Labeling male anorectal malformations: objective evaluation of radiologic imaging before surgery.

Purpose: Prone cross-table lateral x-ray (CTLxR) and colostogram aid surgical planning for anorectal malformations (ARMs) without perineal fistulas. We suggest objective imaging tools to classify ARMs. Methods: Three observers prospectively evaluated CTLxR and colostograms of male ARM patients (2012-2022) without perineal fistulas. The level of the rectal pouch was estimated with pubococcygeal (PC) and ischiatic (I) lines. On CTLxR, we described the "pigeon sign", defined as the rectal pouch ending with a beak-like image, suspicious for a rectourinary fistula. ARM was defined as rectobulbar when the rectal pouch was below the I line, rectoprostatic when between PC and I lines, and rectovesical when above the PC line. Concordance was assessed with Fleiss' kappa. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the "pigeon sign" were calculated. Results: Thirteen patients were included in this study. The interobserver agreement on CTLxR was 69.2% (k = 0.54) on pouch ending, 84.6% (k = 0.69) on the "pigeon sign", and 76.9% (k = 0.69) on diagnosis; concordance between observers and intraoperative diagnosis was 66.6% (k = 0.56). The "pigeon sign" had 75% sensitivity, 100% specificity, 100% PPV, and 50% NPV. The interobserver agreement on colostograms was 84.6% (k = 0.77) on pouch ending and 89.7% (k = 0.86) on diagnosis; concordance between observers and intraoperative diagnosis was 92.3% (k = 0.90). Conclusion: PC and I lines and the "pigeon sign" are useful tools in examining CTLxR and colostograms. Adequate CTLxR interpretation may modify surgical strategy.

Voiding cystourethrography and 99MTC-MAG3 renal scintigraphy in pediatric vesicoureteral reflux: what is the role of indirect cystography?

BACKGROUND: Primary vesicoureteral reflux (VUR) is the most common urological anomaly in children. Voiding cystourethrography (VCUG) is considered the reference standard for the diagnosis of VUR. Even if it is a secure and standardized technique, it is still an invasive method, hence, the effort to find an alternative method to diagnose VUR. The aim of the study is to evaluate the diagnostic accuracy of 99mTC-MAG3 scintigraphy with indirect cystography in detecting VUR and to estimate any interobserver variability in 99mTC-MAG3 scintigraphy interpretation. METHODS: The authors retrospectively reviewed all the pediatric patients who underwent both a VCUG and a 99mTC-MAG3 renal scintigraphy at the study institution between 2012 and 2016. RESULTS: A total of 86 children (and 168 renal units) were included. MAG3 scan revealed a sensitivity of 54% and a specificity of 90% with positive predictive value of 79% and negative predictive value of 73%. Each MAG3 scintigraphy was then independently and blindly evaluated by a pediatric urologist and two nuclear physicians. After revision, the concordance between VCUG and MAG3 in reflux cases dropped from 54% to 27% (on average), and the reviewers reclassified most examinations as non-conclusive. CONCLUSIONS: 99mTC-MAG3 renal scintigraphy with indirect cystography showed low sensitivity in detecting VUR of any grade and cannot, therefore, be proposed as completely alternative to VCUG in the diagnosis of VUR. Moreover, MAG3 scintigraphy interpretation for the diagnosis of VUR has a very high interobserver variability, mostly because of the lack of a correct and complete voiding phase.

CDKN2A and BAP1 germline mutations predispose to melanoma and mesothelioma.

BAP1 germline mutations predispose to a cancer predisposition syndrome that includes mesothelioma, cutaneous melanoma, uveal melanoma and other cancers. This co-occurrence suggests that these tumors share a common carcinogenic pathway. To evaluate this hypothesis, we studied 40 Italian families with mesothelioma and/or melanoma. The probands were sequenced for BAP1 and for the most common melanoma predisposition genes (i.e. CDKN2A, CDK4, TERT, MITF and POT1) to investigate if these genes may also confer susceptibility to mesothelioma. In two out of six families with both mesothelioma and melanoma we identified either a germline nonsense mutation (c.1153C > T, p.Arg385*) in BAP1 or a recurrent pathogenic germline mutation (c.301G > T, p.Gly101Trp) in CDKN2A. Our study suggests that CDKN2A, in addition to BAP1, could be involved in the melanoma and mesothelioma susceptibility, leading to the rare familial cancer syndromes. It also suggests that these tumors share key steps that drive carcinogenesis and that other genes may be involved in inherited predisposition to malignant mesothelioma and melanoma.

