DNA methylation epi-signature is associated with two molecularly and phenotypically distinct clinical subtypes of Phelan-McDermid syndrome.

BACKGROUND: Phelan-McDermid syndrome is characterized by a range of neurodevelopmental phenotypes with incomplete penetrance and variable expressivity. It is caused by a variable size and breakpoint microdeletions in the distal long arm of chromosome 22, referred to as 22q13.3 deletion syndrome, including the SHANK3 gene. Genetic defects in a growing number of neurodevelopmental genes have been shown to cause genome-wide disruptions in epigenomic profiles referred to as epi-signatures in affected individuals. RESULTS: In this study we assessed genome-wide DNA methylation profiles in a cohort of 22 individuals with Phelan-McDermid syndrome, including 11 individuals with large (2 to 5.8 Mb) 22q13.3 deletions, 10 with small deletions (< 1 Mb) or intragenic variants in SHANK3 and one mosaic case. We describe a novel genome-wide DNA methylation epi-signature in a subset of individuals with Phelan-McDermid syndrome. CONCLUSION: We identified the critical region including the BRD1 gene as responsible for the Phelan-McDermid syndrome epi-signature. Metabolomic profiles of individuals with the DNA methylation epi-signature showed significantly different metabolomic profiles indicating evidence of two molecularly and phenotypically distinct clinical subtypes of Phelan-McDermid syndrome.

Has adherence to treatment guidelines for mid/low rectal cancer affected the management of patients? A monocentric study of 604 consecutive patients.

INTRODUCTION: In 2006 under the supervision of the French health authorities (HAS), recommendations for clinical practice (RCP) in the management of rectal cancers were first published. The primary objective of this study was to assess the impact of these guidelines on multidisciplinary management in terms of therapeutic strategies based on disease staging and quality indicators for surgical excision. Secondarily, we assessed the impact of the RCPs on postoperative and oncological outcomes. METHODS: All consecutive patients having undergone curative surgical excision for middle and low (subperitoneal) rectal cancer from 1995 to 2017 in the university hospital of Caen were included in accordance with the relevant French guidelines. They were divided into two groups: before (Gr1) and after (Gr2) 2006. For each group, a chart review was conducted on demographic variables, preoperative rectal tumor features, disease severity variables and quality of surgery variables. Postoperative and oncological outcomes were likewise assessed and compared between the two groups. RESULTS: Six hundred and four patients were included (Gr1, n=266; Gr2, n=338). Compliance with French guidelines significantly improved (i) use of magnetic resonance imaging (P<0.0001) and CT-scan (P<0.0001)]; (ii) organization of multidisciplinary tumor boards (P<0.0001) leading to suitable neo-adjuvant treatment plan classification (P<0.0001). Consequently, compliance improved widespread total mesorectal excision (P<0.0001), sphincter-sparing surgery (P=0,0005), and completeness of curative resection in the specimen (P<0.0001). Although postoperative 90-day mortality was similar, overall postoperative morbidity significantly increased in Gr2 (P<0.0001). Overall (P=0.0005) and disease-free survival (P=0.0016) of patients in Gr2 were significantly prolonged and correlated with a significant reduction in local and distant recurrences. CONCLUSION: Compliance with the relevant French guidelines improved the quality of multidisciplinary management of patients undergoing curative surgery for subperitoneal rectal cancer. However, further progress is still needed to render accession to the recommendations more comprehensive.

Anterior resection syndrome: What should we tell practitioners and patients in 2018?

