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Purpose: The severity of bleeding events is heterogeneously defined during peripheral veno-arterial extracorporeal membrane oxygenation (pVA-ECMO). We studied three bleeding definitions in pVA-ECMO: the Extracorporeal Life Support Organization (ELSO)-serious bleeding, the Bleeding Academic Research Consortium (BARC), and the universal definition of postoperative bleeding (UPDB) classifications. Methods: We included consecutive adult patients supported by pVA-ECMO for refractory cardiogenic shock admitted to Lille academic hospitals between January 2013 and December 2019. We assessed the association of bleeding definitions with the primary endpoint of 28-day all-cause mortality with the use of multivariate models accounting for time-dependent and competing variables. We compared models’ performances using the Harrell’s C-Index and the Akaike information criteria. Results: Twenty-eight-day mortality occurred in 128/308 (42%) 308 patients. The ELSO-serious bleeding (hazard ratio [HR], 1.67; 95% confidence interval [CI], 1.09 to 2.56) and BARC ≥ type 2 (HR, 1.55; 95% CI, 1.01 to 2.37) were associated with 28-day mortality (Harrell’s C-index, 0.69; 95% CI, 0.63 to 0.74 for both). Predictors of ELSO-serious bleeding were postcardiotomy, body mass index, baseline platelets count, fibrinogen, and hemoglobin levels. Conclusion: Extracorporeal Life Support Organization-serious bleeding and BARC ≥ type 2 are relevant definitions of major bleeding regarding their association with mortality in critically ill patients who survived the first 24 hr while supported with pVA-ECMO for cardiogenic shock. Study registration: CERAR (IRB 00010254-2022-050, Paris, France); first submitted on 18 April 2022.

Background: Prostate cancer remains the most frequently diagnosed cancer among men. High-Intensity Focused Ultrasound (HIFU) has emerged as a thermal ablative technique for partial-gland-ablation (PGA), aiming to minimize collateral damage while maximizing tumor control. Monitoring after HIFU PGA relies on serial PSA testing, multiparametric-MRI, and biopsies. The diagnostic accuracy of MRI for clinically-significant cancer(csPCa) recurrence is challenging. Objective: This systematic review and meta-analysis aim to evaluate the accuracy of MRI in detecting early recurrence of localized prostate cancer following HIFU PGA. Methods: Adhering to PRISMA guidelines, a comprehensive literature search was conducted until May 8th2024 using MEDLINE and Scopus. The inclusion criteria encompassed randomized controlled trials and cohort studies involving men diagnosed with localized prostate cancer who had as primary treatment HIFU PGA. The primary outcome measures included the sensitivity, specificity, positive-predictive value (PPV), and negative-predictive value (NPV) of MRI for csPCa(ISUP ≥ 2) based on biopsy results. We pooled data from studies with sufficient csPCa and csPCa-free patients (≥5) post HIFU for statistical analysis. Results: Fifteen studies meet the inclusion criteria, encompassing 1093 patients and 12 studies were eligible for meta-analysis. MRI sensitivity in detecting clinically-significant prostate cancer (csPCa) recurrence post HIFU PGA varied widely (0–89%), with a pooled sensitivity of 0.52 (95% CI:0.36–0.68). Specificity ranged from 44% to 100%, with a pooled specificity of 0.81 (95% CI:0.68–0.91). The pooled NPV was 0.82 (95% CI:0.72–0.90), and the pooled PPV was 0.50 (95% CI:0.35–0.65). Three studies reported in-field diagnostic performance with sensitivities ranging from 0.42 to 0.80 and specificities from 0.45 to 0.97. Conclusion: MRI accuracy for clinically-significant recurrence after partial gland ablation with HIFU for localized prostate cancer shows low diagnostic performance in the treated lobe with pooled sensitivity of 0.52 (95% CI:0.36–0.68) and specificity of 0.81 (95% CI:0.68–0.91). Limits of this review include the low number of studies reporting about site of recurrence in or out of the treated lobe.

