Olmesartan-associated enteropathy: new insights on the natural history? Report of two cases.

INTRODUCTION: The association between olmesartan and an enteropathy histologically indistinguishable from untreated celiac disease has recently been described. However, pathogenetic mechanisms leading to villous atrophy, prevalence, natural history and genetic background of this condition have not yet been defined. PATIENTS: We describe here two cases of olmesartan-associated enteropathy and discuss some aspects of the natural history of this condition. RESULTS: In both patients, an infectious episode seems to have triggered the severe malabsorption syndrome which led them to hospitalization. High titer positive antinuclear antibodies with homogeneous pattern were found. CONCLUSIONS: Our reports add to a growing body of evidence suggesting that olmesartan-associated enteropathy should be considered in the presence of villous atrophy and negative celiac serology and in the diagnostic algorithm of non-responsive celiac disease.

Effect of Anakinra on Recurrent Pericarditis Among Patients With Colchicine Resistance and Corticosteroid Dependence: The AIRTRIP Randomized Clinical Trial.

Importance: Anakinra, an interleukin 1ß recombinant receptor antagonist, may have potential to treat colchicine-resistant and corticosteroid-dependent recurrent pericarditis. Objective: To determine the efficacy of anakinra for colchicine-resistant and corticosteroid-dependent recurrent pericarditis. Design, Setting, and Participants: The Anakinra-Treatment of Recurrent Idiopathic Pericarditis (AIRTRIP) double-blind, placebo-controlled, randomized withdrawal trial (open label with anakinra followed by a double-blind withdrawal step with anakinra or placebo until recurrent pericarditis occurred) conducted among 21 consecutive patients enrolled at 3 Italian referral centers between June and November 2014 (end of follow-up, October 2015). Included patients had recurrent pericarditis (with ≥3 previous recurrences), elevation of C-reactive protein, colchicine resistance, and corticosteroid dependence. Interventions: Anakinra was administered at 2 mg/kg per day, up to 100 mg, for 2 months, then patients who responded with resolution of pericarditis were randomized to continue anakinra (n = 11) or switch to placebo (n = 10) for 6 months or until a pericarditis recurrence. Main Outcomes and Measures: The primary outcomes were recurrent pericarditis and time to recurrence after randomization. Results: Eleven patients (7 female) randomized to anakinra had a mean age of 46.5 (SD, 16.3) years; 10 patients (7 female) randomized to placebo had a mean age of 44 (SD, 12.5) years. All patients were followed up for 12 months. Median follow-up was 14 (range, 12-17) months. Recurrent pericarditis occurred in 9 of 10 patients (90%; incidence rate, 2.06% of patients per year) assigned to placebo and 2 of 11 patients (18.2%; incidence rate, 0.11% of patients per year) assigned to anakinra, for an incidence rate difference of -1.95% (95% CI, -3.3% to -0.6%). Median flare-free survival (time to flare) was 72 (interquartile range, 64-150) days after randomization in the placebo group and was not reached in the anakinra group (P <.001). During anakinra treatment, 20 of 21 patients (95.2%) experienced transient local skin reactions: 1 (4.8%) herpes zoster, 3 (14.3%) transaminase elevation, and 1 (4.8%) ischemic optic neuropathy. No patient permanently discontinued the active drug. No adverse events occurred during placebo treatment. Conclusion and Relevance: In this preliminary study of patients with recurrent pericarditis with colchicine resistance and corticosteroid dependence, the use of anakinra compared with placebo reduced the risk of recurrence over a median of 14 months. Larger studies are needed to replicate these findings as well as to assess safety and longer-term efficacy. Trial Registration: clinicaltrials.gov Identifier: NCT02219828.

Efficacy and safety of colchicine for treatment of multiple recurrences of pericarditis (CORP-2): a multicentre, double-blind, placebo-controlled, randomised trial.

