Selective immunisation strategy to protect newborns at risk for transmission of hepatitis B: retrospective audit of vaccine uptake

BACKGROUND: 90% of newborns infected perinatally will develop chronic hepatitis B infection with the risk of liver cirrhosis or hepatocellular carcinoma. In Switzerland, screening of all pregnant women for hepatitis B virus (HBV) has been recommended since 1983. Neonates at risk for perinatally acquired HBV are passively and actively immunised immediately after birth as well as at 1 and 6 months of age. The objective of this study was to evaluate the proportion of newborns immunised in accordance with the proposed vaccination schedule. METHODS: Patient records of 3997 mothers who gave birth to a liveborn infant during a two-year period at Zürich University Hospital were screened by computer. 128 women were identified as HBsAg positive or anti-HBc alone positive. Of 133 infants born to these mothers, complete data were available for 94 (71%). RESULTS: Immunisation was started in 88 infants (94%), but only in 78 (83%) within the first 24 hours of life. 85 (90%) received the 2nd immunisation but only 72 (77%) within the given time limit. 80 (85%) of the infants received the 3rd immunisation but only 69 (73%) within the correct time limit. In summary, only 51 (54%) of the infants at risk for HBV infection were immunised correctly (immunoglobulin within 24 hours and active prophylaxis at 0, 1 and 6 months). CONCLUSIONS: The success of the immunisation strategy following maternal screening and selective immunisation of newborns at risk for HBV infection is limited for various reasons (lack of screening results at birth, problems with correct documentation and communication). To overcome these drawbacks, selective vaccination strategy should be improved and general vaccination strategy, including infants, should be reconsidered.

Preischemic iloprost application for improvement of graft preservation: which route is superior in experimental pig lung transplantation: inhaled or intravenous?

BACKGROUND: Optimal allograft protection is essential in lung transplantation to reduce postoperative organ dysfunction. Although intravenous prostanoids are routinely used to ameliorate reperfusion injury, the latest evidence suggests a similar efficacy of inhaled prostacyclin. Therefore, we compared donor lung-pretreatment using inhaled lioprost (Ventavis) with the commonly used intravenous technique. METHODS: Five pig lungs were each preserved with Perfadex and stored for 27 hours without (group 1) or with (group-2, 100 prior aerosolized of iloprost were (group 3) or iloprost (IV). Following left lung transplantation, hemodynamics, Po(2)/F(i)o(2), compliance, and wet-to-dry ratio were monitored for 6 hours and compared to sham controls using ANOVA analysis with repeated measures. RESULTS: The mortality was 100% in group 3. All other animals survived (P < .001). Dynamic compliance and PVR were superior in the endobronchially pretreated iloprost group as compared with untreated organs (P < .05), whereas oxygenation was comparable overall W/D-ratio revealed significantly lower lung water in group 2 (P = .027) compared with group 3. CONCLUSION: Preischemic alveolar deposition of iloprost is superior to IV pretreatment as reflected by significantly improved allograft function. This strategy offers technique to optimize pulmonary preservation.

Comparison of tendency-oriented perimetry and dynamic strategy in octopus perimetry as a screening tool in a clinical setting: a prospective study

OBJECTIVE: The aim of this study was to compare the results of tendency-oriented perimetry (TOP) and a dynamic strategy in octopus perimetry as screening methods in clinical practice. DESIGN: A prospective single centre observational case series was performed. PARTICIPANTS AND METHODS: In a newly opened general ophthalmologic practice 89 consecutive patients (171 eyes) with a clinical indication for octopus static perimetry testing (ocular hypertension or suspicious optic nerve cupping) were examined prospectively with TOP and a dynamic strategy. The visual fields were graded by 3 masked observers as normal, borderline or abnormal without any further clinical information. RESULTS: 83% eyes showed the same result for both strategies. In 14% there was a small difference (with one visual field being abnormal or normal, the other being borderline). In only 2.9% of the eyes (5 cases) was there a contradictory result. In 4 out of 5 cases the dynamic visual field was abnormal and TOP was normal. 4 of these cases came back for a second examination. In all 4 the follow-up examination showed a normal second dynamic visual field. CONCLUSIONS: Octopus static perimetry using a TOP strategy is a fast, patient-friendly and very reliable screening tool for the general ophthalmological practice. We found no false-negative results in our series.

