Serum Proteome Pool Changes in Type 2 Diabetic Patients Treated with Anakinra

Introduction

High glucose concentrations induce the production of IL-1β in human pancreatic beta cells leading to impaired insulin secretion, decreased cell proliferation and apoptosis. Blockade of IL-1 signalling with the recombinant human IL-1 receptor antagonist anakinra reduces HbA_1c in patients with type 2 diabetes. The aims of the present study were to identify: (1) candidate surrogates for improved glycemia in type 2 diabetic patients following treatment with anakinra, (2) proteins that change serum concentration because of anakinra treatment and (3) candidate biomarkers that may predict improved glycemia in type 2 diabetic subjects treated with anakinra.

Methods

Surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry was used to analyse serum from 67 type 2 diabetic patients who had received either placebo or anakinra for 13 weeks. Immunodepletion with magnetic protein G bead-coupled antibodies were used to identify three proteins and Western blotting confirmed the biomarker concentration pattern of four proteins.

Results

Twelve proteins, including transthyretin (TTR) and transferrin (Tf), were identified as candidate surrogates for improved glycemia. Six proteins, including retinol-binding protein 4 (RPB4) and a protein tentatively identified as modified apolipoprotein-A1 (apo-AI), increased expression as a consequence of anakinra treatment and four proteins were candidate biomarkers that may predict improved glycemia following anakinra treatment. Furthermore, we found increased RBP4 to be associated with improved beta cell secretory function and increased TTR, RBP4 and modified apo-AI (peak at 28,601 Da) to be associated with decreased inflammation.

Conclusions

Anakinra-induced changes in the serum proteome pool associated with a decreased cardiovascular disease risk, reduced inflammation and improved beta cell secretory function.     

Aldolase predicts subsequent myopathy occurrence in systemic sclerosis

Introduction

In early rheumatoid arthritis (RA), low-dose oral prednisone (PDN) co-medication yields better clinical results than monotherapy with disease-modifying anti-rheumatic drugs (DMARDs). In addition, ultrasonography (US) evaluation reveals rapid and significant effects of glucocorticosteroids on subclinical synovitis. No data currently exist that examine the clinical and US results offered by glucocorticoid co-medication over DMARD monotherapy in early RA patients.

Methods

Two hundred and twenty patients with early RA (< 1 year from clinical onset) were treated according to a low disease activity (LDA) targeted step-up protocol including methotrexate (MTX) and, in the active treatment arm, low-dose (6.25 mg/day) oral PDN over 12 months. Clinical disease activity measures were collected at baseline, 2, 4, 6, 9 and 12 months, and US examination of hands was performed at baseline, 6 and 12 months. Grey-scale and power Doppler (PD) synovitis were scored (0 to 3) for each joint. At 12 months, clinical remission according to the disease activity score among 28 joints was defined as the clinical outcome, and a total joint PD score of 0 (PD negativity) as the imaging outcome.

Results

Each group included 110 patients with comparable demographic, clinical, laboratory and US characteristics. At 12 months, the LDA rate was similar in the two groups, whilst the clinical remission rate (risk ratio = 1.61 (95% confidence interval = 1.08, 2.04)) and PD negativity rate (risk ratio = 1.31 (95% confidence interval = 1.04, 1.64)) were significantly higher in the MTX+PDN group.

Conclusion

In early RA, despite a similar response rate in terms of LDA, low-dose oral PDN co-medication led to a higher proportion of clinical remission and PD negativity compared with MTX monotherapy, thus ensuring a better disease activity control.

Trial registration number

Current Controlled Trials ISRCTN2486111     

The schedule of administration of canakinumab in cryopyrin associated periodic syndrome is driven by the phenotype severity rather than the age

Introduction

Interleukin-1 (IL-1) blockade is the treatment of choice of cryopyrin associated periodic syndromes (CAPS). Anti-IL-1 monoclonal antibody (canakinumab) was recently registered. However no clear data are available on the optimal schedule of administration of this drug. The aim of the present study was to analyse the impact of canakinumab on CAPS patients in daily clinical practice and to identify the best schedule of administration according to age and phenotype.

