Memory-like differentiation enhances NK cell responses against colorectal cancer.

Metastatic (m) colorectal cancer (CRC) is an incurable disease with a poor prognosis and thus remains an unmet clinical need. Immune checkpoint blockade (ICB)-based immunotherapy is effective for mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) mCRC patients, but it does not benefit the majority of mCRC patients. NK cells are innate lymphoid cells with potent effector responses against a variety of tumor cells but are frequently dysfunctional in cancer patients. Memory-like (ML) NK cells differentiated after IL-12/IL-15/IL-18 activation overcome many challenges to effective NK cell anti-tumor responses, exhibiting enhanced recognition, function, and in vivo persistence. We hypothesized that ML differentiation enhances the NK cell responses to CRC. Compared to conventional (c) NK cells, ML NK cells displayed increased IFN-γ production against both CRC cell lines and primary patient-derived CRC spheroids. ML NK cells also exhibited improved killing of CRC target cells in vitro in short-term and sustained cytotoxicity assays, as well as in vivo in NSG mice. Mechanistically, enhanced ML NK cell responses were dependent on the activating receptor NKG2D as its blockade significantly decreased ML NK cell functions. Compared to cNK cells, ML NK cells exhibited greater antibody-dependent cytotoxicity when targeted against CRC by cetuximab. ML NK cells from healthy donors and mCRC patients exhibited increased anti-CRC responses. Collectively, our findings demonstrate that ML NK cells exhibit enhanced responses against CRC targets, warranting further investigation in clinical trials for mCRC patients, including those who have failed ICB.

Acute Corneal Edema in a Middle-Aged Patient.

A middle-aged patient who had bilateral penetrating keratoplasty 20 years ago for keratoconus presented with pain and blurriness of the right eye for 2 days. Despite prompt corticosteroid therapy, they had no vision improvement and reported occasional pain. What would you do next?

Cancer-associated fibroblast-derived Dickkopf-1 suppresses NK cell cytotoxicity in breast cancer.

Breast cancer is poorly immunogenic, hence able to evade T cell recognition and respond poorly to immune checkpoint blockade. Breast cancer cells can also evade NK cell-mediated immune surveillance, but the mechanism remains enigmatic. Dickkopf-1 (DKK1) is a Wnt/b-catenin inhibitor, whose levels are increased in breast cancer patients and correlate with reduced overall survival. DKK1 is expressed by cancer-associated fibroblasts (CAFs) in orthotopic breast tumors and patient samples, and at higher levels by bone cells. While bone-derived DKK1 contributes to the systemic elevation of DKK1 in tumor-bearing mice, CAFs represent the primary source of DKK1 at the tumor site. Systemic or bone-specific DKK1 targeting reduces primary tumor growth. Intriguingly, specific deletion of CAF-derived DKK1 also limits breast cancer progression, regardless of its elevated levels in circulation and in the bone. DKK1 does not support tumor proliferation directly but rather suppresses the activation and tumoricidal activity of NK cells. Importantly, increased DKK1 levels and reduced number of cytotoxic NK cells are detected in breast cancer patients with progressive bone metastases compared to those with stable disease. Our findings indicate that DKK1 creates a tumor-supporting environment through the suppression of NK cells in breast cancer.

Mental Distress, Label Avoidance, and Use of a Mental Health Chatbot: Results From a US Survey.

