INTRODUCTION:Postoperative cognitive dysfunction constitutes an extremely prevalent implication in individuals subjected to cardiac or noncardiac surgery. This study aimed to assess the validity and reliability of a culturally adapted Greek version of the Addenbrooke's Cognitive Examination III (ACE-III) scale as a screening tool for perioperative neurocognitive status determination in elderly surgical patients. METHODS:A cross-cultural adaptation and validation of instruments throughout the cross-sectional study was conducted. The study sample consisted of 128 individuals over 55 years old scheduled for surgical intervention. All participants were screened twice: at the preadmission clinic and the day before surgery using the already established MoCA scale and the culturally adapted Greek version of the ACE-III scale. Subjects with a MoCA score of <26 constituted the cognitively impaired group. RESULTS:Regarding construct validity, ACE-III's performance in detecting cognitive impairment was excellent (AUC = 0.942; 95% CI: 0.899-0.971). Convergent validity between ACE-III and MoCA scales was excellent (r = 0.876; 95% CI: 0.839-0.905). Known group validity was confirmed since advanced age and lower educational attainment adversely impacted ACE-III's total score (p < 0.001). Additionally, specialists suggested face validity (mean 8.7 out of 10, SD 1.1). In terms of reliability, ACE-III demonstrated good internal consistency (Cronbach's alpha 0.786) and high inter-rater (intraclass correlation coefficient [ICC] = 0.936 [95% CI: 0.921-0.941]) and test-retest reliability (ICC = 0.972 [95% CI: 0.958-0.981]). CONCLUSION:The Greek version of ACE-III is a valid and reliable screening tool that could be routinely employed perioperatively as a valid alternative to the MoCA test to distinguish the mild cognitively impaired from healthy elderly candidates for surgical interventions.

Background and Objectives: Lung cancer represents one of the principal causes of cancer-associated mortality worldwide. Despite the numerous novel therapeutic agents, surgical resection remains, in many cases, the mainstay treatment. A growing body of evidence indicates that the anesthetic technique of choice contributes to perioperative immunosuppression, thus having an impact on cancer recurrence and prognosis. The aim of this systematic review is to provide a thorough summary of the current literature regarding the modulation of the immune response induced by the various anesthetic techniques that are used in lung cancer surgery, with a particular emphasis on cellular immunity. Materials and Methods: PubMed, Scopus, and the Cochrane databases were systematically searched from November 2023 up to March 2024 to identify randomized controlled trials (RCTs) that met the eligibility criteria. Results: A total of seven RCTs were included. Four of the RCTs compared the administration of general anesthesia alone versus general anesthesia combined with epidural anesthesia. The subsequent meta-analysis showed that the combination of general and epidural anesthesia exerted a positive impact on the cell counts of the CD3+ cells (SMD −0.42, 95% Cl −0.70 to −0.13 24 h postoperatively and SMD −0.86 95% Cl −1.48 to −0.23 72 h postoperatively), the CD4+ cells (SMD −0.41 95% Cl −0.69 to −0.12 at the end of surgery and SMD −0.56 95% Cl −0.85 to −0.27 72 h later), and the CD4+/CD8+ ratio (SMD −0.31 95% Cl −0.59 to −0.02 immediately after surgery, SMD −0.50 95% Cl −0.86 to −0.14 24 h postoperatively, and SMD −0.60 95% Cl −0.89 to −0.31 72 h later). The pooled results regarding CD8+ and NK cell counts were inconclusive. The remaining three studies compared volatile-based anesthesia with total intravenous anesthesia (TIVA). Due to disparities between these studies, qualitative analysis was inconclusive, whereas quantitative analysis was not feasible. Conclusions: The supplementation of general anesthesia with epidural anesthesia favorably impacts CD3+ and CD4+ cell counts, as well as the CD4+/CD8+ ratio. The present results and the effects of anesthetic technique on other immune cells must be consolidated with further high-quality studies.

