KDM6A Regulates Immune Response Genes in Multiple Myeloma.

The histone H3K27 demethylase KDM6A is a tumor suppressor in multiple cancers, including multiple myeloma (MM). We created isogenic MM cells disrupted for KDM6A and tagged the endogenous protein to facilitate genome wide studies. KDM6A binds genes associated with immune recognition and cytokine signaling. Most importantly, KDM6A binds and activates NLRC5 and CIITA encoding regulators of Major Histocompatibility Complex (MHC) genes. Patient data indicate that NLRC5 and CIITA, are downregulated in MM with low KDM6A expression. Chromatin analysis shows that KDM6A binds poised and active enhancers and KDM6A loss led to decreased H3K27ac at enhancers, increased H3K27me3 levels in body of genes bound by KDM6A and decreased gene expression. Reestablishing histone acetylation with an HDAC3 inhibitor leads to upregulation of MHC expression, offering a strategy to restore immunogenicity of KDM6A deficient tumors. Loss of Kdm6a in murine RAS-transformed fibroblasts led to increased growth in vivo associated with decreased T cell infiltration.

Huntingtin is an RNA binding protein and participates in NEAT1-mediated paraspeckles.

Huntingtin protein, mutated in Huntington's disease, is implicated in nucleic acid-mediated processes, yet the evidence for direct huntingtin-nucleic acid interaction is limited. Here, we show wild-type and mutant huntingtin copurify with nucleic acids, primarily RNA, and interact directly with G-rich RNAs in in vitro assays. Huntingtin RNA-immunoprecipitation sequencing from patient-derived fibroblasts and neuronal progenitor cells expressing wild-type and mutant huntingtin revealed long noncoding RNA NEAT1 as a significantly enriched transcript. Altered NEAT1 levels were evident in Huntington's disease cells and postmortem brain tissues, and huntingtin knockdown decreased NEAT1 levels. Huntingtin colocalized with NEAT1 in paraspeckles, and we identified a high-affinity RNA motif preferred by huntingtin. This study highlights NEAT1 as a huntingtin interactor, demonstrating huntingtin's involvement in RNA-mediated functions and paraspeckle regulation.

Liver stiffness measurement by magnetic resonance elastography predicts cirrhosis and decompensation in alcohol-related liver disease.

PURPOSE: To evaluate magnetic resonance elastography (MRE)-based liver stiffness measurement as a biomarker to predict the onset of cirrhosis in early-stage alcohol-related liver disease (ALD) patients, and the transition from compensated to decompensated cirrhosis in ALD. METHODS: Patients with ALD and at least one MRE examination between 2007 and 2020 were included in this study. Patient demographics, liver chemistries, MELD score (within 30 days of the first MRE), and alcohol abstinence history were collected from the electronic medical records. Liver stiffness and fat fraction were measured. Disease progression was assessed in the records by noting cirrhosis onset in early-stage ALD patients and decompensation in those initially presenting with compensated cirrhosis. Nomograms and cut-off values of liver stiffness, derived from Cox proportional hazards models were created to predict the likelihood of advancing to cirrhosis or decompensation. RESULTS: A total of 182 patients (132 men, median age 57 years) were included in this study. Among 110 patients with early-stage ALD, 23 (20.9%) developed cirrhosis after a median follow-up of 6.2 years. Among 72 patients with compensated cirrhosis, 33 (45.8%) developed decompensation after a median follow-up of 4.2 years. MRE-based liver stiffness, whether considered independently or adjusted for age, alcohol abstinence, fat fraction, and sex, was a significant and independent predictor for both future cirrhosis (Hazard ratio [HR] = 2.0-2.2, p = 0.002-0.003) and hepatic decompensation (HR = 1.2-1.3, p = 0.0001-0.006). Simplified Cox models, thresholds, and corresponding nomograms were devised for practical use, excluding non-significant or biased variables. CONCLUSIONS: MRE-based liver stiffness assessment is a useful predictor for the development of cirrhosis or decompensation in patients with ALD.

