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Thomas JP Mangnus, Maaike Dirckx, Frank JPM Huygen Department of Anesthesiology, Center for Pain Medicine, Erasmus MC University Medical Center, Rotterdam, the NetherlandsCorrespondence: Thomas JP Mangnus, Email t.mangnus@erasmusmc.nlAbstract: Complex regional pain syndrome (CRPS) is a debilitating painful state of an extremity that can develop after trauma. CRPS is diagnosed by the new International Association for the Study of Pain (IASP) diagnostic criteria for CRPS. The syndrome is characterized by continuing regional pain with abnormal sensory, motor, sudomotor, vasomotor, edema, and/or trophic signs. The clinical presentation of CRPS can be very heterogeneous because CRPS is a multi-mechanism syndrome. Therefore, mechanism-based subgroups have been suggested to personalize treatment for CRPS. Additionally, the presentation of symptom pain may also be able to identify different subgroups of CRPS. In this review, the types of pain recognized by the IASP―nociceptive, neuropathic, and nociplastic pain―will be discussed as possible subgroups for CRPS. Each pain type should be identified in CRPS patients, with a thorough history taking, physical examination, and diagnostic tests or (novel) biomarkers to optimize treatment effectiveness. Over the course of the syndrome, patients with CRPS probably experience more than one distinct pain type. Therefore, pain specialists should be alert to not only adjust their treatment if underlying pathophysiologic mechanisms tend to change but also to personalize the treatment of the associated type of pain in the CRPS patient.Keywords: CRPS, nociceptive pain, neuropathic pain, nociplastic pain, mixed pain, personalized medicine

Corinne van den Berg, Maaike Dirckx, Frank JPM Huygen, Jitske Tiemensma Department of Anesthesiology, Center for Pain Medicine, Erasmus University Medical Center, Rotterdam, the NetherlandsCorrespondence: Corinne van den Berg, Department of Anesthesiology, Center for Pain Medicine, Erasmus University Medical Center, Postbus 2040, Rotterdam, 3000CA, the Netherlands, Tel +31 107040140, Fax +31 107035184, Email c.vandenberg.6@erasmusmc.nlPurpose: Complex regional pain syndrome (CRPS) is a multi-mechanism disease, with an exaggerated inflammatory response as an important underlying mechanism. Auto-inflammation can theoretically be combated by anti-inflammatories, such as TNF-α inhibitors. This study’s aim was to assess the effectiveness of intravenous infliximab, a TNF-α inhibitor, in patients with CRPS.Patients and Methods: CRPS patients treated with infliximab between January 2015 and January 2022 were approached to participate in this retrospective study. Medical records were screened for age, gender, medical history, CRPS duration, and CRPS severity score. Additionally, treatment effect, dose and duration, and side effects were extracted from medical records. Patients who still receive infliximab completed a short global perceived effect survey.Results: Eighteen patients received infliximab, and all but two gave consent. Trial treatment with three sessions of 5 mg/kg intravenous infliximab was completed in 15 patients (93.7%). Eleven patients (73.3%) were categorized as responders with a positive treatment effect. Treatment was continued in nine patients, and seven patients are currently treated. Infliximab dose is 5 mg/kg, and frequency is every four to six weeks. Seven patients completed a global perceived effect survey. All patients reported improvement (median 2, IQR 1– 2) and treatment satisfaction (median 1, IQR 1– 2). One patient described side effects such as itching and rash.Conclusion: Infliximab proved effective in 11 out of 15 CRPS patients. Seven patients are still being treated. Further research is needed on the role of infliximab in the treatment of CRPS and possible predictors of response to treatment.Keywords: complex regional pain syndrome, CRPS, TNF-α inhibitors, treatment, inflammation, anti-inflammatories