Multidisciplinary management of infra-peritoneal rectal cancer has pushed back the frontiers of sphincter preservation, without impairment of carcinological outcome. However, functional intestinal sequelae, grouping together several symptoms known under the name of anterior resection syndrome (ARS), have emerged and become an increasingly frequent concern for both patients and physicians. The pathophysiology is complex: ARS is a combination in various degrees of stool frequency, incontinence for flatus and/or stools, urgency, and disorders in discrimination and evacuation. The "Low Anterior Resection Score" (LARS), validated in 2012, is currently used to evaluate the severity of ARS and its impact on quality of life. While ARS can show improvement over the first two years, symptoms persist for longer than two years in nearly 60% of patients and in half of these patients, ARS is considered severe. The most frequently reported independent risk factors of severe ARS include neo-adjuvant radiation therapy, the extent of resection (total mesorectal excision that includes inter-sphincteric resection), absence of colonic pouch and anastomotic leak. In the absence of surgical complications and/or local recurrence, physicians can draw from a wide therapeutic armamentarium in order to improve the functional outcome of patients, including diet and lifestyle modifications, gut motility regulators, multimodal rehabilitation (biofeedback, electro-stimulation) and sacral nerve modulation. Permanent colostomy is an alternative of last resort, proposed only when all other solutions fail. A better understanding of the natural history of ARS, its risk factors as well as the array of therapeutic alternatives should provide better patient information and optimize management.

Is pathological complete response after a trimodality therapy, a predictive factor of long-term survival in locally-advanced esophageal cancer? Results of a retrospective monocentric study.

OBJECTIVE: To evaluate long-term (5- and 10-year) survival and recurrence rates on the basis of the pathological complete response (pCR) in the specimens of patients with esophageal carcinoma, treated with trimodality therapy. METHODS: Between 1993 and 2014, all consecutives patients with esophageal locally-advanced non-metastatic squamous cell carcinoma (SCC) or adenocarcinoma (ADC) who received trimodality therapy were reviewed. According to histopathological analysis, patients were divided in two groups with pCR and with pathological residual tumor (pRT). The primary endpoint was overall survival (OS). The secondary endpoints included the disease-free survival (DFS), the recurrence rate, and the predictive factors of overall survival and recurrence. RESULTS: One hundred and three patients were included: 49 patients with pCR and 54 patients with pRT. The median OS was significantly longer in pCR group than in pRT group (132±22.3 vs. 25.5±4 months), with both 5- and 10-years OS rates of 75.2% vs. 29.1%, and 51.1% vs. 13.6%, respectively (P<0.001). Also, pRT, major postoperative complications (Dindo-Clavien grade>IIIb) and recurrence were the 3 independent predictive factors for worse OS. CONCLUSIONS: Patients with locally-advanced oesophageal carcinoma, who responded to trimodality therapy with a pCR, could be achieved a 10-year survival rate of 51%.

An estimation of burden of serious fungal infections in France.

OBJECTIVE OF THE STUDY: An estimation of burden of serious fungal diseases in France is essential data to inform public health priorities on the importance of resources and research needed on these infections. In France, precise data are available for invasive fungal diseases but estimates for several other diseases such as chronic and immunoallergic diseases are by contrast less known. MATERIALS AND METHODS: A systematic literature search was conducted using the Web of Science Platform. Published epidemiology papers reporting fungal infection rates from France were identified. Where no data existed, we used specific populations at risk and fungal infection frequencies in those populations to estimate national incidence or prevalence, depending on the condition. RESULTS: The model predicts high prevalences of severe asthma with fungal sensitization episodes (189 cases/100,000 adults per year), of allergic bronchopulmonary aspergillosis (145/100,000) and of chronic pulmonary aspergillosis (5.24/100,000). Besides, estimated incidence for invasive aspergillosis is 1.8/100,000 annually based on classical high risk factors. Estimates for invasive mucormycosis, pneumocystosis and cryptococcosis are 0.12/100,000, 1/100,000 and 0.2/100,000, respectively. Regarding invasive candidiasis, more than 10,000 cases per year are estimated, and a much higher number of recurrent vaginal candidiasis is probable but must be confirmed. Finally, this survey was an opportunity to report a first picture of the frequency of tinea capitis in France. CONCLUSION: Using local and literature data of the incidence or prevalence of fungal infections, approximately 1,000,000 (1.47%) people in France are estimated to suffer from serious fungal infections each year.

