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Objective: To evaluate the long-term effectiveness, safety, and tolerability of erenumab in a real-world migraine population, looking for putative predictors of responsiveness. Background: Erenumab proved to be effective, safe, and well tolerated in the prevention of episodic migraine (EM) and chronic migraine (CM) in long-term extension studies of double-blind, placebo-controlled trials in patients with no more than two (EM) or three (CM) prior preventive treatment failures. Methods: A 48-week, multicenter, longitudinal cohort real-life study was conducted at 15headache centers across eight Italian regions between December 20, 2018 and July 31, 2020. We considered all consecutive patients with high-frequency episodic migraine (HFEM) or CM aged 18–65years. Each patient was treated with erenumab 70mg, administered monthly. The dose was switched to 140mg in nonresponders and in responders who had become nonresponders for at least 4weeks. Change in monthly migraine days (MMDs) or monthly headache days (MHDs) at Weeks 45–48 compared with baseline was the primary efficacy endpoint. Secondary endpoints encompassed variation in monthly analgesic intake, achievement of a ≥50%, ≥75%, or 100% reduction in migraine or headache days, and any change in the Visual Analogue Scale (VAS) and Headache Impact Test-6 scores (HIT-6) during the same time interval. Results: A total of 242 patients with migraine received at least one dose of erenumab 70mg and were considered for safety analysis, whereas 221 received a monthly erenumab dose for ≥48weeks and were included in the effectiveness and safety analysis set. All patients had previously been treated unsuccessfully with ≥3migraine-preventive medication classes. From baseline to Weeks 45–48, erenumab treatment reduced MMD by 4.3±5.3(mean±SD) in patients with HFEM, and MHD by 12.8±8.9 (mean±SD) in subjects with CM. VAS and HIT-6scores were decreased by 1.8±1.9 (mean±SD) and 12.3±11 (mean±SD) in HFEM, and by 3.0±2.2 (mean±SD) and 13.1±11.2 (mean±SD) in CM. Median monthly analgesic intake passed from 11.0 (interquartile range [IQR] 10.0–13.0) to 5 (IQR 2.0–8.0) in HFEM and from 20.0 (IQR 15.0–30.0) to 6.0 (IQR 3.8–10.0) in CM. The ≥50% responders were 56.1% (32/57) in HFEM and 75.6% (124/164) in CM; ≥75% responders were 31.6% (18/57) and 44.5% (73/164); and 100% responders were 8.8% (5/57) and 1.2% (2/164), respectively. At Week 48, 83.6% (137/164) of patients with CM had reverted to EM. Erenumab was safe and well tolerated. Responsiveness to erenumab was positively associated with cutaneous allodynia (OR: 5.44, 95% CI: 1.52–19.41; p=0.009) in HFEM. In patients with CM, ≥50% responsiveness was positively associated with male sex (OR: 2.99, 95% CI: 1.03–8.7; p=0.044) and baseline migraine frequency (OR: 1.12, 95% CI: 1.05–1.20; p=0.001) and negatively associated with psychiatric comorbidities (OR: 0.37, 95% CI: 0.15–0.87; p=0.023) and prior treatment failures (OR: 0.77, 95% CI: 0.64–0.92; p=0.004). Conclusions: Long-term (48-week) erenumab treatment provides sustained effectiveness, safety, and tolerability in real-life patients with HFEM or CM with ≥3 prior preventive treatment failures. The dose of 140mg was required in most patients along the study and should be taken into consideration as the starting dose. Allodynia (in HFEM), male sex, and baseline migraine frequency (in CM) might represent positive responsiveness predictors. Conversely, psychiatric comorbidities and multiple prior preventive treatment failures could be negative predictors in patients with CM.

Objective: This article reviews current headache disability measures and clinical need, as well as presenting the rationale for a new measure addressing work-related disability in migraine patients and the steps devoted to this aim. Background: Episodic and chronic migraine (EM and CM) constitute an enormous economic burden to societies, and the vast majority of this burden is attributable to indirect costs, ie those associated with productivity loss. A measure of work-related disability is therefore needed to quantify the impact of EM and CM on patients' ability to carry out work tasks. Methods: We briefly present the advantages and disadvantages of the disability measures that have been most commonly used for this purpose and the rationale for developing a new measure. Results: The entire process of development of HEADWORK, a questionnaire designed to assess work-related disability, is presented together with short-term sensitivity to change. Conclusions: Current headache disability measures need improvement. HEADWORK is a valid, reliable, and sensitive questionnaire to address the amount and severity of work-related difficulties and of the factors contributing to such difficulties. HEADWORK is suitable for daily clinical practice, epidemiological research and for clinical trials, and potentially to define work-related disability weights for the calculation of migraine indirect costs.

Background: Lombardy was severely hit by the COVID-19 pandemic since February 2020 and the Health System underwent rapid reorganization. Outpatient clinics were stopped for non-urgent patients: it became a priority to manage hundreds of fragile neurological patients who suddenly had less reference points. In Italy, before the pandemic, Televisits were neither recognized nor priced. Methods: At the Fondazione IRCCS Istituto Neurologico C. Besta, we reorganized outpatient clinics to deliver Neuro-telemedicine services, including Televisits and Teleneurorehabilitation, since March 2020. A dedicated Working Group prepared the procedure, tested the system, and designed satisfaction questionnaires for adults and children. Results: After a pilot phase, we prepared a procedure for Telemedicine outpatient clinics which was approved by hospital directions. It included prescription, booking, consenting, privacy and data protection, secure connection with patients (Teams Microsoft 365), electronic report preparation and delivery, reporting, and accountability of the services. During the March–September 2020 period, we delivered 3167 Telemedicine services, including 1618 Televisits, to 1694 patients (972 adults, 722 children) with a wide range of chronic neurological disorders. We successfully administered different clinical assessment and scales. Satisfaction among patients and caregivers was very high. Conclusions: During the dramatic emergency, we were able to take care of more than 1600 patients by organizing Neuro-telehealth in a few weeks, lessening the impact of the pandemic on fragile patients with chronic neurological disorders; this strategy is now stably embedded in our care pathways. In Italy, Telehealth is at present recognized and priced and is becoming a stable pillar of the health system.

SummaryBackground The nationwide prevalence of latent tuberculosis infection (LTBI) in Italian patients with psoriasis has never been investigated. Objectives To estimate the nationwide prevalence of LTBI in Italian patients with psoriasis who are candidates for systemic treatment. Methods Data were obtained from the Psocare Registry on those patients (n = 4946) with age > 18 years, systemic treatment at entry specified and tuberculin skin test (TST) performed according to the Mantoux method. LTBI diagnosis was based on a positive TST result in the absence of any clinical, radiological or microbiological evidence of active tuberculosis. Results Latent tuberculosis infection was diagnosed in 8·3% of patients with psoriasis (409 of 4946). The prevalence of LTBI was lower in patients on biologics than in those on conventional systemic treatments, ranging from 4·3% (19 of 444) of patients on adalimumab to 31% (eight of 26) of those on psoralen–ultraviolet A (P

