Biopsychosocial Factors Associated With Pain and Pain-Related Outcomes in Adults and Children With Sickle Cell Disease: A Multivariable Analysis of the GRNDaD Multicenter Registry.

Pain is the primary symptomatic manifestation of sickle cell disease (SCD), an inherited hemoglobinopathy. The characteristics that influence pain experiences and outcomes in SCD are not fully understood. The primary objective of this study was to use multivariable modeling to examine associations of biopsychosocial variables with a disease-specific measure of pain interference known as pain impact. We conducted a secondary analysis of data from the Global Research Network for Data and Discovery national SCD registry. A total of 657 children and adults with SCD were included in the analysis. This sample was 60% female with a median age of 34 (interquartile range 26-42 years) and a chronic pain prevalence of 64%. The model accounted for 58% of the variance in pain impact. Low social (P < .001) and emotional (P < .001) functioning, increasing age (P = .004), low income (P < .001), and high acute painful episodes (P = .007) were most strongly associated with high pain impact in our multivariable model. Additionally, multivariable modeling of pain severity and physical function in 2 comparable samples of registry participants revealed that increasing age and low social functioning were also strongly associated with higher pain severity and low physical functioning. Overall, the results suggest that social and emotional functioning are more strongly associated with pain impact in individuals with SCD than previously studied biological modifiers such as SCD genotype, hemoglobin, and percentage fetal hemoglobin. Future research using longitudinally collected data is needed to confirm these findings. PERSPECTIVE: This study reveals that psychosocial (ie, social and emotional functioning) and demographic (ie, age) variables may play an important role in predicting pain and pain-related outcomes in SCD. Our findings can inform future multicenter prospective longitudinal studies aimed at identifying modifiable psychosocial predictors of adverse pain outcomes in SCD.

Management of Acute Sickle Cell Disease Pain.

Pain is a common complication of sickle cell disease. Sickle cell pain can often be effectively managed by pediatricians in outpatient and hospital settings. Acute pain management should be initiated quickly. Patients need to be evaluated for sickle cell complications and other causes of pain. Nonsteroidal anti-inflammatory drugs and opioids are the mainstay of pain treatment, but additional therapies include hydration, local pain control, muscle relaxants, and nonpharmacologic approaches. Healthy lifestyle habits and good behavioral and mental health are important for preventing and coping with sickle cell disease pain. Disease-modifying therapies, such as hydroxyurea, can help prevent sickle hemoglobin polymerization and acute pain episodes. Because sickle cell disease largely affects people who are racialized minorities in the United States, health-care providers need to be aware of how their own personal biases may affect care of these patients.

Predicting chronic postsurgical pain: current evidence and a novel program to develop predictive biomarker signatures.

ABSTRACT: Chronic pain affects more than 50 million Americans. Treatments remain inadequate, in large part, because the pathophysiological mechanisms underlying the development of chronic pain remain poorly understood. Pain biomarkers could potentially identify and measure biological pathways and phenotypical expressions that are altered by pain, provide insight into biological treatment targets, and help identify at-risk patients who might benefit from early intervention. Biomarkers are used to diagnose, track, and treat other diseases, but no validated clinical biomarkers exist yet for chronic pain. To address this problem, the National Institutes of Health Common Fund launched the Acute to Chronic Pain Signatures (A2CPS) program to evaluate candidate biomarkers, develop them into biosignatures, and discover novel biomarkers for chronification of pain after surgery. This article discusses candidate biomarkers identified by A2CPS for evaluation, including genomic, proteomic, metabolomic, lipidomic, neuroimaging, psychophysical, psychological, and behavioral measures. Acute to Chronic Pain Signatures will provide the most comprehensive investigation of biomarkers for the transition to chronic postsurgical pain undertaken to date. Data and analytic resources generatedby A2CPS will be shared with the scientific community in hopes that other investigators will extract valuable insights beyond A2CPS's initial findings. This article will review the identified biomarkers and rationale for including them, the current state of the science on biomarkers of the transition from acute to chronic pain, gaps in the literature, and how A2CPS will address these gaps.

Predictors of herpes zoster severity and immune responses according to pain trajectories: A community-based prospective cohort study.

