Is there a fast track ("Darmstrasse") for fluids in the small intestine? Evidence from magnetic resonance imaging.

BACKGROUND: The transit and distribution pattern of fluids in the small intestine is a key parameter for the dissolution and absorption of drugs. Although some information is known about the small intestinal water content after administration of fluid volumes and meals, the intestinal transit of orally ingested fluids and solutions has been barely investigated. The aim of this three-arm, cross-over, 9-subject human study was to investigate the transit of orally ingested water in the small intestine under fasting and postprandial conditions using MRI. To identify the ingested water, manganese gluconate, which can be identified with T1-weighted MRI sequences, was added as a marker. Using Horos (DICOM software), quantification of the distribution of Mn2+ ions in the gastrointestinal tract in fasted versus fed state (standard meal by FDA guidance and a light meal) was possible. The distribution and approximate wetted intestinal length was very similar in the fasting and postprandial states, suggesting rapid transport of water ingested after a meal through the chyme-filled small intestine in continuation of the "Magenstrasse" (stomach road). In some subjects, manganese gluconate reached deeper parts of the small intestine even more quickly in the postprandial state than in the fasting arm of the study. A deeper understanding of the behaviour of solutes in the gastrointestinal tract is fundamental to a mechanistic explanation for the kinetic interaction between food and drug intake (food effects).

Randomized comparison of HARVesting the Left Internal Thoracic Artery in a skeletonized versus pedicled technique: the HARVITA trial-study protocol.

Latest research has indicated a potential adverse effect on graft patency rates and clinical outcomes with skeletonizing the left internal thoracic artery. We aim to provide a prospective, randomized, multicentre trial to compare skeletonized versus pedicled harvesting technique of left internal thoracic artery concerning graft patency rates and patient survival. A total of 1350 patients will be randomized to either skeletonized or pedicled harvesting technique and undergo surgical revascularization. Follow-up will be performed at 30 days, 1 year, 2 years and 5 years after surgery. The primary outcome will be death or left internal thoracic artery graft occlusion in coronary computed tomography angiography or invasive angiography within 2 years (+/- 3 months) after surgery. The secondary outcome will be major adverse cardiac events (composite outcome of all-cause death, myocardial infarction and repeated revascularization) within 1 year, 2 years and 5 years after surgery. The primary end point will be compared in the modified intention-to-treat population between the two treatment groups using Kaplan-Meier graphs, together with log-rank testing. Hereby, we present the study protocol of the first adequately powered prospective, randomized, multicentre trial which compares skeletonized and pedicled harvesting technique of left internal thoracic artery regarding graft patency rates and patient survival.

Complexity of coronary artery disease and the release of cardiac biomarkers after CABG.

Objective: In patients with complex coronary artery disease (CAD) undergoing cardiac surgery, myocardial protection might be impaired due to microvascular obstruction, resulting in myocardial injury and subsequent biomarker release. Therefore, this study investigated the correlation between the complexity of CAD, reflected by the SYNTAX Score, and the release of cardiac biomarkers after CABG. Methods: In a consecutive series of 919 patients undergoing isolated CABG SYNTAX scores I and II were calculated to assess the complexity of CAD. Levels of high sensitivity cardiac troponin T (hs-cTnT) and creatine kinase-myocardial band (CK-MB) were routinely measured once before and serially after surgery. Patients were divided into tertiles according to their SYNTAX Scores I and II. Spearman correlations and regression models were performed to measure the degree of association between the release of hs-cTnT and CK-MB and the SYNTAX Scores. Results: Patients with a higher SYNTAX Score I had more comorbidities reflected in a higher EuroSCORE II. Preoperatively, higher levels of cardiac biomarkers were found in patients with higher SYNTAX Score II. No correlation was observed between hs-cTnT, CK-MB and SYNTAX Score I or II. Regression models did not show any association between cardiac biomarkers and the complexity of CAD. Conclusion: The complexity of CAD is not associated with the release of cardiac biomarkers after CABG. Factors influencing postoperative biomarker release need to be elucidated in future trials to include postoperative biomarker release into risk stratification models predicting outcome after cardiac surgery.

