An Overview on Postoperative Cognitive Dysfunction; Pathophysiology, Risk Factors, Prevention and Treatment

Postoperative cognitive dysfunction (POCD) is an event that alarms medical personnel owing to its adverse effects, including heightened morbidity and mortality rates, prolonged recovery times, and increased lengths of hospital stay and healthcare expenditure. The populations at high risk are elderly, critical patients, or complicated cases that need prolonged surgery in which the hemodynamics are not stable. Although guidelines have been established to facilitate the early diagnosis of POCD, its prevention is recommended for good patient outcomes. A preoperative assessment is a prerequisite for patient optimization before surgery. Intraoperative, enhanced-recovery protocols have been widely adopted to promote recovery following surgery. Frequent, postoperative assessments of patients’ vital signs and cognitive functions are required for early POCD detection. Patients diagnosed with POCD need regular follow-up, and proper patient counselling is paramount

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

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

Abstract 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

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. The Journal of Immunology, 2011, 187: 424-433

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

Abstract 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)

Data_Sheet_1_The Thai version of the nursing delirium screening scale-Thai: Adaptation and validation study in postoperative patients.PDF

BackgroundThe 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).MethodsThe 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.ResultsThe 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%).ConclusionThe 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.</p