Soluble and membrane-bound interleukin (IL)-15 Rα/IL-15 complexes mediate proliferation of high-avidity central memory CD8+ T cells for adoptive immunotherapy of cancer and infections.

The lack of persistence of infused T cells is a principal limitation of adoptive immunotherapy in man. Interleukin (IL)-15 can sustain memory T cell expansion when presented in complex with IL-15Rα (15Rα/15). We developed a novel in-vitro system for generation of stable 15Rα/15 complexes. Immunologically quantifiable amounts of IL-15 were obtained when both IL-15Rα and IL-15 genes were co-transduced in NIH 3T3 fibroblast-based artificial antigen-presenting cells expressing human leucocyte antigen (HLA) A:0201, ß2 microglobulin, CD80, CD58 and CD54 [A2-artificial antigen presenting cell (AAPC)] and a murine pro-B cell line (Baf-3) (A2-AAPC15Rα/15 and Baf-315Rα/15 ). Transduction of cells with IL-15 alone resulted in only transient expression of IL-15, with minimal amounts of immunologically detectable IL-15. In comparison, cells transduced with IL-15Rα alone (A2-AAPCRα ) demonstrated stable expression of IL-15Rα; however, when loaded with soluble IL-15 (sIL-15), these cells sequestered 15Rα/15 intracellularly and also demonstrated minimal amounts of IL-15. Human T cells stimulated in vitro against a viral antigen (CMVpp65) in the presence of 15Rα/15 generated superior yields of high-avidity CMVpp65 epitope-specific T cells [cytomegalovirus-cytotoxic T lymphocytes (CMV-CTLs)] responding to ≤ 10- 13 M peptide concentrations, and lysing targets cells at lower effector : target ratios (1 : 10 and 1 : 100), where sIL-15, sIL-2 or sIL-7 CMV-CTLs demonstrated minimal or no activity. Both soluble and surface presented 15Rα/15, but not sIL-15, sustained in-vitro expansion of CD62L+ and CCR7+ central memory phenotype CMV-CTLs (TCM ). 15Rα/15 complexes represent a potent adjuvant for augmenting the efficacy of adoptive immunotherapy. Such cell-bound or soluble 15Rα/15 complexes could be developed for use in combination immunotherapy approaches.

Role of a NSAID in the apparent cure of a fungal mycetoma.

UNLABELLED: We report the case of a fungal mycetoma due to Madurella mycetomatis that failed to respond to surgery and antifungal treatment but responded strongly to the addition of a non-steroidal anti-inflammatory drug (NSAID). This African patient was born in Mauritania in 1972. He was a herdsman, living close to the Senegal River. The first nodules appeared on the left foot at the age of 13years (1985). The patient suffered frequent flare-ups with the appearance of black grains and underwent surgery in 1988 and 1992 in Senegal. After remission for several months after surgery, new fistulae occurred. The patient emigrated to France in 1995 and underwent a third surgical intervention in 1996. M. mycetomatis was cultured from the black grains. The patient was otherwise in good health, with no diabetes, and HIV tests were negative. We saw the patient for the first time in 2005, at which time he had flare-ups every two to three months. Imaging disclosed an absence of bone involvement. The patient underwent a fourth operation in October, 2005, and voriconazole treatment was initiated. A new flare-up occurred in February, 2006. CT, MRI, and PET scans revealed calcaneus and tarsal involvement, and posaconazole then replaced voriconazole. Flucytosine was added four months later, due to an absence of improvement. New flares-ups occurred and a fifth surgical intervention was performed in September, 2006. The pain, which had been present for three years, worsened; the patient had to stop working and was no longer able to walk without crutches. Amputation of the foot was considered. Empiric treatment with a NSAID, diclofenac (Voltaren(®); 100mg/day), was added to the antifungal treatment in November 2006, to treat the patient's pain and inflammation. A major improvement was observed within one week. The patient was able to walk without crutches one month later. After two months, clinical examination was normal: no pain, inflammation, nodules or fistulae. Flucytosine was stopped after six months of treatment, in January 2007, diclofenac after 10months, in October 2007, and posaconazole after 18.5months, also in October 2007. No relapse has occurred during the eight years of follow-up since treatment ended. The patient seems to have been cured and has normal CT, MRI, and PET scans. IN SUMMARY: This eumycetoma, which had progressed over 20years despite surgery and antifungal treatments, seems to have been cured by the addition of a NSAID. This observation suggests that inflammation plays a major role in the pathogenesis of fungal mycetoma. Clinical studies of treatments including an NSAID should be conducted to confirm this finding.

