Citations

Background: There are different types of grafts for rhinoplasty, each with certain advantages and disadvantages. Fresh frozen cadaveric costal allograft (CCA) provides an alternative to rhinoplasties. The aim of this study was to compare the outcomes of fresh frozen CCA and traditional autologous costal cartilage in cosmetic and reconstructive rhinoplasty procedures. Methods: This is a prospective, single-center, nonrandomized, open-label clinical trial. Objective assessment to evaluate warping, resorption, and displacement of the cartilage was achieved by measuring the differences of standardized values (deviation angle, nasofrontal angle, total facial convexity, nasofacial angle, and nasolabial angle) obtained at 6-months and 12-months postoperative follow-up on standard two-dimensional photographs (Δ = ∣measurement6 − measurement12∣). Subjective assessment was measured by the FACE-Q assessment. Results: Fifty eligible patients between March 2017 and October 2020 were included. The average age was 43.9 ± 16.6 years and the mean follow-up period was 14.8 months. In the control group, the changes (Δ) in the deviation angle and nasolabial angle were greater than in the CCA group (P < 0.05). In the CCA group, the mean score of satisfaction with nose improved at 6 months and 1 year postoperatively (P < 0.05). The mean score of satisfaction with nostrils and overall facial appearance also increased in the CCA group at 6 months postoperatively (P < 0.05). Six patients from the CCA group and 10 patients from the control group experienced postoperative complications. Conclusions: Fresh frozen CCA is a safe and reliable source of rhinoplasty grafts. It is aseptic, readily available, and free of donor site complications.

Abstract Across scar studies, there is a lack of dark‐skinned individuals, who have a predisposition for keloid formation, altered pigmentation and poorer quality of life (QOL). There is a need for patients of colour to be included in scar scale development and validation. In this study, we evaluate the racial diversity of patients included in the validation of scar assessment scales. A systematic review was conducted for articles reporting on the validation of a scar assessment tool. Racial, ethnic and Fitzpatrick skin type (FST) data were extracted. Fifteen scar scale validation studies were included. Nine of the studies did not mention FST, race or ethnicity of the patients. Two of the studies that reported FST or race information only included White patients or included no FST V/VI patients: mapping assessment of scars (MAPS) and University of North Carolina ‘4P’. Only four studies included non‐White patients or dark‐skinned patients in the validation of their scar scale: the modified Vancouver Scar Scale (VSS), modified Patient and Observer Scar Assessment Scale (POSAS), acne QOL and SCAR‐Q scales. The patients included in the modified VSS validation were 7% and 13% FST V/VI, 14% African in the modified POSAS and 4.5% FST V/VI in the SCAR‐Q. We highlight the severe lack of diversity in scar scale validation, with only 4 out of 15 studies including dark‐skinned patients. Given the susceptibility of darker‐skinned individuals to have poorer scarring outcomes, it is critical to include patients of colour in the very assessment tools that determine their scar prognosis. Inclusion of patients of colour in scar scale development will improve scar assessment and clinical decision‐making.

Abstract AIMS High-grade glioma continues to have dismal survival with current standard-of-care treatment, owing in part to its intra- and inter-patient heterogeneity. Typical diagnostic biopsies are taken from the dense tumor core to determine the presence of abnormal cells and the status of a few key genes (e.g. IDH1, MGMT). However, the tumor core is typically resected, leaving behind possibly genetically, transcriptomically and/or phenotypically distinct invasive margins that repopulate the disease. As these remaining populations are the ones ultimately being treated, it is important to know their compositional differences from the tumor core. We aim to identify the phenotypic niches defined by the relative composition of key cellular populations and understand their variation amongst patients. METHOD We have established an image-localized research biopsy study, that samples from both the invasive margin and tumor core. From this protocol, we currently have 202 samples from 58 patients with available bulk RNA-Seq, collected between Mayo Clinic and Barrow Neurological Institute. Using a single-cell reference dataset from our collaborators at Columbia University, we used CIBERSORTx, a deconvolution method, to predict relative abundances of 7 normal, 6 glioma, and 5 immune cell states for each sample. RESULTS We find that these cell state abundances connect to patient survival and show regional differences. For example, proneural glioma states were higher in invasive regions, whereas proliferative and mesenchymal states were higher in the tumor core. CONCLUSIONS Our analysis demonstrates a need to characterize the residual tissue following glioma resection to better understand the recurrent disease.

