Current state of neuroprotective therapy using antibiotics in human traumatic brain injury and animal models.

TBI is a leading cause of death and disability in young people and older adults worldwide. There is no gold standard treatment for TBI besides surgical interventions and symptomatic relief. Post-injury infections, such as lower respiratory tract and surgical site infections or meningitis are frequent complications following TBI. Whether the use of preventive and/or symptomatic antibiotic therapy improves patient mortality and outcome is an ongoing matter of debate. In contrast, results from animal models of TBI suggest translational perspectives and support the hypothesis that antibiotics, independent of their anti-microbial activity, alleviate secondary injury and improve neurological outcomes. These beneficial effects were largely attributed to the inhibition of neuroinflammation and neuronal cell death. In this review, we briefly outline current treatment options, including antibiotic therapy, for patients with TBI. We then summarize the therapeutic effects of the most commonly tested antibiotics in TBI animal models, highlight studies identifying molecular targets of antibiotics, and discuss similarities and differences in their mechanistic modes of action.

Early postoperative neurocognitive complications in elderly patients: comparing those with and without preexisting mild cognitive impairment- a prospective study.

BACKGROUND: As societies age, increasing numbers of older adults undergo surgeries with anesthesia. Postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) frequently occur in older surgical patients. Most of these patients already have preoperative mild cognitive impairment (MCI). However, the correlation between MCI and POD remains unclear. This study aimed to determine the incidence of POD in elderly patients with and without preexisting MCI. METHODS: A prospective study enrolled patients aged 60 years and above scheduled for major surgeries between December 2017 and April 2022. Preoperative MCI was determined by a Montreal Cognitive Assessment (MoCA) score between 18 and 24. POD was diagnosed using criteria from the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). POCD was characterized by a MoCA score reduction of 2 or more points from the preoperative score. The primary outcome was the incidence of POD within the first 72 h postoperatively. Secondary outcomes encompassed other postoperative complications, including POCD. RESULTS: The study comprised 223 elderly patients with MCI and 56 without MCI. The incidence of POD was 16.6% in the MCI group and 14.3% in the non-MCI group (P = 0.839). POCD occurred in 24.3% of MCI patients and 50% of non-MCI patients (P = 0.001). There were no significant differences in other postoperative complications between the groups. Postoperatively, the MCI group notably declined in visuospatial, attention, and orientation domains, while the non-MCI group declined in all domains except delayed recall. CONCLUSIONS: The incidence of POD was similar in the MCI and non-MCI groups. However, the non-MCI group demonstrated a higher incidence of POCD than the MCI group. This was identified by a reduction in postoperative MoCA scores for the visuospatial, naming, attention, language, abstraction, and orientation domains. These findings underscore the importance of postoperative cognitive assessments for both elderly patients with preexisting MCI and those with previously intact cognitive functions. TRIAL REGISTRATION: This trial was retrospectively registered in the Thai Clinical Trials Registry on 15/01/2019 (registration number: TCTR20190115001).

Psychometric properties of a Thai version of the Richards-Campbell sleep questionnaire.

BACKGROUND: In critically ill patients, a poor sleep quality can escalate mortality and the length of hospital stays. Albeit being the gold standard for sleep assessment, polysomnography (PSG) is expensive and complicated. The Richards-Campbell sleep questionnaire (RCSQ) is another tool with proof of good correlation with PSG. RCSQ was translated into many languages. However, the Thai version (T-RCSQ) has not been developed. AIMS AND OBJECTIVES: Our study aimed to translate the original RCSQ into Thai, to test the content validity and reliability, and to introduce the questionnaire into clinical practice at the surgical intensive care unit (SICU). DESIGN: Prospective cross-sectional study METHODS: This study enrolled 92 patients from the SICU between August 2019 and January 2020. The content validity of T-RCSQ was determined by the index of item-objective congruence (IOC). The reliability was tested by test-retest reliability at 7 am and 9 am after intensive care unit (ICU) admission. The internal consistency was expressed by Cronbach's alpha. Patients' demography was reported as percentage, mean and standard deviation, and median and interquartile range. RESULTS: The content validity and test-retest reliability of the T-RCSQ were 0.8 and 0.97, respectively. The internal consistency was 0.964. Most patients were female with American Society of Anesthesiologist physical status III. The mean RCSQ scores at 7 am and 9 am were 5.82 ± 2.15 cm and 5.61 ± 2.18 cm, respectively. CONCLUSIONS: The T-RCSQ is reliable and could be used as an alternative to PSG for sleep assessment of ICU patients. Further research is required to validate the T-RCSQ against PSG and to assess its impact on improving sleep quality and patients' clinical outcomes. RELEVANCE TO CLINICAL PRACTICE: T-RCSQ is a useful tool for sleep assessment in ICU. According to cost-effectiveness, convenience, and good reliability, it could be applied to determine proper sleep to minimize patient morbidity and mortality.

