Persistence of bDMARD therapy in Rheumatoid Arthritis after first-line TNF-inhibitor failure: the RECORD study of the Italian Society for Rheumatology.

OBJECTIVE: The optimal choice of a second biological disease-modifying anti-rheumatic drug (bDMARD) after failure with first line tumour necrosis factor inhibitor (TNFi) represents a critical therapeutic challenge. This study aims to evaluate the persistence with treatment using second line bDMARDs with different mechanisms of action in rheumatoid arthritis (RA) patients with inadequate response to first line TNFi. METHOD: A retrospective cohort study on administrative healthcare databases was conducted. We analysed the relationship between different bDMARDs and persistence with treatment in RA patients who started second line bDMARD therapy according to two different strategies: cycling (second TNFi) or switching [change in mechanism of action: abatacept (ABA), tocilizumab (TCZ), and rituximab (RTX)] with or without concomitant conventional synthetic (cs) DMARDs. RESULTS: The cohort comprised 1434 patients. The mean age was 53.8 years and 1142 (79.6%) were women. Among second line bDMARDs, 969 patients (67.6%) started TNFi, 204 (14.2%) ABA, 145 (10.1%) RTX, and 116 (8.1%) TCZ. A bDMARD was prescribed as monotherapy in 359 patients (25.0%). The switching strategy showed a lower overall discontinuation rate [hazard ratio (HR) 0.72], while switching compared to cycling showed significantly better survival for ABA (HR 0.61) and RTX (HR 0.76), but no significant difference for TCZ (HR 0.82). A lower impact of better drug survival in the switching strategy occurred in patients with concurrent methotrexate. CONCLUSIONS: Among RA patients failing a first TNFi, switching is associated with marginally better persistence, in particular for ABA and RTX, with only marginal differences in patients on concurrent csDMARDs.

A phase II trial of short course fludarabine, mitoxantrone, rituximab followed by 9°Y-ibritumomab tiuxetan in untreated intermediate/high-risk follicular lymphoma.

BACKGROUND: A prospective, single-arm, open-label, multicenter, nonrandomised phase II trial to evaluate efficacy and safety of short fludarabine, mitoxantrone, and rituximab (FMR) induction followed by radioimmunotherapy, in untreated, intermediate/high-risk follicular non-Hodgkin's lymphoma (NHL) patients. PATIENTS AND METHODS: Fifty-five patients were treated using a sequential treatment schedule of four induction cycles of FMR chemoimmunotherapy, and a subsequent consolidating single administration of (90)Y-ibritumomab tiuxetan ((90)Y-IT), 8-14 weeks later. Patients were eligible for radioimmunotherapy if at least in partial response (PR) after induction, with normal platelet and granulocyte counts and a bone marrow infiltration ≤ 25%. Primary study end points were response rate and hematologic toxic effects; secondary end points were overall survival (OS) and progression-free survival (PFS). RESULTS: All the 55 patients received four induction cycles with an overall response rate of 96% (38 complete responses [CR] and 15 PR). Fifty-one patients (38 in CR and 13 in PR) received (90)Y-IT. By the end of the treatment, 49/55 patients achieved a CR. With a median follow-up of 21 months, the estimated 3-year PFS was 81% and the 3-year OS 100%. CONCLUSIONS: This study has established feasibility, tolerability, and efficacy of a regimen composed by short FMR induction with (90)Y-IT consolidation in untreated intermediate/high-risk follicular NHL patients.

Gemcitabine as single agent in pretreated T-cell lymphoma patients: evaluation of the long-term outcome.

BACKGROUND: Peripheral T-cell lymphoma unspecified (PTCLU) and mycosis fungoides (MF) often show resistance to conventional chemotherapy. Gemcitabine should be considered a suitable option. We report the long-term update of 39 pretreated T-cell lymphoma patients treated with gemcitabine. PATIENTS AND METHODS: From May 1997 to September 2007, 39 pretreated MF and PTCLU patients received gemcitabine. Inclusion criteria were as follows: histologic diagnosis of MF or PTCLU; relapsed/refractory disease; age > or =18 years; and World Health Organization performance status of two or less. Nineteen patients had MF and 20 PTCLU. All patients with MF had a T3-T4, N0, and M0 disease and patients with PTCLU had stage III-IV disease. Gemcitabine was given on days 1, 8, and 15 on a 28-day schedule (1200 mg/m(2)/day) for a total of three to six cycles. RESULTS: Overall response rate was 51% (20 of 39 patients); complete response (CR) and partial response (PR) rates were 23% (9 of 39 patients) and 28% (11 of 39 patients), respectively. Patients with MF had a CR rate of 16% and a PR rate of 32% compared with a CR rate of 30% and a PR rate of 25% of PTCLU patients. Among the CR patients, 7 of 9 are in continuous complete response with a variable disease-free interval (15-120 months). CONCLUSION: In our experience, gemcitabine proved to be effective in pretreated MF and PTCLU patients, even in the long term.

First salvage treatment with bendamustine and brentuximab vedotin in Hodgkin lymphoma: a phase 2 study of the Fondazione Italiana Linfomi.