The authors aimed to identify determinants of the clinical course of herpes zoster and immunological responses, focusing on pain trajectories. This prospective community-based cohort study involved the analysis of responses to a valid pain survey provided by 375 patients diagnosed with herpes zoster based on clinical symptoms and virus identification by polymerase chain reaction. The authors analyzed most patients for humoral/cell-mediated immune response against varicella-zoster virus at the onset and 3 months post-onset. Six months post-initial visit, patients self-reported pain on a scale of 0 (no pain) to 5 (extremely strong pain) at up to 18 time points. Moreover, the pain trajectories were traced using group-based trajectory modeling. Subsequently, the authors used analysis of covariance to explore predictors and the humoral/cell-mediated immune response according to the pain trajectories. In addition, humoral/cell-mediated immune responses were assessed among each trajectory using paired t tests. Amon the five identified trajectories, two were isolated that particularly developed postherpetic neuralgia, with or without severe acute pain. Cancer therapy and corticosteroid use before herpes zoster onset specifically predicted postherpetic neuralgia without severe acute pain. In contrast, prescription of nonsteroidal anti-inflammatory drugs was uniquely associated with postherpetic neuralgia accompanied by severe acute pain. The aforementioned trajectories with postherpetic neuralgia showed increased antibodies and decreased cell-mediated immunity compared with those without postherpetic neuralgia. The authors could successfully distinguish between postherpetic neuralgia trajectories with and without severe acute pain. The identified key predictors and immunological responses against varicella-herpes zoster contribute further evidence to our understanding of the clinical features of herpes zoster and postherpetic neuralgia.

Prescription Opioid Use for Acute Pain and Persistent Opioid Use After Gynecologic Surgery: A Systematic Review.

OBJECTIVE: To assess the amount of opioid medication used by patients and the prevalence of persistent opioid use after discharge for gynecologic surgery for benign indications. DATA SOURCES: We systematically searched MEDLINE, EMBASE, and ClinicalTrials.gov from inception to October 2020. METHODS OF STUDY SELECTION: Studies with data on gynecologic surgical procedures for benign indications and the amount of outpatient opioids consumed, or the incidence of either persistent opioid use or opioid-use disorder postsurgery were included. Two reviewers independently screened citations and extracted data from eligible studies. TABULATION, INTEGRATION, AND RESULTS: Thirty-six studies (37 articles) met inclusion criteria. Data were extracted from 35 studies; 23 studies included data on opioids consumed after hospital discharge, and 12 studies included data on persistent opioid use after gynecologic surgery. Average morphine milligram equivalents (MME) used in the 14 days after discharge were 54.0 (95% CI 39.9-68.0, seven tablets of 5-mg oxycodone) across all gynecologic surgery types, 35.0 (95% CI 0-75.12, 4.5 tablets of 5-mg oxycodone) after a vaginal hysterectomy, 59.5 (95% CI 44.4-74.6, eight tablets of 5-mg oxycodone) after laparoscopic hysterectomy, and 108.1 (95% CI 80.5-135.8, 14.5 tablets of 5-mg oxycodone) after abdominal hysterectomy. Patients used 22.4 MME (95% CI 12.4-32.3, three tablets of 5-mg oxycodone) within 24 hours of discharge after laparoscopic procedures without hysterectomy and 79.8 MME (95% CI 37.1-122.6, 10.5 tablets of 5-mg oxycodone) from discharge to 7 or 14 days postdischarge after surgery for prolapse. Persistent opioid use occurred in about 4.4% of patients after gynecologic surgery, but this outcome had high heterogeneity due to variation in populations and definitions of the outcome. CONCLUSION: On average, patients use the equivalent of 15 or fewer 5-mg oxycodone tablets (or equivalent) in the 2 weeks after discharge after major gynecologic surgery for benign indications. Persistent opioid use occurred in 4.4% of patients who underwent gynecologic surgery for benign indications. Our findings could help surgeons minimize overprescribing and reduce medication diversion or misuse. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42020146120.

Postoperative compression in preventing early complications after groin hernia repair.