Objective: We aimed to systematically evaluate the available clinical evidence concerning the comparable efficacy and safety of currently used anti-epileptic drugs (AEDs) for seizure prophylaxis in patients undergoing craniotomy for brain tumor excision and synthesize this with a network meta-analysis (NMA). Methods: A systematic literature review was performed to identify randomized controlled trials (RCTs) relevant to the prophylactic use of AEDs in seizure-naïve patients subjected to brain tumor excision. Total, early, or late post-craniotomy seizures constituted primary outcome measures, while mortality and treatment-related adverse effects served as secondary endpoints. Pairwise and network meta-analysis were conducted for each pair of interventions to obtain ‘direct’ treatment effect estimates, while NMA was employed to assess the relative efficacy and safety of prophylactic use of AEDs in post-craniotomy epilepsy management in brain tumor cases. Results: Twelve eligible RCTs involving 10 interventions were retrieved. Levetiracetam (OR 0.08; 95%CI 0.02–0.43) and phenytoin (OR 0.43; 95%CI 0.20–0.91) showed superior efficacy over placebo on early seizure control, while none of the applied interventions demonstrated any significant effect on late seizures versus placebo. With the single exception of carbamazepine (OR 3.29; 95%CI 1.21–8.91), none of the implemented AEDs exerted a notable effect on mortality. Phenytoin presented a higher incidence of treatment-related AEs, imposing drug discontinuation compared to other treatment regimens, yet this effect did not reach statistical significance. Conclusions: Our NMA indicates that, in seizure-naive individuals subjected to brain tumor excision, levetiracetam and phenytoin effectively prevent postoperative short-term seizure activity. Notwithstanding the fact that levetiracetam presents an enhanced safety profile over other AEDs, no statistical superiority could be demonstrated. PROSPERO registration CRD42022377136.

BACKGROUND:Surgical tissue trauma induced by cesarean delivery serves as a pivotal stimulus for initiating the activation of nociceptors, leading to severe postoperative pain. Dexamethasone seems to mitigate pain-elicited inflammatory response and potentially serve as an analgesic adjunct in the post-cesarean period. This systematic review and meta-analysis aimed to assess the administration of intravenous dexamethasone for post-cesarean pain management. METHODS:An electronic database search involving PubMed, Scopus, CENTRAL, and the Public Library of Science was conducted to identify all randomized controlled trials (RCTs) pertinent to the analgesic efficacy of intravenous dexamethasone compared with placebo for cesarean delivery. The risk of bias and certainty of evidence in eligible trials were assessed using the ROB2 tool and the GRADE approach, respectively. RESULTS:Seventeen RCTs were included in the qualitative analysis, and 15 in the quantitative analysis. Intravenous dexamethasone was associated with prolonged time to first request for rescue analgesia (mean difference [MD] 3.33 hours, 95% CI 1.67 to 4.99; I2 = 92.7%), lower opioid analgesic consumption (MD, -3.23 mg; 95% CI, -4.04 to -2.41; I2 = 67.5%) within 24 hours and improved pain scores up to 24 hours postoperatively compared with placebo, however prediction intervals failed to confirm these favorable effects. The risk of postoperative nausea and vomiting was reduced with intravenous dexamethasone, but not that of pruritus. CONCLUSIONS:Intravenous perioperative dexamethasone seems to be a promising adjunct to established analgesic modalities in cesarean delivery, with prolonged time to first request for rescue analgesia, reduced analgesic consumption, and reduced pain scores at rest up to 24 hours postoperatively. However, the substantial heterogeneity and low certainty of available evidence preclude any definite conclusions from being drawn.