BACKGROUND: Colchicine is effective for the treatment of acute pericarditis and first recurrences. However, conclusive data are lacking for the efficacy and safety of colchicine for treatment of multiple recurrences of pericarditis. METHODS: We did this multicentre, double-blind trial at four general hospitals in northern Italy. Adult patients with multiple recurrences of pericarditis (≥two) were randomly assigned (1:1) to placebo or colchicine (0·5 mg twice daily for 6 months for patients weighing more than 70 kg or 0·5 mg once daily for patients weighing 70 kg or less) in addition to conventional anti-inflammatory treatment with aspirin, ibuprofen, or indometacin. Permuted block randomisation (size four) was done with a central computer-based automated sequence. Patients and all investigators were masked to treatment allocation. The primary outcome was recurrent pericarditis in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT00235079. FINDINGS: 240 patients were enrolled and 120 were assigned to each group. The proportion of patients who had recurrent pericarditis was 26 (21·6%) of 120 in the colchicine group and 51 (42·5%) of 120 in the placebo group (relative risk 0·49; 95% CI 0·24-0·65; p=0·0009; number needed to treat 5). Adverse effects and discontinuation of study drug occurred in much the same proportions in each group. The most common adverse events were gastrointestinal intolerance (nine patients in the colchicine group vs nine in the placebo group) and hepatotoxicity (three vs one). No serious adverse events were reported. INTERPRETATION: Colchicine added to conventional anti-inflammatory treatment significantly reduced the rate of subsequent recurrences of pericarditis in patients with multiple recurrences. Taken together with results from other randomised controlled trials, these findings suggest that colchicine should be probably regarded as a first-line treatment for either acute or recurrent pericarditis in the absence of contraindications or specific indications. FUNDING: Azienda Sanitaria 3 of Torino (now ASLTO2).

Good prognosis for pericarditis with and without myocardial involvement: results from a multicenter, prospective cohort study.

BACKGROUND: The natural history of myopericarditis/perimyocarditis is poorly known, and recently published studies have presented contrasting data on their outcomes. The aim of the present article is to assess the prognosis of myopericarditis/perimyocarditis in a multicenter, prospective cohort study. METHODS AND RESULTS: A total of 486 patients (median age, 39 years; range, 18-83 years; 300 men) with acute pericarditis or a myopericardial inflammatory syndrome (myopericarditis/perimyocarditis; 85% idiopathic, 11% connective tissue disease or inflammatory bowel disease, 5% infective) were prospectively evaluated from January 2007 to December 2011. The diagnosis of acute pericarditis was based on the presence of 2 of 4 clinical criteria (chest pain, pericardial rubs, widespread ST-segment elevation or PR depression, and new or worsening pericardial effusion). Myopericardial inflammatory involvement was suspected with atypical ECG changes for pericarditis, arrhythmias, and cardiac troponin elevation or new or worsening ventricular dysfunction on echocardiography and confirmed by cardiac magnetic resonance. After a median follow-up of 36 months, normalization of left ventricular function was achieved in >90% of patients with myopericarditis/perimyocarditis. No deaths were recorded, as well as evolution to heart failure or symptomatic left ventricular dysfunction. Recurrences (mainly as recurrent pericarditis) were the most common complication during follow-up and were recorded more frequently in patients with acute pericarditis (32%) than in those with myopericarditis (11%) or perimyocarditis (12%; P<0.001). Troponin elevation was not associated with an increase in complications. CONCLUSIONS: The outcome of myopericardial inflammatory syndromes is good. Unlike acute coronary syndromes, troponin elevation is not a negative prognostic marker in this setting.

Colchicine for prevention of postpericardiotomy syndrome and postoperative atrial fibrillation: the COPPS-2 randomized clinical trial.