Femoral head injuries: Which treatment strategy can be recommended?

Despite different operative and non-operative treatment regimens, the outcome after femoral head fractures has changed little over the past decades. The initial trauma itself as well as secondary changes such as posttraumatic osteoarthritis, avascular necrosis or heterotopic ossification is often responsible for severe loss of function of the afflicted hip joint. Anatomic reduction of all fracture fragments seems to be a major influencing factor in determining the outcome quality. Eight years ago we inaugurated a new surgical approach for better access and visualisation for the treatment of femoral head fractures, using the "trochanteric flip" (digastric) osteotomy. Thus inspection of the entire hip joint and accurate fragment reduction under direct visual control are possible. After good initial experiences with this operative procedure we changed our standard treatment regimen to this approach in an attempt to achieve the most accurate anatomic reduction of the femoral head in every affected patient. Between 1998 and 2006 we operated on 12 patients with femoral head fractures associated with posterior hip dislocation, using the new surgical approach. Patients were followed for 2-96 months and outcome was documented with the Merle d'Aubigne and Postel score as well as the Thompson and Epstein score. The posttraumatic formation of heterotopic bone was documented with the Brooker score. Retrospective analysis of these 12 patients showed good or excellent results in 10 patients (83.3%). The two patients with poor outcome developed an avascular necrosis of the femoral head and underwent total hip arthroplasty. Periarticular heterotopic ossification was seen in five patients. In four patients this caused a significantly reduced range of motion and was therefore considered as a posttraumatic complication. The two patients with the most severe heterotopic bone formation (Brooker III and IV) had initially sustained multiple injuries including brain injury. Comparing our results with earlier published series including our own before changing the treatment protocol, the data suggest a favorable outcome in patients with trochanteric flip (digastric) osteotomy for the treatment of femoral head fractures.

Staged bilateral carotid stenting, an effective strategy in high-risk patients - insights from a prospective multicenter trial

OBJECTIVE: To prospectively evaluate outcomes of high-risk patients undergoing bilateral carotid artery stenting (CAS). METHODS: A total of 747 patients at increased risk for carotid endarterectomy (CEA) were enrolled in a prospective registry at 47 US sites of the Boston Scientific EPI: A Carotid Stenting Trial for Risk Surgical Patients (BEACH) trial. Among them, 78 (10.4%) patients underwent contralateral CAS > 30 days after the primary CAS procedure. Patients were followed at 1, 6, and 12 months, and annually thereafter for 3 years. The primary endpoint was the cumulative incidence of non Q-wave myocardial infarction within 24 hours, periprocedural (istically significant differences between the bilateral and the pivotal groups with regard to any of the components of the primary or secondary endpoints. The univariate 1-year major adverse event (MAE) free survival was 93.6% and 91.6% in the bilateral and pivotal groups, respectively (P = .55). Multivariate logistic regression analysis with adjustment for various clinical baseline factors revealed no differences in the primary endpoint when comparing the bilateral with the pivotal groups at 30 days (odds ratio [OR]: 0.8673, 95% confidence interval [CI] 0.4590-1.6389, P = .66) or 1 year (OR: 0.9102, 95% CI 0.5503-1.5053, P = .73). CONCLUSIONS: Bilateral carotid stenting is an effective treatment strategy in patients determined to be at high-risk for CEA with no increase in morbidity or mortality results extended out to one year in a prospective multicenter trial.

