Efficacy of immunotherapy in mismatch repair-deficient advanced colorectal cancer in routine clinical practice. An AGEO study.

BACKGROUND: Immunotherapy demonstrated remarkable efficacy in metastatic colorectal cancers (mCRCs) with mismatch repair deficiency (MMRd)/microsatellite instability (MSI). However, data regarding efficacy and safety of immunotherapy in the routine clinical practice are scarce. PATIENTS AND METHODS: This is a retrospective, multicenter study aiming to evaluate efficacy and safety of immunotherapy in routine clinical practice and to identify predictive markers for long-term benefit. Long-term benefit was defined as progression-free survival (PFS) exceeding 24 months. All patients who received immunotherapy for an MMRd/MSI mCRC were included. Patients who received immunotherapy in combination with another known effective therapeutic class agent (chemotherapy or tailored therapy) were excluded. RESULTS: Overall, 284 patients across 19 tertiary cancer centers were included. After a median follow-up of 26.8 months, the median overall survival (mOS) was 65.4 months [95% confidence interval (CI) 53.8 months-not reached (NR)] and the median PFS (mPFS) was 37.9 months (95% CI 30.9 months-NR). There was no difference in terms of efficacy or toxicity between patients treated in the real-world or as part of a clinical trial. Overall, 46.6% of patients had long-term benefit. Independent markers associated with long-term benefit were Eastern Cooperative Oncology Group-performance status (ECOG-PS) 0 (P = 0.025) and absence of peritoneal metastases (P = 0.009). CONCLUSIONS: Our study confirms the efficacy and safety of immunotherapy in patients with advanced MMRd/MSI CRC in the routine clinical practice. ECOG-PS score and absence of peritoneal metastases provide simple markers that could help identify patients who benefit the most from this treatment.

[Cutaneous and systemic T-cell lymphoma treated with haploidentical bone marrow transplantation]. / Lymphome T cutané et systémique traité avec succès par greffe haplo-identique.

BACKGROUND: Herein, we report a case of systemic cutaneous T-cell lymphoma refractory to standard therapy, the course of which resulted in haplo-identical bone marrow grafting. PATIENTS AND METHODS: A 53-year-old woman consulted for facial erythema with infiltration, keratotic lesions on the trunk, and adenopathies measuring around 1cm on the axilla and inguinal folds. A diagnosis was made of Sézary syndrome (SS), a leukaemic form of epidermotropic cutaneous T-cell lymphoma. After three years of treatment with methotrexate, the patient developed transformed SS with visceral involvement. Given the high risk of relapse and the absence of an HLA-compatible donor, haploidentical bone marrow grafting was performed. The patient was still in complete remission two and a half years later. The disease course was nevertheless marked by the emergence one year after grafting of a Blaschko-distributed lichenoid eruption having histological features consistent with chronic graft-versus-host disease (GVHD); treatment with topical betamethasone proved efficacious. DISCUSSION: To our knowledge, this is the first reported case of haploidentical grafting for systemic and transformed cutaneous T-cell lymphoma. This approach could henceforth represent a therapeutic option for patients requiring an allograft in the absence of compatible donors. The Blaschko-distributed lichenoid lesions attributed to chronic GVHD could be the result of reduced immune tolerance to abnormal embryological clones leading to a T-lymphocyte-mediated inflammatory reaction.

Interest of next-generation sequencing in BCG-treated high-risk bladder cancer.

