Differential Susceptibility to Propofol and Ketamine in Primary Cultures of Young and Senesced Astrocytes.

The adverse effects of general anesthesia on the long-term cognition of young children and senior adults have become of concern in recent years. Previously, mechanistic and pathogenic investigations focused on neurons, and little is known about the effect of commonly used intravenous anesthetics such as propofol and ketamine on astrocytes. Recently, astrocyte dysfunction has been implicated in a wide range of age-related brain diseases. In this study, we examined the survival and viability of both young and senescent astrocytes in culture after adding propofol and ketamine to the media at varying strengths. Oxidative stimulus was applied to commercially available fetal cell lines of human astrocytes in vitro to induce morphological changes in cellular senescence. Our results indicate that propofol reduces the survival of young astrocytes as compared to controls, as well as to ketamine. These effects were seen in comparisons of total cell count and at both high and low dose concentrations. High doses of propofol also significantly reduced cell viability compared to those exposed to baseline controls and ketamine. Senescent astrocytes, on the other hand, demonstrated cell count reductions as compared to baseline controls and ketamine when exposed to either DMSO or propofol. The data show differential susceptibility of young astrocytes to propofol than to ketamine. The observed cell count reduction may be related to the adverse effects of propofol on mitochondrial function and free radical production, as described in previous studies. We speculate that ketamine may have a more favorable safety profile in infants and young children.

Algae and indigenous bacteria consortium in treatment of shrimp wastewater: A study for resource recovery in sustainable aquaculture system.

Shrimp production facilities produce large quantities of wastewater, which consists of organic and inorganic pollutants. High concentrations of these pollutants in shrimp wastewater cause serious environmental problems and, therefore, a method of treating this wastewater is an important research topic. This study investigated the impact of algae and indigenous bacteria on treating shrimp wastewater. A total of four different microalgae cultures, including Chlorococcum minutus, Porphyridum cruentum, Chlorella vulgaris and Chlorella reinhardtii along with two cyanobacterial cultures, Microcystis aeruginosa and Fishcherella muscicola were used with indigenous bacterial cultures to treat shrimp wastewater. The highest soluble chemical oxygen demand (sCOD) removal rate (95%) was observed in the samples that were incubated using F. muscicola. Total dissolved nitrogen was degraded >90% in the C. vulgaris, M. aeruginosa, and C. reinhardtii seeded samples. Dissolved organic nitrogen removal was significantly higher for C. vulgaris (93%) as compared to other treatments. Similarly, phosphate degradation was very successful for all the algae-bacteria consortium (>99%). Moreover, the degradation kinetics were calculated, and the lowest half-life (t1/2) for sCOD (5 days) was recorded for the samples seeded with M. aeruginosa. Similarly, treatment with F. muscicola and C. reinhardtii showed the lowest t1/2 of NH3-N (2.9 days) and phosphate (2.7 days) values. Overall, the results from this study suggest that the symbiotic relationship between indigenous bacteria and algae significantly enhanced the process of shrimp wastewater treatment within 21 days of incubation. The outcome of this study supports resource recovery in the aquaculture sector and could be beneficial to treat a large-scale shrimp facility's wastewater worldwide.

Traffic light optimization with low penetration rate vehicle trajectory data.

Traffic light optimization is known to be a cost-effective method for reducing congestion and energy consumption in urban areas without changing physical road infrastructure. However, due to the high installation and maintenance costs of vehicle detectors, most intersections are controlled by fixed-time traffic signals that are not regularly optimized. To alleviate traffic congestion at intersections, we present a large-scale traffic signal re-timing system that uses a small percentage of vehicle trajectories as the only input without reliance on any detectors. We develop the probabilistic time-space diagram, which establishes the connection between a stochastic point-queue model and vehicle trajectories under the proposed Newellian coordinates. This model enables us to reconstruct the recurrent spatial-temporal traffic state by aggregating sufficient historical data. Optimization algorithms are then developed to update traffic signal parameters for intersections with optimality gaps. A real-world citywide test of the system was conducted in Birmingham, Michigan, and demonstrated that it decreased the delay and number of stops at signalized intersections by up to 20% and 30%, respectively. This system provides a scalable, sustainable, and efficient solution to traffic light optimization and can potentially be applied to every fixed-time signalized intersection in the world.