BACKGROUND: For almost two decades, researchers and clinicians have argued that certain aspects of mental health treatment can be removed from clinicians' responsibilities and allocated to technology, preserving valuable clinician time and alleviating the burden on the behavioral health care system. The service delivery tasks that could arguably be allocated to technology without negatively impacting patient outcomes include screening, triage, and referral. OBJECTIVE: We pilot-tested a chatbot for mental health screening and referral to understand the relationship between potential users' demographics and chatbot use; the completion rate of mental health screening when delivered by a chatbot; and the acceptability of a prototype chatbot designed for mental health screening and referral. This chatbot not only screened participants for psychological distress but also referred them to appropriate resources that matched their level of distress and preferences. The goal of this study was to determine whether a mental health screening and referral chatbot would be feasible and acceptable to users. METHODS: We conducted an internet-based survey among a sample of US-based adults. Our survey collected demographic data along with a battery of measures assessing behavioral health and symptoms, stigma (label avoidance and perceived stigma), attitudes toward treatment-seeking, readiness for change, and technology readiness and acceptance. Participants were then offered to engage with our chatbot. Those who engaged with the chatbot completed a mental health screening, received a distress score based on this screening, were referred to resources appropriate for their current level of distress, and were asked to rate the acceptability of the chatbot. RESULTS: We found that mental health screening using a chatbot was feasible, with 168 (75.7%) of our 222 participants completing mental health screening within the chatbot sessions. Various demographic characteristics were associated with a willingness to use the chatbot. The participants who used the chatbot found it to be acceptable. Logistic regression produced a significant model with perceived usefulness and symptoms as significant positive predictors of chatbot use for the overall sample, and label avoidance as the only significant predictor of chatbot use for those currently experiencing distress. CONCLUSIONS: Label avoidance, the desire to avoid mental health services to avoid the stigmatized label of mental illness, is a significant negative predictor of care seeking. Therefore, our finding regarding label avoidance and chatbot use has significant public health implications in terms of facilitating access to mental health resources. Those who are high on label avoidance are not likely to seek care in a community mental health clinic, yet they are likely willing to engage with a mental health chatbot, participate in mental health screening, and receive mental health resources within the chatbot session. Chatbot technology may prove to be a way to engage those in care who have previously avoided treatment due to stigma.

Essential gene knockdowns reveal genetic vulnerabilities and antibiotic sensitivities in Acinetobacter baumannii.

The emergence of multidrug-resistant Gram-negative bacteria underscores the need to define genetic vulnerabilities that can be therapeutically exploited. The Gram-negative pathogen, Acinetobacter baumannii, is considered an urgent threat due to its propensity to evade antibiotic treatments. Essential cellular processes are the target of existing antibiotics and a likely source of new vulnerabilities. Although A. baumannii essential genes have been identified by transposon sequencing, they have not been prioritized by sensitivity to knockdown or antibiotics. Here, we take a systems biology approach to comprehensively characterize A. baumannii essential genes using CRISPR interference (CRISPRi). We show that certain essential genes and pathways are acutely sensitive to knockdown, providing a set of vulnerable targets for future therapeutic investigation. Screening our CRISPRi library against last-resort antibiotics uncovered genes and pathways that modulate beta-lactam sensitivity, an unexpected link between NADH dehydrogenase activity and growth inhibition by polymyxins, and anticorrelated phenotypes that may explain synergy between polymyxins and rifamycins. Our study demonstrates the power of systematic genetic approaches to identify vulnerabilities in Gram-negative pathogens and uncovers antibiotic-essential gene interactions that better inform combination therapies.IMPORTANCEAcinetobacter baumannii is a hospital-acquired pathogen that is resistant to many common antibiotic treatments. To combat resistant A. baumannii infections, we need to identify promising therapeutic targets and effective antibiotic combinations. In this study, we comprehensively characterize the genes and pathways that are critical for A. baumannii viability. We show that genes involved in aerobic metabolism are central to A. baumannii physiology and may represent appealing drug targets. We also find antibiotic-gene interactions that may impact the efficacy of carbapenems, rifamycins, and polymyxins, providing a new window into how these antibiotics function in mono- and combination therapies. Our studies offer a useful approach for characterizing interactions between drugs and essential genes in pathogens to inform future therapies.

A multi-epitope/CXCL11 prime/pull coronavirus mucosal vaccine boosts the frequency and the function of lung-resident memory CD4+ and CD8+ T cells and enhanced protection against COVID-19-like symptoms and death caused by SARS-CoV-2 infection.

IMPORTANCE: Although the current rate of SARS-CoV-2 infections has decreased significantly, COVID-19 still ranks very high as a cause of death worldwide. As of October 2023, the weekly mortality rate is still at 600 deaths in the United States alone, which surpasses even the worst mortality rates recorded for influenza. Thus, the long-term outlook of COVID-19 is still a serious concern outlining the need for the next-generation vaccine. This study found that a prime/pull coronavirus vaccine strategy increased the frequency of functional SARS-CoV-2-specific CD4+ and CD8+ memory T cells in the lungs of SARS-CoV-2-infected triple transgenic HLA-DR*0101/HLA-A*0201/hACE2 mouse model, thereby resulting in low viral titer and reduced COVID-19-like symptoms.

Progress in immune checkpoint inhibition in early-stage triple-negative breast cancer.

