Pain Biomarkers in Cancer: An Overview.

BACKGROUND: Pain is a common symptom in oncologic patients and its management is generally guided with reference to pain individually perceived by patients and expressed through self-reported scales. However, the utility of these tools is limited as it strongly depends on patients' opinions. For this reason, more objective instruments are desirable. OBJECTIVE: In this overview, scientific articles indicating potential markers to be used for pain management in cancer were collected and discussed. METHODS: Research was performed on principal electronic scientific databases by using the words "pain", "cancer", "markers" and "biomarkers" as the main keywords, and findings describing potential biomarkers for the management of cancer pain were reported. RESULTS: Studies on pain markers not specific for cancer typology (inflammatory, genetic markers predicting response to analgesic drugs, neuroimaging markers) and pain markers for specific types of cancer (bone cancer, breast cancer, lung cancer, head and neck cancer, prostate cancer, cancer in pediatrics) have been presented and commented on. CONCLUSION: This overview supports the view of the involvement of inflammatory mediators in the mechanisms underlying cancer pain. Only a small amount of data from research up till today is available on markers that can help in the management of pain, except for pro-inflammatory cytokines and other inflammatory indexes such as C-reactive protein (CRP). However, biomarkers are a promising strategy useful to predict pain intensity and to objectively quantify analgesic response in guiding decisions regarding individual-tailored treatments for cancer patients.

Clinical use of omega-3 fatty acids in migraine: A narrative review.

BACKGROUND: Omega-3 fatty acids (FAs) can produce several beneficial effects and are commonly used for the treatment of migraine symptoms. Although current therapeutic measures for migraine included pharmacological therapies, dietary supplements, and herbal ingredients, dietary patterns, acupuncture, relaxation techniques, biofeedback, and psychotherapy, omega-3 FAs therapeutic role seems to be obtained through the inhibition or reduction of the release of inflammatory cytokines. The present review aims to provide updated information about the effects of omega-3 FAs in migraine treatment, investigating their clinical effects alone or in combination with other substances. METHODS: Bibliographic research was conducted by examining scientific literature from January 2000 until January 31, 2020. Ten clinical studies were included in the review. Quality assessment of randomized controlled trials was performed by using the JADAD scale. RESULTS: Clinical studies methodology is not always of good quality and results show moderate evidence concerning the therapeutic role of omega-3 FAs in migraine. CONCLUSION: Further clinical trials are necessary to implement the knowledge concerning the use of omega-3 fatty acids in the treatment of migraine.

Preclinical and Clinical Pharmacology of Hydrocodone for Chronic Pain: A Mini Review.

Hydrocodone is one of the most prescribed oral analgesic drugs and it is one of the most abused drugs in general population. It is a mu-opioid agonist predominantly metabolized to the O-demethylated product hydromorphone and to the N-demethylated product norhydrocodone. The purpose of the study is to summarize the preclinical and clinical characteristics of hydrocodone. Pharmacokinetic aspect (terminal half-life, maximum serum concentration, and time to maximum serum concentration) of hydrocodone and the influence of metabolic genetic polymorphism in analgesic response to hydrocodone are also illustrated and commented. Literature on experimental preclinical pharmacology investigating analgesic activity in laboratory animals is furtherly discussed. Moreover, the authors discuss and comment on the updated data regarding safety profile and effectiveness of hydrocodone in the treatment of chronic pain. A bibliographic research was carried out (from February 01, 2018 to August 28, 2018) independently by two researchers (blinded to the authors and initially on results) in the major scientific databases and research engines of peer-reviewed literature on life sciences and biomedical topics, starting from January 1990 to August 2018. Analysis of results of clinical studies suggests that abuse-deterrent extended-release (ER) hydrocodone formulations can be effective and they are well tolerated in the treatment of chronic low back pain. Weaker is the evidence of the analgesic effectiveness of ER hydrocodone on other chronic pain syndromes and non-cancer non-neuropathic chronic pain. In these conditions, hydrocodone showed to have positive effects in non-controlled open studies and needs to be further studied to assess the real strength of results.

Cannabinoids and spinal cord stimulation for the treatment of failed back surgery syndrome refractory pain.

