Local anesthetics counteract cell proliferation and migration of human triple-negative breast cancer and melanoma cells.

In different retrospective studies, a protective role of regional anesthetics in reducing cancer recurrence after surgery was indicated. Accordingly, it has been previously demonstrated a protective effect of anesthetics in breast cancer cells and in other types of cancer. On the other hand, how anesthetics influence cancer needs in-depth investigations. For this purpose, two different human cancer cell lines, MDA-MB-231, triple-negative breast cancer, and A375, melanoma, were used in this study. By means of Western blotting and immunofluorescence and terminal deoxynucleotidyl transferase dUTP nick end labeling analyses, the signal transduction pathways activated by the anesthetics, such as ropivacaine and levobupivacaine, were analyzed. The data obtained demonstrated that both anesthetics are able to counteract cell proliferation by positively modulating cell death signaling and by decreasing cell proliferation and survival pathways.

Influence of the Menstrual Cycle Phase on Pain Perception and Analgesic Requirements in Young Women Undergoing Gynecological Laparoscopy.

CONTEXT: The influence of the gonadal hormones on some aspects of the human physiology has been studied with uncertain results. Still a confusion exists in relation to the real effects of the female hormones on the perception of pain. The existing data refer mainly to experimental studies and have provided results not always useful in the clinical practice. DATA SOURCE: This study was designed to detect whether there are differences in the perception of the postoperative pain in women, during two clearly defined phases of hormonal asset: luteal and follicular phases. CONCLUSION: The results of this study have demonstrated that in postoperative female patients pain is perceived significantly more in the luteal phase of the menstrual period, than in the follicular phase. This could suggest that female in child-bearing age should be scheduled for elective surgery preferentially during the follicular phase, unless differently necessary. It would guarantee a more comfortable postoperative period, with reduced necessity of analgesics.

Duloxetine and pregabalin for pain management in multiple rheumatic diseases associated with fibromyalgia.

The fibromyalgia syndrome (FMS) is characterized by chronic and widespread musculoskeletal pain and soreness accompanied by sleep disorders, chronic fatigue and affective disorders. FMS is often associated with other forms of immuno-rheumatic diseases. Although FMS pathophysiology is still not fully understood, a number of neuroendocrine, neurotransmission and neurosensitive disorders might generate a mechanism for the elicitation of pain by "central sensitization," which is common to many other painful conditions. The present case describes the success of a therapeutic scheme, which associates two different pharmacological classes, anticonvulsants and new-generation antidepressants, when FMS complicates a rare pathology called Cogan's syndrome. The association of two drugs might noticeably affect the molecular mechanisms of difficult pain, thus solving painful conditions of multifactorial origin.

Emotional arousal and valence in patients with fibromyalgia: a pilot study.

The pathogenesis of pain in fibromyalgia is still not completely understood. A disrupted emotional modulation could affect the physiology of nociception and contributes to an altered perception of pain. The aim of this study was to test the role of emotional arousal and valence in pain susceptibility in fibromyalgia using the International Affective Picture System (IAPS) paradigm and the Fibromyalgia Severity Scale (FSS). The study focused on comparing emotional arousal and valence between patients with fibromyalgia and the control group. The secondary objective was to examine the correlation between emotional indices and scores on the FSS and the duration of the disease. The 20 patients with fibromyalgia enrolled showed a higher mean arousal score for all the stimuli, including a higher score for unpleasant and socially unpleasant stimuli. The valence scores for social-relevant stimuli were also higher. Increased arousal to unpleasant and socially unpleasant images and increased valence of them correlated with the duration of the disease and the severity of symptoms and could reflect impairment in social cognition and marked sensitivity to pain in interaction with central nociceptive dysregulation.

Comparison of different anaesthetic methodologies for sedation during in vitro fertilization procedures: effects on patient physiology and oocyte competence.