Information on bladder cancer (BC) according to the risk scoring for recurrence or progression in a general population is scarce despite its clinical relevance. The objective was to describe the characteristics of incident BC in a general population, with a focus on the initial management of high-risk non-muscle invasive BC (HR-NMIBC).

Most succinate dehydrogenase (SDH)-deficient renal cell carcinomas (RCCs) demonstrate stereotypical morphology characterized by bland eosinophilic cells with frequent intracytoplasmic inclusions. However, variant morphologic features have been increasingly recognized. We therefore sought to investigate the incidence and characteristics of SDH-deficient RCC with variant morphologies. We studied a multi-institutional cohort of 62 new SDH-deficient RCCs from 59 patients. The median age at presentation was 39 years (range 19–80), with a slight male predominance (M:F = 1.6:1). A relevant family history was reported in 9 patients (15%). Multifocal or bilateral tumors were identified radiologically in 5 patients (8%). Typical morphology was present at least focally in 59 tumors (95%). Variant morphologies were seen in 13 (21%) and included high-grade nuclear features and various combinations of papillary, solid, and tubular architecture. Necrosis was present in 13 tumors, 7 of which showed variant morphology. All 62 tumors demonstrated loss of SDHB expression by immunohistochemistry. None showed loss of SDHA expression. Germline SDHmutations were reported in all 18 patients for whom the results of testing were known. Among patients for whom follow-up data was available, metastatic disease was reported in 9 cases, 8 of whom had necrosis and/or variant morphology in their primary tumor. Three patients died of disease. In conclusion, variant morphologies and high-grade nuclear features occur in a subset of SDH-deficient RCCs and are associated with more aggressive behavior. We therefore recommend grading all SDH-deficient RCCs and emphasize the need for a low threshold for performing SDHB immunohistochemistry in any difficult to classify renal tumor, particularly if occurring at a younger age.

Failure to resolve inflammation underlies many prevalent pathologies. Recent insights have identified lipid mediators, typified by lipoxins (LXs), as drivers of inflammation resolution, suggesting potential therapeutic benefit. We report the asymmetric preparation of novel quinoxaline-containing synthetic-LXA4-mimetics (QNX-sLXms). Eight novel compounds were screened for their impact on inflammatory responses. Structure–activity relationship (SAR) studies showed that (R)-6(also referred to as AT-02-CT) was the most efficacious and potent anti-inflammatory compound of those tested. (R)-6significantly attenuated lipopolysaccharide (LPS)- and tumor-necrosis-factor-α (TNF-α)-induced NF-κB activity in monocytes and vascular smooth muscle cells. The molecular target of (R)-6was investigated. (R)-6activated the endogenous LX receptor formyl peptide receptor 2 (ALX/FPR2). The anti-inflammatory properties of (R)-6were further investigated in vivoin murine models of acute inflammation. Consistent with in vitroobservations, (R)-6attenuated inflammatory responses. These results support the therapeutic potential of the lead QNX-sLXm (R)-6in the context of novel inflammatory regulators.

Most succinate dehydrogenase (SDH)-deficient renal cell carcinomas (RCCs) demonstrate stereotypical morphology characterized by bland eosinophilic cells with frequent intracytoplasmic inclusions. However, variant morphologic features have been increasingly recognized. We therefore sought to investigate the incidence and characteristics of SDH-deficient RCC with variant morphologies. We studied a multi-institutional cohort of 62 new SDH-deficient RCCs from 59 patients. The median age at presentation was 39 years (range 19–80), with a slight male predominance (M:F = 1.6:1). A relevant family history was reported in 9 patients (15%). Multifocal or bilateral tumors were identified radiologically in 5 patients (8%). Typical morphology was present at least focally in 59 tumors (95%). Variant morphologies were seen in 13 (21%) and included high-grade nuclear features and various combinations of papillary, solid, and tubular architecture. Necrosis was present in 13 tumors, 7 of which showed variant morphology. All 62 tumors demonstrated loss of SDHB expression by immunohistochemistry. None showed loss of SDHA expression. Germline SDHmutations were reported in all 18 patients for whom the results of testing were known. Among patients for whom follow-up data was available, metastatic disease was reported in 9 cases, 8 of whom had necrosis and/or variant morphology in their primary tumor. Three patients died of disease. In conclusion, variant morphologies and high-grade nuclear features occur in a subset of SDH-deficient RCCs and are associated with more aggressive behavior. We therefore recommend grading all SDH-deficient RCCs and emphasize the need for a low threshold for performing SDHB immunohistochemistry in any difficult to classify renal tumor, particularly if occurring at a younger age.

