Serotonin Reuptake Inhibitors and Their Role in Chronic Pain Management

Serotonin has a particular place in the modulation of pain. Experimental studies have described 5-HT1–7 receptors and their effects on facilitation or inhibition of nociceptive input. Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors showed efficient and safer than tricyclic antidepressants in neuropathic pain. Although there is evidence regarding the beneficial impact of SSRIs in the multimodal acute pain management, studies are still searching for the potentially favorable effect of these drugs in the prevention of chronic postoperative pain. The scope of this chapter would be to update the knowledge regarding serotonin involving in pain pathways and to highlight the importance and contribution of serotonin reuptake inhibitors in the multimodal pain management schemes

Comparing the anti-inflammatory effects of Simvastatin and Rosuvastatin by measuring IL-1β, IL-6 and TNF-α levels using a murinic caecal ligation and puncture induced sepsis model / Compararea efectelor anti-inflamatoare ale Simvastatinei și Rosuvastatinei măsurând nivelele serice ale IL-1β, IL-6 si TNF-α folosind un model de sepsis la șobolan indus prin ligatură și puncție cecală

Introducere: Sepsisul este o boala caracterizată printr-un răspuns sistemic inflamator cauzat o infecție care poate evolua către sepsis sever și șoc septic. Această patologie ridică mari probleme la nivel global din cauza mortalității ridicate (care în anumite situații atinge 30%) precum și din cauza încarcăturii financiare mari. Sepsisul se caracterizează prin declasnșarea unor căi imune pro-inflamatorii cu rol de apărare a organismului dar care ulterior se dovedesc a fi extrem de dezajantajoase. Deși antibioterapia, resuscitarea volemică, terapia vasopresoare și controlul sursei de infecție rămân strategiile recomandate în tratamentul sepsisului, date publicate recent propun statinele ca o noua linie de tratament. Aceste medicamente au fost introduse în practica clinică datorită efectului hipocolesterolemiant însă inhibarea reductazei HMG-CoA și a biosintezei colesterolului induce o serie de efecte mai puțin studiate denumite generic pleiotrope: anti-inflamatoare, antitrombotice, imunomodulatoare și antioxidante. Obiective: În cadrul acestui experiment ne-am propus să evaluăm și să comparăm efectul antiinflamator al Simvastatinei și Rosuvastatinei măsurând nevelele serice ale IL-1β, IL-6 și TNF-α folosind un model consacrat de sepsis la șobolan. Metode: Am alcătuit patru grupuri (C, n=7; SEP, SV, RV, n=8). Statinele au fost administrate în două doze cu 18 și 3 ore înaintea intervenției chirurgicale. Sepsisul a fost obținut prin tehnica ligaturării și puncției cecale. De la fiecare subiect au fost recoltate eșantioane de sânge prin puncție venoasă în zilele 1, 4, 7 și 14 (ultimele eșantioane au fost obținute prin puncție cardiacă). Au fost analizați următorii parametrii: hemoleucograma, Procalcitonina, IL-1β, IL-6 și TNF-α. Rezultate: Numărul total al leucocitelor a fost mai mare pentru grupul septic dar netratat. Procalcitonina a fost reacționată în toate grupurile septice însă valori mai mici au fost observate în grupurile tratate cu Simvastatină și Rosuvastatină în comparație cu grupul netratat. Nivelul de IL-1β a fost mai mare în grupul tratat cu Rosuvastatină. Nivelele de IL-6 au avut o dispersie heterogenă în cadrul experimentului însă au fost înregistrate niveluri mai înalte în cadrul grupului septic netratat. Grupul tratat cu Simvastatină a avut nivele serice mai mari comparativ cu grupul tratat cu Rosuvastatină. Nivelele de TNF-α au fost mai mari pentru grupul septic netratat și cel tratat cu Rosuvastatină. Pentru grupul tratat cu Simvastatină nivelele TNF-α a fost similare cu cele din grupul control. Concluzii: Ambele statine au efecte anti-inflamatorii în cadrul acestui model de sepsis la șobolan indus prin tehnica ligaturării și puncției cecale. Dintre cele două, Simvastatina a avut un impact mai mare prin scăderea nivelelor circulante a unor markeri proinflamatori consacrați

