Primitive neuroectodermal tumor of the myometrium with cardio-vascular symptoms

BACKGROUND: Non-bacterial thrombotic endocarditis is a severe complication of cancer, rarely reported in gynecologic tumors. However, it can be inaugural and lead to complex diagnostic pathways. CASE: A 40-year-old woman presented with a stroke, related to an endocarditis. The valvular vegetation was surgically removed, and a malignant node was resected. A PET-scan led to the diagnosis of a myometrial tumor, which was found to be a primitive neuroectodermal tumor (PNET). The patient underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy, and systemic chemotherapy which allowed a complete remission of tumoral and cardio-vascular symptoms. CONCLUSION: To our knowledge, this is the first case report of a PNET of the myometrium revealed by cardio-vascular symptoms.     

Long-term results of hysteroscopic myomectomy in 235 patients

OBJECTIVE: To assess the efficacy of transcervical resection of submucous fibroids according to type and size. MATERIALS AND METHODS: Retrospective follow-up of 235 women with submucous fibroids at outpatient hysteroscopy who underwent a hysteroscopic transcervical resection. The main indications were the abnormal uterine bleeding and fertility problems. Thirty-seven percent of patients had an associated endometrial ablation and 32% had a polyp resection. Fifty-one percent of women were menopausal. In cases of incomplete resection a repeat procedure was offered. RESULTS: Intra-operative complications were rare (2.6%) and there was no major complication. Eighty-four percent of cases were followed-up. The median follow-up was 40 months (range 18-66 months). The procedure was classed as a success in 94.4% of patients. Among the cases that were classed as a failure, four patients had a repeated hysteroscopic procedure, three patients had a subsequent hysterectomy and four patients presented with abnormal uterine bleeding at follow-up. CONCLUSION: The hysteroscopic transcervical resection of submucous fibroids is a safe and highly effective long-term therapy for carefully selected women presenting with abnormal uterine bleeding and fertility problems. It produces satisfactory long-term results with few complications.     

Cytokine profiles in serum and peritoneal fluid from infertile women with and without endometriosis

OBJECTIVE: To study the serum and peritoneal fluid cytokine profiles in infertile women with minimal/mild active endometriosis. METHODS: Fifty-seven consecutive infertile women undergoing laparoscopy for unexplained infertility had peritoneal fluid and serum samples obtained at the time of laparoscopy. The levels of interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-1 beta (IL-1 beta), vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNF-alpha), monocyte chemotatic protein-1 (MCP-1), RANTES, platelet derived growth factor (PDGF), soluble Fas (sFas), and soluble Fas Ligand (sFasL) in peritoneal fluid and serum were measured to compare the concentration in both biological fluids, in women who have minimal/mild red endometriosis using women with no endometriosis as controls. RESULTS: Peritoneal fluid levels of MCP-1, IL-8 and IL-6 were significantly higher in the endometriosis group (P < 0.012, P = 0.003, and P = 0.015, respectively). There was no significant difference in the peritoneal fluid levels of IL-1 beta, TNF-alpha, RANTES, VEGF, PDGF, sFas and sFasL in the two groups. Although serum levels of IL-8 were higher in women with endometriosis, the difference was not significant (P = 0.07). Serum levels of PDGF, IL-6, RANTES, IL-1 beta, TNF-alpha, and sFas, were not significantly different in the two groups. CONCLUSION: The elevated levels of MCP-1, IL-6, and IL-8 in peritoneal fluid but not serum may indicate the importance of local macrophage activating factors in the pathogenesis of endometriosis.     

Is the beta3-adrenoceptor (ADRB3) a potential target for uterorelaxant drugs?

The management of premature birth still remains unsatisfactory. Since the relative lack of efficiency and/or safety of current tocolytic agents have been highlighted, it is necessary to develop new uterorelaxant drugs deprived of important maternal and foetal side effects. Our work reported in this review focuses on a potential new target for tocolytic drugs, the beta3-adrenoceptor (ADRB3). This third type of ADRB is shown to be present and functional in human myometrium. We demonstrated that ADRB3 agonists are able to inhibit in-vitro spontaneous contractions of myometrial strips, via a cyclic AMP-mediated pathway. Furthermore, we established that ADRB3 is the predominant subtype over the ADRB2 in human myometrium and that its expression is increased in near-term myometrium, compared to non-pregnant myometrium. Finally, we reported that contrary to ADRB2, the human myometrial ADRB3 is resistant to long-term agonist-induced desensitisation. These compelling data confirm the clinical potential interest of ADRB3 agonists in the pharmacological management of preterm labour.     

