Gastrointestinal malformations: impact of prenatal diagnosis on gestational age at birth.

The aim of the study was to analyse the degree to which gestational age (GA) has been shortened due to prenatal diagnosis of gastrointestinal malformations (GIM). The data source for the study was 14 population-based registries of congenital malformations (EUROCAT). All liveborn infants with GIMs and without chromosomal anomalies, born 1997-2002, were included. The 14 registries identified 1047 liveborn infants with one or more GIMs (oesophageal atresia, duodenal atresia, omphalocele, gastroschisis and diaphragmatic hernia). Median GA at birth was lower in prenatally diagnosed cases for all five malformations, although not statistically significant for gastroschisis. There was little difference in median birthweight by GA for the pre- and postnatally diagnosed infants. The difference in GA at birth between prenatally and postnatally diagnosed infants with GIMs is enough to increase the risk of mortality for the prenatally diagnosed infants. Clinicians need to balance the risk of early delivery against the benefits of clinical convenience when making case management decisions after prenatal diagnosis. Very few studies have been able to show benefits of prenatal diagnosis of congenital malformations for liveborn infants. This may be because the benefits of prenatal diagnosis are outweighed by the problems arising from a lower GA at birth.

The postmortem diagnosis of alcoholic ketoacidosis.

AIMS: The aim of this article is to review the forensic literature covering the postmortem investigations that are associated with alcoholic ketoacidosis fatalities and report the results of our own analyses. METHODS: Eight cases of suspected alcoholic ketoacidosis that had undergone medico-legal investigations in our facility from 2011 to 2013 were retrospectively selected. A series of laboratory parameters were measured in whole femoral blood, postmortem serum from femoral blood, urine and vitreous humor in order to obtain a more general overview on the biochemical and metabolic changes that occur during alcoholic ketoacidosis. Most of the tested parameters were chosen among those that had been described in clinical and forensic literature associated with alcoholic ketoacidosis and its complications. RESULTS: Ketone bodies and carbohydrate-deficient transferrin levels were increased in all cases. Biochemical markers of generalized inflammation, volume depletion and undernourishment showed higher levels. Adaptive endocrine reactions involving insulin, glucagon, cortisol and triiodothyronine were also observed. CONCLUSIONS: Metabolic and biochemical disturbances characterizing alcoholic ketoacidosis can be reliably identified in the postmortem setting. The correlation of medical history, autopsy findings and biochemical results proves therefore decisive in identifying pre-existing disorders, excluding alternative causes of death and diagnosing alcoholic ketoacidosis as the cause of death.

Replicative phenotyping adds value to genotypic resistance testing in heavily pre-treated HIV-infected individuals--the Swiss HIV Cohort Study.

BACKGROUND: Replicative phenotypic HIV resistance testing (rPRT) uses recombinant infectious virus to measure viral replication in the presence of antiretroviral drugs. Due to its high sensitivity of detection of viral minorities and its dissecting power for complex viral resistance patterns and mixed virus populations rPRT might help to improve HIV resistance diagnostics, particularly for patients with multiple drug failures. The aim was to investigate whether the addition of rPRT to genotypic resistance testing (GRT) compared to GRT alone is beneficial for obtaining a virological response in heavily pre-treated HIV-infected patients. METHODS: Patients with resistance tests between 2002 and 2006 were followed within the Swiss HIV Cohort Study (SHCS). We assessed patients' virological success after their antiretroviral therapy was switched following resistance testing. Multilevel logistic regression models with SHCS centre as a random effect were used to investigate the association between the type of resistance test and virological response (HIV-1 RNA <50 copies/mL or ≥1.5 log reduction). RESULTS: Of 1158 individuals with resistance tests 221 with GRT+rPRT and 937 with GRT were eligible for analysis. Overall virological response rates were 85.1% for GRT+rPRT and 81.4% for GRT. In the subgroup of patients with >2 previous failures, the odds ratio (OR) for virological response of GRT+rPRT compared to GRT was 1.45 (95% CI 1.00-2.09). Multivariate analyses indicate a significant improvement with GRT+rPRT compared to GRT alone (OR 1.68, 95% CI 1.31-2.15). CONCLUSIONS: In heavily pre-treated patients rPRT-based resistance information adds benefit, contributing to a higher rate of treatment success.

