Original Cohort Research Articles

Secondary Surgery Following Lapidus Bunionectomy

While the Lapidus bunionectomy is a common procedure utilized to address hallux valgus, the incidence of secondary surgery is not well established. Our primary goal was to determine the incidence of revision surgery and hardware removal following the Lapidus bunionectomy in addition to the risk factors associated with each. A retrospective nested case-control study of adult patients who underwent a Lapidus bunionectomy for symptomatic hallux valgus over a 9-year period was performed. The incidence rates and 95% confidence intervals (CI) of secondary surgery in the 3 years following the procedure along with the estimated independent associations and odds ratios between baseline demographic, clinical, and radiographic characteristics were calculated. Of the original cohort of 2540 patients, 127 were identified (5.0%; CI: 4.1%, 5.8%) who underwent revision surgery and 165 (6.5%; CI: 5.5%, 7.5%) who underwent hardware removal following Lapidus bunionectomy. Initially, the hallux valgus angle, intermetatarsal angle, and tibial sesamoid position were risk factors for revision surgery. However, in adjusted analyses for revision surgery, using a screw for third point of fixation emerged as the only independent risk factor (odds ratio [OR] = 3.01; CI: 1.59, 5.69). In adjusted analyses for hardware removal, female sex (OR = 2.33; CI: 1.08, 5.00) and third point of fixation (OR = 2.92; CI: 1.82, 4.69) emerged as independent risk factors. While the overall risks associated with Lapidus bunionectomy are low and the need for revision surgery are low, this study helps to identify specific risk factors for secondary surgery and hardware removal to help in evaluation and discussion with patients.

Remote delivery of cancer genetic testing in veterans with metastatic prostate cancer: A Million Veteran Program study.

1541 Background: Germline pathogenic alterations are found in approximately 10% of men with metastatic prostate cancer (mPC) and can inform precision therapy, surveillance, and cancer prevention for family. National guidelines recommend germline genetic testing be offered to all men with mPC, yet uptake of testing in the community has been documented to be 10-12% with many barriers to testing. We conducted a study to determine uptake of testing using remote consenting and testing for veterans with mPC who had participated in the Department of Veteran’s Affairs (VA) Million Veteran Program (MVP). We wanted to know if remote testing could augment point-of-care counseling and ordering to increase uptake of germline testing. Methods: This prospective study enrolled veterans who participated in MVP study with a diagnosis of mPC. Veterans were contacted by mail with an option to opt-out of future contact. Those who did not opt-out were mailed information about the study and received a follow-up call to establish interest in germline testing with a CLIA-level germline test. Those expressing interest provided verbal informed consent and were mailed a saliva collection kit for a multigene cancer predisposition gene panel test. Results were disclosed by phone and mailed to the patient with genetic counseling support and were sent to the oncology provider by email, phone or both. Two research coordinators and two part-time genetic counselors provided consenting, counseling and return of results. A study evaluating facilitated communication of results to first degree relatives (FDR) and germline testing of FDR was a component of study. Results: As of 2/6/2024, 1952 veterans who were alive with an incident diagnosis of mPC were identified through MVP and did not opt out. Informational letters were sent to the home address of all eligible participants. 683 (35%) of veterans completed informed consent and 457 (23% of total original cohort) completed testing. Among the participants, 70% were White, 21% were Black, 0.5% Asian and 8% unknown, 13% had a germline pathogenic variant. Documentation of positive germline results from study in the chart reports was 58%. Of 30 results relevant for targeted therapy, 16 have received that therapy, 11 were not yet appropriate and 3 patients did not receive targeted therapy. Twenty-nine FDR were contacted and tested through the pilot study of facilitated contact and testing. Conclusions: We evaluated uptake of germline testing using a remote, VA system-wide approach to identify and offer genetic testing for veterans with mPC with access and cost issues removed. We completed germline testing at rates higher than those reported in the community with modest personnel requirements, in a diverse population of patients. Documentation of results in the electronic medical record can be improved. Remote genetic testing can augment uptake of testing in large integrated health care systems.