In-Vitro Comparison of Titanium Disc Surface Roughness and Bacterial Colonization after Ultrasonic Instrumentation with Three Different Tips.

During implant maintenance, preserving a smooth surface on the machined trans-mucosa abutment is critical to reduce biofilm attachment and colonization. The present study compare the surface roughness and bacterial colonization of machined titanium surfaces after instrumentation with various materials. Forty-four machined Grade 23 titanium discs were instrumented with a round Polyether Ether Ketone (PEEK) tip, a plastic curette tip, or a pure titanium curette tip with piezoelectric devices. Before and after instrumentation, the surface roughness (Ra and Rz) values were analyzed with a profilometer and scanning electron microscopy (SEM). Streptococcus sanguinis was cultured and incubated for 24 hours on the instrumented discs, and colony-forming units (CFU)/mL were obtained for each group. Samples instrumented with the metal ultrasonic tip significantly increased surface roughness compared to the other groups. Thisresulted in greater colonization by S. sanguinis than surfaces instrumented with PEEK tips or the negative control. Samples instrumented with PEEK and plastic tips did not exhibit any statistically significant increase in surface roughness. SEM analysis revealed a significantly rougher surface of discs instrumented with metal compared to discs instrumented with plastic or PEEK tip, despite the possibility of debris from tip dissolution. Our results suggested that instrumentation with metal ultrasonic tips with piezoelectric devices significantly increase machined titanium's surface roughness and elicited higher biofilm formation in vitro. Meanwhile, instrumentation of machined titanium with PEEK or plastic ultrasonic tips did not affect the surface roughness or bacterial adhesion.

Positionally distinct interferon stimulated dermal immune acting fibroblasts promote neutrophil recruitment in Sweet's syndrome.

Sweet's syndrome is a poorly understood inflammatory skin disease characterized by neutrophil infiltration to the dermis. Single-nucleus and bulk transcriptomics of archival clinical samples of Sweet's syndrome revealed a prominent interferon signature in Sweet's syndrome skin that was reduced in tissue from other neutrophilic dermatoses. This signature was observed in different subsets of cells, including fibroblasts that expressed interferon-induced genes. Functionally, this response was supported by analysis of cultured primary human dermal fibroblasts that were observed to highly express neutrophil chemokines in response to activation by type I interferon. Furthermore, single-molecule resolution spatial transcriptomics of skin in Sweet's syndrome identified positionally distinct immune acting fibroblasts that included a CXCL1+ subset proximal to neutrophils and a CXCL12+ subset distal to the neutrophilic infiltrate. This study defines the cellular landscape of neutrophilic dermatoses and suggests dermal immune acting fibroblasts play a role in the pathogenesis of Sweet's syndrome through recognition of type I interferons.

CT-based synthetic contrast-enhanced dual-energy CT generation using conditional denoising diffusion probabilistic model.

In this study, a deep learning approach utilizing a conditional denoising diffusion probabilistic model (C-DDPM) was developed to create synthetic contrast-enhanced Dual-energy CT (CE-DECT) images from non-contrast single-energy CT (SECT) scans. CE-DECT scans are crucial in producing iodine density maps and delineating targets and organs-at-risk (OAR), which are essential yet often constrained by the limited availability of Dual-energy CT (DECT) scanners during standard CT simulations for radiation therapy planning. To address this challenge, our proposed approach offers a valuable alternative, mitigating the health risks linked to iodinated contrast agents, particularly for those high-risk patients. In this research, imaging data were collected from 130 head-and-neck (HN) cancer patients, who had undergone both non-contrast SECT and CE-DECT scans. The performance of this approach was evaluated using metrics such as Mean Absolute Error (MAE), Structural Similarity Index (SSIM), and Peak Signal-to-Noise Ratio (PSNR). The evaluation demonstrated promising results, with MAE values of 27.37±3.35 Hounsfield Units (HU) for high-energy CT (H-CT) and 24.57±3.35HU for low-energy CT (L-CT), SSIM values of 0.74±0.22 for H-CT and 0.78±0.22 for L-CT, and PSNR values of 18.51±4.55 decibels (dB) for H-CT and 18.91±4.55 dB for L-CT. These metrics highlight the deep learning model's efficacy and its potential to significantly benefit radiation therapy planning by enabling generation of synthetic contrast DECT, even in facilities that lack DECT scanners. Additionally, it offers a safer alternative imaging solution for patients who are unsuitable for iodine contrast imaging, thereby expanding the reach and effectiveness of advanced imaging in cancer treatment planning. .

