Pregnancy and reproduction in autoimmune rheumatic diseases

Despite evidence for the important role of oestrogens in the aetiology and pathophysiology of chronic immune/inflammatory diseases, the previous view of an unequivocal beneficial effect of oestrogens on RA compared with a detrimental effect on SLE has to be reconsidered. Likewise, the long-held belief that RA remits in the majority of pregnant patients has been challenged, and shows that only half of the patients experience significant improvement when objective disease activity measurements are applied. Pregnancies in patients with SLE are mostly successful when well planned and monitored interdisciplinarily, whereas a small proportion of women with APS still have adverse pregnancy outcomes in spite of the standard treatment. New prospective studies indicate better outcomes for pregnancies in women with rare diseases such as SSc and vasculitis. Fertility problems are not uncommon in patients with rheumatic disease and need to be considered in both genders. Necessary therapy, shortly before or during the pregnancy, demands taking into account the health of both mother and fetus. Long-term effects of drugs on offspring exposed in utero or during lactation is a new area under study as well as late effects of maternal rheumatic disease on children.

A feasibility study for the provision of electronic healthcare tools and services in areas of Greece, Cyprus and Italy

Background Through this paper, we present the initial steps for the creation of an integrated platform for the provision of a series of eHealth tools and services to both citizens and travelers in isolated areas of thesoutheast Mediterranean, and on board ships travelling across it. The platform was created through an INTERREG IIIB ARCHIMED project called INTERMED. Methods The support of primary healthcare, home care and the continuous education of physicians are the three major issues that the proposed platform is trying to facilitate. The proposed system is based on state-of-the-art telemedicine systems and is able to provide the following healthcare services: i) Telecollaboration and teleconsultation services between remotely located healthcare providers, ii) telemedicine services in emergencies, iii) home telecare services for "at risk" citizens such as the elderly and patients with chronic diseases, and iv) eLearning services for the continuous training through seminars of both healthcare personnel (physicians, nurses etc) and persons supporting "at risk" citizens. These systems support data transmission over simple phone lines, internet connections, integrated services digital network/digital subscriber lines, satellite links, mobile networks (GPRS/3G), and wireless local area networks. The data corresponds, among others, to voice, vital biosignals, still medical images, video, and data used by eLearning applications. The proposed platform comprises several systems, each supporting different services. These were integrated using a common data storage and exchange scheme in order to achieve system interoperability in terms of software, language and national characteristics. Results The platform has been installed and evaluated in different rural and urban sites in Greece, Cyprus and Italy. The evaluation was mainly related to technical issues and user satisfaction. The selected sites are, among others, rural health centers, ambulances, homes of "at-risk" citizens, and a ferry. Conclusions The results proved the functionality and utilization of the platform in various rural places in Greece, Cyprus and Italy. However, further actions are needed to enable the local healthcare systems and the different population groups to be familiarized with, and use in their everyday lives, mature technological solutions for the provision of healthcare services.

"Drug mules" as a radiological challenge: Sensitivity and specificity in identifying internal cocaine in body packers, body pushers and body stuffers by computed tomography, plain radiography and Lodox

PURPOSE: The purpose of our study was to retrospectively evaluate the specificity, sensitivity and accuracy of computed tomography (CT), digital radiography (DR) and low-dose linear slit digital radiography (LSDR, Lodox(®)) in the detection of internal cocaine containers. METHODS: Institutional review board approval was obtained. The study collectively consisted of 83 patients (76 males, 7 females, 16-45 years) suspected of having incorporated cocaine drug containers. All underwent radiological imaging; a total of 135 exams were performed: nCT=35, nDR=70, nLSDR=30. An overall calculation of all "drug mules" and a specific evaluation of body packers, pushers and stuffers were performed. The gold standard was stool examination in a dedicated holding cell equipped with a drug toilet. RESULTS: There were 54 drug mules identified in this study. CT of all drug carriers showed the highest diagnostic accuracy 97.1%, sensitivity 100% and specificity 94.1%. DR in all cases was 71.4% accurate, 58.3% sensitive and 85.3% specific. LSDR of all patients with internal cocaine was 60% accurate, 57.9% sensitive and 63.4% specific. CONCLUSIONS: CT was the most accurate test studied. Therefore, the detection of internal cocaine drug packs should be performed by CT, rather than by conventional X-ray, in order to apply the most sensitive exam in the medico-legal investigation of suspected drug carriers. Nevertheless, the higher radiation applied by CT than by DR or LSDR needs to be considered. Future studies should include evaluation of low dose CT protocols in order to address germane issues and to reduce dosage.

