2 IgG+ cases and matched negative cases, we performed mass cytometry time of flight (CyTOF) analysis on the basis of the expression of surface markers. Results: The study included 164 cancer patients on active intravenous treatment and 107 healthcare workers at the cancer center. No symptomatic cases were reported during the study period. Serology analysis revealed four IgG+ patients (2.4%) and two IgG+ healthcare workers (1.9%)-all were asymptomatic. CyTOF analysis demonstrated substantial reduction in myeloid cells in healthcare workers who were SARS-CoV-2 IgG+ compared to those who were SARS-CoV-2 IgG-, whereas in cancer patients, the reduction was relatively milder (≈50% reduction in SARS-CoV-2 IgG+ cancer patients compared with ≈90% reduction in SARS-CoV-2 IgG+ workers). Conclusion: Our results indicate a similar rate of asymptomatic COVID19 infection in cancer patients and healthcare workers in a longitudinal study throughout the pandemic time. Due to differential immune cell profiles of cancer patients who are treated with immunomodulatory agents, the host response to the SARS-COV2 may play a role in COVID19 course and representation. The immunological perspective of cancer treatments on the risk for COVID19 infection should be further explored.

Environmental exposures and fetal growth: the Haifa pregnancy cohort study.

BACKGROUND: The developing fetus is susceptible to environmental insults. Studying the effects of environmental exposures on fetal growth is essential for understanding the causal pathway between prenatal exposures and pregnancy outcomes. Here we describe the Haifa Pregnancy Cohort Study (HPCS) and discuss challenges and opportunities in applying "big data" paradigm. METHODS: Maccabi Healthcare Services (MHS), is the second largest Israeli health maintenance organization (HMO) providing care services to two million beneficiaries. The HPCS cohort potentially includes ~750,000 newborns born between 1998 and 2017. We will estimate daily exposures to air pollutants, temperature and greenness, using satellite-based data and models. We hypothesize that residents of Haifa have higher exposures to environmental pollutants and that in pregnant women this higher exposure is associated with poorer fetal growth. We will evaluate outcomes such as birth-weight, head-circumference and gestational age at birth. We will adjust for pregnancy complications such as pre-eclampsia and gestational diabetes and parental variables, such as maternal weight, age and smoking habits as potential confounders. In addition, we will conduct a multi-tiered field study, nested within this population, among 150 pregnant women residing in two geographical regions-one in the polluted Haifa area, and one in a relatively unpolluted area in central Israel. Blood and urinary samples will be collected, as well as personal and indoor exposure to air pollution. DISCUSSION: Evaluating environmental exposures of pregnant women and assessing in utero growth over the course of the pregnancy during different exposure windows, is of great scientific and public health interest. Recent advances in data collection and analysis pose great promise to provide insights into contribution of environment to the health of the developing fetus, but also pose major challenges and pitfalls, such as data management, proper statistical framework and integration of data in the population-based study and selectiveness in the nested field study. Yet the continuing follow-up of the study cohort, integrating data from different services, health-promotion, and eventually, application later in real life of our main promises. Our study aims to meet these challenges and to provide evidence of the environmental exposures associated with fetal growth.

Prevention of Antidrug Antibody Formation to Infliximab in Crohn's Patients With Prior Failure of Thiopurines.

BACKGROUND & AIMS: Combination thiopurine-infliximab (IFX) therapy is associated with reduced generation of antidrug antibodies (ADA) compared with IFX monotherapy. Whether past clinical response to thiopurine therapy bears an effect on ADA prevention is unknown. METHODS: This was a retrospective observational multicenter study of patients with Crohn's disease (CD) treated by IFX and thiopurines who had serial ADA measurements. Therapy was classified into past thiopurine response or its lack of, de novo combination, or IFX monotherapy. The primary endpoint was risk of ADA appearance. RESULTS: Out of 494 patients with serial ADA measurements 207 eligible patients were included in the final analysis. The 1-year cumulative risk of ADA development was similar in past thiopurine responders (19.3%) compared with past thiopurine failures (16.1%) (log rank P = .54). ADA was found in 46.6% of the monotherapy group and was significantly different compared with past thiopurine responders (P = .007) and past thiopurine failures (P = .007). The adjusted hazards for ADA development were significantly lower in past responders and past failures compared with the monotherapy group (hazard ratio, 0.47 [95% CI, 0.22-1.00] and 0.32 [95% CI, 0.11-0.93], respectively). CONCLUSIONS: Thiopurines-IFX cotherapy in patients with Crohn's disease is associated with reduced ADA formation compared with IFX monotherapy. This is probably regardless of initial thiopurine therapeutic effect.

