High-dose-rate Brachytherapy Monotherapy in Patients With Localised Prostate Cancer: Dose Modelling and Optimisation Using Computer Algorithms.

AIMS: Interstitial high-dose-rate brachytherapy (HDR-BT) is an effective therapy modality for patients with localized prostate carcinoma. The objectives of the study were to optimise the therapy regime variables using two models: response surface methodology (RSM) and artificial neural network (ANN). MATERIALS AND METHODS: Thirty-one studies with 5651 patients were included (2078 patients presented as low-risk, 3077 patients with intermediate-risk, and 496 patients with high-risk). A comparison of these therapy schedules was carried out using an effective biologically effective dose (BEDef) that was calculated assuming the number of treatment days and dose (D) per day. The modelling and optimization of therapy parameters (BEDef and risk level) in order to obtain the maximum biochemical free survival (BFS) were carried out by the RSM and ANN models. RESULTS: An optimal treatment schedule (BFS = 97%) for patients presented with low-risk biochemical recurrence would be D = 26 Gy applied in one application, 2 fractions at least 6 h apart, within an overall treatment time of 1 day (BEDef = 251 Gy) by the RSM and ANN model. For patients presented with intermediate- or high-risk an optimal treatment regime (BFS = 94% and 90%, respectively) would be D = 38 Gy applied in one application, 4 fractions at least 6 h apart, with an overall treatment time of 2 days (BEDef = 279 Gy) by the RSM and ANN models. CONCLUSIONS: The RSM and ANN models determine almost the same optimal values for the set of predicted therapy parameters that make a feasible selection of an optimal treatment regime.

Preoperative Gleason score, percent of positive prostate biopsies and PSA in predicting biochemical recurrence after radical prostatectomy.

PURPOSE: To determine the factors that can improve the prediction of biochemical recurrence after radical prostatectomy for the patients with prostate adenocarcinoma. METHODS: Our study included 182 patients with prostate adenocarcinoma who were biopsied and underwent radical surgical treatment at the Clinic of Urology, Clinical Center of Serbia, Medical Faculty in Belgrade from 1994 to 2004. Patients were prospectively followed-up and monitored for a minimum of 8 years and data were statistically processed by multivariate regression analysis. We arranged the predictors into 3 regressive models. In the first model the predictors were clinical stage of the disease, preoperative Gleason score, F/T PSA ratio and PSA. In the second model these predictors were accompanied with the number of positive biopsies and percent of positive prostate biopsies. In the third model, patient follow-up was added to the predictors. In all 3 models biochemical recurrence was considered as a dependent variable. RESULTS: On multivariate analysis, patient follow-up (p<0.0001), percent of positive prostate biopsies (p<0.0001), bioptic Gleason score (p<0.0001) and preoperative PSA (p<0.003) were significant independent predictors of biochemical recurrence. The most successful prediction of recurrence that provided accurate prognosis for 80% of the patients was obtained by the third model using the percent of positive prostate biopsies, PSA and patient follow-up. CONCLUSION: As stated in multivariate analysis, the independent predictors according to the significance are the follows: patient follow-up, percent of positive prostate biopsies, bioptic Gleason score and preoperative PSA, whereas preoperative F/T PSA ratio is dependent predictor. The number of positive biopsies and clinical stage of the disease are of no significance.

[Guidelines for management of adult sickle cell disease]. / Recommandations pratiques de prise en charge de la drépanocytose de l'adulte.

Sickle cell disease is a systemic disease that can potentially involve all organs. As the prevalence of patients with sickle cell disease increases gradually in France, every physician can be potentially involved in the care of these patients. Complications of sickle cell disease can be acute or chronic. Pain is the main symptom and should be treated quickly and aggressively. Acute chest syndrome is the leading cause of acute death and must be prevented, detected, and treated without delay. Chronic complications are one of the main concerns in adults and should be identified as early as possible in order to prevent sequels. Many organs can be involved, including the bones, kidneys, eyes, lungs... The indications for a specific treatment (blood transfusion or hydroxyurea) should be discussed. Health care should be carefully organized to allow both a regular follow-up near the living place and access to specialized departments. We present in this article the French guidelines for the sickle cell disease management in adulthood.

[What's new in autoinflammatory diseases?]. / Quoi de neuf dans les maladies auto-inflammatoires ?

