Bladder paraganglioma: CT and MR imaging characteristics in 16 patients

Background Bladder paraganglioma (BPG) is a rare extra-adrenal pheochromocytoma with variable symptoms and easy to be misdiagnosed and mishandled. The aim of the study was to document the imaging features of BPG using computed tomography (CT) and magnetic resonance imaging (MRI). Patients and methods We retrospectively enrolled consecutive patients with pathology-proven BPG, who underwent CT or MRI examinations before surgery between October 2009 and October 2017. The clinical characteristics, CT, and MRI features of the patients were described and analysed. Results A total of 16 patients with 16 bladder tumours (median age 51 years, 9 females) were included. Among them, 13 patients underwent CT examinations and eight patients underwent MRI examinations preoperatively. Tumour diameters ranged from 1.6−5.4 cm. Most of the tumours grew into the bladder cavity (n = 11) with oval shapes (n = 10) and well-defined margins (n = 14). Intratumour cystic degeneration or necrosis (n = 2) was observed. Two lesions showed peripheral tissue invasion, suggesting malignant BPGs. All 13 lesions imaged with CT exhibited slight hypoattenuation and moderate to marked enhancement. Compared to the gluteus maximus, all lesions showed slight h yperintensity in T2-weighted images, hyperintensity on diffusion-weighted images (DWI), hypointensity on apparent diffusion coefficient maps, hyperintensity on T1-weighted images and a “fast in and slow out” enhanced pattern on contrast-enhanced MRI images. Conclusions BPGs are mostly oval-shaped, broadly-based and hypervascular bladder tumours with hypoattenuation on non-contrast CT, T2 hyperintensity, slight T1 hyperintensity compared to the muscle, marked restricted diffusion on DWI. Peripheral tissue invasion can suggest malignancy of the BPGs. All of these features contribute to preoperative decision-making.

Vitamin C Improves Microvascular Reactivity and Peripheral Tissue Perfusion in Septic Shock Patients

Background Vitamin C has potential protective effects through anti-oxydant and anti-inflammatory properties. However, the effect of Vitamin C supplementation on microvascular function and peripheral tissue perfusion in human sepsis remains unknown. We aimed to determine vitamin C effect on microvascular endothelial dysfunction and peripheral tissue perfusion in septic shock patients. Methods Patients with septic shock were prospectively included after initial resuscitation. Bedside peripheral tissue perfusion and skin microvascular reactivity in response to acetylcholine iontophoresis in the forearm area were measured before and 1 hour after intravenous Vitamin C supplementation (40 mg/kg). Norepinephrine dose was not modified during the studied period. Results We included 30 patients with septic shock. SOFA score was 11 [8–14], SAPS II was 66 [54-79] and in-hospital mortality was 33%. Half of these patients had vitamin C deficiency at inclusion. Vitamin C supplementation strongly improved microvascular reactivity (AUC 2263 [430-4246] vs 5362 [1744-10585] UI, p=0.0004). In addition, Vitamin C supplementation improved mottling score (p=0.06), finger-tip (p=0.0003) and knee capillary refill time (3.7 [2.6-5.5] vs 2.9 [1.9-4.7] s, p<0.0001), as well as and central-to-periphery temperature gradient (6.1 [4.9-7.4] vs 4.6 [3.4-7.0] °C, p<0.0001). The beneficial effects of Vitamin C were observed both in patients with or without Vitamin C deficiency. Conclusion In resuscitated septic shock patients, vitamin C supplementation improved peripheral tissue perfusion and microvascular reactivity whatever plasma levels of vitamin C.

Use of Topical Nitroglycerine in the Neonatal Population Following Peripheral Tissue Ischaemia: Case Report and Updates about Safety Concerns

Neonatal thrombosis is a well-described morbidity occurring in the neonatal intensive care unit. Critically ill neonates are most vulnerable to developing thrombosis with serious complications. Fingers and toes ischaemia secondary to vascular occlusion following central lines insertion remains an uncommon occurrence. The therapeutic approach for peripheral tissue injury using local warming, anticoagulants, thrombolytics or topical hyaluronidase showed limited benefits and potential side effects. Here we report an unusual case of finger ischaemia treated successfully using topical nitroglycerine. This complements previous reports confirming the efficacy and safety of this drug and highlighting its potential benefit in neonates.