KD Bharwani,1,* AB Kersten,1,* AL Stone,2 F Birklein,3 S Bruehl,2 M Dirckx,1 PD Drummond,4 J Gierthmühlen,5 A Goebel,6 L Knudsen,7 FJPM Huygen1 1Center for Pain Medicine, Department of Anesthesiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands; 2Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN, USA; 3Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; 4Discipline of Psychology, College of Science, Health, Engineering and Education, Murdoch University, Perth, WA, Australia; 5Division of Neurological Pain Research and Therapy, Department Neurology, University Hospital of Schleswig-Holstein, Campus Kiel, Kiel, Germany; 6Director of the Pain Research Institute Reader in Pain Medicine, University of Liverpool Honorary Consultant in Pain Medicine, Walton Centre NHS Foundation Trust, Liverpool, UK; 7The National Rehabilitation Centre for Neuromuscular Diseases, Aarhus, Denmark*These authors contributed equally to this workCorrespondence: KD Bharwani Tel +31107040704Email bharwani.kd@gmail.comPurpose: Several articles have claimed that complex regional pain syndrome (CRPS) does not exist. Although a minority view, it is important to understand the arguments presented in these articles. We conducted a systematic literature search to evaluate the methodological quality of articles that claim CRPS does not exist. We then examined and refuted the arguments supporting this claim using up-to-date scientific literature on CRPS.Methods: A systematic search was conducted in MEDLINE, EMBASE and Cochrane CENTRAL databases. Inclusion criteria for articles were (a) a claim made that CRPS does not exist or that CRPS is not a distinct diagnostic entity and (b) support of these claims with subsequent argument(s). The methodological quality of articles was assessed if possible.Results: Nine articles were included for analysis: 4 narrative reviews, 2 personal views, 1 letter, 1 editorial and 1 case report. Seven points of controversy were used in these articles to argue that CRPS does not exist: 1) disagreement with the label “CRPS”; 2) the “unclear” pathophysiology; 3) the validity of the diagnostic criteria; 4) CRPS as a normal consequence of immobilization; 5) the role of psychological factors; 6) other identifiable causes for CRPS symptoms; and 7) the methodological quality of CRPS research.Conclusion: The level of evidence for the claim that CRPS does not exist is very weak. Published accounts concluding that CRPS does not exist, in the absence of primary evidence to underpin them, can harm patients by encouraging dismissal of patients’ signs and symptoms.Keywords: complex regional pain syndrome, pathophysiology, treatment, chronic pain

Previously, we showed that serum soluble interleukin-2 receptor (sIL-2R) levels, a marker for T-cell activation, were higher in complex regional pain syndrome (CRPS) patients than in healthy controls, suggesting pathogenic T-cell activation in CRPS. Additionally, sIL-2R levels discriminated well between CRPS and healthy controls with a high sensitivity (90%) and specificity (89.5%), suggesting a possible role for sIL-2R in the diagnosis of CRPS. In order to further validate this marker in the diagnostic workup of CRPS, we conducted this prospective cohort study in which we determined sIL-2R levels in patients that were referred to our tertiary referral center with a suspicion of CRPS in a limb, and subsequently compared sIL-2R levels between the patients that were diagnosed with CRPS (CRPS group) and those who were not (no CRPS group). A group of anonymous blood bank donors were used as a healthy control group. Furthermore, we explored the relationship between sIL-2R and CRPS disease severity using the CRPS severity score. Median sIL-2R levels of both the CRPS group (2809.0 pg/ml; Q3-Q1: 3913.0-1589.0) and no CRPS group (3654.0 pg/ml; Q3-Q1: 4429.0-2095.5) were significantly higher than that of the control group (1515.0 pg/ml; Q3-Q1: 1880.0-1150.0): CRPS vs. controls, p <.001 ; no CRPS vs. controls, p < 0.001. Serum sIL-2R levels did not differ significantly between the CRPS and no CRPS group. A statistically significant negative correlation was observed between sIL-2R levels and the CRPS severity score ( r s = − 0.468 , p = 0.024). Our results confirm our previous findings of higher sIL-2R levels in CRPS patients than in healthy controls. We further showed that serum sIL-2R cannot differentiate between CRPS and other pain conditions of a limb in a tertiary referral setting. Interestingly, a negative correlation was found between sIL-2R and CRPS disease severity; this finding warrants further research into the relationship between sIL-2R and CRPS disease severity. [ABSTRACT FROM AUTHOR]

Introduction: Complex regional pain syndrome (CRPS) is a clinical disorder that can develop following surgery or trauma. Based on the most prominent underlying pathophysiological mechanisms, CRPS can be classified into different subtypes, namely inflammatory, nociplastic/neuropathic, vasomotor, and motor. Depending on the subtype, personalized treatment can be applied. If conservative treatments are insufficient or ineffective, more invasive treatments may be recommended. This article provides an overview of the most recent insights into CRPS and discusses the most common invasive treatments., Methods: The literature regarding interventional treatments for CRPS has been systematically reviewed and summarized., Results: Bisphosphonates are effective in treating the inflammatory subtype, while ketamine can provide pain relief for the nociplastic/neuropathic subtype. Sympathetic blocks are effective in addressing vasomotor disturbances. For patients with refractory symptoms, neurostimulation is a viable option due to its multimechanistic properties for all subtypes. End-of-line motor disturbances may benefit from intrathecal baclofen., Conclusions: CRPS is a debilitating condition with an unpredictable course. The effectiveness of treatment varies from patient to patient. When conservative approaches prove insufficient, gradual progression to invasive treatments based on the underlying subtype is recommended., (© 2024 The Author(s). Pain Practice published by Wiley Periodicals LLC on behalf of World Institute of Pain.)