Background. During the first months of life, infants can suffer from many ‘minor’ gastroenterological disturbances. However, little is known about the frequency of these problems and the factors which predispose or facilitate their onset. Aims. (a) To ascertain the frequency of the most common gastrointestinal symptoms in infants during the first 6 months after birth; (b) to evaluate the influence of some variables on the onset of the symptoms. Study design and patients. Each of the 150 paediatricians distributed throughout Italy followed 20 consecutive infants from birth to 6 months. 2879 infants (1422 f, 1457 m) concluded the study. The presence of the following symptoms was evaluated: constipation, diarrhoea, vomiting, regurgitation, failure to thrive and prolonged crying fits (colic). Symptoms were recorded whenever the parents requested a clinical check-up or during a set monthly examination. Results. 1582/2879 (54.9%) infants suffered from one of the gastrointestinal symptoms. Regurgitation was the most common disturbance (present in 23.1% of infants), followed by colic (20.5%), constipation (17.6%), failure to thrive (15.2%), vomiting (6%) and diarrhoea (4.1%). Low birth weight was the factor most frequently associated with the onset of gastrointestinal symptoms, followed by low gestational age. Feeding habits did not influence the onset of symptoms, with the exception of constipation, which was linked to a low frequency of breast-feeding. Ninety-three infants (3.2%) were hospitalised for one or more of the gastrointestinal symptoms which were considered. During the whole study period the type of formula-milk was changed in 60% of the infants with one or more gastrointestinal symptoms, and in 15.5% of the infants who did not suffer from any gastrointestinal troubles. Conclusions. Gastrointestinal symptoms are very common in infants during the first 6 months after birth. These symptoms required hospitalisation only in a small percentage of cases, but led to the prescription of a ‘dietary’ milk formula in approximately 60% of the cases. Low birth weight and low gestational age were the main factors influencing the onset of the symptoms.

Background: Some studies have shown that switching patients from one tumor necrosis factor (TNF)-alfa inhibitor to another may be beneficial when they have an inadequate response or an adverse event. Objective: We sought to assess the variables predicting the efficacy of the second TNF-alfa inhibitor in patients discontinuing the first TNF-alfa inhibitor. Methods: Data from all 5423 consecutive patients starting TNF-alfa inhibitor therapy for psoriasis between September 2005 and September 2010 who were included in the Italian Psocare registry were analyzed. Results: In 105 patients who switched to a second TNF-alfa inhibitor who had complete follow-up data, 75% improvement in the Psoriasis Area Severity Index score (PASI 75) was reached by 29% after 16 weeks and by 45.6% after 24 weeks. Patients who switched because of secondary loss of efficacy (loss of initial PASI 75 response) or adverse events/intolerance were more likely to reach PASI 75 than those who switched as a result of primary inefficacy (PASI 75 never achieved) (hazard ratio 2.7, 95% confidence interval 1.3-5.5 vs hazard ratio 2.0, 95% confidence interval 1.0-3.9 and 1, respectively). Limitations: There was a small number of patients with complete follow-up data. Conclusion: PASI 75 response in patients who switched from one antie-TNF-alfa agent to another was significantly reduced in patients who showed primary inefficacy of the first antie-TNF-alfa.

Dendritic cells are human leucocyte antigen (HLA)-DR positive accessory cells, that play a critical role in the development of cell-mediated immune reactions. Since the pleural space is frequently involved in cell-mediated immune reactions, we sought to isolate dendritic cells from pleural fluid. Pleural effusion mononuclear cells (PEMCs) were obtained by Ficoll centrifugation of exudative pleural effusions recovered from 19 patients with malignant pleurisy. After double-step adherence, firmly-adherent mononuclear cells (FAMs) and loosely-adherent mononuclear cells (LAMs) were recovered. The latter cells were centrifuged on a bovine plasma albumin gradient to obtain a loosely-adherent low density fraction. Nonadherent cells were rosetted with sheep red blood cells (SRBC) to obtain a nonadherent nonrosetting (NANR) cell fraction. Mitomycin C-treated PEMCs, NANRs, FAMs, and LAMs served as stimulatory cells in mixed leucocyte reaction experiments. 3H-thymidine incorporation by purified normal allogeneic blood T-lymphocytes was assessed as an index of accessory cell function. The phenotype of NANR, FAM and LAM cells was characterized using single and double stainings with a panel of monoclonal antibodies (MoAbs). Accessory cell (AC) activity (counts per minute (cpm) x 10(3)(+/-SE); 2.5 x 10(4) AC x well(-1) of LAM (148+/-24) and NANR (108.4+/-11.2) was greater than that observed for FAM (59.3+/-9.4) and for unfractioned PEMC (13.8+/-4.9). The FAM fraction was virtually entirely composed of CD68+ HLA-DR+ mononuclear phagocytes. NANR and LAM contained 51+/-12% and 65+/-6% HLA-DR+ cells, respectively, and most HLA-DR positive cells were negative for CD3, CD19, and CD68, markers for T-, B-lymphocytes and mononuclear phagocytes. Moreover, both NANR and LAM fractions contained significant numbers of cells bearing the RFD1 surface marker, expressed on dendritic cells. These results suggest that dendritic cells are present in exudative pleural effusions, and that they may be involved in the development of cell-mediated immune reactions in the pleural space.

OBJECTIVE: To evaluate variations in laboratory parameters and diagnoses of selected clinical conditions up to 16 weeks after starting a new systemic psoriasis treatment for Psocare Registry enrollees. DESIGN: Prospective cohort study. SETTING: Italian public referral centres for psoriasis treatment. PATIENTS: First-time recipients (n = 10,539) of continuous systemic psoriasis treatment for at least 16 weeks. MAIN OUTCOME MEASURE: Mean variations in (weeks 8 and 16) and proportions of patients reaching a clinically meaningful increase in serum levels (week 16) of total and low-density lipoprotein cholesterol, triglycerides, aspartate amino transferase, alanine amino transferase and creatinine, as well as week-16 cumulative incidences of new diagnoses of diabetes mellitus and arterial hypertension. RESULTS: Mean cholesterol and triglyceride levels significantly increased in patients treated with acitretin or cyclosporine. Mean triglyceride levels also increased in efalizumab- and etanercept-treated patients. Mean transaminase values increased in methotrexate-treated patients, and mean aspartate amino transferase levels increased in infliximab-treated patients. The average serum creatinine value increased in cyclosporine-treated patients. Acitretin and cyclosporine were associated with risk of hypercholesterolaemia (odds ratios 1.51 and 1.34) and acitretin with risk of hypertriglyceridaemia (odds ratio 1.43). Methotrexate and infliximab were associated with risk of more than doubling the upper normal aspartate amino transferase (odds ratios 2.06 and 1.87) and alanine amino transferase (odds ratios 2.38 and 1.74) values. The relative risk of developing arterial hypertension and diabetes was increased for patients receiving cyclosporine (odds ratios 3.31 and 2.88). CONCLUSION: Systemic treatments for psoriasis resulted in heterogeneous effects on the parameters analysed.

To assess the efficacy and tolerability of N-acetylcysteine (NAC) in patients with Raynaud's phenomenon (RP) secondary to systemic sclerosis (scleroderma; SSc).Twenty-two patients with RP secondary to SSc were enrolled in a multicenter, open clinical trial lasting 11 weeks and conducted in winter. Primary outcome measures were frequency and severity of RP attacks, and number of digital ulcers. Secondary outcome measure was improvement in digital cold challenge test assessed by photoelectric plethysmography. Patients received a continuous 5 day intravenous infusion of NAC starting with a 2 h loading dose of 150 mg/kg subsequently adjusted to 15 mg/kg/h.All 22 patients completed the 5 day infusion and 20 of them the posttreatment followup. Both frequency and severity of RP attacks decreased significantly compared to pretreatment values. Active ulcers were significantly less numerous at all followup visits (25.18% of baseline count on Day 33 from the beginning of infusion). In the cold challenge test mean recovery time fell by 69.56%, 67.70%, 71.42%, and 71.05% on Days 12, 19. 33, and 61 from the beginning of treatment. Side effects were minor, easily controlled, and reversible.N-acetylcysteine appears to be safe for the treatment of RP secondary to SSc. These preliminary data warrant further controlled studies.

