Plasma Somatostatin Levels Are Lower in Patients with Coronary Stenosis and Significantly Increase after Stent Implantation.

Background/Objectives: Stimulated capsaicin-sensitive peptidergic sensory nerves release somatostatin (SST), which has systemic anti-inflammatory and analgesic effects, correlating with the severity of tissue injury. Previous studies suggest that SST release into the systemic circulation is likely to serve as a protective mechanism during thoracic and orthopedic surgeries, scoliosis operations, and septic conditions, all involving significant tissue damage, pain, and inflammation. In a severe systemic inflammation rat model, SST released from sensory nerves into the bloodstream enhanced innate defense, reducing mortality. Inflammation is the key pathophysiological process responsible for the formation, progression, instability, and healing of atherosclerotic plaques. Methods: We measured SST-like immunoreactivity (SST-LI) in the plasma of healthy volunteers in different age groups and also that of stable angina patients with coronary heart disease (CHD) using ELISA and tracked changes during invasive coronary interventions (coronarography) with and without stent implantation. Samples were collected at (1) pre-intervention, (2) after coronarography, (3) 2 h after coronarography initiation and coronary stent placement, and (4) the next morning. Results: There was a strong negative correlation between SST-LI concentrations and age; the plasma SST-LI of older healthy volunteers (47-73 years) was significantly lower than in young ones (24-27 years). Baseline SST-LI in CHD patients who needed stents was significantly reduced compared to those not requiring stents. Plasma SST-LI significantly increased two hours post stent insertion and the next morning compared to pre-intervention levels. Conclusions: Age-related SST decrease might be a consequence of lower gene expression within specific hypo-thalamic nuclei as has been previously demonstrated in rodent animals. Reperfusion of ischemic myocardium post-stent implantation may trigger SST release, potentially offering protective benefits in coronary heart disease. Investigating this SST-mediated mechanism could offer valuable insights for future therapies.

Changes in Time to Initial Physician Contact and Cancer Stage Distribution during the COVID-19 Pandemic in Patients with Head and Neck Squamous Cell Carcinoma at a Large Hungarian Cancer Center.

The aim of our study was to compare the characteristics and time to initial physician contact in patients with head and neck squamous cell carcinoma (HNSCC) before and during the COVID-19 pandemic at a large Hungarian cancer center. This was a retrospective study of patients 18 years or older presenting at the regional cancer center of Pécs Clinical Center with HNSCC between 1 January 2017, and 15 March 2020 (the pre-COVID-19 period) and between 16 March 2020, and 13 May 2021 (the COVID-19 period). Demographic and clinical data were collected, and the time between initial symptom onset and initial physician contact (TTP) was determined. Descriptive and exploratory statistical analyses were performed. On average, the number of patients diagnosed with HNSCC per month during the pandemic decreased by 12.4% compared with the pre-COVID-19 period. There was a significant increase in stage I and stage II cancers (from 15.9% to 20.3% and from 12.2% to 13.8%, respectively; p < 0.001); a decrease in stage III and IVa,c cancers; and a significant increase in stage IVb cancers (from 6% to 19.9%; p < 0.001) during the pandemic. The median TTP increased during the pandemic from 43 to 61 days (p = 0.032). To our knowledge, this is the first study investigating the effect of COVID-19 on patients with HNSCC in the Central-Eastern European region. We found a bidirectional shift in cancer stages and increased TTP during the pandemic. Our findings highlight the necessity for more nuanced analyses of the effects of COVID-19.

[Perioperative aspects of anaphylaxis]. / Az anafilaxia perioperatív vonatkozásai.

Anaphylaxis is a generalized, severe, life-threatening reaction, mostly with an allergic origin. Triggers are usually drugs, insect bites, poisons, contrast material and food. It is caused by various mediators (histamine, prostaglandins, leukotrienes etc.) released from mast cells, basophilic granulocytes. Histamine plays a central role in its creation. Immediate recognition and specific treatment instantaneously are essential for successful treatment. In severe conditions, the clinical features are very similar, regardless of their allergic/non-allergic origin. The incidence can vary over time and between patient populations. Its incidence is extremely variable, approximately 1/10 000 anaesthesia. Most studies cite neuromuscular blocking agents as the most common causative factor. In England, the results of the 6th National Audit Project revealed that the most common causes were antibiotics (1/26 845), followed by neuromuscular junction blocking drugs (1/19 070), chlorhexidine (1/127 698), and Patent Blue paint (1/6863). It occurs within 5 minutes in 66% of cases, 6-10 minutes in 17%, 11-15 minutes in 5%, 16-30 minutes in 2%, but usually within 30 minutes. Antibiotic allergy is a growing problem, especially to teicoplanin (16.4/100 000) and co-amoxiclav (8.7/100 000). The risk of anaphylactic shock should not be a determining factor in choosing the type of muscle relaxant drug. The patient's anaesthesia classification, physical condition, obesity, use of beta-blockers and ACE inhibitors influence the clinical characteristics. The initial symptoms can be extremely varied in terms of the effectiveness of the treatment, early recognition and commencement of therapy are the keys to success. Asking about a preoperative allergy history can reduce the risk and incidence of anaphylaxis. Orv Hetil. 2023; 164(22): 871-877.

