Role of Forkhead Box P3 in IFNγ-Mediated PD-L1 Expression and Bladder Cancer Epithelial-to-Mesenchymal Transition.

Antagonism of the PD-1/PD-L1 axis is a critical therapeutic strategy for patients with advanced bladder cancer. IFNγ functions as a key regulator of PD-L1 in both immune as well as cancer cells. Forkhead box P3 (FOXP3) is a transcription factor synonymous in T regulatory cell function but with increasingly described functions in cancer cells. Here, we investigated the relationship between FOXP3 and PD-L1 in bladder cancer. We showed that FOXP3 is critical in the ability for IFNγ to activate PD-L1 in bladder cancer cells. FOXP3 can bind to the PD-L1 promoter and induces a gene program that leads to regulation of multiple immune-related genes and genes involved in epithelial-to-mesenchymal transition (EMT). Using in vitro and in vivo human and murine models, we showed that FOXP3 can influence bladder cancer EMT as well as promote cancer metastases. Furthermore, FOXP3 may be a convergent factor for multiple activators of PD-L1, including the chemotherapeutic drug cisplatin. SIGNIFICANCE: Historically a key transcription factor driving T regulatory cell function, FOXP3 has an increasingly recognized role in cancer cells. In bladder cancer, we defined a novel mechanism whereby FOXP3 mediates the activation of the immune checkpoint PD-L1 by the cytokine IFNγ. We also showed that FOXP3 induces other immune checkpoints as well as genes involved in EMT, promoting immune resistance and cancer metastases.

ISLET-1 expression in soft tissue neoplasms reveals high sensitivity but moderate specificity for desmoplastic small round cell tumors and potential utility as a diagnostic biomarker.

ISLET-1 (ISL1) is a LIM-homeodomain transcription factor. Selective ISL1 expression is shown in neuroendocrine, non-neuroendocrine, and some soft tissue tumors including desmoplastic small round cell tumor (DSRCT). We assessed the specificity of ISL1 (clone EP283, 1:500, Cell Marque) in 288 soft tissue tumors, which included 17 DSRCTs and other histologic mimics. Positive staining threshold for ISL1 was set to >10 % of neoplastic cell nuclei at moderate intensity. ISL1 IHC was positive in 15/16 (94 %) DSRCTs with 75 % showing diffuse (>50 %) expression. ISL1 was positive in 1/10 (10 %) Ewing sarcomas (EWS), 7/13 (54 %) alveolar rhabdomyosarcoma (RMS), 14/22 (63 %) embryonal RMS, 7/14 (50 %) synovial sarcomas, 15/16 (93 %) neuroblastoma, 1/5 (20 %) Wilms tumor, 2/4 (50 %) olfactory neuroblastoma, and all 9 Merkel cell carcinomas. Other tumors, including all CIC::DUX4 sarcomas, were negative except 3/27 leiomyosarcomas, and 1 each of angiosarcoma, myxoid liposarcomas, inflammatory myofibroblastic tumor, malignant peripheral nerve sheath tumor, tenosynovial giant cell tumor, dedifferentiated LPS, and 1 ectomesenchymoma. In summary, among the soft tissue tumors tested, ISL1 is a highly sensitive but moderately specific marker for DSRCT and may be useful to distinguish from round cell mimics including EWS and CIC::DUX4 sarcomas. The oncogenic role of ISL1 in these tumors warrants further investigation.

Multi-modality Regional Alignment Network for Covid X-Ray Survival Prediction and Report Generation.

In response to the worldwide COVID-19 pandemic, advanced automated technologies have emerged as valuable tools to aid healthcare professionals in managing an increased workload by improving radiology report generation and prognostic analysis. This study proposes a Multi-modality Regional Alignment Network (MRANet), an explainable model for radiology report generation and survival prediction that focuses on high-risk regions. By learning spatial correlation in the detector, MRANet visually grounds region-specific descriptions, providing robust anatomical regions with a completion strategy. The visual features of each region are embedded using a novel survival attention mechanism, offering spatially and risk-aware features for sentence encoding while maintaining global coherence across tasks. A cross-domain LLMs-Alignment is employed to enhance the image-to-text transfer process, resulting in sentences rich with clinical detail and improved explainability for radiologists. Multi-center experiments validate the overall performance and each module's composition within the model, encouraging further advancements in radiology report generation research emphasizing clinical interpretation and trustworthiness in AI models applied to medical studies.