Patrolling human SLE haematopoietic progenitors demonstrate enhanced extramedullary colonisation; implications for peripheral tissue injury

Systemic lupus erythematosus (SLE) is an autoimmune disease where bone-marrow-derived haematopoietic cells have a key role in its pathogenesis with accumulating evidence suggesting an aberrant function of haematopoietic stem/progenitor cells (HSPCs). We examined whether patrolling HSPCs differ from bone-marrow HSPCs both in SLE and healthy individuals, and how they participate in peripheral tissue injury. By employing next-generation RNA sequencing, the transcriptomes of CD34+ HSPCs deriving from the bone marrow and those patrolling the bloodstream of both healthy and individuals with SLE were compared. Patrolling SLE and Healthy human HSPC kinetics were examined through their inoculation into humanised mice. Patrolling and bone-marrow HSPCs have distinct molecular signatures, while patrolling SLE HSPCs showed an enhanced extramedullary gene expression profile. Non-mobilised, SLE-derived circulating HSPCs demonstrated altered homing capacities. Xenotransplantation of circulating HSPCs in humanised mice showed that human peripheral blood HSPCs possess the ability for extramedullary organ colonisation to the kidneys. Circulating and bone marrow-derived HSPCs are distinct in steady and diseased states. Patrolling SLE CD34+ HSPCs are able to home at extramedullary sites such as the spleen and kidneys, potentially participating in peripheral tissue injury.

NMDA Receptor Hypofunction in the Aging-Associated Malfunction of Peripheral Tissue

Glutamatergic transmission through NMDA receptors (NMDARs) is important for the function of peripheral tissues. In the bone, NMDARs and its co-agonist, D-serine participate in all the phases of the remodeling. In the vasculature, NMDARs exerts a tonic vasodilation decreasing blood perfusion in the corpus cavernosum and the filtration rate in the renal glomerulus. NMDARs are relevant for the skin turnover regulating the proliferation and differentiation of keratinocytes and the formation of the cornified envelope (CE). The interference with NMDAR function in the skin leads to a slow turnover and repair. As occurs with the brain and cognitive functions, the manifestations of a hypofunction of NMDARs resembles those observed during aging. This raises the question if the deterioration of the glomerular vasculature, the bone remodeling and the skin turnover associated with age could be related with a hypofunction of NMDARs. Furthermore, the interference of D-serine and the effects of its supplementation on these tissues, suggest that a decrease of D-serine could account for this hypofunction pointing out D-serine as a potential therapeutic target to reduce or even prevent the detriment of the peripheral tissue associated with aging.

In Sickness and in Health: The Immunological Roles of the Lymphatic System

The lymphatic system plays crucial roles in immunity far beyond those of simply providing conduits for leukocytes and antigens in lymph fluid. Endothelial cells within this vasculature are distinct and highly specialized to perform roles based upon their location. Afferent lymphatic capillaries have unique intercellular junctions for efficient uptake of fluid and macromolecules, while expressing chemotactic and adhesion molecules that permit selective trafficking of specific immune cell subsets. Moreover, in response to events within peripheral tissue such as inflammation or infection, soluble factors from lymphatic endothelial cells exert “remote control” to modulate leukocyte migration across high endothelial venules from the blood to lymph nodes draining the tissue. These immune hubs are highly organized and perfectly arrayed to survey antigens from peripheral tissue while optimizing encounters between antigen-presenting cells and cognate lymphocytes. Furthermore, subsets of lymphatic endothelial cells exhibit differences in gene expression relating to specific functions and locality within the lymph node, facilitating both innate and acquired immune responses through antigen presentation, lymph node remodeling and regulation of leukocyte entry and exit. This review details the immune cell subsets in afferent and efferent lymph, and explores the mechanisms by which endothelial cells of the lymphatic system regulate such trafficking, for immune surveillance and tolerance during steady-state conditions, and in response to infection, acute and chronic inflammation, and subsequent resolution.