Citations

Purpose To develop a deep learning model for the detection of Segond fractures on anteroposterior (AP) knee radiographs and to compare model performance to that of trained human experts. Methods AP knee radiographs were retrieved from the Hospital for Special Surgery ACL Registry, which enrolled patients between 2009 and 2013. All images corresponded to patients who underwent anterior cruciate ligament reconstruction by 1 of 23 surgeons included in the registry data. Images were categorized into 1 of 2 classes based on radiographic evidence of a Segond fracture and manually annotated. Seventy percent of the images were used to populate the training set, while 20% and 10% were reserved for the validation and test sets, respectively. Images from the test set were used to compare model performance to that of expert human observers, including an orthopaedic surgery sports medicine fellow and a fellowship‐trained orthopaedic sports medicine surgeon with over 10 years of experience. Results A total of 324 AP knee radiographs were retrieved, of which 34 (10.4%) images demonstrated evidence of a Segond fracture. The overall mean average precision (mAP) was 0.985, and this was maintained on the Segond fracture class (mAP = 0.978, precision = 0.844, recall = 1). The model demonstrated 100% accuracy with perfect sensitivity and specificity when applied to the independent testing set and the ability to meet or exceed human sensitivity and specificity in all cases. Compared to an orthopaedic surgery sports medicine fellow, the model required 0.3% of the total time needed to evaluate and classify images in the independent test set. Conclusions A deep learning model was developed and internally validated for Segond fracture detection on AP radiographs and demonstrated perfect accuracy, sensitivity, and specificity on a small test set of radiographs with and without Segond fractures. The model demonstrated superior performance compared with expert human observers. Clinical Relevance Deep learning can be used for automated Segond fracture identification on radiographs, leading to improved diagnosis of easily missed concomitant injuries, including lateral meniscus tears. Automated identification of Segond fractures can also enable large‐scale studies on the incidence and clinical significance of these fractures, which may lead to improved management and outcomes for patients with knee injuries.

Abstract Background: Antibody-drug conjugate (ADC) sequencing raises concerns of cross-resistance due to their shared cytotoxic payloads. Consequently, there is a pressing need for treatments after ADCs, especially in heavily pretreated patients. Immunization with irradiated SV-BR-1-GM, a GM-CSF secreting, antigen-presenting immortalized breast cancer cell line, has emerged as a potential post ADC solution based on a different mechanism of action. This retrospective analysis aims to assess the overall efficacy and safety of SV-BR-1-GM in a subset of ADC treated patients. Methods: Post-hoc subset analysis of the ongoing randomized Phase 2 study identified 23 advanced MBC patients who failed prior ADC therapy. Bria-IMT™ (irradiated SV-BR-1-GM ~20x106 cells, intradermally 48-72 hours after cyclophosphamide (300 mg/m2), followed by interferon-alpha at the inoculation sites 2 days later) was administered q3wks with a CPI. Endpoints included PFS, OS and disease control rate (the proportion of patients with stable disease, partial or complete responses) using the KM method censored to the data-cut date prior to data lock. Adverse events were classified according to their severity and relationship to treatment regimen. Results: All pts were heavily pretreated (median 6 prior lines, range 3 - 13). Median age was 62 (41-83). 14 pts had HR+/HER2-, 5 TNBC, and 2 HR+/HER2+ MBC. The remaining pts were HR-/HER2low or HR-/HER2+. Prior ADCs included: 4 ado-trastuzumab emtansine, 14 trastuzumab deruxtecan, 13 sacituzumab govitecan; 8 pts received > 1 ADC. 7 pts had also received ≥ 1 prior CPI line. To date, pts received a median 3 cycles of Bria-IMT™ + CPI (2-7). Kaplan-Meier analysis revealed a median OS of 42 weeks with survival of 69% at 6 months. The subset experienced a median PFS of 74 days with 40% of pts demonstrating a Bria-IMT PFS (PFS2) similar to or > their prior line PFS (PFS1). 39% of pts experienced a PFS2 ≥ their most recent line of ADC PFS. The disease control rate was 40% among evaluable pts. 43% of pts had a reduction in cancer-associated macrophage-like cell (CAML) levels; median reduction was 36% (22-98%) after 1 cycle. There were no toxicity-related treatment discontinuations. 43% (10/23) reported grade 3 or 4 AEs, independent of study drug causality. No interstitial lung disease (ILD) reported. AEs included injection site reaction (39%), fatigue (26%), and nausea/vomiting (43%), mostly mild to moderate. One case of elevated lipase was the most clinically significant grade 4 AE. Conclusion: The retrospective analysis of the Bria-IMT™ regimen in ADC refractory MBC patients suggests a potential treatment option for this patient population. The absence of serious AEs, notably ILD, and no toxicity-related treatment discontinuations, underscores the regimen's favorable safety profile. Future studies are warranted to confirm these results and explore the potential of Bria-IMT™ in broader clinical settings. Citation Format: Chaitali Nangia, Carmen Calfa, Blaise Bayer, Mingjin Chang, William Williams, Giuseppe Del Priore, Charles Wiseman, Saranya Chumsri. Efficacy and safety of SV-BR-1-GM after progression on ADC in metastatic breast cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT206.

