Heparin-induced thrombocytopenia presenting as splenic hemorrhage following cardiac surgery: a case report.

BACKGROUND: Heparin-induced thrombocytopenia with thrombosis (HITT) is a paradoxical prothrombotic complication of anticoagulant therapy. As many as 3% of patients undergoing cardiac surgery develop clinical HIT presenting as thrombocytopenia with or without thrombosis within 5-10 days of heparin exposure. Thrombotic complications associated with HIT carry a mortality rate of 5-10%. CASE PRESENTATION: We report a case of atraumatic splenic hemorrhage due to splenic vein thrombosis as the main indicator of HIT following cardiac surgery in a 62-year-old woman. She presented to the emergency department on day nine following coronary artery bypass graft surgery with acute weakness, dizziness, and malaise. Her evaluation in the emergency department found anemia and thrombocytopenia. A coagulation profile revealed a markedly elevated d-dimer. She underwent a computed tomography scan of the chest, abdomen and pelvis for suspected bleed and was found to have splenic vein thrombosis, right atrial filling defects consistent with atrial thrombus and mild to moderate hemoperitoneum. Surgical consultation was obtained due to splenic hemorrhage. Hematology was consulted on post-operative day 10, however, she unfortunately developed left sided weakness concerning for stroke. A magnetic resonance imaging scan of the brain demonstrated infarct involving distribution of the right anterior cerebral artery. A transesophageal echocardiogram demonstrated a large immobile thrombus within the right atrium with a second, mobile thrombus arising from the left tricuspid valve annulus. Due to a 4Ts score of 7 and markedly positive platelet factor 4 (PF4) IgG antibody a serotonin release assay was not performed given the high probability of HIT. She was cautiously treated with bivalirudin and was transitioned to warfarin anticoagulation. In the following days her platelet count recovered and 3 months later a transthoracic echocardiogram revealed solution of the intracardiac thrombi. CONCLUSIONS: Atraumatic splenic hemorrhage is an unusual presentation of HIT that is reminiscent of the rare bilateral adrenal hemorrhage due to adrenal necrosis that also occurs in HIT. Alternative anticoagulation is the mainstay of therapy for HIT despite hemorrhage, given the underlying acquired hypercoagulability. Despite similarities of the presentation between splenic hemorrhage and bilateral adrenal hemorrhage, splenic hemorrhage is rarely described in the literature. HIT should be considered in patients presenting with thrombocytopenia following cardiac surgery

The Culture of Primary Motor and Sensory Neurons in Defined Media on Electrospun Poly-L-lactide Nanofiber Scaffolds

Electrospinning is a technique for producing micro- to nano-scale fibers. Fibers can be electrospun with varying degrees of alignment, from highly aligned to completely random. In addition, fibers can be spun from a variety of materials, including biodegradable polymers such as poly-L-lactic acid (PLLA). These characteristics make electrospun fibers suitable for a variety of scaffolding applications in tissue engineering. Our focus is on the use of aligned electrospun fibers for nerve regeneration. We have previously shown that aligned electrospun PLLA fibers direct the outgrowth of both primary sensory and motor neurons in vitro. We maintain that the use of a primary cell culture system is essential when evaluating biomaterials to model real neurons found in vivo as closely as possible. Here, we describe techniques used in our laboratory to electrospin fibrous scaffolds and culture dorsal root ganglia explants, as well as dissociated sensory and motor neurons, on electrospun scaffolds. However, the electrospinning and/or culture techniques presented here are easily adapted for use in other applications

Heritability of overlapping impulsivity and compulsivity dimensional phenotypes

Funder: David Winston Turner Endowment FundAbstract: Impulsivity and compulsivity are traits relevant to a range of mental health problems and have traditionally been conceptualised as distinct constructs. Here, we reconceptualised impulsivity and compulsivity as partially overlapping phenotypes using a bifactor modelling approach and estimated heritability for their shared and unique phenotypic variance within a classical twin design. Adult twin pairs (N = 173) completed self-report questionnaires measuring psychological processes related to impulsivity and compulsivity. We fitted variance components models to three uncorrelated phenotypic dimensions: a general impulsive–compulsive dimension; and two narrower phenotypes related to impulsivity and obsessiveness.There was evidence of moderate heritability for impulsivity (A2 = 0.33), modest additive genetic or common environmental effects for obsessiveness (A2 = 0.25; C2 = 0.23), and moderate effects of common environment (C2 = 0.36) for the general dimension, This general impulsive–compulsive phenotype may reflect a quantitative liability to related mental health disorders that indexes exposure to potentially modifiable environmental risk factors