IMPORTANCE: Postpericardiotomy syndrome, postoperative atrial fibrillation (AF), and postoperative effusions may be responsible for increased morbidity and health care costs after cardiac surgery. Postoperative use of colchicine prevented these complications in a single trial. OBJECTIVE: To determine the efficacy and safety of perioperative use of oral colchicine in reducing postpericardiotomy syndrome, postoperative AF, and postoperative pericardial or pleural effusions. DESIGN, SETTING, AND PARTICIPANTS: Investigator-initiated, double-blind, placebo-controlled, randomized clinical trial among 360 consecutive candidates for cardiac surgery enrolled in 11 Italian centers between March 2012 and March 2014. At enrollment, mean age of the trial participants was 67.5 years (SD, 10.6 years), 69% were men, and 36% had planned valvular surgery. Main exclusion criteria were absence of sinus rhythm at enrollment, cardiac transplantation, and contraindications to colchicine. INTERVENTIONS: Patients were randomized to receive placebo (n=180) or colchicine (0.5 mg twice daily in patients ≥70 kg or 0.5 mg once daily in patients <70 kg; n=180) starting between 48 and 72 hours before surgery and continued for 1 month after surgery. MAIN OUTCOMES AND MEASURES: Occurrence of postpericardiotomy syndrome within 3 months; main secondary study end points were postoperative AF and pericardial or pleural effusion. RESULTS: The primary end point of postpericardiotomy syndrome occurred in 35 patients (19.4%) assigned to colchicine and in 53 (29.4%) assigned to placebo (absolute difference, 10.0%; 95% CI, 1.1%-18.7%; number needed to treat = 10). There were no significant differences between the colchicine and placebo groups for the secondary end points of postoperative AF (colchicine, 61 patients [33.9%]; placebo, 75 patients [41.7%]; absolute difference, 7.8%; 95% CI, -2.2% to 17.6%) or postoperative pericardial/pleural effusion (colchicine, 103 patients [57.2%]; placebo, 106 patients [58.9%]; absolute difference, 1.7%; 95% CI, -8.5% to 11.7%), although there was a reduction in postoperative AF in the prespecified on-treatment analysis (placebo, 61/148 patients [41.2%]; colchicine, 38/141 patients [27.0%]; absolute difference, 14.2%; 95% CI, 3.3%-24.7%). Adverse events occurred in 21 patients (11.7%) in the placebo group vs 36 (20.0%) in the colchicine group (absolute difference, 8.3%; 95% CI; 0.76%-15.9%; number needed to harm = 12), but discontinuation rates were similar. No serious adverse events were observed. CONCLUSIONS AND RELEVANCE: Among patients undergoing cardiac surgery, perioperative use of colchicine compared with placebo reduced the incidence of postpericardiotomy syndrome but not of postoperative AF or postoperative pericardial/pleural effusion. The increased risk of gastrointestinal adverse effects reduced the potential benefits of colchicine in this setting. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01552187.

Post-cardiac injury syndrome and pericardial effusion recurrence after pericardial effusion drainage in chronic idiopathic pericardial effusion.

INTRODUCTION: The management of even large pericardial effusions in asymptomatic patients is still a matter of debate. Aim of the present study is to explore, in a multicenter setting, the rate of post-cardiac injury syndromes (PCIS) and pericardial effusion recurrence after pericardial effusion drainage procedure. MATERIAL AND METHODS: This is a multicenter international retrospective study including a consecutive cohort of patients diagnosed with large, chronic and idiopathic pericardial effusions, prospectively evaluated from January 2003 to December 2021 who underwent a clinically indicated pericardial drainage procedure. Two separate end-points were recorded: 1) recurrence of pericardial effusion after drainage without any sign of pericardial inflammation 2) occurrence of PCIS, defined as the new onset of pericarditis 1 to 6 weeks after pericardial intervention. RESULTS: 124 patients were enrolled (50 % female, mean age 64 years old). A mean follow-up of 29.6 ± 25.6 months was obtained in 110 patients (88 %). 110 patients were treated with pericardiocentesis (89 %), 25 with pleuro-pericardial windows (20 %), and 1 with pericardiectomy (1 %). PCIS occurred in 21 out of 124 patients followed for at least 6 weeks (16.9%). Recurrence of pericardial effusion after drainage without any sign of pericardial inflammation occurred in 68 out of 110 patients at a longer follow-up (61.8 %). At multivariate analysis only inflammatory cells in pericardial fluid was associated with PCIS and pericardiocentesis with pericardial effusion recurrency. CONCLUSION: Our data support the need of caution with the use of pericardiocentesis in asymptomatic patients with large pericardial effusion as it is often associated with pericardial effusion recurrence. Of interest the presence of inflammatory cells in the pericardial fluid is associated with PCIS after pericardial drainage procedures.

Leptin, adiponectin, resistin, visfatin serum levels and idiopathic recurrent pericarditis: biomarkers of disease activity? A preliminary report.

