Clinical Features and Survival of Multiple Primary Melanoma: A Belgian Single Center Cohort.

INTRODUCTION: It remains unclear whether multiple primary melanoma (MPM) patients have a worse survival prognosis compared with single primary melanoma (SPM) patients. OBJECTIVES: To investigate the demographics, histological features, and survival of MPM versus SPM patients. METHODS: Cox regression analyses compared survival between SPM and MPM patients. Furthermore, demographics and histological features of the MPM cohort were compared with the SPM patients retrieved from dermatopathology files between 2000 and 2019. RESULTS: Out of 3853 melanoma patients, 95 MPM patients were retrieved: 81 with two primary melanomas (85.2%) and 14.8% with three or more. Mean Breslow of the first melanoma was 0.84 mm [minimum (min): 0 mm, maximum (max): 16 mm, standard deviation (SD) 1.77] versus 0.37 mm (second MPM) (min: 0 mm, max: 2.5 mm, SD 0.50) and 0.33 mm (third MPM) (min: 0 mm, max: 0.6 mm, SD 0.22). The mean Breslow for the second MPM was significantly higher for men than women (0.59 mm versus 0.27 mm). First and second melanoma in MPM patients developed on preexisting melanocytic nevi in 13% and 12%, respectively. In contrast with the mean age of primary melanoma in Belgium for women (58.2 years) and men (63.3 years), MPM patients developed their first melanoma earlier, at 44.8 years and 54.6 years, respectively. The mean distribution of anatomical localization of primary and secondary melanoma was highly similar in women, whereas in men a shift towards lower extremities was observed (19% versus 28%). The thicker the primary melanoma was, the sooner the second appeared. Follow-up (2-4/year) versus (1/year) yielded a mean Breslow of 0.29 mm and 0.55 mm, respectively. Cox regression analysis with time-varying covariate revealed a tendency for a worse prognosis in 5-year survival rates, but this was not statistically significant (p = 0.09). Patient phenotypes were not available on the histological reports. CONCLUSION: A closer follow-up regimen of MPM versus SPM patients is probably justified.

Monteggia fractures: analysis of patient-reported outcome measurements in correlation with ulnar fracture localization.

BACKGROUND: Monteggia fractures and Monteggia-like lesions result after severe trauma and have high complication rates. Preliminary biomechanical studies suggested a correlation between ulnar fracture localization and clinical result. OBJECTIVES: Key objective was to evaluate whether the site of the ulnar fracture can be correlated to clinical outcome after open reduction and internal stabilization. METHODS: In a retrospective, monocentric study 35 patients who underwent surgical treatment after suffering a Monteggia injury or Monteggia-like lesion were included. Fractures were classified according to Bado and Jupiter, the site of the fracture location at the proximal ulna and regarding the potential accompanying ligamentary injury. In a follow-up examination validated patient-reported outcome measures and functional parameters were evaluated. Furthermore, treatment strategy and complications were analysed. RESULTS: Mean patient age was 51.9 years (± 18.0). 69% were females (n = 24). Follow-up took place after 50.5 months (± 22.1). Fractures were classified according to Bado (I:2, II:27, III:4, IV:2). Bado II-fractures were further classified according to Jupiter (A:7, B:16, C:3, D:1). Cases were divided into subgroups depending upon the distance of the ulnar fracture site in respect to its distal endpoint (A: < 7 cm and B: > 7 cm). Average overall MEPS was 84.1 (± 19.0). Oxford elbow score and DASH were 37.2 (± 10.5) and 20.4 (± 20.5). Average extension capability reached - 7° (± 7.5). Mean flexion was 134.8° (± 19.7). Average pain according to visual analogue scale was 1.6 (± 1.9). We found no differences between the subgroups regarding the PROMs. Subgroup A displayed a worse extension capability (p = 0.027) and patients were significantly older (p < 0.01). Comparing patients with and without fracture of the radial head, we observed no differences. Patients with an accompanying injury of the coronoid process displayed higher pain levels (p = 0.011), a worse functionality (p = 0.027) and overall lower scoring in PROM. CONCLUSION: The presented results suggest that in Monteggia fractures and Monteggia-like lesions, the localization of the ulna fracture can give a hint for its postoperative outcome. However, we could not confirm the hypothesis of an increasing instability in ulnar fractures located further distally (high severity of the potential ligamentous injury). Intraarticular fractures or injuries with a close relation to the joint have a worse prognosis, especially if the coronoid process is injured. Trial registration Registration was done with ClinicalTrials.gov under NCT05325268.

