Intra-abdominal hypertension in cardiac surgery patients: a multicenter observational sub-study of the Accuryn registry.

Intra-abdominal hypertension (IAH) is frequently present in the critically ill and is associated with increased morbidity and mortality. Conventionally, intermittent 'spot-check' manual measurements of bladder pressure in those perceived as high risk are used as surrogates for intra-abdominal pressure (IAP). True patterns of IAH remain unknown. We explored the incidence of IAH in cardiac surgery patients and describe the intra-and postoperative course of IAP using a novel, high frequency, automated bladder pressure measurement system. Sub-analysis of a prospective, multicenter, observational study (NCT04669548) conducted in three large academic medical centers. Continuous urinary output (CUO) and IAP measurements were observed using the Accuryn Monitoring System (Potrero Medical, Hayward, CA). Data collected included demographics, hemodynamic support, and high-frequency IAP and CUO. One Hundred Thirty-Seven cardiac surgery patients were analyzed intraoperatively and followed 48 h postoperatively in the intensive care unit. Median age was 66.4 [58.3, 72.0] years, and 61% were men. Median Foley catheter dwell time was 56.0 [46.8, 77.5] hours, and median baseline IAP was 6.3 [4.0, 8.1] mmHg. 93% (128/137) of patients were in IAH grade I, 82% (113/137) in grade II, 39% (53/137) in grade III, and 5% (7/137) in grade IV for at least 12 cumulative hours. For maximum consecutive duration of IAH, 84% (115/137) of patients spent at least 12 h in grade I, 62% (85/137) in grade II, 18% (25/137) in grade III, and 2% (3/137) in grade IV IAH. During the first 48 h after cardiac surgery, IAH is common and persistent. Improved and automated monitoring of IAP will increase the detection of IAH-which normally would remain undetected using traditional intermittent monitoring methods.

Erector Spinae Regional Anesthesia for Robotic Coronary Artery Bypass Surgery Is Not Associated With Reduced Postoperative Opioid Use: A Retrospective Observational Study.

OBJECTIVE: Regional anesthesia techniques are gaining traction in cardiac surgery. The aim of this study was to compare the analgesic efficacy of erector spinae plane block catheters (ESPBC), serratus anterior plane block catheters (SAPBC), and paravertebral single-shot block (PVB) versus no block after robotic minimally invasive direct coronary artery bypass (MIDCAB). DESIGN: This was a retrospective observational study of routinely recorded data. SETTING: The study was performed at a single healthcare system. PARTICIPANTS: All patients underwent robotic MIDCAB. INTERVENTION: Data were analyzed from 346 patients during a 53-month period. The clinical data warehouse was queried for all robotic MIDCAB surgeries. Variables abstracted included type of nerve block, age, sex, use of adjuncts, Society of Thoracic Surgeons predicted short length of stay (PSLOS), total opioid consumption during the 72 hours after surgery, and postoperative hospital length of stay (LOS). The primary outcome was total oral morphine milligram equivalents (MME) consumed during the first 72 hours after surgery. The secondary outcome was hospital LOS. MEASUREMENTS AND MAIN RESULTS: In a model adjusting for PSLOS, the authors did not observe an association between ESPBC and the reduction of total administered oral MME within 72 hours after surgery. There was no significant difference in MME when comparing patients who received PVB to patients with ESPBC. Older age and female sex were associated with significantly lower MME. Patients who received ESPBC had a significantly shorter hospital LOS than patients with SAPBC. CONCLUSIONS: These findings suggested that postoperative pain after MIDCAB surgery might not be completely covered by ESPBC. Prospective studies are needed to further elucidate the value of this technique for robotic MIDCAB.

Activation of NLRP3 inflammasome complex potentiates venous thrombosis in response to hypoxia.