Background: Oscillation and pulmonary expansion (OPE) therapy can decrease postoperative pulmonary complications in a general surgical population, but its effect after cardiac surgery has not been reported, to our knowledge. We hypothesized that using an OPE device after cardiac surgery before extubation would decrease pulmonary complications. Methods: This retrospective cohort study included adults undergoing elective open cardiac surgery at our institution from January 2018 through January 2019, who had an American Society of Anesthesiologists score of 3 or greater. For mechanically ventilated patients after cardiac surgery, a new OPE protocol was adopted, comprising an initial 10-min OPE treatment administered in-line with the ventilator circuit, then continued treatments for 48 h after extubation. The primary outcome measure was the occurrence of severe postoperative respiratory complications, including the need for antibiotics, increased use of supplemental oxygen, and prolonged hospital length of stay (LOS). Demographic, clinical, and outcome data were compared between patients receiving usual care (involving post-extubation hyperinflation) and those treated under the new OPE protocol. The primary outcome measure was the occurrence of severe postoperative respiratory complications, including the need for antibiotics, increased use of supplemental oxygen, and prolonged hospital length of stay (LOS). Demographic, clinical, and outcome data were compared between patients receiving usual care (involving post-extubation hyperinflation) and those treated under the new OPE protocol. Results: Of 104 patients, 54 patients received usual care, and 50 received OPE. Usual-care recipients had more men (74% vs. 62%; p = 0.19) and were older (median, 70 vs. 67 years; p = 0.009) than OPE recipients. The OPE group had a significantly shorter hospital LOS than the usual-care group (mean, 6.2 vs. 7.4 days; p = 0.04). Other measures improved with OPE but did not reach significance: shorter ventilator duration (mean, 0.6 vs. 1.1 days with usual care; p = 0.06) and shorter LOS in the intensive care unit (mean, 2.7 vs. 3.4 days; p = 0.06). On multivariate analysis, intensive care unit LOS was significantly shorter for the OPE group (mean difference, −0.85 days; 95% CI, −1.65 to −0.06; p = 0.04). The OPE group had a lower percentage of postoperative complications (10% vs. 20%). Conclusions: OPE therapy after cardiac surgery is associated with decreased intensive care unit (ICU) and hospital LOS.

Advanced Care at Home is a Mayo Clinic hospital-at-home (HaH) program that provides hospital-level care for patients. The study examines patient- and community-level factors that influence health outcomes. The authors performed a retrospective study using patient data from July 2020 to December 2022. The study includes 3 Mayo Clinic centers and community-level data from the Agency for Healthcare Research and Quality. The authors conducted binary logistic regression analyses to examine the relationship among the independent variables (patient- and community-level characteristics) and dependent variables (30-day readmission, mortality, and escalation of care back to the brick-and-mortar hospital). The study examined 1433 patients; 53% were men, 90.58% were White, and 68.2% were married. The mortality rate was 2.8%, 30-day readmission was 11.4%, and escalation back to brick-and-mortar hospitals was 8.7%. At the patient level, older age and male gender were significant predictors of 30-day mortality ( P -value <0.05), older age was a significant predictor of 30-day readmission ( P -value <0.05), and severity of illness was a significant predictor for readmission, mortality, and escalation back to the brick-and-mortar hospital ( P -value <0.01). Patients with COVID-19 were less likely to experience readmission, mortality, or escalations ( P -value <0.05). At the community level, the Gini Index and internet access were significant predictors of mortality ( P -value <0.05). Race and ethnicity did not significantly predict adverse outcomes ( P -value >0.05). This study showed promise in equitable treatment of diverse patient populations. The authors discuss and address health equity issues to approximate the vision of inclusive HaH delivery.

