The Place of Pharmacotherapy in Alcohol Use Disorder Management in Family Practice - A Systematic Review.

BACKGROUND AND AIMS: Alcohol use disorders (AUD) are among the most prevalent mental disorders around the world, yet still remain the most undertreated. Many studies report the low rate of treatment uptake, less than 20%, among people with AUD. Among those accessing care, a large majority only approach their GP for help. Therefore, primary care is a strategic setting for the identification and the management of AUD. International recommendations stress AUD pharmacotherapy for withdrawal and craving management, but very few studies have shown interest in the management of AUDs in primary care. The main objective of this study was to analyse pharmacotherapy in AUD management in primary care by means of a systematic literature review. METHODS: A systematic literature review (PRISMA) was carried out. 5 databases were screened: PUBMED via MEDLINE, LiSSa, the SUDOC catalogue, PASCAL and EMBASE. Search algorithms were used integrating the concepts of pharmacotherapy management, alcohol use disorders and primary care, only in the English language. RESULTS: 296 studies were selected and 10 were included. One was a follow-up study on the national prescription database, while four were cross-sectional studies with an auto-questionnaire survey. Of the 10 studies included, two were conducted in Europe, five in North America, two in Australia and one in South Africa. These pharmacotherapy studies were concerned with the anti-craving treatment, and 3 types of medications were used: Disulfiram, Acamprosate and Naltrexone. Factors identified as limiting or facilitating prescriptions concerned cost, indications, efficacy, training and adjuncts to pharmacotherapy. CONCLUSION: Knowledge and prescription of pharmacotherapy for AUD, more specifically, anti-craving treatment, is insufficient in primary care. There is a lack of data and studies on the efficacy of anti-craving treatment in primary care. Guidelines for AUD management, including psychological and medical management and pharmacotherapy, do exist but have not been adapted to primary care practice. Barriers and facilitators of pharmacotherapy prescription in AUD in primary care were identified in this study.

Oyster hemolymph is a complex and dynamic ecosystem hosting bacteria, protists and viruses.

BACKGROUND: The impact of the microbiota on host fitness has so far mainly been demonstrated for the bacterial microbiome. We know much less about host-associated protist and viral communities, largely due to technical issues. However, all microorganisms within a microbiome potentially interact with each other as well as with the host and the environment, therefore likely affecting the host health. RESULTS: We set out to explore how environmental and host factors shape the composition and diversity of bacterial, protist and viral microbial communities in the Pacific oyster hemolymph, both in health and disease. To do so, five oyster families differing in susceptibility to the Pacific oyster mortality syndrome were reared in hatchery and transplanted into a natural environment either before or during a disease outbreak. Using metabarcoding and shotgun metagenomics, we demonstrate that hemolymph can be considered as an ecological niche hosting bacterial, protist and viral communities, each of them shaped by different factors and distinct from the corresponding communities in the surrounding seawater. Overall, we found that hemolymph microbiota is more strongly shaped by the environment than by host genetic background. Co-occurrence network analyses suggest a disruption of the microbial network after transplantation into natural environment during both non-infectious and infectious periods. Whereas we could not identify a common microbial community signature for healthy animals, OsHV-1 µVar virus dominated the hemolymph virome during the disease outbreak, without significant modifications of other microbiota components. CONCLUSION: Our study shows that oyster hemolymph is a complex ecosystem containing diverse bacteria, protists and viruses, whose composition and dynamics are primarily determined by the environment. However, all of these are also shaped by oyster genetic backgrounds, indicating they indeed interact with the oyster host and are therefore not only of transient character. Although it seems that the three microbiome components respond independently to environmental conditions, better characterization of hemolymph-associated viruses could change this picture.

Excess burden associated with Clostridioides difficile infection in haematological patients occurring during hospitalization with induction chemotherapy in the USA.