Evidence, lack of evidence, controversy, and debate in the provision and performance of the surgery of acute type A aortic dissection

Acute type A aortic dissection is a lethal condition requiring emergency surgery. It has diverse presentations, and the diagnosis can be missed or delayed. Once diagnosed, decisions with regard to initial management, transfer, appropriateness of surgery, timing of operation, and intervention for malperfusion complications are necessary. The goals of surgery are to save life by prevention of pericardial tamponade or intra-pericardial aortic rupture, to resect the primary entry tear, to correct or prevent any malperfusion and aortic valve regurgitation, and if possible to prevent late dissection-related complications in the proximal and downstream aorta. No randomized trials of treatment or techniques have ever been performed, and novel therapies-particularly with regard to extent of surgery-are being devised and implemented, but their role needs to be defined. Overall, except in highly specialized centers, surgical outcomes might be static, and there is abundant room for improvement. By highlighting difficulties and controversies in diagnosis, patient selection, and surgical therapy, our over-arching goal should be to enfranchise more patients for treatment and improve surgical outcomes.

Ascending thoracic aorta dimension and outcomes in acute type B dissection (from the International Registry of Acute Aortic Dissection [IRAD])

It is not well known if the size of the ascending thoracic aorta at presentation predicts features of presentation, management, and outcomes in patients with acute type B aortic dissection. The International Registry of Acute Aortic Dissection (IRAD) database was queried for all patients with acute type B dissection who had documentation of ascending thoracic aortic size at time of presentation. Patients were categorized according to ascending thoracic aortic diameters ≤4.0, 4.1 to 4.5, and ≥4.6 cm. Four hundred eighteen patients met inclusion criteria; 291 patients (69.6%) were men with a mean age of 63.2 ± 13.5 years. Ascending thoracic aortic diameter ≤4.0 cm was noted in 250 patients (59.8%), 4.1 to 4.5 cm in 105 patients (25.1%), and ≥4.6 cm in 63 patients (15.1%). Patients with an ascending thoracic aortic diameter ≥4.6 cm were more likely to be men (p = 0.01) and have Marfan syndrome (p <0.001) and known bicuspid aortic valve disease (p = 0.003). In patients with an ascending thoracic aorta ≥4.1 cm, there was an increased incidence of surgical intervention (p = 0.013). In those with an ascending thoracic aorta ≥4.6 cm, the root, ascending aorta, arch, and aortic valve were more often involved in surgical repair. Patients with an ascending thoracic aorta ≤4.0 were more likely to have endovascular therapy than those with larger ascending thoracic aortas (p = 0.009). There was no difference in overall mortality or cause of death. In conclusion, ascending thoracic aortic enlargement in patients with acute type B aortic dissection is common. Although its presence does not appear to predict an increased risk of mortality, it is associated with more frequent open surgical intervention that often involves replacement of the proximal aorta. Those with smaller proximal aortas are more likely to receive endovascular therapy.

Occurrence and severity of concomitant injuries in other areas than the face in children with mandibular and midfacial fractures

To clarify the occurrence, causes, severity, and predictors of concomitant injuries in pediatric patients with facial fractures.

Systemic therapy of atopic dermatitis in children and adults

Systemic therapy is required in patients with severe atopic dermatitis (AD) refractory to adequate topical therapy. The aim of a systemic therapy is the rapid and efficient improvement of skin symptoms and pruritus in acute exacerbation and/or the long-term control of severe chronic disease. A number of immunosuppressive and immunomodulating substances are available that may efficiently reduce skin inflammation and thus lead to a relief of symptoms including pruritus. The excellent effects of cyclosporine as short-term as well as maintenance therapy have been documented in several studies in children and adults. Furthermore, other immunosuppressive substances such as azathioprine, mycophenolate mofetil and methotrexate are effective in patients with moderate to severe AD. Intravenous immunoglobulins and γ-interferon exert immunomodulatory effects and thus may improve severe AD. Biological agents are a new approach in AD therapy since they may specifically target cells, cytokines or mediators involved in the pathogenesis of AD.