Analysis of factors affecting outcome in acute type A aortic dissection complicated by preoperative cardiopulmonary resuscitation.

OBJECTIVES: Cardiopulmonary resuscitation (CPR) aggravates the pre-existing dismal prognosis of patients suffering from acute type A aortic dissection (ATAAD). We aimed to identify factors affecting survival and outcome in ATAAD patients requiring CPR at presentation at 2 European aortic centres. METHODS: Data on 112 surgical candidates and undergoing preoperative CPR were retrospectively evaluated. Patients were divided into 2 groups according to 30-day mortality. A multivariable model identified predictors for 30-day mortality. RESULTS: Preoperative death occurred in 23 patients (20.5%). In the remaining 89 surgical patients (79.5%) circulatory arrest time (41 ± 20 min in 30-day non-survivors vs 30 ± 13 min in 30-day survivor, P = 0.003) as well as cardiopulmonary bypass time (320 ± 132 min in 30-day non-survivors vs 252 ± 140 min in 30-day survivor, P = 0.020) time was significantly longer in patients with worse outcome. Thirty-day mortality of the total cohort was 61.6% (n = 69) with cardiac failure in 48% and aortic rupture or haemorrhagic shock (28%) as predominant reasons of death. Age [odds ratio (OR) 1.04, 95% confidence interval (CI) 1.01-1.09, P = 0.034], preoperative coronary (OR 3.42, 95% CI 1.34-9.26, p = 0.012) and spinal malperfusion (OR 12.49, 95% CI 1.83-225.02, P = 0.028) emerged as independent predictors for 30-day mortality while CPR due to tamponade was associated with improved early survival (OR 0.29, 95% CI 0.091-0.81, P = 0.023). CONCLUSIONS: Assessment of underlying cause for CPR is mandatory. Pericardial tamponade, rapidly resolved with pericardial drainage, is a predictor for improved survival, while age and presence of coronary and spinal malperfusion are associated with dismal outcome in this high-risk patient group.

Postoperative cardiac biomarker release is not associated with myocardial mass in computer tomography scans.

OBJECTIVES: Myocardial hypertrophy results in increased levels of cardiac biomarkers in healthy individuals and in patients suffering from acute myocardial infarction. The influence of cardiac mass on postoperative cardiac biomarkers release remains unclear. This study investigated the correlation between myocardial mass and the release of high-sensitivity cardiac Troponin T (hs-cTnT) and creatine kinase-myocardial band (CK-MB) after isolated aortic valve replacement (AVR) or bypass surgery. METHODS: Myocardial mass of a consecutive retrospective series of patients was measured automatically using preoperative computer tomography scans (636 patients, AVR = 251; bypass surgery = 385). Levels of cardiac biomarkers were measured before and serially after surgery. Spearman and Pearson correlation and a multivariate regression model was performed to measure the degree of association between myocardial mass and the release of hs-cTnT and CK-MB. RESULTS: Patients were divided into 3 tertiles according to their myocardial mass index. Higher biomarker levels were measured preoperatively in the upper tertile of patients undergoing AVR (P = 0.004) or bypass surgery (P < 0.001). Patients with different heart sizes showed no differences in postoperative biomarker release neither after AVR nor bypass surgery. No statistical significant correlation was observed between myocardial mass index and postoperative release of hs-cTnT or CK-MB in any subgroup (ρ maximum 0.106). CONCLUSIONS: Postoperative biomarker release is not correlated with myocardial mass. Patient factors leading to increased postoperative biomarker levels need to be elucidated in future studies.

Open transcatheter double valve-in-valve replacement for degenerated bioprostheses on the arrested heart.