Objective: To determine which locoregional techniques are effective in managing post-operative pain in major open oncologic gynecologic surgery in terms of pain scores and opioid consumption when epidural analgesia is not a feasible option., Methods: A systematic review of the literature, based on the Preferred Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, was conducted. The ROB-2 assessment was used to assess bias. The primary outcomes were opioid consumption and post-operative pain scores. Secondary outcomes included post-operative markers such as time to mobilization and bowel movement., Results: A total of nine studies (n=714) were included in the analysis. Eight studies had a low risk of bias. Five different forms of locoregional analgesia were described. Eight studies compared with placebo and one study compared rectus sheath block with epidural analgesia. Three of the five studies investigating transversus abdominis plane (TAP) blocks showed an improvement in pain scores and opioid consumption when compared with the placebo group. One study investigating rectus sheath blocks and another investigating paravertebral blocks demonstrated significantly less opioid consumption and improved pain scores at certain time points. The studies investigating continuous wound infiltration and superior hypogastric plexus block found no significant effect. No adverse effects of locoregional anesthesia were found., Conclusion: Our study showed that TAP blocks, rectus sheath blocks, and paravertebral blocks may decrease opioid consumption and improve pain scores in patients undergoing open abdominal surgery for gynecologic cancer. Additionally, these techniques might serve as a viable alternative for patients with contraindications to epidural analgesia., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2024. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Background: Evidence-based guidelines for managing anterior cutaneous nerve entrapment syndrome (ACNES) in children are absent. The primary aim of this review was to scrutinize the evidence supporting currently used treatment interventions. In accordance with the World Health Organization (WHO) guidelines for managing chronic pain in children, these patients and their families and caregivers should be treated within the context of the biopsychosocial model; pain should not be treated purely as a biomedical problem. Therefore, our second aim was to evaluate whether these interventions are applied within the context of the biopsychosocial model, utilizing an inter- or multidisciplinary approach., Materials and Methods: A scoping review of the literature was conducted to explore treatment strategies for ACNES in children. To ensure a comprehensive overview of published literature on this topic, the search was not restricted based on study type. Two reviewers independently assessed titles and abstracts. After excluding records unrelated to children, full texts were screened for inclusion. Any discrepancies in judgement were resolved through discussion with a third reviewer., Results: Out of 35 relevant titles, 22 were included in this review. Only 4 articles provided information on long-term outcomes. The overall quality of the review was deemed low. The majority of reports did not address treatment or education within the psychological and social domains. A structural qualitative analysis was not feasible due to the substantial heterogeneity of the data., Conclusion: The evidence supporting current treatment strategies in children with ACNES is of low quality. More research is needed to establish an evidence-based treatment algorithm for patients with this challenging pain problem. In line with the WHO recommendation, greater emphasis should be placed on a biopsychosocial approach. The ultimate goal should be the development of a generic treatment algorithm outlining an approach to ACNES applicable to all professionals involved., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Anke P. C. Top et al.)