Methods

13 CAPS patients (10 children and 3 young adults) treated with canakinumab were followed for 12 months. Clinical and laboratory parameters were collected at each visit. Health-related quality of life (HRQoL) was recorded at month 12. Complete response was defined as absence of clinical manifestations and normal examinations. Clinical and laboratory variables at last follow-up were compared with those registered at the moment of anakinra discontinuation.

Results

seven patients with chronic infantile neurological cutaneous articular (CINCA) syndrome, four patients with Muckle-Wells syndrome (MWS) and two patients with an overlapping MWS/CINCA phenotype were analysed. CINCA patients experienced a higher number of modifications of the treatment (increased dosage or decreased dosing interval) in respect to MWS patients. At the end of the follow-up CINCA patients displayed a higher frequency of administration with a median dose of 3.7 mg/kg (2.1 mg/kg for MWS patients). Canakinumab was withdrawn in a patient with CINCA for incomplete response and poor compliance. The effect of canakinumab on HRQoL was similar to that observed during treatment with anakinra, with the exception of an improvement of the psychosocial concepts after the introduction of canakinumab.

Conclusions

The use of canakinumab in daily practice is associated with persistent satisfactory control of disease activity but needs progressive dose adjustments in more severe patients. The clinical phenotype, rather than the age, represents the main variable able to determine the need of more frequent administrations of the drug at higher dosage.     

Ipilimumab experience in heavily pretreated patients with melanoma in an expanded access program at the University Hospital of Siena (Italy)

Aim of study

To evaluate the feasibility of ipilimumab treatment for metastatic melanoma outside the boundaries of clinical trials, in a setting similar to that of daily practice.

Methods

Ipilimumab was available upon physician request in the Expanded Access Programme for patients with life-threatening, unresectable stage III/IV melanoma who failed or did not tolerate previous treatments and for whom no therapeutic option was available. Induction treatment with ipilimumab 10?mg/kg was administered intravenously every 3?weeks, for a total of 4 doses, with maintenance doses every 12?weeks based on physicians?? discretion and clinical judgment. Tumors were assessed at baseline, Week 12, and every 12?weeks thereafter per mWHO response criteria, and clinical response was scored as complete response (CR), partial response (PR), stable disease (SD), or progressive disease. Durable disease control (DC) was defined as SD at least 24?weeks from the first dose, CR, or PR.

Results

Disease control rate at 24 and 60?weeks was 29.6% and 15%, respectively. Median overall survival at a median follow-up of 8.5?months was 9?months. The 1- and 2-year survival rates were 34.8% and 23.5%, respectively. Changes in lymphocyte count slope and absolute number during ipilimumab treatment appear to correlate with clinical response and survival, respectively. Adverse events were predominantly immune related, manageable, and generally reversible. One patient died from pancytopenia, considered possibly treatment related.

Conclusion

Ipilimumab was a feasible treatment for malignant melanoma in heavily pretreated, progressing patients. A sizeable proportion of patients experienced durable DC, including benefits to long-term survival.     

Effects of cyclophosphamide on pulmonary function in patients with scleroderma and interstitial lung disease: a systematic review and meta-analysis of randomized controlled trials and observational prospective cohort studies

Introduction

The purpose of the present study was to systematically review the effect of cyclophosphamide treatment on pulmonary function in patients with systemic sclerosis and interstitial lung disease.

Methods

The primary outcomes were the mean change in forced vital capacity and in diffusing capacity for carbon monoxide after 12 months of therapy in patients treated with cyclophosphamide.

Results

Three randomized clinical trials and six prospective observational studies were included for analysis. In the pooled analysis, the forced vital capacity and the diffusing capacity for carbon monoxide predicted values after 12 months of therapy were essentially unchanged, with mean changes of 2.83% (95% confidence interval = 0.35 to 5.31) and 4.56% (95% confidence interval = -0.21 to 9.33), respectively.

Conclusions

Cyclophosphamide treatment in patients with systemic sclerosis-related interstitial lung disease does not result in clinically significant improvement of pulmonary function.     