OBJECTIVE: This study aimed to evaluate pain and its symptoms in patients with failed back surgery syndrome (FBSS) refractory to other therapies, treated with a combination of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), in association with spinal cord stimulation (SCS). SETTINGS: Outpatients referred at Pain Unit of San Vincenzo Hospital in Taormina (Italy), between September 2014 and January 2016. SUBJECTS: Eleven FBSS patients diagnosed with neuropathic pain using the Douleur Neuropathique 4 questionnaire and suffering from moderate to severe chronic refractory pain, and undergoing treatment with SCS and a combination of THC/CBD for 12 consecutive months. MATERIALS AND METHODS: All the included patients discontinued previous unsuccessful therapy at least 2 months before the beginning of the cannabinoid therapy, with the exception of the SCS that was continued. Patients received a fixed dosage of cannabinoid agonists (THC/CBD) that could be increased subjective to pain control response. A Brief Pain Inventory questionnaire was administered to measure pain and its interference with characteristic dimensions of feelings and functions. The duration of treatment with SCS and THC/CBD combination was 12 months. RESULTS: Effective pain management as compared to baseline result was achieved in all the cases studied. The positive effect of cannabinoid agonists on refractory pain was maintained during the entire duration of treatment with minimal dosage titration. Pain perception, evaluated through numeric rating scale, decreased from a baseline mean value of 8.18±1.07-4.72±0.9 by the end of the study duration (12 months) (P<0.001). CONCLUSION: The results indicate that cannabinoid agonists (THC/CBD) can have remarkable analgesic capabilities, as adjuvant of SCS, for the treatment of chronic refractory pain of FBSS patients.

An update on anesthetics and impact on the brain.

INTRODUCTION: While anesthetics are indispensable clinical tools and generally considered safe and effective, a growing concern over the potential neurotoxicity of anesthesia or specific anesthetic agents has called into question the safety of general anesthetics, especially when administered at extremes of age. Areas covered: This article reviews and updates research findings on the safety of anesthesia and anesthetics in terms of long-term neurotoxicity, with particular focus on postoperative cognitive dysfunctions, Alzheimer's disease and dementias, developing brain, post-operative depression and autism spectrum disorder. Expert opinion: Exposure to general anesthetics is potentially harmful to the human brain, and the consequent long-term cognitive deficits should be classified as an iatrogenic pathology, and considered a public health problem. The fact that in laboratory and clinical research only certain anesthetic agents and techniques, but not others, appear to be involved, raises the problem on what is the safest and the least safe anesthetic to maximize anesthesia efficiency, avoid occurrence of adverse events, and ensure patient safety. New trends in research are moving toward the theory that neuroinflammation could be the hallmark of, or could have a pivotal role in, several neurological disorders.

Peritoneal carcinomatosis of colorectal origin.

Peritoneal carcinomatosis is, after liver metastases, the second most frequent cause of death in colorectal cancer patients and at the present time, is commonly inserted and treated as a stage IV tumour. Because there is no published data that outlines the impact of new therapeutic regimens on survival of patients with peritoneal surface diffusion, the story of carcinomatosis can be rewritten in light of a new aggressive approach based on the combination of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Also if these treatment perhaps allow to obtain better results than standard therapies, we suggest, that a large prospective randomised control trial is needed to compare long-term and progression-free survival under the best available systemic therapy with or without cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

Composition of the blood sampled from surgical drainage after joint arthroplasty: quality of return.

BACKGROUND: The quality of blood obtained with a device for postoperative blood drainage and autotransfusion (Bellovac-ABT, Astra Tech AB) was investigated in 50 patients who underwent total hip replacement (THR) or total knee replacement (TKR) surgeries. STUDY DESIGN AND METHODS: The Bellovac-ABT drainage set was inserted and blood collection began after skin closure (THR) or 15 minutes after tourniquet deflation (TKR). A collecting bag stayed in place for less than 6 hours. The product was then returned after sedimentation and discard of supernatant, without anticoagulants. RESULTS: Blood returned with the Bellovac-ABT had optimal hemoglobin levels and red blood cell (RBC) counts; the low platelet count reduced the risk of disseminated intravascular coagulation. Inertia of materials maintained acceptable values of C-reactive protein, whereas cytokines and complement split products rose rapidly. Higher concentrations of adenosine triphosphate and 2,3-diphosphoglycerate than in circulating blood suggested a normal RBC metabolism. No adverse reactions were observed in any participants. CONCLUSION: Because of its simplicity and safety, the Bellovac-ABT autologous blood transfusion system is recommended in THR or TKR without joint infection or malignancy.