Role and possible mechanisms of clenbuterol in enhancing reverse remodelling during mechanical unloading in murine heart failure

Aims Combined left ventricular assist device (LVAD) and pharmacological therapy has been proposed to favour myocardial recovery in patients with end-stage heart failure (HF). Clenbuterol (Clen), a b 2 -adrenoceptor (b 2 -AR) agonist, has been used as a part of this strategy. In this study, we investigated the direct effects of clenbuterol on unloaded myocardium in HF. Methods and results Left coronary artery ligation or sham operation was performed in male Lewis rats. After 4-6 weeks, heterotopic abdominal transplantation of the failing hearts into normal recipients was performed to induce LV unloading (UN). Recipient rats were treated with saline (Sal) or clenbuterol (2 mg/kg/day) via osmotic minipumps (HF þ UN þ Sal or HF þ UN þ Clen) for 7 days. Non-transplanted HF animals were treated with Sal (Sham þ Sal, HF þ Sal) or clenbuterol (HF þ Clen). LV myocytes were isolated and studied using optical, fluorescence, and electrophysiological techniques. Conclusion Clenbuterol treatment of failing rat hearts, alone or in combination with mechanical unloading, improves LV function at the whole-heart and cellular levels by affecting cell morphology, excitation-contraction coupling, and myofilament sensitivity to calcium. This study supports the use of this drug in the strategy to enhance recovery in HF patients treated with LVADs and also begins to elucidate some of the possible cellular mechanisms responsible for the improvement in LV function

Outcomes from a 12-Week, Open-Label, Multicenter Clinical Trial of Teduglutide in Pediatric Short Bowel Syndrome

Objective To determine safety and pharmacodynamics/efficacy of teduglutide in children with intestinal failure associated with short bowel syndrome (SBS-IF). Study design This 12-week, open-label study enrolled patients aged 1-17 years with SBS-IF who required parenteral nutrition (PN) and showed minimal or no advance in enteral nutrition (EN) feeds. Patients enrolled sequentially into 3 teduglutide cohorts (0.0125 mg/kg/d [n = 8], 0.025 mg/kg/d [n = 14], 0.05 mg/kg/d [n = 15]) or received standard of care (SOC, n = 5). Descriptive summary statistics were used. Results All patients experienced ≥1 treatment-emergent adverse event; most were mild or moderate. No serious teduglutide-related treatment-emergent adverse events occurred. Between baseline and week 12, prescribed PN volume and calories (kcal/kg/d) changed by a median of −41% and −45%, respectively, with 0.025 mg/kg/d teduglutide and by −25% and −52% with 0.05 mg/kg/d teduglutide. In contrast, PN volume and calories changed by 0% and −6%, respectively, with 0.0125 mg/kg/d teduglutide and by 0% and −1% with SOC. Per patient diary data, EN volume increased by a median of 22%, 32%, and 40% in the 0.0125, 0.025, and 0.05 mg/kg/d cohorts, respectively, and by 11% with SOC. Four patients achieved independence from PN, 3 in the 0.05 mg/kg/d cohort and 1 in the 0.025 mg/kg/d cohort. Study limitations included its short-term, open-label design, and small sample size. Conclusions Teduglutide was well tolerated in pediatric patients with SBS-IF. Teduglutide 0.025 or 0.05 mg/kg/d was associated with trends toward reductions in PN requirements and advancements in EN feeding in children with SBS-IF

