Leiomyosarcoma of the inferior vena cava--a case report

This paper presents a patient successfully treated for leiomyosarcoma of the vena cava, with no recurrence or symptoms on an 8-year follow-up. A 56-year-old woman presented with chronic and progressive periumbilical and right upper abdominal pain. Physical examination and laboratory tests revealed no abnormalities. Computed tomography showed a high-density image inside the vena cava. Cavography showed a filling defect with complete occlusion of the vena cava involving the renal veins and greatly developed collateral circulation through lumbar veins. Laparotomy was performed and a large caval mass involving the renal veins was dissected and resected. Venous reconstruction was undertaken using a 19-mm bovine pericardium prosthesis (Labcor, MG-Brazil) interposed as a substitute to the vena cava, and the renal veins were anastomosed to the side of the graft. Pathologic examination confirmed a leiomyosarcoma with free surgical margins. The postoperative course was uneventful and the patient was discharged on postoperative day 8. The venous flow through the inferior vena became normal, as confirmed by later cavography. This paper presents a case of successfully managed leiomyosarcoma of the vena cava with a thorough review of the literature. The treatment of such patients and the use of bovine pericardium are also discussed.     

Threshold-based prediction of the coagulation zone in sequential temperature mapping in MR-guided radiofrequency ablation of liver tumours

Objective

To evaluate different cut-off temperature levels for a threshold-based prediction of the coagulation zone in magnetic resonance (MR)-guided radiofrequency (RF) ablation of liver tumours.

Methods

Temperature-sensitive measurements were acquired during RF ablation of 24 patients with primary (6) and secondary liver lesions (18) using a wide-bore 1.5?T MR sytem and compared with the post-interventional coagulation zone. Temperature measurements using the proton resonance frequency shift method were performed directly subsequent to energy application. The temperature maps were registered on the contrast-enhanced follow-up MR images acquired 4?weeks after treatment. Areas with temperatures above 50°, 55° and 60°C were segmented and compared with the coagulation zones. Sensitivity and positive predictive value were calculated.

Results

No major complications occurred and all tumours were completely treated. No tumour recurrence was observed at the follow-up examination after 4?weeks. Two patients with secondary liver lesions showed local tumour recurrence after 4 and 7?months. The 60°C threshold level achieved the highest positive predictive value (87.7?±?9.9) and the best prediction of the coagulation zone.

Conclusions

For a threshold-based prediction of the coagulation zone, the 60°C cut-off level achieved the best prediction of the coagulation zone among the tested levels.

Key Points

? Temperature monitoring can be used to survey MR-guided radiofrequency ablation ? The developing ablation zone can be estimated based on post-interventional temperature measurements ? A 60°C threshold level can be used to predict the ablation zone ? The 50°C and 55°C temperature zones tend to overestimate the ablation zone     

The crystal structure of CREG, a secreted glycoprotein involved in cellular growth and differentiation

The cellular repressor of E1A-stimulated genes (CREG) is a secreted glycoprotein that inhibits proliferation and enhances differentiation of human embryonal carcinoma cells. CREG binds to the cation-independent mannose 6-phosphate (M6P)/insulin-like growth factor II (IGF2) receptor (IGF2R) (M6P/IGF2R), and this receptor has been shown to be required for CREG-induced growth suppression. To better understand CREG function in cellular growth and differentiation, we solved the 3D crystal structure of this protein to 1.9-A resolution. CREG forms a tight homodimeric complex, and CREG monomers display a beta-barrel fold. The three potential glycosylation sites on CREG map to a confined patch opposite the dimer interface. Thus, dimerization of glycosylated CREG likely presents a bivalent ligand for the M6P/IGF2R. Closely related structural homologs of CREG are FMN-binding split-barrel fold proteins that bind flavin mononucleotide. Our structure shows that the putative flavin mononucleotide-binding pocket in CREG is sterically blocked by a loop and several key bulky residues. A mutant of CREG lacking a part of this loop maintained overall structure and dimerization, as well as M6P/IGF2R binding, but lost the growth suppression activity of WT CREG. Thus, analysis of a structure-based mutant of CREG revealed that binding to M6P/IGF2R, while necessary, is not sufficient for CREG-induced growth suppression. These findings indicate that CREG utilizes a known fold for a previously undescribed function [corrected]     

Difficult stem cell mobilization despite adequate CD34+ cell dose predicts shortened progression free and overall survival after autologous HSCT for lymphoma