The main goal of the present retrospective study is to compare four analgesic methodologies (EMLA cream, propofol, thiopental sodium, sevoflurane) for in vitro fertilization (IVF) oocyte retrieval. We found that most anaesthetic parameters were not significantly different among all treatments. In contrast, significant differences were revealed in all groups for total number of oocytes retrieved per patient, rate of mature oocytes at metaphase II stage (MII) and percentage of fertilization and embryo development. In the EMLA cream and thiopental sodium groups we observed the highest percentage of MII oocytes (P < 0.001). Fertilization rate in the EMLA and sevoflurane groups were similar but significantly higher than the propofol and thiopental sodium groups (P < 0.001). The highest rate of anomalous fertilization was observed in the propofol group. Rate of embryo development was similar in all groups but sevoflurane group had a lower percentage of good embryos. In conclusion, by comparing different anaesthetic techniques with different mechanisms of action and administration, potential negative effects of these drugs on the initial stages of human IVF procedure were revealed. Therefore, a local anaesthetic cream is proposed as an acceptable alternative option for anaesthesia during transvaginal oocyte retrieval.

Waiting time and pain during office hysteroscopy.

STUDY OBJECTIVE: To find a correlation between the waiting time between counseling about and performance of office hysteroscopy and the perception of pain. DESIGN: Observational study (Canadian Task Force classification II-2). SETTING: Academic environment. PATIENTS: Two hundred eighty-four women undergoing hysteroscopy. INTERVENTIONS: Diagnostic hysteroscopy with endometrial biopsy. MEASUREMENTS AND MAIN RESULTS: Before examination, patients were asked to complete 2 forms, the STAI-S (State-Trait Anxiety Inventory, State) and STAI-T (State-Trait Anxiety Inventory, Trait) anxiety scales, for evaluation of their usual anxiety state and their state of anxiety during the examination. Patients were asked to quantify on a visual analog scale the pain felt during the examination. A statistically significant positive correlation, even if weak, was demonstrated between pain and waiting time (r = 0.45; p < .01) but not with the values for the anxiety state (r = 0.06; p = .56) and anxiety trait (r = -0.05; p = .66). Pain (≥4) was significantly associated with waiting time (≥60 minutes) (odds ratio [OR], 5.21; 95% confidence interval [CI], 1.29-35.50), age (OR, 1.57; 95% CI, 0.40-5.87) and menopause (OR, 2.81; 95% CI, 1.10-7.40) but not with STAI-S level (≥34) (OR, 0.87; 95% CI, 0.26-3.12) or STAI-T level (≥34) (OR, 0.65; 95% CI, 0.19-2.32). CONCLUSION: Office hysteroscopy is associated with a level of anxiety that can affect patient tolerability of the procedure. However, factors such as reducing waiting time may have a positive effect on patient compliance, making hysteroscopy easier and thereby increasing its diagnostic and therapeutic potential.

The Perioperative Anesthetic Management of the Pediatric Patient with Special Needs: An Overview of Literature.

The perioperative management of pediatric patients with psycho-physical disorders with related relational and cognitive problems must be carefully planned, in order to make the entire hospitalization process as comfortable and as less traumatic as possible. This article reports an overview of the anesthetic management of non-cooperative patients between 6 and 14 years old. The pathologies most frequently responsible for psycho-physical disorders can be summarized into three groups: (1) collaboration difficulties (autism spectrum disorders, intellectual impairment, phobia); (2) motor dysfunction (cerebral palsy, epilepsy, other brain pathologies, neuromuscular disorders), and (3) craniofacial anomalies (Down syndrome, other genetic syndromes). Anesthesia can be performed safely and successfully due to careful management of all specific problems of these patients, such as a difficult preoperative evaluation (medical history, physical examination, blood sampling, evaluation of vital parameters and predictive indices of difficult airway) and the inapplicability of a "standard" perioperative path (timing and length of the hospitalization, anesthetic premedication, postoperative management). It is necessary to ensure a dedicated perioperative process that is safe, comfortable, tailored to specific needs, and as less traumatic as possible. At the same time, all necessary precautions must be taken to minimize possible complications.

The stress response of intensive care unit medical doctors facing repeated severe emergencies.