Cardiovascular changes after extraglottic airway insertion: a prospective, randomized comparison between the laryngeal mask or the new PAXpress.

STUDY OBJECTIVE: To compare hemodynamic responses induced with the new extraglottic airway, PAXpress, and the classic Laryngeal Mask Airway (LMA). DESIGN: Prospective, randomized study. SETTING: Anesthesia department of a university teaching hospital. PATIENTS: 70 ASA physical status I and II patients, aged 18 to 65 years, scheduled to receive general anesthesia for extraabdominal procedures of short duration. INTERVENTIONS: Patients were randomly allocated to receive either a LMA (n = 35) or a PAXpress (n = 35) placement. After midazolam premedication (0.05 mg kg-1) and general anesthesia induction (propofol 2.5 mg kg-1, and fentanyl 1 microg kg-1) the airways were placed according to manufacturer instructions; then general anesthesia was maintained with a 2% sevoflurane concentration and an air/oxygen mixture. MEASUREMENTS AND MAIN RESULTS: Arterial blood pressure [both systolic (SBP) and diastolic (DBP)] and heart rate (HR) values were recorded immediately before airway placement, immediately after airway placement, then every 1 minute during the first 5 minutes. During the first 5 minutes after airway insertion, both SBP and DBP values were higher with the PAXpress than the LMA (repeated measures analysis of variance:p = 0.02 and p = 0.006, respectively), whereas no differences were reported in HR values. Also, the maximum percentage increase in both SBP and DBP values was larger with PAXpress [+19% (range: -19% to +80%) for SBP and +26% (range: -17% to +96%) for DBP] than the LMA [+9% (range: -30% to +90%) for SBP and +10% (range: -30% to +92%) for DBP] (p = 0.006 and p = 0.001, respectively). CONCLUSIONS: Although further studies are required to evaluate safety and airway trauma of this new extraglottic airway, placing the PAXpress produces more marked changes in hemodynamic variables as compared with those produced by the LMA.

Bispectral Index in ICU: correlation with Ramsay Score on assessment of sedation level.

OBJECTIVE: The assessment of sedation level in critically ill patient remains a challenge for the intensivists in order to avoid over- or under-sedation phenomena. Scoring systems commonly used still show some limitation; the introduction of Bispectral Index (an EEG parameter) could bring potential advantages in monitoring sedation. According to the reports, Bispectral Index correlates with levels of sedation on the Ramsay Scale. We report our personal experience in this topic. METHODS: Twenty patients, diagnosed with chronic obstructive pulmonary disease (COPD), were involved in the study. For an optimal adaptation to respiratory prothesis, they were sedated (with Propofol by continuous infusion at an initial dose of 2 mg/kg/h, which could be modulated with steps of 0.5 mg/kg/h), in order to maintain a Ramsay score of 4-5. BIS value was continuously recorded, and manually calculated on a mean average of a minute during the measuring of Ramsay score (T0) and every 30' for 24 hours on par with Ramsay score. EEG, SpO2, non invasive arterial pressure, ventilatory module, ETCO2, FIO2 were also recorded. For the statistic analysis, Friedman test and Spearman coefficient were utilized. Values of p < 0.05 were considered significant. RESULTS: 980 observations were carried out. The variation range of Ramsay Score was between 2 and 6. BIS range varied from 34 to 98. Statistic analysis of the data obtained pointed out some significative correlations, particularly between Ramsay Score and BIS (p < 0.01), and between BIS and dosage of Propofol (p < 0.01). CONCLUSIONS: The results of the study are consistent with those found in the literature on this topic of study. In fact, this study demonstrates the utility of BIS to track levels of consciousness in ICU patients while still maintaining the use of the score systems to care for ICU patients.