[Clinical impact of small bowell capsule endoscopy in obscure gastrointestinal bleeding : retrospective single-center study]. / Impact clinique de la vidéocapsule endoscopique du grêle dans les saignements digestifs inexpliqués. Etude rétrospective monocentrique.

INTRODUCTION: The small-bowel capsule endoscopy (VCE) has been validated in the investigation of obscure gastrointestinal bleeding (OGIB). The aim of this study was to evaluate the clinical impact of VCE for OGIB in routine practice, in terms of subsequent management and the risk of rebleeding. METHODS: Our retrospective study analyzed the VCE at the CHU of Liège from March 2016 to December 2019 (cohort of 110 patients with OGIB). RESULTS: We found a diagnostic yield of 58 %, a change in therapeutic attitude in 39 % of patients and a recurrence rate of 22.5 % (out of 102 patients followed at 2 years). The rate of rebleeding was particularly low in patients with normal VCE and in those for whom a therapeutic modification was made. Finally, about 45 % of patients did not have any change in therapeutic attitude nor recurrence. CONCLUSION: VCE leads to a therapeutic modification in about 40 % of patients with a low risk of relapse. However, VCE could be avoided in some patients as evidenced by a subgroup representing 45 % of patients for whom there was no therapeutic modification nor recurrence.

introduction et but : La vidéocapsule endoscopique grêle (VCE) est validée dans l'exploration des saignements digestifs inexpliqués (OGIB). Le but de notre travail a été d'évaluer l'impact clinique de la réalisation d'une VCE pour OGIB en pratique courante, en termes de prise en charge ultérieure et de risque de récidive du saignement. Méthodes : Notre étude rétrospective a analysé les VCE réalisées au CHU de Liège de mars 2016 à décembre 2019. Résultats : Les VCE de 110 patients ont été rétrospectivement analysées. Nous avons observé un pouvoir diagnostique de 58 % et une modification d'attitude thérapeutique chez 39 % des patients. Le taux de récidive (pour les 102 patients dont le suivi était disponible à maximum 2 ans) était de 22,5 %. Le taux de récidive de saignement était particulièrement faible chez les patients avec VCE normale et chez ceux pour lesquels une modification thérapeutique a été faite. Enfin, environ 45 % des patients n'ont pas eu de modification de l'attitude thérapeutique ni de récidive. Conclusions : La VCE débouche sur une modification thérapeutique chez environ 40 % des patients avec, dans la foulée, un faible risque de récidive. Par contre, la VCE pourrait être évitée chez certains patients comme en témoigne un sous-groupe représentant 45 % des patients pour lesquels il n'y a eu ni modification thérapeutique ni rechute.

The impact of an ultra-trail on the dynamic of cardiac, inflammatory, renal and oxidative stress biological markers correlated with electrocardiogram and echocardiogram.

