Crimean Congo hemorrhagic fever virus nucleoprotein and GP38 subunit vaccine combination prevents morbidity in mice.

Immunizing mice with Crimean-Congo hemorrhagic fever virus (CCHFV) nucleoprotein (NP), glycoprotein precursor (GPC), or with the GP38 domain of GPC, can be protective when the proteins are delivered with viral vectors or as a DNA or RNA vaccine. Subunit vaccines are a safe and cost-effective alternative to some vaccine platforms, but Gc and Gn glycoprotein subunit vaccines for CCHFV fail to protect despite eliciting high levels of neutralizing antibodies. Here, we investigated humoral and cellular immune responses and the protective efficacy of recombinant NP, GP38, and GP38 forms (GP85 and GP160) associated with the highly glycosylated mucin-like (MLD) domain, as well as the NP + GP38 combination. Vaccination with GP160, GP85, or GP38 did not confer protection, and vaccination with the MLD-associated GP38 forms blunted the humoral immune responses to GP38, worsened clinical chemistry, and increased viral RNA in the blood compared to the GP38 vaccination. In contrast, NP vaccination conferred 100% protection from lethal outcome and was associated with mild clinical disease, while the NP + GP38 combination conferred even more robust protection by reducing morbidity compared to mice receiving NP alone. Thus, recombinant CCHFV NP alone is a promising vaccine candidate conferring 100% survival against heterologous challenge. Moreover, incorporation of GP38 should be considered as it further enhances subunit vaccine efficacy by reducing morbidity in surviving animals.

Early Complications of Planned Resection Versus Unplanned Excision of Sarcomas in the Distal Upper Extremity.

Purpose: Unplanned excisions are defined as excisions of malignant tumors performed without preoperative cross-sectional imaging or diagnostic biopsy, frequently resulting in residual disease and re-excision secondary to positive surgical margins. The purpose of this study was to compare the relative morbidity of planned versus unplanned upper-extremity sarcoma excisions. Methods: A single tertiary referral hospital pathology database was queried from January 2015 through 2022 for primary upper-extremity sarcomas (forearm, wrist, hand, and finger). Demographics, tumor features, survival characteristics, and outcomes were retrospectively reviewed. Results: Forty-two upper-extremity sarcoma patients were identified, two-thirds of whom had unplanned excisions. Those with unplanned excisions were more likely to be female (relative risk [RR]: 1.9; P = .002), undergo initial excision at a nonsarcoma center (RR: 14.0; P < .001), have masses distal to the forearm (RR: 1.6; P = .02), and have smaller masses (4.8 vs 7.4 cm, P = .03). 71.4% of tumors were high grade, and 60.7% less than 5 cm in size.Unplanned excisions had positive margins in 96.4% of cases and were more likely to undergo re-excision (odds ratio [OR]: 20.0; P = .001), more total resections (2.7 vs 1.4, P = .009), sacrifice of neurovascular structures (OR: 6.1; P = .04), adjuvant radiation therapy (OR: 4.5; P = .05), adjuvant systemic therapy (OR: 10.9; P = .03), or experience a complication (OR: 17.6; P = .002) at an average of 38.0 months of follow-up.Nearly half of all unplanned excision patients developed a local recurrence or metastatic disease. Six patients required an amputation versus one in the planned cohort (P = .17), and 26.5% of patients died at an average of 32.5 months from presentation. Conclusions: Distal upper-extremity sarcoma excisions are frequently unplanned, with high rates of morbidity compared with planned excisions. Surgeons should have a low threshold for cross-sectional imaging and core needle biopsy of atypical lesions, irrespective of size, with referral to a sarcoma center. Type of study/level of evidence: Prognostic IV.

Treatment of a Carpal Giant Cell Tumor of Bone With Curettage and Cemented Capitohamate Fusion.

Carpal giant cell tumor of bone spanning multiple bones is a rare condition. We present a case of a man in his fifth decade with wrist pain who was found to have giant cell tumor of bone involving his capitate and hamate bones. This condition was successfully treated with intralesional curettage, argon beam coagulation, chemical cauterization and a cemented limited carpal fusion with satisfactory outcomes and no recurrence at 1-year postoperative follow-up.

Association of Opioid Disposal Practices with Parental Education and a Home Opioid Disposal Kit Following Pediatric Ambulatory Surgery.