Peripheral Nerve Blocks for Cesarean Delivery Analgesia: A Narrative Review.

Effective postoperative analgesia using multimodal approach improves maternal and neonatal outcomes after cesarean delivery. The use of neuraxial approach (local anesthetic and opioids) and intravenous adjunctive drugs, such as nonsteroidal anti-inflammatory drugs and acetaminophen, currently represents the standard regimen for post-cesarean delivery analgesia. Peripheral nerve blocks may be considered in patients who are unable to receive neuraxial techniques; these blocks may also be used as a rescue technique in selected patients. This review discusses the relevant anatomy, current evidence, and advantages and disadvantages of the various peripheral nerve block techniques. Further research is warranted to compare the analgesic efficacy of these techniques, especially newer blocks (e.g., quadratus lumborum blocks and erector spinae plane blocks). Moreover, future studies should determine the safety profile of these blocks (e.g., fascial plane blocks) in the obstetric population because of its increased susceptibility to local anesthetic toxicity.

Current and Potential Applications of Green Membranes with Nanocellulose.

Large-scale applications of nanotechnology have been extensively studied within the last decade. By exploiting certain advantageous properties of nanomaterials, multifunctional products can be manufactured that can contribute to the improvement of everyday life. In recent years, one such material has been nanocellulose. Nanocellulose (NC) is a naturally occurring nanomaterial and a high-performance additive extracted from plant fibers. This sustainable material is characterized by a unique combination of exceptional properties, including high tensile strength, biocompatibility, and electrical conductivity. In recent studies, these unique properties of nanocellulose have been analyzed and applied to processes related to membrane technology. This article provides a review of recent synthesis methods and characterization of nanocellulose-based membranes, followed by a study of their applications on a larger scale. The article reviews successful case studies of the incorporation of nanocellulose in different types of membrane materials, as well as their utilization in water purification, desalination, gas separations/gas barriers, and antimicrobial applications, in an effort to provide an enhanced comprehension of their capabilities in commercial products.

The relationship of diabetic retinopathy severity scales with frequency and surface area of diabetic retinopathy lesions.

PURPOSE: To assess the relationship between qualitative diabetic retinopathy (DR) scales with the precise numbers and surface area of DR lesions within the Early Treatment Diabetic Retinopathy Study (ETDRS) standard seven field (S7F) region on ultrawide-field (UWF) color fundus images. METHODS: In this study, we collected UWF images from adult patients with diabetes. Poor-quality images and eyes with any pathology precluding assessment of DR severity were excluded. The DR lesions were manually segmented. DR severity was graded according to the International Clinical Diabetic Retinopathy (ICDR) and AA protocol by two masked graders within the ETDRS S7F. These lesions' numbers and surface area were computed and correlated against the DR scores using the Kruskal-Wallis H test. Cohen's Kappa was performed to determine the agreement between two graders. RESULTS: One thousand five hundred and twenty eyes of 869 patients (294 females, 756 right eyes) with a mean age of 58.7 years were included. 47.4% were graded as no DR, 2.2% as mild non-proliferative DR (NPDR), 24.0% as moderate NPDR, 6.3% as severe NPDR, and 20.1% as proliferative DR (PDR). The area and number of DR lesions generally increased as the ICDR level increased up to severe NPDR, but decreased from severe NPDR to PDR. There was perfect intergrader agreement on the DR severity. CONCLUSION: A quantitative approach reveals that DR lesions' number and area generally correlate with ICDR-based categorical DR severity levels with an increasing trend in the number and area of DR lesions from mild to severe NPDR and a decrease from severe NPDR to PDR.

Complementary and alternative medicine mention and recommendations in inflammatory bowel disease guidelines: systematic review and assessment using AGREE II.

