Cervical spine meniscoids: an update on their morphological characteristics and potential clinical significance

Abstract

Purpose

Cervical spine meniscoids are intra-articular folds of synovial membrane that have been theorised to have potential clinical significance in neck pain. Recent anatomical and clinical research has re-visited the pathoanatomical capacity of these structures. The purpose of this review is to discuss cervical spine meniscoid morphology in light of recently published work, to provide an update on the plausible relevance of these structures to clinical practice.

Methods

Narrative review critically discussing basic science and clinical research regarding cervical spine meniscoids, with focus upon implications for clinical practice.

Results

Basic science research indicates that cervical spine meniscoids can be innervated and appear to vary in morphology in the presence of articular degeneration. In a clinical population, associations have been observed between cervical spine meniscoid morphology and presence of cervical spine symptoms.

Conclusions

Recent studies regarding cervical spine meniscoid morphology provide further evidence of pathoanatomical capacity of these structures. Further research is required, however, in clinical populations to empirically investigate specific theorised mechanisms of cervical spine meniscoid involvement in neck pain.

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The role of deep breathing on stress

Abstract

The objective of this study was to verify, in a sample of university students, whether a relaxing technique called deep breathing (stress Intervention Functional IFA) is capable to improve the mood and to reduce the levels of stress. Thirty-eight adult healthy subjects (aged between 18 and 28 years) volunteered the study. They were randomly divided in two groups, the Experimental Group (N = 19) and the Control Group (N = 19). The subjects of the Experimental Group were submitted, once per week, to 10 treatment's sessions of Anti-stress Protocol, each lasting 90 min, whereas subjects of the Control Group sat ten times for 90 min, once per week, without practicing any treatment. The psychological state of mood and stress was evaluated using Measurement of Psychological Stress (MSP) and Profile of Mood State (POMS), while the biological profile of the stress was detected by measuring the heart rate and the salivary cortisol. The results obtained from the present research support the possibility that deep breathing technique is capable to induce an effective improvement in mood and stress both in terms of self-reported evaluations (MPS and POMS) and of objective parameters, such as heart rate and salivary cortisol levels. No statistically significant difference was found between men and women.

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Production and characterization of a monoclonal antibody specific to 16 kDa antigen of Paramphistomum gracile

Abstract

A number of monoclonal antibodies (MoAbs) against the 16 kDa antigen of Paramphistomum gracile (16 kDaAgPg) were produced in vitro by hybridoma technique. Reactivity and specificity of these MoAbs were evaluated by ELISA and immunoblotting assays. Seven MoAb clones were selected from the stable hybridoma clones, namely 1D10, 2D7, 3B10, 3D9, 4F1, 4G4, and 5G12. It was found to be IgM and kappa light chain isotypes. By immunoblotting and ELISA, all MoAbs reacted with purified 16 kDaAgPg at molecular weight (MW) of 16 kDa and with the native 16 kDa antigen at MW of 16 kDa in the whole body (WB) and excretory-secretory (ES) fractions, but not with tegumental antigens (TA) of adult fluke. All of these MoAbs showed no cross-reactions with antigens of other parasites commonly found in ruminants, including Eurytrema pancreaticum, Gigantocotyle explanatum, Schistosoma spindale, Moniezia benedeni, Avitellina centripunctata, Haemonchus placei, Trichuris sp., and Setaria labiato-papillosa. Localization and distribution of the native 16 kDaAg in adult P. gracile by immunohistochemistry, using MoAbs as probes, showed that the native 16 kDaAg was present in high concentration in the cytoplasm of vitelline cells, eggshell globules, and the shells of eggs, but not in the tegument, muscle, parenchymal cells, and cecum of adult fluke. This finding indicated that the 16 kDaAg is a copiously expressed parasite protein that is released into the ES; thus, 16 kDaAg and its MoAb could be a good candidate for immunodiagnosis of paramphistomosis in ruminants.

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Filarial infection caused by Onchocerca boehmi (Supperer, 1953) in a horse from Italy

Abstract

Equids can be infected by a range of skin-dwelling filarial nematodes, including four species of the genus Onchocerca. Current literature on equine onchocercosis is fragmentary and often limited to isolated case reports. The present study aimed to describe a clinical case of equine onchocercosis caused by Onchocerca boehmi (Supperer, 1953) (syn. Elaeophora boehmi) in an 8-year-old gelding Belgian show jumper from northern Italy. The horse was presented with a firm and painless mass on the proximal third of the right metacarpal region. Ultrasound examination showed a peritendinous enlargement around the palmaro-lateral area of the tendons, characterized by an elongated hypoechoic and well-defined structure, embedding a coiled hyperechoic line. The metacarpal nodule was resected and histologically examined. Fragments of a parasitic nematode were detected, isolated and examined. The morphological analysis allowed identifying the nematode as O. boehmi. In addition, total genomic DNA was extracted from individual fragments using a commercial kit for the nematode identification and a comparative sequence analysis of the nematode cytochrome oxidase subunit 1 (cox1) sequence with data available in the GenBank^TM database revealed the closest identity (i.e. 91 %) with that of Onchocerca lupi. Thus far, O. boehmi has only been reported in Austria and Iran, and information about its life-cycle and vectors is lacking. The systematic position of this species within the genus Onchocerca, not in Elaeophora where it was originally described, is in concordance with the morphological and molecular analysis. In this article, we describe the first autochthonous case of equine onchocercosis in Italy caused by O. boehmi and discuss novel parasitological, clinical, and pathological data on these pathogens of horses.

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The endogenous development and pathogenicity of Eimeria anseris (Kotlan, 1932) in domestic goslings

Abstract

Twenty-one, 25-day-old, artificially reared, coccidia-free goslings (Anser cygnoides var. domestica) were inoculated orally with 0.5 × 10⁴, 1 × 10⁴, or 100 × 10⁴ sporulated oocysts of Eimeria anseris and sacrificed at intervals from 24 to 216 h post-inoculation (HPI). Nine uninfected goslings served as negative controls. Parts of the visceral organs from goslings, including the intestines, kidneys, and liver, were fixed, sectioned, and observed microscopically. The results revealed that two generations of meronts occurred in the life cycle of E. anseris. The first generation of meronts developed at 24–96 HPI and the second generation at 90–128 HPI. Each meront contained 4–10 merozoites. Development of gamonts began at 128 HPI and mature oocysts appeared at 168 HPI. Developmental stages presented mainly in the epithelial cells of crypts and lamina propria in the posterior parts of the jejunum and ileum. Parasites localized mostly in the cytoplasm and occasionally in the nuclei of host cells. Histological lesions were pronounced in the jejunum and ileum. Desquamation and necrosis of the epithelium of intestine and crypts, infiltration of inflammatory cells, and hemorrhage and mucosal edema were associated with aggregates of endogenous stages. The infected goslings mainly showed severe diarrhea, depression, anorexia, and emaciation, suggesting that E. anseris is highly pathogenic in goslings.

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Dantrolene improves in vitro structural changes induced by serum from Trypanosoma cruzi -infected mice

Abstract

Dystrophin, an important protein of the dystrophin-glycoprotein complex, has been implicated in the pathogenesis of experimental Chagas disease. It is important for the maintenance of cell shape and contraction force transmission. Dystrophin loss has been related to end-stage cardiac myopathies and proposed as a common route for myocardial dysfunction and progression to advanced heart failure. Evidence suggests that calpains, calcium-dependent proteases, digest dystrophin when the calcium concentration is compatible with their activation. The objective of this in vitro study was to test the hypothesis that dantrolene, a calcium channel blocker, improves structural changes induced by serum from Trypanosoma cruzi-infected mice. Cultured neonatal cardiac myocytes were incubated with serum from T. cruzi-infected mice and treated with dantrolene for 24 h. Immunofluorescence and immunoblotting were performed to evaluate dystrophin and calpain-1 protein expression. The levels of dystrophin decreased 13 % and calpain increased 17 % after incubation of cultured neonatal cardiac myocytes with serum from T. cruzi-infected mice. The treatment with dantrolene restored the dystrophin and calpain levels near control levels. Our results demonstrate that alterations in calcium homeostasis in cardiac myocytes are responsible, in part, for cardiac structural changes in experimentally induced T. cruzi myocarditis and that calpain inhibitors may be beneficial in Chagasic heart disease.

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Ixodes ventalloi : morphological and molecular support for species integrity

Abstract

Despite their medical and veterinary importance, some tick species are so poorly studied, that their role within pathogen vector transmission cycles is difficult to assess. The tick Ixodes ventalloi is one such species, and its biology and phylogenetic status remain an issue of debate. In the present study, specimens of adult I. ventalloi (n = 65 females; n = 31 males) infesting cats in the Lipari Island (Aeolian archipelago, Sicily, southern Italy) were characterized morphologically and molecularly, the latter based on mitochondrial 16S rRNA and cytochrome c oxidase subunit 1 (cox1) genes. The genetic data and phylogenetic analyses for both mitochondrial genes suggest the existence of two distinct genogroups. The ecological and epidemiological significance of the genetic structure within the I. ventalloi endemic population remains to be determined. The results highlight the need for further analysis of this tick species, including whole mitochondrial genome sequencing and crossbreeding studies, which will be pivotal to complement features of its status as a vector of pathogens.

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Erratum to: Evolutionary modularity and morphological integration in the haptoral anchor structures of Ligophorus spp. (Monogenea: Dactylogyridae)

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Modeling impacts of climate change on the potential distribution of the carcinogenic liver fluke, Opisthorchis viverrini , in Thailand

Abstract

Global climate change is now regarded as imposing a significant threat of enhancing transmission of parasitic diseases. Maximum entropy species distribution modeling (MaxEnt) was used to explore how projected climate change could affect the potential distribution of the carcinogenic liver fluke, Opisthorchis viverrini, in Thailand. A range of climate variables was used: the Hadley Global Environment Model 2—Earth System (HadGEM2-ES) climate change model and also the IPCC scenarios A2a for 2050 and 2070. Occurrence data from surveys conducted in 2009 and 2014 were obtained from the Department of Disease Control, Ministry of Public Health, Thailand. The MaxEnt model performed better than random for O. viverrini with training AUC values greater than 0.8 under current and future climatic conditions. The current distribution of O. viverrini is significantly affected by precipitation and minimum temperature. According to current conditions, parts of Thailand climatically suitable for O. viverrini are mostly in the northeast and north, but the parasite is largely absent from southern Thailand. Under future climate change scenarios, the distribution of O. viverrini in 2050 should be significantly affected by precipitation, maximum temperature, and mean temperature of the wettest quarter, whereas in 2070, significant factors are likely to be precipitation during the coldest quarter, maximum, and minimum temperatures. Maps of predicted future distribution revealed a drastic decrease in presence of O. viverrini in the northeast region. The information gained from this study should be a useful reference for implementing long-term prevention and control strategies for O. viverrini in Thailand.

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Mitochondrial pathways are involved in Eimeria tenella -induced apoptosis of chick embryo cecal epithelial cells

Abstract

Accumulating evidence suggests that Eimeria tenella severely damages the intestinal mucosa in infected poultry, resulting in deadly haemorrhagic typhlocolitis and major economic losses. Damage to host tissue is believed to arise mainly from apoptosis, which is, in general, intimately related to mitochondrial function. However, it is unclear whether mitochondria-dependent apoptotic pathways are specifically involved in parasite-induced apoptosis of chick embryo cecal epithelial cells. Because the mitochondrial permeability transition pore (MPTP) and caspase-9 are important elements in these pathways, we studied the effects of their respective inhibitors (i.e., cyclosporine A [CsA] and Z-LEHD-FMK, respectively) in primary cultures of chicken embryonic cecum epithelial cells using histopathological techniques, terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) assays, flow cytometry (FCM) and ELISA. Results indicated that the inhibitors significantly decreased (p < 0.01) DNA injury, apoptosis and caspase-9 and caspase-3 activity of chick embryo cecal epithelial cells at 24, 48, 72, 96 and 120 h after E. tenella infection. Thus, our data supported that mitochondria-dependent apoptotic pathways were involved in apoptosis of parasitised chick embryo cecal epithelial cells.