This study aims to assess the efficacy and safety of newly approved Janus kinase (JAK) and interleukin-6 (IL-6) inhibitors in patients with moderately-to-severely active rheumatoid arthritis (RA) with inadequate response to or intolerance of conventional disease-modifying antirheumatic drugs. We conducted a systematic review and meta-analysis of all placebo-controlled randomized trials assessing baricitinib, sarilumab, and upadacitinib treatment in RA, published in PubMed and CENTRAL (Cochrane Central Register of Controlled Trials) databases up to October 2023. The study outcomes involved the American College of Rheumatology (ACR) 20%, 50%, and 70% responses, Health Assessment Questionnaire-Disability Index (HAQ-DI), Disease Activity Score in 28 joints (DAS28), serious adverse events, and adverse events leading to drug discontinuation. Twelve randomized controlled trials enrolling 5875 patients were selected for final analysis. Pooled analysis revealed that the implementation of baricitinib (RR = 1.77; 95% CI = 1.58-1.97; I2 = 21%), sarilumab (RR = 1.60; 95% CI = 1.33-1.93; I2 = 0%), and upadacitinib (RR = 1.99; 95% CI = 1.81-2.20; I2 = 15%) was associated with notable therapeutic improvement in RA patients as determined by the ACR20. Considering other efficacy outcomes (ACR50, ACR70, DAS28, HAQ-D), all tested interventions demonstrated a superiority to placebo. None of the tested treatment modalities incurred a higher risk of serious adverse events compared to placebo, yet drug discontinuation was more commonly encountered in baricitinib-treated patients. The newly approved JAK and IL-6 inhibitors, namely, baricitinib, upadacitinib, and sarilumab, seem to be effective in alleviating RA-induced clinical implications and thus improving quality of life. Nonetheless, safety issues could be a matter of concern in baricitinib use, while upadacitinib and sarilumab present an acceptable safety profile.

Background/Objective: Wound infiltration with local anesthetics emerges as a promising modality for postoperative pain alleviation. However, such strategies in neck surgery have not been a well-established practice. To assess wound infiltration with ropivacaine plus magnesium sulfate for pain relief following thyroid surgery. Methods: This prospective, double-blind, randomized study enrolled 68 patients who underwent thyroid surgery. Concerning the solution used for surgical wound infiltration, the study participants were randomly allocated into three groups: (1) 100 mg of ropivacaine (Group R); (2) 100 mg of ropivacaine plus magnesium sulfate 10 mg/kg (Group RMg); and (3) normal saline which served as a placebo (Group P). Pain perception both at rest and at movement, was measured using the Visual Analogue Scale (VAS) at 30 min, as well as at 1, 2, 4, 6, 12, and 24 h postoperatively. The total consumption of analgesics in morphine equivalents was also recorded. Moreover, adverse effects and patient satisfaction were recorded. Cortisol, TNF-α, and IL-6 levels were measured 30 min before infiltration and 6 h and 24 h postoperatively. Results: Demographics and clinical characteristics were similar between the groups. The VAS scores at rest and during movement were significantly lower in the RMg group compared to the saline or ropivacaine groups. Total analgesic consumption was also significantly lower in the RMg group. No operation-, wound-, or infiltration-related adverse effects were recorded in the study groups. Better overall satisfaction was obtained for the RMg group. Conclusions: Ropivacaine plus magnesium sulfate wound infiltration provided better pain control and the analgesic effect was more significant, contributing to effective postoperative analgesia in patients undergoing thyroid surgery.

The emerging need for the implementation of reliable and safe neuromonitoring, both perioperatively and in the Intensive Care unit (ICu) setting, has contributed to the development of contemporary minimally invasive methods of monitoring acute brain injury. Among these, the most important seem to be the ultrasound measurement of the diameter of the optic nerve sheath (optic nerve sheath diameter, ONSD), the pupillometry, and the pressure reactivity index (PRx). ONSD estimation by ultrasound implementation is an easy-to-use, practical, and reliable method of intracranial pressure (ICP) assessment. The digital pupillometry device quantifies with enhanced sensitivity the adequacy of the photokinetic reflex through the Neurological Pupil index (NPi). Current evidence links NPi changes with those provided by invasive ICP monitoring. Finally, PRx is the linear coefficient of variables related both to cerebral perfusion (mean arterial pressure, MAP) and intracranial pressure (ICP) - factors directly linked to cerebral autoregulation monitoring. The above methods of minimally invasive neuromonitoring tools have practical applications in primary brain lesions, in the monitoring of secondary lesions, as well as in the prognosis of patients reliably and with the fewest possible complications compared to invasive methods of intracranial pressure monitoring.