Cognitive Function of Patients with Crohn's Disease is Associated with Intestinal Disease Activity.

BACKGROUND: Systemic inflammation and nutritional deficiencies are characteristics of Crohn's disease (CD) and have been suggested to influence cognitive performance. This study assessed cognitive function in patients with CD. METHODS: Participants were adult patients with CD arriving at routine follow-up. Subjective cognitive complaints, depression, anxiety, fatigue, and sleep were evaluated by validated questionnaires. CD characteristics, blood tests, and Crohn's disease activity index were obtained. Nutritional risk index was derived from serum albumin and change in body weight. Montreal cognitive assessment was used for screening. Patients with either subjective cognitive complaints or Montreal cognitive assessment score ≤ 26 were tested by a computerized cognitive testing battery, with analysis of scores in 7 cognitive domains (CogDs) and an average of the CogD scores-global cognitive score (GCS). Impaired CogD was defined as scoring more than 1 SD below age and education adjusted average. RESULTS: A total of 105 patients were recruited and 61 were tested with computerized cognitive testing battery. Mean age was 39 ± 13 and mean education years were 14 ± 2. The most commonly impaired CogDs were information processing speed (33%) and verbal function (28%). Crohn's disease activity index, nutritional risk index, and hemoglobin were significantly correlated with GCS (r = -0.34, 0.39, 0.33; P = 0.007, 0.003, 0.01). Linear regression revealed significant correlations between Crohn's disease activity index, nutritional risk index, and GCS (ß = -0.3, 0.29; P = 0.03, 0.04), independent of depression. This model explained 24% of the variance in GCS. CONCLUSIONS: Cognitive performance is related to CD activity and nutritional status. The results provide insight into potential influence of nutrition and inflammation on cognitive function. Further studies on cognitive function of patients with CD are warranted.

Thiopurine effectiveness in patients with Crohn's disease: a study of genetic and clinical predictive factors.

BACKGROUND: Thiopurines are efficacious in the treatment of Crohn's disease and were recently shown to induce T-cell apoptosis by modulation of Rac1 activation. To assess whether polymorphisms in Rac1 and other apoptosis-related genes, combined with clinical parameters, can predict response to thiopurines. METHODS: A retrospective cohort of 156 thiopurine-treated patients with Crohn's disease was genotyped for 11 single-nucleotide polymorphisms (SNPs): 9 SNPs in Rac1, 1 SNP in the Fas ligand -843 T>C, and 1 SNP in the Caspase-9 93 C>T. Clinical data were extracted from the medical charts. Odds ratios (ORs) and 95% confidence intervals (CIs) of the association between demographic, clinical, and genetic variables and thiopurine response rates were calculated. RESULTS: The overall response rate to thiopurines was 74% (115/156). The Rac1 SNP rs34932801 heterozygote genotype GC was associated with a lower response rate compared with the wild-type GG genotype (46% versus 76%; OR = 0.26; 95% CI, 0.08-0.91; P = 0.036). Only wild-type homozygotes were found for 5 Rac1 SNPs. None of the other 3 Rac1 SNPs were associated with response to thiopurines. Patients with Montreal B3 behavior pattern responded worse than those with a B1 behavior pattern (59%, versus 80%; OR = 0.37; 95% CI, 0.17-0.83; P = 0.016). Sephardic Jews had a lower response rate to thiopurines compared with Jews of Ashkenazi or mixed ancestry (60% versus 82%; OR = 0.32; 95% CI, 0.15-0.69, P = 0.003). CONCLUSIONS: Rac1 SNP rs34932801carriage, Montreal B3 disease behavior, and a Sephardic Jewish origin were associated with unfavorable response to thiopurines. Corroboration of these associations in larger cohorts is warranted.