A morphoscopic exploration of cranial sexual dimorphism among modern South Africans using computed tomography scans.

Continual re-evaluation of standards for forensic anthropological analyses are necessary, particularly as new methods are explored or as populations change. Indian South Africans are not a new addition to the South African population; however, a paucity of skeletal material is available for analysis from medical school collections, which has resulted in a lack of information on the sexual dimorphism in the crania. For comparable data, computed tomography scans of modern Black, Coloured and White South Africans were included in addition to Indian South Africans. Four cranial morphoscopic traits, were assessed on 408 modern South Africans (equal sex and population distribution). Frequencies, Chi-squared tests, binary logistic regression and random forest modelling were used to assess the data. Males were more robust than females for all populations, while White South African males were the most robust, and Black South African females were the most gracile. Population differences were noted among most groups for at least two variables, necessitating the creation of populations-specific binary logistic regression equations. Only White and Coloured South Africans were not significantly different. Indian South Africans obtained the highest correct classifications for binary logistic regression (94.1%) and random forest modelling (95.7%) and Coloured South Africans had the lowest correct classifications (88.8% and 88.0%, respectively). This study provides a description of the patterns of sexual dimorphism in four cranial morphoscopic traits in the current South African population, as well as binary logistic regression functions for sex estimation of Black, Coloured, Indian and White South Africans.

Who are the people with chronic severe back pain not receiving pain treatment?

There are substantial access to care barriers for persons with chronic pain. Little is known about persons who do not receive treatment for chronic severe back pain as most studies rely on clinical samples. We sought to explore demographic, socioeconomic and clinical characteristics of U.S. adults with chronic severe back pain who had not received pain care in the preceding 3 months. In this cross-sectional study, we used data from the 2019 National Health Interview Survey and identified persons who did/did not receive treatment (including self-management strategies) in the last three months for their chronic severe back pain. We used bivariate and multivariable analyses to explore factors associated with not receiving pain treatment. Almost 21% of persons with chronic severe back pain did not receive treatment in the past three months. The following were independently associated with not having treatment in the preceding 3 months: male sex (OR = 1.40; 95% CI 1.11-1.76), living near or below the poverty level (OR 1.92; 95% CI 1.33-2.77), having less than a high-school education (OR, 2.37; 95% CI 1.52-3.68), not having insurance coverage (OR 1.77; 95% CI 1.21-2.59), living in the South (OR 2.05; 95% CI 1.40-3.00), having heart disease (OR 1.47; 95% CI 1.11-1.93). Being a single parent, having depression and multiple comorbid painful health conditions were associated with having treatment. Our conclusions are that one-fifth of persons with chronic severe back pain did not receive treatment for at least three months and socioeconomic factors were highly associated with not receiving treatment. PERSPECTIVE: In a nationally representative sample of persons with chronic severe back pain, one-fifth did not receive treatment for at least three months. Socioeconomic factors were highly associated with not receiving treatment. There is a need to implement solutions to reduce barriers to care.

Slow dynamic elasticity at short times.

