Paolo Usai

Mortality in patients with coeliac disease and their relatives: a cohort study

BACKGROUND Although previous studies have shown increased mortality in patients with coeliac disease and their relatives, no data are available in relation to different patterns of clinical presentation. We assessed mortality in patients with coeliac disease and their first-degree relatives. METHODS We enrolled, in a prospective cohort study, 1072 adult patients with coeliac disease consecutively diagnosed in 11 gastroenterology units between 1962 and 1994, and their 3384 first-degree relatives. We compared the number of deaths up to 1998 with expected deaths and expressed the comparison as standardised mortality ratio (SMR) and relative survival ratio. FINDINGS 53 coeliac patients died compared with 25.9 expected deaths (SMR 2.0 [95% CI 1.5-2.7]). A significant excess of mortality was evident during the first 3 years after diagnosis of coeliac disease and in patients who presented with malabsorption symptoms (2.5 [1.8-3.4]), but not in those diagnosed because of minor symptoms (1.1 [0.5-2.2]) or because of antibody screening (1.2 [0.1-7.0]). SMR increased with increasing delay in diagnosis and for patients with poor compliance with gluten-free diet. Non-Hodgkin lymphoma was the main cause of death. No excess of deaths was recorded in relatives with coeliac disease. INTERPRETATION Prompt and strict dietary treatment decreases mortality in coeliac patients. Prospective studies are needed to clarify the progression of mild or symptomless coeliac disease and its relation to intestinal lymphoma.

Prevalence of thyroid disorders in untreated adult celiac disease patients and effect of gluten withdrawal: an Italian multicenter study.

OBJECTIVES:Many afflictions have been associated with celiac disease, but chance associations may exists. The aim of this study was to establish, by means of a multicenter prospective study, the prevalence of thyroid impairment among adult patients with newly diagnosed celiac disease and to evaluate the effect of a 1-yr gluten withdrawal on thyroid function.METHODS:A total of 241 consecutive untreated patients and 212 controls were enrolled. In 128 subjects a thorough assessment, including intestinal biopsy, was repeated within 1 yr of dietary treatment. Thyroid function was assayed by measuring the levels of TSH, free T3, free T4, thyroperoxidase, and thyroid microsome antibodies.RESULTS:Thyroid disease was 3-fold higher in patients than in controls (p < 0.0005). Hypothyroidism, diagnosed in 31 patients (12.9%) and nine controls (4.2%), was subclinical in 29 patients and of nonautoimmune origin in 21. There was no difference regarding hyperthyroidism, whereas autoimmune thyroid disease with euthyroidism was present in 39 patients (16.2%) and eight controls (3.8%). In most patients who strictly followed a 1-yr gluten withdrawal (as confirmed by intestinal mucosa recovery), there was a normalization of subclinical hypothyroidism. Twenty-five percent of patients with euthyroid autoimmune disease shifted toward either a subclinical hyperthyroidism or subclinical hypothyroidism; in these subjects, dietary compliance was poor. In addition, 5.5% of patients whose thyroid function was normal while untreated developed some degree of thyroid dysfunction 1 yr later.CONCLUSIONS:The greater frequency of thyroid disease among celiac disease patients justifies a thyroid functional assessment. In distinct cases, gluten withdrawal may single-handedly reverse the abnormality.

Association between panic disorder, major depressive disorder and celiac disease A possible role of thyroid autoimmunity