BACKGROUND: Many patients with inflammatory bowel disease (IBD) use complementary and alternative medicine (CAM) for disease management. There is, however, a communication gap between patients and healthcare professionals regarding CAM use, where patients are hesitant to disclose CAM use to providers. The purpose of this study was to identify the quantity and assess the quality of CAM recommendations in IBD clinical practice guidelines (CPGs) using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument. METHODS: MEDLINE, EMBASE, and CINAHL were systematically searched from 2011 to 2022 to find CPGs for the treatment and/or management of IBD. The Guidelines International Network (GIN) and National Center for Complementary and Integrative Health (NCCIH) websites were also searched. Eligible CPGs were assessed using the AGREE II instrument. RESULTS: Nineteen CPGs made CAM recommendations for IBD and were included in this review. Average scaled domain percentages of CPGs were as follows (overall CPG, CAM section): scope and purpose (91.5%, 91.5%), clarity of presentation (90.3%, 64.0%), editorial independence (57.0%, 57.0%), stakeholder involvement (56.7%, 27.8%), rigour of development (54.7%, 45.9%), and applicability (14.6%, 2.1%). CONCLUSIONS: The majority of CPGs with CAM recommendations were of low quality and their CAM sections scored substantially lower relative to other therapies in the overall CPG. In future updates, CPGs with low scaled-domain percentages could be improved in accordance with AGREE II and other guideline development resources. Further research investigating how CAM therapies can best be incorporated into IBD CPGs is warranted.

Peripapillary Vitreous Traction Syndrome: Expanding the Spectrum of Anterior Optic Neuropathies.

BACKGROUND: Peripapillary vitreous traction (PVT) occurring without any underlying eye disease has been contemplated as a distinct entity from nonarteritic ischemic optic neuropathy (NAION) for many years and is sometimes difficult to differentiate from classical NAION. We report 6 new cases to analyze the clinical features of PVT syndrome that would expand the clinical spectrum of anterior optic neuropathies. METHODS: Prospective case series. RESULTS: PVT syndrome seems to affect optic discs with a small area with a small cup-to-disc (C/D) ratio. The C/D ratio does not significantly increase in the chronic stage, as in NAION. Vitreous traction without detachment can either lead to mild retinal nerve fiber layer (RNFL) injury with attendant ganglion cell layer/inner plexiform layer (GCL/IPL) thinning in 29% or no injury at all in 71%. Eighty-six percent had good visual acuity (VA) and had no relative afferent pupillary defect (RAPD), whereas 14% had a transient RAPD; 71% had no color defect. Vitreous detachment after a period of severe and persistent traction can lead to more damage to the optic nerve head and RNFL that may look like NAION. Our hypothesized mechanically induced injury to the superficial optic nerve head may not lead to much visual impairment. In our study, no further therapeutic interventions were required. CONCLUSIONS: Based on our analysis of previously published cases and our own prospective case series of 6 patients, the PVT syndrome falls within the spectrum of anterior optic neuropathies, often affecting small optic discs with a small C/D ratio. Vitreous traction can lead to a partial or complete anterior optic neuropathy. The PVT syndrome may be a "more" anterior optic neuropathy distinct from classical NAION.

High Dosage of Patient-Controlled Epidural Analgesia (PCEA) with Low Background Infusion during Labor: A Randomized Controlled Trial.

BACKGROUND: Patient-controlled epidural analgesia (PCEA) is well documented; however, it is unclear whether a high dosage of PCEA with a low dosage of background infusion during labor can be a safe and effective application. METHODS: Group LH was administered a continuous infusion (CI) of 0.084 mL/kg/h with PCEA of 5 mL every 40 min. Group HL was given a CI of 0.028 mL/kg/h and PCEA of 10 mL every 40 min; Group HH was given a CI of 0.084 mL/kg/h and PCEA of 10 mL every 40 min. The primary outcomes were VAS pain score, the number of supplemental boluses, incidence of pain outbreaks, drug dose for pain outbreaks, PCA times, effective PCA times, anesthetic consumption, duration of analgesia, duration of labor and delivery outcome. Secondary outcomes included adverse reactions such as itching, nausea and vomiting during analgesia and neonatal Apgar scores 1 min and 5 min after birth. RESULTS: A total of 180 patients, 60 in each group were randomly assigned to one of three groups included group LH, group HL or group HH. The VAS scores were obviously decreased in HL group and HH group in comparison with LL group at 2 h after analgesia and the time point of full cervical dilation and delivery of baby. The time for third stage of labor in HH group was increased compared with LH group and HL group. Incidence of pain outbreaks in LH group was obviously increased compared with HL and HH group. The effective PCA times in HL group and HH group were remarkably reduced compared with those in LH group. CONCLUSIONS: High dose of PCEA with a low background infusion can reduce effective PCA times, incidence of outbreak pain and the total amount of anesthetics without diminishing analgesia effects. However, high dose of PCEA with a high background infusion can enhance analgesia effect but increase the third stage of labor, instrumental delivery ratio and the total amount of anesthetics.