PURPOSE: We conducted this study to investigate the efficacy, safety, and clinical value of postoperative compression in preventing seroma formation, relieving acute pain, and improving QoL after groin hernia repair. METHODS: This multi-center, prospective, observational real-world study was conducted from March 1, 2022, to August 31, 2022. The study was completed in 53 hospitals in 25 provinces in China. A total of 497 patients who underwent groin hernia repair were enrolled. All patients used a compression device to compress the operative region after surgery. The primary outcome was seroma incidence 1 month after surgery. Secondary outcomes included postoperative acute pain and QoL. RESULTS: A total of 497 patients [median (IQR) age 55 (41-67) years, 456 (91.8%) male] were enrolled, of whom 454 underwent laparoscopic groin hernia repair and 43 open hernia repair. The follow-up rate was 98.4% 1 month after surgery. Seroma incidence was 7.2% (35 of 489 patients) overall, lower than reported by previous research. No significant differences were found between the two groups (P > 0.05). VAS scores after compression were significantly lower than before compression overall and in both groups (P < 0.001). The laparoscopic group showed a high level of QoL compared with the open group, but there was no significant difference between the two groups (P > 0.05). CCS score correlated positively with VAS score. CONCLUSION: Postoperative compression, to a certain extent, can reduce seroma incidence, relieve postoperative acute pain, and improve QoL after groin hernia repair. Further large-scale randomized controlled studies are warranted to determine long-term outcomes.

Transabdominal preperitoneal versus hybrid procedures for treating irreducible inguinal hernias: A retrospective controlled study.

BACKGROUND: Inguinal hernia is a common condition; however, irreducible inguinal hernias are rare. In this retrospective study, two laparoscopic procedures for irreducible inguinal hernia were compared. MATERIALS AND METHODS: The study cohort comprised 88 patients who had undergone laparoscopic repair of primary irreducible inguinal hernias between 1 June 2011 and 31 December 2019. The patients were retrospectively divided into Hybrid (Group H) and Standard Transabdominal Preperitoneal (TAPP) Groups (Group S). Patient characteristics, hernia details, and intraoperative and postoperative complications were compared between study groups. RESULTS: There were no significant differences between the two groups in baseline characteristics, including age, sex, body mass index, hernia type, operation time, hospital stay, cost, and duration of follow-up. No recurrence or surgical site infection occurred in either group. There were no significant differences between the two groups in incidence of spermatic vessel injury (0% vs. 2.04%, P = 0.370), vas deferens injury (0% vs. 6.12%, P = 0.116), epigastric vessels injury (0% vs. 4.08%, P = 0.202), scrotal hematoma (7.69% vs. 2.04%, P = 0.206), dysuria (5.13% vs. 8.16%, P = 0.575), fever (17.95% vs. 16.32%, P = 0.841), seroma (25.64% vs. 32.65%, P = 0.474), chronic pain (0% vs. 2.04%, P = 0.370), sensation of a foreign body (2.56% vs. 2.04%, P = 0.870), or pain on ejaculation (0% vs. 2.04%, P = 0.370). The incidence of acute pain was higher in Group H than in Group S (43.59% vs. 8.16%, P = 0.000). CONCLUSION: The hybrid TAPP procedure is a safe and feasible means of treating irreducible inguinal hernias. Though it is associated with a higher incidence of postoperative acute pain than the standard TAPP procedure, it may have advantages in avoiding injuries to the vas deferens and spermatic vessels.

Management of surgical patients on opioid replacement therapy: An audit of current practice.

Patients on opioid replacement therapy hospitalised with acute pain represent a clinical challenge and have poorer perioperative outcomes. There is limited evidence relating to acute pain management of this complex cohort. The primary objectives of this retrospective audit was to establish the number of patients who are admitted on opioid replacement therapy with an acute pain condition under surgical services and evaluate the management of these patients to determine consistency of pain management practices. Secondarily, we aimed to evaluate the documentation of opioid replacement therapy in clinical notes to determine adherence to operational protocols and record clinically relevant outcomes including infection or postoperative complication rates. Forty-four episodes of care for buprenorphine patients and 19 episodes of care for methadone patients were included. There was significant variability in inpatient opioid prescribing, including practice of dose modification, and there was high utilisation of additional opioids, although agent choice varied. Multimodal analgesia was utilised, especially following acute pain service review. There was an 11% readmission rate for complications of the initial presentation. Documentation at transitions of care was poor. There is a need for further clinical studies into specific acute pain management strategies, and their effect on clinically relevant outcomes, to guide consistent management practices.

