Italian guidelines for the management of adult individuals with overweight and obesity and metabolic comorbidities that are resistant to behavioral treatment.

AIM: This guideline (GL) is aimed at providing a clinical practice reference for the management of adult patients with overweight or obesity associated with metabolic complications who are resistant to lifestyle modification. METHODS: Surgeons, endocrinologists, gastroenterologists, psychologists, pharmacologists, a general practitioner, a nutritionist, a nurse and a patients' representative acted as multi-disciplinary panel. This GL has been developed following the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. A systematic review and network meta-analysis was performed by a methodologic group. For each question, the panel identified potentially relevant outcomes, which were then rated for their impact on therapeutic choices. Only outcomes classified as "critical" and "important" were considered in the systematic review of evidence. Those classified as "critical" were considered for clinical practice recommendations. Consensus on the direction (for or against) and strength (strong or conditional) of recommendations was reached through a majority vote. RESULTS: The present GL provides recommendations about the role of both pharmacological and surgical treatment for the clinical management of the adult patient population with BMI > 27 kg/m2 and < 40 kg/m2 associated with weight-related metabolic comorbidities, resistant to lifestyle changes. The panel: suggests the timely implementation of therapeutic interventions in addition to diet and physical activity; recommends the use of semaglutide 2.4 mg/week and suggests liraglutide 3 mg/day in patients with obesity or overweight also affected by diabetes or pre-diabetes; recommends semaglutide 2.4 mg/week in patients with obesity or overweight also affected by non-alcoholic fatty liver disease; recommends semaglutide 2.4 mg/week as first-line drug in patients with obesity or overweight that require a larger weight loss to reduce comorbidities; suggests the use of orlistat in patients with obesity or overweight also affected by hypertriglyceridemia that assume high-calorie and high-fat diet; suggests the use of naltrexone/bupropion combination in patients with obesity or overweight, with emotional eating; recommends surgical intervention (sleeve gastrectomy, Roux-en-Y gastric bypass, or metabolic gastric bypass/gastric bypass with single anastomosis/gastric mini bypass in patients with BMI ≥ 35 kg/m2 who are suitable for metabolic surgery; and suggests gastric banding as a possible, though less effective, surgical alternative. CONCLUSION: The present GL is directed to all physicians addressing people with obesity-working in hospitals, territorial services or private practice-and to general practitioners and patients. The recommendations should also consider the patient's preferences and the available resources and expertise.

[18F]FDG-PET/CT and long-term responses to everolimus in advanced neuroendocrine neoplasia.

PURPOSE: This study aims to identify in patients with neuroendocrine neoplasia (NEN) the potential correlation between FDG-PET findings and responses to everolimus therapy to identify predictors of long-term efficacy. METHODS: Retrospective analysis of patients with sporadic, advanced, progressive NEN treated with everolimus was performed based on the available data on FDG-PET patients obtained before commencing therapy. Data are expressed as the median (25-75th IQR). Risk factor analysis and survival analysis were performed by logistic regression and Cox proportional hazard regression and the determination of Kaplan-Meier curves, as appropriate. RESULTS: Sixty-six patients were evaluated (NET G1 19.7%, NET G2 75.7%, and NET G3 4.6%), including 45.4% with positive FDG-PET findings. Overall, disease stabilization and a partial response were achieved for 71.2% and 6% of patients, respectively. A long-term response (> 24 months) was observed in 33% of patients. Ki67 was the only predictor of tumor progression (p = 0.03). No significant difference in clinical outcomes was observed between patients with positive or negative FDG-PET findings (median PFS was 24 months and 18 months, respectively, p = 0.337; the disease control rate was 83.3% and 70%, respectively, p = 0.245). CONCLUSIONS: Everolimus is a valid therapeutic option for advanced, progressive, well-differentiated NEN, even in patients with positive FDG-PET findings.

SARS-CoV2 RNA detection in a pancreatic pseudocyst sample.

