The appropriate use of neurostimulation: avoidance and treatment of complications of neurostimulation therapies for the treatment of chronic pain.

INTRODUCTION: The International Neuromodulation Society (INS) has determined that there is a need for guidance regarding safety and risk reduction for implantable neurostimulation devices. The INS convened an international committee of experts in the field to explore the evidence and clinical experience regarding safety, risks, and steps to risk reduction to improve outcomes. METHODS: The Neuromodulation Appropriateness Consensus Committee (NACC) reviewed the world literature in English by searching MEDLINE, PubMed, and Google Scholar to evaluate the evidence for ways to reduce risks of neurostimulation therapies. This evidence, obtained from the relevant literature, and clinical experience obtained from the convened consensus panel were used to make final recommendations on improving safety and reducing risks. RESULTS: The NACC determined that the ability to reduce risk associated with the use of neurostimulation devices is a valuable goal and possible with best practice. The NACC has recommended several practice modifications that will lead to improved care. The NACC also sets out the minimum training standards necessary to become an implanting physician. CONCLUSIONS: The NACC has identified the possibility of improving patient care and safety through practice modification. We recommend that all implanting physicians review this guidance and consider adapting their practice accordingly.

Acute Complications of Crohn's Disease: Comparison of Multidetector-Row Computed Tomographic Enterography with Magnetic Resonance Enterography.

Objective: To compare multidetector-row computed tomographic (MDCT) enterography with magnetic resonance (MR) enterography performed upon acute exacerbation of Crohn's disease. Subjects and Methods: Fifty-seven patients (mean age 33.5) with proven Crohn's disease and symptoms suggesting acute exacerbation were prospectively included. After oral administration of 1-2 liters of 5% methylcellulose, MDCT and MR enterography were performed on each patient (mean delay <24 h). Three radiologists blindly and independently evaluated each examination for technical quality and in terms of 8 pathological features of Crohn's disease. Observers' agreement, sensitivity and specificity resulted from comparison with the reference standard [surgery (n = 24), endoscopy (n = 17) and long-term follow-up (n = 16)]. Results: MDCT enterography demonstrated fewer artifacts than MR enterography (p < 0.0001). In 48 MDCT/MR enterography examinations, active disease was demonstrated: abscesses (n = 11), fistulas (n = 13), stenoses (n = 23) and/or intestinal inflammation (n = 38). Observers' agreement (range 0.56-0.87) was not significantly different between MDCT and MR enterography, neither in terms of sensitivity (range 58-95%) nor specificity (range 67-100%) for each of the 8 pathological features. Conclusion: Statistically, MR enterography is of similar diagnostic value as MDCT enterography for acute complications of Crohn's disease. Since the typical Crohn's disease patient is young and will very likely undergo life-long imaging, and given concerns about radiation exposure with MDCT, MR enterography should be the preferred modality.

Vascularite rhumatoïde et autres complications systémiques: aspects diagnostique et thérapeutique [Diagnosis and treatment of rheumatoid vasculitis and other systemic complications of rheumatoid arthritis]

Rheumatoid arthritis is a systemic disease that can potentially affect any organ. If the articular manifestations are central to the disease; skin, ophthalmic, neurological, cardiac, pulmonary as well as renal manifestations are well recognized, the latter particularly in the context of a secondary amyloidosis. Although incidence of extraarticular manifestations appears to decrease, likely a result from our more aggressive and early management of rheumatoid arthritis, their consequences remain severe in terms of morbidity and mortality, and their treatments complicated. The new biological therapies seem to be a promising alternative to current therapies, such as cyclophosphamide and high dose prednisone, even if evidences are still limited.

Complications of Valve Lung Volume Reduction in a Case of Previous Pleurodesis.

Lung volume reduction with valves is increasingly used to treat selected patients with severe emphysema. The indications for this procedure have been previously described; however, its contraindications have not yet been conclusively established. This case highlights the potentially severe complications of endobronchial one-way valve placement in the setting of a previous pleurodesis.