OBJECTIVES: There are only few predictive factors for response of non-musculo-invasive bladder cancer (NMIBC) to Bacillus Calmette-Guérin (BCG) therapy. Our study analyzed the results of the sequencing of new generation (NGS) targeted on 50 genes of oncological interest obtained on bladder resection parts in high-risk NMIBC patients treated with BCG, to describe this population from a molecular point of view and try to correlate these results in patients who present or not recurrence after BCG. METHODS: We reviewed 63 patients with high grade NMIBC treated between 2014 and 2016 with BCG after endoscopic resection. Each one had NGS analysis. Association tests between mutations detected by NGS and recurrence or progression were realized. RESULTS: The 45 remaining patients were fully analysed. For 73% of cases a mutation has been found, most frequent one's being FGFR3, TP53 and PIK3CA. With a median follow-up of 24 months (4-40), recurrence was present in 15 patients (33.3%), with 10 NMIBC (22.2%) and 5 progressions to muscular-invasive cancer (11.1%). If some mutations were more frequent in different prognostic groups no significant association has been found. No patient presenting CIS had FGFR3 mutation (P<0.0001). CONCLUSION: Next generation sequencing in NMIBC could be a supplementary aid in treatment decision making in the future. In an area where personalized medicine is rapidly growing in importance we need larger studies to define molecular characteristics in tumours to detect genomic associations between clinical phenotypes and recurrence or progression of the disease. LEVEL OF EVIDENCE: 3.

Randomized phase II trial comparing axitinib with the combination of axitinib and lomustine in patients with recurrent glioblastoma.

Axitinib is a small molecule tyrosine kinase inhibitor with high affinity and specificity for the family of vascular endothelial growth factor receptors. It has previously demonstrated anti-tumor activity in a small cohort of patients with recurrent glioblastoma (rGB). We conducted a non-comparative randomized phase II clinical trial investigating axitinib monotherapy versus axitinib plus lomustine (LOM) in patients with rGB. Primary endpoint was 6 month progression-free survival (6mPFS). Patients who progressed on axitinib-monotherapy were allowed to cross-over. Between August 2011 and July 2015, 79 patients were randomized and initiated axitinib monotherapy (n = 50; AXI) or axitinib plus lomustine (n = 29; AXILOM). Median age was 55y [range 18-80], 50M/28F. Baseline characteristics were well balanced between study arms. Nineteen patients in the AXI-arm crossed-over at the time of progression. Treatment was generally well tolerated. AXILOM patients were at higher risk for grade 3/4 neutropenia (0 vs. 21%) and thrombocytopenia (4 vs. 29%). Best Overall Response Rate (BORR) in the AXI-arm was 28 vs. 38% in the AXILOM-arm. 6mPFS was 26% (95% CI 14-38) versus 17% (95% CI 2-32) for patients treated in the AXI versus AXILOM-arms, respectively. Median overall survival was 29 weeks (95% CI 20-38) in the AXI-arm and 27.4 weeks (95% CI 18.4-36.5) in the AXILOM-arm. MGMT-promoter hypermethylation and steroid treatment at baseline correlated significantly with PFS and OS. We conclude from these results that axitinib improves response rate and progression-free survival in patients with rGB compared to historical controls. There is no indication that upfront combination of axitinib with LOM improves results (European Clinical Trials Database (EudraCT) Study Number: 2011-000900-16).

Reduced-intensity versus reduced-toxicity myeloablative fludarabine/busulfan-based conditioning regimens for allografted non-Hodgkin lymphoma adult patients: a retrospective study on behalf of the Société Francophone de Greffe de Moelle et de Thérapie Cellulaire.

BACKGROUND: Fludarabine/busulfan-based conditioning regimens are widely used to perform allogeneic stem-cell transplantation (allo-SCT) in high-risk non-Hodgkin lymphoma (NHL) patients. The impact of the dose intensity of busulfan on outcomes has not been reported yet. PATIENTS AND METHODS: This was a retrospective with the aim to compare the outcomes of NHL patients who received before allo-SCT a fludarabine/busulfan conditioning regimen, either of reduced intensity (FB2, 2 days of busulfan at 4 mg/kg/day oral or 3.2 mg/kg/day i.v.) (n = 277) or at a myeloablative reduced-toxicity dose (FB3/FB4, 3 or 4 days of busulfan at 4 mg/kg/day oral or 3.2 mg/kg/day i.v.) (n = 101). RESULTS: In univariate analysis, the 2-year overall survival (FB2 66.5% versus 60.3%, P = 0.33), lymphoma-free survival (FB2 57.9% versus 49.8%, P = 0.26), and non-relapse mortality (FB2 19% versus 21.1%, P = 0.91) were similar between both groups. Cumulative incidence of grade III-IV acute graft versus host disease (GVHD) (FB2 11.2% versus 18%, P = 0.08), extensive chronic GVHD (FB2: 17.3% versus 10.7%, P = 0.18) and 2-year GVHD free-relapse free survival (FB2: 44.4% versus 42.8%, P = 0.38) were also comparable. In multivariate analysis there was a trend for a worse outcome using FB3/FB4 regimens (overall survival: HR 1.47, 95% CI: 0.96-2.24, P = 0.08; lymphoma-free survival: HR: 1.43, 95% CI: 0.99-2.06, P = 0.05; relapse incidence: HR 1.54; 95% CI: 0.96-2.48, P = 0.07). These results were confirmed using a propensity score-matching strategy. CONCLUSION: We conclude that reduced toxicity myeloablative conditioning with fludarabine/busulfan does not improve the outcomes compared with reduced-intensity conditioning in adults receiving allo-SCT for NHL.