BACKGROUND: The majority of opioid analgesics prescribed for pain after ambulatory pediatric surgery remain unused. Most parents do not dispose of these leftover opioids or dispose of them in an unsafe manner. We aimed to evaluate the association of optimal opioid disposal with a multidisciplinary quality improvement (QI) initiative that proactively educated parents about the importance of optimal opioid disposal practices and provided a home opioid disposal kit before discharge after pediatric ambulatory surgery. METHODS: Opioid disposal behaviors were assessed during a brief telephone interview pre- (Phase I) and post-implementation (Phase II) after surgery. For each phase, we aimed to contact the parents of 300 pediatric patients ages 0 to 17 years who were prescribed an opioid after an ambulatory surgery. The QI initiative included enhanced education and a home opioid disposal kit including DisposeRX®, a medication disposal packet that renders medications inert within a polymeric gel when mixed with water. Weighted segmented regression models evaluated the association between the QI initiative and outcomes. We considered the association between the QI initiative and outcome significant if the beta coefficient for the change in intercept between the end of Phase I and the beginning of Phase II was significant. Safe opioid disposal and any opioid disposal were evaluated as secondary outcomes. RESULTS: The analyzed sample contained 161 pediatric patients in Phase I and 190 pediatric patients in Phase II. Phase II (post-QI initiative) cohort compared to Phase I cohort reported higher rates of optimal (58%, n = 111/190 vs 11%, n = 18/161) and safe (66%, n = 125/190 vs 34%, n = 55/161) opioid disposal. Weighted segmented regression analyses demonstrated significant increases in the odds of optimal (odds ratio [OR], 26.5, 95% confidence interval [CI], 4.0-177.0) and safe (OR, 4.4, 95% CI, 1.1-18.4) opioid disposal at the beginning of Phase II compared to the end of Phase I. The trends over time (slopes) within phases were nonsignificant and close to 0. The numbers needed to be exposed to achieve one new disposal event were 2.2 (95% CI, 1.4-3.7]), 3.1 (95% CI, 1.6-7.4), and 4.3 (95% CI, 1.7-13.6) for optimal, safe, and any disposal, respectively. CONCLUSIONS: A multidisciplinary approach to educating parents on the importance of safe disposal of leftover opioids paired with dispensing a convenient opioid disposal kit was associated with increased odds of optimal opioid disposal.

Compliance with tetracycline eye ointment during annual mass drug administration for trachoma control in the Amhara region, Ethiopia.

OBJECTIVES: A 6-week course of tetracycline eye ointment is an alternative to single -dose oral azithromycin in annual mass drug administration for trachoma control. Compliance with the recommended tetracycline eye ointment regimen has not been well characterised when administered as part of a trachoma control program. METHODS: A routine mass drug administration for trachoma was carried out in 40 communities in the Amhara region of Ethiopia. Two tubes of tetracycline eye ointment, to be administered twice daily for 6 weeks, was offered to all children under 6 months of age, to pregnant women who declined to take azithromycin, and to all individuals with a macrolide allergy. Seven weeks following the mass drug administration, a treatment compliance survey was performed for all community members documented to have received tetracycline eye ointment during the mass drug administration. RESULTS: Of the 491 individuals documented as having received tetracycline eye ointment from the treatment records, 367 completed the survey, of which 214 recalled being offered tetracycline eye ointment. A total of 105 (49%) respondents reported taking ≥1 daily dose of tetracycline eye ointment on most days of the week for at least the first week. Only 20 (9%) respondents reported taking at least 1 tetracycline eye ointment dose per week for 6 weeks. The most common reasons for low compliance included 'saving it for a future infection' and 'stopped because I (or my child) seemed healthy'. The odds of low compliance were greater for those who reported not having adequate counselling (e.g., odds ratio [OR] 5.3, 95% CI 2.5-28.9 when low compliance was defined as not taking a tetracycline eye ointment dose for most days of at least the first week). CONCLUSIONS: Compliance with tetracycline eye ointment was low when administered by a trachoma program during a routine mass drug administration, especially for those reporting inadequate counselling. Further research with a larger sample size and varied settings is warranted to better understand and improve compliance.

"What choice do we have?" Reactive and proactive decision-making for aging in place with dementia.