Metabolic Signatures: Pioneering the Frontier of Rectal Cancer Diagnosis and Response to Neoadjuvant Treatment with Biomarkers—A Systematic Review

Colorectal cancer (CRC) is one of the most aggressive, heterogenous, and fatal types of human cancer for which screening, and more effective therapeutic drugs are urgently needed. Early-stage detection and treatment greatly improve the 5-year survival rate. In the era of targeted therapies for all types of cancer, a complete metabolomic profile is mandatory before neoadjuvant therapy to assign the correct drugs and check the response to the treatment given. The aim of this study is to discover specific metabolic biomarkers or a sequence of metabolomic indicators that possess precise diagnostic capabilities in predicting the efficacy of neoadjuvant therapy. After searching the keywords, a total of 108 articles were identified during a timeframe of 10 years (2013–2023). Within this set, one article was excluded due to the use of non-English language. Six scientific papers were qualified for this investigation after eliminating all duplicates, publications not referring to the subject matter, open access restriction papers, and those not applicable to humans. Biomolecular analysis found a correlation between metabolomic analysis of colorectal cancer samples and poor progression-free survival rates. Biomarkers are instrumental in predicting a patient’s response to specific treatments, guiding the selection of targeted therapies, and indicating resistance to certain drugs

Post-anaesthesia pulmonary complications after use of muscle relaxants (POPULAR): a multicentre, prospective observational study

Background Results from retrospective studies suggest that use of neuromuscular blocking agents during general anaesthesia might be linked to postoperative pulmonary complications. We therefore aimed to assess whether the use of neuromuscular blocking agents is associated with postoperative pulmonary complications. Methods We did a multicentre, prospective observational cohort study. Patients were recruited from 211 hospitals in 28 European countries. We included patients (aged ≥18 years) who received general anaesthesia for any in-hospital procedure except cardiac surgery. Patient characteristics, surgical and anaesthetic details, and chart review at discharge were prospectively collected over 2 weeks. Additionally, each patient underwent postoperative physical examination within 3 days of surgery to check for adverse pulmonary events. The study outcome was the incidence of postoperative pulmonary complications from the end of surgery up to postoperative day 28. Logistic regression analyses were adjusted for surgical factors and patients’ preoperative physical status, providing adjusted odds ratios (ORadj) and adjusted absolute risk reduction (ARRadj). This study is registered with ClinicalTrials.gov, number NCT01865513. Findings Between June 16, 2014, and April 29, 2015, data from 22803 patients were collected. The use of neuromuscular blocking agents was associated with an increased incidence of postoperative pulmonary complications in patients who had undergone general anaesthesia (1658 [7·6%] of 21694); ORadj 1·86, 95% CI 1·53–2·26; ARRadj –4·4%, 95% CI –5·5 to –3·2). Only 2·3% of high-risk surgical patients and those with adverse respiratory profiles were anaesthetised without neuromuscular blocking agents. The use of neuromuscular monitoring (ORadj 1·31, 95% CI 1·15–1·49; ARRadj –2·6%, 95% CI –3·9 to –1·4) and the administration of reversal agents (1·23, 1·07–1·41; –1·9%, –3·2 to –0·7) were not associated with a decreased risk of postoperative pulmonary complications. Neither the choice of sugammadex instead of neostigmine for reversal (ORadj 1·03, 95% CI 0·85–1·25; ARRadj –0·3%, 95% CI –2·4 to 1·5) nor extubation at a train-of-four ratio of 0·9 or more (1·03, 0·82–1·31; –0·4%, –3·5 to 2·2) was associated with better pulmonary outcomes. Interpretation We showed that the use of neuromuscular blocking drugs in general anaesthesia is associated with an increased risk of postoperative pulmonary complications. Anaesthetists must balance the potential benefits of neuromuscular blockade against the increased risk of postoperative pulmonary complications