Plastid LPAT1 is an integral inner envelope membrane protein with the acyltransferase domain located in the stroma.

KEY MESSAGE: The N-terminal transmembrane domain of LPAT1 crosses the inner membrane placing the N terminus in the intermembrane space and the C-terminal enzymatic domain in the stroma. Galactolipids mono- and di-galactosyl diacylglycerol are the major and vital lipids of photosynthetic membranes. They are synthesized by five enzymes hosted at different sub-chloroplast locations. However, localization and topology of the second-acting enzyme, lysophosphatidic acid acyltransferase 1 (LPAT1), which acylates the sn-2 position of glycerol-3-phosphate (G3P) to produce phosphatidic acid (PA), remain unclear. It is not known whether LPAT1 is located at the outer or the inner envelope membrane and whether its enzymatic domain faces the cytosol, the intermembrane space, or the stroma. Even the size of mature LPAT1 in chloroplasts is not known. More information is essential for understanding the pathways of metabolite flow and for future engineering endeavors to modify glycerolipid biosynthesis. We used LPAT1 preproteins translated in vitro for import assays to determine the precise size of the mature protein and found that the LPAT1 transit peptide is at least 85 residues in length, substantially longer than previously predicted. A construct comprising LPAT1 fused to the Venus fluorescent protein and driven by the LPAT1 promoter was used to complement an Arabidopsis lpat1 knockout mutant. To determine the sub-chloroplast location and topology of LPAT1, we performed protease treatment and alkaline extraction using chloroplasts containing in vitro-imported LPAT1 and chloroplasts isolated from LPAT1-Venus-complemented transgenic plants. We show that LPAT1 traverses the inner membrane via an N-terminal transmembrane domain, with its N terminus protruding into the intermembrane space and the C-terminal enzymatic domain residing in the stroma, hence displaying a different membrane topology from its bacterial homolog, PlsC.

The role of lysophosphatidic acid acyltransferase 1 in reproductive growth of Arabidopsis thaliana.

Lysophosphatidic acid acyltransferase1 (LPAT1) catalyzes the second step of de novo glycerolipid biosynthesis in chloroplasts. However, the embryonic-lethal phenotype of the knockout mutant suggested an unknown role for LPAT1 in non-photosynthetic reproductive organs. Reciprocal genetic crossing of the lpat1-1 heterozygous line suggested a female gametophytic defect of the lpat1-1 knockout mutant. By suppressing LPAT1 specifically during seed development, we showed that LPAT1 suppression affected silique growth and seed production. Glycerolipid analysis of the LPAT1 knockdown lines revealed a pronounced decrease of phosphatidylcholine (PC) content in mature siliques along with an altered polyunsaturation level of the polar glycerolipids. In seeds, the acyl composition of triacylglycerol (TAG) was altered albeit not the content. These results indicate that plastidic LPAT1 plays an important role in reproductive growth and extraplastidic glycerolipid metabolism involving PC and TAG.

Phosphoethanolamine Transferases as Drug Discovery Targets for Therapeutic Treatment of Multi-Drug Resistant Pathogenic Gram-Negative Bacteria.

Antibiotic resistance caused by multidrug-resistant (MDR) bacteria is a major challenge to global public health. Polymyxins are increasingly being used as last-in-line antibiotics to treat MDR Gram-negative bacterial infections, but resistance development renders them ineffective for empirical therapy. The main mechanism that bacteria use to defend against polymyxins is to modify the lipid A headgroups of the outer membrane by adding phosphoethanolamine (PEA) moieties. In addition to lipid A modifying PEA transferases, Gram-negative bacteria possess PEA transferases that decorate proteins and glycans. This review provides a comprehensive overview of the function, structure, and mechanism of action of PEA transferases identified in pathogenic Gram-negative bacteria. It also summarizes the current drug development progress targeting this enzyme family, which could reverse antibiotic resistance to polymyxins to restore their utility in empiric therapy.

[Bilateral breast reconstruction by DIEP flap in two stages: Technical note]. / Reconstruction mammaire bilaterale par lambeau de DIEP en deux temps : note technique.

With the rise of risk prevention surgery, more and more bilateral mastectomies are performed. These present a challenge when patients desire autologous reconstruction. Some surgeons perform reconstructions using a double DIEP flap, but this technique, which requires rapid operation and extensive experience, can sometimes be difficult to implement. Other factors may also favor a two-stage reconstruction, one breast after the other. We present here our technique to harvest two hemi-DIEP during two distinct operating times, by modifying the design of the first flap and by performing a prior autonomization of the second.