The involvement of gastrointestinal system in SARS-CoV2 related disease, COVID-19, is increasingly recognized. COVID-19 associated pancreatic injury has been suggested, but its correlation with pancreatic disease is still unclear. In this case report, we describe the detection of SARS-CoV2 RNA in a pancreatic pseudocyst fluid sample collected from a patient with SARS-CoV2 associated pneumonia and a pancreatic pseudocyst developed as a complication of an acute edematous pancreatitis. The detection of SARS-CoV2 within the pancreatic collection arise the question of whether this virus has a tropism for pancreatic tissue and whether it plays a role in pancreatic diseases occurrence.

Hospital admission for complicated diverticulitis is increasing in Italy, especially in younger patients: a national database study.

BACKGROUND: Epidemiological studies show an increasing trend of hospitalization for acute diverticulitis (AD), but data regarding the trend in hospitalization for complicated AD in Italy are scarce. The aim of this study was to analyze the Italian trend in hospitalization for complicated AD, from 2008 to 2015. METHODS: Using the Italian Hospital Information System, we identified all patients with complicated colonic AD as a discharge diagnosis. Age- and sex-specific rates for AD as well as type of hospital admission (emergency/elective), type of complication (peritonitis, obstruction, bleeding, abscess, fistula, perforation, sepsis) and type of treatment (medical/surgical), were analyzed. RESULTS: A total of 41,622 patients with a discharge diagnosis of complicated AD were identified. Over the study period the admission rate grew from 8.8 to 11.8 per 100,000 inhabitants. The hospitalization rate was highest for patients ≥ 70 years, but the increase in the admission rate was higher among patients aged ≤ 60 years. There were more males in the group < 60 years and more females in the group ≥ 60 years old. The rate of emergency admissions associated with surgery showed a significant mean annual increase (+ 3.9% per year) in the rate of emergency admissions associated with surgery, whereas elective admissions for surgery remained stable. Peritonitis was the most frequent complication (35.5%). The rate of surgery increased in AD complicated by peritonitis (+ 5.1% per year), abscess (+ 5.8% per year) and decreased for obstruction (- 1.8% per year). CONCLUSIONS: From 2008 to 2015, we documented an increasing rate of hospitalization for complicated AD, especially for younger patients, with an increase in surgery for peritonitis and abscess. Further studies are needed to clearly assess the risk factors for complications and risk of surgery.

Trends in hospital admission for acute diverticulitis in Italy from 2008 to 2015.

BACKGROUND: Epidemiological studies in Western countries have documented an increase of hospitalizations for acute diverticulitis (AD) but Italian evidence is scarce. The aim of the present study was to analyse the trend in hospitalization for AD, including in-hospital mortality, in Italy from 2008 to 2015. METHODS: Through the Italian Hospital Information System of the National Health System, we identified diverticulitis of the colon as a discharge diagnosis. Age- and gender-specific rates of hospitalization for AD were assessed. RESULTS: 174,436 hospitalizations were identified with an increasing rate in 2008-2015 from 39 to 48 per 100,000 inhabitants (p < 0.001). The rate of hospitalization was higher for women, but the increasing trend over time was even more pronounced among men (mean increase per year 3.9% and 2.1% among men and women, respectively) (p < 0.001). The increased rate of hospitalization was accounted for by patients less than 70 years old, especially those under 60. In contrast, the hospitalization rate for older patients (age ≥ 70 years) was higher but remained unchanged during the study period. The number of patients with one hospital admissions was significantly higher than the number of patients with at least two hospitalizations (p < 0.001) and both groups showed a significant and comparable increase year by year. The overall in-hospital mortality rate increased from 1.2 to 1.5% (p = 0.017). More specifically, the increase was observed in patients at their first hospitalization [from 1 to 1.4% (mean increase per year of 3%, p = 0.003)]. An increase in mortality was most evident among women (from 1.4 to 1.8% p = 0.025) and in older patients [age 70-79 years from 1.2 to 1.7% (p = 0.034), ≥ 80 years from 2.9 to 4% (p = 0.001)]. CONCLUSIONS: In Italy, between 2008 and 2015, the rate of hospitalization for AD has been constantly increasing due to the hospitalization of younger individuals, especially men. There was a significant increase of in-hospital mortality especially among women, elderly and during the first hospitalization. These findings suggest the need for increased awareness and clinical skills in the management of this common condition.