Sortilin is dispensable for secondary injury processes following traumatic brain injury in mice.

Traumatic brain injury (TBI) is characterized by complex secondary injury processes involving the p75 neurotrophin receptor (p75NTR), which has been proposed as a possible therapeutic target. However, the pathogenic role of the p75NTR co-receptor sortilin in TBI has not been investigated. In this study, we examined whether sortilin contributes to acute and early processes of secondary injury using a murine controlled cortical impact (CCI) model of TBI. Initial expression analysis showed a down-regulation of sortilin mRNA levels 1 and 5 day post injury (dpi) and a reduced expression of sortilin protein 1 dpi. Next, a total of 40 SortilinΔExon14 loss-of-function mouse mutants (Sort1-/-) and wild-type (Sort1+/+) littermate mice were subjected to CCI and examined at 1 and 5 dpi. Neither sensorimotor deficits or brain lesion size nor CCI-induced cell death or calcium-dependent excitotoxicity as evaluated by TUNEL staining or Western blot analysis of alpha II spectrin breakdown products were different between Sort1-/- and Sort1+/+ mice. In addition, CCI induced the up-regulation of pro-inflammatory marker mRNA expression (Il6, Tnfa, Aif1, and Gfap) irrespectively of the genotype. Similarly, the mRNA expressions of neurotrophins (Bdnf, Ngf, Nt3), VPS10P domain receptors others than sortilin (Ngfr, Sorl1, Sorcs2), and the sortilin interactor progranulin were not affected by genotype. Our results suggest that sortilin is a modulatory rather than a critical factor in the acute and early brain tissue response after TBI.

Binding of flavivirus nonstructural protein NS1 to C4b binding protein modulates complement activation.

The complement system plays a pivotal protective role in the innate immune response to many pathogens including flaviviruses. Flavivirus nonstructural protein 1 (NS1) is a secreted nonstructural glycoprotein that accumulates in plasma to high levels and is displayed on the surface of infected cells but absent from viral particles. Previous work has defined an immune evasion role of flavivirus NS1 in limiting complement activation by forming a complex with C1s and C4 to promote cleavage of C4 to C4b. In this study, we demonstrate a second mechanism, also involving C4 and its active fragment C4b, by which NS1 antagonizes complement activation. Dengue, West Nile, or yellow fever virus NS1 directly associated with C4b binding protein (C4BP), a complement regulatory plasma protein that attenuates the classical and lectin pathways. Soluble NS1 recruited C4BP to inactivate C4b in solution and on the plasma membrane. Mapping studies revealed that the interaction sites of NS1 on C4BP partially overlap with the C4b binding sites. Together, these studies further define the immune evasion potential of NS1 in reducing the functional capacity of C4 in complement activation and control of flavivirus infection.

Incidence, risk factors and outcomes of early post-operative stroke in a university-based, tertiary care hospital: A 7-year retrospective case-control study.

Most post-operative stroke cases occur within 24 hours. This retrospective case-control study aimed to investigate the incidence, risk factors, and outcomes of early post-operative stroke that occurred within 24 hours after surgery in a university-based tertiary care hospital. Medical records were collected and reviewed between 2015 and 2021. Early post-operative stroke cases were compared with age-matched controls in a 1:3 ratio, and data regarding patient characteristics, intra-operative events, and post-operative outcomes were analyzed. Multiple logistic regression was performed to identify the risk factors for post-operative stroke. The incidence of early (≤24 hours) post-operative stroke was 0.015% (43 out of 284,105 cases). The multivariable analysis revealed that American Society of Anesthesiologists (ASA) physical status ≥3 (adjusted odds ratio [OR]: 3.12; 95% confidence interval [CI]: 1.22-7.99, P = .017), operation time >120 minutes (adjusted OR: 10.69; 95% CI: 3.95-28.94, P < .001), and intra-operative hypotension and inotrope/vasopressor use (adjusted OR: 2.80; 95% CI: 1.08-7.24, P = .034) were risk factors for early post-operative stroke. Compared to the controls, stroke patients had higher rates of planned and unplanned intensive care unit (ICU) admission, length of stay, ventilator use, and death. Despite its low incidence (0.015%), stroke is associated with poor clinical outcomes and increased mortality. Stratification of potential risks and establishment of risk optimization may help reduce stroke incidence.

