Patient and caregiver involvement in the formulation of guideline questions: findings from the European Academy of Neurology guideline on palliative care of people with severe multiple sclerosis.

BACKGROUND AND PURPOSE: Patient and public involvement in clinical practice guideline development is recommended to increase guideline trustworthiness and relevance. The aim was to engage multiple sclerosis (MS) patients and caregivers in the definition of the key questions to be answered in the European Academy of Neurology guideline on palliative care of people with severe MS. METHODS: A mixed methods approach was used: an international online survey launched by the national MS societies of eight countries, after pilot testing/debriefing on 20 MS patients and 18 caregivers, focus group meetings of Italian and German MS patients and caregivers. RESULTS: Of 1199 participants, 951 (79%) completed the whole online survey and 934 from seven countries were analysed: 751 (80%) were MS patients (74% women, mean age 46.1) and 183 (20%) were caregivers (36% spouses/partners, 72% women, mean age 47.4). Participants agreed/strongly agreed on inclusion of the nine pre-specified topics (from 89% for 'advance care planning' to 98% for 'multidisciplinary rehabilitation'), and <5% replied 'I prefer not to answer' to any topic. There were 569 free comments: 182 (32%) on the pre-specified topics, 227 (40%) on additional topics (16 guideline-pertinent) and 160 (28%) on outcomes. Five focus group meetings (three of MS patients, two of caregivers, and overall 35 participants) corroborated the survey findings. In addition, they allowed an explanation of the guideline production process and the exploration of patient-important outcomes and of taxing issues. CONCLUSIONS: Multiple sclerosis patient and caregiver involvement was resource and time intensive, but rewarding. It was the key for the formulation of the 10 guideline questions and for the identification of patient-important outcomes.

Comparison of CT and chemical-shift MRI for differentiating thymoma from non-thymomatous conditions in myasthenia gravis: value of qualitative and quantitative assessment.

AIM: To evaluate the usefulness of computed tomography (CT) and chemical-shift magnetic resonance imaging (MRI) in patients with myasthenia gravis (MG) for differentiating thymoma (THY) from thymic lymphoid hyperplasia (TLH) and normal thymus (NT), and to determine which technique is more accurate. MATERIALS AND METHODS: Eighty-three patients with generalised MG who underwent surgery were divided into the TLH/NT group (A; 65 patients) and THY group (B; 24 patients). Differences in qualitative characteristics and quantitative data (CT: radiodensity in Hounsfield units; MRI: signal intensity index [SII]) between groups were tested using Fisher's exact test and Student's t-test. Logistic regression models were estimated for both qualitative and quantitative analyses. At quantitative analysis, discrimination abilities were determined according to the area under the receiver operating characteristic (ROC) curve (AUROC) with computation of optimal cut-off points. The diagnostic accuracies of CT and MRI were compared using McNemar's test. RESULTS: At qualitative assessment, MRI had higher accuracy than CT (96.4%, 80/83 and 86.7%, 72/83, respectively). At quantitative analysis, both the radiodensity and SII were significantly different between groups (p<0.0001). For CT, at quantitative assessment, the AUROC of the radiodensity in discriminating between groups was 0.904 (optimal cut-off point, 20 HU) with an accuracy of 77.1% (64/83). For MRI, the AUROC of the SII was 0.989 (optimal cut-off point, 7.766%) with an accuracy of 96.4% (80/83), which was significantly higher than CT (p<0.0001). By using optimal cut-off points for cases with an erroneous diagnosis at qualitative assessment, accuracy improved both for CT (89.2%, 74/83) and MRI (97.6%, 81/83). CONCLUSION: Quantitative analysis is useful in evaluating patients with MG and improves the diagnostic accuracy of CT and MRI based on qualitative assessment. Chemical-shift MRI is more reliable than CT in differentiating THYs from non-thymomatous conditions.

Whole-body MRI with diffusion-weighted imaging: a valuable alternative to contrast-enhanced CT for initial staging of aggressive lymphoma.

AIM: To compare the accuracy of whole-body magnetic resonance imaging (Wb-MRI) with diffusion-weighted imaging (DWI) to that of contrast-enhanced computed tomography (CE-CT) and 2-[(18)F]-fluoro-2-deoxy-d-glucose ((18)F-FDG) positron-emission tomography co-registered with low dose-CT (PET-CT) in defining lymphoma disease stage. MATERIALS AND METHODS: From February 2010 to May 2014, 41 lymphoma patients underwent Wb-MRI-DWI, CE-CT, and (18)F-FDG PET-CT. Histological subtypes included aggressive B-cell (n=11), follicular (n=13), mantle cell (n=3), and Hodgkin's (n=14) lymphoma. To compare the procedures, the reference standard (RS) assessment was defined by combining the results from (18)F-FDG PET-CT, CE-CT, and bone marrow (BM) histology, modifications after therapy, and histological re-assessments of uncertain lesions. RESULTS: Among 1025 nodal sites, 217 had disease involvement according to the RS. CE-CT yielded 23 false-negative and 11 false-positive errors. Wb-MRI-DWI failed to recognise 17 localisations and had six false-positive errors; (18)F-FDG PET-CT had no errors. Among 458 extranodal sites, 37 were positive according to the RS. (18)F-FDG PET-CT yielded four false-negative and two false-positive results. CE-CT yielded 17 false-negative errors. Wb-MRI-DWI yielded a single false-negative error. Wb-MRI-DWI was the most reliable imaging technique for BM evaluation. Considering each procedure alone, the final stage would have been missed in four cases using (18)F-FDG PET-CT, 12 cases using CE-CT, and none using Wb-MRI-DWI. CONCLUSION: The present data support Wb-MRI-DWI as a sensitive and specific imaging technique for lymphoma evaluation, supporting its use in place of CE-CT for staging.

