Eliminating residual neuromuscular blockade: a literature review.

Background and Objective: Although millions of patients receive neuromuscular blocking agents (NMBAs) each year as part of an anesthetic, residual neuromuscular blockade (NMB) remains a too-frequent occurrence and its adverse consequences continue to negatively impact patient outcomes. The goal of this manuscript is to provide clinicians with the information they need to decrease the incidence of residual NMB. Methods: Published literature was reviewed and incorporated into the narrative as appropriate. Search terms for articles included nondepolarizing NMBAs, residual NMB, monitoring depth of NMB, qualitative monitoring, quantitative monitoring, reversal agents, sugammadex, and anticholinesterases. Key Content and Findings: This review will define what is currently considered adequate recovery of neuromuscular function, discuss and compare the different modalities to determine the depth of NMB, discuss the currently available NMBAs-including their durations of action and dosing, describe the incidence and complications associated with residual NMB, and discuss reversal of nondepolarizing NMB with neostigmine or sugammadex. Nondepolarizing NMBAs are commonly used as part of a general anesthetic. Understanding the pharmacology of the neuromuscular blocking and reversal agent, in combination with quantitative monitoring of depth of NMB is essential to avoid residual paralysis. Conclusions: Quantitative monitoring and dosing of either neostigmine or sugammadex based on the results of monitoring is essential to eliminate residual NMB associated with the use of nondepolarizing NMBAs.

Glutathione peroxidase (GPX1) - Selenocysteine metabolism preserves the follicular fluid's (FF) redox homeostasis via IGF-1- NMD cascade in follicular ovarian cysts (FOCs).

Follicular ovarian cysts (FOCs) are characterized by follicles in the ovaries that are >20 mm in diameter and persist for >10 days without the corpus luteum, leading to anovulation, dysregulation of folliculogenesis and subfertility in humans and livestock species. Despite their clinical significance, the precise impact of FOCs on oocyte reserve, maturation, and quality still needs to be explored. While FOCs are observed in both human and livestock populations, they are notably prevalent in livestock species. Consequently, livestock species serve as valuable models for investigating the molecular intricacies of FOCs. Thus, in this study, using goat FOCs, we performed integrated proteomic, metabolomic and functional analyses to demonstrate that oocyte maturation is hampered due to increased reactive oxygen species (ROS) in FOCs follicular fluid (FF) via downregulation of glutathione peroxidase (GPX1), a critical antioxidant seleno enzyme required to negate oxidative stress. Notably, GPX1 reduction was positively correlated with the FF's decline of free selenium and selenocysteine metabolic enzymes, O-phosphoryl-tRNA (Sec) selenium transferase (SEPSECS) and selenocysteine lyase (SCLY) levels. Adding GPX1, selenocysteine, or selenium to the culture media rescued the oocyte maturation abnormalities caused by FOCs FF by down-regulating the ROS. Additionally, we demonstrate that substituting GPX1 regulator, Insulin-like growth factor-I (IGF-1) in the in vitro maturation media improved the oocyte maturation in the cystic FF by down-regulating the ROS activity via suppressing Non-sense-mediated decay (NMD) of GPX1. In contrast, inhibition of IGF-1R and the target of rapamycin complex 1 (mTORC1) hampered the oocyte maturation via NMD up-regulation. These findings imply that the GPX1 regulation via selenocysteine metabolism and the IGF-1-mediated NMD may be critical for the redox homeostasis of FF. We propose that GPX1 enhancers hold promise as therapeutics for enhancing the competence of FOCs oocytes. However, further in vivo studies are necessary to validate these findings observed in vitro.

The impact of aggressive and conservative propensity for initiation of neuromuscular blockade in mechanically ventilated patients with hypoxemic respiratory failure.

