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SUMMARY: Myotonic dystrophy is classified as one of the myotonic syndromes although myotonia is only a minor characteristic of it. It is, in fact, also a multisystem disease with cardiac, digestive, ocular, and endocrine abnormalities. Two subgroups are currently identified with many similarities: DM1 refers to classic dystrophia myotonica (Steinert disease), while DM2, formerly called proximal myotonic myopathy has a later onset. The congenital form is present only in DM1. The genetic causes of DM1 and 2 are different but end up in a similar way of altering RNAm processing and splicing of other genes. The anesthetic risk is increased in case of DM1 type. This review summarizes current knowledge concerning the pathophysiology and anesthetic management of this disease in children and adults.

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To explain a bimodal pattern of hazard of relapse among early stage breast cancer patients identified in multiple databases, we proposed that late relapses result from steady stochastic progressions from single dormant malignant cells to avascular micrometastases and then on to growing deposits. However in order to explain early relapses, we had to postulate that something happens at about the time of surgery to provoke sudden exits from dormant phases to active growth and then to detection. Most relapses in breast cancer are in the early category. Recent data from Forget et al. suggest an unexpected mechanism. They retrospectively studied results from 327 consecutive breast cancer patients comparing various perioperative analgesics and anesthetics in one Belgian hospital and one surgeon. Patients were treated with mastectomy and conventional adjuvant therapy. Relapse hazard updated Sept 2011 are presented. A common Non-Steroidal Anti-Inflammatory Drug (NSAID) analgesic used in surgery produced far superior disease-free survival in the first 5 years after surgery. The expected prominent early relapse events in months 9-18 are reduced 5-fold. If this observation holds up to further scrutiny, it could mean that the simple use of this safe, inexpensive and effective anti-inflammatory agent at surgery might eliminate early relapses. Transient systemic inflammation accompanying surgery could facilitate angiogenesis of dormant micrometastases, proliferation of dormant single cells, and seeding of circulating cancer stem cells (perhaps in part released from bone marrow) resulting in early relapse and could have been effectively blocked by the perioperative anti-inflammatory agent.

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Growth of tumors can accelerate during the peri-operative period. Understanding the complex role of inflammation and its consequences, positive and deleterious could lead to identify inflammatory-related biomarkers and therapeutic opportunities. In the works described here, we show how the neutrophil:lymphocyte ratio can be used as a prognostic factor before breast, lung and kidney cancer surgery, and how and why the intraoperative use of a single dose of ketorolac, a non-steroidal anti-inflammatory drug, has been identified as a promising way to prevent, at least some, postoperative cancer relapses., (MED - Sciences médicales) -- UCL, 2013

BACKGROUND: Iron overload is responsible for severe morbidity and mortality in polytransfused patients. Although repeated blood transfusions are needed during the treatment of most cancers, pediatric patients are not routinely screened for subsequent iron overload. PROCEDURE: Seventy-five patients were identified as candidates for cancer treatment and enrolled prospectively in a yearly protocol including a cardiac and liver magnetic resonance imaging coupled with ferritin level measurements. Patients were divided into four groups using the intensity of treatment rating (ITR-3). RESULTS: Fifty-nine patients reached 1-year of follow-up and liver iron overload was found in up to 66% of them. Such overload correlated with the total volume of red blood cells transfused and persisted at least 2 years after the initiation of therapy. Moderate myocardial overload was also, but less frequently (14%), observed in these patients. CONCLUSIONS: Our study demonstrated that severe liver iron overload as well as moderate myocardial iron overload can be found 1 year after cancer treatment and that this overload persists overtime. The patients with higher ITR and those who have received more than a liter of blood red cells per square meter, regardless of their diagnosis or ITR, are at risk of iron overload and should be screened carefully. Pediatr Blood Cancer 2013;60:1982-1987. © 2013 Wiley Periodicals, Inc.