A Guide to Preclinical Models of Zoster-Associated Pain and Postherpetic Neuralgia.

Reactivation of latent varicella-zoster virus (VZV) causes herpes zoster (HZ), which is commonly accompanied by acute pain and pruritus over the time course of a zosteriform rash. Although the rash and associated pain are self-limiting, a considerable fraction of HZ cases will subsequently develop debilitating chronic pain states termed postherpetic neuralgia (PHN). How VZV causes acute pain and the mechanisms underlying the transition to PHN are far from clear. The human-specific nature of VZV has made in vivo modeling of pain following reactivation difficult to study because no single animal can reproduce reactivated VZV disease as observed in the clinic. Investigations of VZV pathogenesis following primary infection have benefited greatly from human tissues harbored in immune-deficient mice, but modeling of acute and chronic pain requires an intact nervous system with the capability of transmitting ascending and descending sensory signals. Several groups have found that subcutaneous VZV inoculation of the rat induces prolonged and measurable changes in nociceptive behavior, indicating sensitivity that partially mimics the development of mechanical allodynia and thermal hyperalgesia seen in HZ and PHN patients. Although it is not a model of reactivation, the rat is beginning to inform how VZV infection can evoke a pain response and induce long-lasting alterations to nociception. In this review, we will summarize the rat pain models from a practical perspective and discuss avenues that have opened for testing of novel treatments for both zoster-associated pain and chronic PHN conditions, which remain in critical need of effective therapies.

Cortical function and sensorimotor plasticity are prognostic factors associated with future low back pain after an acute episode: the Understanding persistent Pain Where it ResiDes prospective cohort study.

ABSTRACT: Predicting the development of chronic low back pain (LBP) at the time of an acute episode remains challenging. The Understanding persistent Pain Where it ResiDes study aimed to identify neurobiological and psychological risk factors for chronic LBP. Individuals with acute LBP (N = 120) participated in a prospective cohort study with 6-month follow-up. Candidate predictors were selected from the neurobiological (eg, sensorimotor cortical excitability assessed by sensory and motor-evoked potentials and brain-derived neurotrophic factor genotype), psychological (eg, depression and anxiety), symptom-related (eg, LBP history), and demographic domains. Analyses involved multivariable linear regression models with pain intensity or disability degree as continuous variables. Secondary analyses involved a multivariable logistic model with the presence of LBP at 6 months (thresholding pain intensity and disability degree) as a dichotomous variable. Lower sensory cortex and corticomotor excitability, higher baseline pain intensity, higher depression, stress, and pain catastrophizing were the strongest predictors ( R2 = 0.47) of pain intensity at 6 months. Older age and higher pain catastrophizing were the strongest predictors ( R2 = 0.30) of disability at 6 months. When the LBP outcome was dichotomised, sensory cortex and corticomotor excitability, brain-derived neurotrophic factor genotype, depression and anxiety, LBP history and baseline pain intensity, discriminated between those who did and did not report LBP at 6 months (C-statistic 0.91). This study identifies novel risk factors for the development of future LBP. Neurobiological risk factors, when added to a multivariable linear regression model, explained a further 15% of the variance in the 6-month pain intensity.

Robotic-Assisted Esophagectomy Leads to Significant Reduction in Postoperative Acute Pain: A Retrospective Clinical Trial.

