Abdominal fascia dehiscence: is there a connection to a special microbial spectrum?

INTRODUCTION: Acute fascia dehiscence (FD) is a threatening complication occurring in 0.4-3.5% of cases after abdominal surgery. Prolonged hospital stay, increased mortality and increased rate of incisional hernias could be following consequences. Several risk factors are controversially discussed. Even though surgical infection is a known, indisputable risk factor, it is still not proven if a special spectrum of pathogens is responsible. In this study, we investigated if a specific spectrum of microbial pathogens is associated with FD. METHODS: We performed a retrospective matched pair analysis of 53 consecutive patients with an FD after abdominal surgery in 2010-2016. Matching criteria were gender, age, primary procedure and surgeon. The primary endpoint was the frequency of pathogens detected intraoperatively, the secondary endpoint was the occurrence of risk factors in patients with (FD) and without (nFD) FD. RESULTS: Intraabdominal pathogens were detected more often in the FD group (p = 0.039), with a higher number of Gram-positive pathogens. Enterococci were the most common pathogen (p = 0.002), not covered in 73% (FD group) compared to 22% (nFD group) by the given antibiotic therapy. Multivariable analysis showed detection of Gram-positive pathogens, detection of enterococci in primary laparotomy beside chronic lung disease, surgical site infections and continuous steroid therapy as independent risk factors. CONCLUSION: Risk factors are factors that reduce wound healing or increase intra-abdominal pressure. Furthermore detection of Gram-positive pathogens especially enterococci was detected as an independent risk factor and its empirical coverage could be advantageous for high-risk patients.

Serum C-reactive protein level after ventral hernia repair with mesh reinforcement can predict infectious complications: a retrospective cohort study.

PURPOSE: Infectious complications (ICs) after mesh-reinforced ventral hernioplasty often lead to prolonged and complicated hospitalizations. As early diagnosis and management can mitigate complications, early prediction is important. Our aim was to determine whether postoperative blood tests are valuable predictors of IC. METHODS: We retrospectively analyzed 373 patients who underwent conventional ventral hernioplasty with mesh augmentation between 2008 and 2011. The clinical outcome was correlated with postoperative serum C-reactive protein (CRP) and white blood cell counts (WBC) and assessed by area under the curve (AUC) analysis of the receiver operating characteristics curve. RESULTS: ICs occurred in 51 (13.7%) patients, who required further management. Among these, 48 patients developed a procedure-related complication, the most frequent being surgical site infection (n = 44). The infections appeared after a median postoperative delay of 12 days. Serum CRP was superior to WBC in the prediction of a complicated course. A maximum CRP < 105 mg/L on postoperative day (POD) 2 or 3 had the highest negative predictive value (NPV; 100%) in ruling out ICs [positive predictive value (PPV) 29%; sensitivity 100%; specificity 55%]. The PPV for occurrence of IC improved each day after surgery, reaching up to 46% on POD 5 or 6 for a CRP cut-off of 63.2 mg/L (NPV 93%; sensitivity 69%; specificity 83%). The AUC was 0.80 at both time points. CONCLUSIONS: Our results indicate that postoperative serum CRP allows for early prediction of the postoperative course. Low CRP during the initial PODs is associated with lower risk of ICs. Higher levels on POD 5 or 6 behoove close surveillance.

Radiation therapy and immunotherapy-a potential combination in cancer treatment.

Background: Radiation therapy (rt) is a longstanding treatment modality for cancer. In addition, immune checkpoint blockade has been a significant development in the field of immunotherapy, modifying key immunosuppressive pathways of cancer cells. Methods: The aim of the present work was to review current concepts of rt and immunotherapy synergism, the abscopal effect, and the molecular effects of rt in the tumour microenvironment, its influence on immune stimulation, and potential clinical outcomes that might evolve from ongoing studies. We also discuss potential predictors of clinical response. Results: Up-to-date literature concerning the mechanisms, interactions, and latest knowledge about rt and immunotherapy was reviewed and summarized, and is presented here. Conclusions: The possibility of using hyperfractionated rt to combine an abscopal effect with the enhanced effect of immune treatment using checkpoint blockade is a very promising method for future tumour treatments.