The aim of this study was to describe the effects of a 64.2 km ultra-trail on the biomarkers of muscle damage, inflammation and oxidative stress, and compare the results observed with an ECG and an echocardiogram, both performed before and after the race.Thirty-three ultra-trail volunteers (45.8 ± 8.7 years old) were enrolled in our study. Three blood tests were drawn from each runner, one just before (TPRE), one just after (TPOST) and the last 3 h after the end of the race (TPOST3h).All the markers increased. The maximum concentrations observed were at TPOST3h and were significant (p < 0.001) for creatine kinase, creatine kinase isoform MB, high-sensitivity C-reactive protein, uric acid and for the ratio of reduced glutathione to oxidised glutathione. However, in the case of myoglobin, high-sensitive troponin T, N-terminal pro-brain natriuretic peptide, oxidised glutathione, myeloperoxidase, cystatin C and creatinine, the most significant increases were at TPOST (p < 0.001). Modifications were observed in the medical imaging using echocardiography such as reduction of left ventricule end-sytolic and diastolic volumes and left ventricular global longitudinal strain. ECG showed electrical criteria for left ventricular hypertrophy and incomplete right bundle branch block after the race.Endurance races cause significant physiological stress to the body that can be measured by the increase of different biomarkers. From a laboratory perspective, it is important to take into account the possible exercise performed previous to the testing to avoid a misinterpretation of the results. From a training perspective, due to these increases in biomarkers, it is recommended that runners wait at least 72 h after an ultra-trail before subsequent training. In addition a transient impairment of ventricular function due to dehydration were observed.

Ustekinumab in bio-naïve and bio-failure Crohn's disease patients: Results from a « real-life ¼ monocentric cohort.

BACKGROUND: The pivotal clinical trials have largely demonstrated the efficacy and safety of ustekinumab in Crohn's disease. Real-life cohorts published so far only include very few bio-naïve patients. This study assesses effectiveness and safety of ustekinumab in bio-naïve and bio-failure patients treated with ustekinumab in routine practice and look for predictors of response. METHODS: We performed a retrospective monocentric study. Initial response was assessed by maintenance therapy beyond week 16. Sustained response was assessed by the continuation or cessation of therapy over time for another reason than stopping in sustained remission. Treatment persistence was assessed by Kaplan Meier curves and predictors of treatment persistence were studied by univariate and multivariate Cox model. RESULTS: Out of 156 recorded patients, three patients were still in their induction phase at time of analysis and 5 patients were lost to follow-up, leaving 148 patients for clinical effectiveness analyses, including 35 bio-naïve when starting ustekinumab. A maintenance therapy was initiated in 79.7%. At one year, the probability to be still treated with ustekinumab was 73.8%. Treatment cessation increased with smoking in multivariate analysis. Previous biologic failure (as a whole), CRP and fecal calprotectin baseline levels did not influence initial response and treatment persistence. CONCLUSION: A large proportion of CD patients initially respond to ustekinumab and continue this treatment beyond one year. Treatment persistence is as high in bio-failure as in bio-naïve patients.

Use of methotrexate in the treatment of ectopic pregnancies: a retrospective single center study.

INTRODUCTION: The aim of this study was to evaluate the efficacy of methotrexate (MTX) in the treatment of ectopic pregnancies. We identified predictive factors of success or failure and compared our results with previous studies to make recommendations for its use. MATERIAL AND METHODS: A cohort of 61 patients from a single center was retrospectively analyzed. Inclusion criteria were a diagnosis of ectopic pregnancy and treatment with a single-dose injection of MTX. The need to perform surgery despite MTX was defined as treatment failure while needing a second MTX injection was not. RESULTS: In our cohort, MTX demonstrated a success rate of 80%. This rate rose to 84% when patients with human Chorionic Gonadotropin (hCG ) > 5,000 IU/L were excluded. Twenty percent underwent surgery for pain, increased mass size and/or suboptimal hCG kinetics. Low hCG levels on days 0, 4 and 7 as well as the absence of pain, metrorrhagia and hemoperitoneum were predictive of success. MTX was also efficient in the treatment of persisting pregnancies of unknown location (PUL). CONCLUSION: Our results are consistent with previous studies and emphasize the fact that MTX is less effective above a certain level of hCG. We obtained a cut-off value of 2439 IU/L with a sensitivity of 66.7% and a specificity of 93.9%. MTX should not be used when hCG is higher than 5,000 IU/L and laparoscopic surgery should be performed. Our results bring additional data about the efficacy of MTX in the management of persisting pregnancies of unknown location.