Association of a variable number tandem repeat in the NLRP3 gene in women with susceptibility to RVVC.

Vaginal infections with Candida spp. frequently occur in women of childbearing age. A small proportion of these women experience recurrent vulvovaginal candidosis (RVVC), which is characterized by at least three episodes of infection in one year. In addition to known risk factors such as antibiotics, diabetes, or pregnancy, host genetic variation and inflammatory pathways such as the IL-1/Th17 axis have been reported to play a substantial role in the pathogenesis of RVVC. In this study, we assessed a variable number tandem repeat (VNTR) polymorphism in the NLRP3 gene that encodes a component of the inflammasome, processing the proinflammatory cytokines IL-1ß and IL-18. A total of 270 RVVC patients and 583 healthy controls were analyzed, and increased diseases susceptibility was associated with the presence of the 12/9 genotype. Furthermore, functional studies demonstrate that IL-1ß production at the vaginal surface is higher in RVVC patients bearing the 12/9 genotype compared to controls, whereas IL-1Ra levels were decreased and IL-18 levels remained unchanged. These findings suggest that IL-1ß-mediated hyperinflammation conveyed by the NLRP3 gene plays a causal role in the pathogenesis of RVVC and may identify this pathway as a potential therapeutic target in the disease.

Utility and impact of early t(15;17) identification by Fluorescence In Situ Hybridization (FISH) in clinical decision making for patients in Acute Promyelocytic Leukemia (APL).

INTRODUCTION: Acute Promyelocytic Leukemia (APL) is a curable malignancy with studies showing above 90% survival. However, population-based studies looking at survival suggest that approximately 30% of patients with APL die during induction. Early demonstration of t(15;17) will lead to accurate decision making regarding treatment. The aim of this project was to validate earlier time frames for the Abbott Molecular Vysis LSI promyelocytic leukemia (PML)/ retinoic acid receptor alpha (RARA) fluorescence in situ hybridization (FISH) probe (ASR 6-16 h). METHODS: Twenty patients (15 APL cases and five non-APL cases) were selected for validating various hybridization times for the FISH probe. Expected normal signal pattern was two red and two green signals (2R2G), and the most common expected abnormal signal pattern was two fusion (yellow) signals, one red and one green (2F1R1G) and/or one fusion, one red and one green (1F1R1G). RESULTS: The specificity of the probe ranged from 84% at 2 h, 86% at 4 h, 84% at 6 h, and 87% for overnight hybridization. The sensitivity increased from 79% at 2 h, 80% at 4 h, 81% at 6 h to 87% for overnight hybridization. CONCLUSION: Based on the validation studies, we recommend reading of FISH results at the 4-h incubation mark for a preliminary diagnosis and confirmation with overnight hybridization.

Late occurrence of Histoplasma duboisii cutaneous and pulmonary infection 18 years after exposure.

We report an imported case of Histoplasma capsulatum var. duboisii (H. duboisii) infection in a white French woman revealed by cutaneous lesions of the scalp, 18 years after her last stay in West and Central Africa. Asymptomatic bilateral pulmonary infiltrates were discovered on thoracic computed tomography. Skin biopsy allowed the positive diagnosis showing the typical yeasts; culture of biopsy specimens was positive for H. capsulatum. In the absence of criteria of severity, the patient was treated for one year with oral itraconazole 400mg/day. The outcome was favourable, skin and pulmonary lesions resolved slowly. The follow up is 5 years without relapse after the end of treatment. This case illustrates the possibility of late occurrence of H. duboisii infection, many years after exposure and the major importance of asking any patient for travelling or residency in tropical countries.