Abstract Anti‐glomerular basement membrane (anti‐GBM) disease (formerly known as Goodpasture's syndrome) is a rare autoinflammatory condition that affects the renal and/or pulmonary capillaries. The standard therapeutic regimen for anti‐GBM disease involves therapeutic plasma exchange (TPE), cyclophosphamide, and corticosteroids to rapidly remove and inhibit autoantibody production and reduce organ inflammation. Herein we report an 82‐year‐old female who developed anti‐GBM disease but expired despite therapy, secondary to multi‐organ failure in the setting of disseminated adenovirus disease. We discuss the utility and potential adverse effect of daily TPE for a protracted course (ie, 10‐14 days), the recommended TPE intensity in the 2023 American Society for Apheresis guidelines, updated from every‐other‐day TPE in the 2019 guidelines, despite no new data. We also highlight the potential for unusual infections to occur in these patients due to the profound immunosuppression, and discuss the importance of balancing immunosuppression to treat the disease with close surveillance of any potential opportunistic infections.

Abstract BACKGROUND Treatment of recurrent high-grade glioma remains a clinical challenge. There are very few agents active in this disease and short of enrollment in a clinical trial, the choice of therapy for a patient at the time of recurrence remains challenging. Several groups, including our own have developed ex vivo drug sensitivity assays to evaluate susceptibility of the tumor tissue to specific chemotherapeutics. To our knowledge, there is only one commercially available platform from the US based company Kiyatec. This tool, in addition to the molecular analysis of the tumor might provide another layer of confidence in choosing treatments for patients with recurrent high-grade gliomas. MATERIAL AND METHODS We present the data from our initial experience with the 3D PredictTM platform (Kiyatec, Greenville, SC, USA). We used the platform for 6 patients with recurrent high-grade gliomas undergoing tumor resection at the time of recurrence. We followed the company protocol for obtaining, preserving and shipping the tissue. RESULTS Out of the 6 specimens shipped for analysis, 4 assays were completed with full results available for analysis and clinical use. In two cases, the ex vivo tissue expansion was unsuccessful and drug testing was not completed. For the remaining 4 cases, spheroids created from the expansion of the harvested tissue were exposed to 12 drugs (temozolomide, lomustine, procarbazine, abemaciclib, carboplatin, dabrafenib, etoposide, everolimus, irinotecan, osimertinib, rucaparib and trametinib). We have observed different levels of sensitivity to several agents graded as: NO RESPONSE, MODERATE RESPONSE and RESPONSE. In 3 cases the results were used for clinical decision making and 2 patients were started on temozlomidede and carboplatin respectively and remain on treatment. In one case where sensitivity to etoposide was detected, we were not able to proceed with therapy due to insurance denial for the chosen drug. CONCLUSION In our experience, this platform is easy to use in a standard clinical setting, the success rate for creating viable spheroids for testing is high and the information derived from the drug sensitivity testing can be useful in clinical practice. Large, prospective clinical trial is need to validate this approach for routine clinical use.