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Immunization of rhesus macaques with Echinococcus multilocularis recombinant 14-3-3 antigen leads to specific antibody response

Abstract

E. multilocularis (Em) is the etiologic agent of alveolar echinococcosis (AE), a severe and potentially fatal disease, primarily affecting the liver of and occurring in aberrant intermediate hosts, e.g., humans and non-human primates. Due to increasing numbers of spontaneous cases of AE in the Old World monkey colonies of the German Primate Center, the question arose as to whether vaccination of non-human primates may represent a useful prophylactic approach. In this pilot study, the recombinant antigen Em14-3-3, which has provided a 97 % protection against E. multilocularis challenge infection in rodent models, was used for the first time to immunize rhesus macaques. In order to increase immunogenicity, the antigen was formulated with different adjuvants including Quil A®, aluminum hydroxide (alum), and muramyl dipeptide (MDP). Also, different vaccination regimens were tested. All vaccinated animals developed antigen-specific antibodies. While Quil A® induced a local adverse reaction, alum proved to be the most potent adjuvant in terms of induced antibody levels, longevity as well as tolerability. In conclusion, our pilot study demonstrated that recombinant Em14-3-3 is safe and immunogenic in rhesus monkeys. As a next step, efficacy of the vaccination remains to be explored.

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A novel myxosporean parasite Myxobolus klamathellus n. sp. (Cnidaria: Myxosporea) from native blue chub ( Gila coerulea ) in Klamath Lake, Oregon

Abstract

Blue chub, Gila coerulea Girard, 1856 is a freshwater cyprinid fish native to inland drainages of western North America. It has not previously been recorded as a host of any myxosporean parasite (Cnidaria: Myxosporea), despite myxosporeans being cosmopolitan in freshwater and marine fishes worldwide and sympatric with this host. Herein, we describe a novel myxosporean from subcutaneous cysts in native blue chub from Klamath Lake, Oregon. Myxospores were consistent with genus Myxobolus, being obovoid but compressed in thickness, length 14.3 ± 0.4 (13–15) μm, width 9.7 ± 0.4 (9–10) μm, thickness 7.7 ± 0.3 (7–8) μm; two polar capsules ovoid slightly dissimilar in size, length 6.4 ± 0.4 (6–7) μm, width 3.8 ± 0.3 (3–4) μm, with four (3–5) turns of the polar filament (tubule); capsule openings apical, one in each valve cell. The small subunit ribosomal DNA sequence was up to 97 % similar to Myxobolus spp. from other cyprinids from North America and Europe. Given the novel host, unique myxospore morphometrics, and DNA sequence, we describe this as Myxobolus klamathellus n. sp.

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Evaluation of the infectivity and the persistence of Trichinella patagoniensis in muscle tissue of decomposing guinea pig ( Cavia porcellus )

Abstract

Trichinella patagoniensis, a new species of Trichinella, is widespread in Argentina. The success of parasite transmission depends, among other factors, on the resistance of L1 larvae present in the muscle tissue (ML) of dead hosts undergoing the decomposition process in different environmental conditions. The aim of the present work was to study the infectivity of T. patagoniensis muscle larvae in Cavia porcellus and the capability of the parasite to survive in decomposed muscle tissue of guinea pigs subjected to different environmental conditions. Thirty-two female Ssi:AL guinea pigs were orally inoculated with 2000 ML of T. patagoniensis (ISS2311). All the animals were sacrificed 42 days post-infection. Twenty-six animals were eviscerated, and carcasses were placed on the surface of soil inside plastic boxes that were exposed to environmental conditions in the summer 2014–2015 and autumn of 2015 in Buenos Aires, Argentina. Carcasses from six animals were placed into a plastic box inside the refrigerator at a temperature of 4 °C. The muscle tissue samples from the carcasses were examined weekly for the presence of larvae, and the infectivity of recovered ML was tested in BALB/c mice. Our results showed for the first time the ability of T. patagoniensis to complete its life cycle in guinea pigs, thus serving as a potential natural host. Also, larvae of T. patagoniensis remained infective in muscle tissue for several weeks while undergoing decomposition under different environmental conditions.

http://ift.tt/2hN96yz

Morphological and ultrastructural characteristics of Myxobolus ridibundae n. sp. (Myxosporea: Bivalvulida) infecting the testicular tissue of the marsh frog Rana ridibunda (Amphibia: Ranidae) in Egypt

Abstract

Myxozoans are one of the most economically important groups of protozoan parasites causing many serious diseases of their hosts. In the present study, a total of 60 live adult male specimens of the marsh frog Rana ridibunda have been randomly captured during the period of January–December 2015 in different areas at Kafr El-Sheikh Governorate, Egypt and were examined for infection by myxosporidian parasites. A total of 48 (80.0 %) out of 60 frog specimens were found to be infected with Myxobolus species. Parasitic infection was restricted to the testicular tissue of the examined frogs. Macroscopic cysts (plasmodia) which heavily infested different parts of the testes were recovered. Morphological and ultrastructural characteristics of these myxosporidian species were carried out using light and transmission electron microscopy. Plasmodia measured 0.16–0.53 (0.34 ± 0.01) mm in diameter. Mature spores appeared oval in frontal view, measuring 8.9–11.5 (9.6 ± 0.1) μm in length and 7.5–9.1 (8.4 ± 0.1) μm in width containing 5–6 turns of polar filaments. Morphometric characterization revealed that the very small size of the present Myxobolus species was the most distinctive feature that separates them from all previously described Myxobolus species. Ultrastructural analysis showed that the plasmodia are surrounded by a plasma membrane with numerous pinocytotic protrusions extending toward the host cell. The generative cells and the different developmental stages are arranged at the periphery of the plasmodia, while immature and mature spores are centrally located. Sporogenesis, capsulogenesis, valvogenesis, and spore maturation of the present parasite are also described. The present species is described as Myxobolus ridibundae and represents a new species.

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Thubunaea eleodori sp. nov. (Nematoda: Physalopteridae) from Liolaemus eleodori (Sauria: Liolaemidae) from Argentina

Abstract

Thubunaea eleodori sp. nov. is described from the stomach of Liolaemus eleodori (Sauria: Liolaemidae) from San Guillermo National Park, Province of San Juan, Argentina. T. eleodori is most similar to those species lacking spicules, T. cnemidophorus, T. fitsimonsi, T. parkeri, T. schukurovi, and T. smogorzhewskii. T. eleodori is separated from these species based on the papilla pattern. T. eleodori has 12 pedunculate papillae and 14 sessile papillae, T. smogorzhewskii lacks pedunculate papillae, T. fitsimonsi and T. parkeri lack sessile papillae, and T. cnemidophorus has14–16 pedunculate papillae and 12 sessile papillae. T. eleodori represents the first member of the genus to be reported from Argentina.

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Urate as a Marker of Risk and Progression of Neurodegenerative Disease

Abstract

Urate is a naturally occurring antioxidant whose levels are associated with reduced risk of developing Parkinson's disease (PD) and Alzheimer's disease. Urate levels are also associated with favorable progression in PD, amyotrophic lateral sclerosis, Huntington's disease, and multisystem atrophy. These epidemiological data are consistent with laboratory studies showing that urate exhibits neuroprotective effects by virtue of its antioxidant properties in several preclinical models. This body of evidence supports the hypothesis that urate may represent a shared pathophysiologic mechanism across neurodegenerative diseases. Most importantly, beyond its role as a molecular predictor of disease risk and progression, urate may constitute a novel therapeutic target. Indeed, clinical trials of urate elevation in PD and amyotrophic lateral sclerosis are testing the impact of raising peripheral urate levels on disease outcomes. These studies will contribute to unraveling the neuroprotective potential of urate in human pathology. In parallel, preclinical experiments are deepening our understanding of the molecular pathways that underpin urate's activities. Altogether, these efforts will bring about new insights into the translational potential of urate, its determinants, and its targets and their relevance to neurodegeneration.

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Toward Personalized Targeted Therapeutics: An Overview

Abstract

In neuro-oncology, there has been a movement towards personalized medicine, or tailoring treatment to the individual patient. Ideally, tumor and patient evaluations would lead to the selection of the best treatment (based on tumor characterization) and the right dosing schedule (based on patient characterization). The recent advances in the molecular analysis of glioblastoma have created optimism that personalized targeted therapy is within reach. Although our understanding of the molecular complexity of glioblastoma has increased over the years, the path to developing effective targeted therapeutic strategies is wrought with many challenges, as described in this review. These challenges include disease heterogeneity, clinical and genomic patient variability, limited number of effective treatments, clinical trial inefficiency, drug delivery, and clinical trial support and accrual. To confront these challenges, it will be imperative to devise innovative and adaptive clinical trials in order to accelerate our efforts in improving the outcomes for our patients who have been in desperate need.

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Effect on Cognition of Estroprogestins Combined with Interferon Beta in Multiple Sclerosis: Analysis of Secondary Outcomes from a Randomised Controlled Trial

Abstract

Introduction

Cognitive impairment is a disabling symptom in multiple sclerosis (MS). While its management remains challenging, beneficial effects on cognition of interferon beta (IFN-β) have been reported and a positive effect from estroprogestins has been hypothesised, suggesting that the combination of the two medications in women with MS could offer a promising treatment strategy.

Objectives

We investigated whether a combination of estroprogestins and IFN-β can improve cognition in women with MS.

Methods

Women with relapsing-remitting (RR) MS were randomly assigned (1:1:1) to receive subcutaneous IFN-β-1a (Rebif^®, Merck Serono, Geneva, Switzerland) 44 mcg three times a week (tiw) (group 1), subcutaneous IFN-β-1a 44 mcg tiw plus ethinyl estradiol 20 mcg and desogestrel 150 mcg (Mercilon^®, MSD Italia SRL, Rome, Italy) (group 2) or subcutaneous IFN-β-1a 44 mcg tiw plus ethinyl estradiol 40 mcg and desogestrel 125 mcg (Gracial^®, Organon Italia S.p.A., Rome, Italy) (group 3) in a randomised controlled trial, for which we report the analysis of secondary outcomes. At baseline and at 24 months, all patients underwent magnetic resonance imaging (MRI) and a comprehensive cognitive assessment, including Rao's Brief Repeatable Battery (RBRB) and questionnaires for depression, fatigue and quality of life. Failure in at least two of the RBRB tests defined 'cognitive impairment'.

Results

At baseline, there was no difference in the proportion of cognitively impaired patients. At month 24, the proportion of patients with cognitive impairment was lower in group 3 (34.8%) than in group 1 (47.6%) (p = 0.03). The risk of developing cognitive impairment over 24 months was lower in group 3 (p = 0.02). Mood and fatigue scores were comparable across the groups over time at both time points. However, at month 24, group 3 showed worsening on the sexual function subscale of the 54-item MS quality-of-life questionnaire (p = 0.03).

