Promoting Collaborative Scholarship During the COVID-19 Pandemic Through an Innovative COVID-19 Data Explorer and Repository at Yale School of Medicine: Development and Usability Study.

BACKGROUND: The COVID-19 pandemic sparked a surge of research publications spanning epidemiology, basic science, and clinical science. Thanks to the digital revolution, large data sets are now accessible, which also enables real-time epidemic tracking. However, despite this, academic faculty and their trainees have been struggling to access comprehensive clinical data. To tackle this issue, we have devised a clinical data repository that streamlines research processes and promotes interdisciplinary collaboration. OBJECTIVE: This study aimed to present an easily accessible up-to-date database that promotes access to local COVID-19 clinical data, thereby increasing efficiency, streamlining, and democratizing the research enterprise. By providing a robust database, a broad range of researchers (faculty and trainees) and clinicians from different areas of medicine are encouraged to explore and collaborate on novel clinically relevant research questions. METHODS: A research platform, called the Yale Department of Medicine COVID-19 Explorer and Repository (DOM-CovX), was constructed to house cleaned, highly granular, deidentified, and continually updated data from over 18,000 patients hospitalized with COVID-19 from January 2020 to January 2023, across the Yale New Haven Health System. Data across several key domains were extracted including demographics, past medical history, laboratory values during hospitalization, vital signs, medications, imaging, procedures, and outcomes. Given the time-varying nature of several data domains, summary statistics were constructed to limit the computational size of the database and provide a reasonable data file that the broader research community could use for basic statistical analyses. The initiative also included a front-end user interface, the DOM-CovX Explorer, for simple data visualization of aggregate data. The detailed clinical data sets were made available for researchers after a review board process. RESULTS: As of January 2023, the DOM-CovX Explorer has received 38 requests from different groups of scientists at Yale and the repository has expanded research capability to a diverse group of stakeholders including clinical and research-based faculty and trainees within 15 different surgical and nonsurgical specialties. A dedicated DOM-CovX team guides access and use of the database, which has enhanced interdepartmental collaborations, resulting in the publication of 16 peer-reviewed papers, 2 projects available in preprint servers, and 8 presentations in scientific conferences. Currently, the DOM-CovX Explorer continues to expand and improve its interface. The repository includes up to 3997 variables across 7 different clinical domains, with continued growth in response to researchers' requests and data availability. CONCLUSIONS: The DOM-CovX Data Explorer and Repository is a user-friendly tool for analyzing data and accessing a consistently updated, standardized, and large-scale database. Its innovative approach fosters collaboration, diversity of scholarly pursuits, and expands medical education. In addition, it can be applied to other diseases beyond COVID-19.

Utility of 64Cu-Sarcophagine-Bombesin PET/CT in Men with Biochemically Recurrent Prostate Cancer and Negative or Equivocal Findings on 68Ga-PSMA-11 PET/CT.

Despite a high detection rate of 68Ga-prostate-specific membrane antigen (PSMA) PET/CT in biochemical recurrence (BCR) of prostate cancer, a significant proportion of men have negative 68Ga-PSMA-11 PET/CT results. Gastrin-releasing peptide receptor, targeted by the copper-chelated bombesin analog 64Cu-sarcophagine-bombesin (SAR-BBN) PET/CT, is also overexpressed in prostate cancer. In this prospective imaging study, we investigate the detection rate of 64Cu-SAR-BBN PET/CT in patients with BCR and negative or equivocal 68Ga-PSMA-11 PET/CT results. Methods: Men with confirmed adenocarcinoma of the prostate, prior definitive therapy, and BCR (defined as a prostate-specific antigen [PSA] level > 0.2 ng/mL) with negative or equivocal 68Ga-PSMA-11 PET/CT results within 3 mo were eligible for enrollment. 64Cu-SAR-BBN PET/CT scans were acquired at 1 and 3 h after administration of 200 MBq of 64Cu-SAR-BBN, with further delayed imaging undertaken optionally at 24 h. PSA (ng/mL) was determined at baseline. All PET (PSMA and bombesin) scans were assessed visually. Images were read with masking of the clinical results by 2 experienced nuclear medicine specialists, with a third reader in cases of discordance. Accuracy was defined using a standard of truth that included biopsy confirmation, confirmatory imaging, or response to targeted treatment. Results: Twenty-five patients were enrolled. Prior definitive therapy was radical prostatectomy (n = 24, 96%) or radiotherapy (n = 1, 4%). The median time since definitive therapy was 7 y (interquartile range [IQR], 4-11 y), and the Gleason score was 7 or less (n = 15, 60%), 8 (n = 3, 12%), or 9 (n = 7, 28%). The median PSA was 0.69 ng/mL (IQR, 0.28-2.45 ng/mL). Baseline PSMA PET scans were negative in 19 patients (76%) and equivocal in 6 (24%). 64Cu-SAR-BBN PET-avid disease was identified in 44% (11/25): 12% (3/25) with local recurrence, 20% (5/25) with pelvic node metastases, and 12% (3/25) with distant metastases. The κ-score between readers was 0.49 (95% CI, 0.16-0.82). Patients were followed up for a median of 10 mo (IQR, 9-12 mo). Bombesin PET/CT results were true-positive in 5 of 25 patients (20%), false-positive in 2 of 25 (8%), false-negative in 7 of 25 (28%), and unverified in 11 of 25 (44%). Conclusion: 64Cu-SAR-BBN PET/CT demonstrated sites of disease recurrence in 44% of BCR cases with negative or equivocal 68Ga-PSMA-11 PET/CT results. Further evaluation to confirm diagnostic benefit is warranted.

