Pulmonary Sarcoid-like Granulomatosis after Multiple Vaccinations of a Long-term Surviving Patient with Metastatic Melanoma.

Autoimmune side effects are frequent in patients with cancer treated with immune checkpoint-targeting antibodies, but are rare with cancer vaccines. Here, we present a case report on a patient with metastatic melanoma who developed pulmonary sarcoid-like granulomatosis following repetitive vaccinations with peptides and CpG. Despite multiple metastases, including one lesion in the brain, the patient is alive and well more than 13 years after the diagnosis of metastatic disease. The strongly activated tumor-specific CD8(+) T cells showed robust long-term memory and effector functions. It is possible that long-term survival and adverse autoimmune events may become more common for vaccines inducing robust anticancer immune responses as were present in this patient. Cancer Immunol Res; 2(12); 1148-53. ©2014 AACR.

Hospital volume and patient outcomes in pulmonary embolism.

BACKGROUND: In numerous high-risk medical and surgical conditions, a greater volume of patients undergoing treatment in a given setting or facility is associated with better survival. For patients with pulmonary embolism, the relation between the number of patients treated in a hospital (volume) and patient outcome is unknown. METHODS: We studied discharge records from 186 acute care hospitals in Pennsylvania for a total of 15 531 patients for whom the primary diagnosis was pulmonary embolism. The study outcomes were all-cause mortality in hospital and within 30 days after presentation for pulmonary embolism and the length of hospital stay. We used logistic models to study the association between hospital volume and 30-day mortality and discrete survival models to study the association between in-hospital mortality and time to hospital discharge. RESULTS: The median annual hospital volume for pulmonary embolism was 20 patients (interquartile range 10-42). Overall in-hospital mortality was 6.0%, whereas 30-day mortality was 9.3%. In multivariable analysis, very-high-volume hospitals (> or = 42 cases per year) had a significantly lower odds of in-hospital death (odds ratio [OR] 0.71, 95% confidence interval [CI] 0.51-0.99) and of 30-day death (OR 0.71, 95% CI 0.54-0.92) than very-low-volume hospitals (< 10 cases per year). Although patients in the very-high-volume hospitals had a slightly longer length of stay than those in the very-low-volume hospitals (mean difference 0.7 days), there was no association between volume and length of stay. INTERPRETATION: In hospitals with a high volume of cases, pulmonary embolism was associated with lower short-term mortality. Further research is required to determine the causes of the relation between volume and outcome for patients with pulmonary embolism.

Phénotype de la trisomie 9q distale chez un enfant présentant un chromosome surnuméraire remanié [t(X;9)]. [Distal 9q trisomy phenotype in a patient with a supernumerary rearranged chromosome [t(X:9)] (author's transl).]

A child with clinical features associated a trisomy for the distal part of 9q was shown to have the following abnormal chromosome complement : 47,XY,+t)X;9) (Xpter yields Xq24:9q31 yields 9qter), inv 9(p11q13), var 14 (14pQFQ34).

On-pump beating heart coronary surgery for high risk patients requiring emergency multiple coronary artery bypass grafting.

BACKGROUND: Cardiopulmonary bypass (CPB) with aortic cross-clamping and cardioplegic arrest remains the method of choice for patients requiring standard myocardial revascularization. Therefore, very high-risk patients presenting with acute coronary syndrome, unstable angina, onset of cardiac decompensation and requiring emergency multiple myocardial revascularization, can have a poor outcome. The on-pump beating heart technique can reduce the mortality and the morbidity in such a selected group of patients and this report describes our clinical experience. METHODS: Out of 290 patients operated for CABG from January 2005 to January 2006, 25 (8.6%) selected high-risk patients suffering from life threatening coronary syndrome (mean age 69 +/- 7 years) and requiring emergency multiple myocardial revascularization, underwent on-pump beating heart surgery. The mean pre-operative left ventricle ejection fraction (LVEF) was 27 +/- 8%. The majority of them (88%) suffered of tri-vessel coronary disease and 6 (24%) had a left main stump disease. Nine patients (35%) were on severe cardiac failure and seven among them (28%) received a pre-operative intra-aortic balloon pump. The pre-operative EuroScore rate was equal or above 8 in 18 patients (73%). RESULTS: All patients underwent on-pump-beating heart coronary revascularization. The mean number of graft/patient was 2.9 +/- 0.6 and the internal mammary artery was used in 23 patients (92%). The mean CPB time was 84 +/- 19 minutes. Two patients died during the recovery stay in the intensive care unit, and there were no postoperative myocardial infarctions between the survivors. Eight patients suffered of transitorily renal failure and 1 patient developed a sternal wound infection. The mean hospital stay was 12 +/- 7 days. The follow-up was complete for all 23 patients survived at surgery and the mean follow-up time was 14 +/- 5 months. One patient died during the follow-up for cardiac arrest and 2 patients required an implantable cardiac defibrillator. One year after surgery they all had a standard trans-thoracic echocardiogram showing a mean LVEF rate of 36 +/- 11.8%. CONCLUSION: Standard on-pump arrested heart coronary surgery has higher mortality and morbidity in emergencies. The on-pump beating heart myocardial revascularization seems to be a valid alternative for the restricted and selected cohort of patients suffering from life threatening coronary syndrome and requiring multiple emergency CABG.