AbstractPurposePepinemab, a humanized IgG4 monoclonal antibody, targets the SEMA4D (CD100) antigen to inhibit binding to its high‐affinity receptors (plexin B1/PLXNB1, plexin B2/PLXNB2) and low‐affinity receptor (CD72). SEMA4D blockade leads to increased cytotoxic T‐cell infiltration, delayed tumor growth, and durable tumor rejection in murine tumor models. Pepinemab was well tolerated and improved T cell infiltration in clinical studies in adults with refractory tumors. SEMA4D was identified as a strong candidate proto‐oncogene in a model of osteosarcoma. Based on these preclinical and clinical data, we conducted a phase 1/2 study to determine the recommended phase 2 dose (RP2D), pharmacokinetics, pharmacodynamics, and immunogenicity, of pepinemab in pediatric patients with recurrent/refractory solid tumors, and activity in osteosarcoma.Experimental designPepinemab was administered intravenously on Days 1 and 15 of a 28‐day cycle at 20 mg/kg, the adult RP2D. Part A (phase 1) used a Rolling 6 design; Part B (phase 2) used a Simon 2‐stage design in patients with osteosarcoma. Pharmacokinetics and target saturation were evaluated in peripheral blood.ResultsPepinemab (20 mg/kg) was well tolerated and no dose‐limiting toxicities were observed during Part A. There were no objective responses. Two patients with osteosarcoma achieved disease control and prolonged stable disease. Pepinemab pharmacokinetics were similar to adults.ConclusionsPepinemab (20 mg/kg) is safe, well tolerated and resulted in adequate and sustained target saturation in pediatric patients. Encouraging disease control in two patients with osteosarcoma warrants further investigation with novel combination strategies to modulate the tumor microenvironment and antitumor immune response.Clinical trial registryThis trial is registered as NCT03320330 at Clinicaltrials.gov.DisclaimerThe content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Abstract Background: Circulating tumor cell clusters (CTCCs) are aggregated groups of tumor cells that detached from primary tumors and circulate the bloodstream. However, while Circulating Tumor Cells (CTCs) are a well studied phenomenon, CTCCs remain relatively unexplored and ill-defined, with only a few descriptive investigations evaluating their clinical utility. Adding to CTCC complexity is that various subtypes exist, including homotypic clusters consisting of a homogenous population of tumor cells and heterotypic CTCCs made of CTCs with immune/stromal white blood cells (WBCs). Furthermore, CTCs can undergo Epithelial-Mesenchymal Transition (EMT), a process characterized by loss of epithelial traits and upregulation of mesenchymal traits, and can form clustered EMTs (CEMTs). Moreover, CTCs can fuse with macrophages forming Tumor Macrophage Hybrid Cells, aka Cancer-Associated Macrophage Like cells (CAMLs) when in circulation. We enumerated all these types of cells and complex aggregates in the peripheral blood of patients with metastatic breast cancer (mBC). Methods: We enumerated the 6 populations from patient samples enrolled in IRB aproved prospective pilot studies. Whole peripheral blood (7.5mL) was filtered and stained with cytokeratin (CK) & CD45/CD14 to identify CTCs. CTCs were defined as an intact DAPI nuclei and strong filamentous CK. Homotypic CTCCs were defined as ≥2 CTCs attached together. Heterotypic CTCCs were defined as ≥1 CTC attached to ≥1 WBC. EMTs were defined as having DAPI nuclei and weak non-filamentous CK. CEMTS were defined as ≥2 EMTs. CAMLs were defined as having an enlarged polynucleated DAPI, and positive for CD45/CD14 or non-filamentous CK. Median progression free survival (mPFS) and median overall survival (mOS) over 24 months (m) were evaluated. Results: We evaluated the blood of 79 mBC patients. Single CTCs were found in 57% of patients (n=34/79), homotypic CTCCs 15% (n=12/79), heterotypic CTCCs 66% (n=27/79), EMTs 56% (n=44/79), CEMTs 23% (n=18/79) and CAMLs 97% (n=77/79). Over 24 ms, patierns with detectable heterotypic CTCCs & homotypic CTCCs had the shortest response times at mPFS=2.8 & mOS=5.8 ms, or mPFS=2.1 & mOS=4.3 ms, respectively. This was followed by CTCs mPFS=3.7 & mOS=13.7 ms, EMTs mPFS=4.3 & mOS=14.4 ms, CAMLs mPFS=4.3 & mOS=14.4 ms, and CEMT mPFS=4.7 & mOS=13.2 ms. Additionally, CTCCs were rare in HER2+ patients at 4.4% (n=1/23), but no associations to other hormone statuses were found. Conclusion: CTCCs appear to represent an array of subtypes with different biological and clinical meanings. Here we enumerated CTCC subtypes in the blood of mBC patients and stratified the various types to clinical outcomes. These data suggest CTCCs are clinically important and further understanding of their biology in the context of tumor pathogenesis is needed. Citation Format: Daniel L. Adams, Carolina Reduzzi, Aravind Aryasomayajula, R. Katherine Alpaugh, Saranya Chumsri, Cha-Mei Tang, Giuseppe Del Priore, William V. Williams, Massimo Cristofanilli. Identifying and stratifying circulating tumor cell cluster subtypes in metastatic breast cancer patients and evaluating their clinical outcomes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2303.

