Association between smoking and central sensitization pain: a web-based cross-sectional study.

PURPOSE: This study aimed to investigate whether smoking is an independent risk factor for central sensitization syndrome (CSS) in individuals with pain as measured by the Central Sensitization Inventory (CSI). METHODS: In 2020, we conducted an Internet survey targeting 2000 ordinary residents of Japan (aged 20-69 years) who had pain symptoms from October to November 2020. A multiple regression analysis was performed on the association between smoking status (nonsmokers and current smokers; Brinkman index) and CSI values. Moreover, compared to nonsmokers, the relative risk (RR) of the CSI cut-off score of 40 points or higher among current smokers was calculated using a modified Poisson regression model. Covariates included age, sex, body mass index, marital status, equivalized income, exercise habits, history of hypertension, history of hyperlipidemia, history of diabetes, pain chronicity, and Pain Catastrophizing Scale score. RESULTS: This study analyzed 1,822 individuals (1,041 men and 781 women). Among those experiencing pain, current smoking was associated with the increase in CSI values (ß = 0.07). The Brinkman index was also significantly associated with the increase in CSI values (ß = 0.06). Current smoking also increased the risk of being over the CSI cut-off score, with a relative risk (RR) of 1.29 (95% confidence intervals, 1.04-1.60). Younger age, being women, experiencing chronic pain, and higher pain catastrophizing thinking were also significantly associated with increased CSS severity, independent of smoking status. CONCLUSION: Smoking is an independent risk factor for CSS. This indicates that smoking may be an important factor in the management of central pain disorders.

Sex-Specific Impact of Pain Severity, Insomnia, and Psychosocial Factors on Disability due to Spinal Degenerative Disease.

Purpose: Pain experience due to spinal degenerative disease decreases activity of daily living and quality of life. The present cross-sectional study was aimed at examining the sex-specific impact of pain severity, psychosocial factors, and insomnia on the disability due to chronic pain arising from spinal degenerative disease. Methods: In total, 111 outpatients with chronic spinal degenerative on initial diagnosis were analyzed. The definition of chronic spinal degenerative disease was (1) pain duration ≥3 months, (2) findings of nerve root compression on neurological examination and imaging, and (3) localized neck or lower back pain (not widespread, upper or lower limb pain). We used Numerical Rating Scale (NRS), Pain Disability Assessment Scale (PDAS), Hospital Anxiety and Depression Scale (HADS), Pain Catastrophizing Scale (PCS), and Athens Insomnia Scale (AIS) to assess patients. Univariate regression analysis was performed to investigate whether sex influences the PDAS score, and sex-stratified multivariate regression analysis was conducted to identify the variables associated with the PDAS score. Results: Sex was identified as a predictor of the PDAS score (standardized coefficient (ß) = 0.28; 95% confidence interval (CI), 0.10-0.46; p=0.003). In men, the AIS score was associated with PDAS (ß = 0.36, 95% CI 0.09-0.63). Age (ß = 0.31, 95% CI 0.06-0.55) and NRS (ß = 0.40, 95% CI 0.14-0.67) were associated with PDAS in women. HADS-A, HADS-D, and PCS were not associated with PDAS in both sexes. Conclusion: Insomnia was associated with disability in men, whereas aging and pain severity were associated with disability in women. Catastrophic thinking was not associated with disability in both sexes.

Association between change in self-efficacy and reduction in disability among patients with chronic pain.

