Citations

Abstract Background and Aims Accurate differentiation of cardiac amyloidosis (CA) from phenotypic mimics remains challenging using current clinical and echocardiographic techniques. The accuracy of a novel artificial intelligence (AI) screening algorithm for echocardiography-based CA detection was assessed. Methods Utilizing a multisite, multiethnic dataset (n = 2612, 52% CA), a convolutional neural network was trained to differentiate CA from phenotypic controls using transthoracic apical four-chamber video clips. External validation was conducted globally across 18 sites including 597 CA cases and 2122 controls. Classification accuracy was assessed on the entire external validation dataset, and subgroup analyses were performed both on technetium pyrophosphate scintigraphy referrals, and individuals matched for age, sex, and wall thickness. Model accuracy was also compared with the transthyretin CA score and the increased wall thickness score within a subset of older heart failure with preserved ejection fraction patients with increased wall thickness. Results Cardiac amyloidosis patients and controls displayed similar age, sex, race, and comorbidities. After the removal of uncertain AI predictions (13%), model discrimination and classification were excellent for the entire external validation dataset [area under the receiver operating characteristic curve (AUROC) 0.93, sensitivity 85%, specificity 93%], irrespective of CA subtype (sensitivity: light-chain = 84%, wild-type transthyretin = 85%, and hereditary transthyretin = 86%). Performance was maintained in subgroup analysis in patients clinically referred for technetium pyrophosphate scintigraphy imaging (AUROC 0.86, sensitivity 77%, specificity 86%) and matched patients (AUROC 0.92, sensitivity 84%, specificity 91%). The AI model (AUROC 0.93) also outperformed transthyretin CA score (AUROC 0.73) and increased wall thickness (AUROC 0.80) scores. Conclusions This AI screening model—using only an apical four-chamber view—effectively differentiated CA from other causes of increased left ventricular wall thickness.

PURPOSE Many trials ask patients to complete patient-reported outcome measures (PROMs) via the web, excluding patients unable to use/access the Internet. The PRO-TECT trial (AFT-39, ClinicalTrials.gov identifier: NCT03249090 ) also offered a telephone interface option (interactive voice response [IVR]). We compared patients choosing IVR versus web on alert rates to nurses and clinical outcomes to determine if a telephone option can close disparities in symptom management. METHODS PRO-TECT randomized 26 community oncology practices to the PROM intervention arm where concerning symptoms generated automated alerts to nurses. IVR and web patients were compared for social determinants of health (SDOH) using analysis of variance and chi-square tests. After accounting for clustering and confounders, we used generalized estimating equations to compare alert rates, mixed models for quality of life (QOL) at 3 months, and Cox regression for emergency visits and survival at 12 months. RESULTS Among 593 patients, 215 (36%) chose IVR and 378 (64%) chose web. IVR patients were older (65.2 v 60.8 years) and were more often rural residents (32% v 23%), Black (27% v 11%), and with less education (54% v 27% ≤high school; all P < .01). Patients choosing IVR had more surveys with concerning symptoms (49% v 37%) and nurses felt clinical attention was warranted more often (4.8 surveys v 3.4 surveys; all P < .001) but ultimately experienced similar benefits as web in QOL, emergency visits, and survival. CONCLUSION One third of community patients choose a telephone option over the web for reporting PROMs during cancer care. These patients are disproportionately from SDOH backgrounds at risk of poor clinical outcomes and have higher symptom management needs but ultimately experience similar clinical benefits as patients choosing the web. PROM programs should offer web alternatives to close disparities in symptom management.

Abstract This study aimed to investigate the association between objective and subjective olfactory assessments in patients with recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection undergoing endoscopic endonasal skull base surgery (EESBS). Retrospective cohort study. Academic medical center. Adult patients with and without recent SARS-CoV-2 infection who underwent EESBS for sellar and parasellar lesion resection between 2020 and 2024 at the Mayo Clinic in Florida, Jacksonville, FL. Pre- and postoperative self-reported olfactory dysfunction and University of Pennsylvania Smell Identification Test (UPSIT) scores were collected. Patients with recent SARS-CoV-2 infection had a similar rate of discrepant preoperative objective olfactory assessments (38.2%, 26/68) compared with SARS-CoV-2-negative patients (39.9%, 127/318). SARS-CoV-2-positive patients were twice as likely to report postoperative subjective olfactory dysfunction (46.2%, 12/26) compared with SARS-CoV-2-negative patients (18.1%, 23/127, p = 0.002). There was no statistically significant difference in the mean preoperative (p = 0.162) or postoperative (p = 0.724) UPSIT scores between both groups. Patients with recent SARS-CoV-2 infection and discrepant preoperative objective olfactory assessments were twice as likely to self-report olfactory dysfunction following EESBS compared with SARS-CoV-2-negative controls. This increase in self-reported olfactory dysfunction was not accompanied by changes in objective psychophysical testing. These findings suggest that SARS-CoV-2 infection may impact subjective olfactory recovery following EESBS.