Effect of L-arginine supplement on liver regeneration after partial hepatectomy in rats

Background

To assess the outcome of neoadjuvant chemohormonal therapy comprising complete androgen blockade followed by treatment with docetaxel and estramustine phosphate before radical prostatectomy in Japanese patients with a high risk of localized prostate cancer (PCa).

Methods

Complete androgen blockade followed by 6 cycles of docetaxel (30 mg/m²) with estramustine phosphate (560 mg) were given to 18 PCa patients before radical prostatectomy. Subsequently, the clinical and pathological outcomes were analyzed.

Results

No patients had severe adverse events during chemohormonal therapy, and hence they were treated with radical prostatectomy. Two patients (11.1%) achieved pathological complete response. Surgical margins were negative in all patients. At a median follow-up of 18 months, 14 patients (77.8%) were disease-free without PSA recurrence. All 4 patients with PSA recurrence had pathologic T3b or T4 disease and 3 of these 4 patients had pathologic N1 disease.

Conclusion

We found that neoadjuvant chemohormonal therapy with complete androgen blockade followed by treatment with docetaxel and estramustine phosphate before radical prostatectomy was safe, feasible, and associated with favorable pathological outcomes in patients with a high risk of localized PCa.     

Immunological and biological changes during ipilimumab treatment and their potential correlation with clinical response and survival in patients with advanced melanoma

Background

Ipilimumab can induce durable disease control and long-term survival in patients with metastatic melanoma. Identification of a biomarker that correlates with clinical benefit and potentially provides an early marker of response is an active area of research.

Patients and methods

Ipilimumab was available upon physician request for patients aged ≥16 years with stage III (unresectable) or IV cutaneous, ocular or mucosal melanoma, who had failed or did not tolerate previous treatments and had no other therapeutic option available. Patients received ipilimumab 3 mg/kg every 3 weeks for four doses. Tumour assessments were conducted at baseline, Week 12 and Week 24 using immune-related response criteria. Patients were monitored continuously for adverse events (AEs), including immune-related AEs. Candidate immunological markers were evaluated in peripheral blood and sera samples collected at baseline and Weeks 4, 7, 10 and 12.

Results

Among 95 patients treated with ipilimumab 3 mg/kg, the immune-related disease control rate at Week 24 was 38 %. With a median follow-up of 24 months, median overall survival was 9.6 months. Both disease control and survival were significantly associated with decreasing levels of lactate dehydrogenase, C-reactive protein and FoxP3/regulatory T cells, and increasing absolute lymphocyte count, between baseline and the end of dosing (Week 12).

Conclusion

Ipilimumab is a feasible treatment option for heavily pretreated patients with metastatic melanoma. Changes in some immunological markers between baseline and the fourth ipilimumab infusion appear to be associated with disease control and survival, but verification in prospective clinical trials is required.     

Health care utilisation after defibrillator implantation for primary prevention according to the guidelines in 2 Dutch academic medical centres

Background

The benefit of implantable defibrillators (ICDs) for primary prevention remains debated. We analysed the implications of prophylactic ICD implantation according to the guidelines in 2 tertiary hospitals, and made a healthcare utilisation inventory.

Methods

The cohort consisted of all consecutive patients with coronary artery disease (CAD) or dilated cardiomyopathy (DCM) receiving a primary prophylactic ICD in a contemporary setting (2004–2008). Follow-up was obtained from hospital databases, and mortality checked at the civil registry. Additional data came from questionnaires sent to general practitioners.

Results

There were no demographic differences between the 2 centres; one had proportionally more CAD patients and more resynchronisation therapy (CRT-D). The 587 patients were followed over a median of 28 months, and 50 (8.5%) patients died. Appropriate ICD intervention occurred in 123 patients (21%). There was a small difference in intervention-free survival between the 2 centres. The questionnaires revealed 338 hospital admissions in 52% of the responders. Device-related admissions happened on 68 occasions, in 49/276 responders. The most frequently reported ICD-related admission was due to shocks (20/49 patients); for other cardiac problems it was mainly heart failure (52/99). Additional outpatient visits occurred in 19%.