Practice parameters for the treatment of colonic diverticular disease: Italian Society of Colon and Rectal Surgery (SICCR) guidelines.

The mission of the Italian Society of Colorectal Surgery (SICCR) is to optimize patient care. Providing evidence-based practice guidelines is therefore of key importance. About the present report it concernes the SICCR practice guidelines for the diagnosis and treatment of diverticular disease of the colon. The guidelines are not intended to define the sole standard of care but to provide evidence-based recommendations regarding the available therapeutic options.

Chronic idiophatic urticaria and Helicobacter pylori: a specific pattern of gastritis and urticaria remission after Helicobacter pylori eradication.

Chronic urticaria (CU) is defined as the occurrence of spontaneous wheals for a duration of more than 6 weeks and is the most frequent skin disease, with prevalence ranging between 15 and 25%, and is a seriously disabling condition, with social isolation and mood changes causing a significant degree of dysfunction and quality of life impairment to many patients. The main clinical features of CU are the repeated occurrence of transient eruptions of pruritic wheals or patchy erythema on the skin that last less than 24 hours and disappear without sequelae. CU is often defined as chronic idiopathic urticaria (CIU) because the causes of CU remain unknown in the great majority (70-95%) of patients. Drugs, food, viruses, alimentary conservative substances or inhalant substances often seem to be involved in determining CIU skin flare. Despite a general agreement that bacteria infections and parasitic infestations can be involved in the pathogenesis of CIU, proven evidence of these relationships is lacking. The aim of the present study is to evaluate the prevalence of Helicobacter pylori (Hp) infection, and the extension and severity of gastritis in a group of CIU patients compared to controls and to evaluate the effectiveness of eradication of Hp on the CIU symptomatology, and the role of Hp infection in pathogenesis of CIU.

Systematic review and meta-analysis: Artificial intelligence for the diagnosis of gastric precancerous lesions and Helicobacter pylori infection.

BACKGROUND: The endoscopic diagnosis of Helicobacter-pylori(H.pylori) infection and gastric precancerous lesions(GPL), namely atrophic-gastritis and intestinal-metaplasia, still remains challenging. Artificial intelligence(AI) may represent a powerful resource for the endoscopic recognition of these conditions. AIMS: To explore the diagnostic performance(DP) of AI in the diagnosis of GPL and H.pylori infection. METHODS: A systematic-review was performed by two independent authors up to September 2021. Inclusion criteria were studies focusing on the DP of AI-system in the diagnosis of GPL and H.pylori infection. The pooled accuracy of studies included was reported. RESULTS: Overall, 128 studies were found (PubMed-Embase-Cochrane Library) and four and nine studies were finally included regarding GPL and H.pylori infection, respectively. The pooled-accuracy(random effects model) was 90.3%(95%CI 84.3-94.9) and 79.6%(95%CI 66.7-90.0) with a significant heterogeneity[I2=90.4%(95%CI 78.5-95.7);I2=97.9%(97.2-98.6)] for GPL and H.pylori infection, respectively. The Begg's-test showed a significant publication-bias(p = 0.0371) only among studies regarding H.pylori infection. The pooled-accuracy(random-effects-model) was similar considering only studies using CNN-model for the diagnosis of H.pylori infection: 74.1%[(95%CI 51.6-91.3);I2=98.9%(95%CI 98.5-99.3)], Begg's-test(p = 0.1416) did not show publication-bias. CONCLUSION: AI-system seems to be a good resource for an easier diagnosis of GPL and H.pylori infection, showing a pooled-diagnostic-accuracy of 90% and 80%, respectively. However, considering the high heterogeneity, these promising data need an external validation by randomized control trials and prospective real-time studies.