Quantitative Optical Redox Imaging of Melanoma Xenografts with Different Metastatic Potentials.

To develop imaging biomarkers for tumors aggressiveness, our previous optical redox imaging (ORI) studies of the reduced nicotinamide adenine dinucleotide (NADH) and oxidized flavoproteins (Fp, containing flavin adenine dinucleotide, i.e., FAD) in tumor xenografts of human melanoma associated the high optical redox ratio (ORR = Fp/(Fp + NADH)) and its heterogeneity to the high invasive/metastatic potential, without having reported quantitative results for NADH and Fp. Here, we implemented a calibration procedure to facilitate imaging the nominal concentrations of tissue NADH and Fp in the mouse xenografts of two human melanoma lines, an indolent less metastatic A375P and a more metastatic C8161. Images of the redox indices (NADH, Fp, ORR) revealed the existence of more oxidized areas (OAs) and more reduced areas (RAs) within individual tumors. ORR was found to be higher and NADH lower in C8161 compared to that of A375P xenografts, both globally for the whole tumors and locally in OAs. The ORR in the OA can differentiate xenografts with a higher statistical significance than the global averaged ORR. H&E staining of the tumors indicated that the redox differences we identified were more likely due to intrinsically different cell metabolism, rather than variations in cell density.

Bizarre parosteal osteocondromatous proliferation (BPOP) of the acromion with soft tissue recurrence.

Bizarre parosteal osteochondromatous proliferation (BPOP) is a benign but rare periosteal-originating chondrogenic tumor. It commonly arises from the hands and feet. It is slow-growing and often presents as a painless lump. On imaging, the mass is well-marginated and almost always remains contiguous with the cortical bone. Histologically, the lesion is composed of a disorganized admixture of fibrous tissue, bone, and cartilage with bizarre features. Treatment is surgical and local recurrence is common contiguous with bone. This case report demonstrates an uncommon acromial BPOP with the first reported recurrence not contiguous with the underlying cortex.

Clinical validation of a fast-acting acetaminophen: a randomized, active and placebo controlled dental pain study.

OBJECTIVES: To address the need for faster pain relief of over-the-counter (OTC) analgesic users, a novel drug delivery technology was developed to achieve faster absorption of orally administered acetaminophen with the goal of delivering earlier onset of pain relief. Previous development studies suggested that a 1000 mg dose of this fast-acting acetaminophen (FA-acetaminophen) formulation provided faster absorption and onset of action versus, commercially available OTC fast-acting analgesics, 1000 mg of extra-strength acetaminophen (ES-acetaminophen) or 400 mg of liquid-filled ibuprofen capsules (LG-ibuprofen). This study was designed as the definitive trial evaluating the onset of pain relief of FA-acetaminophen versus these same OTC comparators. METHODS: This single-dose, randomized, double-blind, placebo- and active-controlled clinical trial compared analgesic onset, overall efficacy, and safety of FA-acetaminophen 1000 mg, ES-acetaminophen 1000 mg, LG-ibuprofen 400 mg, and placebo over 4 h in a postsurgical dental pain model. Following removal of 3 to 4 impacted third molars, 664 subjects with moderate-to-severe pain were randomized in a 4:4:2:1 ratio to FA-acetaminophen (249), ES-acetaminophen (232), LG-ibuprofen (124), or placebo (59). Mean age was 18.9 years; 45.5% were male; 57.5% had severe baseline pain intensity. Subjects stopped a first stopwatch if/when they had perceptible pain relief and a second stopwatch if/when their pain relief became meaningful to them. Pain intensity difference (PID) and pain relief (PAR) were obtained using an 11-point numerical rating scale. FINDINGS: FA-acetaminophen 1000 mg had faster median time to onset of pain relief (15.7 min) compared to ES-acetaminophen 1000 mg (20.2 min, p = 0.035), LG-ibuprofen 400 mg (23.2 min, p < 0.001), and placebo (non-estimable), statistically greater mean PAR and PID scores than other treatment groups at 15 and 30 min, and a statistically greater percentage of subjects with confirmed perceptible pain relief at 15 and 20 min. At 25 min, FA-acetaminophen 1000 mg had a statistically significantly greater percentage of subjects with confirmed perceptible pain relief than LG-ibuprofen 400 mg and placebo. No clinically significant adverse events were reported. CONCLUSIONS: This study supports previous studies, demonstrating faster onset of analgesia with FA-acetaminophen 1000 mg compared to OTC ES-acetaminophen 1000 mg and OTC LG-ibuprofen 400 mg. CLINICALTRIALS.GOV IDENTIFIER: NCT03224403 https://clinicaltrials.gov/ct2/show/NCT03224403.