Conclusion

Over a median follow-up of 2 years, one fifth of prophylactic ICD patients receive appropriate interventions. A substantial group undergoes readmission and additional visits. The high number of admissions points to a very ill population. Overall mortality was 8.5%. The 2 centres employed a similar procedure with respect to patient selection. One centre used more CRT-D, and observed more appropriate ICD interventions.     

Molecular monitoring of the Leu-164 mutation of dihydrofolate reductase in a highly sulfadoxine/pyrimethamine-resistant area in Africa

Background

Procalcitonin (PCT) is closely correlated with parasite burden and clinical outcome in falciparum malaria. The role of PCT in tertian malaria has not previously been investigated.

Patients and methods

PCT serum levels in 37 patients with tertian malaria were analysed. Clinical and laboratory parameters were assessed and statistically correlated both to the initial PCT levels and during the course of the disease.

Results

PCT levels rose for one day after commencing treatment and declined thereafter. However, there was no significant correlation with parasite burden, clinical parameters, laboratory values, or the presence of semi-immunity. Before treatment, the majority of patients showed normal or slightly elevated PCT levels (< 2.5 ng/ml), but PCT was markedly elevated (4.8 – 47 ng/ml) in one third of the population. The two groups did not differ by any other of the assessed parameters. Thus, while the post-treatment course of PCT resembles falciparum malaria, the lack of correlation between disease severity and even high PCT levels in a large proportion of patients is intriguing.

Conclusions

There is a fundamental difference in the relationship of PCT with tertian malaria not seen in other infectious diseases in which elevated PCT levels have been observed. This suggests distinct pathophysiological pathways in malaria.     

T cell receptor transgenic lymphocytes infiltrating murine tumors are not induced to express foxp3

Background

The CyberKnife is an appealing delivery system for hypofractionated stereotactic body radiation therapy (SBRT) because of its ability to deliver highly conformal radiation therapy to moving targets. This conformity is achieved via 100s of non-coplanar radiation beams, which could potentially increase transitory testicular irradiation and result in post-therapy hypogonadism. We report on our early experience with CyberKnife SBRT for low- to intermediate-risk prostate cancer patients and assess the rate of inducing biochemical and clinical hypogonadism.

Methods

Twenty-six patients were treated with hypofractionated SBRT to a dose of 36.25 Gy in 5 fractions. All patients had histologically confirmed low- to intermediate-risk prostate adenocarcinoma (clinical stage ≤ T2b, Gleason score ≤ 7, PSA ≤ 20 ng/ml). PSA and total testosterone levels were obtained pre-treatment, 1 month post-treatment and every 3 months thereafter, for 1 year. Biochemical hypogonadism was defined as a total serum testosterone level below 8 nmol/L. Urinary and gastrointestinal toxicity was assessed using Common Toxicity Criteria v3; quality of life was assessed using the American Urological Association Symptom Score, Sexual Health Inventory for Men and Expanded Prostate Cancer Index Composite questionnaires.

Results

All 26 patients completed the treatment with a median 15 months (range, 13-19 months) follow-up. Median pre-treatment PSA was 5.75 ng/ml (range, 2.3-10.3 ng/ml), and a decrease to a median of 0.7 ng/ml (range, 0.2-1.8 ng/ml) was observed by one year post-treatment. The median pre-treatment total serum testosterone level was 13.81 nmol/L (range, 5.55 - 39.87 nmol/L). Post-treatment testosterone levels slowly decreased with the median value at one year follow-up of 10.53 nmol/L, significantly lower than the pre-treatment value (p < 0.013). The median absolute fall was 3.28 nmol/L and the median percent fall was 23.75%. There was no increase in biochemical hypogonadism at one year post-treatment. Average EPIC sexual and hormonal scores were not significantly changed by one year post-treatment.

Conclusions

Hypofractionated SBRT offers the radiobiological benefit of a large fraction size and is well-tolerated by men with low- to intermediate-risk prostate cancer. Early results are encouraging with an excellent biochemical response. The rate of new biochemical and clinical hypogonadism was low one year after treatment.     

