Parity and the risk of breast and ovarian cancer in BRCA1 and BRCA2 mutation carriers.

Environmental or lifestyle factors are likely to explain part of the heterogeneity in breast and ovarian cancer risk among BRCA1 and BRCA2 mutation carriers. We assessed parity as a risk modifier in 515 and 503 Spanish female carriers of mutations in BRCA1 and BRCA2, respectively. Hazard ratios (HR) and their corresponding 95% confidence intervals (CI) were estimated using weighted Cox proportional hazards regression, adjusted for year of birth and study centre. The results for ever being parous and number of live-births were very similar for carriers of mutations in both genes. For all mutation carriers combined, the estimated HR associated with ever having had a live-birth was 0.74 (95% confidence interval [CI] = 0.55-1.01, P = 0.06), and that associated with each live-birth was 0.87 (95%CI = 0.77-0.98, P = 0.02). The latter association was observed only in women aged 40 and above (HR = 0.81, 95%CI = 0.70-0.94, P = 0.004 vs. HR = 0.99, 95%CI = 0.83-1.18, P = 0.9 for women under age 40), and this trend was highly consistently observed for carriers of mutations in each gene. There was no evidence of an association between breast cancer risk and age at first birth for parous BRCA1 or BRCA2 mutation carriers (P-trend >or= 0.3). The power to detect associations with ovarian cancer risk was much lower, especially for BRCA2 mutation carriers. Nevertheless, having a live-birth was associated with protection for BRCA1 mutation carriers (HR = 0.41, 95%CI = 0.18-0.94, P = 0.03), and a strong and consistent protective effect of age at first birth was observed for parous carriers of mutations in both genes (HR = 0.65, 95%CI = 0.52-0.83, P < 0.001). This is the third independent study to find that, as in the general population, parity appears to be associated with protection from breast cancer in women with mutations in BRCA1 and BRCA2. Parity appears to be protective for ovarian cancer in BRCA1 mutation carriers, but its role in BRCA2 mutation carriers remains unclear. Whether later age at first birth is also protective for ovarian cancer in mutation carriers requires further confirmation.

Impact of dementia on hospitalization.

BACKGROUND: The purpose of this study was to analyze and determine the prevalence and clinical characteristics of hospitalized dementia patients compared with nondemented patients. METHODS: We examined hospital discharge database records dated 1998-2003 from public hospitals in Andalusia, Spain. We used ICD-9-CM codes to identify patients with dementia. The variables examined included age, length of stay, discharge diagnosis, diagnostic-related groups, and mortality of both dementia and nondementia patients over 65 years of age. RESULTS: A diagnosis of dementia was documented for 40,482 cases. The prevalence of dementia increased from 3.43% to 4.64% between 1998 and 2003 and was higher among older patients and women. Dementia was the reason for admission in 5.6% of cases. Medical reasons constituted 82.4% of admittances. Dementia patients had hip surgery more frequently than patients without dementia, and other procedures (orthopedic surgery, cataracts, or hernia repair) were less frequent (p < 0.001). The mean duration of the hospital stay was longer (13.4 vs. 10.7 days) and the intra-hospital mortality rate was greater (19.3% vs. 8.7%) for patients with dementia compared to those without dementia. Dementia was an independent predictor of mortality (OR 1.77; 95% CI 1.72-1.82). CONCLUSIONS: Dementia is increasing among hospitalized patients. Dementia patients have different reasons for hospitalization and higher mortality. It is necessary to identify these differences and to improve the hospital care of dementia patients.

Analysis of FANCB and FANCN/PALB2 fanconi anemia genes in BRCA1/2-negative Spanish breast cancer families.

Recent reports have shown that mutations in the FANCJ/BRIP1 and FANCN/PALB2 Fanconi Anemia (FA) genes confer a moderate breast cancer risk. Discussion has been raised on the phenotypic characteristics of the PALB2-associated families and tumors. The role of FANCB in breast cancer susceptibility has not been tested to date. Likewise PALB2 mutation frequency has not been studied in Spanish population. We analyzed the complete coding sequence and splicing sites of FANCB and PALB2 in 95 index cases of BRCA1/2-negative Spanish breast cancer families. We also performed an exhaustive screening of three previously described rare but recurrent PALB2 mutations in 725 additional probands. Pathogenic changes were not detected in FANCB. We found a novel PALB2 truncating mutation c.1056_1057delGA (p.K353IfsX7) in one of the 95 screened patients, accounting for a mutation frequency of 1% in our series. Further comprehensive screening of the novel mutation and of previously reported rare but recurrent PALB2 mutations did not reveal any carrier patient. We report the first example of LOH occurring in a PALB2-associated tumor. Our results rule out a major contribution of FANCB to hereditary breast cancer. Our data are consistent with the notion of individually rare PALB2 mutations, lack of mutational hot-spots in the gene and existence of between-population disease-allele heterogeneity. We show evidence that PALB2 loss of function might also conform to the inactivation model of a classic tumor-suppressor gene and present data that adds to the clinically relevant discussion about the existence of a PALB2-breast cancer phenotype.