Item does not contain fulltext PURPOSE: To confirm the safety and compare the efficacy of intravitreal pegaptanib sodium 0.3 mg versus sham injections in subjects with diabetic macular edema (DME) involving the center of the macula associated with vision loss not due to ischemia. DESIGN: Randomized (1:1), sham-controlled, multicenter, parallel-group trial. PARTICIPANTS: Subjects with DME. INTERVENTION: Subjects received pegaptanib 0.3 mg or sham injections every 6 weeks in year 1 (total = 9 injections) and could receive focal/grid photocoagulation beginning at week 18. During year 2, subjects received injections as often as every 6 weeks per prespecified criteria. MAIN OUTCOME MEASURES: The primary efficacy endpoint was the proportion gaining >/= 10 letters of visual acuity (VA) from baseline to year 1. Safety was monitored throughout. RESULTS: In all, 260 (pegaptanib, n = 133; sham, n = 127) and 207 (pegaptanib, n = 107; sham, n = 100) subjects were included in years 1 and 2 intent-to-treat analyses, respectively. A total of 49 of the 133 (36.8%) subjects from the pegaptanib group and 25 of the 127 (19.7%) from the sham group experienced a VA improvement of >/= 10 letters at week 54 compared with baseline (odds ratio [OR], 2.38; 95% confidence interval, 1.32-4.30; P = 0.0047). For pegaptanib-treated subjects, change in mean VA from baseline by visit was superior (P

BACKGROUND\Helicobacter Pylori (H. Pylori) is a key pathogenetic factor in gastritis, peptic ulcer disease, gastric carcinoma and lymphoma but its relationship with gastroesophageal reflux disease (GERD) is controversial. The aim of the study is to estimate the possible association between the presence of H. pylori and GERD.In this retrospective study we examined the endoscopy and pathology reports of all the 638 consecutive patients who had upper gastrointestinal endoscopy and adequate mucosal sampling in 2005 in our department at the University of Padova. Yates corrected chi2 test was used to compare the H. Pylori frequency in the different histological groups. Multinomial logistic regression was used to identify possible predictors of H. Pylori infection.In this selected population 133 patients were affected by H. Pylori infection (20.8%) and 107 were affected by GERD according to Montreal definition. No significant relation between H. Pylori infection and GERD or NERD (non erosive reflux disease) was evidenced. As expected histological gastritis at the examination confirmed to be the strongest predictor of infection with a odds ratio of 39.4 (95% CI 5.4-287.4, p0.01). Upper abdominal pain showed to be the only clinical independent predictors for the presence of H. Pylori infection with a odds ratio of 1.5 (95% CI 1.0-2.3, p = 0.04).Our study showed that in north eastern Italy there is no association between H. Pylori infection and GERD. On the contrary presence of histological gastritis and upper abdominal pain were confirmed to be significant predictors of H. Pylori infection. No endoscopic characteristic is significantly related to the presence of H. Pylori.

The study aim is to confirm feasibility and usefulness of endovascular stent-graft placement for superior mesenteric artery acute bleeding in presence of local sepsis. A superior mesenteric artery resection concomitant to a pancreaticoduodenectomy for carcinoma of the pancreas was followed by a saphenous vein bypass. A pancreatic leak associated to infection developed early in the postoperative course. Three weeks later, a massive haemorrhage due to rupture of an acute pseudoaneurysm was successfully treated with an endoluminal covered stent. This occluded two weeks later without important signs of bowel ischemia. The covered-stent placement allowed obtaining primary hemostasis and bowel perfusion preservation in spite of early occlusion. The patient did well after chemotherapy for one year and presented local recurrence at 16 months. Endovascular treatment of acute haemorrhage in presence of an intra-abdominal sepsis is feasible and useful following pancreatic surgery.

The central nervous system inflammatory disease can be due to any kind of infective agent (bacterial viral, fungal and parasitic), but entails also multiple sclerosis, a primary demyelinating disease in which the causal agent is unknown. MR imaging is, in most often, the procedure of choice, due to her multiplanar and multiparametric imaging, and to her better contrast resolution. The post-contrast imaging with double dose of gadolinium and late sequences enable visualisation of smallest pathologic foci or slightest blood-brain barrier alterations, with a sensibility very higher than post-contrast CT scan. In addition, RM provide to many functional informations, by means of diffusion, perfusion and spectroscopy studies, Bold technique for cortical activation studies and Fiber Tracking technique, in order to demonstrate pathologic modification earlier than they are evident on morphologic imaging. Functional imaging is also employed to monitor response to treatment and damage reversibility.

Vertebral fractures are a relevant problem for the heavy clinical implications and carrying disability. Vertebral fractures can be traumatic or pathologic, the latter can be benign or malignant, both mostly frequent in the elderly. An initial approach to this issue can use plain radiographs, but the correct extension and evaluation must involve CT and MR imaging. In particular MR is a useful tool for the prognostic evaluation of spine marrow injuries and the differential diagnosis of osteoporotic and metastatic fractures.

Genitourinary complications occur in 4 to 35% of Crohn's disease patients. The aim of this study was to assess the threshold to suspect urologic involvement in Crohn's disease in order to plan the correct surgical management.Medical records of 258 consecutive patients who have undergone bowel resection for Crohn's disease were reviewed. We evaluated recurrent urinary tract infections, fever, dysuria, pneumaturia, fecaluria, abdominal mass at palpation or lower back pain at percussion, abdominal ultrasound and computerized tomography scan reports. Univariate analysis and multivariate analysis were performed with Fisher exact and log-linear tests respectively.Urologic complications were found in 11 patients (4.3%). Fistulizing disease, female gender and inflammatory mass were significantly increased in Crohn's disease patients with urinary tract involvement (p0.01). Ultrasound and computerized tomography scan demonstrated good specificity, sensibility, positive and negative predicting values for urologic complications.In the presence of abdominal mass in a Crohn's disease patient, the following step should be abdominal ultrasound or computerized tomography scan to rule out involvement of the ureter that should be treated previously to improve the intraoperative picture and patient general status.

Anastomotic recurrence after bowel resection is a major problem in Crohn's disease surgery. The aim of this study is to compare recurrence rate after stapled side-to-side ileo-colonic anastomosis to those after stapled end-to-side or hand-sewn side-to-side anastomosis to distinguish the role of suture technique and anastomotic configuration in the prevention of Crohn's disease recurrence.Eighty-four consecutive patients who had undergone ileo-colonic resection for Crohn's disease were enrolled: 12 of them had stapled side-to-side anastomosis, 36 stapled end-to-side anastomosis and 36 hand-sewn side-to-side anastomosis. We evaluated duration of operation, first bowel movement after operation, postoperative hospital staying, postoperative surgical complications, clinical recurrence and reoperation rate. The statistical analysis was performed using Student's t-test and Fisher exact test. Cumulative recurrence rates were compared using F Cox test and Kaplan-Meier method.No statistically significant difference between the three groups was observed in early postoperative follow up. The stapled side-to-side anastomosis group obtained a better symptom-free survival than the stapled end-to-side group (p=0.04). In the stapled and hand-sewn side-to-side groups reoperation rates were significantly lower than in the stapled end-to-side group (p=0.01 and p=0.05 respectively).All the three types of anastomosis were demonstrated to be equally safe in early postoperative outcome. A longer follow-up showed a significantly lower incidence of reoperation recurrence in the stapled and hand-sewn side-to-side anastomosis compared to the stapled end-to-side anastomosis group. This result may suggest the configuration of the anastomosis as the key point in the recurrence of anastomotic Crohn's disease.