Conclusions

This study suggests that the combination of high-dose estroprogestins and IFN-β may have positive effects on cognition. However, the effect of this treatment on sexual function requires caution to be exercised.

Protocol Number NCT00151801, registered in ClinicalTrials.gov

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Pedicle screw augmentation in osteoporotic spine: indications, limitations and technical aspects

Abstract

Purpose

The need for spinal instrumented fusion in osteoporotic patients is rising. In this review, we try to give an overview of the current spectrum of pedicle screw augmentation techniques, safety aspects and indications.

Methods

Review of literature and discussion of indications, limitations and technical aspects.

Results

Various studies have shown higher failure rates in osteoporotic patients, most probably due to reduced bone quality and a poor bone-screw interface. Augmentation of pedicle screws with bone cement, such as polymethylmethacrylate or calcium based cements, is one valid option to enhance fixation if required.

Conclusions

Crucial factors for success in the use of augmented screws are careful patient selection, a proper technique and choice of the ideal cement augmentation option.

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Vertrauen und Verlässlichkeit in der Chirurgie

Zusammenfassung

Soziale Interaktionen sind ohne Vertrauen kaum denkbar. Ärztliche und insbesondere chirurgische Handlungen können das Leben von Personen mittelbar und unmittelbar existenziell verändern. Damit stellt die Beziehung zwischen Arzt und Patient eine Sonderform der sozialen Interaktion dar, wie sie an anderer Stelle kaum zu finden sein wird. Die Beschaffenheit der Arzt-Patienten-Beziehung entscheidet auch über den Erfolg einer Behandlung. Der Kern und die Bedeutung von Vertrauen, als ein zentraler Bestandteil dieser Beziehung, werden in dieser Arbeit rekonstruiert. Die zunehmenden Möglichkeiten der Informationsgewinnung moderner Gesellschaften, und die allgegenwärtige Forderung nach Transparenz, bestimmen immer mehr die Arzt-Patienten-Beziehung und lassen Konzepte von Vertrauen, auf den ersten Blick, nachrangig werden. Auch die aktuellen Entwicklungen zur Vergütung der Leistungen im Medizinsystem tragen das Risiko, die Bedeutung von Vertrauen in der Arzt-Patienten-Beziehung immer mehr zu bestimmen. Dabei ist es notwendig, Verlässlichkeit von Vertrauen abzugrenzen. Aufgrund der Bedingungen, die für die operativen Disziplinen konstituierend sind, ist hierbei ein Klima des Vertrauens, auch in einer modernen Informationsgesellschaft, notwendiger denn je.

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Die kolovesikale Fistel

Zusammenfassung

Hintergrund

Behandlungsziel für Patienten mit kolovesikaler Fistel ist eine rasche Beseitigung der Infektion und auch der sozialen Belastung. Wir stellten die Frage: Ist dieses Ziel auch rein minimalinvasiv in operativer Kooperation von Chirurgen und Urologen sicher möglich? Dazu ist eine effektive Diagnostik vor der operativen Therapie erforderlich.

Methodik

Bei 32 Patienten, seit 2007 mit der klinischen Verdachtsdiagnose kolovesikale Fistel, führten wir eine umfangreiche präoperative Diagnostik durch. Die operative Versorgung erfolgte primär unter einer minimalinvasiven Intention. Wir überprüften die präoperative Diagnostik auf ihre Wertigkeit, die operativen Ergebnisse auf ihren Erfolg, Komplikationen und Langzeitergebnisse.

Ergebnisse

Die Anamnese und ein nachgewiesener Harnwegsinfekt konnten als das sicherste Indiz für eine kolovesikale Fistel ermittelt werden. Die Zystoskopie, die Computertomographie und die Koloskopie konnten nur teilweise die später histologisch gesicherte Fistel voraussagen. 28-mal trat die Fistel infolge einer Sigmadivertikulitis auf, 3‑mal waren eine gynäkologische oder eine entzündliche Darmerkrankung die Ursache. Einmal lag eine maligne Erkrankung zugrunde. 29-mal erfolgte die Sanierung laparoskopisch mit 3 Konversionen bei intraoperativen Komplikationen. Die anderen wurden konventionell behandelt. Die krankheitsbezogenen Komplikationen in der Nachbeobachtung lagen bei 10 %.

Diskussion

Die laparoskopische Sanierung einer kolovesikalen Fistel ist bei empfohlener präoperativer Ureterschienung sicher möglich. In der Diagnostik sind die Anamnese und der damit verbundene nachgewiesene Harnwegsinfekt als die sichersten Parameter anzusehen. Bei dieser Kombination gepaart mit einem anderen Diagnoseverfahren empfehlen wir immer die Operation. Die Rezidivquote beträgt 0 %.

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Versterben vor und nach dem „Patientenverfügungsgesetz“

Zusammenfassung

Hintergrund

Bisher ist nicht bekannt, in welchem Ausmaß das Dritte Gesetz zur Änderung des Betreuungsrechts vom 29.07.2009 die Prozesse, die mit dem Versterben auf einer Intensivstation verbunden sind, beeinflusst hat.

Methodik

Wir verglichen retrospektiv Sterbeprozesse auf einer chirurgischen Intensivstation in zwei 3‑jährigen Beobachtungszeiträumen (nach Inkrafttreten des „Patientenverfügungsgesetzes" [Zeitraum II: 2009–2012] und 10 Jahre zuvor [Zeitraum I: 1999–2002]). Unabhängige Assoziationen wurden mittels logistischer Regression berechnet.

Ergebnisse

Im Beobachtungszeitraum II (n = 137 verstorbene Patienten) verringerte sich die Zeit bis zum Tod signifikant (19,3 Tage [95 %-KI 14,8–23,8]; p = 0,008 vs. 29,2 Tage [95 %-KI 23,7–34,6] im Beobachtungszeitraum I [n = 163]). Der Todesprozess war im Zeitraum II bei 42,3 % der Verstorbenen unter Berücksichtigung des Patientenwillens abgelaufen (Zeitraum I: 8,6 %, p < 0,001). Gleichzeitig nahm die Häufigkeit einer präoperativen schweren Komorbidität (mehr als ein Organversagen) zu (26,8 % der Verstorbenen, p = 0,001 vs. 5,5 % im Beobachtungszeitraum I). Eine Behandlung im Beobachtungszeitraum II war – neben hohem Alter und erhöhter Komorbidität – ein signifikanter, unabhängiger Prädiktor für die Wahrscheinlichkeit, dass eine Willensentscheidung des Patienten dem Tode voranging (Odds Ratio 7,42; 95 %-KI 3,77–14,60).

Schlussfolgerung

Seit Inkrafttreten des „Patientenverfügungsgesetztes" ist – unabhängig von Kovariablen – eine vermehrte und frühzeitigere Berücksichtigung des Patientenwillens und damit eine Verkürzung der Zeit bis zum Versterben zu beobachten.

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Aktuelle Trends in der onkologischen Ösophaguschirurgie

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Clusters of Monoisotopic Elements for Calibration in (TOF) Mass Spectrometry

Abstract

Precise calibration in TOF MS requires suitable and reliable standards, which are not always available for high masses. We evaluated inorganic clusters of the monoisotopic elements gold and phosphorus (Au_n⁺/Au_n^- and P_n⁺/P_n^-) as an alternative to peptides or proteins for the external and internal calibration of mass spectra in various experimental and instrumental scenarios. Monoisotopic gold or phosphorus clusters can be easily generated in situ from suitable precursors by laser desorption/ionization (LDI) or matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). Their use offers numerous advantages, including simplicity of preparation, biological inertness, and exact mass determination even at lower mass resolution. We used citrate-stabilized gold nanoparticles to generate gold calibration clusters, and red phosphorus powder to generate phosphorus clusters. Both elements can be added to samples to perform internal calibration up to mass-to-charge (m/z) 10–15,000 without significantly interfering with the analyte. We demonstrated the use of the gold and phosphorous clusters in the MS analysis of complex biological samples, including microbial standards and total extracts of mouse embryonic fibroblasts. We believe that clusters of monoisotopic elements could be used as generally applicable calibrants for complex biological samples.

Graphical Abstract

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Investigation and Applications of In-Source Oxidation in Liquid Sampling-Atmospheric Pressure Afterglow Microplasma Ionization (LS-APAG) Source

Abstract

A liquid sampling-atmospheric pressure afterglow microplasma ionization (LS-APAG) source is presented for the first time, which is embedded with both electrospray ionization (ESI) and atmospheric pressure afterglow microplasma ionization (APAG) techniques. This ion source is capable of analyzing compounds with diverse molecule weights and polarities. An unseparated mixture sample was detected as a proof-of-concept, giving complementary information (both polarities and non-polarities) with the two ionization modes. It should also be noted that molecular mass can be quickly identified by ESI with clean and simple spectra, while the structure can be directly studied using APAG with in-source oxidation. The ionization/oxidation mechanism and applications of the LS-APAG source have been further explored in the analysis of nonpolar alkanes and unsaturated fatty acids/esters. A unique [M + O – 3H]⁺ was observed in the case of individual alkanes (C₅–C₁₉) and complex hydrocarbons mixture under optimized conditions. Moreover, branched alkanes generated significant in-source fragments, which could be further applied to the discrimination of isomeric alkanes. The technique also facilitates facile determination of double bond positions in unsaturated fatty acids/esters due to diagnostic fragments (the acid/ester-containing aldehyde and acid oxidation products) generated by on-line ozonolysis in APAG mode. Finally, some examples of in situ APAG analysis by gas sampling and surface sampling were given as well.

Graphical Abstract

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Tripartite Motif 8 (TRIM8) Positively Regulates Pro-inflammatory Responses in Pseudomonas aeruginosa -Induced Keratitis Through Promoting K63-Linked Polyubiquitination of TAK1 Protein

Abstract

Pseudomonas aeruginosa (PA)-induced keratitis is a rapidly progressive ocular infectious disease that often leads to inflammatory epithelial edema, stromal infiltration, tissue destruction, corneal ulceration, and vision loss. In this study, we investigate the role of tripartite motif 8 (TRIM8) in regulating the inflammatory process of PA-induced keratitis. The expression of TRIM8 was increased in mouse corneas and in vitro-cultured macrophages after PA infection. Knockdown of the expression of TRIM8 significantly inhibited the activation of NF-κB signaling and decreased the production of pro-inflammatory cytokines both in vivo and in vitro after infected with PA. Furthermore, we investigated the potential mechanism and we found after PA infection that TRIM8 could promote K63-linked polyubiquitination of transforming growth factor β-activated kinase 1 (TAK1), leading to the activation of TAK1 and enhanced inflammatory responses. Taken together, we demonstrated that TRIM8 has pro-inflammatory effect on PA-induced keratitis and suggest TRIM8 as a potential therapeutic target for keratitis.

