Plasma proteins and persistent postsurgical pelvic pain among adolescents and young adults with endometriosis.

BACKGROUND: Noninvasive biomarkers that predict surgical treatment response would inform personalized treatments and provide insight into potential biologic pathways underlying endometriosis-associated pain and symptom progression. OBJECTIVE: To use plasma proteins in relation to the persistence of pelvic pain following laparoscopic surgery in predominantly adolescents and young adults with endometriosis using a multiplex aptamer-based proteomics biomarker discovery platform. STUDY DESIGN: We conducted a prospective analysis including 142 participants with laparoscopically-confirmed endometriosis from the Women's Health Study: From Adolescence to Adulthood observational longitudinal cohort with study enrollment from 2012-2018. Biologic samples and patient data were collected with modified World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonization Project tools. In blood collected before laparoscopic ablation or excision of endometriosis, we simultaneously measured 1305 plasma protein levels, including markers for immunity, angiogenesis, and inflammation, using SomaScan. Worsening or persistent postsurgical pelvic pain was defined as having newly developed, persistent (ie, stable), or worsening severity, frequency, or persistent life interference of dysmenorrhea or acyclic pelvic pain at 1-year postsurgery compared with presurgery. We calculated odds ratios and 95% confidence intervals using logistic regression adjusted for age, body mass index, fasting status, and hormone use at blood draw. We applied Ingenuity Pathway Analysis and STRING analysis to identify pathophysiologic pathways and protein interactions. RESULTS: The median age at blood draw was 17 years (interquartile range, 15-19 years), and most participants were White (90%). All had superficial peritoneal lesions only and were treated by excision or ablation. One-year postsurgery, pelvic pain worsened or persisted for 76 (54%) of these participants with endometriosis, whereas pelvic pain improved for 66 (46%). We identified 83 proteins associated with worsening or persistent pelvic pain 1-year postsurgery (nominal P<.05). Compared with those with improved pelvic pain 1-year postsurgery, those with worsening or persistent pelvic pain had higher plasma levels of CD63 antigen (odds ratio, 2.98 [95% confidence interval, 1.44-6.19]) and CD47 (odds ratio, 2.68 [95% confidence interval, 1.28-5.61]), but lower levels of Sonic Hedgehog protein (odds ratio, 0.55 [95% confidence interval, 0.36-0.84]) in presurgical blood. Pathways related to cell migration were up-regulated, and pathways related to angiogenesis were down-regulated in those with worsening or persistent postsurgical pelvic pain compared with those with improved pain. When we examined the change in protein levels from presurgery to postsurgery and its subsequent risk of worsening or persistent postsurgical pain at 1-year follow-up, we observed increasing levels of Sonic Hedgehog protein from presurgery to postsurgery was associated with a 4-fold increase in the risk of postsurgical pain (odds ratio [quartile 4 vs 1], 3.86 [1.04-14.33]). CONCLUSION: Using an aptamer-based proteomics platform, we identified plasma proteins and pathways associated with worsening or persistent pelvic pain postsurgical treatment of endometriosis among adolescents and young adults that may aid in risk stratification of individuals with endometriosis.

Metabolomic profiling of pediatric post-tonsillectomy pain: A proof-of-concept study.

INTRODUCTION: Tonsillectomies are among the most common surgical procedures in children, with over 500 000 cases annually in the United States. Despite universal administration of intraoperative opioid analgesia, three out of five children undergoing tonsillectomy report moderate-to-severe pain upon recovering from anesthesia. The underlying molecular mechanisms of post-tonsillectomy pain are not well understood, limiting the development of targeted treatment strategies. Our study aimed to identify candidate serum metabolites associated with varying severity of post-tonsillectomy pain. METHODS: Venous blood samples and pain scores were obtained from 34 children undergoing tonsillectomy ± adenoidectomy, and metabolomic analysis was performed. Supervised orthogonal projections to latent structures discriminant analysis were employed to identify differentially expressed metabolites between children with severe and mild pain, as well as between moderate and mild pain. RESULTS: Pain scores differentiated children as mild (n = 6), moderate (n = 14), or severe (n = 14). Four metabolites (fatty acid 18:0(OH), thyroxine, phosphatidylcholine 38:5, and branched fatty acids C27H54O3) were identified as candidate biomarkers that differentiated severe vs. mild post-tonsillectomy pain, the combination of which yielded an AUC of 0.91. Similarly, four metabolites (sebacic acid, dicarboxylic acids C18H34O4, hydroxy fatty acids C18H34O3, and myristoleic acid) were identified as candidate biomarkers that differentiated moderate vs. mild post-tonsillectomy pain, with AUC values ranging from 0.85 to 0.95. CONCLUSION: This study identified novel candidate biomarker panels that effectively differentiated varying severity of post-tonsillectomy pain. Further research is needed to validate these data and to explore their clinical implications for personalized pain management in children undergoing painful surgeries.