Summary: Perfluoro-n-octane (PFO) is a heavy liquid that is used as an aid for complicated retinal surgical procedures. Although PFO is usually removed intraoperatively, the radiographic appearance of retained PFO may mimic an intraocular foreign body or vitreous hemorrhage. As the use of PFO in retinal procedures has become more widespread, recognition of its imaging appearance has become important in the differential diagnosis of intraocular foreign body and ocular trauma.

Free peritoneal perforation is a rare complication of Crohn's disease.We evaluated the incidence of free peritoneal perforation among 208 patients with Crohn's disease surgically treated in the period 1992-2000.Five patients (2.4%) suffered from free peritoneal perforation. In 1 patient free peritoneal perforation was the first symptom of Crohn's disease. In 3 cases the perforation was in the small bowel and in 2 in the large bowel. All patients underwent surgery: all cases had a resection of the involved bowel and in two cases an ileostomy was performed in order to prevent severe peritonitis. We did not observed mortality or major complications.Free peritoneal perforation is rare with about 100 cases reported in literature. No correlation seems to exist with previous corticosteroid treatment. The surgical treatment is mandatory. Simple suture should be avoided. The most appropriate treatment, whenever it is feasible, is resection of the involved bowel with immediate or, in case of severe sepsis, delayed anastomosis.

A multicenter study was carried out in 10 Italian Headache Centers to investigate the prevalence of psychosocial stress and psychiatric disorders listed by the IHS classification as the "most likely causative factors" of tension-type headache (TTH). Two hundred and seventeen TTH adult outpatients consecutively recruited underwent a structured psychiatric interview (CIDI-c). The assessment of psychosocial stress events was carried out using an ad hoc questionnaire. The psychiatric disorders that we included in the three psychiatric items of the fourth digit of the IHS classification were depressive disorders for the item depression, anxiety disorders for the item anxiety, and somatoform disorders for the item headache as a delusion or an idea. Diagnoses were made according to DSM-III-R criteria. At least one psychosocial stress event or a psychiatric disorder was detected in 84.8% of the patients. Prevalence of psychiatric comorbidity was 52.5% for anxiety, 36.4% for depression, and 21.7% for headache as a delusion or an idea. Psychosocial stress was found in 29.5% of the patients and did not differ between patients with and without psychiatric comorbidity. Generalized anxiety disorder (83.3%) and dysthymia (45.6%) were the most frequent disorders within their respective psychiatric group. The high prevalence of psychiatric disorders observed in this wide sample of patients emphasizes the need for a systematic investigation of psychiatric comorbidity aimed at a more comprehensive and appropriate clinical management of TTH patients.

At the turn of the new century, liver transplant procedures can finally be considered an efficient treatment option. Technology has helped transplant intervention become a preferred treatment for patients with progressive and irreversible liver failure. New immuno-suppressive drugs have been introduced which reduce the patient's immunological reaction to the implanted organ, entail minimal side effects and improve practical applications of liver transplantation. As a result of these technological advanced and proper disease management, liver transplant procedures are no longer thought of as an elite therapy, reserved for selected patients with end stage liver disease. In our opinion, it is now a sound and valid surgical option with strictly defined characteristics, indications and well-understood limits. Throughout the past decade, we have studied and applied this type of intervention and have come to terms with its rapid expansion at both the theoretical and practical levels. The most significant obstacle remaining today is the discrepancy between the ever increasing demand and limited supply of organs. The future of liver transplant lies in overcoming this obstacle. Liver transplant practice began at our Institute on 23 November 1990 with the first surgical intervention to replace an organ. In the past 10 years, we have exceeded 200 liver transplant procedures.

30 citazioni su Scopus. 46 citazioni su GoogleScholar. ------ http://www.scopus.com/record/display.url?eid=2-s2.0-0347771343&origin=resultslist&sort=plf-f&src=s&sid=1BklTwBDkRxWaxt9FLi7YAz%3a70&sot=aut&sdt=a&sl=37&s=AU-ID%28%22Benassai%2c+Giacomo%22+6602920646%29&relpos=11&relpos=11&searchTerm=AU-ID(\"Benassai, Giacomo\" 6602920646) ------ An open-label prospective, randomized, parallel multicentre study was undertaken to compare the efficacy and tolerability of 1.5 g/day intravenous imipenem/cilastatin with 3 g/day intravenous meropenem in the treatment of intra-abdominal infections, A total of 287 patients mere enrolled; 201 patients, divided between the 2 treatment groups, were evaluable. Clinical outcome, bacteriological outcome, untoward microbiological effects, and clinical and laboratory adverse experiences mere evaluated, 98% of patients receiving imipenem/cilastatin therapy mere cured, with 96% showing eradication of infection, 95% of those on meropenem mere cured, with 98% showing eradication. These differences in clinical and bacteriological outcome between the 2 treatments were not statistically significant, Two patients receiving imipenem/cilastatin and 5 receiving meropenem had untoward microbiological effects. There mas a 0.7% frequency (1/139 patients) of possibly or probably drug-related clinical or laboratory adverse experiences with imipenem/cilastatin and a 2.7% frequency (4/148) with meropenem, The mean time to defervescence was significantly less for patients in the imipenem/cilastatin treatment group than for those receiving meropenem. This study shows that 1.5 g/day of imipenem/cilastatin is equivalent to 3.0 g/day meropenem in clinical and bacteriological outcome, as well as in incidence of side effects.

Twenty-five patients with ileo-anal "reservoir" have been evaluated by clinical examination, manometry, proctography, endoscopy and biopsy, at least six months from the closure of ileostomy. 80% of them presented with a satisfactory condition, although only one third reached a normal function; 20% suffered for one or more dysfunctions which lead to a variable degree of social handicap. The most frequent dysfunctions were incontinence (13 patients), urgency (10), frequency (9), pouchitis (6), incapacity to evacuate (2). The mean values at manometry showed a halved anal tone, a slightly impaired external sphincter, a halved compliance of the pouch in comparison to normal rectum. Radiology demonstrated that half the patients with dysfunctions had a reduced motility of the pouch and anomalies in sphincter coordination. Endoscopy and biopsies demonstrated inflammation in 12 patients and 6 of them developed an acute pouchitis. From a general point of view, apart from particular conditions, it has been impossible to correlate clinical dysfunctions with a specific abnormality at the instrumental evaluation. Therefore, while good results are assumed to be due to a normally restored anatomical and motility condition, we must recognize that most clinical dysfunctions are not univocally correlated to abnormalities of the pouch or of the sphincteric apparatus.