BACKGROUND: Promoting options for aging in place (AIP) has broad appeal to policymakers and professionals providing services to persons living with dementia (PWD). However, the benefits or burdens of AIP likely vary among individuals and families. We sought to describe factors influencing decision-making to age in place versus seek a higher level of residential care for PWD. METHODS: A qualitative study was undertaken as part of a larger mixed-methods study utilizing semi-structured interviews with PWD, family care partners, and dementia clinicians. Interview transcripts were analyzed using qualitative content analysis with constant comparison. Sample size was determined by thematic saturation within subgroups. RESULTS: We conducted 74 interviews among 14 PWD, 36 care partners, and 24 clinicians. Preferences for AIP were driven by (1) desire to preserve independence, (2) a sense that the "best care" is delivered by loved ones and in a familiar environment, (3) distrust and fear of care facilities, and (4) caregiver guilt. PWD and care partners frequently considered moving from home as a "last resort" and wanted to avoid planning for future care needs. Many decisions to move were reactive and triggered by patient safety events, physical dependency, or the loss of caregiver. Proactive decision-making was facilitated by (1) prior experience witnessing the challenges of caring for a person with advanced dementia in the home; and (2) having substantial financial resources such that participants could seek major home adaptations or avoid "lower quality" institutions. CONCLUSIONS: Decisions regarding care setting for PWD frequently do not feel like a choice and are made under imperfect conditions. Programs using AIP as an outcome measure should recognize the various patient-centered and non-patient-centered factors that influence such choices, and interventions should be designed to promote more informed and equitable decision-making for care setting in dementia.

Spatial memory encoding is associated with the anterior and posterior hippocampus: An fMRI activation likelihood estimation meta-analysis.

It has been hypothesized that differential processing occurs along the longitudinal (anterior-posterior) axis of the hippocampus. One hypothesis is that spatial memory (during both encoding and retrieval) is associated with the posterior hippocampus. An alternative hypothesis is that memory encoding (either spatial or nonspatial) is associated with the anterior hippocampus and memory retrieval is associated with the posterior hippocampus. Of importance, during spatial memory encoding, the spatial-posterior hypothesis predicts posterior hippocampal involvement, whereas the encoding-retrieval hypothesis predicts anterior hippocampal involvement. To distinguish between these hypotheses, we conducted a coordinate-based fMRI activation likelihood estimation (ALE) meta-analysis of 26 studies (with a total of 435 participants) that reported hippocampal activity during spatial memory encoding and/or spatial memory retrieval. Both spatial memory encoding and spatial memory retrieval produced extensive activity along the longitudinal axis of the hippocampus as well as the entorhinal cortex, the perirhinal cortex, and the parahippocampal cortex. Critically, the contrast of spatial memory encoding and spatial memory retrieval produced activations in both the anterior hippocampus and the posterior hippocampus. That spatial memory encoding produced activity in both the anterior and posterior hippocampus can be taken to reject strict forms of the spatial-posterior hypothesis, which stipulates that all forms of spatial memory produce activity in the posterior hippocampus, and the encoding-retrieval hypothesis, which stipulates that all forms of encoding versus retrieval produce activity in only the anterior hippocampus. Our results indicate that spatial memory encoding can involve the anterior hippocampus and the posterior hippocampus.

Evaluation of Tibial Slope on Radiographs in Pediatric Patients With Tibial Spine Fractures: An Age- and Sex-Matched Study.

Background: A recent study has reported that the radiographic measurement of posterior tibial slope (PTS) is larger in male pediatric patients with tibial spine fractures (TSF) than in controls. However, they found no difference in PTS between female patients and controls. Purpose: (1) To identify whether PTS is larger in female pediatric patients with TSF than in female controls and (2) to validate the relationship between PTS and pediatric TSF in male patients. Study Design: Cross-sectional study; Level of evidence, 3. Methods: After an a priori power analysis, 84 pediatric patients with TSF (50 female patients and 34 male patients) and 84 age- and sex-matched controls were enrolled in this study. Demographic information, including sex, age, and race, was recorded. Skeletal maturity was determined based on the stage of epiphyseal union on knee radiographs. PTS was defined as the angle between a line perpendicular to the longitudinal axis of the tibia and the posterior inclination of the medial tibial plateau on standard knee lateral radiographs. Results: The mean age when the TSF occurred was 11.2 ± 2.7 years for female patients and 12.9 ± 2.5 years for male patients. There was no significant difference in skeletal maturity between female patients and female controls or between male patients and male controls. The mean PTS was not significantly different between female patients (8.8°± 2.8°) and female controls (8.3°± 3.1°) (P = .366) or between male patients (9.0°± 2.8°) and male controls (9.3°± 2.6°) (P = .675). Those with a PTS >1 SD (2.9°) above the mean (8.8°) had no greater odds (1.0 [95% CI, 0.4-2.5]; P≥ .999) of having a TSF than others. Conclusion: PTS was not found to be a risk factor for pediatric TSF in female or male patients in this study.