Reasons for and functional results of repeated hip arthroscopy: A continuous prospective study of 17 revisions out of 295 primary hip arthroscopies at mean 28months' follow-up.

INTRODUCTION: The rate of iterative arthroscopy has been increasing over the last decade as the technique has grown. The results of and reasons for these revision procedures, however, are not exactly known. We therefore conducted a prospective study to shed light on: 1) functional results and patient satisfaction following repeated arthroscopy, and 2) the relevant indications. HYPOTHESIS: Functional scores and patient satisfaction increase following repeated arthroscopy. MATERIALS AND METHOD: A single-center continuous prospective study without control group included patients undergoing repeated hip arthroscopy between September 2010 and September 2014, with a mean 28months' follow-up (median, 23.3months; range, 12-62months). Preoperative and follow-up functional assessment used the modified Harris hip, WOMAC and Christensen (NHAS) questionnaires, and a satisfaction scale. On etiological analysis, repeated arthroscopy was indicated if a cause of recurrent or persistent pain accessible to arthroscopic treatment was identified. RESULTS: Seventeen patients were included out of 295 primary arthroscopies (5.7%): 9 male, 8 female; median age, 29.6years (range, 16-48years). Indications for primary arthroscopy comprised 13 cases of femoroacetabular impingement, 3 labrum lesions with instability, 1 chondromatosis and 1 case of osteoarthritis. Eleven of the 17 primary lesions showed persistence, including 9 of the 13 cases of femoroacetabular impingement. There were 3 failures in 17 repeated arthroscopies. All functional scores improved, with a gain of 7 points (P<0.06) on modified Harris hip score, 25 points (P<0.0006) on WOMAC score, and 27 points (P<0.001) on NHAS score. Ten of the 17 patients were satisfied or very satisfied with the repeated arthroscopy (59%). CONCLUSION: Although less good than on primary arthroscopy, functional results on repeated hip arthroscopy were satisfactory in the short term. The main reason for repeated arthroscopy was persistence of initial abnormality due to insufficient treatment.

Reduced-intensity and non-myeloablative allogeneic stem cell transplantation from alternative HLA-mismatched donors for Hodgkin lymphoma: a study by the French Society of Bone Marrow Transplantation and Cellular Therapy.

Allogeneic stem cell transplantation (allo-SCT) following a non-myeloablative (NMA) or reduced-intensity conditioning (RIC) is considered a valid approach to treat patients with refractory/relapsed Hodgkin lymphoma (HL). When an HLA-matched donor is lacking a graft from a familial haploidentical (HAPLO) donor, a mismatched unrelated donor (MMUD) or cord blood (CB) might be considered. In this retrospective study, we compared the outcome of patients with HL undergoing a RIC or NMA allo-SCT from HAPLO, MMUD or CB. Ninety-eight patients were included. Median follow-up was 31 months for the whole cohort. All patients in the HAPLO group (N=34) received a T-cell replete allo-SCT after a NMA (FLU-CY-TBI, N=31, 91%) or a RIC (N=3, 9%) followed by post-transplant cyclophosphamide. After adjustment for significant covariates, MMUD and CB were associated with significantly lower GvHD-free relapse-free survival (GRFS; hazard ratio (HR)=2.02, P=0.03 and HR=2.43, P=0.009, respectively) compared with HAPLO donors. In conclusion, higher GRFS was observed in Hodgkin lymphoma patients receiving a RIC or NMA allo-SCT with post-transplant cyclophosphamide from HAPLO donors. Our findings suggest they should be favoured over MMUD and CB in this setting.

