Antimicrobial-Resistant Bacteria Carriage in Rodents According to Habitat Anthropization.

It is increasingly suggested that the dynamics of antimicrobial-resistant bacteria in the wild are mostly anthropogenically driven, but the spatial and temporal scales at which these phenomena occur in landscapes are only partially understood. Here, we explore this topic by studying antimicrobial resistance in the commensal bacteria from micromammals sampled at 12 sites from a large heterogenous landscape (the Carmargue area, Rhone Delta) along a gradient of anthropization: natural reserves, rural areas, towns, and sewage-water treatment plants. There was a positive relationship between the frequency of antimicrobial-resistant bacteria and the level of habitat anthropization. Although low, antimicrobial resistance was also present in natural reserves, even in the oldest one, founded in 1954. This study is one of the first to support the idea that rodents in human-altered habitats are important components of the environmental pool of resistance to clinically relevant antimicrobials and also that a "One Health" approach is required to assess issues related to antimicrobial resistance dynamics in anthropized landscapes.

Multiresistant Enterobacteriaceae in yellow-legged gull chicks in their first weeks of life.

Wild animal species living in anthropogenic areas are commonly carriers of antimicrobial-resistant bacteria (AMRB), but their role in the epidemiology of these bacteria is unclear. Several studies on AMRB in wildlife have been cross-sectional in design and sampled individual animals at only one point in time. To further understand the role of wildlife in maintaining and potentially transmitting these bacteria to humans and livestock, longitudinal studies are needed in which samples are collected from individual animals over multiple time periods. In Europe, free-ranging yellow-legged gulls (Larus michahellis) commonly live in industrialized areas, forage in landfills, and have been found to carry AMRB in their feces. Using bacterial metagenomics and antimicrobial resistance characterization, we investigated the spatial and temporal patterns of AMRB in a nesting colony of yellow-legged gulls from an industrialized area in southern France. We collected 54 cloacal swabs from 31 yellow-legged gull chicks in 20 nests on three dates in 2016. We found that AMRB in chicks increased over time and was not spatially structured within the gull colony. This study highlights the complex occurrence of AMRB in a free-ranging wildlife species and contributes to our understanding of the public health risks and implications associated with ARMB-carrying gulls living in anthropogenic areas.

Evaluation of the impact of HMS Plus on postoperative blood loss compared with ACT Plus in cardiac surgery.

BACKGROUND: The standardized management of anticoagulation during the cardiopulmonary bypass seems inaccurate because of patients and surgeries variability. This study evaluates if an individualized management of heparin and protamine guided by the HMS Plus system during cardiopulmonary bypass could reduce postoperative blood loss. METHODS: We conducted a prospective, controlled, unblinded, single-center study. One-hundred and eighthy-eight patients operated for cardiac surgery were included. Patients were divided in ACT Plus group (standardized approach) and HMS Plus group (individualized approach). The primary outcome was blood-loss volume during the first 24 postoperative hours. The main secondary outcomes were the need for allogeneic blood transfusions and the final protamine/heparin ratio. RESULTS: There was no difference between the two groups for baseline characteristics. Medium blood-loss volume in the ACT Plus group was 522±260 mL vs. 527±255 mL in the HMS Plus group (P=0.58). The final protamine/heparin ratio in the ACT Plus group was 0.94±0.1 vs. 0.58±0.1 in the HMS Plus group (P<0.0001). The transfusion rate during surgery in the ACT Plus group was 25% vs. 14% in the HMS Plus group (P=0.09). CONCLUSIONS: HMS Plus did not reduce the mean blood-loss volume during the first 24 postoperative hours compared with ACT Plus. Its utility for potential transfusion rate reduction remains to be proven.

Management of cardiogenic shock by circulatory support during reverse Tako-Tsubo following amphetamine exposure: A report of two cases.

Stress-induced cardiomyopathy, also known by various names such as Tako-Tsubo cardiomyopathy (TTC), is a cardiomyopathy that presents different types of transient left ventricular dysfunction. We present two cases of reverse TTC occurring in two young men after amphetamine use and complicated by cardiogenic shock necessitating venoarterial extra-corporeal membrane oxygenation (VA-ECMO). Levosimendan was used in one case to prevent subsequent aggravation of left ventricular function provoked by the use of catecholamine in this context. In both cases, myocardial function recovered rapidly. Amphetamine use can lead to reverse TTC requiring transient mechanical assistance and inotropic support.

