High impact of COVID-19 outbreak in a nursing home in the Nouvelle-Aquitaine region, France, March to April 2020.

BACKGROUND: Elderly people in nursing homes are particularly vulnerable to COVID-19 due to their age, the presence of comorbidities, and community living. On March 14, 2020, at the beginning of the first epidemic wave of COVID-19 in France, a cluster was reported in a nursing home in the Nouvelle-Aquitaine region. We monitored the outbreak as well as the infection prevention and control (IPC) measures implemented. METHODS: A confirmed case was defined as laboratory-confirmed COVID-19 in a resident or staff member present in the nursing home between March 7 and May 1, 2020; and a probable case as a person presenting an acute respiratory illness after contact with a confirmed case. Symptomatic inpatient residents and symptomatic staff members were systematically tested for SARS-CoV-2. In addition, two screening sessions were held on site. RESULTS: We identified 109 cases (98 confirmed, 11 probable). The attack rate was 66% among residents and 45% among staff. Half of all cases were identified during the screening sessions. One-quarter of cases had minor symptoms or were asymptomatic. The case fatality rate among residents was 29%. IPC measures were rapidly implemented such as the quarantine of residents, the reinforcement of staff personal protective equipment, and home quarantine of staff testing positive, which were supplemented in April by systematic controls at the entrance of the nursing home and the creation of additional staff break rooms. CONCLUSIONS: This outbreak confirmed the considerable health impact of SARS-CoV-2 transmission in a nursing home. In addition to the implementation of IPC measures, the early detection of cases through the screening of residents and staff is essential to identify asymptomatic and pre-symptomatic cases and limit the spread of the virus.

Effect of fipronil on side-specific antennal tactile learning in the honeybee.

In the honeybee, the conditioning of the proboscis extension response using tactile antennal stimulations is well suited for studying the side-specificity of learning including the possible bilateral transfer of memory traces in the brain, and the role of inhibitory networks. A tactile stimulus was presented to one antenna in association with a sucrose reward to the proboscis. The other antenna was either not stimulated (A+/0 training), stimulated with a non-reinforced tactile stimulus B (A+/B- training) or stimulated with B reinforced with sucrose to the proboscis (A+/B+ training). Memory tests performed 3 and 24h after training showed in all situations that a tactile stimulus learnt on one side was only retrieved ipsilaterally, indicating no bilateral transfer of information. In all these groups, we investigated the effect of the phenylpyrazole insecticide fipronil by applying a sublethal dose (0.5 ng/bee) on the thorax 15 min before training. This treatment decreased acquisition success and the subsequent memory performances were lowered but the distribution of responses to the tactile stimuli between sides was not affected. These results underline the role of the inhibitory networks targeted by fipronil on tactile learning and memory processes.

[Conjunctival in situ carcinoma in a patient with Waldenström's disease]. / Carcinome in situ de la conjonctive chez un patient porteur d'une maladie de Waldenström.

A 73-year-old male patient was treated for conjunctival in situ carcinoma invading the cornea of his right eye. The patient had been previously operated on for two corneoconjunctival lesions on the same eye (one was a pterygium, the other was simple epithelial hyperplasia) and was regularly followed for a systemic lymphoplasmocytic lymphoma (Waldenström's disease). After a corneoconjunctival excision of the tumor, the histological analysis was performed and established the diagnosis of in situ carcinoma. The tumor recurred a few months later and radiation therapy was then given. No recurrence was observed after this latter treatment.

Splenic marginal zone lymphoma with or without plasmacytic differentiation.

We report a series of 31 cases of splenic marginal zone lymphomas with an enlarged spleen and a multimicronodular macroscopic pattern. Two groups, A and B, were distinguished based on the presence (A) or absence (B) of a lymphoplasmacytic component with monoclonal immunoglobulin expression in the cytoplasm. There were no differences between the groups as far as age, sex, spleen weight, and progression. The only difference was the presence in group A of a monoclonal serum component and autoimmune disorders, particularly autoimmune hemolytic anemia. In most cases in which a liver and/or bone marrow biopsy was performed, lymphomatous infiltration was detected. Seven cases had a seric monoclonal IgM of 5 g/L or more and liver or bone marrow infiltration, corresponding to the definition of Waldenstrom's macroglobulinemia. Lymphoma cells had a monocytoid, centrocytoid and, in group A, lymphoplasmacytic morphology. The lymphomatous cells were positive for CD20, CD45 RA, and bcl-2. They expressed IgD in 9 cases, partially in 6, and were negative for IgD in 9 of the 24 cases studied. Progression seems to be slow, with a long survival. Three patients presented with transformation into a large B-cell lymphoma, which was responsible for death in two patients.

Defective cell migration in an ovarian cancer cell line is associated with impaired urokinase-induced tyrosine phosphorylation.

