ABSTRACT
Current guidelines increasingly consider some dual antiretroviral therapies as bona fide alternatives to triple therapy as these regimens are proven to be safe and efficacious. These drug sparing regimens have many advantages such as a reduction of drug burden and subsequent toxicity, preservation of future treatment options, cost reduction and avoidance of drug-drug interactions. In the past, some dual therapies were associated with a higher risk of selecting resistance mutations. Nevertheless, current and future dual regimens based on powerful drugs with a high genetic barrier are non-inferior to triple therapies and could become the future gold standard for HIV treatment.
Grâce à l'arrivée de nouvelles molécules antirétrovirales plus puissantes, de plus en plus de recommandations internationales mentionnent quelques bithérapies antirétrovirales comme étant une alternative valable à certaines trithérapies, vu leur efficacité et leur sécurité démontrées dans de nombreuses études. Parmi les potentiels avantages de ces doubles associations, mentionnons la simplification du schéma thérapeutique, la réduction potentielle du coût et de la toxicité, la limitation des interactions médicamenteuses et l'épargne de certaines molécules qui pourront, alors, être utilisées en seconde ligne. Certaines de ces bithérapies ont montré un risque majoré d'échappement thérapeutique et de sélection de souches virales résistantes en comparaison avec des trithérapies réputées robustes. Toutefois, certaines bithérapies récemment mises sur le marché, comprenant des médications plus puissantes, plus sûres, moins toxiques et avec une plus grande barrière génétique à l'apparition de résistances, présentent un risque très faible d'échappement thérapeutique lié à la sélection de souches résistantes. Les bithérapies présentent donc plusieurs avantages les rendant intéressantes et leur garantissant, probablement, une place grandissante dans les futures stratégies de traitement.
Subject(s)
Anti-HIV Agents , HIV Infections , Anti-HIV Agents/therapeutic use , Drug Therapy, Combination , HIV , HIV Infections/drug therapy , HumansSubject(s)
Frail Elderly , Perioperative Period/psychology , Resuscitation Orders/psychology , Aged, 80 and over , Female , HumansABSTRACT
In order to end the AIDS pandemic, new infections must be avoided. This prevention can be divided into four axes depending on the risk of exposure to the HIV virus. Over the past decade, new prevention strategies supported by various studies have emerged. These are effective when they are used in combination. Some are not without risk or even controversial according to some authors.
Afin d'endiguer l'épidémie du syndrome d'immunodéficience acquise (SIDA), il faut contrôler les nouvelles acquisitions. Cette prévention peut être divisée en quatre axes en fonction du risque d'exposition au virus d'immunodéficience humaine (VIH). Lors de la dernière décennie, de nouvelles stratégies de prévention, soutenues par diverse études, ont vu le jour. Celles-ci sont efficaces à condition d'être utilisées de façon combinée. Certaines ne sont pas dénuées de risque, voire controversées par certains auteurs.
Subject(s)
Acquired Immunodeficiency Syndrome , HIV Infections , Acquired Immunodeficiency Syndrome/prevention & control , Acquired Immunodeficiency Syndrome/transmission , HIV Infections/prevention & control , HIV Infections/transmission , HumansABSTRACT
Malaria is a worldwide public health problem. In Europe, data show an increasing trend of imported cases in the last ten years. Following an alarming observation reporting resistance to anti-malarial drugs, new effective treatments have been developed in early 21st century. These are artemisinin and its derivatives. Artemisinin-based combination therapies (ACT) are now recommended by the World Health Organisation (WHO) since 2006 as the first-line treatment for uncomplicated Plasmodium falciparum malaria. However, resistance phenomena to these new drugs have been described in South-East Asia since 2009. It is thus necessary to use them properly and to monitor their use to preserve their effectiveness in the future.
Le paludisme représente un problème majeur en termes de santé publique mondiale et l'on décèle une augmentation du nombre de cas d'importation en Europe au cours des dix dernières années. Suite au constat alarmant faisant état de phénomènes de résistance aux anciens anti-paludéens et grâce aux recherches activement menées, de nouveaux traitements extrêmement efficaces ont été développés au début du XXIème siècle. Il s'agit de l'artémisinine et de ses dérivés. L'Organisation Mondiale de la Santé (OMS) recommande depuis 2006 l'utilisation en première intention de dérivés semi-synthétiques combinés de l'artémisinine (ACT) dans le traitement des formes non sévères de paludisme à Plasmodium falciparum. Toutefois, des phénomènes de résistance partielle aux ACT sont décrits en Asie du sud-est depuis 2009. Il est donc nécessaire de les utiliser de manière judicieuse et de majorer la surveillance par le biais de programmes de monitoring standardisés afin de maintenir leur efficacité sur le long terme.
