[Physiological hydronephrosis in pregnancy: Occurrence and possible causes. An MRI study]. / L'hydronéphrose physiologique durant la grossesse : prévalences et causes possibles. Une étude basée sur l'IRM.

INTRODUCTION: The etiology of the uretero-hydronephrosis in pregnancy is just hypothesis: hormonal or mechanical hypothesis, only investigated by echographic studies. MRI permits to visualize the entirety of the urinary tract, which can be helpful to find out a mechanical cause. METHODOLOGY: We have analysed the MRI of 100 asymptomatic pregnant women. We have determined the number and locations of the uretero-hydronephroses and researched whether there is any relationship between the uretero-hydronephrosis and certain abdominal structures. We focused on the psoas muscle and measured its depth, width and calculated its surface by a reproducible method. RESULTS: The analysis revealed that the uretero-hydronephrosis was predominantly at the right side (63%) and in the majority of the cases limited to the kidney (42%) and/or the proximal third of the ureter (42%). We were able to rule out some proposed etiologies: a compression of the ureter between the uterus and the iliac or ovarian vessels; a protective effect of the left intestinal structures. A link was observed between the psoas muscle and the physiological uretero-hydronephrosis: the ipsilateral psoas muscle seemed smaller in pregnant women presenting a uretero-hydronephrosis. CONCLUSION: We have highlighted a link between a physiological uretero-hydronephrosis during pregnancy and a lesser developped psoas muscle. The hypothesis proposed is that a smaller psoas muscle would have a less protective effect of the ureter due to a lesser development. This study offers a practical conclusion: a left sided uretero-hydronephrosis during pregnancy and/or including the entirety of the ureter is more probably a pathological hydronephrosis. LEVEL OF EVIDENCE: 4.

Appropriateness of Antibiotic Prescription During Teleconsultation.

Teleconsultation has become a new means of using care which has taken off significantly since the COVID crisis, The pooling of the technological environment within the TC makes it possible to set up practice reviews by reusing the data collected. Our aim was to evaluate the relevance of antibiotic therapy during teleconsultations carried out on the national teleconsultation platform "Qare" in 4 common infections. 143,428 TCs with structured prescriptions were analyzed, with an appropriate prescription in more than 82% of cases, higher than in the literature. The use of data makes it possible to quickly assess practices and inform doctors to improve their practices.

Unexpected substitution of dominant rotavirus G genotypes in French hospitalized children over five consecutive seasons.

The study was designed to evaluate the circulation of group A rotaviruses in French hospitalized children, and to detect unusual strains. This prospective study was conducted from 2001 to 2006 in children consulting for acute diarrhea at the pediatric emergency department in three French University Hospitals. The rotaviruses were detected by rapid test and genotyped by RT-PCR on the basis of their outer capsid proteins VP4 (P-type) and VP7 (G-type). The stools from 757 children were analyzed. G1P[8] strains were predominant (44.0%), followed by G9P[8] (17.7%), G3P[8] 13.1%, G4P[8] (9.5%), and G2P[4] (1.8%); mixed rotavirus infections occurred in 2.3%. G9 rotaviruses emerged during the 2004-2005 season (73.4%) and remained the second most prevalent strains. Few unusual strains, G6, G8, G12 and P[6]-types, were detected. The monitoring of rotavirus infections should be maintained to document strain distribution and to assess the emergence of new reassortants that may not respond to current rotavirus vaccines.

NF-kappaB inhibition sensitizes to starvation-induced cell death in high-risk myelodysplastic syndrome and acute myeloid leukemia.

