Erratum. Identifying Preferred Features of Weight Loss Programs for Adults With or at Risk of Type 2 Diabetes: A Discrete Choice Experiment With 3,960 Adults in the U.K.. Diabetes Care 2024;47:739-746.

In the article cited above, funding information was inadvertently omitted for authors Paul Aveyard and Susan A. Jebb. The following text has been added: "P.A. is an NIHR senior investigator. P.A. and S.A.J. are funded by NIHR Oxford Biomedical Research Centre, NIHR Oxford Health Biomedical Research Centre, and NIHR Oxford and Thames Valley Applied Research Collaboration." The authors apologize for the omission. The online version of the article (https://doi.org/10.2337/dc23-2019) has been updated to correct the error.

Platform-directed allostery and quaternary structure dynamics of SAMHD1 catalysis.

SAMHD1 regulates cellular nucleotide homeostasis, controlling dNTP levels by catalysing their hydrolysis into 2'-deoxynucleosides and triphosphate. In differentiated CD4+ macrophage and resting T-cells SAMHD1 activity results in the inhibition of HIV-1 infection through a dNTP blockade. In cancer, SAMHD1 desensitizes cells to nucleoside-analogue chemotherapies. Here we employ time-resolved cryogenic-EM imaging and single-particle analysis to visualise assembly, allostery and catalysis by this multi-subunit enzyme. Our observations reveal how dynamic conformational changes in the SAMHD1 quaternary structure drive the catalytic cycle. We capture five states at high-resolution in a live catalytic reaction, revealing how allosteric activators support assembly of a stable SAMHD1 tetrameric core and how catalysis is driven by the opening and closing of active sites through pairwise coupling of active sites and order-disorder transitions in regulatory domains. This direct visualisation of enzyme catalysis dynamics within an allostery-stabilised platform sets a precedent for mechanistic studies into the regulation of multi-subunit enzymes.

Effect of Human Activity and Presence on the Behavior of Long-Tailed Macaques (Macaca fascicularis) in an Urban Tourism Site in Kuala Selangor, Malaysia.

The increasing overlap of resources between human and long-tailed macaque (Macaca fascicularis) (LTM) populations have escalated human-primate conflict. In Malaysia, LTMs are labeled as a 'pest' species due to the macaques' opportunistic nature. This study investigates the activity budget of LTMs in an urban tourism site and how human activities influence it. Observational data were collected from LTMs daily for a period of four months. The observed behaviors were compared across differing levels of human interaction, between different times of day, and between high, medium, and low human traffic zones. LTMs exhibited varying ecological behavior patterns when observed across zones of differing human traffic, e.g., higher inactivity when human presence is high. More concerning is the impact on these animals' welfare and group dynamics as the increase in interactions with humans takes place; we noted increased inactivity and reduced intra-group interaction. This study highlights the connection that LTMs make between human activity and sources of anthropogenic food. Only through understanding LTM interaction can the cause for human-primate conflict be better understood, and thus, more sustainable mitigation strategies can be generated.

Identifying Preferred Features of Weight Loss Programs for Adults With or at Risk of Type 2 Diabetes: A Discrete Choice Experiment With 3,960 Adults in the U.K.