Objective: Gastric carcinoma (GC) is the fifth most commonly diagnosed cancer and the third leading cause of cancer-related deaths globally. The tumor microenvironment plays a significant role in the pathogenesis, prognosis, and response to immunotherapy. However, the immune-related molecular mechanisms underlying GC remain elusive. Bioinformatics analysis of the gene expression of GC and paracancerous healthy tissues from the same patient was performed to identify the key genes and signaling pathways, as well as their correlation to the infiltration of the tumor microenvironment (TME) by various immune cells related to GC development. Methods: We employed GSE19826, a gene expression profile from the Gene Expression Omnibus (GEO), for our analysis. Functional enrichment analysis of Differentially Expressed Genes (DEGs) was conducted using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes database. Results: Cytoscape software facilitated the identification of nine hub DEGs, namely, FN1, COL1A1, COL1A2, THBS2, COL3A1, COL5A1, APOE, SPP1, and BGN. Various network analysis algorithms were applied to determine their high connectivity. Among these hub genes, FN1, COL1A2, THBS2, COL3A1, COL5A1, and BGN were found to be associated with a poor prognosis for GC patients. Subsequent analysis using the TIMER database revealed the infiltration status of the TME concerning the overexpression of these six genes. Specifically, the abovementioned genes demonstrated direct correlations with cancer-associated fibroblasts, M1 and M2 macrophages, myeloid-derived suppressor cells, and activated dendritic cells. Conclusion: Our findings suggest that the identified hub genes, particularly BGN, FN1, COL1A2, THBS2, COL3A1, and COL5A1, play crucial roles in GC prognosis and TME cell infiltration. This comprehensive analysis enhances our understanding of the molecular mechanisms underlying GC development and may contribute to the identification of potential therapeutic targets and prognostic markers for GC patients.

Abstract Objective: To assess wound infiltration with ropivacaine plus magnesium sulfate for pain relief following thyroid surgery. Background: Analgesia with local anesthetics following surgery is a critical element of alleviating postoperative pain. However, such strategies in neck surgery has not been a well-established practice. Methods: This prospective double-blind randomized study enrolled 68 patients who underwent thyroid surgery. Concerning the solution used for surgical wound infiltration the study participants were randomly allocated into three groups: 1) 100 mg of ropivacaine (Group R), 2) 100mg of ropivacaine plus magnesium sulfate 10mg/kg (Group RMg), and 3) normal saline which served as placebo (Group P). Pain perception both at rest and at movement, was measured using the Visual Analogue Scale (VAS) at 30 minutes, as well as 1, 2, 4, 6, 12, and 24 hours postoperatively. The total consumption of analgesics in morphine equivalents was also recorded. Moreover, adverse effects and patient satisfaction were recorded. Cortisol, TNF-α, and IL-6 levels were measured 30 minutes before infiltration, 6 hours and 24 hours postoperatively. Results: Demographics and clinical characteristics were similar between the groups. The VAS scores at rest and during movement were significantly lower in the RMg group compared to saline or ropivacaine groups. Total analgesic consumption was also significantly lower in the RMg group. No operational, wound or infiltration-related adverse effects were recorded in the study groups. Better overall satisfaction was obtained for the group RMg. Conclusions: Ropivacaine plus magnesium sulfate wound infiltration provided better pain control and analgesic effect was more significant, contributing to effective postoperative analgesia in patients undergoing thyroid surgery.