Objectives: This study assesses the psychopathological distress experienced by doctors working in an Intensive care unit (ICU) during the COVID-19 pandemic. These doctors were the same who faced the consequences of a previous natural disaster, a severe 6.3 magnitude earthquake. A second objective is to evaluate their current mental attitude, professional performances and coping strategies adopted in the pandemic in relation to the conditioning effect of that first emergency, the earthquake. Methods: Thirty-seven ICU medical doctors were recruited and assessed using Rapid Stress Assessment (RSA) rating scale, Symptom Checklist-90 Revised (SCL-90-R), Zung Self-Rating Anxiety Scale, Beck Depression Inventory, Beck Hopelessness Scale, Millon Clinical Multiaxial Inventory III. Comparison between exposure to the earthquake and COVID pandemic has been made in terms of professional role and psychological burden. Results: Comparison between 2009 earthquake catastrophe and COVID pandemic conditions evidenced relevant changes in professional role, team, environment, shifts, and work organization. Conclusion: The doctors, who already experienced the 2009 earthquake reported a feeling of greater insecurity facing this latter catastrophe, the COVID pandemic, as well as perception of greater concern for their family and the global situation. However, having participated in the medical management of another emergency (the 2009 earthquake) appears to have contributed to limiting demoralization and psychological distress. The feeling of having greater decision-making possibilities and participation in the organization of work, strengthen coping skills in the face of the emergency.

Use of Video Laryngoscope in Sedated Spontaneously Breathing Patients with Predicted Difficult Tracheal Intubation and Impossibility of Using Fibreoptic Bronchoscopy.

Intubation with a flexible fibrobronchoscope in an awake patient is frequently considered the technique of choice in patients with predicted difficult intubation. There are, however, situations in which the use of the fibrobronchoscope is not applicable, particularly due to problems attributable to the patient or to limited use of the instrument. In such situations, the video laryngoscope can be a useful alternative, as long as it is associated with adequate sedation of the patient. In fact, it ensures excellent viewing of the glottis, allowing for successful orotracheal intubation to be performed even in case of difficult airways, while keeping the patient spontaneously breathing throughout the procedure. From the data present in the literature, this technique seems to ensure a success rate and a safety profile similar to those obtained with the fibrobronchoscope, moreover, with greater ease of use by the anaesthesiologist. The main purpose of this work is to provide a valid and safe alternative to intubation with a fibrobronchoscope while awake in those patients with anticipated difficult airway management and in whom, for different reasons, fibrobronchoscope cannot be used.

Italian Expert Consensus on Clinical and Therapeutic Management of Multiple Chemical Sensitivity (MCS).

Multiple chemical sensitivity (MCS) is a multisystem, recurrent, environmental disorder that flares in response to different exposures (i.e., pesticides, solvents, toxic metals and molds) under the threshold limit value (TLV) calculated for age and gender in the general population. MCS is a syndrome characterized by cutaneous, allergic, gastrointestinal, rheumatological, endocrinological, cardiological and neurological signs and symptoms. We performed a systematic review of the literature to summarize the current clinical and therapeutic evidence and then oriented an eDelphi consensus. Four main research domains were identified (diagnosis, treatment, hospitalization and emergency) and discussed by 10 experts and an MCS patient. Thus, the first Italian MCS consensus had the double aim: (a) to improve MCS knowledge among healthcare workers and patients by standardizing the clinical and therapeutic management to MCS patients; and (b) to improve and shed light on MCS misconceptions not supported by evidence-based medicine (EBM).

Pathophysiologic Approach to Pain Therapy for Complex Pain Entities: A Narrative Review.

Pain management is challenging for both clinicians and patients. In fact, pain patients are frequently undertreated or even completely untreated. Optimal treatment is based on targeting the underlying mechanisms of pain and tailoring the management modality for each patient using a personalized approach. This narrative review deals with pain conditions that have a complex underlying mechanism and need an individualized and frequently multifactorial approach to pain management. The research is based on previously conducted studies, and does not contain any studies with human participants or animals performed by any of the authors. This is not an exhaustive review of the current evidence. However, it provides the clinician with a perspective on pain therapy targeting the underlying pain mechanism(s). When dealing with complex pain conditions, the prudent physician benefits from having a deep knowledge of various underlying pain mechanisms in order to provide a plan for optimal pharmacological pain relief to patients.

Correction to: Pathophysiologic Approach to Pain Therapy for Complex Pain Entities: A Narrative Review.

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Pathophysiology and Therapeutic Perspectives of Oxidative Stress and Neurodegenerative Diseases: A Narrative Review.