Prolonged survival in poor-risk diffuse large B-cell lymphoma following front-line treatment with rituximab-supplemented, early-intensified chemotherapy with multiple autologous hematopoietic stem cell support: a multicenter study by GITIL (Gruppo Italiano Terapie Innovative nei Linfomi).

A prospective multicenter program was performed to evaluate the combination of rituximab and high-dose (hd) sequential chemotherapy delivered with multiple autologous peripheral blood progenitor cell (PBPC) support (R-HDS-maps regimen) in previously untreated patients with diffuse large B-cell lymphoma (DLB-CL) and age-adjusted International Prognostic Score (aaIPI) score 2-3. R-HDS-maps includes: (i) three APO courses; (ii) sequential administration of hd-cyclophosphamide (CY), hd-Ara-C, both supplemented with rituximab, hd-etoposide/cisplatin, PBPC harvests, following hd-CY and hd-Ara-C; (iii) hd-mitoxantrone (hd-Mito)/L-Pam + 2 further rituximab doses; (iv) involved-field radiotherapy. PBPC rescue was scheduled following Ara-C, etoposide/cisplatin and Mito/L-Pam. Between 1999 and 2004, 112 consecutive patients aged <65 years (74 score 2, 38 score 3) entered the study protocol. There were five early and two late toxic deaths. Overall 90 patients (80%) reached clinical remission (CR); at a median 48 months follow-up, 87 (78%) patients are alive, 82 (73%) in continuous CR, with 4 year overall survival (OS) and event-free survival (EFS) projections of 76% (CI 68-85%) and 73% (CI 64-81%), respectively. There were no significant differences in OS and EFS between subgroups with Germinal-Center and Activated B-cell phenotype. Thus, life expectancy of younger patients with aaIPI 2-3 DLB-CL is improved with the early administration of rituximab-supplemented intensive chemotherapy compared with the poor outcome following conventional chemotherapy.

Characteristics of an Effective Preceptor: Dietetics Education as a Paradigm.

PURPOSE: To examine the characteristics of effective preceptors, using the perceptions of students who are enrolled in a Dietetic Internship (DI), and to evaluate the influence of the following factors on preceptor behavior: a preceptors' area of practice, credentials, and type of DI program where the student is enrolled. METHODS: Three hundred fifty-one students from 129 randomly selected DI programs completed an online survey to evaluate their preceptors, using a 40-item Preceptor Behavior Scale that included four categories: knowledge and professional competence, interpersonal skills, personality characteristics, and teaching ability. RESULTS: The students ranked knowledge and professional competence as the most important category for effective preceptors. Teaching ability had the largest difference in mean scores between an effective and ineffective preceptor. Preceptors who were considered more effective included: a) preceptors in clinical and "other" practice areas such as community and private practice vs those in food service; b) preceptors who were registered dietitians (RD) vs non-RD; and c) preceptors in hospital-based DI programs vs university-based DI programs. CONCLUSIONS: Preceptor training should emphasize skills in all of the categories from the Preceptor Behavior Scale so that preceptors can effectively help students meet the competencies required for entry-level practice. A web-based preceptor training module that can reach offsite preceptors should be developed that includes scenarios for all areas of practice, teaching skills based on the principles of adult learning, and a credential and/or a professional incentive.

Supratracheal laryngectomy: current indications and contraindications.

Cancer of the larynx in the intermediate/advanced stage still presents a major challenge in terms of controlling the disease and preserving the organ. Supratracheal partial laryngectomy (STPL) has been described as a function-sparing surgical procedure for laryngeal cancer with sub-glottic extension. The aim of the present multi-institutional study was to focus on the indications and contraindications, both local and general, for this type of surgery based on the long-term oncological and functional results. We analysed the clinical outcomes of 142 patients with laryngeal cancer staged pT2-pT4a who underwent STPL. Five-year overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS) and loco-regional control (LRC) rates were: glottic pT2 [71.4%, 95.2%, 76.0%, 76.0%], glottic-transglottic pT3 [85.3%, 91.1%, 86.4%, 88.7%], and pT4a [73.2%, 88.1%, 52.7%, 60.7%], respectively. DFS and LRC prevalences at 5 years were greatly affected by pT4a staging. Five-year laryngeal function preservation (LFP) and laryngectomy free survival (LFS) were: glottic pT2 [90.9%, 95.2%], glottic-transglottic pT3 [84.4%, 93.1%], and pT4a [63.7%, 75.5%], respectively, being affected by pT staging and age 65 ≥ years (LFP 54.1%). As a result of Type III open horizontal partial laryngectomies (OPHLs) (supratracheal laryngectomies), the typical subsites of local failure inside the larynx were the mucosa at the passage between the remnant larynx and trachea, the mucosa at the level of the posterior commissure and the contralateral cricoarytenoid unit as well as outside the larynx at the level of the outer surface of the remnant larynx. For patients with glottic or transglottic tumours and with sub-glottic extension, the choice of STPL can be considered to be effective, not only in prognostic terms, but also in terms of functional results.