Disability Mortality Disparity: Risk Of Mortality For Disabled Adults Nearly Twice That For Nondisabled Adults, 2008-19.

After years of advocacy by the disability community and allied organizations, on September 26, 2023, the National Institute on Minority Health and Health Disparities (NIMHD) designated disabled people as a health disparities population in the US. During its deliberations, the NIMHD emphasized that there was not sufficient empirical evidence on health disparities between disabled and nondisabled adults. My study addressed this gap by examining 2008-19 data from the National Health Interview Survey Linked Mortality Files on people ages eighteen and older to identify, categorize, and quantify disparities in mortality risk among disabled and nondisabled adults. The risk of mortality during the study period was 1.9 times higher overall for disabled compared with nondisabled adults. The risk increased with the number of reported disabilities and varied by disability category. These findings underscore the need to improve access to high-quality, evidence-based health care among disabled people. To gain a full understanding of the scope of disparity and the interventions needed to mitigate it, it is critical to develop more equitable and inclusive measures of disability and ableism for use in population health surveys.

CALMER Conflict: A Novel Curriculum for Graduating Medical Students to Manage and Defuse Patient-Provider Conflict.

BACKGROUND: Workplace violence disproportionately affects healthcare workers and verbal aggression from patients frequently occurs. While verbal de-escalation is the first-line approach to defusing anger, there is a lack of consistent curricula or robust evaluation in undergraduate medical education. AIM: To develop a medical school curriculum focused on de-escalation skills for adult patients and evaluate effectiveness with surveys and an objective structured clinical examination (OSCE). SETTING: We implemented this curriculum in the "Get Ready for Residency Bootcamp" of a single large academic institution in 2023. PARTICIPANTS: Forty-four fourth-year medical students PROGRAM DESCRIPTION: The curriculum consisted of an interactive didactic focused on our novel CALMER framework that prioritized six evidence-based de-escalation skills and a separate standardized patient practice session. PROGRAM EVALUATION: The post-curriculum survey (82% response rate) found a significant increase from 2.79 to 4.11 out of 5 (p ≤ 0.001) in confidence using verbal de-escalation. Preparedness improved with every skill and curriculum satisfaction averaged 4.79 out of 5. The OSCE found no differences in skill level between students who received the curriculum and those who did not. DISCUSSION: This evidence-based and replicable de-escalation skill curriculum improves medical student confidence and preparedness in managing agitated patients.

Electrically polarized nanoscale surfaces generate reactive oxygenated and chlorinated species for deactivation of microorganisms.

Because of the decreasing supply of new antibiotics, recent outbreaks of infectious diseases, and the emergence of antibiotic-resistant microorganisms, it is imperative to develop new effective strategies for deactivating a broad spectrum of microorganisms and viruses. We have implemented electrically polarized nanoscale metallic (ENM) coatings that deactivate a wide range of microorganisms including Gram-negative and Gram-positive bacteria with greater than 6-log reduction in less than 10 minutes of treatment. The electrically polarized devices were also effective in deactivating lentivirus and Candida albicans. The key to the high deactivation effectiveness of ENM devices is electrochemical production of micromolar cuprous ions, which mediated reduction of oxygen to hydrogen peroxide. Formation of highly damaging species, hydroxyl radicals and hypochlorous acid, from hydrogen peroxide contributed to antimicrobial properties of the ENM devices. The electric polarization of nanoscale coatings represents an unconventional tool for deactivating a broad spectrum of microorganisms through in situ production of reactive oxygenated and chlorinated species.

Molecular basis of product recognition during PIP5K-mediated production of PI(4,5)P2 with positive feedback.

The ability for cells to localize and activate peripheral membrane binding proteins is critical for signal transduction. Ubiquitously important in these signaling processes are phosphatidylinositol phosphate (PIP) lipids, which are dynamically phosphorylated by PIP lipid kinases on intracellular membranes. Functioning primarily at the plasma membrane, phosphatidylinositol-4-phosphate 5-kinases (PIP5K) catalyzes the phosphorylation of PI(4)P to generate most of the PI(4,5)P2 lipids found in eukaryotic plasma membrane. Recently, we determined that PIP5K displays a positive feedback loop based on membrane-mediated dimerization and cooperative binding to its product, PI(4,5)P2. Here, we examine how two motifs contribute to PI(4,5)P2 recognition to control membrane association and catalysis of PIP5K. Using a combination of single molecule TIRF microscopy and kinetic analysis of PI(4)P lipid phosphorylation, we map the sequence of steps that allow PIP5K to cooperatively engage PI(4,5)P2. We find that the specificity loop regulates the rate of PIP5K membrane association and helps orient the kinase to more effectively bind PI(4,5)P2 lipids. After correctly orienting on the membrane, PIP5K transitions to binding PI(4,5)P2 lipids near the active site through a motif previously referred to as the substrate or PIP binding motif (PIPBM). The PIPBM has broad specificity for anionic lipids and serves a role in regulating membrane association in vitro and in vivo. Overall, our data supports a two-step membrane binding model where the specificity loop and PIPBM act in concert to help PIP5K orient and productively engage anionic lipids to drive the positive feedback during PI(4,5)P2 production.