It has been reported that slow dynamic nonlinear elastic relaxations, widely thought to proceed universally in proportion to the logarithm of time after cessation of mechanical conditioning, actually recover with a smaller slope at early times, with a time of transition that varies with the grain size of the material. This would constitute a heretofore unreported failure of the claimed universality, while suggesting application to nondestructive evaluation and structural health monitoring. Here, we present further observations at short times, in the single bead system, in cement paste, mortar, concrete, sandstone, and granite. Within the limits imposed by finite-duration ring-down such that the effective instant of conditioning cessation is imprecise, and the corresponding ambiguity as to the time at which relaxation begins, we find no reliable sign of such a transition, even in samples of large grain-size mortar and concrete similar to those described elsewhere as having clear and late cutoffs.

Bystander intervention is associated with reduced early mortality among injury victims in Cameroon.

Despite high injury mortality rates, Cameroon currently lacks a formal prehospital care system. In other sub-Saharan African low and middle-income countries, Lay First Responder (LFR) programs have trained non-medical professionals with high work-related exposure to injury in principles of basic trauma care. To develop a context-appropriate LFR program in Cameroon, we used trauma registry data to understand current layperson bystander involvement in prehospital care and explore associations between current non-formally trained bystander-provided prehospital care and clinical outcomes. The Cameroon Trauma Registry (CTR) is a longitudinal, prospective, multisite trauma registry cohort capturing data on injured patients presenting to four hospitals in Cameroon. We assessed prevalence and patterns of prehospital scene care among all patients enrolled the CTR in 2020. Associations between scene care, clinical status at presentation, and outcomes were tested using univariate and multivariate logistic regression. Injury severity was measured using the abbreviated injury score. Data were analyzed using Stata17. Of 2212 injured patients, 455 (21%) received prehospital care (PC) and 1699 (77%) did not receive care (NPC). Over 90% (424) of prehospital care was provided by persons without formal medical training. PC patients were more severely injured (p<0.001), had markers of increased socioeconomic status (p = 0.01), and longer transport distances (p<0.001) compared to NPC patients. Despite increased severity of injury, patients who received PC were more likely to present with a palpable pulse (OR = 6.2, p = 0.02). Multivariate logistic regression adjusted for injury severity, socioeconomic status and travel distance found PC to be associated with reduced emergency department mortality (OR = 0.14, p<0.0001). Although prehospital injury care in Cameroon is rarely performed and is provided almost entirely by persons without formal medical training, prehospital intervention is associated with increased early survival after injury. Implementation of LFR training to strengthen the frequency and quality of prehospital care has considerable potential to improve trauma survival.

Molecular profiling of 888 pediatric tumors informs future precision trials and data-sharing initiatives in pediatric cancer.

To inform clinical trial design and real-world precision pediatric oncology practice, we classified diagnoses, assessed the landscape of mutations, and identified genomic variants matching trials in a large unselected institutional cohort of solid tumors patients sequenced at Dana-Farber / Boston Children's Cancer and Blood Disorders Center. Tumors were sequenced with OncoPanel, a targeted next-generation DNA sequencing panel. Diagnoses were classified according to the International Classification of Diseases for Oncology (ICD-O-3.2). Over 6.5 years, 888 pediatric cancer patients with 95 distinct diagnoses had successful tumor sequencing. Overall, 33% (n = 289/888) of patients had at least 1 variant matching a precision oncology trial protocol, and 14% (41/289) were treated with molecularly targeted therapy. This study highlights opportunities to use genomic data from hospital-based sequencing performed either for research or clinical care to inform ongoing and future precision oncology clinical trials. Furthermore, the study results emphasize the importance of data sharing to define the genomic landscape and targeted treatment opportunities for the large group of rare pediatric cancers we encounter in clinical practice.

Phenome-wide association study identifies new clinical phenotypes associated with Staphylococcus aureus infections.