Quality of endoscopic screening for colorectal cancer in Italy: A national survey.

BACKGROUND: Colorectal cancer (CRC) is a major healthcare problem all over the world and screening is effective in reducing mortality and increasing survival. Since colonoscopy has a central role in faecal immunochemical test (FIT)-based CRC screening and surveillance, consistent quality measures are essential to ensure quality and outcomes. Nevertheless, screening modalities in clinical practice may differ according to the centers experience and the local availability of instrumentation and devices. AIMS: to assess the quality of endoscopic screening for CRC and adherence to international guidelines across Gastroenterology Departments in Italy. METHODS: All members of the Italian Society of Gastroenterology (SIGE) were invited to answer a web-based survey. RESULTS: Data from 64 hospitals from 17 Italian regions were analyzed. 32/64 (50.0%) were from northern, 12/64 (18.75%) from central and 20/64 (31.25%) from southern Italy. Each center is equipped with a median of 5.0 (3.5-7.0) endoscopists involved in CRC screening, 71.4% of which are gastroenterologists. After a positive FIT, most centers (93.8%) schedule a colonoscopy within 3 months. High-definition video endoscopy is routinely performed in 68.8% and chromoendoscopy in 53.1% of centers. Withdrawal time is ≥6 min in 79.9% and cecal intubation rate is ≥90% in 94.4% of departments. Finally, in 92.7% of centers adenoma detection rate (ADR) overcome the minimum standard of 25%. Analyzing the data by regional areas, a significant higher number of median endoscopic examinations/year (6500 vs 4000 and 3000, respectively, p = 0.024) and of endoscopists per center (6.5 vs 5.0 and 3.5, respectively, p < 0.001) has been registered in the northern compared to central-southern centers. CONCLUSIONS: Data from this survey show adequacy and good quality of endoscopic screening for CRC in Italy, highlighting, at the same time, relevant deficiencies and a discrepancy in procedural attitudes between the different centers. These findings call for a urgent action to overcome the shortcomings, refine and homogenize the behaviour of all screening centers in the national territory and improve the outcomes.

Efficacy of Lactobacillus paracasei sub. paracasei F19 on abdominal symptoms in patients with symptomatic uncomplicated diverticular disease: a pilot study.

AIM: The standard therapeutic approach for symptomatic uncomplicated diverticular disease (DD) remains to be defined, and only a few studies have tested the efficacy of probiotics in these patients. METHODS: Patients with symptomatic uncomplicated DD were randomized to a control arm, i.e., (group A, [N.=16], high-fibre diet alone), or to Group B ([n=18], twice daily 1 sachet of probiotic + high-fibre diet), or group C ([N.=16], twice daily 2 sachets of probiotic + high-fibre diet). The probiotic Genefilus F19© containing Lactobacillus paracasei sub. paracasei F19 was administered for 14 days/month for 6 months. The primary endpoint under consideration was a decrease in abdominal pain and bloating intensity after treatment. RESULTS: Bloating decreased significantly in Groups B and C VAS score group B: 4.6 ± 2.6 vs. 2.3 ± 2.0, P<0.05, group C: 3.9 ± 2.9 vs. 1.8 ± 2.1, P<0.05). The decrease in abdominal pain within 24 hours in these groups did not reach statistical significance. During treatment, none of the group B (N.=4) or group C patients (N=3) with abdominal pain >24 hours reported the recurrence of this symptom, while the 3 group A patients reported at least one episode (P=0.016). No significant difference regarding abdominal pain <24 hours and bloating was observed between the two groups of patients treated with a low or high probiotic dose. CONCLUSION: Lactobacillus paracasei F19, in association with a high-fibre diet, is effective in reducing abdominal bloating and prolonged abdominal pain in symptomatic uncomplicated diverticular disease, and could thus be a promising option in the treatment of these patients.