PURPOSE: This study aimed to investigate whether changes in psychosocial factors and pain severity were associated with reduction in disability due to pain among patients with chronic pain. We hypothesized that increased self-efficacy would reduce disability. PATIENTS AND METHODS: This longitudinal observational study included 72 patients. Patients' psychological and physical variables were assessed before and after 3 months of treatment. Demographic and clinical information were collected, including the Pain Disability Assessment Scale (PDAS), the Pain Self-Efficacy Questionnaire (PSEQ), the Hospital Depression and Anxiety Scale, and the Numeric Rating Scale (NRS) to assess pain intensity. First, univariate regression analyses were conducted to clarify associations between change in PDAS and sex, age, pain duration, changes in psychosocial factors (self-efficacy, anxiety, and depression) and change in pain intensity. Second, multivariate regression was conducted using the variables identified in the univariate analyses (PSEQ and NRS) to detect the most relevant factor for reducing disability. RESULTS: Univariate regression analyses clarified that changes in PSEQ (ß = -0.31; 95% CI: -0.54--0.08, p = 0.008) and NRS (ß = 0.24; 95% confidence interval [CI]: 0.01-0.47, p = 0.04) were associated with reduction in PDAS. Multivariate regression analysis demonstrated that change in PSEQ (ß = 0.26; 95% CI: -0.50--0.02; p = 0.01) was associated with a reduction in disability, independent of change in NRS. CONCLUSION: These findings suggest improved self-efficacy is associated with reduced disability in patients with chronic pain, independent of reduction in pain intensity. Focusing on improvement in self-efficacy may be an effective strategy in chronic pain treatment in addition to pain relief.

The protective effects of nasal PcrV-CpG oligonucleotide vaccination against Pseudomonas aeruginosa pneumonia.

An effective vaccine against Pseudomonas aeruginosa would be hugely beneficial to people who are susceptible to the serious infections it can cause. Vaccination against PcrV of the P. aeruginosa type III secretion system is a potential prophylactic strategy for improving the incidence and prognosis of P. aeruginosa pneumonia. Here, the effect of nasal PcrV adjuvanted with CpG oligodeoxynucleotide (CpG) was compared with a nasal PcrV/aluminum hydroxide gel (alum) vaccine. Seven groups of mice were vaccinated intranasally with one of the following: 1, PcrV-CpG; 2, PcrV-alum; 3, PcrV alone; 4, CpG alone; 5, alum alone; 6 and 7, saline control. Fifty days after the first immunization, anti-PcrV IgG, IgA and IgG isotype titers were measured; significant increases in these titers were detected only in the PcrV-CpG vaccinated mice. The vaccinated mice were then intratracheally infected with a lethal dose of P. aeruginosa and their body temperatures and survival monitored for 24 hr, edema, bacteria, myeloperoxidase activity and lung histology also being evaluated at 24 hr post-infection. It was found that 73% of the PcrV-CpG-vaccinated mice survived, whereas fewer than 30% of the mice vaccinated with PcrV-alum or adjuvant alone survived. Lung edema and other inflammation-related variables were less severe in the PcrV-CpG group. The significant increase in PcrV-specific IgA titers detected following PcrV-CpG vaccination is probably a component of the disease protection mechanism. Overall, our data show that intranasal PcrV-CpG vaccination has potential efficacy for clinical application against P. aeruginosa pneumonia.

Efficacy comparison of adjuvants in PcrV vaccine against Pseudomonas aeruginosa pneumonia.

Vaccination against the type III secretion system of P. aeruginosa is a potential prophylactic strategy for reducing the incidence and improving the poor prognosis of P. aeruginosa pneumonia. In this study, the efficacies of three different adjuvants, Freund's adjuvant (FA), aluminum hydroxide (alum) and CpG oligodeoxynucleotide (ODN), were examined from the viewpoint of inducing PcrV-specific immunity against virulent P. aeruginosa. Mice that had been immunized intraperitoneally with recombinant PcrV formulated with one of the above adjuvants were challenged intratracheally with a lethal dose of P. aeruginosa. The PcrV-FA immunized group attained a survival rate of 91%, whereas the survival rates of the PcrV-alum and PcrV-CpG groups were 73% and 64%, respectively. In terms of hypothermia recovery after bacterial instillation, PcrV-alum was the most protective, followed by PcrV-FA and PcrV-CpG. The lung edema index was lower in the PcrV-CpG vaccination group than in the other groups. PcrV-alum immunization was associated with the greatest decrease in myeloperoxidase in infected lungs, and also decreased the number of lung bacteria to a similar number as in the PcrV-FA group. There was less neutrophil recruitment in the lungs of mice vaccinated with PcrV-alum or PcrV-CpG than in those of mice vaccinated with PcrV-FA or PcrV alone. Overall, in terms of mouse survival the PcrV-CpG vaccine, which could be a relatively safe next-generation vaccine, showed a comparable effect to the PcrV-alum vaccine.