Heme oxygenase-1 is a critical regulator of nitric oxide production in enterohemorrhagic Escherichia coli-infected human enterocytes

Enterohemorrhagic Escherichia coli (EHEC) are the causative agent of hemolytic-uremic syndrome. In the first stage of the infection, EHEC interact with human enterocytes to modulate the innate immune response. Inducible NO synthase (iNOS)-derived NO is a critical mediator of the inflammatory response of the infected intestinal mucosa. We therefore aimed to analyze the role of EHEC on iNOS induction in human epithelial cell lines. In this regard, we show that EHEC down-regulate IFN-gamma-induced iNOS mRNA expression and NO production in Hct-8, Caco-2, and T84 cells. This inhibitory effect occurs through the decrease of STAT-1 activation. In parallel, we demonstrate that EHEC stimulate the rapid inducible expression of the gene hmox-1 that encodes for the enzyme heme oxygenase-1 (HO-1). Knock-down of hmox-1 gene expression by small interfering RNA or the blockade of HO-1 activity by zinc protoporphyrin IX abrogated the EHEC-dependent inhibition of STAT-1 activation and iNOS mRNA expression in activated human enterocytes. These results highlight a new strategy elaborated by EHEC to control the host innate immune response.

Is intravenous iron supplementation with erythropoiesis-stimulating agents beneficial in cancer patients with anemia?

Chemotherapy-induced anemia is often an important problem for cancer patients, and this complication can be treated with erythropoiesis-stimulating agents (ESAs). This commentary discusses the findings of a study by Bastit et al., in which 396 patients with nonmyeloid malignancies and chemotherapy-induced anemia were treated with darbepoetin alfa with or without intravenous iron. This phase III trial showed that intravenous iron supplementation increases the hematopoietic response rates to ESAs in cancer patients; however, this study provides no information as to whether all cancer patients with anemia should receive intravenous iron as well as treatment with ESAs. Further data are needed to identify those patients who might benefit from intravenous iron supplementation in addition to ESAs, in order to avoid overtreatment of patients who are unlikely to benefit from the additional iron. As both ESAs and intravenous iron have known short-term and long-term risks, identification of reliable predictors of response that can guide these treatments is necessary before this strategy can be implemented into practice.

Beta-caryophyllene is a dietary cannabinoid

The psychoactive cannabinoids from Cannabis sativa L. and the arachidonic acid-derived endocannabinoids are nonselective natural ligands for cannabinoid receptor type 1 (CB(1)) and CB(2) receptors. Although the CB(1) receptor is responsible for the psychomodulatory effects, activation of the CB(2) receptor is a potential therapeutic strategy for the treatment of inflammation, pain, atherosclerosis, and osteoporosis. Here, we report that the widespread plant volatile (E)-beta-caryophyllene [(E)-BCP] selectively binds to the CB(2) receptor (K(i) = 155 +/- 4 nM) and that it is a functional CB(2) agonist. Intriguingly, (E)-BCP is a common constituent of the essential oils of numerous spice and food plants and a major component in Cannabis. Molecular docking simulations have identified a putative binding site of (E)-BCP in the CB(2) receptor, showing ligand pi-pi stacking interactions with residues F117 and W258. Upon binding to the CB(2) receptor, (E)-BCP inhibits adenylate cylcase, leads to intracellular calcium transients and weakly activates the mitogen-activated kinases Erk1/2 and p38 in primary human monocytes. (E)-BCP (500 nM) inhibits lipopolysaccharide (LPS)-induced proinflammatory cytokine expression in peripheral blood and attenuates LPS-stimulated Erk1/2 and JNK1/2 phosphorylation in monocytes. Furthermore, peroral (E)-BCP at 5 mg/kg strongly reduces the carrageenan-induced inflammatory response in wild-type mice but not in mice lacking CB(2) receptors, providing evidence that this natural product exerts cannabimimetic effects in vivo. These results identify (E)-BCP as a functional nonpsychoactive CB(2) receptor ligand in foodstuff and as a macrocyclic antiinflammatory cannabinoid in Cannabis.