BACKGROUND: Patients with haematological diseases are at high risk of developing Clostridioides difficile infection (CDI). AIM: The study aim was to describe excess length of stay and costs associated with CDI during the hospital stay for induction chemotherapy in the United States (USA). METHODS: A retrospective analysis was conducted utilizing data from US databases of Truven Health Analytics®. Comprehensive hospitalization data of patients with induction chemotherapy due to acute myeloid leukaemia (AML), acute lymphoblastic leukaemia, Hodgkin lymphoma and non-Hodgkin lymphoma (NHL) were analysed. Patients with CDI occurring during the hospital stay were compared to controls through a case-control comparison of the direct treatment costs and length of stay was performed with an exact matching algorithm. FINDINGS: A total of 2611 patients were included between January 2014 and December 2017. NHL (43.5%) and AML (38.4%) were the predominant underlying diseases and 15% of patients received a stem cell transplantation. During the matching, 105 CDI cases (CDI+) were compared with 801 controls (CDI-). On average, hospitalization costs were increased by US$36,113 in CDI+ compared to CDI- patients (P=0.009) and patients with CDI spent on average 8.9 additional days in hospital (P=0.003). CONCLUSIONS: The findings highlight a significant burden associated with CDI in haematological patients undergoing induction chemotherapy in the USA. There is an important need for prevention of CDI in this specific patient population.

[Spontaneous lung volume reduction following pneumonia in a patient with emphysema]. / Normalisation ventilatoire après réduction de volume pulmonaire naturelle consécutive à une infection pulmonaire.

INTRODUCTION: Lung volume reduction can be effective in appropriately selected patients with severe emphysema and is associated with reduced breathlessness and improved survival. Spontaneous resolution of emphysematous bullae can also sometimes occur. CASE REPORT: We report a case of severe smoking-related emphysema in a 60-year-old patient, who presented in October 2013 with a right upper lobe acute community-acquired pneumonia on the background of previously undocumented emphysema. The patient improved following treatment with co-amoxiclav and serial radiology showed progressive cicatricial retraction. Nine months later there had been a major functional improvement characterized by a complete normalization of the patient's ventilatory parameters, specifically a 45% improvement in FEV1. In the literature, the average FEV1 improvement obtained by surgical or endoscopic lung volume reduction techniques does not exceed 28%. CONCLUSION: Rarely, emphysematous bullae resolve following infections. Further studies of the mechanisms involved in these natural regressions may be of interest in the development of new therapeutics.

The Sentinel Lymph Node in Breast Cancer: Problems Posed by Examination During Surgery. A Review of Current Literature and Management.

The presence of tumor cells can be identified in the lymph node when metastasis has occurred from the primary cancer site into the lymph node (1) If the sentinel lymph node ganglion is negative for the presence of tumor cells at the time of histological examination, the other lymph nodes are also negative in 99% of cases. If no tumor cells are identified in the sentinel lymph node ganglion by histological examination, the other lymph nodes are also negative for the presence of tumor cells in 99% of cases. The sentinel lymph node advantageously replaces axillary dissection as a staging method in breast cancer T1 and T2 (2). Approximately 40% of breast cancers metastasize to axillary lymph nodes and metastatic extension depends on disease stage. Sentinel lymph nodes are affected in the following stages: T1a (4.3%), T1b (19.5%), T1c (23.8%), T2 (48.9%), T3 (66.7%).

Paget's Breast Disease: A Case Report and Review of the Literature.

Paget's disease of the breast is a rare cancer. This typical clinical case illustrates the different epidemiological, clinical, histological, therapeutic, and evolving aspects of the disease. We report a case of Paget's disease in a 43-year-old woman who presented eczema of the nipple. Mammography and ultrasounds did reveal a lesion in situ. The patient was scheduled for mastectomy and sentinel node biopsy. She had chosen a radical bilateral surgery. The histological diagnosis was Paget's disease of the breast with a carcinoma in situ. There was no metastasis in either of the sentinel nodes. Paget's disease must be considered with the presence of a persistent eczematous involvement of the nipple, which does not respond to local treatment. Ultrasounds, mammography, and magnetic resonance imaging can allow searching an underlying cancer and guiding the surgical management. There is no evidence at this time that one of the two surgical techniques (conservative or mastectomy) would improve survival. The prognosis depends on the presence of a palpable mass and the invasiveness of the cancer.

Significant Change in Marine Plankton Structure and Carbon Production After the Addition of River Water in a Mesocosm Experiment.

