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The association between local oral inflammation and cardiovascular risk has been extensively studied, with results indicating a bidirectional relationship. The aim of the present study was to investigate the associations between blood cells and a large number of salivary cytokines, chemokines, and growth factors. The study consisted of 165 individuals who were referred to the Oral and Maxillofacial Surgery clinic at Falun County hospital, Sweden, for surgical removal of impacted lower third molar. The study subjects did not have any known inflammatory disorders. Complete blood cell counts were analyzed using the routine laboratory at Falun Hospital, Falun, Sweden. Proteomic analysis of 92 inflammation-related protein biomarkers in saliva was performed using a multiplex proximity extension assay. After adjustment for multiplicity testing using the false discovery rate approach, there remained significant association between several saliva cytokines, chemokines, and growth factors and white blood cell counts (n = 19), neutrophil counts (n = 18), erythrocyte counts (n = 13), hemoglobin concentrations (n = 20), erythrocyte volume fractions (n = 22), and platelet counts (n = 12). There are several significant associations between local inflammatory cytokines in the oral cavity and blood cell parameters indicating a relationship between local and systemic inflammatory activity.

The cytokine network plays a crucial role in regulating immune responses and facilitating intercellular communication. Cytokines are essential in numerous physiological and pathological processes. This study aimed to investigate associations between blood cell counts and a broad range of cytokines, chemokines, and growth factors. We included one hundred and sixty-five essentially healthy individuals in this study, which was approved by the Swedish Ethical Review Authority (Dnr 2015/378) and registered in EudraCT (2014-004235-39). Blood samples were collected for blood cell counts and analysis of cytokines, chemokines, and growth factors using the Proseek Multiplex Inflammation kit, Olink Bioscience, Uppsala, Sweden. Correlations between the different markers were calculated using Spearman rank correlations, adjusted for multiplicity and for multiple testing, with a significance threshold of p < 0.05. There were significant associations between platelet count and 23 cytokines, between white blood cell count and 8 cytokines, and between erythrocyte volume fractions and 19 cytokines. IL-6 had a central role within the cytokine network associated with platelets and was also associated with white blood cells and neutrophil cells. These findings emphasize the integrated nature of immune and hematological responses, where blood cell parameters are associated with systemic cytokine activity. The observed intercytokine associations, including cross-family interactions, may help to highlight regulatory pathways, providing potential targets for biomarker development and therapeutic intervention in immune-mediated conditions.

Cardiovascular disease (CVD) remains the leading global cause of morbidity and mortality, largely driven by atherosclerosis, a chronic inflammatory process involving lipids and immune cells. Although traditional lipid biomarkers such as low-density lipoprotein (LDL) and high-density lipoprotein (HDL) are well-established in CVD risk stratification, the interplay between cytokines, chemokines, growth factors (CCGFs), lipid metabolism, and hematological parameters in non-cardiac populations remains underexplored. We investigated associations between plasma cytokines and lipid-related biomarkers and their relationships with circulating blood cell counts in a cohort of 164 essentially healthy adults aged 18–44 years. CCGF profiling was performed using a proximity extension assay (PEA), and statistical correlations were adjusted for multiple testing using false discovery rate (FDR) correction. The CCGFs that were associated with HDL and apolipoprotein A1 all displayed negative associations. Several pro-inflammatory cytokines, including CCL3, IL-6, and TNFSF10, showed strong positive associations with triglycerides, remnants, non-HDL, and body mass index (BMI). Furthermore, triglycerides and remnants were consistently correlated with elevated leukocyte, neutrophil, and platelet counts. HGF and FGF-21, mainly considered as anti-inflammatory, were positively associated with BMI and negatively associated with HDL, which is compliant with a multitude of actions, depending on the local milieu and the cellular interplay. Our results support the existence of a complex immunometabolic network involving lipids, CCGFs, and blood cells, even in non-diseased individuals. The observed patterns underscore the importance of understanding the intricate cytokine–lipid–cell interactions that may occur in early pathophysiological processes and highlight their potential utility in refining cardiovascular risk assessment beyond traditional lipid metrics.

Purpose

To study patient safety in third molar surgery, where two different doses of S-ketamine were administered for pain relief and compared to a placebo (saline). The primary focus was capillary oxygen saturation of the blood (SpO2) and secondarily, alterations in respiratory rate, blood pressure, pulse or adverse events.

Methods

One hundred and sixty-eight subjects were included in a randomised, placebo-controlled, double-blind trial. The two subanaesthetic study drugs were low-dose S-ketamine (0.125 mg/kg) and high-dose S-ketamine (0.25 mg/kg). Every patient was sedated with midazolam prior to infusion of the investigational drug. The teeth were surgically removed according to a routine clinical procedure, under local anaesthesia.