Model for enhancing the research conducted by the university medical staff: Participatory action research.

This study employed mixed methods with a participatory action research approach to explore factors currently undermining the conduction of research and to develop strategies to boost research productivity. A questionnaire was distributed to 64 staff members of the Department of Anesthesiology at a university-based hospital. Thirty-nine staff members (60.9%) gave informed consent and responses. Staff views were also collected through focus group discussions. The staff reported that limited research methodology skills, time management, and complex managerial processes were the limitations. Age, attitudes, and performance expectancy were significantly correlated with research productivity. A regression analysis demonstrated that age and performance expectancy significantly influenced research productivity. A Business Model Canvas (BMC) was implemented to gain insight into the goal of enhancing the conduct of research. Business Model Innovation (BMI) established a strategy to improve research productivity. The concept, comprising personal reinforcement (P), aiding systems (A), and a lifting-up of the value of research (L), the PAL concept, was considered key to enhancing the conduct of research, with the BMC providing details and integrating with the BMI. To upgrade the research performance, the involvement of management is imperative, and future action will involve the implementation of a BMI model to increase research productivity.

Hard-Candy Consumption Does Not Have an Effect on Volume and pH of Gastric Content in Patients Undergoing Elective Gastrointestinal Endoscopic Procedures: A Randomized Controlled Trial.

Purpose: This study aimed to determine the effect of hard candies on gastric content volume and pH in patients undergoing elective esophagogastroduodenoscopy and colonoscopy. Additionally, the study evaluated the difficulty of the procedure, complications, and satisfaction levels of the endoscopist and patient. Patients and Methods: A randomized controlled study equally recruited 108 outpatients to candy and control groups. The patients in the candy group could consume sugar-free candies within 2 hours before anesthesia, while the controls remained fasted. The endoscopic procedure began under topical pharyngeal anesthesia and intravenous sedation. A blinded endoscopist suctioned the gastric volume through an endoscope. A blinded anesthesia provider tested the gastric pH with a pH meter. The primary outcome variables were gastric volume and pH. The secondary outcome variables were complications, the difficulty of the procedure, and endoscopist and patient satisfaction. Results: The characteristics of both patient groups were comparable. The mean gastric volume of the candy group (0.43 [0.27-0.67] mL/kg) was not significantly different from that of the control group (0.32 [0.19-0.55] mL/kg). The gastric pH of both groups was similar: 1.40 (1.10-1.70) for the candy group and 1.40 (1.20-1.90) for the control group. The procedure-difficulty score of the candy group was higher than that of the control group. The satisfaction scores rated by the endoscopist and the patients in both groups were comparable. In addition, most endoscopists and patients in the candy and control groups reported being "very satisfied". No complications were observed in either group. Conclusion: Hard candies did not affect gastric volume or pH. Elective gastrointestinal endoscopic procedures in adult patients who preoperatively consume candies could proceed to prevent delays and disruption of workflows.

The Thai version of the nursing delirium screening scale-Thai: Adaptation and validation study in postoperative patients.

Background: The Nursing Delirium Screening Scale (Nu-DESC) is an effective instrument for assessing postoperative delirium (POD). This study translated the Nu-DESC into Thai ("Nu-DESC-Thai"), validated it, and compared its accuracy with the Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5). Methods: The translation process followed the International Society for Pharmacoeconomics Outcome Research guidelines. Recruited participants were ≥ 70 years old, fluent in Thai, and scheduled for surgery. The exclusion criteria were cancellation or postponement of an operation, severe visual or auditory impairment, and patients with a Richmond Agitation Sedation Scale score of -4 or less before delirium assessment. Post-anesthesia care unit (PACU) nurses and residents on wards each used the Nu-DESC to assess delirium in 70 participants (i.e., 140 assessments) after the operation and after patient arrival at wards, respectively. Geriatricians confirmed the diagnoses using video observations and direct patient contact. Results: The participants' mean age was 76.5 ± 4.6 years. The sensitivity and specificity of the Nu-DESC-Thai at a threshold of ≥ 2 were 55% (95% CI, 31.5-76.9%) and 90.8% (84.2-95.3%), respectively, with an area under a receiver operating characteristic curve (AUC) of 0.73. At a threshold of ≥ 1, the sensitivity and specificity were 85% (62.1-96.8%) and 71.7% (62.7-79.5%), respectively (AUC, 0.78). Adding 1 point for failing backward-digit counting (30-1) to the Nu-DESC-Thai and screening at a threshold of ≥ 2 increased its sensitivity to 85% (62.1-96.8%) with the same specificity of 90.8% (84.2-95.3%). Conclusion: The Nu-DESC-Thai showed good validity and reliability for postoperative use. Its sensitivity was inadequate at a cutoff ≥ 2. However, the sensitivity improved when the threshold was ≥ 1 or with the addition of backward counting to Nu-DESC-Thai and screening at a threshold of ≥ 2.