INTRODUCTION: Immune checkpoint inhibitors have been particularly effective in treating cancers with robust immune microenvironments and have been successfully incorporated into the management of metastatic ER-negative and HER2-negative breast cancer. This has prompted investigation of immunotherapy in early-stage triple negative breast cancer (TNBC) to address the suboptimal clinical outcomes and limited therapeutic options. AREAS COVERED: This review highlights the studies examining the use of neoadjuvant immunotherapy with standard chemotherapy in the management of early-stage TNBC and explores ongoing areas of study including the role of adjuvant checkpoint inhibition and novel combination therapies with immunotherapy. EXPERT OPINION: The current standard of care for early-stage ER-negative, HER2-negative breast cancer measuring ≥2 cm or with lymph node involvement is neoadjuvant chemotherapy with pembrolizumab followed by ongoing pembrolizumab in the adjuvant setting to complete 1 year of total therapy as per the KEYNOTE-522 study. This approach is associated with improved pathologic complete response (pCR) rate and event free survival, irrespective of PD-L1 status. Many questions remain regarding the optimization of chemotherapy partner(s) for immunotherapy, necessity of adjuvant immunotherapy for patients who achieve pCR, inclusion of other therapies in the adjuvant setting (particularly capecitabine or olaparib), and use of adjuvant immunotherapy when it was not received in the neoadjuvant setting.

Locoregional recurrence in triple negative breast cancer: past, present, and future.

INTRODUCTION: Triple negative breast cancer (TNBC) is a rare but aggressive biological subtype of breast cancer associated with higher locoregional and distant recurrence rates and lower overall survival despite advancements in diagnostic and treatment strategies. AREAS COVERED: This review explores the evolving landscape of locoregional recurrence (LRR) in TNBC with improved surgical and radiation therapy delivery techniques including salvage breast conserving surgery (SBCS), re-irradiation, and thermo-radiation. We review current retrospective and prospective, albeit limited, clinical data highlighting the optimal management of locoregionally recurrent TNBC. We also discuss tumor genomic profiling and transcriptome analysis and review potential investigational directions. EXPERT OPINION: Significant progress has been made in the prevention of LRR but rates remain suboptimal, particularly in the TNBC population, and outcomes following LRR are poor. Further prospective studies are needed to identify the most effective and safest systemic therapy regimens and to whom it should be offered. There has been growing interest in the role of molecular markers, genomic signatures, and tumor microenvironment in predicting outcomes and guiding LRR treatment. Transcriptome analyses and biomarker-driven investigations are currently being studied and represent a promising era of development in the management of LRR.

A Suicide Prevention Intervention for Emerging Adult Sexual and Gender Minority Groups: Protocol for a Pilot Hybrid Effectiveness Randomized Controlled Trial.

BACKGROUND: Suicide attempts and suicide death disproportionately affect sexual and gender minority emerging adults (age 18-24 years). However, suicide prevention strategies tailored for emerging adult sexual and gender minority (EA-SGM) groups are not widely available. The Safety Planning Intervention (SPI) has strong evidence for reducing the risk for suicide in the general population, but it is unclear how best to support EA-SGM groups in their use of a safety plan. Our intervention (Supporting Transitions to Adulthood and Reducing Suicide [STARS]) builds on content from an existing life skills mobile app for adolescent men who have sex with men (iREACH) and seeks to target core risk factors for suicide among EA-SGM groups, namely, positive affect, discrimination, and social disconnection. The mobile app is delivered to participants randomized to STARS alongside 6 peer mentoring sessions to support the use of the safety plan and other life skills from the app to ultimately reduce suicide risk. OBJECTIVE: We will pilot-test the combination of peer mentoring alongside an app-based intervention (STARS) designed to reduce suicidal ideation and behaviors. STARS will include suicide prevention content and will target positive affect, discrimination, and social support. After an in-person SPI with a clinician, STARS users can access content and activities to increase their intention to use SPI and overcome obstacles to its use. EA-SGM groups will be randomized to receive either SPI alone or STARS and will be assessed for 6 months. METHODS: Guided by the RE-AIM (reach, efficacy, adoption, implementation, and maintenance) framework, we will recruit and enroll a racially and ethnically diverse sample of 60 EA-SGM individuals reporting past-month suicidal ideation. Using a type-1 effectiveness-implementation hybrid design, participants will be randomized to receive SPI (control arm) or to receive SPI alongside STARS (intervention arm). We will follow the participants for 6 months, with evaluations at 2, 4, and 6 months. Preliminary effectiveness outcomes (suicidal ideation and behavior) and hypothesized mechanisms of change (positive affect, coping with discrimination, and social support) will serve as our primary outcomes. Secondary outcomes include key implementation indicators, including participants' willingness and adoption of SPI and STARS and staff's experiences with delivering the program. RESULTS: Study activities began in September 2021 and are ongoing. The study was approved by the institutional review board of the University of Pennsylvania (protocol number 849500). Study recruitment began on October 14, 2022. CONCLUSIONS: This project will be among the first tailored, mobile-based interventions for EA-SGM groups at risk for suicide. This project is responsive to the documented gaps for this population: approaches that address chosen family, focus on a life-course perspective, web approaches, and focus on health equity and provision of additional services relevant to sexual and gender minority youth. TRIAL REGISTRATION: ClinicalTrials.gov NCT05018143; https://classic.clinicaltrials.gov/ct2/show/NCT05018143. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/48177.