Retrospective analysis of complications of immunosuppressive therapies (steroidsand immunosuppressive therapies) in pediatric uveitis

Purpose¦The purpose of this study is to analyze the incidence rate of side effects occurring during systemic therapy (corticosteroids, methotrexate, azathioprine, cyclosporine A or biologic agents) of auto-immune uveitis.¦Material and methods¦Retrospective study including 23 / 71 patients aged between 0-16 years old presenting with a chronic non-infectious uveitis. All children were treated in the Jules-Gonin Eye Hospital and paediatric rheumatology unit of the CHUV (Centre Hospitalier Universitaire Vaudois) between January 2000 and December 31st 2010. Side effects were reported as minor (without subsequent change in systemic medication), moderate (associated with a change in systemic dosage or class of immunosuppressive therapy or in the presence of Cushingoid face or weight gain) or severe (hospitalization or life threatening).¦Results¦52% of boys and 48% of girls are present in the cohort with a mean age at the first visit of 8.1 years (1.7-15.6). Intermediate uveitis consisted of the commonest aetiology with 8 patients (35%), juvenile idiopathic arthritis (JIA) in 7 (30%), Behçet's disease in 3 (13%) and others in 5 (22%). The overall length of therapy was longer for prednisone (26.6 ± 5.4 patient / year), but was similar between methotrexate (22.1 ± 5.4 patient / year) and azathioprine (15.2 patient / year). Moderate side effects were respectively 64% for corticosteroids therapy, 54% with methotrexate and 14% with azathioprine. One severe and one moderate side effect were observed with anti-TNFα respectively stage III anaphylactic shock and pain during injection associated with a redness of the site of injection and limping after the injection.¦Discussion¦Immunomodulating agents allow a rapid decrease in corticosteroid therapy, but one severe side effect was observed with anti-TNFa agents. These agents are considered in most countries as third line therapeutic agents.

Les complications de la cirrhose hépatique: varices oesophagiennes, ascite et carcinome hépato-cellulaire [Complications of liver cirrhosis: oesophageal varices, ascites and hepato-cellular carcinoma]

The principal treatment for bleeding oesophageal varices is endoscopic ligation. Non-cardioselective beta-blockers are the gold-standard of primary prophylaxis. The principal treatment for ascites is a salt-free diet and diuretics, mainly spironolactone, if necessary associated with a loop diuretic. In refractory ascites, paracentesis or installation of a transjugular intrahepatic portosystemic shunt (TIPS) are two possible treatment options. Cirrhosis patients are at higher risk of developing hepato-cellular carcinoma. Surgery is only possible in a small number of cases. Percutaneous destruction techniques have nearly the same survival rate as that obtained by surgery and should be proposed to patients where surgery is not an option.

Safety of artemether-lumefantrine exposure in first trimester of pregnancy: an observational cohort.

BACKGROUND: There is limited data available regarding safety profile of artemisinins in early pregnancy. They are, therefore, not recommended by WHO as a first-line treatment for malaria in first trimester due to associated embryo-foetal toxicity in animal studies. The study assessed birth outcome among pregnant women inadvertently exposed to artemether-lumefantrine (AL) during first trimester in comparison to those of women exposed to other anti-malarial drugs or no drug at all during the same period of pregnancy. METHODS: Pregnant women with gestational age <20 weeks were recruited from Maternal Health clinics or from monthly house visits (demographic surveillance), and followed prospectively until delivery. RESULTS: 2167 pregnant women were recruited and 1783 (82.3%) completed the study until delivery. 319 (17.9%) used anti-malarials in first trimester, of whom 172 (53.9%) used (AL), 78 (24.4%) quinine, 66 (20.7%) sulphadoxine-pyrimethamine (SP) and 11 (3.4%) amodiaquine. Quinine exposure in first trimester was associated with an increased risk of miscarriage/stillbirth (OR 2.5; 1.3-5.1) and premature birth (OR 2.6; 1.3-5.3) as opposed to AL with (OR 1.4; 0.8-2.5) for miscarriage/stillbirth and (OR 0.9; 0.5-1.8) for preterm birth. Congenital anomalies were identified in 4 exposure groups namely AL only (1/164[0.6%]), quinine only (1/70[1.4%]), SP (2/66[3.0%]), and non-anti-malarial exposure group (19/1464[1.3%]). CONCLUSION: Exposure to AL in first trimester was more common than to any other anti-malarial drugs. Quinine exposure was associated with adverse pregnancy outcomes which was not the case following other anti-malarial intake. Since AL and quinine were used according to their availability rather than to disease severity, it is likely that the effect observed was related to the drug and not to the disease itself. Even with this caveat, a change of policy from quinine to AL for the treatment of uncomplicated malaria during the whole pregnancy period could be already envisaged.