АНАЛИЗ ВЛИЯНИЯ ОБЛУЧЕНИЯ НА МУЛЬТИМОРБИДНОСТЬ УЧАСТНИКОВ ЛИКВИДАЦИИ ПОСЛЕДСТВИЙ АВАРИИ НА ЧЕРНОБЫЛЬСКОЙ АЭС

Purpose: To give a general idea of the most common combinations of diseases in the male population of the Russian Federation and to identify the combinations of diseases, the development of which could be influenced by ionising radiation. Material and methods: Cohort study of the influence of external gamma irradiation on multimorbidity of the Chernobyl accident liquidation participants according to the data of the National Radiation Epidemiological Registry. Multimorbidity was defined as the presence in one participant of the cohort of two or more diseases from the list consisting of ten groups of diagnoses: diseases of lower respiratory tract, diseases of musculoskeletal system, diseases of endocrine system, mental disorders, oncology, neurology, diseases of digestive organs, diseases of cardiovascular system, diseases of genitourinary system, diseases of sense organs. The cohort consisted of men born between 1919 and 1969 who worked in the accident zone from 1986 to 1987 and had a documented whole-body external gamma dose. Cohort follow-up period: 1992–2021. The cohort size at the beginning of the follow-up was 59 290 people. The study participants were divided into two groups according to external gamma dose: up to 150 mGy – 34602 individuals, 150 mGy and more – 24 688 individuals. For all possible combinations of diagnoses, relative radiation risk was calculated as a measure of the association of exposure with diseases. The relative radiation risk was considered statistically significant if the left border of the one-sided 95 % confidence interval was greater than 1. Statistical analyses were performed using the R programming language for statistical computing and the R arules package. Results: During 30 years of follow-up, multimorbidity was noted in 62 % of individuals. The most common combinations of chronic diseases were combinations of cardiovascular diseases with digestive diseases (23 % of the original cohort), with lower respiratory diseases (22 %) and with musculoskeletal diseases (18 %). A combination of all four diagnosis groups was identified in 5 % of individuals. Nineteen multimorbid combinations with statistically significant relative radiation risk in the range (1.07–1.23) were identified. Conclusions: No effect of radiation exposure on the number of individuals with multimorbidity was found, but in the studied cohort there are individuals with cardiovascular diseases, endocrine diseases, oncology and combinations of these groups of diagnoses with diseases of other body systems may be caused by radiation exposure. The statistically significant relative radiation risk for combinations of diagnoses is, in general, greater than for the individual diseases that make up these combinations.

Difference between kidney function by cystatin C versus creatinine and association with muscle mass and frailty.

A higher difference in estimated glomerular filtration rate by cystatin C versus creatinine (eGFRDiff = eGFRCys - eGFRCreat) is associated with decreased frailty risk. Since eGFRCreat is influenced by muscle more than eGFRCys, muscle mass may explain this association. Previous work could not account for this when considering regional muscle measures by imaging. Deuterated creatine (D3Cr) dilution measures whole body muscle mass (kilograms). We aimed to determine whether eGFRDiff is associated with D3Cr muscle mass and whether muscle mass explains the association between eGFRDiff and frailty. Cross-sectional analysis within the multicenter MrOS Study at Year 14 (visit 4). 490 men of the original cohort of 5994 MrOS participants (aged ≥65 at enrollment) were included. Exposure was eGFRDiff (= eGFRCys - eGFRCreat), calculated using CKD-EPI equations 2012/2021. Primary outcome was D3Cr muscle mass. Secondary outcome was phenotypic pre-frailty (one or two criteria) and frailty (≥three criteria) including the following: weight loss, weakness, slow gait, physical activity, poor energy. The association of eGFRDiff with D3Cr muscle mass was examined by linear regression, that with prefrailty / frailty by multinomial logistic regression. Mean ± SD age was 84 ± 4 years, eGFRCreat 68 ± 16, eGFRCys 52 ± 16, eGFRDiff -15 ± 12 mL/min/1.73 m2 and D3Cr muscle mass 24 ± 4 kg. For each SD increment in eGFRDiff, D3Cr muscle mass was 1.4 kg higher on average, p < 0.0001 (fully adjusted). Higher eGFRDiff was associated with lower odds of frailty (OR = 0.63 95% CI [0.45;0.89]), but this was partially attenuated and insignificant after additionally adjusting for D3Cr muscle mass (OR = 0.85 95% CI [0.58; 1.24]). Higher eGFRDiff is associated with lower odds of frailty among late-life men. D3Cr muscle mass accounts for some of this association. This suggests that non-GFR determinants of creatinine and cystatin C, such as muscle mass, play a role in explaining the association of eGFRDiff with frailty. Future studies are needed to confirm.

Interdisciplinary approach to identify language markers for post-traumatic stress disorder using machine learning and deep learning

Post-traumatic stress disorder (PTSD) lacks clear biomarkers in clinical practice. Language as a potential diagnostic biomarker for PTSD is investigated in this study. We analyze an original cohort of 148 individuals exposed to the November 13, 2015, terrorist attacks in Paris. The interviews, conducted 5–11 months after the event, include individuals from similar socioeconomic backgrounds exposed to the same incident, responding to identical questions and using uniform PTSD measures. Using this dataset to collect nuanced insights that might be clinically relevant, we propose a three-step interdisciplinary methodology that integrates expertise from psychiatry, linguistics, and the Natural Language Processing (NLP) community to examine the relationship between language and PTSD. The first step assesses a clinical psychiatrist's ability to diagnose PTSD using interview transcription alone. The second step uses statistical analysis and machine learning models to create language features based on psycholinguistic hypotheses and evaluate their predictive strength. The third step is the application of a hypothesis-free deep learning approach to the classification of PTSD in our cohort. Results show that the clinical psychiatrist achieved a diagnosis of PTSD with an AUC of 0.72. This is comparable to a gold standard questionnaire (Area Under Curve (AUC) ≈ 0.80). The machine learning model achieved a diagnostic AUC of 0.69. The deep learning approach achieved an AUC of 0.64. An examination of model error informs our discussion. Importantly, the study controls for confounding factors, establishes associations between language and DSM-5 subsymptoms, and integrates automated methods with qualitative analysis. This study provides a direct and methodologically robust description of the relationship between PTSD and language. Our work lays the groundwork for advancing early and accurate diagnosis and using linguistic markers to assess the effectiveness of pharmacological treatments and psychotherapies.