Background: Failing bioprosthesis is an emerging issue due to (i) a shift towards liberal bioprosthesis implantation instead of mechanical prosthesis and (ii) an ageing population. Management of high-risk patients with bioprosthesis degeneration remains challenging. Case summary: An 82-year-old patient with history of aortic and mitral valve replacement six years before presents with severe dyspnoea. Echocardiograpic assessment reveals (i) structural valve degeneration of the mitral prosthesis (severe stenosis and regurgitation) with concomitant major annular calcifications and (ii) structural valve degeneration of the aortic prosthesis with low-flow, low-gradient restenosis. Due to mitral annular calcifications, the risk of double valve re-replacement and the age of the patient conventional reoperation was deemed very high. The patient is evaluated for transapical double valve implantation. This option is rejected due to the high risk of left ventricular outflow obstruction. The patient is treated with an open transcatheter double valve-in-valve procedure at the following sequence: leaflet resection of the mitral bioprosthesis, mitral valve implantation and fixation under direct view, leaflet resection of the aortic bioprosthesis, and valve frame cracking and aortic valve implantation under direct view. Post-bypass echocardiography shows neither left ventricular outflow tract obstruction nor paravalvular leak or prosthesis dysfunction. The patient is extubated on the first post-operative day and transferred to normal care unit. Discussion: Open transcatheter double valve-in-valve replacement for degenerated bioprostheses on the arrested heart might be a valuable alternative to treat selected high-risk patients with bioprosthetic valve degeneration.

Isolated annuloplasty in elderly patients with secondary mitral valve regurgitation: short- and long-term outcomes with a less invasive approach.

Background: Long-term outcomes of elderly and frail patients with secondary mitral valve regurgitation (MR) are inconclusive. Especially in patients with co-morbidities such as atherosclerosis who are suffering from heart failure, optimal medical therapy (OMT) is the preferred therapy relative to surgical or percutaneous interventions. It remains challenging to identify the most successful therapy to improve symptoms and increase life expectancy. To reduce surgical trauma for these patients, minimally invasive mitral valve surgery (MIMVS) was developed; this has shown promising medium-term results, but there is still a lack of evidence regarding long-term results. The aim of this investigation was to describe the long-term outcomes of less invasive mitral valve surgery (MVS) in elderly patients. Methods: In this longitudinal retrospective analysis, 67 patients (aged ≥70 years) with secondary MR who underwent MV repair ± tricuspid valve repair (TVR) were identified. MVS was performed via minithoracotomy (MT) in most cases (n = 54); in patients with contraindications for MIMVS, partial upper sternotomy (PS) was the preferred route for surgical access (n = 13). The appropriate access route was chosen according to the patient's clinical condition and comorbidities. We analyzed reoperation-free long-term survival, combined operative success (lack of residual MR, conversion to MV replacement, or larger thoracic incisions), and perioperative safety (at 30 days: mortality, re-thoracotomy, ECMO, pacemaker implantation, dialysis, longer ventilation, stroke, myocardial infarction). In a subgroup analysis, we compared long-term survival in MVS patients with and without TVR. Results: The median age of patients (62.7% female) was 74 years (interquartile range: 72-76 years), with a median EuroSCORE2 of 2.8% (1.5%-4.6%) and N-terminal pro-brain natriuretic peptide plasma levels of 1,434 ng/L (1035-2149 ng/L). The median follow-up period was 5.6 years (2.7-8.5 years). The reoperation-free long-term survival rate up to 10 years was 66.2%. Combined operative success and perioperative safety were achieved in 94% and 76% of patients, respectively. Additional TVR was performed in 56.7% of patients, without any significant difference in survival rates compared to the group without TVR (p = 0.417; HR 1.473, 95% CI 0.578-3.757). Conclusion: Less invasive MV repair for secondary MR shows excellent operative success and safety in selected patients. Freedom from significant MR and from the need for reoperation indicates long-lasting efficacy. These results should be considered in heart team discussions regarding allocation of patients to surgical mitral procedures.

In Vivo Evaluation of a Gastro-Resistant Enprotect® Capsule under Postprandial Conditions.