OBJECTIVE: To understand preferences for features of weight loss programs among adults with or at risk of type 2 diabetes in the U.K. RESEARCH DESIGN AND METHODS: We conducted a discrete choice experiment with 3,960 U.K. adults living with overweight (n = 675 with type 2 diabetes). Preferences for seven characteristics of weight loss programs were analyzed. Simulations from choice models using the experimental data predicted uptake of available weight loss programs. Patient groups comprising those who have experience with weight loss programs, including from minority communities, informed the experimental design. RESULTS: Preferences did not differ between individuals with and without type 2 diabetes. Preferences were strongest for type of diet. Healthy eating was most preferred relative to total diet replacement (odds ratio [OR] 2.24; 95% CI 2.04-2.44). Individual interventions were more popular than group interventions (OR 1.40; 95% CI 1.34-1.47). Participants preferred programs offering weight loss of 10-15 kg (OR 1.37; 95% CI 1.28-1.47) to those offering loss of 2-4 kg. Online content was preferred over in-person contact (OR 1.24; 95% CI 1.18-1.30). There were few differences in preferences by gender or ethnicity, although weight loss was more important to women than to men, and individuals from ethnic minority populations identified more with programs where others shared their characteristics. Modeling suggested that tailoring programs to individual preferences could increase participation by ∼17 percentage points (68% in relative terms). CONCLUSIONS: Offering a range of weight loss programs targeting the preferred attributes of different patient groups could potentially encourage more people to participate in weight loss programs and support those living with overweight to reduce their weight.

The impact of the COVID-19 pandemic and associated disruptions in health-care provision on clinical outcomes in people with diabetes: a systematic review.

The COVID-19 pandemic triggered disruptions to health care and lifestyles that could conceivably impact diabetes management. We set out to identify the impact of disruptions caused by COVID-19 on clinical outcomes in people with diabetes. We performed a systematic review of the available literature in the MEDLINE and OVID databases from Jan 1, 2020, to June 7, 2023, and included 138 studies (n>1 000 000 people). All but five studies were judged to be at some risk of bias. All studies compared prepandemic with pandemic periods. All-cause mortality (six studies) and diabetes-related mortality (13 studies) showed consistent increases, and most studies indicated increases in sight loss (six studies). In adult and mixed samples, data generally suggested no difference in diabetic ketoacidosis frequency or severity, whereas in children and adolescents most studies showed increases with some due to new-onset diabetes (69 studies). Data suggested decreases in hospital admissions in adults but increases in diabetes-related admissions to paediatric intensive care units (35 studies). Data were equivocal on diabetic foot ulcer presentations (nine studies), emergency department admissions (nine studies), and overall amputation rates (20 studies). No studies investigated renal failure. Where reported, the impact was most pronounced for females, younger people, and racial and ethnic minority groups. Further studies are needed to investigate the longer-term impact of the pandemic and the on potential differential impacts, which risk further exacerbating existing inequalities within people with diabetes.

[WITHDRAWN] Predicting breast cancer with AI for individual risk-adjusted MRI screening and early detection.

This paper has been withdrawn by Lukas Hirsch. Major revisions and rewriting in progress.

Genicular Artery Embolization: A Review of Essential Anatomic Considerations.

Genicular artery embolization is increasingly recognized as a safe and effective treatment option for symptomatic knee osteoarthritis and recurrent hemarthrosis after total knee arthroplasty. Genicular arteries are an essential contributor to vascular supply for the knee joint and demonstrate considerable variability. Familiarity with the anatomy and common variations is critical for preprocedural planning, accurate target selection, and minimizing adverse events in transarterial embolization procedures. This review aimed to provide a detailed discussion of the genicular artery anatomy that is relevant to interventional radiologists performing genicular artery embolization.

Prospective implementation of AI-assisted screen reading to improve early detection of breast cancer.

Artificial intelligence (AI) has the potential to improve breast cancer screening; however, prospective evidence of the safe implementation of AI into real clinical practice is limited. A commercially available AI system was implemented as an additional reader to standard double reading to flag cases for further arbitration review among screened women. Performance was assessed prospectively in three phases: a single-center pilot rollout, a wider multicenter pilot rollout and a full live rollout. The results showed that, compared to double reading, implementing the AI-assisted additional-reader process could achieve 0.7-1.6 additional cancer detection per 1,000 cases, with 0.16-0.30% additional recalls, 0-0.23% unnecessary recalls and a 0.1-1.9% increase in positive predictive value (PPV) after 7-11% additional human reads of AI-flagged cases (equating to 4-6% additional overall reading workload). The majority of cancerous cases detected by the AI-assisted additional-reader process were invasive (83.3%) and small-sized (≤10 mm, 47.0%). This evaluation suggests that using AI as an additional reader can improve the early detection of breast cancer with relevant prognostic features, with minimal to no unnecessary recalls. Although the AI-assisted additional-reader workflow requires additional reads, the higher PPV suggests that it can increase screening effectiveness.