BACKGROUND: Robot-assisted minimally invasive esophagectomy (RAMIE) shows promising results regarding postoperative complications in patients with esophageal cancer. To date, no data are available regarding postoperative analgesic consumption. The aim of this work is to evaluate analgesic consumption after esophagectomy. METHODS: A total of 274 Ivor Lewis esophageal resections performed sequentially from January 2012 to December 2020 were evaluated. RAMIE cases (n = 51) were compared with the hybrid technique (laparoscopic abdominal phase followed by open thoracotomy, n = 59) and open abdominothoracic esophagectomy (OTE) (n = 164). Data were collected retrospectively. The primary endpoint was the overall postoperative morphine consumption, which represents a reliable indirect measurement of pain. Pain levels recorded on the first, third, and fifth postoperative days were assessed as secondary endpoints. RESULTS: A total of 274 patients were included. The postoperative opioid consumption rate for patients who underwent RAMIE (quartiles: 0.14, 0.23, 0.36 mg morphine milligram equivalents (MME)/kg body weight (bw)/day) was significantly lower than in the open group (0.19, 0.33, 0.58 mg MME/kg bw/day, p = 0.016). The overall postoperative opioid consumption for patients who underwent RAMIE was significantly lower (2.45, 3.63, 7.20 mg MME/kg bw/day; morphine milligram equivalents per kilogram body weight) compared with the open (4.85, 8.59, 14.63 MME/kg bw/day, p < 0.0001) and hybrid (4.13, 6.84, 11.36 MME/kg bw/day, p = 0.008) groups. Patients who underwent RAMIE reported lower pain scores compared with the open group on the fifth postoperative day, both at rest (p = 0.004) and while performing activities (p < 0.001). CONCLUSIONS: This study shows that patients who underwent RAMIE experienced similar postoperative pain while requiring significantly lower amounts of opioids compared with patients who underwent open and hybrid surgery. Further studies are required to verify the results.

Uncontrolled pain in critically ill patients and acute kidney injury: a hypothesis-generating cohort study.

BACKGROUND: In critically ill patients, acute pain occurs frequently, causes sympathetic activation, release of inflammatory mediators, and potential organ dysfunction, with the kidneys potentially sensitive to inflammation-mediated injury. This study aimed to explore the association between acute pain in critically ill patients and the occurrence of acute kidney injury (AKI). METHODS: Data from a retrospective cohort of adult patients admitted between June 2013 and June 2016 to the Intensive Care Unit (ICU) of a tertiary hospital in São Paulo, Brazil, were analyzed. The main exclusion criteria were ICU length of stay < 48 h, coma, and prior kidney dysfunction. The outcome (AKI) was defined as an elevation in the baseline serum creatinine level of ≥ 0.3 mg/dl and/or > 50% at any time after the first 48 h in the ICU. Multivariable logistic regression and hierarchical cluster analysis were performed. RESULTS: The isolated incidence of pain was 23.6%, and the incidence of pain duration > 5 days was 10.6%. AKI occurred in 31.7% of the cohort. In multivariable logistic analysis, duration of pain > 5 days (OR 5.25 CI 2.19-12.57 p < 0.01) and mechanical ventilation (MV) ≥ 3 days (OR 5.5 CI 2.3-13.5 p < 0.01) were the variables with positive association with AKI. The hierarchical cluster analysis reinforced the relation between AKI, MV and duration of pain. CONCLUSIONS: Pain is an especially important issue in critically ill patients and in this exploratory study it appears to be associated with AKI development. The search for more rigorous pain control in ICU is crucial and can influence organ dysfunction.

Longus colli tendinitis: acute neck pain with retropharyngeal swelling.

Longus colli tendinitis (LCT) has been described in several case reports, and is likely underdiagnosed due to its non-specific symptoms and self-limiting nature. It usually presents as acute neck pain with retropharyngeal swelling seen on nasoendoscopy and imaging studies. This may lead to unnecessary invasive interventions if physicians are unaware of the disease course. We discuss a case of LCT in a young woman who was treated at our institution, with recommendations on how to identify and treat such cases accurately without overtreatment.

Testicular infarction and spontaneous scrotal rupture secondary to acute epididymo-orchitis.

Epididymo-orchitis is a common cause of acute unilateral testicular pain. Both infectious or non-infectious causes have been proposed and, rarely, testicular abscess formation and even infarction can occur as a severe complication. We present here a case of acute epididymo-orchitis leading to testicular abscess formation, infarction and spontaneous rupture through the scrotal wall despite appropriate antibiotic treatments. Orchidectomy and partial scrotectomy were performed during surgical exploration for management of the non-viable testis and associated scrotal sinus. Clinical vigilance is important to prevent this complication by close clinical follow up with ultrasonography and even early surgical decompression to prevent testicular loss.

