Citations

AbstractThe intricate role of the autonomic nervous system (ANS) in regulating cardiac physiology has long been recognized. Aberrant function of the ANS is central to the pathophysiology of cardiovascular diseases. It stands to reason, therefore, that neuroscience‐based cardiovascular therapeutics hold great promise in the treatment of cardiovascular diseases in humans. A decade after the inaugural edition, this White Paper reviews the current state of understanding of human cardiac neuroanatomy, neurophysiology and pathophysiology in specific disease conditions, autonomic testing, risk stratification, and neuromodulatory strategies to mitigate the progression of cardiovascular diseases. image

Abstract This mini review explores the association of interstitial lung disease (ILD) with antineutrophil cystoplasmic antibodies (ANCA) and the clinical syndrome of microscopic polyangiitis (MPA). Reports on radiographic and histopathologic findings as well as genetic predispositions are reviewed. Based on this evidence a concept for the pathogenesis of the relationship of ILD, MPO-ANCA and MPA is proposed. Finally, a practical clinical management approach to patients presenting either with ILD and a positive ANCA test result, or to patients with MPA found to have pulmonary abnormalities qualifying as an ILD, is derived from the currently available literature. Treatment of these patients is based on up-to-date guidelines for the management of ILD as well as ANCA-associated vasculitis.

Abstract The session on other forms of vasculitis included a masterful review on IgG4-related disease (IgG4-RD) following which two research studies evaluating therapeutic agents and one study on histopathologic findings of IgG4-RD were presented. Peyronel F., et al. discussed the results of a prospective multicentre randomized clinical trial evaluating methotrexate for patients with retroperitoneal fibrosis. Methotrexate, in combination with a tapering regimen of glucocorticoids, was effective in inducing remission and allows use of lower cumulative prednisone doses. Hobbelink J., et al. evaluated the histopathologic scoring system from the ACR/EULAR Classification criteria for IgG4-RD. Their study found that these criteria were able to distinguish patients with confirmed and suspected IgG4-RD. Trivioli G et al. retrospectively evaluated rituximab in adult-onset IgA Vasculitis (IgAV) and crescentic IgA Nephropathy (cIgAN). Rituximab resulted in high rate of renal response in IgAV but remission rates in cIgAN remained lower with poorer renal outcomes compared with IgAV.

The NCCN Guidelines for Myelodysplastic Syndromes (MDS) provide recommendations for the evaluation, diagnosis, and comprehensive care of patients with MDS based on a review of recent clinical evidence that has led to important advances in treatment or has yielded new information on biologic factors that may have prognostic significance in MDS. The multidisciplinary panel of MDS experts is convened at least on an annual basis. During the annual meeting, the panel evaluates new and emerging data to inform their recommendations. These NCCN Guidelines Insights review the recent updates, including treatment recommendations both for lower-risk and higher-risk MDS, preference stratification of therapeutic agents, and emerging data on novel therapeutics.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Pediatric Central Nervous System Cancers provide multidisciplinary diagnostic workup, staging, and treatment recommendations for diffuse high-grade gliomas and medulloblastomas in children and adolescents. This article summarizes the studies and panel discussion that serve as the rationale for comprehensive care recommendations included in the NCCN Guidelines for Pediatric Central Nervous System Cancers.

Objective: This study evaluated the feasibility and satisfaction of using a wearable brain activity sensing device for stress reduction among patients experiencing Long COVID (LC). Patients and Methods: Patients with LC (N = 45) were invited to participate in an open-label pilot study. Participants were asked to use a brain-sensing electroencephalogram (S-EEG) wearable device (Muse-S™) daily for 90 days and followed for an additional 90 days (180 days total participation). Study enrollment began June 28, 2022, and ended July 28, 2023. Results: Patients were predominantly female (82%), white (96%), and with an average age of 47.6 (±12.5) years. At the end of treatment (90 days), cognition, sleep, self-efficacy, and quality-of-life quality of life improved ( P < .001 to P = .04). In addition, stress and anxiety were significantly reduced ( P < .001). These significant changes persisted by end-of-study (180 days). For stress ( P = .023) and anxiety ( P = .033), a change from the baseline during follow-up was significantly associated with the amount of S-EEG usage. The end-of-study satisfaction survey indicated that patients were very satisfied with the S-EEG device, and 97% planned to continue using it. Conclusion: Results suggest that the S-EEG device improved cognition in LC, which is one of the main severe symptoms we see in our LC clinic. In addition, it helped reduce stress and anxiety. These findings have important clinical implications for LC patients using S-EEG as an adjunct to concurrent LC clinical care which includes pharmacotherapies.

