Fibromyalgia - etiology, diagnosis and treatment including perioperative management in patients with fibromyalgia.

Fibromyalgia (FM) is considered a multifactorial disorder/syndrome with not fully understood etiology. Chronic generalized pain is the main symptom. A broad spectrum of factors is proposed to explain the etiology. Its multifactorial nature is inherently associated with challenges in diagnosis and therapy. Various evidence of etiology has been evaluated with the aim of establishing a novel therapeutic approach. The main issue in the diagnosis and management is to focus on the evaluation of strict diagnostic criteria to minimize under- and overdiagnosis. Fibromyalgia is a challenge for perioperative management because of the increased risk of possible complications and poorer outcomes, including postoperative pain chronification. The authors have proposed an up-to-date evaluation of perioperative management considering the current guidelines. Multimodal analgesia combined with tailored perioperative care is the most appropriate assessment. Interdisciplinary research with special interest in pain management, including perioperative medicine, seems to be the main theme for the future.

The Kinetics of Humoral and Cellular Responses after the Booster Dose of COVID-19 Vaccine in Inflammatory Arthritis Patients.

Impaired immunogenicity of COVID-19 vaccinations in inflammatory arthritis (IA) patients results in diminished immunity. However, optimal booster vaccination regimens are still unknown. Therefore, this study aimed to assess the kinetics of humoral and cellular responses in IA patients after the COVID-19 booster. In 29 IA patients and 16 healthy controls (HC), humoral responses (level of IgG antibodies) and cellular responses (IFN-γ production) were assessed before (T0), after 4 weeks (T1), and after more than 6 months (T2) from the booster vaccination with BNT162b2. IA patients, but not HC, showed lower anti-S-IgG concentration and IGRA fold change at T2 compared to T1 (p = 0.026 and p = 0.031). Furthermore, in IA patients the level of cellular response at T2 returned to the pre-booster level (T0). All immunomodulatory drugs, except IL-6 and IL-17 inhibitors for the humoral and IL-17 inhibitors for the cellular response, impaired the immunogenicity of the booster dose at T2. Our study showed impaired kinetics of both humoral and cellular responses after the booster dose of the COVID-19 vaccine in IA patients, which, in the case of cellular response, did not allow the vaccination effect to be maintained for more than 6 months. Repetitive vaccination with subsequent booster doses seems to be necessary for IA patients.

Automatic air volume control system for ventilation of two patients using a single ventilator: a large animal model study.

The COVID-19 pandemic outbreak led to a global ventilator shortage. Hence, various strategies for using a single ventilator to support multiple patients have been considered. A device called Ventil previously validated for independent lung ventilation was used in this study to evaluate its usability for shared ventilation. We performed experiments with a total number of 16 animals. Eight pairs of pigs were ventilated by a ventilator or anesthetic machine and by Ventil for up to 27 h. In one experiment, 200 ml of saline was introduced to one subject's lungs to reduce their compliance. The experiments were analyzed in terms of arterial blood gases and respiratory parameters. In addition to the animal study, we performed a series of laboratory experiments with artificial lungs (ALs). The resistance and compliance of one AL (affected) were altered, while the tidal volume (TV) and peak pressure (Ppeak) in the second (unaffected) AL were analyzed. In addition, to assess the risk of transmission of pathogens between AL respiratory tracts, laboratory tests were performed using phantoms of virus particles. The physiological level of analyzed parameters in ventilated animals was maintained, except for CO2 tension, for which a permissive hypercapnia was indicated. Experiments did not lead to injuries in the animal's lungs except for one subject, as indicated by CT scan analysis. In laboratory experiments, changes in TV and Ppeak in the unaffected AL were less than 11%, except for 2 cases where the TV change was 20%. No cross-contamination was found in simulations of pathogen transmission. We conclude that ventilation using Ventil can be considered safe in patients undergoing deep sedation without spontaneous breathing efforts.

Humoral and cellular immunogenicity of COVID-19 booster dose vaccination in inflammatory arthritis patients.