INTRODUCTION: Neuromuscular blockade (NMB) in ventilated patients may cause benefit or harm. We applied "incremental interventions" to determine the impact of altering NMB initiation aggressiveness. METHODS: Retrospective cohort study of ventilated patients with PaO2/FiO2 ratio < 150 mmHg and PEEP≥ 8cmH2O from the Medical Information Mart of Intensive Care IV database (MIMIC-IV version 1.0) estimating the effect of incremental interventions on in-hospital mortality and ventilator-free days, modifying hourly propensity for NMB initiation to be aggressive or conservative relative to usual care, adjusting for confounding with inverse probability weighting. RESULTS: 5221 patients were included (13.3% initiated on NMB). Incremental interventions estimated a strong effect on NMB usage: 5-fold higher hourly odds of initiation increased usage to 36.5% (CI = [34.3%,38.7%]) and 5-fold lower odds decreased usage to 3.8% (CI = [3.3%,4.3%]). Aggressive and conservative strategies demonstrated a U-shaped mortality relationship. 5-fold higher or lower propensity increased in-hospital mortality by 2.6% (0.95 CI = [1.5%,3.7%]) or 1.3% (0.95 CI = [0.1%,2.5%]) respectively. In secondary analysis of a healthier patient cohort, results were similar, however conservative strategies also improved ventilator-free days. INTERPRETATION: Aggressive or conservative initiation of NMB may worsen mortality. In healthier populations, marginally conservative NMB initiation strategies may lead to increased ventilator free days with minimal impact on mortality.

Underneath Images and Robots, Looking Deeper into the Pneumoperitoneum: A Narrative Review.

Laparoscopy offers numerous advantages over open procedures, minimizing trauma, reducing pain, accelerating recovery, and shortening hospital stays. Despite other technical advancements, pneumoperitoneum insufflation has received little attention, barely evolving since its inception. We explore the impact of pneumoperitoneum on patient outcomes and advocate for a minimally invasive approach that prioritizes peritoneal homeostasis. The nonlinear relationship between intra-abdominal pressure (IAP) and intra-abdominal volume (IAV) is discussed, emphasizing IAP titration to balance physiological effects and surgical workspace. Maintaining IAP below 10 mmHg is generally recommended, but factors such as patient positioning and surgical complexity must be considered. The depth of neuromuscular blockade (NMB) is explored as another variable affecting laparoscopic conditions. While deep NMB appears favorable for surgical stillness, achieving a balance between IAP and NMB depth is crucial. Temperature and humidity management during pneumoperitoneum are crucial for patient safety and optical field quality. Despite the debate over the significance of temperature drop, humidification and the warming of insufflated gas offer benefits in peritoneal homeostasis and visual clarity. In conclusion, there is potential for a paradigm shift in pneumoperitoneum management, with dynamic IAP adjustments and careful control of insufflated gas temperature and humidity to preserve peritoneal homeostasis and improve patient outcomes in minimally invasive surgery.

Optimizing neuromuscular blockade management for improving patient safety and peri-operative outcomes: a pilot phase of a quality improvement initiative.

INTRODUCTION: Although quantitative monitoring of neuromuscular blockade (NMB) is recommended, it is not routinely used in daily practice. The optimizing NMB management to improve patient safety and perioperative outcomes (OBISPO) quality improvement (QI) initiative intends to address this issue and change clinicians' behaviors. MATERIAL AND METHODS: A pilot phase of the prospective QI intervention was conducted. The primary objective was implement clinical practice change that emphasizes improving NMB monitoring in patients undergoing elective cardiac surgery who are eligible for fast-track extubation between February 2021 and December 2021. The secondary objective was to reduce the train-of-four ratio (TOFR) < 0.9 incidence before tracheal extubation to less than 20%. The intervention included educational sessions for teams. RESULTS: A total of 859 patients underwent elective cardiac surgery, 40% were eligible for fast-track extubation. From our cohort of fast-track cardiac cases, 69% had reported TOFR; 47% of them had residual paralysis (TOFR < 0.9) on arrival to PACU, 22% persisted with residual paralysis after extubation, and 27% were extubated without monitoring. The survey identified cognitive biases, knowledge gaps, unfamiliarity, and lack of trust in quantitative monitoring devices. Workflow disruptions imposed by COVID and changes in NMB monitoring devices have negatively affected our initiative. CONCLUSIONS: Our study showed that changes in clinician behavior are among the most challenging issues in perioperative medicine. Continuous teaching and QI initiatives, focused on quantitative NMB monitors and adequate reversal agent use, are mandatory to improve perioperative outcomes. Therefore, new proposals are required to promote changes in current practices.