Post-traumatic coronoid deficiency in the elbow can lead to chronic pain, instability and arthritis. A variety of osteochondral grafts have been used to reconstruct the coronoid, and restore elbow stability. The radial head and iliac crest grafts are the most common in the literature but have limitations. The olecranon tip is a promising alternative, with both cadaveric and computer models demonstrating superior congruency, without compromising elbow stability or disrupting the extensor mechanism. We present a small, case series demonstrating the technique for contralateral and ipsilateral grafts in both the acute and chronic setting., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Objective: A potentially useful biomarker for Complex Regional Pain Syndrome (CRPS) is the serum soluble interleukin-2 receptor (sIL-2R) level, which is a marker for T-cell activation. Elevated serum sIL-2R levels have been described in CRPS patients compared to healthy controls. In T-cell mediated inflammatory diseases such as sarcoidosis and rheumatoid arthritis, the serum sIL-2R levels correlate with disease severity. In this study, we investigate whether an association exists between serum sIL-2R levels in CRPS patients and CRPS severity., Methods: A cross-sectional cohort study was conducted in a tertiary pain referral center in the Netherlands. Adult CRPS patients diagnosed by the IASP criteria were included between October 2018 until October 2022. The main study parameters were serum sIL-2R levels and the CRPS severity score., Results: Fifty-three CRPS patients were included with a mean syndrome duration of 84 months (Q3 - Q1:180 - 48). The majority had persistent CRPS with a syndrome duration >1 year (n = 52, 98%). The median pain Numerical Rating Score (NRS) was 7 (Q3 - Q1: 8 - 5) and the mean CRPS severity score was 11 (SD ± 2.3). The median serum sIL-2R level was 330 U/mL (Q3 - Q1:451 - 256). No statistically significant correlation was observed between serum sIL-2R levels and the CRPS severity score (rs = 0.15, P = .28)., Conclusions: Our findings suggest that serum sIL-2R levels cannot be used as a biomarker for syndrome severity in persistent CRPS (syndrome duration >1 year). Serial measurements of serum sIL-2R from early CRPS to persistent CRPS are needed to investigate whether serum sIL-2R levels can be used to monitor T-cell mediated inflammatory syndrome activity., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Academy of Pain Medicine.)

Background: Complex regional pain syndrome (CRPS) is a chronic pain condition of an extremity. While achieving pain relief in CRPS is challenging, esketamine infusions can accomplish pain relief for several weeks post-infusion in a subgroup of CRPS patients. Unfortunately, CRPS esketamine protocols are very heterogeneous in advice on dosage, administration and treatment setting. Currently, no trials are available that study differences between intermittent and continuous esketamine infusions for CRPS. With the current situation of bed shortages, it is difficult to admit patients for several consecutive days for inpatient esketamine treatments. In this study, we investigate whether 6 intermittent outpatient esketamine treatments are not inferior to a continuous 6-day inpatient esketamine treatment in establishing pain relief. In addition, several secondary study parameters will be assessed in order to investigate mechanisms responsible for pain relief by esketamine infusions. Furthermore, the cost-effectiveness will be analyzed., Methods: In this RCT, the primary objective is to demonstrate that an intermittent esketamine dosing regimen is non-inferior to a continuous esketamine dosing regimen at 3 months follow-up. We will include 60 adult CRPS patients. The inpatient treatment group receives a continuous intravenous esketamine infusion for 6 consecutive days. The outpatient treatment group receives a 6-hour intravenous esketamine infusion every 2 weeks for 3 months. Esketamine dose will be individually tailored and is started at 0.05 mg/kg/h and can be increased to a maximum of 0.2 mg/kg/h. Each patient will be followed for 6 months. The primary study parameter is perceived pain intensity, measured by an 11-point Numerical Rating Scale. Secondary study parameters are conditioned pain modulation, quantitative sensory testing, adverse events, thermography, blood inflammatory parameter, questionnaires about functionality, quality of life and mood and costs per patient., Discussion: If our study reveals non-inferiority between intermittent and continuous esketamine infusions, these findings can be beneficial to increase the availability and flexibility of esketamine infusions through outpatient treatments. Furthermore, the costs of outpatient esketamine infusions could be lower than inpatient esketamine infusions. In addition, secondary parameters may predict response to esketamine treatment., Trial Registration: ClinicalTrials.gov Identifier NCT05212571 , date of registration 01-28-2022., Protocol Version: Version 3, February 2022., (© 2023. The Author(s).)