Essential Gene Knockdowns Reveal Genetic Vulnerabilities and Antibiotic Sensitivities in Acinetobacter baumannii.

The emergence of multidrug-resistant Gram-negative bacteria underscores the need to define genetic vulnerabilities that can be therapeutically exploited. The Gram-negative pathogen, Acinetobacter baumannii, is considered an urgent threat due to its propensity to evade antibiotic treatments. Essential cellular processes are the target of existing antibiotics and a likely source of new vulnerabilities. Although A. baumannii essential genes have been identified by transposon sequencing (Tn-seq), they have not been prioritized by sensitivity to knockdown or antibiotics. Here, we take a systems biology approach to comprehensively characterize A. baumannii essential genes using CRISPR interference (CRISPRi). We show that certain essential genes and pathways are acutely sensitive to knockdown, providing a set of vulnerable targets for future therapeutic investigation. Screening our CRISPRi library against last-resort antibiotics uncovered genes and pathways that modulate beta-lactam sensitivity, an unexpected link between NADH dehydrogenase activity and growth inhibition by polymyxins, and anticorrelated phenotypes that underpin synergy between polymyxins and rifamycins. Our study demonstrates the power of systematic genetic approaches to identify vulnerabilities in Gram-negative pathogens and uncovers antibiotic-essential gene interactions that better inform combination therapies.

Memory-like Differentiation, Tumor-Targeting mAbs, and Chimeric Antigen Receptors Enhance Natural Killer Cell Responses to Head and Neck Cancer.

PURPOSE: Head and neck squamous cell carcinoma (HNSCC) is an aggressive tumor with low response rates to frontline PD-1 blockade. Natural killer (NK) cells are a promising cellular therapy for T cell therapy-refractory cancers, but are frequently dysfunctional in patients with HNSCC. Strategies are needed to enhance NK cell responses against HNSCC. We hypothesized that memory-like (ML) NK cell differentiation, tumor targeting with cetuximab, and engineering with an anti-EphA2 (Erythropoietin-producing hepatocellular receptor A2) chimeric antigen receptor (CAR) enhance NK cell responses against HNSCC. EXPERIMENTAL DESIGN: We generated ML NK and conventional (c)NK cells from healthy donors, then evaluated their ability to produce IFNγ, TNF, degranulate, and kill HNSCC cell lines and primary HNSCC cells, alone or in combination with cetuximab, in vitro and in vivo using xenograft models. ML and cNK cells were engineered to express anti-EphA2 CAR-CD8A-41BB-CD3z, and functional responses were assessed in vitro against HNSCC cell lines and primary HNSCC tumor cells. RESULTS: Human ML NK cells displayed enhanced IFNγ and TNF production and both short- and long-term killing of HNSCC cell lines and primary targets, compared with cNK cells. These enhanced responses were further improved by cetuximab. Compared with controls, ML NK cells expressing anti-EphA2 CAR had increased IFNγ and cytotoxicity in response to EphA2+ cell lines and primary HNSCC targets. CONCLUSIONS: These preclinical findings demonstrate that ML differentiation alone or coupled with either cetuximab-directed targeting or EphA2 CAR engineering were effective against HNSCCs and provide the rationale for investigating these combination approaches in early phase clinical trials for patients with HNSCC.

Assessment of oral overlap with antipsychotic long-acting injectables initiated in an inpatient setting.

