A Systematic Online Living Evidence Summary of experimental Alzheimer's disease research.

BACKGROUND: Despite extensive investment, the development of effective treatments for Alzheimer's disease (AD) has been largely unsuccessful. To improve translation, it is crucial to ensure the quality and reproducibility of foundational evidence generated from laboratory models. Systematic reviews play a key role in providing an unbiased overview of the evidence, assessing rigour and reporting, and identifying factors that influence reproducibility. However, the sheer pace of evidence generation is prohibitive to evidence synthesis and assessment. NEW METHOD: To address these challenges, we have developed AD-SOLES, an integrated workflow of automated tools that collect, curate, and visualise the totality of evidence from in vivo experiments. RESULTS: AD-SOLES is a publicly accessible interactive dashboard aiming to surface and expose data from in vivo experiments. It summarises the latest evidence, tracks reporting quality and transparency, and allows research users to easily locate evidence relevant to their specific research question. COMPARISON WITH EXISTING METHODS: Using automated screening methodologies within AD-SOLES, systematic reviews can begin at an accelerated starting point compared to traditional approaches. Furthermore, through text-mining approaches within the full-text of publications, users can identify research of interest using specific models, outcomes, or interventions without relying on details in the title and/or abstract. CONCLUSIONS: By automating the collection, curation, and visualisation of evidence from in vivo experiments, AD-SOLES addresses the challenges posed by the rapid pace of evidence generation. AD-SOLES aims to offer guidance for research improvement, reduce research waste, highlight knowledge gaps, and support informed decision making for researchers, funders, patients, and the public.

Trace amine-associated receptor 1 (TAAR1) agonism for psychosis: a living systematic review and meta-analysis of human and non-human data.

Background: Trace amine-associated receptor 1 (TAAR1) agonism shows promise for treating psychosis, prompting us to synthesise data from human and non-human studies. Methods: We co-produced a living systematic review of controlled studies examining TAAR1 agonists in individuals (with or without psychosis/schizophrenia) and relevant animal models. Two independent reviewers identified studies in multiple electronic databases (until 17.11.2023), extracted data, and assessed risk of bias. Primary outcomes were standardised mean differences (SMD) for overall symptoms in human studies and hyperlocomotion in animal models. We also examined adverse events and neurotransmitter signalling. We synthesised data with random-effects meta-analyses. Results: Nine randomised trials provided data for two TAAR1 agonists (ulotaront and ralmitaront), and 15 animal studies for 10 TAAR1 agonists. Ulotaront and ralmitaront demonstrated few differences compared to placebo in improving overall symptoms in adults with acute schizophrenia (N=4 studies, n=1291 participants; SMD=0.15, 95%CI: -0.05, 0.34), and ralmitaront was less efficacious than risperidone (N=1, n=156, SMD=-0.53, 95%CI: -0.86, -0.20). Large placebo response was observed in ulotaront phase-III trials. Limited evidence suggested a relatively benign side-effect profile for TAAR1 agonists, although nausea and sedation were common after a single dose of ulotaront. In animal studies, TAAR1 agonists improved hyperlocomotion compared to control (N=13 studies, k=41 experiments, SMD=1.01, 95%CI: 0.74, 1.27), but seemed less efficacious compared to dopamine D 2 receptor antagonists (N=4, k=7, SMD=-0.62, 95%CI: -1.32, 0.08). Limited human and animal data indicated that TAAR1 agonists may regulate presynaptic dopaminergic signalling. Conclusions: TAAR1 agonists may be less efficacious than dopamine D 2 receptor antagonists already licensed for schizophrenia. The results are preliminary due to the limited number of drugs examined, lack of longer-term data, publication bias, and assay sensitivity concerns in trials associated with large placebo response. Considering their unique mechanism of action, relatively benign side-effect profile and ongoing drug development, further research is warranted. Registration: PROSPERO-ID: CRD42023451628.