[Juvenile chronic arthritis: therapeutic strategy 1990]

Therapeutic strategies based on experience with 119 patients with juvenile chronic arthritis are reviewed. Therapeutic goals are formulated and the means of attaining them (NSAIDs, the so-called disease modifying drugs gold, chloroquine and penicillamine, the antimetabolite methotrexate, intra-articular and systemic corticosteroids, physio- and ergotherapy, technical and orthopedic measures, as well as vocational and medicosocial aspects) are discussed. As the individual prognosis normally depends less on drugs than on preventive and rehabilitative measures, the outcome is largely determined by the quality of a well-coordinated inter-disciplinary team approach.

Novel cell-free strategy for therapeutic angiogenesis: in vitro generated conditioned medium can replace progenitor cell transplantation

BACKGROUND: Current evidence suggests that endothelial progenitor cells (EPC) contribute to ischemic tissue repair by both secretion of paracrine factors and incorporation into developing vessels. We tested the hypothesis that cell-free administration of paracrine factors secreted by cultured EPC may achieve an angiogenic effect equivalent to cell therapy. METHODOLOGY/PRINCIPAL FINDINGS: EPC-derived conditioned medium (EPC-CM) was obtained from culture expanded EPC subjected to 72 hours of hypoxia. In vitro, EPC-CM significantly inhibited apoptosis of mature endothelial cells and promoted angiogenesis in a rat aortic ring assay. The therapeutic potential of EPC-CM as compared to EPC transplantation was evaluated in a rat model of chronic hindlimb ischemia. Serial intramuscular injections of EPC-CM and EPC both significantly increased hindlimb blood flow assessed by laser Doppler (81.2+/-2.9% and 83.7+/-3.0% vs. 53.5+/-2.4% of normal, P<0.01) and improved muscle performance. A significantly increased capillary density (1.62+/-0.03 and 1.68+/-0.05/muscle fiber, P<0.05), enhanced vascular maturation (8.6+/-0.3 and 8.1+/-0.4/HPF, P<0.05) and muscle viability corroborated the findings of improved hindlimb perfusion and muscle function. Furthermore, EPC-CM transplantation stimulated the mobilization of bone marrow (BM)-derived EPC compared to control (678.7+/-44.1 vs. 340.0+/-29.1 CD34(+)/CD45(-) cells/1x10(5) mononuclear cells, P<0.05) and their recruitment to the ischemic muscles (5.9+/-0.7 vs. 2.6+/-0.4 CD34(+) cells/HPF, P<0.001) 3 days after the last injection. CONCLUSIONS/SIGNIFICANCE: Intramuscular injection of EPC-CM is as effective as cell transplantation for promoting tissue revascularization and functional recovery. Owing to the technical and practical limitations of cell therapy, cell free conditioned media may represent a potent alternative for therapeutic angiogenesis in ischemic cardiovascular diseases.

Effect of initial treatment strategy on survival of patients with advanced-stage Hodgkin's lymphoma: a systematic review and network meta-analysis