Implementing the NCTSN Trauma-Informed Organizational Assessment (TIOA) for Improving Trauma-Informed Care in Inpatient Child Psychiatry.

BACKGROUND: Children and adolescents receiving inpatient psychiatric services have disproportionately high levels of exposure to trauma and adversity. The National Child Traumatic Stress Network Trauma-Informed Organizational Assessment (TIOA) is a comprehensive tool intended to guide implementation of trauma-informed care, but it has not yet been applied in inpatient settings. AIMS: The purpose of this quality improvement project was to describe trauma-informed care in inpatient child/adolescent psychiatry with the TIOA, examine relatedness among trauma-informed care domains, and explore barriers or facilitators to applying trauma-informed care. METHODS: This quality improvement project used mixed methods. We conducted a web-based survey in Summer 2022 with staff members (clinical and administrative) at two inpatient child/adolescent psychiatric units in California to assess trauma-informed care practices with the TIOA (87 items). Qualitative follow-up interviews were offered to interested participants. A correlation matrix and cluster analyses were used to examine relationships among TIOA domains; qualitative data were analyzed thematically. RESULTS: There were 69 survey respondents and seven qualitative interviews. TIOA domain scores ranged from a low of 2.3 to a high of 3.2, indicating that practices were occurring only "rarely" to "sometimes." There were two major themes identified from qualitive interviews: (a) barriers to trauma-informed care in an inpatient context that can be resource-constrained or coercive; and (b) discovering strategies to provide trauma-informed care despite structural barriers. CONCLUSION: Organizational interventions targeting any domains of trauma-informed care are needed in inpatient settings given limited uptake of trauma-informed care.

Association of Breast Cancer Odds with Background Parenchymal Enhancement Quantified Using a Fully Automated Method at MRI: The IMAGINE Study.

Background Background parenchymal enhancement (BPE) at breast MRI has been associated with increased breast cancer risk in several independent studies. However, variability of subjective BPE assessments have precluded its use in clinical practice. Purpose To examine the association between fully objective measures of BPE at MRI and odds of breast cancer. Materials and Methods This prospective case-control study included patients who underwent a bilateral breast MRI examination and were receiving care at one of three centers in the United States from November 2010 to July 2017. Breast volume, fibroglandular tissue (FGT) volume, and BPE were quantified using fully automated software. Fat volume was defined as breast volume minus FGT volume. BPE extent was defined as the proportion of FGT voxels with enhancement of 20% or more. Spearman rank correlation between quantitative BPE extent and Breast Imaging Reporting and Data System (BI-RADS) BPE categories assigned by an experienced board-certified breast radiologist was estimated. With use of multivariable logistic regression, breast cancer case-control status was regressed on tertiles (low, moderate, and high) of BPE, FGT volume, and fat volume, with adjustment for covariates. Results In total, 536 case participants with breast cancer (median age, 48 years [IQR, 43-55 years]) and 940 cancer-free controls (median age, 46 years [IQR, 38-55 years]) were included. BPE extent was positively associated with BI-RADS BPE (rs = 0.54; P < .001). Compared with low BPE extent (range, 2.9%-34.2%), high BPE extent (range, 50.7%-97.3%) was associated with increased odds of breast cancer (odds ratio [OR], 1.74 [95% CI: 1.23, 2.46]; P for trend = .002) in a multivariable model also including FGT volume (OR, 1.39 [95% CI: 0.97, 1.98]) and fat volume (OR, 1.46 [95% CI: 1.04, 2.06]). The association of high BPE extent with increased odds of breast cancer was similar for premenopausal and postmenopausal women (ORs, 1.75 and 1.83, respectively; interaction P = .73). Conclusion Objectively measured BPE at breast MRI is associated with increased breast cancer odds for both premenopausal and postmenopausal women. Clinical trial registration no. NCT02301767 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Bokacheva in this issue.