Rivers are known to be major contributors to eutrophication in marine coastal waters, but little is known on the short-term impact of freshwater surges on the structure and functioning of the marine plankton community. The effect of adding river water, reducing the salinity by 15 and 30%, on an autumn plankton community in a Mediterranean coastal lagoon (Thau Lagoon, France) was determined during a 6-day mesocosm experiment. Adding river water brought not only nutrients but also chlorophyceans that did not survive in the brackish mesocosm waters. The addition of water led to initial increases (days 1-2) in bacterial production as well as increases in the abundances of bacterioplankton and picoeukaryotes. After day 3, the increases were more significant for diatoms and dinoflagellates that were already present in the Thau Lagoon water (mainly Pseudo-nitzschia spp. group delicatissima and Prorocentrum triestinum) and other larger organisms (tintinnids, rotifers). At the same time, the abundances of bacterioplankton, cyanobacteria, and picoeukaryote fell, some nutrients (NH4+, SiO43-) returned to pre-input levels, and the plankton structure moved from a trophic food web based on secondary production to the accumulation of primary producers in the mesocosms with added river water. Our results also show that, after freshwater inputs, there is rapid emergence of plankton species that are potentially harmful to living organisms. This suggests that flash flood events may lead to sanitary issues, other than pathogens, in exploited marine areas.

Dynamic monitoring of cell mechanical properties using profile microindentation.

We have developed a simple and relatively inexpensive system to visualize adherent cells in profile while measuring their mechanical properties using microindentation. The setup allows simultaneous control of cell microenvironment by introducing a micropipette for the delivery of soluble factors or other cell types. We validate this technique against atomic force microscopy measurements and, as a proof of concept, measure the viscoelastic properties of vascular endothelial cells in terms of an apparent stiffness and a dimensionless parameter that describes stress relaxation. Furthermore, we use this technique to monitor the time evolution of these mechanical properties as the cells' actin is depolymerized using cytochalasin-D.

Verrucous Carcinoma of the Vulva: A Case Report and Review of the Literature.

Verrucous carcinoma of the vulva is a rare lesion (1). Affecting essentially postmenopausal women, this lesion is a distinct and particular entity in vulval carcinoma classification and its scalability is uncertain and unpredictable. Here, we present a case concerning a 48-year-old patient, without follow-up after a condyloma acuminate of the vulva (large left lip). The origin of this case will be discussed in this article. The treatment decided was only surgical. A review of literature shows the rarity of this lesion of the female genital tract.

Heterogeneous distribution in sediments and dispersal in waters of Alexandrium minutum in a semi-enclosed coastal ecosystem.

Within the framework of research aimed at using genetic methods to evaluate harmful species distribution and their impact on coastal ecosystems, a portion of the ITS1rDNA of Alexandrium minutum was amplified by real-time PCR from DNA extracts of superficial (1-3cm) sediments of 30 subtidal and intertidal stations of the Bay of Brest (Brittany, France), during the winters of 2013 and 2015. Cell germinations and rDNA amplifications of A. minutum were obtained for sediments of all sampled stations, demonstrating that the whole bay is currently contaminated by this toxic species. Coherent estimations of ITS1rDNA copy numbers were obtained for the two sampling cruises, supporting the hypothesis of regular accumulation of A. minutum resting stages in the south-eastern, more confined embayments of the study area, where fine-muddy sediments are also more abundant. Higher ITS1rDNA copy numbers were detected in sediments of areas where blooms have been seasonally detected since 2012. This result suggests that specific genetic material estimations in superficial sediments of the bay may be a proxy of the cyst banks of A. minutum. The simulation of particle trajectory analyses by a Lagrangian physical model showed that blooms occurring in the south-eastern part of the bay are disconnected from those of the north-eastern zone. The heterogeneous distribution of A. minutum inferred from both water and sediment suggests the existence of potential barriers for the dispersal of this species in the Bay of Brest and encourages finer analyses at the population level for this species within semi-enclosed coastal ecosystems.

Interplay between the genetic clades of Micromonas and their viruses in the Western English Channel.