Neuromedin B receptor as a potential therapeutic target for corticotroph adenomas.

PURPOSE: Cushing's disease (CD) results from autonomous adrenocorticotropic hormone (ACTH) secretion by corticotroph adenomas, leading to excessive cortisol production, ultimately affecting morbidity and mortality. Pasireotide is the only FDA approved tumor directed treatment for CD, but it is effective in only about 25% of patients, and is associated with a high rate of hyperglycemia. Neuromedin B (NMB), a member of the bombesin-like peptide family, regulates endocrine secretion and cell proliferation. Here, we assessed NMB and NMB receptor (NMBR) expression in human corticotroph adenomas and the effects of NMBR antagonist PD168368 on murine and human corticotroph tumors. METHODS: To investigate NMB and NMBR expression, real-time qPCR and immunostaining on human pathological specimens of corticotroph, non-functional and somatotroph adenomas were performed. The effects of PD168368 on hormone secretion and cell proliferation were studied in vitro, in vivo and in seven patient-derived corticotroph adenoma cells. NMB and NMBR were expressed in higher extent in human corticotroph adenomas compared with non-functional or somatotroph adenomas. RESULTS: In murine AtT-20 cells, PD168368 reduced proopiomelanocortin (Pomc) mRNA/protein expression and ACTH secretion as well as cell proliferation. In mice with tumor xenografts, tumor growth, ACTH and corticosterone were downregulated by PD168368. In patient-derived adenoma cells, PD168368 reduced POMC mRNA expression in four out of seven cases and ACTH secretion in two out of five cases. A PD168368-mediated cyclin E suppression was also identified in AtT-20 and patient-derived cells. CONCLUSION: NMBR antagonist represents a potential treatment for CD and its effect may be mediated by cyclin E suppression.

Deciphering the Biomolecules from Bacillus atrophaeus NMB01 Untangles the Anti-Oomycetes Action of Trioxsalen and Corynan-17-ol, Against Phytophthora infestans Inciting Late Blight of Potato.

The antagonistic Bacillus spp. is known well for the production of versatile antimicrobial biomolecules with broad spectrum of action against different types of plant pathogens. Considering the significance of metabolically active biomolecules, attempts were made to decipher the anti-oomycete nature of biomolecules produced by Bacillus atrophaeus NMB01 during di-trophic interaction with Phytophthora infestans. Ten biomolecules produced by B. atrophaeus NMB01 during di-trophic interaction with P. infestans were docked against the twelve target proteins of P. infestans. Molecular docking of biomolecules reported trioxsalen and corynan-17-ol,18,19-didehydro-10-methoxy-acetate(ester) as best hits with highest binding energy in the range of - 7.5 to - 5 kcal/mol against target proteins of P. infestans. Comparatively less binding energy was observed for commercially available fungicides mandipropamid and metalaxyl on docking against the target proteins of P. infestans. We also confirmed the direct impact of trioxsalen andcorynan-17-ol, on P. infestans under in vitro with 66% and 50% inhibition of mycelial growth of P. infestans, respectively. This is the first study attempted to untangle the role of bioactive anti-oomycete compounds produced by B. atrophaeus strain NMB01 during di-trophic interaction with P. infestans against late blight pathogen P. infestans infecting potato. From the present study, we conclude that the biomolecules, trioxsalen and corynan-17-ol, can be explored for the management of P. infestans, the incitant of late blight of potato. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-022-01044-7.

