Intra-individual fasting versus postprandial variation of biochemical markers of liver fibrosis (FibroTest) and activity (ActiTest)

BACKGROUND: Biochemical marker combinations, including α(2)-macroglobulin, haptoglobin, apolipoprotein A1, γ-glutamyl transpeptidase, and total bilirubin (all part of FibroTest) plus alanine aminotransferase (all part of ActiTest), are being developed as alternatives to liver biopsy in patients with chronic hepatitis C and other various chronic liver diseases. Considering this premise, the primary aim of this study was to assess the impact of meal intake on FibroTest and ActiTest results. Such studies are very important for patients, as many clinical errors have been related to the absence of baseline evidence. RESULTS: Intra-individual variation was assessed for the 6 above components and for FibroTest and ActiTest, by measuring time dependent variations before and one hour after a standard meal in 64 subjects. These consisted of 29 healthy volunteers and 35 patients with chronic liver diseases. Meal intake had no significant impact on any of the six components, or on FibroTest or ActiTest, as assessed by repeated measure variance analyses (ANOVA all p > 0.90); the Spearman correlation coefficient ranged from 0.87 (total bilirubin) to 0.995 (γ-glutamyl transpeptidase). The coefficients of variation (CV) between fasting and postprandial measurements fluctuated for the six components from 0.09 (apolipoprotein A1) to 0.14 (α(2)-macroglobulin), and from 0.09 for FibroTest to 0.13 for ActiTest. In contrast, meal intake had a significant impact on triglycerides (ANOVA p = 0.01, CV = 0.65) and glucose (ANOVA p = 0.04, CV = 0.31). As for the prediction of liver injury, the concordance between fasting and postprandial predicted histological stages and grades was almost perfect, both for FibroTest (kappa = 0.91, p < 0.001) and ActiTest (kappa = 0.80, p < 0.001). CONCLUSIONS: The intra-individual variation of biochemical markers was low, and it was shown that measurements of FibroTest, ActiTest and their components are not significantly modified by meal intake. This fact makes the screening of patients at risk of chronic liver diseases more convenient

Facing the outcome of prematurity – opinions from the general practitioner

Preterm birth is a leading cause of neonatal mortality and morbidity, affecting more than 15 million babies worldwide each year. Preterm infants also have higher rates of motor, functional, and cognitive deficits. Modern imaging has contributed significantly to a better understanding of the etiology of various forms of brain injury in neonates. The follow-up of premature newborns is essential to prevent and diminish neurological sequelae in time. A multi-disciplinary team is needed to adequately monitor this category of children, in which the family doctor has a significant role. The variety of adverse events that preterm infants can be exposed to before, during, and after birth poses significant obstacles to developing therapeutic interventions to prevent brain damage, including developmental vulnerability to injury during a particular gestational age. In addition, several procedures required for neonatal critical care, reduce mortality but increase the risk of brain injury. This review is aimed to update the reader about the complications of preterm birth, current therapeutic uses, imaging techniques, as well as present and future research on preterm birth

Synchronous rectal and breast cancer in a 40-year-old woman

Multiple primary malignancies have an increasing incidence in the general population due to better diagnostic tools and the increased life expectancy. However, synchronous lesions are still rare and have a rate which varies between 0,17 and 0,69%. Second primary tumours usually develop after some time from the first cancer diagnosis. Although there is an arsenal of therapeutical options – the order and priority of the therapeutic choices are debatable and need to be tailored to every patient. The present paper illustrates the case of a 40 years old woman who presented to the emergency department with diffuse abdominal pain, nausea and bloating. The patient had done a fine needle biopsy of a suspicious lump in her right breast one week before the presentation and had no other relevant medical history. The CT scan revealed intraperitoneal free liquid with a paracolic mass at the rectosigmoid junction. The surgical team decided to perform an exploratory laparoscopy. At exploration, the mass was intensely adherent to the uterus and fixed to the pelvis. Conversion to laparotomy and extemporaneous exam of the mass were undertaken, which revealed adenocarcinoma. En-bloc rectosigmoidian resection with hysterectomy and bilateral adnexectomy. The histopathology report staged the tumour as pT4N2M0 adenocarcinoma. Breast biopsy pathology report revealed no special type (NST) carcinoma, with luminal B breast cancer on immunohistochemistry. Clinical staging of the breast was cT1N0. After discussion of the case in the multidisciplinary team, it was decided for Madden mastectomy with axillary lymphadenectomy. Breast reconstruction with retropectoral expander was done in the same operating procedure. Post-mastectomy pathology report revealed pT1N0 and no metastases were present at standard imaging. The immunohistochemical profile of the resected breast tumour proved to be Luminal A. Adjuvant therapy consisted in chemoradiation for the rectum. The breast neoplasia was treated with tamoxifen as adjuvant therapy. Synchronous primary neoplasia exists and even if they have a low incidence once identified their treatment requires particular treatment for each case. A multidisciplinary approach is essential