Clinical characteristics and prognostic factors of plasmablastic lymphoma patients: analysis of 135 patients from the LYSA group.

Background: Plasmablastic lymphoma (PBL), initially described in 1997 in the oral cavity of HIV positive patients, is now recognized as a distinct aggressive and rare entity of diffuse large B-cells lymphoma by the World Health Organization (WHO) classification. Since the original description, others cases have been reported. However, these are largely derived from case reports or small series limiting any definitive conclusions on clinical characteristics and outcome. Patients and methods: The clinical, biological, pathological features and outcome of a cohort including 135 patients with PBL, from LYSA centers in France and Belgium, were reported and analyzed. Results: The median age was 58 years, with a male predominance. The cohort was divided into 56 HIV-positive patients, 17 post-transplant patients and 62 HIV-negative/non-transplanted patients. Within HIV-negative/non-transplanted, a relative immunosuppression was found in most cases (systemic inflammatory disease, history of cancer, increased age associated with weakened immune system). We have also described a new subtype, PBL arising in a chronic localized inflammatory site, without any sign of immunosuppression. At presentation, 19% of patients showed oral involvement. Immunophenotype showed CD138 positivity in 88% of cases and CD20 negativity in 90% of cases. Chemotherapy was administered to 80% of patients, with a complete response (CR) rate of 55%. The median overall survival (OS) was 32 months. In univariate analysis, HIV positive status showed better OS when compared with HIV negative status. In multivariate analysis, International Prognostic Index score, chemotherapy and CR were associated with survival benefit. Conclusion(s): This cohort, the largest reported to date, increases the spectrum of knowledge on PBL, rarely described. However, specific guidelines to clarify treatment are lacking, and may improve the poor prognosis of this rare disease.

Circulating Cd34+ cell count differentiates primary myelofibrosis from other Philadelphia-negative myeloproliferative neoplasms: a pragmatic study.

A high number of circulating CD34+ cells has been advocated to distinguish primary myelofibrosis from other Philadelphia-negative myeloproliferative neoplasms. We re-evaluated the diagnostic interest of measuring circulating CD34+ cells in 26 healthy volunteers and 256 consecutive patients at diagnosis for whom a myeloproliferative neoplasm was suspected. The ROC curve analysis showed that a number of CD34+ <10/µl excludes the diagnosis of primary myelofibrosis with a sensitivity of 97 % and a specificity of 90 % (area under the curve: 0.93 [0.89-0.98]; p < 0.001). Patients with PMF harboring a CALR mutation had more circulating CD34+ cells than patients with either a JAK 2 or MPL mutation (p = 0.02 and p < 0.01, respectively). These results suggest that this fast, simple, non-invasive, and standardized test is of particular interest to exclude the diagnosis of primary myelofibrosis.

What type of imaging work-up will help to confirm the diagnosis of gossypiboma in the limb? Review of literature.

