There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

다중혈관 관상동맥 환자에서 y-문합을 이용하여 양쪽 내흉동맥만을 사용한 우회술의 조기 성적

Osteoclasts are specialized cells derived from the monocyte/macrophage haematopoietic lineage that develop and adhere to bone matrix, then secrete acid and lytic enzymes that degrade it in a specialized, extracellular compartment. Discovery of the RANK signalling pathway in the osteoclast has provided insight into the mechanisms of osteoclastogenesis and activation of bone resorption, and how hormonal signals impact bone structure and mass. Further study of this pathway is providing the molecular basis for developing therapeutics to treat osteoporosis and other diseases of bone loss.

Osteoclast differentiation and activation

Background Sipuleucel-T, an autologous active cellular immunotherapy, has shown evidence of efficacy in reducing the risk of death among men with metastatic castration-resistant prostate cancer. Methods In this double-blind, placebo-controlled, multicenter phase 3 trial, we randomly assigned 512 patients in a 2:1 ratio to receive either sipuleucel-T (341 patients) or placebo (171 patients) administered intravenously every 2 weeks, for a total of three infusions. The primary end point was overall survival, analyzed by means of a stratified Cox regression model adjusted for baseline levels of serum prostate-specific antigen (PSA) and lactate dehydrogenase. Results In the sipuleucel-T group, there was a relative reduction of 22% in the risk of death as compared with the placebo group (hazard ratio, 0.78; 95% confidence interval [CI], 0.61 to 0.98; P = 0.03). This reduction represented a 4.1-month improvement in median survival (25.8 months in the sipuleucel-T group vs. 21.7 months in the placebo group). The 36-month survival probability was 31.7% in the sipuleucel-T group versus 23.0% in the placebo group. The treatment effect was also observed with the use of an unadjusted Cox model and a log-rank test (hazard ratio, 0.77; 95% CI, 0.61 to 0.97; P = 0.02) and after adjustment for use of docetaxel after the study therapy (hazard ratio, 0.78; 95% CI, 0.62 to 0.98; P = 0.03). The time to objective disease progression was similar in the two study groups. Immune responses to the immunizing antigen were observed in patients who received sipuleucel-T. Adverse events that were more frequently reported in the sipuleucel-T group than in the placebo group included chills, fever, and headache. Conclusions The use of sipuleucel-T prolonged overall survival among men with metastatic castration-resistant prostate cancer. No effect on the time to disease progression was observed. (Funded by Dendreon; ClinicalTrials.gov number, NCT00065442.)

/pdf/sipuleucel-t-immunotherapy-for-castration-resistant-prostate-31dll2jbjc.pdf

Sipuleucel-T immunotherapy for castration-resistant prostate cancer.

admission. This proportion could already be greater in some parts of the country and may increase if referrals of cases of self-poisoning increase faster than the facilities for their assessment and management. The provision of social work and psychiatric expertise in casualty departments may be one means of preventing unnecessary medical admissions without risk to the patients. Dr Blake's and Dr Bramble's figures do not demonstrate, however, that any advantage would attach to medical teams taking over assessment from psychiatrists except that, by implication, assessments would be completed sooner by staff working on the ward full time. What the figures actually suggest is that if assessment of overdoses were left to house doctors there would be an increase in admissions to psychiatric units (by 19°U), outpatients (by 5O°'), and referrals to social services (by 140o). So for house doctors to assess overdoses would provide no economy for the psychiatric or social services. The study does not tell us what the consequences would have been for the six patients who the psychiatrists would have admitted but to whom the house doctors would have offered outpatient appointments. E J SALTER

Vitamin D deficiency.

2007 POSTER Recommendations for the prevention of aromatase inhibitor-associated bone loss in women with breast cancer

Osteoporosis is now considered as a major public health issue and a serious threat for the quality of life of elderly women. Several new compounds are currently marketed for the prevention and treatment of involutional osteoporosis in women. Therefore, it is important to offer to the practitioners pragmatic solutions to be used for the rational management of this disorder. This article is the result of a national consensus offering practical guidelines for the management of osteoporotic patients, based on the current published data.

L'ostéoporose involutive de la femme: stratégie thérapeutique. Un point de vue actualisé du Belgian Bone Club.

To the Editor: We read with interest the article from Borgen and colleagues recently published in the Journal of Bone Mineral Research (JBMR), proposing a reclassification of the sites of fractures in central and peripheral fractures because of clinical and densitometric similarities in patients who underwent either central fractures or peripheral fractures. They found that, indeed, patients with an index fracture at central sites exhibited lower BMD, lower trabecular bone score (TBS), and higher prevalence of vertebral fractures on vertebral fracture assessment (VFA) than patients with peripheral fractures. This new classification differs from the classical grouping of major osteoporotic fractures (MOFs) because MOFs do not include central sites such as the pelvis, but include a peripheral site, the wrist, and it could modify the fracture prediction strategy, which is based essentially on MOFs. MOFs are presently the main pillar of osteoporosis diagnosis and treatment: they are used as predictor of future incident fractures; in countries using the FRAX© to help decision of osteoporosis treatment, the main concern is about the absolute risk of MOFs, with a usual threshold of 20% at 10 years. In order to examine how the classification proposed by Borgen and colleagues would change the prediction power of a prevalent fracture for an incident fracture, we analyzed data of our ongoing Fracture Risk Brussels Epidemiological Enquiry (FRISBEE) cohort and compared the hazard ratio (HR) for a MOF or a new central fracture after a first incident fracture. The FRISBEE study is an ongoing prospective epidemiological study in a population-based cohort (Brussels, Belgium) of 3560 postmenopausal women aged 60 to 85 years at baseline. Patients were included between July 2007 and June 2013 and are followed annually by phone call interviews. Risk factors and fracture incidence are then collected. All fractures were validated by radiological report. Until September 2019, among our cohort, 754 first osteoporotic incident fractures were validated during follow-up. We examined the predictive power of a first fracture during follow-up on the incidence of a new fracture during amedian period of 58months (range, 0.1 to 135 months; IQR, 31 to 84 months). For our analysis, we somewhat modified and simplified the classification proposed by Borgen and colleagues. We also considered as central fractures those of the ribs, scapula, clavicles, and sternum, which belong to the trunk, and all others as peripheral (Borgen and colleagues did not have rib fractures in their cohort, did not mention sternum or scapula, and