SARS-CoV-2-Triggered Hemophagocytic Lymphohistiocytosis with Complications of Posterior Reversible Encephalopathy Syndrome.

In this article, we describe a novel case of SARS-CoV-2-associated-hemophagocytic lymphohistiocytosis (HLH) complicated by posterior reversible encephalopathy syndrome (PRES). Initially diagnosed with multisystem inflammatory response in children (MIS-C), the patient received a large corticosteroid dose days before the onset of neurological symptoms. After developing PRES, the patient was treated with antihypertensives, antiepileptics, dexamethasone, and anakinra, leading to neurologic normalization. We propose that given the challenging diagnostic picture of PRES developing in patients with HLH or MIS-C, institutionalized standards for blood pressure management during corticosteroid induction may significantly improve outcomes in patients being treated for hyperinflammatory syndromes who develop neurological symptoms.

AI-based automation of enrollment criteria and endpoint assessment in clinical trials in liver diseases.

Clinical trials in metabolic dysfunction-associated steatohepatitis (MASH, formerly known as nonalcoholic steatohepatitis) require histologic scoring for assessment of inclusion criteria and endpoints. However, variability in interpretation has impacted clinical trial outcomes. We developed an artificial intelligence-based measurement (AIM) tool for scoring MASH histology (AIM-MASH). AIM-MASH predictions for MASH Clinical Research Network necroinflammation grades and fibrosis stages were reproducible (κ = 1) and aligned with expert pathologist consensus scores (κ = 0.62-0.74). The AIM-MASH versus consensus agreements were comparable to average pathologists for MASH Clinical Research Network scores (82% versus 81%) and fibrosis (97% versus 96%). Continuous scores produced by AIM-MASH for key histological features of MASH correlated with mean pathologist scores and noninvasive biomarkers and strongly predicted progression-free survival in patients with stage 3 (P < 0.0001) and stage 4 (P = 0.03) fibrosis. In a retrospective analysis of the ATLAS trial (NCT03449446), responders receiving study treatment showed a greater continuous change in fibrosis compared with placebo (P = 0.02). Overall, these results suggest that AIM-MASH may assist pathologists in histologic review of MASH clinical trials, reducing inter-rater variability on trial outcomes and offering a more sensitive and reproducible measure of patient responses.

Willingness to trade-off years of life for an HIV cure - an experimental exploration of affective forecasting.

BACKGROUND: In the US, 1.2 million people live with HIV (PWH). Despite having near-normal life expectancies due to antiretroviral therapy (ART), many PWH seek an HIV cure, even if it means risking their lives. This willingness to take risks for a cure raises questions about "affective forecasting biases," where people tend to overestimate the positive impact of future events on their well-being. We conducted a study to test two interventions to mitigate affective forecasting in the decisions of PWH about taking HIV cure medication. METHODS: We recruited PWH to complete a 30-minute survey about their current quality of life (QoL) and the QoL they anticipate after being cured of HIV, and assigned them to either no additional intervention, to one of two interventions intended to reduce affective forecasting bias, or to both interventions: (1) a defocusing intervention designed to broaden the number of life domains people consider when imagining life changes associated with new circumstances (e.g. HIV cure); and (2) an adaptation intervention to help them gauge fading of strong emotions over time. The study design included a 2 × 2 design: defocusing (yes/no) x adaptation (yes/no) intervention. We assessed PWH's willingness to take hypothetical HIV sterilizing cure medication using the Time Trade-Off (TTO) and their quality of life predictions with WHOQOL-HIV. RESULTS: 296 PWH participated. Counter to what we had hypothesized, neither intervention significantly reduced PWH's willingness to trade time for a cure. Instead, the defocusing intervention increased their willingness to trade time (IRR 1.77, p = 0.03). Exploratory analysis revealed that PWH with lower current quality of life who received the defocusing intervention were more willing to trade time for a cure. CONCLUSION: These negative findings suggest that either these biases are difficult to overcome in the settings of HIV curative medication or other factors beyond affective forecasting biases influence willingness to participate in HIV curative studies, such as respondents' current quality of life.