Background: Intra-articular distal humerus fractures in the older population remain a challenge to fix, due to the comminution of fragments and poor bone stock. Recently Elbow Hemiarthroplasty (EHA) has gained popularity to treat these fractures, however no studies exist comparing EHA to Open Reduction Internal Fixation (ORIF)., Objectives: To compare the clinical outcomes of patients over the age of 60 years treated with ORIF or EHA for multi-fragmentary distal humerus fractures., Methods: Thirty-six patients (mean age 73 years) treated surgically for a multi-fragmentary intra-articular distal humeral fracture were followed up for a mean duration of thirty-four months (12-73 months). Eighteen patients were treated with ORIF and eighteen with EHA. The groups were matched for fracture type, demographic characteristics and follow up time. Outcome measures collected included Oxford Elbow Score (OES), Visual Analogue pain Score (VAS), range of motion (ROM), complications, re-operations and radiographic outcomes. The quality of ORIF was judged against set radiographic criteria in order to understand the effect of sub-optimal ORIF technique., Results: No significant clinical difference was found between EHA and ORIF in mean OES (42.5 vs 39.6, p  = 0.28), mean VAS (0.5 vs 1.7, p   =  0.08) or mean flexion-extension arc (123° vs 112°, p   =  0.12). There were significantly more complications associated with ORIF compared to EHA (39% vs 6%, p  = 0.04). ORIF executed with satisfactory fixation technique had a comparable complication rate compared to EHA (17% vs 6%, p  = 0.6). Two ORIF patients required revision to Total Elbow Arthroplasty (TEA). None of the EHA patients required revision surgery., Conclusion: This study demonstrated similar short-term functional outcomes between EHA and ORIF for the treatment of multi-fragmentary intra-articular distal humeral fractures in patients >60 years of age. Early complications and re-operations were higher in the ORIF group, although this could be related to improper ORIF technique and patient selection., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Background: Preoperative CT-based planning is established in shoulder arthroplasty surgery. Automated planning software has become available to assist the surgeon and may increase reliability and efficiency. This study aims to evaluate the reliability of an automated 3-dimensional (3D) planning software package (Blueprint™ v2.1.5, Wright Medical Ltd) in the assessment of the arthritic shoulder against manual multiplanar measurement (MM)., Methods: 74 CT studies acquired for preoperative shoulder arthroplasty planning were reviewed on two occasions by four different evaluators, taking manual measurement (MM) of glenoid version and inclination adjusted with multiplanar reformation and adhering to modified Freidman and Maurier methods. 15 scans were not processed by Blueprint due to incompatible scanning protocols or severe scapular dysmorphia. 59 Blueprint measures were compared with the manual data., Results: Version : Intra-observer reliability of glenoid version MM was excellent (mean ICC 0.92). Inter-observer reliability between all four readers was good (ICC 0.89). A Bland-Altman analysis of Blueprint versus MM for version measurements demonstrated a mean pair difference of -5.77 (95% CI -7.25 to 4.29). Inclination : Intra-rater and inter-rater reliabilities were good (ICC 0.85 and 0.80 respectively). Blueprint and MM values for inclination followed a more convergent pattern than for version. Bland-Altman analysis for inclination did not show substantial bias, with a mean pair difference of 1.4 (95% CI -0.1 to 2.9)., Conclusion: Manual preoperative planning for shoulder arthroplasty is time consuming and requires experience. Automated 3D planning offers a consistent tool to assist the surgeon, notwithstanding intra-operative anatomical and technical variation, and margin of error. Surgeons should as ever be mindful of the specifics of a given automated program and our data quantified a bias for retroversion which may be important for measures close to the thresholds for augmentation or customised implants., Competing Interests: None., (© 2022 Professor P K Surendran Memorial Education Foundation. Published by Elsevier B.V. All rights reserved.)

Aims: The conventionally described mechanism of distal biceps tendon rupture (DBTR) is of a 'considerable extension force suddenly applied to a resisting, actively flexed forearm'. This has been commonly paraphrased as an 'eccentric contracture to a flexed elbow'. Both definitions have been frequently used in the literature with little objective analysis or citation. The aim of the present study was to use video footage of real time distal biceps ruptures to revisit and objectively define the mechanism of injury., Methods: An online search identified 61 videos reporting a DBTR. Videos were independently reviewed by three surgeons to assess forearm rotation, elbow flexion, shoulder position, and type of muscle contraction being exerted at the time of rupture. Prospective data on mechanism of injury and arm position was also collected concurrently for 22 consecutive patients diagnosed with an acute DBTR in order to corroborate the video analysis., Results: Four videos were excluded, leaving 57 for final analysis. Mechanisms of injury included deadlift, bicep curls, calisthenics, arm wrestling, heavy lifting, and boxing. In all, 98% of ruptures occurred with the arm in supination and 89% occurred at 0° to 10° of elbow flexion. Regarding muscle activity, 88% occurred during isometric contraction, 7% during eccentric contraction, and 5% during concentric contraction. Interobserver correlation scores were calculated as 0.66 to 0.89 using the free-marginal Fleiss Kappa tool. The prospectively collected patient data was consistent with the video analysis, with 82% of injuries occurring in supination and 95% in relative elbow extension., Conclusion: Contrary to the classically described injury mechanism, in this study the usual arm position during DBTR was forearm supination and elbow extension, and the muscle contraction was typically isometric. This was demonstrated for both video analysis and 'real' patients across a range of activities leading to rupture.Cite this article: Bone Jt Open  2022;3(10):826-831.