Screening for partial AZFa microdeletions in the Y chromosome of infertile men: is it of clinical relevance?

OBJECTIVE: To evaluate the frequency of complete and partial AZFa Y-chromosome microdeletions among infertile Israeli men. To review the published frequencies and histologic findings of AZFa deletions. DESIGN: Retrospective study. SETTING: Academic medical center. PATIENT(S): A total of 1,260 infertile Israeli men. Literature review (2000-2010) of reports on men with AZFa deletions and their testicular findings. INTERVENTION(S): The DNA of 1,260 infertile men was evaluated for AZF microdeletions. The DNA of 657 of them with undetected microdeletions was analyzed for partial AZFa deletion in the USP9Y and DDX3Y genes using sequence-tagged sites beyond EAA/EMQN recommendations. MAIN OUTCOME MEASURE(S): The frequency of complete and partial AZFa microdeletions. Availability of sperm cells for intracytoplasmic sperm injection in men with complete/partial microdeletions. RESULT(S): Two men had complete AZFa deletion (a frequency of 0.28% among nonobstructive azoospermic men). None had partial AZFa deletions. CONCLUSION(S): The likelihood of finding sperm cells in men with complete AZFa deletions is negligible. Complete AZFa deletion is rare and usually associated with azoospermia and absence of sperm cells in testicular tissue. The low frequency of partial AZFa deletions and the inconsistent prospects for spermatogenesis reported in the literature question the need for routine assessment of microdeletions in genes, such as USP9Y or DDX3Y.

Fecal occult blood test performance indicators in warfarin-treated patients.

BACKGROUND: Antithrombotic drugs such as warfarin cause a general increase in bleeding tendency and therefore could influence fecal occult blood test results. METHODS: A population-based retrospective cohort study was conducted to investigate the performance of the fecal occult blood test for colorectal cancer screening in patients taking warfarin. The study population included 1356 tests performed in warfarin-treated patients and 64,088 tests in those not taking antithrombotics. Data on lower gastrointestinal evaluation were collected on 425 cases with a positive fecal occult blood test: all positives on warfarin and positive cases of a subsample of those tests in the group without antithrombotic treatment. RESULTS: The positivity rate of the fecal occult blood test in the warfarin group was found to be doubled (7.7% (95%CI, 6.3%-9.2%)) compared with those not taking antithrombotics (3.6% (95%CI, 3.4%-3.7%)) (P <.0001). No significant difference in the positive predictive value for carcinoma and significant adenomas was found comparing the warfarin group to the no-antithrombotic group. The detection rates of both clinically significant adenomas and findings not indicative of significant neoplasia were increased in the warfarin group (8.9/1000 and 32.5/1000 respectively) compared with the no-antithrombotic group (4.0/1000 and 11.3/1000) (P = .02 and P <.0001 respectively), whereas that of carcinoma was not found to be different (3.7/1000 in the warfarin group vs 3.3/1000, P = .85). CONCLUSIONS: Fecal occult blood test screening in warfarin users results in a higher, yet reasonable, positivity load and in a higher detection of premalignant lesions than in the general population. We consider fecal occult blood test screening appropriate for the warfarin-taking population.

BRCA1 breast cancer risk is modified by CYP19 polymorphisms in Ashkenazi Jews.