Disruption of MBD5 contributes to a spectrum of psychopathology and neurodevelopmental abnormalities.

Microdeletions of chromosomal region 2q23.1 that disrupt MBD5 (methyl-CpG-binding domain protein 5) contribute to a spectrum of neurodevelopmental phenotypes; however, the impact of this locus on human psychopathology has not been fully explored. To characterize the structural variation landscape of MBD5 disruptions and the associated human psychopathology, 22 individuals with genomic disruption of MBD5 (translocation, point mutation and deletion) were identified through whole-genome sequencing or cytogenomic microarray at 11 molecular diagnostic centers. The genomic impact ranged from a single base pair to 5.4 Mb. Parents were available for 11 cases, all of which confirmed that the rearrangement arose de novo. Phenotypes were largely indistinguishable between patients with full-segment 2q23.1 deletions and those with intragenic MBD5 rearrangements, including alterations confined entirely to the 5'-untranslated region, confirming the critical impact of non-coding sequence at this locus. We identified heterogeneous, multisystem pathogenic effects of MBD5 disruption and characterized the associated spectrum of psychopathology, including the novel finding of anxiety and bipolar disorder in multiple patients. Importantly, one of the unique features of the oldest known patient was behavioral regression. Analyses also revealed phenotypes that distinguish MBD5 disruptions from seven well-established syndromes with significant diagnostic overlap. This study demonstrates that haploinsufficiency of MBD5 causes diverse phenotypes, yields insight into the spectrum of resulting neurodevelopmental and behavioral psychopathology and provides clinical context for interpretation of MBD5 structural variations. Empirical evidence also indicates that disruption of non-coding MBD5 regulatory regions is sufficient for clinical manifestation, highlighting the limitations of exon-focused assessments. These results suggest an ongoing perturbation of neurological function throughout the lifespan, including risks for neurobehavioral regression.

Randomised clinical trial: enteral nutrition does not improve the long-term outcome of alcoholic cirrhotic patients with jaundice.

BACKGROUND: Malnutrition and jaundice are independent prognostic factors in cirrhosis. AIM: To assess the impact of enteral nutrition on the survival of alcoholic cirrhotic patients with jaundice but without acute alcoholic hepatitis. METHODS: The study was a multicentre prospective randomised controlled trial comparing effects of enteral nutrition vs. a symptomatic support in patients with alcoholic cirrhosis and jaundice (bilirubin ≥51 µmol/L) but without severe acute alcoholic hepatitis. A total of 99 patients were randomised to receive either the conventional symptomatic treatment (55 patients) or the symptomatic support associated with 35 kcal/Kg/day of enteral nutrition during 4 weeks followed by an oral nutritional support during 2 months (44 patients). Randomisation was stratified on nutritional status. One-year survival curves were compared using the Kaplan-Meier method and Logrank test. RESULTS: Populations in both arms were similar. One-year survival was similar in the overall population (27/44 patients (61.4%) in the enteral nutrition arm vs. 36/55 (65.5%) in the control arm; Logrank P = 0.60) and in the subgroup suffering from malnutrition [18/29 patients (62.1%) in the enteral nutrition arm vs. 20/32 (62.5%) in the control arm; Logrank P = 0.99]. There was no statistical difference for bilirubin, prothrombin rate, Child-Pugh score, albumin or nutritional assessment. Complications during treatment (bleeding, encephalopathy, infection) occurred in 23% of patients in the enteral nutrition group (10/44) vs. 16% (9/55) of the control patients (P = 0.59). CONCLUSION: Enteral nutrition does not improve the survival and hepatic or nutritional parameters of cirrhotic patients with jaundice.