Statin therapy inhibits remyelination in the central nervous system

Remyelination of lesions in the central nervous system contributes to neural repair following clinical relapses in multiple sclerosis. Remyelination is initiated by recruitment and differentiation of oligodendrocyte progenitor cells (OPCs) into myelinating oligodendrocytes. Simvastatin, a blood-brain barrier-permeable statin in multiple sclerosis clinical trials, has been shown to impact the in vitro processes that have been implicated in remyelination. Animals were fed a cuprizone-supplemented diet for 6 weeks to induce localized demyelination in the corpus callosum; subsequent return to normal diet for 3 weeks stimulated remyelination. Simvastatin was injected intraperitoneally during the period of coincident demyelination and OPC maturation (weeks 4 to 6), throughout the entire period of OPC responses (weeks 4 to 9), or during the remyelination-only phase (weeks 7 to 9). Simvastatin treatment (weeks 4 to 6) caused a decrease in myelin load and both Olig2(strong) and Nkx2.2(strong) OPC numbers. Simvastatin treatment (weeks 4 to 9 and 7 to 9) caused a decrease in myelin load, which was correlated with a reduction in Nkx2.2(strong) OPCs and an increase in Olig2(strong) cells, suggesting that OPCs were maintained in an immature state (Olig2(strong)/Nkx2.2(weak)). NogoA+ oligodendrocyte numbers were decreased during all simvastatin treatment regimens. Our findings suggest that simvastatin inhibits central nervous system remyelination by blocking progenitor differentiation, indicating the need to monitor effects of systemic immunotherapies that can access the central nervous system on brain tissue-repair processes

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Artificial intelligence for photovoltaic systems

Photovoltaic systems have gained an extraordinary popularity in the energy generation industry. Despite the benefits, photovoltaic systems still suffer from four main drawbacks, which include low conversion efficiency, intermittent power supply, high fabrication costs and the nonlinearity of the PV system output power. To overcome these issues, various optimization and control techniques have been proposed. However, many authors relied on classical techniques, which were based on intuitive, numerical or analytical methods. More efficient optimization strategies would enhance the performance of the PV systems and decrease the cost of the energy generated. In this chapter, we provide an overview of how Artificial Intelligence (AI) techniques can provide value to photovoltaic systems. Particular attention is devoted to three main areas: (1) Forecasting and modelling of meteorological data, (2) Basic modelling of solar cells and (3) Sizing of photovoltaic systems. This chapter will aim to provide a comparison between conventional techniques and the added benefits of using machine learning methods

RAIphy: Phylogenetic classification of metagenomics samples using iterative refinement of relative abundance index profiles

Background: Computational analysis of metagenomes requires the taxonomical assignment of the genome contigs assembled from DNA reads of environmental samples. Because of the diverse nature of microbiomes, the length of the assemblies obtained can vary between a few hundred bp to a few hundred Kbp. Current taxonomic classification algorithms provide accurate classification for long contigs or for short fragments from organisms that have close relatives with annotated genomes. These are significant limitations for metagenome analysis because of the complexity of microbiomes and the paucity of existing annotated genomes. Results: We propose a robust taxonomic classification method, RAIphy, that uses a novel sequence similarity metric with iterative refinement of taxonomic models and functions effectively without these limitations. We have tested RAIphy with synthetic metagenomics data ranging between 100 bp to 50 Kbp. Within a sequence read range of 100 bp-1000 bp, the sensitivity of RAIphy ranges between 38%-81% outperforming the currently popular composition-based methods for reads in this range. Comparison with computationally more intensive sequence similarity methods shows that RAIphy performs competitively while being significantly faster. The sensitivityspecificity characteristics for relatively longer contigs were compared with the PhyloPythia and TACOA algorithms. RAIphy performs better than these algorithms at varying clade-levels. For an acid mine drainage (AMD) metagenome, RAIphy was able to taxonomically bin the sequence read set more accurately than the currently available methods, Phymm and MEGAN, and more accurately in two out of three tests than the much more computationally intensive method, PhymmBL. Conclusions: With the introduction of the relative abundance index metric and an iterative classification method, we propose a taxonomic classification algorithm that performs competitively for a large range of DNA contig lengths assembled from metagenome data. Because of its speed, simplicity, and accuracy RAIphy can be successfully used in the binning process for a broad range of metagenomic data obtained from environmental samples

Optical Atomic Clock Comparison through Turbulent Air

We use frequency comb-based optical two-way time-frequency transfer (O-TWTFT) to measure the optical frequency ratio of state-of-the-art ytterbium and strontium optical atomic clocks separated by a 1.5 km open-air link. Our free-space measurement is compared to a simultaneous measurement acquired via a noise-cancelled fiber link. Despite non-stationary, ps-level time-of-flight variations in the free-space link, ratio measurements obtained from the two links, averaged over 30.5 hours across six days, agree to $6\times10^{-19}$, showing that O-TWTFT can support free-space atomic clock comparisons below the $10^{-18}$ level