Ready-to-fill enteric hard capsule shells are an evolving field of oral drug and nutraceutical products. Lonza Capsugel® Enprotect® capsules were recently proven to provide reliable release in the small intestine after fasted intake, but robustness against postprandial intake needed to be proven. In this study, the capsules were administered to 16 healthy young subjects after intake of a light meal. The Enprotect® capsules were labelled with 5 mg black iron oxide and 25 mg 13C3-caffeine. Magnetic Resonance Imaging was used to identify the localization and visual dispersion of the capsule filling. The salivary appearance of caffeine was considered a second independent and sensitive marker for the initial release. Whereas the fasted gastric residence time of the capsules amounted to 43 ± 32 min, it was increased to 158 ± 36 min after postprandial intake. Therefore, the mean dispersion time according to MRI and the mean caffeine appearance time were increased to 196 ± 37 min and 189 ± 37 min, respectively. But, similar to fasted administration, no capsule disintegration or leakage was observed in the stomach and 38% of the capsules disintegrated in the jejunum and 62% in the ileum. The mean dispersion time after gastric emptying and the mean caffeine appearance time after gastric emptying amounted to 38 ± 21 min and 31 ± 17 min, respectively. Both did not relevantly change compared to the fasted intake. Only the absolute dispersion time and caffeine appearance were prolonged due to the increased gastric residence and no relevant influence of the light meal was observed on the disintegration or release behavior of Enprotect® capsules after gastric emptying. The capsules also showed robust enteric properties after postprandial administration.

Determination of Gastric Water Emptying in Fasted and Fed State Conditions Using a Compression-Coated Tablet and Salivary Caffeine Kinetics.

Because of the importance of gastric emptying for pharmacokinetics, numerous methods have been developed for its determination. One of the methods is the salivary tracer technique, which utilizes an ice capsule containing caffeine as a salivary tracer. Despite the ice capsule's advantage in labeling ingested fluids with caffeine for subsequent salivary detection, its risk of premature melting before swallowing, and its complicated storage and preparation, limit its application, particularly in special populations (e.g., older people). For this reason, here, a compression-coated tablet was developed and validated against the ice capsule in a cross-over clinical trial. The two dosage forms were administered simultaneously to 12 volunteers in an upright position under fasted and fed state conditions. To distinguish the caffeine concentrations in saliva from each dosage form, regular type of caffeine (12C) was added to the tablet, while for the ice capsule 13C3 labelled caffeine was used. The salivary caffeine concentrations showed no statistically significant differences for the pharmacokinetic parameters tmax and AUC0→60 (p > 0.05). Thus, the new formulation is a useful tool for determining gastric emptying that can also be used in special populations.

Survival outcomes seen with neoadjuvant chemotherapy in the management of locally advanced inflammatory breast cancer (IBC) versus matched controls.

Inflammatory breast cancer (IBC) poses an ongoing challenge as rates of disease recurrence and mortality remain high compared to stage-matched controls. However, frontline therapy has evolved through the years, including the widespread use of neoadjuvant chemotherapy (NAC) given the prognostic importance of pathologic complete response (pCR). Due to these sweeping changes, we need new data to assess current recurrence and survival outcomes for locally advanced IBC in the context of matched non-inflammatory controls. We conducted a retrospective analysis of institutional IBC data from 2010 to 2016 with the primary objective of comparing overall survival (OS), relapse-free survival (RFS), and distant relapse-free survival (DRFS). We matched IBC patients to non-inflammatory controls based on age, receptor status, tumor grade, clinical stage, and receipt of prior NAC. Secondary objectives included assessing pCR rates and identifying prognostic factors. Among NAC recipients, we observed similar pCR rates (47.6 % vs. 49.4 %, p = 0.88) between IBC (n = 84) and matched non-IBC (n = 81) cohorts. However, we noted a significant worsening of OS (p = 0.0001), RFS (p = 0.0001), and DRFS (p = 0.001) in the IBC group. Specifically, 5-year OS in the IBC cohort was 58.9 % vs. 86.7 % for matched controls (p = 0.0003). Older age was a weak negative predictor for OS (HR 1.03, p = 0.001) and RFS (HR 1.02, p = 0.01). For DRFS, older age was also a weak negative predictor (HR 1.02, p = 0.02), whereas the use of NAC was a positive predictor (HR 0.47, p = 0.02). Despite no clear difference in pCR, survival outcomes remain poor for IBC compared to matched non-inflammatory controls.