CD34(+) bone marrow blasts from high-risk myelodysplastic syndrome (MDS) patients as well as MDS patient-derived cell lines (P39 and MOLM13) constitutively activate the nuclear factor-kappaB (NF-kappaB) pathway and undergo apoptosis when NF-kappaB is inhibited. Here, we show that the combination of conventional chemotherapeutic agents (daunorubicin, mitoxantrone, 5-azacytidine or camptothecin) with the NF-kappaB inhibitor BAY11-7082 did not yield a synergistic cytotoxicity. In contrast, BAY11-7082 (which targets the NF-kappaB-activating I-kappaB kinase (IKK) complex) or knockdown of essential components of the NF-kappaB system (such as the IKK1 and IKK2 subunits of the IKK complex and the p65 subunit of NF-kappaB), by small interfering RNAs sensitized MDS cell lines to starvation-induced apoptosis. The combination of BAY11-7082 and nutrient depletion synergistically killed the acute myeloid leukemia (AML) cell line U937 as well as primary CD34(+) bone marrow blasts from AML and high-risk MDS patients. The synergistic killing by BAY11-7082, combined with nutrient depletion, led to cell death accompanied by all hallmarks of apoptosis, including an early loss of the mitochondrial transmembrane potential, the release of cytochrome c and apoptosis-inducing factor (AIF) from mitochondria, activation of caspase-3, phosphatidylserine exposure on the plasma membrane surface and nuclear chromatin condensation. Transmission electron microscopy revealed the presence of numerous autophagic vacuoles in the cytoplasm before cells underwent nuclear apoptosis. Nonetheless, cell death was neither inhibited by the pan-caspase inhibitor z-VAD-fmk nor by knockdown of AIF or of essential components of the autophagy pathway (ATG5, ATG6/Beclin-1, ATG10, ATG12). In contrast, external supply of glucose, insulin or insulin-like growth factor-I could retard the cell death induced by BAY11-7082 combined with starvation. These results suggest that in MDS cells, NF-kappaB inhibition can precipitate a bioenergetic crisis that leads to an autophagic stress response followed by apoptotic cell death.

Inhibition of NEMO, the regulatory subunit of the IKK complex, induces apoptosis in high-risk myelodysplastic syndrome and acute myeloid leukemia.

In high-risk myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), blasts constitutively activate the antiapoptotic transcription factor nuclear factor-kappaB (NF-kappaB). Here, we show that this NF-kappaB activation relies on the constitutive activation of the IkappaB kinase (IKK) complex, which is formed by the IKKalpha, IKKbeta and IKKgamma/NF-kappaB essential modulator (NEMO) subunits. A cell-permeable peptide that mimics the leucine zipper subdomain of IKKgamma, thus preventing its oligomerization, inhibited the constitutive NF-kappaB activation and induced apoptotic cell death in a panel of human MDS and AML cell lines (P39, MOLM13, THP1 and MV4-11). Small interfering RNA-mediated knockdown of the p65 NF-kappaB subunit or the three IKK subunits including IKKgamma/NEMO also induced apoptotic cell death in P39 cells. Cell death induced by the IKKgamma/NEMO-antagonistic peptide involved the caspase-independent loss of the mitochondrial transmembrane potential as well as signs of outer mitochondrial membrane permeabilization with the consequent release of cytochrome c, apoptosis-inducing factor and endonuclease G. Primary bone marrow CD34(+) cells from high-risk MDS and AML patients also succumbed to the IKKgamma/NEMO-antagonistic peptide, but not to a mutated control peptide. Altogether, these data indicate that malignant cells in high-risk MDS and AML cells critically depend on IKKgamma/NEMO to survive. Moreover, our data delineate a novel procedure for their therapeutic removal, through inhibition of IKKgamma/NEMO oligomerization.

Factors favouring palliative treatment multidisciplinary decisions for newly diagnosed visceral and soft tissue sarcomas.

