Background The COVID-19 pandemic led to dramatic increases in telemedicine use to provide outpatient care without in-person contact risks. Telemedicine increases options for health care access, but a “digital divide” of disparate access may prevent certain populations from realizing the benefits of telemedicine. Objectives The study aimed to understand telemedicine utilization patterns after a widespread deployment to identify potential disparities exacerbated by expanded telemedicine usage. Methods We performed a cross-sectional retrospective analysis of adults who scheduled outpatient visits between June 1, 2020 and August 31, 2020 at a single-integrated academic health system encompassing a broad range of subspecialties and a large geographic region in the Upper Midwest, during a period of time after the initial surge of COVID-19 when most standard clinical services had resumed. At the beginning of this study period, approximately 72% of provider visits were telemedicine visits. The primary study outcome was whether a patient had one or more video-based visits, compared with audio-only (telephone) visits or in-person visits only. The secondary outcome was whether a patient had any telemedicine visits (video-based or audio-only), compared with in-person visits only. Results A total of 197,076 individuals were eligible (average age = 46 years, 56% females). Increasing age, rural status, Asian or Black/African American race, Hispanic ethnicity, and self-pay/uninsured status were significantly negatively associated with having a video visit. Digital literacy, measured by patient portal activation status, was significantly positively associated with having a video visit, as were Medicaid or Medicare as payer and American Indian/Alaskan Native race. Conclusion Our findings reinforce previous evidence that older age, rural status, lower socioeconomic status, Asian race, Black/African American race, and Hispanic/Latino ethnicity are associated with lower rates of video-based telemedicine use. Health systems and policies should seek to mitigate such barriers to telemedicine when possible, with efforts such as digital literacy outreach and equitable distribution of telemedicine infrastructure.

Pulmonary endothelial cell (EC) apoptosis has been implicated in the pathogenesis of emphysema. Cigarette smoke (CS) causes lung EC apoptosis and emphysema. In this study, we show that CS exposure increased lung tissue adenosine levels in mice, an effect associated with increased lung EC apoptosis and the development of emphysema. Adenosine has a protective effect against apoptosis via adenosine receptor-mediated signaling. However, sustained elevated adenosine increases alveolar cell apoptosis in adenosine deaminase-deficient mice. We established an in vitro model of sustained adenosine exposure by incubating lung EC with adenosine in the presence of an adenosine deaminase inhibitor, deoxycoformicin. We demonstrated that sustained adenosine exposure caused lung EC apoptosis via nucleoside transporter-facilitated intracellular adenosine uptake, subsequent activation of p38 and JNK in mitochondria, and ultimately mitochondrial defects and activation of the mitochondria-mediated intrinsic pathway of apoptosis. Our results suggest that sustained elevated adenosine may contribute to CS-induced lung EC apoptosis and emphysema. Our data also reconcile the paradoxical effects of adenosine on apoptosis, demonstrating that prolonged exposure causes apoptosis via nucleoside transporter-mediated intracellular adenosine signaling, whereas acute exposure protects against apoptosis via activation of adenosine receptors. Inhibition of adenosine uptake may become a new therapeutic target in treatment of CS-induced lung diseases.

