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Marion Voute,1 Véronique Morel,1 Gisèle Pickering1,2 1CHU Clermont-Ferrand, Plateforme d’Investigation Clinique - Centre d’Investigation Clinique, CIC Inserm 1405, Clermont–Ferrand, F-63000, France; 2Université Clermont Auvergne, Inserm 1107, Clermont-Ferrand, F-63000, FranceCorrespondence: Gisèle PickeringCHU Clermont-Ferrand, Plateforme d’Investigation Clinique - Centre d’Investigation Clinique, CIC Inserm 1405, Clermont–Ferrand, F-63000, FranceTel +33 4 73 17 84 16Fax +33 4 73 17 84 12Email gisele.pickering@uca.frAbstract: Topical lidocaine is widely used in current practice for a variety of pain conditions. This literature review shows that its limited absorption and relative lack of systemic adverse events are an attractive analgesic option for a number of vulnerable patients. Topical lidocaine has been approved by health authorities for the treatment of post-herpetic neuralgia in a number of countries, and studies present some degree of evidence of its efficacy and safety in postsurgical pain, diabetic peripheral neuropathy, carpal tunnel syndrome, chronic lower back pain and osteoarthritis. Topical lidocaine may be a great alternative alone or in addition to systemic drugs and non-pharmacological approaches for an optimized pain management and in multimodal analgesia.Keywords: lidocaine plaster, topical, local, neuropathic pain, musculoskeletal pain

Previous reports on the prognostic value of diabetes mellitus for cardiac complications after vascular surgery show divergent results, especially in regards to the role of type 2 diabetes as a cardiac risk factor, which remains unclear. The aim of this study was to assess the impact of type 2 diabetes on 30-day cardiac complications after vascular surgery. Patients undergoing elective vascular surgery between 2002 and 2011 were included in this retrospective cohort study. Previous diagnosis of type 1 and 2 diabetes and use of oral glucose-lowering medications and insulin were recorded. Patients with type 1 diabetes were excluded from the analysis. The main outcome parameter was cardiac complications, a composite of cardiovascular death, non-fatal myocardial infarction, congestive heart failure, severe arrhythmia and asymptomatic troponin release within 30 days of surgery. In multivariate analysis, corrections were made for comorbidities, demographics, medication use and surgical risk. Of 1462 patients, 329 (22.5%) patients had type 2 diabetes. Cardiac complications occurred in 155 (13.7%) patients without diabetes and in 68 (20.7%) with type 2 diabetes. In multivariate analysis, type 2 diabetes was associated with a significantly increased risk of 30-day cardiac complications (odds ratio 1.80; 95% confidence interval 1.25 to 2.60). Results were similar for type 2 diabetes patients managed with (odds ratio 1.84; 95% confidence interval 1.01 to 3.37) and without (odds ratio 1.79; 95% confidence interval 1.19 to 2.70) insulin. Type 2 diabetes is an independent risk factor for cardiac complications after vascular surgery and should be treated as such in preoperative cardiac risk stratification. [ABSTRACT FROM AUTHOR]

A response from the authors of the article "Type 2 Diabetes Mellitus, Independent of Insulin Use, Is Associated With an Increased Risk of Cardiac Complications After Vascular Surgery" published in the journal in 2013 is presented.