AIMS: The multidisciplinary medical decision-making process is a key element of the clinical management of cancers, especially rare cancers such as visceral and soft tissue sarcomas. One of the most important decisions stated is to discriminate patients considered for palliative-intent treatment. The aim of this retrospective study was to establish the rationale parameters that justify this decision for newly diagnosed sarcomas. PATIENTS AND METHODS: From a retrospective cohort of 341 patients we investigated the parameters justifying a palliative-intent strategy decision in univariate and multivariate analyses, based on the logistic regression model. We also measured the effect of this decision on overall survival using the Cox model. RESULTS: Seventy-one of 341 patients (20%) were considered for a palliative-intent strategy. In multivariate analysis, five variables justified this decision: contraindication for general anaesthesia (adjusted odds ratio 10.5), head and neck location (odds ratio 3.7), visceral sarcoma (odds ratio 2.8), tumour size over 8 cm (odds ratio 3.5) and presence of metastasis (odds ratio 39.5). In the Cox model we found that two independent factors were associated with poor outcome: grade 3 (hazard ratio 2.7) and palliative-intent strategy (hazard ratio 3.3). CONCLUSIONS: About 20% of newly diagnosed sarcomas were considered for palliative strategy by multidisciplinary committee. This decision was based on rationale parameters and had an intrinsic prognostic value.

Prognostic factors for adult sarcomas of head and neck.

The optimal management of adult soft-tissue sarcomas is not clearly established. To assess prognostic factors and survival, the experience of 45 recent successive cases was reviewed. Data were collected from a retrospective database (1993-2005) and statistically analyzed. Rhabdomyosarcomas were excluded. The mean age was 50.1 years; there were 24 men and 21 women. The main histological subtypes were undifferentiated sarcoma (14) and angiosarcoma (10); 21 tumours were grade 3 (46%). The most frequent primary sites were neck muscles (15, 33%) and scalp (11, 24%). At presentation, 5 (20%) cases with lymph-node involvement and another 11 cases (24%) with distant metastasis were observed. The treatment was with curative intent in 33 cases (73%). This entailed surgery, with adjuvant radiotherapy in 15 cases and adjuvant chemotherapy in 5 cases. The 5-year overall survival was 52% (+/-8%). In univariate analysis, the poor prognostic factors were high grade, initial metastasis or lymph nodes, absence of surgery, and number of surgical procedures. In multivariate analysis, two factors remained significant: grade (P=0.006) and absence of surgery (P=0.005). After taking into account grade and metastasis at presentation, quality of surgery has prognostic value. The primary aim of a multidisciplinary approach to these tumours must favour complete resection.

Targeting NF-kappaB in hematologic malignancies.

The transcription factor nuclear factor kappa B (NF-kappaB) can intervene in oncogenesis by virtue of its capacity to regulate the expression of a plethora of genes that modulate apoptosis, and cell survival as well as proliferation, inflammation, tumor metastasis and angiogenesis. Different reports demonstrate the intrinsic activation of NF-kappaB in lymphoid and myeloid malignancies, including preneoplastic conditions such as myelodysplastic syndromes, underscoring its implication in malignant transformation. Targeting intrinsic NF-kappaB activation, as well as its upstream and downstream regulators, may hence constitute an additional approach to the oncologist's armamentarium. Several small inhibitors of the NF-kappaB-activatory kinase IkappaB kinase, of the proteasome, or of the DNA binding of NF-kappaB subunits are under intensive investigation. Currently used cytotoxic agents can induce NF-kappaB activation as an unwarranted side effect, which confers apoptosis suppression and hence resistance to these drugs. Thus, NF-kappaB inhibitory molecules may be clinically useful, either as single therapeutic agents or in combination with classical chemotherapeutic agents, for the treatment of hematological malignancies.

[Transposition of the great arteries with pulmonary valvular stenosis and intact interventricular septum. Discussion of management strategies with respect to one case]. / Transposition des gros vaisseaux avec sténose valvulaire pulmonaire à septum interventriculaire intact. Discussion des enjeux thérapeutiques à propos d'un cas.