Gender differences in female and male Australian football concussion injury: A prospective observational study of emergency department presentations.

To examine gender differences in Australian football (AF)-related concussion presentations to EDs in regional Australia. A prospective observational study of patients presenting to 1 of the 10 EDs in Western Victoria, Australia, with an AF-related concussion was conducted. Patients were part of a larger study investigating AF injuries over a complete AF season, including pre-season training and practice matches. Information regarding concussion injuries was extracted from patient medical records, including clinical features, concurrent injuries, mechanism and context of injury. Female and male data were compared with chi-squared and Fisher's exact tests. P < 0.05 was considered significant. From the original cohort of 1635 patients with AF-related injuries (242 female and 1393 male), 231 (14.1%) patients were diagnosed with concussion. Thirty-eight (15.7%) females had concussions versus 193 (13.9%) males (P > 0.05). Females over the age of 16 were more likely to be concussed than males in the same age range (females n = 26, 68.4% vs males n = 94, 48.7%; P = 0.026). Neurosurgically significant head injury was rare (one case). Similar rates of concurrent injury were found between females 15 (39.5%) and males 64 (33.2%), with neck injury the single most common in 24 (10.3%) concussions. Sixty-nine patients (29%) were admitted for observation or to await the results of scans. The majority of concussions occurred in match play (87.9%). Females were more likely injured in contested ball situations (63.2% vs 37.3%; P < 0.05). Concussion rates for community-level AF presentations to regional EDs were similar between genders. Serious head injury was rare, although hospital admission for observation was common. Concurrent injuries were common, with associated neck injury most often identified. Match play accounted for the majority of head injuries.

Whole exome sequencing in young atrial fibrillation patients

Abstract Background Up to 10% of atrial fibrillation (Afib) patients develop the condition in the young age and in the absence of any related risk factors. Recent publications emphasized the importance of genetic testing in this population. However, the yield of the investigation is highly variable and ranges from 1 to 24% precents. Purpose The purpose of this study is to evaluate the prevalence of causative genetic variants in young Afib patients without risk factors and evaluate any structural changes of the heart. Methods We performed whole exome sequencing in 54 young (age of Afib onset less than 65 years) Afib patients without any Afib related risk factors (original cohort). Using ACMG guidelines we performed analysis of 349 previously described cardiomyopathy and arrhythmia associated genes. If a pathogenic (P) or likely pathogenic (LP) variant was found, a cardiac magnetic resonance imaging (CMR) was performed to exclude any structural abnormalities of the heart. We also extracted 107 young Afib patients without any risk factors from UK Biobank (UK Biobank cohort) and performed analysis of the same genes in the subgroup. Results The prevalence of P and LP variants was 24% (13 cases) in the original cohort and 8% (9 cases) in the UK Biobank cohort (p=0.006). We observed variants in cardiac structural and developmental genes only in both cohorts (Table 1 and 2). In the original cohort there were nine (17%) patients with P and LP variant in TTN gene. Moreover, five patients were positive for the same TTN variant NM_001267550.2:c.13696C&amp;gt;T p.(Gln4566Ter). In six (46%) original cohort patients we observed structural changes of the heart on CMR – in five patients there was dilation of one or both ventricles and in one there was increased T1 mapping intensity of septal wall segments. Conclusions 1. There is a high prevalence of pathogenic and likely pathogenic causative genetic variants in young atrial fibrillation patients without any risk factors. 2. All variants are localized in cardiac structural or developmental genes only. 3. There is a high grade of structural changes of the heart observed on cardiac magnetic resonance imaging in patients with monogenic atrial fibrillation.Table 1.WES data in original cohortTable 2.WES data in UK Biobank cohort

Albumin levels and cerebral collateral circulation in patients with acute ischemic stroke due to intracranial arteriosclerotic: A propensity score-matched analysis.

Cerebral collateral circulation (CC) is associated with the recurrence and severity of acute ischemic stroke (AIS), and early identification of poor CC is helpful for the prevention of AIS. In this study we evaluated the association between serum albumin levels and CC in AIS using logistic regression. Propensity score (PS) matching was used to eliminate the effect of confounders, and restricted cubic splines (RCS) were employed to explore potential nonlinear associations between albumin and CC. In unadjusted logistic regression analysis, lower albumin (OR = 0.85, 95% CI = 0.79-0.92) was associated with poor CC, and after adjusting for covariates, the odds of lower albumin for poor CC compared to good CC were 0.86 (95% CI = 0.79-0.94). In the PS cohort, the association of albumin with CC was consistent with those of the original cohort. RCS results showed a linear relationship between albumin and CC (P values of .006 and .08 for overall and nonlinear associations, respectively). The results of this study suggest that lower serum albumin is independently associated with an increased risk of poor CC, which may serve as an effective predictive indicator for poor CC in patients with severe intracranial atherosclerotic stenosis.