Successful Neuromuscular Blockade Reversal Using Sugammadex and Neostigmine Failed to Prevent Myasthenic Crisis After Emergency Surgery: A Case Report.

Recent literature suggests that the use of sugammadex for the reversal of neuromuscular blocking agents (NMBAs) reduces the risk of postoperative myasthenic crisis (MC) in patients with myasthenia gravis (MG), particularly after thymectomy, but studies are lacking on emergency surgeries. We achieved successful intraoperative reversal of neuromuscular blockade (NMB) using a combination of sugammadex and neostigmine (with glycopyrrolate). However, MC was not avoided and reintubation was required on postoperative day 1. A 65-year-old male with a longstanding history of MG presented to the emergency department with complaints of abdominal pain, diarrhea, vomiting, chills, and fatigue for three days. A computed tomography (CT) scan of the abdomen showed acute appendicitis, for which he underwent a laparoscopic appendectomy on hospital day 1. The patient received successful general anesthesia with a rapid sequence induction using a smaller than average dose of rocuronium, given his history of MG. At the conclusion of the case, sugammadex followed by neostigmine/glycopyrrolate and a subsequent dose of sugammadex were given, with reversal of NMB. The patient was successfully extubated but required reintubation on postoperative day 1 for hypercapnic respiratory failure. Our case report on this patient with MG yields two topics that have not been extensively examined. First, dual therapy with sugammadex and neostigmine/glycopyrrolate may provide significant clinical benefit over individual therapy for NMBA reversal, given that their mechanisms of action are different and particularly when sugammadex is given prior to neostigmine/glycopyrrolate. Second, anesthesia literature is lacking on MG patients undergoing emergency surgeries. While sugammadex has been promising in medically optimized non-emergent surgeries, we discuss here a case where sugammadex failed to prevent MC in the emergency surgery setting and a look into what may provide patients with the best chance for avoiding postoperative MC.

Integrated single-cell transcriptomic analyses reveal that GPNMB-high macrophages promote PN-MES transition and impede T cell activation in GBM.

BACKGROUND: Glioblastoma (GBM) is the most aggressive type of primary brain tumor and is often resistant to current therapies. Tumor microenvironment-centered therapies may unleash new hope for GBM treatment. Therefore, an in-depth understanding of tumor-stroma communication is urgently needed to identify promising therapeutic targets. METHODS: We systematically analyzed GBM single-cell RNA sequencing (scRNA-seq), bulk RNA-seq and spatial scRNA-seq data from various human and mice studies to characterize the network within the microenvironment. Moreover, we applied ex vivo co-culture system, flow cytometry analysis and immunofluorescent staining to validate our findings. FINDINGS: Our integrative analyses revealed that highly heterogeneous GBM tumor cells can be classified into MES-like, AC-like, OPC-like and NPC-like subtypes based on molecular studying. Additionally, trajectory and regulatory network inference implied a PN to MES cell state transition regulated by specific transcriptional factor (TF) regulons. Importantly, we discovered that glycoprotein nonmetastatic B (GPNMB) derived from macrophages played a crucial role in this transition through immune cell-tumor interplay. Besides, through deep signal transduction analyses and cell co-culture studies, we further disclosed that these GPNMB-high macrophage subpopulations, originating from monocytes, could also ineffectively retain T cells from activating by dendritic cells (DCs). INTERPRETATION: Our study suggests that targeting this particular GPNMB-high macrophage subset may provide a new strategy to control GBM plasticity and facilitate T cell-based immunotherapy. FUNDING: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

Postoperative respiratory depression caused by iatrogenic hypermagnesaemia.