OBJECTIVES: Idiopathic recurrent acute pericarditis (IRAP) represents the most troublesome complication of acute pericarditis and is an autoimmune process. White adipose tissue produces more than 50 adipokines that participate in inflammation and autoimmunity. This study investigated whether serum leptin, resistin, visfatin and adiponectin are increased in IRAP versus healthy controls and if their levels correlate with parameters of disease activity. METHODS: Serum leptin, resistin, visfatin and adiponectin levels were assayed by enzyme-linked immunosorbent assay in 14 IRAP patients during recurrences (group 1), in 23 IRAP patients during symptom-free intervals (group 2) and in 18 healthy controls (group 3). Assessment parameters included demographic characteristics of patients and controls, clinical characteristics of patients and markers of inflammation. Comparisons between groups as well as reciprocal comparisons were evaluated. RESULTS: Group 1 showed serum leptin (p<0.008), visfatin (p<0.002), and adiponectin (p<0.04) significantly higher than group 2 and control group, whereas resistin serum levels did not significantly differ (p=0.69). Among IRAP patients, serum leptin significantly correlated with serum amyloid A (SAA) levels (rs=0.43, r2= 0.27, p<0.02). Other than this correlation, none of the considered adipokines significantly correlated with the other considered variables in univariate analysis. CONCLUSIONS: Leptin, adiponectin and visfatin are increased in IRAP patients versus healthy controls. Our data suggest that these adipokines might be involved in IRAP pathogenesis and that a possible increased cardiovascular risk in these patients, through an early onset atherosclerosis, should be kept in mind. SAA might be a link between IRAP and increased cardiovascular diseases.

Prevalence of C-reactive protein elevation and time course of normalization in acute pericarditis: implications for the diagnosis, therapy, and prognosis of pericarditis.

BACKGROUND: The role of inflammatory markers is not well defined for either diagnosis or treatment of pericarditis. The aim of this study is to prospectively evaluate the frequency of high-sensitivity C-reactive protein (hs-CRP) elevation in patients with acute pericarditis, its time course of normalization, and the possible importance for diagnosis, therapy, and prognosis. METHODS AND RESULTS: Two hundred consecutive patients with viral or idiopathic acute pericarditis (mean age, 53 ± 15.5 years; 103 men) were studied from August 2005 to August 2007 in 2 Italian referral centers. Hs-CRP was determined at presentation and then every week until normalization. Hs-CRP elevation was recorded in 156 of 200 cases (78%) at presentation. Recognized causes of a negative hs-CRP at presentation were early assessment in 15 of 44 cases (34%) and previous anti-inflammatory therapies in 22 of 44 cases (50%). Hs-CRP normalization was achieved with the following time course: 120 of 200 (60%) at week 1, 170 of 200 (85%) at week 2, 190 of 200 (95%) at week 3, and all cases (100%) at week 4. In multivariable analysis, incomplete response to empirical anti-inflammatory therapy at week 1 (hazard ratio, 2.98; 95% confidence interval, 1.80 to 4.94; P < 0.001), corticosteroid therapy (hazard ratio, 2.80; 95% confidence interval, 1.59 to 4.95; P < 0.001), and the presence of elevated hs-CRP at week 1 (hazard ratio, 2.36; 95% confidence interval, 1.32 to 4.21; P = 0.004) were independent risk factors for recurrence. CONCLUSIONS: Hs-CRP is elevated at the initial presentation in ≈ 3 of 4 cases of acute pericarditis, identifies patients at higher risk of recurrence, and could be used to monitor disease activity and select appropriate therapy length.

Risk of constrictive pericarditis after acute pericarditis.

BACKGROUND: Constrictive pericarditis (CP) is considered a rare, dreaded possible complication of acute pericarditis. Nevertheless, there is a lack of prospective studies that have evaluated the specific risk according to different etiologies. The aim of this study is to evaluate the risk of CP after acute pericarditis in a prospective cohort study with long-term follow-up. METHODS AND RESULTS: From January 2000 to December 2008, 500 consecutive cases with a first episode of acute pericarditis (age, 51±16 years; 270 men) were prospectively studied to evaluate the evolution toward CP. Etiologies were viral/idiopathic in 416 cases (83.2%), connective tissue disease/pericardial injury syndromes in 36 cases (7.2%), neoplastic pericarditis in 25 cases (5.0%), tuberculosis in 20 cases (4.0%), and purulent in 3 cases (0.6%). During a median follow-up of 72 months (range, 24 to 120 months), CP developed in 9 of 500 patients (1.8%): 2 of 416 patients with idiopathic/viral pericarditis (0.48%) versus 7 of 84 patients with a nonviral/nonidiopathic etiology (8.3%). The incidence rate of CP was 0.76 cases per 1000 person-years for idiopathic/viral pericarditis, 4.40 cases per 1000 person-years for connective tissue disease/pericardial injury syndrome, 6.33 cases per 1000 person-years for neoplastic pericarditis, 31.65 cases for 1000 person-years for tuberculous pericarditis, and 52.74 cases per 1000 person-years for purulent pericarditis. CONCLUSIONS: CP is a relatively rare complication of viral or idiopathic acute pericarditis (<0.5%) but, in contrast, is relatively frequent for specific etiologies, especially bacterial.