There is a need for more effective treatments for psychosis, including schizophrenia. Psychosis is a collection of mental health symptoms, such as hearing voices, that can cause distress and impair functioning. These symptoms are thought to be caused by changes in a chemical messenger system in the brain called dopamine. Currently used antipsychotic medications target brain receptors that respond to dopamine. They are not effective in some people and can cause uncomfortable adverse events, such as weight gain and movement disorders, especially with long-term use. A new type of drug is the trace amine-associated receptor 1 (TAAR1) agonists. These drugs act on different brain receptors that can affect the activity of the dopamine system, but do not directly bind to dopamine receptors. We aimed to understand if TAAR1 agonists can reduce symptoms of psychosis, what adverse events they might have, and how they work. We did this by reviewing and collating all available evidence until November 2023. This is a "living" systematic review, so it will be regularly updated in the future. We looked at both human and animal studies investigating TAAR1 agonists. Human studies suggested that two TAAR1 agonists (namely, ulotaront or ralmitaront) might have little to no effect on reducing symptoms of psychosis compared to placebo in people with schizophrenia. They seemed to cause fewer adverse events than current antipsychotics. Data from animal studies suggested that TAAR1 agonists had some positive effects but potentially smaller than other antipsychotics. There were little to no data from both human and animal studies about how TAAR1 agonists actually work. From the current evidence we are uncertain about these results. With the ongoing development of new TAAR1 agonists, more evidence is needed to understand their potential role in the treatment of psychosis.

Multimodal Mass Spectrometry Imaging of an Osteosarcoma Multicellular Tumour Spheroid Model to Investigate Drug-Induced Response.

A multimodal mass spectrometry imaging (MSI) approach was used to investigate the chemotherapy drug-induced response of a Multicellular Tumour Spheroid (MCTS) 3D cell culture model of osteosarcoma (OS). The work addresses the critical demand for enhanced translatable early drug discovery approaches by demonstrating a robust spatially resolved molecular distribution analysis in tumour models following chemotherapeutic intervention. Advanced high-resolution techniques were employed, including desorption electrospray ionisation (DESI) mass spectrometry imaging (MSI), to assess the interplay between metabolic and cellular pathways in response to chemotherapeutic intervention. Endogenous metabolite distributions of the human OS tumour models were complemented with subcellularly resolved protein localisation by the detection of metal-tagged antibodies using Imaging Mass Cytometry (IMC). The first application of matrix-assisted laser desorption ionization-immunohistochemistry (MALDI-IHC) of 3D cell culture models is reported here. Protein localisation and expression following an acute dosage of the chemotherapy drug doxorubicin demonstrated novel indications for mechanisms of region-specific tumour survival and cell-cycle-specific drug-induced responses. Previously unknown doxorubicin-induced metabolite upregulation was revealed by DESI-MSI of MCTSs, which may be used to inform mechanisms of chemotherapeutic resistance. The demonstration of specific tumour survival mechanisms that are characteristic of those reported for in vivo tumours has underscored the increasing value of this approach as a tool to investigate drug resistance.

Multisite Study of the Management of Musculoskeletal Infection After Trauma: The MMUSKIT Study.

Background: The optimal duration and choice of antibiotic for fracture-related infection (FRI) is not well defined. This study aimed to determine whether antibiotic duration (≤6 vs >6 weeks) is associated with infection- and surgery-free survival. The secondary aim was to ascertain risk factors associated with surgery- and infection-free survival. Methods: We performed a multicenter retrospective study of patients diagnosed with FRI between 2013 and 2022. The association between antibiotic duration and surgery- and infection-free survival was assessed by Cox proportional hazard models. Models were weighted by the inverse of the propensity score, calculated with a priori variables of hardware removal; infection due to Staphylococcus aureus, Staphylococcus lugdunensis, Pseudomonas or Candida species; and flap coverage. Multivariable Cox proportional hazard models were run with additional covariates including initial pathogen, need for flap, and hardware removal. Results: Of 96 patients, 54 (56.3%) received ≤6 weeks of antibiotics and 42 (43.7%) received >6 weeks. There was no association between longer antibiotic duration and surgery-free survival (hazard ratio [HR], 0.95; 95% CI, .65-1.38; P = .78) or infection-free survival (HR, 0.77; 95% CI, .30-1.96; P = .58). Negative culture was associated with increased hazard of reoperation or death (HR, 3.52; 95% CI, 1.99-6.20; P < .001) and reinfection or death (HR, 3.71; 95% CI, 1.24-11.09; P < .001). Need for flap coverage had an increased hazard of reoperation or death (HR, 3.24; 95% CI, 1.61-6.54; P = .001). Conclusions: The ideal duration of antibiotics to treat FRI is unclear. In this multicenter study, there was no association between antibiotic treatment duration and surgery- or infection-free survival.

Analysis of animal-to-human translation shows that only 5% of animal-tested therapeutic interventions obtain regulatory approval for human applications.