The urokinase receptor (u-PAR), a protein anchored to cell membrane by a glycosyl phosphatidylinositol, plays a central role in cancer cell invasion and metastasis by binding urokinase plasminogen activator (u-PA), thereby facilitating plasminogen activation. Plasmin can promote cell migration either directly or by activating metalloproteinases that degrade some of the components of the extra cellular matrix. However, the IGR-OV1-Adria cell line contains the u-PAR but does not migrate even in the presence of exogenous u-PA, although the parental IGR-OV1 cell line migrates normally in the presence of u-PA. We therefore investigated the role of cell signalling for u-PA induced cell locomotion. We show that cell migration induced by u-PA-u-PAR complex is always associated with tyrosine kinase activation for the following reasons: (1) the blockade of the u-PAR by a chimeric molecule (albumin-ATF) inhibits not only the u-PA-induced cell migration, but also the signalling in IGR-OV1 line; (2) the binding of u-PA to u-PAR on non-migrating IGR-OV1-Adria cells was not associated with tyrosine kinase activation; (3) the inhibition of tyrosine kinase also blocked cell migration of IGR-OV1. Therefore tyrosine kinase activation seems to be essential for the u-PA-induced cell locomotion possibly by the formation of a complex u-PAR-u-PA with a protein whose transmembrane domain can ensure cell signalling. Thus, IGR-OV1 and IGR-OV1-Adria cell lines represent a good model for the analysis of the mechanism of u-PA-u-PAR-induced cell locomotion.

Mediastinal infusion of epirubicin and 5-fluorouracil. A complication of totally implantable central venous systems. Report of a case.

Perforation of the wall of the superior vena cava by a central venous catheter is reported. The resultant inadvertent infusion of 5-fluorouracil and epirubicin caused a severe acute inflammatory reaction in the right-lobe bronchus, mediastinal infiltration and pleural and pericardial effusions. The patient recovered but has residual mild oesophageal dysfunction.

Peripheral-T-cell lymphoma with hemophagocytic histiocytosis localised to the bone marrow associated with inappropriate secretion of antidiuretic hormone.

A patient with high fever, loss of weight and profound pancytopenia is reported. Peripheral T-cell lymphoma with hemophagocytosis was diagnosed. Bone marrow was the only localisation of the lymphoma. At presentation there were (i) a coagulopathy consistent with hemophagocytic histiocytosis (ii) the features of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). These different abnormalities disappeared after chemotherapy and reappeared during each of the 2 periods of disease progression. The patient died 6 months after diagnosis without ever achieving complete remission. As far as we are aware this is the first case report of T-cell lymphoma with hemophagocytic syndrome localised to the bone marrow and associated with SIADH.

[Resistance to chemotherapy in cancers of the kidney and therapeutic perspectives]. / Résistance à la chimiothérapie dans les cancers du rein et perspectives thérapeutiques.

Usual treatments combining surgery, radiation therapy, chemotherapy and hormonotherapy are poorly effective. The immunotherapy gave and objective response rate of 25% but is associated with many side effects. Multidrug resistance (MDR) can be explained, in part, by an mdr1 gene overexpression in renal carcinoma. The MDR is related to expression of a 170 Kda membrane glycoprotein, the so-called P glycoprotein (Pgp). This protein is able to extrude from cytoplasm drugs with various structures and mechanisms. Reversal compounds capable of inhibiting Pgp, given with antineoplastic drugs, could be able to increase their intracellular concentrations. Nevertheless, renal cell carcinomas are characterized by their multifactorial resistance and a better knowledge in this field will allow to design new circumvention resistance to chemotherapy.

Full-term pregnancy with embryos from donated oocytes in a 36-year-old woman allografted for chronic myeloid leukemia.

We report the first case of full-term pregnancy arising from donated oocytes in a 36-year-old woman with chronic myeloid leukemia (CML), 6 years after allogeneic bone marrow transplantation (BMT) following total body irradiation (TBI) (12 Gy) and cyclophosphamide 120 mg/kg. The first attempt at implantation with her own cryopreserved ovocytes was unsuccessful. Thereafter, she became pregnant after donated oocyte implantation using estradiol and progesterone support replacing the defective ovarian function. The baby was normal. Unfortunately, 6 months later, she relapsed in chronic phase of CML.

The plasminogen-activation system in ovarian tumors.

We studied the plasminogen activation system in tumor tissue by measuring the antigen level of the 2 plasminogen activators, tissue-type (t-PA) and urokinase-type (U-PA) and their inhibitors, plasminogen-activator inhibitors type-I (PAI-I) and type-2 (PAI-2) in the tissue extracts of 43 human benign and malignant ovarian tumors. U-PA levels were significantly higher in malignant than in benign tumors. In addition, U-PA antigen levels were higher in the metastatic tissue of advanced disease (FIGO stage III) than in the primary localized tumor (FIGO stage I/II). Also PAI-I concentrations tended to be higher in malignant than in benign tumors, but this difference was not statistically significant. In contrast, t-PA levels were lower in metastatic than in non-metastatic tumors, whereas PAI-2 levels were unrelated to the stage of ovarian malignancy. These results were integrated in a plasminogen-activation-dependent malignancy index (U-PA x PAI-I/t-PA). This index distinguished the different groups of benign ovarian tumors, localized and metastatic ovarian carcinomas better than U-PA levels. It could be useful as a prognostic indicator in ovarian cancer.

