Epidemiology, clinical characteristics, outcome, morbidity and mortality in acromegaly based on the Spanish Acromegaly Registry (Registro Espanol de Acromegalia, REA)

OBJECTIVE: To undertake a multicentre epidemiological study reflecting acromegaly in Spain. DESIGN: Voluntary reporting of data on patients with acromegaly to an online database, by the managing physician. METHODS: Data on demographics, diagnosis, estimated date of initial symptoms and diagnosis, pituitary imaging, visual fields, GH and IGF-I concentrations (requested locally), medical, radiotherapy and neurosurgical treatments, morbidity and mortality were collected. RESULTS: Data were included for 1219 patients (60.8% women) with a mean age at diagnosis of 45 years (s.d. 14 years). Reporting was maximal in 1997 (2.1 cases per million inhabitants (c.p.m.) per year); prevalence was globally 36 c.p.m., but varied between 15.7 and 75.8 c.p.m. in different regions. Of 1196 pituitary tumours, most were macroadenomas (73%); 81% of these patients underwent surgery, 45% received radiotherapy and 65% were given medical treatment (somatostatin analogues in 68.3% and dopamine agonists in 31.4%). Cures (GH values (basal or after an oral glucose tolerance test) <2 ng/ml, normal IGF-I, or both) were observed in 40.3% after surgery and 28.2% after radiotherapy. Hypertension (39.1%), diabetes mellitus (37.6%), hypopituitarism (25.7%), goitre (22.4%), carpal tunnel syndrome (18.7%) and sleep apnoea (13.2%) were reported as most frequent morbidities; 6.8% of the patients had cancer (breast in 3.1% of the women and colon in 1.2% of the cohort). Fifty-six patients died at a mean age of 60 years (s.d. 14 years), most commonly of a cardiovascular cause (39.4%); mortality was greater in patients given radiotherapy (hazard ratio 2.29; 95% confidence interval 1.03 to 5.08; P=0.026), and in those in whom GH and IGF-I concentrations were never normal (P<0.001). CONCLUSIONS: This acromegaly registry offers a realistic overview of the epidemiological characteristics, treatment outcome and morbidity of acromegaly in Spain. As active disease and treatment with radiotherapy are associated with an increase in mortality, efforts to control the disease early are desirable.     

Aortic valve replacement with pulmonary autograft (the Ross procedure) in adult and pediatric patients

Aortic valve replacement with pulmonary autograft was first performed by Donald Ross in 1967. Initially, the procedure was not widely accepted, by Cardiologists and Cardiac surgeons fundamentally due to its complexity and demanding surgical technique, and because innumerous series two cardiac valves were at risk. The results published in the last 10-15 years established the pulmonary autograft as one of the best methods of aortic valve replacement, especially in pediatric patients and young adults. In the present article, we reviewed present indications and contraindications, and our clinical experience with 26 patients (pediatrics and adults). Analysis of the first 22 the patients with a minimum of 6 months of follow-up (180-620 days) was performed. Follow-up is complete (100%). Mean age was 31.4 +/- 12.6 years. Five patients were pediatrics (<= 14 years). Three patients (11%) with previous percutaneous procedures and 4 patients (14%) with previous surgical procedures. There was no early or late mortality. In the last follow-up, 19 of 22 (86.36%) had no autograft insufficiency (>= grade 1), and in one patient it was moderate (grade 2). The 2 remaining patients developed severe autograft insufficiency (grade 4) and were reoperated on, with satisfactory postoperative outcome. Mean maximal gradient was 7.85 +/- 5 mmHg at 18 months (3-29). Patients with preoperative aortic stenosis showed a significant reduction in myocardial mass index (208.7 +/- 32 a 95.8 +/- 28.8 g/m2) at 18 months. In these patients, septal and posterior wall thickness decreased significantly, in the first month. Two pediatric patients have developed transpulmonar gradient > 50 mmHg. One of them underwent successful stent implantation. We have not observed significant homograft insufficiency in any of our patients. All our patients remain asymptomatic (functional class I) without medical treatment. We have not observed either thromboembolic or haemorrhagic episodes, nor endocarditis. No patient is receiving anticoagulants. Clinical and echocardiographic mid term results in pulmonary autograft and homograft in our series, are excellent after the Ross procedure.     

Pancreatic hyperplasia after small bowel resection in the rat: dissociation from endogenous gastrin levels

Extensive small bowel resection produces pancreatic hyperplasia and increases plasma gastrin levels in the rat. Because gastrin is known as a trophic factor for the exocrine pancreas, we studied the effect of endogenous variations of gastrin induced by different gastric operations on the rat pancreas in both resected and transected animals. Vagotomy increased plasma gastrin level while antrectomy decreased it; pyloroplasty was without any effect. These gastric operations enhanced slightly but not significantly the pancreatic weight, its protein and DNA content. A 90% jejunoileal resection alone increased markedly these parameters while mitotic figures appeared in acinar cells. Pyloroplasty, vagotomy and antrectomy did not modify the changes induced by intestinal resection itself except the level of protein. These findings suggest that hypergastrinemia produced by intestinal resection is not responsible for pancreatic hyperplasia.     