Neutrophil gelatinase-associated lipocalin is a biomarker of acute-on-chronic liver failure and prognosis in cirrhosis.

BACKGROUND & AIMS: Acute-on-chronic liver failure (ACLF) is a syndrome that occurs in cirrhosis characterized by organ failure(s) and high mortality rate. There are no biomarkers of ACLF. The LCN2 gene and its product, neutrophil gelatinase-associated lipocalin (NGAL), are upregulated in experimental models of liver injury and cultured hepatocytes as a result of injury by toxins or proinflammatory cytokines, particularly Interleukin-6. The aim of this study was to investigate whether NGAL could be a biomarker of ACLF and whether LCN2 gene may be upregulated in the liver in ACLF. METHODS: We analyzed urine and plasma NGAL levels in 716 patients hospitalized for complications of cirrhosis, 148 with ACLF. LCN2 expression was assessed in liver biopsies from 29 additional patients with decompensated cirrhosis with and without ACLF. RESULTS: Urine NGAL was markedly increased in ACLF vs. no ACLF patients (108(35-400) vs. 29(12-73)µg/g creatinine; p<0.001) and was an independent predictive factor of ACLF; the independent association persisted after adjustment for kidney function or exclusion of variables present in ACLF definition. Urine NGAL was also an independent predictive factor of 28day transplant-free mortality together with MELD score and leukocyte count (AUROC 0.88(0.83-0.92)). Urine NGAL improved significantly the accuracy of MELD in predicting prognosis. The LCN2 gene was markedly upregulated in the liver of patients with ACLF. Gene expression correlated directly with serum bilirubin and INR (r=0.79; p<0.001 and r=0.67; p<0.001), MELD (r=0.68; p<0.001) and Interleukin-6 (r=0.65; p<0.001). CONCLUSIONS: NGAL is a biomarker of ACLF and prognosis and correlates with liver failure and systemic inflammation. There is remarkable overexpression of LCN2 gene in the liver in ACLF syndrome. LAY SUMMARY: Urine NGAL is a biomarker of acute-on-chronic liver failure (ACLF). NGAL is a protein that may be expressed in several tissues in response to injury. The protein is filtered by the kidneys due to its small size and can be measured in the urine. Ariza, Graupera and colleagues found in a series of 716 patients with cirrhosis that urine NGAL was markedly increased in patients with ACLF and correlated with prognosis. Moreover, gene coding NGAL was markedly overexpressed in the liver tissue in ACLF.

Surgical margin marking for high-risk basal cell carcinomas of the cephalic region: a single-centre experience.

AIM: Mohs micrographic surgery is the treatment of choice for basal cell carcinomas (BCCs) at high risk for local recurrence. This procedure is scarcely employed in Italy, even when it appears necessary, for different causes, including high costs, organization problems, or low professional experience with the technique. Aim of this study is to report our experience with the "surgical margin marking", as alternative to standard Mohs micrographic surgery in the management of high-risk BCCs of the head and neck region. METHODS: A retrospective analysis on 102 (64 males and 38 females; mean age: 66.8 years; median: 68 years; range: 53-87 years) of 208 patients with high-risk basal cell carcinomas of the head and neck region, submitted to surgical margin marking has been made. All cases had completed a 3-year follow-up. Primary tumours were 52 (51%), recurrent tumours were 50 (49%). RESULTS: The mean number of micrographic surgery stages for a complete tumour clearance was 1.65 (range: 1-4 stages). In 47% (N.=49) of cases the tumours were removed by a single stage, while in 42.1% (N.=43) of patients two stages were required. Only 2 patients (2%) showed recurrences during a mean follow-up of 61.2 months (median: 62 months; range: 37-84 months). CONCLUSION: Our experience supports the effectiveness of the surgical margin marking technique in the treatment of high-risk basal cell carcinomas of the cephalic region. It may represent an alternative approach to Mohs micrographic surgery in dermatologic departments of many hospitals, where standard Mohs micrographic surgery is more difficult to perform.

Right ventricular end-diastolic volume index as a predictor of preload status in patients with low right ventricular ejection fraction during orthotopic liver transplantation.