Diagnostic Accuracy of EndoFaster® and Narrow-Band Imaging Endoscopy in Patients with Impaired Gastric Acid Secretion: A Real-Time Prospective Study.

BACKGROUND: EndoFaster® analyzes gastric juice in real time during gastroscopy allowing the detection of hypo-achlorhydric conditions, like corpus atrophic gastritis. Narrow-band imaging (NBI) endoscopy allows to accurately detect and perform target biopsies in areas of intestinal metaplasia, a histological change often associated to corpus atrophic gastritis. AIMS: To compare the diagnostic accuracy of EndoFaster® with histological evaluation for corpus atrophic gastritis through high-resolution (HR) NBI targeted biopsies. METHODS: Prospective study on consecutive adult patients undergoing gastroscopy between April and November 2018. Patients in therapy with proton pump inhibitors, previous gastric surgery, and/or known gastric neoplasia were excluded. At the beginning of gastroscopy, gastric juice was aspirated and analyzed by EndoFaster® in 15 seconds. Endoscopists were blinded to the report of EndoFaster®. Evaluation of gastric mucosa in HR-white light was firstly performed, then with HR-NBI allowing to perform targeted biopsies on areas suspected for intestinal metaplasia; otherwise, biopsies were performed according to the updated Sydney System protocol and sent for histopathological evaluation. RESULTS: Overall, 124 patients were included [64% F; 56 (18-85) years]. Corpus atrophic gastritis was present in 41.9% of patients. EndoFaster® showed an accuracy for corpus atrophic gastritis diagnosis, compared to histopathological evaluation as gold standard, of 87.1% and a sensitivity, specificity, PPV, and NPV of 78.8%, 93.1%, 89.1%, and 85.9%, respectively. pH showed a positive correlation with the severity score of atrophy (r = 0.67, 95% CI: 0.73-0.81, and p < 0.0001). EndoFaster® allowed to diagnose corpus atrophic gastritis in 3.7% of patients negative to NBI (corpus atrophic gastritis without intestinal metaplasia). CONCLUSION: EndoFaster® seems a promising tool to diagnose corpus atrophic gastritis. The evaluation of hypo-achlorhydria during gastroscopy can address bioptic sampling in corpus atrophic gastritis patients without intestinal metaplasia.

Second primary neoplasms in patients with lung and gastroenteropancreatic neuroendocrine neoplasms: Data from a retrospective multi-centric study.

BACKGROUND: Patients with sporadic neuroendocrine neoplasms may exhibit a higher risk of a second primary tumor than the general population. AIM: This study aimed to analyze the occurrence of second primary malignancies. METHODS: A retrospective cohort of 2757 patients with sporadic lung and gastro-entero-pancreatic neuroendocrine neoplasms, managed at eight Italian tertiary referral Centers, was included. RESULTS: Between 2000 and 2019, a second primary malignancy was observed in 271 (9.8%) neuroendocrine neoplasms patients with 32 developing a third tumor. There were 135 (49.8%) females and the median age was 64 years. The most frequent locations of the second tumors were breast (18.8%), prostate (12.5%), colon (9.6%), blood tumors (8.5%), and lung (7.7%). The second primary tumor was synchronous in 19.2% of cases, metachronous in 43.2%, and previous in 37.6%. As concerned the neuroendocrine neoplasms, the 5- and 10-year survival rates were 87.8% and 74.4%, respectively. PFS for patients with a second primary malignancy was shorter than for patients without a second primary malignancy. Death was mainly related to neuroendocrine neoplasms. CONCLUSION: In NEN patients the prevalence of second primary malignancies was not negligible, suggesting a possible neoplastic susceptibility. Overall survival was not affected by the occurrence of a second primary malignancy.