Hypermagnesaemia is an uncommon electrolyte disorder which can be fatal if not recognised and treated promptly. The signs and symptoms of hypermagnesaemia are non-specific, making it an under-diagnosed cause of cardiovascular dysfunction, hypocalcaemia, and neurological and respiratory depression. Since magnesium homeostasis is handled almost exclusively by the kidneys, symptomatic hypermagnesaemia seldom occurs in the context of normal renal function; when it does, it is usually iatrogenic. Here, we report a case of iatrogenic hypermagnesaemia which presented as respiratory depression, preventing weaning from mechanical ventilation following cardiac surgery in a patient in the early stages of chronic kidney disease. On investigation he was found to have isolated severe hypermagnesaemia, following an intravenous bolus of magnesium sulphate administered intra-operatively to treat tachyarrhythmia. Before administering intravenous magnesium therapeutically, it is important for clinicians to assess renal function and baseline serum magnesium along with other possible risk factors for hypermagnesaemia, and to actively look for signs and symptoms of magnesium toxicity when the patient is receiving therapeutic magnesium.

Glycoprotein NMB promotes tumor formation and malignant progression of laryngeal squamous cell carcinoma.

Laryngeal squamous cell carcinoma (LSCC), although one of the most common head and neck cancers, has a static or slightly decreased survival rate because of difficulties in early diagnosis, lack of effective molecular targeting therapy, and severe dysfunction after radical surgical treatments. Therefore, a novel therapeutic target is crucial to increase treatment efficacy and survival rates in these patients. Glycoprotein NMB (GPNMB), whose role in LSCC remains elusive, is a type 1 transmembrane protein involved in malignant progression of various cancers, and its high expression is thought to be a poor prognostic factor. In this study, we showed that GPNMB expression levels in LSCC samples are significantly higher than those in normal tissues, and GPNMB expression is observed mostly in growth-arrested cancer cells. Furthermore, knockdown of GPNMB reduces monolayer cellular proliferation, cellular migration, and tumorigenic growth, while GPNMB protein displays an inverse relationship with Ki-67 levels. Therefore, we conclude that GPNMB may be an attractive target for future LSCC therapy.

Peri-operative management of an adult with POLG-related mitochondrial disease.

POLG-related mitochondrial disease is a rare mitochondrial disorder that is potentially associated with anaesthetic complications such as propofol-related infusion syndrome. A 19-year-old man with mitochondrial DNA deletions and POLG-related disorders presented for an elective robotic Heller-Dor myotomy for the treatment of oesophageal pseudo-achalasia associated with severe gastro-oesophageal reflux. The fasting period was minimised to reduce the risk of metabolic stress. The anaesthetic technique included a rapid sequence induction with propofol and rocuronium, a remifentanil and sevoflurane-based general anaesthesia with multimodal monitoring and peri-operative lactate-free intravenous fluids with added dextrose. The patient did not experience propofol-related infusion syndrome but did have delayed tracheal extubation due to residual neuromuscular blockade requiring a second dose of sugammadex. This report demonstrates the safety of single-use, low-dose propofol in this patient group. Patients with POLG-related mitochondrial disease may be at risk of prolonged neuromuscular blockade, and appropriate dosing of neuromuscular blocking agents with monitoring of neuromuscular blockade is strongly encouraged.

Glutamate in primary afferents is required for itch transmission.

Whether glutamate or itch-selective neurotransmitters are used to confer itch specificity is still under debate. We focused on an itch-selective population of primary afferents expressing MRGPRA3, which highly expresses Vglut2 and the neuropeptide neuromedin B (Nmb), to investigate this question. Optogenetic stimulation of MRGPRA3+ afferents triggers scratching and other itch-related avoidance behaviors. Using a combination of optogenetics, spinal cord slice recordings, Vglut2 conditional knockout mice, and behavior assays, we showed that glutamate is essential for MRGPRA3+ afferents to transmit itch. We further demonstrated that MRGPRA3+ afferents form monosynaptic connections with both NMBR+ and NMBR- neurons and that NMB and glutamate together can enhance the activity of NMBR+ spinal DH neurons. Moreover, Nmb in MRGPRA3+ afferents and NMBR+ DH neurons are required for chloroquine-induced scratching. Together, our results establish a new model in which glutamate is an essential neurotransmitter in primary afferents for itch transmission, whereas NMB signaling enhances its activities.