Distinctly localized lipid phosphate phosphatases mediate endoplasmic reticulum glycerolipid metabolism in Arabidopsis.

Inter-organelle communication is an integral subcellular process in cellular homeostasis. In plants, cellular membrane lipids are synthesized in the plastids and endoplasmic reticulum (ER). However, the crosstalk between these organelles in lipid biosynthesis remains largely unknown. Here, we show that a pair of lipid phosphate phosphatases (LPPs) with differential subcellular localizations is required for ER glycerolipid metabolism in Arabidopsis (Arabidopsis thaliana). LPPα2 and LPPε1, which function as phosphatidic acid phosphatases and thus catalyze the core reaction in glycerolipid metabolism, were differentially localized at ER and chloroplast outer envelopes despite their similar tissue expression pattern. No mutant phenotype was observed in single knockout mutants; however, genetic suppression of these LPPs affected pollen growth and ER phospholipid biosynthesis in mature siliques and seeds with compromised triacylglycerol biosynthesis. Although chloroplast-localized, LPPε1 was localized close to the ER and ER-localized LPPα2. This proximal localization is functionally relevant, because overexpression of chloroplastic LPPε1 enhanced ER phospholipid and triacylglycerol biosynthesis similar to the effect of LPPα2 overexpression in mature siliques and seeds. Thus, ER glycerolipid metabolism requires a chloroplast-localized enzyme in Arabidopsis, representing the importance of inter-organelle communication in membrane lipid homeostasis.

Understanding a Care Management System's Role in Influencing a Transitional-Aged Youth Program's Practice: Mixed Methods Study.

BACKGROUND: Extended foster care programs help prepare transitional-aged youth (TAY) to step into adulthood and live independent lives. Aspiranet, one of California's largest social service organizations, used a social care management solution (SCMS) to meet TAY's needs. OBJECTIVE: We aimed to investigate the impact of an SCMS, IBM Watson Care Manager (WCM), in transforming foster program service delivery and improving TAY outcomes. METHODS: We used a mixed methods study design by collecting primary data from stakeholders through semistructured interviews in 2021 and by pulling secondary data from annual reports, system use logs, and data repositories from 2014 to 2021. Thematic analysis based on grounded theory was used to analyze qualitative data using NVivo software. Descriptive analysis of aggregated outcome metrics in the quantitative data was performed and compared across 2 periods: pre-SCMS implementation (before October 31, 2016) and post-SCMS implementation (November 1, 2016, and March 31, 2021). RESULTS: In total, 6 Aspiranet employees (4 leaders and 2 life coaches) were interviewed, with a median time of 56 (IQR 53-67) minutes. The majority (5/6, 83%) were female, over 30 years of age (median 37, IQR 32-39) with a median of 6 (IQR 5-10) years of experience at Aspiranet and overall field experience of 10 (IQR 7-14) years. Most (4/6, 67%) participants rated their technological skills as expert. Thematic analysis of participants' interview transcripts yielded 24 subthemes that were grouped into 6 superordinate themes: study context, the impact of the new tool, key strengths, commonly used features, expectations with WCM, and limitations and recommendations. The tool met users' initial expectations of streamlining tasks and adopting essential functionalities. Median satisfaction scores around pre- and post-WCM workflow processes remained constant between 2 life coaches (3.25, IQR 2.5-4); however, among leaders, post-WCM scores (median 4, IQR 4-5) were higher than pre-WCM scores (median 3, IQR 3-3). Across the 2 study phases, Aspiranet served 1641 TAY having consistent population demographics (median age of 18, IQR 18-19 years; female: 903/1641, 55.03%; race and ethnicity: Hispanic or Latino: 621/1641, 37.84%; Black: 470/1641, 28.64%; White: 397/1641, 24.19%; Other: 153/1641, 9.32%). Between the pre- and post-WCM period, there was an increase in full-time school enrollment (359/531, 67.6% to 833/1110, 75.04%) and a reduction in part-time school enrollment (61/531, 11.5% to 91/1110, 8.2%). The median number of days spent in the foster care program remained the same (247, IQR 125-468 years); however, the number of incidents reported monthly per hundred youth showed a steady decline, even with an exponentially increasing number of enrolled youth and incidents. CONCLUSIONS: The SCMS for coordinating care and delivering tailored services to TAY streamlined Aspiranet's workflows and processes and positively impacted youth outcomes. Further enhancements are needed to better align with user and youth needs.