Molecular screening indicates high prevalence and mixed infections of Hepatozoon parasites in wild felines from South Africa.

Genetic diversity within partial 18S rRNA sequences from Hepatozoon protozoan parasites from wild felines in South Africa was assessed and compared with data from domestic cats to assess patterns of host specificity. Lions, leopards, servals, a caracal and an African wildcat were all positive for parasites of the Hepatozoon felis-complex. However, haplotypes were not species-specific, and potential mixed infections were widespread. Additional genetic markers are needed to untangle the extremely complex situation of these parasites in both domestic cats and wild felines in South Africa.

Occurrence and characterisation of tongue worms, Linguatula spp., in South Africa.

A total of 509 mammalian vertebrates, belonging to 76 species, were examined for infection with pentastomid parasites. These animals were from 8 of the 9 provinces in South Africa. Linguatulid pentastomes were found only in 7 animals, specifically the African Lion (n = 3) and African Buffalo (n = 4). Adult parasites were found in the lion but nymphs, of various stages, were found in the buffalo. A detailed morphological examination of adult parasites using both light and scanning electron microscopy techniques suggested the specimens were Linguatula nuttalli Sambon1922. Sequences of 18S ribosomal DNA and Cox1 regions obtained from both adult and nymph stages suggested they belong to the one species. Phylogenetic analyses of Linguatula spp. based on the 18S and Cox1 sequences available in GenBank and obtained in the present study showed a clear distinction between L. nuttalli, L. arctica and L. serrata (from Europe and Australia). Several specimens from the Palearctic region which were previously assumed to be L. serrata formed a distinct group in the phylogenetic tree suggesting they probably belong to a different, and as of yet, unknown species.

Fumarate production with Rhizopus oryzae: utilising the Crabtree effect to minimise ethanol by-product formation.

BACKGROUND: The four-carbon dicarboxylic acids of the tricarboxylic acid cycle (malate, fumarate and succinate) remain promising bio-based alternatives to various precursor chemicals derived from fossil-based feed stocks. The double carbon bond in fumarate, in addition to the two terminal carboxylic groups, opens up an array of downstream reaction possibilities, where replacement options for petrochemical derived maleic anhydride are worth mentioning. To date the most promising organism for producing fumarate is Rhizopus oryzae (ATCC 20344, also referred to as Rhizopus delemar) that naturally excretes fumarate under nitrogen-limited conditions. Fumarate excretion in R. oryzae is always associated with the co-excretion of ethanol, an unwanted metabolic product from the fermentation. Attempts to eliminate ethanol production classically focus on enhanced oxygen availability within the mycelium matrix. In this study our immobilised R. oryzae process was employed to investigate and utilise the Crabtree characteristics of the organism in order to establish the limits of ethanol by-product formation under growth and non-growth conditions. RESULTS: All fermentations were performed with either nitrogen excess (growth phase) or nitrogen limitation (production phase) where medium replacements were done between the growth and the production phase. Initial experiments employed excess glucose for both growth and production, while the oxygen partial pressure was varied between a dissolved oxygen of 18.4% and 85%. Ethanol was formed during both growth and production phases and the oxygen partial pressure had zero influence on the response. Results clearly indicated that possible anaerobic zones within the mycelium were not responsible for ethanol formation, hinting that ethanol is formed under fully aerobic conditions as a metabolic overflow product. For Crabtree-positive organisms like Saccharomyces cerevisiae ethanol overflow is manipulated by controlling the glucose input to the fermentation. The same strategy was employed for R. oryzae for both growth and production fermentations. It was shown that all ethanol can be eliminated during growth for a glucose addition rate of 0.07 g L - 1 h - 1 . The production phase behaved in a similar manner, where glucose addition of 0.197 g L - 1 h - 1 resulted in fumarate production of 0.150 g L - 1 h - 1 and a yield of 0.802 g g - 1 fumarate on glucose. Further investigation into the effect of glucose addition revealed that ethanol overflow commences at a glucose addition rate of 0.395 g g - 1 h - 1 on biomass, while the maximum glucose uptake rate was established to be between 0.426 and 0.533 g g - 1 h - 1 . CONCLUSIONS: The results conclusively prove that R. oryzae is a Crabtree-positive organism and that the characteristic can be utilised to completely discard ethanol by-product formation. A state referred to as "homofumarate production" was illustrated, where all carbon input exits the cell as either fumarate or respiratory CO 2 . The highest biomass-based "homofumarate production": rate of 0.243 g g - 1 h - 1 achieved a yield of 0.802 g g - 1 on glucose, indicating the bounds for developing an ethanol free process. The control strategy employed in this study in conjunction with the uncomplicated scalability of the immobilised process provides new direction for further developing bio-fumarate production.