Results

Primary end-point for the safety aspects was capillary oxygen saturation (SpO2) after administration of the investigational drug was finished. A significant difference was found between the placebo and the high-dose group at that point (p = .021), with a decrease of saturation in the high-dose group. The lowest saturation and the number of registrations of SpO2 <90% did not show any difference between groups. Oxygen supplementation was given in circa 40% of the cases with no differences between the intervention groups. No other significant differences between groups regarding saturation or respiratory rate were noted.

Conclusion

In this study, it was safe to use adjunct preoperative single-dose intravenous S-ketamine 0.25 mg/kg body weight for pain relief, in midazolam-sedated patients receiving third molar surgery. There were no serious adverse events or symptoms of overdose nor any clinically relevant effects on circulatory or respiratory parameters.

Background

In most cases, a combination of paracetamol and ibuprofen are the optimal treatment for postoperative pain in third molar surgery. If stronger analgesia is required, opioids are traditionally administered. In day-case, surgery; however, opioids should be avoided. Thus, the anaesthetic agent S-ketamine in analgesic doses might be preferred.

Methods

The study was designed as a randomized placebo-controlled double-blind clinical trial. The study enrolled healthy subjects according to the American Society of Anaesthesiologists classification; I or II (ASA), aged 18 to 44 years, with a body weight between 50 and 100 kg. The patients were randomized into three groups where two doses of S-ketamine were compared (high: 0.25 mg/kg or low: 0.125 mg/kg) with placebo (saline).

Results

A primary outcome of the study was that VAS at 4 h postoperatively, showed no significant difference between the placebo and high-dose S-ketamine group or in the low-dose group. We found a significant difference between the groups for the first 24 h, with a lower VAS-score in the high-dose S-ketamine group. The time to when 50% had taken their first rescue medication was 12 min later in the high-dose ketamine group.

Conclusions

Pre-emptive S-ketamine 0.25 mg/kg gave a global significant reduction of pain by VAS during the first 24 h postoperatively. The time from end of surgery to first rescue medication were longer in the high-dose ketamine group compared to both low-dose ketamine and placebo groups.

PURPOSE:

The purpose of this study was to evaluate patient safety, in terms of adverse events, alterations in blood pressure or oxygen saturation (SpO2) in two routine sedation procedures, with and without intravenous analgesia.

METHODS:

Patients referred for surgical removal of mandibular third molars were treated in a randomized, controlled, single-blinded procedure. Eighty-seven men and women, aged 18 to 44 years, were allotted to either of two treatment groups, midazolam + tramadol (M + T) and midazolam + saline (M + S) or to a control group (C), given no sedation.

RESULTS:

Tramadol at 1 mg/kg body weight resulted in a higher frequency of oxygen desaturation (SpO2 < 90 %) than a placebo (p = 0.002) but had no effect on mean SpO2 at the end point or at the end of surgery. In both the test groups, there was a significant decrease in diastolic blood pressure (p < 0.001) from baseline to the end of surgery.

CONCLUSION:

The results confirm that pre-emptive intravenous tramadol, administered at 1 mg/kg body weight as an adjunct to midazolam sedation for third molar surgery, offers a safe method. But, it should be noted that our previous study shows that it is not a particularly effective analgesic. Further testing is therefore warranted, using other doses or other drugs, to find a better intravenous protocol for postoperative analgesia, with maximum effect and minimal risk, in outpatient oral and maxillofacial surgery procedures.

INTRODUCTION:

This study aims to compare two routine procedures of sedation, with and without intravenous adjunct analgesia, in third molar surgery regarding postoperative pain and consumption of analgesics.

MATERIAL AND METHODS:

In a randomized, controlled, single-blinded procedure, 87 men and women aged 18-44 years were divided into two treatment groups, midazolam + tramadol (M + T) and midazolam + saline (M + S), and one control group (C), with no additional medication. After removal of a third lower molar, patients recorded postoperative pain on a visual analog scale (VAS) and consumption of analgesics during the first day after surgery.

RESULTS:

Time from the end of operation until first rescue pill (400 mg Ibuprofen tablet) differed significantly between the M + S group (193 min) and the C group (110 min) (p = 0.001) as well as the M + T group (157 min) and the C group (p = 0.049). The study did not show any significant reduction of postoperative pain, VAS, after third molar surgery in patients who received adjunct pre-emptive intravenous administration of 1 mg/kg tramadol under midazolam sedation.

DISCUSSION AND CONCLUSION:

The lack of significant difference between the study and placebo groups indicates that tramadol at 1 mg/kg might be an insufficient dose, though the suitability for tramadol in oral and maxillofacial surgery has already been settled in other studies.