WITHDRAWN: A single center experience in resectable pancreatic ductal adenocarcinoma : the limitations of the surgery-first approach. Critical review of the literature and proposals for practice update.

The article has been withdrawn at the request of the authors and editor because of incorrect authorship, which is considered a form of unethical publication. The Publisher apologizes for any inconvenience this may cause.

A single center experience in resectable pancreatic ductal adenocarcinoma : the limitations of the surgery-first approach. Critical review of the literature and proposals for practice update.

BACKGROUND AND STUDY AIMS: The current standard of care for resectable pancreatic ductal adenocarcinoma (PDAC) is surgery-first followed by adjuvant chemotherapy. We review our single center experience in a PDAC cohort managed by the surgery-first strategy. We then compare our data to those of Belgian and international literature. PATIENTS METHODS: We reviewed a series of 83 consecutive resectable patients with PDAC, treated by the surgery-first approach in a Belgian Academic Hospital between 2007 and 2013. The outcomes were assessed with univariate and multivariate Cox regression analysis. Kaplan-Meier curves were drawn according to patient groups. RESULTS: For the entire population, the median survival (MS) was 18.4 months; the 1-year relapse-free survival was 56%, and the 5-year overall survival (OS) was 13%. The size of the primary tumor larger than 3 cm (OS, HR = 1.76, p = 0.033) and vascular resection (DFS, HR = 2.1, p = 0.024) were the single independent prognostic factors in the multivariate analysis of this cohort. Only 69% of the patients received adjuvant chemotherapy, and more than 75% of them demonstrated no chance of survival beyond 3 years because they harbored poor prognostic factors, recognized only postoperatively. CONCLUSIONS: Our results and those published in the literature brought to light the limited perspectives of the surgery-first strategy in a population of apparently resectable pancreatic cancers. In comparison, data from reported neo-adjuvant series deserve our interest to bring this strategy upfront in selected patients in the context of close observational monitoring and randomized trials. The actual standard of care for resectable PDAC is surgery-first followed by adjuvant chemotherapy. The performance of this strategy relies on the dedicated imaging that does not accurately recognize the limits of the tumor and the high prevalence of adverse prognostic factors. Moreover, pancreatectomy remains associated with high postoperative complication rates and the poor completion of adjuvant therapy. This translates into poor long-term survival figures. In our series the MS was 18.4 months and 5-year OS was 13%. The disease-free survival (DFS) was 15.6 months, 1 and 3-year DFS were 56 and 26%, respectively. The variables that significantly correlated with OS in univariate analysis are tumor size and lymph node involvement. Regarding DFS, vascular resection was the only significant factor. In the multivariate analysis, the only significant factor related to OS remained the tumor size >3 cm in greatest diameter. Vascular resection remained significant for DFS. 31% of the patients did not receive any chemotherapy at all before the 6-month period following resection. The rates of complete resections compared favorably with those of a surgery-first strategy with no excess of operative mortality, complications and early relapse rates. The advantages of a chemotherapy-first approach, eventually combined with chemo-radiotherapy, are to offer higher combined therapy completion rates and improve the level of free resection margins, lymph node involvement and patient selection. The advent of safe, more potent chemotherapy combinations has the potential to further improve survival when administered upfront.

Oncological and surgical outcome after oncoplastic breast surgery.