Learning naturalistic driving environment with statistical realism.

For simulation to be an effective tool for the development and testing of autonomous vehicles, the simulator must be able to produce realistic safety-critical scenarios with distribution-level accuracy. However, due to the high dimensionality of real-world driving environments and the rarity of long-tail safety-critical events, how to achieve statistical realism in simulation is a long-standing problem. In this paper, we develop NeuralNDE, a deep learning-based framework to learn multi-agent interaction behavior from vehicle trajectory data, and propose a conflict critic model and a safety mapping network to refine the generation process of safety-critical events, following real-world occurring frequencies and patterns. The results show that NeuralNDE can achieve both accurate safety-critical driving statistics (e.g., crash rate/type/severity and near-miss statistics, etc.) and normal driving statistics (e.g., vehicle speed/distance/yielding behavior distributions, etc.), as demonstrated in the simulation of urban driving environments. To the best of our knowledge, this is the first time that a simulation model can reproduce the real-world driving environment with statistical realism, particularly for safety-critical situations.

Dense reinforcement learning for safety validation of autonomous vehicles.

One critical bottleneck that impedes the development and deployment of autonomous vehicles is the prohibitively high economic and time costs required to validate their safety in a naturalistic driving environment, owing to the rarity of safety-critical events1. Here we report the development of an intelligent testing environment, where artificial-intelligence-based background agents are trained to validate the safety performances of autonomous vehicles in an accelerated mode, without loss of unbiasedness. From naturalistic driving data, the background agents learn what adversarial manoeuvre to execute through a dense deep-reinforcement-learning (D2RL) approach, in which Markov decision processes are edited by removing non-safety-critical states and reconnecting critical ones so that the information in the training data is densified. D2RL enables neural networks to learn from densified information with safety-critical events and achieves tasks that are intractable for traditional deep-reinforcement-learning approaches. We demonstrate the effectiveness of our approach by testing a highly automated vehicle in both highway and urban test tracks with an augmented-reality environment, combining simulated background vehicles with physical road infrastructure and a real autonomous test vehicle. Our results show that the D2RL-trained agents can accelerate the evaluation process by multiple orders of magnitude (103 to 105 times faster). In addition, D2RL will enable accelerated testing and training with other safety-critical autonomous systems.

Sevoflurane Exposure of Clinical Doses in Pregnant Rats Induces Vcan Changes without Significant Neural Apoptosis in the Offspring.