Hematopoietic growth factors alone or in combination with myelosuppressive chemotherapy are used to mobilize peripheral blood stem cells for autologous transplantation. To identify characteristics of successful mobilization with granulocyte colony-stimulating factor (G-CSF) alone and to study the impact of immediate chemotherapy mobilization following G-CSF mobilization, we treated 175 chemotherapy sensitive lymphoma patients with G-CSF (G) mobilization and leukapheresis followed by chemotherapy plus G-CSF (CG) mobilization and leukapheresis and then autologous transplantation. Patients with stage I/II disease at diagnosis and < or =5 years from diagnosis were more likely to mobilize successfully with G-CSF alone (G). CG mobilization led to superior stem cell yields compared to the preceding mobilization with G (median 2.37 vs 1.37 ( x 10(6)CD34+ cells/kg); P<0.0001). Patients (n=58, 33%) with successful G-CSF mobilization (> or =2 x 10(6) CD34+ cells/kg) had quicker platelet recovery and improved progression free and overall survival compared to patients who had adequate collection only after chemotherapy mobilization or to those who failed to collect an adequate graft with either type of mobilization. The poor clinical outcome of patients with difficult mobilization using either method identifies them as a high-risk group who might benefit from alternative therapies.     

Collateral artery growth (arteriogenesis) after experimental arterial occlusion is impaired in mice lacking CC-chemokine receptor-2

Arteriogenesis has been associated with the presence of monocytes/macrophages within the collateral vessel wall. Induced macrophage migration in vivo is driven by the binding of monocyte chemoattractant protein-1 (MCP-1, or CCL2 in the new nomenclature) to the CCR2-chemokine receptor on macrophages. To determine whether the CCL2-CCR2 signaling pathway is involved in the accumulation of macrophages in growing collateral vessels, we used mice that are deficient in CCR2 in a model of experimental arterial occlusion and collateral vessel growth. In an in vitro CCL2-driven chemotaxis assay, mononuclear cells isolated from wild-type BALB/c mice exhibited CCL2 concentration-dependent migration, whereas this migration was abolished in cells from CCR2(-/-) mice on a BALB/c genetic background. In vivo, blood flow recovery as measured by laser Doppler (LDI) and MRI (MRI) was impaired in CCR2(-/-) mice on either the BALB/c or C57BL/6 genetic backgrounds. Three weeks after femoral artery ligation, LDI perfusion ratio of operated versus nonoperated distal hindlimb in BALB/c wild-type mice increased to 0.45+/-0.06 and in CCR2(-/-) animals only to 0.21+/-0.03 (P<0.01). In C57BL/6 mice, ratio increased to 0.96+/-0.09 and 0.85+/-0.08 (P<0.05), respectively. MRI at 3 weeks (0.76+/-0.06 versus 0.62+/-0.01; P<0.05) and hemoglobin oxygen saturation measurements confirmed these findings. Active foot movement score significantly decreased and gastrocnemius muscle atrophy was significantly greater in CCR2(-/-) mice. Morphometric analysis showed a lesser increase in collateral vessel diameters in CCR2(-/-) mice. Importantly, the number of invaded monocytes/macrophages in the perivascular space of collateral arteries of CCR2(-/-) animals was dramatically reduced in comparison to wild-type mice. In conclusion, our results demonstrate that the CCR2 signaling pathway is essential for efficient collateral artery growth.     

Vascular smooth muscle cell-derived adiponectin: a paracrine regulator of contractile phenotype

Adiponectin is a cardioprotective adipokine derived predominantly from visceral fat. We recently demonstrated that exogenous adiponectin induces vascular smooth muscle cell (VSMC) differentiation via repression of mTORC1 and FoxO4. Here we report for the first time that VSMC express and secrete adiponectin, which acts in an autocrine and paracrine manner to regulate VSMC contractile phenotype. Adiponectin was found to be expressed in human coronary artery and mouse aortic VSMC. Importantly, siRNA knock-down of endogenous adiponectin in VSMC significantly reduced the expression of VSMC contractile proteins. Contractile protein deficiency was also observed in primary VSMC isolated from Adiponectin(-/-) mice. This deficiency could be rescued by culturing Adiponectin(-/-) VSMC in conditioned media from wild type (WT) VSMC. Moreover, the paracrine effect of VSMC-derived adiponectin was confirmed as adiponectin neutralizing antibody blocked the rescue. Overexpressed adiponectin also exerted paracrine effects on neighboring untransfected VSMC, which was also blocked by adiponectin neutralizing antibody. Interestingly, adiponectin expression was inducible by the PPARγ agonist rosiglitazone. Our data support an important role for VSMC-derived adiponectin in maintaining VSMC contractile phenotype, contributing to critical cardioprotective functions in the vascular wall. This article is part of a Special Issue entitled "Local Signaling in Myocytes".     