UNLABELLED: Gossypiboma imaging features are not well known and are often confused with soft tissue tumours. Publications on this topic mainly consist of case reports and small cohorts. Its appearance on various imaging modalities is not well defined. This led us to carry out a review of literature to determine specifically: (1) which imaging modalities should be used in cases of suspected gossypiboma, (2) what are the most common imaging findings that contribute to the diagnosis of gossypiboma. An exhaustive review of literature was carried out in June 2015 in the Medline, PubMed and Cochrane databases using the keywords "gossypiboma/textiloma/foreign body". We found 205 articles describing one or multiple cases of gossypiboma in various locations. Of these, the 32 articles that had imaging data were chosen - 16 for the limbs and 16 for other locations. The type of imaging carried out, description of the gossypiboma and circumstances of the discovery and occurrence were recorded. Descriptive statistics were generated to define the type of imaging used and the various findings. Imaging consisted of X-rays in 21/32 cases (66%), computed tomography (CT) in 14/32 cases (43%), magnetic resonance imaging (MRI) in 21/32 cases (65%) and ultrasonography in 14/32 cases (43%). On X-rays, bone involvement was found in 9/15 cases (60%); there was peripheral contrast product uptake on the CT scans in 9/14 cases (64%), a hypointense signal on T1-weighted sequences on MRI in 6/13 cases (46%) and lack of vascularisation in 8/13 cases (62%) and a acoustic shadow on ultrasonography in 9/14 cases (64%). In a patient presenting with a soft tissue lump and history of surgery, an imaging work-up including X-rays, ultrasonography and MRI must be performed. Bone involvement on X-rays, acoustic shadowing on ultrasonography and hypointense signal on T1-weighted MRI sequences with lack of vascularisation in combination with a history of surgery can bring up the possibility of gossypiboma. If there is a possibility of soft tissue tumour, the case should be discussed in a multidisciplinary meeting and a biopsy should be performed first. LEVEL OF EVIDENCE: IV - systematic analysis of published retrospective studies.

Randomized phase II study of axitinib versus physicians best alternative choice of therapy in patients with recurrent glioblastoma.

We conducted a randomized, non-comparative, multi center, phase II clinical trial in order to investigate the efficacy of axitinib, an oral small molecule tyrosine kinase inhibitor with high affinity and specificity for the vascular endothelial growth factor receptors, in patients with recurrent glioblastoma following prior treatment with radiation and temozolomide. Forty-four patients were randomly assigned to receive treatment with axitinib (5 mg BID starting dose; N = 22) or "physicians best alternative choice of therapy" that consisted of bevacizumab (N = 20) or lomustine (N = 2). Six-month progression-free survival served as the primary endpoint. The estimated 6-month progression-free survival rate was 34 % (95 % CI 14-54) for patients treated with axitinib and 28 % (95 % CI 8-48) with best alternative treatment; median overall survival was 29 and 17 weeks, respectively. Objective responses according to RANO criteria were documented in 28 % of patients treated with axitinib and 23 % of patients treated with best alternative therapy. A decrease in maximal uptake of 18F-fluoro-ethyL-tyrosine (18F-FET) by the glioblastoma on PET imaging was documented in 85 % of patients at the time of response on axitinib. Corticosteroid treatment could be stopped in four and tapered in seven out of the 15 patients who were treated with steroids at baseline in the axitinib cohort. Most frequent axitinib related grade ≥3 adverse events consisted of fatigue (9 %), diarrhea (9 %), and oral hyperesthesia (4.5 %). We conclude that axitinib has single-agent clinical activity and a manageable toxicity profile in patients with recurrent glioblastoma.

[How molecular biology can improve the clinical diagnosis of gliomas?] / Comment la biologie moléculaire améliore le diagnostic clinique des gliomes?

Gliomas are the most common primary brain tumors and include different diagnoses associated with a different prognosis. Histology remains the gold standard for the diagnosis of these tumors. However, pathologists may encounter diagnostic difficulties due to tumor heterogeneity or to the small size of the samples. Recently, major advances in discovery of molecular alterations of these cancers have led to the development of new molecular markers, some with a diagnostic role, others with a prognostic impact and / or predictive of therapeutic response. The testing of different molecular alterations such as 1p / 19q codeletion, mutations of IDH genes, p16 deletion, EGFR amplification or MGMT promoter methylation has been included in the daily practice in order to confirm the diagnosis, assess the patient prognosis and guide treatment choices.