Fitz-Hugh-Curtis syndrome with disseminated intra-abdominal gonorrhoea.

Neisseria gonorrhoea continues to be implicated in a large proportion of sexually transmitted infections worldwide. Prompt recognition of infection is required to prevent further complications which include pelvic inflammatory disease and less commonly, perihepatitis which is known eponymously as Fitz-Hugh-Curtis syndrome. Third generation cephalosporins such as ceftriaxone remain effective in the treatment of gonococcal infection, however failure in initiation of appropriate antibiotic therapy in a timely manner can result in further disseminated disease. We describe an atypical case of Fitz-Hugh-Curtis syndrome presenting with multiple intra-abdominal gonococcal collections. Our case highlights the importance of a detailed sexual history in the evaluation of acute abdominal pain in at-risk patient demographics.

Single-Shot 3D Reconstruction via Nonlinear Fringe Transformation: Supervised and Unsupervised Learning Approaches.

The field of computer vision has been focusing on achieving accurate three-dimensional (3D) object representations from a single two-dimensional (2D) image through deep artificial neural networks. Recent advancements in 3D shape reconstruction techniques that combine structured light and deep learning show promise in acquiring high-quality geometric information about object surfaces. This paper introduces a new single-shot 3D shape reconstruction method that uses a nonlinear fringe transformation approach through both supervised and unsupervised learning networks. In this method, a deep learning network learns to convert a grayscale fringe input into multiple phase-shifted fringe outputs with different frequencies, which act as an intermediate result for the subsequent 3D reconstruction process using the structured-light fringe projection profilometry technique. Experiments have been conducted to validate the practicality and robustness of the proposed technique. The experimental results demonstrate that the unsupervised learning approach using a deep convolutional generative adversarial network (DCGAN) is superior to the supervised learning approach using UNet in image-to-image generation. The proposed technique's ability to accurately reconstruct 3D shapes of objects using only a single fringe image opens up vast opportunities for its application across diverse real-world scenarios.

Worsening of anemia increases the risks of complications and prolonged length of stay following revision total shoulder arthroplasty.

Background: There are no studies currently in the literature that assesses complications following revision total shoulder arthroplasty (TSA) in patients with varying severity of anemia. The purpose of this study was to determine the impact of preoperative anemia severity on postoperative complications following revision TSA. Methods: Patients undergoing revision TSA from 2013 to 2019 were queried in a national database. Based on previous studies' definitions of anemia, three subgroups were stratified: patients without anemia (hematocrit >36% for women, hematocrit >39% for men), patients with mild anemia (hematocrit 33% to 36% for women, hematocrit 33% to 39% for men) and patients with moderate to severe anemia (hematocrit <33% for both women and men). In this analysis, patient demographics, comorbidities, and postoperative complications were compared between the three groups. Results: Of 1559 total patients undergoing revision TSA, 1178 patients (75.6%) did not have anemia, 255 (16.3%) had mild anemia, and 126 (8.1%) had moderate/severe anemia. Following adjustment on multivariate analysis, patients with mild anemia were more likely to have postoperative transfusion and extended length of stay compared to non-anemic patients. Patients with moderate/severe anemia were at increased risk of postoperative transfusion, sepsis, extended length of stay, and reoperation compared to non-anemic patients. Discussion: From mild anemia to moderate/severe anemia, there was a stepwise increase in the risk of postoperative complications. Our study showed that there is clinical value in the preoperative correction of anemia for these patients as it relates to complications and hospital stay. Level of Evidence: III.