Absolute timing of the photoelectric effect.

Photoemission spectroscopy is central to understanding the inner workings of condensed matter, from simple metals and semiconductors to complex materials such as Mott insulators and superconductors1. Most state-of-the-art knowledge about such solids stems from spectroscopic investigations, and use of subfemtosecond light pulses can provide a time-domain perspective. For example, attosecond (10-18 seconds) metrology allows electron wave packet creation, transport and scattering to be followed on atomic length scales and on attosecond timescales2-7. However, previous studies could not disclose the duration of these processes, because the arrival time of the photons was not known with attosecond precision. Here we show that this main source of ambiguity can be overcome by introducing the atomic chronoscope method, which references all measured timings to the moment of light-pulse arrival and therefore provides absolute timing of the processes under scrutiny. Our proof-of-principle experiment reveals that photoemission from the tungsten conduction band can proceed faster than previously anticipated. By contrast, the duration of electron emanation from core states is correctly described by semiclassical modelling. These findings highlight the necessity of treating the origin, initial excitation and transport of electrons in advanced modelling of the attosecond response of solids, and our absolute data provide a benchmark. Starting from a robustly characterized surface, we then extend attosecond spectroscopy towards isolating the emission properties of atomic adsorbates on surfaces and demonstrate that these act as photoemitters with instantaneous response. We also find that the tungsten core-electron timing remains unchanged by the adsorption of less than one monolayer of dielectric atoms, providing a starting point for the exploration of excitation and charge migration in technologically and biologically relevant adsorbate systems.

mTORC1 Controls Phase Separation and the Biophysical Properties of the Cytoplasm by Tuning Crowding.

Macromolecular crowding has a profound impact on reaction rates and the physical properties of the cell interior, but the mechanisms that regulate crowding are poorly understood. We developed genetically encoded multimeric nanoparticles (GEMs) to dissect these mechanisms. GEMs are homomultimeric scaffolds fused to a fluorescent protein that self-assemble into bright, stable particles of defined size and shape. By combining tracking of GEMs with genetic and pharmacological approaches, we discovered that the mTORC1 pathway can modulate the effective diffusion coefficient of particles ≥20 nm in diameter more than 2-fold by tuning ribosome concentration, without any discernable effect on the motion of molecules ≤5 nm. This change in ribosome concentration affected phase separation both in vitro and in vivo. Together, these results establish a role for mTORC1 in controlling both the mesoscale biophysical properties of the cytoplasm and biomolecular condensation.

[Enterococci and surgical site infections : Causal agent or harmless commensals?] / Enterokokken und postoperative Wundinfektionen : Verursacher oder harmloser Kommensale?

BACKGROUND: The role of enterococci in the context of peritonitis and surgical site infections (SSI) has not yet been definitively clarified but enterococci are being detected more frequently. Numerous resistances reduce the available antibiotic options. OBJECTIVE: This article gives an overview of the pathogenic importance of enterococci and of current recommendations for therapy and prophylaxis. On the basis of our own data we discuss the relevance of enterococci for SSI. MATERIAL AND METHODS: All colorectal resections carried out between January 2008 and September 2016 were retrospectively documented. Revision surgery, SSI and intra-abdominally or subcutaneously detected pathogens were recorded. RESULTS: A total of 2713 interventions were evaluated with 28.3% having primary peritonitis. In 587 patients (21.6%) SSI followed, and pathogen determination was possible in 431 cases (73.4%). Enterococci were frequently found in re-operations (58.4%) and SSI (46.1%), with E. faecalis and E. faecium in approximately equal proportions. If intra-abdominal enterococci were detectable in patients with primary peritonitis, it was more common to develop SSI and enterococci were more frequently detected subcutaneously. Enterococci in SSI were found to be significantly more frequent in left hemicolectomies as well as in pre-existing renal insufficiency. CONCLUSION: It can be inferred that enterococci are not adequately covered by commonly used perioperative antibiotic therapy or preoperative prophylaxis, which increases the risk for SSI by enterococci. This could be favored by selection of these pathogens due to the use of antibiotics without enterococcal efficacy (e. g. cephalosporins). The consideration in the choice of perioperative antibiotic prophylaxis by the additional administration of ampicillin or vancomycin could be advantageous.