ABSTRACT Pneumonia may be caused by a diverse group of microorganisms; however, a microbiologic diagnosis is not universally made. Molecular tests such as the BIOFIRE FILMARRAY Pneumonia Panel (BF-PP) offer the possibility of rapid identification of potential pneumonia pathogens. This retrospective analysis was conducted as a sub-study of a recently published randomized controlled trial. Specimens from patients with suspected pneumonia were tested by the BF-PP, with results compared to cultures. The overall BF-PP positivity rate was 44.8% (252/563), and was higher [64.6% (164/254)] in specimens from patients ultimately diagnosed with pneumonia. Discrepancies between the BF-PP and cultures were most common for Streptococcus pneumoniae , Haemophilus influenzae , Moraxella catarrhalis, and Streptococcus agalactiae . Positive percent agreement (PPA) and negative percent agreement (NPA) between the BF-PP and culture were 91.4% (CI 86.3%–94.9%) and 83.6% (CI 79.5%–87.2%), respectively. For most bacteria, a correlation between high genomic abundance (genomic copies/mL) reported from the BF-PP and culture growth abundance was found. In specimens from patients ultimately diagnosed with pneumonia, clinical consistency—assessed based on whether BF-PP results aligned with associated culture results—was 79.9% and was highest for bronchoalveolar lavage fluid specimens. The BF-PP has reliable analytical performance and offers the potential advantage over conventional cultures of providing higher detection rates and more rapid results. Interestingly, despite the use of this advanced molecular diagnostic tool, one-third of pneumonia cases remained without a microbiologic etiology. IMPORTANCE This study evaluates the BIOFIRE FILMARRAY Pneumonia Panel by comparing its performance to conventional cultures in a real-world patient population (including patients ultimately diagnosed as not having pneumonia) using different types of specimens. Findings show a higher detection rate of microorganisms with the panel compared to cultures, suggesting that this test could aid in tailoring treatments for pneumonia. However, challenges remain and require further study, including distinguishing true pathogens from colonizing microorganisms and determinig why one-third of patients diagnosed with pneumonia still lacked a microbiologic etiology.

BACKGROUND Treatment of tubo-ovarian high-grade serous carcinoma (HGSC) includes cytoreductive surgery, platinum-based chemotherapy, and often poly(ADP-ribose) polymerase (PARP) inhibitors. While homologous recombination (HR) deficiency is a well-established predictor of therapy sensitivity, over 50% of HR-proficient HGSCs also exhibit sensitivity. Currently, there are no biomarkers to identify which HR-proficient HGSCs will be sensitive to standard-of-care therapy. Replication stress may serve as a key determinant of response. METHODS We evaluated phospho–RPA2-T21 (p-RPA2) foci via immunofluorescence as a biomarker of replication stress in formalin-fixed, paraffin-embedded HGSC samples collected at diagnosis from patients treated with platinum chemotherapy (discovery cohort, n = 31; validation cohort, n = 244) or PARP inhibitors ( n = 63). Recurrent HGSCs ( n = 38) were also analyzed. p-RPA2 score was calculated using automated imaging analysis. RESULTS Samples were defined as p-RPA2-high if more than 16% of cells had ≥2 p-RPA2 foci on automated analysis. In the discovery cohort, HR-proficient, p-RPA2-high HGSCs demonstrated significantly higher rates of a chemotherapy response score of 3 to platinum chemotherapy than HR-proficient, p-RPA2-low HGSCs. In the validation cohort, patients with HR-proficient, p-RPA2-high HGSCs had significantly longer survival after platinum treatment than those with HR-proficient, p-RPA2-low HGSCs. Additionally, the p-RPA2 assay effectively predicted survival outcomes in patients treated with PARP inhibitors and in recurrent HGSC samples. CONCLUSION Our study underscores the importance of considering replication stress markers, such as p-RPA2, alongside HR status in therapeutic planning. This approach has the potential to increase the number of patients receiving effective therapy while reducing unnecessary toxicity. FUNDING The Reproductive Scientist Development Program, GOG Foundation, Pilot Translational and Clinical Studies function of the Washington University Institute of Clinical and Translational Sciences, the Foundation for Barnes-Jewish Hospital, Washington University School of Medicine Dean’s Scholar Program, The Cancer Biology Pathway Training Grant (5T32CA113275-17), The Lucy, Anarcha, and Betsey (L.A.B.) Award from the Department of Obstetrics and Gynecology at Washington University School of Medicine, and Veterans Affairs Office of Research and Development (I01BX006020).

ABSTRACTA core tenant of the Geriatric Emergency care Applied Research Network 2.0—Advancing Dementia Care (GEAR 2.0‐ADC) is the inclusion of community members during all stages of clinical research. As such, we deliberately integrated and supported patient and public involvement in the evaluation and selection of GEAR 2.0‐ADC Pilot Research Grants by developing and adapting traditional grant application review structures, with input from community members, to create the GEAR 2.0‐ADC Community Review Committee approach. Community members, including persons living with dementia, effectively participated in all three rounds of research grant application review and selection, complementing the traditional scientific review process. The structure and flexibility of the GEAR 2.0‐ADC Community Review Committee approach serve as a model for patient and public grant application review involvement with strong potential for applications across grant reviews in other medical specialties.