Reciprocal translocations in myelodysplastic syndromes and chronic myelomonocytic leukemias: Review of 5,654 patients with an evaluable karyotype

The infrequency of translocations in myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemias (CMML) makes their identification and reporting interesting for the recognition of the recurrent ones and the genes involved in these neoplasias. The aims of this study were to identify new translocations associated with MDS and CMML and to establish their frequency in a cohort of 8,016 patients from the Spanish Group of MDS database. The karyotype was evaluable in 5,654 (70%) patients. Among those, 2,014 (36%) had chromosomal abnormalities, including 213 (10%) translocations identified in 195 patients. The translocations were balanced in 183 (86%) cases and unbalanced in 30 (14%) cases. All chromosomes were found to be involved in translocations, with the single exception of the Y chromosome. The chromosomes most frequently involved were in decreasing frequency: 3, 1, 7, 2, 11, 5, 12, 6, and 17. Translocations were found in karyotypes as the unique chromosomal abnormality (33%), associated with another chromosomal abnormality (11%), as a part of a complex karyotype (17%), and as a part of a monosomal karyotype (38%). There were 155 translocations not previously described in MDS or CMML and nine of them appeared to be recurrent. © 2013 Wiley Periodicals, Inc.     

Acute pulmonary embolism in elderly: clinical characteristics and outcome

OBJECTIVE: To evaluate the clinical characteristics and outcome of acute pulmonary embolism in elderly in comparison to the younger patients. METHODS: Study population consisted of 136 patients with a confirmed diagnosis of acute pulmonary embolism. Clinical characteristics and thromboembolic risk factors were analyzed between the elderly (> or =65 years of age) and the younger (<65 years of age) patients. In-hospital mortality was used as a measure of outcome. RESULTS: Elderly group consisted of 70 patients (age 76.4+/-8.3 years, range 65-96 years; females 58%) and younger group of 66 patients (age 48.5+/-12 years, range 18-64 years, females 59%). Syncope was more frequent in elderly group (19% vs. 6%, P=0.03) but the symptoms of shortness of breath and pleuritic chest pain were not significantly different between groups. Malignancy was the most common risk factor for thrombo-embolism, but immobilization predominated among patients in elderly group (21% vs. 6%, P=0.01). Tachycardia was common in younger patients compared to the elderly. Ventilation-perfusion scan was used more commonly in younger patients (76% vs. 57%, P=0.02), whereas, helical computed-tomography scan was used equally in both groups. Most of the patients had lower extremity duplex study (97% in each group). Inferior vena cava filter placement was common and thrombolytic therapy rare among elderly patients. Patients in elderly group had higher in-hospital mortality (17% vs. 5%, P=0.02). CONCLUSIONS: Syncope is a more frequent presenting symptom and immobilization a common risk factor in elderly patients with acute pulmonary embolism. In addition, they have higher in-hospital mortality.     

A new genetic abnormality leading to TP53 gene deletion in chronic lymphocytic leukaemia

The analysis of chromosomal abnormalities provides significant prognostic information in patients with chronic lymphocytic leukaemia (CLL), a disease with a highly heterogeneous clinical course. Chromosomal abnormalities commonly found are trisomy 12, del(13)(q14), del(11)(q22-23), del(17)(p13) and del(6)(q21). Translocations are present in some patients and affect regions recurrently involved in CLL. This report describes the clinical and pathological characteristics of four CLL patients showing a new recurrent chromosomal abnormality dic(8;17)(p11;p11), that implied loss of the TP53 gene in all cases. In addition, TP53 gene was mutated in three out of four patients. Mechanically, Low Copy Repeats (LCR) in 17p12 and 8p11 may explain the origin of the translocation by non-allelic homologous recombination (NAHR). Isolated dic(8;17)(p11;p11) in patients with mutated IGHV genes status may not have the same prognostic impact as other mutations or deletions affecting the TP53 gene. Larger series are needed to better evaluate the clinical impact of this chromosomal aberration during the course of the disease.     

Gender-specific association of the PTPN22 C1858T polymorphism with achalasia

The protein tyrosine phosphatase N22 (PTPN22) gene encodes a lymphoid-specific phosphatase (LYP), a downregulator of T-cell activation. Because a functional PTPN22 polymorphism, C1858T, has been found to be associated with different autoimmune diseases, we aimed to elucidate the role of this variant in predisposition to achalasia. We performed a case-control study with 231 nonrelated Spanish patients of white ethnicity diagnosed with achalasia and in 554 healthy control subjects, all genotyped for PTPN22 C1858T using TaqMan chemistry. The frequency of the 1858T allele was higher in the achalasia patients than in the healthy controls (carriers of allele T vs CC: OR = 1.38, 95% confidence interval [95% CI] 0.88-2.16, p = 0.13). Moreover a different genotype distribution was found between female and male patients (carriers of allele T vs CC: OR = 2.06, 95% CI 0.96-4.42, p = 0.04) and also between female patients and controls (OR = 1.94, 95% CI 1.12-3.36, p = 0.01), but not between male patients and controls (OR = 0.94, 95% CI 0.50-1.77, p = 0.85). We conclude that the PTPN22 1858T allele is a susceptibility factor for Spanish women with achalasia.