HLA‐DQA1*05:101 differs from HLA‐DQA1*05:01:01:02 by one nucleotide substitution at codon 221 (CGT>TGT) in exon 4.

Objective To investigate whether flexible nasopharyngoscopy, when performed in addition to magnetic resonance imaging (MRI), influences the type of surgery selected or success of surgery in patients with velopharyngeal insufficiency (VPI). Design Cohort study. Setting A metropolitan children's hospital. Patients Patients with non-syndromic, repaired cleft palate presenting for management of VPI. Interventions MRI and nasopharyngoscopy or MRI alone for preoperative imaging of the velopharyngeal mechanism. Main Outcome Measures (1) Surgical selection and (2) resolution of hypernasality. All speech, MRI, and nasopharyngoscopy measurements were performed by raters blinded to patients’ medical and surgical history. Results Of the 25 patients referred for nasopharyngoscopy, 76% completed the exam. Of the 41 patients referred for MRI, the scan was successfully completed by 98% of patients. Completion of nasopharyngoscopy was significantly (p=0.01) lower than MRI. Surgical selection did not significantly differ (p=0.73) between the group receiving MRI and nasopharyngoscopy and the group receiving MRI alone, nor was there a significant difference between these groups in the proportion of patients achieving resolution of hypernasality postoperatively (p=0.63). Percent total velopharyngeal closure assessments on nasopharyngoscopy and MRI were strongly correlated (r=0.73). Conclusions In patients receiving MRI as part of their preoperative VPI evaluation, the addition of nasopharyngoscopy did not result in a difference in surgical selection or resolution of hypernasality. Routine inclusion of nasopharyngoscopy may not be necessary for the evaluation of velopharyngeal anatomy when MRI is available.

We report the apparent aspiration of a bee followed by anaphylaxis and respiratory arrest in an adult male. The patient’s subjective experience of “swallowing a bee” is supported by clinical and radiographic findings.

ImportanceRedirection of care refers to withdrawal, withholding, or limiting escalation of treatment. Whether maternal social determinants of health are associated with redirection of care discussions merits understanding.ObjectiveTo examine associations between maternal social determinants of health and redirection of care discussions for infants born extremely preterm.Design, Setting, and ParticipantsThis is a retrospective analysis of a prospective cohort of infants born at less than 29 weeks’ gestation between April 2011 and December 2020 at 19 National Institute of Child Health and Human Development Neonatal Research Network centers in the US. Follow-up occurred between January 2013 and October 2023. Included infants received active treatment at birth and had mothers who identified as Black or White. Race was limited to Black and White based on service disparities between these groups and limited sample size for other races. Maternal social determinant of health exposures were education level (high school nongraduate or graduate), insurance type (public/none or private), race (Black or White), and ethnicity (Hispanic or non-Hispanic).Main Outcomes and MeasuresThe primary outcome was documented discussion about redirection of infant care. Secondary outcomes included subsequent redirection of care occurrence and, for those born at less than 27 weeks’ gestation, death and neurodevelopmental impairment at 22 to 26 months’ corrected age.ResultsOf the 15 629 infants (mean [SD] gestational age, 26 [2] weeks; 7961 [51%] male) from 13 643 mothers, 2324 (15%) had documented redirection of care discussions. In unadjusted comparisons, there was no significant difference in the percentage of infants with redirection of care discussions by race (Black, 1004/6793 [15%]; White, 1320/8836 [15%]) or ethnicity (Hispanic, 291/2105 [14%]; non-Hispanic, 2020/13 408 [15%]). However, after controlling for maternal and neonatal factors, infants whose mothers identified as Black or as Hispanic were less likely to have documented redirection of care discussions than infants whose mothers identified as White (Black vs White adjusted odds ratio [aOR], 0.84; 95% CI, 0.75-0.96) or as non-Hispanic (Hispanic vs non-Hispanic aOR, 0.72; 95% CI, 0.60-0.87). Redirection of care discussion occurrence did not differ by maternal education level or insurance type.Conclusions and RelevanceFor infants born extremely preterm, redirection of care discussions occurred less often for Black and Hispanic infants than for White and non-Hispanic infants. It is important to explore the possible reasons underlying these differences.