The genus Micromonas comprises distinct genetic clades that commonly dominate eukaryotic phytoplankton community from polar to tropical waters. This phytoplankter is also recurrently infected by abundant and genetically diverse prasinoviruses. Here we report on the interplay between prasinoviruses and Micromonas with regard to the genetic diversity of this host. For 1 year, we monitored the abundance of three clades of Micromonas and their viruses in the Western English Channel, both in the environment using clade-specific probes and flow cytometry, and in the laboratory using clonal strains of Micromonas clades to assay for their viruses by plaque-forming units. We showed that the seasonal fluctuations of Micromonas clades were closely mirrored by the abundance of their corresponding viruses, indicating that the members of Micromonas genus are susceptible to viral infection, regardless of their genetic affiliation. The characterization of 45 viral isolates revealed that Micromonas clades are attacked by specific virus populations, which exhibit distinctive clade specificity, life strategies and genetic diversity. However, some viruses can also cross-infect different host clades, suggesting a mechanism of horizontal gene transfer within the Micromonas genus. This study provides novel insights into the impact of viral infection for the ecology and evolution of the prominent phytoplankter Micromonas.

Two case reports of a malignant germ cell tumor of ovary and a granulosa cell tumor: interest of tumoral immunochemistry in the identification and management.

OBJECTIVE: In this article, we present two case reports. The first case was a malignant germ cell tumor of the right ovary in a 23-year old woman and the second case was a bilateral undifferentiated granulosa cell tumor in a 71-year old woman. The aim of these reports is to illustrate the interest of the immunohistochemical analysis to define the correct diagnosis, to better classify these ovarian tumors and improve their management. METHODS: In this study, we report two cases. The first case concerns a 23-year old woman (A) with a mixed germ cell tumor of the right ovary [dysgerminoma (75%), yolk sac tumor (20%), and a mature teratoma (5%)], and the second case concerns a 71-year old woman (B) with a bilateral non-differentiated and necrotic granulosa cell tumor of both ovaries. The staging system was used according to both the classifications: International Federation of Gynaecology and Obstetrics 1987 for ovarian cancer and TNM code 2009. RESULTS: The immunostaining establishes the malignancy and the immunochemistry contributes to confirm effectively the right diagnosis (Tables 2 and 3). CONCLUSION: An immunohistochemical analysis is mandatory for the choice of chemotherapy to obtain a better response of the disease and improve the survival prognosis. The efficiency of the chemotherapy authorizes a conservative surgery including a unilateral salpingo-oophorectomy preserving fertility (A). Concerning the non-dysgerminoma tumor (B), and after a surgical staging and debulking, chemotherapy was recommended. The type of tumor and its histological feature conditioned the choice of treatment. The benefit of the immunohistological analysis in this case allowed the right adjuvant treatment.

Spatiotemporal changes in the genetic diversity of harmful algal blooms caused by the toxic dinoflagellate Alexandrium minutum.

Organisms with sexual and asexual reproductive systems benefit from both types of reproduction. Sexual recombination generates new combinations of alleles, whereas clonality favours the spread of the fittest genotype through the entire population. Therefore, the rate of sexual vs. clonal reproduction has a major influence on the demography and genetic structure of natural populations. We addressed the effect of reproductive system on populations of the dinoflagellate Alexandrium minutum. More specifically, we monitored the spatiotemporal genetic diversity during and between bloom events in two estuaries separated by 150 km for two consecutive years. An analysis of population genetic patterns using microsatellite markers revealed surprisingly high genotypic and genetic diversity. Moreover, there was significant spatial and temporal genetic differentiation during and between bloom events. Our results demonstrate that (i) interannual genetic differentiation can be very high, (ii) estuaries are partially isolated during bloom events and (iii) genetic diversity can change rapidly during a bloom event. This rapid genetic change may reflect selective effects that are nevertheless not strong enough to reduce allelic diversity. Thus, sexual reproduction and/or migration may regularly erase any genetic structure produced within estuaries during a bloom event.

Synovial sarcomas usually metastasize after >5 years: a multicenter retrospective analysis with minimum follow-up of 10 years for survivors.