Upper and lower gastrointestinal causes of iron deficiency anemia in elderly compared with adult outpatients.

AIM: In the elderly, prevalence of bleeding- and/or iron malabsorption-related gastrointestinal (GI) causes of iron deficiency anemia (IDA) has not been addressed yet. The aim of this study was to assess the occurrence of malabsorptive diseases and bleeding lesions of the upper and lower GI tract in early (65-74 year-old) and late (over 75 year-old) elderly group compared with adult (50-64 year-old) outpatients. METHODS: The study enrolled 136 consecutive adult (N.=31), early (N.=48) and late elderly (N.=57) IDA outpatients who were referred to the Gastroenterology Department for IDA evaluation and underwent gastroscopy/histology and colonoscopy. RESULTS: Bleeding lesions were significantly less frequent in adult patients than in elderly patients (29% vs. 49.5%, P=0.0252). The most common bleeding lesions were large hiatal hernia (14.7%) and colon cancer (12.5%). Iron malabsorption diseases (Hp-related pangastritis, atrophic body gastritis and celiac disease) were more frequent in the adult group than in the early elderly group (80.6% vs. 56.2%, P=0.0367). In elderly patients, the observed prevalence of bleeding and iron malabsorption IDA causes was similar, whereas in adult patients iron malabsoptive diseases were more frequently detected (P<0.0001). The occurrence of concomitant IDA causes was not different among the three age-groups. CONCLUSION: In the early and late elderly, almost half of GI IDA causes are related to bleeding lesions which are more frequently observed respect to the adult patients. Iron malabsorption diseases affect almost 60% of early and late elderly groups. As for adult patients, an accurate upper and lower endoscopical/histological evaluation diagnoses IDA causes in the vast majority of the elderly outpatients.

Impact of the COVID-19 pandemic on Gastroenterology Divisions in Italy: A national survey.

BACKGROUND: In Italy, the spread of the COVID-19 pandemic has stressed the entire healthcare system and required a huge re-organization of many Divisions, including those of Gastroenterology. AIMS: to assess the impact of COVID-19 pandemic on Gastroenterology Divisions across Italy. METHODS: All members of the Italian Society of Gastroenterology (SIGE) were invited to answer a web-based survey. RESULTS: Data of 121 hospitals from all 20 Italian regions were analyzed. Overall, 10.7% Gastroenterology Divisions have been converted to Covid Units. Outpatients consultations, endoscopic and ultrasound procedures were limited to urgencies and oncology indications in 85.1%, 96.2% and 72.2% of Units, respectively, and 46.7% of them suspended the screening for colorectal cancer. Moreover, 72.2% of the staff received a training for use of personal protective equipment, although 45.5% did not have sufficient devices for adequate replacement. Overall, 132 healthcare workers in 41 Gastroenterology Divisions were found to be infected. CONCLUSION: This is the first study to evaluate, at a country level, the impact of COVID-19 outbreak on Gastroenterology Divisions. Substantial changes of practice and reduction of procedures have been recorded in the entire country. The long-term impact of such modifications is difficult to estimate but potentially very risky for many digestive diseases.

Cameron lesions: A still overlooked diagnosis. Case report and systematic review of literature.