There is an ongoing debate about the value of animal experiments to inform medical practice, yet there are limited data on how well therapies developed in animal studies translate to humans. We aimed to assess 2 measures of translation across various biomedical fields: (1) The proportion of therapies which transition from animal studies to human application, including involved timeframes; and (2) the consistency between animal and human study results. Thus, we conducted an umbrella review, including English systematic reviews that evaluated the translation of therapies from animals to humans. Medline, Embase, and Web of Science Core Collection were searched from inception until August 1, 2023. We assessed the proportion of therapeutic interventions advancing to any human study, a randomized controlled trial (RCT), and regulatory approval. We meta-analyzed the concordance between animal and human studies. The risk of bias was probed using a 10-item checklist for systematic reviews. We included 122 articles, describing 54 distinct human diseases and 367 therapeutic interventions. Neurological diseases were the focus of 32% of reviews. The overall proportion of therapies progressing from animal studies was 50% to human studies, 40% to RCTs, and 5% to regulatory approval. Notably, our meta-analysis showed an 86% concordance between positive results in animal and clinical studies. The median transition times from animal studies were 5, 7, and 10 years to reach any human study, an RCT, and regulatory approval, respectively. We conclude that, contrary to widespread assertions, the rate of successful animal-to-human translation may be higher than previously reported. Nonetheless, the low rate of final approval indicates potential deficiencies in the design of both animal studies and early clinical trials. To ameliorate the efficacy of translating therapies from bench to bedside, we advocate for enhanced study design robustness and the reinforcement of generalizability.

Persistent racial disparities in postoperative management after tibia fracture fixation: A matched analysis of US medicaid beneficiaries.

INTRODUCTION: Racial and ethnic disparities in orthopaedic surgery are well documented. However, the extent to which these persist in fracture care is unknown. This study sought to assess racial disparities in the postoperative surgical and medical management of patients after diaphyseal tibia fracture fixation. METHODS: Patients with surgically treated tibial shaft fractures from October 1, 2015, to December 31, 2020, were identified in the MarketScan® Medicaid Database. Exclusion criteria included concurrent fractures or amputation. Outcomes included 2-year postoperative complications, reoperation rates, and filled prescriptions. Surgically-treated Black and White cohorts were propensity-score matched using nearest-neighbor matching on patient demographics, comorbidities, fracture pattern and severity, and fixation type. Chi-square tests and survival analyses (Kaplan-Meier and Cox proportional hazard models) were conducted. RESULTS: 5,472 patients were included, 2,209 Black and 3,263 White patients. After matching, 2,209 were retained in each cohort. No significant differences in complication rates were observed in the matched Black vs White cohorts. Rates of reoperation, however, were significantly lower in Black as compared to White patients (28.5 % vs. 35.5 % rate, risk difference = 7.0 % (95 % confidence interval (CI): 4.2 % to 9.7 %)). Implant removal was also significantly lower in Black (17.9 %) vs. White (25.1 %) patients (Risk difference = 7.2 %, (95 %CI: 4.8 % to 9.6 %)). The adjusted hazard ratio comparing the reoperation rate in Black versus White patients was 0.77 (95 %CI: 0.69-0.82, p < 0.0001). Significantly lower proportions of Black vs White patients filled at least one prescription for benzodiazepine, antidepressants, strong opiates, or antibiotics at every time point post-index. DISCUSSION: Fewer resources were used in post-operative management after surgical treatment of tibial shaft fractures for Black versus White Medicaid-insured patients. These results may be reflective of the undertreatment of complications after tibia fracture surgery for Black patients and highlight the need for further interventions to address racial disparities in trauma care.

Chest x-ray has low sensitivity to detect silicosis in artificial stone benchtop industry workers.