Can we predict kidney involvement in patients with systemic lupus erythematosus? A retrospective cohort study with independent validation.

To discern predictive factors for incident kidney involvement in patients with systemic lupus erythematosus (SLE). Patients with SLE from the 'Attikon' Lupus cohort were monitored for lupus nephritis (LN), defined by kidney histology and/or classification criteria. Demographic and clinical characteristics at baseline were compared against patients who did not develop LN. LN-free survival curves were generated by Kaplan-Meier. A multivariate Cox proportional hazards model was used to identify independent predictors of LN. Independent validation was performed in the University of Crete Lupus registry. Among the 570 patients in the derivation cohort, 59 exhibited LN as their initial presentation, while an additional 66 developed LN during the follow-up period (collectively, 21.9% incidence). In the latter group, baseline factors predictive of subsequent kidney involvement were male sex (multivariable-adjusted [a]HR 4.31, 95% CI: 1.82-10.2), age of SLE diagnosis below 26 years (aHR 3.71, 95% CI: 1.84-7.48), high anti-dsDNA titre (aHR 2.48, 95% CI: 1.03-5.97) and low C3 and/or C4 (although not statistically significant, aHR 2.24, 95% CI: 0.83-6.05, p= 0.11). A combination of these factors at time of diagnosis conferred an almost 90-fold risk compared with serologically inactive, older, female patients (aHR 88.77, 95% CI : 18.75-420.41), signifying a very high-risk group. Independent validation in the Crete Lupus registry showed concordant results with the original cohort. Male sex, younger age and serologic activity at SLE diagnosis are strongly associated with subsequent kidney involvement. Vigilant surveillance and consideration of early use of disease-modifying drugs is warranted in these subsets of patients.

History of periodontitis as a risk factor for implant failure and incidence of peri-implantitis: A systematic review, meta-analysis, and trial sequential analysis of prospective cohort studies.

Dental implants are widely employed as dependable replacements for lost teeth. However, it is crucial to establish, solely through prospective cohort studies, whether a history of periodontitis indeed constitutes a significant risk factor for implant failure. A systematic literature search was conducted in October 2022 in several electronic databases with subsequent manual updates. Only original prospective cohort studies evaluating the implant (loss) rate ≥1 year after implant loading were included. Logarithmic risk ratio and weighted mean differences were calculated. Study results were summarized using random effects meta-analyses evaluated by trial sequential analyses. The Newcastle-Ottawa scale evaluated study bias and the GRADE approach assessed the certainty/quality of the evidence. A total of 14 publications reporting on 12 prospective cohort studies were included. Low evidence certainty/quality evidence due to the absence of randomized clinical trials revealed significantly greater odds of failure in patients with a history of periodontitis at follow-ups both after ≤5 years (RR = 1.62; 95% CI: 1.71-2.37; p = 0.013) and >5 years (RR = 2.26; 95% CI: 1.12-4.53; p = 0.023). The incidence of peri-implantitis (RR = 4.09; 95% CI: 1.93-8.58; p < 0.001) and the weighted mean (WM) of marginal bone loss (WM difference = 0.75 mm; 95% CI: 0.18-1.31; p < 0.05) were statistically significantly greater in the periodontally compromised group, whereas there was no significant difference between the two groups for peri-implant probing depth. A history of periodontitis can be considered a significant risk factor for incident implant failure, peri-implantitis, and greater marginal bone loss.

Inflammatory subphenotypes previously identified in ARDS are associated with mortality at intensive care unit discharge: a secondary analysis of a prospective observational study

BackgroundIntensive care unit (ICU)-survivors have an increased risk of mortality after discharge compared to the general population. On ICU admission subphenotypes based on the plasma biomarker levels of interleukin-8, protein C and bicarbonate have been identified in patients admitted with acute respiratory distress syndrome (ARDS) that are prognostic of outcome and predictive of treatment response. We hypothesized that if these inflammatory subphenotypes previously identified among ARDS patients are assigned at ICU discharge in a more general critically ill population, they are associated with short- and long-term outcome.MethodsA secondary analysis of a prospective observational cohort study conducted in two Dutch ICUs between 2011 and 2014 was performed. All patients discharged alive from the ICU were at ICU discharge adjudicated to the previously identified inflammatory subphenotypes applying a validated parsimonious model using variables measured median 10.6 h [IQR, 8.0–31.4] prior to ICU discharge. Subphenotype distribution at ICU discharge, clinical characteristics and outcomes were analyzed. As a sensitivity analysis, a latent class analysis (LCA) was executed for subphenotype identification based on plasma protein biomarkers at ICU discharge reflective of coagulation activation, endothelial cell activation and inflammation. Concordance between the subphenotyping strategies was studied.ResultsOf the 8332 patients included in the original cohort, 1483 ICU-survivors had plasma biomarkers available and could be assigned to the inflammatory subphenotypes. At ICU discharge 6% (n = 86) was assigned to the hyperinflammatory and 94% (n = 1397) to the hypoinflammatory subphenotype. Patients assigned to the hyperinflammatory subphenotype were discharged with signs of more severe organ dysfunction (SOFA scores 7 [IQR 5–9] vs. 4 [IQR 2–6], p < 0.001). Mortality was higher in patients assigned to the hyperinflammatory subphenotype (30-day mortality 21% vs. 11%, p = 0.005; one-year mortality 48% vs. 28%, p < 0.001). LCA deemed 2 subphenotypes most suitable. ICU-survivors from class 1 had significantly higher mortality compared to class 2. Patients belonging to the hyperinflammatory subphenotype were mainly in class 1.ConclusionsPatients assigned to the hyperinflammatory subphenotype at ICU discharge showed significantly stronger anomalies in coagulation activation, endothelial cell activation and inflammation pathways implicated in the pathogenesis of critical disease and increased mortality until one-year follow up.