The prediction capability of a cataract surgery risk stratification model based on a large electronic medical record dataset.

Purpose: The aim of this study was to develop a risk stratification system that predicts visual outcomes (uncorrected corrected visual acuity at one week and five weeks postoperative) in patients undergoing cataract surgery. Methods: This was a retrospective analysis in a multitier ophthalmology network. Data from all patients who underwent phacoemulsification or manual small-incision cataract surgery between January 2018 and December 2019 were retrieved from an electronic medical record system. There were 122,911 records; 114,172 (92.9%) had complete data included. Logistic regression analyzed unsatisfactory postoperative outcomes using a main effects model only. The final model was cross-checked using forward stepwise selection. The Hosmer-Lemeshow goodness of fit test, the Bayesian information criterion, and Nagelkerke's R2 assessed model fit. Dispersion was calculated from deviance and degrees of freedom and C-stat from receiving operating characteristics analysis. Results: The final phacoemulsification model (n = 48,169) had a dispersion of 1.08 with a Hosmer-Lemeshow goodness of fit of 0.20, a Nagelkerke R2 of 0.19, and a C-stat of 0.72. The final manual small-incision cataract surgery model (n = 66,003) had a dispersion of 1.05 with a Hosmer-Lemeshow goodness of fit of 0.00015, a Nagelkerke R2 of 0.14, and a C-stat of 0.68. Conclusion: The phacoemulsification model had reasonable model fit; the manual small-incision cataract surgery model had poor fit and was likely missing variables. The predictive capability of these models based on a large, real-world cataract surgical dataset was suboptimal to determine which patients could benefit most from sight-restoring surgery. Appropriate patient selection for cataract surgery in developing settings should still rely on clinician thought processes, intuition, and experience, with more complex cases allocated to more experienced surgeons.

Embracing technology in cataract surgical training - The way forward.

While ophthalmology as a surgical branch itself has evolved technologically with newer instruments, techniques and procedures; ophthalmic surgical training appears to have stagnated in terms of how it is delivered and how trainees' learning and performance are assessed. This collaborative editorial attempts to identify the lacunae in ophthalmic residency training and highlight how technological tools such as surgical simulators can be incorporated into ophthalmic training even in limited-resource settings with good results.

Concentrated incarceration and the public-housing-to-prison pipeline in New York City neighborhoods.

Using public housing developments as a strategic site, our research documents a distinct pathway linking disadvantaged context to incarceration-the public-housing-to-prison pipeline. Focusing on New York City Housing Authority (NYCHA) housing developments as a case study, we find that incarceration rates in NYCHA tracts are 4.6 times higher than those in non-NYCHA tracts. More strikingly, 94% of NYCHA tracts report rates above the median value for non-NYCHA tracts. Moreover, 17% of New York State's incarcerated population originated from just 372 NYCHA tracts. Compared with non-NYCHA tracts, NYCHA tracts had higher shares of Black residents and were significantly more disadvantaged. This NYCHA disadvantage in concentrated incarceration is also robust at different spatial scales. Our findings have implications for policies and programs to disrupt community-based pipelines to prison.

Novel small molecules that increase the susceptibility of Neisseria gonorrhoeae to cationic antimicrobial peptides by inhibiting lipid A phosphoethanolamine transferase.

OBJECTIVES: Neisseria gonorrhoeae is an exclusively human pathogen that commonly infects the urogenital tract resulting in gonorrhoea. Empirical treatment of gonorrhoea with antibiotics has led to multidrug resistance and the need for new therapeutics. Inactivation of lipooligosaccharide phosphoethanolamine transferase A (EptA), which attaches phosphoethanolamine to lipid A, results in attenuation of the pathogen in infection models. Small molecules that inhibit EptA are predicted to enhance natural clearance of gonococci via the human innate immune response. METHODS: A library of small-fragment compounds was tested for the ability to enhance susceptibility of the reference strain N. gonorrhoeae FA1090 to polymyxin B. The effect of these compounds on lipid A synthesis and viability in models of infection were tested. RESULTS: Three compounds, 135, 136 and 137, enhanced susceptibility of strain FA1090 to polymyxin B by 4-fold. Pre-treatment of bacterial cells with all three compounds resulted in enhanced killing by macrophages. Only lipid A from bacterial cells exposed to compound 137 showed a 17% reduction in the level of decoration of lipid A with phosphoethanolamine by MALDI-TOF MS analysis and reduced stimulation of cytokine responses in THP-1 cells. Binding of 137 occurred with higher affinity to purified EptA than the starting material, as determined by 1D saturation transfer difference NMR. Treatment of eight MDR strains with 137 increased susceptibility to polymyxin B in all cases. CONCLUSIONS: Small molecules have been designed that bind to EptA, inhibit addition of phosphoethanolamine to lipid A and can sensitize N. gonorrhoeae to killing by macrophages.