Association of High-Sensitivity Cardiac Troponin T With 30-Day and 5-Year Mortality After Cardiac Surgery.

BACKGROUND: The relevance of perioperative myocardial injury (PMI) after cardiac surgery for 30-day mortality and long-term survival remains to be determined. OBJECTIVES: This study assessed the association of PMI after cardiac surgery, reflected by postoperative troponin release, with 30-day mortality and long-term survival after: 1) coronary artery bypass grafting (CABG); 2) isolated aortic valve replacement (AVR) surgery; and 3) all other cardiac surgeries. METHODS: A consecutive cohort of 8,292 patients undergoing cardiac surgery with serial perioperative high-sensitivity cardiac troponin T (hs-cTnT) measurements was retrospectively analyzed. The relationship between postoperative hs-cTnT release and 30-day mortality or 5-year mortality was analyzed after adjustment with EuroSCORE II using a Cox proportional hazards model. hs-cTnT thresholds for 30-day and 5-year mortality were determined for isolated CABG (32.3%), AVR (14%), and other cardiac surgery (53.8%). RESULTS: High postoperative hs-cTnT levels were associated with higher 30-day mortality but not 5-year mortality. In CABG, median peak concentration of postoperative hs-cTnT was 1,044 ng/L, in AVR it was 502 ng/L, and in other cardiac surgery it was 1,110 ng/L. hs-cTnT thresholds defining mortality-associated PMI were as follows: for CABG, 2,385 ng/L (170× the upper reference limit of normal in a seemingly healthy population [URL]); for AVR, 568 ng/L (41× URL); and for other cardiac procedures, 1,873 ng/L (134× URL). hs-cTnT levels above the cutoffs resulted in an HR for 30-day mortality for CABG of 12.56 (P < 0.001), for AVR of 4.44 (P = 0.004), and for other cardiac surgery of 3.97 (P < 0.001). CONCLUSIONS: PMI reflected by perioperative hs-cTnT release is associated with the expected 30-day mortality but not 5-year mortality. Postoperative hs-cTnT cutoffs to identify survival-relevant PMI are higher than suggested in current definitions.

Determination of Mucoadhesion of Polyvinyl Alcohol Films to Human Intestinal Tissue.

The absorption of drugs with narrow absorption windows in the upper small intestine can be improved with a mucoadhesive drug delivery system such as enteric films. To predict the mucoadhesive behaviour in vivo, suitable in vitro or ex vivo methods can be performed. In this study, the influence of tissue storage and sampling site on the mucoadhesion of polyvinyl alcohol film to human small intestinal mucosa was investigated. Tissue from twelve human subjects was used to determine adhesion using a tensile strength method. Thawing of tissue frozen at -20 °C resulted in a significantly higher work of adhesion (p = 0.0005) when a low contact force was applied for one minute, whereas the maximum detachment force was not affected. When the contact force and time were increased, no differences were found for thawed tissue compared to fresh tissue. No change in adhesion was observed depending on the sampling location. Initial results from a comparison of adhesion to porcine and human mucosa suggest that the tissues are equivalent.

Exploring Functions and Predictors of Digital Health Engagement Among German Internet Users: Survey Study.