Les gliomes représentent les tumeurs cérébrales primitives les plus fréquentes et regroupent différentes entités au pronostic très différent. L'examen anatomopathologique est le gold standard pour le diagnostic de ces tumeurs. Cependant, les pathologistes peuvent rencontrer des difficultés diagnostiques dues, entre autres, à l'hétérogénéité tumorale ou à la petite taille des prélèvements. Nous avons assisté, ces dernières années, à des avancées majeures dans la découverte des altérations moléculaires de ces cancers, ce qui a mené au développement de nouveaux marqueurs moléculaires, certains avec un rôle diagnostique, d'autres avec un impact pronostique et/ou prédictif de la réponse thérapeutique. Dans la pratique quotidienne, il est donc devenu utile de tester la présence de différentes altérations moléculaires telles que la codélétion 1p/19q, les mutations des gènes IDH, la délétion du gène CDKN2A/p16, l'amplification du gène EGFR ou la méthylation du promoteur du gène MGMT, afin de confirmer le diagnostic, d'évaluer le pronostic des patients ainsi que d'orienter les choix thérapeutiques.

[Next generation sequencing]. / Une nouvelle technologie pour améliorer le diagnostic des cancers thyroïdiens.

Fine needle aspiration is the gold standard method to differentiate benign thyroid nodules from malignant. However, for 15 to 30% of the cases the cytological diagnosis is indeterminate, leading to surgery. Integration of new molecular markers is opening new perspectives in order to increase the diagnostic precision of thyroid nodules with an indeterminate cytology.

La méthode diagnostique de référence pour différencier les nodules thyroïdiens bénins des nodules malins est la ponction écho-guidée à l'aiguille fine. Cependant dans 15 à 30 % des cas le diagnostic cytologique est indéterminé, menant à une intervention chirurgicale. L'intégration de nouveaux marqueurs moléculaires nous ouvrent de nouvelles perspectives pour augmenter la précision diagnostique des nodules thyroïdiens de diagnostic cytologique indéterminé.

IGF-IR: a new prognostic biomarker for human glioblastoma.

BACKGROUND: Glioblastomas (GBMs) are the most common malignant primary brain tumours in adults and are refractory to conventional therapy, including surgical resection, radiotherapy and chemotherapy. The insulin-like growth factor (IGF) system is a complex network that includes ligands (IGFI and IGFII), receptors (IGF-IR and IGF-IIR) and high-affinity binding proteins (IGFBP-1 to IGFBP-6). Many studies have reported a role for the IGF system in the regulation of tumour cell biology. However, the role of this system remains unclear in GBMs. METHODS: We investigate the prognostic value of both the IGF ligands' and receptors' expression in a cohort of human GBMs. Tissue microarray and image analysis were conducted to quantitatively analyse the immunohistochemical expression of these proteins in 218 human GBMs. RESULTS: Both IGF-IR and IGF-IIR were overexpressed in GBMs compared with normal brain (P<10(-4) and P=0.002, respectively). Moreover, with regard to standard clinical factors, IGF-IR positivity was identified as an independent prognostic factor associated with shorter survival (P=0.016) and was associated with a less favourable response to temozolomide. CONCLUSIONS: This study suggests that IGF-IR could be an interesting target for GBM therapy.

Miconazole mucoadhesive buccal tablet in high-dose therapy with autologous stem cell transplantation (HDT/ASCT)-induced mucositis.

Oral mucositis is a major cause of morbidity in high-dose therapy/autologous stem cell transplantation (HDT/ASCT), where microbial colonization has an important pathological implication. In this study, we evaluated the impact of miconazole mucoadhesive buccal tablet (MBT) on mucositis-related complications. During two consecutive 34-month periods, patients treated with HDT/ASCT in our hematology department received either miconazole MBT (60 patients) or conventional oral amphotericin B suspensions three times a day (44 patients) in order to prevent or decrease chemotherapy-induced mucositis. The use of miconazole MBT is associated with less infectious complications as indicated by shorter antibiotic use (7.8 vs. 12.3 days; p < 0.0001), shorter intravenous antifungal use (1.4 vs. 3.6 days; p = 0.02), and a trend towards less yeast contamination in stool samples. Less patients required any analgesic drugs during hospitalization in the miconazole MBT group (18 vs. 7 %; p = 0.09). Indirect indicators of chemotherapy-induced mucositis (duration of hospitalization, morphine use) were in favor of miconazole MBT in patients with multiple myeloma (MM) but not for those with lymphoma. This study suggests that miconazole MBT provides a valid alternative to oral amphotericin B suspensions in regards to mucositis-related complications. A prospective and randomized study is warranted to establish the definite role of miconazole MBT.