Morphological Studies of Developmental Stages of Oculotrema hippopotami (Monogenea: Polystomatidae) Infecting the Eye of Hippopotamus amphibius (Mammalia: Hippopotamidae) Using SEM and EDXA with Notes on Histopathology.

The present study was performed to observe histopathological effects of Oculotrema hippopotami Stunkard, 1924 infection in the eye of Hippopotamus amphibius, as well as to reveal new details of morphology and structural features of this monogenean and its comparison between 2 age stages of the parasite. This was done using both light and scanning electron microscopy, energy dispersive X-ray analysis (EDXA) and histopathology. The presence of a mixture of different generations (adult and sub-adult) in one host individual is common for Oculotrema Stunkard, 1924 in contrast to Polystoma Zeder, 1800. New metrical and graphical information obtained for adults and sub-adults compared with the previous studies. Here we show the presence of genital papillae in adults, metrical data on the distal part of the vas deferens. SEM micrographs of sperm ejaculatory structures and information about the flattened dorsal side of the body provided for the first time. Histopathological changes, such as necrosis and hemorrhage in host tissues as a result of O. hippopotami attachment structures are described. Structural analysis of different body parts of O. hippopotami of both age groups are also included. We show qualitative differences in the presence of hardening ions (S, P, Ca) in attachment structures (oral and haptor suckers) that increase with the age of the worm. The presence of sub-adults and adults on the same host, together with high levels of infection without high pathogenicity may account for Oculotrema being one of the most successful parasites among the Monogenea.

Echinococcus felidis in hippopotamus, South Africa.

Hydatid cysts of Echinococcus felidis are described from the hippopotamus (Hippopotamus amphibius) from Mpumalanga Province, South Africa. Among six hippopotami investigated, hepatic hydatids were found in three. The identification was based on mitochondrial and nuclear DNA sequences. In addition, the rostellar hook morphology was analysed. This is the first morphological description of the metacestode of E. felidis, and the first molecularly confirmed report of the intermediate host of E. felidis in South Africa. The definitive host of E. felidis in South Africa is the lion (Panthera leo).

Surgical Management of Spinal Synovial Cysts: A Series of 23 Patients and Systematic Analysis of the Literature.

STUDY DESIGN: Retrospective cohort and review of the literature. OBJECTIVE: To compare surgical strategies for the management of spinal synovial cysts. SUMMARY OF BACKGROUND DATA: The recent multiplication of retrospective series of patients with spinal synovial cysts has led to a reappraisal of their incidence and clinical significance. Although surgery is considered the treatment of choice, there is still no agreement over which surgical technique should be used. METHODS: We retrospectively reviewed 23 consecutive patients undergoing surgery for a spinal synovial cyst in our department between 2004 and 2010. Surgical procedures were classified into the following 4 categories: cystectomy by an interlaminar approach, hemilaminectomy, laminectomy, or associated with instrumented spinal fusion. Clinical outcome, cyst recurrence, need for subsequent fusion, and perioperative complications were compared between these groups. RESULTS: Of the patients included in the present cohort, 11 underwent cyst excision by an interlaminar approach, 8 had a hemilaminectomy, 2 had a laminectomy, and 2 underwent instrumented fusion. "Excellent" or "good" clinical outcome on the Macnab modified scale were achieved for 16 patients (69.6%), and there were 2 perioperative complications, 2 cyst recurrences, and 1 secondary fusion. Of the 519 patients reported in the literature, overall clinical outcome was either "excellent" or "good" for 83% of all patients. However, unfavorable outcome was more likely in patients treated with decompression alone (80/396) than decompression with fusion (10/123) (20.2% vs. 8.1%; P=0.003) and cyst recurrence (13/396 vs. 0/123; P=0.028). In contrast, the rate of perioperative complications was significantly higher in the fusion group (23/123) compared with decompression alone (11/396) (18.7% vs. 2.8%; P<0.0001). CONCLUSIONS: In patients with spinal synovial cyst, spinal fusion seems to decrease the risk of unfavorable clinical outcome and cyst recurrence and associated with a considerably higher rate of perioperative complications.