Background: Postprandial vascular endothelial dysfunction is an early marker of atherosclerosis. Meal protein has been reported to reduce endothelial dysfunction in adults, and the effect could be mediated by the amino acid content., Objectives: This trial aims to assess the effect of a specifically designed plant-protein blend that contains high leucine, arginine, and cysteine on postprandial endothelial function in the elderly., Methods: In a randomized, double-blind, 3-period crossover (2-wk washout), controlled trial, we compared the vascular effects of 3 high-saturated-fat high-sucrose (HFHS) meals containing either our specific plant-protein blend, or milk protein, or without added protein. The trial was conducted on 29 healthy adults aged >65 y presenting ≥2 cardiometabolic risk factors. Postprandial vascular function was evaluated at fasting, 3 h, and 5 h postprandially, using brachial flow-mediated dilation (FMD), hand microvascular reactivity (using Flowmetry Laser Doppler, FLD), and finger reactive hyperemia index (using Peripheral Arterial Tonometry, RHI). Immune cell count and gene expression in peripheral blood mononuclear cells (PBMCs) were also assessed postprandially. Data were analyzed using mixed linear models with repeated measurements on participants for meal composition and time of sampling. This trial was registered at clinicaltrials.gov as NCT04923555., Results: FMD incremental AUC value decreased after meals (time effect P < 0.01), with no significant differences between meals. RHI also decreased with time (P < 0.01). PBMC count and monocyte chemoattractant protein-1 (MCP1), IL-1β, and IL-6 expression increased after meals showing postprandial endothelial activation (P < 0.05). Overall, meal composition had no effect on any of the postprandial changes (Ps>0.10)., Conclusions: In healthy adults aged >65 y presenting cardiometabolic risk, adding protein to an HFHS challenge meal does not mitigate postprandial impairments in vascular endothelial function and inflammatory activation. Further studies are needed to explore the potential differences with younger adults., Competing Interests: Conflict of interest The authors report no conflicts of interest., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Importance: Repeated ketamine administration is common in treatment-refractory chronic pain, but ketamine analgesic and antidepressant effects are poorly understood in patients with chronic pain with depression symptoms., Objective: To determine clinical pain trajectories with repeated ketamine administrations, exploring whether ketamine dose and/or pretreatment depressive and/or anxiety symptoms may mediate pain relief., Design, Setting, and Participants: This nationwide, multicenter, prospective cohort study included patients in France with treatment-refractory chronic pain who received repeated ketamine administration, over 1 year, according to ketamine use in their pain clinic. Data were collected from July 7, 2016, through September 21, 2017. Linear mixed models for repeated data, trajectory analysis, and mediation analysis were performed from November 15 to December 31, 2022., Interventions: Ketamine administration in cumulative dose (milligrams) over 1 year., Main Outcomes and Measures: Primary outcome was mean pain intensity (0-10 on the Numerical Pain Rating Scale [NPRS]), assessed every month for 1 year by telephone, after inclusion in the hospital. Depression and anxiety (Hospital Anxiety and Depression Scale [HADS]), quality of life (12-item Short Form Health Survey [SF-12]), cumulative ketamine dose, adverse effects, and concomitant treatments were secondary outcomes., Results: A total of 329 patients (mean [SD] age, 51.4 [11.0] years; 249 women [75.7%] and 80 men [24.3%]) were enrolled. Repeated ketamine administration was associated with a decrease of NPRS (effect size = -0.52 [95% CI, -0.62 to -0.41]; P < .001) and an increase of SF-12 mental health (39.7 [10.9] to 42.2 [11.1]; P < .001) and physical health (28.5 [7.9] to 29.5 [9.2]; P = .02) dimension scores over 1 year. Adverse effects were in the normal range. There was a significant difference between patients without and with depressive symptoms in pain diminution (regression coefficient, -0.04 [95% CI, -0.06 to -0.01]; omnibus P = .002 for interaction of time × baseline depression [HADS score ≤7 or >7]). The mediation model showed that ketamine dose was not associated with pain diminution (r = 0.01; P = .61) and not correlated with depression (r = -0.06; P = .32), and that depression was associated with pain diminution (regression coefficient, 0.03 [95% CI, 0.01-0.04]; P < .001), whereas ketamine dose was not (regression coefficient, 0.00 [95% CI, -0.01 to 0.01]; P = .67). The proportion of reduction of pain mediated by baseline depression was 64.6%., Conclusions and Relevance: The findings of this cohort study on chronic refractory pain suggest that depression (and not ketamine dose or anxiety) was the mediator of the association of ketamine with pain diminution. This finding provides radically new insights on how ketamine reduces pain primarily by dampening depression. This reinforces the need for systematic holistic assessment of patients with chronic pain to diagnose severe depressive symptoms where ketamine would be a very valuable therapeutic option.

Patients suffering from fibromyalgia often report stress and pain, with both often refractory to usual drug treatment. Magnesium supplementation seems to improve fibromyalgia symptoms, but the level of evidence is still poor. This study is a randomized, controlled, double-blind trial in fibromyalgia patients that compared once a day oral magnesium 100 mg (Chronomag ® , magnesium chloride technology formula) to placebo, for 1 month. The primary endpoint was the level of stress on the DASS-42 scale, and secondary endpoints were pain, sleep, quality of life, fatigue, catastrophism, social vulnerability, and magnesium blood concentrations. After 1 month of treatment, the DASS-42 score decreased in the magnesium and placebo groups but not significantly (21.8 ± 9.6 vs. 21.6 ± 10.8, respectively, p = 0.930). Magnesium supplementation significantly reduced the mild/moderate stress subgroup (DASS-42 stress score: 22.1 ± 2.8 to 12.3 ± 7.0 in magnesium vs. 21.9 ± 11.9 to 22.9 ± 11.9 in placebo, p = 0.003). Pain severity diminished significantly ( p = 0.029) with magnesium while the other parameters were not significantly different between both groups. These findings show, for the first time, that magnesium improves mild/moderate stress and reduces the pain experience in fibromyalgia patients. This suggests that daily magnesium could be a useful treatment to improve the burden of disease of fibromyalgia patients and calls for a larger clinical trial.