Detailed analysis of metastatic colorectal cancer patients who developed cardiotoxicity on another fluoropyrimidine and switched to S-1 treatment (subgroup analysis of the CardioSwitch-study).

The CardioSwitch-study demonstrated that patients with solid tumors who develop cardiotoxicity on capecitabine or 5-fluorouracil (5-FU) treatment can be safely switched to S-1, an alternative fluoropyrimidine (FP). In light of the European Medicines Agency approval of S-1 in metastatic colorectal cancer (mCRC), this analysis provides more detailed safety and efficacy information, and data regarding metastasectomy and/or local ablative therapy (LAT), on the mCRC patients from the original study. This retrospective cohort study was conducted at 12 European centers. The primary endpoint was recurrence of cardiotoxicity after switch. For this analysis, safety data are reported for 78 mCRC patients from the CardioSwitch cohort (N = 200). Detailed efficacy and outcomes data were available for 66 mCRC patients. Data for the safety of S-1 in mCRC patients were similar to the original CardioSwitch cohort and that expected for FP-based treatment, with no new concerns. Recurrent cardiotoxicity (all grade 1) with S-1-based treatment occurred in 4/78 (5%) mCRC patients; all were able to complete FP treatment. Median progression-free survival from initiation of S-1-based treatment was 9.0 months and median overall survival 26.7 months. Metastasectomy and/or LAT was performed in 33/66 (50%) patients, and S-1 was successfully used in recommended neoadjuvant/conversion or adjuvant-like combination regimens and schedules as for standard FPs. S-1 is a safe and effective FP alternative when mCRC patients are forced to discontinue 5-FU or capecitabine due to cardiotoxicity and can be safely used in the standard recommended regimens, settings, and schedules.

Abstract PO5-17-03: Relative Dose Intensity and Protraction of Neoadjuvant Chemotherapy in Early-Stage and Locally Advanced Breast Cancer: A collaborative multicenter analysis in Colombia

Abstract Introduction: Breast cancer (BC) is the most frequent neoplasm in Colombia. In contrast to high-income countries, the expected 5-year overall survival (OS) remains below 80% over the last years. Neoadjuvant chemotherapy (NACT) has reduced the risk of relapse and death by achieving higher pathological complete response (ypCR) rates, but delays and dose reductions could impact prognosis negatively. We have previously reported the outcomes of NACT from a real-world multicenter historical cohort of Colombian early and locally advanced BC patients. We aimed to analyze NACTRelative Dose Intensity (RDI) and protraction data as related to clinical outcomes in the same cohort. Methods: We performed a secondary analysis of the primary database of 312 BC patients treated with NACT where ypCR rate was 34·6%, with 88·2% 5-year OS. We considered RDI and protraction as independent variables for the same outcomes. The RDI was estimated using the Hrynuik method, and protraction was defined as the difference between planned and actual completion time for the NACT exceeding 7 days from standard 21-day cycles. Chemotherapy regimens are based on the National Hematology and Oncology Association (ACHO) guidelines. We excluded cases with missing or conflicting data. Univariate, and bivariate analysis, and partition survival trees were performed to examine variable interactions. Results: From the original cohort of 312 patients, 47 and 7 additional patients were excluded due to missing protraction and RDI data, respectively; the final analysis included 261 and 254 patients, respectively. The average days to complete planned chemotherapy cycles were 154,4 (SD 32,29 days). 203 patients (77,8%), 26 patients (10%), and 11 patients (4,2%) received complete 8,7 and 6 NACT cycles, respectively. Overall, 175 patients (67%) had protracted chemotherapy cycles, being highest in the 7-cycle subgroup (77%). 169 patients (66,5%) had a dose intensity over 85% and 90 patients (35.43%) achieved an RDI of 100% or more. The mean RDI for the cohort was 79,8% (SD 19,91%) and it differed according to expression profile subgroups in decreasing order as follows: HER2 pure 98,85% (SD 19,59%), Luminal A 96,03% (SD 21,28%), Triple Negative 97,81% (SD 19,73%), Luminal B HER+ and HER2- being lowest with 90,43% (SD 19,47%) and 87,75% (SD 23,22%), respectively. Neither NACT RDI nor protraction was associated significantly with ypCR, conservative surgery, or all-cause OS. Although statistically not-significant, sensitivity analysis through different RDI thresholds (20%-100%) demonstrated improved discriminatory capacity over ypCR for RDI &amp;gt;= 85%. Conclusion: On average, NACT-RDI greater than 85% was observed in Colombian patients with early and locally advanced BC similar to other cohorts. However, it was not associated with ypCR, conservative surgery, or OS. Also, NACT protraction beyond 7 days did not adversely affect clinical outcomes. However, this conclusion is limited due to the retrospective nature and loss of real-world data. Adverse events and their impact on RDI were not analyzed either. Further research is warranted to understand RDI's impact on clinical outcomes, and a large-scale trial is proposed to validate these findings. Citation Format: Alejandro Murillo, Andres Acevedo, Santiago Betancur, Mariana Borras-Osorio, Isabel Munevar, William Mantilla, Luis Pino. Relative Dose Intensity and Protraction of Neoadjuvant Chemotherapy in Early-Stage and Locally Advanced Breast Cancer: A collaborative multicenter analysis in Colombia [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-17-03.