Primary Breast Tuberculosis Mastitis Manifested as Nonhealing Abscess.

Primary breast tuberculosis (TB) is a rare extrapulmonary TB mainly affecting young women of childbearing age from endemic countries. Its incidence is increasing in immunocompromised and HIV-infected people and with the emergence of drug-resistant strains of Mycobacterium tuberculosis (MTB). There are no specific clinical signs suggestive of this disease, it often presents as a hard mass or breast abscess. There is an overlap of features with other inflammatory, infectious, benign lesions, fat necrosis and malignant neoplasms of the breast. The detection of MTB remains the gold standard for diagnosis. Several other diagnostic modalities are used, with varying lack of sensitivity and specificity, and with a range of false negatives. A quarter of cases were treated solely on the basis of clinical, imaging or histological suspicion, without confirmation of the diagnosis. Therefore, we report the case of a young Vietnamese woman, presented for a nonhealing breast abscess, and diagnosed with breast TB based on the patient's ethnicity, histological findings, lack of clinical response to conventional antibiotic therapy, and a good clinical response to anti-TB treatment.

Update of a Simple Model to Calculate the Annual Global Productivity Loss Due to Blindness and Moderate and Severe Vision Impairment.

PURPOSE: To develop a simple but more precise model to calculate potential annual productivity losses due to blindness and moderate and severe vision impairment (MSVI) at the national, regional, and global level. METHODS: Productivity loss was defined as the loss of minimum wage/Gross National Income per capita (GNI) incurred by people aged 50-64 years with blindness or MSVI, who were not able to work or worked with reduced earnings in 2020. We developed a global list of minimum wage data from on-line sources. All other model data were sourced from international, standardised, and open-access databases. For blindness, the total productivity loss (not working) incurred by 64%-90% of the affected population was summed up with partial productivity loss, defined as 10%-36% of the affected population earning one-third of that of the sighted population. For MSVI, the total productivity loss for 30%-55% of the affected population was summed with the partial productivity loss, defined as 45%-70% of the affected population having 35% reduced earnings. The costs of blindness and MSVI were summed to obtain the cost of combined vision loss. RESULTS: The global cost of vision loss based on minimum wage was US$160-US$216.32 billion for 2020. The global cost of vision loss using GNI was US$449.36-US$584.66 billion. CONCLUSIONS: A parsimonious model that considers minimum wage and GNI potentially lost due to blindness and MSVI can be used for eye care programming planning and advocacy at the national, regional, and global level.

Functional divergence of a pair of Arabidopsis phospho-base methyltransferases, PMT1 and PMT3, conferred by distinct N-terminal sequences.

In seed plants, phospho-base N-methyltransferase (PMT) catalyzes a key step in the biosynthesis pathway of phosphatidylcholine (PC), the most abundant phospholipid class. Arabidopsis thaliana possesses three copies of PMT, with PMT1 and PMT3 play a primary role because the pmt1 pmt3 double mutant shows considerably reduced PC content with a pale seedling phenotype. Although the function of PMT1 and PMT3 may be redundant because neither of the parental single mutants showed a similar mutant phenotype, major developmental defects and possible functional divergence of these PMTs underlying the pale pmt1 pmt3 seedling phenotype are unknown. Here, we show the major developmental defect of the pale seedlings in xylem of the hypocotyl with partial impairments in chloroplast development and photosynthetic activity in leaves. Although PMT1 and PMT3 are localized at the endoplasmic reticulum, their tissue-specific expression pattern was distinct in hypocotyls and roots. Intriguingly, the function of PMT3 but not PMT1 requires its characteristic N-terminal sequence in addition to the promoter because truncation of the N-terminal sequence of PMT3 or substitution with PMT1 driven by the PMT3 promoter failed to rescue the pale pmt1 pmt3 seedling phenotype. Thus, PMT3 function requires the N-terminal sequence in addition to its promoter, whereas the PMT1 function is defined by the promoter.

Meta-analysis of gender inequities in cataract surgical coverage in Latin America.