ABSTRACT Background Several hematological and biochemical parameters have been related to the COVID‐19 infection severity and outcomes. However, less is known about clinical indicators reflecting lung involvement of COVID‐19 patients at hospital admission. Computed tomography (CT) represents an established imaging tool for the detection of lung injury, and the quantitative analysis software CALIPER has been used to assess lung involvement in COVID‐19 patients. Herein, the relationship between the lung involvement expressed by CALIPER interstitial lung disease (ILD) percentage and a set of blood parameters related to tissue oxygenation and damage in COVID‐19 patients at hospital admission was evaluated. Methods We performed a retrospective and a prospective study involving 321 and 75, respectively, COVID‐19‐positive patients recruited from Pisa University Hospital. The association between CALIPER ILD percentages and selected blood parameters was investigated by a regression tree approach, after multiple imputations of the dataset missing values. Results High serum lactate dehydrogenase (LDH) values appeared to be predictive of high CALIPER ILD percentages at hospital admission in both retrospective and prospective datasets, even if the predictive performance of the algorithm was not optimal. Conclusions LDH levels could be evaluated as a tool for early identification of COVID‐19 patients at risk of extensive lung injury, as well as in fast screening procedures before hospitalization.

AbstractHeightened muscle sympathetic nerve activity (MSNA) contributes to impaired vasodilatory capacity and vascular dysfunction associated with aging and cardiovascular disease. The contribution of elevated MSNA to the vasodilatory response during passive leg movement (PLM) is not fully understood. This study tested the hypothesis that elevated MSNA diminishes the vasodilatory response to PLM in healthy young males (n = 11, 25 ± 2 yr). Post exercise circulatory occlusion (PECO) following 2 min of isometric handgrip (HG) exercise performed at 25% (ExPECO 25%) and 40% (ExPECO 40%) maximum voluntary contraction was used to incrementally engage the metaboreceptors and augment MSNA. Control trials were performed without PECO (ExCON 25% and ExCON 40%) to account for changes due to HG exercise. PLM was performed 2 min after exercise and hemodynamics were assessed. MSNA was recorded by microneurography in the peroneal nerve (n = 8). Measures of MSNA (i.e., burst incidences) increased during ExPECO 25% (+15 ± 5 burst/100 bpm) and ExPECO 40% (+22 ± 4 burst/100 bpm) and returned to pre‐HG levels during ExCON trials. Leg vascular conductance (vasodilation) during PLM was reduced by 16% and 44% during ExPECO 25% and ExPECO 40%, respectively. These findings indicate elevated MSNA attenuates the vasodilatory response to PLM and the magnitude of reduction in vasodilation during PLM is graded with the degree of sympathoexcitation.

ABSTRACTBackground and AimsOne strategy to minimize the risk of posttransplant lymphoproliferative disorder (PTLD) is to avoid an Epstein–Barr Virus (EBV) mismatch through kidney paired donation. We aimed to estimate the incidence of PTLD in EBV‐negative kidney transplant recipients with EBV‐positive donors (D+/R−) and evaluate the excess risk of death following the occurrence of PTLD.MethodsWe included adult patients in OPTN database who underwent kidney transplants between 2012 and 2022. Cox regression analysis was employed to evaluate the impact of EBV serostatus on the development of PTLD, and to assess mortality following PTLD diagnosis in D+/R− individuals.ResultsA total of 179 068 patients were included, with 92.8% in the R+, 6.4% in the D+/R−, and 0.8% in the D−/R− group. D+/R− exhibited a significantly higher risk of PTLD compared to R+ and D−/R− groups. D+/R− had a greater risk of PTLD when compared to D−/R− recipients (aHR: 3.82; p < 0.001). Among D+/R− recipients, those who developed PTLD had a significantly higher risk of mortality (aHR: 2.28; p < 0.001 in deceased donor kidney transplant [DDKT] and aHR: 5.22; p < 0.001 in living donor kidney transplant [LDKT]).ConclusionsD+/R− recipients have nearly a fourfold higher risk of PTLD compared to D−/R− recipients, suggesting that choosing an EBV D−/R− transplant could reduce the PTLD risk by about 73%. This data is crucial for counseling EBV‐negative patients considering kidney paired donation to avoid an EBV serostatus mismatch.

Abstract Solid tumors develop within a complex environment called the tumor microenvironment (TME), which is sculpted by the presence of other cells, such as cancer‐associated fibroblasts (CAFs) and immune cells like macrophages (Mφs). Despite the presence of immune cells, tumor cells orchestrate a tumor‐supportive environment through intricate interaction with the components of the TME. However, the specific mechanism by which this intercellular dialogue is regulated is not fully understood. To that end, the development of an organotypic 3D breast TME‐on‐a‐chip (TMEC) model, integrated with single‐cell RNA sequencing analysis, is reported to mechanistically evaluate the progression of triple‐negative breast cancer (TNBC) cells in the presence of patient‐derived CAFs and Mφs. Extensive functional assays, including invasion and morphometric characterization, reveal the synergistic influence of CAFs and Mφs on tumor cells. Furthermore, gene expression and pathway enrichment analyses identify the involvement of the KYNU gene, suggesting a potential immune evasion mechanism through the kynurenine pathway. Lastly, the pharmacological targeting of the identified pathway is investigated.