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Bone Morphogenetic Protein-Modulator BMPER Regulates Endothelial Barrier Function

Abstract

The endothelium serves as a selective barrier and controls the exchange of nutrients, hormones, and leukocytes between blood and tissues. Molecular mechanisms contributing to the pathogenesis of endothelial barrier dysfunction remain incompletely understood. Accumulating evidence implicates bone morphogenetic protein (BMP)-modulator BMPER as a key regulator in endothelial biology. Herein, we analyze the impact of BMPER in the control of endothelial barrier function. To assess the role of BMPER in vascular barrier function in mice, we measured the leakage of Evans blue dye from blood into interstitial lung tissue. BMPER^+/− mice exhibited a significantly higher degree of vascular leak compared with wild-type siblings. In accordance with our in vivo observation, siRNA-based BMPER knockdown in human umbilical endothelial cells increased endothelial permeability measured by FITC-dextran passage in transwell assays. Mechanistically, BMPER knockdown reduced the expression of VE-cadherin, a pivotal component of endothelial adherens junctions. Conversely, recombinant human BMPER protein upregulated VE-cadherin protein levels and improved endothelial barrier function in transwell assays. The effects of BMPER knockdown on VE-cadherin expression and endothelial permeability were induced by enhanced BMP activity. Supporting this notion, activation of BMP4-Smad-Id1 signaling reduced VE-cadherin levels and impaired endothelial barrier function in vitro. In vivo, Evans blue dye accumulation was higher in the lungs of BMP4-treated C57BL/6 mice compared to controls indicating that BMP4 increased vascular permeability. High levels of BMPER antagonized BMP4-Smad5-Id1 signaling and prevented BMP4-induced downregulation of VE-cadherin and endothelial leakage, suggesting that BMPER exerts anti-BMP effects and restores endothelial barrier function. Taken together, this data demonstrates that BMPER-modulated BMP pathway activity regulates VE-cadherin expression and vascular barrier function.

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Direct Percutaneous Endoscopic Jejunostomy (DPEJ) Tube Placement: A Single Institution Experience and Outcomes to 30 Days and Beyond

Abstract

Introduction

Patients with prior foregut surgery requiring long-term enteral access typically undergo operative jejunostomy tube placement; however, direct percutaneous endoscopic jejunostomy (DPEJ) is a viable alternative.

Methods

All de novo DPEJ procedures performed by surgical and advanced endoscopists from May 2003 to June 2015 were retrospectively reviewed following approval by the Institutional Review Board. There were 59 cases identified.

Results

Our cohort had a mean age of 50.3 ± 16.9 years and 35 (59.3%) were female. All but two patients previously had foregut surgery including 19 patients (34.5%) with prior bariatric surgery. The composite of malnutrition and dehydration was the indication for DPEJ in 29 patients (49.1%) and was the initial enteral access placed in 47 patients (79.7%). Moderate sedation was used in 32 cases (54.2%), and 29 procedures (49.2%) were performed in the operating room. Within 30 days, there were six complications in five patients, giving a peri-procedural complication rate of 12.5%. Beyond 30 days, the most common complications were peri-tube leakage and dislodgement (each 16.9%). The median time to complication was 197 days.

Conclusions

In patients with surgically altered foregut anatomy, DPEJ offers a less invasive alternative to operative jejunostomy tube placement. DPEJ can be placed in the endoscopy suite or operating room with an acceptable risk of perioperative complications.

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Efficacy and Safety of Calcipotriol Plus Betamethasone Dipropionate Aerosol Foam Compared with Betamethasone 17-Valerate-Medicated Plaster for the Treatment of Psoriasis

Abstract

Background

Fixed combination calcipotriol as hydrate (Cal) 50 µg/g plus betamethasone as dipropionate (BD) 0.5 mg/g aerosol foam is an alcohol-free treatment for psoriasis. Betamethasone 17-valerate 2.25 mg (BV)-medicated plasters are recommended for treating psoriasis plaques localized in difficult-to-treat (DTT; elbow, knee, anterior face of the tibia) areas.

Objective

The aim of this study was to compare the efficacy of Cal/BD foam with BV-medicated plaster in patients with plaque psoriasis.

Methods

In this phase IIa, randomized, single-center, investigator-blinded, 4-week study, both Cal/BD foam and BV-medicated plaster were applied once daily to six test sites (three for each treatment). The primary efficacy endpoint was absolute change in total clinical score (TCS; sum of erythema, scaling, and infiltration); secondary endpoints were changes from baseline in each individual clinical score, ultrasonographic changes (total skin and echo-poor band thickness), and safety; and post hoc analysis was change from baseline in TCS on DTT areas.

Results

Thirty-five patients were included. Least-squares mean change in TCS from baseline was significantly greater for Cal/BD foam (−5.8) than BV-medicated plaster (−3.7; difference −2.2; 95% confidence interval −2.6 to −1.8; p < 0.001); greater changes for Cal/BD foam were observed from day 8 for each clinical sign. Absolute total skin and echo-poor band thickness change was significantly greater for Cal/BD foam than for BV-medicated plaster (both p < 0.001). Post hoc analyses showed that Cal/BD foam was significantly more effective than BV-medicated plaster on DTT areas after 4 weeks (p < 0.001), and both treatments were well tolerated.

Conclusion

Cal/BD foam demonstrated superior efficacy versus BV-medicated plasters, including on DTT areas, in patients with plaque psoriasis.

Clinical trial registration number: NCT02518048.

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Prophylactic mesh to prevent parastomal hernia after end colostomy: a meta-analysis and trial sequential analysis

Abstract

Purpose

Prevention of parastomal hernia (PSH) formation is crucial, given the high prevalence and difficulties in the surgical repair of PSH. To investigate the effect of a preventive mesh in PSH formation after an end colostomy, we aimed to meta-analyze all relevant randomized controlled trials (RCTs).

Methods

We searched five databases. For each trial, we extracted risk ratios (RRs) of the effects of mesh or no mesh. The primary outcome was incidence of PSH with a minimum follow-up of 12 months with a clinical and/or computed tomography diagnosis. RRs were combined using the random-effect model (Mantel–Haenszel). To control the risk of type I error, we performed a trial sequential analysis (TSA).

Results

Seven RCTs with low risk of bias (451 patients) were included. Meta-analysis for primary outcome showed a significant reduction of the incidence of PSH using a mesh (RR 0.43, 95% CI 0.26–0.71; P = 0.0009). Regarding TSA calculation for the primary outcome, the accrued information size (451) was 187.1% of the estimated required information size (RIS) (241). Wound infection showed no statistical differences between groups (RR 0.77, 95% CI 0.39–1.54; P = 0.46). PSH repair rate showed a significant reduction in the mesh group (RR 0.28 (95% CI 0.10–0.78; P = 0.01).

Conclusions

PSH prevention with mesh when creating an end colostomy reduces the incidence of PSH, the risk for subsequent PSH repair and does not increase wound infections. TSA shows that the RIS is reached for the primary outcome. Additional RCTs in the previous context are not needed.

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New surgical scoring system to predict postoperative mortality

Abstract

Purpose

There is still no easy and highly useful method to comprehensively assess both preoperative and intraoperative patient statuses to predict postoperative outcomes. We attempted to develop a new scoring system that would enable a comprehensive assessment of preoperative and intraoperative patient statuses instantly at the end of anesthesia, predicting postoperative mortality.

Methods

The study included 32,555 patients who underwent surgery under general or regional anesthesia from 2008 to 2012. From the anesthesia records, extracted factors, including patient characteristics and American Society of Anesthesiologists physical status classification (ASA-PS), and three intraoperative indexes (the lowest heart rate, lowest mean arterial pressure, and estimated volume of blood loss) are used to calculate the surgical Apgar score (sAs). The sAs and ASA-PS, and surgical Apgar score combined with American Society of Anesthesiologists physical status classification (SASA), which combines the sAs and ASA-PS into a single adjusted scale, were compared and analyzed with postoperative 30-day mortality.

Results

Increased severity of the sAs, ASA-PS and SASA was correlated with significantly higher mortality. The risk of death was elevated by 3.65 for every 2-point decrease in the sAs, by 6.4 for every 1-point increase in the ASA-PS, and by 9.56 for every 4-point decrease in the SASA. The ROC curves of the sAs and ASA-PS alone also individually demonstrated high validity (AUC = 0.81 for sAs and 0.79 for ASA-PS, P < 0.001). The SASA was even more valid (AUC = 0.87, P < 0.001).

Conclusions

The sAs and ASA-PS were shown to be extremely useful for predicting 30-day mortality after surgery. An even higher predictive ability was demonstrated by the SASA, which combines these simple and effective scoring systems.

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Cytomegalovirus (CMV) Infection Causes Degeneration of Cochlear Vasculature and Hearing Loss in a Mouse Model

Abstract

Cytomegalovirus (CMV) infection is one of the most common causes of congenital hearing loss in children. We have used a murine model of CMV infection to reveal functional and structural cochlear pathogenesis. The cerebral cortex of Balb/c mice (Mus musculus) was inoculated with 2000 pfu (plaque forming units) of murine CMV on postnatal day 3. At 6 weeks of age, cochlear function was monitored using auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) measures. Histological assessment of cochlear vasculature using a corrosion cast technique was made at 8 weeks. Vascular casts of mCMV-damaged cochleas, and those of untreated control animals, were examined using scanning electron microscopy. We find very large variations in the degree of vascular damage in animals given identical viral injections (2000 pfu). The primary lesion caused by CMV infection is to the stria vascularis and to the adjacent spiral limbus capillary network. Capillary beds of the spiral ligament are generally less affected. The initial vascular damage is found in the mid-apical turn and appears to progress to more basal cochlear regions. After viral migration to the inner ear, the stria vascularis is the primary affected structure. We suggest that initial auditory threshold losses may relate to the poor development or maintenance of the endocochlear potential caused by strial dysfunction. Our increased understanding of the pathogenesis of CMV-related hearing loss is important for defining methods for early detection and treatment.

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Zur Umsetzung alternativer Behandlungsmodelle für Flüchtlinge in der BRD

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Psychiatrische und psychotherapeutische Versorgung geflüchteter Personen

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Transposition of Great Arteries with Complex Coronary Artery Variants: Time-Related Events Following Arterial Switch Operation

Abstract

Coronary artery anatomy represents a challenging and, often, determining predictor of outcome in an arterial switch operation (ASO). Impact of specific coronary artery variants, such as single, intramural and inverted, on time-related events following ASO, is, yet, to be determined. We sought to compare early and late outcomes within the group of nonstandard coronary artery variants. Patients who underwent ASO from January 1995 to October 2010 were reviewed. Patients with coronary artery variants other than L1Cx1R2 ("standard" by Leiden classification) were included. Patients with single, intramural and inverted coronary artery variants incorporated in group A. All other nonstandard coronary variants incorporated in group B. Demographics, perioperative variables, early and late outcomes were assessed. Of the 123 ASO, 24 patients (19.5%) with nonstandard coronary variant were studied. Thirteen were in group A and 11 in group B. There were two early deaths (1 in group A and 1 in group B) (p > 0.05). There is one death early after hospital discharge (group A). Mean follow-up was 59.4 ± 55.1 months. There was no structural coronary artery failure after hospital discharge following ASO. Freedom from any reintervention at 8 years was (78.3 ± 9.6%) (p 0.55) with no late neo-aortic or mitral valve intervention. ASO with single, intramural or inverted coronary artery course carries no added longitudinal risk for structural or flow impairment within the group of nonstandard coronary artery variants. There is an early hazard period with no late survival attrition. Aortic arch repair as part of staged strategy prior to ASO might influence early and late outcome.