BACKGROUND Several treatment strategies are available for adults with advanced-stage Hodgkin's lymphoma, but studies assessing two alternative standards of care-increased dose bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPPescalated), and doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD)-were not powered to test differences in overall survival. To guide treatment decisions in this population of patients, we did a systematic review and network meta-analysis to identify the best initial treatment strategy. METHODS We searched the Cochrane Library, Medline, and conference proceedings for randomised controlled trials published between January, 1980, and June, 2013, that assessed overall survival in patients with advanced-stage Hodgkin's lymphoma given BEACOPPbaseline, BEACOPPescalated, BEACOPP variants, ABVD, cyclophosphamide (mechlorethamine), vincristine, procarbazine, and prednisone (C[M]OPP), hybrid or alternating chemotherapy regimens with ABVD as the backbone (eg, COPP/ABVD, MOPP/ABVD), or doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin, etoposide, and prednisone combined with radiation therapy (the Stanford V regimen). We assessed studies for eligibility, extracted data, and assessed their quality. We then pooled the data and used a Bayesian random-effects model to combine direct comparisons with indirect evidence. We also reconstructed individual patient survival data from published Kaplan-Meier curves and did standard random-effects Poisson regression. Results are reported relative to ABVD. The primary outcome was overall survival. FINDINGS We screened 2055 records and identified 75 papers covering 14 eligible trials that assessed 11 different regimens in 9993 patients, providing 59 651 patient-years of follow-up. 1189 patients died, and the median follow-up was 5·9 years (IQR 4·9-6·7). Included studies were of high methodological quality, and between-trial heterogeneity was negligible (τ(2)=0·01). Overall survival was highest in patients who received six cycles of BEACOPPescalated (HR 0·38, 95% credibility interval [CrI] 0·20-0·75). Compared with a 5 year survival of 88% for ABVD, the survival benefit for six cycles of BEACOPPescalated is 7% (95% CrI 3-10)-ie, a 5 year survival of 95%. Reconstructed individual survival data showed that, at 5 years, BEACOPPescalated has a 10% (95% CI 3-15) advantage over ABVD in overall survival. INTERPRETATION Six cycles of BEACOPPescalated significantly improves overall survival compared with ABVD and other regimens, and thus we recommend this treatment strategy as standard of care for patients with access to the appropriate supportive care.

Multiplex strategy for multilocus sequence typing, fla typing, and genetic determination of antimicrobial resistance of Campylobacter jejuni and Campylobacter coli isolates collected in Switzerland

We present an optimized multilocus sequence typing (MLST) scheme with universal primer sets for amplifying and sequencing the seven target genes of Campylobacter jejuni and Campylobacter coli. Typing was expanded by sequence determination of the genes flaA and flaB using optimized primer sets. This approach is compatible with the MLST and flaA schemes used in the PubMLST database and results in an additional typing method using the flaB gene sequence. An identification module based on the 16S rRNA and rpoB genes was included, as well as the genetic determination of macrolide and quinolone resistances based on mutations in the 23S rRNA and gyrA genes. Experimental procedures were simplified by multiplex PCR of the 13 target genes. This comprehensive approach was evaluated with C. jejuni and C. coli isolates collected in Switzerland. MLST of 329 strains resulted in 72 sequence types (STs) among the 186 C. jejuni strains and 39 STs for the 143 C. coli isolates. Fourteen (19%) of the C. jejuni and 20 (51%) of the C. coli STs had not been found previously. In total, 35% of the C. coli strains collected in Switzerland contained mutations conferring antibiotic resistance only to quinolone, 15% contained mutations conferring resistance only to macrolides, and 6% contained mutations conferring resistance to both classes of antibiotics. In C. jejuni, these values were 31% and 0% for quinolone and macrolide resistance, respectively. The rpoB sequence allowed phylogenetic differentiation between C. coli and C. jejuni, which was not possible by 16S rRNA gene analysis. An online Integrated Database Network System (SmartGene, Zug, Switzerland)-based platform for MLST data analysis specific to Campylobacter was implemented. This Web-based platform allowed automated allele and ST designation, as well as epidemiological analysis of data, thus streamlining and facilitating the analysis workflow. Data networking facilitates the exchange of information between collaborating centers. The described approach simplifies and improves the genotyping of Campylobacter, allowing cost- and time-efficient routine monitoring.

Double arterial perfusion strategy for extensive thoracic aortic surgery to avoid lower body hypothermic circulatory arrest