Cameron lesions are erosive-ulcerative alterations of gastric mucosa occurring in patients with large hiatal hernia, potentially causing gastrointestinal bleeding and iron deficiency anaemia. Diagnosis may be challenging, and not infrequently erosions are overlooked at endoscopy, so that repeated and unnecessary diagnostic procedures are performed, particularly in those patients with chronic anaemia. We described two peculiar cases of patients with iron deficiency anaemia in whom Cameron lesions were either overlooked or misinterpreted. By reviewing data of 22publications reporting endoscopic and clinical data of 140patients, we noted a large prevalence of females (75%). The most frequent presenting symptoms were anaemia (62%) and overt gastrointestinal bleeding (36%). Noteworthy, as many as 69% of patients underwent one or more previous upper endoscopy before diagnosis of Cameron lesion was achieved. Patients were mainly treated with proton pump inhibitor (PPI) therapy and iron supplementation. Moreover, endoscopic haemostasis was performed in 10% of case, blood transfusion was required in one third of cases, and a similar quote of patients underwent a surgical approach for hiatal hernia repair. The observation that as many as 60% patients were already receiving standard PPI therapy when diagnosis was performed would suggest that either long-term treatment with adequate dose PPI or surgical approach for hiatal hernia repair is required. In conclusion, Cameron lesion is still an overlooked diagnosis in patients with iron deficiency anaemia in whom a 5-9.2% prevalence has been reported.

Corpus-predominant gastritis as a risk factor for false-negative 13C-urea breath test results.

BACKGROUND: Urea breath test sensitivity seems affected by increased intragastric acidity during therapy with antisecretory drugs. Intragastric pH is increased in patients with corpus gastritis with/without atrophy. AIM: To test the hypothesis that urea breath test results may also be affected by this gastritis phenotype. METHODS: 123 untreated patients underwent gastroscopy plus biopsies and intragastric pH measurement. The study included 82 endoscopically proven Helicobacter pylori-positive patients who were offered urea breath test with an acidic meal. Histological findings, urea breath test results and intragastric pH were compared in 66 of the subjects. RESULTS: 21 of 66 (31.8%) patients had a false-negative urea breath test. In these patients corpus-predominant gastritis (85.7% vs. 37.7%; P = 0.0004) and fundic atrophy (66.6% vs. 17.7%; P = 0.0001) were more frequent than in patients with true-positive urea breath test. Intragastric pH was higher in false-negative patients (mean 6.3 vs. 4.4; P = 0.001). In a multivariate analysis, the only risk factor for a false-negative urea breath test was the presence of corpus-predominant gastritis (OR = 5.6; 95% CI: 1.1-27). There was a negative correlation between the intragastric pH and the delta over baseline values (r = -0.378; P = 0.0023). CONCLUSIONS: Our results support the hypothesis that the pattern of gastritis can affect the sensitivity of urea breath test, and suggest that patients with corpus-predominant gastritis have a high risk of false-negative urea breath test results.

Unawareness of gastrointestinal symptomatology in adult coeliac patients with unexplained iron-deficiency anaemia presentation.

BACKGROUND: Most adults with coeliac disease have a subclinical form of the disease and iron-deficiency anaemia may be the sole presenting symptom. AIM: To evaluate demographic, clinical and biochemical characteristics of adult coeliac disease patients presenting with iron-deficiency anaemia. PATIENTS: A total of 108 iron-deficiency anaemia patients in whom coeliac disease has been diagnosed were studied. As a control group 108 non-coeliac iron-deficiency anaemia patients, comparable for sex and age, were studied. RESULTS: Of the 108 coeliac disease patients, 95 (88%) were female (mean age 34 years, range 19-72) and 13 (12%) were male (mean age 33 years, range 15-65). The median duration of iron-deficiency anaemia before diagnosis was 66 months in coeliac disease patients and 14 months in the iron-deficiency anaemia control group (P = 0.0001). The occurrence of at least one gastrointestinal symptom, not spontaneously reported, was observed in 92 (85%) patients with coeliac disease and in 67 (62%) patients in the control group (P = 0.001). The concomitant presence of diarrhoea, abdominal pain and abdominal bloating was detected in 14% patients with coeliac disease with respect to 3% in the control group (P = 0.005). CONCLUSIONS: The vast majority of coeliac disease patients with iron-deficiency anaemia presentation were unaware of the gastrointestinal symptoms and this relationship is useful for diet compliance.