Pacemakers and magnetic resonance imaging: Current status and survey in Switzerland

Electromagnetic fields arising from magnetic resonance imaging (MRI) can cause various clinically relevant functional disturbances in patients with cardiac pacemakers. Consequently, an implanted pacemaker is generally considered a contraindication for an MRI scan. With approximately 60 million MRI scans performed worldwide per year, MRI may be indicated for an estimated majority of pacemaker patients during the lifetime of their pacemakers. The availability of MR conditional pacemakers with CE labelling is of particular advantage since they allow the safe use of pacemakers in MRI. In this article the current state of knowledge on pacemakers and MR imaging is discussed. We present the results of a survey conducted among Swiss radiologists to assess current practice in patients with pacemakers.

Viral genotype-specific role of PNPLA3, PPARG, MTTP, and IL28B in hepatitis C virus-associated steatosis

Steatosis is a prominent feature of hepatitis C, especially in patients infected with genotype 3. The analysis of genetic polymorphisms influencing steatosis in chronic hepatitis C has been limited by the studies' small sample size, and important single nucleotide polymorphisms (SNPs), such as those in the patatin-like phospholipase family 3 protein (PNPLA3), were never evaluated.

Predicting bacteremia in children with cancer and fever in chemotherapy-induced neutropenia: results of the prospective multicenter SPOG 2003 FN study

To develop a score predicting the risk of bacteremia in cancer patients with fever and neutropenia (FN), and to evaluate its performance.

Immune response to influenza vaccination in children treated with methotrexate or/and tumor necrosis factor-alpha inhibitors

In children treated with immunosuppressive medication such as methotrexate and tumor necrosis factor-alpha (TNF-α) inhibitors, additional immunizations are recommended because of increased susceptibility to infections. However, it is unclear if adequate antibody response to vaccinations can be established in children receiving methotrexate and/or TNF-α inhibitors. In a prospective open label study, we assessed seroprotection and seroconversion following influenza vaccination during 2 seasons (6 strains) in 36 children with autoimmune disease treated either with methotrexate (n=18), TNF-α inhibitors (n=10) or both (n=8) and a control group of 16 immunocompetent children. Influenza antibody titers were determined by hemagglutinin inhibition assay, before and 4-8 weeks after vaccination. Post-vaccination seroprotection (defined as a titer ≥1:40) did not significantly differ between immunosuppressed and immunocompetent subjects. Seroconversion, defined as the change from a nonprotective (< 1:40) to a protective titer (≥1:40) with at least a 4-fold titer increase, was less likely to occur in immunosuppressed patients, although no significant difference from the control group was established. Safety evaluation of vaccination showed no serious adverse events. Children receiving methotrexate and/or TNF-α inhibitors can be safely and effectively immunized against influenza, with a seroprotection after vaccination comparable to immunocompetent children.

Fondaparinux - data on efficacy and safety in special situations

New anticoagulants promise to have better efficacy, more safety and/or a better manageability than traditional anticoagulants. However, knowledge is limited regarding special situations such as renal insufficiency, obesity, pregnancy, long-term therapy, heparin-induced thrombocytopenia, treatment in patients with mechanical heart valves, use for children, and in patients with a high risk of thromboembolic complications. These situations have rarely or even never been the objective of randomised controlled trials. The purpose of the present article is to summarize and discuss available data on efficacy and safety in these special situations for one of the first new anticoagulants, the indirect factor-Xa inhibitor fondaparinux. Furthermore, we discuss safety in licensed indications and management of bleeding complications and comment on measuring of drug concentration in plasma.