Influence of CYP2D6 activity on pre-emptive analgesia by the N-methyl-D-aspartate antagonist dextromethorphan in a randomized controlled trial of acute pain.

BACKGROUND: There is some evidence that dextromethorphan (DM) is effective as a pre-emptive analgesic agent.  DM is mainly metabolized to dextrorphan (DOR) by CYP2D6 whose activity can be inhibited by pharmacologic intervention. OBJECTIVES: To investigate the efficacy of DM as a pre-emptive analgesic agent and describe the population pharmacokinetics in the presence of normal and poor CYP2D6 metabolism in acute post-operative pain. STUDY DESIGN: Double blind, randomized, placebo-controlled trial SETTING: Post-surgical analgesic consumption after knee ligament surgery, a setting of acute pain. METHODS: Forty patients were randomized to a single oral dose of 50 mg quinidine or placebo, administered 12 hours before 50 mg DM. Patients were genotyped for the major CYP2D6 and ABCB1 variants and phenotyped for CYP2D6 using urine DM/DOR metabolic ratios and blood samples for population pharmacokinetic modeling. RESULTS: Quinidine was effective in inhibiting CYP2D6 activity, with 2-fold reduction of DM to DOR biotransformation clearance, prolonged DM half-life, and increased DM systemic availability. Patients in the quinidine group required significantly less often NSAIDs than patients in the placebo group (35.3% vs. 75.0%, P = 0.022). The odds ratio for NSAID consumption in the placebo vs. quinidine group was 5.5 (95% confidence interval (CI) 1.3 - 22.7) at 48 hours after surgery. LIMITATIONS: While this study shows an impact of DM on pre-emptive analgesia and is mechanistically interesting, the findings need to be confirmed in larger trials. CONCLUSION: CYP2D6 inhibition by quinidine influenced the pre-emptive analgesic effectiveness of DM confirming that CYP2D6 phenotypic switch increases the neuromodulatory effect of oral dextromethorphan.

The prognostic value of semi-quantitative i-123 mibg scintigraphy at diagnosis in high risk neuroblastoma: validation of the siopen score method

Purpose: SIOPEN scoring of 123I mIBG imaging has been shown to predict response to induction chemotherapy and outcome at diagnosis in children with HRN.Method: Patterns of skeletal 123I mIBG uptake were assigned numerical scores (Mscore) ranging from 0 (no metastasis) to 72 (diffuse metastases) within 12 body areas as described previously. 271 anonymised, paired image data sets acquired at diagnosis and on completion of Rapid COJEC induction chemotherapy were reviewed, constituting a representative sample of 1602 children treated prospectively within the HR-NBL1/SIOPEN trial. Pre-and post-treatment Mscores were compared with bone marrow cytology (BM) and 3 year event free survival (EFS).Results: Results 224/271 patients showed skeletal MIBG-uptake at diagnosis and were evaluable forMIBG-response. Complete response (CR) on MIBG to Rapid COJEC induction was achieved by 66%, 34% and 15% of patients who had pre-treatment Mscores of <18 (n¼65, 29%), 18-44 (n¼95,42%) and Y ´ 45 (n¼64, 28.5%) respectively (chi squared test p<.0001). Mscore at diagnosis and on completion of Rapid COJEC correlated strongly with BM involvement (p<0.0001). The correlation of pre score with post scores and response was highly significant (p<0.001). Most importantly, the 3 year EFS in 47 children with Mscore 0 at diagnosis was 0.68 (A ` 0.07), by comparison with 0.42 (A` 0.06), 0.35 (A` 0.05) and 0.25 (A` 0.06) for patients in pre-treatment score groups <18, 18-44 and Y ´ 45, respectively (p<0.001). AnMscore threshold ofY ´ 45 at diagnosis was associated with significantly worse outcome by comparison with all other Mscore groups (p¼0.029). The 3 year EFS of 0.53 (A` 0.07) of patients in metastatic CR (mIBG and BM) after Rapid Cojec (33%) is clearly superior to patients not achieving metastatic CR (0.24 (A ` 0.04), p¼0.005).Conclusion: SIOPEN scoring of 123I mIBG imaging has been shown to predict response to induction chemotherapy and outcome at diagnosis in children with HRN.