Characterization of a genomic signature of pregnancy identified in the breast.

The objective of this study was to comprehensively compare the genomic profiles in the breast of parous and nulliparous postmenopausal women to identify genes that permanently change their expression following pregnancy. The study was designed as a two-phase approach. In the discovery phase, we compared breast genomic profiles of 37 parous with 18 nulliparous postmenopausal women. In the validation phase, confirmation of the genomic patterns observed in the discovery phase was sought in an independent set of 30 parous and 22 nulliparous postmenopausal women. RNA was hybridized to Affymetrix HG_U133 Plus 2.0 oligonucleotide arrays containing probes to 54,675 transcripts, scanned and the images analyzed using Affymetrix GCOS software. Surrogate variable analysis, logistic regression, and significance analysis of microarrays were used to identify statistically significant differences in expression of genes. The false discovery rate (FDR) approach was used to control for multiple comparisons. We found that 208 genes (305 probe sets) were differentially expressed between parous and nulliparous women in both discovery and validation phases of the study at an FDR of 10% and with at least a 1.25-fold change. These genes are involved in regulation of transcription, centrosome organization, RNA splicing, cell-cycle control, adhesion, and differentiation. The results provide initial evidence that full-term pregnancy induces long-term genomic changes in the breast. The genomic signature of pregnancy could be used as an intermediate marker to assess potential chemopreventive interventions with hormones mimicking the effects of pregnancy for prevention of breast cancer.

EORTC topics in neurooncology: The long path from a focus on neurological complications of cancer towards molecularly defined trials and therapies in neurooncology

Over the past decade a series of trials of the EORTC Brain Tumor Group (BTG) has substantially influenced and shaped the standard-of-care of primary brain tumors. All these trials were coupled with biological research that has allowed for better understanding of the biology of these tumors. In glioblastoma, EORTC trial 26981/22981 conducted jointly with the National Cancer Institute of Canada Clinical Trials Group showed superiority of concomitant radiochemotherapy with temozolomide over radiotherapy alone. It also identified the first predictive marker for benefit from alkylating agent chemotherapy in glioblastoma, the methylation of the O6-methyl-guanyl-methly-transferase (MGMT) gene promoter. In another large randomized trial, EORTC 26951, adjuvant chemotherapy in anaplastic oligodendroglial tumors was investigated. Despite an improvement in progression-free survival this did not translate into a survival benefit. The third example of a landmark trial is the EORTC 22845 trial. This trial led by the EORTC Radiation Oncology Group forms the basis for an expectative approach to patients with low-grade glioma, as early radiotherapy indeed prolongs time to tumor progression but with no benefit in overall survival. This trial is the key reference in deciding at what time in their disease adult patients with low-grade glioma should be irradiated. Future initiatives will continue to focus on the conduct of controlled trials, rational academic drug development as well as systematic evaluation of tumor tissue including biomarker development for personalized therapy. Important lessons learned in neurooncology are to dare to ask real questions rather than merely rapidly testing new compounds, and the value of well designed trials, including the presence of controls, central pathology review, strict radiology protocols and biobanking. Structurally, the EORTC BTG has evolved into a multidisciplinary group with strong transatlantic alliances. It has contributed to the maturation of neurooncology within the oncological sciences.

