The Transcription Factor T-bet Resolves Memory B Cell Subsets with Distinct Tissue Distributions and Antibody Specificities in Mice and Humans.

B cell subsets expressing the transcription factor T-bet are associated with humoral immune responses and autoimmunity. Here, we examined the anatomic distribution, clonal relationships, and functional properties of T-bet+ and T-bet- memory B cells (MBCs) in the context of the influenza-specific immune response. In mice, both T-bet- and T-bet+ hemagglutinin (HA)-specific B cells arose in germinal centers, acquired memory B cell markers, and persisted indefinitely. Lineage tracing and IgH repertoire analyses revealed minimal interconversion between T-bet- and T-bet+ MBCs, and parabionts showed differential tissue residency and recirculation properties. T-bet+ MBCs could be subdivided into recirculating T-betlo MBCs and spleen-resident T-bethi MBCs. Human MBCs displayed similar features. Conditional gene deletion studies revealed that T-bet expression in B cells was required for nearly all HA stalk-specific IgG2c antibodies and for durable neutralizing titers to influenza. Thus, T-bet expression distinguishes MBC subsets that have profoundly different homing, residency, and functional properties, and mediate distinct aspects of humoral immune memory.

Mapping the Anatomy of the Human Lymphatic System.

BACKGROUND: While substantial anatomical study has been pursued throughout the human body, anatomical study of the human lymphatic system remains in its infancy. For microsurgeons specializing in lymphatic surgery, a better command of lymphatic anatomy is needed to further our ability to offer surgical interventions with precision. In an effort to facilitate the dissemination and advancement of human lymphatic anatomy knowledge, our teams worked together to create a map. The aim of this paper is to present our experience in mapping the anatomy of the human lymphatic system. METHODS: Three steps were followed to develop a modern map of the human lymphatic system: (1) identifying our source material, which was "Anatomy of the human lymphatic system," published by Rouvière and Tobias (1938), (2) choosing a modern platform, the Miro Mind Map software, to integrate the source material, and (3) transitioning our modern platform into The Human BioMolecular Atlas Program (HuBMAP). RESULTS: The map of lymphatic anatomy based on the Rouvière textbook contained over 900 data points. Specifically, the map contained 404 channels, pathways, or trunks and 309 lymph node groups. Additionally, lymphatic drainage from 165 distinct anatomical regions were identified and integrated into the map. The map is being integrated into HuBMAP by creating a standard data format called an Anatomical Structures, Cell Types, plus Biomarkers table for the lymphatic vasculature, which is currently in the process of construction. CONCLUSION: Through a collaborative effort, we have developed a unified and centralized source for lymphatic anatomy knowledge available to the entire scientific community. We believe this resource will ultimately advance our knowledge of human lymphatic anatomy while simultaneously highlighting gaps for future research. Advancements in lymphatic anatomy knowledge will be critical for lymphatic surgeons to further refine surgical indications and operative approaches.

Kidney Lymphatics.

Following significant advances in lymphatic biology, the important role of kidney lymphatics in kidney function and dysfunction is now being more fully appreciated. Kidney lymphatics begin in the cortex as blind-ended lymphatic capillaries and then coalesce into larger lymphatics that follow the main blood vessels out through the kidney hilum. Their function in draining interstitial fluid, macromolecules, and cells underpins their important role in kidney fluid and immune homeostasis. This article provides a comprehensive overview of recent and more established research findings on kidney lymphatics and the implications of these findings for kidney function and disease. The use of lymphatic molecular markers has greatly expanded our knowledge of the development, anatomy, and pathophysiology of kidney lymphatics. Significant recent discoveries include the diverse embryological source of kidney lymphatics, the hybrid nature of the ascending vasa recta, and the effects of lymphangiogenesis on kidney diseases such as acute kidney injury and renal fibrosis. On the basis of these recent advances, there is now an opportunity to link information from across multiple research disciplines to drive a new era of lymphatic-targeted therapies for kidney disease. © 2023 American Physiological Society. Compr Physiol 13:4945-4984, 2023.

Changes of thoracic duct flow and morphology in an animal model of elevated central venous pressure.