Sperm Concentration Remains Stable Among Fertile American Men: A Systematic Review and Meta-Analysis.

IMPORTANCE: Findings from several high-profile meta-analyses have raised concerns about an ongoing global decline in sperm concentration and male fertility. However, these studies exhibit considerable heterogeneity in key variables including study population, methodology, fertility status, and geographic region. OBJECTIVE: To perform a systematic review and meta-analysis exploring temporal trends in sperm concentration among fertile men and men unselected for fertility status in the United States. DATA SOURCES: A literature search performed in Scopus and PubMed databases for studies published between 1970-2023. Additional studies were included from citations of prior global meta-analyses and reviews evaluating temporal trends in sperm count. Study selection and synthesis: Studies were included if they presented original data on sperm concentration in U.S. men without known infertility from 1970 to 2023. Aggregate data were assessed across all study populations, with additional subgroup analyses stratified by fertility status and U.S. region. MAIN OUTCOMES: Weighted generalized linear models were generated to evaluate the association between mean sperm concentration and sample collection year. RESULTS: A total of 874 articles were screened, with 58 meeting the inclusion criteria. These represented 75 unique study populations totaling 11,787 men in the U.S. Across all study populations, no change in sperm concentration was observed between 1970-2018 in unadjusted models (ß=0.14million/mL/year, p=0.42). When adjusting for U.S. region, no statistically significant decline in sperm concentration was seen. When adjusting for both region and fertility status, a modest annual decline was observed to meet statistical significance (ß=-0.35million/ml/year, p=0.04). Of the 49 study populations reporting adequate data to determine mean total sperm count, there was a significant increase in total sperm count of 2.9 million/year between 1970 and 2018 (p=0.03). Subgroup analysis found no statistically significant change in mean sperm concentration among any U.S. census region or fertility status cohort. CONCLUSION AND RELEVANCE: In contrast to prior global studies, this analysis suggests no clinically significant decline in sperm concentration among confirmed fertile men and the general male U.S. population without known infertility. While these findings provide some reassurance against a widespread rapid decline, further studies are necessary to better understand this important topic.

Sperm chromatin dispersion assay reliability and assisted reproductive technology outcomes: Systematic review and meta-analysis.

OBJECTIVE: Elevated sperm DNA fragmentation has potential implications for semen quality and fertility. The commonly used sperm chromatin dispersion test offers an indirect estimation but has limitations in terms of bias and variability. This study aimed to assess the reliability of the sperm chromatin dispersion assay for predicting assisted reproductive technology outcomes. MATERIALS AND METHODS: This systematic review included studies published until December 2023 that adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed/MEDLINE, Scopus, and Google Scholar databases were searched. Various assisted reproductive technology outcomes in patients with high (≥ 30%) versus low (< 30%) sperm DNA fragmentation were compared using a sperm chromatin dispersion assay and including a sub-analysis of intracytoplasmic sperm injection versus in vitro fertilization. A comprehensive meta-analysis software facilitated quantitative analysis with statistical comparisons between cases and controls. Interstudy heterogeneity was assessed, and sensitivity and publication bias tests were performed. RESULTS: Of the 199 abstracts assessed, 64 full-text articles were screened, and 44 articles were qualitatively synthesized. Fourteen articles representing 5346 participants were quantitatively analyzed. Using the sperm chromatin dispersion assay, elevated sperm DNA fragmentation was associated with lower fertilization and embryo cleavage rates. Notably, high sperm DNA fragmentation levels did not affect the clinical pregnancy, implantation, miscarriage, or live birth outcomes. Sub-analysis revealed lower fertilization, embryo cleavage, clinical pregnancy, live birth rates, and higher miscarriage rates in the intracytoplasmic sperm injection subgroup only. CONCLUSIONS: The sperm chromatin dispersion assay did not show significant differences in pregnancy or live birth rates between the high- and low-sperm DNA fragmentation groups. Noteworthy, high sperm DNA fragmentation was associated with worse assisted reproductive technology outcomes in the intracytoplasmic sperm injection group. Given the current quality of the evidence, affected by the experimental design and the absence of correction for female factors of infertility, clinicians should be wary of the assay's limited predictive power for pregnancy and live birth outcomes.