Exposure to sex hormones is a major risk factor for breast cancer and current treatments include hormone modifying drugs, among them aromatase inhibitors. We studied the association of CYP19 (Val(80) and [TTTA](n)) polymorphisms, the gene translated to aromatase, and the risk of breast cancer in BRCA carriers and noncarriers. The study consisted of 958 cancer cases and 931 healthy controls, including 474 carriers and 1,415 noncarriers. Cases and controls came from a population-based study of breast cancer in Israel, enriched with BRCA carriers from a clinical familial cancer service. Val(80) G/G genotype was associated with significantly increased risk of breast cancer compared with the Val(80) A/A genotype in BRCA1 carriers ages <50 years (odds ratio, 2.81; 95% confidence interval, 1.09-7.22; P = 0.032) but not in BRCA2 carriers or noncarriers of any age. A similar magnitude suggestive association, although nonstatistically significant, was found between Val(80) polymorphism and estrogen receptor-negative status of the breast tumors. A common haplotype composed of the Val(80) G allele and three haplotype-tagging single nucleotide polymorphisms (rs727479, rs10046, and rs4646) in the CYP19 coding region showed a trend to association with breast cancer risk in BRCA1 carriers ages <50 years. Published expression data show higher estrogen levels with higher repeats in [TTTA](n) found in linkage disequilibrium with Val(80). The present study suggests that the CYP19 Val(80) polymorphism and a haplotype that includes this polymorphism are associated with increased breast cancer risk in young women with BRCA1 mutations.

The public prefers fecal occult blood test over colonoscopy for colorectal cancer screening.

The acceptability of colorectal cancer (CRC) screening tests to the population influences adherence. Population preferences between fecal occult blood test (FOBT) and colonoscopy for CRC screening were examined by previous test experience. The study population was a random sample of 413 members of Israel's largest Health Maintenance Organization (HMO) aged 48-68 years. In a telephone interview, an explanation was provided regarding FOBT and colonoscopy. Participants were asked which they preferred and their degree (1-6) of agreement with each of eight test characteristics. Overall Attitude Scores toward FOBT and colonoscopy were compared. Predictors of colonoscopy preference and of refusal to undergo screening were examined using a logistic regression model. FOBT was preferred as a screening test by 70.2% of the participants, colonoscopy by 9.3%, 7.4% were indecisive, and 13.1% were not interested in screening. FOBT and colonoscopy similarly scored highly as life saving (5.2 vs. 5.1, respectively), with colonoscopy scoring significantly higher as time consuming (3.8 vs. 1.3, P<0.0001), disturbing (4.6 vs. 1.8, P<0.0001), painful (4.1 vs. 1.0, P<0.0001), annoying (4.8 vs. 1.9, P<0.0001), and involving risk (3.2 vs. 1.0, P<0.0001). In a logistic multivariate analysis, preference of colonoscopy was associated with the perception of being at CRC risk [odds ratio (OR): 3.1 (95% confidence interval (CI): 1.3-7.6)], with more positive attitude scores towards this test [OR: 2.2 (95% CI: 1.6-3.0)], and with a more negative one toward FOBT [OR: 0.4 (95% CI: 0.3-0.7)]. Target population preferences for CRC screening supports a policy of FOBT screening for an average risk population and colonoscopy for high-risk individuals.

Quality control in a National Program for the Early Detection of Breast Cancer: women's satisfaction with the mammography process.

INTRODUCTION: The experience of the mammography testing process and related satisfaction influence women's willingness to undergo the test again. The study goal was to assess women's overall satisfaction with the mammography examination service provided by participating units in the National Program for the Early Detection of Breast Cancer in Israel. METHODS: Between August 2003 and March 2004, a random sample of 3,295 women from 38 mammography units nationwide was drawn. Women were interviewed within 48 hours of their mammography, regarding their assessment of the examination process: discomfort, overall satisfaction, and intention to rescreen. Overall satisfaction and process items were measured on an ordinal scale ranging from 1 (lowest) to 6 (highest). Multivariate binomial regression was performed to identify significant predictors of being less satisfied and to estimate the associated relative risks with 95% confidence interval (CI). RESULTS: A response of "very satisfied" (score 6), indicating overall satisfaction with the mammography process, was reported by 77% (95% CI, 73%-80%) of the women, 19% (95% CI, 17%-21%) said they were satisfied. Willingness to rescreen was reported by 95%. Negative assessment of staff attitude was the most influential predictor of being less satisfied. Twenty-six percent of women reported experiencing very discomforting pain. This response was associated with a diagnostic test indication, and with process items directly related to the test (technician's attitude toward the patient; information provided by her; privacy during the test). CONCLUSIONS: Women's satisfaction was high, as was intention to rescreen. The gap between intention and rescreening begs further investigations as to other types of barriers preventing women from adherence to rescreening.