Familial Mediterranean Fever (FMF) is a rare autosomal recessive autoinflammatory disorder involving the innate immunity and affecting almost exclusively populations with Mediterranean origin. ...Clinical features include recurrent episodes of fever, leukocitosis, serositis (peritonitis or pleuritis, arthritis), myalgia or erysipelas-like skin lesions, lasting 12-72 hrs. The MEFV gene mutations on chromosome 16p13.3 encodes the abnormal pyrin (marenostrin), a protein expressed in granulocytes, monocytes, serosal and synovial fibroblasts and involved in the activation of caspase-1 and the processing and release of active pro-inflammatory IL-1β. Since the first report in 1972, maintenance therapy with colchicine, a tricyclic neutral alkaloid, remains the mainstay of treatment in symptomatic FMF patients since it reduces the disease activity and prevents the development of secondary amyloidosis and renal damage. Adjunctive symptomatic therapy to colchicine includes nonsteroideal antinflammatory drugs and corticosteroids. In a small group of colchicine-intolerant or colchicine-resistant FMF patients, alternative treatments must be considered. Evolving experiences have focussed on the potential effectiveness of biologic agents working as TNF-α inhibitors (etanercept, infliximab), IL-1 trap (Rilonacept), IL-1 inhibitors (Anakinra, Canakinumab) and IL-6 receptor antibody (Tocilizumab). Interferon-α and thalidomide have also been employed in FMF patients. Still, clinical trials are mainly uncontrolled and restricted to few cases, thus requiring definitive conclusions. Old, and new treatments are discussed in the rare FMF disease, with the concept that any ideal treatment has to stand the test of time.
Abstract Background A growing body of evidence has suggested that metformin potentially reduces the risk of cancer. Objective We performed a meta-analysis of available studies to better define the ...effect of metformin on colon neoplasia (cancer and polyps) in patients with type 2 diabetes. Methods Medical literature searches for human studies were performed through December 2015, using suitable keywords. Pooled estimates were obtained using fixed or random-effects models. Heterogeneity between studies was evaluated with the Cochran Q test whereas the likelihood of publication bias was assessed by constructing funnel plots. Their symmetry was estimated by the Begg and Mazumdar adjusted rank correlation test and by the Egger's regression test. In addition subgroup and sensitivity analyses were performed. Results A total number of 709,980 patients, with type 2 diabetes, were included in 17 studies eligible for meta-analysis 1 RCT and 16 observational studies (13 cohort and 3 case–controls). The risk of colon neoplasia was significantly lower among metformin users than controls (non-metformin users) pooled RRs (95% CI) = 0.75 (0.65–0.87), test for overall effect Z = − 3.95, p < 0.001. This observation applied separately for colon cancer 0.79 (0.69–0.91), Z = − 3.34, p < 0.001 and for colon polyps 0.58 (0.42–0.80), Z = − 3.30, p < 0.001. Conclusion This meta-analysis shows that the use of metformin in patients with type 2 diabetes is associated with significantly lower risk of colon neoplasia.
The majority of gallstone patients remain asymptomatic; however, interest toward the gallstone disease is continuing because of the high worldwide prevalence and management costs and the development ...of gallstone symptoms and complications. For cholesterol gallstone disease, moreover, a strong link exists between this disease and highly prevalent metabolic disorders such as obesity, dyslipidemia, type 2 diabetes, hyperinsulinemia, hypertriglyceridemia and the metabolic syndrome. Information on the natural history as well as the diagnostic, surgical (mainly laparoscopic cholecystectomy) and medical tools available to facilitate adequate management of cholelithiasis and its complications are, therefore, crucial to prevent the negative outcomes of gallstone disease. Moreover, some risk factors for gallstone disease are modifiable and some preventive strategies have become necessary to reduce the onset and the severity of complications.
Familial Mediterranean fever (FMF), an inherited autosomal recessive disorder, is characterized by sporadic, paroxysmal attacks of fever and serosal inflammation, lasting 1–3 days. Patients may ...develop renal amyloidosis, arthritis, serositis, and skin and oral lesions. Diagnosis is based on clinical features, response to treatment with colchicine, and genetic analysis. Colchicine prevents attacks and renal amyloidosis, in addition to reversing proteinuria. Nonresponders may receive novel therapy, including interleukin (IL)‐1 receptor antagonists and IL‐1 decoy receptor. Recently, new options have been considered.
Clinical Pharmacology & Therapeutics (2013); 95 1, 89–97 advance online publication 2 October 2013. doi:10.1038/clpt.2013.148
Breath tests represent a valid and non-invasive diagnostic tool in many gastroenterological conditions. The rationale of hydrogen-breath tests is based on the concept that part of the gas produced by ...colonic bacterial fermentation diffuses into the blood and is excreted by breath, where it can be quantified easily. There are many differences in the methodology, and the tests are increasingly popular.
The Rome Consensus Conference was convened to offer recommendations for clinical practice about the indications and methods of H2-breath testing in gastrointestinal diseases.
Experts were selected on the basis of a proven knowledge/expertise in H2-breath testing and divided into Working Groups (methodology; sugar malabsorption; small intestine bacterial overgrowth; oro-coecal transit time and other gas-related syndromes). They performed a systematic review of the literature, and then formulated statements on the basis of the scientific evidence, which were debated and voted by a multidisciplinary Jury. Recommendations were then modified on the basis of the decisions of the Jury by the members of the Expert Group.
