Neutrophils are indispensable for adverse cardiac remodeling in heart failure.

Persistent immune activation contributes significantly to left ventricular (LV) dysfunction and adverse remodeling in heart failure (HF). In contrast to their well-known essential role in acute myocardial infarction (MI) as first responders that clear dead cells and facilitate subsequent reparative macrophage polarization, the role of neutrophils in the pathobiology of chronic ischemic HF is poorly defined. To determine the importance of neutrophils in the progression of ischemic cardiomyopathy, we measured their production, levels, and activation in a mouse model of chronic HF 8 weeks after permanent coronary artery ligation and large MI. In HF mice, neutrophils were more abundant both locally in failing myocardium (more in the border zone) and systemically in the blood, spleen, and bone marrow, together with increased BM granulopoiesis. There were heightened stimuli for neutrophil recruitment and trafficking in HF, with increased myocardial expression of the neutrophil chemoattract chemokines CXCL1 and CXCL5, and increased neutrophil chemotactic factors in the circulation. HF neutrophil NETotic activity was increased in vitro with coordinate increases in circulating neutrophil extracellular traps (NETs) in vivo. Neutrophil depletion with either antibody-based or genetic approaches abrogated the progression of LV remodeling and fibrosis at both intermediate and late stages of HF. Moreover, analogous to murine HF, the plasma milieu in human acute decompensated HF strongly promoted neutrophil trafficking. Collectively, these results support a key tissue-injurious role for neutrophils and their associated cytotoxic products in ischemic cardiomyopathy and suggest that neutrophils are potential targets for therapeutic immunomodulation in this disease.

Getting Your Foot in the Door: Access to Surgical Care for Thyroid Disease.

INTRODUCTION: Access to specialty care can be challenging for patients, often involving multiple evaluations, laboratory tests, and referrals. To better understand the different pathways to specialty care, we examined the outcomes of patients evaluated for surgical thyroid disease at a single tertiary referral clinic. METHODS: We reviewed 691 patients seen in the endocrine surgery clinic for thyroid disease (2018-2021). Patient demographics, referral source, referral reason, and reason for not receiving an operation were collected. The number of days from referral to initial clinic visit and from initial clinic visit to an operation were also collected. The Chi-square test, the independent t-test, the Kruskal-Wallis test, the Dunn-Bonferroni post hoc test, and multiple logistic regression tests were performed using SPSS. RESULTS: The top reasons for referral were thyroid nodules (54.4%), hyperthyroidism (26.5%), and multinodular goiter (10.3%). Specialty clinic referrals came from endocrinologists (56.0%), self-referrals (15.5%), and primary care physicians (PCP; 14.4%). Self-referred patients had a shorter waiting time for an appointment than those referred by endocrinologists and PCPs. [median (IQR) (days) 12 (6-17) versus 16 (9-24) versus 16 (9-25), P < 0.001]. Overall, 450 (72.7%) patients underwent thyroid surgery. For those who underwent thyroidectomy, self-referred patients had a shorter time between initial clinic visit and the operation compared to those referred by endocrinologists and PCPs [median (IQR) (days) 2 (1-19) versus 19 (8-33) versus 16 (1-48), P < 0.001]. Patients referred for hyperthyroidism (odds ratio [OR] = 2.2, 95% confidence interval [CI] 1.3-10.5, P = 0.012 were more likely to undergo an operation than those referred for other reasons. CONCLUSIONS: Access to specialty care for thyroid disease is facilitated and optimized when self-referrals are permitted. Reducing or eliminating the requirement for a provider referral may improve patients' access.

Parathyroid allotransplantation for the treatment of permanent hypoparathyroidism: A systematic review.

BACKGROUND: Hypoparathyroidism is the most common complication of bilateral operations in the central neck. No formal guidelines exist for the management of permanent hypoparathyroidism. Current treatment involving medical supplementation increases resource utilization and patient morbidity while decreasing quality of life. Parathyroid allotransplant (PA) offers a promising therapy; however, the optimal technique and role of immunosuppression (IS) in PA remain unclear. METHODS: We performed a systematic search of the Embase, MEDLINE, and Cochrane Library databases to identify studies investigating PA for treatment of hypoparathyroidism. RESULTS: A total of 24 studies including 186 individual allograft transplants in 146 patients were identified. Pooled graft survival for allotransplants in transplant-naïve vs prior transplant recipients was 29.9% and 80%, respectively. CONCLUSIONS: PA using normocellular, fresh parathyroid donor tissue that is ABO-compatible, with induction and, at minimum, short-term maintenance IS presents a potentially safe and effective therapeutic option for permanent hypoparathyroidism in patients tolerating IS.