Complex regional pain syndrome (CRPS) is a debilitating painful condition of a distal extremity that can develop after tissue damage. CRPS is thought to be a multimechanism syndrome and ideally the most prominent mechanism(s) should be targeted by drugs in an individually tailored manner. This review gives an overview of the action and evidence of current and future pharmacotherapeutic options for CRPS. The available options are grouped in four categories by their therapeutic actions on the CRPS mechanisms, i.e. inflammation, central sensitisation, vasomotor disturbances and motor disturbances. More knowledge about the underlying mechanisms of CRPS helps to specifically target important CRPS mechanisms. In the future, objective biomarkers could potentially aid in selecting appropriate mechanism-based drugs in order to increase the effectiveness of CRPS treatment. Using this approach, current and future pharmacotherapeutic options for CRPS should be studied in multicentre trials to prove their efficacy. The ultimate goal is to shift the symptom-based selection of therapy into a mechanism-based selection of therapy in CRPS., (© 2022. The Author(s).)

Objective: The objective of this study was to assess the effectiveness of a low-dose intravenous S-ketamine treatment on refractory pain in patients with Complex Regional Pain Syndrome (CRPS)., Methods: In this retrospective study, patients with CRPS who received intravenous S-ketamine from March 2010 to April 2019 were included. According to our inpatient protocol, S-ketamine dose was increased until pain reduction was achieved or side effects were observed. Maximum dose was 14 mg/h and treatment duration was 7 days. Primary outcome parameters were pain scores (Numeric Rating Scale) at baseline (T0), end of infusion (T1), and approximately 4 weeks postinfusion (T2). Patients were categorized as responder/nonresponder at T1 and T2. Patients were considered a responder in case there was pain score reduction of greater than or equal to 2 points or if treatment was reported as successful., Results: Forty-eight patients were included. Mean disease duration was 5 years (interquartile range [IQR] = 6 years). Median pain score significantly decreased from 8 (IQR = 2) at T0 to 6 (IQR = 4) at T1 (p < 0.001). At T1, 62% of the patients were responders. At T2, 48% of the patients remained a responder. A significant proportion of the responders at T1 turned into nonresponders at T2 (p = 0.03)., Conclusion: In a group of patients with CRPS with refractory pain, low-dose intravenous S-ketamine treatment resulted in effective pain relief during infusion. Although a significant proportion of initial responders became nonresponders at follow-up, half of the patients were still a responder at ~ 4 weeks postinfusion. Further research is needed to investigate mechanisms responsible for pain relief by S-ketamine infusions and to ascertain possible predictors of response to the treatment., (© 2021 The Authors. Pain Practice published by Wiley Periodicals LLC on behalf of World Institute of Pain.)