Introduction: Previous studies have shown a reduction in the effectiveness of primary COVID-19 vaccination in patients with rheumatic diseases. However, limited data is available regarding the effectiveness of the COVID-19 vaccine booster dose, especially on cellular response. The study aimed to assess the humoral and cellular immunogenicity of a booster dose in patients with inflammatory arthritis (IA). Patients and methods: 49 IA and 47 age and sex-matched healthy controls (HC) were included in a prospective cohort study. Both groups completed primary COVID-19 vaccination and after more than 180 days received a BNT162b2 booster shot. Humoral responses (level of IgG antibodies) and cellular responses (IFN-γ production) were assessed before and after 4 weeks from the booster dose of the vaccine. Results: After the booster dose, all participants showed an increased humoral response, although significantly reduced antibody levels were observed in IA patients compared to HC (p=0.004). The cellular response was significantly lower both before (p<0.001) and after (p<0.001) the booster dose in IA patients as compared to HC. Among the immunomodulatory drugs, only biological and targeted synthetic drugs lowered the humoral response after booster vaccination. However, the cellular response was decreased after all immunomodulatory drugs except IL-17 inhibitors and sulfasalazine. Conclusion: Our data indicate that patients with rheumatic diseases present lower humoral and cellular responses after the COVID-19 booster vaccine in comparison to HC. This may translate into a recommendation for subsequent booster doses of the COVID-19 vaccine for rheumatic patients.

Analysis of Antidepressant, Benzodiazepine Anxiolytic, and Hypnotic Use When Treating Depression, Anxiety, and Aggression in Pain Clinic Patients Treated for Neuropathic Pain.

Depression, anxiety, and aggression accompany neuropathic pain. Effective treatment of these comorbidities enhances the outcomes of pain management. Therefore, the study was designed to analyze the relationship between the intensity of depression, anxiety, and aggression and the pharmacotherapy applied in the daily practice of treating neuropathic pain. The aim of the study was to evaluate the frequency of using antidepressants (ADs), benzodiazepine anxiolytics (BDAs), and hypnotics, and the influence of administering these on the intensity of depression, anxiety, and aggression in patients diagnosed with neuropathic pain. A multi-center survey was conducted among 421 patients. An evaluation of the severity of depression, anxiety, and aggression was made using the Hospital Anxiety and Depression Scale-Modified Version (HADS-M). Among the patients treated due to neuropathic pain, ADs are used much more often than BDAs and hypnotics. Depression was well controlled, while anxiety was identified as a possible uncontrolled therapeutic problem in these patients, despite the correlation between the frequency of AD and hypnotics usage and the severity of anxiety. We also found that women show a higher level of intensity in both anxiety and depression, but this does not influence the frequency of their being administered ADs, BDAs, and hypnotics.

Causes, Effects and Methods of Monitoring Gas Exchange Disturbances during Equine General Anaesthesia.

Horses, due to their unique anatomy and physiology, are particularly prone to intraoperative cardiopulmonary disorders. In dorsally recumbent horses, chest wall movement is restricted and the lungs are compressed by the abdominal organs, leading to the collapse of the alveoli. This results in hypoventilation, leading to hypercapnia and respiratory acidosis as well as impaired tissue oxygen supply (hypoxia). The most common mechanisms disturbing gas exchange are hypoventilation, atelectasis, ventilation-perfusion (V/Q) mismatch and shunt. Gas exchange disturbances are considered to be an important factor contributing to the high anaesthetic mortality rate and numerous post-anaesthetic side effects. Current monitoring methods, such as a pulse oximetry, capnography, arterial blood gas measurements and spirometry, may not be sufficient by themselves, and only in combination with each other can they provide extensive information about the condition of the patient. A new, promising, complementary method is near-infrared spectroscopy (NIRS). The purpose of this article is to review the negative effect of general anaesthesia on the gas exchange in horses and describe the post-operative complications resulting from it. Understanding the changes that occur during general anaesthesia and the factors that affect them, as well as improving gas monitoring techniques, can improve the post-aesthetic survival rate and minimize post-operative complications.