AbstractBackgroundThe feasibility of oral dark contrast media is under exploration in abdominal computed tomography (CT) applications. One of the experimental contrast media in this class is dark borosilicate contrast media (DBCM), which has a CT attenuation lower than that of intra‐abdominal fat.PurposeTo evaluate the performances of DBCM using single‐ and multi‐energy CT imaging on a clinical photon‐counting‐detector CT (PCD‐CT).MethodsFive vials, three with iodinated contrast agent (5, 10, and 20 mg/mL; Omnipaque 350) and two with DBCM (6% and 12%; Nextrast, Inc.), and one solid‐water rod (neutral contrast agent) were inserted into two multi‐energy CT phantoms, and scanned on a clinical PCD‐CT system (NAEOTOM Alpha) at 90, 120, 140, Sn100, and Sn140 kV (Sn: tin filter) in multi‐energy mode. CARE keV IQ level was 180 (CTDIvol: 3.0 and 12.0 mGy for the small and large phantoms, respectively). Low‐energy threshold images were reconstructed with a quantitative kernel (Qr40, iterative reconstruction strength 2) and slice thickness/increment of 2.0/2.0 mm. Virtual monoenergetic images (VMIs) were reconstructed from 40 to 140 keV at 10 keV increments. On all images, average CT numbers for each vial/rod were measured using circular region‐of‐interests and averaged over eight slices. The contrast‐to‐noise ratio (CNR) of iodine (5 mg/mL) against DBCM was calculated and plotted against tube potential and VMI energy level, and compared to the CNR of iodine against water. Similar analyses were performed on iodine maps and VNC images derived from the multi‐energy scan at 120 kV.ResultsWith increasing kV or VMI keV, the negative HU of DBCM decreased only slightly, whereas the positive HU of iodine decreased across all contrast concentrations and phantom sizes. CT numbers for DBCM decreased from −178.5 ± 9.6 to −194.4 ± 6.3 HU (small phantom) and from −181.7 ± 15.7 to −192.1 ± 11.9 HU (large phantom) for DBCM‐12% from 90 to Sn140 kV; on VMIs, the CT numbers for DBCM decreased minimally from −147.1 ± 15.7 to −185.1 ± 9.2 HU (small phantom) and −158.8 ± 28.6 to −188.9 ± 14.7 HU (large phantom) from 40 to 70 keV, but remained stable from 80 to 140 keV. The highest iodine CNR against DBCM in low‐energy threshold images was seen at 90 or Sn140 kV for the small phantom, whereas all CNR values from low‐energy threshold images for the large phantom were comparable. The CNR values of iodine against DBCM computed on VMIs were highest at 40 or 70 keV depending on iodine and DBCM concentrations. The CNR values of iodine against DBCM were consistently higher than iodine to water (up to 460% higher dependent on energy level). Further, the CNR of iodine compared to DBCM is less affected by VMI energy level than the identical comparison between iodine and water: CNR values at 140 keV were reduced by 46.6% (small phantom) or 42.6% (large phantom) compared to 40 keV; CNR values for iodine compared to water were reduced by 86.3% and 83.8% for similar phantom sizes, respectively. Compared to 70 keV VMI, the iodine CNR against DBCM was 13%–79% lower on iodine maps and VNC.ConclusionsWhen evaluated at different tube potentials and VMI energy levels using a clinical PCD‐CT system, DBCM showed consistently higher CNR compared to iodine versus water (a neutral contrast).

Abstract This manuscript describes a novel approach for treating patients with long‐term sequelae from hemoglobin Evans (Hb Evans). After instituting conservative therapies for approximately 2 years, our patient's symptoms continually worsened. Therefore, we performed red blood cell exchange (RBCx) to reduce his Hb Evans percentage and his co‐existing elevation of methemoglobin. Our assumptions of clinical benefit were based on our collective experience performing RBCx for patients with sickle cell disease. After the first exchange, pre‐ and post‐laboratory results supported our approach and the patient experienced marked improvement in his clinical signs and symptoms. This report provides preliminary proof of principle for the use of RBCx to treat Hb Evans and other non‐Hb S hemoglobinopathies.