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Assessing Myocardial Function in Infants with Pulmonary Hypertension: The Role of Tissue Doppler Imaging and Tricuspid Annular Plane Systolic Excursion

Abstract

Transthoracic echocardiography is the most common noninvasive method of evaluating pulmonary hypertension (PH) in infants. Identification of reliable, quantitative indices of myocardial function may enhance the diagnostic value of echocardiography in this population. We hypothesized that pulsed wave tissue Doppler imaging (TDI) and tricuspid annular plane systolic excursion (TAPSE) would be reproducible measurements and would suggest decreased ventricular function, in infants with PH. This retrospective case–control study involved subjects diagnosed clinically and echocardiographically with PH at <12 months of age, matched with controls by age and gestational age (GA). TAPSE was measured by M-mode in the apical 4-chamber view. TDI velocities were averaged from three consecutive cardiac cycles. Observers were blinded to patient identity and clinical status. Fifty-seven subjects, including 35 term or near-term infants ≥35 weeks GA [mean GA 39 weeks (±1.7), median age 1 day (range 0–2)] and 22 preterm infants [median GA 25.4 weeks (24.1–26.6), age 66 days (4–128)], were matched with 57 controls. Subjects with PH had lower TAPSE (term p < 0.001, preterm p = 0.03) and TAPSE indexed to body surface area (term p < 0.001, preterm p = 0.005). Mitral annular, septal, and tricuspid annular systolic (S') and early diastolic (E') TDI velocities were also decreased compared to controls (all p < 0.05). Intraclass correlation demonstrated 84–99% agreement between observers in measuring TDI and 92% for TAPSE. Intraobserver reliability for these measures was 98–99% and 96%, respectively. We concluded that TDI and TAPSE are reproducible indices of myocardial function and may serve as useful adjuncts to standard echocardiographic measures in infants with PH.

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Nadolol for Treatment of Supraventricular Tachycardia in Infants and Young Children

Abstract

Supraventricular tachycardia (SVT) is a common infant arrhythmia, for which beta-blockers are frequently chosen as therapy. Propranolol is a common choice though it is dosed every 6–8 h. We reviewed the clinical results of treating infant SVT with an extemporaneous preparation of nadolol. Retrospective cohort study of patients under 2 years old receiving nadolol for SVT at a single center. Patients were ascertained by patient and pharmacy databases. Twenty-eight infants received nadolol, of whom 25 had regular narrow complex tachycardia, 2 atrial flutter, and 1 focal atrial tachycardia. Patient age at initiation was a median 54 days (range 10–720). The final dose was 1 mg/kg/day in 22/28 patients (range 0.5–2). Once-daily dosing was used in 20 patients (71.4%); dosing was BID in 7, TID in 1. Among regular narrow complex tachycardia patients, 18/25 received nadolol monotherapy and 7 required additional agents; flecainide in 6, digoxin in 1. The median age of tachyarrhythmia onset was 18 days (range 1–180) with a median age of nadolol initiation of 30 days (range 11–390). Of the 20 regular narrow complex tachycardia patients initiated on nadolol monotherapy, 85% had no recurrences as of 1-year follow-up. Side effects were suspected in 3 of 28 (10.7%), including wheezing (n = 1, 3.5%), irritability and diarrhea (n = 1, 3.5%), and bradycardia (n = 1, 3.5%). Oral nadolol suspension was a successful treatment for SVT in 85% of patients with minimal adverse effects. Single daily dosing was used in the majority of patients.

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The Fetus with Ectopia Cordis: Experience and Expectations from Two Centers

Abstract

Ectopia cordis (EC) is a rare congenital anomaly often associated with congenital heart disease (CHD). There is a lack of contemporary information on EC diagnosed prenatally. We sought to combine the experiences of two regional referral centers in order to evaluate current outcomes for EC. Clinical, echocardiographic features and perinatal outcomes of fetuses with EC managed at two large cardiac centers from 1995 to 2014 were retrospectively reviewed. Seventeen fetuses with EC were diagnosed at a median gestational age of 23 weeks (range 17–36). There were 6 thoracic EC and 11 thoracoabdominal. Fifteen had associated CHD: 10 conotruncal defects, 2 tricuspid atresia, 1 aortic stenosis, 1 atrial septal defect, and 1 atrioventricular septal defect. There were 2 terminations of pregnancy, 2 fetal deaths, 2 lost to follow-up, and 11 live born. Mean gestational age at birth was 36.4 weeks (range 26–39). Three patients died shortly after birth with comfort care, and 8 were actively managed. Six patients underwent postnatal cardiac intervention and are currently alive with a mean follow-up of 7.3 years (range 1.4–11.4), 2 of them with chronic dependency on ventilatory support. Two patients without CHD died after attempted chest closure. When diagnosed in utero, a high proportion of pregnancy termination or fetal demise is expected. In our cohort, conotruncal anomalies were the most common associated CHD. Though mortality in actively managed patients was not as high as previously reported, and cardiac surgical intervention may be achieved, EC is still associated with high mortality and significant long-term morbidity.

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Interpretation of the Elecsys Toxo IgG avidity results for very low and very high index: study on 741 sera with a determined date of toxoplasmosis

Abstract

Initial results with the Elecsys Toxo IgG Avidity assay showed some potential for interpretation of a very low or very high index result. We aimed to examine these new insights into interpretation using a large panel of serum samples and to define the optimal thresholds. A total of 741 patient serum samples with known date of infection (from a few weeks to more than 9 months after infection), were analysed with the Elecsys Toxo IgG Avidity assay. Values ≥80% (threshold defined by the manufacturer) were reported in 289 sera; 288 sera were sampled more than 4 months after infection. Thus, avidity values ≥80% excluded an infection less than 4 months. Avidity values ≥90% were reported in 112 sera sampled more than 9 months after infection. Thus, avidity values ≥90% excluded infection less than 9 months. Moreover avidity values ≤15% were reported in the 62 sera sampled less than 3 months after infection. Thus avidity values ≤15% excluded infection more than 3 months.

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Obstructive sleep apnea is the triggering factor for massive hemoptysis

Abstract

Purpose

The purpose of this study was to investigate the prevalence of obstructive sleep apnea (OSA) in patients with hemoptysis.

Methods

Files of patients who had undergone bronchial arterial embolization due to hemoptysis between 1 December 2009 and 2015 were evaluated and interviews of patients were conducted until 1 June 2016. Pittsburgh Sleep Quality Index (PSQI), STOP and STOP-BANG surveys were administered. OSA risk was determined with Berlin Questionnaire.

Results

Study group consisted of 53 patients and 58 control subjects. Mean age was 46.94 ± 14.36 and 41.97 ± 12.92 in patient and control group, respectively. Of these patients, seven had re-embolization procedure because of recurrence of hemoptysis. High OSA risk was more common among patients with hemoptysis (24.5%, n = 13) than the control group (8.6%, n = 5) (p = 0.023). Percentage of high risk OSA patients with massive hemoptysis, nonmassive hemoptysis, and control subjects was 29.7% (n = 11), 12.5% (n = 2), and 8.6% (n = 5), respectively (p = 0.022). There were more high OSA risk subjects among patients with idiopathic hemoptysis 44.4% (four out of nine), while 20.5% (nine out of 53) patients with a known etiology had high risk (p = 0.127). The number of patients with high OSA risk was also higher in patients who required a second embolization procedure (four out of seven, 57.1%), while 19.6% of patients without need for re-embolization had high risk (p = 0.031).

Conclusions

OSA is found to be a risk factor for hemoptysis and also may provoke massive hemoptysis. It seems reasonable to consider OSA as an underlying condition in idiopathic hemoptysis. OSA may contribute to embolization failure.

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Comparative Analysis of Proteome Patterns of Francisella tularensis Isolates from Patients and the Environment

Abstract

Francisella tularensis is the causative agent of tularemia. Although major contributors and the main mechanism of the virulence are well known, some of the molecular details are still missing. Proteomics studies regarding F. tularensis have provided snapshot pictures of the organism grown under different culture conditions to understand the mechanism of virulence. In general, such studies were carried out with standard strains e.g., LVS and did not involve comparisons of F. tularensis isolates from either clinical or environmental sources. In this study, we performed two-dimensional gel electrophoresis (2DE)-based proteomic analysis and compared the protein profiles of the F. tularensis subsp. holarctica strains isolated from the clinical and the environmental samples. Regulations were detected in 14 spots when twofold regulation criteria were applied. The regulated protein spots were subjected to MALDI-TOF/TOF analysis and identified. Classification of the identified proteins based on metabolic functions revealed that the translation machinery was the most varying metabolic processes among the isolates. Using normalized protein spot intensities, PCA analysis was also performed. The results indicated that the strain isolated from water source was different then the strains isolated from the patients. Most interestingly, the isolates were strikingly distinguishable from the standard NCTC 10857 strain.

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Comment on: “A Review of the Acute Effects and Long-Term Adaptations of Single- and Multi-Joint Exercises During Resistance Training”

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Authors’ Reply to Ribeiro et al.: “A Review of the Acute Effects and Long-Term Adaptations of Single- and Multi-Joint Exercises During Resistance Training”

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Advancing Leadership in Sport: Time to ‘Actually’ Take the Blinkers Off?

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Self-Reported Outcome Measures of the Impact of Injury and Illness on Athlete Performance: A Systematic Review

Abstract

Background

Self-reported outcome measures of athlete health, wellbeing and performance add information to that obtained from clinical measures. However valid, universally accepted outcome measures are required.

Objective

To determine which athlete-reported outcome measures of performance have been used to measure the impact of injury and illness on performance in sport and assess evidence to support their validity.

Methods

The authors searched Ovid MEDLINE, Ovid EMBASE, CINAHL Plus, SPORTDiscus with Full Text and Cochrane library to January 2016. Predefined inclusion and exclusion criteria were applied and papers included if an outcome measure of performance, assessed in relation to illness, injury or a related intervention, was reported by an elite, adult, able-bodied athlete. A checklist was used to assess eligible outcome measures for aspects of validity. Reporting of this study was guided by PRISMA guidelines for systematic reviews.

Results

Twenty athlete-reported outcome measures in 21 papers were identified. Of these 20, only four cited validation. Of these four, three reported evidence to support validity in elite athlete groups as defined by the predetermined checklist. Fifteen patient-reported outcome measures were identified, of which four demonstrated validity in young athletic populations.

Conclusions

Most athlete-reported outcome measures of performance have been designed for individual studies with no reported assessment of validity. Despite some limitations, the Oslo Sports Trauma Centre overuse injury questionnaire demonstrates validity and potential utility to investigate the self-reported impact of pre-defined conditions on athletic performance across different sports.

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Authors’ Reply to Mills and Boardley: “Advancing Leadership in Sport: Time To Take Off the Blinkers?”

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Acid and light dual- stimuli-cleavable polymeric micelles

Abstract

In this study, acid and light dual- stimuli-responsive amphiphilic AB-type methoxy poly(ethylene glycol)-acetal-ONB-poly(4-substituted-ε-caprolactone) (MPEG-a-ONB-PXCL) diblock copolymers were synthesized using ring-opening polymerization and nucleophilic substitution reactions. The prepared copolymer features an acid-cleavable acetal group and photocleavable o-nitrobenzyl linkage between the hydrophilic MPEG and hydrophobic PXCL blocks. The design enables the diblock copolymers to respond to both acid and ultraviolet (UV) light while ensuring the minimum number of stimuli-reactive moieties in the copolymer structure. The disruption of the copolymeric micelles in aqueous solution was examined under the action of pH or UV light alone or under the combined stimulation pH and UV light. Under the combined stimulation of UV irradiation and pH, the micellar nanoparticles could dissociate; therefore, the loaded molecules could be released from the assemblies more efficiently than under either stimulus alone. The nanoparticles exhibited nonsignificant toxicity against human cervical cancer (HeLa) cells at concentrations ≤300 μg mL⁻¹. Doxorubicin (DOX)-loaded micelles facilitated the uptake of DOX by the HeLa cells at the initial stage. The dual stimuli-cleavable polymeric micelles show promising potential as new nanocarrier for precisely controlled release of encapsulated drug.