Comment la sérologie peut-elle aider à l'établissement du diagnostic des parasites [How can serology contribute to the diagnosis of parasitic diseases?].

From a technical standpoint the most widely used tests for serology include the ELISA (enzyme linked immunosorbent assay), the IFA (indirect fluorescence assay), and the immunoblot. ELISA tests are widely used as screening assays since they harbor a high sensitivity. The main pitfall of serologies is the frequency of cross-reactions, especially between the different helminths. This is why positive results should be confirmed by a second test method with a higher specificity. Results need also to be put in the perspective of the patient history, clinical signs and laboratory findings. Serological tests are most appropriate when the parasite cannot be documented by direct examination (by eye or under the microscope) and during the pre-patent period. Serologies for parasites are also useful when an unexplained eosinophilia is present.

ESCMID* guideline for the diagnosis and management of Candida diseases 2012: patients with HIV infection or AIDS.

Mucosal candidiasis is frequent in immunocompromised HIV-infected highly active antiretroviral (HAART) naive patients or those who have failed therapy. Mucosal candidiasis is a marker of progressive immune deficiency. Because of the frequently marked and prompt immune reconstitution induced by HAART, there is no recommendation for primary antifungal prophylaxis of mucosal candidiasis in the HIV setting in Europe, although it has been evidenced as effective in the pre-HAART era. Fluconazole remains the first line of therapy for both oropharyngeal candidiasis and oesophageal candidiasis and should be preferred to itraconazole oral solution (or capsules when not available) due to fewer side effects. For patients who still present with fluconazole-refractory mucosal candidiasis, oral treatment with any other azole should be preferred based on precise Candida species identification and susceptibility testing results in addition to the optimization of HAART when feasible. For vaginal candidiasis, topical therapy is preferred.

Deficit in memory consolidation (abnormal forgetting rate) in childhood temporal lobe epilepsy. Pre and postoperative long-term observation.

Deficits in memory consolidation have been reported in adult patients with epilepsy but, not to our knowledge, in children. We report the long-term follow-up (9 y. o. to 18 y. o.) of a boy who suffered from temporal lobe epilepsy and underwent a left temporal lobectomy with amygdalo-hippocampal resection at the age of 10. He showed an abnormal forgetting rate when trying to encode new information and a significant deficit for retrieving remote episodic memories (when compared with his twin brother), both consistent with a consolidation disorder. His memory condition slightly improved after cessation of the epilepsy, nevertheless did not normalize. No standard memory assessment could pinpoint his memory problem, hence an adapted methodology was needed. We discuss the nature of the memory deficit, its possible causes and its clinical implications.

Peri-operative management of antiplatelet therapy in patients with coronary artery disease. Joint position paper by members of the working group on Perioperative Haemostasis of the Society on Thrombosis and Haemostasis Research (GTH), the working group on Perioperative Coagulation of the Austrian Society for Anesthesiology, Resuscitation and Intensive Care (ÖGARI) and the Working Group Thrombosis of the European Society for Cardiology (ESC).