Background and Objectives: Sevoflurane is a commonly used inhalational anaesthetic in clinics. Prolonged exposure to sevoflurane can induce significant changes in lipid metabolism and neuronal damage in the developing brain. However, the effect of exposure of pregnant rats to clinical doses of sevoflurane remains unclear. Materials and Methods: Twenty-eight pregnant rats were randomly and equally divided into sevoflurane exposure (S) group, control (C) and a blank group at gestational day (G) 18; Rats in S group received 2% sevoflurane with 98% oxygen for 6 h in an anesthetizing chamber, while C group received 100% oxygen at an identical flow rate for 6 h in an identical chamber. Partial least squares discriminant analysis (PLS-DA), ultra performance liquid chromatography/time-of-flight mass spectrometry(UPLC/TOF-MS) and MetaboAnalyst were used to analysis acquire metabolomics profiles, and immunohistochemical changes of neuronalapoptosis in hippocampus and cortex of neonatal rats were also analyzed. Results: This study aimed to explore lipidomics and transcriptomics changes related to 2% sevoflurane exposure for 6 h in the developing brains of newborn offspring rats. Ultra-performance liquid chromatography/time-of-flight mass spectrometry (UPLC/TOF-MS) and RNA sequencing (RNA-seq) analyses were used to acquire metabolomics and transcriptomics profiles. We used RNA-seq to analyse the expression of the coding and non-coding transcripts in neural cells of the cerebral cortex. No significant differences in arterial oxygen tension (PaO2), arterial carbon dioxide tension (PaCO2), or arterial blood gas were found between the groups. The relative standard deviation (RSD) of retention times was <1.53%, and the RSDs of peak areas ranged from 2.13% to 8.51%. Base peak chromatogram (BPC) profiles showed no differences between the groups. We evaluated the partial least square-discriminant analysis (PLS-DA) model. In negative ion mode, R2X was over 70%, R2Y was over 93%, and Q2 (cum) was over 80%. Cell apoptosis was not remarkably enhanced by TUNEL and haematoxylin and eosin (HE) staining in the sevoflurane-exposed group compared to the control group (p > 0.05). Glycerophospholipid (GP) and sphingolipid metabolism disturbances might adversely influence neurodevelopment in offspring. The expression of mRNAs (Vcan gene, related to neuronal development, function and repair) of the sevoflurane group was significantly increased in the differential genes by qRT-PCR verification. Conclusions: GP and sphingolipid metabolism homeostasis may be potential therapeutic approaches against inhalational anaesthetic-induced neurodegenerative disorders. Meanwhile, sevoflurane-induced Vcan changes indicated some lipidomic and transcriptomic changes, even if neural cell apoptosis was not significantly changed in the usual clinical dose of sevoflurane exposure.

Hemoglobin-Based Oxygen Carriers: Where Are We Now in 2023?

The pursuit for blood a substitute has spanned over a century, but a majority of the efforts have been disappointing. As of today, there is no widely accepted product used as an alternative to human blood in clinical settings with severe anemic condition(s). Blood substitutes are currently also termed oxygen therapeutics. There are two major categories of oxygen therapeutics, hemoglobin-based and perfluorocarbon-based products. In this article, we reviewed the most developed but failed products and products still in active clinical research in the category of hemoglobin-based oxygen carriers. Among all of the discussed hemoglobin-based oxygen therapeutics, HemAssist, PolyHeme, Hemolink, Hemospan, and Hemoximer were discontinued. Hemopure is in clinical use in South Africa and Russia. Oxyglobin, the sister product of Hemopure, has been approved for veterinary use in the European Union and the United States. HemO2life has recently been approved for organ preservation in organ transplantation in the European Union. OxyVita and Sanguinate are still undergoing active clinical studies. The field of oxygen therapeutics seems to be entering a phase of rapid growth in the coming 10-20 years.

Characteristics of bibliometric analyses of the complementary, alternative, and integrative medicine literature: A scoping review protocol.

Background: There is a growing body of literature on complementary, alternative, and integrative medicine (CAIM), which offers a holistic approach to health and the maintenance of social and cultural values. Bibliometric analyses are an increasingly commonly used method employing quantitative statistical techniques to understand trends in a particular scientific field. The objective of this scoping review is to investigate the quantity and characteristics of evidence in relation to bibliometric analyses of CAIM literature. Methods: The following bibliographic databases will be searched: MEDLINE, EMBASE, PsycINFO, AMED, CINAHL, Scopus and Web of Science. Studies published in English, conducting any type of bibliometric analysis involving any CAIM therapies, as detailed by an operational definition of CAIM adopted by Cochrane Complementary Medicine, will be included. Conference abstracts and study protocols will be excluded. The following variables will be extracted from included studies: title, author, year, country, study objective, type of CAIM, health condition targeted, databases searched in the bibliometric analysis, the type of bibliometric variables assessed, how bibliometric information was reported, main findings, conclusions, and limitations. Findings will be summarized narratively, as well as in tabular and graphical format. Conclusions: To the best of our knowledge, this scoping review will be the first to investigate the characteristics of evidence in relation to bibliometric analyses on CAIM literature. The findings of this review may be useful to identify variations in the objectives, methods, and results of bibliometric analyses of CAIM research literature.

Effects of propofol and sevoflurane on T-cell immune function and Th cell differentiation in children with SMPP undergoing fibreoptic bronchoscopy.