OBJECTIVE: To perform an updated meta-analysis of cataract surgical coverage (CSC) data in Latin American studies to confirm that gender equity exists in terms of receiving cataract surgery. MATERIALS AND METHODS: A literature search of Rapid Assessment of Avoidable Blindness (RAAB) studies in Latin American published since 2011 was done. Older studies from countries that did not have newer data published were also included. Using summary original study data of CSC rates on an individual basis, a random effects model of meta-analysis was performed to evaluate the differences in CSC between men and women. RESULTS: Nineteen studies from 17 countries were included (Mexico data were pooled). The odds ratios at a visual acuity (VA) of <3/60 and <6/18 were 1.04 [95% confidence interval (CI): 0.82-1.32] and 1.04 (95% CI: 0.90-1.19), respectively, without heterogeneity. There were no significant gender differences for CSC at any VA level. CONCLUSIONS: This updated meta-analysis of CSC data from Latin American countries supports that gender inequity in terms of receiving cataract surgery is not an issue in the region. The results do not provide insight into gender inequity in terms of the quality of cataract surgery and other types of eye care services.

OBJETIVO: Realizar un metaanálisis actualizado de la cobertura de cirugía de catarata en estudios latinoamericanos para confirmar que existe equidad de género en términos del acceso a cirugía de catarata. MATERIAL Y MÉTODOS: Se realizó una búsqueda de la literatura de "Rapid Assessments of Avoidable Blindness (Encuestas Rápida de Ceguera Evitable)" publicados en Latinoamérica desde el 2011. Se incluyeron también estudios anteriores de países que no tenían publicados datos más recientes. Utilizando el compendio de datos de los estudios originales de la cobertura de cirugía de catarata (Cataract Surgery Coverage, CSC por sus siglas en inglés) en base individual, se realizó un modelo de efectos aleatorios de metaanálisis para evaluar las diferencias en la CSC entre hombres y mujeres. RESULTADOS: Se incluyeron 19 estudios de 17 países (los datos de México fueron agrupados). La oportunidad relativa (razón de probabilidades) para una agudeza visual (AV) de <3/60 y <6/18 fueron de 1.04 [95% Intervalo de confianza (IC): 0.82-1.32] y 1.04 (95% IC: 0.90-1.19), respectivamente, sin heterogeneidad. No hubo diferencias significativas para la CSC a ningún nivel de AV. CONCLUSIONES: Este metaanálisis actualizado de la CSC de Latinoamérica, confirma que no existe inequidad de género en términos de acceso a cirugía de catarata en esta región.

Digital Health Interventions to Enhance Prevention in Primary Care: Scoping Review.

BACKGROUND: Disease prevention is a central aspect of primary care practice and is comprised of primary (eg, vaccinations), secondary (eg, screenings), tertiary (eg, chronic condition monitoring), and quaternary (eg, prevention of overmedicalization) levels. Despite rapid digital transformation of primary care practices, digital health interventions (DHIs) in preventive care have yet to be systematically evaluated. OBJECTIVE: This review aimed to identify and describe the scope and use of current DHIs for preventive care in primary care settings. METHODS: A scoping review to identify literature published from 2014 to 2020 was conducted across multiple databases using keywords and Medical Subject Headings terms covering primary care professionals, prevention and care management, and digital health. A subgroup analysis identified relevant studies conducted in US primary care settings, excluding DHIs that use the electronic health record (EHR) as a retrospective data capture tool. Technology descriptions, outcomes (eg, health care performance and implementation science), and study quality as per Oxford levels of evidence were abstracted. RESULTS: The search yielded 5274 citations, of which 1060 full-text articles were identified. Following a subgroup analysis, 241 articles met the inclusion criteria. Studies primarily examined DHIs among health information technologies, including EHRs (166/241, 68.9%), clinical decision support (88/241, 36.5%), telehealth (88/241, 36.5%), and multiple technologies (154/241, 63.9%). DHIs were predominantly used for tertiary prevention (131/241, 54.4%). Of the core primary care functions, comprehensiveness was addressed most frequently (213/241, 88.4%). DHI users were providers (205/241, 85.1%), patients (111/241, 46.1%), or multiple types (89/241, 36.9%). Reported outcomes were primarily clinical (179/241, 70.1%), and statistically significant improvements were common (192/241, 79.7%). Results were summarized across the following 5 topics for the most novel/distinct DHIs: population-centered, patient-centered, care access expansion, panel-centered (dashboarding), and application-driven DHIs. The quality of the included studies was moderate to low. CONCLUSIONS: Preventive DHIs in primary care settings demonstrated meaningful improvements in both clinical and nonclinical outcomes, and across user types; however, adoption and implementation in the US were limited primarily to EHR platforms, and users were mainly clinicians receiving alerts regarding care management for their patients. Evaluations of negative results, effects on health disparities, and many other gaps remain to be explored.