Acute imaging does not improve ASTRAL score's accuracy despite having a prognostic value.

BACKGROUND: The ASTRAL score was recently shown to reliably predict three-month functional outcome in patients with acute ischemic stroke. AIM: The study aims to investigate whether information from multimodal imaging increases ASTRAL score's accuracy. METHODS: All patients registered in the ASTRAL registry until March 2011 were included. In multivariate logistic-regression analyses, we added covariates derived from parenchymal, vascular, and perfusion imaging to the 6-parameter model of the ASTRAL score. If a specific imaging covariate remained an independent predictor of three-month modified Rankin score > 2, the area-under-the-curve (AUC) of this new model was calculated and compared with ASTRAL score's AUC. We also performed similar logistic regression analyses in arbitrarily chosen patient subgroups. RESULTS: When added to the ASTRAL score, the following covariates on admission computed tomography/magnetic resonance imaging-based multimodal imaging were not significant predictors of outcome: any stroke-related acute lesion, any nonstroke-related lesions, chronic/subacute stroke, leukoaraiosis, significant arterial pathology in ischemic territory on computed tomography angiography/magnetic resonance angiography/Doppler, significant intracranial arterial pathology in ischemic territory, and focal hypoperfusion on perfusion-computed tomography. The Alberta Stroke Program Early CT score on plain imaging and any significant extracranial arterial pathology on computed tomography angiography/magnetic resonance angiography/Doppler were independent predictors of outcome (odds ratio: 0·93, 95% CI: 0·87-0·99 and odds ratio: 1·49, 95% CI: 1·08-2·05, respectively) but did not increase ASTRAL score's AUC (0·849 vs. 0·850, and 0·8563 vs. 0·8564, respectively). In exploratory analyses in subgroups of different prognosis, age or stroke severity, no covariate was found to increase ASTRAL score's AUC, either. CONCLUSIONS: The addition of information derived from multimodal imaging does not increase ASTRAL score's accuracy to predict functional outcome despite having an independent prognostic value. More selected radiological parameters applied in specific subgroups of stroke patients may add prognostic value of multimodal imaging.

Fièvre, adénopathie: une situation clinique de toxoplasmose aiguë chez une patiente immunocompétente [Fever and lymphadenopathy: acute toxoplasmosis in an immunocompetent patient].

Toxoplasmosis is an infectious disease caused by the intracellular parasite Toxoplasma gondii. In Switzerland about a third of the population has antibodies against this pathogen and has thus already been in contact with the parasite or has contracted the disease. Immunocompetent patients are usually asymptomatic (80-90%) during primary infection. The most common symptom is neck or occipital lymphadenopathy. Serology is the diagnostic gold standard in immunocompetent individuals. The presence of IgM antibodies is however not sufficient to make a definite diagnosis of acute toxoplasmosis. Distinction between acute and chronic toxoplasmosis requires additional serological tests (IgG avidity test). If required, the most used and probably most effective treatment is the combination of pyrimethamine and sulfadiazine, with folinic acid.

Gérer un semainier a plusieurs chez un patient bénéficiaire de soins a domicile [Interprofessional pill box management in an ambulatory care setting].

Complex multimorbid patients are now more common in ambulatory care and the management of their medication more frequently needs interprofessional collaboration. This qualitative study explored health professional's main challenges when introducing, preparing and sharing the use of a pill box for a patient. Another objective of this study was to explore options for improving care in these situations.

Immunological and clinical consequences of treating a patient with natalizumab.

BACKGROUND: Long-term therapy with natalizumab increases the risk of progressive multifocal leukoencephalopathy (PML). OBJECTIVES: We present a patient study through therapy, the diagnosis of PML (after 29 infusions), plasma exchange (PE) and development of immune reconstitution inflammatory syndrome (IRIS). METHODS: Routine diagnostics, magnetic resonance imaging (MRI), immunological status (flow cytometry, T-cell migration assays and T-cell repertoire analysis), and brain biopsy with immunohistological analysis. RESULTS: CD49d decreased after 12 months of treatment. At PML diagnosis, CD49d expression and migratory capacity of T cells was low and peripheral T-cell receptor (TCR) complexity showed severe perturbations. The distribution of peripheral monocytes changed from CCR5+ to CCR7+. After PE some changes reverted: CD49d increased and overshot earliest levels, migratory capacities of T cells recovered and peripheral TCR complexity increased. With no clinical, routine laboratory or cerebrospinal fluid (CSF) changes, MRI 2 months after PE demonstrated progressive lesion development. Brain histopathology confirmed the presence of infiltrates indicative of IRIS without clinical signs, immunologically accompanied by CCR7/CCR5 recovery of peripheral monocytes. CONCLUSION: Natalizumab-associated immunological changes accompanying PML were reversible after PE; IRIS can occur very late, remain asymptomatic and be elusive to CSF analysis. Our study may provide insights into the changes under treatment with natalizumab associated with JC virus control.