Chronic pain is usually underestimated in children, due to lack of knowledge and its specific signs. In addition to suffering, chronic pain causes a physical, psychological, emotional, social, and financial burden for the child and his family. Practitioners may find themselves in a situation of failure with depletion of medical resources. Some types of chronic pain are refractory to conventional systemic treatment and may require the use of regional anesthesia. Cancer pain is common in children and its medical management is sometimes insufficient. It is accessible to neuroaxial or peripheral techniques of regional anesthesia if it is limited to an area accessible to one of these techniques and no contraindications (e.g., thrombopenia) are present. Complex regional pain syndrome 1 is not rare in children and adolescents, but it often goes undiagnosed. Regional anesthesia may contribute to the treatment of complex regional pain syndrome 1, mainly in case of recurrence, because it provides rapid effective analgesia and allows rapid implementation of intensive physiotherapy. These techniques have also shown interest in phantom limb pain after limb amputation, but they remain controversial for erythromelalgia pain or chronic abdominopelvic pain. Finally, the treatment of postdural puncture headache due to cerebrospinal fluid leak can be treated by performing an epidural injection of the patient’s blood, called a blood-patch. Finally, the management of children with chronic pain should be multidisciplinary (pediatrician, physiotherapist, psychologist, surgeon, anesthesiologist) to support the child and her problem in its entirety. 2013 Published by Elsevier Masson SAS.

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Spinal microglial activation plays a major role in the development of neuropathic pain following peripheral nerve injury. We here provide evidence for an elevated expression of the microglial marker Iba-1 in the lumbar dorsal horn ipsilateral to L5 spinal nerve transection that persists for at least 14 weeks, a time at which mechanical hypersensitivity had fully resolved. Iba-1 expression was, however; significantly lower than at 4 weeks. We therefore conclude that microglia remain partly activated beyond the phase of pain hypersensitivity. Thus, the relation between microglial cells and neuropathic pain outcome is subject to change over time after nerve injury.

Il faut distinguer le retard de réveil et l’apparition de troubles neurologiques ou du comportement après une anesthésie, la phase d’agitation transitoire, ou délire du réveil, habituelle après une anesthésie à base d’agents halogénés, étant exclue. En dehors des fausses causes de retard de réveil que sont la curarisation résiduelle et la rachianesthésie totale, le retard de réveil est en général dû à un surdosage absolu ou relatif en agents anesthésiques. Pour ce qui concerne les troubles neurologiques et les troubles du comportement postopératoires, il est utile de distinguer les situations à risque, les patients à risque, l’iatrogénicité et les incidents imprévisibles tels que la maladie métabolique ou la tumeur cérébrale inconnue ou la réponse idiosyncrasique à un médicament.

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To explain a bimodal relapse hazard among early stage breast cancer patients treated by mastectomy we postulated that relapses within 4 years of surgery resulted from something that happened at about the time of surgery to provoke sudden exits from dormant phases to active growth. Relapses at 10 months appeared to be surgery-induced angiogenesis of dormant avascular micrometastases. Another relapse mode with peak about 30 months corresponded to sudden growth from a single cell. Late relapses were not synchronized to surgery. This hypothesis could explain a wide variety of breast cancer observations. We have been looking for new data that might provide more insight concerning the various relapse modes. Retrospective data reported in June 2010 study of 327 consecutive patients compared various perioperative analgesics and anesthetics in one Belgian hospital and one surgeon. Patients were treated with mastectomy and conventional adjuvant therapy. Follow-up was average 27.3 months with range 13-44 months. Updated hazard as of September 2011 for this series is now presented. NSAID ketorolac, a common analgesic used in surgery, is associated with far superior disease-free survival in the first few years after surgery. The expected prominent early relapse events are all but absent. In the 9-18 month period, there is fivefold reduction in relapses. If this observation holds up to further scrutiny, it could mean that the simple use of this safe and effective anti-inflammatory agent at surgery might eliminate most early relapses. Transient systemic inflammation accompanying surgery could be part of the metastatic tumor seeding process and could have been effectively blocked by perioperative anti-inflammatory agents. In addition, antiangiogenic properties of NSAIDs could also play a role. Triple negative breast cancer may be the ideal group with which to test perioperative ketorolac to prevent early relapses.

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Introduction Les patients se plaignent fréquemment de symptômes urinaires causés par le sondage. Dans la chirurgie avec réhabilitation rapide (Fast-Track), le retrait de la sonde urinaire en fin de procédure chirurgicale pourrait être associé à une faible morbidité, un faible risque de rétention urinaire postopératoire (RUPO), une mobilisation plus facile et un confort accru. Patients et Méthodes Avec l’accord du Comité d’Ethique, les patients programmés pour une résection colique avec réhabilitation rapide, analgésie péridurale thoracique (T6-T8) et sans indication de sondage urinaire prolongé, ont été inclus dans cette étude prospective observationnelle. La sonde urinaire a été retirée à la fin de la chirurgie. Les critères d’évaluation étaient l’incidence de RUPO, d’infections urinaires, le temps avant la première marche, la distance maximum parcourue (J1) et la satisfaction des patients.