Which idea is better with regard to immune response? Opioid anesthesia or opioid free anesthesia.

The stress of surgery is characterized by an inflammatory response with immune suppression resulting from many factors, including the type of surgery and the kind of anesthesia, linked with the drugs that are used and the underlying disease of the patient. The trauma of surgery triggers a cascade of reactions involving the immune response and nociception. As strong analgesics, opioids provide the analgesic component of general anesthesia with bi-directional effect on the immune system. Opioids influence almost all aspects of the immune response in regards to leukocytes, macrophages, mast cells, lymphocytes, and NK cells. The suppressive effect of opioids on the immune system is limiting their use, especially in patients with impaired immune response, so the possibility of using multimodal anesthesia without opioids, known as opioid-free anesthesia (OFA), is gaining more and more sympathizers. The idea of OFA is to eliminate opioid analgesia in the treatment of acute pain and to replace it with drugs from other groups that are assumed to have a comparable analgesic effect without affecting the immune system. Here, we present a review on the impact of anesthesia, with and without the use of opioids, on the immune response to surgical stress.

The Effect of the Treatment at a Pain Clinic on the Patients' Assessment of Their Pain Intensity and the Incidence of Mental Disorders in the form of Anxiety, Depression, and Aggression.

The aim of the study was to analyze the effect of the treatment given to patients in a pain clinic on their assessment of pain intensity and the incidence of emotional disturbances in the form of anxiety, depression, and aggression. The study was conducted from January 2014 to April 2018 among patients under the care of two Warsaw pain clinics. The study tools were the Hospital Anxiety and Depression Scale-Modified Version (HADS-M) and the Numerical Rating Scale (NRS). The project enrolled 325 patients, with women comprising 60.62% of patients, and the age bracked of 65⁻79 years comprising 39.38% of patient. The major reasons for attending the pain clinic were osteoarticular pain (44.92%) and neuropathic pain (42.77%). The therapy applied lowered the patients' pain intensity (4.98 vs. 3.83), anxiety (8.71 vs. 8.12), aggression (3.30 vs. 3.08), and the overall HADS-M score (18.93 vs. 17.90), which shows that the treatment of both the pain symptoms and the associated emotional disturbances in the form of anxiety and aggression was effective. Sex is a factor affecting pain intensity. The level of mental disorders was influenced by the sex and age of the patients and how long they had been treated in the pain clinics.

Lights and shadows of NSAIDs in bone healing: the role of prostaglandins in bone metabolism.

In this review, we discuss the current data about the anatomy and function of bone tissue with particular regard to influence of prostaglandins. Bone tissue dynamics are characterized by a constant remodeling process that involves all bone tissue cells. The communication between bone component cells and other organs is necessary for bone remodeling equilibrium and confirms the dynamic character of bone tissue. Remodeling is also a vital element of healing processes and in adapting bone tissue to stress responses. Therefore, in our review we present the role and significance of bone cells and signaling pathways enabling maintenance of bone homeostasis and remodeling process stability. Cyclooxygenase (COX) is a crucial enzyme in the production of prostaglandins and thromboxane. We focus on the role of COX isoenzymes with highlighting their connection with bone formation, resorption and repair. Prostaglandins are known as arachidonic acid metabolites acting through specific membrane receptors and play an important role in the regulation of osteoblast and osteoclast functions. Prostaglandin PGE2 with its four defined receptors (EP1R, EP2R, EP3R and EP4R) is crucial to maintain balanced bone turnover. Their stimulatory or inhibitory effects appear to depend on different structure-activity relations and signaling pathways. We have described the role of these receptors in bone metabolism and healing. We conclude that the activity of prostaglandins in bone tissue is defined by maintaining bone remodeling balance and its reactions to humoral mediators and mechanical stress. Most data confirm that among prostaglandins, PGE2 takes part in all processes of trauma response, including homeostasis, inflammation and healing, and plays a key role in bone physiology.