Clinical insights into hematologic malignancies and comparative analysis of molecular signatures of acute myeloid leukemia in different ethnicities using an artificial intelligence offering.

ABSTRACT: Next generation sequencing generates copious amounts of genomics data, causing manual interpretation to be laborious and non-scalable while remaining subjective (even for highly trained specialists). We evaluated the performance of the artificial intelligence-based offering Watson for Genomics (WfG), a variant interpretation platform, in hematologic malignancies for the first time.Next generation sequencing was performed for patients treated for various hematological malignancies at Hallym University Sacred Heart Hospital, South Korea, between December 2017 and August 2020 using a 54-gene panel. Both WfG and expert manual curation were used to evaluate the performance of WfG. Acute myeloid leukemia (AML) molecular profiles were compared between Koreans and other ethnic groups using a publicly available dataset.Seventy-seven patients were analyzed (AML: 45, myeloproliferative neoplasms: 12, multiple myeloma: 7, myelodysplastic syndromes: 6, and others: 7). The concordance between the manual and WfG interpretations of 35 variants in 11 random patients was 94%. Among all patients, WfG identified 39 (51%) with at least 1 clinically actionable therapeutic alteration (i.e., a variant targeted by a United States Food and Drug Administration [US FDA]-approved drug, off-label drug, or clinical trial). Moreover, 46% of these patients (18/39) had genes that were targeted by a US FDA-approved therapy. WfG identified diagnostic or prognostic insights in 65% of the patients with no targetable alterations. In those with AML, FLT3-internal tandem duplications or tyrosine kinase domain mutations were less frequent among Koreans than among Caucasians (6.7% vs 30.2%, P < .001) or Hispanics (6.7% vs 28.3%, P = .005), suggesting ethnic differences.Variant interpretation using WfG correlated well with manually curated expert opinions. WfG provided therapeutic insights (including variant-specific drugs and clinical trials that cannot easily be provided by expert manual curation), as well as diagnostic and/or prognostic information.

Effectiveness of Contact Tracing for Viral Disease Mitigation and Suppression: Evidence-Based Review.

BACKGROUND: Contact tracing in association with quarantine and isolation is an important public health tool to control outbreaks of infectious diseases. This strategy has been widely implemented during the current COVID-19 pandemic. The effectiveness of this nonpharmaceutical intervention is largely dependent on social interactions within the population and its combination with other interventions. Given the high transmissibility of SARS-CoV-2, short serial intervals, and asymptomatic transmission patterns, the effectiveness of contact tracing for this novel viral agent is largely unknown. OBJECTIVE: This study aims to identify and synthesize evidence regarding the effectiveness of contact tracing on infectious viral disease outcomes based on prior scientific literature. METHODS: An evidence-based review was conducted to identify studies from the PubMed database, including preprint medRxiv server content, related to the effectiveness of contact tracing in viral outbreaks. The search dates were from database inception to July 24, 2020. Outcomes of interest included measures of incidence, transmission, hospitalization, and mortality. RESULTS: Out of 159 unique records retrieved, 45 (28.3%) records were reviewed at the full-text level, and 24 (15.1%) records met all inclusion criteria. The studies included utilized mathematical modeling (n=14), observational (n=8), and systematic review (n=2) approaches. Only 2 studies considered digital contact tracing. Contact tracing was mostly evaluated in combination with other nonpharmaceutical interventions and/or pharmaceutical interventions. Although some degree of effectiveness in decreasing viral disease incidence, transmission, and resulting hospitalizations and mortality was observed, these results were highly dependent on epidemic severity (R0 value), number of contacts traced (including presymptomatic and asymptomatic cases), timeliness, duration, and compliance with combined interventions (eg, isolation, quarantine, and treatment). Contact tracing effectiveness was particularly limited by logistical challenges associated with increased outbreak size and speed of infection spread. CONCLUSIONS: Timely deployment of contact tracing strategically layered with other nonpharmaceutical interventions could be an effective public health tool for mitigating and suppressing infectious outbreaks by decreasing viral disease incidence, transmission, and resulting hospitalizations and mortality.