Manganese(III) Porphyrin-based Potentiometric Sensors for Diclofenac Assay in Pharmaceutical Preparations

Two manganese(III) porphyrins: manganese(III) tetraphenylporphyrin chloride and manganese(III)-tetrakis(3-hydroxyphenyl)porphyrin chloride were tested as ionophores for the construction of new diclofenac–selective electrodes. The electroactive material was incorporated either in PVC or a sol–gel matrix. The effect of different plasticizers and additives (anionic and cationic) on the potentiometric response was studied. The best results were obtained for the PVC membrane plasticized with dioctylphtalate and having sodium tetraphenylborate as a lipophilic anionic additive incorporated. The sensor response was linear in the concentration range 3 × 10−6 – 1 × 10−2 M with a slope of −59.7 mV/dec diclofenac, a detection limit of 1.5 × 10−6 M and very good selectivity coefficients. It was used for the determination of diclofenac in pharmaceutical preparations, by direct potentiometry. The results were compared with those obtained by the HPLC reference method and a good agreement was found between the two methods

Achievement of therapeutic antibiotic exposures using Bayesian dosing software in critically unwell children and adults with sepsis

PURPOSE: Early recognition and effective treatment of sepsis improves outcomes in critically ill patients. However, antibiotic exposures are frequently suboptimal in the intensive care unit (ICU) setting. We describe the feasibility of the Bayesian dosing software Individually Designed Optimum Dosing Strategies (ID-ODS™), to reduce time to effective antibiotic exposure in children and adults with sepsis in ICU. METHODS: A multi-centre prospective, non-randomised interventional trial in three adult ICUs and one paediatric ICU. In a pre-intervention Phase 1, we measured the time to target antibiotic exposure in participants. In Phase 2, antibiotic dosing recommendations were made using ID-ODS™, and time to target antibiotic concentrations were compared to patients in Phase 1 (a pre-post-design). RESULTS: 175 antibiotic courses (Phase 1 = 123, Phase 2 = 52) were analysed from 156 participants. Across all patients, there was no difference in the time to achieve target exposures (8.7 h vs 14.3 h in Phase 1 and Phase 2, respectively, p = 0.45). Sixty-one courses in 54 participants failed to achieve target exposures within 24 h of antibiotic commencement (n = 36 in Phase 1, n = 18 in Phase 2). In these participants, ID-ODS™ was associated with a reduction in time to target antibiotic exposure (96 vs 36.4 h in Phase 1 and Phase 2, respectively, p < 0.01). These patients were less likely to exhibit subtherapeutic antibiotic exposures at 96 h (hazard ratio (HR) 0.02, 95% confidence interval (CI) 0.01-0.05, p < 0.01). There was no difference observed in in-hospital mortality. CONCLUSIONS: Dosing software may reduce the time to achieve target antibiotic exposures. It should be evaluated further in trials to establish its impact on clinical outcomes

Optimising Treatment Outcomes for Children and Adults Through Rapid Genome Sequencing of Sepsis Pathogens. A Study Protocol for a Prospective, Multi-Centre Trial (DIRECT)