Treatment of Muckle-Wells syndrome: analysis of two IL-1-blocking regimens

Objectives

Muckle-Wells syndrome (MWS) is an autoinflammatory disease characterized by excessive interleukin-1 (IL-1) release, resulting in recurrent fevers, sensorineural hearing loss, and amyloidosis. IL-1 inhibition with anakinra, an IL-1 receptor antagonist, improves clinical symptoms and inflammatory markers. Subclinical disease activity is commonly observed. Canakinumab, a fully human IgG1 anti-IL-1β monoclonal antibody, can abolish excess IL-1β. The study aim was to analyze the efficacy and safety of these two anti-IL-1 therapies.

Methods

Two cohorts of patients with severe MWS and confirmed NLRP3 mutation were treated with anakinra and/or canakinumab. Clinical and laboratory features including ESR, CRP, SAA, and the neutrophil marker S100A12 were determined serially. Disease activity was captured by MWS disease activity scores (MWS-DAS). Remission was defined as MWS-DAS ≤5 plus normal CRP and SAA. Treatment efficacy and safety were analyzed.

Results

The study included 12 anakinra- and 14 canakinumab-treated patients; the median age was 33.5 years (3.0 years to 72.0 years); 57% were female patients. Both treatment regimens led to a significant reduction of clinical disease activity and inflammatory markers. At last follow-up, 75% of anakinra-treated and 93% of canakinumab-treated patients achieved remission. During follow-up, S100A12 levels mirrored recurrence of disease activity. Both treatment regimens had favorable safety profiles.

Conclusions

IL-1 blockade is an effective and safe treatment in MWS patients. MWS-DAS in combination with MWS inflammatory markers provides an excellent monitoring tool set. Canakinumab led to a sustained control of disease activity even after secondary failure of anakinra therapy. S100A12 may be a sensitive marker to detect subclinical disease activity.     

Clinical and immunological responses in metastatic melanoma patients vaccinated with a high-dose poly-epitope vaccine

Background

Safety and cellular immunogenicity of rising doses and varying regimens of a poly-epitope vaccine were evaluated in advanced metastatic melanoma. The vaccine comprised plasmid DNA and recombinant modified vaccinia virus Ankara (MVA) both expressing a string (Mel3) of seven HLA.A2/A1 epitopes from five melanoma antigens.

Methods

Forty-one HLA-A2 positive patients with stage III/IV melanoma were enrolled. Patient groups received one or two doses of DNA.Mel3 followed by escalating doses of MVA.Mel3. Immunisations then continued eight weekly in the absence of disease progression. Epitope-specific CD8+ T cell responses were evaluated using ex-vivo tetramer and IFN-γ ELISPOT assays. Safety and clinical responses were monitored.

Results

Prime-boost DNA/MVA induced Melan-A-specific CD8+ T cell responses in 22/31 (71%) patients detected by tetramer assay. ELISPOT detected a response to at least one epitope in 10/31 (32%) patients. T cell responder rates were <50% with low-dose DNA/MVA, or MVA alone, rising to 91% with high-dose DNA/MVA. Among eight patients showing evidence of clinical benefit—one PR (24 months+), five SD (5 months+) and two mixed responses—seven had associated immune responses. Melan-A-tetramer+ immunity was associated with a median 8-week increase in time-to-progression (P = 0.037) and 71 week increase in survival (P = 0.0002) compared to non-immunity. High-dose vaccine was well tolerated. The only significant toxicities were flu-like symptoms and injection-site reactions.

Conclusions

DNA.Mel3 and MVA.Mel3 in a prime-boost protocol generated high rates of immune response to melanoma antigen epitopes. The treatment was well tolerated and the correlation of immune responses with patient outcomes encourages further investigation.     

Efficacy of anakinra in gouty arthritis: a retrospective study of 40 cases

Introduction

Gout is a common arthritis that occurs particularly in patients who frequently have associated comorbidities that limit the use of conventional therapies. The main mechanism of crystal-induced inflammation is interleukin-1 production by activation of the inflammasome. We aimed to evaluate the efficacy and tolerance of anakinra in gouty patients.

Methods

We conducted a multicenter retrospective review of patients receiving anakinra for gouty arthritis. We reviewed the response to treatment, adverse events and relapses.