Supplemental Digital Content is available in the text.Eosinophilic solid and cystic renal cell carcinoma (ESC RCC) has been recently described as a unique and indolent renal neoplasm, found in female patients with and without tuberous sclerosis complex. Although ESC RCC has a distinct morphology and frequent CK20 reactivity, its molecular karyotype has been previously studied only in few cases. We identified 19 ESC RCC from multiple institutions; all patients were female individuals without clinical features of tuberous sclerosis complex. Molecular karyotyping was performed in 13 cases (12 with informative result). The median age was 55 years (range: 32 to 79 y). The tumors were yellow-gray with a median size of 31 mm (range: 12 to 135 mm) and showed solid and cystic gross appearance. All tumors demonstrated typical microscopic features with solid areas admixed with variably sized macrocysts and microcysts. The cells showed eosinophilic cytoplasm with granular cytoplasmic stippling and round-to-oval nuclei. CK20 was positive in 14/19 (74%) cases. Stage pT1 was found in 17/19 (89%) patients (pT1a in 12, pT1b in 5); 1 patient each had pT2a and pT3a. A total of 15/16 patients with available follow-up were alive and without evidence of disease progression, after 1 to 169 months (median: 44 mo; mean: 49.6 mo); 3 died of other causes. The most common copy number gains were 16p13.3-16q23.1 (33% to 67%), 7p21.2-7q36.2 (42% to 50%), 13q14.2 (33%), and 19p12 (33%). The most common copy number losses included Xp11.21 (42%) and 22q11.23 (33%). Loss of heterozygosity was most frequently found at 16p11.2-11.1 (75%), Xq11.1-13.1 (75%), Xq13.1-21.1 (33%), 11p11.2-11.11 (33%), 9q21.1-22.2 (33%), and 9q33.1 (33%). ESC RCC demonstrates common molecular karyotype alterations, which further support its distinct nature.

Nous rapportons l’observation d’un enfant âgé de 3ans, décédé des suites d’un arrêt cardio-respiratoire, malgré la réanimation. L’échographie cardiaque et l’imagerie par résonance magnétique (IRM) révélaient une masse de la paroi libre du ventricule gauche. L’autopsie confirmait l’existence d’une tumeur myocardique unique, bien circonscrite, ferme, d’aspect fasciculé et de couleur blanche. À l’examen histologique, la tumeur se composait de faisceaux de cellules fusiformes régulières, mêlées à des fibres collagènes et élastiques, s’insinuant entre les myocytes en périphérie. Des calcifications étaient présentes. En immuno-histochimie, les cellules étaient marquées par l’anticorps anti-actine fibre musculaire lisse, mais elles n’étaient pas marquées par les anticorps anti-desmine, anti-β caténine et anti-Ki67. Le diagnostic de fibrome cardiaque était posé. Les tumeurs cardiaques primitives de l’enfant sont rares et le plus souvent bénignes. Elles sont essentiellement représentées par les rhabdomyomes et les fibromes. Le fibrome cardiaque survient préférentiellement durant la première année de vie. Il peut être révélé par une insuffisance cardiaque, un trouble du rythme, une douleur thoracique ou une mort subite.