Intradural extramedullary spinal metastases of non-neurogenic origin: a distinct clinical entity or a subtype of leptomeningeal metastasis? A case-control study.

BACKGROUND: Leptomeningeal metastases from carcinoma are still poorly understood. OBJECTIVE: To better define the management of unique intradural extramedullary spinal metastases (IESM) from solid cancers of non-neurogenic origin, in particular regarding leptomeningeal metastasis (LM). METHODS: We conducted a retrospective, multicenter, case-control study including 11 patients with IESM matched with 11 patients with LM. Primary endpoint was overall survival; secondary endpoints were diagnostic criteria and prognostic factors. RESULTS: Descriptive analysis showed a clinically significant difference between IESM and LM patients regarding preexisting neurological deficit (45.5% vs 90.1%, P = .06) and malignant cells in cerebrospinal fluid (0% vs 54.5%, P = .03). The median overall survival was significantly higher for IESM patients (732 days) than for patients with LM (53 days; P < .0002). Multivariate analysis showed that preexisting neurological deficit was a negative prognostic factor for overall survival (hazard ratio: 10.2; 95% confidence interval: 1.88-102; P = .04), in contrast to functional improvement with treatment (hazard ratio: 0.01; 95% confidence interval: 0.00-0.52; P = .04). We propose the following diagnostic criteria for IESM: (1) a solid lesion located within the intradural extramedullary space, (2) the absence of other leptomeningeal lesion seen on full-spine injected magnetic resonance imaging, (3) the absence of malignant cells in cerebrospinal fluid, and (4) a histological confirmation of the metastatic nature of the lesion. CONCLUSION: The significant difference in survival between IESM and LM suggests that they are 2 distinct evolutions of the metastatic disease. Distinguishing IESM also has therapeutic consequences because patients can benefit from a focal surgical treatment with functional improvement and extended survival.

Elucidating the aetiology of human Campylobacter coli infections.

There has been little research on the determinants of Campylobacter coli infection, despite its contributing up to 10% of human Campylobacter infections. A case-control and two case-case study methods explored the aetiology of C. coli over a one year period across Scotland. The case-control multivariate model found an increased risk of C. coli infection in people older than 19 years (O.R. = 3.352), and during the summer months (O.R. = 2.596), while residing in an urban area decreased the risk (O.R. = 0.546). The first case-case study compared C. coli and C. jejuni cases and also showed a higher risk of C. coli during the summer (O.R. = 1.313) and in people older than 19 years (O.R. = 0.791). Living in an urban area was associated with a reduced risk of infection (O.R. = 0.769). Multi-locus sequence typing (MLST) indicated that sheep and chicken C. coli sequence types (STs) were most frequently found in humans whilst those from cattle and pigs were rarer. MLST diversity was high in isolates from pigs and chicken, intermediate in human isolates, and low in ruminant isolates. The second case-case study used MLST data to ascribe putative sources of infection to the cases. The putative source for 40% of cases was chicken, with 60% acquired from other sources (ruminants 54% and pigs 6%). The case-case analysis also showed that female gender was a risk factor (O.R. = 1.940), which may be explained by females being more likely to prepare poultry in the home. These findings indicate differences between the aetiology of C. coli and C. jejuni infections: this should be taken into account by public health professionals when developing strategies to reduce the burden of human campylobacteriosis.

Quantitative characterization of the imaging limits of diffuse low-grade oligodendrogliomas.