Decreased CREB phosphorylation impairs embryonic retinal neurogenesis in the Oa1-/- mouse model of Ocular albinism.

Mutations in the human Ocular albinism type-1 gene OA1 are associated with abnormal retinal pigment epithelium (RPE) melanogenesis and poor binocular vision resulting from misrouting of ipsilateral retinal ganglion cell (iRGC) axons to the brain. We studied the latter using wild-type (WT) and Oa1-/- mouse eyes. At embryonic stages, the WT RPE-specific Oa1 protein signals through cAMP/Epac1-Erk2-CREB. Following CREB phosphorylation, a pCREB gradient extends from the RPE to the differentiating retinal amacrine and RGCs. In contrast to WT, the Oa1-/- RPE and ventral ciliary-margin-zone, a niche for iRGCs, express less pCREB while their retinas have a disrupted pCREB gradient, indicating Oa1's involvement in pCREB maintenance. Oa1-/- retinas also show hyperproliferation, enlarged nuclei, reduced differentiation, and fewer newborn amacrine and RGCs than WT retinas. Our results demonstrate that Oa1's absence leads to reduced binocular vision through a hyperproliferation-associated block in differentiation that impairs neurogenesis. This may affect iRGC axon's routing to the brain.

Prevalence of Mild Cognitive Impairment and Alzheimer's Disease Identified in Veterans in the United States.

Background: Diagnostic codes can be instrumental for case identification in Alzheimer's disease (AD) research; however, this method has known limitations and cannot distinguish between disease stages. Clinical notes may offer more detailed information including AD severity and can complement diagnostic codes for case identification. Objective: To estimate prevalence of mild cognitive impairment (MCI) and AD using diagnostics codes and clinical notes available in the electronic healthcare record (EHR). Methods: This was a retrospective study in the Veterans Affairs Healthcare System (VAHS). Health records from Veterans aged 65 years or older were reviewed during Fiscal Years (FY) 2010-2019. Overall, 274,736 and 469,569 Veterans were identified based on a rule-based algorithm as having at least one clinical note for MCI and AD, respectively; 201,211 and 149,779 Veterans had a diagnostic code for MCI and AD, respectively. During FY 2011-2018, likely MCI or AD diagnosis was defined by≥2 qualifiers (i.e., notes and/or codes)≥30 days apart. Veterans with only 1 qualifier were considered as suspected MCI/AD. Results: Over the 8-year study, 147,106 and 207,225 Veterans had likely MCI and AD, respectively. From 2011 to 2018, yearly MCI prevalence increased from 0.9% to 2.2%; yearly AD prevalence slightly decreased from 2.4% to 2.1%; mild AD changed from 22.9% to 26.8%, moderate AD changed from 26.5% to 29.1%, and severe AD changed from 24.6% to 30.7. Conclusions: The relative distribution of AD severities was stable over time. Accurate prevalence estimation is critical for healthcare resource allocation and facilitating patients receiving innovative medicines.

An Evaluation of Risk Factors for Intracranial Metastases of Sarcomas: A Systematic Review and Meta-Analysis.

INTRODUCTION: Sarcomas, a group of neoplasms comprising both tissue and bone soft tissue tumors, has an increasing prevalence in recent years. Prognosis significantly hinges on early detection, and if not detected early, may consequently metastasize. This review will be the first systematic review and meta-analysis characterizing the presentation and progression of brain metastases from bone and soft tissue cancers. METHODS: The PubMed, Scopus, and Web of Science databases were queried to identify studies reporting the incidence of intracranial brain metastases from primary sarcoma to the present. Abstract and full-text screening of 1822 initial articles returned by preliminary search yielded 28 studies for inclusion and data extraction. Qualitative assessment of the studies was conducted in accordance with the Newcastle-Ottawa Scale criteria. Meta-analyses were applied to assess risk factors on outcomes. RESULTS: The average age within the cohort was 27.9 years with a male and female prevalence of 59.1% and 40.9%, respectively. The odds ratio for living status (dead/alive) was calculated for several risk factors - male/female [OR 1.14, 95% CI 0.62, 2.07], single/multiple metastases [OR 0.67, 95% CI 0.35, 1.28], lung metastases/not [OR 1.63, 95% CI 0.85, 3.13], surgery/no surgery [OR 0.49, 95% CI 0.20, 1.21]. The standardized mean differences for duration from diagnoses to metastases were likewise analyzed - male/female [SMD 0.13, 95% CI -0.15, 0.42], single/multiple metastases [SMD 0.11, 95% CI -0.20, 0.42], lung metastases/not [SMD -0.03, 95% CI -0.38, 0.32], surgery/no surgery [SMD 0.45, 95% CI -0.18, 1.09]. The standardized mean differences for duration from metastases to death were analyzed - lung metastases/not [SMD 0.43, 95% CI -0.08, 0.95]. CONCLUSIONS: Our study observed no statistically significant differences in mortality rate among several patient risk factors. Consequentially, there lacks a clear answer as to whether or not an association between mortality rates exists with these patient factors. As such, it is important to continue research in brain-metastasizing sarcomas despite their relative rarity.