Impact of reaction parameters on the chemical profile of 3,4-methylenedioxymethamphetamine synthesized via reductive amination: target analysis based on GC-qMS compared to non-targeted analysis based on GC×GC-TOF-MS.

The most common clandestine manufacturing procedure for the ecstasy derivative 3,4-methylenedioxymethamphetamine (MDMA), is the reductive amination of piperonylmethylketone (PMK) via platinum(IV) oxide/hydrogen. Deviations of the reaction conditions during the synthesis may result in different chemical profiles of the products. The chemical analysis of these profiles is an important objective for forensic drug intelligence. In this work we studied the impact of a systematic variation of the hydrogenation time, the reaction temperature and the precursor batch on the resulting organic chemical profiles of the MDMA bases and MDMA hydrochlorides. Target analysis was based on a gas chromatography mass spectrometry (GC-MS) method which was harmonized during the European project CHAMP.(2) In addition, samples were analyzed by comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry (GC×GC-TOFMS) and subjected to non-targeted data analysis for a comprehensive analysis of the complete profiles. The reaction temperature, followed by the used precursor batch, revealed the highest impact on the chemical profile. The effect on individual impurity compounds is discussed in detail. With respect to the interpretation of the data, the profiles were compared to the profiles of MDMA samples obtained by reductive amination using sodium borohydride ("cold method") and aluminium/mercury amalgam as alternative reducing agents. Non-targeted analysis revealed that the discrimination according to the synthetic route and the batch of precursor used for the synthesis strongly depends on the selected target compounds.

Treatment of astrocytoma grade III with Photofrin II as a radiosensitizer. A case report.

INTRODUCTION: Astrocytomas are neoplasms that originate from glial cells. Anaplastic astrocytoma is classified as WHO III, with 27 % of the individuals with grade III astrocytoma living for at least 5 years even after treatment (radiation and chemotherapy). Photofrin II has been demonstrated to serve as a specific and selective radiosensitizing agent in both in vitro and in vivo tumor models. MATERIAL AND METHODS: This case report presents a woman suffering from an inoperable astrocytoma WHO III since 2004. The patient was treated with radiation therapy and Photofrin II as a radiosensitiser. The patient underwent irradiation with 40 + 20 Gy boost. The patient was given a single intravenous dose of 1 mg/kg Photofrin II 24 h prior to the initiation of radiation therapy. RESULTS: The patient is still alive without any significant side effect with a follow up of 106 months. MRI shows no evidence of disease. CONCLUSION: The follow-up results are encouraging regarding the application of Photofrin II as an effective radiosensitizing agent in the treatment of inoperable WHO III astrocytoma.

Forensic profiling of sassafras oils based on comprehensive two-dimensional gas chromatography.

Safrole, the main compound in the essential oil of several plants of the Laurel family (Lauraceae), and its secondary product piperonylmethylketone are the predominantly used precursors for the illicit synthesis of 3,4-methylenedioxymethamphetamine (MDMA) which is, in turn, the most common active ingredient in Ecstasy tablets. Analytical methods with adequate capacity to identify links and origin of precursors, such as safrole, provide valuable information for drug-related police intelligence. Authentic sassafras oil samples from police seizures were subjected to comparative analysis based on their chemical profiles obtained by comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry (GC × GC-TOFMS). The enhanced separation power and increased sensitivity of GC × GC allowed for the detection of minor compounds present in the essential oils which were of particular interest in case of very pure samples whose impurity profiles were not very pronounced. Discrimination of such samples was still possible even in the absence of characteristic main compounds.