[Knowledge of the general population about hypertension and diabetes mellitus in South Kivu, Democratic Republic of Congo]. / Connaissances de la population générale sur l'hypertension artérielle et le diabète sucré au Sud-Kivu, République démocratique du Congo.

BACKGROUND: In the Democratic Republic of Congo (DRC), a country in a post-conflict period, high priority cannot be given to non-communicable diseases other than to emergencies. This certainly involves inadequacy in raising awareness for prevention of these diseases. OBJECTIVE: To evaluate the level of knowledge of the Congolese general population on hypertension and diabetes mellitus. METHODS: Responses to a questionnaire from 3% of the general population aged 15 and older in the city of Bukavu and two rural areas: Hombo and Walungu (South Kivu, eastern DRC), recruited after stratification by ward in the city of Bukavu and a group of prone villages were expected. The questions focused on identification, testing, causes, complications and treatment of hypertension and diabetes mellitus. RESULTS: Of the 7770 respondents, screening for hypertension and diabetes mellitus affected only 14.9% and 7.3% of subjects respectively. Knowledge of these two conditions was generally low in the general population, although better in the subgroups of patients and those with higher socioeconomic level (P<0.05). Use of the medias was also associated with better knowledge (P<0.05). CONCLUSIONS: This study shows that knowledge about hypertension and diabetes mellitus and their testing in South Kivu is low. It is imperative that the Congolese government includes non-communicable diseases in its priorities of the millennium. Similarly, the WHO should actively contribute to screening for them in low-income countries.

Zygomycosis in Europe: analysis of 230 cases accrued by the registry of the European Confederation of Medical Mycology (ECMM) Working Group on Zygomycosis between 2005 and 2007.

Zygomycosis is an important emerging fungal infection, associated with high morbidity and mortality. The Working Group on Zygomycosis of the European Confederation of Medical Mycology (ECMM) prospectively collected cases of proven and probable zygomycosis in 13 European countries occurring between 2005 and 2007. Cases were recorded by a standardized case report form, entered into an electronic database and analysed descriptively and by logistic regression analysis. During the study period, 230 cases fulfilled pre-set criteria for eligibility. The median age of the patients was 50 years (range, 1 month to 87 years); 60% were men. Underlying conditions included haematological malignancies (44%), trauma (15%), haematopoietic stem cell transplantation (9%) and diabetes mellitus (9%). The most common manifestations of zygomycosis were pulmonary (30%), rhinocerebral (27%), soft tissue (26%) and disseminated disease (15%). Diagnosis was made by both histology and culture in 108 cases (44%). Among 172 cases with cultures, Rhizopus spp. (34%), Mucor spp. (19%) and Lichtheimia (formerly Absidia) spp. (19%) were most commonly identified. Thirty-nine per cent of patients received amphotericin B formulations, 7% posaconazole and 21% received both agents; 15% of patients received no antifungal therapy. Total mortality in the entire cohort was 47%. On multivariate analysis, factors associated with survival were trauma as an underlying condition (p 0.019), treatment with amphotericin B (p 0.006) and surgery (p <0.001); factors associated with death were higher age (p 0.005) and the administration of caspofungin prior to diagnosis (p 0.011). In conclusion, zygomycosis remains a highly lethal disease. Administration of amphotericin B and surgery, where feasible, significantly improve survival.

Cost effectiveness of posaconazole in the prophylaxis of invasive fungal infections in acute leukaemia patients for the French healthcare system.