Background: There is no recommendation in Europe for the use of ketamine in patients with chronic pain. The heterogeneity of practice highlights the need to seek the advice of experts in order to establish a national consensus. This Delphi survey aimed to reach a national consensus on the use of ketamine in chronic pain in Pain clinics., Methods: A collaborative four-round internet-based questionnaire was used. It was created after literature search on ketamine administration in chronic pain and included about 96 items. It discussed utility and advantages, adverse events and deleterious aspects, methods of administration, concomitant treatments and assessment of results., Results: Twenty-eight experts completed all rounds of the survey with a total of 81.3% items reaching a consensual answer. Neuropathic pain represents the first indication to use ketamine, followed, with a good to moderate utility, by other situations (fibromyalgia, complex regional pain syndrome, central neuropathic pain, peripheral neuropathic pain, nociceptive pain, sensitization, opioid withdrawal, palliative care, depression). Experts agreed on the rare occurrence of adverse events. Concerning routes of administration, intravenous infusion with doses of 0.5-0.9 mg/kg/d for 4 days of treatment is preferred. Place of care is hospital, as in- or out-patient, with a quarterly administration of ketamine. Finally, ketamine effectiveness is assessed 1 month after infusion, and experts encourage combination with non-pharmacological treatment., Conclusions: This Delphi survey established a consensus of pain specialists on the use of ketamine in refractory chronic pain, thus providing a basis for future comparative trials., Significance: This Delphi survey in chronic pain reached agreement on four main aspects: (1) Priority to treat neuropathic pain with evaluation of effectiveness at 1 month; (2) No deleterious effects in the majority of listed diseases/situations with the absence or <3% of suggested adverse events; (3) 0.5-0.9 mg/kg/d IV infusion; (4) Combination with non-pharmacological treatment., (© 2022 European Pain Federation - EFIC®.)

Abstract: Ketamine is often used in pain clinics for refractory chronic pain, but its long-term efficacy is poorly reported. The main objective was to assess the long-term effect of ketamine on pain and health variables in patients with refractory chronic pain. A prospective, multicenter, 1-year follow-up observational study (NCT03319238) was conducted in 30 French pain clinics where ketamine is commonly prescribed. This study focused on patients with 1 ketamine delivery procedure (n = 256). The primary endpoint was pain intensity (0-10 numerical pain rating scale) before and after ketamine every month for 1 year. Secondary outcomes aimed to identify pain trajectories by semiparametric mixture models and to collect adverse events. The following data were obtained for 256 patients: Pain intensity decreased significantly (6.8 ± 1.8, n = 240 at baseline vs 5.7 ± 1.8, n = 93 at 12 months; P < 0.001). The effect size of the main endpoint was 0.61 (95% confidence interval: [0.40-0.80]; P < 0.001). Three pain trajectories were identified: 16.0% of patients in "mild pain" (mostly neuropathic pain), 35.3% in "moderate pain," and 45.7% in "severe pain" (mostly fibromyalgia) trajectory. Neuropathic pain and fibromyalgia presented opposite outcomes, pain severity being associated with anxiety, depression, and a poorer quality of life. Adverse events occurred at 1 week in 108/218 [50%] patients, and this rate gradually decreased throughout the follow-up. This real-life study in chronic pain identified distinct pain trajectories and predictive variables of ketamine efficacy. It is now pivotal to further study and optimize the subtyping of patients to provide the most effective and safe ketamine treatment in this vulnerable population., (Copyright © 2021 International Association for the Study of Pain.)

The impact of psychosocial vulnerability on pain in the year following breast cancer diagnosis has been little studied. To identify a score of psychosocial vulnerability (cognitive, emotional, quality of life and precariousness parameters) as a predictor of a pain trajectory, we conducted an observational prospective study and included women with newly diagnosed breast cancer. One year follow-up with 3 visits (day of breast cancer diagnosis; 6 and 12 months) aimed to identify distinct pain-time trajectories. Baseline psychosocial vulnerability was characterized by z-score transformation, a higher score representing a more vulnerable patient. A total of 89 patients were included (59.3 ± 10.7 years). Two trajectories of pain were identified-"Transient Pain trajectory" (TP) (39/89 patients) and "Persistent Pain trajectory" (PP) (50/89). A significant difference of pain over time between trajectories (PP vs. TP at 6 months: 2.23 ± 0.23 vs. 0.27 ± 0.09, p < 0.001) was observed. Psychosocial vulnerability showed a large effect size (d, -0.82; 95% CI, -1.25 to -0.38; p < 0.001) and a higher score in "Persistent pain trajectory" (PP vs. TP: 0.12 ± 0.36 vs. -0.14 ± 0.26, p < 0.001). A predictive vulnerability marker of pain development is proposed and could be used at cancer diagnosis to orientate the care pathway of patients experiencing breast cancer.