Neuromuscular blockade effects of cisatracurium in 11 cats undergoing ophthalmological surgery anaesthetised with isoflurane.

CASE SERIES SUMMARY: This case series describes the neuromuscular blockade (NMB) following 0.15 mg/kg intravenous (IV) cisatracurium administration in 11 cats undergoing ophthalmological surgery and anaesthetised with isoflurane. Anaesthetic records were analysed retrospectively. Neuromuscular function was assessed by a calibrated train-of-four (TOF) monitor. Cats were 73 ± 53 months old, weighed 4 ± 1 kg and were of American Society of Anesthesiologists' physical classification 2. Duration of anaesthesia and surgery were 144 ± 27 and 94 ± 24 mins, respectively. The lowest TOF count was zero in four cats, four in six cats and for one cat the TOF ratio never decreased below 31%. The time of onset was between 1 and 6 mins after the administration of cisatracurium and the mean duration of action was 20.4 ± 10.1 mins. RELEVANCE AND NOVEL INFORMATION: Cisatracurium at a dose of 0.15 mg/kg IV did not consistently induce a TOF count of zero in all cats. The dose used in these cats did not produce any remarkable cardiovascular side effects. Although the NMB was not complete, the dose given was sufficient to produce central eyeball position, which was the goal of the ophthalmic surgeries.

Adaptive resistance in tumors to anti-PD-1 therapy through re-immunosuppression by upregulation of GPNMB expression.

Acquired resistance to the antitumor activity of antibodies targeting the programmed death 1 (PD-1): programmed death ligand 1 (PD-L1) immune checkpoint in various types of cancers has increasingly been observed during treatment. To gain insight into the molecular mechanism underlying anti-PD-1 therapy resistance, we developed a mouse MC38 colon adenocarcinoma cell line that was made resistant to anti-PD-1 treatment through repeated in vivo selection. We compared the transcriptomic profiles of anti-PD-1 therapy-resistant and -sensitive tumors using RNA sequencing analysis. The immunosuppressive molecule transmembrane glycoprotein NMB (GPNMB) was significantly upregulated in resistant tumor cells, as determined using quantitative real-time polymerase chain reaction and immunofluorescence analyses. Furthermore, deletion of GPNMB in resistant cells successfully restored sensitivity to anti-PD-1 treatment in vivo. Collectively, our results indicate that tumors may develop resistance to anti-PD-1 therapy by upregulating their expression of the immunosuppressive molecule GPNMB. Furthermore, GPNMB is a potential, targetable biomarker for monitoring adaptive resistance to therapeutic PD-1 blockade, and identification of this immunosuppressive molecule may be a breakthrough for new therapies.

Neuromedin B promotes chondrocyte differentiation of mesenchymal stromal cells via calcineurin and calcium signaling.

BACKGROUND: Articular cartilage is a complex tissue with poor healing capacities. Current approaches for cartilage repair based on mesenchymal stromal cells (MSCs) are often disappointing because of the lack of relevant differentiation factors that could drive MSC differentiation towards a stable mature chondrocyte phenotype. RESULTS: We used a large-scale transcriptomic approach to identify genes that are modulated at early stages of chondrogenic differentiation using the reference cartilage micropellet model. We identified several modulated genes and selected neuromedin B (NMB) as one of the early and transiently modulated genes. We found that the timely regulated increase of NMB was specific for chondrogenesis and not observed during osteogenesis or adipogenesis. Furthermore, NMB expression levels correlated with the differentiation capacity of MSCs and its inhibition resulted in impaired chondrogenic differentiation indicating that NMB is required for chondrogenesis. We further showed that NMB activated the calcineurin activity through a Ca2+-dependent signaling pathway. CONCLUSION: NMB is a newly described chondroinductive bioactive factor that upregulates the key chondrogenic transcription factor Sox9 through the modulation of Ca2+ signaling pathway and calcineurin activity.