Incubation of monocytes with adriamycin increases secretion of hepatocyte stimulating factor for fibrinogen biosynthesis.

This work provides evidence that the production by monocytes of hepatocyte stimulating factor(s) for fibrinogen biosynthesis was dramatically increased when monocytes were exposed to Adriamycin. This effect was related to an increased production of leukaemia inhibiting factor (LIF), a cytokine known to stimulate fibrinogen biosynthesis by hepatic cells. Adriamycin also induces an increase in membrane-associated urokinase on monocytes. These results are consistent with the clinical observation in patients with ovarian cancer that when the CA-125 tumour marker decreases during chemotherapy, an increased level of D-dimer is a marker of good prognosis.

D-dimer and CA 125 levels in patients with ovarian cancer during antineoplastic therapy. Prognostic significance for the success of anti-cancer treatment.

In patients with ovarian cancer before they receive chemotherapy, the level of fibrin degradation products (D-dimer), is correlated with the tumor load. In this study, the evolution of D-dimer was compared in patients receiving antineoplastic therapy with the evolution of the disease. The patients could be classified into three groups. In Group 1 (nine patients), both plasma CA 125 (a tumor-associated antigen) and D-dimer remained elevated; the prognosis was always poor. In Group 2 (eight patients), CA 125 and D-dimer decreased simultaneously, complete remission was observed in two patients, and significant residual tumor was observed in the others. In Group 3 (nine patients), despite an important decrease in CA 125, D-dimer remained elevated during therapy. In this group, complete remission was observed in six patients, and three others showed a large decrease in their tumor load. The combination of a decrease in CA 125 levels with a continuous enhanced level of D-dimer during chemotherapy identified a subgroup of patients with a favorable prognosis.

Large anaplastic cell Ki-1 positive malignant lymphoma with peculiar endocytotic vacuoles.

Unusual intracytoplasmic inclusions are occasionally seen in some variants of malignant lymphoma. We report here a case of large anaplastic cell malignant lymphoma with peculiar vacuoles of probable endocytotic origin. Immunological findings demonstrated the characteristics of activated cells typical of a large anaplastic cell Ki-1 positive lymphoma. The tumour cells exhibited a phenotype of peripheral helper-inducer T-cells. The intracytoplasmic vacuoles were positive with the T surface marker antibodies. Ultrastructurally, these inclusions were closely related to the microvesicle-containing vacuoles reported in signet ring cell lymphomas of B or T cell lineage. The mechanism of cytoplasmic vacuole formation is discussed. An endocytotic origin is possible. The resemblance to the "capping" phenomenon in small lymphocytes is stressed.

[Peripheral T-cell malignant lymphomas. Clinical, morphologic and developmental features in 22 cases]. / Lymphomes malins T périphériques. Aspects cliniques, morphologiques et évolutifs de 22 cas.

Peripheral T-cell lymphomas (PTCL) represent a new subset of malignant lymphomas, which demonstrates a marked morphological, immunological and clinical diversity. They seem to have a worse prognosis globally than B-cell lymphomas. The main clinical characteristics and outcome of PTCL are analysed in this series of 22 cases. The majority of patients had an advanced disease (stages III and IV; 55 percent) and constitutional symptoms (59 percent) at presentation; extranodal localizations were particularly frequent (41 percent). Three patients presented with isolated or predominant spleen enlargement and fever. According to the updated Kiel classification, there were 7 low-grade PTCL and 15 high-grade PTCL. Phenotypic analysis on fresh frozen tissue was available in 16 cases, showing a predominant helper/inducer phenotype (CD4+, CD8-). The complete remission rate was 76 percent for the whole population, but the median of global survival was only 40 months. The few patients who received radiation therapy and subsequently relapsed did not relapse in the irradiated fields, which suggests that radiotherapy might be included in the therapeutic strategy, the best modalities of which remain to be defined.

Histopathological study of bone marrow biopsies in 30 cases of T-cell lymphoma with clinical, biological and survival correlations.

Forty-five bone marrow (BM) biopsies have been studied in 30 T-cell malignant lymphoma (ML). According to the updated Kiel classification, these ML comprised 12 low grade ML and 18 high grade ML. BM involvement was not significantly more frequent in low grade ML (41.6 per cent) than in high grade (33.3 per cent). This involvement was discovered in 85 per cent of the cases at the time of diagnosis. A correlation was found between BM and other visceral localizations for histological type in all cases. Infiltrates principally showed a nodular pattern in low grade and a diffuse pattern in high grade ML. Hematopoietic hyperplastic reaction was frequent (66.6 per cent) not correlated to involvement. Clinical staging showed extensive spreading. Our patients had an overall median survival of 40 months, worse in high grade ML (median: 19 months) than in low grade ML (41 months) but not statistically different (p = 0.25). Extranodal localizations are a significant criteria for poor prognosis (p = 0.018). Among them, BM involvement appears to be the most significant criteria (Cox model, p = 0.006). Patients with BM localization had a median survival of 9 months contrasting with 40 months in patients without BM localization (p = 0.007). Thus, BM biopsy is useful for the diagnosis of patients with T-ML and essential to establish the prognosis.