Venous thromboembolism (VTE), caused by altered hemostasis, remains the third most common cause of mortality among all cardiovascular conditions. In addition to established genetic and acquired risk factors, low-oxygen environments also predispose otherwise healthy individuals to VTE. Although disease etiology appears to entail perturbation of hemostasis pathways, the key molecular determinants during immediate early response remain elusive. Using an established model of venous thrombosis, we here show that systemic hypoxia accelerates thromboembolic events, functionally stimulated by the activation of nucleotide binding domain, leucine-rich-containing family, pyrin domain containing 3 (NLRP3) inflammasome complex and increased IL-1ß secretion. Interestingly, we also show that the expression of NLRP3 is mediated by hypoxia-inducible factor 1-alpha (HIF-1α) during these conditions. The pharmacological inhibition of caspase-1, in vivo knockdown of NLRP3, or HIF-1α other than IL-1ß-neutralizing antibodies attenuated inflammasome activation and curtailed thrombosis under hypoxic conditions. We extend the significance of these preclinical findings by studying modulation of this pathway in patients with altitude-induced venous thrombosis. Our results demonstrate distinctive, increased expression of NLRP3, caspase-1, and IL-1ß in individuals with clinically established venous thrombosis. We therefore propose that an early proinflammatory state in the venous milieu, orchestrated by the HIF-induced NLRP3 inflammasome complex, is a key determinant of acute thrombotic events during hypoxic conditions.

Complement activation sustains neuroinflammation and deteriorates adult neurogenesis and spatial memory impairment in rat hippocampus following sleep deprivation.

BACKGROUND: An association between neuroinflammation, reduced adult neurogenesis, and cognitive impairment has been established in sleep deprivation (SD). Complement receptors are expressed on neuronal and glial cells, thus, regulate the neuroinflammation, neurogenesis and learning/memory. However, understanding of the effect of SD on the brain-immune system interaction associated with cognitive dysfunction and its mechanisms is obscure. We hypothesized that complement activation induced changes in inflammatory and neurogenesis related proteins might be involved in the cognitive impairment during SD. METHODOLOGY: Adult male Sprague Dawley rats were used. Rats were sleep deprived for 48 h using a novel automated SD apparatus. Dosage of BrdU (50 mg/kg/day, i.p. in 0.07 N NaOH), complement C3a receptor antagonist (C3aRA; SB290157; 1 mg/kg/day, i.p.) in 1.16% v/v PBS and complement C5a receptor antagonist (C5aRA; W-54011; 1 mg/kg/day, i.p.) in normal saline were used. Rats were subjected to spatial memory evaluation following SD. Hippocampal tissue was collected for biochemical, molecular, and immunohistochemical studies. T-test and ANOVA were used for the statistical analysis. RESULTS: An up-regulation in the levels of complement components (C3, C5, C3a, C5a) and receptors (C3aR and C5aR) in hippocampus, displayed the complement activation during SD. Selective antagonism of C3aR/C5aR improved the spatial memory performance of sleep-deprived rats. C3aR antagonist (C3aRA) or C5aR antagonist (C5aRA) treatment inhibited the gliosis, maintained inflammatory cytokines balance in hippocampus during SD. Complement C3aR/C5aR antagonism improved hippocampal adult neurogenesis via up-regulating the BDNF level following SD. Administration of C3aRA and C5aRA significantly maintained synaptic homeostasis in hippocampus after SD. Gene expression analysis showed down-regulation in the mRNA levels of signal transduction pathways (Notch and Wnt), differentiation and axogenous proteins, which were found to be improved after C3aRA/C5aRA treatment. These findings were validated at protein and cellular level. Changes in the corticosterone level and ATP-adenosine-NO pathway were established as the key mechanisms underlying complement activation mediated consequences of SD. CONCLUSION: Our study suggests complement (C3a-C3aR and C5a-C5aR) activation as the novel mechanism underlying spatial memory impairment via promoting neuroinflammation and adult neurogenesis decline in hippocampus during SD, thereby, complement (C3aR/C5aR) antagonist may serve as the novel therapeutics to improve the SD mediated consequences.

The Role of Complementary and Alternative Medicine Treatments in Fibromyalgia: a Comprehensive Review.