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Production of the immunosuppressant cyclosporin A by a new soil isolate, Aspergillus fumigatus , in submerged culture

Abstract

Cyclosporin A (CyA) has received meticulous attention owing to its immunosuppressive and biological activities. In this study, a soil isolate, capable of producing CyA, was named Zag1 strain and identified as Aspergillus fumigatus based on macroscopic and microscopic characteristics, 18S rDNA sequence, and phylogenetic characteristic analysis. To maximize the production of CyA, the fungal culture was grown under various fermentation conditions including selection of the cultivation medium, agitation rate, fermentation time, incubation temperature, pH value, inoculum nature, and medium volume. A simple medium (pH 5.0) containing 5% maltose as a carbon source and 2% potassium nitrate as a nitrogen source favored the highest CyA production when the fermentation process was maintained at 120 rpm for 9 days and at 30 °C using 3% standard inoculum of 5-day-old. The final CyA titer under these conditions was intensified to 2.23–3.31-fold, as compared with the amount obtained with seven types of basal media. A. fumigatus Zag1 appears to possess a good biotechnological potential for CyA production under favorable culture conditions.

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Characterization of three pyranose dehydrogenase isoforms from the litter-decomposing basidiomycete Leucoagaricus meleagris (syn. Agaricus meleagris )

Abstract

Multigenicity is commonly found in fungal enzyme systems, with the purpose of functional compensation upon deficiency of one of its members or leading to enzyme isoforms with new functionalities through gene diversification. Three genes of the flavin-dependent glucose–methanol–choline (GMC) oxidoreductase pyranose dehydrogenase (AmPDH) were previously identified in the litter-degrading fungus Agaricus (Leucoagaricus) meleagris, of which only AmPDH1 was successfully expressed and characterized. The aim of this work was to study the biophysical and biochemical properties of AmPDH2 and AmPDH3 and compare them with those of AmPDH1. AmPDH1, AmPDH2 and AmPDH3 showed negligible oxygen reactivity and possess a covalently tethered FAD cofactor. All three isoforms can oxidise a range of different monosaccarides and oligosaccharides including glucose, mannose, galactose and xylose, which are the main constituent sugars of cellulose and hemicelluloses, and judging from the apparent steady-state kinetics determined for these sugars, the three isoforms do not show significant differences pertaining to their reaction with sugar substrates. They oxidize glucose both at C2 and C3 and upon prolonged reaction C2 and C3 double-oxidized glucose is obtained, confirming that the A. meleagris genes pdh2 (AY753308.1) and pdh3 (DQ117577.1) indeed encode CAZy class AA3_2 pyranose dehydrogenases. While reactivity with electron donor substrates was comparable for the three AmPDH isoforms, their kinetic properties differed significantly for the model electron acceptor substrates tested, a radical (the 2,2′-azino-bis[3-ethylbenzothiazoline-6-sulphonic acid] cation radical), a quinone (benzoquinone) and a complexed iron ion (the ferricenium ion). Thus, a possible explanation for this PDH multiplicity in A. meleagris could be that different isoforms react preferentially with structurally different electron acceptors in vivo.

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Comparison of lipases and glycoside hydrolases as catalysts in synthesis reactions

Abstract

Lipases and glycoside hydrolases have large similarities concerning reaction mechanisms. Acyl-enzyme intermediates are formed during lipase-catalyzed reactions and in an analogous way, retaining glycoside hydrolases form glycosyl-enzyme intermediates during catalysis. In both cases, the covalent enzyme intermediates can react with water or other nucleophiles containing hydroxyl groups. Simple alcohols are accepted as nucleophiles by both types of enzymes. Lipases are used very successfully in synthesis applications due to their efficiency in catalyzing reversed hydrolysis and transesterification reactions. On the other hand, synthesis applications of glycoside hydrolases are much less developed. Here, important similarities and differences between the enzyme groups are reviewed and approaches to reach high synthesis yields are discussed. Useful strategies include the use of low-water media, high nucleophile concentrations, as well as protein engineering to modify the selectivity of the enzymes. The transglycosylases, hydrolases which naturally catalyze mainly transfer reactions, are of special interest and might be useful guides for engineering of other hydrolases.

http://ift.tt/2hNW3zi

Black phosphorus based saturable absorber for Nd-ion doped pulsed solid state laser operation

Abstract

In this paper, the use of black phosphorus (BP) as a saturable absorber in a Q-switched Nd-ion doped solid state laser is presented. Few layers of BP in isopropyl alcohol are obtained by liquid phase exfoliation. The BP nanosheets with thicknesses in the range of 15–20 nm are deposited onto a K9 glass substrate. By inserting the BP nanosheets into a diode pumped Nd-ion doped solid state laser, stable Q-switched lasing at 0.9, 1.06, 1.3 μm is obtained. Using this approach, we have achieved a short pulse duration down to 219 ns, a high pulse energy of up to 6.5 μJ, and the corresponding peak power of 30 W. Our results show that the BP saturable absorber functions well in a Nd-ion doped solid state laser for pulsed laser generation.

http://ift.tt/2h3V4tE

Diabetes and breast cancer mortality in Black women

Abstract

Purpose

Breast cancer mortality is higher in Black women than in White women. The prevalence of type 2 diabetes mellitus is also higher, yet data on whether diabetes affects breast cancer mortality in this population are lacking. We investigated the relation of diabetes at the time of breast cancer diagnosis to breast cancer mortality in the Black Women's Health Study, a prospective cohort study.

Methods

1,621 Black women with invasive breast cancer diagnosed in 1995–2013 were followed by mailed questionnaires and searches of the National Death Index. Multivariable Cox regression analysis was used to compute hazard ratios (HRs) for diabetes in relation to breast cancer mortality and all-cause mortality, with adjustment for age, stage, treatment modality, estrogen receptor (ER) status, and body mass index.

Results

There were 368 deaths during follow-up, of which 273 were due to breast cancer. Breast cancer mortality was significantly increased in women who had been diagnosed with diabetes at least 5 years before breast cancer occurrence, HR 1.86 (95% CI 1.20–2.89), with elevations observed for both ER+ and ER− breast cancer. All-cause mortality was also higher in diabetics, with HRs of 1.54 (95% CI 1.12–2.07) overall and 2.26 (95% CI 1.62–3.15) for ≥5-year duration of diabetes relative to non-diabetics.

Conclusions

Our results present the first solid evidence of a positive association of type 2 diabetes with breast cancer mortality in Black women. Given the higher prevalence and earlier onset of type 2 diabetes in Black women, it is likely that diabetes contributes to racial disparities in breast cancer mortality.

http://ift.tt/2hO9y1Z

Short-term and long-term survival of interval breast cancers taking into account prognostic features

Abstract

Purpose

The aim of this population-based study was to estimate short-term and long-term survival of interval breast cancers and to compare them to clinically detected cancers, taking into account prognostic features.

Methods

This study included all interval cancers and clinically detected cancers diagnosed in the Loire-Atlantique population-based cancer registry from 2000 to 2010 in women aged 50–76 years. We used the Pohar-Perme method to estimate 5- and 10 year net survival rates and a flexible parametric model to compare interval cancer and clinically detected cancer prognosis with and without adjustment for the main prognostic factors (age, stage, histological grade, and phenotype).

Results

This study included 813 interval cancers and 1,354 clinically detected cancers. Interval cancers were diagnosed at a significantly less advanced stage than clinically detected cancers, but more often with a triple-negative phenotype. Interval cancer age-standardised net survival was 88.0% at 5 years (95% CI 84.9–91.2) and 81.7% at 10 years (95% CI 76.9–86.9), whereas clinically detected cancer age-standardised net survival was 77.8% (95% CI 75.1–80.6) and 64.6% (95% CI 60.7–68.7), respectively. After adjustment for covariates, survival no longer differed between interval cancers and clinically detected cancers at 5 and 10 years.

Conclusion

Although the interval cancer net survival rate was higher, interval cancers had a similar short-term and long-term prognosis than clinically detected cancers after taking into account the main prognostic factors.

http://ift.tt/2hT4fM2

Metal Hypersensitivity Reactions to Orthopedic Implants

Abstract

Total hip and knee replacement surgery using metal alloy devices is common. Type IV allergic reactions to these implants occur, though infrequently. While uncommon, peri-implant metal allergic reactions may cause significant morbidity for the affected individual—including aseptic loosening, pseudotumor formation and frank device failure. It is challenging to predict who will have these reactions, even in those with established pre-implant metal allergy. At this time, the scientific literature clearly supports few conclusions. Despite this, we believe several conclusions can be made: routine pre-implant testing in asymptomatic individuals is not indicated; listen to patient's concerns about metal allergy if the concern arises; patch testing is probably the best pre- and post-implant screening test; post-implantation testing is controversial and even positive LTT or patch test does not definitively diagnose morbidity from a metal allergy; and complete recovery following revision placement of an immunologically inert device is diagnostic. More research is needed to scientifically approach this issue.

http://ift.tt/2i8xPMK

Efficacy and Safety of 5-Fluorouracil 0.5%/Salicylic Acid 10% in the Field-Directed Treatment of Actinic Keratosis: A Phase III, Randomized, Double-Blind, Vehicle-Controlled Trial

Abstract

Introduction

Due to the high prevalence of actinic keratosis (AK) and potential for lesions to become cancerous, clinical guidelines recommend that all are treated. The objective of this study was to evaluate the efficacy and safety of 5-fluorouracil (5-FU) 0.5%/salicylic acid 10% as field-directed treatment of AK lesions.

Methods

This multicenter, double-blind, vehicle-controlled study (NCT02289768) randomized adults, with a 25 cm² area of skin on their face, bald scalp, or forehead covering 4–10 clinically confirmed AK lesions (grade I/II), 2:1 to treatment or vehicle applied topically once daily for 12 weeks. The primary endpoint was the proportion of patients with complete clinical clearance (CCC) of lesions in the treatment field 8 weeks after the end of treatment. Secondary endpoints included partial clearance (PC; ≥75% reduction) of lesions. Safety outcomes were assessed.

Results

Of 166 patients randomized, 111 received 5-FU 0.5%/salicylic acid 10% and 55 received vehicle. At 8 weeks after the end of treatment, CCC was significantly higher with 5-FU 0.5%/salicylic acid 10% than with vehicle [49.5% vs. 18.2%, respectively; odds ratio (OR) 3.9 (95% CI) 1.7, 8.7; P = 0.0006]. Significantly more patients achieved PC of lesions with treatment than with vehicle [69.5% vs. 34.6%, respectively; OR 4.9 (95% CI 2.3, 10.5); P < 0.0001]. Treatment-emergent adverse events, predominantly related to application- and administration-site reactions, were more common with 5-FU 0.5%/salicylic acid 10% than with vehicle (99.1% vs. 83.6%).

Conclusions

Compared with vehicle, field-directed treatment of AK lesions with 5-FU 0.5%/salicylic acid 10% was effective in terms of CCC. Safety outcomes were consistent with the known and predictable safety profile.

Trial registration

NCT02289768.