Factors influencing preoperative chest radiography request for elective endoscopic procedures among medical personnel.

BACKGROUND: Chest radiography is not routinely recommended before elective endoscopies. A high incidence of perioperative chest radiography requests was observed at our institution. This study aims to investigate factors influencing preoperative chest radiography request for patients undergoing elective gastrointestinal (GI) endoscopies. METHODS: This cross-sectional clinical study recruited 264 participants from different medical specialties who were responsible for preoperative endoscopic chest x-ray (CXR) ordering including anesthesiologists, surgeons and gastroenterologists. They completed questionnaires exploring their general knowledge and attitudes about preoperative chest radiography. Demographic characteristic of the participants affecting the knowledge on preoperative chest radiography was determined. A Structural Equation Model (SEM) was constructed from validated conceptual framework to find causal relationships between hypothesized factors and intention for preoperative endoscopic chest radiography request. Statistical analyses were performed using the SPSS software version 18.0 and Analysis of Moment Structures (AMOS) version 18.0. RESULTS: The questionnaire response rate was 53.79%. Baseline general knowledge on preoperative chest radiography of the participants was comparable. The SEM results showed unsupported relationship between hypothesized factors and the intention for preprocedural GI endoscopic CXR request (p < 0.1). CONCLUSIONS: General knowledge of medical personnel on tuberculosis needs improvement. To rectify the unnecessary chest radiography request before elective GI endoscopic procedures, awareness of the patients' health conditions, adherence to the hospital's policy and realizing of possible patient-related mishaps are not the determinants for preprocedural endoscopic chest radiography request. Future works are required to explore other alternative factors involved for reducing chest radiography requests which are not indicated.

N-linked glycosylation of dengue virus NS1 protein modulates secretion, cell-surface expression, hexamer stability, and interactions with human complement.

Dengue virus (DENV) NS1 is a versatile non-structural glycoprotein that is secreted as a hexamer, binds to the cell surface of infected and uninfected cells, and has immune evasive functions. DENV NS1 displays two conserved N-linked glycans at N130 and N207. In this study, we examined the role of these two N-linked glycans on NS1 secretion, stability, and function. Because some groups have reported reduced yields of infectious DENV when N130 and N207 are changed, we analyzed glycosylation-deficient NS1 phenotypes using a transgenic expression system. We show that the N-linked glycan at position 130 is required for stabilization of the secreted hexamer whereas the N-linked glycan at residue 207 facilitates secretion and extracellular protein stability. Moreover, NS1 mutants lacking an N-linked glycan at N130 did not interact efficiently with complement components C1s and C4. In summary, our results elucidate the contribution of N-linked glycosylation to the function of DENV NS1.

Antagonism of the complement component C4 by flavivirus nonstructural protein NS1.

The complement system plays an essential protective role in the initial defense against many microorganisms. Flavivirus NS1 is a secreted nonstructural glycoprotein that accumulates in blood, is displayed on the surface of infected cells, and has been hypothesized to have immune evasion functions. Herein, we demonstrate that dengue virus (DENV), West Nile virus (WNV), and yellow fever virus (YFV) NS1 attenuate classical and lectin pathway activation by directly interacting with C4. Binding of NS1 to C4 reduced C4b deposition and C3 convertase (C4b2a) activity. Although NS1 bound C4b, it lacked intrinsic cofactor activity to degrade C4b, and did not block C3 convertase formation or accelerate decay of the C3 and C5 convertases. Instead, NS1 enhanced C4 cleavage by recruiting and activating the complement-specific protease C1s. By binding C1s and C4 in a complex, NS1 promotes efficient degradation of C4 to C4b. Through this mechanism, NS1 protects DENV from complement-dependent neutralization in solution. These studies define a novel immune evasion mechanism for restricting complement control of microbial infection.