Biochemical, Biomarker, and Behavioral Characterization of the GrnR493X Mouse Model of Frontotemporal Dementia.

Heterozygous loss-of-function mutations in the progranulin gene (GRN) are a major cause of frontotemporal dementia due to progranulin haploinsufficiency; complete deficiency of progranulin causes neuronal ceroid lipofuscinosis. Several progranulin-deficient mouse models have been generated, including both knockout mice and knockin mice harboring a common patient mutation (R493X). However, the GrnR493X mouse model has not been characterized completely. Additionally, while homozygous GrnR493X and Grn knockout mice have been extensively studied, data from heterozygous mice is still limited. Here, we performed more in-depth characterization of heterozygous and homozygous GrnR493X knockin mice, which includes biochemical assessments, behavioral studies, and analysis of fluid biomarkers. In the brains of homozygous GrnR493X mice, we found increased phosphorylated TDP-43 along with increased expression of lysosomal genes, markers of microgliosis and astrogliosis, pro-inflammatory cytokines, and complement factors. Heterozygous GrnR493X mice did not have increased TDP-43 phosphorylation but did exhibit limited increases in lysosomal and inflammatory gene expression. Behavioral studies found social and emotional deficits in GrnR493X mice that mirror those observed in Grn knockout mouse models, as well as impairment in memory and executive function. Overall, the GrnR493X knockin mouse model closely phenocopies Grn knockout models. Lastly, in contrast to homozygous knockin mice, heterozygous GrnR493X mice do not have elevated levels of fluid biomarkers previously identified in humans, including neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in both plasma and CSF. These results may help to inform pre-clinical studies that use this Grn knockin mouse model and other Grn knockout models.

Beyond Prostate Imaging Reporting and Data System: Combining Magnetic Resonance Imaging Prostate Imaging Reporting and Data System and Prostate-Specific Membrane Antigen-Positron Emission Tomography/Computed Tomography PRIMARY Score in a Composite (P) Score for More Accurate Diagnosis of Clinically Significant Prostate Cancer.

PURPOSE: The Prostate Imaging Reporting and Data System (PI-RADS) score is standard of care for clinically significant prostate cancer (csPCa) diagnosis. The PRIMARY score (prostate-specific membrane antigen [PSMA]-positron emission tomography [PET]/CT) also has high diagnostic accuracy for csPCa. This study aimed to develop an easily calculated combined (P) score for csPCa detection (International Society of Urological Pathology [ISUP] ≥2) incorporating separately read PI-RADS and PRIMARY scores, with external validation. MATERIALS AND METHODS: Two datasets of men with suspected PCa, no prior biopsy, recent MRI and 68Ga-PSMA-11-PET/CT, and subsequent transperineal biopsy were evaluated. These included the development sample (n = 291, 56% csPCa) a prospective trial and the validation sample (n = 227, 67% csPCa) a multicenter retrospective database. Primary outcome was detection of csPCa (ISUP ≥2), with ISUP ≥ 3 cancer detection a secondary outcome. Score performance was evaluated by area under the curve, sensitivity, specificity, and decision curve analysis. RESULTS: The 5-point combined (P) score was developed in a prospective dataset. In the validation dataset, csPCa was identified in 0%, 20%, 52%, 96%, and 100% for P score 1 to 5. The area under the curve was 0.93 (95% CI: 0.90-0.96), higher than PI-RADS 0.89 (95% CI: 0.85-0.93, P = .039) and PRIMARY score alone 0.84 (95% CI: 0.79-0.89, P < .001). Splitting scores at 1/2 (negative) vs 3/4/5 (positive), P score sensitivity was 94% (95% CI: 89-97) compared to PI-RADS 89% (95% CI: 83-93) and PRIMARY score 86% (95% CI: 79-91). For ISUP ≥ 3, P score sensitivity was 99% (95% CI: 95-100) vs 94% (95% CI: 88-98) and 92% (95% CI: 85-97) for PI-RADS and PRIMARY scores respectively. A maximum standardized uptake value > 12 (P score 5) was ISUP ≥ 2 in all cases with 93% ISUP ≥ 3. CONCLUSIONS: The P score is easily calculated and improves accuracy for csPCa over both PI-RADS and PRIMARY scores. It should be considered when PSMA-PET is undertaken for diagnosis.