BACKGROUND: Oncoplastic surgery combines breast-conserving treatment and plastic surgery techniques. The aim of the study was to identify breast and tumor-related characteristics that contribute to the rate of complications and recurrence. METHODS: This retrospective study included 72 patients with a median follow-up of 32 months. For each patient, a comprehensive set of data was collected, including epidemiology, tumor characteristics, preoperative information, detailed pathology reports, radiotherapy treatment and type of surgical technique. The rate of complications, recurrence and survival were studied. RESULTS: Complete tumor removal was performed with clear margins in all patients but in 25 of them margins were less than 2 mm. One patient had local recurrence and another developed distant metastases. The study showed that the size of the margin was not predictive of recurrence as long as not positive; the greater the resection volume, the larger the excision margin. The resection size was the only factor influencing complications and no specific tumor-related factor significantly increased the complication rate. Surgical complications did not delay the initiation of chemotherapy and radiotherapy. CONCLUSIONS: This is the first oncoplastic study where both tumor and breast characteristics were analyzed using the most recent criteria of the literature. Oncoplastic surgery can be considered as oncologically safe. The resection size was the sole significant risk factor for postoperative complications. Complications after oncoplastic breast surgery did not differ neoadjuvant therapy. Long-term event-free survival was excellent (96% at 7 years).

Oncological and Surgical Outcome after Oncoplastic Breast Surgery.

BACKGROUND: Oncoplastic surgery combines breast-conserving treatment and plastic surgery techniques. The aim of the study was to identify breast and tumor-related characteristics that contribute to the rate of complications and recurrence. MATERIAL & METHODS: This retrospective study included 72 patients with a median follow-up of 32 months. For each patient, a comprehensive set of data was collected, including epidemiology, tumor characteristics, preoperative information, detailed pathology reports, radiotherapy treatment and type of surgical technique. The rate of complications, recurrence and survival were studied. RESULTS: Complete tumor removal was performed with clear margins in all patients but in 25 of them margins were less than 2 mm. One patient had local recurrence and another developed distant metastases. The study showed that the size of the margin was not predictive of recurrence as long as not positive; the greater the resection volume, the larger the excision margin. The resection size was the only factor influencing complications and no specific tumor-related factor significantly increased the complication rate. Surgical complications did not delay the initiation of chemotherapy and radiotherapy. CONCLUSION: This is the first oncoplastic study where both tumor and breast characteristics were analyzed using the most recent criteria of the literature. Oncoplastic surgery can be considered as oncologically safe. The resection size was the sole significant risk factor for postoperative complications. Complications after oncoplastic breast surgery did not differ neoadjuvant therapy. Long-term event-free survival was excellent (96% at 7 years).

Depth of remission in Crohn's disease patients seen in a referral centre : associated factors and impact on disease outcome.

INTRODUCTION: Our goals were to assess the prevalence of biological and tissue remission in routine practice in Crohn's disease, and to evaluate the correlation between biological or tissue remission and clinical or demographic characteristics as well as their impact on disease outcome. METHODS: We performed a retrospective monocenter study. Biological remission was defined by a CRP < 5 mg/I. Tissue remission was defined by the absence of ulcer at endoscopy and/or absence of signs of acute inflammation at MRI. Association with demographic, clinical and laboratory markers was studied by logistic regression models and rates of relapses, hospitalizations and surgeries were compared using the logrank test. RESULTS: Among the 263 patients included, 147 were in clinical remission; 102/147 (69%) were in biological remission. Fifty-six patients also had morphological evaluation: 37 (66%) were in tissue remission. Biological remission was associated with older age, higher hemoglobin and lower BMI. Tissue remission was associated with older age, lower platelets count, absence of previous surgery, and the use of immunosuppressant. Time-to-relapse was significantly longer in patients with biological remission and in patients with tissue remission as compared to patients without biological or tissue remission. CONCLUSIONS: Among the patients in clinical remission seen as outpatients, two thirds were either in biological and/or tissue remission. Biological and/or tissue remission was associated with a better outcome than clinical remission alone.

Serum calprotectin as a biomarker for Crohn's disease.