AIM: The aim of this study was to evaluate the role of 18F fluorodeoxyglucose-positron emission tomography (FDG-PET), differentiated thyroid carcinoma (DTC) treated with therapeutic (131)I because of elevated thyroglobulin (Tg) levels during follow up. The results of FDG-PET/CTwere compared with post-therapy (131)I whole body scan (131I-t-WBS) and Tg at short term follow up. METHODS: Forty-five patients with DTC underwent a new therapeutic (131I) administration based upon Tg values >1.5 ng/mL. All patients underwent (131I-t-WBS) 5-7 days after 131I therapy. A few days before 131I administration, a FDG-PET scan was performed in all patients. FDG-PET/CT was considered positive (PET+) when at least one abnormal focus of FDG uptake was found; likewise, 131I-t-WBS was considered positive(WBS+) when at least on abnormal focus of uptake was found. Assessment of short-term response to radioiodine was performed by measuring Tg values. RESULTS: FDG-PET/CT was positive in 32 patients, 23 of which had positive 131I-t-WBS and negative in 13, 8 of which had a negative 131I-t-WBS. Overall agreement was 69%. Tg values were significantly higher in FDG-PET/CT positive (502+/-1 027 ng/mL) than in FDG-PET/CT negative patients(57+/-94 ng/mL). A significant difference emerged between 131I-t-WBS positive (561 +/- 1 086 ng/mL) and 131I-t-WBS negative (65+/- 120 ng/mL) findings. In these 45 patientsTg normalized in 36%, was reduced by at least 50% in 24% and remained unchanged in the remaining 40%. Overall, at short-term follow-up, Tg values normalized in 77% of the 13 patients with negative FDG-PET/CT and in 19% of the 32 patients with positive FDG-PET/CT. CONCLUSION: FDG-PET/CTis a powerful and useful tool for assessing patients with DTC. it can provide additional information in those patientswith high Tg at follow-up and eligible for 131I therapy. A negative FDG-PET/CT could also represent a prognostic tool combined with serum Tg testing a short term follow-up.

12 patients were investigated with IC (Datex, Deltatrac) preoperatively and during the surgical procedure of OLTX, VO2, VCO2 were continuously measured and RQ, EE and SU were calculated considering the different periods of the procedure: preoperative resting EE: (PREE), anaesthesiological procedures (ANEE), liver preparation EE (LPEEE), liver removal EE (LREE), anhepatic phase EE (APEE), reperfusion, EE (RPEE) and end of operation EE (EOEE). EE were expressed as % respect value calculated with H.B. (Harris-Benedict) formula. Data were analyzed with Student T-test and p0.01** or0.05* PREE is typical in end stage liver disease with low RQ values and increased EE. Energy production depends on lipid utilization since liver gluconeogenesis and glycogen stores are impaired. Anesthesia reduces energy needs and production up to 50% of the preoperative values, reducing VO2 more than VCO2 and therefore an augmented RQ value over 1.0. SU analysis indicates an increased glucose and aminoacid utilization coupled with high nitrogen catabolism that continues in the postoperative period (from 0.08 0.01 gN/kg b.w. to 0.20 0.06 gN/kg b.w.). When the new liver is reperfused, VO2 increases more than VCO2 indicating the risk of reperfusion injury.

Primary hyperparathyroidism is the most common cause of hypercalcemia and 80-85% of the patients have parathyroid tumors. The purpose of this retrospective review was to analyse whether differences exist between patients with parathyroid tumors treated in the 1980s and 1990s. Between 1980-1997, 253 patients underwent initial surgical neck exploration for hyperfunctioning parathyroid tumors. Renal (polyuria, nocturia, renal colic due to lithiasis), rheumatologic (bone and joint pain), neurological (fatigue, memory loss, depression) and gastrointestinal (dyspepsia, anorexia, nausea) symptoms were recorded and main biochemical parameters were measured. In all patients one or more preoperative localization procedures were carried out prior to successful parathyroidectomy, and the confirmation of imaging findings was obtained after surgery. The patients were divided in two groups. Group A: 121 (47.8%) patients who underwent surgery from 1980-1989; Group B: 132 (52.2%) patients in whom parathyroidectomy was performed from 1990-1997. There were no differences (p=NS) between the two groups in average age, preoperative serum creatinine and intact-PTH levels. Symptoms were most common in Group A, and pre-operative serum calcium levels were significantly lower in Group B. Ultrasonography (n=191) sensitivity did not improve significantly (82.8% vs 82.9%), but positive predictive value (PPV) was higher (89.8% vs 96.0%). CT-scan (n=73) sensitivity was 79.2% and 82.6%, and PPV was 95.0% and 100% in Groups A and B, respectively. 201Tl/99mTc subtraction scintigraphy (n=111, Group A) was 84.6% sensitive (PPV=92.6%) whereas 99mTc-sestamibi scanning (n=90, Group B) was 85.1% sensitive (PPV=96.1%). In conclusion, the clinical features of parathyroid tumors has changed in the nineties and increasing asymptomatic pHPT rate has been found. Although sensitivity and PPV of preoperative localization procedures has improved moderately, at present noninvasive techniques may offer excellent results and should be used in all patients with suspected parathyroid tumors.

Objective To assess the efficacy of recombinant human erythropoietin (rhEPO) in amyotrophic lateral sclerosis (ALS). Methods Patients with probable laboratory-supported, probable or definite ALS were enrolled by 25 Italian centres and randomly assigned (1:1) to receive intravenous rhEPO 40 000 IU or placebo fortnightly as add-on treatment to riluzole 100 mg daily for 12 months. The primary composite outcome was survival, tracheotomy or >23 h non-invasive ventilation (NIV). Secondary outcomes were ALSFRS-R, slow vital capacity (sVC) and quality of life (ALSAQ-40) decline. Tolerability was evaluated analysing adverse events (AEs) causing withdrawal. The randomisation sequence was computer-generated by blocks, stratified by centre, disease severity (ALSFRS-R cut-off score of 33) and onset (spinal or bulbar). The main outcome analysis was performed in all randomised patients and by intentionto-treat for the entire population and patients stratified by severity and onset. The study is registered, EudraCT 2009-016066-91. Results We randomly assigned 208 patients, of whom 5 (1 rhEPO and 4 placebo) withdrew consent and 3 ( placebo) became ineligible (retinal thrombosis, respiratory insufficiency, SOD1 mutation) before receiving treatment; 103 receiving rhEPO and 97 placebo were eligible for analysis. At 12 months, the annualised rate of death (rhEPO 0.11, 95% CI 0.06 to 0.20; placebo: 0.08, CI 0.04 to 0.17), tracheotomy or >23 h NIV (rhEPO 0.16, CI 0.10 to 0.27; placebo 0.18, CI 0.11 to 0.30) did not differ between groups, also after stratification by onset and ALSFRS-R at baseline. Withdrawal due to AE was 16.5% in rhEPO and 8.3% in placebo. No differences were found for secondary outcomes. Conclusions RhEPO 40 000 IU fortnightly did not change the course of ALS.

True spleen cysts are uncommon and rarely associated with elevated serum and intracystic tumor markers CA 19-9 and CEA levels. A 19-year-old woman with a left subcostal mass was observed. Echinococcus granulosus serology was negative, and serum tumor markers CA 19-9 and CEA levels were 273 kU/L and 33 ng/mL, respectively. CT-scanning showed a splenic cyst of 18 cm in greatest diameter. The patient underwent total laparoscopic splenectomy and the serum tumor markers progressively decreased and became normal three months after surgery. Splenic cysts derive from an invagination of the splenic capsule in the splenic pulp with a subsequent squamous metaplasia. This last evidence could be confirmed from the variable cellular differentiation lines of the mesothelial squamous cells in the cyst wall. We should not exclude a higher degenerative potential of cystic epithelium that produces de-differentiation proteins. The lowering of the serum levels of the two markers after the cyst removal is witness of the direct relationship between the increment of the serum tumor markers and the presence of the epidermoid cyst.