Plasma Somatostatin Levels Increase during Scoliosis Surgery, but Not Herniated Disc Operations: Results of a Pilot Study.

Somatostatin (SST) released from capsaicin-sensitive sensory nerves in response to stimulation exerts systemic anti-inflammatory, analgesic actions. Its elevation correlates with the extent of tissue injury. We measured plasma SST alterations during spine operations (scoliosis and herniated disc) to determine whether its release might be a general protective mechanism during painful conditions. Sampling timepoints were baseline (1), after: soft tissue retraction (2), osteotomy (3), skin closure (4), the following morning (5). Plasma SST-like immunoreactivity (SST-LI) determined by radioimmunoassay was correlated with pain intensity and the correction angle (Cobb angle). In scoliosis surgery, postoperative pain intensity (VAS 2.) 1 day after surgery significantly increased (from 1.44 SEM ± 0.68 to 6.77 SEM ± 0.82, p = 0.0028) and positively correlated with the Cobb angle (p = 0.0235). The baseline Cobb degree negatively correlated (p = 0.0459) with the preoperative SST-LI. The plasma SST-LI significantly increased in fraction 3 compared to the baseline (p < 0.05), and significantly decreased thereafter (p < 0.001). In contrast, in herniated disc operations no SST-LI changes were observed in either group. The VAS decreased after surgery both in the traditional (mean 6.83 to 2.29, p = 0.0005) and microdiscectomy groups (mean 7.22 to 2.11, p = 0.0009). More extensive and destructive scoliosis surgery might cause greater tissue damage with greater pain (inflammation), which results in a significant SST release into the plasma from the sensory nerves. SST is suggested to be involved in an endogenous postoperative analgesic (anti-inflammatory) mechanism.

Developing intercultural competences for more effective patient care and international medical and research collaborations / Interkulturális kompetenciák fejlesztése a hatékonyabb betegellátás és a nemzetközi gyógyító és kutatói együttmuködések érdekében

Introduction: In our globalised world, the role of intercultural competence in healthcare is increasing as societies become multicultural. The development of this competence should start in medical education. Objective: In our qualitative study among Hungarian medical students, we sought to find out to what extent the multicultural student composition of our elective course contributes to the development of their intercultural competence. Method: In our action research, semistructured focus group interviews were conducted with 35 Hungarian medical students between April and November, 2021. The transcripts of the digitally recorded interviews were evaluated using qualitative methods. Results: After a thematic analysis of the interviews, the vast majority of the students' opinions could be classified into one of the following four thematic categories: 1) the benefits of studying together with international students, 2) the development of cultural awareness, 3) the development of an open mindset, and 4) the expected longterm impact of intercultural competence on medical work. Overall, Hungarian students evaluated their learning in the multicultural course positively. Based on the results of the focus group interviews, it can be claimed that by the end of the semester, the Hungarian students' perceived intercultural competence had improved due to the course and its multicultural composition. Conclusion: The course, with its multicultural student population, can contribute to and promote the acquisition of intercultural competence, which in the long run can be effectively used by future doctors both in patient care and in effective communication within healthcare teams as well as in international medical, research and scientific collaborations. Providing a multicultural student environment in the classroom, including interactive teaching methodologies and intercultural project work, have many potentials to make the learning-teaching process more effective and could be applied in the future when developing new courses.

Antibacterial effect of local anaesthetics / Helyi érzéstelenítok antibakteriális hatása.