Three-month mortality in permanently bedridden medical non-oncologic patients. The BECLAP study (permanently BEdridden, creatinine CLearance, albumin, previous hospital admissions study).

OBJECTIVE: To predict the 3-months mortality in permanently bedridden medical non-oncologic inpatients. PATIENTS AND METHODS: 2788 consecutive patients admitted in 5 Italian Internal Medicine units from January 2016 through January 2017 were prospectively screened; 644 oncologic patients were excluded; 2144 non-oncologic patients (1021 female) were followed-up for mortality for 6 months. Main outcome was 3-months mortality in permanently bedridden inpatients with at least 2 of: creatinine clearance <35 ml/min; albumin < 2.5 g/dl; at least 2 hospital admissions in the previous 6 months. Advanced dementia and dysphagia were also recorded. RESULTS: Mean age of the 2144 patients was 73.9 (SD, 14.9) years; 374 (17%) were permanently bedridden, 435 (20%) had a creatinine clearance <35 ml/min, 217 (10%) albumin <2,5 g/dl, 112 (5%) at least 2 hospital admissions in the previous 6 months. Seventy-seven (4%) patients were permanently bedridden with at least 2 of the above mentioned items, and 48 of them died within 3 months (62%) (p < 0.001;95% CI 51-73%). Regression coefficients of the variables associated with 3-months mortality in multivariate analysis in 998 patients of unit 1 (training cohort) were used to create a simple score, which was validated in the 1146 patients of the other units (validation cohort) and performed well in predicting the 3-months mortality (https://www.ejcrim.com/beclap/). CONCLUSIONS: Approximately two out of three non-oncologic medical patients permanently bedridden having 2 of the abovementioned items are dead 3 months after index admission; a simple score including bedridden status, creatinine clearance, albumin, dysphagia, age and sex may help discuss management priorities.

Corticosteroids for recurrent pericarditis: high versus low doses: a nonrandomized observation.

BACKGROUND: Corticosteroid use is widespread in recurrent pericarditis, even if rarely indicated, and high doses (eg, prednisone 1.0 to 1.5 mg . kg(-1) . d(-1)) are generally recommended, although only weak evidence supports their use with possible severe side effects. The aim of this work was to compare side effects, recurrences and other complications, and hospitalizations of a low- versus high-dose regimen of prednisone for recurrent pericarditis. METHODS AND RESULTS: A retrospective review of all cases of recurrent pericarditis treated with corticosteroids according to different regimens from January 1996 to June 2004 was performed in 2 Italian referral centers. One hundred patients with recurrent pericarditis (mean age, 50.1+/-15.8 years; 57 females) were included in the study; 49 patients (mean age, 47.5+/-16.0; 25 females) were treated with low doses of prednisone (0.2 to 0.5 mg . kg(-1) . d(-1)), and 51 patients (mean age, 52.6+/-15.3; 32 females) were treated with prednisone 1.0 mg . kg(-1) . d(-1). Baseline demographic and clinical characteristics were well balanced across the groups. Each initial dose was maintained for 4 weeks and then slowly tapered. After adjustment for potential confounders (age, female gender, nonidiopathic origin), only high doses of prednisone were associated with severe side effects, recurrences, and hospitalizations (hazard ratio, 3.61; 95% confidence interval, 1.96 to 6.63; P<0.001). CONCLUSIONS: Use of higher doses of prednisone (1.0 mg . kg(-1) . d(-1)) for recurrent pericarditis is associated with more side effects, recurrences, and hospitalizations. Lower doses of prednisone should be considered when corticosteroids are needed to treat pericarditis.