[Retropharyngeal tendinitis : Rare differential diagnosis of acute neck pain]. / Retropharyngeale Tendinitis : Seltene Differenzialdiagnose bei akuten Nackenschmerzen.

Atraumatic neck pain is a frequent reason for patients to attend the emergency department (ED). It remains a challenge for the treating physician to rule out possible life-threatening causes, such as a retropharyngeal abscess, meningitis or septic spondylodiscitis. Herein, we report the rare case of a patient suffering from retropharyngeal tendinitis. This rare cause of atraumatic neck pain is characterized by a significant decrease in the range of motion of the cervical spine, elevated infection parameters and pathognomonic MRI findings. In addition to presenting the rare case of retropharyngeal tendinitis, we also review selected previous case reports and thereby not only raise awareness for this rare disease but also suggest the best practice for treatment.

Nutritional deficiency presenting as acute pain, fatigue and bruising in a college health clinic.

A previously healthy university student presents to Health Services with sudden onset of pain, fatigue, bruising, and a rapidly progressive anemia. There was not any previous significant health history. The case discussion will emphasize the critical overlap of physical and mental health assessments in identifying the cause and cure of a potentially life-threatening health crisis for a young adult student.

Low Somatosensory Cortex Excitability in the Acute Stage of Low Back Pain Causes Chronic Pain.

Determining the mechanistic causes of complex biopsychosocial health conditions such as low back pain (LBP) is challenging, and research is scarce. Cross-sectional studies demonstrate altered excitability and organization of the somatosensory and motor cortex in people with acute and chronic LBP, however, no study has explored these mechanisms longitudinally or attempted to draw causal inferences. Using sensory evoked potential area measurements and transcranial magnetic stimulation derived map volume we analyzed somatosensory and motor cortex excitability in 120 adults experiencing acute LBP. Following multivariable regression modelling with adjustment for confounding, we identified lower primary (OR = 2.08, 95% CI = 1.22-3.57) and secondary (OR = 2.56, 95% CI = 1.37-4.76) somatosensory cortex excitability significantly increased the odds of developing chronic pain at 6-month follow-up. Corticomotor excitability in the acute stage of LBP was associated with higher pain intensity at 6-month follow-up (B = -0.15, 95% CI: -0.28 to -0.02) but this association did not remain after confounder adjustment. These data provide evidence that low somatosensory cortex excitability in the acute stage of LBP is a cause of chronic pain. PERSPECTIVE: This prospective longitudinal cohort study design identified low sensorimotor cortex excitability during the acute stage of LBP in people who developed chronic pain. Interventions that target this proposed mechanism may be relevant to the prevention of chronic pain.

Sevuparin for the treatment of acute pain crisis in patients with sickle cell disease: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial.

BACKGROUND: There are no approved treatments for vaso-occlusive crises in sickle cell disease. Sevuparin is a novel non-anticoagulant low molecular weight heparinoid, with anti-adhesive properties. In this study, we tested whether sevuparin could shorten vaso-occlusive crisis duration in hospitalised patients with sickle cell disease. METHODS: We did a multicentre, double-blinded, placebo-controlled, phase 2 study in 16 public access clinical hospitals in the Netherlands, Lebanon, Turkey, Bahrain, Oman, Saudi Arabia, and Jamaica. Patients aged 12-50 years with a diagnosis of sickle cell disease (types HbSS, HbSC, HbSß0-thalassaemia, or HbSß+-thalassaemia) on a stable dose of hydroxyurea, hospitalised with vaso-occlusive crisis for parenteral opioid analgesia with a projected stay of more than 48 h were included in the study. Patients were randomly assigned (1:1) using a computer-generated randomisation scheme to receive sevuparin (18 mg/kg per day) or placebo (NaCl, 0·9% solution) intravenously for 2-7 days until vaso-occlusive crisis resolution. All individuals involved in the trial were masked to treatment allocation. The analysis was done in the intention-to-treat population. The primary endpoint was time to vaso-occlusive crisis resolution defined as freedom from parenteral opioid use (in preceding 6-10 h); and readiness for discharge as judged by the patient or physician. The trial is registered with ClinicalTrials.gov, NCT02515838. FINDINGS: Between Oct 7, 2015, and Feb 10, 2019, 144 patients were randomly assigned and administered sevuparin (n=69) or placebo (n=75). The median age was 22·2 years (range 12·2-33·6), 104 (72%) 144 were adults (18 years or older), and 90 (63%) were male and 54 (37%) were female. The intention-to-treat analysis for the primary endpoint showed no significant difference in median time to vaso-occlusive crisis resolution between the sevuparin and placebo groups (100·4 h [95% CI 85·5-116·8]) vs 86·4 h [70·6-95·1]; hazard ratio 0·89 [0·6-1·3]; p=0·55). Serious adverse events occurred in 16 (22%) of 68 patients in the sevuparin group and in 21 (22%) of patients in the placebo group. The most frequent treatment-emergent adverse events were pyrexia (17 [25%] in the sevuparin group vs 17 [22%] in the placebo group), constipation (12 [18%] vs 17 [22%]), and decreased haemoglobin (18 [26%] vs 9 [12%]). There were no deaths in the sevuparin group and there was one (1%) death in the placebo group after a hyper-haemolytic episode due to alloimmunisation. INTERPRETATION: This result, as well as the results seen in other clinical studies of inhibitors of adhesion in sickle cell disease, suggest that selectin-mediated adhesion might be important in the initiation, but not maintenance of vaso-occlusion, indicating that strategies to treat vaso-occlusive crises differ from strategies to prevent this complication. FUNDING: Modus Therapeutics.