Positives and negatives of nonsteroidal anti-inflammatory drugs in bone healing: the effects of these drugs on bone repair.

Tissue damage following injury triggers the processes of coagulation, inflammation and healing. In tissues surrounding the bone, the result of the healing process is a scar, while bone tissue has a unique ability to achieve shape, strength and pre-injury function. Bone healing is a process of regeneration rather than classic recovery. The result of this process is the formation of new, healthy bone tissue instead of a scar. Many factors can inhibit or impair the bone healing process, and their influence is critical during the stages of inflammation and angiogenesis and finally on the clinical outcome. Nonsteroidal anti-inflammatory drugs (NSAIDs) play an essential role associated with their analgesic potency and anti-inflammatory effects. NSAIDs are also the most often used drugs in patients who require pain control and inflammation reduction due to musculoskeletal diseases or injures. Although their analgesic effect is well documented, NSAIDs also interfere with bone healing; therefore, the relative benefits and disadvantages connected with their administration should be taken into consideration. Despite the negative effect, NSAIDs have beneficial properties, but their clinical benefits in relation to dose and time of use are still unclear. Therefore, in this review, we focus on bone healing with relation to the impact of NSAIDs.

Application of titration methods for measuring the contents of ammonium nitrogen and volatile fatty acids in agricultural biogas plants.

The aim of our research was to assess a relatively new method of estimating ammonium nitrogen concentration in anaerobic digestion of plant substrates. We analysed our own data, received from the anaerobic digestion of maize silage (PM), as well as data published by Purser et al. (2014) who measured energy crops and slurry (ECS), and food waste (FW). In our study, the process was monitored for VFA content that was determined by gas chromatography, and for the content of ammonium nitrogen determined using the HACH LANGE LCK 303 cuvette test. We created polynomial regression models that bind the content of ammonium nitrogen with the volume of H2SO4 used to titrate the sample from initial pH to pH 5. To estimate parameters of model, the PM dataset was used. The obtained models were positively validated using ECS and FW datasets. Our results confirmed the effectiveness of the Purser et al. method with an average absolute error of less than 223mgl-1 of the VFA concentration, which was approximately 20-times less than the level that caused inhibition. In conclusion, we can affirm the suitability of using titration methods to assess the ammonium nitrogen content of bioreactors with a stable composition.

The dynamics of an anaerobic digestion of crop substrates with an unfavourable carbon to nitrogen ratio.

The purpose of this study was to investigate the effects of the characteristics of basic crop substrates, such as the carbon, nitrogen, ash and volatile fatty acids contents, on the dynamics of the anaerobic digestion process. For this purpose, the stepwise anaerobic digestion of silage from six different plant species was carried out. Scaled probability distributions (log-normal, log-logistic, logistic, Weibull and Gompertz) were used to approximate the cumulative methane production curves obtained. The results indicated that the Gompertz distribution best fit the process. The hazard function of the Gompertz distribution was used to describe the process change dynamics. Ridge regression models were made and tested to clarify the impact of the crop properties on the distribution parameters. The analysis results indicated that the initial rate of the process depended on the reactor acidity and that the nitrogen content of the substrate was a key factor that affected the process dynamics.

Substance P and Acute Pain in Patients Undergoing Orthopedic Surgery.

OBJECTIVE: There is a limited information about the role of Substance P (SP) in acute pain nociception following surgical stimulation in patients with a chronic inflammatory state not to mention the link between this neuropeptide level changes and intensity of pain. The goal of the research was to find the correlation between SP level changes and acute pain intensity in patients with rheumatoid arthritis undergoing elective orthopedic surgery. MATERIAL AND METHODS: Patients with rheumatoid arthritis (RA) were enrolled in the study. The correlation between acute pain intensity and concentration of SP in serum as well as in drainage fluid from postoperative wound was assessed in patients with RA who underwent Total Knee Replacement (TKA) under spinal anesthesia. RESULTS: In patients with RA a correlation between intensity of acute pain and serum SP was found postoperatively, whereas there was no correlation between intensity of acute pain and concentration of SP in drainage fluid. CONCLUSIONS: 1. The correlation between acute pain intensity and SP serum concentration was found postoperatively in patients with RA. 2. The correlation between acute pain intensity and SP concentration in drainage fluid was not found postoperatively in patients with RA.