BACKGROUND: Supratentorial diffuse low-grade gliomas in adults extend beyond maximal visible MRI-defined abnormalities, and a gap exists between the imaging signal changes and the actual tumor margins. Direct quantitative comparisons between imaging and histological analyses are lacking to date. However, they are of the utmost importance if one wishes to develop realistic models for diffuse glioma growth. METHODS: In this study, we quantitatively compared the cell concentration and the edema fraction from human histological biopsy samples (BSs) performed inside and outside imaging abnormalities during serial imaging-based stereotactic biopsy of diffuse low-grade gliomas. RESULTS: The cell concentration was significantly higher in BSs located inside (1189 ± 378 cell/mm(2)) than outside (740 ± 124 cell/mm(2)) MRI-defined abnormalities (P = .0003). The edema fraction was significantly higher in BSs located inside (mean, 45% ± 23%) than outside (mean, 5 %± 9%) MRI-defined abnormalities (P < .0001). At borders of the MRI-defined abnormalities, 20% of the tissue surface area was occupied by edema and only 3% by tumor cells. The cycling cell concentration was significantly higher in BSs located inside (10 ± 12 cell/mm(2)), compared with outside (0.5 ± 0.9 cell/mm(2)), MRI-defined abnormalities (P = .0001). CONCLUSIONS: We showed that the margins of T2-weighted signal changes are mainly correlated with the edema fraction. In 62.5% of patients, the cycling tumor cell fraction (defined as the ratio of the cycling tumor cell concentration to the total number of tumor cells) was higher at the limits of the MRI-defined abnormalities than closer to the center of the tumor. In the remaining patients, the cycling tumor cell fraction increased towards the center of the tumor.

Dysembryoplastic neuroepithelial tumors: an MRI-based scheme for epilepsy surgery.

OBJECTIVE: To determine optimal resections in the 3 dysembryoplastic neuroepithelial tumor (DNT) histologic subtypes (simple, complex, and nonspecific) based on MRI features. METHODS: In 78 consecutive epilepsy patients operated for DNT, MRI features were classified as follows: type 1 (cystic/polycystic-like, well-delineated, strongly hypointense T1), type 2 (nodular-like, heterogeneous), or type 3 (dysplastic-like, iso/hyposignal T1, poor delineation, gray-white matter blurring). Correlations between histology, neurophysiologic findings, and surgical outcome were established for each MRI subtype. RESULTS: Type 1 MRI (25 cases, in temporal and extratemporal areas) always corresponded to simple or complex DNTs. Type 2 MRI (25 cases, predominantly in neocortical areas) and type 3 MRI (28 cases, mainly in the mesial temporal lobe) corresponded to nonspecific forms. The epileptogenic zone (EZ) differed significantly according to the MRI subtype (p = 0.0029). It colocalized with the tumor in type 1 MRI, included perilesional cortex in type 2 MRI, and involved extensive areas in type 3 MRI. Cortical dysplasia was predominantly found in type 3 MRI (p < 0.0001). The main prognostic factors for seizure-free outcome (83%) were complete tumor (p < 0.0001) and EZ (p = 0.0115) removal. Other factors favorably influencing the outcome were a short epilepsy duration (p = 0.013) and absence of cortical-subcortical damage at the resection site (p = 0.053). Age at surgery was not related to outcome; however, cortical-subcortical damage was correlated with old age (p = 0.021). Treatment discontinuation was correlated with young age at surgery (p = 0.004) and short epilepsy duration (p = 0.001). CONCLUSION: We propose that resection might be restricted to the tumor in type 1 MRI and be more extensive in other MRI subtypes, especially in type 3 MRI. Early surgery and clean surgical margins are crucial for curing epilepsy.

Symptomatic extensive thoracolumbar epidural hematoma following lumbar disc surgery treated by single level laminectomy.

Spinal epidural hematomas (SEHs) are rare complications following spine surgery, especially for single level lumbar discectomies. The appropriate surgical management for such cases remains to be investigated. We report a case of an extensive spinal epidural hematoma from T11-L5 following a L3-L4 discectomy. The patient underwent a single level L4. A complete evacuation of the SEH resulted in the patient's full recovery. When presenting symptoms limited to the initial surgical site reveal an extensive postoperative SEH, we propose: to tailor the surgical exposure individually based on preoperative findings of the SEH; and to begin the surgical exposure with a limited laminectomy focused on the symptomatic levels that may allow an efficient evacuation of the SEH instead of a systematic extensive laminectomy based on imaging.

Neuronal immunoexpression and a distinct subtype of adult primary supratentorial glioblastoma with a better prognosis.