Subject(s)
Antimalarials , Malaria, Falciparum , Antimalarials/therapeutic use , Drug Resistance , Europe , Humans , Malaria, Falciparum/drug therapyABSTRACT
BACKGROUND: Adenocarcinomas or combined adeno-neuroendocrine carcinomas (MANEC) of small bowel usually have a dismal prognosis with limited systemic therapy options. This is the first description of a patient showing a germline-related BRCA1 mutated MANEC of his ileum. The tumor presented a susceptibility to a combined chemotherapy and the PARP1-inhibitor olaparib. CASE PRESENTATION: A 74-year old male patient presented with a metastasized MANEC of his ileum. Due to clinical symptoms his ileum-tumor and the single brain metastasis were removed. We verified the same pathogenic (class 5) BRCA1 mutation in different tumor locations. There was no known personal history of a previous malignant tumor. Nevertheless we identified his BRCA1 mutation as germline-related. A systemic treatment was started including Gemcitabine followed by selective internal radiotherapy (SIRT) to treat liver metastases and in the further course Capecitabine but this treatment finally failed after 9 months and all liver metastases showed progression. The treatment failure was the reason to induce an individualized therapeutic approach using combined chemotherapy of carboplatin, paclitaxel and the Poly (ADP-ribose) polymerase- (PARP)-inhibitor olaparib analogous to the treatment protocol of Oza et al. All liver metastases demonstrated with significant tumor regression after 3 months and could be removed. In his most current follow up from December 2017 (25 months after his primary diagnosis) the patient is in a very good general condition without evidence for further metastases. CONCLUSION: We present first evidence of a therapy susceptible germline-related BRCA1 mutation in small bowel adeno-neuroendocrine carcinoma (MANEC). Our findings offer a personalized treatment option. The germline background was unexpected in a 74-year old man with no previously known tumor burden. We should be aware of the familiar background in tumors of older patients as well.
Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , BRCA1 Protein/genetics , Carcinoma, Neuroendocrine/drug therapy , Germ-Line Mutation , Ileal Neoplasms/drug therapy , Adenocarcinoma/genetics , Adenocarcinoma/secondary , Aged , Brain Neoplasms/secondary , Carboplatin/therapeutic use , Carcinoma, Neuroendocrine/genetics , Carcinoma, Neuroendocrine/secondary , Humans , Ileal Neoplasms/genetics , Ileal Neoplasms/pathology , Liver Neoplasms/secondary , Male , Paclitaxel/therapeutic use , Poly(ADP-ribose) Polymerase Inhibitors/therapeutic useABSTRACT
BACKGROUND: The impact of the weekday of surgery in major elective cases of the upper-GI has been discussed controversially. The objective of this study was to assess whether weekday of surgery influences outcome in patients undergoing D2-gastrectomy. MATERIALS AND METHODS: Patients who underwent D2-gastrectomy for gastric adenocarcinoma between 1996 and 2016 were included. Weekday of surgery was recognized, and subgroups were analyzed regarding clinical and histopathological differences. Survival analysis was performed based on weekday of surgery, and early weekdays (Monday-Tuesday) were compared with late weekdays (Wednesday-Friday). RESULTS: In total, 460 patients, 71% male and 29% female, were included into analysis. The median age was 65 years. Distribution to each weekday was equal and ranged from 86 cases (Wednesday) to 96 cases (Tuesday). The pT, pN and M category and the rate of patients who underwent neoadjuvant treatment did not show significant differences (p = 0.641; p = 0.337; p = 0.752; p = 0.342, respectively). The subgroups did not differ regarding the number of dissected lymph nodes and rate of R-1/2 resections (p = 0.590; p = 0.241, respectively). Survival analysis showed a median survival of 43 months (95% CI 31-55 months), and there was no single weekday or a combination of weekdays (Mon/Tue vs Wed/Thu/Fri) with a significant favorable or worse outcome (p = 0.863; p = 0.30, respectively). The outcome did not differ regarding mortality within the first 90 days after surgery (p = 0.948). CONCLUSIONS: The present study does not show any evidence for a significant impact of weekday of surgery on short- and long-term outcome of patients undergoing gastrectomy for gastric adenocarcinoma.
Subject(s)
Adenocarcinoma/surgery , Gastrectomy/methods , Stomach Neoplasms/surgery , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young AdultABSTRACT
BACKGROUND: Multimodal therapies are the standard of care for advanced adenocarcinomas of the oesophagus and gastro-oesophageal junction (AEG Types I and II). Only three randomised trials have compared preoperative chemotherapy with and without radiation. The results showed a small benefit for combined chemoradiation. In the meantime, newer therapy protocols are available. AIM: In a propensity-score matched study, we analysed patients with locally advanced AEG type I or II, treated with chemotherapy (FLOT-protocol) or chemoradiation (CROSS-protocol), followed by oesophagectomy, in a single high-volume centre. PATIENTS AND METHODS: Between 2011 and 2015, 137 patients with advanced (cT3NxcM0) adenocarcinoma received pre-operative therapy; 70% had chemoradiation (CROSS-protocol) and 30% had chemotherapy (FLOT-protocol). After propensity-score matching, 40 patients from the CROSS-group were selected for analysis. Postoperative histopathological response and prognosis were analysed. RESULTS: The two groups were comparable according to the matching criteria age, gender, tumour location, and year of surgery. R0-resection was achieved in 97% of patients in the CROSS-group and 85% of the FLOT-group (p = 0.049). Major response of the primary tumour was evident more often in the CROSS-group (17/40 pts. 43%) versus FLOT-group (11/40 pts. 27%) as well no lymph node metastasis (ypN0 = 68% versus ypN0 = 40%) (p = 0.014). Prognosis were not significantly different between the two groups. In multivariate analysis, only ypN-category was an independent prognostic factor. CONCLUSION: Compared to FLOT-chemotherapy, neoadjuvant chemoradiotherapy with the CROSS-protocol in locally advanced adenocarcinoma AEG types I and II resulted in better response by the primary tumour and less lymph node metastasis but without superior survival.