Pharmacokinetic fluvoxamine-clomipramine interaction with favorable therapeutic consequences in therapy-resistant depressive patient.

We describe the case of a depressive patient who was a rapid metabolizer of CYP2D6 substrates and a heavy smoker, and who did not respond to several courses of treatment with antidepressants, as a result of unusually low drug-plasma levels. During hospitalization, he did not improve after treatment with clomipramine (150-225 mg/day during three weeks), but showed a response within four days after addition of fluvoxamine (100 mg/day). Plasma levels of clomipramine and desmethylclomipramine changed from 58 ng/ml and 87 ng/ml to 223 ng/ml and 49 ng/ml respectively one week after addition of fluvoxamine. Present knowledge of the role of cytochrome P-450 isozymes, such as CYP1A2, CYP2C19, CYP2D6, and CYP3A4, in the metabolism of psychotropic drugs as well as therapeutic drug-plasma level monitoring may thus help to determine individual treatment.

Difficulties associated with out-patient management of drug abusers by general practitioners. A cross sectional survey of general practitioners with and without methadone patients in Switzerland

Résumé de l'article Contexte : En Suisse, les médecins de premier recours traitent la plupart des patients dépendants aux opiacés méthadone en tant que traitement de substitution. Méthode : Nous avons étudié les difficultés rencontrées dans la prise en charge des patients toxicodépendants en envoyant par poste un questionnaire d'enquête. Nous avons envoyé ce questionnaire à tous les médecins de premier recours de Suisse Romande prescrivant de la méthadone (556 médecins). Nous avons envoyé un autre questionnaire, plus court, à des médecins de premier recours du Canton de Vaud qui ne prescrivent pas de méthadone. Résultats : le taux de réponse global est de 63,3 %. La plus haute dose de méthadone donnée par les médecins de premier recours est de 120,4 mg/j (moyenne). Questionnés au sujet de l'aide qu'ils désireraient recevoir face à ces patients, les médecins de premier recours avec patients substitués par méthadone ont mentionné premièrement l'importance d'un meilleur remboursement des services prodigués. Les autres éléments demandés ont été une meilleure formation, de meilleures connaissances des pathologies psychiatriques et des groupes de discussion de cas cliniques. Les médecins sans patients sous méthadone refusent de traiter ces patients surtout pour des raisons émotionnelles et relationnelles. En conclusion : les médecins acceptant des patients sous méthadone rencontrent des difficultés relationnelles et émotionnelles. Ils désirent un meilleur remboursement pour les services prodigués.

Early profiles of clinical evolution after intravenous thrombolysis in an unselected stroke population.

BACKGROUND: Intravenous recombinant tissular plasminogen activator (rt-PA) is the only approved pharmacological treatment for acute ischaemic stroke. The authors aimed to analyse potential causes of the variable effect on early course and late outcome. METHODS AND RESULTS: 136 patients (42% women, 58% men) treated with intravenous rt-PA within 3 h of stroke onset in an acute stroke unit over a 3-year period, were included. Early clinical profiles of evolution at 48 h were divided into clinical improvement (CI) (decrease >4 points in the National Institute of Health Stroke Scale (NIHSS)); clinical worsening (CW) (increase >4 points NIHSS); clinical worsening after initial improvement (CWFI) (variations of >4 points in the NIHSS). Patients with clinical stability (no NIHSS modification or <4 points) were excluded. The patients showed in 66.9% CI, 13.2% CW 8.1 % CWFI and 11.8% remained stable. Female sex, no hyperlipaemia and peripheral arterial disease were associated with CW. Male sex and smoking were associated with CI. Absence of arterial occlusion on admission (28.4%) and arterial recanalisation at 24 h were associated with CI. Main causes of clinical deterioration included symptomatic intracranial haemorrhage (sICH), persistent occlusion and cerebral oedema. 23.5% developed ICH, 6.6% of which had sICH. At 3 months, 15.5% had died. Mortality was increased in CW, mainly related to sICH and cerebral oedema. The outcome of CWFI was intermediate between CW and CI. CONCLUSIONS: Early clinical profiles of evolution in thrombolysed patients vary considerably. Even with CI, it is critical to maintain vessel permeability to avoid subsequent CW.

Quand référer aux urgences un patient présentant un trauma de l'appareil locomoteur [When should a patient with musculoskeletal trauma be referred to emergency ward?].

Standardized clinical examination can obviate the need for osteoarticular radiographs for trauma. This paper summarizes a number of decision rules that allow clinical exclusion of significant fracture of the cervical spine, elbow, knee or ankle, making radiographs unnecessary. These criteria were all derived from large cohort studies (Nexus, Ottawa, CCS, etc..., and have been prospectively validated. The rigorous use of these criteria in daily practice improves treatment times and costs with no adverse effect on treatment quality.