OBJECT: In this study, the authors address whether neurofilament protein (NFP) expression can be used as an independent prognostic factor in primary glioblastoma multiformes (GBMs). METHODS: Three hundred and two consecutive adult patients with newly diagnosed supratentorial primary GBMs were analyzed (January 2000-August 2008). Detailed data regarding clinical, imaging, and pathological findings, oncological treatments, and outcomes were recorded. Neurofilament protein immunoexpression served to identify NFP-positive tumor cells (normal entrapped neurons and mature ganglion-like cells excluded). RESULTS: Neurofilament-positive cells were identified in 177 GBMs (58.6%). Patients with NFP-positive GBMs were younger (p < 0.0001), and their GBMs presented with more temporal lobe tumor localization (p = 0.029) and more cortical involvement (p = 0.0003). Neurofilament-negative GBMs presented with more ventricular contact (p < 0.0001) and more tumor midline crossing (p = 0.03). Median overall survival and progression-free survival (PFS) were 13.0 and 7.6 months, respectively, for NFP-positive GBMs, and 7.0 and 5.1 months, respectively, for NFP-negative GBMs. Multivariate analysis revealed NFP immunoexpression, tumor midline crossing, complete resection, and radiotherapy combined with chemotherapy as independent factors associated with overall survival. Neurofilament protein-positive immunoexpression was associated with longer overall survival (hazard ratio [HR] 0.54, 95% CI 0.40-0.74; p < 0.0001) and longer PFS (HR 0.71, 95% CI 0.53-0.96; p = 0.02). CONCLUSIONS: Neurofilament protein-positive immunoexpression represents a strong, therapeutically independent prognostic factor for primary supratentorial GBM clinical outcome among adult patients. Neurofilament protein-GBM's unique pathological features are not only associated with distinct clinical and anatomical behavior, but are also predictive of overall patient survival and PFS. Neurofilament protein immunoexpression may help identify a distinct subgroup of primary GBMs with a favorable prognosis, which should be considered in the design of future targeted therapies.

Dynamic imaging response following radiation therapy predicts long-term outcomes for diffuse low-grade gliomas.

Quantitative imaging assessment of radiation therapy (RT) for diffuse low-grade gliomas (DLGG) by measuring the velocity of diametric expansion (VDE) over time has never been studied. We assessed the VDE changes following RT and determined whether this parameter can serve as a prognostic factor. We reviewed a consecutive series of 33 adults with supratentorial DLGG treated with first-line RT with available imaging follow-up (median follow-up, 103 months). Before RT, all patients presented with a spontaneous tumor volume increase (positive VDE, mean 5.9 mm/year). After RT, all patients demonstrated a tumor volume decrease (negative VDE, mean, -16.7 mm/year) during a mean 49-month duration. In univariate analysis, initial tumor volume (>100 cm(3)), lack of IDH1 expression, p53 expression, high proliferation index, and fast post-RT tumor volume decrease (VDE at -10 mm/year or faster, fast responders) were associated with a significantly shorter overall survival (OS). The median OS was significantly longer (120.8 months) for slow responders (post-RT VDE slower than -10.0 mm/year) than for fast responders (47.9 months). In multivariate analysis, fast responders, larger initial tumor volume, lack of IDH1 expression, and p53 expression were independent poor prognostic factors for OS. A high proliferation index was significantly more frequent in the fast responder subgroup than in the slow responder subgroup. We conclude that the pattern of post-RT VDE changes is an independent prognostic factor for DLGG and offers a quantitative parameter to predict long-term outcomes. We propose to monitor individually the post-RT VDE changes using MRI follow-up, with particular attention to fast responders.

Hyperplasia-adenoma sequence in pituitary tumorigenesis related to aryl hydrocarbon receptor interacting protein gene mutation.