Results

We examined data for 40 gouty patients (32 men; mean age 60.0 ± 13.9 years) receiving anakinra. Mean disease duration was 8.7 ± 8.7 years. All patients showed contraindications to and/or failure of at least two conventional therapies. Most (36; 90%) demonstrated good response to anakinra. Median pain on a 100-mm visual analog scale was rapidly decreased (73.5 (70.0 to 80.0) to 25.0 (20.0 to 32.5) mm, P <0.0001), as was median C-reactive protein (CRP) level (130.5 (55.8 to 238.8) to 16.0 (5.0 to 29.5) mg/l, P <0.0001). After a median follow-up of 7.0 (2.0 to 13.0) months, relapse occurred in 13 patients after a median delay of 15.0 (10.0 to 70.0) days. Seven infectious events, mainly with long-term use of anakinra, were noted.

Conclusions

Anakinra may be efficient in gouty arthritis, is relatively well tolerated with short-term use, and could be a relevant option in managing gouty arthritis when conventional therapies are ineffective or contraindicated. Its long-term use could be limited by infectious complications.     

Change in CD3 positive T-cell expression in psoriatic arthritis synovium correlates with change in DAS28 and magnetic resonance imaging synovitis scores following initiation of biologic therapy - a single centre, open-label study

Introduction

With the development of increasing numbers of potential therapeutic agents in inflammatory disease comes the need for effective biomarkers to help screen for drug efficacy and optimal dosing regimens early in the clinical trial process. This need has been recognized by the Outcome Measures in Rheumatology Clinical Trials (OMERACT) group, which has established guidelines for biomarker validation. To seek a candidate synovial biomarker of treatment response in psoriatic arthritis (PsA), we determined whether changes in immunohistochemical markers of synovial inflammation correlate with changes in disease activity scores assessing 28 joints (ΔDAS28) or magnetic resonance imaging synovitis scores (ΔMRI) in patients with PsA treated with a biologic agent.

Methods

Twenty-five consecutive patients with PsA underwent arthroscopic synovial biopsies and MRI scans of an inflamed knee joint at baseline and 12 weeks after starting treatment with either anakinra (first 10 patients) or etanercept (subsequent 15 patients) in two sequential studies of identical design. DAS28 scores were measured at both time points. Immunohistochemical staining for CD3, CD68 and Factor VIII (FVIII) was performed on synovial samples and scored by digital image analysis (DIA). MRI scans performed at baseline and at 12 weeks were scored for synovitis semi-quantitatively. The ΔDAS28 of the European League Against Rheumatism good response definition (>1.2) was chosen to divide patients into responder and non-responder groups. Differences between groups (Mann Whitney U test) and correlations between ΔDAS28 with change in immunohistochemical and MRI synovitis scores (Spearman's rho test) were calculated.

Results

Paired synovial samples and MRI scans were available for 21 patients (8 anakinra, 13 etanercept) and 23 patients (8 anakinra, 15 etanercept) respectively. Change in CD3 (ΔCD3) and CD68 expression in the synovial sublining layer (ΔCD68sl) was significantly greater in the disease responders compared to non-responders following treatment (P = 0.005 and 0.013 respectively). ΔCD3, but not ΔCD68 or ΔFVIII, correlated with both ΔDAS28 (r = 0.49, P = 0.025) and ΔMRI (r = 0.58, P = 0.009).

Conclusions

The correlation of ΔCD3 with ΔDAS28 and ΔMRI following biologic treatment in this cohort contributes to the validation of ΔCD3 as a synovial biomarker of disease response in PsA, and supports the further evaluation of ΔCD3 for predictive properties of future clinical outcomes.     

Evaluation of SHOX copy number variations in patients with Müllerian aplasia

Background

Thymic epithelial tumours (thymoma and carcinoma) are exceptionally rare in children. We describe a national multicentre series with a view to illustrating their clinical behaviour and the results of treatment.

Methods

From January 2000 all patients under 18 years of age diagnosed with "rare paediatric tumours" were centrally registered by the Italian centres participating in the TREP project (Tumori Rari in Età Pediatrica [Rare Tumours in Paediatric Age]). The clinical data of children with a thymic epithelial tumour registered as at December 2009 were analyzed for the purposes of the present study.