Hepatitis C prevalences in the psychiatric setting: Cost-effectiveness of scaling-up screening and direct-acting antiviral therapy.

BACKGROUND & AIMS: Patients hospitalised because of mental illness often have risk factors for contracting HCV. Scaling-up HCV screening for all psychiatric inpatients as a case-detection strategy for viral elimination is underexplored. This study aimed to evaluate the cost-effectiveness of scaling-up HCV screening and treatment for psychiatry hospital admissions in Switzerland vs. the current standard-of-care risk-based approach, where only those with a history of substance misuse disorder are offered testing. METHODS: HCV prevalence by history of substance misuse disorder was analysed in medical records from inpatient admissions to a Swiss psychiatry department. Cost-effectiveness was analysed from a healthcare provider perspective through a decision-tree screening model, using these HCV prevalence data. Model and parameter uncertainty were assessed using deterministic and probabilistic sensitivity analyses. RESULTS: Prevalence of HCV in psychiatry inpatients with a history of substance misuse disorder (n = 1,013) was 25.7%, compared with 3.5% among the remaining inpatients (n = 3,535). Scaling up HCV screening and treatment for all psychiatry admissions was cost-effective vs. the risk-based approach, with an incremental cost-effectiveness ratio of US$9,188 per quality-adjusted life-year gained. The incremental cost-effectiveness ratio remained cost-effective considering a HCV prevalence as low as 0.07%. The population-level net monetary benefit of the generalised screening approach was US$435,156,348, with 917 additional patients per year detected and treated at a cost of US$3,294 per person (vs. US$2,122 under risk-based screening). CONCLUSIONS: Scaling up HCV screening and treatment at diagnosis with all-oral, interferon-free regimens as a generalised approach for psychiatric admissions was cost-effective and could support reaching World Health Organization targets for HCV elimination by 2030. LAY SUMMARY: Patients hospitalised because of mental illness often have risk factors for HCV. We found that testing all psychiatry patients in hospital for HCV was cost-effective compared with testing only patients who have a history of substance misuse. Scaling up HCV testing and treatment could help to wipe out HCV.

Clinical Impact of Sugammadex in the Reversal of Neuromuscular Blockade.

Background A neuromuscular blockade (NMB) is used in general anesthesia to facilitate endotracheal intubation and muscle relaxation during procedural and surgical interventions. Rapid and complete reversal of the NMB allows for patient recovery to the preoperative baseline with ventilation and motor function, along with the complete return of gastroesophageal motility, thereby expediting recovery and preventing microaspiration in the postoperative period. Sugammadex is a modified gamma cyclodextrin that complexes with steroidal neuromuscular blocking agents (specifically, rocuronium and vecuronium), leading to a molecular gradient and removal of the agents from the neuromuscular junction. Sugammadex has been shown to have a more rapid reversal of neuromuscular blockade compared to neostigmine. The purpose of this study was to evaluate if perioperative efficiency was increased when sugammadex was used for paralytic reversal compared to the traditional regimen of neostigmine and glycopyrrolate. Methods A retrospective cohort study of patients admitted for surgical intervention in June 2019 was conducted. Two groups were compared: those who received sugammadex for reversal and those who received neostigmine, plus glycopyrrolate. The primary outcome was time to extubation from the administration of the reversal agent. Results Two hundred seventy-one surgical cases were evaluated. Average doses of sugammadex for those with profound neuromuscular blockade as indicated by a train of four (TOF) of 0 - 2 was 2.47 (0.9) mg/kg for sugammadex and 0.042 (0.01) mg/kg for neostigmine, plus glycopyrrolate. Seventeen patients in the sugammadex group experienced bradycardia after reversal compared to 22 in the neostigmine, plus glycopyrrolate, group (p = 0.73). Reintubation was required for three patients in the neostigmine, plus glycopyrrolate, group and no patients in the sugammadex group. The mean time to extubation from the procedure end comparing reversal with sugammadex and neostigmine, plus glycopyrrolate, was 12.5 (7.6) minutes versus 13.7 (8.8) minutes (p = 0.44), respectively. Comparison of reversal with sugammadex versus neostigmine, plus glycopyrrolate, and time spent in the post-anesthesia care unit was 83.6 (48.6) minutes versus 81.7 (46.6) (p = 0.73), respectively. Conclusions In this retrospective cohort study, we observed a deviation in the recommended sugammadex dosage and increased reintubation rates but no difference in time to extubation or Post-Anesthesia Care Unit (PACU) length of stay times when patients received sugammadex compared to neostigmine, plus glycopyrrolate, for neuromuscular blockade reversal. Understanding the PACU flow and culture, education of providers about dosages, along with completion of prospective studies, to correlate acceleromyograph values to reversal and postoperative ventilatory and deglutary function can help assess the true clinical value of sugammadex.