Mutations of the aryl hydrocarbon receptor interacting protein (AIP) gene are associated with pituitary adenomas that usually occur as familial isolated pituitary adenomas (FIPA). Detailed pathological and tumor genetic data on AIP mutation-related pituitary adenomas are not sufficient. Non-identical twin females presented as adolescents to the emergency department with severe progressive headache caused by large pituitary macroadenomas require emergency neurosurgery; one patient had incipient pituitary apoplexy. Post-surgically, the patients were found to have silent somatotrope adenomas on pathological examination. Furthermore, the light microscopic, immunohistochemical, and electron microscopic studies demonstrated tumors of virtually identical characteristics. The adenomas were accompanied by multiple areas of pituitary hyperplasia, which stained positively for GH, indicating somatotrope hyperplasia. Genetic analyses of the FIPA kindred revealed a novel E216X mutation of the AIP gene, which was present in both the affected patients and the unaffected father. Molecular analysis of surgical specimens revealed loss of heterozygosity (LOH) in the adenoma but showed that LOH was not present in the hyperplastic pituitary tissue from either patient. AIP immunostaining confirmed normal staining in the hyperplastic tissue and decreased staining in the adenoma in the tumors from both patients. These results demonstrate that patients with AIP germline mutation can present with silent somatotrope pituitary adenomas. The finding of somatotrope hyperplasia unaccompanied by AIP LOH suggests that LOH at the AIP locus might be a late event in a potential progression from hyperplastic to adenomatous tissue.

Microbiogical data, but not procalcitonin improve the accuracy of the clinical pulmonary infection score.

OBJECTIVE: Early and adequate treatment of ventilator-associated pneumonia (VAP) is mandatory to improve the outcome. The aim of this study was to evaluate, in medical ICU patients, the respective and combined impact of the Clinical Pulmonary Infection Score (CPIS), broncho-alveolar lavage (BAL) gram staining, endotracheal aspirate and a biomarker (procalcitonin) for the early diagnosis of VAP. DESIGN: Prospective, observational study SETTING: A medical intensive care unit in a teaching hospital. PATIENTS: Over an 8-month period, we prospectively included 57 patients suspected of having 86 episodes of VAP. INTERVENTION: The day of suspicion, a BAL as well as alveolar and serum procalcitonin determinations and evaluation of CPIS were performed. MEASUREMENTS AND MAIN RESULTS: Of 86 BAL performed, 48 were considered positive (cutoff of 10(4) cfu ml(-1)). We found no differences in alveolar or serum procalcitonin between VAP and non-VAP patients. Including procalcitonin in the CPIS score did not increase its accuracy (55%) for the diagnosis of VAP. The best tests to predict VAP were modified CPIS (threshold at 6) combined with microbiological data. Indeed, both routinely twice weekly performed endotracheal aspiration at a threshold of 10(5) cfu ml(-1) and BAL gram staining improved pre-test diagnostic accuracy of VAP (77 and 66%, respectively). CONCLUSION: This study showed that alveolar procalcitonin performed by BAL does not help the clinician to identify VAP. It confirmed that serum procalcitonin is not an accurate marker of VAP. In contrast, microbiological resources available at the time of VAP suspicion (BAL gram staining, last available endotracheal aspirate) combined or not with CPIS are helpful in distinguishing VAP diagnosed by BAL from patients with a negative BAL.

The protective status of subtotal obliteration of arteriovenous malformations after radiosurgery: significance and risk of hemorrhage.

OBJECTIVE: Arteriovenous malformations (AVMs) treated by radiosurgery with complete obliteration of the nidus but a persisting early draining vein on follow-up angiography can be termed subtotally obliterated. However, these are persistent circulating AVMs. The significance of these lesions, their hemorrhage rate, and their management are analyzed. METHODS: In a series of 862 consecutive patients with AVMs treated by radiosurgery, 121 patients (14%) achieved subtotal obliteration (STO). The angiographic evolution and rate of obliteration were studied. The pretreatment angiographic features, dosimetric parameters, and postradiosurgery hemorrhage rate were compared with those in the rest of the treated population. Finally, the options for follow-up and treatment were analyzed. RESULTS: Of 121 subtotally obliterated AVMs, the bleeding rate was 0%; 53% of patients achieved complete obliteration. This occurred in 71% of those who had STO at 1 year. In the cases in which STO was detected at 2, 3, and 4 years, total obliteration eventually occurred in 43%, 28.5%, and 0%, respectively. Comparative analysis with AVMs in which a part of the nidus persisted showed a significant difference in the bleeding rate. Except for volume, no significant statistical difference in angiographic and dosimetric parameters was found between the STO group and the rest of the studied population with residual nidus. Six cases received further treatment, resulting in 2 cures and 2 treatment-related complications. CONCLUSION: Subtotally obliterated AVMs are different from other partially obliterated AVMs, with a 0% bleeding rate. Their complete obliteration is a function of delay of appearance on follow-up angiography. Invasive follow-up and further treatment of these AVMs do not seem warranted.