Objective: Investigation of lymph fluid dynamics in thoracic duct during central venous pressure elevation. Background: Lymphatic flow is affected by elevated central venous pressure (CVP) in congestive heart failure. The changes of thoracic duct (TD) lymph flow have not been studied chronically in the setting of elevated CVP. This study is to investigate fluid dynamics and remodeling of the TD in the elevated CVP animal model. Methods: A flow probe was implanted on the swine TD (n = 6) and tricuspid regurgitation (TR) was created by cutting tricuspid chordae percutaneously. Six swine were used as control group animals. The TD flow was measured for 2 weeks (baseline) before TR and 4 weeks postop-TR surgery. Arterial pressure and CVP were measured. The pressure and flow in the TD were measured percutaneously. Histological and morphological analyses were performed. Results: TR resulted in an increase in CVP from 4.2 ± 2.6 to 10.1 ± 4.3 mmHg (p < 0.05). The lymph flow in the TD increased from 0.78 ± 1.06 before TR to 8.8 ± 4.8 ml/min (p < 0.05) 2 days post-TR and remained plateau for 4 weeks, i.e., the TD flow remained approximately 8-11 fold its baseline. Compared to the 8.1 ± 3.2 mmHg control group, the TD average pressures at the lymphovenous junction increased to 14.6 ± 5.7 mmHg in the TR group (p < 0.05). The TD diameter and wall thickness increased from 3.35 ± 0.37 mm and 0.06 ± 0.01 mm in control to 4.32 ± 0.57 mm and 0.26 ± 0.02 mm (p < 0.05) in the TR group, respectively. Conclusion: The elevated CVP results in a significant increase in TD flow and pressure which causes the TD's outward remodeling and thickening. Our study implicates that the outward remodeling may result in the TD valve incompetence due to failure coaptation of leaflets.

Significant radiation reduction in interventional fluoroscopy using a novel eye controlled movable region of interest.

PURPOSE: This paper reports the first results obtained using a novel technology called eye controlled region of interest (ECR) that substantially reduces both staff and patient irradiation during an interventional fluoroscopy procedure without interfering with workflow. Its collimator includes a partially x-ray attenuating plate with a nonattenuating aperture. An eye tracker follows the operator's gaze to automatically position the aperture to the clinical region of interest (CROI) anywhere in the image in real-time. METHODS: Experiments were performed in a swine model using a mobile fluoroscope with a 30 cm image intensifier and manual control of fluoroscopic factors. The factory collimator and image display monitor were replaced with different components for this study. The full 30 cm field-of-view (FOV) of the image intensifier was irradiated at normal levels, and served as a baseline, when ECR was disengaged. With ECR engaged, most of the 30 cm FOV was irradiated to less than 20% of normal levels while the CROI was normally irradiated. Animal irradiation was determined by physical KAP (kerma area product) measurements. Operator irradiation was characterized by air kerma and air kerma rate measurements near the operator. Data were collected from three pairs of interventions in each of five swine models. RESULTS: When ECR was engaged, KAP was reduced to 0.22 (p < 0.001) of baseline and operator irradiation to 0.27 (p < 0.001) of baseline. Overall procedure time had a borderline increase (p = 0.07) but fluoroscopy time was unchanged (p = 0.36) (Wilcoxon signed rank). Measured staff and patient radiation reductions are consistent with this collimator's design. Subjective impressions of imaging improvements are consistent with less scatter reaching the CROI. Engaging ECR reduced irradiation without subjectively or objectively increasing operator workload. CONCLUSIONS: The first in vivo evaluation of ECR demonstrated that this technology has objectively reduced KAP and operator irradiation by approximately 75% without interfering with the performance of fluoroscopically guided interventional procedures. In addition, reduced scatter production subjectively improved device visualization. These findings indicate the practicability of achieving better radiation optimization.

High rate of fistula placement in a cohort of dialysis patients in a single payer system.

Arteriovenous fistulas (AVFs) are considered superior to arteriovenous grafts and catheters. Nevertheless, AVF prevalence in the United States remains under the established target. The complication rates and financial cost of vascular access continue to rise and disproportionately contribute to the burgeoning health care costs. The relationship between financial incentives for a type of vascular access and rate of access placement is unclear. All chronic hemodialysis patients (n=99) receiving care at Philadelphia Veterans Affairs Medical Center as of August 1, 2008 were participants. Demographic characteristics, vascular access type, and nonrelative value unit compensation were assessed as predictors, and the vascular access prevalence rate, operative times, and frequency of access interventions were analyzed. A 73.7% AVF rate was achieved in this cohort of patients with 51.5% diabetes mellitus. The number of access procedures per patient per year remained constant over time. The Philadelphia Veterans Affairs Medical Center, a single payer system, achieved superior AVF prevalence and exceeded the national AVF target. Financial incentives for arteriovenous graft placement currently exist in the United States, as there is similar Medicare reimbursement for arteriovenous graft and basilic vein transposition, despite longer operative times for basilic vein transpositions. The high AVF prevalence at the Philadelphia Veterans Affairs Medical Center may be due to the VA nonrelative value unit-driven system that allows for interdisciplinary care, priority of AVFs, and frequent use of basilic vein transposition surgery, when appropriate. We have identified an important, hypothesis-generating example of a nonrelative value unit-based approach to vascular access yielding superior results with respect to patient care and cost.