VEGFR Inhibitors for Uterine Metastatic Perivascular Epithelioid Tumors (PEComa) Resistant to mTOR Inhibitors. A Case Report and Review of Literature.

Uterine perivascular epithelioid cell tumors (PEComas) are rare neoplasms. PI3K/AKT/mTOR pathway upregulation is critical for their pathogenesis and is often associated with TSC1/TSC2 inactivation. Although first line mTOR inhibitors are an effective treatment, metastatic PEComas eventually progress. A 53-year-old woman presented a 4-month history of post-menopausal vaginal bleeding. Clinical and radiological examination detected a uterine mass and a single S1 bone lesion. The patient underwent a radical hysterectomy and bone biopsy. The anatomopathological evaluation concluded to an oligo-metastatic uterine PEComa. The tumor harbored a heterozygous deletion of 9q34 that contains the TSC1 gene. Concerning the primary lesion, the resection was complete and the single bone metastasis was treated with radiotherapy. Three months later, the patient presented bone, lung and subcutaneous metastatic progression. An everolimus and denosumab treatment was initiated. After 2 years of treatment, a clinically significant bone, lung and subcutaneous progression was detected. Following a literature review of the possible therapeutic options, we initiated a second line treatment by pazopanib. This treatment resulted in regression of the subcutaneous lesions and stability of lung and bone metastases. In this challenging, rare setting, our report suggests single agent, anti-angiogenic, tyrosine kinase inhibitor to be effective as second line treatment of metastatic uterine PEComa progressing on mTOR inhibitors

A Locally Advanced Endometrioid Adenocarcinoma Arising from Vaginal Endometriosis: Management and Review of the Literature

Endometrioid adenocarcinoma associated with endometriosis at extrauterine or extraovarian localization is a rare entity. Often presenting with local spread without nodal and distant metastasis, this entity has no specific staging system nor treatment guidelines. In the case of nodal and distant spread, the treatment decision requires personalization. In this article, we present the diagnosis and surgical and systemic treatment of a 56-year-old woman diagnosed with an endometriosis-associated advanced endometrioid adenocarcinoma of the vagina with nodal involvement. Following an extensive review of the scarce data reported to guide the treatment choices in this rare setting, we proposed a multidisciplinary treatment with laparoscopic surgical cytoreduction, four cycles of adjuvant chemotherapy with carboplatin and paclitaxel, and radiotherapy with brachytherapy. Due to an anaphylactic reaction on the first administration, paclitaxel was replaced with nab-paclitaxel. Despite many negative prognostic factors, the patient is free from relapse after 48 months. We report the case of a locally advanced endometrioid adenocarcinoma associated with endometriosis of the vagina, with pelvic nodal spread, and the relevant literature review of similar cases

Burstiness and fractional diffusion on complex networks

Many dynamical processes on real world networks display complex temporal patterns as, for instance, a fat-tailed distribution of inter-events times, leading to heterogeneous waiting times between events. In this work, we focus on distributions whose average inter-event time diverges, and study its impact on the dynamics of random walkers on networks. The process can naturally be described, in the long time limit, in terms of Riemann-Liouville fractional derivatives. We show that all the dynamical modes possess, in the asymptotic regime, the same power law relaxation, which implies that the dynamics does not exhibit time-scale separation between modes, and that no mode can be neglected versus another one, even for long times. Our results are then confirmed by numerical simulations. </p

BIBO stability for funnel control: semilinear internal dynamics with unbounded input and output operators

This note deals with Bounded-Input-Bounded-Output (BIBO) stability for semilinear infinite-dimensional dynamical systems allowing for boundary control and boundary observation. We give sufficient conditions that guarantee BIBO stability based on Lipschitz conditions with respect to interpolation spaces. Our results can be applied to guarantee feasibility of funnel control for coupled ODE-PDE systems, as shown by means of an example from chemical engineering

So-Called Serous Carcinoma of the Uterine Cervix with BRCA2 Mutation: Case Report and Review of the Literature.

Serous carcinoma of the uterine cervix (SCUC) is now believed to be a morphological variant of an HPV-associated endocervical adenocarcinoma or a metastasis from a serous carcinoma of the upper tract. In terms of mutational status as detected by next-generation sequencing (NGS), this controversial entity has not been characterized yet. We describe the case of a patient with a carcinoma categorized as stage IVB SCUC, initially treated with carboplatin, paclitaxel, and bevacizumab, followed by maintenance with bevacizumab. After locoregional progression, radiotherapy was administered. Unfortunately, further progression was observed, and carboplatin was resumed. Considering the presence of a BRCA2 mutation as detected by NGS, treatment with a PARP inhibitor (olaparib) was decided and allowed disease control for 6 months. We believe that BRCA mutation may be systematically searched in patients suffering from carcinomas formerly referred to as SCUC and that targeted treatments should be considered

Cloning and sequencing of the low-affinity penicillin-binding protein 3r-encoding gene of Enterococcus hirae S185: modular design and structural organization of the protein.

The clinical isolate Enterococcus hirae S185 has a peculiar mode of resistance to penicillin in that it possesses two low-affinity penicillin-binding proteins (PBPs): the 71-kDa PBP5, also found in other enterococci, and the 77-kDa PBP3r. The two PBPs have the same low affinity for the drug and are immunochemically related to each other. The PBP3r-encoding gene has been cloned and sequenced, and the derived amino acid sequence has been compared by computer-assisted hydrophobic cluster analysis with that of the low-affinity PBP5 of E. hirae R40, the low-affinity PBP2' of Staphylococcus aureus, and the PBP2 of Escherichia coli used as the standard of reference of the high-M(r) PBPs of class B. On the basis of the shapes, sizes, and distributions of the hydrophobic and nonhydrophobic clusters along the sequences and the linear amino acid alignments derived from this analysis, the dyad PBP3r-PBP5 has an identity index of 78.5%, the triad PBP3r-PBP5-PBP2' has an identity index of 29%, and the tetrad PBP3r-PBP5-PBP2'-PBP2 (of E. coli) has an identity index of 13%. In spite of this divergence, the low-affinity PBPs are of identical modular design and possess the nine amino acid groupings (boxes) typical of the N-terminal and C-terminal domains of the high-M(r) PBPs of class B. At variance with the latter PBPs, however, the low-affinity PBPs have an additional approximately 110-amino-acid polypeptide stretch that is inserted between the amino end of the N-terminal domain and the carboxy end of the membrane anchor. While the enterococcal PBP5 gene is chromosome borne, the PBP3r gene appears to be physically linked to the erm gene, which confers resistance to erythromycin and is known to be plasmid borne in almost all the Streptococcus spp. examined

Infarctus musculaire multifocal diabétique.

Diabetic muscle infarction is a rare and often unrecognized complication of diabetes. It typically occurs in patients with poorly controlled and multi-complicated diabetes. Typical clinical presentation is an indurate muscle pain, mainly localized in the lower limb with an acute onset. In most cases, diabetes myonecrosis is focal and sometimes can be recurrent. Diagnosis is clinical but can used magnetic resonance imaging (MRI). Muscle biopsy is sometimes necessary in cases of doubt or to confirm the imaging diagnosis. Elevation of muscle enzymes (CPK) is present in half of cases. Management is conservative and the clinical and imaging evolution is usually favourable. We report the case of a patient presenting a subacute hyperalgesic lomboradiculopathy.Case ReportsEnglish AbstractJournal ArticleSCOPUS: ar.jinfo:eu-repo/semantics/publishe