Development of a Visually Calculated SUVmean (HIT Score) on Screening PSMA PET/CT to Predict Treatment Response to 177Lu-PSMA Therapy: Comparison with Quantitative SUVmean and Patient Outcomes.

177Lu-PSMA therapy is an effective treatment in patients with metastatic castration-resistant prostate cancer. SUVmean is a valuable screening biomarker to assess the suitability for 177Lu-PSMA therapy but requires quantitative software. This study aims to develop a simple, clinically applicable prostate-specific membrane antigen PET/CT score that encompasses the elements of SUVmean without requiring additional quantification. Methods: Datasets from ethics-approved trials of patients with metastatic castration-resistant prostate cancer after androgen receptor signaling inhibition and taxane chemotherapy (or unfit for taxane), who were treated with 177Lu-PSMA-617 and 177Lu-PSMA I&T with a pretreatment screening with 68Ga-PSMA-11 PET/CT, and clinical outcome data, including a prostate-specific antigen (PSA) 50% response rate (PSA50), PSA progression-free survival (PSA-PFS), and overall survival (OS), were included. The screening 68Ga-PSMA-11 PET/CT of all participants was analyzed both semiquantitatively and visually. Semiquantitative analysis was used to derive the SUVmean Visual analysis of the 68Ga-PSMA-11 PET/CT images involved a binary visual heterogeneity assessment (homogeneous or heterogeneous), allocating a tumor SUVmax range (<15, 15-29, 30-49, 50-79, or ≥80). A 4-category score incorporating both heterogeneity and intensity of tumors (HIT) was then developed as a combination of heterogeneity and intensity (SUVmax range). The SUVmax was less than 15 for score 1, 15-79 with heterogeneous intensity for score 2, 15-79 with homogeneous intensity for score 3, and 80 or greater for score 4. This score was evaluated according to clinical outcomes (PSA50, PSA-PFS, and OS) and compared with SUVmean Results: Data from 139 participants were analyzed. In total, 75 (54%) patients achieved a PSA50 with a median PSA-PFS of 5.5 mo (95% CI, 4.1-6.0 mo) and an OS of 13.5 mo (95% CI, 11.1-17.9 mo). SUVmean was associated with PSA50 and survival outcomes when analyzed as a continuous variable or as quartiles. The PSA50 for HIT scores 1-4 was 0%, 39%, 65%, and 76%, respectively. The HIT score was strongly related to PSA-PFS and OS (log-rank test, P < 0.001 and P = 0.002). The median PSA-PFS for HIT scores 1-4 was 1.0, 4.1, 6.0, and 8.5, respectively, and the median OS was 7.6, 12.0, 18.5, and 16.9 mo, respectively. Cohen κ between readers for the HIT score was 0.71. Conclusion: A prostate-specific membrane antigen PET/CT score incorporating HIT derived from tools on a standard PET workstation is comparable with quantitative SUVmean as a prognostic tool following 177Lu-PSMA therapy.

[177Lu]Lu-PSMA-617 plus enzalutamide in patients with metastatic castration-resistant prostate cancer (ENZA-p): an open-label, multicentre, randomised, phase 2 trial.