BACKGROUND AND AIMS: In Crohn's disease, correlation between clinical assessment and disease activity at tissue level is weak. Our aim was to evaluate the value of serum calprotectin as a biomarker for Crohn's disease. METHODS: The STORI trial patients (n=115) were studied at baseline, in clinical remission before infliximab withdrawal, or at the time of relapse after infliximab withdrawal. Forty healthy controls were also studied. Serum calprotectin level was measured by ELISA. Data were analyzed through correlation analyses, Kaplan Meier curves and Cox model, using available Crohn's Disease Activity Index (CDAI), Crohn's Disease Endoscopic Index of Severity (CDEIS), fecal calprotectin and C-reactive protein levels (hsCRP). RESULTS: Median serum calprotectin was 8892 ng/mL (range: 410-125,000 ng/mL) in Crohn disease patients as compared with 1318 ng/mL (range: 215.8-3770 ng/mL) in controls (P<0.0001). Serum calprotectin was significantly higher for active disease (median=19,584 ng/mL) than for inactive disease (median=8353 ng/mL) (P<0.0001). Serum calprotectin correlated with hsCRP (r=0.4092, P<0.0001) and CDAI (r=0.4442, P<0.0001), but not with CDEIS, on the contrary to fecal calprotectin (r=0.6458, 0.5515, 0.2577 with P<0.0001, P<0.0001, P=0.019 respectively). In multivariate analysis, serum calprotectin used as a discrete variable (threshold: 5675 ng/ml), appeared complementary to hsCRP (>5 mg/l) and fecal calprotectin (>250 µg/g) to predict relapse after infliximab withdrawal (P=0.0173, 0.0024 and 0.0002; HR: 3.191, 3.561 and 4.120). CONCLUSIONS: As a CD biomarker, serum calprotectin has a similar profile as hsCRP. It is also complementary to fecal calprotectin and hsCRP for prediction of relapse after infliximab withdrawal.

Does co-treatment with immunosuppressors improve outcome in patients with Crohn's disease treated with adalimumab?

BACKGROUND: There is clear benefit from combination therapy with infliximab and immunosuppressive drugs (IS), but few data are available for adalimumab (ADA). AIM: To assess the efficacy of ADA monotherapy and ADA+IS for induction and maintenance therapy in Crohn's disease. METHODS: Retrospective study of patients with Crohn's disease treated with ADA in Oxford, UK or Liège, Belgium. Treatment periods were divided into 6-month semesters. A combination therapy semester was defined as ADA+IS for at least 3 months; successful induction meant clinical response; a semester with flare as ADA dose escalation, starting steroids, perianal complication, or surgery; and ADA failure as ADA withdrawal for secondary loss of response or intolerance. Semesters with and without flares were compared through univariate and multivariate analysis. RESULTS: Successful induction was achieved in 171/207 (83%) patients, with no significant difference between ADA+IS and ADA monotherapy (85% vs. 82%, P = 0.50). Five hundred and sixty-two semesters in 181 patients were included for maintenance analysis. ADA+IS was not associated with fewer semesters with flare (34% vs. 35%, P = 0.96), or with ADA failure (6% vs. 8%, P = 0.43). Nevertheless, combination therapy in the first semester was associated with a lower risk of ADA failure (5% vs. 10%, P = 0.04, OR = 0.48) and combination therapy beyond 6 months was associated with fewer semesters with flares (14% vs. 36%, P = 0.02, OR = 0.31). CONCLUSIONS: There may be a benefit from adalimumab+immunosuppressive drugs combination therapy during the first semester of initiating adalimumab, with a slight decrease in adalimumab failure and lower need for adalimumab dosage escalation.

Diffuse large B-cell lymphoma of Waldeyer's ring has distinct clinicopathologic features: a GELA study.