The final statements, graded according to the level of evidence and strength of recommendation, are presented in this document; they identify the indications for the use of H2-breath testing in the clinical practice and methods to be used for performing the tests.
Summary
Background
Placebo‐controlled studies in maintaining remission of symptomatic uncomplicated diverticular disease (SUDD) of the colon are lacking.
Aim
To assess the effectiveness of mesalazine ...and/or probiotics in maintaining remission in SUDD.
Methods
A multicentre, double‐blind, placebo‐controlled study was conducted. Two hundred and ten patients were randomly enrolled in a double‐blind fashion in four groups: Group M (active mesalazine 1.6 g/day plus Lactobacillus casei subsp. DG placebo), Group L (active Lactobacillus casei subsp. DG 24 billion/day plus mesalazine placebo), Group LM (active Lactobacillus casei subsp. DG 24 billion/day plus active mesalazine), Group P (Lactobacillus casei subsp. DG placebo plus mesalazine placebo). Patients received treatment for 10 days/month for 12 months. Recurrence of SUDD was defined as the reappearance of abdominal pain during follow‐up, scored as ≥5 (0: best; 10: worst) for at least 24 consecutive hours.
Results
Recurrence of SUDD occurred in no (0%) patient in group LM, in 7 (13.7%) patients in group M, in 8 (14.5%) patients in group L and in 23 (46.0%) patients in group P (LM group vs. M group, P = 0.015; LM group vs. L group, P = 0.011; LM group vs. P group, P = 0.000; M group vs. P group, P = 0.000; L group vs. P group, P = 0.000). Acute diverticulitis occurred in six group P cases and in one group L case (P = 0.003).
Conclusion
Both cyclic mesalazine and Lactobacillus casei subsp. DG treatments, particularly when given in combination, appear to be better than placebo for maintaining remission of symptomatic uncomplicated diverticular disease. (ClinicalTrials.gov: NCT01534754).
Patients with irritable bowel syndrome (IBS) often associate their symptoms to certain foods. In congenital sucrase-isomaltase deficiency (CSID), recessive mutations in the SI gene (coding for the ...disaccharidase digesting sucrose and 60% of dietary starch)1 cause clinical features of IBS through colonic accumulation of undigested carbohydrates, triggering bowel symptoms.2 Hence, in a previous study,3 we hypothesized that CSID variants reducing SI enzymatic activity may contribute to development of IBS symptoms. We detected association with increased risk of IBS for 4 rare loss-of-function variants typically found in (homozygous) CSID patients, because carriers (heterozygous) of these rare variants were more common in patients than in controls.1,4 Through a 2-step computational and experimental strategy, the present study aimed to determine whether other (dys-)functional SI variants are associated with risk of IBS in addition to known CSID mutations. We first aimed to identify all SI rare pathogenic variants (SI-RPVs) on the basis of integrated Mendelian Clinically Applicable Pathogenicity (M-CAP) and Combined Annotation Dependent Depletion (CADD) predictive (clinically relevant) scores; next, we inspected genotype data currently available for 2207 IBS patients from a large ongoing project to compare SI-RPV case frequencies with ethnically matched population frequencies from the Exome Aggregation Consortium (ExAC).
Purpose
Aims of this study were to evaluate the agreement between the short and long versions of the International Physical Activity Questionnaire (IPAQ: Italian versions), their reproducibility ...(agreement and reliability) and construct validity (relative to pedometry) in a clinical population.
Methods
Ninety patients affected by obesity (
N
= 39), type 2 diabetes mellitus (
N
= 26) or both (
N
= 25) were recruited. They were asked to maintain their usual physical activity habits during two consecutive weeks and to fill the questionnaires twice (at the end of each week). They were also asked to wear a pedometer for 7 consecutive days after the first administration of the questionnaires.
Results
We found acceptable agreement between the IPAQ short and long versions (ICC
2,1
values were 0.81 and 0.77 for the 1st and 2nd administration), uncertain reproducibility (acceptable reliability but poor agreement) and inadequate validity relative to pedometry (the correlation coefficients between all IPAQ scores and daily steps were <0.50) for both IPAQ short and IPAQ long.
Conclusions
The IPAQ use may be justified in daily clinical practice and in clinical research (e.g., in cross-sectional studies) for a simple and rapid evaluation of the physical activity level for discriminative purposes. However, the use of these questionnaires does not appear suitable for prospective interventional studies in which the level of physical activity of the recruited patients has to be assessed over time.
We previously reported that statins improve the symptoms of X‐linked nephrogenic diabetes insipidus (X‐NDI) in animal models. The aim of this study was to verify whether the pleiotropic effect of ...statins on AQP2 trafficking and kidney‐concentrating ability, observed in rodents, was attainable in humans at therapeutic doses. We enrolled 24 naïve hypercholesterolemic patients and measured urine excretion of AQP2 (uAQP2) at baseline and during 12 weeks of treatment with simvastatin 20 mg/day. Simvastatin induced a rapid and significant increase of uAQP2, reduced the 24‐hour diuresis, and increased urine osmolality. These effects were also maintained in patients chronically treated with statins for at least 1 year. This study strongly suggests that statins may effectively enhance the efficacy of current pharmacological treatment of patients with urine‐concentrating defects caused by defective AQP2 plasma membrane trafficking, like X‐NDI.
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