BACKGROUND: Enzalutamide and lutetium-177 [177Lu]Lu-prostate-specific membrane antigen (PSMA)-617 both improve overall survival in patients with metastatic castration-resistant prostate cancer. Androgen and PSMA receptors have a close intracellular relationship, with data suggesting complementary benefit if targeted concurrently. In this study, we assessed the activity and safety of enzalutamide plus adaptive-dosed [177Lu]Lu-PSMA-617 versus enzalutamide alone as first-line treatment for metastatic castration-resistant prostate cancer. METHODS: ENZA-p was an open-label, randomised, controlled phase 2 trial done at 15 hospitals in Australia. Participants were men aged 18 years or older with metastatic castration-resistant prostate cancer not previously treated with docetaxel or androgen receptor pathway inhibitors for metastatic castration-resistant prostate cancer, gallium-68 [68Ga]Ga-PSMA-PET-CT (PSMA-PET-CT) positive disease, Eastern Cooperative Oncology Group performance status of 0-2, and at least two risk factors for early progression on enzalutamide. Participants were randomly assigned (1:1) by a centralised, web-based system using minimisation with a random component to stratify for study site, disease burden, use of early docetaxel, and previous treatment with abiraterone acetate. Patients were either given oral enzalutamide 160 mg daily alone or with adaptive-dosed (two or four doses) intravenous 7·5 GBq [177Lu]Lu-PSMA-617 every 6-8 weeks dependent on an interim PSMA-PET-CT (week 12). The primary endpoint was prostate-specific antigen (PSA) progression-free survival, defined as the interval from the date of randomisation to the date of first evidence of PSA progression, commencement of non-protocol anticancer therapy, or death. The analysis was done in the intention-to-treat population, using stratified Cox proportional hazards regression. This trial is registered with ClinicalTrials.gov, NCT04419402, and participant follow-up is ongoing. FINDINGS: 162 participants were randomly assigned between Aug 17, 2020, and July 26, 2022. 83 men were assigned to the enzalutamide plus [177Lu]Lu-PSMA-617 group, and 79 were assigned to the enzalutamide group. Median follow-up in this interim analysis was 20 months (IQR 18-21), with 32 (39%) of 83 patients in the enzalutamide plus [177Lu]Lu-PSMA-617 group and 16 (20%) of 79 patients in the enzalutamide group remaining on treatment at the data cutoff date. Median age was 71 years (IQR 64-76). Median PSA progression-free survival was 13·0 months (95% CI 11·0-17·0) in the enzalutamide plus [177Lu]Lu-PSMA-617 group and 7·8 months (95% CI 4·3-11·0) in the enzalutamide group (hazard ratio 0·43, 95% CI 0·29-0·63, p<0·0001). The most common adverse events (all grades) were fatigue (61 [75%] of 81 patients), nausea (38 [47%]), and dry mouth (32 [40%]) in the enzalutamide plus [177Lu]Lu-PSMA-617 group and fatigue (55 [70%] of 79), nausea (21 [27%]), and constipation (18 [23%]) in the enzalutamide group. Grade 3-5 adverse events occurred in 32 (40%) of 81 patients in the enzalutamide plus [177Lu]Lu-PSMA-617 group and 32 (41%) of 79 patients in the enzalutamide group. Grade 3 events that occurred only in the enzalutamide plus [177Lu]Lu-PSMA-617 group included anaemia (three [4%] of 81 participants) and decreased platelet count (one [1%] participant). No grade 4 or 5 events were attributed to treatment on central review in either group. INTERPRETATION: The addition of [177Lu]Lu-PSMA-617 to enzalutamide improved PSA progression-free survival providing evidence of enhanced anticancer activity in patients with metastatic castration-resistant prostate cancer with risk factors for early progression on enzalutamide and warrants further evaluation of the combination more broadly in metastatic prostate cancer. FUNDING: Prostate Cancer Research Alliance (Movember and Australian Federal Government), St Vincent's Clinic Foundation, GenesisCare, Roy Morgan Research, and Endocyte (a Novartis company).

The Role of Mental Health Conditions in Early Detection and Treatment of Veterans With Alzheimer's Dementia.

INTRODUCTION: The benefits of early detection of Alzheimer's disease (AD) have become increasingly recognized. Veterans with mental health conditions (MHCs) may be less likely to receive a specific AD diagnosis compared to veterans without MHCs. We investigated whether rates of MHCs differed between veterans diagnosed with unspecified dementia (UD) vs. AD to better understand the role MHCs might play in establishing a diagnosis of AD. MATERIALS AND METHODS: This retrospective analysis (2015-2022) identified UD and AD with diagnostic code-based criteria. We determined the proportion of veterans with MHCs in UD vs. AD cohorts. Secondarily, we assessed the distribution of UD/AD diagnoses in veterans with and without MHCs. RESULTS: We identified 145,309 veterans with UD and 33,996 with AD. The proportion of each MHC was consistently higher in UD vs. AD cohorts: 41.4% vs. 33.2% (depression), 26.9% vs. 20.3% (post-traumatic stress disorder), 23.4% vs. 18.2% (anxiety), 4.3% vs. 2.1% (bipolar disorder), and 3.9% vs. 1.5% (schizophrenia). The UD diagnostic code was used in 84% of veterans with MHCs vs. 78% without MHCs (P < .001). CONCLUSIONS: Mental health conditions were more likely in veterans with UD vs. AD diagnoses; comorbid MHC may contribute to delayed AD diagnosis.

Treatment Response Imaging in Prostate Cancer.