Results

Our series comprised 4 patients with thymoma and 5 with carcinoma (4 males, 5 females; median age 12.4 years). The tumour masses were mainly large, exceeding 5 cm in largest diameter. Based on the Masaoka staging system, 3 patients were stage I, 1 was stage III, 1 was stage IVa and 4 were stage IVb. All 3 patients with stage I thymoma underwent complete tumour resection at diagnosis and were alive 22, 35 and 93 months after surgery. One patient with a thymoma metastasizing to the kidneys died rapidly due to respiratory failure. Thymic carcinomas were much more aggressive, infiltrating nearby organs (in 4 cases) and regional nodes (in 5), and spreading to the bone (in 3) and liver (in 1). All patients received multidrug chemotherapy (platinum derivatives + etoposide or other drugs) with evidence of tumour reduction in 3 cases. Two patients underwent partial tumour resection (after chemo-radiotherapy in one case) and 4 patients were given radiotherapy (45-54 Gy). All patients died of their disease.

Conclusions

Children with thymomas completely resected at diagnosis have an excellent prognosis while thymic carcinomas behave aggressively and carry a poor prognosis despite multimodal treatment.     

Maladie de La Peyronie: Bilan IRM chez 28 patients

Purpose

to determine diagnosis and prognosis value of MRI in Peyronie’s disease.

Material and Methods

thirty one penile MR examinations have been performed in 28 patients aged between 21 and 73. (1 tesla; surface coil; sagittal SET1, axial SET2 weighted, T1 before and after Gadolinium)

- In all cases but one, fibrous plaques were clinically palpable.

- Images were compared with clinical examination and evolution under anti-inflammatory drugs.

Results

- In 3 cases, MRI misdiagnosed one unique plague.

- In 2 additional cases, one of the 2 clinical plaques was not detected.

- In 5 cases, MRI depicted more lesions than palpation.

- Gadolinium Enhancement was always correlated with a good response to anti-inflamatory drugs but this treatment was also useful in one case who showed no enhancement.

Conclusion

MRI can be helpfull in the pretreatment assessment and int he follow-up of Peyronie’s disease.     

Glucose challenge increases circulating progenitor cells in Asian Indian male subjects with normal glucose tolerance which is compromised in subjects with pre-diabetes: A pilot study

Background

Patients with acute myocardial infarction and newly detected abnormal glucose regulation have been shown to have a less favourable prognosis compared to patients with normal glucose regulation. The importance and timing of oral glucose tolerance testing (OGTT) in patients with acute myocardial infarction without known diabetes is uncertain. The aim of the present study was to evaluate the impact of abnormal glucose regulation classified by an OGTT in-hospital and at three-month follow-up on clinical outcome in patients with acute ST elevation myocardial infarction (STEMI) without known diabetes.

Methods

Patients (n = 224, age 58 years) with a primary percutanous coronary intervention (PCI) treated STEMI were followed for clinical events (all-cause mortality, non-fatal myocardial re-infarction, recurrent ischemia causing hospital admission, and stroke). The patients were classified by a standardised 75 g OGTT at two time points, first, at a median time of 16.5 hours after hospital admission, then at three-month follow-up. Based on the OGTT results, the patients were categorised according to the WHO criteria and the term abnormal glucose regulation was defined as the sum of impaired fasting glucose, impaired glucose tolerance and type 2-diabetes.

Results

The number of patients diagnosed with abnormal glucose regulation in-hospital and at three-month was 105 (47%) and 50 (25%), respectively. During the follow up time of (median) 33 (27, 39) months, 58 (25.9%) patients experienced a new clinical event. There were six deaths, 15 non-fatal re-infarction, 33 recurrent ischemia, and four strokes. Kaplan-Meier analysis of survival free of composite end-points showed similar results in patients with abnormal and normal glucose regulation, both when classified in-hospital (p = 0.4) and re-classified three months later (p = 0.3).

Conclusions

Patients with a primary PCI treated STEMI, without previously known diabetes, appear to have an excellent long-term prognosis, independent of the glucometabolic state classified by an OGTT in-hospital or at three-month follow-up.

Trial registration

The trial is registered at http://www.clinicaltrials.gov, NCT00926133.