PURPOSE: The concept of auto-inflammation was initially coined to define the group of mendelian disorders characterized by recurrent inflammatory symptoms. The core of this group mainly consists of hereditary recurrent fevers, which has been lately enlarged to other inflammatory mendelian disorders as well as to some sporadic diseases with a genetic component relevant to innate immunity. CURRENT KNOWLEDGE AND KEY POINTS: Cryopyrin, the product of the CIAS1/PYPPAF1/NALP3/NLRP gene, whose mutations underline some mendelian syndromes (Mückle-Wells and chronic infantile neurological cutaneous and articular (CINCA), familial cold urticaria) can now be considered as a major factor of the regulation of interleukin-1 production within the multiprotein complex called inflammasome. This discovery has lit up our view of innate immunity. FUTURE PROSPECTS AND PROJECTS: The contribution of the innate immunity mechanisms in inflammatory disorders have led to a new look to the current nosology of this vast group of diseases and to suggest a classification with two poles. The first would be defined by the predominance of auto-inflammation, whereas in the second one auto-immunity predominates.

EMG-based Real Time Facial Gesture Recognition for Stress Monitoring.

An electromyogram (EMG) signal acquisition system capable of real time classification of several facial gestures is presented. The training data consist of the facial EMG collected from 10 individuals (5 female/5 male). A custom-designed sensor interface integrated circuit (IC) consisting of an amplifier and an ADC, implemented in 65nm CMOS technology, has been used for signal acquisition [1]. It consumes 3.8nW power from a 0.3V battery. Feature extraction and classification is performed in software every 300ms to give real-time feedback to the user. Discrete wavelet transforms (DWT) are used for feature extraction in the time-frequency domain. The dimensionality of the feature vector is reduced by selecting specific wavelet decomposition levels without compromising the accuracy, which reduces the computation cost of feature extraction in embedded implementations. A support vector machine (SVM) is used for the classification. Overall, the system is capable of identifying several jaw movements such as clenching, opening the jaw and resting in real-time from a single channel EMG data, which makes the system suitable for providing biofeedback during sleeping and awake states for stress monitoring, bruxism, and several orthodontic applications such as temporomandibular joint disorder (TMJD).

Evidence for CTL-mediated selection of Tat and Rev mutants after the onset of the asymptomatic period during HIV type 1 infection.

The evolution of HIV-1 sequences over time is the result of the selection of mutant variants that have escaped from host immune responses or the outgrowth of mutants with increased viral replication, or both. We investigated the contribution of both selection processes to the overall evolution of the Tat and Rev regulatory gene sequences from four individuals, ranging in time from just prior to seroconversion to stable asymptomatic infection. After sequencing at least 15 clones per sample per gene, we analyzed the sequence evolution of the MHC-I motifs that were predicted from the MHC-I haplotypes of these patients. For each identified Tat sequence, we tested the activity of the corresponding encoded protein in a transactivation assay in vitro. Our results suggest that the evolution of the Tat and Rev sequences from these individuals can be explained by mutational escape of the MHC-I epitopes and that no mutations that replaced the original sequences in the viral population are associated with either an increase or decrease in Tat activity. CTL-mediated selection appears to be an important determinant of HIV-1 regulatory gene sequence evolution during the early stages of infection.

[Carcinoma of unknown primary site]. / Les carcinomes de primitif inconnu.

PURPOSE: Carcinoma of unknown primary site is a common clinical syndrome, accounting for 2% of cancer patients. Diagnosis is a recurrent challenge for internists. Treatment is difficult and prognosis is still poor. This review presents one synthesis of diagnosis strategies and therapeutic trials. It envisages the interest of new molecular biology methods as well as therapeutic perspectives. CURRENT KNOWLEDGE AND KEY POINTS: Pathologic examination completed with immunohistochemical tests, and, depending on cases, with electron microscopy, cytogenetics, and molecular biology is a key-point for diagnosis. Diagnosis work-up, based on histological type and on individualization of some clinical presentation, proceeds in three steps. Positron emission tomography is recommended when a curative treatment is planed, particularly in cases of isolated metastasis. Functional status analysed using the performance status and simple biologic parameters (serum lactate dehydrogenase, serum alkaline phosphatase) permit us to assess prognosis. Chemotherapy is offered for patients with a good general health status. FUTURE PROSPECTS AND PROJECTS: Further evaluation of positron emission tomography, as well as cost-benefit analyses, is warranted. Further randomised trials are necessary to determine the optimal chemotherapy regimen in good-risk patients and the interest of chemotherapy in patients with poor-risk disease. Gene expression profiling and proteomic evaluation, as well as pharmacogenomic offer new investigation fields.

[Aspergillosis in systemic diseases treated with steroids and/or immunosuppressive drugs: report of 9 cases and review of the literature]. / Aspergilloses au cours de maladies systémiques traitées par corticoïdes et/ou immunosuppresseurs: analyse de neuf cas et revue de la littérature.