Background Brexucabtagene autoleucel (brexu-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved in the USA for adults with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) and in the European Union for patients ≥26 years with R/R B-ALL. After 2 years of follow-up in ZUMA-3, the overall complete remission (CR) rate (CR+CR with incomplete hematological recovery (CRi)) was 73%, and the median overall survival (OS) was 25.4 months in 78 Phase 1 and 2 patients with R/R B-ALL who received the pivotal dose of brexu-cel. Outcomes by prior therapies and subsequent allogeneic stem cell transplantation (alloSCT) are reported. Methods Eligible adults had R/R B-ALL and received one infusion of brexu-cel (1×10⁶ CAR T cells/kg) following conditioning chemotherapy. The primary endpoint was the CR/CRi rate per central review. Post hoc subgroup analyses were exploratory with descriptive statistics provided. Results Phase 1 and 2 patients (N=78) were included with median follow-up of 29.7 months (range, 20.7–58.3). High CR/CRi rates were observed across all prior therapy subgroups examined: 1 prior line of therapy (87%, n=15) and ≥2 prior lines (70%, n=63); prior blinatumomab (63%, n=38) and no prior blinatumomab (83%, n=40); prior inotuzumab (59%, n=17) and no prior inotuzumab (77%, n=61); and prior alloSCT (76%, n=29) and no prior alloSCT (71%, n=49). The frequency of Grade ≥3 cytokine release syndrome, neurological events, and treatment-related Grade 5 adverse events were largely similar among prior therapy subgroups. Median duration of remission (DOR) in responders with (n=14) and without (n=43) subsequent alloSCT was 44.2 (95% CI, 8.1 to not estimable (NE)) and 18.6 months (95% CI, 9.4 to NE); median OS was 47.0 months (95% CI, 10.2 to NE) and not reached (95% CI, 23.2 to NE), respectively. Median DOR and OS were not reached in responders without prior or subsequent alloSCT (n=22). Conclusions In ZUMA-3, adults with R/R B-ALL benefited from brexu-cel, regardless of prior therapies and subsequent alloSCT status, though survival appeared better in patients without certain prior therapies and in earlier lines of therapy. Additional studies are needed to determine the impact prior therapies and subsequent alloSCT have on outcomes of patients who receive brexu-cel.

Abstract Objective Adverse childhood experiences (ACEs) are reported in more than half of the women in the United States and have been shown to negatively impact the menopause experience. The objective of this study was to evaluate the association between ACEs and age at natural menopause. Methods This is a cross-sectional study conducted among participants of the Data Registry on the Experiences of Aging, Menopause, and Sexuality (DREAMS). The registry included women who were seen for consultations in the women's health clinic at Mayo Clinic, Rochester, between May 2015 and December 2016. Only postmenopausal women were included in this analysis. Childhood adversity was assessed with the validated ACE questionnaire. Age at natural menopause was self-reported. The association between ACEs and age at menopause was evaluated using a multivariable linear regression model adjusting for multiple confounders. Results A total of 350 women were evaluated. The mean age was 59.2 years, and a majority were White (92.9%), married/partnered (82%), and educated (91.2% with at least some college education). Women with a history of at least four ACEs were estimated to reach natural menopause 1.3 years sooner than women with no ACE in multivariable analysis, but the results were not statistically significant (95% confidence interval, −3.2 to 0.6; P = 0.18). Conclusions Although stressful life experiences such as ACEs may negatively influence health for midlife women, this study did not find an association with the age at natural menopause.

We introduce tumor connectomics, a novel MRI-based complex graph theory framework that describes the intricate network of relationships within the tumor and surrounding tissue, and combine this with multiparametric radiomics (mpRad) in a machine-learning approach to distinguish radiation necrosis (RN) from true progression (TP). Pathologically confirmed cases of RN vs. TP in brain metastases treated with SRS were included from a single institution. The region of interest was manually segmented as the single largest diameter of the T1 post-contrast (T1C) lesion plus the corresponding area of T2 FLAIR hyperintensity. There were 40 mpRad features and 6 connectomics features extracted, as well as 5 clinical and treatment factors. We developed an Integrated Radiomics Informatics System (IRIS) based on an Isomap support vector machine (IsoSVM) model to distinguish TP from RN using leave-one-out cross-validation. Class imbalance was resolved with differential misclassification weighting during model training using the IRIS. In total, 135 lesions in 110 patients were analyzed, including 43 cases (31.9%) of pathologically proven RN and 92 cases (68.1%) of TP. The top-performing connectomics features were three centrality measures of degree, betweenness, and eigenvector centralities. Combining these with the 10 top-performing mpRad features, an optimized IsoSVM model was able to produce a sensitivity of 0.87, specificity of 0.84, AUC-ROC of 0.89 (95% CI: 0.82–0.94), and AUC-PR of 0.94 (95% CI: 0.87–0.97).