Evaluation properties of the French version of the OUT-PATSAT35 satisfaction with care questionnaire according to classical and item response theory analyses.

PURPOSE: The present study investigates the properties of the French version of the OUT-PATSAT35 questionnaire, which evaluates the outpatients' satisfaction with care in oncology using classical analysis (CTT) and item response theory (IRT). METHODS: This cross-sectional multicenter study includes 692 patients who completed the questionnaire at the end of their ambulatory treatment. CTT analyses tested the main psychometric properties (convergent and divergent validity, and internal consistency). IRT analyses were conducted separately for each OUT-PATSAT35 domain (the doctors, the nurses or the radiation therapists and the services/organization) by models from the Rasch family. We examined the fit of the data to the model expectations and tested whether the model assumptions of unidimensionality, monotonicity and local independence were respected. RESULTS: A total of 605 (87.4%) respondents were analyzed with a mean age of 64 years (range 29-88). Internal consistency for all scales separately and for the three main domains was good (Cronbach's α 0.74-0.98). IRT analyses were performed with the partial credit model. No disordered thresholds of polytomous items were found. Each domain showed high reliability but fitted poorly to the Rasch models. Three items in particular, the item about "promptness" in the doctors' domain and the items about "accessibility" and "environment" in the services/organization domain, presented the highest default of fit. A correct fit of the Rasch model can be obtained by dropping these items. Most of the local dependence concerned items about "information provided" in each domain. A major deviation of unidimensionality was found in the nurses' domain. CONCLUSIONS: CTT showed good psychometric properties of the OUT-PATSAT35. However, the Rasch analysis revealed some misfitting and redundant items. Taking the above problems into consideration, it could be interesting to refine the questionnaire in a future study.

Impact of a goal-directed therapy protocol on postoperative fluid balance in patients undergoing liver transplantation: a retrospective study.

OBJECTIVE: Liver transplantation carries major risks during the perioperative period. Few studies focused on the hemodynamics of patients undergoing liver transplantation. The present study was aimed to evaluate the impact of the implementation of a protocol including goal-directed therapy in patients undergoing liver transplantation. Our first goal was to determine its impact on the fluid balance. Secondarily, we evaluated possible improvements in the patient outcomes. STUDY DESIGN: A before and after study. PATIENTS AND METHODS: Fifty patients undergoing liver transplantation were included during two successive six-month periods. During the first period, the management of the patients was left at the discretion of the senior physicians (control group, n=25). During the second period, the patients were treated according to a predetermined protocol including a specific hemodynamic monitoring (protocol group, n=25). RESULTS: The fluid balance was negative in the protocol group and positive in the control group at 24h (-606mL vs. +3445mL, P<0.01) and 48h (-2315mL vs. +1170mL, P<0.01) after liver transplantation. The volume of the crystalloid administration was lower in the protocol group than in the control group (5000mL vs. 8000mL, P<0.01, and 1500mL vs. 6000mL, P<0.01, during surgery and 48h after liver transplantation, respectively). The duration of mechanical ventilation and postoperative ileus were significantly reduced in the protocol group, as compared with the control group, 20h vs. 94h (P<0.01) and 4days vs. 6days (P<0.01), respectively. CONCLUSION: For patients undergoing liver transplantation, the implementation of a protocol aiming to optimize hemodynamics was associated with reduced fluid balance and decreased requirement for mechanical ventilation and postoperative ileus duration.

Response shift effects on measuring post-operative quality of life among breast cancer patients: a multicenter cohort study.