BackgroundSepsis contributes significantly to morbidity and mortality globally. In Australia, 20,000 develop sepsis every year, resulting in 5,000 deaths, and more than AUD$846 million in expenditure. Prompt, appropriate antibiotic therapy is effective in improving outcomes in sepsis. Conventional culture-based methods to identify appropriate therapy have limited yield and take days to complete. Recently, nanopore technology has enabled rapid sequencing with real-time analysis of pathogen DNA. We set out to demonstrate the feasibility and diagnostic accuracy of pathogen sequencing direct from clinical samples, and estimate the impact of this approach on time to effective therapy when integrated with personalised software-guided antimicrobial dosing in children and adults on ICU with sepsis.MethodsThe DIRECT study is a pilot prospective, non-randomized multicentre trial of an integrated diagnostic and therapeutic algorithm combining rapid direct pathogen sequencing and software-guided, personalised antibiotic dosing in children and adults with sepsis on ICU.Participants and interventionsDIRECT will collect microbiological and pharmacokinetic samples from approximately 200 children and adults with sepsis admitted to one of four ICUs in Brisbane. In Phase 1, we will evaluate Oxford Nanopore Technologies MinION sequencing direct from blood in 50 blood culture-proven sepsis patients recruited from consecutive patients with suspected sepsis. In Phase 2, a further 50 consecutive patients with suspected sepsis will be recruited in whom MinION sequencing will be combined with Bayesian software-guided (ID-ODS) personalised antimicrobial dosing.Outcome measuresThe primary outcome is time to effective antimicrobial therapy, defined as trough drug concentrations above the MIC of the pathogen. Secondary outcomes are diagnostic accuracy of MinION sequencing from whole blood, time to pathogen identification and susceptibility testing using sequencing direct from whole blood and from positive blood culture broth.DiscussionRapid pathogen sequencing coupled with antimicrobial dosing software has great potential to overcome the limitations of conventional diagnostics which often result in prolonged inappropriate antimicrobial therapy. Reduced time to optimal antimicrobial therapy may reduce sepsis mortality and ICU length of stay. This pilot study will yield key feasibility data to inform further, urgently needed sepsis studies. Phase 2 of the trial protocol is registered with the ANZCTR (ACTRN12620001122943).Trial registrationRegistered with the Australia New Zealand Clinical Trials Registry Number ACTRN1262000112294

Design of Mixing Device Shafts Based on a Proposed Calculation Method Supported by Finite Element Method Analysis

The elasticity of bearings as well as their clearance have an essential influence on the total arrow and, therefore, on their own pulsation. In most of the literature, this elasticity is neglected in the calculation of shaft deflections. In some work, the elasticity of the bearings has been taken into account when calculating the deflection of the mixing device shaft, but this has been carried out on the basis of a high degree of customization: the behavior of the bearings has been considered linearly elastic, which does not correspond to reality because according to the elastic response of the bearing, it is a nonlinear function of the radial displacement. When the shaft of a mixing device operates in a pressure vessel, at the outlet of the pressure vessel, the shaft is provided with a sealing device, which can be considered a third bearing. This aspect is also not taken into account in the calculation of the shaft’s deflection, which leads to a certain degree of error in its determination. This study aims to highlight the influence of the elasticity of the bearings and the sealing device on the stiffness of the shaft and to propose a method that supports a calculation program for calculating the elastic line of a vertical cantilever shaft, considering the role played by the bearings in the case that they behave nonlinearly and the sealing device as the third bearing. This problem was solved both by applying our own method and with the help of the FEM

Computational Fluid Dynamics in Solid Earth Sciences–a HPC challenge

Presently, the Solid Earth Sciences started to move towards implementing High Performance Computational (HPC) research facilities. One of the key tenants of HPC is performance, which strongly depends on the interaction between software and hardware. In this paper, they are presented benchmark results from two HPC systems. Testing a Computational Fluid Dynamics (CFD) code specific for Solid Earth Sciences, the HPC system Horus, based on Gigabit Ethernet, performed reasonably well compared with its counterpart CyberDyn, based on Infiniband QDR fabric. However, the HPCC CyberDyn based on low-latency high-speed QDR network dedicated to MPI traffic outperformed the HPCC Horus. Due to the high-resolution simulations involved in geodynamic research studies, HPC facilities used in Earth Sciences should benefit from larger up-front investment in future systems that are based on high-speed interconnects.</p

Extensive unilateral nevus comedonicus without genetic abnormality

Nevus comedonicus is considered a genodermatosis characterized by the presence of multiple groups of dilated pilosebaceous orifices filled with black keratin plugs, with sharply unilateral distribution mostly on the face, neck, trunk, upper arms. Lesions can appear at any age, frequently before the age of 10 years, but they are usually present at birth. We present a 2.7-year-old girl with a very severe form of nevus comedonicus. She exhibited lesions located initially at the left side of the body with a linear characteristic, following Blascko lines T1/T2, T5, T7, S1 /S2, but progressively developed lesions on the right side of the scalp and left gluteal area