Background: Hyperosmolar therapy is the mainstay of treatment to reduce brain bulk and optimize surgical exposure during craniotomy. This study investigated the effect of equiosmolar doses of 7.5% hypertonic saline (HTS) and 20% mannitol on intraoperative cerebral oxygenation and metabolic status, systemic hemodynamics, brain relaxation, markers of cerebral injury, and perioperative craniotomy outcomes. Methods: A total of 51 patients undergoing elective supratentorial craniotomy were randomly assigned to receive 7.5% HTS (2 mL/kg) or 20% mannitol (4.6 mL/kg) at scalp incision. Intraoperative arterial and jugular bulb blood samples were collected at predefined time intervals for assessment of various indices of cerebral oxygenation; multiple hemodynamic variables were concomitantly recorded. S100B protein and neuron-specific enolase levels were determined at baseline, and at 6 and 12 hours after surgery for assessment of neuronal injury. Brain relaxation and perioperative outcomes were also assessed. Results: Demographic and intraoperative data, brain relaxation score, and perioperative outcomes were comparable between groups. Jugular bulb oxygen saturation and partial pressure of oxygen, arterial jugular oxygen and carbon dioxide differences, and brain oxygen extraction ratio were favorably affected by 7.5% HTS up to 240 minutes postinfusion (P< 0.05), whereas mannitol was associated with only a short-lived (up to 15 min) improvement of these indices (P < 0.05). The changes in cerebral oxygenation corresponded to transient expansion of intravascular volume and improvements of cardiovascular performance. Increases in S100B and neuron-specific enolase levels at 6 and 12 hours after surgery (P < 0.0001) were comparable between groups. Conclusions: The conclusion is that 7.5% HTS has a more beneficial effect on cerebral oxygenation than an equiosmolar dose of 20% mannitol during supratentorial craniotomy, yet no clear-cut clinical superiority of either solution could be demonstrated.

Background: Gastric and colorectal carcinomas are associated with increased mortality and an increasing incidence worldwide, while surgical resection remains the primary approach for managing these conditions. Emerging evidence suggests that the immunosuppression induced by the chosen anaesthesia approach, during the perioperative period, can have a significant impact on the immune system and consequently the prognosis of these patients. Aim: This systematic review aims to comprehensively summarize the existing literature on the effects of different anaesthesia techniques on immune system responses, focusing on cellular immunity in patients undergoing the surgical removal of gastric or colorectal carcinomas. There is no meta-analysis investigating anaesthesia’s impact on immune responses in gastric and colorectal cancer surgery. Anaesthesia is a key perioperative factor, yet its significance in this area has not been thoroughly investigated. The clinical question of how the anaesthetic technique choice affects the immune system and prognosis remains unresolved. Methods: Major electronic databases were searched up to February 2023 to May 2023 for relevant randomized controlled trials (RCTs). The study protocol has been registered with Prospero (CRD42023441383). Results: Six RCTs met the selection criteria. Among these, three RCTs investigated the effects of volatile-based anaesthesia versus total intravenous anaesthesia (TIVA), while the other three RCTs compared general anaesthesia alone to the combination of general anaesthesia with epidural anaesthesia. According to our analysis, there were no significant differences between TIVA and volatile-based anaesthesia, in terms of primary and secondary endpoints. The combination of general anaesthesia with epidural analgesia had a positive impact on NK cell counts (SMD 0.61, 95% CI 0.28 to 0.94, I2 0.0% at 24 and 72 h after the operation), as well as on CD4+ cells (SMD 0.59, CI 95% 0.26 to 0.93, I2 0.0%). However, the CD3+ cell count, CD4+/CD8+ ratio, neutrophil-to-lymphocyte ratio (NLR), IL-6 and TNF-α levels remained unaffected. Conclusions: The combination of epidural analgesia and general anaesthesia can potentially improve, postoperatively, the NK cell count and CD4+ cell levels in gastric or colon surgery patients. However, the specific impact of TIVA or volatile-based anaesthesia remains uncertain. To gain a better understanding of the immunomodulatory effects of anaesthesia, in this particular group of cancer patients, further well-designed trials are required.

The first few hours following thyroidectomy are the most crucial for pain management. Adequate postoperative pain control, reduction in opioid abuse and the possibility of implementing one-day operations are the considered parameters when developing the postoperative analgesic strategy. A study of the available literature was conducted, exploring the efficacy of (open) thyroidectomy wound infiltration. Seventeen full-text RCTs were extracted. Local anesthetics and non-steroidal anti-inflammatory drugs were infiltrated. Emphasis was given to postoperative pain scores and requirements for rescue analgesia with opioids. Most authors agree that local wound infiltration for thyroidectomized patients is effective in the management of postoperative pain parameters. In the era of multimodal analgesia, thyroidectomy wound infiltration could represent an essential adjunct contributing to lower VAS scores and reduced opioid requirements.