BACKGROUND AND OBJECTIVE: Chest x-ray (CXR) remains a core component of health monitoring guidelines for workers at risk of exposure to crystalline silica. There has however been a lack of evidence regarding the sensitivity of CXR to detect silicosis in artificial stone benchtop industry workers. METHODS: Paired CXR and high-resolution computed tomography (HRCT) images were acquired from 110 artificial stone benchtop industry workers. Blinded to the clinical diagnosis, each CXR and HRCT was independently read by two thoracic radiologists from a panel of seven, in accordance with International Labour Office (ILO) methodology for CXR and International Classification of HRCT for Occupational and Environmental Respiratory Diseases. Accuracy of screening positive (ILO major category 1, 2 or 3) and negative (ILO major category 0) CXRs were compared with identification of radiological features of silicosis on HRCT. RESULTS: CXR was positive for silicosis in 27/110 (24.5%) workers and HRCT in 40/110 (36.4%). Of the 83 with a negative CXR (ILO category 0), 15 (18.1%) had silicosis on HRCT. All 11 workers with ILO category 2 or 3 CXRs had silicosis on HRCT. In 99 workers ILO category 0 or 1 CXRs, the sensitivity of screening positive CXR compared to silicosis identified by HRCT was 48% (95%CI 29-68) and specificity 97% (90-100). CONCLUSION: Compared to HRCT, sensitivity of CXR was low but specificity was high. Reliance on CXR for health monitoring would provide false reassurance for many workers, delay management and underestimate the prevalence of silicosis in the artificial stone benchtop industry.

Successful coil embolization of a ruptured pseudoaneurysm of the superior gluteal artery after a percutaneous awake robot-assisted sacroiliac joint fusion: illustrative case.

BACKGROUND: Robot-assisted sacroiliac joint (SIJ) fusion has gained popularity, but it carries the risk of complications such as injury to the superior gluteal artery (SGA). The authors present the case of an awake percutaneous robot-assisted SIJ fusion leading to an SGA pseudoaneurysm. OBSERVATIONS: An 80-year-old male, who had undergone an awake percutaneous robot-assisted SIJ fusion, experienced postoperative left hip pain and bruising. Subsequent arteriography demonstrated an SGA branch pseudoaneurysm requiring coil embolization. LESSONS: An SGA injury, although uncommon (1.2% incidence), can arise from percutaneous screw placement, aberrant anatomy, or hardware contact. Thorough preoperative imaging, precise robot-assisted screw insertion, and soft tissue protection are crucial to mitigate risks. Immediate angiography aids in prompt diagnosis and effective intervention. Comprehensive knowledge of anatomical variants is essential for managing complications and optimizing preventative measures in robot-assisted SIJ fusion.

Psychometric properties of the Perceived Stress Scale (PSS-10) in silica-exposed workers from diverse cultural and linguistic backgrounds.

BACKGROUND: The Perceived Stress Scale (PSS-10) has been used in a range of occupational cohorts, but only recently in stone benchtop workers undergoing screening for silicosis. The aim of this study was to compare psychometric properties of the PSS-10 in stone benchtop workers amongst those born overseas or who used an interpreter. METHODS: Stone benchtop workers in Melbourne, Australia completed the PSS-10 as part of their occupational screening for silicosis. Internal consistency was assessed with Cronbach's α for the total score and the positive and negative subscales. Validity was assessed using confirmatory factor analysis (CFA). Analysis was performed for the total group and for subgroups according to sex, interpreter use, overseas-born, and language spoken at home. RESULTS: The results of 682 workers with complete PSS-10 scores were included in analysis. Most participants were male (93%), with mean age 36.9 years (SD 11.4), with just over half (51.6%) born in Australia, 10.1% using an interpreter, and 17.5% using a language other than English at home. Cronbach's α for the overall group (α = 0.878) suggested good internal consistency. DISCUSSION: CFA analysis for validity testing suggested PSS-10 performance was good for both sexes, moderate for country of birth and language spoken at home categories, but poorer for those who used an interpreter. Whilst professional interpreters provide a range of benefits in the clinical setting, the use of translated and validated instruments are important, particularly in cohorts with large numbers of migrant workers. CONCLUSION: This study describes the psychometric properties of the PSS-10 in a population of stone benchtop workers, with good internal consistency, and mixed performance from validity testing across various subgroups.

Divergent maturational patterns of the infant bacterial and fungal gut microbiome in the first year of life are associated with inter-kingdom community dynamics and infant nutrition.