Thyroid nodule shape suggests malignancy.

OBJECTIVE: To evaluate if a nodule with shape taller than wide (anteroposterior/transverse diameter ratio, A/T > or = 1) is a good predictor of malignancy independent of the size. METHODS: We retrospectively examined the cytological and histological results of 7455 nodules (5198 patients) referred for ultrasound-guided-fine needle aspiration cytology (US-FNAC) in our hospital from January 1991 to September 2004. RESULTS: A suitable FNAC was obtained from 6135 nodules (4495 patients); 34.6% were less than 1 cm in diameter (small nodules, SN). A diagnosis of carcinoma was histologically confirmed in 284/349 suspicious lesions after FNAC. The size of carcinoma nodules was not significantly associated with the occurrence of extracapsular growth (large nodules (LN): 10.5%, SN: 4.9%, NS) and lymph node metastasis (LN: 23.6%, SN: 25.0%, NS). Malignant lesions showed microcalcifications more frequently than benign nodules (72.2 vs 28.7%; P < 0.001; (odds ratio, OR(confidence intervals, CI) = 9.9(7.2-13.4)). Similarly, A/T > or = 1 (76 vs 40%; P < 0.001; OR(CI) = 8.6(5.5-13.1)), blurred margins (52.8 vs 18.8%; P < 0.001; OR(CI) = 7.7(5.6-10.2)), solid hypo-echoic appearance (80.6 vs 52.4%; P < 0.001; OR(CI) = 3.2(2.2-4.3)) and intranodular vascular pattern (type 2) (61.6 vs 49.7%; P < 0.001; OR(CI) = 1.7(1.3-2.3)) were significantly more frequent in malignant than in benign nodules. CONCLUSIONS: Our data show that no single parameter, including nodule size, satisfactorily identifies a subset of patients to be electively investigated by FNAC. We concluded that A/T > or = 1 with at least two of US features (microcalcification, blurred margins, hypo-echoic pattern) is today the best compromise between missing cancers and cost-benefit.

CEACAM1 and MICA as novel serum biomarkers in patients with acute and recurrent pericarditis.

BACKGROUND: The immune response plays a significant role in pericarditis, but the mechanisms of disease are poorly defined. Further, efficient monitoring and predictive clinical tools are unavailable. Carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) is an immune-inhibitory protein, while MHC class I chain related protein A (MICA) and B (MICB) have an immune-stimulating function. METHODS AND RESULTS: Serum CEACAM1, MICA and MICB concentrations were measured by ELISA in ~50 subjects of each group: acute pericarditis (AP), recurrent pericarditis (RP) and lupus (SLE) patients, metastatic melanoma patients as well as healthy donors. Serum CEACAM1 was dramatically elevated in AP and RP patients, but not in SLE patients, and displayed a highly accurate profile in ROC curve analyses. MICA and MICB were elevated in some pericarditis patients. All markers were enhanced in metastatic melanoma patients irrespective of neoplastic pericardial involvement. Etiology-guided analysis of RP patients showed that very low MICA levels were associated with idiopathic RP, while high MICA was associated with autoimmune and post-operative RP. Importantly, MICA was significantly associated with recurrences, independently of other potentially confounding parameters such as age, time of follow up or treatment modality. CONCLUSIONS: Here we report for the first time on CEACAM1 as a potentially novel biomarker for pericarditis, as well as on MICA as an innovative prognostic marker in these patients. Determination of the roles of these immune factors, as well as their diagnostic and prognostic values should be determined in future prospective studies.

Recurrent pericarditis in children and adolescents: a multicentre cohort study.