BACKGROUND: Synovial sarcoma (SS) is a malignant soft tissue sarcoma with a poor prognosis because of late local recurrence and distant metastases. To our knowledge, no studies have minimum follow-up of 10 years that evaluate long-term outcomes for survivors. PATIENTS AND METHODS: Data on 62 patients who had been treated for SS from 1968 to 1999 were studied retrospectively in a multicenter study. Mean follow-up of living patients was 17.2 years and of dead patients 7.7 years. RESULTS: Mean age at diagnosis was 35.4 years (range 6-82 years). Overall survival was 38.7%. The 5-year survival was 74.2%; 10-year survival was 61.2%; and 15-year survival was 46.5%. Fifteen patients (24%) died of disease after 10 years of follow-up. Local recurrence occurred after a mean of 3.6 years (range 0.5-14.9 years) and metastases at a mean of 5.7 years (range 0.5-16.3 years). Only four patients were treated technically correctly with a planned biopsy followed by a wide resection or amputation. Factors associated with significantly worse prognosis included larger tumor size, metastases at the time of diagnosis, high-grade histology, trunk-related disease, and lack of wide resection as primary surgical treatment. CONCLUSIONS: In SS, metastases develop late with high mortality. Patients with SS should be followed for >10 years.

High frequency of beta-catenin heterozygous mutations in extra-abdominal fibromatosis: a potential molecular tool for disease management.

BACKGROUND: Fibromatosis comprises distinct clinical entities, including sporadic extra-abdominal fibromatosis, which have a high tendency for recurrence, even after adequate resection. There are no known molecular biomarkers of local recurrence. We searched for beta-catenin mutations in a European multicentre series of fibromatosis tumours to relate beta-catenin mutational status to disease outcome. METHODS: Direct sequencing of exon 3 beta-catenin gene was performed for 155 frozen fibromatosis tissues from all topographies. Correlation of outcome with mutation rate and type was performed on the extra-abdominal fibromatosis group (101 patients). RESULTS: Mutations of beta-catenin were detected in 83% of all cases. Among 101 extra-abdominal fibromatosis, similar mutation rates (87%) were observed, namely T41A (39.5%), S45P (9%), S45F (36.5%), and deletion (2%). None of the clinico-pathological parameters were found to be significantly associated with beta-catenin mutational status. With a median follow-up of 62 months, 51 patients relapsed. Five-year recurrence-free survival was significantly worse in beta-catenin-mutated tumours regardless of a specific genotype, compared with wild-type tumours (49 vs 75%, respectively, P=0.02). CONCLUSION: A high frequency (87%) of beta-catenin mutation hallmarks extra-abdominal fibromatosis from a large multicentric retrospective study. Moreover, wild-type beta-catenin seems to be an interesting prognostic marker that might be useful in the therapeutic management of extra-abdominal fibromatosis.

[Fibro-osseous pseudotumor of the thumb. Report of a case]. / Pseudotumeur ostéofibreuse du pouce. A propos d'un cas.

Fibro-osseous tumor of the digits is an uncommon, benign condition with an excellent prognosis after local excision. Like myositis ossificans, clinical and histological features may mimic a malignant tumour, especially an extraskeletal osteosarcoma. A correct interpretation of clinical, radiological and histological data is a prerequisite to avoid misdiagnosis and unnecessary radical surgery (for example, amputation). We report the case of a 15-year-old boy who presented with a slow-growing mass of the left thumb, which turned out to be a fibro-osseous tumor on microscopic examination. A complete excision was performed without loss of function. Fifteen months postoperatively, there was no local recurrence.

Soft tissue sarcomas of the trunk wall (STS-TW): a study of 343 patients from the French Sarcoma Group (FSG) database.