Funding

Almirall S.A.

http://ift.tt/2h3Oxzk

A global analysis of residential heating and cooling service demand and cost-effective energy consumption under different climate change scenarios up to 2050

Abstract

Climate change and energy service demand exert influence on each other through temperature change and greenhouse gas emissions. We have consistently evaluated global residential thermal demand and energy consumption up to the year 2050 under different climate change scenarios. We first constructed energy service demand intensity (energy service demand per household) functions for each of three services (space heating, space cooling, and water heating). The space heating and cooling demand in 2050 in the world as a whole become 2.1–2.3 and 3.8–4.5 times higher than the figures for 2010, whose ranges are originated from different global warming scenarios. Cost-effective residential energy consumption to satisfy service demand until 2050 was analyzed keeping consistency among different socio-economic conditions, ambient temperature, and carbon dioxide (CO₂) emission pathways using a global energy assessment model. Building shell improvement and fuel fuel-type transition reduce global final energy consumption for residential thermal heating by 30% in 2050 for a 2 °C target scenario. This study demonstrates that climate change affects residential space heating and cooling demand by regions, and their desirable strategies for cost-effective energy consumption depend on the global perspectives on CO₂ emission reduction. Building shell improvement and energy efficiency improvement and fuel fuel-type transition of end-use technologies are considered to be robust measures for residential thermal demand under uncertain future CO₂ emission pathways.

http://ift.tt/2hkipVJ

Hydrodynamic Assessment of Aortic Valves Prepared from Porcine Small Intestinal Submucosa

Abstract

Infants and children born with severe cardiac valve lesions have no effective long term treatment options since currently available tissue or mechanical prosthetic valves have sizing limitations and no avenue to accommodate the growth of the pediatric patient. Tissue engineered heart valves (TEHVs) which could provide for growth, self-repair, infection resistance, and long-term replacement could be an ideal solution. Porcine small intestinal submucosa (PSIS) has recently emerged as a potentially attractive bioscaffold for TEHVs. PSIS may possess the ability to recruit endogenous cardiovascular cells, leading to phenotypically-matched replacement tissue when the scaffold has completely degraded. Our group has successfully implanted custom-made PSIS valves in 4 infants with critical valve defects in whom standard bioprosthetic or mechanical valves were not an option. Short term clinical follow-up has been promising. However, no hydrodynamic data has been reported to date on these valves. The purpose of this study was to assess the functional effectiveness of tri-leaflet PSIS bioscaffolds in the aortic position compared to standard tri-leaflet porcine bioprosthetic valves. Hydrodynamic evaluation of acute PSIS function was conducted using a left heart simulator in our laboratory. Our results demonstrated similar flow and pressure profiles (p > 0.05) between the PSIS valves and the control valves. However, forward flow energy losses were found to be significantly greater (p < 0.05) in the PSIS valves compared to the controls possibly as a result of stiffer material properties of PSIS relative to glutaraldehyde-fixed porcine valve tissue. Our findings suggest that optimization of valve dimensions and shape may be important in accelerating de novo valve tissue growth and avoidance of long-term complications associated with higher energy losses (e.g. left ventricular hypertrophy). Furthermore, long term animal and clinical studies will be needed in order to conclusively address somatic growth potential of PSIS valves.

http://ift.tt/2h3LVBu

Fourier Transform Infrared Spectroscopic Imaging-Derived Collagen Content and Maturity Correlates with Stress in the Aortic Wall of Abdominal Aortic Aneurysm Patients

Abstract

Abdominal aortic aneurysm (AAA) is a degenerative disease of the aorta characterized by severe disruption of the structural integrity of the aortic wall and its major molecular constituents. From the early stages of disease, elastin in the aorta becomes highly degraded and is replaced by collagen. Questions persist as to the contribution of collagen content, quality and maturity to the potential for rupture. Here, using our recently developed Fourier transform infrared imaging spectroscopy (FT-IRIS) method, we quantified collagen content and maturity in the wall of AAA tissues in pairs of specimens with different wall stresses. CT scans of AAAs from 12 patients were used to create finite element models to estimate stress in different regions of tissue. Each patient underwent elective repair of the AAA, and two segments of the AAA tissues from anatomic regions more proximal or distal with different wall stresses were evaluated by histology and FT-IRIS after excision. For each patient, collagen content was generally greater in the tissue location with lower wall stress, which corresponded to the more distal anatomic regions. The wall stress/collagen ratio was greater in the higher stress region compared to the lower stress region (1.01 ± 1.09 vs. 0.55 ± 0.084, p = 0.02). The higher stress region also corresponded to the location with reduced intraluminal thrombus thickness. Further, collagen maturity tended to decrease with increased collagen content (p = 0.068, R = 0.38). Together, these results suggest that an increase in less mature collagen content in AAA patients does not effectively compensate for the loss of elastin in the aortic wall, and results in a reduced capability to endure wall stresses.

http://ift.tt/2i8GUFc

A case of liver hemangioma with markedly reduced tumor size after metformin treatment: a case report

Abstract

A 52-year-old man with a 9-year history of hepatic hemangioma was treated with the anti-diabetic drug metformin, resulting in complete remission of the tumor. In 2006, a hemangioma with diameter of 20 × 25 mm was detected incidentally in the liver. The results of imaging studies including ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI) were all compatible with that of hepatic hemangioma. The patient consequently underwent imaging annually from 2006 to 2015. The tumor size increased slightly, to 30 × 35 mm in 2012; however, the general tumor characteristics in imaging were not changed. Beginning May 2012, metformin (750 mg/day) was administered because of an increase in blood sugar and hemoglobin A1c levels. After the start of metformin treatment, the tumor size on US gradually decreased. Finally, in October 2015, the tumor was no longer detected. Dynamic CT study also demonstrated markedly reduced tumor size, with a decrease of 2–3 mm in diameter. These results indicate that metformin treatment strongly suppressed cell proliferation in liver hemangioma. The anti-angiogenic effect of metformin was indicated as a possible cause of the reduction in tumor size.

http://ift.tt/2h3Pasp

A case of gastrojejunocolic fistula with steatohepatitis

Abstract

A man in his 30s, who had undergone retrocolic Billroth II reconstruction for perforated duodenal ulcer, presented with watery diarrhea for 2 years and suspected fatty liver. He was referred to our hospital for management of chronic diarrhea, weight loss, hepatopathy and hypoalbuminemia. Initial upper and lower gastrointestinal endoscopies were negative. Since a small bowel lesion was suspected, peroral single-balloon enteroscopy was performed, which identified feces-like residue near the Billroth II anastomotic site and a connection to the colon separate from the afferent and efferent loops. Transanal single-balloon enteroscopy identified a fistula between the gastrojejunal anastomosis and transverse colon, with the scope reaching the stomach transanally. Barium enema confirmed flow of contrast medium from the transverse colon through the fistula to the anastomotic site, allowing the diagnosis of gastrojejunocolic fistula. Liver biopsy showed relatively severe steatohepatitis (Brunt's classification: stage 2–3, grade 3). Resection of the anastomotic site and partial transverse colectomy were performed to remove the fistula, followed by Roux-en-Y reconstruction. Postoperatively, watery diarrhea resolved and the stools became normal. Hepatopathy and hypoproteinemia improved. One year later, liver biopsy showed marked improvement of steatosis. This case demonstrated marked improvement of both diarrhea/nutritional status and steatohepatitis after treatment of gastrojejunocolic fistula, suggesting that the fistula caused non-alcoholic steatohepatitis.

http://ift.tt/2i8uCge

Alpha-fetoprotein-producing esophageal adenocarcinoma: a mimicker of hepatocellular carcinoma

Abstract

Alpha-fetoprotein (AFP)-producing esophageal adenocarcinoma (EAC) is a rare occurrence. Elevation of serum AFP is commonly associated with hepatocellular carcinoma and yolk sac tumors, but rarely with esophageal carcinoma. Here, we report a rare case of AFP-producing EAC. A 51-year-old man presented with two weeks of acid reflux and a 35-lb weight loss. Laboratory data were notable for transaminitis and AFP was 2524 ng/mL. Computed tomography of the abdomen revealed abnormal thickening of the esophagus and multiple metastatic masses throughout the liver. Biopsy of one of the masses revealed adenocarcinoma of gastrointestinal origin. Subsequent upper endoscopy revealed an esophageal mass with biopsy notable for ulcerated dysplastic glandular mucosa with likely underlying malignancy. The patient underwent palliative esophageal stent placement but died two months later. Elevated AFP levels are an unusual occurrence in EAC. Prognosis is poor given its advanced presenting stage and high metastatic potential. Most cases are unsuccessfully treated with surgery and chemotherapy. Serial measurement of serum AFP may be useful for monitoring clinical status and treatment response. Clinicians should consider AFP-producing EAC in their differential diagnosis in the work-up of a liver mass in the setting of elevated AFP or liver function impairment, especially in the absence of chronic liver disease.

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News from the field

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Entry of severe fever with thrombocytopenia syndrome virus

Abstract

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a globe-shaped virus covered by a dense icosahedral array of glycoproteins Gn/Gc that mediate the attachment of the virus to host cells and the fusion of viral and cellular membranes. Several membrane factors are involved in virus entry, including C-type lectins and nonmuscle myosin heavy chain IIA. The post-fusion crystal structure of the Gc protein suggests that it is a class II membrane fusion protein, similar to the E/E1 protein of flaviviruses and alphaviruses. The virus particles are internalized into host cell endosomes through the clathrin-dependent pathway, where the low pH activates the fusion of the virus with the cell membrane. With information from studies on other bunyaviruses, herein we will review our knowledge of the entry process of SFTSV.

http://ift.tt/2i2Sd68

Characterization of two monoclonal antibodies, 38F10 and 44D11, against the major envelope fusion protein of Helicoverpa armigera nucleopolyhedrovirus

Abstract

The envelope fusion protein F of baculoviruses is a class I viral fusion protein which play a significant role during virus entry into insect cells. F is initially synthesized as a precursor (F₀) and then cleaved into a disulfide-linked F₁ and F₂ subunits during the process of protein maturation and secretion. To facilitate further investigation into the structure and function of F protein during virus infection, monoclonal antibodies (mAbs) against the F₂ subunit of Helicoverpa armigera nucleopolyhedrovirus (HearNPV) (HaF) were generated. Two kinds of mAbs were obtained according to their different recognition epitopes: one kind of mAbs, as represented by 38F10, recognizes amino acid (aa) 85 to 123 of F₂ and the other kind, represented by 44D11, recognizes aa 148 to 173 of F₂. Western blot and immunofluorescence assay confirmed that both of the mAbs recognized the F protein expressed in HearNPV infected cells, however, only 44D11 could neutralize HearNPV infection. The results further showed that 44D11 may not interact with a receptor binding epitope, rather it was demonstrated to inhibit syncytium formation in cells expressing the HaF protein. The results imply that the monoclonal antibody 44D11 recognizes a region within HaF2 that may be involved in the F-mediated membrane fusion process.

http://ift.tt/2i2KeGa

Population Pharmacokinetic Approach Applied to Positron Emission Tomography: Computed Tomography for Tumor Tissue Identification in Patients with Glioma

Abstract

Background and Aims

18F-fluoro-ethyl-tyrosine (FET) is a radiopharmaceutical used in positron emission tomography (PET)-computed tomography in patients with glioma. We propose an original approach combining a radiotracer-pharmacokinetic exploration performed at the voxel level (three-dimensional pixel) and voxel classification to identify tumor tissue. Our methodology was validated using the standard FET-PET approach and magnetic resonance imaging (MRI) data acquired according to the current clinical practices.

Methods

FET-PET and MRI data were retrospectively analyzed in ten patients presenting with progressive high-grade glioma. For FET-PET exploration, radioactivity acquisition started 15 min after radiotracer injection, and was measured each 5 min during 40 min. The tissue segmentation relies on population pharmacokinetic modeling with dependent individuals (voxels). This model can be approximated by a linear mixed-effects model. The tumor volumes estimated by our approach were compared with those determined with the current clinical techniques, FET-PET standard approach (i.e., a cumulated value of FET signal is computed during a time interval) and MRI sequences (T1 and T2/fluid-attenuated inversion recovery [FLAIR]), used as references. The T1 sequence is useful to identify highly vascular tumor and necrotic tissues, while the T2/FLAIR sequence is useful to isolate infiltration and edema tissue located around the tumor.