OBJECTIVE: Limited data are available about recurrent pericarditis in children. We sought to explore contemporary causes, characteristics, therapies and outcomes of recurrent pericarditis in paediatric patients. METHODS: A multicentre (eight sites) cohort study of 110 consecutive cases of paediatric patients with at least two recurrences of pericarditis over an 11-year period (2000-2010) [median 13 years, interquartile range (IQR) 5, 69 boys]. RESULTS: Recurrences were idiopathic or viral in 89.1% of cases, followed by postpericardiotomy syndrome (9.1%) and familial Mediterranean fever (0.9%). Recurrent pericarditis was treated with nonsteroidal anti-inflammatory drugs (NSAIDs) in 80.9% of cases, corticosteroids in 64.8% and colchicine was added in 61.8%. Immunosuppressive therapies were administered in 15.5% of patients after subsequent recurrences. After a median follow-up of 60th months, 528 subsequent recurrences were recorded (median 3, range 2-25). Corticosteroid-treated patients experienced more recurrences (standardized risk of recurrence per 100 person-years was 93.2 for patients treated with corticosteroids and 45.2 for those without), side effects and disease-related hospitalizations (for all P < 0.05). Adjuvant therapy with colchicine was associated with a decrease in the risk of recurrence from 3.74 per year before initiation of colchicine to 1.37 per year after (P < 0.05). Anakinra therapy (n = 12) was associated with a drop in the number of recurrences from 4.29 per year before to 0.14 per year after (P < 0.05). Transient constrictive pericarditis developed in 2.7% of patients. CONCLUSION: Recurrent pericarditis has an overall favourable prognosis in children, although it may require frequent readmissions and seriously affect the quality of life, especially in patients treated with corticosteroids. Colchicine or anakinra therapies were associated with significant decrease in the risk of recurrence.

Clues to detect tumor necrosis factor receptor-associated periodic syndrome (TRAPS) among patients with idiopathic recurrent acute pericarditis: results of a multicentre study.

BACKGROUND: The potential clinical expression of tumor necrosis factor receptor-associated periodic syndrome (TRAPS), in the form of idiopathic recurrent acute pericarditis (IRAP) has not been explored in the medical literature. The aim of this study was to evaluate the incidence of TRAPS mutations in patients with recurrent pericarditis and identify possible clues to TRAPS diagnosis. METHODS: Therefore, 131 consecutive Caucasian IRAP patients were investigated for mutations of the TRAPS gene and prospectively evaluated. RESULTS: Out of 131 patients, 8 (6.1%) carried a mutation in the TNFRSF1A gene. Compared with those without genetic mutations, patients with TRAPS mutations had more frequently a positive family history for pericarditis and periodic fever syndromes (p < 0.001), a higher mean number of recurrences after the first year (p < 0.001), on colchicine treatment (p < 0.001), and a higher need of immunosuppressive therapies (p < 0.001). CONCLUSION: TRAPS is a cause of recurrent pericarditis in 6% of unselected cases with recurrent pericarditis. A positive family history for pericarditis or periodic fever syndromes, a poor response to colchicine, recurrences after the first year from the index attack or on colchicine treatment, as well as the need of immunosuppressive agents are clues of the possible presence of TNFRSF1A gene mutations in patients with recurrent pericarditis.

Recurrent pericarditis: autoimmune or autoinflammatory?

Idiopathic recurrent acute pericarditis (IRAP) represents the most troublesome complication of acute pericarditis and occurs in up to 20-50% of patients. It is generally idiopathic or postcardiac injury. IRAP is a disease of suspected immune-mediated pathogenesis. On the other hand, it has been suggested that some of these patients might have an atypical or subclinical form of an autoinflammatory disease, e.g. genetic disorders characterized by primary dysfunction of the innate immune system and caused by mutations of genes involved in the inflammatory response. We found that IRAP patients were negative for mutations associated with familial Mediterranean fever, but 6% (8/131 patients) carry a mutation in the TNFRSF1A gene, encoding the receptor for tumor necrosis factor-alfa. C-reactive protein (CRP) may be useful to follow the disease activity and guide the appropriate length of therapy, with continuation of the attack doses of the drugs until CRP normalization, at which time tapering may be considered. IRAP often needs a multidrug therapy: NSAIDs or aspirin at high dosages every 6-8h, corticosteroids only rarely, at low dosages and with a very gradual tapering (months) and colchicine at low dosages if tolerated. Anakinra could be a solution for patients who do not tolerate other therapies.

Recurrent pericarditis: infectious or autoimmune?