AMPAkines potentiate the corticostriatal pathway to reduce acute and chronic pain.

The corticostriatal circuit plays an important role in the regulation of reward- and aversion-types of behaviors. Specifically, the projection from the prelimbic cortex (PL) to the nucleus accumbens (NAc) has been shown to regulate sensory and affective aspects of pain in a number of rodent models. Previous studies have shown that enhancement of glutamate signaling through the NAc by AMPAkines, a class of agents that specifically potentiate the function of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, reduces acute and persistent pain. However, it is not known whether postsynaptic potentiation of the NAc with these agents can achieve the full anti-nociceptive effects of PL activation. Here we compared the impact of AMPAkine treatment in the NAc with optogenetic activation of the PL on pain behaviors in rats. We found that not only does AMPAkine treatment partially reconstitute the PL inhibition of sensory withdrawals, it fully occludes the effect of the PL on reducing the aversive component of pain. These results indicate that the NAc is likely one of the key targets for the PL, especially in the regulation of pain aversion. Furthermore, our results lend support for neuromodulation or pharmacological activation of the corticostriatal circuit as an important analgesic approach.

Group-based trajectory analysis of postoperative pain and outcomes after liver cancer surgery.

BACKGROUND: Although previous studies have shown connections between pain and worse cancer outcomes, few clinical studies have evaluated their direct association, and the current study aimed to investigate the potential association between acute pain trajectories and postoperative outcomes after liver cancer surgery. METHODS: This retrospective study was conducted in a single medical center and included patients who received liver cancer surgery between January 2010 and December 2016. Maximal pain intensity was recorded daily using a numerical rating scale during the first postoperative week. Group-based trajectory analysis was performed to classify the variations in pain scores over time. Cox and linear regression analyses were used to assess the effect of pain trajectories on recurrence-free survival, overall survival, and length of hospital stay (LOS) after surgery and to explore predictors of these outcomes. RESULTS: A total of 804 patients with 5396 pain score observations were analyzed within the present study. Group-based trajectory analysis categorized the changes in postoperative pain into three groups: group 1 had constantly mild pain (76.6%), group 2 had moderate/severe pain dropping to mild (10.1%), and group 3 had mild pain rebounding to moderate (13.3%). Multivariable analysis demonstrated that on average, group 3 had a 7% increase in LOS compared with the group 1 (p = 0.02) and no significant difference in the LOS was noted between pain trajectory groups 2 and 1 (p = 0.93). Pain trajectories were not associated with recurrence-free survival or overall survival after liver cancer surgery. CONCLUSION: Acute pain trajectories were associated with LOS but not cancer recurrence and survival after liver cancer surgery. Group-based trajectory analysis provided a promising approach for investigating the complex relationships between variations in postoperative pain over time and clinical outcomes.