Flow-dynamics assessment of mitral-valve surgery by intraoperative vector flow mapping.

OBJECTIVES: We assessed vortex patterns and energy loss in left ventricular flow in patients who underwent mitral valve repair or replacement with bioprosthetic valves. METHODS: Vector flow mapping was performed before and after the procedure in 15 and 17 patients who underwent repair and replacement, respectively. The preprocedure mitral-septal angle was measured in all patients. Relationships between vortex patterns or energy loss change (ELC) and annuloplasty ring or bioprosthetic valve sizes or the effect of mitral leaflet resection in the repair group were statistically analysed. RESULTS: Normal vortex patterns were observed in 13 and 1 patients who underwent repair and replacement, respectively. Abnormal vortex patterns were observed in 2 and 16 patients who underwent repair and replacement, respectively. ELC was significantly higher in the replacement group (196.6 ± 180.8) than in the repair group (71.9 ± 43.9). In the repair group, preoperative mitral-septal angles in patients with normal vortex patterns (79.2° ± 3.4°) were significantly larger than those in patients with abnormal vortex patterns (67.5° ± 3.5°). No significant differences were observed in the effects of annuloplasty ring and bioprosthetic valve sizes on vortex patterns and ELC, and in the effect of mitral valve resection (80.4 ± 56.3) and respect (without leaflet resection) (53.8 ± 28.4) on ELC in the repair group. CONCLUSIONS: Mitral valve replacement alters the intraventricular vortex pattern and increases flow energy loss. A small mitral-septal angle is a risk factor for abnormal vortex patterns after mitral valve repair surgery.

Vector flow mapping analysis of left ventricular energetic performance in healthy adult volunteers.

BACKGROUND: Vector flow mapping, a novel flow visualization echocardiographic technology, is increasing in popularity. Energy loss reference values for children have been established using vector flow mapping, but those for adults have not yet been provided. We aimed to establish reference values in healthy adults for energy loss, kinetic energy in the left ventricular outflow tract, and the energetic performance index (defined as the ratio of kinetic energy to energy loss over one cardiac cycle). METHODS: Transthoracic echocardiography was performed in fifty healthy volunteers, and the stored images were analyzed to calculate energy loss, kinetic energy, and energetic performance index and obtain ranges of reference values for these. RESULTS: Mean energy loss over one cardiac cycle ranged from 10.1 to 59.1 mW/m (mean ± SD, 27.53 ± 13.46 mW/m), with a reference range of 10.32 ~ 58.63 mW/m. Mean systolic energy loss ranged from 8.5 to 80.1 (23.52 ± 14.53) mW/m, with a reference range of 8.86 ~ 77.30 mW/m. Mean diastolic energy loss ranged from 7.9 to 86 (30.41 ± 16.93) mW/m, with a reference range of 8.31 ~ 80.36 mW/m. Mean kinetic energy in the left ventricular outflow tract over one cardiac cycle ranged from 200 to 851.6 (449.74 ± 177.51) mW/m with a reference range of 203.16 ~ 833.15 mW/m. The energetic performance index ranged from 5.3 to 37.6 (18.48 ± 7.74), with a reference range of 5.80 ~ 36.67. CONCLUSIONS: Energy loss, kinetic energy, and energetic performance index reference values were defined using vector flow mapping. These reference values enable the assessment of various cardiac conditions in any clinical situation.

Pseudomonas aeruginosa Type III Secretory Toxin ExoU and Its Predicted Homologs.