Objectives : To review the incidence of cancer mortality after surgery for colorectal cancer in the way to investigate the possible impact of epidural analgesia, sufentanil and NSAIDs.

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Adult mesenchymal stem cells (MSCs) exhibit neuroprotective properties when introduced into the degenerating central nervous system through different putative mechanisms including secretion of growth factors and transdifferentiation. In the present study, we injected MSCs into the cerebrospinal fluid of symptomatic hSOD1(G93A) rats, a transgenic animal model of familial amyotrophic lateral sclerosis (ALS) expressing a mutated form of the human superoxide dismutase. MSCs were found to infiltrate the nervous parenchyma and migrate substantially into the ventral gray matter, where motor neurons degenerate. Even though overall astrogliosis was not modified, MSCs differentiated massively into astrocytes at the site of degeneration. The intrathecal delivery of MSCs and the subsequent generation of healthy astrocytes at symptomatic stage decreased motor neuron loss in the lumbar spinal cord, preserving motor functions and extending the survival of hSOD1(G93A) rats. This neuroprotection was correlated with decreased inflammation, as shown by the lower proliferation of microglial cells and the reduced expressiontion of COX-2 and NOX-2. Together, these data highlight the protective capacity of adult MSC-derived astrocytes when grafted into the central nervous system and illustrate an attractive strategy to target excessive inflammation in ALS. (c) 2009 Wiley-Liss, Inc.

Childbirth ranks among the most intense experiences of acute pain. Neuraxial analgesia (i.e. epidural or combined spinal-epidural technique) is the most effective way to relieve that pain but it is contraindicated or impossible to perform for some parturients. We designed a survey of the current use of analgesic alternatives to epidural analgesia (EA) for labor pain, specifically the use of opioid patient-controlled intravenous analgesia (PCIA), in the French part of Belgium (Wallonia and Brussels). A questionnaire was mailed to the departmental chair of the hospitals with an obstetric unit, both in university and non-university centers (total of 53 centers). The questionnaire evaluated the availability of EA, the alternatives used when EA was contraindicated, the use of opioid-based PCIA for labor analgesia as well as opioid preference and doses, and finally the reasons for not using opioid PCIA. The response rate was 67.5% (36 centers). Among the responding hospitals, EA was available for 68% (range 25-85%) of labors and deliveries. When EA was not available or contraindicated, a parenteral opioid (piritramide, tramadol or pethidine) was proposed in 19% (7/36) of the centers, Entonox in 11% (4/36), a pudendal block by obstetricians in 28% (10/36) and non-pharmacologic alternatives (i.e. hypnosis, sophrology, baths and massages) in 19% (7/36). In 28% (10/36) of the centers however, no analgesic alternative was proposed. Opioid PCIA was employed in 36% (13/36) of the centers and for an additional 11% (4/36) only in case of intrauterine death. Remifentanil was the first choice (76.5% of the PCIA), followed by sufentanil (23.5%). Other opioids (piritramide, morphine, fentanyl) and ketamine were also administered by PCIA. Forty-five percents of the centers reported never using opioid PCIA by either lack of knowledge (7%), fear of maternal or fetal side effects (48%) and unability to provide a correct supervision of the parturient during PCIA use (48%), opposition from

OBJECTIVE: The Natural Killer cells (NK) are an important part of non-specific cellular-mediated and antitumoral immunity. The goal of this review is to recapitulate data published over NK activity during the perioperative period and the influence of anaesthesia, analgesia and modulation of sympathetic system. DATA SOURCES: Pubmed/Medline database. STUDY SELECTION AND DATA EXTRACTION: Keywords-based selection, without limit of date: fundamental studies, randomized controlled trials and non-randomized comparative studies. DATA SYNTHESIS: In human as in animal studies, an important correlation exists between NK activity and prognosis linked to the development of metastasis. The great depression of this cytotoxicity during the perioperative period could be able to compromise host defenses. The influence of anaesthetics and analgesics is important. The effects of the opioids, the agonists and the antagonists of the sympathetic nervous system, the prostaglandins, the NSAIDs, the ketamine, the hypnotics and the locoregional anaesthesia are systematically reviewed. The limits of experimental model presented are covered. CONCLUSION: The effects of anaesthetic/analgesic drugs and techniques, the consequences of sympathomodulation on NK activity are numerous and sometimes opposite. It is important for the anaesthesiologist to keep in mind that the long term consequences of his techniques on the patients' outcome must be clarified.