Substance P and Chronic Pain in Patients with Chronic Inflammation of Connective Tissue.

OBJECTIVE: Evidence suggests that substance P (SP) is involved in chronic joint inflammation, such as the pathogenesis of rheumatoid arthritis and osteoarthritis. The goal of the research was to evaluate the correlation between chronic pain and changes in the SP level in patients with chronic inflammation of the connective tissue. METHODS: Patients with osteoarthritis and rheumatoid arthritis were enrolled in this study. The relationship between chronic pain intensity and the serum SP concentration was evaluated in these groups of patients with osteoarthritis and rheumatoid arthritis. RESULTS: The results showed a positive correlation between the serum SP concentrations and chronic pain intensity. CONCLUSIONS: 1. The SP serum concentration was significantly different between the groups of patients with OA and RA. 2. There was a positive correlation between the serum SP concentration and chronic pain intensity in OA and RA patients.

Anesthesiology and the cytokine network.

The immune response is a highly specific reaction carried out by means of specialized cells that belong to the immune system. There are two types of immune response mechanisms aimed towards pathogens: non-specific, innate reactions, and specific, acquired reactions. Acquired immunity, characterized by its specificity, is comprised of lymphocytes, including both T cell and B cell populations. The role of B lymphocytes is not limited to the humoral response, though the cellular immune response is carried out mainly by various T lymphocyte subpopulations. The reactions of the humoral and cellular responses complement and stimulate one another mutually - cytokines are their common linking element. The attachment of cytokines to their specific receptors activates a sequence of signals - either intracellular or between the cells of various systems. This organization of respective connections and reactions, including the functional relations between cells of the immune response, in its complexity, is best described as a cytokine network. The response of the immune system to surgical trauma can be looked at from both a local and a general perspective. Not only surgical trauma caused by tissue damage, however, influences the functioning of the immune system, but also the drugs and techniques used during anesthesia. Our article is a presentation of the effects of medications used in anesthesia with respect to their influence on the cytokine network.

Comparison of rheumatoid articular adipose and synovial tissue reactivity to proinflammatory stimuli: contribution to adipocytokine network.

OBJECTIVES: (1) To compare spontaneous and stimuli-induced adipocytokine secretion by articular adipose tissue (AAT) and synovial membrane (SM) explants obtained from patients with rheumatoid arthritis (RA). (2) To investigate the biological activity of AAT and SM released factors. METHODS: Tissues were obtained from patients undergoing joint replacement surgery. Tissue explants were treated with proinflammatory cytokines relevant to RA pathogenesis (interleukin 1ß (IL-1ß), tumour necrosis factor (TNF), interferon γ, IL-15, IL-17, IL-23). Selected adipocytokine (TNF, IL-6, IL-8, IL-1ß, IL-1Ra, adiponectin, leptin) concentrations were measured in culture supernatants using ELISA. The biological activity of tissue-conditioned media was evaluated by measuring production of selected factors (IL-6, IL-8, Dickkopf-1, osteoprotegerin) by fibroblast-like synoviocytes (FLS). RESULTS: Spontaneous cytokine release from AAT was ≤12% of that produced by SM, while leptin was secreted in similar amounts. AAT was highly reactive to proinflammatory cytokines (IL-1ß>TNF). AAT treated with IL-1ß released four times more leptin, similar amounts of IL-6 and IL-8 and about 20% of TNF, as compared with SM. Upon activation, the IL-1 receptor antagonist (IL-1Ra)/IL-1ß ratio was higher in AAT than in SM cultures. Irrespective of activation status, SM produced twice as much adiponectin as AAT. Conditioned media from AAT and SM cultures similarly upregulated IL-6, IL-8, Dickkopf-1 and osteoprotegerin production by rheumatoid FLS. CONCLUSION: Rheumatoid AAT is highly reactive tissue which upon stimulation secretes considerable amounts of proinflammatory (IL-6, IL-8, TNF) and anti-inflammatory (IL-1Ra) cytokines and classical adipokines. This tissue releases biologically active factors that intensify pathogenic activities of rheumatoid FLS. Thus, AAT should be considered an important contributor to the pathological processes taking place in the RA joint.