Failure to meet extubation criteria in the setting of suspected buffalo chest physiology.

We report the case of a patient who failed to meet tracheal extubation criteria due to low tidal volumes from suspected buffalo chest, which is a single pleural space physiology. This presentation followed the resection of a large pleural mass in a 59-year-old woman with a history of exercise-induced asthma, hypertension and tumour-related chronic respiratory failure. Creation of a pleuro-pleural communication during the resection of this large, unilateral pleural mass led to bilateral pneumothoraces and contributed to patients inability to generate negative inspiratory force leading to failure to meet extubation criteria. Buffalo chest may be more prevalent than suspected and should be a differential diagnosis for low tidal volumes with spontaneous ventilation following thoracic surgery. It can be differentiated from other causes of decreased tidal volume using clinical examination, ultrasound and radiography. Bilateral chest tube placement can be considered to expedite pneumothorax resolution and tracheal extubation.

Intranasal immunization with a rNMB0315 and combination adjuvants induces protective immunity against Neisseria meningitidis serogroup B in mice.

Neisseria meningitidis (N. meningitidis) is a human-specific pathogen and a major cause of meningitis and septicemia with a high case fatality rate. N. meningitidis may penetrate the nasopharyngeal mucosal membrane and cause severe meningitis, a mucosal immune response plays a key role in the defense against meningococcal infections. Our previous study demonstrated that N. meningitidis serogroup B 0315 (NMB0315) was a vaccine candidate against N. meningitidis serogroup B (NMB) through parenteral immunization. In this study, immunopotentiators (C48/80 or CpG-ODN) were loaded into chitosan nanoparticle (Chi NP) to form combination adjuvants (Chi-CpG NP and Chi-C48/80 NP) and adopted to enhance the immunogenicity of NMB0315 through intranasal immunization. The experimental results have indicated that both Chi-CpG NP and Chi-C48/80 NP are effective mucosal adjuvants for the induction of significantly higher rNMB0315-specific IgG, IgG1, IgG2a and sIgA antibodies. Meanwhile, Chi-CpG NP and Chi-C48/80 NP could change the ratio of IgG1/IgG2a, inducing a more balanced cellular/humoral immune response. Chi-CpG NP and Chi-C48/80 NP also boosted interleukin-4 (IL-4), interferon-γ (IFN-γ) and interleukin-17 A (IL-17A) production by splenocytes. The bactericidal antibodies have been detected in sera from mice immunized with rNMB0315 + Chi-CpG NP and rNMB0315 + Chi-C48/80 NP. Overall, the combination adjuvants could be applicable to the development of a mucosal vaccine against NMB.