Background: Acute-on-chronic liver failure (ACLF) mostly occurs when there is an acute insult to the liver in patients with pre-existing liver disease, and it is characterized by a high mortality rate. Various therapeutic approaches have been used thus far, with orthotopic liver transplantation being the only definitive cure. Clinical trials and meta-analyses have investigated the use of granulocyte colony-stimulating factor (G-CSF) to mobilize bone marrow-derived stem cells. Some studies have suggested that G-CSF may have a significant role in the management and survival of patients with ACLF. However, the results are conflicting, and the efficacy of G-CSF still needs to be confirmed. Aim: The aim was to assess the efficacy of G-CSF in patients with ACLF. Methods: Electronic databases were searched until May 2023 for randomized controlled trials investigating the use of G-CSF in adult patients with ACLF. Outcome measures were the effects of G-CSF on overall survival, changes in liver disease severity scores, complications of cirrhosis, other G-CSF-related adverse effects, and all-cause mortality. The study’s protocol has been registered with Prospero (CRD42023420273). Results: Five double-blind randomized controlled trials involving a total of 421 participants met the inclusion criteria. The use of G-CSF demonstrated a significant effect on overall survival (HR 0.63, 95% CI 0.41 to 0.95, and I2 48%), leading to a decreased mortality (LogOR-0.97, 95% CI −1.57 to −0.37, and I2 37.6%) and improved Model for End-Stage Liver Disease (MELD) scores (SMD −0.87, 95% CI −1.62 to −0.13, and I2 87.3%). There was no correlation between the improvement of the Child–Pugh score and the use of G-CSF(SMD −2.47, 95% CI −5.78 to 0.83, and I2 98.1%). The incidence of complications of cirrhosis did not decrease significantly with G-CSF treatment (rate ratio 0.51, 95% CI 0.26 to 1.01, and I2 90%). A qualitative synthesis showed that the use of G-CSF is safe. Conclusions: The administration of G-CSF has demonstrated a positive impact on overall survival, liver function, and the MELD score. The presence of heterogeneity in the included studies prohibits conclusive recommendations.

Purpose To assess the efficacy and safety of perioperative parenteral administration or submucosal infiltration of tramadol for perioperative pain control on the basis of pain intensity or analgesics consumption and perioperative outcomes in mandibular third molar surgery. Material-methods An electronic database search was conducted up to 10 November 2022 to retrieve all randomized controlled trials (RCTs), assessing the analgesic efficacy of parenteral use of tramadol implemented as an adjunct to local anesthesia or intraoperative sedation/general anesthesia, in surgical extraction of mandibular third molars. Modified Jadad scale and Cochrane bias tool were used for the qualitative appraisal. Results Nineteen RCTs were selected for qualitative analysis. Nine studies involved intravenous, and 5 intramuscular administration of tramadol, while 5 evaluated submucosal infiltration with tramadol. Intravenous or intramuscular tramadol provided a weaker analgesic effect compared with non-steroidal anti-inflammatory drugs (NSAIDs), while intravenous tramadol induced an enhanced analgesic effect than oral tramadol. Parenteral administration of tramadol improved the quality of postoperative analgesia versus placebo. No notable adverse effects were recorded. Conclusions Parenteral or submucosal infiltration of tramadol constitutes an effective and safe alternative analgesic approach in surgical extraction of mandibular third molars, yet the nociceptive effect of this analgesic modality could not supersede that of NSAIDs. Trial registration PROSPERO No CRD42021227574.