Hypertension et grossesse [Hypertension in pregnancy]

Hypertension in pregnancy Hypertension in pregnancy, whether chronic or recently diagnosed, is always a matter of concern for the general practitioner or the obstetrician. Even if this situation often evolves favorably, and although a "wait and see" attitude may be preferred to an aggressive one in such cases, one should also be aware of how dramatic the outcome may also be. As a matter of fact, what is considered as one of the most frequent complications of pregnancy can run out of control, a possibility which shouldn't be dismissed. In this article, we shall discuss the various strategies for managing this disorder.

Determinants of maternal sex steroids during the first half of pregnancy.

OBJECTIVE: To examine the associations of maternal and child characteristics with early pregnancy maternal concentrations of testosterone, androstenedione, progesterone, 17-hydroxyprogesterone, and estradiol (E2). METHODS: We analyzed these hormones among 1,343 women with singleton pregnancies who donated serum samples to the Finnish Maternity Cohort from 1986 to 2006 during the first half of pregnancy (median 11 weeks). The associations of maternal and child characteristics with hormone concentrations were investigated by correlation and multivariable regression. RESULTS: Women older than age 30 years had lower androgen and E2 but higher progesterone concentrations than women younger than that age. Multiparous women had 14% lower testosterone, 11% lower androstenedione and 17-hydroxyprogesterone, 9% lower progesterone, and 16% lower E2 concentrations compared with nulliparous women (all P<.05). Smoking mothers had 11%, 18%, and 8% higher testosterone, androstenedione, and 17-hydroxyprogesterone levels, respectively, but 10% lower progesterone compared with nonsmoking women (all P<.05). E2 concentrations were 9% higher (P<.05) among women with a female fetus compared with those with a male fetus. CONCLUSION: Parity, smoking, and, to a lesser extent, maternal age and child sex are associated with sex steroid levels during the first half of a singleton pregnancy. The effects of smoking on the maternal hormonal environment and the possible long-term deleterious consequences on the fetus deserve further evaluation. LEVEL OF EVIDENCE: II.

Complications of different ventilation strategies in endoscopic laryngeal surgery: a 10-year review.

BACKGROUND: Spontaneous ventilation, mechanical controlled ventilation, apneic intermittent ventilation, and jet ventilation are commonly used during interventional suspension microlaryngoscopy. The aim of this study was to investigate specific complications of each technique, with special emphasis on transtracheal and transglottal jet ventilation. METHODS: The authors performed a retrospective single-institution analysis of a case series of 1,093 microlaryngoscopies performed in 661 patients between January 1994 and January 2004. Data were collected from two separate prospective databases. Feasibility and complications encountered with each technique of ventilation were analyzed as main outcome measures. RESULTS: During 1,093 suspension microlaryngoscopies, ventilation was supplied by mechanical controlled ventilation via small endotracheal tubes (n = 200), intermittent apneic ventilation (n = 159), transtracheal jet ventilation (n = 265), or transglottal jet ventilation (n = 469). Twenty-nine minor and 4 major complications occurred. Seventy-five percent of the patients with major events had an American Society of Anesthesiologists physical status classification of III. Five laryngospasms were observed with apneic intermittent ventilation. All other 24 complications (including 7 barotrauma) occurred during jet ventilation. Transtracheal jet ventilation was associated with a significantly higher complication rate than transglottal jet ventilation (P < 0.0001; odds ratio, 4.3 [95% confidence interval, 1.9-10.0]). All severe complications were related to barotraumas resulting from airway outflow obstruction during jet ventilation, most often laryngospasms. CONCLUSIONS: The use of a transtracheal cannula was the major independent risk factor for complications during jet ventilation for interventional microlaryngoscopy. The anesthetist's vigilance in clinically detecting and preventing outflow airway obstruction remains the best prevention of barotrauma during subglottic jet ventilation.