Relative supersaturation values distinguish between feline urinary and non-urinary foods and align with expected urine analytes contributions to uroliths.

Introduction: Uroliths are concretions formed in the urinary tract. These can be problematic in humans and companion animals such as cats. Magnesium ammonium phosphate (struvite) and calcium oxalate (CaOx) are the most common forms of uroliths. The relative supersaturation (RSS) is a relative risk index of crystal formation. Here, an updated program for calculating RSS, EQUIL-HL21, was used to detect differences in RSS values when cats were fed foods formulated for urinary and non-urinary conditions. In addition, the contributions of urinary analytes to RSS values were examined via regression analyses. Methods: Historical data from feeding trials including foods indicated for use in urinary or non-urinary conditions were analyzed for nutrient composition and urinary parameters. RSS was calculated by EQUIL-HL21. The relationship between RSS values calculated by EQUIL-HL21 and urinary analytes was examined by regression models, which were selected by R2 and stepwise methods. Results: Cats that consumed urinary foods had significantly greater levels of urinary sodium and chloride compared with those that consumed non-urinary foods, consistent with the greater amounts of sodium and chloride in the urinary foods. Those that consumed non-urinary foods had higher urine pH, ammonium, potassium, phosphorus, magnesium, oxalate, citrate, and sulfate. Struvite RSS value and number of urinary crystals were significantly lower in cats fed the urinary foods. Mean CaOx RSS values were similar in both foods, though the number of CaOx crystals were significantly higher in cats that consumed non-urinary foods. A model predicting the natural log of struvite RSS values indicated that these values would increase with increasing urine pH, ammonium, chloride, calcium, phosphorus, and magnesium, and would decrease with increasing urine citrate and sulfate. CaOx RSS was predicted to increase as urinary chloride, calcium, and oxalates increased, and would decrease as urine pH, sodium, phosphorus, citrate, and sulfate increased. Discussion: These analyses demonstrate that the EQUIL-HL21 program can accurately detect expected differences between foods formulated for urinary and non-urinary indications. Regression models showed the eight urinary analytes that, respectively, contribute to the predicted RSS values for struvite and CaOx.

Genicular Artery Embolization for Treatment of Knee Osteoarthritis: Interim Analysis of a Prospective Pilot Trial Including Effect on Serum Osteoarthritis-Associated Biomarkers.

PURPOSE: To characterize the safety, efficacy, and potential role of genicular artery embolization (GAE) as a disease-modifying treatment for symptomatic knee osteoarthritis (OA). MATERIALS AND METHODS: This is an interim analysis of a prospective, single-arm clinical trial of patients with symptomatic knee OA who failed conservative therapy for greater than 3 months. Sixteen patients who underwent GAE using 250-µm microspheres and had at least 1 month of follow-up were included. Six patients completed the 12-month follow-up, and 10 patients remain enrolled. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was evaluated at baseline and at 1, 3, and 12 months. Serum and plasma samples were collected for biomarker analysis. The primary end point was the percentage of patients who achieved the minimal clinically important difference (MCID) for WOMAC pain score at 12 months. Baseline and follow-up outcomes were analyzed using the Wilcoxon matched-pairs signed-rank test. RESULTS: Technical success of the procedure was 100%, with no major adverse events. The MCID was achieved in 5 of the 6 (83%) patients at 12 months. The mean WOMAC pain score decreased from 8.6 ± 2.7 at baseline to 4.9 ± 2.7 (P = .001), 4.4 ± 2.8 (P < .001), and 4.7 ± 2.7 (P = .094) at 1, 3, and 12 months, respectively. There was a statistically significant decrease in nerve growth factor (NGF) levels at 12 months. The remaining 8 biomarkers showed no significant change at 12 months. CONCLUSIONS: GAE is a safe and efficacious treatment for symptomatic knee OA. Decreased NGF levels after GAE may contribute to pain reduction and slowing of cartilage degeneration.