BACKGROUND: Diffuse large B-cell lymphomas (DLBCLs) arising in specific extranodal sites have peculiar clinicopathologic features. PATIENTS AND METHODS: We analyzed a cohort of 187 primary Waldeyer's ring (WR) DLBCLs retrieved from GELA protocols using anthracyclin-based polychemotherapy. RESULTS: Most patients (92%) had stage I-II disease. A germinal center B-cell-like (GCB) immunophenotype was observed in 61%, and BCL2 expression in 55%, of WR DLBCLs. BCL2, BCL6, IRF4 and MYC breakpoints were observed in, respectively, 3 of 42 (7%), 9 of 36 (25%), 2 of 26 (8%) and 4 of 40 (10%) contributive cases. A variable follicular pattern was evidenced in 30 of 68 (44%) large biopsy specimens. The 5-year progression-free survival (PFS) and the overall survival (OS) of 153 WR DLBCL patients with survival information were 69.5% and 77.8%, respectively. The GCB immunophenotype correlated with a better OS (P = 0.0015), while BCL2 expression predicted a worse OS (P = 0.037), an effect overcome by the GCB/non-GCB classification. Compared with matched nodal DLBCLs, WR DLBCLs with no age-adjusted international prognostic index factor disclosed a better 5-year PFS rate (77.5% versus 70.7%; P = 0.03). CONCLUSIONS: WR DLBCLs display distinct clinicopathologic features compared with conventional DLBCLs, with usual localized-stage disease, common follicular features and a high frequency of GCB immunophenotype contrasting with a low rate of BCL2 rearrangements. In addition, they seem to be associated with a better outcome than their nodal counterpart.

Is FENO50 useful diagnostic tool in suspected asthma?

BACKGROUND: Asthma diagnosis is based on the presence of symptoms and the demonstration of airflow variability. Airway inflammation measured by fractional exhaled nitric oxide, measured at a flow rate of 50 ml/s (FE(NO50)) remains a controversial diagnostic tool. AIM: To assess the ability of FE(NO50) to identify bronchial hyperresponsiveness (BHR) to methacholine (provocative concentration of methacholine causing a 20% fall in FEV(1); PC20M ≤ 16 mg/ml) and to establish whether or not symptoms relate to FE(NO50) and PC20M in patients with no demonstrated reversibility to ß(2) -agonist. METHODS: We conducted a prospective study on 174 steroid naive patients with respiratory symptoms, forced expiratory volume in 1 s (FEV(1) ) ≥ 70% predicted and no demonstrated reversibility to ß(2) -agonist. Patients answered to a standardised symptom questionnaire and underwent FE(NO50) and methacholine challenge. Receiver-operating characteristic (ROC) curve and logistic regression analysis assessed the relationship between PC20M and FE(NO50) , taking into account covariates (smoking, atopy, age, gender and FEV(1)). RESULTS: A total of 82 patients had a PC20M ≤ 16 mg/ml and had significantly higher FE(NO50) (19 ppb vs. 15 ppb; p < 0.05). By constructing ROC curve, we found that FE(NO50) cut-off value of 34 ppb was able to identify not only BHR with high specificity (95%) and positive predictive value (88%) but low sensitivity (35%) and negative predictive value (62%). When combining all variables into the logistic model, FE(NO50) (p = 0.0011) and FEV(1) (p < 0.0001) were independent predictors of BHR whereas age, gender, smoking and atopy had no influence. The presence of diurnal and nocturnal wheezing was associated with raised FE(NO50) (p < 0.001 and p < 0.05, respectively). CONCLUSION: The value of FE(NO50) > 34 ppb has high predictive value of PC20M < 16 in patients with suspected asthma in whom bronchodilating test failed to demonstrate reversibility or was not indicated. However, FE(NO50) ≤ 34 ppb does not rule out BHR and should prompt the clinician to ask for a methacholine challenge.

Elevations of tumor necrosis factor receptor 1 at day 7 and acute graft-versus-host disease after allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning.