The etiology and pathogenesis of idiopathic recurrent acute pericarditis (IRAP) remain controversial standing like a bridge that crosses infectious, autoimmune and autoinflammatory pathways. Anything may cause acute pericarditis; Echo-virus, and Coxsackie are the most frequently involved viruses, Mycobacterium tuberculosis and Coxiella burnetii the most common bacteria, but in 85% of cases it remains "idiopathic". Recurrences occur in up to 20-50% of patients. An immuno-mediated pathogenesis is suggested by the presence of pro-inflammatory cytokines in pericardial fluid, the presence of antinuclear autoantibodies (ANA) in sera of the patients, the occurrence of new autoimmune diagnoses and the good response to anti-inflammatory or immunosuppressive therapy. Nonsteroidal anti-inflammatory drugs (NSAIDs) must be used at recommended dosages, till the resolution of symptoms and normalization of C-reactive protein and erythrocyte sedimentation rate. Corticosteroids should be used rarely, at low doses, with an extremely low tapering and with osteoporosis prevention. Colchicine leads to a clinically important and statistically significant benefit, reducing recurrences by 50%. The long term outcome of IRAP is good, without evidence of constriction even after a very long follow-up.

Outcome of patients surgically treated for various forms of hyperthyroidism with differentiated thyroid cancer: experience at an endocrine center in Italy.

PURPOSE: The incidence and aggressiveness of thyroid cancer associated with hyperthyroidism remains a subject of much controversy. The aim of this study was to analyze the frequency of coexisting hyperthyroidism and thyroid cancer, and to determine whether cancer becomes more aggressive with different forms of hyperthyroidism. METHODS: We retrospectively studied 2,449 patients assessed for hyperthyroidism between 1985 and 2001. All patients with a "cold" nodule on scintigraphy, such as those with Graves' disease and a concomitant solid nodule, underwent fine-needle aspiration biopsy (FNAB). Criteria for surgery were cytological findings indicative of malignancy, goiter with signs of tracheal or esophageal compression, side effects of antithyroid drug therapy, or Graves' disease with multiple relapses after therapy withdrawal or responsiveness to antithyroid drugs. RESULTS: Thyroid cancer was diagnosed more frequently in patients with Graves' disease (6.5%) than in those with uninodular toxic goiter (UTG) (4.4%) or multinodular toxic goiter (MTG) (3.9%). Lymph node involvement was found in 56% of the patients with Graves' disease, in 23% of those with MTG, and in none of those with UTG. Distant metastases were found in one patient with Graves' disease. CONCLUSIONS: Cancers associated with Graves' disease seems to be more aggressive than those associated with MTG or UTG. Thus, we suggest that patients with Graves' disease be carefully monitored for the detection of thyroid nodules. Ultrasonography seems to be the best modality to detect such nodules.

Is the anteroposterior and transverse diameter ratio of nonpalpable thyroid nodules a sonographic criteria for recommending fine-needle aspiration cytology?

BACKGROUND: As a consequence of the increasing application of ultrasound (US) technology, the detection of asymptomatic nonpalpable thyroid nodules has generally increased. The aim of our study was to assess if the anteroposterior and transverse diameter ratio of nonpalpable thyroid nodules (A/T) > or = 1 could be a sonographic criterion for recommending fine-needle aspiration cytology (FNAC). METHODS: From January 2002 to January 2004, 828 consecutive solid nonpalpable thyroid nodules were evaluated by ultrasonography, colour-Doppler and FNAC in our department. Cases were selected from 2217 patients, referred to our thyroid unit for US-guided FNAC from the greater Brescia area, an endemic zone for goitre. Entry criteria included the presence at US of a solid thyroid nodule that was nonpalpable at physical examination, euthyroid condition and no previous diagnosis of thyroid malignancy. All patients with suspicious or malignant cytology underwent surgery. RESULTS: One hundred and twenty-seven nodules with inadequate cytology were excluded from the study. Thyroid malignancy was observed in 67 (9.6%) nodules. At US, cancers presented a solid hypoechoic appearance in 79.1% of cases, blurred margins in 47.8%, microcalcification in 73.1%, intranodular vascular pattern in 56.7% and A/T > or = 1 in 83.6%. A hypoechoic appearance (OR 4.3), blurred margins (OR 2.6), microcalcification (OR 6.1), intranodular vascular pattern (OR 10.2) and A/T > or = 1 (OR 22.4) were independent risk factors of malignancy. CONCLUSIONS: A/T > or = 1 in conjunction with at least one other sonographic risk factor is able to detect the majority of carcinoma and, moreover, it limits the FNAC procedures to only 15.9% of all the nodules.