An increasing number of patients suffering from cardiovascular disease, especially coronary artery disease (CAD), are treated with aspirin and/or clopidogrel for the prevention of major adverse events. Unfortunately, there are no specific, widely accepted recommendations for the perioperative management of patients receiving antiplatelet therapy. Therefore, members of the Perioperative Haemostasis Group of the Society on Thrombosis and Haemostasis Research (GTH), the Perioperative Coagulation Group of the Austrian Society for Anesthesiology, Reanimation and Intensive Care (ÖGARI) and the Working Group Thrombosis of the European Society of Cardiology (ESC) have created this consensus position paper to provide clear recommendations on the perioperative use of anti-platelet agents (specifically with semi-urgent and urgent surgery), strongly supporting a multidisciplinary approach to optimize the treatment of individual patients with coronary artery disease who need major cardiac and non-cardiac surgery. With planned surgery, drug eluting stents (DES) should not be used unless surgery can be delayed for ≥12 months after DES implantation. If surgery cannot be delayed, surgical revascularisation, bare-metal stents or pure balloon angioplasty should be considered. During ongoing antiplatelet therapy, elective surgery should be delayed for the recommended duration of treatment. In patients with semi-urgent surgery, the decision to prematurely stop one or both antiplatelet agents (at least 5 days pre-operatively) has to be taken after multidisciplinary consultation, evaluating the individual thrombotic and bleeding risk. Urgently needed surgery has to take place under full antiplatelet therapy despite the increased bleeding risk. A multidisciplinary approach for optimal antithrombotic and haemostatic patient management is thus mandatory.

Diagnosis of periprosthetic joint infections.

Advances in implant design, surgical technique, peri-operative antimicrobial prophylaxis and laminar airflow operating room environment have made total joint arthroplasty one of the most successful surgical procedures of all times. Orthopaedic implants, however, remain prone to microbial contamination resulting in persistent risk of implant-associated infection. Treatment of infections associated with orthopaedic devices usually requires appropriate surgical intervention combined with a prolonged antimicrobial therapy. The choice of the best possible treatment regimen depends on duration and pathogenesis of infection, stability of the implant, antimicrobial susceptibility of the pathogen and condition of the surrounding soft tissue. In addition towell known diagnostic procedures new promising tools for rapid and correct microbial diagnosis are being developed as correct diagnosis of the responsible micro-organism and this is paramount for successful treatment of prosthetic joint infection.

Functional compensation of motor function in pre-symptomatic Huntington's disease.

Involuntary choreiform movements are a clinical hallmark of Huntington's disease. Studies in clinically affected patients suggest a shift of motor activations to parietal cortices in response to progressive neurodegeneration. Here, we studied pre-symptomatic gene carriers to examine the compensatory mechanisms that underlie the phenomenon of retained motor function in the presence of degenerative change. Fifteen pre-symptomatic gene carriers and 12 matched controls performed button presses paced by a metronome at either 0.5 or 2 Hz with four fingers of the right hand whilst being scanned with functional magnetic resonance imaging. Subjects pressed buttons either in the order of a previously learnt 10-item finger sequence, from left to right, or kept still. Error rates ranged from 2% to 7% in the pre-symptomatic gene carriers and from 0.5% to 4% in controls, depending on the condition. No significant difference in task performance was found between groups for any of the conditions. Activations in the supplementary motor area (SMA) and superior parietal lobe differed with gene status. Compared with healthy controls, gene carriers showed greater activations of left caudal SMA with all movement conditions. Activations correlated with increasing speed of movement were greater the closer the gene carriers were to estimated clinical diagnosis, defined by the onset of unequivocal motor signs. Activations associated with increased movement complexity (i.e. with the pre-learnt 10-item sequence) decreased in the rostral SMA with nearing diagnostic onset. The left superior parietal lobe showed reduced activation with increased movement complexity in gene carriers compared with controls, and in the right superior parietal lobe showed greater activations with all but the most demanding movements. We identified a complex pattern of motor compensation in pre-symptomatic gene carriers. The results show that preclinical compensation goes beyond a simple shift of activity from premotor to parietal regions involving multiple compensatory mechanisms in executive and cognitive motor areas. Critically, the pattern of motor compensation is flexible depending on the actual task demands on motor control.

Diagnosis and treatment of malignant oddian tumors.