BACKGROUND: Digital health engagement may serve many support functions, such as providing access to information; checking or evaluating one's state of health; and tracking, monitoring, or sharing health data. Many digital health engagement behaviors are associated with the potential to reduce inequalities in information and communication. However, initial studies suggest that health inequalities may persist in the digital realm. OBJECTIVE: This study aimed to explore the functions of digital health engagement by describing how frequently respective services are used for a range of purposes and how these purposes can be categorized from the users' perspective. This study also aimed to identify the prerequisites for successfully implementing and using digital health services; therefore, we shed light on the predisposing, enabling, and need factors that may predict digital health engagement for different functions. METHODS: Data were gathered via computer-assisted telephone interviews during the second wave of the German adaption of the Health Information National Trends Survey in 2020 (N=2602). The weighted data set allowed for nationally representative estimates. Our analysis focused on internet users (n=2001). Engagement with digital health services was measured by their reported use for 19 different purposes. Descriptive statistics showed the frequency with which digital health services were used for these purposes. Using a principal component analysis, we identified the underlying functions of these purposes. Using binary logistic regression models, we analyzed which predisposing factors (age and sex), enabling factors (socioeconomic status, health- and information-related self-efficacy, and perceived target efficacy), and need factors (general health status and chronic health condition) can predict the use of the distinguished functions. RESULTS: Digital health engagement was most commonly linked to acquiring information and less frequently to more active or interactive purposes such as sharing health information with other patients or health professionals. Across all purposes, the principal component analysis identified 2 functions. Information-related empowerment comprised items on acquiring health information in various forms, critically assessing one's state of health, and preventing health problems. In total, 66.62% (1333/2001) of internet users engaged in this behavior. Health care-related organization and communication included items on patient-provider communication and organizing health care. It was applied by 52.67% (1054/2001) of internet users. Binary logistic regression models showed that the use of both functions was determined by predisposing factors (female and younger age) and certain enabling factors (higher socioeconomic status) and need factors (having a chronic condition). CONCLUSIONS: Although a large share of German internet users engage with digital health services, predictors show that existing health-related disparities prevail in the digital realm. To make use of the potential of digital health services, fostering digital health literacy at different levels, especially in vulnerable groups, is key.

Natural mineral fibers: conducting inhalation toxicology studies-part B: development of a nose-only exposure system for repeat-exposure in vivo study of Libby amphibole aerosol.

BACKGROUND: Exposure to asbestos is associated with malignant and nonmalignant respiratory disease. To strengthen the scientific basis for risk assessment on fibers, the National Institute of Environmental Health Sciences (NIEHS) has initiated a series of studies to address fundamental questions on the toxicology of naturally occurring asbestos and related mineral fibers after inhalation exposure. A prototype nose-only exposure system was previously developed and validated. The prototype system was expanded to a large-scale exposure system in this study for conducting subsequent in vivo rodent inhalation studies of Libby amphibole (LA) 2007, selected as a model fiber. RESULTS: The exposure system consisting of six exposure carousels was able to independently deliver stable LA 2007 aerosol to individual carousels at target concentrations of 0 (control group), 0.1, 0.3, 1, 3, or 10 mg/m3. A single aerosol generator was used to provide aerosol to all carousels to ensure that exposure atmospheres were chemically and physically similar, with aerosol concentration as the only major variable among the carousels. Transmission electron microscopy (TEM) coupled with energy dispersive spectrometry (EDS) and selected area electron diffraction (SAED) analysis of aerosol samples collected at the exposure ports indicated the fiber dimensions, chemical composition, and mineralogy were equivalent across exposure carousels and were comparable to the bulk LA 2007 material. CONCLUSION: The exposure system developed is ready for use in conducting nose-only inhalation toxicity studies of LA 2007 in rats. The exposure system is anticipated to have applicability for the inhalation toxicity evaluation of other natural mineral fibers of concern.

Natural mineral fibers: conducting inhalation toxicology studies - part A: Libby Amphibole aerosol generation and characterization method development.