OBJECTIVE: The objective of this study was to compare the accuracy of 2 variables: pulmonary artery occlusion pressure (PAOP) and right ventricular end diastolic volume index (RVEDVI) as predictors of the hemodynamic response to fluid challenge as well as definition of the overall correlation between RVEDVI and change in PAOP, right ventricular ejection fraction (RVEF), central venous pressure (CVP), and determination of the right ventricular function during orthotopic liver transplantation. MATERIALS AND METHODS: A modified pulmonary artery catheter equipped with a fast response thermistor was used to determine RVEF, allowing calculation of RVEF end-diastolic volume index (EDVI, as the ratio of stroke index [SI] to EF). The above-mentioned hemodynamic measures were taken in 4 phases: T0, after induction of anesthesia; T1, during anhepatic phase; T2, 30' after graft reperfusion; and T3, at the end of surgery. RESULTS: The variation of the REF value was 36 +/- 4% and 39 +/- 6%. Linear regression analysis showed a significant correlation between RVEDVI (range, 133 +/- 33-145 +/- 40 mL/m(2)) and stroke volume index (SVI) in each phase (r(2) = 0.49, P < .01; r(2) = 0.57, P < .01) at T0 and T1, respectively, and at T2 and T3 (r(2) = 0.51, P < .01; r(2) = 0.44, P < .01), respectively. No significant variations in the linear regression analysis between RVEDVI, PAOP, CVP, and RVEF were observed. No relationship was found between PAOP (range, 10 +/- 2-6 +/- 2 mm Hg) and SVI. CONCLUSION: RVEDVI may be the best clinical estimate of right ventricular preload. In fact, minor changes of RVEF have been recorded, confirming that RV function was not altered during uncomplicated orthotopic liver transplantation.

Ultrastructural morphometry of nucleoli: potential usefulness for objective grading of clear cell renal cell carcinoma.

The authors attempted to determine the potential prognostic value of several ultrastructural morphometric parameters, including nuclear, nucleolar, and cytoplasmic features, that could be used in the objective and reproducible histological grading of clear cell renal cell carcinoma. Several nuclear and cytoplasmic parameters were assessed by ultrastructural morphometry in 26 consecutive cases of clear cell renal cell carcinoma. The nuclear and nucleolar sizes, the number of nucleoli per nuclear section and the number of marginated nucleoli, Fuhrman's nuclear grade, and Robson's stage were recorded. In addition, the proportion of cytoplasmic components was semiquantitatively estimated and compared to light microscopic appearance. Follow-up ranged from 5 to 15 years (mean = 10 years). Statistical evaluations were performed by means of the Pearson or Spearman correlation coefficient tests, and differences in survival were estimated, using the Mantel-Cox proportional risk method. Differences in survival among patients with a mean nuclear area over and under 160 microm2, and among those with a mean nucleolar area over and under 10 microm2, were statistically significant. (Cutoff points were selected at the median value for both parameters; Mantel-Cox test: chi2 = 7.102, p < .01; and chi2 = 11.096, p < .001, respectively). Fuhrman's nuclear grade (p < .01) and tumor stage at diagnosis (p < .001) were also related to survival. These data suggest that, out of all the ultrastructural morphometric features, nucleolar area is the most useful in the reproducible and accurate grading of clear cell renal cell carcinoma.

Dirofilariasis due to Dirofilaria repens in Italy, an emergent zoonosis: report of 60 new cases.

AIMS: Sixty new cases of human dirofilariasis due to Dirofilaria repens, occurring in Italy between 1990 and 1999, are presented. This is the most extensive case study of this zoonosis reported worldwide by a single study group. The aim is to utilize this large experience to characterize the different histopathological findings in the parasitic lesions in man. METHODS AND RESULTS: Diagnosis was performed on histological sections of the nematode enclosed in the nodules excised at biopsy or surgery. The nematode was located in the subcutaneous tissue (49 cases), the epididymis (two cases), the spermatic cord (two cases), the lung (two cases), the breast (two cases), the omentum (two cases) and under the conjunctival tissue (one case). The majority of cases (46) were from Piedmont; the remainder were from Emilia-Romagna, Sardinia, Sicily, Tuscany, Apulia and Lombardy. The histopathological features of the lesions are described and the clinical and epidemiological aspects of the zoonosis are discussed. The prevalence in Italy in general and in the area of Piedmont in particular, comprising the provinces of Alessandria, Asti, Novara and Vercelli, which is one of the most severely affected areas of the world, is emphasized. The evident increase in the number of cases in the last few years is a clear indication that it is an emergent zoonosis. CONCLUSIONS: We recommend that each and every case observed be recorded, to enable the true extent of human dirofilariasis in Italy to be assessed, and that a reference centre be set up in the area to collate the data. The importance of the histopathologist's role in the diagnosis is stressed.