The authors report the case of a neonate with transposition of the great arteries (TGA) with pulmonary stenosis (PS) and intact Interventricular septum. The child was born at full term without a prenatal diagnosis with cyanosis developing at the 12th hour. After emergency atrioseptostomy, detransposition was performed on the 6th day. Commissurotomy and shaving of the much thickened bicuspid pulmonary valve was also performed. The postoperative course was complicated by a non-compliant left ventricle. After two months, myocardial ischaemia and persistent obstruction of the outflow tract led to severe cardiac failure and the death of the child. TGA with PS and intact interventricular septum is a very rare cardiac malformation. The prognosis is closely related to the anatomy of the pulmonary valve and the impact on the left ventricle. The therapeutic options are complex and are discussed in relation to this case.

[Ultra-late metastasis of ocular melanoma: about two cases]. / Dissémination métastatique ultratardive de mélanome oculaire : à propos de deux cas.

INTRODUCTION: Ocular melanoma is associated with extended risk of metastases, mainly liver metastases. Nevertheless, the late and ultra-late recurrence (respectively 10 and 15 years after initial treatment) are exceptional events. EXEGESIS: We describe hereafter two cases. In the first case, the treatment is palliative chemotherapy with death 12 months after metastasis diagnosis. In the second case, the patient underwent two resections of metastases (lung and liver). This patient had excellent quality of live, and survived 11 months later after palliative surgery. DISCUSSION: Follow-up of ocular melanoma patients should include liver enzymes and ultrasonography of liver in the long run.

[Prognosis of post-irradiation soft-tissue sarcoma: case-control study]. / Pronostic des sarcomes des tissus mous en territoire irradié: étude cas-témoins.

PURPOSE: We describe clinical and pathological aspects and survival of 12 recent of radio-induced soft tissue sarcoma. METHOD: We performed a single center case-control study, with 23 control matched by grade (according to Federation nationale des centres de lutte contre le cancer Grading) and by location. Survival comparison used Log Rank test. RESULTS: The development of these 12 cases was a result of 12 previous cancer treatment (including 4 breast cancers and 2 cervix cancers) with radiotherapy (median dose of 58 Grays). The median latency period was 10 years. There were nine women and three men. The median age was 68.5 years. The main location was chest wall (5 cases). The two main histologic subtypes were malignant histiocytofibromas (6 cases) and angiosarcomas (3 cases). Five cases were high grade. Treatments were performed with curative intent in 9 cases, including complete resection in six cases. Clinical and pathological aspects and treatments of controls were similar, but postoperative radiotherapy was most frequent and malignant histiocytofibroma was less common. Median overall survival (47 months vs. 30 months, P = 0.6), median metastatic disease-free survival (37 vs. 15 m., P = 0.6) and median locoregional disease-free survival (14 vs. 24 m., P = 0.07) were similar for cases and control. CONCLUSION: This study suggests that prognosis of radio-induced soft-tissue sarcomas is similar as other soft tissue sarcoma of same grade and same location.

Human cytomegalovirus quantification in toddlers saliva from day care centers and emergency unit: a feasibility study.

BACKGROUND: Cytomegalovirus (CMV) infection is the most important cause of congenital viral infection in developed countries. In utero transmission occurs at higher rates in seronegative women during primary infection, especially those in contact with young children in day-care centers (DCC). Nevertheless data on variability of CMV excretion among children in French DCCs are lacking, and are important for public health planning. OBJECTIVES: Our main objective was to assess the feasibility of a salivary sample in DCCs in order to study CMV excretion among toddlers. Our secondary aims were to assess prevalence of CMV excretion in children attending Hospital Emergency Unit (EU) in comparison with various types of DCCs and to validate the analytical chain for collected specimens. STUDY DESIGN: Excretion of CMV in saliva was quantified using a real-time PCR assay in children aged from 3 months to 6 years old in EU and in DCC, with gB, gH and gN genotypes determined in infected children. Salivary sampling was performed using small sponges placed into a DNA conservation medium. Socio cultural and medical information were collected from attending parents. RESULTS: A total of 625 children were included, with 256 from six DCCs and 369 from one EU. In DCCs, the acceptability of the procedure was 87.3% (95%CI 78.5-96.2) amongst parents and children, and in the EU, acceptability was higher at 97.6% (95%CI 95.5-98.9). CMV shedding overall prevalence was 21.7% (95%CI 17.6-26.2), with CMV shedding prevalence in DCCs of 51.9% (95%CI 22.8-81.1). CONCLUSION: We validated the feasibility and acceptability of measuring CMV shedding in the saliva of French toddlers. The discrepancy between CMV infection rates in day care centers and in the general population (as sampled in the EU) indicates the need for a further study to determine risk factors and shedding levels in the DCC population.