Traditional bolus vaccine administration leads to rapid clearance of vaccine from lymphoid tissue. However, there is increasing evidence suggesting that the kinetics of antigen delivery can impact immune responses to vaccines, particularly when tailored to mimic natural infections. Here, we present the specific enhancements sustained release immunization confers to seasonal influenza vaccine, including the magnitude, durability, and breadth of humoral responses. To achieve sustained vaccine delivery kinetics, we have developed a microneedle array patch (MIMIX), with silk fibroin-formulated vaccine tips designed to embed in the dermis after a short application to the skin and release antigen over 1-2 weeks, mimicking the time course of a natural influenza infection. In a preclinical murine model, a single influenza vaccine administration via MIMIX led to faster seroconversion, response-equivalence to prime-boost bolus immunization, higher HAI titers against drifted influenza strains, and improved protective efficacy upon lethal influenza challenge when compared with intramuscular injection. These results highlight infection mimicry, achieved through sustained release silk microneedles, as a powerful approach to improve existing seasonal influenza vaccines, while also suggesting the broader potential of this platform technology to enable more efficacious next-generation vaccines and vaccine combinations., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Vaxess Technologies is developing MIMIX-Flu for commercial use. K.M.K., J.A.K., M.D., and N.W.H. are current employees of Vaxess Technologies. J.A.S., A.V.B., Y.Z., M.D., J.A.K., and K.M.K. are inventors on patent applications related to this work. K.M.K. is a founder/shareholder of Vaxess Technologies., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: Ketamine is used to treat chronic refractory pain. However, there are no scientific guidelines for ketamine use in the Netherlands. The aim of this survey was to provide an overview of the use of ketamine for chronic pain in the Netherlands., Methods: All pain clinics in the Netherlands were contacted. A digital survey, available from June 2019 to January 2020, was sent to 68 pain clinics. The survey was completed by one pain physician as a representative of the entire pain department. The survey included questions about ketamine treatment indications, administration, dose, duration, treatment repetition and the inpatient or outpatient setting., Results: The survey was completed by 51 pain clinics (75.0%). Thirty-one clinics used ketamine for chronic pain treatment. The most common indication was Complex Regional Pain Syndrome (83.9%). Pain clinics administered ketamine via intravenous infusions (96.8%), iontophoresis (61.3%), subcutaneous (3.2%) or oral administration (3.2%). Intravenous ketamine treatment was offered in an inpatient setting in 14 pain clinics, in both an inpatient and outpatient setting in 11 pain clinics and in six pain clinics in an outpatient setting. In the outpatient setting, the median starting dose was 5 mg/h (IQR=17.5-5). The median maximum dose was 27.5 mg/h (IQR=100-11.9). The median infusion duration was 6 h (IQR=8-4). In the inpatient setting, the median starting dose was 5 mg/h (IQR=5-1.5) and the median maximum dose was 25 mg/h (IQR=25-14). Patients were admitted to hospital for a median of 4 days (IQR=5-1)., Conclusions: The results of this Dutch nationwide survey study show that there are heterogeneous treatment protocols with different indications, treatment setting and dosing regimen for the treatment of chronic pain with ketamine. This study encourages the formulation of a broader consensus and the development of evidence based guidelines for ketamine treatment., (© 2021 Thomas J.P. Mangnus et al., published by De Gruyter, Berlin/Boston.)

Multi-fragmentary intra-articular fractures of the distal humerus remain a challenge for both patients and surgeons. Open Reduction internal fixation remains the gold standard, however in older patients with comminuted fractures this might not be feasible. There is a growing interest in hemi-arthroplasty as a solution for these cases. However the current experience and follow-up in limited. This review article intends to describe the current concepts in elbow hemiarthroplasty in dept. we will discuss the historical use of these implants, as well as the intricacies of more modern devices. Next we will elaborate an surgical planning, approach, and technical pearls. We will lay out a rehab protocol used by the senior author, and with some considerations for the future., Competing Interests: None., (© 2021 Delhi Orthopedic Association. All rights reserved.)

Complex regional pain syndrome (CRPS) is characterized by continuous pain that is often accompanied by sensory, motor, vasomotor, sudomotor, and trophic disturbances. If left untreated, it can have a significant impact on the quality of life of patients. The diagnosis of CRPS is currently based on a set of relatively subjective clinical criteria: the New International Association for the Study of Pain clinical diagnostic criteria for CRPS. There are still no objective laboratory tests to diagnose CRPS and there is a great need for simple, objective, and easily measurable biomarkers in the diagnosis and management of this disease. In this review, we discuss the role of inflammation in the multi-mechanism pathophysiology of CRPS and highlight the application of potential biomarkers of inflammation in the diagnosis and management of this disease.

Dipyrone has analgesic, spasmolytic, and antipyretic effects and is used to treat pain. Due to a possible risk of agranulocytosis with the use of dipyrone, it has been banned in a number of countries. The most commonly used data for the use of dipyrone are related to adults. Information relating to the use of dipyrone in children is scarce. Given the potential added value of dipyrone in the treatment of pain, a review of the literature was conducted to obtain more insight into the analgesic efficacy of dipyrone in children as well as the safety of dipyrone in terms of adverse events. A literature search was done for original articles (in English, German, or Spanish language) which met the following criteria: the use of dipyrone for pain and children up to the age of 17 years old. All titles and abstracts retrieved were reviewed, independently, by two of the authors, for their suitability for inclusion. The references of the selected articles were also checked for additional relevant papers. The publications were categorized into case reports, observational studies, or randomized controlled trials. To assess the methodological quality of the studies, the Jadad score was used. In the limited available data, the analgesic efficacy of intravenous dipyrone appears similar to that of intravenous paracetamol. Evidence is lacking to support the claim that dipyrone is equivalent or even superior to Non-Steroid-Anti-Inflammatory-Drugs in pediatric pain. While the absolute risk of agranulocytosis with dipyrone in children, based on available literature, cannot be determined, case reports suggest that this risk is not negligible., (© 2017 John Wiley & Sons Ltd.)