https://asbmr.onlinelibrary.wiley.com/doi/epdf/10.1002/jbmr.3960

Postfracture risk assessment: target the centrally sited fractures first! a substudy of NoFRACT

Gabapentin (GBP) is a new antiepileptic agent with an original spectrum of activity. Its mechanism of action has not yet been fully elucidated but appears not to involve binding to GABA receptors despite being a structural analogue of GABA and is distinct from tricyclic antidepressants (TCAs). It has been shown to modulate high threshold calcium currents in brain neurons. As some other anticonvulsants, GBP has been recently proposed for the treatment of noncancer neuropathic pain like diabetic neuropathy and post herpetic neuralgia (double blind studies with placebo). We prospectively followed 20 cancer patients with advanced disease suffering from neuropathic pain. All were already treated for their pain syndrome. We started with 300 mg of GBP given orally in order to reach a dose of 900 mg on D3. All coanalgesics were stopped before entering the study. The only relevant side effect due to GBP was somnolence, otherwise time limited. GBP treatment was associated with a decrease of opioids doses in 9 patients and a decrease of VAS for pain intensity in all cases. Furthermore, the need of rescue doses decreased in all cases but 2. GBP appears to be one of the most effective drugs for the treatment of neuropathic pain. It is well tolerated and its effectiveness appears shortly after its administration. A synergistic action with opioids is suggested. Despite the small number of patients, our study suggests that GBP could be a treatment of neuropathic pain in cancer. Comparative trials should be performed with other neuropathic pain drugs including TCAs and antiepileptic drugs, especially carbamazepine.

https://www.amub.be/revue-medicale-bruxelles/download/132

La gabapentine (Neurontin) et les douleurs cancéreuses: etude pilote.

We give an overview of the available medical solutions to help a patient with refractory symptoms at the end of his life. Patient "competence" must first be evaluated and, even if their diagnosis is difficult, organic mental disorders and depression must be diagnosed and adequately treated to allow a real, personal and honest dialog. Administration of high doses of morphine is frequently used at the end of life not only to fully relieve pain but also to accelerate death, even if this is not clearly stated. This technique is not devoid of hypocrisy and high doses of morphine can have quite unpleasant side effects. Treatment withdrawal or withholding is generally not sufficient to allow a correct end of life. The arrest of ventilation, dialysis, artificial nutrition and even more hydration must often be coupled with techniques inducing unconsciousness, which makes imprecise the limits between such a "passive" ending of life and "active" euthanasia. The technique of terminal sedation, frequently based on the use of midazolam, has been more recently introduced in some palliative care units. Such a "controlled sedation" is supposed to allow a "natural" death by inducing a profound sleep. In opposition with active euthanasia, which allows a quiet and rapid death at a moment chosen by the patient himself, this technique of "sedation" has an undetermined duration, has legal implications which could be viewed as quite similar as the ones of euthanasia, and, moreover, this prolonged agony can be extremely stressful and distressing for the family. Medical-assisted suicide is allowed in The Netherlands under the same conditions as euthanasia. Death is generally obtained after a few hours but the technique is not always successful and the process of death can sometimes be prolonged and uncomfortable. This technique can nevertheless be preferred by some physicians and patients. As compared to active euthanasia, the proportion of medically-assisted suicides (1/6) is low in The Netherlands. Euthanasia is the only technique able to induce a peaceful and rapid death. The proportion of various techniques to actively induce death is probably quite similar in our country than in The Netherlands but, most of the time, these interventions occur at the very end of life when the patient is no longer able to participate in the decision process and thus occur without his explicit request. We think that, as for all medical decisions, the use of one or the other of these various techniques should be selected after a quiet and free discussion between the patient and his physician, preferably in advance and not in a situation of emergency and panic.

Jean-Jacques Body

Papers

2007 POSTER Recommendations for the prevention of aromatase inhibitor-associated bone loss in women with breast cancer

L'ostéoporose involutive de la femme: stratégie thérapeutique. Un point de vue actualisé du Belgian Bone Club.

Postfracture risk assessment: target the centrally sited fractures first! a substudy of NoFRACT

La gabapentine (Neurontin) et les douleurs cancéreuses: etude pilote.

Les interventions medicales de dernier recours : Aspects psychosociaux, medicaux, ethiques et juridiques