Localized neuropathic pain symptoms are reported after knee surgery in 30% to 50% of patients. 5% lidocaine plaster (LP5) is recommended for localized neuropathic pain, but evidence in postsurgery neuropathic pain is missing. This study focuses on the effectiveness of LP5 on allodynia, hyperalgesia, and thermal stimuli in postsurgery knee localized neuropathic pain. A randomized double-blind, 2 parallel groups, controlled trial (NCT02763592) took place in 36 patients (age, 69.4 ± 7.3 years) at the Clinical Pharmacology Center, University Hospital Clermont-Ferrand, France. Patients randomly received LP5 or placebo plaster during 3 months. Neuropathic pain intensity and several parameters (dynamic mechanical allodynia, mechanical [von Frey], heat and cold detection and pain thresholds [Pathway Medoc], and size of the allodynic area were recorded at each visit [inclusion, day 7, 15, month 1, 2, and 3]). From day 7 onwards, dynamic mechanical allodynia diminished progressively of ≥ 30% over 3 months (P = 0.003) in 96% of patients (23/24) and of ≥ 50% in 83% of patients (20/24). Cold pain and maximal mechanical pain thresholds improved over 3 months (P = 0.001 and P = 0.007, respectively). This study shows for the first time the effectiveness of LP5 on dynamic mechanical allodynia, pain, pressure, and cold thresholds over 3 months in knee localized neuropathic pain. Beyond the inhibition of sodium channels by LP5, these findings suggest the involvement of cold and mechanical receptors that participate to pain chronicisation and also of the non-negligible placebo effect of the patch, items that need to be explored further and challenged in other etiologies of localized neuropathic pain.

Neuropathic pain frequently affects older people, who generally also have several comorbidities. Elderly patients are often poly-medicated, which increases the risk of drug-drug interactions. These patients, especially those with cognitive problems, may also have restricted communication skills, making pain evaluation difficult and pain treatment challenging. Clinicians and other healthcare providers need a decisional algorithm to optimize the recognition and management of neuropathic pain. We present a decisional algorithm developed by a multidisciplinary group of experts, which focuses on pain assessment and therapeutic options for the management of neuropathic pain, particularly in the elderly. The algorithm involves four main steps: (1) detection, (2) evaluation, (3) treatment, and (4) re-evaluation. The detection of neuropathic pain is an essential step in ensuring successful management. The extent of the impact of the neuropathic pain is then assessed, generally with self-report scales, except in patients with communication difficulties who can be assessed using behavioral scales. The management of neuropathic pain frequently requires combination treatments, and recommended treatments should be prescribed with caution in these elderly patients, taking into consideration their comorbidities and potential drug-drug interactions and adverse events. This algorithm can be used in the management of neuropathic pain in the elderly to ensure timely and adequate treatment by a multidisciplinary team., Competing Interests: IB is employed by Sanofi Pasteur MSD who funded editorial assistance. GP, MMa, SC, LD, PR, MMi, MV and BW have no conflicts of interest. Funding No funding was used to support the work described in this manuscript. All authors acknowledge editorial assistance from Margaret Haugh (MediCom Consult, Villeurbanne, France), funded by Sanofi Pasteur MSD.

Endoleaks are the most common problem following endovascular aneurysm repair. The importance of a type II endoleak has often been subject of discussion in scientific literature. Conflicting data on the natural history of type II endoleak have been published. There is no consensus on the threshold for treatment of type II endoleak and controversy exists about the optimal treatment modality. This paper discusses the evidence behind treating type II endoleak and investigates the need for treatment.