This is a multicentric retrospective study of aspergillosis in patients treated by corticosteroids and/or immunosuppressive drugs for systemic diseases and a review of the literature. Nine patients, 5 men and 4 women, mean age of 62.8 years old were included among which Horton's diseases (3 cases), systemic lupus erythematosus (2), polymyositis (1), microscopic polyangiitis (1), idiopathic thrombocytopenic purpura (1), rheumatoid polyarthritis (1). Aspergillosis occurred in average 28.4 month after the diagnosis of systemic disease, and 28 months after the beginning of its treatment: corticosteroids in all cases, at a dose of 50.8 mg/day (equivalent prednisone) in average, cyclophosphamide (2 cases), methotrexate (1), intravenous immunoglobulins (1), leflunomide (1). All cases were invasive or chronic pulmonary aspergillosis located in the lungs (6 cases), or in the brain (3). Revealing symptoms were mild and non specific. Lymphopenia was severe in most cases, in average 472 lymphocytes/mm3 and 283 CD4+/mm3. The diagnosis was confirmed 20.75 days after the first symptoms in invasive aspergillosis, and 18.5 months in the chronic pulmonary cases, by cultures in 7 cases (broncho-alveolar lavage: 4; cerebral biopsy: 3), and direct microscopy examination of broncho-alveolar lavage in 2 cases. Specific serology was positive in 4 cases. Patients were treated by voriconazole (4 cases), itraconazole (2), amphotericin B (1), association of caspofungin and voriconazole (1), successive voriconazole and itraconazole (1). Six patients recovered from aspergillosis with 10.8 months of following time, 3 patients died a few days after confirmation of the diagnosis. Fifty-four cases of the literature are analysed.

[Lemierre syndrome variant: Hepatic abscesses and hepatic venous thrombosis due to Fusobacterium nucleatum septicemia]. / Un variant du syndrome de Lemierre: abcès hépatiques et thrombose veineuse sus-hépatique secondaire à une septicémie à Fusobacterium nucleatum.

INTRODUCTION: Like Fusobacterium necrophorum, Fusobacterium nucleatum is capable causing Lemierre's syndrome. Various locations of venous thrombosis have been described associated with Fusobacterium sp. septicemia. EXEGESIS: We describe a 43-year old alcoholic patient with F.nucleatum septicemia complicated with hepatic abscesses, middle hepatic venous thrombosis, osteomyelitis and infiltrative pneumonia. A pancreatic prosthesis was the only potentially identified infectious entrance. CONCLUSION: Our patient showed an alternative presentation of Lemierre's syndrome, a "digestive variant". To the best of our knowledge, this is the first report of Fusobacterium septicemia associated with hepatic venous thrombosis. This report is close to the cases of portal thrombosis and opens the clinical sphere of the lemierre's syndrome, whose incidence is increasing.

[French guidelines for the management of adult sickle cell disease: 2015 update]. / Recommandations françaises de prise en charge de la drépanocytose de l'adulte: actualisation 2015.

Sickle cell disease is a systemic genetic disorder, causing many functional and tissular modifications. As the prevalence of patients with sickle cell disease increases gradually in France, every physician can be potentially involved in the care of these patients. Complications of sickle cell disease can be acute and chronic. Pain is the main symptom and should be treated quickly and aggressively. In order to reduce the fatality rate associated with acute chest syndrome, it must be detected and treated early. Chronic complications are one of the main concerns in adults and should be identified as early as possible in order to prevent end organ damage. Many organs can be involved, including bones, kidneys, eyes, lungs, etc. The indications for a specific treatment (blood transfusion or hydroxyurea) should be regularly discussed. Coordinated health care should be carefully organized to allow a regular follow-up near the living place and access to specialized departments. We present in this article the French guidelines for the sickle cell disease management in adulthood.

Localization of pH regulating proteins H+ATPase and Cl-/HCO3- exchanger in the guinea pig inner ear.

Mechanisms that regulate endolymphatic pH are unknown. It has long been recognized that, because of the large positive endolymphatic potential in the cochlea, a passive movement of protons would be directed out of endolymph leading to endolymphatic alkalization. However, endolymphatic pH is close to that of blood, suggesting that H+ is being secreted into endolymph. Since the kidney and the inner ear are both actively engaged in fluid and electrolyte regulation, we attempted to determine whether proteins responsible for acid secretion in the kidney also exist in the guinea pig inner ear. To that end, a monoclonal antibody against a 31 kDa subunit of a vacuolar vH+ATPase and a polyclonal, affinity purified antibody against the AE2 Cl-/HCO3- exchanger (which can also recognize AE1 under some conditions) were used. In the cochlea, the strongest immunoreactivity for the vH+ATPase was found in apical plasma membranes and apical cytoplasm of strial marginal cells. These cells were negative for the Cl-/HCO3- exchanger. Certain cells of the inner ear demonstrated both apical staining for vH+ATPase and basolateral staining for the Cl-/HCO3- exchanger; these included interdental cells and epithelial cells of the endolymphatic sac. Cochlear cell types with diffuse cytoplasmic staining for vH+ATPase and a basolaterally localized Cl-/HCO3- exchanger included inner hair cells, root cells and a subset of supporting cells in the organ of Corti. Hair cells of the utricle, saccule and cristae ampullaris also expressed both vH+ATPase and the Cl-/HCO3- exchanger, but immunostaining for the vH+ATPase was less intense and less polarized than in the cochlea. These immunocytochemical results support a role for the vH+ATPase and Cl-/HCO3- exchanger in the regulation of endolymphatic pH and suggest that certain cells (including strial marginal cells and epithelial cells of the endolymphatic sac) may be specialized for this regulation.