OBJECTIVES: The potentially different effects of commonly used anaesthetic agents propofol and sevoflurane on T-cell immune function and Th cell differentiation were investigated in patients with severe mycoplasmal pneumonia (SMPP) undergoing fibreoptic bronchoscopy. METHODS: Sixty children (2-12 years of age) with SMPP were randomized into the sevoflurane group and the propofol group. Patients in the sevoflurane group were anaesthetised with inhalational sevoflurane and intravenous remifentanil. Patients in the propofol group were anaesthetised with intravenous propofol and remifentanil. Patients in both groups underwent fibreoptic bronchoscopy and lavage therapy. We compared the clinical outcomes, cellular immunity function, and Th cell differentiation into Th1 and Th2 levels in both groups. RESULTS: There was no significant difference in clinical outcomes and hospital stay between the two groups (7.94 vs 7.36, p > .05). However, the CD3+ T cells, CD4+ T cells, and CD4+/CD8+ in the propofol group were significantly higher than those in the sevoflurane group (T1 51.96 vs 48.33, T2 58.08 vs 55.31, p < .05). The ratio of Th1/Th2 in the two groups was significantly increased postoperatively in both groups (Sevoflurane 8.53 vs 7.23, Propofol 9.35 vs 7.18), and the propofol group was significantly higher than the sevoflurane group (9.35 vs 8.53, p < .05). CONCLUSIONS: Propofol might have a less inhibitory effect on T lymphocytes in children with SMPP than sevoflurane. And propofol may have less impact on the differentiation of Th cells into Th1 cells and better preserving the Th1/Th2 ratio than sevoflurane. KEY MESSAGESThe pathogenesis of SMPP is still unclear, likely through alveolar infiltration with neutrophils and lymphocytes, lymphocyte/plasma cell infiltrates in the peri-bronchovascular area, and immune dysfunction.Recent experimental and clinical studies showed that sevoflurane might have immunosuppressive effects, and multiple studies confirmed that the immune function of children with SMPP had been reduced.This study found that propofol administered in children with SMPP had a less inhibitory effect on T lymphocytes than inhalational sevoflurane, had little inhibitory effect on the differentiation of Th cells into Th1 cells, and better preserve Th1/Th2 ratio and maintain the balanced immune function.

Radial Hemostasis Is Facilitated With a Potassium Ferrate Hemostatic Patch: The STAT2 Trial.

OBJECTIVES: The aim of this trial was to test whether the potassium ferrate hemostatic patch (PFHP) as an adjunct to the TR Band (TRB) facilitated an early deflation protocol. BACKGROUND: Shorter TRB compression times may reduce the rate of radial artery occlusion (RAO) and reduce observation time after transradial access. METHODS: A total of 443 patients were randomized to the TRB or PFHP + TRB, with complete TRB deflation attempted 60 minutes postprocedure. The primary outcome was the time to successful full deflation of the TRB without bleeding, with secondary outcomes of time to discharge and complications including hematoma, RAO, or bleeding requiring intervention beyond TRB reinflation. RESULTS: Time to complete TRB deflation was 66 ± 14 minutes with the PFHP vs 113 ± 56 minutes for the TRB alone (P < 0.001). Minor rebleeding requiring TRB reinflation was much more frequent without the PFHP (0% vs 67.7%; P < 0.001) with 2.3 ± 1.3 additional reinflation and deflation attempts needed for hemostasis. Hematomas developed in 4.0% of the PFHP group and 6.8% of the TRB group (P = 0.20). RAO was rare (<1%), although 41% of patients received <5,000 U heparin. Among percutaneous coronary intervention patients, time to TRB deflation (68 ± 15 minutes vs 138 ± 62 minutes; P < 0.001) and composite complications (10.0% vs 24.2%; P = 0.04) were reduced with the PFHP. CONCLUSIONS: Compared with the TRB alone, the PFHP facilitated early 60-minute TRB deflation following transradial catheterization, with a numeric reduction in vascular complications. RAO occurs rarely with early deflation regardless of heparin dose. (Comparing TR Band to StatSeal in Conjunction With TR Band II [StatSeal II]; NCT04046952).

In vivo topical gene therapy for recessive dystrophic epidermolysis bullosa: a phase 1 and 2 trial.