Between 1959 and 1987 we operated on 18 patients for malignant oddian tumor. Eleven had a Whipple resection, 3 a bilio-enteric anastomosis, 4 a local excision with or without bilio-enteric anastomosis. The overall operative mortality was 11% and the median survival was 13.8 months. Three patients are living and without evidence of disease 12, 29 and 30 months, respectively, after a Whipple resection. Because of their anatomy and favourable behaviour, malignant oddian tumors must be separated from the other periampullary tumors. Echography and endoscopic retrograde cholangiopancreatography with deep biopsies are the most efficient diagnostic modalities. With the aim of cure, the treatment is always surgical and relies mainly on duodenopancreatectomy. Those patients with unresectable tumors or unfit for a major procedure should benefit from internal or external biliary drainage. By coexisting duodenal obstruction, a surgical double derivation should be done.

Review of CT features of saprophytic aspergillosis (Aspergilloma) and correlation with final diagnosis : P21

Purpose: 1. To review Ct features suggestive of saprophytic aspergillosis (aspergilloma) and to correlate them with the final pathological results. 2. To illustrate the wide range of differential diagnosis. Methods and materials: The electronic database of our department from 1995 to 2007 revealed CT reports of 48 patients that had been considered very suggestive of aspergilloma. Two radiologists with 6 and 12 years experience in thoracic radiology jointly reviewed the corresponding CT features including ancillary findings and the underlying lung diseases and correlated them with the final pathological diagnosis. Results: Forty patients could be included in the study (12 women, mean age 52), while in 8 patients there was no adequate clinical follow-up. In 17 patients the diagnosis "mycetoma" due to aspergillus fumigatus infection was confirmed, either by surgery, biopsy or bronchoscopy. In 23 patients, differential diagnoses were found, such as cavitating bronchial carcinoma (n = 7), bacterial abscess (n = 3), typical (n = 2) and atypical (n = 2) tuberculosis, as well as inflammatory changes due to mucoviscidosis (n = 1), Wegener's disease (n = 1) or chronic obstructive pulmonary disease (n = 3). Fibromyxoide hamartoma, lung infarction and bronchomucocele were responsible for the typical CT feature in one patient each. Conclusion: 1. The typical CT feature suggesting mycetoma is softtissue proliferation within a pre-existing wall-thickened lung cavity, oten even considered "pathognomonic". However, this diagnosis was finally confirmed by surgery or laboratory findings in less than 50% of patients only. 2. Since differential diagnoses are very large, not only including cavitating lung cancer and tuberculosis, the individual underlying lung disease needs strongly being taken into account often giving the best clue for the correct diagnosis.

Prevalence, prenatal diagnosis and clinical features of oculo-auriculo-vertebral spectrum: a registry-based study in Europe.

Oculo-auriculo-vertebral spectrum is a complex developmental disorder characterised mainly by anomalies of the ear, hemifacial microsomia, epibulbar dermoids and vertebral anomalies. The aetiology is largely unknown, and the epidemiological data are limited and inconsistent. We present the largest population-based epidemiological study to date, using data provided by the large network of congenital anomalies registries in Europe. The study population included infants diagnosed with oculo-auriculo-vertebral spectrum during the 1990-2009 period from 34 registries active in 16 European countries. Of the 355 infants diagnosed with oculo-auriculo-vertebral spectrum, there were 95.8% (340/355) live born, 0.8% (3/355) fetal deaths, 3.4% (12/355) terminations of pregnancy for fetal anomaly and 1.5% (5/340) neonatal deaths. In 18.9%, there was prenatal detection of anomaly/anomalies associated with oculo-auriculo-vertebral spectrum, 69.7% were diagnosed at birth, 3.9% in the first week of life and 6.1% within 1 year of life. Microtia (88.8%), hemifacial microsomia (49.0%) and ear tags (44.4%) were the most frequent anomalies, followed by atresia/stenosis of external auditory canal (25.1%), diverse vertebral (24.3%) and eye (24.3%) anomalies. There was a high rate (69.5%) of associated anomalies of other organs/systems. The most common were congenital heart defects present in 27.8% of patients. The prevalence of oculo-auriculo-vertebral spectrum, defined as microtia/ear anomalies and at least one major characteristic anomaly, was 3.8 per 100,000 births. Twinning, assisted reproductive techniques and maternal pre-pregnancy diabetes were confirmed as risk factors. The high rate of different associated anomalies points to the need of performing an early ultrasound screening in all infants born with this disorder.