Objective criteria for measuring treatment response in prostate cancer are critical to clinical research and practice. The Prostate Cancer Working Group 3 criteria are widely accepted relying only on conventional imaging for radiographic treatment response. Prostate-specific membrane antigen PET/computed tomography was proven to be superior to conventional imaging in initial diagnosis and biochemical recurrence of prostate cancer. Moreover, there is growing evidence of its role in treatment response assessment in prostate cancer. This study will review the different criteria for imaging treatment response on conventional and advanced molecular imaging for different therapies, and the future perspective in posttherapy imaging.

Explainable Machine Learning Model to Preoperatively Predict Postoperative Complications in Inpatients With Cancer Undergoing Major Operations.

PURPOSE: Preoperative prediction of postoperative complications (PCs) in inpatients with cancer is challenging. We developed an explainable machine learning (ML) model to predict PCs in a heterogenous population of inpatients with cancer undergoing same-hospitalization major operations. METHODS: Consecutive inpatients who underwent same-hospitalization operations from December 2017 to June 2021 at a single institution were retrospectively reviewed. The ML model was developed and tested using electronic health record (EHR) data to predict 30-day PCs for patients with Clavien-Dindo grade 3 or higher (CD 3+) per the CD classification system. Model performance was assessed using area under the receiver operating characteristic curve (AUROC), area under the precision recall curve (AUPRC), and calibration plots. Model explanation was performed using the Shapley additive explanations (SHAP) method at cohort and individual operation levels. RESULTS: A total of 988 operations in 827 inpatients were included. The ML model was trained using 788 operations and tested using a holdout set of 200 operations. The CD 3+ complication rates were 28.6% and 27.5% in the training and holdout test sets, respectively. Training and holdout test sets' model performance in predicting CD 3+ complications yielded an AUROC of 0.77 and 0.73 and an AUPRC of 0.56 and 0.52, respectively. Calibration plots demonstrated good reliability. The SHAP method identified features and the contributions of the features to the risk of PCs. CONCLUSION: We trained and tested an explainable ML model to predict the risk of developing PCs in patients with cancer. Using patient-specific EHR data, the ML model accurately discriminated the risk of developing CD 3+ complications and displayed top features at the individual operation and cohort level.

Apnea Testing on Conventional Mechanical Ventilation During Brain Death Evaluation.

INTRODUCTION: The use of continuous positive airway pressure has been shown to improve the tolerance of the apnea test, a critical component of brain death evaluation. The ability to deactivate the apnea backup setting has made apnea testing possible using several conventional mechanical ventilators. Our goal was to evaluate the safety and efficacy of apnea testing performed on mechanical ventilation, compared with the oxygen insufflation technique, for the determination of brain death. METHODS: This was a retrospective study. In 2016, our institution approved a change in policy to permit apnea testing on conventional mechanical ventilation. We examined the records of consecutive adults who underwent apnea testing as part of the brain death evaluation process between 2016 and 2022. Using an apnea test technique was decided at the discretion of the attending physician. Outcomes were successful apnea test and the occurrence of patient instability during the test. This included oxygen desaturation (SpO2) < 90%, hypotension (mean arterial pressure < 65 mm Hg despite titration of vasopressor), cardiac arrhythmia, pneumothorax, and cardiac arrest. RESULTS: Ninety-two adult patients underwent apnea testing during the study period: 58 (63%) with mechanical ventilation, 32 (35%) with oxygen insufflation, and 2 (2%) lacked documentation of technique. Apnea tests could not be completed successfully in 3 of 92 (3%) patients-two patients undergoing the oxygen insufflation technique (one patient with hypoxemia and one patient with hypotension) and one patient on mechanical ventilation (aborted for hemodynamic instability). Hypoxemia occurred in 4 of 32 (12.5%) patients with oxygen insufflation and in zero patients on mechanical ventilation (p = 0.01). Hypotension occurred during 3 of 58 (5%) tests with mechanical ventilation and 4 of 32 (12.5%) tests with oxygen insufflation (p = 0.24). In multivariate analysis, the use of oxygen insufflation was an independent predictor of patient instability during the apnea test (odds ratio 37.74, 95% confidence interval 2.74-520.14). CONCLUSIONS: Apnea testing on conventional mechanical ventilation is feasible and offers several potential advantages over other techniques.

Clinical outcomes of hepatocellular carcinoma surveillance in Melbourne, Australia.