Effective salvage options inducing high complete metabolic response (CMR) rates without significant toxicity are needed for Hodgkin lymphoma (HL) patients failing induction treatment and who are candidate to autologous stem cell transplantation (ASCT). Brentuximab vedotin (BV) and bendamustine are active monotherapies in the relapsed/refractory setting and their combination (the BBV regimen) possibly enhances their activity. This single-arm multicenter phase 2 study investigated the efficacy and safety of BBV as first salvage therapy in 40 patients with relapsed/refractory HL. Thirty-eight patients were evaluable for efficacy: 30 (78.9%) had a CMR and 2 (5.3%) a partial response, leading to an overall response rate (ORR) of 84.2%. The ORR in the primary refractory subset was 75.0%, among relapsed patients it was 94.4%. Thirty-five patients could mobilize peripheral blood stem cells and 33 underwent ASCT. At a median follow-up of 23 months, the estimated 3-year overall survival and progression-free survival are 88.1% and 67.3%. During therapy, only 3 grade IV cases of neutropenia occurred and resolved within a week. No grade 4 extrahematologic toxicities were reported; skin reactions were however rather frequent (65%). These results suggest that the BBV regimen exhibits promising efficacy and a manageable toxicity in a challenging subpopulation of HL patients.

[Role of MR cholangiopancreatography in the evaluation of biliary disease]. / II ruolo della colangiopancreatografia a risonanza magnetica nello studio della patologia biliare.

PURPOSE: To evaluate the diagnostic accuracy of MR cholangiopancreatography (MRCP) in biliary tree patology in comparison with percutaneous transhepatic cholangiography (PTC), endoscopic retrograde cholangiopancreatography (ERCP) and surgical findings. MATERIALS AND METHODS: Forty-six patients , with clinical and laboratory findings suggestive of biliary tree pathology, and after an abdominal US, underwent MRCP with a 1.5 T superconductive magnet equipped with a phased-array body coil. MR exam was performed with baseline sequences for the examination of the upper abdomen, followed by specific MRCP sequences and, in cases of suspected neoplastic disease, completed with abdominal sequences after a bolus injection of paramagnetic contrast. RESULTS: MRCP showed normal findings in 16/46 patients, biliary duct dilatation in 25/46 patients (7 choledocolithiasis, 10 benign obstructions and 8 neoplastic stenoses) and stenoses without dilatation of biliary tree in 5/46 patients. In 25 patients with biliary duct dilatation, CPRM correctly identified the level of in 100% of patients (25/25) and the nature in 88% of patients (22/25). In 5 patients with stenosis without dilatation of biliary tree, CPRM identified 2 true positives (sclerosing cholangitis), 2 false positives and 1 patient is still in follow-up. CONCLUSIONS: In our experience MRCP proved to be highly accurate as fundamental diagnostic step in patients with clinical and laboratory findings suggestive of biliary disease. The workload of ERCP, invasive method with risk of complications, in the diagnosis stage could therefore be reduced and its use be reserved for therapeutic indications.

Short-course R-CHOP followed by (90)Y-Ibritumomab tiuxetan in previously untreated high-risk elderly diffuse large B-cell lymphoma patients: 7-year long-term results.

An update at 7 years was conceived for our multicenter phase II study in which 55 elderly high-risk untreated diffuse large B-cell lymphoma patients were treated with (90)Y-ibritumomab tiuxetan after a short course of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) as long-term follow-up analyses of this combined therapeutic modality are lacking. The overall response rate to the entire regimen was 80%, including 73% (40/55) of complete response (CR) rate and 7% (4/55) of partial response rate. At the time of writing, 24/55 (43.6%) patients experienced a progression disease and 20 of 40 (50%) patients who obtained a CR are still alive in continuous CR. With a median follow-up of 7 years, the disease-free survival was 43.3% and the progression-free survival was 36.1%. The overall survival at 7.9 years was 38.9% (27 deaths mainly because of lymphoma). Two patients developed secondary hematological malignancies, an acute myeloid leukemia and a myelodysplastic syndrome, at 4 and 3 years from radioimmunotherapy, respectively. Our data confirm the feasibility, efficacy and safety of four cycles of R-CHOP followed by radioimmunotherapy consolidation even in the long term: this combination allows dispensing less chemotherapy in a frail group of patients without invalidating response quality and duration.

Alpha lipoic acid and superoxide dismutase in the treatment of chronic low back pain.