Cinnamon extract inhibits degranulation and de novo synthesis of inflammatory mediators in mast cells.

BACKGROUND: Mast cells (MC) are main effector cells of allergic and other inflammatory reactions; however, only a few anti-MC agents are available for therapy. It has been reported that cinnamon extract (CE) attenuates allergic symptoms by affecting immune cells; however, its influence on MC was not studied so far. Here, we analyzed the effects of CE on human and rodent MC in vitro and in vivo. METHODS: Expression of MC-specific proteases was examined in vivo in duodenum of mice following oral administration of CE. Release of mediators and phosphorylation of signaling molecules were analyzed in vitro in human MC isolated from intestinal tissue (hiMC) or RBL-2H3 cells challenged with CE prior to stimulation by FcεRI cross-linking. RESULTS: Following oral treatment with CE, expression of the mast cell proteases MCP6 and MC-CPA was significantly decreased in mice. In hiMC, CE also caused a reduced expression of tryptase. Moreover, in hiMC stimulated by IgE cross-linking, the release of ß-hexosaminidase was reduced to about 20% by CE. The de novo synthesis of cysteinyl leukotrienes, TNFα, CXCL8, CCL2, CCL3, and CCL4, was almost completely inhibited by CE. The attenuation of mast cell mediators by CE seems to be related to particular signaling pathways, because we found that activation of the MAP kinases ERK, JNK, and p38 as well as of Akt was strongly reduced by CE. CONCLUSION: CE decreases expression of mast cell-specific mediators in vitro and in vivo and thus is a new plant-originated candidate for anti-allergic therapy.

16(th) IHIW: population global distribution of killer immunoglobulin-like receptor (KIR) and ligands.

In the last fifteen years, published reports have described KIR gene-content frequency distributions in more than 120 populations worldwide. However, there have been limited studies examining these data in aggregate to detect overall patterns of variation at regional and global levels. Here, we present a summary of the collection of KIR gene-content data for 105 worldwide populations collected as part of the 15th and 16th International Histocompatibility and Immunogenetics Workshops, and preliminary results for data analysis.

Graft failure in the modern era of allogeneic hematopoietic SCT.

Graft failure may contribute to increased morbidity and mortality after allogeneic hematopoietic SCT (allo-HSCT). Here, we present risk factors for graft failure in all first allo-HSCTs performed at our center from 1995 to mid-2010 (n=967). Graft failure was defined as >95% recipient cells any time after engraftment with no signs of relapse, or re-transplantation because of primary or secondary neutropenia (<0.5 × 10(9)/L) and/or thrombocytopenia (<30 × 10(9)/L). Fifty-four patients (5.6%) experienced graft failure. The majority were because of autologous reconstitution (n=43), and only a few patients underwent re-transplantation because of primary (n=6) or secondary (n=5) graft failures. In non-malignant disorders, graft failure had no effect on survival, whereas in malignant disease graft failure was associated with reduced 5-year survival (22 vs 53%, P<0.01). In multivariate analysis, ex vivo T-cell depletion (relative risk (RR) 8.82, P<0.001), HLA-mismatched grafts (RR 7.64, P<0.001), non-malignant disorders (RR 3.32, P<0.01) and reduced-intensity conditioning (RR 2.58, P<0.01) increased the risk for graft failure, whereas graft failures were prevented by total nucleated cell doses of ≥ 2.5 × 10(8)/kg (RR 0.36, P<0.01). In conclusion, graft failure was only associated with inferior survival in malignant disease. Non-malignant disorders, HLA match, conditioning intensity, immunosuppression regimen and cell dose all influenced graft failure risk.