PURPOSE OF REVIEW: Fibromyalgia is a complex chronic pain syndrome that can have debilitating consequences for affected patients. When compared to the general population, patients with fibromyalgia experience lowered mechanical and thermal pain thresholds, altered temporal summation of painful stimuli, and higher than normal pain ratings for known noxious stimuli. RECENT FINDINGS: There is no definitive cure for fibromyalgia and treatment primarily focuses on both symptom management and improving patient quality of life. This treatment strategy involves a comprehensive multidisciplinary approach consisting of lifestyle modifications, pharmacologic measures, and other complementary approaches including but not limited to acupuncture, yoga, tai chi, and meditation. This manuscript will discuss the diagnosis and treatment of fibromyalgia, as well as complementary and alternative therapies that should be considered by healthcare providers.

Metabolic and the Surgical Stress Response Considerations to Improve Postoperative Recovery.

PURPOSE OF REVIEW: Enhanced recovery pathways are a multimodal, multidisciplinary approach to patient care that aims to reduce the surgical stress response and maintain organ function resulting in faster recovery and improved outcomes. RECENT FINDINGS: A PubMed literature search was performed for articles that included the terms of metabolic surgical stress response considerations to improve postoperative recovery. The surgical stress response occurs due to direct and indirect injuries during surgery. Direct surgical injury can result from the dissection, retraction, resection, and/or manipulation of tissues, while indirect injury is secondary to events including hypotension, blood loss, and microvascular changes. Greater degrees of tissue injury will lead to higher levels of inflammatory mediator and cytokine release, which ultimately drives immunologic, metabolic, and hormonal processes in the body resulting in the stress response. These processes lead to altered glucose metabolism, protein catabolism, and hormonal dysregulation among other things, all which can impede recovery and increase morbidity. Fluid therapy has a direct effect on intravascular volume and cardiac output with a resultant effect on oxygen and nutrient delivery, so a balance must be maintained without excessively loading the patient with water and salt. All in all, attenuation of the surgical stress response and maintaining organ and thus whole-body homeostasis through enhanced recovery protocols can speed recovery and reduce complications. The present investigation summarizes the clinical application of enhanced recovery pathways, and we will highlight the key elements that characterize the metabolic surgical stress response and improved postoperative recovery.

Inhibiting the microglia activation improves the spatial memory and adult neurogenesis in rat hippocampus during 48 h of sleep deprivation.

BACKGROUND: Sleep deprivation (SD) leads to cognitive impairment. Neuroinflammation could be a significant contributing factor in the same. An increase in regional brain pro-inflammatory cytokines induces cognitive deficits, however, the magnitude of the effect under SD is not apparent. It is plausible that microglia activation could be involved in the SD-induced cognitive impairment by modulation of neuronal cell proliferation, differentiation, and brain-derived neuronal factor (BDNF) level. The present study aimed to evaluate the possible beneficial effect of minocycline in amelioration of spatial memory decline during SD by its anti-inflammatory and neuroprotective actions. We scrutinized the effect of minocycline on the inflammatory cytokine levels associated with glial cells (microglia and astrocytes) activity and neurogenesis markers crucial for behavioral functions during SD. METHODS: Male Sprague-Dawley rats weighing 230-250 g were sleep deprived for 48 h using automated cage shaking apparatus. The spatial memory was tested using MWM apparatus immediately after completion of SD with and without minocycline. The animals were euthanized, blood was collected, and brain was extracted for neuroinflammation and neurogenesis studies. The set of experiments were also conducted with use of temozolomide, a neurogenesis blocker. RESULTS: Minocycline treatment increased the body weight, food intake, and spatial memory performance which declined during SD. It reduced the pro-inflammatory and increased the anti-inflammatory cytokine levels in hippocampus and plasma and inhibited the reactive gliosis in the hippocampus evidenced by improved cell count, morphology, and immunoreactivity. Additionally, minocycline administration promoted neurogenesis at different stages: proliferation (BrdU, Ki-67), differentiation (DCX) cells and growth factor (BDNF). However, no significant change was observed in maturation (NeuN) during SD. In addition, molecules related to behavior, inflammation, and neurogenesis were shown to be more affected after temozolomide administration during SD, and changes were restored with minocycline treatment. We observed a significant correlation of neurogenesis with microglial activation, cytokine levels, and spatial memory during SD. CONCLUSION: The present study demonstrated that the SD-induced decline in spatial memory, neuronal cells proliferation, differentiation, and BDNF level could be attributed to upregulation of neuroinflammatory molecules, and minocycline may be an effective intervention to counteract these changes. Microglial activation is involved in SD-induced changes in inflammatory molecules, neurogenesis, and spatial memory.

