Citations

Identification of a CD4 + helper T cell population providing in situ help to B and CD8 + T cells in the respiratory mucosa.

Analysis of CD4 + T cell heterogeneity in the lung uncovers a Bcl6-dependent subset that supports mucosal antibody production.

AbstractBackgroundLittle is known about the ablation outcomes of premature ventricular contractions (PVCs) that originate from the periprosthetic aortic valve (PPAV) regions of patients with aortic valve replacement (AVR).Methods and ResultsOur study had 11 patients who underwent catheter ablation for PVCs arising from the PPAV regions (bioprosthetic aortic valve, n = 5; mechanical aortic valve, n = 6). The PVC characteristics, procedure characteristics, and efficacy of ablation were compared with the control group (n = 33). At baseline, the PPAV group had a lower left ventricular ejection fraction (mean [SD], 41% [12%] vs. 51% [8%]; p = .002). The rate of acute ablation success was 90.9% in the PPAV group. Ablation sites were identified above the left coronary cusp (LCC) and right coronary cusp commissure (LRCC) in one PVC, below the prosthetic valve in eight PVCs (four below LCC and four below LRCC), and within the distal coronary sinus in two PVCs. The mean procedure time, fluoroscopy time, and radiation in the PPAV group were all significantly greater than those in the control group (all p < .05). However, the number of radiofrequency ablation energy deliveries was not different. The PPAV group had a long‐term success rate compared with the control group (72.7% vs. 87.9%, p = .48) and an increase of left ventricular ejection fraction from 43% to 49% after successful PVC ablation at follow‐up (p < .001). Echocardiography showed no significant change in valve regurgitation after ablation. No new atrioventricular block occurred.ConclusionPVCs arising from PPAV regions can be successfully ablated in patients with prior AVR, without damaging the prosthetic aortic valve and atrioventricular conduction.

Background: Periprosthetic joint infections (PJIs) following total hip arthroplasty (THA) and total knee arthroplasty (TKA) are associated with substantial morbidity. A better understanding of the costs of PJI treatment can inform prevention, treatment, and reimbursement strategies. The purpose of the present study was to describe direct inpatient medical costs associated with the treatment of hip and knee PJI. Methods: At a single tertiary care institution, 176 hips and 266 knees that underwent 2-stage revisions for the treatment of PJI from 2009 to 2015 were compared with 1,611 hips and 1,276 knees that underwent revisions for aseptic indications. In addition, 84 hips and 137 knees that underwent irrigation and debridement (I&D) with partial component exchange were compared with 39 hips and 138 knees that underwent partial component exchange for aseptic indications. Line-item details of services billed during hospitalization were retrieved, and standardized direct medical costs were calculated in 2018 inflation-adjusted dollars. Results: The mean direct medical cost of 2-stage revision THA performed for the treatment of PJI was significantly higher than that of aseptic revision THA ($58,369 compared with $22,846, p < 0.001). Similarly, the cost of 2-stage revision TKA performed for the treatment of PJI was significantly higher than that of aseptic revision TKA ($56,900 compared with $24,630, p < 0.001). Even when the total costs of aseptic revisions were doubled for a representative comparison with 2-stage procedures, the costs of PJI procedures were 15% to 28% higher than those of the doubled costs of aseptic revisions (p < 0.001). The mean direct medical cost of I&D procedures for PJI was about twofold higher than of partial component exchange for aseptic indications. Conclusions: The direct medical costs of operative treatment of PJI following THA and TKA are twofold higher than the costs of similar aseptic revisions. The high economic burden of PJI warrants efforts to reduce the incidence of PJI. Reimbursement schemes should account for the high costs of treating PJI in order to ensure sustainable patient care. Level of Evidence: Economic Level IV . See Instructions for Authors for a complete description of levels of evidence.

ABSTRACT Copper is an essential transition metal for all eukaryotes. In mammals, intestinal copper absorption is mediated by the ATP7A copper transporter, whereas copper excretion occurs predominantly through the biliary route and is mediated by the paralog ATP7B. Both transporters have been shown to be recycled actively between the endosomal network and the plasma membrane by a molecular machinery known as the COMMD/CCDC22/CCDC93 or CCC complex. In fact, mutations in COMMD1 can lead to impaired biliary copper excretion and liver pathology in dogs and in mice with liver-specific Commd1 deficiency, recapitulating aspects of this phenotype. Nonetheless, the role of the CCC complex in intestinal copper absorption in vivo has not been studied, and the potential redundancy of various COMMD family members has not been tested. In this study, we examined copper homeostasis in enterocyte-specific and hepatocyte-specific COMMD gene-deficient mice. We found that, in contrast to effects in cell lines in culture, COMMD protein deficiency induced minimal changes in ATP7A in enterocytes and did not lead to altered copper levels under low- or high-copper diets, suggesting that regulation of ATP7A in enterocytes is not of physiological consequence. By contrast, deficiency of any of three COMMD genes (Commd1, Commd6 or Commd9) resulted in hepatic copper accumulation under high-copper diets. We found that each of these deficiencies caused destabilization of the entire CCC complex and suggest that this might explain their shared phenotype. Overall, we conclude that the CCC complex plays an important role in ATP7B endosomal recycling and function.

Abstract An ongoing outbreak of Coronavirus Disease 2019 (COVID-19) has spread around the world. However, the clinical characteristics and outcomes of patients with COVID-19 related to different modes of exposure have not been well defined. We aimed to explore the clinical features and outcomes of COVID-19 related to one-time community exposure versus continuous household exposure. Retrospective case–control study involving COVID-19 patients admitted to a tertiary designated center in China was performed. Patients were enrolled if they had known exposure history of one-time community exposure or continuous household exposure. Twenty patients were compared in terms of demographic characteristics, clinical presentation, chest CT images, laboratory results, treatments, and clinical outcomes at 1-month follow-up. There were 10 patients in one-time community and continuous household exposure groups respectively. Males compromised 80% and 40% while the median ages were 37.5 and 51 years old in the 2 groups, respectively. Fever and cough were most common symptoms. Ground-glass opacities were presented on chest CT scan in 90% and 70% of the patients, and the median CT scores were 7 and 16 on admission, respectively. Three patients ranked severe in the community exposure group while 7 patients were severe or critical in household exposure group. On 1-month follow-up, all patients were improved clinically but COVID-19 IgG antibody detected positive. Median follow-up CT scores were 0 and 13 while pulmonary function test abnormalities were 0/9 and 2/7 in the 2 groups, respectively. COVID-19 patients with one-time community exposure tended to be mild in severity and had better outcomes, comparing to those with continuous household exposure.

Age-associated T RM cell malfunction supports chronic lung inflammation and tissue fibrosis after respiratory viral infection.