Acinetobacter baumannii isolates from pets and horses in Switzerland: molecular characterization and clinical data

OBJECTIVES: We investigated whether Acinetobacter baumannii isolates of veterinary origin shared common molecular characteristics with those described in humans. METHODS: Nineteen A. baumannii isolates collected in pets and horses were analysed. Clonality was studied using repetitive extragenic palindromic PCR (rep-PCR) and multilocus sequence typing (MLST). PCR and DNA sequencing for various beta-lactamase, aminoglycoside-modifying enzyme, gyrA and parC, ISAba1 and IS1133, adeR and adeS of the AdeABC efflux pump, carO porin and class 1/2/3 integron genes were performed. RESULTS: Two main clones [A (n = 8) and B (n = 9)] were observed by rep-PCR. MLST indicated that clone A contained isolates of sequence type (ST) ST12 (international clone II) and clone B contained isolates of ST15 (international clone I). Two isolates of ST10 and ST20 were also noted. Seventeen isolates were resistant to gentamicin, 12 to ciprofloxacin and 3 to carbapenems. Isolates of ST12 carried bla(OXA-66), bla(ADC-25), bla(TEM-1), aacC2 and IS1133. Strains of ST15 possessed bla(OXA-69), bla(ADC-11), bla(TEM-1) and a class 1 integron carrying aacC1 and aadA1. ISAba1 was found upstream of bla(ADC) (one ST10 and one ST12) and/or bla(OXA-66) (seven ST12). Twelve isolates of different STs contained the substitutions Ser83Leu in GyrA and Ser80Leu or Glu84Lys in ParC. Significant disruptions of CarO porin and overexpressed efflux pumps were not observed. The majority of infections were hospital acquired and in animals with predisposing conditions for infection. CONCLUSIONS: STs and the molecular background of resistance observed in our collection have been frequently described in A. baumannii detected in human patients. Animals should be considered as a potential reservoir of multidrug-resistant A. baumannii.

Characterization of CDKN2A(p16) methylation and impact in colorectal cancer: systematic analysis using pyrosequencing

Background The aim of this study is to analyse CDKN2A methylation using pyrosequencing on a large cohort of colorectal cancers and corresponding non-neoplastic tissues. In a second step, the effect of methylation on clinical outcome is addressed. Methods Primary colorectal cancers and matched non-neoplastic tissues from 432 patients underwent CDKN2A methylation analysis by pyrosequencing (PyroMarkQ96). Methylation was then related to clinical outcome, microsatellite instability (MSI), and BRAF and KRAS mutation. Different amplification conditions (35 to 50 PCR cycles) using a range of 0-100% methylated DNA were tested. Results Background methylation was at most 10% with ≥35 PCR cycles. Correlation of observed and expected values was high, even at low methylation levels (0.02%, 0.6%, 2%). Accuracy of detection was optimal with 45 PCR cycles. Methylation in normal mucosa ranged from 0 to >90% in some cases. Based on the maximum value of 10% background, positivity was defined as a ≥20% difference in methylation between tumor and normal tissue, which occurred in 87 cases. CDKN2A methylation positivity was associated with MSI (p = 0.025), BRAF mutation (p < 0.0001), higher tumor grade (p < 0.0001), mucinous histology (p = 0.0209) but not with KRAS mutation. CDKN2A methylation had an independent adverse effect (p = 0.0058) on prognosis. Conclusion The non-negligible CDKN2A methylation of normal colorectal mucosa may confound the assessment of tumor-specific hypermethylation, suggesting that corresponding non-neoplastic tissue should be used as a control. CDKN2A methylation is robustly detected by pyrosequencing, even at low levels, suggesting that this unfavorable prognostic biomarker warrants investigation in prospective studies.

Bioabsorbable pins for treatment of osteochondral fractures of the knee after acute patella dislocation in children and young adolescents

A retrospective study was performed on the use of bioabsorbable pins in the fixation of osteochondral fractures (OCFs) after traumatic patellar dislocation in children. Eighteen children (13 females, 5 males) aged 11 to 15 years (mean age 13.1 years) with osteochondral fracture (OCF) of the knee joint were treated at the authors' institution. Followup ranged from 22 months to 5 years. Diagnosis was verified by X-ray and magnetic resonance imaging (MRI) of the knee and patella. In seven patients the osteochondral fragment was detached from the patella and in 11 it was detached from the lateral femoral condyle. All patients were subjected to open reduction and fixation of the lesion with bioabsorbable pins. Postoperatively, the knee was immobilized in a cast and all patients were mobilized applying a standardized protocol. Bone consolidation was successful in 17 of the 18 patients. Bioabsorbable pins reliably fix OCF in children and adolescents, demonstrating a high incidence of consolidation of the detached osteochondral fragment in short- and middle-term followup without requiring further operative procedures.