Techniques to Optimize Multimodal Analgesia in Ambulatory Surgery.

PURPOSE OF REVIEW: Ambulatory surgery has grown in popularity in recent decades due to the advancement in both surgical and anesthetic techniques resulting in quicker recovery times, fewer complications, higher patient satisfaction, and reduced costs of care. We review common approaches to multimodal analgesia. RECENT FINDINGS: A multimodal approach can help reduce perioperative opioid requirements and improve patient recovery. Analgesic options may include NSAIDs, acetaminophen, gabapentinoids, corticosteroids, alpha-2 agonists, local anesthetics, and the use of regional anesthesia. We highlight important aspects related to pain management in the ambulatory surgery setting. A coordinated approach is required by the entire healthcare team to help expedite patient recovery and facilitate a resumption of normal activity following surgery. Implementation and development of standardized analgesic protocols will further improve patient care and outcomes.

Preoperative Assessment for Ambulatory Surgery.

PURPOSE OF REVIEW: Ambulatory surgery has grown in recent decades in volume and represents a significant number of anesthetics delivered throughout the USA. Preoperative anesthetic assessment in the ambulatory setting has become important because patients with numerous complex comorbidities are now commonplace in this arena. Disease states involving the lungs, the heart, the kidneys, and subpopulations including those who are obese and the elderly commonly receive anesthetics in an ambulatory setting. RECENT FINDINGS: This review presents key aspects of current thinking with regard to preoperative assessment and considerations for different critical disease states and subpopulations that are now being managed under ambulatory surgery. Same day surgery centers require patient safety, and expectations are high for patient satisfaction. Advancements in surgical and anesthetic technique have allowed for more complex patients to partake in ambulatory surgery. Anesthesiologists must be familiar with guidelines, state-of-the-art pain management, and standards of preoperative patient evaluation to accurately stratify patient risk and to advocate for patient safety.

Drug Formulation Advances in Extended-Release Medications for Pain Control.

Prescription opioid abusers frequently tamper with opioid tablets in order to either accelerate the delivery of the euphoria-inducing agent or to alter the route of delivery, such that it may be delivered intranasally or intravenously. As one strategy to combat the opioid epidemic in the USA, drug manufacturers have begun to explore formulations which resist such tampering by abusers. Techniques to prevent tampering consist of physical barriers to crushing, chewing, and drug extraction, or aversive or antagonistic agents, incorporated within the formulation itself. Recent years have seen the development of numerous extended-release opioid agents, which are described in this review. This article provides a comprehensive summary of the pharmacology, benefits, risks, and processes behind the development of currently available extended-release opioid drugs, as well as a glimpse into promising future formulations.

Novel drug development for neuromuscular blockade.

Pharmacological advances in anesthesia in recent decades have resulted in safer practice and better outcomes. These advances include improvement in anesthesia drugs with regard to efficacy and safety profiles. Although neuromuscular blockers were first introduced over a half century ago, few new neuromuscular blockers and reversal agents have come to market and even fewer have remained as common clinically employed medications. In recent years, newer agents have been studied and are presented in this review. With regard to nondepolarizer neuromuscular blocker agents, the enantiomers Gantacurium and CW002, which are olefinic isoquinolinium diester fumarates, have shown potential for clinical application. Advantages include ultra rapid reversal of neuromuscular blockade via cysteine adduction and minimal systemic hemodynamic effects with administration.

Concepts in creating an evidence-based anesthetic protocol for robot-assisted laparoscopic pelvic surgery.