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder with characteristic tumors involving multiple organ systems. Whereas renal angiomyolipoma (AML) is common in TSC, renal cell carcinoma (RCC) is rarely reported. Fifty-seven RCCs from 13 female and 5 male TSC patients were reviewed. Age at surgery ranged from 7 to 65 years (mean: 42 y). Nine patients (50%) had multiple synchronous and/or metachronous RCCs (range of 2 to 20 RCCs) and 5 had bilateral RCCs (28%). Seventeen patients (94%) had histologically confirmed concurrent renal AMLs, including 15 with multiple AMLs (88%) and 9 (50%) with AMLs with epithelial cysts. None of the 15 patients with available clinical follow-up information had evidence of distant metastatic disease from 6 to 198 months after their initial surgery (mean: 52 mo). The 57 RCCs exhibited 3 major distinct morphologies: (1) 17 RCCs (30%) had features similar to tumors previously described as “renal angiomyoadenomatous tumor” or “RCC with smooth muscle stroma”; (2) 34 RCCs (59%) showed features similar to chromophobe RCC; and (3) 6 RCCs (11%) showed a granular eosinophilic-macrocystic morphology. Distinct histologic changes were also commonly present in the background kidney parenchyma and included cysts or renal tubules lined by epithelial cells with prominent eosinophilic cytoplasm, nucleomegaly, and nucleoli. Immunohistochemically, all RCCs tested showed strong nuclear reactivity for PAX8 and HMB45 negativity. Compared with sporadic RCCs, TSC-associated RCCs have unique clinicopathologic features including female predominance, younger age at diagnosis, multiplicity, association with AMLs, 3 recurring histologic patterns, and an indolent clinical course. Awareness of the morphologic and clinicopathologic spectrum of RCC in this setting will allow surgical pathologists to better recognize clinically unsuspected TSC patients.

The objectives of this study were to compare demographic, clinical, radiographic, scintigraphic, and histologic differences between the 2 main types of condylar hyperplasia (CH) and to suggest a new therapeutic management based on such findings.

Les cancers de l’ouraque représentent une maladie rare (moins de 1 % de l’ensemble des tumeurs vésicales) avec un pronostic péjoratif, tout stade confondu, du fait d’une grande latence clinique responsable d’un retard au diagnostic, d’un diagnostic différentiel parfois difficile à faire avec le cancer de la vessie, et de l’absence d’harmonisation quant à sa prise en charge, notamment pour la chimiothérapie dans les stades avancés, en raison de l’absence de données issues d’études prospectives. Si un traitement chirurgical curatif peut être réalisé dans les stades localisés, il n’existe pas de consensus pour le traitement des récidives locales et des évolutions métastatiques. Ces cancers sont peu radio- et chimiosensibles, cependant, les données de recherche fondamentale sont quasiment inexistantes. Du fait de leur rareté, ils n’ont jamais été testés pour les thérapies ciblées. L’objectif de la revue est de présenter les principales caractéristiques cliniques et paracliniques de ces cancers, ainsi que les traitements habituellement réalisés.

Upper urinary tract urothelial carcinoma (UUTUC) is an uncommon neoplasm frequently discovered at a high-stage disease. The prognosis of disseminated UUTUCs is poor despite the use of platinum-based chemotherapy. The aim of the study was to evaluate HER2 overexpression and amplification in a series of 83 UUTUCs.

Les fibrosarcomes (FS) sont des cancers rares en pédiatrie, classés au sein du groupe hétérogène des tumeurs mésenchymateuses malignes non rhabdomyosarcomes. Les FS dits «infantiles »(FSI) sont retrouvés, par définition, chez l’enfant de moins de deux ans, et comprennent aussi les FS « congénitaux » survenant en général chez le nourrisson de moins de trois mois. Le diagnostic histologique peut être difficile et est confirmé par la mise en évidence de la protéine de fusion ETV6-NTRK3. La maladie est souvent localisée au diagnostic et touche les membres. La prise en charge de ces malades se doit d’être pluridisciplinaire, et éviter les gestes chirurgicaux mutilants. Les « néphromes mésoblastiques atypiques » ou cellulaires (NM cellulaires) sont un sous-type de tumeur rénale maligne pédiatrique, touchant le plus souvent le nourrisson de moins de trois mois. Les caractéristiques histopathologiques du NM cellulaire sont très proches de celles du FS congénital avec un transcrit de fusion commun à ces deux maladies. Les traitements sont fonction du stade, principalement local, de la maladie. Les fibrosarcomes dits « de type adulte » (FSA), retrouvés exceptionnellement chez l’enfant, surviennent le plus souvent après l’Âge de dix ans. Leur traitement nécessite le plus souvent chirurgie large, chimiothérapie±radiothérapie. Les FSA diffèrent des FSI dans leur présentation clinique du fait d’une agressivité locale marquée et un mode évolutif plus sévère avec apparition de métastases dans 50 % des cas environ, parfois tardivement. Ces trois maladies présentent donc des similitudes histologiques. Deux ont une dénomination commune mais une présentation clinique et un mode évolutif différents : les FS infantiles et les FS de type adulte. Deux ont une dénomination ainsi qu’une localisation initiale différentes mais une histologie, un remaniement chromosomique, une sensibilité à la chimiothérapie avec une évolution semblant comparables : les FS congénitaux et les NM cellulaires. Les auteurs font le point sur les données de la littérature concernant ces trois entités en pédiatrie.