Recessive dystrophic epidermolysis bullosa (RDEB) is a lifelong genodermatosis associated with blistering, wounding, and scarring caused by mutations in COL7A1, the gene encoding the anchoring fibril component, collagen VII (C7). Here, we evaluated beremagene geperpavec (B-VEC), an engineered, non-replicating COL7A1 containing herpes simplex virus type 1 (HSV-1) vector, to treat RDEB skin. B-VEC restored C7 expression in RDEB keratinocytes, fibroblasts, RDEB mice and human RDEB xenografts. Subsequently, a randomized, placebo-controlled, phase 1 and 2 clinical trial (NCT03536143) evaluated matched wounds from nine RDEB patients receiving topical B-VEC or placebo repeatedly over 12 weeks. No grade 2 or above B-VEC-related adverse events or vector shedding or tissue-bound skin immunoreactants were noted. HSV-1 and C7 antibodies sometimes presented at baseline or increased after B-VEC treatment without an apparent impact on safety or efficacy. Primary and secondary objectives of C7 expression, anchoring fibril assembly, wound surface area reduction, duration of wound closure, and time to wound closure following B-VEC treatment were met. A patient-reported pain-severity secondary outcome was not assessed given the small proportion of wounds treated. A global assessment secondary endpoint was not pursued due to redundancy with regard to other endpoints. These studies show that B-VEC is an easily administered, safely tolerated, topical molecular corrective therapy promoting wound healing in patients with RDEB.

Anticoagulation with Argatroban in a Patient with Heparin-Induced Thrombocytopenia and Renal Insufficiency Undergoing Orthotopic Heart Transplantation.

Unfractionated heparin is the anticoagulant of choice for cardiac surgery that requires cardiopulmonary bypass. However, it can cause serious side effects like heparin-induced thrombocytopenia (HIT), an immune-mediated process where antibodies are directed against heparin and platelet 4 complexes. In such cases, alternative pharmacologic strategies are implemented to facilitate safe bypass conditions. A woman with severe decompensated heart failure was heparinized for intra-aortic balloon pump and subsequent LVAD placement. On day 6, a fall in platelets from 113,000 to 26,000 was noted. She was diagnosed with HIT. Heparin was discontinued and replaced with an argatroban infusion for the duration of her care until heart transplantation was completed. We review the mechanism, diagnosis, and complications of HIT. We discuss cardiopulmonary bypass and its relation to heparin, HIT, and heparin alternatives. We discuss argatroban's relevant pharmacology, clinical use, advantages, and disadvantages.

New Serotonin-Norepinephrine Reuptake Inhibitors and Their Anesthetic and Analgesic Considerations.

Serotonin-norepinephrine reuptake inhibitors (SNRIs) inhibit the presynaptic neuronal uptake of serotonin and norepinephrine and prolong the effects of the monoamines in the synaptic cleft within the central nervous system, leading to increased postsynaptic receptor activation and neuronal activities. Serotonin-norepinephrine reuptake inhibitors can have multiple clinical indications, including as the first-line agents for the management of depression and anxiety, and as analgesics in the treatment of chronic pain. The effects of reuptake inhibition of norepinephrine and serotonin are often dose-dependent and agent-dependent. There are five FDA-approved serotonin-norepinephrine reuptake inhibitors (desvenlafaxine, duloxetine, levomilnacipran, milnacipran and sibutramine) currently being marketed in the United States. As the COVID-19 pandemic significantly increased the incidence and prevalence of anxiety and depression across the country, there are significantly increased prescriptions of these medications perioperatively. Thus, anesthesiologists are more likely than ever to have patients administered with these agents and scheduled for elective or emergency surgical procedures. A thorough understanding of these commonly prescribed serotonin-norepinephrine reuptake inhibitors and their interactions with commonly utilized anesthetic agents is paramount. There are two potentially increased risks related to the continuation of SNRIs through the perioperative period: intraoperative bleeding and serotonin syndrome. SNRIs have some off-label uses, more new indications, and ever-increasing new applications in perioperative practice. This article aims to review the commonly prescribed serotonin-norepinephrine reuptake inhibitors and the current clinical evidence regarding their considerations in perioperative anesthesia and analgesia.