The average cumulative risks of breast and ovarian cancer for carriers of mutations in BRCA1 and BRCA2 attending genetic counseling units in Spain.

PURPOSE: It is not clear that the published estimates of the breast and ovarian cancer penetrances of mutations in BRCA1 and BRCA2 can be used in genetic counseling in countries such as Spain, where the incidence of breast cancer in the general population is considerably lower, the prevalence of BRCA2 mutations seems to be higher, and a distinct spectrum of recurrent mutations exists for both genes. We aimed to estimate these penetrances for women attending genetic counseling units in Spain. EXPERIMENTAL DESIGN: We collected phenotype and genotype data on 155 BRCA1 and 164 BRCA2 mutation carrier families from 12 centers across the country. Average age-specific cumulative risks of breast cancer and ovarian cancer were estimated using a modified segregation analysis method. RESULTS: The estimated average cumulative risk of breast cancer to age 70 years was estimated to be 52% [95% confidence interval (95% CI), 26-69%] for BRCA1 mutation carriers and 47% (95% CI, 29-60%) for BRCA2 mutation carriers. The corresponding estimates for ovarian cancer were 22% (95% CI, 0-40%) and 18% (95% CI, 0-35%), respectively. There was some evidence (two-sided P = 0.09) that 330A>G (R71G) in BRCA1 may have lower breast cancer penetrance. CONCLUSIONS: These results are consistent with those from a recent meta-analysis of practically all previous penetrance studies, suggesting that women with BRCA1 and BRCA2 mutations attending genetic counseling services in Spain have similar risks of breast and ovarian cancer to those published for other Caucasian populations. Carriers should be fully informed of their mutation- and age-specific risks to make appropriate decisions regarding prophylactic interventions such as oophorectomy.

A study of hospital discharges for venous thromboembolism in the south of Spain. An analysis of 19,170 cases from a regional database from 1998 to 2001.

BACKGROUND: Our objective was to learn about the incidence of hospitalization for venous thromboembolism (VTE) in the public health care system in Andalusia and to define the profile of the patients, with special reference to the Department of Internal Medicine. METHODS: We analyzed the discharged data set of 32 hospitals in the Andalusian Health Care Service between 1998 and 2001, identifying the cases in whom the diagnosis was VTE. The age, sex, length of stay, outcome, number of diagnoses, diagnosis-related group (DRG), and coded procedures were studied. RESULTS: During the period studied, there were 2,228,894 discharges, 19,170 of which involved VTE. In 8494 of these, VTE was the cause of the admission. Some 3961 patients (46.6%) were admitted for pulmonary embolism (PE); 45% were discharged from internal medicine, 41% from pneumology, and 14% from other departments. The average patient age was 65, the length of stay 13.8 days, and the global in-hospital mortality rate 13%. Some 4533 cases (53.4%) were admitted due to deep vein thrombosis (DVT): 38.5% to internal medicine, 21.30% to general surgery, 12.35% to angiology, and the remainder to other departments. The length of stay was 10.6 days with an in-hospital mortality rate of 2.20%. In 7721 cases, VTE was the secondary diagnosis (after excluding 2955 cases of superficial thrombophlebitis of the upper limbs); 74% was associated with a medical DRG. CONCLUSIONS: VTE is a frequent pathology in our hospitals. It shows a great variability in clinical practice although there are differences between patients treated by different specialists. VTE as secondary diagnosis was more frequent in medical inpatients.

Chromosome 21 tandem repetition and AML1 (RUNX1) gene amplification.

In two patients with hematological neoplasias a tandem repetition of chromosome 21 in the bone marrow was revealed by cytogenetic analysis. The disease was different in the two patients: one was of the lymphoid type, acute lymphoblastic leukemia type L1, and the other was of the myeloid type, acute nonlymphoblastic leukemia type M2. In one case this chromosomal abnormality resulted in amplification of the AML1 gene (HUGO nomenclature: RUNX1), whereas in the other case the AML1 gene was not included in the tandem repetition, showing that apparently similar cytogenetic aberrations may be different at the molecular level.

Bleeding and venous thromboembolism arising in acutely ill hospitalized medical patients. Findings from the Spanish national discharge database.

BACKGROUND: There is scarce evidence to identify which acutely ill medical patients might benefit from prophylaxis against venous thromboembolism (VTE). METHODS: The Spanish National Discharge Database was used to identify predictors of bleeding and VTE during hospitalization for an acute medical illness. RESULTS: Of 1,148,301 patients, 3.10% bled, 1.21% were diagnosed with VTE, and 8.64% died. The case-fatality rate was: 20.8% for bleeding and 19.7% for VTE. Eight clinical variables were independently associated with an increased risk for VTE and bleeding, one with a decreased risk for both events, 4 with an increased risk for VTE and a decreased risk for bleeding, 2 with an increased risk for bleeding but a decreased risk for VTE, and 1 with a decreased risk for bleeding. When all these variables were considered, we composed a risk scoring system, in which we assigned points to each variable according to the ratio between the odds ratio for bleeding and for VTE. Overall, 21% of patients scored less than 0 points and had a bleeding vs. VTE ratio of 1.19; 55% scored 0 to 1.0 points and had a ratio of 2.13; and 24% scored over 1.0 points and had a ratio of 6.10. CONCLUSIONS: A risk score based on variables documented at admission can identify patients with different ratios (near 1.0; about 2.0; and >6.0) between the rate of bleeding and of VTE.