Accidental potassium dichromate poisoning. Toxicokinetics of chromium by ICP-MS-CRC in biological fluids and in hair.

Intoxications by chromium (Cr) compounds are very life threatening and often lethal. After oral ingestion of 2 or 3g of hexavalent Cr (Cr(VI)), gastrointestinal injury, but also hepatic and renal failure, often occurs which each leads to a fatal outcome in most patients. Cellular toxicity is associated with mitochondrial and lysosomal injury by biologically Cr(VI) reactive intermediates and reactive oxygen species. After Cr(VI) has been absorbed, there is not much that can be done except to control the main complications as the treatment is only symptomatic. The biotransformation of Cr(VI) to Cr(III) reduces the toxicity because the trivalent form does not cross cellular membranes as rapidly. In fact, more than 80% of Cr(VI) is cleared in urine as Cr(III). We report the case of a 58-year-old male patient who was admitted to hospital after accidental oral ingestion of a 30 g/L potassium dichromate (the estimated amount of ingested Cr is about 3g). ICP-MS equipped with a collision/reaction cell (CRC) and validated methods were used to monitor plasma (P), red blood cells (RBCs), urine (U) and hair chromium. For urine the results were expressed per gram of creatinine. After 7 days in the intensive care unit, the patient was discharged without renal or liver failure. P, RBC and U were monitored during 49 days. During this period Cr decreased respectively from 2088 µg/L to 5 µg/L, 631 µg/L to 129 µg/L and 3512 µg/g to 10 µg/g. The half-life was much shorter in P than in RBC as the poison was more quickly cleared from the P than from the RBC, suggesting a cellular trapping of the metal. Hair was collected 2 months after the intoxication. We report a very rare case of survival after accidental Cr poisoning which has an extremely poor prognosis and usually leads to rapid death. For the first time, this toxicokinetic study highlights a sequestration of chromium in the RBC and probably in all the cells.

Direct genotyping of cytomegalovirus envelope glycoproteins from toddler's saliva samples.

BACKGROUND: The polymorphism of genes encoding CMV envelope protein is used for strain classification and may influence pathogenesis and/or infectivity. CMV genotyping is usually based on sequencing or acrylamide gel-RFLP, but these methods are not suited to rapid screening of large populations. OBJECTIVES: We developed a high-throughput method to analyze CMV strains diversity and to detect multiple-strain infection in a large population of toddlers (six daycare centers (DCC) and an emergency unit (EU)). METHODS: We developed a new PCR-RFLP method coupled with capillary electrophoresis fragment detection for UL55-gB, UL75-gH and UL73-gN genotyping. To detect gB recombinants, gpUL55 typing was applied to two variable zones (NTerminal and central). We applied this method to 212 CMV-positive saliva samples and controlled the results by direct sequencing of PCR products. RESULTS: We identified 112 strains, that fell into eight groups in UL55-gB, two groups in UL75-gH, and seven groups in UL73-gN. The 79 samples from the emergency unit contained 30 strains, 28 children harboring 2 strains. The samples (n=133) from the six daycare centers contained respectively 4, 1, 6, 1 and 11 strains. Fifteen percent of strains were UL55-gB recombinants. CONCLUSION: Our new method can simultaneously determine gB, gH and gN genotypes and offers more precise classification of CMV strains than previous RFLP-based methods. This could constitute the basis for a new classification, particularly in UL55-gB. Easy direct identification of multiple strains and recombinants in pathological samples could facilitate large epidemiologic studies.