P3a amplitude to trauma-related stimuli reduced after successful trauma-focused PTSD treatment.

An elevated P3a amplitude to trauma-related stimuli is strongly associated with posttraumatic stress disorder (PTSD), yet little is known about whether this response to trauma-related stimuli is affected by treatment that decreases PTSD symptoms. As an analysis of secondary outcome measures from a randomized controlled trial, we investigated the latency and amplitude changes of the P3a in responses in a three-condition oddball visual task that included trauma-related (combat scenes) and trauma-unrelated (threatening animals) distractors. Fifty-five U.S. veterans diagnosed with combat-related PTSD were randomized to receive either active or sham repetitive transcranial magnetic stimulation (rTMS). All received cognitive processing therapy, CPT+A, which requires a written account of the index trauma. They were tested before and 6 months after protocol completion. P3a amplitude and response time decreases were driven largely by the changes in the responses to the trauma-related stimuli, and this decrease correlated to the decrease in PTSD symptoms. The amplitude changes were greater in those who received rTMS + CPT than in those who received sham rTMS + CPT, suggesting that rTMS plays beneficial role in reducing arousal and threat bias, which may allow for more effective engagement in trauma-focused PTSD treatment.

Economic evaluation of supplemental breast cancer screening modalities to mammography or digital breast tomosynthesis in women with heterogeneously and extremely dense breasts and average or intermediate breast cancer risk in US healthcare.

OBJECTIVE: To evaluate the cost-effectiveness of supplemental breast imaging modalities for women with heterogeneously and extremely dense breasts and average or intermediate risk of breast cancer (BC) in the USA, and analyze capacity requirements for supplemental magnetic resonance imaging (MRI) and contrast-enhanced mammography (CEM). METHODS: Clinical and economic outcomes for supplemental imaging modalities including full- and abbreviated-protocol MRI (Fp-MRI, Ab-MRI), CEM, and ultrasound (U/S) as add-on to x-ray mammography (XM) or digital breast tomosynthesis (DBT), were compared to XM or DBT alone, in a decision tree linked to a Markov chain validated by comparison with a microsimulation analysis. A Delphi panel supplemented model input parameters from the literature. A capacity model evaluated the number of additional daily scans and scanners required for Fp-MRI and CEM. RESULTS: Compared to XM or DBT alone, all supplemental imaging protocols were cost-effective. Both Fp- and Ab-MRI, and to a lesser extent CEM and U/S, yielded superior clinical outcomes to XM or DBT. Compared to XM alone, U/S and Ab-MRI had the lowest incremental cost-effectiveness ratios (ICER). For U/S, the ICER was $23,394 for the average-risk population and $13,241 for the intermediate-risk population. For CEM, the ICER was $38,423 and $23,772, respectively. For the extremely dense subpopulation with intermediate risk, supplemental screening requirements could be accommodated by conducting one Fp-MRI scan per day per existing general scanner. CONCLUSIONS: While ultrasound had the lowest ICER, MRI and CEM demonstrated the best clinical outcomes, compared to XM or DBT alone for women with dense breasts and intermediate and high risk. Existing MRI scanner capacity has the potential to meet most of the supplemental screening needs of this population.

Imaging of breast cancer-beyond the basics.