Impact of Communication Method and Timeliness on Student and Faculty Perception of Professionalism and Value

Objective. This study sought to evaluate the impact of faculty, preceptor, and student preferences for type of communication received and timeliness of communication on their perceptions of professionalism and personal value.Methods. An anonymous questionnaire was designed to assess pharmacy faculty, preceptor, and students’ preferred method of communication, response time expectations, impact on their perception of the sender’s professionalism, and personal perception of being valued. The questionnaire was sent to 924 faculty, preceptors, and students.Results. Of the 253 responses received, 27 (11%) were from full-time faculty, 94 (37%) from part-time faculty preceptors, and 132 (52%) from students. Overall, email was the preferred communication method for receiving information that was not time sensitive (98%), with a majority of faculty, preceptors, and students indicating that 48 hours was a reasonable response time. Most participants felt that less than 24 hours was a reasonable response time for texts or phone calls. Most students indicated that response time was somewhat or not impactful (58%) on their view of the faculty or preceptor’s professionalism, while faculty and preceptors indicated that response time was neutral or somewhat impactful on their view of the student’s professionalism (60%). Most students (77%) indicated that a faculty or preceptor’s response time to their text or phone call impacted their perceptions of feeling valued and important.Conclusion. Communication preferences among faculty, preceptors, and students differ. Professionalism related to communication was important to all groups, and timeliness of communication between faculty, preceptors, and students impacted their perception of their value and self-worth.     

Empagliflozin Improves Insulin Sensitivity of the Hypothalamus in Humans With Prediabetes: A Randomized,Double-Blind,Placebo-Controlled,Phase 2 Trial

OBJECTIVEInsulin action in the human brain reduces food intake, improves whole-body insulin sensitivity, and modulates body fat mass and its distribution. Obesity and type 2 diabetes are often associated with brain insulin resistance, resulting in impaired brain-derived modulation of peripheral metabolism. So far, no pharmacological treatment for brain insulin resistance has been established. Since sodium–glucose cotransporter 2 (SGLT2) inhibitors lower glucose levels and modulate energy metabolism, we hypothesized that SGLT2 inhibition may be a pharmacological approach to reverse brain insulin resistance.RESEARCH DESIGN AND METHODSIn this randomized, double-blind, placebo-controlled clinical trial, 40 patients (mean ± SD; age 60 ± 9 years; BMI 31.5 ± 3.8 kg/m²) with prediabetes were randomized to receive 25 mg empagliflozin every day or placebo. Before and after 8 weeks of treatment, brain insulin sensitivity was assessed by functional MRI combined with intranasal administration of insulin to the brain.RESULTSWe identified a significant interaction between time and treatment in the hypothalamic response to insulin. Post hoc analyses revealed that only empagliflozin-treated patients experienced increased hypothalamic insulin responsiveness. Hypothalamic insulin action significantly mediated the empagliflozin-induced decrease in fasting glucose and liver fat.CONCLUSIONSOur results corroborate insulin resistance of the hypothalamus in humans with prediabetes. Treatment with empagliflozin for 8 weeks was able to restore hypothalamic insulin sensitivity, a favorable response that could contribute to the beneficial effects of SGLT2 inhibitors. Our findings position SGLT2 inhibition as the first pharmacological approach to reverse brain insulin resistance, with potential benefits for adiposity and whole-body metabolism.     

Citywide Integrated Aedes aegypti Mosquito Surveillance as Early Warning System for Arbovirus Transmission,Brazil

Arbovirus epidemiology lacks efficient and timely surveillance systems with accurate outbreak alert signals. We devised a citywide integrated surveillance system combining entomologic, epidemiologic, and entomo-virologic data gathered during 2017–2020 in Foz do Iguaçu, Brazil. We installed 3,476 adult mosquito traps across the city and inspected traps every 2 months. We compared 5 entomologic indices: traditional house and Breteau indices for larval surveys and trap positivity, adult density, and mosquitoes per inhabitant indices for adult trapping. We screened for dengue, Zika, and chikungunya viruses in live adult Aedes aegypti mosquitoes collected from traps. Indices based on adult mosquito sampling had higher outbreak predictive values than larval indices, and we were able to build choropleth maps of infestation levels <36 h after each round of trap inspection. Locating naturally infected vectors provides a timely support tool for local public health managers to prioritize areas for intervention response to prevent virus outbreaks.