A novel quantitative grading system for implant fixation in revision total knee arthroplasty.

Obtaining solid implant fixation is crucial in revision total knee arthroplasty (rTKA) to avoid aseptic loosening, a major reason for re-revision. This study aims to validate a novel grading system that quantifies implant fixation across three anatomical zones (epiphysis, metaphysis, diaphysis). Based on pre-, intra-, and postoperative assessments, the novel grading system allocates a quantitative score (0, 0.5, or 1 point) for the quality of fixation achieved in each anatomical zone. The criteria used by the algorithm to assign the score include the bone quality, the size of the bone defect, and the type of fixation used. A consecutive cohort of 245 patients undergoing rTKA from 2012 to 2018 were evaluated using the current novel scoring system and followed prospectively. In addition, 100 first-time revision cases were assessed radiologically from the original cohort and graded by three observers to evaluate the intra- and inter-rater reliability of the novel radiological grading system. At a mean follow-up of 90 months (64 to 130), only two out of 245 cases failed due to aseptic loosening. Intraoperative grading yielded mean scores of 1.87 (95% confidence interval (CI) 1.82 to 1.92) for the femur and 1.96 (95% CI 1.92 to 2.0) for the tibia. Only 3.7% of femoral and 1.7% of tibial reconstructions fell below the 1.5-point threshold, which included the two cases of aseptic loosening. Interobserver reliability for postoperative radiological grading was 0.97 for the femur and 0.85 for the tibia. A minimum score of 1.5 points for each skeletal segment appears to be a reasonable cut-off to define sufficient fixation in rTKA. There were no revisions for aseptic loosening at mid-term follow-up when this fixation threshold was achieved or exceeded. When assessing first-time revisions, this novel grading system has shown excellent intra- and interobserver reliability.

Doppler ultrasound surveillance of recently formed haemodialysis arteriovenous fistula: the SONAR observational cohort study.