Pseudomonas aeruginosa ExoU, a type III secretory toxin and major virulence factor with patatin-like phospholipase activity, is responsible for acute lung injury and sepsis in immunocompromised patients. Through use of a recently updated bacterial genome database, protein sequences predicted to be homologous to Ps. aeruginosa ExoU were identified in 17 other Pseudomonas species (Ps. fluorescens, Ps. lundensis, Ps. weihenstephanensis, Ps. marginalis, Ps. rhodesiae, Ps. synxantha, Ps. libanensis, Ps. extremaustralis, Ps. veronii, Ps. simiae, Ps. trivialis, Ps. tolaasii, Ps. orientalis, Ps. taetrolens, Ps. syringae, Ps. viridiflava, and Ps. cannabina) and 8 Gram-negative bacteria from three other genera (Photorhabdus, Aeromonas, and Paludibacterium). In the alignment of the predicted primary amino acid sequences used for the phylogenetic analyses, both highly conserved and nonconserved parts of the toxin were discovered among the various species. Further comparative studies of the predicted ExoU homologs should provide us with more detailed information about the unique characteristics of the Ps. aeruginosa ExoU toxin.

The prophylactic effects of human IgG derived from sera containing high anti-PcrV titers against pneumonia-causing Pseudomonas aeruginosa.

The PcrV cap structure of the type III secretory apparatus of Pseudomonas aeruginosa is a vaccine target. Human immunoglobulin G (IgG) molecules extracted from sera containing high or low anti-PcrV titers were tested for their effects against P. aeruginosa pneumonia in a mouse model. Among 198 volunteers, we selected the top 10 high anti-PcrV titer sera and the bottom 10 low anti-PcrV titer sera and extracted the IgG fraction from each serum sample. First, we examined the effects of the IgG against virulent P. aeruginosa. A lethal dose of P. aeruginosa premixed with saline, low titer human IgG, high titer human IgG, or rabbit-derived polyclonal anti-PcrV IgG was intratracheally administered into the lungs of mice, and their survival and lung inflammation were evaluated for 24 h. The high anti-PcrV titer human IgG had a prophylactic effect. Next, the prophylactic effects of intravenous administration of extracted and pooled high or low anti-PcrV titer human IgG were examined. Here, prophylactic intravenous administration of pooled high anti-PcrV titer human IgG, which showed binding capacity to P. aeruginosa PcrV, was more effective than the administration of its low titer pooled equivalent, and the measured physiological and inflammatory parameters correlated with the anti-PcrV titer levels. This result indirectly implies that high anti-PcrV titers in blood can help to protect against virulent P. aeruginosa infections. In addition, the IgG fractions from such high titer sera have potential to be a source of specific intravenous immunoglobulin products for passive vaccination against virulent P. aeruginosa infections.

Management of Anesthesia under Extracorporeal Cardiopulmonary Support in an Infant with Severe Subglottic Stenosis.

A 4-month-old female infant who weighed 3.57 kg with severe subglottic stenosis underwent tracheostomy under extracorporeal cardiopulmonary support. First, we set up extracorporeal cardiopulmonary support to the infant and then successfully intubated an endotracheal tube with a 2.5 mm inner diameter before tracheostomy by otolaryngologists. Extracorporeal cardiopulmonary support is an alternative for maintenance of oxygenation in difficult airway management in infants.

Protective effects of intravenous immunoglobulin and antimicrobial agents on acute pneumonia in leukopenic mice.

Multi-drug resistant Pseudomonas aeruginosa causes the type of acute lung injury that is strongly associated with bacteremia, sepsis, and mortality, especially under immunocompromised conditions. Although administration of immunoglobulin solution is an applicable immunotherapy in immunocompromised patients, efficacy of immunoglobulin administration against multi-drug resistant P. aeruginosa pneumonia has not been well evaluated. In this study, we investigated the effectiveness of prophylactic administration of immunoglobulin solution (IVIG) in comparison with that of other types of antimicrobial agents, such as anti-PcrV IgG, piperacillin/tazobactam, or colistin in an immunocompromised mouse model of P. aeruginosa pneumonia. Colistin was the most effective agent for preventing acute lung injury, bacteremia, cytokinemia, and sepsis. Among the four tested antimicrobial agents, after colistin, anti-PcrV IgG and IVIG were the most effective at protecting mice from mortality. Piperacillin/tazobactam did not prevent acute lung injury or bacteremia; rather, it worsened lung histology. The data suggest that using an agent for which a positive result in an in vitro susceptibility test has been obtained may not always prevent acute lung injury in a leukopenic host infected with P. aeruginosa. Clinicians should consider the possibility of discrepancies between in vitro and in vivo tests because the absence of in vitro bactericidal activity in an antimicrobial agent is not always a reliable predictor of its lack of ability to eradicate bacteria in vivo, even in immunocompromised hosts. Based on our findings, the potential protective effects of IVIG against the acute lung injury induced by P. aeruginosa should be reevaluated.