BACKGROUND: Robotic-assisted surgery has increased in popularity in recent years. Benefits have been observed for both the patient and hospital system as the technology shifts surgery from the open to the laparoscopic arena. Some of the advantages of robotic-assisted surgery include increased patient satisfaction along with shorter hospital stays, decreased risk of infection, and improved postsurgical cosmetic outcomes. METHODS: We developed an evidence-based protocol for the anesthetic management of the preoperative, intraoperative, and postoperative phases of patient care based on the review of primary literature and consensus from surgeons and anesthesiologists at our institution. RESULTS: Robotic-assisted surgery creates a unique set of anesthetic considerations to ensure patient safety. Anesthetic considerations include the physiological changes associated with steep Trendelenburg patient positioning, pneumoperitoneum, fluid management, management of pressure points, and spatial restrictions imposed by the robot relative to the conventional anesthetic area. CONCLUSION: A perioperative protocol can help ensure optimal clinical care, patient safety, and better patient and provider satisfaction with the utilization of robotic surgery.

Medication errors in anesthesia.

Medication errors represent one of the most common causes of morbidity and mortality in hospitalized patients. Anesthesia has specific medication-related risks; providers must administer many potent intravenous medications quickly, often with minimal to no supervision. Well-described reasons for medication administration errors in anesthesia include medication ampoules with similar appearance and packaging, clinician inattention, ineffective communication, fatigue, and haste. Technologies that are used widely in other parts of the hospital, such as barcoding, are a challenge to implement in anesthesia, and systemic approaches, including color-coding of syringe labels and barcoding technology of syringes, have been evaluated with mixed results. Emphasis should be placed on implementing forcing functions when possible, utilizing technology, standardization, and education about the need for awareness in specific situations. More studies need to be done to define the epidemiology of medication errors in anesthesia, and more importantly, to assess interventions for preventing them.

Novel improvements in perioperative sterility.

Operative sterility is a critical factor with regard to infection in the postoperative period. In recent years, techniques and devices have been developed to reduce the potential for exposure to pathogens. This brief review details the SteriCup, a unique product that has the potential to reduce the risk of healthcare-acquired infections. The SteriCup provides a designated sterile area to store suction catheters and removed endotracheal tubes and allows for their simple and safe disposal. Devices such as the SteriCup have the potential to improve operating room systems and minimize potential for operative infection.

Blood plasma separation in elevated dimension T-shaped microchannel.

In recent years, microfluidic chips have proven ideal tools for biochemical analysis, which, however, demands a unique and compatible plasma separation scheme. Various research groups have established continuous flow separation methods in microfluidic devices; however, they have worked with relatively small dimension microchannels (similar to the blood cell diameter). The present work demonstrates separation of plasma by utilizing the hydrodynamic separation techniques in microchannels with size of the order of mm. The separation process exploits the phenomenon, which is very similar to that of plasma skimming explained under Zweifach-Fung bifurcation law. The present experiments demonstrates for, the first time, that applicability of the Zweifach-Fung bifurcation law can be extended to dimensions much higher than the suspended particle size. The T-microchannel device (comprising perpendicularly connected blood and plasma channels) were micro-fabricated using conventional PDMS micro-molding techniques. Three variables (feed hematocrit, main channel width, and flow rate distributions) were identified as the important parameters which define the device's efficiency for the blood plasma separation. A plasma separation efficiency of 99.7 % was achieved at a high flow ratio. Novel concepts of 2-stage or multiple plasma channel designs are also proposed to yield high separation efficiency with undiluted blood. The possible underlying principle causing plasma separation (viz. aggregation and shear thinning) are investigated in detail as part of this work. The results are significant because they show nearly 100 % separations in microchannels which are much easier to fabricate than previously designed devices.

Anesthetic management of the patient with amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS), with an incidence of 1.5-2.5 for 100 000 per year, is a rare but rapid progression neuromuscular degeneration disorder that poses unique perioperatively challenges to clinical anesthesiologists. The progressive degeneration of motor neurons causes a constellation of symptoms, including muscular weakness, atrophy, fasciculations, spasticity, and hyperreflexia. Therapeutic and experimental treatments, including riluzole, beta lactams, methylcobalamin, dexpramipexole, antiepileptics, antioxidant agents, neutrophin, antiinflammatory agents, and antiapoptosis drugs, are described. Newer therapies, such as neural stem cells and diaphragmatic pacing, are presented. Because of the inherent muscle weakness and associated respiratory insufficiency, certain precautions must be utilized during anesthetic care of ALS patients. In particular, certain neuromuscular agents are contraindicated and anesthetics that leave the body more rapidly present logical and attractive options in this population. A solid understanding of the disease process, therapeutic interventions, and anesthesia considerations are all paramount for the successful management of a patient with ALS in the perioperative setting.