BACKGROUND: Acute myeloblastic leukaemia (AML) patients are at high risk of suffering from invasive fungal infections (IFI). Posaconazole demonstrated higher efficacy than standard azole agents (SAA) in the prophylaxis of IFI in this population. The authors estimated the cost effectiveness of posaconazole versus SAA in France. METHODS: A decision-tree model was developed to compare posaconazole with SAA with the results of a published clinical trial. Clinical events were modelled with chance nodes reflecting probabilities of IFI, IFI-related death, and death from other causes. Medical resource consumption and costs were obtained from results of the clinical trial and from a dedicated survey on the costs of treating IFI using a retrospective chart review design. RESULTS: IFI treatment costs were estimated using medical files from 50 AML patients from six French centres, with a proven and probable IFI, who had been followed-up for 298 days on average. Direct costs directly related to IFI were estimated at €51,033, including extra costs of index hospitalisation, costs of antifungal therapy and additional hospitalisations related to IFI treatment. The model indicated that the healthcare costs for the posaconazole strategy were €5,223 (€2,697 for prophylaxis and €2,526 for IFI management), which was €859 less than the €6,083 in costs with SAA (€469 for prophylaxis and €5614 for IFI management). A sensitivity analysis indicated that there was an 80% probability that prophylaxis using the posaconazole strategy would be superior. CONCLUSION: The findings from this analysis suggest that posaconazole use is a clinically and economically dominant strategy in the prophylaxis of IFI in AML patients, given the usual limits of economic models and the uncertainty of costs estimates.

Diagnostic contribution of positron emission tomography with [18F]fluorodeoxyglucose for invasive fungal infections.

Optimal staging and evaluation of residual lesions of invasive fungal infections (IFIs) are major challenges in the immunocompromised host. Preliminary data have suggested that [¹8F]fluorodeoxyglucose ([¹8F]FDG) uptake may be observed in the course of active invasive fungal infections. The aim of this study was to assess the role of positron emission tomography with [¹8F]FDG ([¹8F]FDG-PET) in the diagnosis and staging of IFI. A prospective monocentric study evaluating [¹8F]FDG-PET in 30 consecutive adults and children with European Organization for Research and Treatment of Cancer/Mycoses Study Group probable or proven IFI was performed. Twenty males and ten females (median age, 45 years (range 6-7 years)) were enrolled. Twenty-six were immunocompromised, as follows: haematological malignancy (18) with allogeneic stem cell transplantation (16/18), solid tumour (three), solid organ transplantation (two), diabetes mellitus (two) and cystic fibrosis (one). IFIs were acute invasive aspergillosis (ten), chronic disseminated candidiasis (ten), zygomycosis (two), black grains eumycetoma (two), pulmonary Histoplasma capsulatum var. capsulatum histoplasmosis (two), and Phomopsis sp. osteoarthritis, Scedosporium apiospermum and Candida krusei spondylodiscitis, and acute pulmonary coccidioidomycosis in one case each. An increased uptake of [¹8F]FDG was observed in all areas previously identified by computed tomography and/or magnetic resonance imaging to be involved by IFI. In 4/10 chronic disseminated candidiasis cases, [¹8F]FDG-PET revealed small splenic abscesses that were unapparent on the corresponding computed tomography scan. [¹8F]FDG uptake disappeared after 6 months of antifungal therapy in three patients with chronic disseminated candidiasis for whom the [¹8F]FDG-PET was performed to assess the evolution of the disease. [¹8F]FDG-PET could potentially be useful for the initial diagnosis and staging of IFI. Whether or not [¹8F]FDG-PET might be useful for assessing the optimal duration of IFI therapy should now be assessed in a specific prospective study.

The trauma surgeon in the emergency department, a life saver?

BACKGROUND: The golden age of trauma has gone. 25 years ago the trauma surgeon was the life saver in the emergency department. He was the leader of the resuscitation team and made the important decisions in the process. Nowadays different factors have diminished the role of the trauma surgeon. DISCUSSION: Thanks to the decrease of severely injured patients in Europe and the advances in diagnostic and treatment possibilities the approach to trauma victims is less often operative. Furthermore, the uprising of emergency medicine specialists has taken many tasks out of the hands of the trauma surgeon. However, experienced trauma surgeons can do both critical care and acute care surgery and should be included in the decision-making process in the emergency room. CONCLUSION: Although the trauma surgeon often is no longer the captain of the ship in the emergency department, he can still play an important role in trauma care. They still are life savers.