[Value of positron emission tomography and computer tomography (PET/CT) for urologic malignancies]. / Intérêt de la tomographie par émission de positons couplée à la scanographie (TEP/TDM) dans les cancers urologiques.

Positron emission tomography is a functional imaging technique that allows the detection of the regional metabolic rate, and is often coupled with other morphological imaging technique such as computed tomography. The rationale for its use is based on the clearly demonstrated fact that functional changes in tumor processes happen before morphological changes. Its introduction to the clinical practice added a new dimension in conventional imaging techniques. This review presents the current and proposed indications of the use of positron emission/computed tomography for prostate, bladder and testes, and the potential role of this exam in radiotherapy planning.

Global requirements for DNA sample collections: results of a survey of 204 ethics committees in 40 countries.

The Industry Pharmacogenomics Working Group has an interest in attaining a better understanding of global requirements for sample collections intended for pharmacogenetics research. To have adequately powered pharmacogenetics studies representative of the clinical trial population, it is important to collect DNA samples from a majority of consenting study participants under many institutional review board/ethics committee (IRB/EC) jurisdictions. A survey was distributed to gather information from local and central IRBs/ECs. The survey included questions related to the approval of pharmacogenetics studies, collection and banking of samples, and return of data to subjects. A total of 204 responses were received from global IRBs/ECs with pharmacogenetic experience. The data show that requirements for approval of pharmacogenetic research differ between IRBs/ECs within and between countries but not between regions of the United States. A better understanding of differing requirements should facilitate global sample collection of DNA for pharmacogenetics research and may provide the basis for harmonized regulations for collection of genetic samples in the future.

Positron Emission Tomography and Computer Tomography (PET/CT) in Prostate, Bladder, and Testicular Cancers

Positron emission computed tomography (PET) is a functional, noninvasive method for imaging regional metabolic processes that is nowadays most often combined to morphological imaging with computed tomography (CT). Its use is based on the well-founded assumption that metabolic changes occur earlier in tumors than morphologic changes, adding another dimension to imaging. This article will review the established and investigational indications and radiopharmaceuticals for PET/CT imaging for prostate cancer, bladder cancer and testicular cancer, before presenting upcoming applications in radiation therapy.

Identification of a novel KIR3DL1*072 allele by sequence-based typing.

We report a novel KIR3DL1*072 allele that was found using a sequence-based typing approach.

Curcumin as an anti-cancer agent: review of the gap between basic and clinical applications.

Curcumin, commonly called diferuloyl methane, is a hydrophobic polyphenol derived from rhizome (turmeric) of the herb Curcuma longa. Extensive research over the last half century has revealed important functions of curcumin. In vitro and in vivo research has shown various activities, such as anti-inflammatory, cytokines release, antioxidant, immunomodulatory, enhancing of the apoptotic process, and anti-angiogenic properties. Curcumin has also been shown to be a mediator of chemo-resistance and radio-resistance. The anti-cancer effect has been seen in a few clinical trials, mainly as a native chemoprevention agent in colon and pancreatic cancer, cervical neoplasia and Barrets metaplasia. Some clinical studies with healthy volunteers revealed a low bioavailability of curcumin, casting doubt on the use of curcumin only as food additive. Our clinical experience with curcumin, along with the anti-metabolite gemcitabine in the treatment of patients with advanced pancreatic carcinoma, produced an objective response in less than 10% of patients, with a minor effect on survival. However, the safety of this combination was proved. Curcumin's potent anti-proliferative activity interacting with several intracellular signal transduction pathways may potentiate the anti-tumor effect of gemcitabine. The preclinical data lead to various, but still scarce, clinical studies (some on-going) that demonstrated the possible efficacy of this treatment as a chemopreventive or chemotherapeutic agent. This review will focus on the clinical evidence, including our experience with curcumin as a chemopreventive and therapeutic agent and the in vitro background results.