Effective management of pain remains an important indicator of the quality of care provided to neonates. Since the review of McIntosh in this journal over a decade ago, an extensive number of papers on assessment, prevention, and treatment of pain have been reported. In addition, preclinical insights into neurodevelopmental aspects of pain processing and the neuro-apoptotic effects of analgesics and sedatives were unveiled. Based on the newly collected evidence, the practice of "one-drug, one dose and one treatment fits all" became obsolete, necessitating a more individualized analgesia, based on non-pharmacological and pharmacological therapies and preventive strategies for effective management of neonatal pain. The progress made is impressive, but the current major challenge is to implement the available knowledge in clinical care. Future research should therefore focus on the evaluation of the effectiveness of non-opioid and moderately potent opioids compared to morphine and should also describe the methods to facilitate effective implementation. Finally, there is an extensive field of procedural techniques that need to be evaluated on their pain related response.

Les enfants atteints de maladies chroniques à risque vital demandent une prise en charge spécifique dont la dimension palliative est importante. Ces patients développent une importante morbidité bronchopulmonaire. Leur mortalité est fréquemment attribuée à des causes respiratoires. Ces enfants dont le diagnostic premier n=est pas respiratoire développent progressivement une pathologie respiratoire évolutive, qui comporte souvent des complications infectieuses chroniques, une insuffisance respiratoire chronique, pouvant évoluer vers l=insuffisance respiratoire aigue. De nouvelles technologies respiratoires sont maintenant disponibles : échelles de dyspnée, techniques d=aide à la toux (cough-assist ), à la mobilisation des sécrétions, ventilation non invasive nocturne, ventilation invasive sur trachéotomie avec utilisation de micro L=intégration de ces moyens de diagnostic et de traitement à la prise en charge de la pathologie respiratoire chronique de ces patients soulève des questions d=ordre éthique, concernant l=incertitude du pronostic et du temps qui reste à vivre, l=amélioration de l=espérance de vie due au traitement de l=insuffisance respiratoire, la valeur de quelques mois ou quelques années de vie d=un enfant. Nous observons que les enfants atteints de maladies chroniques à risque vital sont le plus souvent traités lorsqu=ils présentent des épisodes aigus, mais qu=ils ne bénéficient pas de traitement de fond visant à prévenir les récidives infectieuses, à ralentir l=évolution de l=insuffisance respiratoire. La prise en charge palliative de ces enfants, qui se doit d=être la plus précoce possible, devrait intégrer une réflexion stratégique, réfléchie, multidisciplinaire, incluant l=enfant et sa famille, de la pathologie respiratoire chronique dont il est et sera atteint

Recent anatomic findings, technological progress, and both in vitro and in vivo studies of the pressure generated in the cuff of endotracheal tubes and supraglottic airways should lead to modification of the way we control the pediatric upper airway

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We report a case of life-threatening intoxication and a controlled re-exposure study to dextromethorphan. A 60-year-old man developed postsurgical neuropathic cervical pain treated by hydromorphone, gabapentin, clonazepam, and amitriptyline. He received a dextromethorphan preparation for a catarrhal syndrome. Two days later, he was admitted into an emergency department in a profound coma. Thirty-six hours later, after withdrawal of all drugs, the situation normalized. A genotyping for UDP-glucuronyltransferase 1A1 and CYP2D6 was followed by a re-exposure study. During the three days, vital parameters and side effects of drugs were prospectively recorded. The second day, dextromethorphan was introduced. No significant impairment in parameters nor influence on analgesic efficacy were noted. Dextromethorphan concentrations suggest an accumulation without reaching any steady state. Somnolence was noted for plasma concentrations around 100ng/mL. The CYP2D6*4 variant leading to a poor metabolizer phenotype was founded. Moreover, this phenotype was potentially aggravated by amitriptyline intake. This study allowed the identification and the confirmation of the cause of the coma. In conclusion, it is probably wise to recommend avoiding dextromethorphan in patients taking tricyclic antidepressants or another inhibitor of CYP2D6. Drug-drug interactions are probably underdiagnosed and underreported, and drugs considered as safe may induce serious complications.