INTRODUCTION: Neurodegeneration is the term describing the death of neurons both in the central nervous system and periphery. When affecting the central nervous system, it is responsible for diseases like Alzheimer's disease, Parkinson's disease, Huntington's disorders, amyotrophic lateral sclerosis, and other less frequent pathologies. There are several common pathophysiological elements that are shared in the neurodegenerative diseases. The common denominators are oxidative stress (OS) and inflammatory responses. Unluckily, these conditions are difficult to treat. Because of the burden caused by the progression of these diseases and the simultaneous lack of efficacious treatment, therapeutic approaches that could target the interception of development of the neurodegeneration are being widely investigated. This review aims to highlight the most recent proposed novelties, as most of the previous approaches have failed. Therefore, older approaches may currently be used by healthcare professionals and are not being presented. METHODS: This review was based on an electronic search of existing literature, using PubMed as primary source for important review articles, and important randomized clinical trials, published in the last 5 years. Reference lists from the most recent reviews, as well as additional sources of primary literature and references cited by relevant articles, were used. RESULTS: Eighteen natural pharmaceutical substances and 24 extracted or recombinant products, and artificial agents that can be used against OS, inflammation, and neurodegeneration were identified. After presenting the most common neurodegenerative diseases and mentioning some of the basic mechanisms that lead to neuronal loss, this paper presents up to date information that could encourage the development of better therapeutic strategies. CONCLUSIONS: This review shares the new potential pharmaceutical and not pharmaceutical options that have been recently introduced regarding OS and inflammatory responses in neurodegenerative diseases.

DF3016A induces increased BDNF transcription in ischemic neuroinflammation injury.

C5a is a crucial terminal effector of the C cascade, mostly involved in pain and neuroinflammatory conditions. DF3016A is a novel potent and selective C5a receptor (C5aR) inhibitor that crosses the blood-brain barrier (BBB) and may have pharmacological properties. We have previously demonstrated a protective effect of DF3016A on injured primary cortical neurons by oxygen-glucose deprivation-reoxygenation (OGD/R) model to mimic the neuroinflammatory process. Here, we investigated the molecular pathway and factors involved in the neuroprotection previously reported. Our findings show that DF3016A protects against the neuroinflammatory insult by activating brain-derived neurotrophic factor (BDNF) transcription pathway, which involves methyl CpG-binding protein 2 (MeCP2) and microRNA-132 (miR-132) regulatory factors, both required in nociceptive signaling and neuroinflammation. Further in vivo investigations will confirm the functionality of the DF3016A molecule as a therapeutic resource in neuroinflammation and pain injuries.

Different Solutions for Damaged Nasotracheal Tube during Maxillofacial Surgery: A Case Series.

Difficult airway management and intraoperative tube damage are important problems during maxillofacial surgery. Damage occurs frequently during the surgery, and the anesthesiologist must be ready to find a quick and safe solution. Replacing the damaged endotracheal tube involves additional difficulties, and various factors must be evaluated. We present two cases of nasotracheal tube (NTT) damage suffered during maxillofacial surgery. The different intraoperative conditions led us to decide for the replacement of NTT in one case and for conservative action in the other. The purpose of this article is to highlight the difficulties that the anesthesiologist may have in deciding quickly what is the best approach in case the endotracheal tube is damaged during maxillofacial surgery and possibly try to provide a rapid and safe solution for the situation.

The Novel C5aR Antagonist DF3016A Protects Neurons Against Ischemic Neuroinflammatory Injury.

The central nervous system (CNS) constitutively expresses complement (C) membrane receptors and complement proteins, including the component C5a. This is a crucial terminal effector of the C cascade, mostly involved in pain and neuroinflammatory conditions. Aberrant activation of C5a protein and its receptor C5aR has been reported to play a critical role in neurodegenerative diseases, with important clinical consequences. Here we have investigated the effects of DF3016A, a novel selective C5aR antagonist, able to penetrate the blood-brain barrier (BBB), on cortical neurons exposed to oxygen-glucose deprivation-reoxygenation (OGD/R), a neuroinflammation-related process. We demonstrated that a mild ischemic insult induces an early upregulation of C5aR associated with the over-production of pro-inflammatory cytokines and the over-expression of the transcriptional regulatory factor miR-181. Furthermore, we report the first experimental evidence of the effect of DF3016A, modulating complement component C5a, on neurons in a model of injury. Interestingly, DF3016A protects neuronal viability by restoring intracellular calcium levels, thus opposing the increase in pro-inflammatory cytokine levels and miR-181 expression. Based on our results, we suggest that DF3016A is a novel C5aR antagonist promoting protective effects against OGD/R-induced damage that could be a new therapeutic approach to controlling CNS neuroinflammatory conditions.