La photothérapie dynamique (PDT) est une modalité thérapeutique innovante en cancérologie urologique.

Objectives/Hypothesis:To examine the level of expression of galectin‐3 in relation to neoplastic progression of hypopharyngeal squamous cell carcinomas (HSCCs) and laryngeal squamous cell carcinomas (LSCCs).

Abstract: We propose a benchmark to compare theorem-proving systems on their ability to express proofs of compiler correctness. In contrast to the first POPLmark, we emphasize the connection of proofs to compiler implementations, and we point out that much can be done without binders or alpha-conversion. We propose specific criteria for evaluating the utility of mechanized metatheory systems; we have constructed solutions in both Coq and Twelf metatheory, and we draw conclusions about those two systems in particular. [Copyright &y& Elsevier]

Polyunsaturated fatty acid (PUFA) immunomodulatory properties have been studied extensively in chronic infections. Few studies have focused on acute infection; thus, PUFA effects in a mouse model of Pseudomonas aeruginosa (PA)-induced lung injury were evaluated. C57BL/6 mice were randomized to be fed for 3 wk with an eicosapentaenoic acid (EPA) diet, an arachidonic acid (AA) diet, or a control diet [saturated fatty acids]. Lung injury was induced by intratracheal instillation of 107CFU of PA per mouse. In each diet group, animals were studied either without or after PA–inducing lung injury. Evaluation criteria were early mortality; inflammatory response assessed with tumor necrosis factor-a (TNF-a), IL-1ß, IL-6 and IL-10 levels in bronchoalveolar lavage; lung injury evaluation; and extravascular lung water, assessed 24 h after the injury. After PA-induced lung injury, no difference in early mortality was observed; TNF-a level was significantly higher in the EPA diet than in the other two diet groups. No difference for the other cytokines was found among the groups. Lung edema was also more important in the EPA group, consistent with the variations of TNF-a levels. Our study clearly shows that in PA-induced acute lung injury, n-3 PUFA induces differences in the inflammatory response with a higher level of lung edema. Modulation of the inflammatory response with n-3 PUFA can influence the response to a bacterial challenge.

Polyunsaturated fatty acid (PUFA) immunomodulatory properties have been studied extensively in chronic infections. Few studies have focused on acute infection; thus, PUFA effects in a mouse model of Pseudomonas aeruginosa(PA)-induced lung injury were evaluated. C57BL/6 mice were randomized to be fed for 3 wk with an eicosapentaenoic acid (EPA) diet, an arachidonic acid (AA) diet, or a control diet saturated fatty acids. Lung injury was induced by intratracheal instillation of 107CFU of PA per mouse. In each diet group, animals were studied either without or after PA–inducing lung injury. Evaluation criteria were early mortality; inflammatory response assessed with tumor necrosis factor- (TNF-), IL-1, IL-6 and IL-10 levels in bronchoalveolar lavage; lung injury evaluation; and extravascular lung water, assessed 24 h after the injury. After PA-induced lung injury, no difference in early mortality was observed; TNF- level was significantly higher in the EPA diet than in the other two diet groups. No difference for the other cytokines was found among the groups. Lung edema was also more important in the EPA group, consistent with the variations of TNF- levels. Our study clearly shows that in PA-induced acute lung injury, n-3 PUFA induces differences in the inflammatory response with a higher level of lung edema. Modulation of the inflammatory response with n-3 PUFA can influence the response to a bacterial challenge.