BACKGROUND: Phenome-Wide Association study (PheWAS) is a powerful tool designed to systematically screen clinical observations derived from medical records (phenotypes) for association with a variable of interest. Despite their usefulness, no systematic screening of phenotypes associated with Staphylococcus aureus infections (SAIs) has been done leaving potential novel risk factors or complications undiscovered. METHOD AND COHORTS: We tailored the PheWAS approach into a two-stage screening procedure to identify novel phenotypes correlating with SAIs. The first stage screened for co-occurrence of SAIs with other phenotypes within medical records. In the second stage, significant findings were examined for the correlations between their age of onset with that of SAIs. The PheWAS was implemented using the medical records of 754,401 patients from the Marshfield Clinic Health System. Any novel associations discovered were subsequently validated using datasets from TriNetX and All of Us, encompassing 109,884,571 and 118,538 patients respectively. RESULTS: Forty-one phenotypes met the significance criteria of a p-value < 3.64e-5 and odds ratios of > 5. Out of these, we classified 23 associations either as risk factors or as complications of SAIs. Three novel associations were discovered and classified either as a risk (long-term use of aspirin) or complications (iron deficiency anemia and anemia of chronic disease). All novel associations were replicated in the TriNetX cohort. In the All of Us cohort, anemia of chronic disease was replicated according to our significance criteria. CONCLUSIONS: The PheWAS of SAIs expands our understanding of SAIs interacting phenotypes. Additionally, the novel two-stage PheWAS approach developed in this study can be applied to examine other disease-disease interactions of interest. Due to the possibility of bias inherent in observational data, the findings of this study require further investigation.

Palbociclib in Patients With Soft Tissue Sarcoma With CDK4 Amplifications: Results From the Targeted Agent and Profiling Utilization Registry Study.

PURPOSE: Targeted Agent and Profiling Utilization Registry (TAPUR) is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and genomic alterations known to be drug targets. Results of a cohort of patients with soft tissue sarcoma with cyclin-dependent kinase 4 (CDK4) amplification treated with palbociclib are reported. METHODS: Eligible patients had measurable disease, Eastern Cooperative Oncology Group performance status 0 to 2, adequate organ function, and no standard treatment options. The primary end point was disease control (DC), defined as objective response (OR) or stable disease (SD) of at least 16+ weeks duration (SD16+) according to RECIST v1.1. The DC rate was estimated with a 90% CI. Secondary end points included OR, progression-free survival (PFS), overall survival (OS), duration of response, duration of SD, and safety. RESULTS: Forty-two patients with CDK4 amplification were enrolled. One patient was not evaluable for efficacy. One patient with partial response and 18 with SD16+ were observed for DC and OR rates of 46% (90% CI, 36 to 100) and 2% (95% CI, <1 to 13), respectively. Median PFS was 16 weeks (95% CI, 9 to 28) and median OS was 69 weeks (95% CI, 31 to 111) for evaluable patients. Twenty patients had at least one grade 3 to 4 adverse event (AE) at least possibly related to palbociclib, including alanine aminotransferase increase, anemia, fatigue, hypophosphatemia, leukopenia, neutropenia, and thrombocytopenia. No serious AEs were reported. CONCLUSION: Palbociclib met prespecified criteria to declare a signal of antitumor activity in patients with sarcoma and CDK4 amplification.

Head and neck complications of cancer therapies: taste and smell.

Sensory deficits affect awareness of the environment and information processing, leading to dysfunction that may have significant consequences. Deterioration of taste and/or smell sensation has been linked to impaired nutritional intake, and overall decreased quality of life (QoL). Recent data suggest that loss of these senses is also associated with cognitive decline and worse overall cancer treatment prognosis. Cancer therapies have commonly been associated with sensory deterioration. We review these associations with taste and smell in light of new findings and discuss potential prophylactic and therapeutic modalities for taste and smell function.

Genome-based taxonomic analysis of the genus Pseudoalteromonas reveals heterotypic synonyms.