BACKGROUND: The gut microbiome undergoes primary ecological succession over the course of early life before achieving ecosystem stability around 3 years of age. These maturational patterns have been well-characterized for bacteria, but limited descriptions exist for other microbiota members, such as fungi. Further, our current understanding of the prevalence of different patterns of bacterial and fungal microbiome maturation and how inter-kingdom dynamics influence early-life microbiome establishment is limited. RESULTS: We examined individual shifts in bacterial and fungal alpha diversity from 3 to 12 months of age in 100 infants from the CHILD Cohort Study. We identified divergent patterns of gut bacterial or fungal microbiome maturation in over 40% of infants, which were characterized by differences in community composition, inter-kingdom dynamics, and microbe-derived metabolites in urine, suggestive of alterations in the timing of ecosystem transitions. Known microbiome-modifying factors, such as formula feeding and delivery by C-section, were associated with atypical bacterial, but not fungal, microbiome maturation patterns. Instead, fungal microbiome maturation was influenced by prenatal exposure to artificially sweetened beverages and the bacterial microbiome, emphasizing the importance of inter-kingdom dynamics in early-life colonization patterns. CONCLUSIONS: These findings highlight the ecological and environmental factors underlying atypical patterns of microbiome maturation in infants, and the need to incorporate multi-kingdom and individual-level perspectives in microbiome research to improve our understandings of gut microbiome maturation patterns in early life and how they relate to host health. Video Abstract.

Acute coronary occlusion and percutaneous coronary intervention after out-of-hospital cardiac arrest.

OBJECTIVES: Early coronary angiography (CAG) has been recommended in selected patients following out-of-hospital-cardiac-arrest (OHCA). We aimed to identify clinical features associated with acute coronary occlusion (ACO) and evaluate the associations between ACO, successful percutaneous coronary intervention (PCI) and outcomes in this population. METHODS: We included comatose OHCA patients treated with targeted temperature management (TTM) between December 2005 and September 2016 who underwent early CAG within 24 hours. The co-primary outcomes were all-cause 30-day mortality and good neurological outcome (modified Rankin Score [mRS] ≤2) at hospital discharge. RESULTS: Among 155 patients (93% shockable arrest rhythm, 55% with ST elevation), 133 (86%) had coronary artery stenosis ≥50% and 65 (42%) had ACO. ST elevation (sensitivity 74%, specificity 59%, OR 4.0, 95% CI 2.0-8.1) and elevated first troponin (sensitivity 88%, specificity 26%, OR 2.5, 95% CI 1.1-6.1) had limited sensitivity and specificity for ACO. Unadjusted 30-day mortality did not differ significantly by coronary disease severity or ACO. Successful PCI was associated with a lower risk of 30-day mortality (adjusted HR 0.5, 95% CI 0.2-0.9, P=.03), especially among patients with ACO (adjusted HR 0.4, 95% CI 0.1-0.9, P=0.03). After adjustment, ACO and PCI were not associated with the probability of good neurological outcome. CONCLUSIONS: In this select cohort of resuscitated OHCA patients undergoing CAG, unstable coronary disease is highly prevalent and successful PCI was associated with a higher probability of 30-day survival, especially among those with ACO. Neither ACO nor successful PCI were independently associated with good neurological outcome.

Connected language performance in neurotypical and persons with aphasia: Use of the Brazilian-Portuguese Story Retell Procedure (SRP-BP).

INTRODUCTION: It is important to analyze the micro- and macrostructure of connected language production across languages in neurotypical and impaired speakers such as people with aphasia (PWA). However, the validity, reliability, sensitivity, or specificity of the available Brazilian-Portuguese connected language production batteries remains untested. OBJECTIVE: The purpose of this study was to provide a preliminary assessment of the translated Brazilian-Portuguese Story Retell Procedure (SRP-BP) in PWA and neurotypical control participants (NCP) and investigate whether the SRP can serve as a measure of overall communication impairment in PWA. METHODS: This cross-sectional study was developed at the Federal University of São Paulo. Seven right-handed PWA and 14 NCP were recruited. PWA had a single left-hemisphere post-stroke lesion and were without severe aphasia or non-fluent aphasia that might interfere with performing the SRP. The connected language measures calculated from the SRP-BP were the numbers of words, information units, and propositions produced. The data were analyzed with the non-parametric Mann-Whitney test. RESULTS: The NCP produced significantly more information units and propositions in each of the 12 SRP-BP stories than the PWA group. The same group results were found for the number of words for 11 of the 12 stories, with no statistically significant difference between groups for the Água (Water) story. CONCLUSION: The SRP-BP distinguished the connected language production of PWA from that of NCP. These results motivate additional psychometric assessment and test development of the SRP-BP in neurotypical, PWA, and other language and cognitively impaired populations.

Interferon-epsilon is a novel regulator of NK cell responses in the uterus.