PURPOSE: To characterize response shift effects in patients with breast cancer (BC). METHODS: The QLQ-C30, BR23, and EurQOL-EQ-5D were assessed at baseline and at the end of the first hospitalization. We used the then-test approach to characterize changes in internal standards by calculating the mean difference between the then-test (retrospective measure) and pre-test baseline QoL assessments. The Ideal Scale Approach was also used to assess changes in standards by comparing health and QoL expectancies between baseline and the end of the first hospitalization. Successive Comparison Approach was used to assess changes in values through the longitudinal assessment of the relative importance of EuroQOL dimensions. RESULTS: The results of this study showed that recalibration RS effects occurred early after the first hospitalization for 6/15 dimensions of QLQ-C30 (emotional, cognitive, fatigue, insomnia, appetite loss, diarrhea) and 2/8 of BR-23 (future perspective, systemic therapy side effects). Moreover, health and QoL expectancies changed between the baseline and the end of the first hospitalization, and changes in values were seen for the self-care and usual activities dimensions of the EuroQOL-EQ-5D. CONCLUSIONS: The occurrence of RS early after the first hospitalization suggests that it needs to be taken into account to interpret QoL changes in BC.

Occurrence of and risk factors for electroencephalogram burst suppression during propofol-remifentanil anaesthesia.

BACKGROUND: Suppression ratio (SR) derived from bispectral index (BIS) monitoring is correlated to EEG burst suppression. It may occur during deep anaesthesia, but also in the case of metabolic or haemodynamic brain injury. The goal of the study was to describe the occurrence of SR and to determine factors associated with SR during propofol-remifentanil general anaesthesia maintenance. METHODS: We conducted a post hoc analysis of BIS recordings in consecutive patients included in two multi-centre trials, undergoing non-cardiac surgery using a dual closed-loop BIS controller allowing automated propofol-remifentanil administration. The percentage of time spent with a BIS value between 40 and 60 (T(BIS 40-60)) was measured. Two groups of patients were defined: the SR group, including patients with at least one episode of SR value >10% lasting more than 1 min, and the control group. Factors associated with SR were analysed using a stepwise multivariate analysis. RESULTS: A total of 1494 patients [age=57 (17) yr; T(BIS 40-60)=76 (17%)] were analysed and 131 (8.7%) patients constituted the SR group. The main independent factors associated with SR were advanced age [odds ratio (95% confidence interval)=4.80 (1.85-12.43) (P=0.027), 10.59 (3.76-29.81) (P<0.0001), for categories of age 60-80 and >80 yr, respectively], history of coronary artery disease (CAD) [2.53 (1.47-4.37) (P=0.001)] and male gender [1.57 (1.03-2.40) (P=0.03)]. CONCLUSIONS: The occurrence of SR during BIS-controlled propofol and remifentanil anaesthesia is mainly observed in elderly male patients or in patients with a history of CAD. The mechanisms underlying SR and the potential consequences for the patient's postoperative outcome remain unsolved.

Investigating the genetic structure of Phytophthora capsici populations.

Phytophthora capsici Leonian is a destructive soilborne pathogen that infects economically important solanaceous, cucurbitaceous, fabaceous, and other crops in the United States and worldwide. The objective of this study was to investigate the genetic structure of 255 P. capsici isolates assigned to predefined host, geographical, mefenoxam-sensitivity, and mating-type categories. Isolates from six continents, 21 countries, 19 U.S. states, and 26 host species were genotyped for four mitochondrial and six nuclear loci. Bayesian clustering revealed some population structure by host, geographic origin, and mefenoxam sensitivity, with some clusters occurring more or less frequently in particular categories. Bayesian clustering, split networks, and statistical parsimony genealogies also detected the presence of non-P. capsici individuals in our sample corresponding to P. tropicalis (n = 9) and isolates of a distinct cluster closely related to P. capsici and P. tropicalis (n = 10). Our findings of genetic structuring in P. capsici populations highlight the importance of including isolates from all detected clusters that represent the genetic variation in P. capsici for development of diagnostic tools, fungicides, and host resistance. The population structure detected will also impact the design and interpretation of association studies in P. capsici. This study provides an initial map of global population structure of P. capsici but continued genotyping of isolates will be necessary to expand our knowledge of genetic variation in this important plant pathogen.