We analyse the costimulating role of CD40/CD40 ligand and B7/CD28 in inflammatory bowel diseases (IBD) as a potential target of antibody therapy. CD40, expressed by lamina propria B lymphocytes in gut mucosa, interacts with CD40 ligand on T cell. This interaction is implicated in the pathogenesis of IBD. In some animal models of colitis the anti-CD40L therapy demonstrated to be effective. Phase II trials on Crohn's disease are ongoing. B7.1 and B7.2, expressed by macrophages, interact with CD28, on T cell. B7.2 resulted implicated in ulcerative colitis, determining a Th2 pattern, whereas B7.1, a major Th1 stimulator, could be involved in Crohn's disease. In some animal models of colitis anti-B7.1, but not anti-B7.2, was effective. Anti B7 therapy was not yet tested in humans.

Interactions between blood pressure control, sleep and headache have been largely studied, although not well understood. We designed a study trying to simultaneously evaluate all three aspects in the same subjects. We particularly concentrated on the observation of physiological blood pressure circadian rhythm, and the presence of cutaneous allodynia correlated to headache. Objective of the study was to investigate blood pressure during nocturnal sleep in patients that underwent a blood pressure 24 hours monitoring, and at the same time the presence of headache and of sleep behavioural alterations.Blood pressure 24 hours monitoring was performed by an ambulatory blood pressure (ABP) monitor (Space Labs) with its ad hoc software. Headache diagnosis was made according to ICHD-II criteria. Presence of allodynia and sleep behavior were evaluated through semi-structured ad hoc questionnaires.A total of 195 subjects were included, of which 122 without headache (mean age 60.4±11.6 years, 78 men and 44 women) and 73 with history of headache, (mean age 54.2±12.5 years, 18 men and 55 women). Fifty-one headache patients had migraine (mean age 52.6±11.7 years, 11 men and 40 women) and 22 tension type headache (TTH - mean age 58.0±13.5 years, 7 men and 15 women). Allodynia was found in 30 out of 73 headache patients: 23 out of 51 in the migraine group and in 7 out of 22 in the tension-type one. The physiological reduction of blood pressure during night (dipping) was more conserved among headache patients (34 dippers out of 73 subjects, 46,6%) with respect to subjects without headache (40 dippers out of 122, 32,8%) and that this border-line difference was more strongly significant comparing allodynic subjects (19 dippers out of 30, 63.3%) with both non-headache (40 dippers out of 122, 32.8%, P0.001) and non-allodynic (15 out of 43, 34.9%, P0.05) ones. No significant difference was observed between headache patients and subjects without headache in terms of mean systolic and diastolic pressure, neither between migraine and TTH.Allodynic headache patients seem to maintain a more physiologic pressure circadian rhythm. While considering the possibility of selection bias, the hypothesis of an allostatic function of headache and allodynia in patients with unbalanced blood pressure could be made.

Factor VII coagulant, prothrombine time, fibrinogen, prealbumin and a fetoprotein have been evaluated in a patient operated on for right hepatectomy, in order to identify the best markers in prognosing liver regeneration. Factor VII and prothrombine time progressively increased, starting from the 5th-7th day, entering normal range by the 10th and demonstrated a good correlation with both liver scintiscan and ultrasonography. Prealbumin and fibrinogen did not provide any useful information and a fetoprotein levels progressively decreased, demonstrating the complete removal of the neoplastic tissue. Factor VII and prothrombine time seem therefore to be the most reliable markers, among those investigated in this study, of liver regeneration after partial hepatectomy.

Thermal homeostasis represents the major issue during liver transplantation (OLT) since severe hypothermia may have a deleterious effect on both liver recipient organism and postoperative graft functioning. Because of the known negative influence of hypothermia on intraoperative cardiovascular activity and coagulation system, numerous methods have been suggested to reduce intraoperative heat loss and promote active warming (continuous temperature monitoring, external heat sources, improvement in surgical technique and technologies). A good intraoperative OLT course has an obvious influence on post OLT graft function recovery, but thermal homeostasis has also an essential direct effect on the graft as a constitutive component of conventional cold preservation methods. Hypothermia, however, contributes directly to the graft ischemia-reperfusion injury particularly in marginal and partial organs by several angiogenic mechanisms. For these reasons, on the light of the development of new strategies to increase the donor pool, clinical research is focusing on new preservation methods such as extracorporeal circuits with normothermic oxygenated perfusion.

Background The degree to which work-related difficulties are recognized in headache research is poor and often carried out with inadequate information such as “reduced ability to work as usual”, which do not capture at all the variety of difficulties and the factors that impact over them. The aim of this paper is to present the validation of the HEADWORK questionnaire, which addresses the amount and severity of difficulties in work-related tasks and the factors that impact over them. Methods We developed a set of items based on a previous literature review and patients’ focus groups and tested it on a wide set of patients with episodic and chronic migraine attending eight different Italian headache centers. HEADWORK factor structure was assessed with exploratory and confirmatory factor analysis; internal consistency and construct validity were addressed as well. Results The validation sample (N = 373) was mostly composed of patients with episodic migraine without aura (64.3%) and of females (81%). Factor analysis retrieved two different scales: “Work-related difficulties”, composed of eleven items which explain 67.1% of the total variance, and “Factors contributing to work difficulties”, composed of six items which explain 52.1% of the total variance. Both HEADWORK subscales have good measurement properties, with higher scores being associated to higher disability, lower quality of life, lower productivity, higher headache frequency and pain intensity. Conclusions HEADWORK is a 17-item, two-scale questionnaire addressing the impact of migraine on work-related difficulties in terms of difficulties in general or specific skills, and the factors contributing to these difficulties, defined as negative impact on work tasks. It can be used to address disability weights for the purpose of calculating the burden of migraine, and to assess the balance between therapeutic and side effects of medication on productivity.

BACKGROUND: There is good evidence that radiotherapy is beneficial in advanced rectal cancer, but its application in Italy has not been investigated. METHODS: We conducted a nationwide survey among members of the Italian Society of Colo-Rectal Surgery (SICCR) on the use of radiation therapy for rectal cancer in the year 2005. Demographic, clinical and pathologic data were retrospectively collected with an online database. Italy was geographically divided into 3 regions: north, center and south which included the islands. Hospitals performing 30 or more surgeries per year were considered high volume. Factors related to radiotherapy delivery were identified with multivariate analysis. RESULTS: Of 108 centers, 44 (41%) responded to the audit. We collected data on 682 rectal cancer patients corresponding to 58% of rectal cancers operated by SICCR members in 2005. Radiotherapy was used in 307/682 (45.0%) patients. Preoperative radiotherapy was used in 236/682 (34.6%), postoperative radiotherapy in 71/682 (10.4%) cases and no radiotherapy in 375 (55.0%) cases. Of the 236 patients who underwent preoperative radiotherapy, only 24 (10.2%) received short-course radiotherapy, while 212 (89.8%) received long-course radiotherapy. Of the 339 stage II-III patients, 159 (47%) did not receive any radiotherapy. Radiotherapy was more frequently used in younger patients (P < 0.0001), in patients undergoing abdominoperineal resection (APR) (P < 0.01) and in the north and center of Italy (P < 0.001). Preoperative radiotherapy was more frequently used in younger patients (P < 0.001), in large volume centers (P < 0.05), in patients undergoing APR (P < 0.005) and in the north-center of Italy (P < 0.05). CONCLUSION: Our study first identified a treatment disparity among different geographic Italian regions. A more systematic audit is needed to confirm these results and plan adequate interventions.