BACKGROUND: Neuropathic mechanisms largely contribute to low back pain (LBP) and oxidative stress is acknowledged as one of the causes of nerve damage typical of neuropathic pain: antioxidant agents may be a useful choice in the multimodal treatment strategy for chronic LBP patients. AIM: The aim of this study was to detect changes in perceived pain, functional activity and in the assumption of analgesics in patients with chronic LBP treated with a combination of alpha-lipoic acid (ALA) and superoxide dismutase (SOD). DESIGN: Prospective non-randomized open-label study. SETTING: Outpatient at TAMMEF (Therapeutic Application of Musically Modulated Electromagnetic Fields) Centre of the University of Siena. POPULATION: The study enrolled 98 adult patients with chronic (≥12 weeks) LBP with or without radiculopathy and without neoplastic or inflammatory pathologies. METHODS: Patients were treated for 60 days with 600 mg ALA and 140 UI SOD/die. The Roland Morris Disability Questionnaire and Pain Rating Scale were used and concomitant use of medications (with particular attention to analgesics) and adverse events (toxicity) were recorded during treatment. Differences between all the study time points were calculated for the scores of the two tools and for the need of concomitant treatment with analgesics. RESULTS: At the end of the study only 8% of patients still used analgesics versus 73.5% registered at baseline (P<0.01). Regarding self-reported tools, a statistically significant improvement both for perceived pain and functional disabilities occurred: pain ameliorated after 40 days of therapy and the improvement was significant both statistically (P<0.05) and clinically. Only 4 patients stopped the treatment due to unacceptable pain (not related to the treatment). CONCLUSION: Oral treatment with ALA and SOD improves functionality and reduces the use of analgesics in chronic LBP patients. CLINICAL REHABILITATION IMPACT: Oral combination of ALA and SOD may be a powerful adjuvant in multimodal therapy of chronic LBP patients.

Food habits and nutritional status of adolescents in Emilia-Romagna, Italy.

INTRODUCTION: The prevalence of childhood and adolescent obesity is increasing, with negative medical and psychosocial consequences. AIMS: This study examines the association between weight status and nutrient intake, sport and leisure habits of middle school students in Bologna (Italy). METHODS: Anthropometric data (height, weight) of 598 subjects (321 males and 277 females) 11-14 years old were collected. Questionnaires on nutrient intake, sport and leisure behaviour were administered. RESULTS: Protein, carbohydrate and total fat intakes of the adolescents were higher than the recommended ranges in all age groups and in both sexes. The proportion of energy from protein and total fat was higher than recommended, but the percentage from carbohydrate was lower. A significant proportion of the adolescents had a cholesterol intake above the Italian RDA and lower than recommended intakes for micronutrients. The prevalence of overweight and obesity is higher in males than in females at all ages (overweight: 35.2 vs 31.6 at 11 yrs.; 27.5 vs 20.2 at 12 yrs.; 18.6 vs 17.8 at 13 yrs.; 18.7 vs 10.9 at 14 yrs.; obesity: 5.5 vs 3.2 at 12 yrs.; 3.9 vs 1.1 at 13 yrs.; 5.3 vs 3.6 at 14 yrs.), except in subjects 11 years old (obesity: 7.4 vs 10.5). The overweight and obese adolescents consumed less carbohydrates and less fibre than their normal weight and underweight counterparts. CONCLUSION: The results of the present study indicate an unbalanced diet of the Bologna adolescents, which could damage their health and quality of life.

Weight status and body image perception in Italian children.

BACKGROUND: Previous research suggests there is a tendency in overweight subjects to underestimate their weight status. This study investigated the perception of body image in Italian children, with particular regard to overweight children. METHODS: Primary school children (n = 866) were recruited for this cross-sectional nutritional survey in northern Italy. Anthropometric measurements were performed to determine body mass index (BMI). Body image perception was assessed with the Body Silhouette Chart for preadolescent children shown to the children and to their mothers (n = 778) during an interview. A new scheme to identify wrong (F.1, F.2) or inappropriate (F.3) self figure responses in overweight subjects was used. RESULTS: More than one-third of the Italian children examined were above the normal BMI range (prevalence of overweight: 35.8%, girls; 37.2%, boys). A higher degree of dissatisfaction was expressed by girls than by boys, and the percentage increased in overweight/obese children. A discrepancy between the self figure perception and the real nutritional status of the subject occurred in 6-9% of the overweight/obese children. CONCLUSION: The comparison of body image perception and anthropometric assessment of nutritional status could play an important role in future programs of nutritional surveillance as they provide indications of dissatisfaction and body image disturbances.

Growth of Chinese Italian infants in the first 2 years of life.

BACKGROUND: Numerous studies have been carried out on the growth of human migrant populations. However, studies on the auxological pattern of Chinese migrant population are limited in Italy. AIMS: In this paper we examine the growth pattern from birth to 24 months and the body composition of Chinese infants born and living in Bologna (north Italy). SUBJECTS AND METHODS: A longitudinal study was conducted recruiting 224 healthy Chinese children. The anthropometric measurements were collected when the children were immunized. Body mass index (BMI), Arm Muscle Area and Arm Fat Area were calculated. RESULTS: The growth of Chinese Italian children is adequate, being within the normal limits according to the NCHS reference standard. In comparison with Chinese children living in China and abroad, their body length is greater. Comparisons with growth curves for Italian children (Emilia-Romagna) show that weight and length values are higher in Chinese children than in Italians until 12 months, and comparable thereafter. The weight and length growth velocities are similar to those reported for Italian children. CONCLUSION: As a whole, the results of the present study support the hypothesis that Chinese children born and living in Italy grow in an appropriate environment to achieve their growth potential.