Imaging of breast cancer is the backbone of breast cancer screening, diagnosis, preoperative/treatment assessment and follow-up. The main modalities are mammography, ultrasound and magnetic resonance imaging, each with its own advantages and disadvantages. New emerging technologies have also enabled each modality to improve on their weaknesses. Imaging-guided biopsies have allowed for accurate diagnosis of breast cancer, with low complication rates. The purpose of this article is to review the common modalities for breast cancer imaging in current practice with emphasis on the strengths and potential weaknesses, discuss the selection of the best imaging modality for the specific clinical question or patient population, and explore new technologies / future directions of breast cancer imaging.

Small Bowel Transit Scintigraphy in Children With Pediatric Intestinal Pseudo-Obstruction.

INTRODUCTION: Objective evidence of small intestinal dysmotility is a key criterion for the diagnosis of pediatric intestinal pseudo-obstruction (PIPO). Small bowel scintigraphy (SBS) allows for objective measurement of small bowel transit (SBT), but limited data are available in children. We aimed to evaluate the utility of SBS in children suspected of gastrointestinal dysmotility. METHODS: Patients undergoing gastric emptying studies for suspected foregut dysmotility, including PIPO, from 2016 to 2022 at 2 tertiary children's hospitals were recruited to an extended protocol of gastric emptying studies to allow for assessment of SBT. PIPO was classified based on antroduodenal manometry (ADM). SBT was compared between PIPO and non-PIPO patients. Scintigraphic parameters were assessed and correlated against ADM scores. RESULTS: Fifty-nine patients (16 PIPO and 43 non-PIPO diagnoses) were included. SBS was performed with liquid and solid meals in 40 and 26 patients, respectively. As compared to the non-PIPO group, PIPO patients had a significantly lower median percentage of colonic filling at 6 hours, with both liquid (48% vs 83%) and solid tests (5% vs 65%). SBT in PIPO patients with myopathic involvement was significantly slower than in patients with neuropathic PIPO, both for liquid and solid meal. A significant correlation was found between solid SBT and ADM scores (r = -0.638, P = 0.036). DISCUSSION: SBS provides a practically feasible assessment of small intestinal motility. It shows a potential utility to help diagnose and characterize PIPO. SBS seems most discriminative in PIPO patients with myopathic involvement. Studies in a larger pediatric population and across different ages are required.

Rice protein concentrate is a well-accepted, highly digestible protein source for adult cats.

Introduction: The use of rice protein concentrate (RPC) as a protein source in cat food is uncommon. Therefore, this study aimed to determine the acceptability and digestibility of foods formulated to contain increasing levels of RPC to support its inclusion in foods for adult (non-gravid, non-lactating) cats. Methods: Increasing levels of RPC (0, 7, 14, and 28%) were formulated into test foods fed to 24 cats in a Latin square design with 15-day periods and no washout between periods. Food intake and fecal scores were measured to determine the acceptability of test foods. Fecal output was measured on days 11-15. Food and fecal samples from day 15 of each period were analyzed for nutrient composition to calculate the macronutrient digestibility of the test foods. Analysis of variance and orthogonal contrasts were used to assess the effects of RPC inclusion on food intake, fecal output, fecal scores, and macronutrient digestibility. Results: The results showed that as-fed (AF), dry matter (DM), and gross energy (GE) intake increased with increasing RPC levels (p > 0.05). Fecal output, both as-is and DM, was unaffected by RPC inclusion (p > 0.05); however, fecal scores increased linearly with increasing RPC inclusion (p < 0.001). Furthermore, true protein and apparent DM, GE, and carbohydrate (NFE) digestibility increased linearly with RPC inclusion (p < 0.05). Apparent fat digestibility was high for all test foods but was unaffected by RPC inclusion (p = 0.690). Discussion: Overall, the inclusion of RPC was well-accepted, improved fecal characteristics, and increased the apparent and true macronutrient digestibility compared to the control. Therefore, this study demonstrated that RPC can serve as a high-quality and acceptable protein source for adult cats.

Attenuation of reverse transcriptase facilitates SAMHD1 restriction of HIV-1 in cycling cells.