Correction to: The Novel C5aR Antagonist DF3016A Protects Neurons Against Ischemic Neuroinflammatory Injury.

The article The Novel C5aR Antagonist DF3016A Protects Neurons Against Ischemic Neuroinflammatory Injury, written by Laura Brandolini, Marta Grannonico, Gianluca Bianchini, Alessia Colanardi, Pierluigi Sebastiani, Antonella Paladini, Alba Piroli, Marcello Allegretti, and Giustino Varrassi.

Postural counseling represents a novel option in pain management of fibromyalgia patients.

BACKGROUND: Chronic pain is a key symptom in fibromyalgia (FM), and its management is still challenging for rheumatologists in daily practice. FM patients show psychological and psychiatric manifestations, going from mood and emotional disorders to depression and alexithymia that negatively impact their quality of life, limiting their daily activities. Since pharmacological strategies have a limited efficacy in FM pain, alternative or complementary non-pharmacological approaches have been introduced in the clinical management of FM. PATIENTS AND METHODS: This is a retrospective study on FM patients (n=52) treated with a novel integrated postural counseling (PC) rehabilitation program carried out by a counselor physiotherapist. The clinical impact of PC was evaluated by 1) a semi-structured interview using an ad hoc modified questionnaire McGill Illness Narrative Interview (MINI) 1 to obtain data on pain management by highlighting everyday experience of living with pain and 2) an FM impact questionnaire (FIQ) total score. RESULTS: Two main structures of narrative emplotment of FM illness were recognized: 1) the cumulative life narrative structure (46.15%) and 2) the broken life (53.85%) narrative structure. Baseline FIQ score was 77.38±7.77, and it was significantly reduced after PC to 39.12±13.27 (P<0.0001). Although well-being still requires further definition as outcome in pain management, it is important for FM patients, dealing with pain-related sensations, thoughts and feelings and limiting their daily activities. In our study, 87.5% of interviewed FM patients reported an improvement in their well-being after PC. CONCLUSION: Our data suggest that an integrated PC program positively impacts chronic pain and fatigue based on self-management strategies. PC allows FM patients to resume their own life and regenerate their own image. Finally, we propose the introduction of the evaluation of the ability to resume daily activities as the target of rehabilitation programs in FM.

Palmitoylethanolamide in the Treatment of Failed Back Surgery Syndrome.

INTRODUCTION: This observational study was designed to evaluate the efficacy of ultramicronized palmitoylethanolamide (um-PEA) (Normast®) administration, as add-on therapy for chronic pain, in the management of pain-resistant patients affected by failed back surgery syndrome. METHODS: A total of 35 patients were treated with tapentadol (TPD) and pregabalin (PGB). One month after the start of standard treatment, um-PEA was added for the next two months. Pain was evaluated by the Visual Analogue Scale (VAS) at the time of enrollment (T0) and after one (T1), two (T2), and three (T3) months. RESULTS: After the first month with TDP + PGB treatment only, VAS score decreased significantly from 5.7 ± 0.12 at the time of enrollment (T0) to 4.3 ± 0.11 (T1) (p < 0.0001); however, it failed to provide significant subjective improvement in pain symptoms. Addition of um-PEA led to a further and significant decrease in pain intensity, reaching VAS scores of 2.7 ± 0.09 (T2) and 1.7 ± 0.11 (T3, end of treatment) (p < 0.0001) without showing any side effects. CONCLUSIONS: This observational study provides evidence, albeit preliminary, for the efficacy and safety of um-PEA (Normast) as part of a multimodal therapeutic regimen in the treatment of pain-resistant patients suffering from failed back surgery syndrome.