Effects of recent, short-term hyperglycemia on responses to hypoglycemia in humans. Relevance to the pathogenesis of hypoglycemia unawareness and hyperglycemia-induced insulin resistance.

A single episode of recent hypoglycemia increases, whereas long-term hyperglycemia decreases, the glycemic thresholds of responses of counterregulatory hormone and symptoms to subsequent hypoglycemia in humans. To assess whether short-term, antecedent hyperglycemia exerts effects opposite to those observed after acute hypoglycemia, seven normal, nondiabetic subjects and eight insulin-dependent diabetes mellitus (IDDM) patients were studied during hyperinsulinemic-hypoglycemic clamp (sequential, 90-min plateaus of plasma glucose [PG] of 4.3, 3.7, 3.0, and 2.4 mmol/l). Nondiabetic subjects were studied the morning after either 6-h clamped hyperglycemia (PG approximately 13.5 mmol/l) or euglycemia (PG approximately 5 mmol/l) between 1600 and 2200 the previous day (glucose and insulin infused on both occasions), as well as after nocturnal hyperglycemia (PG approximately 13.5 mmol/l) or euglycemia between 2300 and 0500. The IDDM patients were studied after 15 h of euglycemia or hyperglycemia (approximately 17 mmol/l) but identical hyperinsulinemia (approximately 225 pmol/l) between 1600 and 0700. Neither PG thresholds of counterregulatory hormone, symptoms, onset of cognitive dysfunction to hypoglycemia, nor maximal responses were affected by antecedent, short-term hyperglycemia in normal nondiabetic subjects and IDDM patients (NS). However, the rate of glucose infusion required to maintain hypoglycemic plateaus during hypoglycemia was lower after hyperglycemia (nondiabetic subjects 31.2 +/- 3.4 vs. 36.7 +/- 4 mumol.kg-1.min-1, IDDM patients 33 +/- 3.1 vs. 42.5 +/- 3.9 mumol.kg-1.min-1; P < 0.05) indicating greater insulin resistance induced by antecedent hyperglycemia. In conclusion, in contrast to acute hypoglycemia and long-term hyperglycemia, recent, short-term hyperglycemia does not affect physiological responses to hypoglycemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Meticulous prevention of hypoglycemia normalizes the glycemic thresholds and magnitude of most of neuroendocrine responses to, symptoms of, and cognitive function during hypoglycemia in intensively treated patients with short-term IDDM.

To test the hypothesis that hypoglycemia unawareness is largely secondary to recurrent therapeutic hypoglycemia in IDDM, we assessed neuroendocrine and symptom responses and cognitive function in 8 patients with short-term IDDM (7 yr) and hypoglycemia unawareness. Patients were assessed during a stepped hypoglycemic clamp, before and after 2 wk and 3 mo of meticulous prevention of hypoglycemia, which resulted in a decreased frequency of hypoglycemia (0.49 +/- 0.05 to 0.045 +/- 0.03 episodes/patient-day) and an increase in HbA1c (5.8 +/- 0.3 to 6.9 +/- 0.2%) (P < 0.05). We also studied 12 nondiabetic volunteer subjects. At baseline, lower than normal symptom and neuroendocrine responses occurred at lower than normal plasma glucose, and cognitive function deteriorated only marginally during hypoglycemia. After 2 wk of hypoglycemia prevention, the magnitude of symptom and neuroendocrine responses (with the exception of glucagon and norepinephrine) nearly normalized, and cognitive function deteriorated at the same glycemic threshold and to the same extent as in nondiabetic volunteer subjects. At 3 mo, the glycemic thresholds of symptom and neuroendocrine responses normalized, and surprisingly, some of the responses of glucagon recovered. We concluded that hypoglycemia unawareness in IDDM is largely reversible and that intensive insulin therapy and a program of intensive education may substantially prevent hypoglycemia and at the same time maintain the glycemic targets of intensive insulin therapy, at least in patients with IDDM of short duration.