OBJECTIVE To evaluate the association between celiac disease and specific anxiety and depressive disorders and to identify potential common pathogenetic links, with particular regard to thyroid function and autoimmunity. METHODS Cases included 36 adult celiac patients, 25 females and 11 males, aged 18-64 years. Controls comprised 144 healthy subjects matched by sex and age with no clinical evidence or family history of celiac disease. Diagnosis of celiac disease was made on the basis of clinical history and serological criteria. Psychiatric diagnoses were formulated using the International Composite Diagnostic Interview, according to DSM-IV criteria. Thyroid was evaluated by palpation, echography and measurement of serum-free thyroid hormones (FT4, FT3), thyroid-stimulating hormone (TSH) and antithyroid autoantibodies (anti-TPO). RESULTS Compared to controls, a significantly higher number of celiac patients met criteria for lifetime [15 (41.7%) versus 30 (29.8%), P < .01] and 6-month [7 (19.4%) versus 9 (6.2%), OR = 3.2, chi(2) = 5.2, P < .05] major depressive disorder (MDD) and lifetime [5 (13.9%) versus 3 (2.1%), P < .001] and 6-month [3 (8.1%) versus 2 (1.4%), P < .05] panic disorder (PD). Anti-TPO prevalence was significantly higher in celiac patients than in the control group (11/36 = 30.5% versus 14/144 = 9.7%, P < .001). A higher frequency of PD and MDD was found in celiac patients with positive anti-TPO when compared to negative anti-TPO patients (4/11 = 36.4% PD in TPO+ versus 1/25 = 4% PD in TPO-, P < .01; 9/11 = 81.8% MD in TPO+ versus 6/25 = 9.5% MD in TPO-, P < .01). CONCLUSION Patients affected by celiac disease tend to show a high prevalence of PD and MDD and association with subclinical thyroid disease appears to represent a significant risk factor for these psychiatric disorders.

Autonomic dysfunction and upper digestive functional disorders in untreated adult coeliac disease

There is recent evidence that upper‐gut motor abnormalities may be present in coeliac disease. However, to date, the pathophysiological mechanisms responsible for the above have not been explored. The purpose of the present study was to investigate upper‐gut motor activity in coeliac disease and explore the role played by the autonomic nervous system in motility disturbances. Thirty untreated adult coeliac patients were recruited into the study. Oesophageal manometry and cardiovascular autonomic tests were performed in all patients; oesophageal pH‐metry was carried out in 20 patients, gastrointestinal manometry in eight and scintigraphic gastric emptying in 13. Oesophageal motor abnormalities were detected in about 50% of patients, pH‐metry was abnormal in 30% of them, and up to 75% of coeliac patients displayed gastrointestinal motility alterations. Delayed gastric emptying was documented in about 50% of patients and was correlated with manometric post‐prandial hypomotility. Autonomic tests were positive in 45% of patients as a group, and reached pathological score in 19% of them. Autonomic score correlated significantly with the percentage of bi‐peaked waves and with the number of fasting intestinal clusters. This study confirms that upper‐gut motor abnormalities are frequently present in adult coeliac disease. Extrinsec autonomic neuropathy may play a role, although other pathophysiological mechanisms are likely to occur.

Case control study on health-related quality of life in adult coeliac disease.

AIMS To evaluate whether health-related quality of life in adult coeliac disease is related to: 1) adhesion to gluten-free diet; 2) manifestation of clinical features; and 3) associated diseases. PATIENTS AND METHODS A total of 68 coeliac patients (54 female and 14 male) aged between 18 and 74 years, on gluten-free diet for at least two years were studied. The subjective health status was measured by means of the Short Form 36 Health Survey. A series of 136 subjects, matched according to sex, age and ethnic group, were evaluated as control group. RESULTS Patients obtained worse scores with respect to healthy controls at all domains of Short Form 36 Health Survey (p<0.05); compliers showed better results than non-compliers. The lowest scores were obtained in patients with more than six symptoms, mostly in non-compliers, the highest in compliers with less than six symptoms. Patients with two or more associated diseases presented significantly worse scores than patients with only one associated disease. CONCLUSIONS The importance of gluten-free diet in clinical management of coeliac disease is confirmed by results of the present study; moreover, the results seem to indicate that a complex interplay of factors should be taken into account in evaluating health-related quality of life in adult coeliac disease. Accordingly, our data show that health-related quality of life of coeliac patients is impaired not only by poor compliance but also by different negative factors such as severity of illness (in terms of number of symptoms) at diagnosis and comorbidity.

Oral versus combination mesalazine therapy in active ulcerative colitis: a double‐blind, double‐dummy, randomized multicentre study

Oral and topical mesalazine formulations are effective in active ulcerative colitis, but little is known on the efficacy of combined treatment.