The uterus is a unique mucosal site where immune responses are balanced to be permissive of a fetus, yet protective against infections. Regulation of natural killer (NK) cell responses in the uterus during infection is critical, yet no studies have identified uterine-specific factors that control NK cell responses in this immune-privileged site. We show that the constitutive expression of IFNε in the uterus plays a crucial role in promoting the accumulation, activation, and IFNγ production of NK cells in uterine tissue during Chlamydia infection. Uterine epithelial IFNε primes NK cell responses indirectly by increasing IL-15 production by local immune cells and directly by promoting the accumulation of a pre-pro-like NK cell progenitor population and activation of NK cells in the uterus. These findings demonstrate the unique features of this uterine-specific type I IFN and the mechanisms that underpin its major role in orchestrating innate immune cell protection against uterine infection.

Patients Aged 90 Years and Above With Acute Coronary Syndrome in the Cardiac Intensive Care Unit: Management and Outcomes.

Limited data exist regarding outcomes after coronary angiography (CAG) and percutaneous coronary intervention (PCI) in patients aged ≥90 years admitted to the cardiac intensive care unit (CICU) with acute coronary syndrome (ACS). We studied sequential CICU patients ≥90 years admitted with ACS from 2007 to 2018. Three therapeutic approaches were defined: (1) No CAG; (2) CAG without PCI (CAG/No PCI); and (3) CAG with PCI (CAG/PCI). In-hospital mortality was evaluated using multivariable logistic regression. All-cause 1-year mortality was evaluated using Kaplan-Meier and multivariable Cox proportional hazards analysis. The study included 239 patients with a median age of 92 (range 90 to 100) years (57% females; 45% ST-elevation myocardial infarction; 8% cardiac arrest; 16% shock). The No CAG group had higher Day 1 Sequential Organ Failure Assessment scores, more co-morbidities, worse kidney function, and fewer ST-elevation myocardial infarctions. In-hospital mortality was 20.8% overall and did not differ between the No CAG (n = 103; 21.4%), CAG/No PCI (n = 47; 21.3%), and CAG/PCI (n = 90; 20.0%) groups, before or after adjustment. Overall 1-year mortality was 52.5% and did not differ between groups before or after adjustment. Median survival was 6.9 months overall and 41.2% of hospital survivors died within 1 year of CICU admission. CICU patients aged ≥90 years with ACS have a substantial burden of illness with high in-hospital and 1-year mortality that was not lower in those who underwent CAG or PCI. These results suggest that careful patient selection for invasive coronary procedures is essential in this vulnerable population.

Nodal positivity in patients with clinically and radiologically node-negative breast cancer treated with neoadjuvant chemotherapy: multicentre collaborative study.

BACKGROUND: The necessity of performing a sentinel lymph node biopsy in patients with clinically and radiologically node-negative breast cancer after neoadjuvant chemotherapy has been questioned. The aim of this study was to determine the rate of nodal positivity in these patients and to identify clinicopathological features associated with lymph node metastasis after neoadjuvant chemotherapy (ypN+). METHODS: A retrospective multicentre study was performed. Patients with cT1-3 cN0 breast cancer who underwent sentinel lymph node biopsy after neoadjuvant chemotherapy between 2016 and 2021 were included. Negative nodal status was defined as the absence of palpable lymph nodes, and the absence of suspicious nodes on axillary ultrasonography, or the absence of tumour cells on axillary nodal fine needle aspiration or core biopsy. RESULTS: A total of 371 patients were analysed. Overall, 47 patients (12.7%) had a positive sentinel lymph node biopsy. Nodal positivity was identified in 22 patients (29.0%) with hormone receptor+/human epidermal growth factor receptor 2- tumours, 12 patients (13.8%) with hormone receptor+/human epidermal growth factor receptor 2+ tumours, 3 patients (5.6%) with hormone receptor-/human epidermal growth factor receptor 2+ tumours, and 10 patients (6.5%) with triple-negative breast cancer. Multivariable logistic regression analysis showed that multicentric disease was associated with a higher likelihood of ypN+ (OR 2.66, 95% c.i. 1.18 to 6.01; P = 0.018), whilst a radiological complete response in the breast was associated with a reduced likelihood of ypN+ (OR 0.10, 95% c.i. 0.02 to 0.42; P = 0.002), regardless of molecular subtype. Only 3% of patients who had a radiological complete response in the breast were ypN+. The majority of patients (85%) with a positive sentinel node proceeded to axillary lymph node dissection and 93% had N1 disease. CONCLUSION: The rate of sentinel lymph node positivity in patients who achieve a radiological complete response in the breast is exceptionally low for all molecular subtypes.