Arteriovenous fistulas are considered the best option for haemodialysis provision, but as many as 30% fail to mature or suffer early failure. To assess the feasibility of performing a randomised controlled trial that examines whether, by informing early and effective salvage intervention of fistulas that would otherwise fail, Doppler ultrasound surveillance of developing arteriovenous fistulas improves longer-term arteriovenous fistula patency. A prospective multicentre observational cohort study (the 'SONAR' study). Seventeen haemodialysis centres in the UK. Consenting adults with end-stage renal disease who were scheduled to have an arteriovenous fistula created. Participants underwent Doppler ultrasound surveillance of their arteriovenous fistulas at 2, 4, 6 and 10 weeks after creation, with clinical teams blinded to the ultrasound surveillance findings. Fistula maturation at week 10 defined according to ultrasound surveillance parameters of representative venous diameter and blood flow (wrist arteriovenous fistulas: ≥ 4 mm and > 400 ml/minute; elbow arteriovenous fistulas: ≥ 5 mm and > 500 ml/minute). Mixed multivariable logistic regression modelling of the early ultrasound scan data was used to predict arteriovenous fistula non-maturation by 10 weeks and fistula failure at 6 months. A total of 333 arteriovenous fistulas were created during the study window (47.7% wrist, 52.3% elbow). By 2 weeks, 37 (11.1%) arteriovenous fistulas had failed (thrombosed), but by 10 weeks, 219 of 333 (65.8%) of created arteriovenous fistulas had reached maturity (60.4% wrist, 67.2% elbow). Persistently lower flow rates and venous diameters were observed in those fistulas that did not mature. Models for arteriovenous fistulas' non-maturation could be optimally constructed using the week 4 scan data, with fistula venous diameter and flow rate the most significant variables in explaining wrist fistula maturity failure (positive predictive value 60.6%, 95% confidence interval 43.9% to 77.3%), whereas resistance index and flow rate were most significant for elbow arteriovenous fistulas (positive predictive value 66.7%, 95% confidence interval 48.9% to 84.4%). In contrast to non-maturation, both models predicted fistula maturation much more reliably [negative predictive values of 95.4% (95% confidence interval 91.0% to 99.8%) and 95.6% (95% confidence interval 91.8% to 99.4%) for wrist and elbow, respectively]. Additional follow-up and modelling on a subset (n = 192) of the original SONAR cohort (the SONAR-12M study) revealed the rates of primary, assisted primary and secondary patency arteriovenous fistulas at 6 months were 76.5, 80.7 and 83.3, respectively. Fistula vein size, flow rate and resistance index could identify primary patency failure at 6 months, with similar predictive power as for 10-week arteriovenous fistula maturity failure, but with wide confidence intervals for wrist (positive predictive value 72.7%, 95% confidence interval 46.4% to 99.0%) and elbow (positive predictive value 57.1%, 95% confidence interval 20.5% to 93.8%). These models, moreover, performed poorly at identifying assisted primary and secondary patency failure, likely because a subset of those arteriovenous fistulas identified on ultrasound surveillance as at risk underwent subsequent successful salvage intervention without recourse to early ultrasound data. Although early ultrasound can predict fistula maturation and longer-term patency very effectively, it was only moderately good at identifying those fistulas likely to remain immature or to fail within 6 months. Allied to the better- than-expected fistula patency rates achieved (that are further improved by successful salvage), we estimate that a randomised controlled trial comparing early ultrasound-guided intervention against standard care would require at least 1300 fistulas and would achieve only minimal patient benefit. This trial is registered as ISRCTN36033877 and ISRCTN17399438. This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR135572) and is published in full in Health Technology Assessment; Vol. 28, No. 24. See the NIHR Funding and Awards website for further award information.

Three- and five-year outcomes of an inception cohort of Australian children with juvenile idiopathic arthritis.

To describe the 3- and 5-year outcomes of an inception cohort of Australian children with JIA for whom 1-year outcomes have previously been published. Data regarding clinical outcomes of the original cohort of 134 patients at 3 and 5 years were sought. Relevant clinical features and medication exposures entered prospectively into an electronic record were collected and analyzed using descriptive statistics. Data were available for 110 and 98 patients at 3 and 5 years, respectively. The proportion of patients with active joints progressively decreased from 34% at 12 months to 21% at 3 years and 16% at 5 years. Cumulative exposure to methotrexate increased between 3 and 5 years (75%-80%), however, point prevalence use decreased (45%-41%). Cumulative exposure and point prevalence use of bDMARDS both increased between 3 and 5 years; 30%-42% and 29%-33%, respectively. Thirty-five percent of patients had inactive joint disease off medications at 5 years, which occurred most frequently in patients with sJIA and oligoarthritis. Five-year outcomes of Australian children with JIA are good, with only a small minority having ongoing active joint disease at 5 years. bDMARDS play an increasing role in management over time; however, methotrexate use remains significant. A majority of children remain on medications at 5 years.

Pharmacogene expression during progression of metabolic dysfunction-associated steatotic liver disease: Studies on mRNA and protein levels and their relevance to drug treatment

Metabolic dysfunction-associated steatotic liver disease (MASLD) is common worldwide. Genes and proteins contributing to drug disposition may show altered expression as MASLD progresses. To assess this further, we undertook transcriptomic and proteomic analysis of 137 pharmacogenes in liver biopsies from a large MASLD cohort.We performed sequencing on RNA from 216 liver biopsies (206 MASLD and 10 controls). Untargeted mass spectrometry proteomics was performed on a 103 biopsy subgroup. Selected RNA sequencing signals were replicated with an additional 187 biopsies.Comparison of advanced MASLD (fibrosis score 3/4) with milder disease (fibrosis score 0–2) by RNA sequencing showed significant alterations in expression of certain phase I, phase II and ABC transporters. For cytochromes P450, CYP2C19 showed the most significant decreased expression (30 % of that in mild disease) but significant decreased expression of other CYPs (including CYP2C8 and CYP2E1) also occurred. CYP2C19 also showed a significant decrease comparing the inflammatory form of MASLD (MASH) with non-MASH biopsies. Findings for CYP2C19 were confirmed in the replication cohort. Proteomics on the original discovery cohort confirmed decreased levels of several CYPs as MASLD advanced but this decrease was greatest for CYP2C19 where levels fell to 40 % control. This decrease may result in decreased CYP2C19 activity that could be problematic for prescription of drugs activated or metabolized by CYP2C19 as MASLD advances. More limited decreases for other P450s suggest fewer issues with non-CYP2C19 drug substrates. Negative correlations at RNA level between CYP2C19 and several cytokine genes provided initial insights into the mechanism underlying decreased expression.