BACKGROUND: Ultrasound surveillance for hepatocellular carcinoma (HCC) may improve early tumour detection but may additionally result in surveillance-related harm through increased evaluation of non-HCC lesions. The incidence of these outcomes has not been reported outside North America. AIMS: We aimed to report the outcomes of HCC surveillance with respect to both surveillance-related benefits and harms. METHODS: We reviewed all HCC surveillance ultrasounds at a large Victorian tertiary hospital network in 2017 and followed their outcomes until 2021. Surveillance-related benefits were defined as early-stage HCC detection. Surveillance-related harm was defined as contrast imaging, biopsies or surgery performed to evaluate non-HCC liver lesions or false-positive alpha-fetoprotein levels. RESULTS: Five hundred and fifty-three patients were included (mean age 54.5 ± 12.3 years, males 67.5%, cirrhosis 50.3%). The most common liver disease aetiology was hepatitis B (53.9%). Over a median of 4.7 years follow-up, early-stage HCC was detected in 3.3% (5.4% in cirrhotic vs 1.1% in non-cirrhotic patients, P < 0.01). 75% of all HCCs were early-stage. Surveillance-related harm occurred in 12.5% (15.5% in cirrhotic vs 9.5% in non-cirrhotic patients, P < 0.04), although most harm was mild (12.1%). In subgroup analysis, the detection of early-stage HCC ranged between 0% (screened outside of guideline criteria and alcoholic cirrhotic patients) and 7.2% (hepatitis C cirrhosis). Harm occurred between 9% (non-cirrhotic hepatitis B) and 20.8% (thrombocytopenia). CONCLUSION: In our study, HCC surveillance was associated with early tumour detection, although many patients experienced mild surveillance-related harm. Novel surveillance strategies and pathways are required to improve detection in high-risk patients and minimise harm in low-risk patients.

SuperMap algorithm: an efficient, safe and accurate modality for mapping and eliminating challenging cardiac arrhythmias.

Even with the development of advanced catheter-based mapping systems, there remain several challenges in the electrophysiological evaluation and elimination of atrial arrhythmias. For instance, atrial tachycardias with irregular rates cannot be reliably mapped by systems that require stability in order to sequentially gather data points to be organized thereafter. Separately, these arrhythmias often arise following initial ablation for atrial fibrillation, posing logistic challenges. Here, we present the available literature summarizing the use of a non-contact mapping catheter, the AcQMap catheter, in conjunction with SuperMap, an algorithm that compiles a large number of non-contact data points from multiple catheter positions within the atria. These studies demonstrate the efficiency, safety and accuracy of this technology.

Irregular heart rhythms (arrhythmias) are often treatable with medications, but sometimes require expert evaluation in a cardiac electrophysiology laboratory. They are often studied and treated using thin, flexible catheters which enter the body through blood vessels in the leg and reach the internal walls of the heart. Time, expertise and specialized equipment are necessary to identify characteristics specific to each patient's arrhythmia. For each arrhythmia, a unique electrical blueprint is created before trying to eliminate it. The fleeting nature of certain arrhythmias can make it difficult to generate these blueprints, and many take a lot of time to accurately identify, leading to procedural challenges. Here we evaluate studies discussing the use of a new catheter (AcQMap) and its accompanying strategy for identifying arrhythmias. Unlike traditional catheters that require direct contact with the internal walls of the heart, the AcQMap catheter floats within these blood-filled chambers and does not touch the walls when obtaining data points. Instead, using ultrasound waves and electrical signals, it can generate data points to create blueprints. This technology also uses a new algorithm that enables the catheter to move freely within the heart, obtaining numerous data points and grouping them together to create maps efficiently and safely, even for fleeting or challenging arrhythmias.

Automated Plaque Detection and Agatston Score Estimation on Non-Contrast CT Scans: A Multicenter Study.

Coronary artery calcification (CAC) is a strong and independent predictor of cardiovascular disease (CVD). However, manual assessment of CAC often requires radiological expertise, time, and invasive imaging techniques. The purpose of this multicenter study is to validate an automated cardiac plaque detection model using a 3D multiclass nnU-Net for gated and non-gated non-contrast chest CT volumes. CT scans were performed at three tertiary care hospitals and collected as three datasets, respectively. Heart, aorta, and lung segmentations were determined using TotalSegmentator, while plaques in the coronary arteries and heart valves were manually labeled for 801 volumes. In this work we demonstrate how the nnU-Net semantic segmentation pipeline may be adapted to detect plaques in the coronary arteries and valves. With a linear correction, nnU-Net deep learning methods may also accurately estimate Agatston scores on chest non-contrast CT scans. Compared to manual Agatson scoring, automated Agatston scoring indicated a slope of the linear regression of 0.841 with an intercept of +16 HU (R2 = 0.97). These results are an improvement over previous work assessing automated Agatston score computation in non-gated CT scans.