Venous thromboembolism and bleeding after total knee and hip arthroplasty. Findings from the Spanish National Discharge Database.

The impact of venous thromboembolism (VTE) and bleeding in patients undergoing major joint surgery has not been thoroughly studied. The Spanish National Discharge Database during the years 2005-2006 was used to assess the frequency and clinical impact of VTE and bleeding after elective total knee (TKA) or hip (THA) arthroplasty. Of 58,037 patients undergoing TKA, 0.18% (95% confidence interval [CI]: 0.15-0.22) were diagnosed with pulmonary embolism (PE), 0.57% (95% CI: 0.51-0.63) with deep-vein thrombosis (DVT), 1.20% (95% CI: 1.12-1.30) had bleeding complications, and 0.09% (95% CI: 0.07-0.12) died. Of 54 patients who died, 20.4% (95% CI: 10.7-35.4) had been diagnosed with PE, 3.70% (95% CI: 0.63-11.7) with DVT, and 13.0% (95% CI: 5.67-25.6) had bled. Of 31,769 patients undergoing elective THA, 0.23% (95% CI: 0.18-0.29) were diagnosed with PE, 0.44% (95% CI: 0.37-0.52) with DVT, 1.21% (95% CI: 1.10-1.34) bled, and 0.16% (95% CI: 0.12-0.21) died. Of 52 patients who died, 13.5% (95% CI: 6.08-24.8) had been diagnosed with PE, and 9.61% (95% CI: 3.52-21.3) had bled. On multivariable analysis, PE (odds ratio [OR]: 157; 95% CI: 75-328), DVT (OR: 6.3; 95% CI: 1.5-27) and bleeding (OR: 8.5; 95% CI: 3.6-20) were independent predictors for death after TKA. After THA, only PE (OR: 65; 95% CI: 26-160) and bleeding (OR: 6.4; 95% CI: 2.3-17) predicted the risk for death. Bleeding, DVT, and PE, arising after TKA were all independent predictors for death. Their increase in risk was, however, substantially higher for PE. After THA, only PE and bleeding independently predicted death.

Intestinal perforation caused by magnetic toys.

Accidental ingestion of foreign bodies is a common problem in children, but ingestion of magnets is rare. When multiple magnets are ingested, they may attract each other through the intestinal walls, causing pressure necrosis, perforation, fistula formation, or intestinal obstruction; as has been reported in 13 cases in the past 10 years. We report the fifth case in the literature of intestinal perforation and fistula caused by the ingestion of 2 small magnetic pieces of a toy by a 3-year-old boy. We find it necessary that sanitary authorities give more information to parents and physicians about the potential risks of these magnetic toys.

Long-term assessment of the treatment of recurrent tracheoesophageal fistula with fibrin glue associated with diathermy.

PURPOSE: Recurrent tracheoesophageal fistula (RTF) is a serious common complication of the surgical treatment of esophageal atresia. We report the results of our technique of bronchoscopic treatment of RTF with fibrin glue (Tissucol), with a follow-up of over 1 decade. METHODS: A retrospective review between 1993 and 2004 was conducted, including all patients diagnosed with RTF and treated bronchoscopically with Tissucol, with over 1 year of follow-up. The procedure was implemented under general anesthesia using a rigid neonatal bronchoscope. A magnification chamber and previous diathermia using a urethral catheter were used in the latter 4 patients. The fibrin glue was injected through a clear catheter. The number of endoscopic sessions per patient was limited to 3. RESULTS: Seven patients were treated, with evidence of fistular closure in 6 (85%). One patient with satisfactory results, but a follow-up of 4 months, was not included. The age at bronchoscopy ranged from 14 to 20 days (mean, 16.7 days), and a total of 12 sessions were required (mean, 1.7). In the latter 4 patients, diathermia was associated with good results in all and a lower number of sessions (mean, 1.5). All patients were evaluated clinically and radiologically, and a control endoscopy was performed in 4 patients. The follow-up lasted from 2 to 11 years (mean, 7.4 years). CONCLUSIONS: Because we started to use Tissucol (1994), other authors have reported successful isolated cases, but a relatively large series and a long-term follow-up were lacking. We consider that the success of the procedure depends on several technical factors such as an early diagnosis, before epithelium is formed in the fistula, and the use of initial diathermia, associated in the latter 4 patients. The results obtained with 85% success with a follow-up over 1 year show that the fibrin adhesive is the reference substance for the treatment of RTF; we recommend its endoscopic application associated with diathermia as initial measure.