Results

With our kinetic approach, the volumes of tumor tissue were larger than the tissues identified by the standard FET-PET and MRI T1, while they were smaller than those determined with MRI T2/FLAIR.

Conclusion

Our results revealed the presence of suspected tumor voxels not identified by the standard PET approach.

http://ift.tt/2i8DYZm

A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Normal or Reduced Hepatic Function

Abstract

Objective

The aim of this study was to evaluate the pharmacokinetics (PK) of trastuzumab emtansine (T-DM1) and relevant analytes in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer and hepatic impairment.

Methods

Patients were enrolled in three independent parallel cohorts based on hepatic function per Child–Pugh criteria: normal hepatic function, mild hepatic impairment, and moderate hepatic impairment. Patients received T-DM1 3.6 mg/kg intravenously every 3 weeks. PK samples were collected during cycles 1 and 3, and the PK of T-DM1 and relevant analytes were characterized and compared across cohorts.

Results

Compared with patients with normal hepatic function (n = 10), T-DM1 clearance at cycle 1 was 1.8- and 4.0-fold faster in the mild (n = 10) and moderate (n = 8) cohorts, respectively. The trend of faster clearance was less apparent in cycle 3, with similar T-DM1 clearance across cohorts (mean ± standard deviation 8.16 ± 3.27 [n = 9], 9.74 ± 3.62 [n = 7], and 8.99 and 10.2 [individual values, n = 2] mL/day/kg for the normal, mild, and moderate cohorts, respectively). T-DM1 clearance at cycle 1 correlated significantly with baseline albumin, aspartate aminotransferase, and HER2 extracellular domain concentrations (p < 0.05). Plasma concentrations of DM1 and DM1-containing catabolites were low and were comparable across cohorts.

Conclusions

No increase in systemic DM1 concentration was observed in patients with mild or moderate hepatic impairment versus those with normal hepatic function. The faster T-DM1 clearance observed at cycle 1 in patients with hepatic impairment appeared to be transient. After repeated dosing (three cycles), T-DM1 exposure in patients with mild and moderate hepatic impairment was within the range seen in those with normal hepatic function.

http://ift.tt/2h3Oa80

CYP2C8 Genotype Significantly Alters Imatinib Metabolism in Chronic Myeloid Leukaemia Patients

Abstract

Objective

The aims of this study were to determine the effects of the CYP2C8*3 and *4 polymorphisms on imatinib metabolism and plasma imatinib concentrations in chronic myeloid leukaemia (CML) patients.

Methods

We genotyped 210 CML patients from the TIDELII trial receiving imatinib 400–800 mg/day for CYP2C8*3 (rs11572080, rs10509681) and *4 (rs1058930). Steady-state trough total plasma N-desmethyl imatinib (major metabolite):imatinib concentration ratios (metabolic ratios) and trough total plasma imatinib concentrations were compared between genotypes (one-way ANOVA with Tukey post hoc).

Results

CYP2C8*3 (n = 34) and *4 (n = 15) carriers had significantly higher (P < 0.01) and lower (P < 0.01) metabolic ratios, respectively, than CYP2C8*1/*1 (n = 147) patients (median ± standard deviation: 0.28 ± 0.08, 0.18 ± 0.06 and 0.22 ± 0.08, respectively). Plasma imatinib concentrations were consequently > 50% higher for CYP2C8*1/*4 than for CYP2C8*1/*1 and CYP2C8*3 carriers (2.18 ± 0.66 vs. 1.45 ± 0.74 [P < 0.05] and 1.36 ± 0.98 μg/mL [P < 0.05], respectively).

Conclusions

CYP2C8 genotype significantly alters imatinib metabolism in patients through gain- and loss-of-function mechanisms.

http://ift.tt/2i8DYsk

Roux-en-Y Gastric Bypass Versus Sleeve Gastrectomy as Revisional Procedures after Adjustable Gastric Band: 5-Year Outcomes

Abstract

Introduction

In 2013, a worldwide bariatric surgery survey showed that laparoscopic adjustable gastric banding (LAGB) has been abandoned in favor of laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-y gastric bypass (LRYGBP).

Purpose

The aim of this study was to compare results of LRYGBP and LSG performed as a revisional procedure after LAGB.

Materials and Methods

All patients converted from LAGB to LSG or to LRYGBP from January 2007 to December 2011 were included in the study. Clinical data collected were age, gender, indications for revision, complications, body mass index (BMI), and body weight at revisional procedures. Weight loss was calculated at 1, 3, and 5 years after conversion.

Results

Fifty-one patients were included in this study, 43 females and 8 males. Twenty-four patients were converted to LRYGBP (LRYGBP group) and 27 to LSG (LSG group). Indication for conversion was weight loss failure in 34 (67%) patients and band complications in 17 (33%) patients. No significant difference in age, BMI, and body weight in the two groups was found at the time of revision. One patient converted to LRYGBP had an internal hernia; one patient initially scheduled for LSG was intraoperatively converted to LRYGBP due to staple line leak. No other major perioperative complication was observed. Follow-up rate at 5 years was 84.3% (43 patients out of 51 patients) Delta-BMI and percentage of excess weight loss (%EWL) were not significantly different in the two groups at 1, 3, and 5 years (p > 0.05).

Conclusion

LRYGBP or LSG are feasible and effective surgical options after LAGB. Satisfactory weight loss was achieved after both procedures.

http://ift.tt/2hN4qsx

Weight Loss Analysis According to Different Formulas after Sleeve Gastrectomy With or Without Antral Preservation: a Randomised Study

Abstract

Background

The measurement of weight loss after bariatric surgery is under constant review in order to obtain the ideal standard for reporting weight loss. Several formulas have been proposed for this purpose. Our goal is to analyse weight loss after sleeve gastrectomy, with or without antrum preservation through different measurement formulas.

Methods

A prospective randomised study of 60 patients (30 patients with initial section at 3 cm from pylorus and 30 patients at 8 cm from the pylorus). We calculate the following variables at 3, 6 and 12 months from surgery: BMI, excess weight loss (%EWL), percentage of excess of BMI loss (%PEBMIL), expected BMI, % PEBMIL corrected by EBMI and percentage of total weight loss (%TWL).

Results

Weight evolution is similar in both groups, reaching a mean BMI of 33.62 ± 4.35 and 34.48 ± 4.23 kg/m² respectively 12 months after surgery, closer to expected BMI. TWL follows the same trend, with losses exceeding 30%, although 3 cm group is above the tables of percentiles made with our series. Regarding PEBMIL, the 3 cm group reaches 67.8% classified as excellent, while 8 cm group reaches 62.8% classified as a good result. EWL situates the best results for 3 cm group.

Conclusions

Group 3 cm obtained a lower percentage of suboptimal results using EWL. %TWL places the 3 cm group in higher percentile than 8 cm group. Through EBMI, both groups are equally effective. It is necessary to have standardised dynamic tables for each surgical technique, becoming essential elements to measure weight loss after surgery.

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Erratum to: Effects of Neighborhood Walkability on Physical Activity and Sedentary Behavior Long-Term Post-Bariatric Surgery

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Depression During Pregnancy and Adverse Birth Outcomes Among Predominantly Puerto Rican Women

Abstract

Objectives To examine associations between depression and preterm birth and small-for gestational age (SGA) among women of predominantly Puerto Rican descent, a population who experiences disparities in adverse birth outcomes and one of the highest infant mortality rates in the United States. Methods Proyecto Buena Salud (PBS) was a prospective cohort study conducted from 2006 to 2011 at a large tertiary care center in Western Massachusetts. Caribbean Islander (i.e., Puerto Rican and Dominican Republic) women were interviewed in early, mid and late pregnancy. Among 1262 participants, associations between depression, assessed using the Edinburgh Postnatal Depression Scale, and risk of preterm birth and small-for-gestational age (SGA) were evaluated. Results Women with at least probable minor depression [odds ratio (OR) = 1.77 (95% confidence interval (CI) = 1.02, 3.07)] or probable major depression [OR = 1.82 (95% CI = 1.01, 3.25)] in mid-pregnancy had an increased risk of SGA compared to non-depressed women in adjusted analyses. Borderline significant associations were observed between increasing levels of depressive symptom scores in early and mid-pregnancy [OR = 1.05 (95% CI = 1.00, 1.11) and OR = 1.04 (95% CI = 1.00, 1.09), respectively] and each additional trimester of exposure to probable major depression across mid- to late pregnancy [OR = 1.66 (95% CI = 1.00, 2.74)] and SGA. Late pregnancy depression was not associated with SGA; depression during pregnancy was not associated with preterm birth. Conclusions for Practice In this population of predominantly Puerto Rican women, mid-pregnancy depression increased risk for SGA. Findings can inform culturally appropriate, targeted interventions to identify and treat pregnant women with depression.

http://ift.tt/2gViApm

Application of Activated Biomaterial in the Rapid Start-up and Stable Operation of Biological Processes for Removal Cadmium from Effluent

Abstract

With the aim of treating effluent containing Cd²⁺, a low-cost and efficient technique has been established in this work. By a combination of sulfate-reducing bacteria (SRB), carboxymethyl konjac glucomannan (CMKGM), and nickel–iron bimetallic (Ni/Fe) nanoparticles, we greatly enhanced Cd²⁺ removal and bacteria resistance to metals toxicity. Furthermore, it had much higher removal efficiencies (99.72%) than SRB (57.38%), CMKGM (52.46%), and Ni/Fe (58.91%) systems after 48 h in the treat processes. The parameters effecting Cd²⁺ removal of this system were obtained: the initial Cd²⁺ concentrations 150 mg/L, optimum pH 7.0, optimum temperature 37 °C, optimum time 48 h, respectively. CMKGM and SRB played significant roles in Cd²⁺ adsorption as they contained many functional groups on their surfaces. In addition, SRB promoted the degeneration of inorganic contaminants. The mechanism of adsorption was clarified by a serious of analysis. Overall, this study provided a highly efficient activated biomaterial for the practical treatment of Cd²⁺ in wastewater.

http://ift.tt/2hO0c6m

A Community-Based Outreach Navigator Approach to Establishing Partnerships for a Safety Net Mammography Screening Center

Abstract

Washington, DC, has one of the highest incidence and mortality rates for breast cancer in the USA. Patient navigation coupled with informational and community resources are important strategies that assist patients' access and help them understand the complex world of cancer care. The Georgetown Lombardi Comprehensive Cancer Center's Capital Breast Care Center (CBCC) is a safety net mammography screening center that utilizes a community-based navigation program. In addition to providing assistance with coordination of clinical services, navigators at CBCC are integral in establishing intra-community partnerships to educate members of the community about breast cancer screening. The aim of this study was to detail the role of patient navigation at the CBCC, with an emphasis on community engagement and community-based partnerships. We describe the process by which CBCC established partnerships with multiple community organizations between 2004 and 2015 and analyzed data of women screened in relationship to the evolution of the patient navigation services. Application of the CBCC navigation model that integrates individual patient outreach with community engagement has yielded viable and lasting community partnerships that have resulted in an increase in mammography uptake, especially among medically underserved minority women.

http://ift.tt/2h3GS3X