[Continuous brachial plexus blockade for shoulder surgery]. / Il blocco continuo del plesso brachiale per la chirurgia della spalla.

Continuous brachial plexus block is the technique of choice for postoperative shoulder pain treatment. The localization of the plexus is usually obtained drawing landmarks on the skin and using the electrical nerve stimulator; these and other different modalities are applied in order to reach safely and precisely nerve roots to be blocked with an anaesthetic solution. The Author presents a new anatomical perspective to guide the localization of the brachial plexus. It is shown how it is possible to detect the pathway of the brachial plexus from the cutaneous surface, linking between each other various landmarks: a) the apex of the scalene triangle, at the cross of a line leaving from the cricoid process and directed posterior to the posterior border of the sternocleidomastoid muscle, b) the midline of the clavicle c)the deltoid-pectoral sulcus d) the midpoint between the coracoid process and the chest profile e) the pulsation of the artery in the axylla. Following the guide of the so formed anesthetic line, is possible to place the needle, with a direction from distal to proximal, in a tangential route towards the interscalenic groove, thus allowing to perform a block of the plexus in a simple and efficacious way.

[Two in one block for carotid surgery]. / Blocco 2 in per la chirurgia della carotide.

The choose of the best anaesthesia for carotid surgery is a very debated item: the locoregional techniques probably offer more hemodynamic stability and a direct neurologic monitoring, while general anaesthesia allows the complete control of airways and ventilation and reduces the global stress for the patient. This review analyzes the data of studies that compare general and locoregional anaesthesia. Among the latter, possibly elective techniques, the one described by Winnie combines an optimal analgesic efficacy with the lowest rate of adverse effects. A single bolus of a local anesthetic injected at a C4 level (apex of scalene muscles triangle) guarantees a complete block of the superficial and deep cervical plexuses.

Electron microscopy in pathology articles: a retrospective appraisal.

Electron microscopy (EM) is a valuable standard tool in basic research and teaching. However, its use in diagnosis is limited, either for strategic reasons or budgetary constraints. This means that its many potential applications are more often neglected, either as an ancillary tool, quality control method, or gold standard, to complement, support, or confirm results of pathological studies. To evaluate the use of EM in this setting, the authors analyzed all articles (n = 2,531) in the three top indexed diagnostic pathology journals for a period of 60 months from July 1993 to June 1998. A total of 448 articles in which the use of EM was indicated, according to standard surgical pathology textbooks, were selected. Both the actual and the potential EM content of each article were scored, as follows: zero, illustrative, supportive, gold standard (for confirmation of research results), extensive, and predominant. Of the total number of articles in which EM was indicated, 77% made use of the technique. EM support was lacking most frequently in articles on serosal neoplasms and on new diagnostic strategies (p < .00005). There was no definite trend toward an increase or decrease in the use of EM during the period analyzed. The authors conclude that EM is used in most reports on diagnostic pathology, when it is indicated. However, a small but non-negligible percentage of articles (23%) could benefit from including EM as an ancillary, control, or gold standard method to complement, support, or confirm their results.

Six-month outcome in unstable angina patients without previous myocardial infarction according to the use of tertiary cardiologic resources. RESCATE Investigators. Recursos Empleados en el Síndrome Coronario Agudo y Tiempos de Espera.