A simple cost-effective microfluidic platform for rapid synthesis of diverse metal nanoparticles: A novel approach towards fighting SARS-CoV-2.

The latest addition to the family of Coronaviruses, SARS-CoV-2, unleashed its wrath across the globe. The outbreak has been so rapid and widespread that even the most developed countries are still struggling with ways to contain the spread of the virus. The virus began spreading from Wuhan in China in December 2019 and has currently affected more than200 countries worldwide. Nanotechnology has huge potential for killing viruses as severe as HIV, herpes, human papilloma virus, and viruses of the respiratory tract, both inside as well as outside the host. Metal-nanoparticles can be employed for biosensing methodology of viruses/bacteria, along with the development of novel drugs and vaccines for COVID-19 and future pandemics. It is thus required for the nanoparticles to be synthesized quickly along with precise control over their size distribution. In this study, we propose a simple microfluidic-reactor-platform for in-situ metal-nanoparticle synthesis to be used against the pandemic for the development of preventive, diagnostic, and antiviral drug therapies. The device has been fabricated using a customized standard photolithography process using a simple and cost-effective setup. The confirmation on standard silver and gold metal nanoparticle formation in the microfluidic reactor platform was analysed using optical fiber spectrophotometer. This novel microfluidic platform provides the advantage of in-situ synthesis, flow parameter control and reduced agglomeration of nanoparticles over the bulk synthesis due to segregation of nucleation and growth stages inside a microchannel. The results are highly reproducible and hence scaling up of the nanoparticle production is possible without involving complex instrumentation.

Essential role of the amino-terminal region of Drosha for the Microprocessor function.

Drosha is a core component of the Microprocessor complex that cleaves primary-microRNAs (pri-miRNAs) to generate precursor-miRNA and regulates the expression of ∼80 ribosomal protein (RP) genes. Despite the fact that mutations in the amino-terminal region of Drosha (Drosha-NTR) are associated with a vascular disorder, hereditary hemorrhagic telangiectasia, the precise function of Drosha-NTR remains unclear. By deleting exon 5 from the Drosha gene and generating a Drosha mutant lacking the NTR (ΔN), we demonstrate that ΔN is unable to process pri-miRNAs, which leads to a global miRNA depletion, except for the miR-183/96/182 cluster. We find that Argonaute 2 facilitates the processing of the pri-miR-183/96/182 in ΔN cells. Unlike full-length Drosha, ΔN is not degraded under serum starvation, resulting in unregulated RP biogenesis and protein synthesis in ΔN cells, allowing them to evade growth arrest. This study reveals the essential role of Drosha-NTR in miRNA production and nutrient-dependent translational control.

Reversal of pulmonary veno-occlusive disease phenotypes by inhibition of the integrated stress response.

Pulmonary veno-occlusive disease (PVOD) is a rare form of pulmonary hypertension arising from EIF2AK4 gene mutations or mitomycin C (MMC) administration. The lack of effective PVOD therapies is compounded by a limited understanding of the mechanisms driving the vascular remodeling in PVOD. We show that the administration of MMC in rats mediates the activation of protein kinase R (PKR) and the integrated stress response (ISR), which lead to the release of the endothelial adhesion molecule VE-Cadherin in the complex with Rad51 to the circulation, disruption of endothelial barrier, and vascular remodeling. Pharmacological inhibition of PKR or ISR attenuates the depletion of VE-Cadherin, elevation of vascular permeability, and vascular remodeling instigated by MMC, suggesting potential clinical intervention for PVOD. Finally, the severity of PVOD phenotypes was increased by a heterozygous BMPR2 mutation that truncates the carboxyl tail of BMPR2, underscoring the role of deregulated BMP signal in the development of PVOD.