A comparison of three urobilinogen tests in trie urine, (the watson,Sparkman, and Wallace and diamond methods) in jaundice and diseases of the liver

The American Journal of Digestive Diseases -     

Factors Associated with Macular Staphyloma Area on Ultra-widefield Fundus Images

PurposeTo assess the feasibility of applying ultra-widefield fundus (UWF) images for macular staphyloma area (MSA) measurement and investigate the associated factors with MSA.MethodsThis is a retrospective study. MSA was measured by UWF imaging. Central foveal thickness, subfoveal choroidal thickness, subfoveal scleral thickness were measured on spectral domain optical coherence tomography. Intraclass correlation coefficients of MSA measurement would be evaluated. Multiple linear regression analysis was used to analyze the associated factors with MSA.ResultsIn total, 135 eyes of 92 patients were enrolled. The mean age was 64.73 ± 10.84 years. Mean MSA on UWF image was 279.67 ± 71.70 mm². Intraclass correlation coefficients of MSA measurement was 0.965 (95% confidence interval [CI], 0.946 to 0.977; p < 0.001). In the multiple linear regression analysis, after adjusting for subfoveal choroidal thickness, best-corrected visual acuity, central foveal thickness, and subfoveal scleral thickness, the factors independently related to MSA were axial length (β = 8.352; 95% CI, 3.306 to 13.398; p = 0.001), sex (β = −26.673; 95% CI, −51.759 to −1.586; p = 0.037), age (β = 1.184; 95% CI, 0.020 to 2.348; p = 0.046).ConclusionsIt is feasible to measure MSA on UWF image. Female, longer axial length, and older age may indicate larger MSA.     

Dual IGF1R/IR inhibitors in combination with GD2-CAR T-cells display a potent anti-tumor activity in diffuse midline glioma H3K27M-mutant

BackgroundDiffuse midline gliomas (DMG) H3K27M-mutant, including diffuse intrinsic pontine glioma (DIPG), are pediatric brain tumors associated with grim prognosis. Although GD2-CAR T-cells demonstrated significant anti-tumor activity against DMG H3K27M-mutant in vivo, a multimodal approach may be needed to more effectively treat patients. We investigated GD2 expression in DMG/DIPG and other pediatric high-grade gliomas (pHGG) and sought to identify chemical compounds that would enhance GD2-CAR T-cell anti-tumor efficacy.MethodsImmunohistochemistry in tumor tissue samples and immunofluorescence in primary patient-derived cell lines were performed to study GD2 expression. We developed a high-throughput cell-based assay to screen 42 kinase inhibitors in combination with GD2-CAR T-cells. Cell viability, western blots, flow-cytometry, real time PCR experiments, DIPG 3D culture models, and orthotopic xenograft model were applied to investigate the effect of selected compounds on DIPG cell death and CAR T-cell function.ResultsGD2 was heterogeneously, but widely, expressed in the tissue tested, while its expression was homogeneous and restricted to DMG/DIPG H3K27M-mutant cell lines. We identified dual IGF1R/IR antagonists, BMS-754807 and linsitinib, able to inhibit tumor cell viability at concentrations that do not affect CAR T-cells. Linsitinib, but not BMS-754807, decreases activation/exhaustion of GD2-CAR T-cells and increases their central memory profile. The enhanced anti-tumor activity of linsitinib/GD2-CAR T-cell combination was confirmed in DIPG models in vitro, ex vivo, and in vivo.ConclusionOur study supports the development of IGF1R/IR inhibitors to be used in combination with GD2-CAR T-cells for treating patients affected by DMG/DIPG and, potentially, by pHGG.     

Early SARS-CoV-2 Reinfections within 60 Days and Implications for Retesting Policies

Illustrated by a clinical case supplemented by epidemiologic data, early reinfections with SARS-CoV-2 Omicron BA.1 after infection with Delta variant, and reinfection with Omicron BA.2 after Omicron BA.1 infection, can occur within 60 days, especially in young, unvaccinated persons. The case definition of reinfection, which influences retesting policies, should be reconsidered.