OBJECTIVES: The study assessed whether varying accessibility of patients with unstable angina (UA) to coronary angiography and revascularization determined differing usages and outcomes. BACKGROUND: The appropriate use rate of coronary angiography and revascularization procedures in UA remains to be established. METHODS: A total of 791 consecutive patients with UA without previous acute myocardial infarction (AMI) admitted to four reference teaching hospitals (one with tertiary facilities) were followed for six months. End points were six-month mortality and readmission for AMI, UA, heart failure, or severe ventricular arrhythmias. RESULTS: Patients admitted to the tertiary hospital were 3.27 (95% confidence interval [CI] 2.32 to 4.62) times more likely to undergo coronary angiography after adjustment for comorbidity and severity than were those admitted to nontertiary facilities (overall six-month use rates 70.1% and 48.3%, respectively). Revascularization procedures were performed in 36.2% of patients in the tertiary hospital and 24.6% in the others (p = 0.0007); adjusted relative risk (RR) 2.37 (95% CI 1.55 to 3.63). Median delay for urgent coronary angiography was shorter in the tertiary hospital (24 h vs. 4 days, p < 0.0002). Six-month mortality and readmission rates were similar in tertiary and nontertiary hospitals: 3.9% versus 5.3% and 16.9% versus 21.2%, respectively. Adjusted RR of death or readmission for the nontertiary hospitals was 1.23 (95% CI 0.57 to 2.67). CONCLUSIONS: The use of coronary angiography and revascularization procedures in UA patients with no previous AMI is higher in tertiary than in nontertiary hospitals, but the more selective use of these procedures in nontertiary centers does not imply worse outcome.

Postoperative analgesia for early extubation after cardiac surgery. A prospective, randomized trial.

BACKGROUND: Early extubation after cardiac surgery is a procedure recently gaining interest due to its ability to shorten intensive care unit and hospital stay and to limit the operation-related costs. Its use, however, raised new problems in terms of pain control in the early postoperative course, due to the need for limiting opioid analgesia. This study deals with non-opioid pain control after cardiac surgery and early extubation. METHODS: Prospective, randomized trial aimed to investigate the effectiveness of three intravenous analgesic drugs (ketorolac, 60 mg i.v.; propacetamol, 2 g i.v.; tramadol, 200 mg i.v.) for the management of postoperative pain in early extubated cardiac surgical patients. Each treatment group comprised 20 patients. RESULTS: The pain assessment (5-item verbal scale) demonstrated a significant (p < 0.05) lower value in patients treated with ketorolac vs propacetamol, while patients treated with tramadol did not significantly differ from the other two groups. There was a significantly (p < 0.05) higher rate of patients with severe pain in propacetamol group. Patients treated with tramadol had a significantly (p < 0.01) higher PaCO2 (48 +/- 6 mmHg) versus patients treated with ketorolac (43.4 +/- 3.7 mmHg) or propacetamol (42.9 +/- 3.4 mmHg). CONCLUSIONS: Tramadol and ketorolac seem to be the best options for treating postoperative pain in the specific setting of early extubation after cardiac surgery; high doses of tramadol may result in a significant even if clinically not relevant respiratory depression.

Mortality differences between men and women following first myocardial infarction. RESCATE Investigators. Recursos Empleados en el Síndrome Coronario Agudo y Tiempo de Espera.

CONTEXT: Mortality after acute myocardial infarction is worse in women than in men, even after adjustment for comorbidity and age dissimilarities between sexes. OBJECTIVE: To assess the influence of sex on survival after acute myocardial infarction. DESIGN: Inception cohort obtained in a prospective registry of patients with acute myocardial infarction from 1992 through 1994. SETTING: Four teaching hospitals in northeastern Spain. PATIENTS: All consecutive patients aged 80 years or younger with first acute myocardial infarction. A total of 331 women and 1129 men were included. MAIN OUTCOME MEASURE: Survival at 28 days and mortality or readmission at 6 months. RESULTS: Women were older (mean, 68.6 vs 60.1 years), presented more often with diabetes (52.9% vs 23.3%), hypertension (63.9% vs 42.3%), or previous angina (44.6% vs 37.4%), and developed more severe myocardial infarctions than men (acute pulmonary edema or cardiogenic shock occurred in 24.8% of women and 10.5% of men) (all P<.02). Men were more likely than women to receive thrombolytic therapy (41.3% vs 23.9%; P<.001), but rates of percutaneous transluminal angioplasty and coronary artery bypass graft surgery at 28 days were similar among men and women. The 28-day mortality rate was significantly higher among women (18.5% for women, 8.3% for men; P<.001). Revascularization procedures at 6 months were performed in a similar proportion of women and men. However, women had higher 6-month mortality rates (25.8% in women, 10.8% in men; P<.001) and readmission rates (23.3% for women, 12.2% for men; P<.001). After adjustment, women had greater risk of death than men at 28 days (odds ratio [OR], 1.72; 95% confidence interval [CI], 1.12-2.65) and at 6 months (OR, 1.73; 95% CI, 1.18-2.52). CONCLUSIONS: In this study population, women experienced more lethal and severe first acute myocardial infarction than men, regardless of comorbidity, age, or previous angina.