Introduction: Long-acting injectable (LAI) antipsychotics are a promising solution to combating issues related to nonadherence to oral antipsychotics. Oral overlap is utilized when an LAI is initiated to achieve therapeutic concentrations. The place in therapy in which additional overlap is warranted is often mistaken, and providers may prescribe additional overlap based on the presentation of the patient or misunderstanding of appropriate overlap. Methods: This retrospective chart review assesses patients who were initiated on an LAI while admitted to the acute inpatient psychiatric unit from January 1, 2016, to December 31, 2019. The primary outcome assesses the appropriateness of oral overlap with LAIs. Secondary outcomes include adherence to oral overlap, discontinuation of an LAI within 4 months, and reason for discontinuation of LAI. Results: A total of 62 patients were included: 40 (65%) had appropriate overlap, and 22 (35%) had inappropriate overlap. The most common LAI was paliperidone (n = 50, 81%). Patients were adherent to oral overlap in 67% (n = 6) of the appropriate overlap group and 85% (n = 17) of the inappropriate overlap group. Discontinuation of an LAI in 4 months occurred in 62.5% (n = 25) of the appropriate group and 40.9% (n = 9) of the inappropriate group. There were no significant differences in secondary outcomes when comparing adherence to oral overlap (p = .26), discontinuation of LAI within 4 months (p = .62), and reason for discontinuation (p = .69). Discussion: This study identified that a majority of patients had appropriate prescribing of oral antipsychotic overlap.

Synthesis and activity of ß-carboline antimalarials targeting the Plasmodium falciparum heat shock 90 protein.

A collection of ß-carbolines based on the natural product harmine, a compound known to target the heat shock 90 protein of Plasmodium falciparum, was synthesized and tested for antimalarial activity and potential toxicity. Several of these novel compounds display promising bioactivity, providing a new potential therapeutic with a mode of action that differs versus any currently available clinical treatment.

T-BET and EOMES sustain mature human NK cell identity and antitumor function.

Since the T-box transcription factors (TFs) T-BET and EOMES are necessary for initiation of NK cell development, their ongoing requirement for mature NK cell homeostasis, function, and molecular programming remains unclear. To address this, T-BET and EOMES were deleted in unexpanded primary human NK cells using CRISPR/Cas9. Deleting these TFs compromised in vivo antitumor response of human NK cells. Mechanistically, T-BET and EOMES were required for normal NK cell proliferation and persistence in vivo. NK cells lacking T-BET and EOMES also exhibited defective responses to cytokine stimulation. Single-cell RNA-Seq revealed a specific T-box transcriptional program in human NK cells, which was rapidly lost following T-BET and EOMES deletion. Further, T-BET- and EOMES-deleted CD56bright NK cells acquired an innate lymphoid cell precursor-like (ILCP-like) profile with increased expression of the ILC-3-associated TFs RORC and AHR, revealing a role for T-box TFs in maintaining mature NK cell phenotypes and an unexpected role of suppressing alternative ILC lineages. Our study reveals the critical importance of sustained EOMES and T-BET expression to orchestrate mature NK cell function and identity.

"A Great Way to Start the Conversation": Evidence for the Use of an Adolescent Mental Health Chatbot Navigator for Youth at Risk of HIV and Other STIs.

Chatbot use is increasing for mobile health interventions on sensitive and stigmatized topics like mental health because of their anonymity and privacy. This anonymity provides acceptability to sexual and gendered minority youth (ages 16-24) at increased risk of HIV and other STIs with poor mental health due to higher levels of stigma, discrimination, and social isolation. This study evaluates the usability of Tabatha-YYC, a pilot chatbot navigator created to link these youth to mental health resources. Tabatha-YYC was developed using a Youth Advisory Board (n = 7). The final design underwent user testing (n = 20) through a think-aloud protocol, semi-structured interview, and a brief survey post-exposure which included the Health Information Technology Usability Evaluation Scale. The chatbot was found to be an acceptable mental health navigator by participants. This study provides important design methodology considerations and key insights into chatbot design preferences of youth at risk of STIs seeking mental health resources.

Non-Invasive Treatment of Basal Cell Carcinoma: Photodynamic Therapy Following Curettage.