Thyroid and celiac disease: clinical, serological, and echographic study

Abstract Objective: We sought to reevaluate the prevalence of thyroid dysfunction and thyroid autoimmunity in 47 patients with celiac disease; 91 healthy subjects were studied as controls. Both patients and controls were from Sardinia, Italy. Methods: Diagnosis of celiac disease was made on the basis of clinical history, presence of positive antigliadin IgA (AGA-A) and IgG (AGA-G) antibodies, antireticulin antibodies (ARA), antiendomysium antibodies (EMA), and was confirmed by jejunal biopsy. HLA class II typing for DQB1 and DQA1 alleles was performed in 36/47 celiac patients. Thyroid was evaluated by palpation and echography; serum free thyroid hormones (FT4, FT3), thyrotropic hormone (TSH), and antithyroid peroxidase autoantibodies (anti-TPO) were assayed by radioimmunoassays. Results: The prevalence of anti-TPO was higher in celiac patients (29.7%) than in healthy controls (9.6%) (p

Oesophageal motility in adult coeliac disease.

Abstract Coeliac sprue is a relatively frequent disease with protean clinical manifestations. Recent studies suggest that gastrointestinal motor abnormalities may explain some symptoms complained of by such patients. We investigated whether coeliac patients have oesophageal motor abnormalities from both a clinical and a physiological point of view. Thirty‐six consecutive adult sprue subjects (14 during the florid phase and 22 on gluten‐free diet) were studied. A clinical questionnaire on gastrointestinal symptoms (with emphasis on those of oesophageal origin) was administered. Moreover, 18 patients (13 on free and five on gluten‐free diet) gave their consent for oesophageal manometry and eight subjects for pH‐metry also. Oesophageal clinical symptoms were compared with those of 144 age‐ and sex‐matched controls from a general population sample, and manometry with that of 34 healthy volunteers. Of coeliac patients 50% complained of dysphagia (P < 0.001 vs. controls) and 14% noncardiac chest pain (P = NS vs. controls). Manometric examination showed motor abnormalities in 67% of the subjects examined, consisting of nutcracker oesophagus, hypotonic lower oesophageal sphincter associated with simultaneous contractions, and frequent repetitive (>3 peaks) contractions. These abnormalities were equally distributed among free and gluten‐free diet patients. pH‐metry showed only one pathological reflux out of eight subjects studied. We conclude that patients with coeliac sprue may display abnormal oesophageal motility. This confirms previous studies suggesting that gastrointestinal motor abnormalities should probably be added to the clinical spectrum of the disease.

Position: prone or supine is the issue of percutaneous nephrolithotomy.

INTRODUCTION The prone position has been considered the only position for percutaneous access to the kidney for the past 25 years, whereas the supine Valdivia position has recently started to gain acceptance, although it was originally described in the late 1980s. Even more recently, the Galdakao-modified supine Valdivia position was described. However, there is no consensus on which is the best position for percutaneous nephrolithotomy, and the choice is currently based on the surgeons preference. MATERIALS AND METHODS The prone, supine, and modified supine positions are described, pointing out the advantages, disadvantages, and results of each technique. RESULTS A number of potential advantages have been described for the supine over the prone position: less cardiovascular change; no need for patient repositioning (with less associated risk of central and peripheral nervous system injury); less X-ray exposure to the surgeon; and less risk of colonic injury. The recently described Galdakao-modified supine Valdivia position allows for a simultaneous anterograde and retrograde approach to the renal cavities for the one-stage treatment of complex renal stones or concurrent renal and ureteral calculi. Moreover, the use of a flexible ureteroscope allows for Endovision puncture to achieve perfect access to the kidney. CONCLUSIONS The prone position still represents the standard for percutaneous access to the kidney, and other positions should be compared with this position. However, the supine and the modified supine positions have potentially important advantages for both patients and surgeons that need to be investigated in a large randomised trial to define their superiority over the traditional prone position.

Symptom patterns can distinguish diverticular disease from irritable bowel syndrome

Diverticular disease (DD) and irritable bowel syndrome (IBS) share a similar symptom pattern. However, comparative studies are flawed by different age at onset of symptoms. We aimed to verify whether clinical features distinguish DD from IBS.