Correlation Between Blood Levels of Cysteine Protease Caspase-1 (Casp1) and Pain Scores (NRS) Post-surgery: A Prospective Randomized Study of Patients With Cholelithiasis.

BACKGROUND/AIM: Cysteine protease caspase-1 (Casp1) plays a crucial role in the conversion of pro-cytokines to active cytokines (CYTs). The purpose of this work was to determine Casp1 blood levels in a cohort of 114 cholecystectomy patients and assess their association with other CYTs and numeric rating scale (NRS) pain scores, postoperatively. PATIENTS AND METHODS: Blood levels of Casp1 and seven CYTs (IL-18, IL-18BP, IL-1ra, IL-6, IL-10, IL-1ß, and IL-8) were measured at three time points; before operation, immediately after operation, and six hours after operation in 114 patients with cholelithiasis (Chole). RESULTS: Casp1 blood levels correlated with NRS pain scores at 24 h following surgery (p=0.016). In addition, Casp1 blood levels correlated significantly to IL-18 blood levels (p<0.001). CONCLUSION: This is the first report to evaluate Casp1 blood levels in Chole patients in correlation with other CYTs. The findings confirm a significant correlation between Casp1 blood levels and NRS pain scores. Moreover, this study provides initial evidence suggesting that inhibition of the activity of Casp1 may reduce postsurgical acute phase immune response possibly through the Casp1/pro-Il-18 pathway.

Brief Pain Inventory (BPI) Pain Survey Versus Cysteine Protease Caspase-1 (Casp1) Blood Levels Following Midline Laparotomy: A Prospective Randomized Study of Patients With Benign Disease and Patients With Cancer.

BACKGROUND/AIM: There is lack of studies assessing the correlation between pain scales and acute phase immune response (APR) following surgery. The purpose of this work was to assess the correlation between cysteine protease caspase-1 (Casp1) blood levels and two pain scales in a cohort of 56 midline laparotomy (MLa) patients and to assess their link with other cytokines (CYTs). PATIENTS AND METHODS: Blood levels of Casp1 and other CYTs (IL-18, IL-18BP, IL-1ra, IL-6, IL-8, IL-10, IL-1ß) were measured before operation and following surgery in patients with MLa. Pain levels were assessed using the Numerical Rating Scale (NRS) and Brief Pain Inventory (BPI) scale, both preoperatively and postoperatively. RESULTS: Casp1 blood levels showed an increasing trend at postoperative day 1 (POP1) and this increase was almost significant in a linear mixed effect model (LME) analysis (p=0.06). Additionally, Casp1 blood levels were higher in patients with cancer than those with benign disease and correlated with IL-18 blood levels (r=0.24, p=0.007). Furthermore, Casp1 blood levels correlated with BPIsev (severity) score values in MLa patients (r=-0.49, p=0.048). A significant correlation was also observed between Casp1 blood levels and NRS scores in patients with MLa. CONCLUSION: This is the first report to evaluate two pain surveys (NRS and BPI) in MLa patients in relation to blood levels of Casp1 and eight CYTs. This analysis is important in confirming the significant correlation between NRS and BPI pain scales and Casp1 blood levels. Our study is also the first to demonstrate that adequate postoperative analgesia in patients with MLa provides better functional ability and improved patient satisfaction.

The relationship between neutrophil to lymphocyte ratio and postoperative pain in total knee and hip arthroplasty / Relação entre a proporção neutrófilo/linfócito e a dor pós-operatória em artroplastia total de joelho e quadril