Brain Injury Associated Shock: An Under-Recognized and Challenging Prehospital Phenomenon.

Hemodynamic collapse in multi-trauma patients with severe traumatic brain injury (TBI) poses both a diagnostic and therapeutic challenge for prehospital clinicians. Brain injury associated shock (BIAS), likely resulting from catecholamine storm, can cause both ventricular dysfunction and vasoplegia but may present clinically in a manner similar to hemorrhagic shock. Despite different treatment strategies, few studies exist describing this phenomenon in the early post-injury phase. This retrospective observational study aimed to describe the frequency of shock in isolated TBI in prehospital trauma patients and to compare their clinical characteristics to those patients with hemorrhagic shock and TBI without shock. All prehospital trauma patients intubated by prehospital medical teams from New South Wales Ambulance Aeromedical Operations (NSWA-AO) with an initial Glasgow Coma Scale (GCS) of 12 or less were investigated. Shock was defined as a pre-intubation systolic blood pressure under 90mmHg and the administration of blood products or vasopressors. Injuries were classified from in-hospital computed tomography (CT) reports. From this, three study groups were derived: BIAS, hemorrhagic shock, and isolated TBI without shock. Descriptive statistics were then produced for clinical and treatment variables. Of 1,292 intubated patients, 423 had an initial GCS of 12 or less, 24 patients (5.7% of the original cohort) had shock with an isolated TBI, and 39 patients had hemorrhagic shock. The hemodynamic parameters were similar amongst these groups, including values of tachycardia, hypotension, and elevated shock index. Prehospital clinical interventions including blood transfusion and total fluids administered were also similar, suggesting they were indistinguishable to prehospital clinicians. Hemodynamic compromise in the setting of isolated severe TBI is a rare clinical entity. Current prehospital physiological data available to clinicians do not allow for easy delineation between these patients from those with hemorrhagic shock.

Risk Stratification with Sarculator and MSKCC in Patients with Primary and Secondary Angiosarcoma.

Sarculator and Memorial Sloan Kettering Cancer Center (MSKCC) nomograms are freely available risk prediction scores for surgically treated patients with primary sarcomas. Due to the rarity of angiosarcomas, these scores have only been tested on small cohorts of angiosarcoma patients. In neither the original patient cohort upon which the Sarculator is based nor in subsequent studies was a distinction made between primary and secondary angiosarcomas, as the app is intended to be applied to primary sarcomas. Therefore, the objective of our investigation was to assess whether the Sarculator reveals a difference in prognosis and whether such differentiation aligns with actual clinical data. Thirty-one patients with primary or secondary soft tissue angiosarcoma, treated at our Sarcoma Center from 2001 to 2023, were included in the study. Actual survival rates were compared with nomogram-derived data for predicted 5-year survival (Sarculator), as well as 4-, 8- and 12-year sarcoma-specific death probabilities (MSKCC). Harrell's c-index was utilized to assess predictive validity. In total, 31 patients were analyzed. The actual overall 5-year survival was 22.57% with a predicted 5-year survival rate of 25.97%, and the concordance index was 0.726 for the entire cohort. The concordance index results from MSKCC for angiosarcoma patients were below 0.7 indicating limited predictive accuracy in this cohort, particularly when compared to Sarculator. Nomogram-based predictive models are valuable tools in clinical practice for rapidly assessing prognosis. They can streamline the decision-making process for adjuvant treatments and improve patient counselling especially in the treatment of rare and complicated tumor entities such as angiosarcomas.

Efficacy of metastatic lesion radiotherapy in patients with metastatic nasopharyngeal carcinoma: A multicenter retrospective study

ObjectiveWe investigated the efficacy of metastatic lesion radiotherapy (MLRT) in patients with metastatic nasopharyngeal carcinoma (mNPC). Materials and methodsPatients with mNPC from three institutions were included in this study. Propensity score matching (PSM) was employed to ensure comparability between patient groups. Overall survival (OS) rates were assessed using the Kaplan–Meier method and compared using the log-rank test. Prognostic factors were identified using univariate and multivariate Cox hazard analyses. Subgroup analyses were conducted to assess the effects of MLRT on specific patient populations. ResultsWe analyzed data from 1157 patients with mNPC. Patients who received MLRT had significantly better OS than those who did not, both in the original (28 vs. 21 months) and PSM cohorts (26 vs. 23 months). MLRT was identified as an independent favorable predictor of OS in multivariate analyses, with hazard ratios of 0.67. The subgroup analysis results indicated that radiotherapy effectively treated liver, lung, and bone metastatic lesions, particularly in patients with a limited tumor burden. Higher total radiation doses of MLRT (biologically effective dose (BED) ≥ 56 Gy) were associated with improved OS, while neither radiation technique nor dose fractionation independently influenced prognosis. ConclusionsMLRT offers survival advantages to patients diagnosed with mNPC. Patients with limited metastatic burden derive the most benefit from MLRT, and the recommended regimen for MLRT is a minimum BED of 56 Gy for optimal outcomes.