ImportancePapillary thyroid microcarcinomas (PTMCs) have been associated with increased thyroid cancer incidence in recent decades. Total thyroidectomy (TT) has historically been the primary treatment, but current guidelines recommend hemithyroidectomy (HT) for select low-risk cancers; however, the risk-benefit ratio of the 2 operations is incompletely characterized.ObjectiveTo compare surgical complication rates between TT and HT for PTMC treatment.Data SourcesSCOPUS, Medline via the PubMed interface, and the Cochrane Central Register of Controlled Trials (CENTRAL); through January 1, 2021, with no starting date restriction. Terms related to papillary thyroid carcinoma and its treatment were used for article retrieval. This meta-analysis used the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline and was written according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) proposal.Study SelectionOriginal investigations of adults reporting primary surgical treatment outcomes in PTMC and at least 1 complication of interest were included. Articles evaluating only secondary operations or non–open surgical approaches were excluded. Study selection, data extraction, and risk of bias assessment were performed by 2 independent reviewers and conflicts resolved by a senior reviewer.Data Extraction and SynthesisPooled effect estimates were calculated using a random-effects inverse-variance weighting model. Studies that directly compared outcomes between HT and TT were considered in a weighted meta-analysis for determination of effect sizes.Main Outcomes and MeasuresCancer recurrence and site, mortality (all-cause and disease-specific), vocal fold paralysis, hypoparathyroidism, and hemorrhage/hematoma. Risk of bias was assessed using the McMaster Quality Assessment Scale of Harms scale.ResultsIn this systematic review and meta-analysis, 17 studies were analyzed and included 1416 patients undergoing HT and 2411 patients undergoing TT (HT: pooled mean [SD] age, 47.0 [10.0] years; 1139 [84.6%] were female; and TT: pooled mean [SD] age, 48.8 [10.0] years; 1671 [77.4%] were female). Five studies directly compared outcomes between HT and TT, 5 reported solely on HT outcomes, and 7 reported solely on TT outcomes. Patients undergoing HT had significantly lower risk of temporary vocal fold paralysis compared with patients undergoing TT (2.0% vs 4.2%) (weighted risk ratio [RR], 0.4; 95% CI, 0.2-0.7), temporary hypoparathyroidism (2.2% vs 21.3%) (weighted RR, 0.1; 95% CI, 0.0-0.4), and permanent hypoparathyroidism (0% vs 1.8%) (weighted RR, 0.2; 95% CI, 0.0-0.8). Contralateral lobe malignant neoplasm recurrence was 2.4% in the HT group, while no such events occurred in the TT group. Hemithyroidectomy was associated with a higher overall recurrence rate compared with TT (3.9% vs 1.3%) (weighted RR, 2.8; 95% CI, 1.4-5.7), but there was no difference in recurrence in the thyroid bed or neck.Conclusions and RelevanceThe results of this systematic review and meta-analysis help characterize current knowledge of the risk-benefit ratio of HT vs TT for treatment of PTMC and provide data that may have utility for patient counseling surrounding treatment decisions.

Previous studies by our group as well as others have shown that acute adenosine exposure enhances lung vascular endothelial barrier integrity and protects against increased permeability lung edema. In contrast, there is growing evidence that sustained adenosine exposure has detrimental effects on the lungs, including lung edema. It is well established that adenosine modulates lung inflammation. However, little is known concerning the effect of sustained adenosine exposure on lung endothelial cells (ECs), which are critical to the maintenance of the alveolar-capillary barrier. We show that exogenous adenosine plus adenosine deaminase inhibitor caused sustained elevation of adenosine in lung ECs. This sustained adenosine exposure decreased EC barrier function, elevated cellular reactive oxygen species levels, and activated p38, JNK, and RhoA. Inhibition of equilibrative nucleoside transporters (ENTs) prevented sustained adenosine-induced p38 and JNK activation and EC barrier dysfunction. Inhibition of p38, JNK, or RhoA also partially attenuated sustained adenosine-induced EC barrier dysfunction. These data indicate that sustained adenosine exposure causes lung EC barrier dysfunction via ENT-dependent intracellular adenosine uptake and subsequent activation of p38, JNK, and RhoA. The antioxidant N-acetylcysteine and the NADPH inhibitor partially blunted sustained adenosine-induced JNK activation but were ineffective in attenuation of p38 activation or barrier dysfunction. p38 was activated exclusively in mitochondria, whereas JNK was activated in mitochondria and cytoplasm by sustained adenosine exposure. Our data further suggest that sustained adenosine exposure may cause mitochondrial oxidative stress, leading to activation of p38, JNK, and RhoA in mitochondria and resulting in EC barrier dysfunction.Keywords: adenosine deaminase; equilibrative nucleoside transporters; oxidative stress; MAP kinases; RhoA Increased permeability pulmonary edema is a life-threatening complication characteristic of acute lung injury (ALI) and acute respiratory distress syndrome. The purine nucleoside adenosine has been shown to protect (1-4) and cause (5) pulmonary edema and inflammation in animal models of ALI. The mechanisms governing these paradoxical effects of adenosine are poorly understood.Adenosine is a potent signaling molecule. Under homeostatic conditions, extracellular adenosine concentrations are low (40-600 nM) (6). However, extracellular adenosine levels are increased in response to tissue injury. High plasma adenosine (10-190 mM) has been reported in patients with sepsis-induced ALI (7, 8) and tissue ischemia (9). Adenosine is also significantly elevated in the lungs of animals with ALI caused by acute hypoxia (10-13), high tidal volume ventilation (14), endotoxin (15), and bleomycin (16). Acutely elevated adenosine has been shown to have a protective, antiinflammatory effect in various animal models of ALI (1-4). However, nonsurviving patients with sepsis have much higher plasma adenosine than survivors (7), suggesti...