Conventional conformal radiotherapy vs intracavitary brachytherapy for the adjuvant postoperative treatment of cervical cancer: a comparative dosimetric study.

OBJECTIVES: The aim of this pilot study is to evaluate the feasibility of 3D-conformal radiotherapy (3D-CRT) in the adjuvant postoperative radiotherapy of the vaginal cuff and upper third of present vaginal tissue. METHODS: The representative patient (FIGO IB; PH: squamous cell carcinoma) was referred for adjuvant post-hysterectomy radiotherapy. A whole pelvis irradiation with concomitant high-dose-rate intracavitary brachytherapy (HDR-ICBT) was applied. HDR-ICBT total dose of 24 Gy in four fractions/one fraction per week was delivered to the vaginal cuff using two Fletcher-Suit ovoids. The feasibility of change from HDR-ICBT to CRT was evaluated by generating of three different plans using 10 MV photon beams shaped by multileaf collimator. RESULTS AND DISCUSSION: The referent volume received HDR-ICBT prescribed dose. The maximum ICBT percentage dose to the rectum and urinary bladder was 101% and 106% respectively. In all 3D-CRT plans almost 100% of planning target volume (PTV) was covered by 95% therapy isodose surface. From 12 - 13% of the rectum and 1-3% urinary bladder volume were covered by 100% isodose surface, with the highest maximum dose of 104% and 101%, respectively. Comparison of the PTV dose coverage and the maximum dose to the rectum and urinary bladder for HDR-ICBT and 3D-CRT plans showed no major difference. CONCLUSION; 3D-CRT could be considered as adequate replacement for ICBT in the adjuvant postoperative treatment of the vaginal cuff and upper thi-rd of present vaginal tissue. Time-dose-fractionation pattern for HDR-ICBT may be safely applied for 3D-CRT.

Kawasaki-like syndromes in HIV-infected adults.

BACKGROUND: Kawasaki-like syndrome (KLS) is rare in adults; one third of these patients are infected by Human immunodeficiency virus (HIV). Our study reports cases of KLS occurring in HIV-positive adults and reviews the literature to compare their characteristics with HIV-negative adults and children with Kawasaki disease (KD). METHODS: Report of cases and review of the literature. RESULTS: Amongst 20 cases reviewed, including 4 who were managed at our institution, KLS was associated with severe immunosuppression and a high HIV viral load. There was frequent co-infection by hepatitis viruses. Desquamation and liver abnormalities were more frequent in HIV-negative adults whereas headaches and gastrointestinal disorders more common in HIV-positive adults. Intravenous immunoglobulin was effective therapy. Relapse was more frequent among HIV-positive patients. No cardiovascular complications or deaths occurred. CONCLUSIONS: Advanced immunosuppression due to HIV may predispose to KLS. The differential diagnosis that must be considered includes drug hypersensitivity reactions and staphylococcal infections.

External beam radiotherapy plus brachytherapy boost in treatment of anal canal carcinoma.

PURPOSE: Radiotherapy has been the standard treatment of anal canal carcinoma for the last three decades. However, there are still many open questions such as optimal radiation technique, adequate boost dose or best chemotherapy regimen. Beside cure and local control, other important goals are sphincter salvage and avoidance of a permanent colostomy, i.e. morbidity minimization. MATERIAL AND METHODS: At the Institute for Oncology and Radiology of Serbia, between March 1997 and May 2004, patients with anal canal carcinoma were treated with combined external beam radiotherapy and brachytherapy boost as primary treatment modality. Initially, external beam radiotherapy was applied with two opposed parallel fields and dose ranged from 40-50 Gy and after that patient continued the treatment with brachytherapy boost (intraluminal or interstitial) with doses ranged from 10-25 Gy. Total tumor dose in combined radiotherapy treatment ranged from 55-70 Gy. RESULTS: Out of 21 patients, acute complications were registered in 15 patients (71.4%) and the most frequent was dermatitis. Complete response after radiotherapy was registered in 17 patients (81%). In the median follow up time of 42 months, five-year overall survival was 71% and disease free survival was 61%. Late sequelas were registered in 14 patients (66.7%), but they were low grade. CONCLUSIONS: Our study shows results using external beam radiotherapy and brachytherapy boost as single modality treatment, but we need more randomized trial to improve better local control and minimize toxicity.