Cesarean delivery rates continue to increase, and surgery is associated with chronic pain, often co-existing with depression. Also, acute pain in the days after surgery is a strong predictor of chronic pain. Here we tested if mode of delivery or acute pain played a role in persistent pain and depression after childbirth. In this multicenter, prospective, longitudinal cohort study, 1288 women hospitalized for cesarean or vaginal delivery were enrolled. Data were obtained from patient interviews and medical record review within 36h postpartum, then via telephone interviews 8 weeks later to assess persistent pain and postpartum depressive symptoms. The impact of delivery mode on acute postpartum pain, persistent pain and depressive symptoms and their interrelationships was assessed using regression analysis with propensity adjustment. The prevalence of severe acute pain within 36h postpartum was 10.9%, while persistent pain and depression at 8 weeks postpartum were 9.8% and 11.2%, respectively. Severity of acute postpartum pain, but not mode of delivery, was independently related to the risk of persistent postpartum pain and depression. Women with severe acute postpartum pain had a 2.5-fold increased risk of persistent pain and a 3.0-fold increased risk of postpartum depression compared to those with mild postpartum pain. In summary, cesarean delivery does not increase the risk of persistent pain and postpartum depression. In contrast, the severity of the acute pain response to childbirth predicts persistent morbidity, suggesting the need to more carefully address pain treatment in the days following childbirth.

Patients with Duchenne and Becker muscular dystrophy suffer from a progressive deterioration in muscle secondary to a defect in the dystrophin gene. As such, they are susceptible to perioperative respiratory, cardiac and other complications, such as rhabdomyolysis. Inhalational anesthetic agents have been implicated as a cause of acute rhabdomyolysis that can resemble malignant hyperthermia (MH). This article reviews perioperative 'MH-like' reactions reported in muscular dystrophy patients and groups them into three categories according to clinical presentation. The etiology and underlying pathophysiological process responsible for these reactions is discussed and recommendations are proposed for the safe anesthetic management of these patients.

BACKGROUND: Intrathecal clonidine improves intraoperative anesthesia and postoperative analgesia after cesarean delivery. Clonidine also possesses antihyperalgesic properties. Hyperalgesia contributes to postoperative pain and may be associated with increased risk of chronic pain after surgery. In this study, we evaluated the postoperative antihyperalgesic effect of intrathecal clonidine after caesarean delivery. METHODS: Ninety-six parturients undergoing elective cesarean delivery were randomly assigned to receive intrathecal bupivacaine-sufentanil (BS group), bupivacaine-sufentanil-clonidine 75 microg (BSC group), or bupivacaine-clonidine 150 microg (BC group). The primary outcome was the extent and the incidence of periincisional punctate mechanical hyperalgesia as assessed by response to application of a von Frey filament at 24 and 48 h after cesarean delivery. Postoperative morphine requirements and pain scores, as well as residual pain at 1, 3, and 6 mo, were also assessed. RESULTS: The BC group had a significantly reduced area of periincisional hyperalgesia at 48 h (median, 25th-75th percentiles): 1.0 (1.0 - 3.3) cm(2) vs 9.5 (5.0-14.0) cm(2) in the BS group vs 5.0 (2.5-12.3) cm(2) in the BSC group (P = 0.02 with the BS group). The incidence of hyperalgesia at 48 h was also lower in the BC group: 16% vs 41% in the BS group vs 34% in the BSC group (P = 0.03 with BS group). Postoperative morphine consumption, pain scores, and incidence and intensity of residual pain did not differ among groups. CONCLUSIONS: Intrathecal clonidine 150 mug combined with bupivacaine had a postoperative antihyperalgesic effect expressed as a significant reduction in the extent and incidence of periincisional punctate mechanical hyperalgesia at 48 h after elective cesarean delivery compared with intrathecal bupivacaine-sufentanil and intrathecal clonidine 75 mug-bupivacaine-sufentanil.