Background Perioperative anesthetic and/or analgesic demand present considerable variation, and part of that variation appears to be genetic in origin. Here we investigate the impact of common polymorphisms in OPRM1, COMT, SLC6A4, ABCB1, and CYP2B6 genes, on the intra-operative consumption of remifentanil and propofol, as well as the postoperative analgesic needs, in patients subjected to thyroidectomy surgery. Methods We conducted a prospective cohort study with 90 patients scheduled to undergo elective thyroidectomy, under total intravenous anesthesia achieved by target control infusion (TCI) of propofol and remifentanil. Postoperative analgesics were administered by protocol and on-demand by the individual patient. Genotyping was established by PCR–RFLP methods. Genotyping data, intra-operative hemodynamics, and total consumption of remifentanil and propofol, as well as postoperative analgesic needs and pain perception, were recorded for each individual. Results Patients with the ABCB1 3435TT genotype appeared to experience significantly less pain within one hour post-operatively, compared to C carriers [mean VAS (SD) = 0.86 (1.22) vs. 2.42 (1.75); p = 0.017], a finding limited to those seeking rescue analgesic treatment. Intra-operatively, homozygotes patients for the minor allele of OPRM1 A118G and CYP2B6 G516T appeared to consume less remifentanil [mean (SD) = 9.12 (1.01) vs. 13.53 (5.15), for OPRM1 118GG and A carriers] and propofol [median (range) = 14.95 (11.53, 1359.5) vs. 121.4 (1.43, 2349.4), for CYP2B6 516TT and G carriers, respectively] but the difference was not statistically significant in our sample. Conclusions The ABCB1 C3435T polymorphism appears to affect the postoperative perception of surgical pain among patients with low pain threshold. The small number of minor allele homozygotes for the OPRM1 A118G and CYP2B6 G516T polymorphisms precludes a definitive conclusion regarding the inclusion of the latter in a TCI-programming algorithm, based on the results of this study. Clinical trial registration number ACTRN12616001598471.

The role of probiotics in the prevention of ventilator-associated pneumonia (VAP) remains inconclusive. The aim of this study was to assess the efficacy of a probiotic regimen for VAP prophylaxis in mechanically ventilated multi-trauma patients, intubated immediately after the injurious insult. In a randomized, placebo-controlled study enrolling multi-trauma patients, patients expected to require mechanical ventilation for >10 days were assigned at random to receive prophylaxis with a probiotic formula (n= 59) or placebo (n= 53). The probiotic formula was a preparation of Lactobacillus acidophilus LA-5 [1.75 x10(9) colony-forming units (cfu)], Lactobacillus plantarum (0.5 x10(9) cfu), Bifidobacterium lactis BB-12 (1.75 x109 cfu) and Saccharomyces boulardii (1.5 x10(9) cfu) in sachets. Each patient received two sachets twice daily for 15 days: one through the nasogastric tube and one spread on the oropharynx. The incidence of VAP was the primary endpoint. The incidence of other infections and sepsis, and the duration of hospital stay were the secondary endpoints. Administration of probiotics reduced the incidence of VAP [11.9% vs 28.3%, hazard ratio (HR) 0.34, 95% confidence interval (CI) 0.13-0.92; P=0.034] and sepsis [6.8% vs 24.5%, odds ratio 0.22, 95% CI 0.07-0.74: P= 0.016]. Furthermore, probiotic prophylaxis reduced the time of stay in the intensive care unit (ICU) and the length of hospital stay. The prophylactic use of probiotics with a combination of enteral and topical application to the oropharynx had a positive effect on the incidence of VAP and sepsis, as well as on ICU and total hospital stay in patients receiving protracted mechanical ventilation. (C) 2021 The Authors. Published by Elsevier Ltd.