[The role of strong opioids in the treatment of the chronic musculoskeletal pain]. / Rola silnych opioidów w leczeniu bólu przewleklego, towarzyszacego chorobom narzadu ruchu.

This article concentrates on recent evidence about opioid analgesics for persistent musculoskeletal pain. Chronic musculoskeletal pain is a major health problem for which opioids provide one treatment option. Pain is an experience that affects all aspects of a patient's life and effective pain management with strong opioids may help the patient to focus on the positive aspects of life, decreasing the focus on pain. This therapy should be reserved for patients who fail to respond to other lower-risk options and only after proper consideration is given to the long-term consequences of strong opioid use according to the WHO three-step ladder. Several reviews and our experience have shown that opioids are typically reserved for moderate to severe musculoskeletal pain that cannot be relieved by other drugs. In this article are presented the strong opioid drugs, routes of administration, dosage guidelines and potential adverse effects. The management of patients with chronic musculoskeletal pain is a common clinical challenge.

Anaesthesiological problems in patients with rheumatoid arthritis undergoing orthopaedic surgeries.

The article presents anaesthesiological problems in patients with rheumatoid arthritis (RA) scheduled for orthopaedic surgeries. Organ changes due to RA and related treatment were taken into account. The anaesthetic techniques used for patients with RA underwent orthopaedic procedures were presented.

[Spinal anesthesia and postoperative analgesia with intrathecal morphine for orthopedic surgery]. / Znieczulenie podpajeczynówkowe i analgezja pooperacyjna z zastosowaniem Morfini Sulfas Spinal u chorych poddanych operacjom ortopedycznym.

The aim of this study was to evaluate the analgesic efficacy and side effects of intrathecal morphine in the dose range 0.2-0.5 mg. One-hundred patients scheduled for elective lower limb orthopedic operation under spinal anesthesia using hyperbaric or isobaric bupivacaine 0.5% with morphine in dose from 0.2 to 0.5 mg. Pain score, duration of analgesia and the incidence of adverse effects like nausea, vomiting, pruritus, urinary retention and respiratory depression were assessed for 48 hr postoperatively. There were significant differences in the duration and efficacy analgesia and the incidence of pruritus the morphine dose-related. We did not observe the increased frequency of nausea and vomiting with increased dose. The respiratory depression not observed in connection with intrathecal morphine. The evidence from this current study suggests that spinal anesthesia with combination of local anesthetic and morphine can be employed to provide safe and efficacious analgesia in patients undergoing orthopedic operations. The adverse effects which developed due to intrathecal morphine were able to treat with success.

Postoperative evaluation of plasma interleukin-6 concentration in patients after total hip arthroplasty.

Background. The aim of this study was to examine the circulating IL-6 in patients after orthopedic surgery, and the correlation between IL-6, body temperature and the level of postoperative pain. Material and methods. We studied 27 patients undergoing orthopedic hip arthroplasty, including 14 with osteoarthritis and 13 with rheumatoid arthritis. The local medical ethics committee approved the study, and all patients signed informed consent upon being enrolled. All patients received spinal anesthesia. Samples were collected just before and at 24, 48, and 72 hours after surgery; at the same time, body temperature and reported pain were monitored. Results. Plasma IL-6 levels showed a decrease after surgery. This suggests some influence of plasma cytokines on the possible beneficial effects of regional anesthesia on the clinical course after surgery. The level of IL-6 was associated with body temperature and pain in patients after operation. Conclusions. The plasma concentration of IL-6 is a significant factor affecting body temperature and pain after surgery in patients who have undergone hip arthroplasty.