Összefoglaló. Gyógyszereink egy részének jelentos, az eredeti alkalmazástól eltéro hatása is van. Ezek felismerése fontos, hogy elkerüljük a nem várt mellékhatásokat, vagy kihasználjuk ezeket a kedvezo adottságokat. A helyi érzéstelenítok antibakteriális hatása 1909 óta ismert, de ennek több évtizeden keresztül nem tulajdonítottak jelentoséget. Az 1960-as években figyeltek fel eloször az álnegatív mikrobiológiai eredmények lehetoségére, helyi érzéstelenítoket használva a mintavételhez. Tanulmányok igazolták, hogy a bronchoszkópiás, seb-, bor- vagy fül-, orr-, gégészeti bakteriológiai eredmények is érintve lehetnek. A ma is használt gyógyszerek közül a 0,5%-os bupivakainnak és a 2%-os lidokainnak van jelentos antibakteriális hatása Gram-pozitív és Gram-negatív baktériumokkal szemben, ami kifejezettebb 37 °C-on, mint szobahomérsékleten. A legerosebb antibakteriális hatást a 0,5%-os bupivakain mutatta. A napi gyakorlatban alkalmazott koncentrációjuk magasabb, mint a különbözo klinikai izolátumokkal szemben meghatározott minimális gátló koncentráció. Fenti tulajdonságaik alapján felmerült szerepük a kórházi sebfertozések csökkentésében is. A hatásmechanizmus több pontja ismert, károsítják a sejthártya integritását, és több bakteriális enzim muködését gátolják. Orv Hetil. 2021; 162(5): 171-176. Summary. Medications may have important impacts other than the original effect. It is important to know about these to avoid side effects or use these beneficial capabilities. The antibacterial effect of local anaesthetics has been known since 1909. For decades, no attention has been payed to this fact. In the 1960s, the high number of negative microbiological results when local anaesthetics were used before sampling drew attention to the possible antibacterial effect. Studies suggested that cultures from bronchoscopy, wound, skin or nasal samples may be affected. Bupivacaine 0,5% and lidocaine 2% have the most noticeable effect against both Gram-positive and Gram-negative bacteria. This impact is more pronounced at 37 °C than at room temperature. Bupivacaine 0,5% has the most pronounced effect. The concentration of local anaesthetics in daily routine is higher than the minimal inhibitory concentration against various clinical isolates. In the view of these results, they may contribute to reduce surgical site infections. There are known details regarding the mechanism of action. Local anaesthetics have target sites on cellular membrane and inhibit bacterial enzymes. Orv Hetil. 2021; 162(5): 171-176.

Plasma somatostatin-like immunoreactivity increases in the plasma of septic patients and rats with systemic inflammatory reaction: experimental evidence for its sensory origin and protective role.

Alterations of somatostatin-like immunoreactivity (SST-LI) in the plasma of 11 systemic inflammatory response syndrome (SIRS) patients were investigated in correlation with cytokines, adhesion molecules and coagulation markers repeatedly during 4 days. The origin and role of SST were studied in the cecum ligation and puncture (CLP) rat SIRS model. Capsaicin-sensitive peptidergic sensory nerves were defunctionalized by resiniferatoxin (RTX) pretreatment 2 weeks earlier, in a separate group animals were treated with the somatostatin receptor antagonist cyclo-somatostatin (C-SOM). Plasma SST-LI significantly elevated in septic patients compared to healthy volunteers during the whole 4-day period. Significantly decreased Horowitz score showed severe lung injury, increased plasma C-reactive protein and procalcitonin confirmed SIRS. Soluble P-selectin, tissue plasminogen activator and the interleukin 8 and monocyte chemotactic protein-1 significantly increased, interleukin 6 and soluble CD40 ligand did not change, and soluble Vascular Adhesion Molecule-1 decreased. SST-LI significantly increased in rats both in the plasma and the lung 6h after CLP compared to sham-operation. After RTX pretreatment SST-LI was not altered in intact animals, but the SIRS-induced elevation was absent. Lung MPO activity significantly increased 6h following CLP compared to sham operation, which was significantly higher both after RTX-desensitization and C-SOM-treatment. Most non-pretreated operated rats survived the 6h, but 60% of the RTX-pretreated ones died showing a significantly worse survival. This is the first comprehensive study in humans and animal experiments providing evidence that SST is released from the activated peptidergic sensory nerves. It gets into the bloodstream and mediates a potent endogenous protective mechanism.

Surgery and sepsis increase somatostatin-like immunoreactivity in the human plasma.

We have previously shown in animals that somatostatin released from capsaicin-sensitive afferents in response to inflammation and tissue damage exerts systemic anti-nociceptive and anti-inflammatory actions. Since peptidergic sensory innervation of the airways and the joints are particularly dense, we aimed at investigating the alterations of plasma somatostatin-like immunoreactivity (SST-LI) in response to thoracic and orthopedic surgery, as well as sepsis. Thoracotomy, video-assisted thoracoscopy, hip and knee endoprosthesis were performed under general anesthesia. Blood was taken before, during and after the surgical procedures, as well as at admission and every consecutive morning from septic patients receiving exclusively total parenteral nutrition. SST-LI was determined from the plasma with specific and sensitive radioimmunoassay developed in our laboratory. Plasma SST-LI in healthy volunteers and preoperatively was 8-12fmol/ml. Both thoracotomy and thoracoscopy significantly increased SST-LI by 55-60% at the end of the procedures when the thoracic cavity and the skin were closed. Hip endoprosthesis implantation elevated SST-LI by 30% after skin incision, which increased further to 55% by the time the surgery was completed. In contrast, knee operations performed under tourniquet did not alter SST-LI in the systemic circulation. SST-LI was almost 3-fold higher in the plasma of septic patients than in healthy volunteers. This human study revealed that thoracic/hip surgery and sepsis elevate SST-LI in the systemic circulation, presumably by inducing its release from sensory fibres. It is concluded, that the endogenous protective mechanism mediated by neural somatostatin, which has been evidenced in animals, is likely to operate in patients.