Background: The recently reintroduced bicruciate retaining Total Knee Arthroplasty (BCR TKA) is an effort to reproduce kinematics closer to the native knee. However, there is no data on appropriate balancing with this implant. Balancing is crucial and challenging as medial and lateral polyethylene (PE) inlays are modular, which allows for placement of different thicknesses in the medial and lateral compartments. This study aimed at providing a detailed kinematic view on balancing BCR TKA., Methods: Seven fresh frozen cadaver legs were mounted in a kinematic rig that applied squatting under application of physiologic quadriceps and hamstring forces. Additionally, specimen laxity was assessed using Lachman tests and varus/valgus stress tests. Following testing on the native knee, a BCR TKA was implanted in each specimen and all trials were repeated. Using one millimeter increments, five inlay thicknesses were tested to simulate optimal balancing, symmetric under-, and overstuffing, valgus constellation, and varus constellation., Results: Overall, knee kinematics following BCR TKA seem to be very close to the native knee. The changes as introduced to tibiofemoral kinematics through over- or understuffing the polyethylene inserts are affecting the system only to a minor degree and generally lack statistical significance. Reproduction of the tibial varus via PE-Inlays did not lead to kinematics much closer to the native knee., Conclusions: The changes introduced to tibiofemoral kinematics by removal of the conforming meniscus and cartilage and replacement with a flat PE insert and femoral component are of more impact than different inlay sizes and their combinations for a BCR TKA., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose: The recently reintroduced bicruciate-retaining Total Knee Arthroplasty (BCR TKA) is an interesting approach in the quest for close replication of knee joint biomechanics and kinematics closer to the native knee. Therefore, this study aimed at providing a detailed biomechanical view on the functional resemblance of BCR TKA to the native knee joint., Methods: Seven fresh-frozen full leg cadaver specimens (76 ± 10 year) were mounted in a 6 degrees-of-freedom kinematic rig that applied a dynamic squatting motion knee flexion. Two motion patterns were performed pre- and post-implantation of a fixed bearing BCR TKA: passive flexion-extension and squatting while an infrared camera system tracked the location of reflective markers attached to the tibia and femur. Additionally, specimen laxity was assessed using Lachman tests and varus/valgus stress tests in triplicate., Results: Overall, differences in tibiofemoral kinematics between native knee and BCR TKA were small. Some minor differences appeared under the load of a squat: less internal tibial rotation and some minor paradoxical anterior translation of the medial femoral condyle during mid-flexion. BCR TKA may slightly elevate the joint line. Knee laxity as measured by the Lachman and varus/valgus tests was not significantly influenced by BCR TKA implantation., Conclusion: As both cruciate ligaments are preserved with BCR TKA the unloaded knee closely resembles native knee kinematics including preserving the rollback mechanism. The loss of the conforming anatomy of menisci and tibial cartilage and replacement via a relatively flat polyethylene inlay may account for the loss of tibial internal rotation and the slight paradoxical AP motion of the medial femoral condyle with BCR TKA. This phenomenon reproduces findings made earlier with fixed bearing unicondylar knee arthroplasty.

The immune system has long been thought to be involved in the pathophysiology of complex regional pain syndrome (CRPS). However, not much is known about the role of the immune system and specifically T-cells in the onset and maintenance of this disease. In this study, we aimed to evaluate T-cell activity in CRPS by comparing blood soluble interleukin-2 receptor (sIL-2R) levels between CRPS patients and healthy controls. CRPS patients had statistically significant elevated levels of sIL-2R as compared to healthy controls (median sIL-2R levels: 4151 pg/ml (Q3 - Q1 = 5731 pg/ml - 3546 pg/ml) versus 1907 pg/ml (Q3 - Q1: 2206 pg/ml - 1374 pg/ml), p < 0.001, resp.). Furthermore, sIL-2R level seems to be a good discriminator between CRPS patients and healthy controls with a high sensitivity (90%) and specificity (89.5%). Our finding indicates increased T-cell activity in patients with CRPS. This finding is of considerable relevance as it could point towards a T-cell-mediated inflammatory process in this disease. This could pave the way for new anti-inflammatory therapies in the treatment of CRPS. Furthermore, sIL-2R could be a promising new marker for determining inflammatory disease activity in CRPS.