In acute lung injury (ALI), a coagulation/fibrinolysis imbalance leads to fibrin deposition, persistence of which contributes to fibrotic evolution. Our study evaluated the effects of early inhibition of coagulation in Pseudomonas aeruginosa(Pa)-induced ALI through the use of recombinant human antithrombin (rhAT). The study was conducted in vivoon a murine model of Pa-induced ALI. Intravenous rhAT was administered simultaneously with intratracheal Pa. Four experimental groups were compared: CTR, intratracheal saline (0.5 mL/kg)/intravenous saline (1 mL); PNP, intratracheal Pa(0.5 mL/kg of 2 × 109cfu)/intravenous saline; AT, intratracheal saline/intravenous rhAT (500 IU/kg); ATPNP, intratracheal Pa/intravenous rhAT. Epithelial and endothelial permeabilities were evaluated with radiolabeled albumin flux across the alveolar barrier (125I- and 131I-labeled albumin). Thrombin-antithrombin (TAT) complexes levels were used as markers of coagulation activation in blood samples and in BAL fluid. Epithelial and endothelial protein permeability were increased in Pa-induced ALI versus control. Intravenous rhAT administration led to further permeability disorders. Administration of rhAT in PaALI led to a rise in TAT complexes in ATPNP blood serum and BAL fluids compared with the other groups. In Pa-induced ALI the administration intravenous rhAT leads to major histologic damage, alveolar capillary barrier injury, and permeability increase. Such effects of the inhibition of thrombin activation by rhAT lead to the hypothesis of a probable beneficial role of early coagulation activation in ALI as a factor limiting both the extent of injury and permeability disorders. Our study suggests that inhibition of this initial procoagulative imbalance is potentially dangerous.

Human mucin genes encode large O-glycoproteins, which are expressed in various epithelial tissues. The proteins are the main components of mucus, but also might be involved in morphogenesis of or carcinogenesis in many organs. We studied the expression of human mucin genes during fetal kidney development and in malformed cystic renal diseases in 10 normal fetal kidneys and 12 malformed kidneys by in situ hybridization and immunohistochemical analysis. MUC1, MUC3, and MUC6 were expressed in normal fetal kidney. MUC1 was expressed from 7.5 weeks of gestation in the metanephric blastema and throughout fetal life in the ureteric buds, distal convoluted tubules, and collecting ducts. MUC3 was expressed weakly in immature tubules from 8 weeks of gestation, after which it was expressed weakly and focally in the proximal convoluted tubules. MUC6 was expressed at 9.5 weeks of gestation in the tips of the ureteric buds and later in the collecting ducts. In malformative cystic diseases, only MUC1 expression was retained; no expression of MUC6 and MUC3 was observed. These results implicate human mucin genes (MUC1, MUC3, and MUC6) in renal morphogenesis processes.

Bytecode verification is a crucial security component for Java applets, on the Web and on embedded devices such as smart cards. This paper reviews the various bytecode verification algorithms that have been proposed, recasts them in a common framework of dataflow analysis, and surveys the use of proof assistants to specify bytecode verification and prove its correctness.

We studied, by immunohistochemical analysis, the expression of MUC1 and epithelial membrane antigen in 44 stage pT1 renal cell carcinomas (RCCs). Six patients had a metastatic evolution. The percentage of stained cells was determined for each tumor. All tumors and normal adjacent renal parenchyma were stained. In normal kidney, distal convoluted tubules and collecting ducts stained strongly with an apical distribution. In tumors, there was a significant statistical correlation of the MUC1 expression level with the nuclear grade and with tumor progression. High-grade tumors had more stained cells than did low-grade tumors. Metastatic tumors also were more stained than nonmetastatic lesions. By using the Kaplan-Meier method and the log-rank test, we observed that patients with fewer than 10% of stained cells had no metastatic evolution. In contrast, patients with 70% or more stained cells had significantly lower metastasis-free survival rates. We conclude that MUC1 is expressed in RCC and is associated with tumor progression in pT1 RCC.