Background: Coronavirus disease-19 (COVID-19) is implicated by active endotheliitis, and cardiovascular morbidity. The long-COVID-19 syndrome implications in atherosclerosis have not been elucidated yet. We assessed the immediate, intermediate, and long-term effects of COVID-19 on endothelial function.& nbsp;Methods: In this prospective cohort study, patients hospitalized for COVID-19 at the medical ward or Intensive Care Unit (ICU) were enrolled and followed up to 6 months post-hospital discharge. Medical history and labo-ratory examinations were performed while the endothelial function was assessed by brachial artery flow-mediated dilation (FMD). Comparison with propensity score-matched cohort (control group) was performed at the acute (upon hospital admission) and follow-up (1 and 6 months) stages.& nbsp;Results: Seventy-three patients diagnosed with COVID-19 (37% admitted in ICU) were recruited. FMD was significantly (p < 0.001) impaired in the COVID-19 group (1.65 +/- 2.31%) compared to the control (6.51 +/- 2.91%). ICU-treated subjects presented significantly impaired (p = 0.001) FMD (0.48 +/- 1.01%) compared to those treated in the medical ward (2.33 +/- 2.57%). During hospitalization, FMD was inversely associated with Interleukin-6 and Troponin I (p < 0.05 for all). Although, a significant improvement in FMD was noted during the follow-up (acute: 1.75 +/- 2.19% vs. 1 month: 4.23 +/- 2.02%, vs. 6 months: 5.24 +/- 1.62%; p = 0.001), FMD remained impaired compared to control (6.48 +/- 3.08%) at 1 month (p < 0.001) and 6 months (p = 0.01) post-hospital discharge.& nbsp;Conclusion: COVID-19 patients develop a notable endothelial dysfunction, which is progressively improved over a 6-month follow-up but remains impaired compared to healthy controls subjects. Whether chronic dysregulation of endothelial function following COVID-19 could be accompanied by a residual risk for cardiovascular and thrombotic events merits further research.

Traditional and novel analgesic modalities have been extensively tested for post-craniotomy pain management, yet the role of newer antiepileptic drugs in this area remains obscure. This study investigates the impact of levetiracetam (LEV) on pain modulation and neurobehavioral performance in a craniotomy model. Fifty-six Wistar rats were randomly assigned into seven groups: no intervention (CTRL), administration of placebo or LEV with no further intervention (PBO and LEV, respectively), and sham-operation or craniotomy in placebo (PBO-SHAM and PBO-CR, respectively) or LEV-treated rats (LEV-SHAM and LEV-CR, respectively). Pain was assessed by the rat grimace scale before, and at 8 and 24 h after craniotomy, following intraperitoneal injections of LEV (100 mg/kg twice daily) or normal saline two consecutive days before and on the craniotomy day. Elevated plus-maze and olfactory social memory tests were performed at 24-and 48 h post-craniotomy, respectively. Upon testing conclusion blood samples were collected for cytokines estimation. Levetiracetam administration enhanced antinociception in sham and craniotomy groups. In the elevated plus-maze test, LEV-CR rats spent more time in investigating open arms and performed more open arm entries than PBO-SHAM and PBO-CR animals. The olfactory test revealed no between-groups difference in acquisition time during first contact with a juvenile rat, while LEV-CR rats spent less time to recognize the same juvenile rat compared to PBO-SHAM and PBO-CR groups. Furthermore, LEV-treatment attenuated cortisol, interleukin-6 and TNF-a release, in sham and craniotomy animals. In conclusion, preemptive use of LEV decreases nociception, improves pain-evoked behavior and attenuates stress response in rats subjected to craniotomy.

Nowadays, there is an increasing knowledge that probiotic bacteria, topically applied, affects skin pathology. The objective of this study is to evaluate the effect on wound healing of locally applied probiotics by calculating the 3-D configuration of a standardized excisional wound. Fifty-two male Wistar rats were randomly allocated into groups: control, PRO1 [L. plantarum] and PRO2 [L. rhamnosus, B. longum]. Six excisional full-thickness wounds were created on each dorsum by an 8-mm circular biopsy punch; probiotics or saline were applied on days 0, 2, 4, 8, 16, photos of the wounds taken and specimens excised for histology [4 rats/group/time-point]. Both probiotic-groups exhibited accelerated healing significantly faster than the control, throughout, PRO2 exhibiting finally the best results [day 16]. However, only on day 2, did PRO1 exhibit the best results [wounded area, borders distance and epitheliazation line]. The results clearly demonstrate that the topical application of probiotics significantly improves the healing process, each strain working differently and more effectively in different healing phases. Thus, a combined formula containing different probiotics to modulate various healing phases is desirable. To this end our research continous.