AIDA Cefalee is a database for the management of headache patients developed on behalf of the Italian Neurological Association for Headache Research (ANIRCEF). The system integrates a diagnostic expert system able to suggest the correct ICHD-II diagnosis once all clinical characteristics of a patient's headache have been collected. The software has undergone a multicentre validation study to assess: its diagnostic accuracy; the impact of using the software on visit duration; the userfriendliness degree of the software interface; and patients' acceptability of computer-assisted interview. Five Italian headache centres participated in the study. The results of this study validate AIDA Cefalee as a reliable diagnostic tool for primary headaches that can improve diagnostic accuracy with respect to the standard clinical method without increasing the time length of visits even when used by operators with basic computer experience.

Psychiatric comorbidity (prevalence and types) was tested in a naturalistic sample of adult patients with pure migraine without aura, and in two control groups of patients, one experiencing pure tension-type headache and the other combined migraine and tension-type headaches. The study population included 374 patients (158, 110 and 106) from nine Italian secondary and tertiary centres. Psychiatric comorbidity was recorded through structured interview and also screened with the Mini International Neuropsychiatry Interview (MINI). Only anxiety and depression were investigated. Psychiatric disorders were reported by 49 patients (14.6%; 10.9% of patients with migraine, 12.8% of those with tension-type headache and 21.4% of those with combined migraine and tension-type headaches). The MINI interview detected a depressive episode in 59.9% of patients with migraine, 68.3% of patients with tension-type headache and 69.6% of patients with combined migraine and tension-type headaches. Depression subtypes were significantly different across groups (p=0.03). Anxiety (mostly generalised) was reported by 18.4% of patients with migraine, 19.3% of patients with tension-type headache, and 18.4% of patients with combined migraine and tension-type headaches. The values for panic disturbance were 12.7, 5.5 and 14.2, and those for obsessive-compulsive disorders were 2.3, 1.1 and 9.4% (p=0.009). Based on these results, psychopathology of primary headache can be a reflection of the burden of the disease rather than a hallmark of a specific headache category.

Cachexia is a multifactorial and multi-organ syndrome that is a major cause of morbidity and mortality in late-stage chronic diseases. The main clinical features of cancer-related cachexia are chronic inflammation, wasting of skeletal muscle and adipose tissue, insulin resistance, anorexia, and impaired myogenesis. A multimodal treatment has been suggested to approach the multifactorial genesis of cachexia. In this context, physical exercise has been found to have a general effect on maintaining homeostasis in a healthy life, involving multiple organs and their metabolism. The purpose of this review is to present the evidence for the relationship between inflammatory cytokines, skeletal muscle, and fat metabolism and the potential role of exercise training in breaking the vicious circle of this impaired tissue cross-talk. Due to the wide-ranging effects of exercise training, from the body to the behavior and cognition of the individual, it seems to be able to improve the quality of life in this syndrome. Therefore, studying the molecular effects of physical exercise could provide important information about the interactions between organs and the systemic mediators involved in the overall homeostasis of the body.

OBJECTIVE To clarify whether the clinical response after the first 2 cycles with Onabotulinumtoxin A can accurately predict the long-term response. BACKGROUND Onabotulinumtoxin-A (OBT-A) is an approved preventive treatment option for chronic migraine (CM). Nowadays, it remains to be clarified if the treatment has to be prolonged for at least an entire year (4 injections every 3 months - ie, quarterly, as proposed in the PREEMPT trials) or it can be halted after the second or third injection if not clinically effective. DESIGN AND METHODS We conducted a multicenter observational cohort study based on real-life data on the usage of OBT-A in CM patients from 2 Italian headache centers, Roma Campus Bio-Medico and Milano Besta, adopting the whole 4-injections protocol. We performed a retrospective analysis of medical records of consecutive patients treated in the 2 centers. The main statistical analysis aimed to evaluate longitudinal measures related to headache (monthly headache frequency, monthly number of analgesic drugs, MIDAS). We hypothesized from our clinical practice with OBT-A that only 2 cycles of treatment were not enough to actually define the non-responder status to botulinum toxin A and that probably a longer time of treatment is needed to get the condition of long-term (delayed) responder. RESULTS We considered 115 patients from the 2 centers: 53 in Roma and 62 in Milano. Regarding the main analysis, a clear improvement in each measure was obtained at the 6 months assessment and maintained up to 12 months. Comparing patients with

Metastases to pituitary gland, suprasellar region or skull base from endometrial carcinoma are an extremely rare occurrence. We report the case of a 77-year-old woman with metastasis to the sellar/suprasellar region from endometrial carcinoma revealed by F-18-FDG PET/CT and confirmed by subsequent CT and MRI of the brain. This case highlights the usefulness of a whole-body imaging methodology such as F-18-FDG PET/CT in the detection of distant and/or atypical sites of metastasis therefore being of help in guiding towards the correct diagnosis.

To optimize chronic migraine (CM) ascertainment and phenotype definition, provide adequate clinical management and health care procedures, and rationalize economic resources allocation, we performed an exploratory multicenter pilot study aimed at establishing a CM database, the first step for developing a future Italian CM registry. We enrolled 63 consecutive CM patients in four tertiary headache centers screened with face-to-face interviews using an ad hoc dedicated semi-structured questionnaire gathering detailed information on life-style, behavioral and socio-demographic factors, comorbidities, and migraine features before and after chronicization and healthcare resource use. Our pilot study provided useful insights revealing that CM patients (1) presented in most cases symptoms of peripheral trigeminal sensitization, a relatively unexpected feature which could be useful to unravel different CM endophenotypes and to predict trigeminal-targeted treatments’ responsiveness; (2) had been frequently admitted to emergency departments; (3) had undergone, sometime repeatedly, unnecessary or inappropriate investigations; (4) got rarely illness benefit exemption or disability allowance only. We deem that the expansion of the database—shortly including many other Italian headache centers—will contribute to more precisely outline CM endophenotypes, hence improving management, treatment, and economic resource allocation, ultimately reducing CM burden on both patients and health system.

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Although anti-endomysial antibodies (EmA) have been found in the supernatants of cultured intestinal mucosa from patients with coeliac disease (CD), in no study has the clinical reliability of this new diagnostic tool been investigated. Our aims were to evaluate the clinical usefulness of the in vitro production of EmA in CD diagnosis in consecutive patients with suspected CD, and to evaluate the reliability of the in vitro challenge in CD patients on a gluten-free diet (GFD).For the former aim, consecutive patients who were due to undergo intestinal biopsy for suspected diagnosis of CD were enrolled: according to the final diagnosis, these patients were divided into two groups: Group 1 comprised 91 newly diagnosed CD patients (40 males; age range 7 months to 84 years), Group 2 included 100 subjects with diseases other than CD (44 males; age range 9 months to 76 years). For the latter aim, we also studied 21 CD patients on a gluten-free diet after 16-123 months (8 males; age range 3-51 years), with normal intestinal architecture (Group 3) and 22 patients who served as controls (12 males; age range 4-60 years) with gastroesophageal reflux disease-like symptoms (Group 4). All patients underwent determination of serum anti-gliadin (AGA) and EmA antibodies, histology evaluation of the intestinal biopsies and EmA assay in the supernatants of in vitro gliadin-challenged duodenal mucosa.EmA assay in the supernatants showed a sensitivity and specificity of 96% and 100%, respectively; these were not significantly different from those observed for serum EmA (88% and 99%, respectively). However, EmA assay in the supernatants was useful in CD patients with mild intestinal histology lesions (infiltrative/hyperplastic type): in this subgroup it was positive in 9/12 of cases, but serum EmA was positive in only 2/12. As regards the reliability of the in vitro gliadin challenge, EmA production in supernatants was recorded only in 10/21 CD patients on a gluten-free diet. The patients with a positive in vitro challenge had a higher number of intra-epithelial lymphocytes than patients with a negative challenge.1) EmA assay in the medium of cultured intestinal biopsy can detect gluten-sensitive enteropathy, characterized by an infiltrative/hyperplastic histological pattern, which is often associated with negative serum EmA. 2) The in vitro challenge in CD patients on a gluten-free diet detects EmA production in the culture medium only in half of the cases and other studies must be performed to evaluate whether EmA production after in vitro challenge can be considered a reliable test for confirming CD diagnosis.