The Pseudoalteromonas genus comprises members that have been demonstrated to play significant ecological roles and produce enzymes, natural products, and activities that are beneficial to the environment and economy. A comprehensive evaluation of the genus revealed that the genomes of several Pseudoalteromonas species are highly similar to each other, exceeding species cutoff values. This evaluation involved determining and comparing the average nucleotide identity, in silico DNA-DNA hybridization, average amino acid identity, and the difference in G + C% between Pseudoalteromonas type strains with publicly available genomes. The genome of the Pseudoalteromonas elyakovii type strain was further assessed through additional sequencing and genomic comparisons to historical sequences. These findings suggest that six Pseudoalteromonas species, namely P. mariniglutinosa, P. donghaensis, P. maricaloris, P. elyakovii, P. profundi, and P. issachenkonii, should be reclassified as later heterotypic synonyms of the following validly published species: P. haloplanktis, P. lipolytica, P. flavipulchra, P. distincta, P. gelatinilytica, and P. tetraodonis. Furthermore, two names without valid standing, 'P. telluritireducens' and 'P. spiralis', should be associated with the validly published Pseudoalteromonas species P. agarivorans and P. tetraodonis, respectively.

Glucose-based biofuel cells and their applications in medical implants: A review.

In glucose biofuel cells (G-BFCs), glucose oxidation at the anode and oxygen reduction at the cathode yield electrons, which generate electric energy that can power a wide range of electronic devices. Research associated with the development of G-BFCs has increased in popularity among researchers because of the eco-friendly nature of G-BFCs (as related to their construction) and their evolution from inexpensive bio-based materials. In addition, their excellent specificity towards glucose as an energy source, and other properties, such as small size and weight, make them attractive within various demanding applied environments. For example, G-BFCs have received much attention as implanted devices, especially for uses related to cardiac activities. Envisioned pacemakers and defibrillators powered by G-BFCs would not be required to have conventional lithium batteries exchanged every 5-10 years. However, future research is needed to develop G-BFCs demonstrating more stable power consistency and improved lifespan, as well as solving the challenges in converting laboratory-made implantable G-BFCs into implanted devices in the human body. The categorization of G-BFCs as a subcategory of different biofuel cells and their performance is reviewed in this article.

Association of hepatitis B virus treatment with all-cause and liver-related mortality among individuals with HBV and cirrhosis: a population-based cohort study.

Background: We evaluated the association of hepatitis B virus (HBV) treatment with all-cause, and liver-related mortality among individuals with HBV and cirrhosis in British Columbia (BC), Canada. Methods: This analysis included people diagnosed with HBV and had cirrhosis in the BC Hepatitis Testers Cohort, including data on all individuals diagnosed with HBV from 1990 to 2015 in BC and integrated with healthcare administrative data. We followed people with cirrhosis from the first cirrhosis diagnosis date until death or December 31, 2020. We compared all-cause and liver related mortality between those who received treatment and those who did not. HBV treatment was considered a time-varying variable. We performed multivariable Cox proportional hazards model and competing risk regression models to assess the association of HBV treatment with all causes, and liver-related mortality respectively using inverse probability of treatment weighted population. Findings: Among 4962 individuals with HBV and cirrhosis, 48.1% received HBV treatment. Treated individuals had a median follow-up of 2.97 years, compared to 2.87 years for untreated individuals. The treated group was older (median age 57 vs 54 years), had higher proportion of treated of males [1802 (75.50%) vs 1766 (68.8%)], from urban area [2318 (97.2%) vs 2355 (91.8%)], and from East and South Asian ethnicity [1506 (63.1%) vs 709 (27.5%)] compared to untreated group. Untreated people experienced higher all-cause mortality (115.47 vs. 35.72 per 1000 person-years) and liver-related mortality (49.86 vs. 11.39 per 1000 person-years). Multivariable models showed that HBV treatment significantly lowered the risk of all-cause mortality (adjusted hazard ratio (aHR) 0.74; 95% CI: 0.65, 0.84) and liver-related mortality (adjusted subdistribution hazard ratio (asHR) 0.72; 95% CI: 0.58, 0.89) compared to untreated individuals. Among untreated individuals with HBV, those with HCV coinfection had a higher risk of both all-cause and liver-related mortality (aHR 1.57; 95% CI: 1.22, 2.04, and asHR 1.60; 95% CI: 1.25, 2.05, respectively). Interpretation: HBV treatment was associated with a significant reduction in all-cause and liver-related mortality among individuals with cirrhosis. The findings highlight the need for treatment among individuals with HBV related cirrhosis especially those with coinfection with hepatitis C virus. Funding: This work was supported by the BC Centre for Disease Control and the Canadian Institutes of Health Research (CIHR) [Grant # NHC-142832, PJT-156066, and SC1 -178736]. JDM has received doctoral fellowship from the Canadian Network on Hepatitis C (CanHepC). DJ has received Doctoral Research Award (#201910DF1-435705-64343) from the Canadian Institutes of Health Research (CIHR) and doctoral fellowship from the CanHepC. CanHepC is funded by a joint initiative of the Canadian Institutes of Health Research (CIHR) (NHC-142832) and the Public Health Agency of Canada (PHAC).