Abstract Background and objectives: Neutrophil to lymphocyte ratio is a simple, cost-effective and easily applicable inflammation indicator that is being used frequently in mortality, morbidity and prognosis studies in the recent years. We evaluated the relationship between neutrophil to lymphocyte ratio and postoperative pain in patients undergoing total hip arthroplasty and total knee arthroplasty. Material and methods: We included 101 patients who preferred spinal anesthesia and intravenous patient-controlled analgesia in accordance and divided them into two groups, total hip arthroplasty and total knee arthroplasty. We recorded demographic information, duration of operation, length of hospital stay, analgesics consumption, neutrophil to lymphocyte ratio results and postoperative pain using Visual Analog Scale. Results: The morphine consumption of the patients was as follows in group total hip arthroplasty and total knee arthroplasty: at the 4th hour: 7.38 mg, 7.80 mg; 8th hour: 12.19 mg, 13.29 mg; 12th hour: 16.94 mg, 19.18 mg; 24th hour: 25.97 mg, 27.98 mg; 48th hour: 36.38 mg, 39.59 mg. The Visual Analog Scale scores of the patients was as follows in group total hip arthroplasty and total knee arthroplasty: at the 4th hour: 4.10, 4.51; 8th hour: 3.02, 3.43; 12th hour: 2.29, 2.55; 24th hour: 1.90, 1.87; 48th hour: 1.08, 1.13. In group total hip arthroplasty, we found a statistically significant association between postoperative neutrophil to lymphocyte ratio and the Visual Analog Scale values on the 48th hour in a positive direction (r = 0.311; P = 0.031; P < 0.05). Conclusion: Neutrophil to lymphocyte ratio can be accepted as a relatively objective method for the diagnosis of postoperative pain.

Resumo Justificativa e objetivos: A proporção entre neutrófilo/linfócito é um indicador de inflamação simples, custo-efetivo e de fácil aplicação que vem sendo usado com frequência em estudos de mortalidade, morbidade e prognóstico nos últimos anos. Avaliamos a relação entre a proporção neutrófilo/linfócito e a dor pós-operatória em pacientes submetidos à artroplastia total de quadril e artroplastia total de joelho. Material e métodos: No total, 101 pacientes que preferiram a raquianestesia e a analgesia venosa controlada pelo paciente foram incluídos e divididos em dois grupos neste estudo: artroplastia total de quadril e artroplastia total de joelho. Os dados demográficos e os tempos de operação, internação hospitalar e consumo de analgésicos e os resultados da proporção neutrófilo/linfócito e da dor pós-operatória foram registrados usando uma escala visual analógica. Resultados: O consumo de morfina dos pacientes submetidos à artroplastia total de quadril e artroplastia total de joelho nas horas 4, 8, 12, 24 e 45 foi de, respectivamente: 7,38 mg e 7,80 mg; 12,19 mg e 13,29 mg; 16,94 mg e 19,18 mg; 25,97 mg e 27,98 mg; 36,38 mg e 39,59 mg. Os escores obtidos na escala visual analógica dos pacientes submetidos à artroplastia total de quadril e artroplastia total de joelho nas horas 4, 8, 12, 24 e 48 foram, respectivamente: 4,10 e 4,51; 3,02 e 3,43; 2,29 e 2,55; 1,90 e 1,87; 1,08 e 1,13. Na artroplastia total do quadril, uma associação estatisticamente significativa foi encontrada entre a proporção neutrófilo/linfócito no pós-operatório e os valores da escala visual analógica na 48ª hora em uma direção positiva (r = 0,311; p = 0,031; p < 0,05). Conclusão: A proporção neutrófilo/linfócito pode ser aceita como um método relativamente objetivo para o diagnóstico da dor pós-operatória.

Transabdominal preperitoneal (TAPP) versus open Lichtenstein hernia repair. Comparison of the systemic inflammatory response and the postoperative pain

Abstract Purpose: To compare open Lichtenstein repair and laparoscopic transabdominal preperitoneal (TAPP) repair to treat primary unilateral hernia, regarding systemic inflammatory response, postoperative pain, and complications. Methods: A non-randomized prospective cohort study, with the preoperative and postoperative (24 hours) collection of blood samples for C reactive protein (CRP), interleukin 6 (IL-6), leukocyte and neutrophil analysis. Visual Analog Scale (VAS) was used to quantify the level of pain, and the operative time was correlated with the inflammatory response. VAS and CRP were also obtained on the 8th postoperative day. Results: Groups were homogeneous regarding preoperative characteristics. There were no differences between groups in 24h values of CRP, IL-6, leukocytes, neutrophils or VAS. Similarly, CRP and VAS did not differ between groups on the 8th postoperative day. However, the operative time for laparoscopic hernia repair was longer than the time for the open procedure. There was a weak correlation (r coefficient 0.31) between the duration of the surgical procedure and the VAS score at the eighth day. Conclusions: There were no statistically significant differences in the inflammatory response, pain scores, or complications between groups. We conclude that there is no advantage performing a primary unilateral hernia repair by laparoscopy.