BACKGROUND: Asbestos has been classified as a human carcinogen, and exposure may increase the risk of diseases associated with impaired respiratory function. As the range of health effects and airborne concentrations that result in health effects across asbestos-related natural mineral fiber types are not fully understood, the National Institute of Environmental Health Sciences has established a series of research studies to characterize hazards of natural mineral fibers after inhalation exposure. This paper presents the method development work of this research project. RESULTS: A prototype nose-only exposure system was fabricated to explore the feasibility of generating natural mineral fiber aerosol for in vivo inhalation toxicity studies. The prototype system consisted of a slide bar aerosol generator, a distribution/delivery system and an exposure carousel. Characterization tests conducted using Libby Amphibole 2007 (LA 2007) demonstrated the prototype system delivered stable and controllable aerosol concentration to the exposure carousel. Transmission electron microscopy (TEM) analysis of aerosol samples collected at the exposure port showed the average fiber length and width were comparable to the bulk LA 2007. TEM coupled with energy dispersive spectrometry (EDS) and selected area electron diffraction (SAED) analysis further confirmed fibers from the aerosol samples were consistent with the bulk LA 2007 chemically and physically. CONCLUSIONS: Characterization of the prototype system demonstrated feasibility of generating LA 2007 fiber aerosols appropriate for in vivo inhalation toxicity studies. The methods developed in this study are suitable to apply to a multiple-carousel exposure system for a rat inhalation toxicity testing using LA 2007.

The Immunomodulatory Effects of Dexamethasone on Neoadjuvant Chemotherapy for Triple-Negative Breast Cancer.

INTRODUCTION: The immunomodulatory impact of corticosteroids and concurrent chemotherapy is poorly understood within triple-negative breast cancer (TNBC). On a biochemical level, steroids have been linked to the signaling of chemotherapy-resistant pathways. However, on a clinical level, steroids play an essential role in chemotherapy tolerance through the prevention of chemotherapy-induced nausea and vomiting (CINV) and hypersensitivity reactions. Given these conflicting roles, we wanted to evaluate this interplay more rigorously in the context of early-stage TNBC. METHODS: We performed a retrospective analysis of patients with operable TNBC who received neoadjuvant chemotherapy (NAC) between January 2012 and November 2018, with the primary goal of examining the dose-dependent relationship between pathological complete response (pCR) rates and corticosteroid use. Secondary endpoints included the impact of steroid dosing on overall survival (OS) and recurrence-free survival (RFS), along with a breakdown in pCR rates based on steroid doses provided during each chemotherapy phase. Further adjusted analyses were performed based on patient age, diabetic status, and anatomical stage. Finally, we explored the relationship between tumor-infiltrating lymphocytes (TILs) seen on tissue samples at baseline and dexamethasone doses in terms of pCR rates. RESULTS: In total, of the 174 patients screened within this study period, 116 met full eligibility criteria. Of these eligible patients, all were female, with a median age of 51.5 years (27.0 to 74.0) and a mean body mass index (BMI) of 29.7 [standard deviation (SD) 7.04]. The majority were nondiabetic (80.2%). For cancer stage, 69.8% (n = 81) had stage 2 breast cancer. We found no statistically significant association between pCR rates and dexamethasone use, both in terms of the total dose (p = 0.55) and mean dose per NAC cycle (p = 0.74). Similarly, no difference was noted when adjusting for diabetic status, metformin use, or age at diagnosis, regardless of the total steroid dose provided (p = 0.72) or mean dose per cycle (p = 0.49). No meaningful changes to pCR rate were seen with higher mean or higher total steroid doses during the paclitaxel (T) phase (adjusted p = 0.16 and p = 0.76, respectively) or doxorubicin and cyclophosphamide (AC) phase (adjusted p = 0.83 and p = 0.77, respectively). Furthermore, we found no clinically significant association between dexamethasone dose and either RFS (p = 0.45) or OS (p = 0.89). Of the 56 patients who had available pre-treatment biopsy tissue samples, 27 achieved pCR, with higher TILs at baseline being associated with higher pCR rates, regardless of the mean dexamethasone dose used. CONCLUSION: Our findings demonstrate that dexamethasone has no clinically significant impact on pCR, RFS, or OS when given concurrently with NAC in patients with curative TNBC, regardless of diabetic status.