BACKGROUND: Soft tissue sarcomas of the trunk wall (STS-TW) are usually studied together with soft tissue sarcomas of other locations. We report a study on STS-TW forming part of the French Sarcoma Group database. PATIENTS AND METHODS: Three hundred and forty-three adults were included. We carried out univariate and multivariate analysis for overall survival (OS), metastasis-free survival (MFS) and local recurrence-free survival (LRFS). RESULTS: Tumor locations were as follows: thoracic wall, 82.5%; abdominal wall, 12.3% and pelvic wall, 5.2%. Median tumor size was 6.0 cm. The most frequent tumor types were unclassified sarcoma (27.7%) and myogenic sarcoma (19.2%). A total of 44.6% of cases were grade 3. In all, 21.9% of patients had a previous medical history of radiotherapy (PHR). Median follow-up was 7.6 years. The 5-year OS, MFS and LRFS rates were 60.4%, 68.9% and 58.4%, respectively. Multivariate analysis retained PHR and grade for predicting LRFS and PHR, size and grade as prognostic factors of MFS. Factors influencing OS were age, size, PHR, depth, grade and surgical margins. The predictive factors of incomplete response were PHR, size and T3. CONCLUSIONS: Our results suggest similar classical prognostic factors as compared with sarcomas of other locations. However, a separate analysis of STS-TW revealed a significant poor prognosis subgroup of patients with PHR.

Widespread occurrence and genetic diversity of marine parasitoids belonging to Syndiniales (Alveolata).

Syndiniales are a parasitic order within the eukaryotic lineage Dinophyceae (Alveolata). Here, we analysed the taxonomy of this group using 43655 18S rRNA gene sequences obtained either from environmental data sets or cultures, including 6874 environmental sequences from this study derived from Atlantic and Mediterranean waters. A total of 5571 out of the 43655 sequences analysed fell within the Dinophyceae. Both bayesian and maximum likelihood phylogenies placed Syndiniales in five main groups (I-V), as a monophyletic lineage at the base of 'core' dinoflagellates (all Dinophyceae except Syndiniales), although the latter placement was not bootstrap supported. Thus, the two uncultured novel marine alveolate groups I and II, which have been highlighted previously, are confirmed to belong to the Syndiniales. These groups were the most diverse and highly represented in environmental studies. Within each, 8 and 44 clades were identified respectively. Co-evolutionary trends between parasitic Syndiniales and their putative hosts were not clear, suggesting they may be relatively 'general' parasitoids. Based on the overall distribution patterns of the Syndiniales-affiliated sequences, we propose that Syndiniales are exclusively marine. Interestingly, sequences belonging to groups II, III and V were largely retrieved from the photic zone, while Group I dominated samples from anoxic and suboxic ecosystems. Nevertheless, both groups I and II contained specific clades preferentially, or exclusively, retrieved from these latter ecosystems. Given the broad distribution of Syndiniales, our work indicates that parasitism may be a major force in ocean food webs, a force that is neglected in current conceptualizations of the marine carbon cycle.

Kinetic analysis of cardiac troponin I release is no more accurate than a single 24-h measurement in predicting in-hospital outcome after cardiac surgery.

BACKGROUND AND OBJECTIVE: A single cardiac troponin I (cTnI) 24-h measurement is an independent predictor of short- and long-term adverse outcome after coronary surgery. We compared a single cTnI 24-h measurement and kinetic analysis of cTnI release in predicting in-hospital outcome in unselected cardiac surgery patients. METHODS: Consecutive patients (n = 184) undergoing cardiac surgery with cardiopulmonary bypass were included and divided into two groups according to the time course of postoperative peak serum cTnI (6 or 24 h after surgery). Serial measurements of cTnI were performed the day before surgery, at the end of surgery and 6, 24 and 120 h after surgery in all patients. The total amount of cTnI released (integrated area under the curve), postoperative major adverse cardiac events (ventricular arrhythmias, myocardial infarction and congestive heart failure) and in-hospital death were recorded. Data are expressed as median (95% CI). RESULTS: In all, 152 (83%) patients had an early peak cTnI (6 h after surgery) and 32 (17%) patients had a late peak cTnI (24 h after surgery). The integrated area under the curve differed between both groups: 159 (142-178) vs. 321 (255-590), respectively, P < 0.001. Major adverse cardiac events and/or death (22 vs. 9%, P = 0.04) was greater in patients with a late peak cTnI. The integrated area under the curve and the peak value of cTnI were no more accurate than a single 24-h measurement in predicting the occurrence of major adverse cardiac events and/or death. CONCLUSIONS: Kinetic analysis of cTnI release was no more accurate than a single 24-h measurement in predicting in-hospital poor outcome.