[Retroperitoneal extraskeletal myxoid chondrosarcoma]. / Condrosarcoma mixoide extrascheletrico del retroperitoneo.

INTRODUCTION: Extraskeletal myxoid chondrosarcoma is a rare soft tissue tumor included by WHO in the group of tumors of uncertain differentiation because well formed cartilage is rarely seen in its setting; moreover some of the immunophenotype features of the tumor are still controversial. The reciprocal translocation t(9;22)(q22;q12) has recently been identified in many cases, and this chromosomal aberration is currently considered high specific of this tumor. CASE REPORT: We report the case of a 75-year-old female submitted to radical nephrectomy for a voluminous kidney tumor with radiological evidence of extrarenal extension. RESULTS: Grossly the lesion was set in the perirenal fat tissue. Histological examination revealed a malignant mesenchimal tumor with myxoid f eatures and areas of chondroid differentiation consistent with the diagnosis of extraskeletal myxoid chondrosarcoma. According with the diagnosis the tumor showed focal positivity to NSE by immunohistochemistry. DISCUSSION: Differentiated cartilage is seen in extraskeletal myxoid chondrosarcoma in about 30% of the cases. Our case is then interesting not only for the rare site of tumor location but also for the extension of chondroid differentiation areas found on histologic examination in the tumor setting. Moreover immunohistochemistry showed focal positivity of the neoplastic cells for NSE, according with recent studies demonstrating expression of some neural/neuroendocrine markers in extrascheletal myxoid chondrosarcoma.

Metabisulfite oral challenge: incidence of adverse responses in chronic childhood asthma and its relationship with bronchial hyperreactivity.

Fifty-six children with chronic asthma, 6 to 14 years of age, were studied to evaluate bronchoconstrictive airway responses after ingestion of varying doses of potassium bisulfite administered in one occasion in capsule and in another occasion in solution. With methacholine challenge before and after metabisulfite (MBS) provocation, the relationship of bronchoconstrictive responses and bronchial hyperreactivity was evaluated. Positive bronchoconstrictive responses were observed in only four children after the ingestion of a maximum dose of MBS in capsule and in two children after the ingestion of different doses of MBS solution. A high reactivity to methacholine challenge was present in all the reactive children. After MBS challenge, no additional changes in bronchial reactivity were observed either in the reactors or nonreactors.

Antigen avoidance in a mountain environment: influence on basophil releasability in children with allergic asthma.

BACKGROUND: The influence of natural antigen avoidance in an environment free of relevant allergens (Istituto Pio XII, Misurina, Italian Alps, 1756 m) and of antigen exposure (sea level) on basophil releasability, as well as on bronchial hyperreactivity (BHR) and specific IgE serum level, were investigated in a group of children with asthma who were allergic to Dermatophagoides pteronyssinus. METHODS: Twenty allergic children with asthma participated in the study. Spontaneous and antigen-induced histamine release, BHR, and serum IgE were investigated at the time of admission, after 40 and 80 days of antigen avoidance, and after 15 days of exposure at sea level. RESULTS: Significant drops in antigen-induced basophil histamine release, BHR, and specific IgE serum level but not in spontaneous basophil histamine release were observed after 40 days of antigen avoidance and were confirmed at a further evaluation after 40 more days. After 15 days of antigen exposure at sea level, specific antigen-induced basophil histamine release, BHR, and serum IgE but not spontaneous basophil histamine release increased promptly, even if not significantly. CONCLUSION: In children with allergic asthma, antigen-induced basophil releasability, BHR, and specific IgE serum levels appear to be modifiable by periods of antigen avoidance or exposure.

Penile straightening with crural graft of the corpus cavernosum.

PURPOSE: We present a surgical alternative to penile straightening in Peyronie's disease that avoids penile shortening by using tissue from the crural segment of the corpora cavernosa as a graft. MATERIALS AND METHODS: We treated 7 patients with stable Peyronie's disease and satisfactory penile rigidity but significant curvature that precluded intercourse with this technique. An incision is made in the fibrous area and after stretching the gap is covered with a graft removed from the crural segment of the corpora cavernosa. RESULTS: In 6 of the 7 men straightening was satisfactory but in 1 it was not complete. No patient reported worse penile rigidity postoperatively. Donor site healing was uneventful. CONCLUSIONS: Use of tissue from the corpus cavernosum to correct penile curvature is effective. However, our results are preliminary, and long-term effectiveness and safety must be confirmed in a larger number of cases.