IV Immunoglobulin for Acute Lung Injury and Bacteremia in Pseudomonas aeruginosa Pneumonia.

OBJECTIVES: Virulent and multidrug-resistant Pseudomonas aeruginosa causes a lethal pneumonia, especially in patients who are artificially ventilated. It has been reported that the virulence mechanism used by P. aeruginosa, which is linked to acute lung injury, is strongly associated with the type III secretion system, and specific antibodies targeting this system have shown a protective effect in both experimental and clinical settings. We investigated the effect of administering IV immunoglobulins on P. aeruginosa pneumonia, including its associated bacteremia and mortality, although focusing especially on type III secretion system-associated P. aeruginosa virulence. DESIGN: Prospective randomized and controlled animal study. SETTING: University laboratory. SUBJECTS: Male ICR mice. INTERVENTIONS: Mice were infected intratracheally with a lethal dose of the virulent P. aeruginosa PA103 strain. IV immunoglobulin administration was examined in three different settings: 1) premixed; 2) pre-IV, prophylactic administration before bacterial infection; and 3) post-IV, therapeutic administration after bacterial infection. The effect of specific antigen titer depletion of IV immunoglobulins was also examined. MEASUREMENTS AND MAIN RESULTS: Survival and body temperature were monitored for 24 hours. Bacteremia, cytokine concentration, myeloperoxidase activity, WBC counts in the blood, and lung bacterial load were evaluated. Survival improved significantly in mice that received IV immunoglobulins (p < 0.05). Lung edema, lung bacteriologic load, and bacteremia decreased significantly in the IV immunoglobulin-treated mice (p < 0.05). The mechanism of protection was associated with the presence of antibodies against both PcrV and some bacterial surface antigens in the IV immunoglobulins. CONCLUSIONS: IV immunoglobulin administration had a significantly protective effect against lethal infection from virulent P. aeruginosa. Prophylactic IV immunoglobulin administration at the highest dose was comparable with that achieved by administrating a specific anti-PcrV polyclonal IgG into the mice. The mechanism of protection is likely to involve the synergic action of anti-PcrV titers and antibodies against some surface antigen(s) that block the type III secretion system-associated virulence of P. aeruginosa.

Epidemiological analysis of serum anti-Pseudomonas aeruginosa PcrV titers in adults.

Of the various virulence mechanisms of the opportunistic pathogen Pseudomonas aeruginosa, the type III secretion system (TTSS) has been characterized as a major factor associated with acute lung injury, bacteremia and mortality. In addition, PcrV, a component protein of the TTSS, has been characterized as a protective antigen against infection with P. aeruginosa. This study comprised an epidemiological analysis of serum anti-PcrV titers in a cohort of Japanese adults. From April 2012 to March 2013, serum anti-PcrV titers of 198 volunteer participants undergoing anesthesia for scheduled surgeries were measured. The median, minimum and maximum serum anti-PcrV titers among the 198 participants were 4.09 nM, 1.01 nM and 113.81 nM, respectively. The maximum peaks in the histogram were within the anti-PcrV 2.00-4.99 nM titer range; values for 115 participants (58.1%) were within this range. Anti-PcrV titers were more than approximately three-fold greater (>12 nM) than the median value in 21 participants (10.6%). Ten-year interval age increases, history of treatment for traffic trauma, and a history of past surgery each showed statistically significant associations with higher anti-PcrV titers (i.e., >10 nM) than did the other factors assessed by binomial analysis. This study revealed a considerable variation in anti-PcrV titers in adult subjects without any obvious histories of infection with P. aeruginosa.