What Encourages Patients to Recommend Their Doctor After an Online Medical Consultation? The Influence of Patient-Centered Communication, Trust, and Negative Health Information Seeking Experiences.

The doctor-patient relationship in China has become increasingly tense, with patients lacking trust in doctors. Meanwhile, online healthcare flourished, accelerated by the COVID-19 pandemic. This study utilized the direct and indirect pathway model of clinician-patient communication to health outcomes and online trust theory to examine the associations between online patient-centered communication (OPCC), benevolence and ability trust in doctors, negative online health information seeking experiences, and willingness to recommend doctors. The findings revealed that benevolence and ability trust mediated the relationship between OPCC and willingness to recommend doctors. Additionally, when participants had a high level of negative online health information seeking experiences, OPCC had a stronger effect on ability trust; meanwhile, the mediation effect of ability trust between the relationship of OPCC and willingness to recommend was stronger. This study also discussed theoretical and practical implications.

Physician and Practice Characteristics Influencing Telemedicine Uptake Among Frontline Clinicians in the Early COVID-19 Pandemic Response: National Survey Study.

BACKGROUND:  Telemedicine expanded rapidly during the COVID-19 pandemic, as key policy changes, financial support, and pandemic fears tipped the balance toward internet-based care. Despite this increased support and benefits to patients and clinicians, telemedicine uptake was variable across clinicians and practices. Little is known regarding physician and institutional characteristics underlying this variability. OBJECTIVE:  This study aimed to evaluate factors influencing telemedicine uptake among frontline physicians in the early pandemic response. METHODS:  We surveyed a national stratified sample of frontline clinicians drawn from the American Medical Association Physician Professional Data in June or July 2020. The survey inquired about the first month and most recent month (June 2020) of pandemic telemedicine use; sample data included clinician gender, specialty, census region, and years in practice. Local pandemic conditions were estimated from county-level data on COVID-19 rates at the time of survey response. Data were analyzed in a weighted logistic regression, controlling for county-specific pandemic data, and weighted to account for survey data stratification and nonresponse. RESULTS:  Over the first 3-4 months of the pandemic, the proportion of physicians reporting use of telemedicine in >30% of visits increased from 29.2% (70/239) to 35.7% (85/238). Relative to primary care, odds of substantial telemedicine use (>30%) both during the first month of the pandemic and in June 2020 were increased among infectious disease and critical care physicians and decreased among hospitalists and emergency medicine physicians. At least minimal prepandemic telemedicine use (odds ratio [OR] 11.41, 95% CI 1.34-97.04) and a high 2-week moving average of local COVID-19 cases (OR 10.16, 95% CI 2.07-49.97) were also associated with substantial telemedicine use in June 2020. There were no significant differences according to clinician gender, census region, or years in practice. CONCLUSIONS:  Prepandemic telemedicine use, high local COVID-19 case counts, and clinician specialty were associated with higher levels of substantial telemedicine use during the early pandemic response. These results suggest that telemedicine uptake in the face of the pandemic may have been heavily influenced by the level of perceived threat and the resources available for implementation. Such understanding has important implications for reducing burnout and preparation for future public health emergencies.