OBJECTIVE To analyse our results of using a double arterial perfusion strategy to avoid lower body hypothermic circulatory arrest after extensive thoracic aortic surgery. METHODS We analysed the intra- and perioperative courses of 10 patients (median age 58 years, median logistic EuroSCORE 14.6) who underwent extensive thoracic aortic surgery with a double arterial perfusion strategy. The main goal of double arterial perfusion is to separate myocardial and supra-aortic from systemic perfusion. Aortic repair starts at the most distal level of the descending aorta, followed by reinsertion of the supra-aortic vessels, and ends with completion of the proximal anastomosis or by any kind of root repair as needed. RESULTS Seven of 10 patients had prior surgery of the thoracic aorta. Indications for surgery were post-dissection aneurysm in 4 patients, true aneurysm in 3, anastomotic aneurysms in 2 and Type B aortic dissection with pseudo-coarctation in 1. Surgical access was performed through median sternotomy with left hemi-clamshell extension in all cases. There was no in-hospital mortality, but perioperative neurological symptoms occurred in 2 patients. These 2 patients developed delayed stroke (after awaking) after an initial uneventful clinical course, and in 1 of them, neurological symptoms resolved completely during follow-up. The median follow-up was 7 (±13) months. There was no death and no need for additional redo surgery during this observational period. CONCLUSIONS Extensive surgery of the thoracic aorta using a double arterial perfusion technique in order to avoid lower body hypothermic circulatory arrest is an attractive option. Further refinements of this technique may enable the safe and effective simultaneous multisegmental treatment of thoracic aortic pathology in patients who would otherwise have to undergo a two-step surgical approach.

Transcatheter aortic valve implantation: the transfemoral access route is the default access

Transcatheter aortic valve implantation (TAVI) is a widely accepted alternative to surgical aortic valve replacement (SAVR) among non-operable patients or selected high-risk patients with degenerative, severe aortic stenosis. TAVI is considered less invasive when compared with SAVR; however, there remain significant differences between different TAVI access routes. The transfemoral approach is considered the least invasive access route, and can be performed as a fully percutaneous procedure in a spontaneously breathing patient under local anaesthesia and mild sedation only. Moreover, transfemoral TAVI patients are typically transferred to coronary care rather than to an intensive care unit after the procedure, and benefit from early ambulation and a reduction in overall length of hospital stay. Considering these patient-specific and health-economic advantages, several TAVI centres follow the least invasive strategy for their patients and have implemented the transfemoral access route as the default access in their institutions. This article provides an overview on the prerequisites for a successful transfemoral TAVI procedure, describes the procedural advantages compared to alternative access routes, and highlights differences in clinical outcomes.

Tumor regression grade of urothelial bladder cancer after neoadjuvant chemotherapy: a novel and successful strategy to predict survival.

Histopathologic tumor regression grades (TRGs) after neoadjuvant chemotherapy predict survival in different cancers. In bladder cancer, corresponding studies have not been conducted. Fifty-six patients with advanced invasive urothelial bladder cancer received neoadjuvant chemotherapy before cystectomy and lymphadenectomy. TRGs were defined as follows: TRG1: complete tumor regression; TRG2: >50% tumor regression; TRG3: 50% or less tumor regression. Separate TRGs were assigned for primary tumors and corresponding lymph nodes. The prognostic impact of these 2 TRGs, the highest (dominant) TRG per patient, and competing tumor features reflecting tumor regression (ypT/ypN stage, maximum diameter of the residual tumor) were determined. Tumor characteristics in initial transurethral resection of the bladder specimens were tested for response prediction. The frequency of TRGs 1, 2, and 3 in the primary tumors were n=16, n=19, and n=21; corresponding data from the lymph nodes were n=31, n=9, and n=16. Interobserver agreement in determination of the TRG was strong (κ=0.8). Univariately, all evaluated parameters were significantly (P≤0.001) related to overall survival; however, the segregation of the Kaplan-Meier curves was best for the dominant TRG. In multivariate analysis, only dominant TRG predicted overall survival independently (P=0.035). In transurethral resection specimens of the chemotherapy-naive bladder cancer, the only tumor feature with significant (P<0.03) predictive value for therapy response was a high proliferation rate. In conclusion, among all parameters reflecting tumor regression, the dominant TRG was the only independent risk factor. A favorable chemotherapy response is associated with a high proliferation rate in the initial chemotherapy-naive bladder cancer. This feature might help personalize neoadjuvant chemotherapy.