Objectives: To investigate gender disparities in disease-specific health status (HS), 3- and 5-year post-intervention in peripheral arterial disease (PAD) patients., Design: Cohort study., Methods: Data of 711 consecutively enrolled vascular surgery patients were collected in 11 hospitals in The Netherlands in 2004. HS was assessed with the Peripheral Artery Questionnaire (PAQ). Our sample included patients for whom it was possible to calculate a PAQ summary score at 3- and 5-year follow-up (n = 351)., Results: Women experienced worse physical health (52.1 vs. 62.0, P = 0.012), greater disability (64.5 vs. 71.1, P = 0.026), and worse overall HS (58.1 vs. 66.7, P = 0.007) at 3-year follow-up than men. At 5-year follow-up, however, male and female patients reported similar levels of HS. Mean changes in overall HS from 3- to 5-year follow-up were significantly different for men and women (-4.12 vs. 1.69, P = 0.014). In male patients, overall HS was significantly lower at 5-year follow-up compared to the 3-year follow-up (66.7 vs. 62.6, P = 0.001). In female patients, there was no significant difference (58.1 vs. 59.8, P = 0.393)., Conclusions: Men and women experience different levels of HS over time. Attention should be paid to gender disparities in postoperative PAD patients., (Copyright © 2011 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Objectives: This article describes the rationale and design of the DECREASE-XIII trial, which aims to evaluate the potential of esmolol infusion, an ultra-short-acting beta-blocker, during surgery as an add-on to chronic low-dose beta-blocker therapy to maintain perioperative haemodynamic stability during major vascular surgery., Design: A double-blind, placebo-controlled, randomised trial., Materials & Methods: A total of 260 vascular surgery patients will be randomised to esmolol or placebo as an add-on to standard medical care, including chronic low-dose beta-blockers. Esmolol is titrated to maintain a heart rate within a target window of 60-80 beats per minute for 24 h from the induction of anaesthesia. Heart rate and ischaemia are assessed by continuous 12-lead electrocardiographic monitoring for 72 h, starting 1 day prior to surgery. The primary outcome measure is duration of heart rate outside the target window during infusion of the study drug. Secondary outcome measures will be the efficacy parameters of occurrence of cardiac ischaemia, troponin T release, myocardial infarction and cardiac death within 30 days after surgery and safety parameters such as the occurrence of stroke and hypotension., Conclusions: This study will provide data on the efficacy of esmolol titration in chronic beta-blocker users for tight heart-rate control and reduction of ischaemia in patients undergoing vascular surgery as well as data on safety parameters., (Copyright © 2011 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Introduction: Cardiac arrhythmias are a major cause for morbidity and mortality in patients undergoing non-cardiac vascular surgery., Report: An implantable loop recorder (Reveal(®) XT) was used for continuous heart rhythm monitoring to detect perioperative arrhythmias in a 69-year-old man undergoing major vascular surgery for an infected aortobifemoral prosthesis. The Reveal(®) detected several episodes of asymptomatic new-onset atrial fibrillation postoperatively, associated with elevated serum levels of troponin-T and N-terminal pro-B-type natriuretic peptide NT-proBNP)., Discussion: Continuous heart rhythm monitoring with assessment of serum cardiac biomarkers may allow early identification and treatment of patients at high risk of perioperative cardiovascular complications, in particular, cardiac arrhythmias., (Copyright © 2010 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Abdominal aortic aneurysms (AAA) have a prevalence between 1.3-8.9% in men and 1.0-2.2% in women aged above 55 years. Furthermore, AAA cause 1-3% of all deaths among men aged 65-85 years in developed countries. As the disorder is invariably associated with severe atherosclerotic damage of the arterial wall, it has traditionally been regarded as a direct consequence of generalized atherosclerotic disease. In patients with occlusive aortic disease, dyslipidemia is a well established risk factor. However, in patients with aneursymatic aortic disease, the association between dyslipidemia and the development of AAA is less clear. Large clinical trials in patients with cardiac and peripheral arterial disease have shown the strong relation between dyslipidemia, statin therapy and the risk of cardiovascular disease. Importantly, the effects of statin therapy were still present irrespective of the decrease in serum cholesterol levels. These findings resulted in the discussion of potential non-lipid lowering effects of statin therapy. These ''pleiotropic effects'' compose a diversity of cellular events which have an effect on several components of the arterial wall, including: 1) endothelial cells; 2) smooth muscle cells; 3) platelets; 4) monocytes/macrophages; and 5) the process of inflammation. In the general population the role of dyslipidemia as an independent risk factor for AAA is debated. However, as patients with AAA frequently have concomitant arterial disease, statin therapy is often recommended. As a result, the non-lipid lowering effects of statins on aneurysm expansion rate are hardly studied, and most evidence comes from experimental and animal studies. In the current review article we provide an overview of all available literature on the effects of dyslipidemia, statin therapy and the risk of AAA expansion and rupture. In the first part we summarize all population-based studies that investigated the relation between hypercholesterolemia and the development of AAA. In the second part, the available literature regarding the effects of statins on aneurysm growth, expansion rate and the risk of rupture is summarized, including in vitro, animal and clinical human studies.