Acute GVHD has remained a significant cause of nonrelapse mortality after allogeneic hematopoietic cell transplantation (HCT) with nonmyeloablative conditioning. The role of TNF-alpha in the biology of acute GVHD after nonmyeloablative conditioning has not been studied thus far. Here, we measured TNF receptor 1 (TNFR1) as a surrogate marker for TNF-alpha in 106 patients before the start of the conditioning regimen (baseline) and 7 days after allogeneic HCT with nonmyeloablative conditioning. The nonmyeloablative regimen consisted of 2 Gy TBI alone (n=15), 2 Gy TBI plus fludarabine 90 mg/m2 (n=73), or 4 Gy TBI plus fludarabine 90 mg/m2 (n=18). TNFR1 levels increased significantly from baseline to day 7 after nonmyeloablative HCT (P<0.0001). Patients conditioned with 4 Gy TBI had higher TNFR1 day 7/baseline ratio than those conditioned with 2 Gy TBI (median 1.65 versus 1.25; P=0.01). In a multivariate Cox model, high TNFR1 day7/baseline ratio was associated with grades II-IV (HR=2.2, P=0.01) and grades III-IV (HR=2.9, P=0.007) acute GVHD, but had no impact on overall survival (P=0.8). In summary, our data suggest that nonmyeloablative conditioning induces the generation of TNF-alpha, and that the magnitude of TNF-alpha generation depends on the conditioning intensity (2 Gy versus 4 Gy TBI). Further, assessment of TNFR1 levels before and on day 7 after nonmyeloablative HCT provided useful information on subsequent risk of experiencing acute GVHD.

Comparison of thrombotic microangiopathy after allogeneic hematopoietic cell transplantation with high-dose or nonmyeloablative conditioning.

The role of conditioning intensity on occurrence of thrombotic microangiopathy (TMA) after allogeneic hematopoietic cell transplantation (HCT) has remained unclear thus far. Here, we retrospectively compared the incidence of TMA in patients given allogeneic hematopoietic stem cells after either nonmyeloablative (n=176) or high-dose (n=111) conditioning. The 1-year cumulative incidence of TMA was 13% in nonmyeloablative recipients versus 15% in high-dose conditioning recipients (P=0.5). In multivariate Cox analysis, occurrence of grade 3-4 acute graft-versus-host disease (GVHD) (hazard ratio (HR)=2.3, P<0.001), older age (HR=1.01, P=0.045), and unrelated donors (HR=1.6, P=0.01) were each associated with a higher risk of TMA, whereas nonmyeloablative conditioning was associated with a lower risk of TMA (HR=0.6, P=0.01). We conclude that acute GVHD, age, donor type, and conditioning intensity might have a role in the physiopathology of TMA after allogeneic HCT.

Low vs. high concentration of levobupivacaine for post-operative epidural analgesia: influence of mode of delivery.

BACKGROUND: Although the use of continuous epidural infusion (CEI) and patient-controlled epidural analgesia (PCEA) has become commonplace in pain management, there is still controversy regarding the relative effects of mass, volume and concentration of the local anaesthetic. This prospective study evaluated the influence of two concentrations of levobupivacaine on the quality of analgesia in two modes of delivery after lower abdominal surgery. METHODS: Eighty-two patients were randomly assigned to four groups to receive combined low thoracic epidural analgesia and general anaesthesia followed by post-operative CEI or PCEA using 1.5 or 5 mg/ml levobupivacaine (15 mg/h in CEI and bolus 5 mg, lockout 20 min in PCEA). Sensory block, pain scores, levobupivacaine and rescue morphine consumption, motor blockade, haemodynamics, side-effects and patient satisfaction were registered within 48 h. RESULTS: The four groups were similar with regard to demographics, quality of analgesia, morphine consumption and satisfaction rate. No difference in the quality of analgesia was observed for the two modes of delivery with regard to the concentration of levobupivacaine, but the consumption of the local anaesthetic was higher in the CEI groups. The Bromage scores in the PCEA groups were reduced to zero for all except one patient, whereas eight patients presented scores of one or more in the CEI population. CONCLUSION: Levobupivacaine in thoracic epidurals provides an equal quality of post-operative analgesia in low and high volume independent of the delivery mode, i.e. CEI or PCEA. This is in accordance with the assumption that the total dose of the local anaesthetic determines the quality of analgesia.