PURPOSE:The aim of this study was to assess independent predictors of 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F-FDG) uptake in brown adipose tissue (BAT) in patients undergoing repeated positron emission tomography (PET)/computed tomography (CT) scans. PROCEDURES:Eight hundred forty-eight (mean age 50.9 ± 16 years) patients in whom PET/CT scan was repeated (mean interval 5 ± 1.5 months) constituted the study group. (18)F-FDG uptake in characteristic areas of BAT, with CT density of adipose tissue, greater than background soft-tissue activity was considered as evidence of BAT uptake. Both distribution and maximum standardized uptake values (SUVmax) were registered. Clinical and anamnestic data were collected for each patient. RESULTS:(18)F-FDG uptake in BAT was present in 8.6% patients at first scan. Independent predictors of presence of uptake were age (younger), gender (female), body mass index (lower), and maximum outdoor temperature (lower). Age was the only independent predictor of BAT (18)F-FDG uptake distribution, while SUVmax was related to both age and outdoor temperature. Independent determinants of persistence of BAT (18)F-FDG uptake at second PET/CT were outdoor temperature at time of second scan and extension of metabolically active BAT at first scan. CONCLUSIONS:Age, body mass index, and outdoor temperature are significant determinants of BAT evidence at (18)F-FDG PET/CT. Moreover, extension of BAT and outdoor temperature are the strongest determinants of persistence of BAT evidence on (18)F-FDG PET/CT in repeated scan.

The objective of this paper was to assess prevalence and characteristics of anxiety and depression in migraine without aura and tension-type headache, either isolated or in combination. Although the association between headache and psychiatric disorders is undisputed, patients with migraine and/or tension-type headache have been frequently investigated in different settings and using different tests, which prevents meaningful comparisons. Psychiatric comorbidity was tested through structured interview and the MINI inventory in 158 adults with migraine without aura and in 216 persons with tension-type headache or migraine plus tension-type headache. 49 patients reported psychiatric disorders: migraine 10.9%, tension-type headache 12.8%, and migraine plus tension-type headache 21.4%. The MINI detected a depressive episode in 59.9, 67.0, and 69.6% of cases. Values were 18.4, 19.3, and 18.4% for anxiety, 12.7, 5.5, and 14.2%, for panic disorder and 2.3, 1.1 and 9.4% (p = 0.009) for obsessive–compulsive disorder. Multivariate analysis showed panic disorder prevailing in migraine compared with the other groups (OR 2.9; 95% CI 1.2–7.0). The association was higher (OR 6.3; 95% CI 1.4–28.5) when migraine (with or without tension-type headache) was compared to pure tension-type headache. This also applied to obsessive–compulsive disorder (OR 4.8; 95% CI 1.1–20.9) in migraine plus tension-type headache. Psychopathology of primary headache can reflect shared risk factors, pathophysiologic mechanisms, and disease burden.

Introduction. Long-term steroid administration may predispose liver transplant recipients to infectious and metabolic complication. Maintaining effective immunoprophylaxis while minimizing the negative consequences of steroid therapy could be a key factor in improving clinical outcomes.Methods. Six hundred two patients were randomized to receive tacrolimus (TAC) immunosuppression with a single-steroid bolus and two doses of daclizumab (DAC) or mycophenolate mofetil (MMF).Results. The incidence of biopsy-proven acute rejection was 19.7% in the TAC/DAC group and 16.2% in the TAC/ MMF group (ns). Three-month patient and graft survival were similar. Steroid use at month-3 was low at 5.5% in the TAC/DAC group and 3.9% in the TAC/MMF group. Significantly higher incidences of causally related adverse events (AEs) and significantly more dose modifications, interruptions, or discontinuations due to an AE were reported with TAC/MMF. Study withdrawal due to leucopenia was significantly higher with TAC/MMF (0.0% vs. 1.7%. P = 2 fasting plasma glucose values >= 7.0 mmol/L) were low at 9.5% (TAC/DAC) and 11.0% (TAC/MMF).Conclusion. Both TAC-based regimens allowed optimization of immunoprophylaxis while eliminating some of the negative consequences associated with steroids. Efficacy outcomes were comparable; however, TAC monotherapy after DAC induction was associated with significantly less leucopenia and less bacterial infection than a dual regimen incorporating MMF.

Summary Gemtuzumab ozogamicin (GO) is a humanized anti-CD33 antibody conjugated with the cytotoxic drug calicheamicin and approved for the treatment of relapsed acute myeloid leukaemia. As approximately 18% of acute lymphoblastic leukaemias (ALL) are also CD33 positive, we have investigated the cytotoxic activity of GO on CD33+ ALL cells in vitro and in vivo. 10 ng/ml GO induced 30–95% inhibition of thymidine uptake and 30–70% cell death in four freshly isolated and one in vivo passaged CD33+ ALL-cell cultures. Furthermore, an in vivo model of a CD33+ ALL carrying the Philadelphia chromosome [t(9;22)] was established. 5 × 106 ALL-2 cells inoculated in the tail vein of severe combined immunodeficient mice engrafted into haematopoietic organs, reaching a mean of 70%, 61% and 69% human CD45+ cells in bone marrow, spleen and liver, respectively, at 35 d. To test the therapeutic activity of GO, 50 or 100 μg immunotoxin was inoculated i.p. on days 7, 11 and 15 following tumour-cell inoculation. GO treatment dramatically inhibited expansion of ALL-2 cells in all tested organs and increased survival of tumour-injected animals by 28–41 d, relative to controls. These data demonstrated that GO is active both in vitro and in vivo against CD33+ ALL cells.

Background/Aims : Prognosis assessment in patients with hepatocellular carcinoma (HCC) remains controversial. The most widely used HCC prognostic tool is the Okuda classification, but new staging systems (Cancer of the Liver Italian Program score, Chinese University Prognostic Index, French classification and Barcelona Clinic Liver Cancer, BCLC, staging) have been recently described. We investigated the value of known prognostic systems in the particular setting of a surgically oriented Liver Unit where 187 HCC Italian patients were mainly treated with radical therapies (resection and percutaneous ablation). Methods : A retrospective analysis of 187 HCCs observed at a single Institution from 1990 and 1999 was performed. By using survival time as the only outcome measure (Kaplan–Meier method and Cox regression), the performance of any prognostic system was assessed according the criteria of discriminatory and stratification abilities between different stages, homogeneity of survival within each stage and additional explanatory power respect to the other classifications. Results : In the particular cohort studied, BCLC proved the best HCC prognostic system. This was true for the whole study group and for the 2 subgroups of surgical and non-surgical patients. Conclusions : BCLC staging showed the best interpretation of the survival distribution in an HCC population comprising a large proportion of tumors treated with potentially radical therapies.