BACKGROUND: To investigate the effectiveness, safety, patient satisfaction, and cosmetic outcome of Methyl Aminolevulinate-Photodynamic Therapy (MAL-PDT) following curettage in order to make recommendations for its use in dermatology practices. METHODS: A retrospective chart review of patients who received MAL-PDT following curettage for the indication of basal cell carcinoma (BCC) between 2009 and 2016 at a single private clinic in Ontario, Canada. Two hundred and seventy-eight patients with 352 BCC lesions were included, consisting of 44.2% males (n=123) and 55.8% females (n=155) with a mean age of 57.24 years. The primary outcome measurement consisted of the cure rate. Secondary outcome measurements included side effects, patient satisfaction, and cosmetic outcome, as reported in the medical charts. RESULTS: The overall cure rate was 90.3% (n=318). After controlling for age, sex, and lesion type, nasal lesions were approximately 2.82 (95% CI: 1.24-6.40, P=0.01) times more likely to experience a recurrence. 18.3% of patients (n=51) reported side effects, the most common being burning (n=19). Of those who expressed satisfaction, 100% (n=25) reported being happy. Of lesions with cosmetic data, 90.3% displayed a good response (n=149). CONCLUSION: MAL-PDT following curettage is an effective and safe treatment option for BCC lesions with a good cosmetic outcome and suggested high patient satisfaction. J Drugs Dermatol. 2023;22(5): doi:10.36849/JDD.7133.

Rapid and precise tracking of water influx and efflux across cell membranes induced by a pulsed electric field.

Quantitative measurements of water content within a single cell are notoriously difficult. In this work, we introduce a single-shot optical method for tracking the intracellular water content, by mass and volume, of a single cell at video rate. We utilize quantitative phase imaging and a priori knowledge of a spherical cellular geometry, leveraging a two-component mixture model to compute the intracellular water content. We apply this technique to study CHO-K1 cells responding to a pulsed electric field, which induces membrane permeabilization and rapid water influx or efflux depending upon the osmotic environment. The effects of mercury and gadolinium on water uptake in Jurkat cells following electropermeabilization are also examined.

Mucosal CCL28 Chemokine Improves Protection against Genital Herpes through Mobilization of Antiviral Effector Memory CCR10+CD44+ CD62L-CD8+ T Cells and Memory CCR10+B220+CD27+ B Cells into the Infected Vaginal Mucosa.

Four major mucosal-associated chemokines, CCL25, CCL28, CXCL14, and CXCL17, play an important role in protecting mucosal surfaces from infectious pathogens. However, their role in protection against genital herpes remains to be fully explored. The CCL28 is a chemoattractant for the CCR10 receptor-expressing immune cells and is produced homeostatically in the human vaginal mucosa (VM). In this study, we investigated the role of the CCL28/CCR10 chemokine axis in mobilizing protective antiviral B and T cell subsets into the VM site of herpes infection. We report a significant increase in the frequencies of HSV-specific memory CCR10+CD44+CD8+ T cells, expressing high levels of CCR10, in herpes-infected asymptomatic (ASYMP) women compared with symptomatic women. Similarly, a significant increase in the CCL28 chemokine (a ligand of CCR10), was detected in the VM of herpes-infected ASYMP C57BL/6 mice, associated with the mobilization of high frequencies of HSV-specific effector memory CCR10+CD44+CD62L-CD8+ TEM cells and memory CCR10+B220+CD27+ B cells in the VM of HSV-infected ASYMP mice. Inversely, compared with wild-type C57BL/6 mice, the CCL28 knockout (CCL28-/-) mice (1) appeared to be more susceptible to intravaginal infection and reinfection with HSV type 2, and (2) exhibited a significant decrease in the frequencies of HSV-specific effector memory CCR10+CD44+CD62L-CD8+ TEM cells and of memory CD27+B220+ B cells in the infected VM. These findings suggest a critical role of the CCL28/CCR10 chemokine axis in the mobilization of antiviral memory B and T cells within the VM to protect against genital herpes infection and disease.

Paired analysis of ED efficiency for low-acuity children treated by PAs and pediatricians.

OBJECTIVE: To determine if there was a clinically important difference (15 minutes or more) in length of stay (LOS) for low-acuity pediatric ED patients treated by PAs compared with those treated by pediatricians. METHODS: Between July 2017 and February 2020, shifts were identified that had shared PA and pediatrician staffing in the low-acuity care area for a large, urban ED. LOS was collected for every patient during the 6 hours of overlap for each shift. Using a paired analysis, we calculated the difference in mean LOS for these shifts. RESULTS: Mean shift LOS for children seen by PAs (160.1 minutes, SD: 48.6) was 10.1 minutes longer (95% CI: 6.1, 14.1) than mean shift LOS for children seen by pediatricians (150 minutes, SD: 47.3). CONCLUSIONS: No clinically important difference in LOS was found for low-acuity children treated by PAs compared with those treated by pediatricians in a large, urban ED.