BACKGROUND: SAMHD1 is a deoxynucleotide triphosphohydrolase that restricts replication of HIV-1 in differentiated leucocytes. HIV-1 is not restricted in cycling cells and it has been proposed that this is due to phosphorylation of SAMHD1 at T592 in these cells inactivating the enzymatic activity. To distinguish between theories for how SAMHD1 restricts HIV-1 in differentiated but not cycling cells, we analysed the effects of substitutions at T592 on restriction and dNTP levels in both cycling and differentiated cells as well as tetramer stability and enzymatic activity in vitro. RESULTS: We first showed that HIV-1 restriction was not due to SAMHD1 nuclease activity. We then characterised a panel of SAMHD1 T592 mutants and divided them into three classes. We found that a subset of mutants lost their ability to restrict HIV-1 in differentiated cells which generally corresponded with a decrease in triphosphohydrolase activity and/or tetramer stability in vitro. Interestingly, no T592 mutants were able to restrict WT HIV-1 in cycling cells, despite not being regulated by phosphorylation and retaining their ability to hydrolyse dNTPs. Lowering dNTP levels by addition of hydroxyurea did not give rise to restriction. Compellingly however, HIV-1 RT mutants with reduced affinity for dNTPs were significantly restricted by wild-type and T592 mutant SAMHD1 in both cycling U937 cells and Jurkat T-cells. Restriction correlated with reverse transcription levels. CONCLUSIONS: Altogether, we found that the amino acid at residue 592 has a strong effect on tetramer formation and, although this is not a simple "on/off" switch, this does correlate with the ability of SAMHD1 to restrict HIV-1 replication in differentiated cells. However, preventing phosphorylation of SAMHD1 and/or lowering dNTP levels by adding hydroxyurea was not enough to restore restriction in cycling cells. Nonetheless, lowering the affinity of HIV-1 RT for dNTPs, showed that restriction is mediated by dNTP levels and we were able to observe for the first time that SAMHD1 is active and capable of inhibiting HIV-1 replication in cycling cells, if the affinity of RT for dNTPs is reduced. This suggests that the very high affinity of HIV-1 RT for dNTPs prevents HIV-1 restriction by SAMHD1 in cycling cells.

Performance of Supplemental Imaging Modalities for Breast Cancer in Women With Dense Breasts: Findings From an Umbrella Review and Primary Studies Analysis.

Breast cancer screening performance of supplemental imaging modalities by breast density and breast cancer risk has not been widely studied, and the optimal choice of modality for women with dense breasts remains unclear in clinical practice and guidelines. This systematic review aimed to assess breast cancer screening performance of supplemental imaging modalities for women with dense breasts, by breast cancer risk. Systematic reviews (SRs) in 2000 to 2021, and primary studies in 2019 to 2021, on outcomes of supplemental screening modalities (digital breast tomography [DBT], MRI (full/abbreviated protocol), contrast enhanced mammography (CEM), ultrasound (hand-held [HHUS]/automated [ABUS]) in women with dense breasts (BI-RADS C&D) were identified. None of the SRs analyzed outcomes by cancer risk. Meta-analysis of the primary studies was not feasible due to lack of studies (MRI, CEM, DBT) or methodological heterogeneity (ultrasound); therefore, findings were summarized narratively. For average risk, a single MRI trial reported a superior screening performance (higher cancer detection rate [CDR] and lower interval cancer rate [ICR]) compared to HHUS, ABUS and DBT. For intermediate risk, ultrasound was the only modality assessed, but accuracy estimates ranged widely. For mixed risk, a single CEM study reported the highest CDR, but included a high proportion of women with intermediate risk. This systematic review does not allow a complete comparison of supplemental screening modalities for dense breast populations by breast cancer risk. However, the data suggest that MRI and CEM might generally offer superior screening performance versus other modalities. Further studies of screening modalities are urgently required.