Asbestos lung burden and asbestosis after occupational and environmental exposure in an asbestos cement manufacturing area: a necropsy study.

OBJECTIVE: The largest Italian asbestos cement factory had been active in Casale Monferrato until 1986: in previous studies a substantial increase in the incidence of pleural mesothelioma was found among residents without occupational exposure to asbestos. To estimate exposure to asbestos in the population, this study evaluated the presence of histological asbestosis and the lung burden of asbestos fibres (AFs) and asbestos bodies (ABs). METHODS: The study comprises the consecutive series of necropsies performed at the Hospital of Casale Monferrato between 1985 and 1988. A sample of lung parenchima was collected and stored for 48 out of 55 necropsies. The AF concentration was measured with a TEM electron microscope with x ray mineralogical analysis. The ABs were counted and fibrosis evaluated by optical microscopy. The nearest relative of each subject was interviewed on occupational and residential history. Mineralogical and histological analyses and interviews were conducted in 1993-4. RESULTS: Statistical analyses included 41 subjects with AF, AB count, and interview. Subjects without occupational exposure who ever lived in Casale Monferrato had an average concentration of 1500 AB/g dried weight (gdw); Seven of 18 presented with asbestosis or small airway lung disease (SAL). G2 asbestosis was diagnosed in two women with no occupational asbestos exposure. One of them had been teaching at a school close to the factory for 12 years. Ten subjects had experienced occupational asbestos exposure, seven in asbestos cement production: mean concentrations were 1.032 x 10(6) AF/gdw and 96,280 AB/gdw. Eight of the 10 had asbestosis or SAL. CONCLUSION: The high concentration of ABs and the new finding of environmental asbestosis confirm that high asbestos concentration was common in the proximity of the factory. Subjects not occupationally exposed and ever living in Casale Monferrato tended to have higher AB concentration than subjects never living in the town (difference not significant). The concentrations of ABs and AFs were higher than those found in other studies on nonoccupationally exposed subjects.

High prevalence of cardiovascular risk factors in Gerona, Spain, a province with low myocardial infarction incidence. REGICOR Investigators.

STUDY OBJECTIVE: To establish the prevalence of main cardiovascular risk factors in the province of Gerona, where the incidence of myocardial infarction is known to be low. DESIGN: This was a cross sectional study of prevalence of cardiovascular risk factors conducted on a large random population sample. SETTING: The province of Gerona, Spain. PARTICIPANTS: Two thousand four hundred and four eligible inhabitants of Gerona aged between 25 and 74 years were randomly selected for a multi-stage sample stratified by age and sex. The following were standardly measured: lipids (total cholesterol, high density, low density, lipoprotein (a) and triglycerides), fibrinogen, basal glycaemia, arterial pressure, anthropometric variables, smoking, history of angina (Rose questionnaire), and a medical history questionnaire. Population measurements were standardised for the world population of 24 to 74 years of age. RESULTS: The participation rate was 72.7% (1748). Total mean cholesterol was 5.69 mmol/l in men and 5.61 mmol/l in women and mean high density cholesterol was 1.22 mmol/l and 1.47 mmol/l, respectively. Median lipoprotein (a) was 0.22 g/l. These three lipids increased significantly with age. Mean fibrinogen was 2.92 g/l in men and 3.09 g/l in women, and was higher in smokers. The prevalence of hypertension (systolic arterial tension > or = 140 mm Hg or diastolic > or = 90 mm Hg or drug treatment) was 31.3% in men and 27.7% in women. The proportion of male smokers was 33.8% and female smokers 22.7%. The proportion of female smokers in the 25-34 year age group exceeded that of the remaining age groups for both men and women. CONCLUSIONS: The prevalence of cardiovascular risk factors in Gerona is relatively high for the low myocardial infarction incidence typical of the area, although similar to that of other Spanish areas. The factors that confer sufficient protection to compensate for the effect of the prevalence of these risk factors remain to be elucidated.