Primary intradural extraosseous Ewing's sarcoma of the L3 nerve root: illustrative case.

BACKGROUND: Ewing's sarcoma is an uncommon, aggressive malignancy that typically presents as an osseous lesion, most commonly in children and adolescents. Very rarely Ewing's sarcoma can present as an intradural extramedullary mass mimicking more common tumors. OBSERVATIONS: A 32-year-old female had a left L3 nerve root-associated lesion identified in the setting of recent-onset radiculopathy. Contrast-enhanced magnetic resonance imaging of the lumbar spine was favored to demonstrate a schwannoma or neurofibroma. Hemilaminectomy, facetectomy, and resection of the mass led to improved radiculopathy and a tissue diagnosis of Ewing's sarcoma. Immediate referral to medical oncology facilitated expeditious initiation of adjuvant chemotherapy and radiation. LESSONS: The differential diagnosis for newly identified nerve root-associated tumors should remain broad, including common benign pathologies and rare malignant entities. Tissue remains the gold standard for diagnosis, as preoperative imaging suggested a nerve sheath tumor. Malignant pathologies such as Ewing's sarcoma must be considered, especially in the setting of rapidly progressive symptoms or interval growth on serial imaging. Early diagnosis allows for the timely initiation of comprehensive oncological care. Long-term multidisciplinary follow-up is necessary for the surveillance of disease progression.

Intra-Abdominal and Retroperitoneal Benign Lipomatous Tumors-An Extremely Rare Mimic of Liposarcoma and its Diagnostic Challenge.

Background. Lipomas are common superficial soft tissue tumors of mature adipocytes. In contrast, well-differentiated/dedifferentiated liposarcoma typically presents in the retroperitoneum as large masses. We provide clinicopathologic and follow-up details of 9 retroperitoneal/intra-abdominal benign lipomatous tumors (BLT) and discuss the utility of ancillary fluorescence in situ hybridization (FISH) in distinguishing from their malignant counterparts. Design. Clinicopathologic details and histology of 9 intra-abdominal and retroperitoneal lipomas were studied along with ancillary CD10 immunohistochemistry (IHC) and FISH for MDM2 and CDK4 amplification. Results. There were 6 females and 3 males. Median age at diagnosis was 52 years (range 36-81 years). Seven were identified incidentally and 2 presented with primary complaints. On imaging, 7 were considered suspicious for liposarcoma. Grossly, the tumors ranged from 3.4 to 41.2 cm (median 16.5 cm). Histologically, all cases showed well-differentiated BLT, further classified as lipoma (n = 7; 1 with metaplastic ossification, 2 with prominent vessels, and 4 ordinary lipomas) and lipoma-like hibernoma (n = 2)-the latter 2 showed intramuscular lesions with interspersed brown fat. CD10 IHC showed strong staining in the 2 hibernomas, whereas the staining was weak in the remaining. MDM2 and CDK4 amplification were negative by FISH in all. Follow-up (median 18 months) did not show recurrence on clinical or imaging evaluation. Conclusion. Retroperitoneal/intra-abdominal BLT are extremely rare and are indistinguishable clinically and radiographically from liposarcoma. This necessitates molecular confirmation even when the histology is convincingly benign, for a confident diagnosis. Our cohort shows that conservative excision without removal of abutted organs is sufficient in most cases.

Islet-1 Is Differentially Expressed Among Neuroendocrine and Non-Neuroendocrine Tumors and Its Potential Diagnostic Implication.

Islet-1 (ISL1) plays key roles in programming the epigenome and facilitating the recruitment of additional regulatory factors. Although it has been used as a marker for pancreatic neuroendocrine tumors (PanNETs), ISL1 reactivity in other tumor types are critically missing. ISL1 immunohistochemistry was performed on 147 neuroendocrine tumors (NET) originated in pancreas, gastrointestinal tract, lung, thyroid, parathyroid, pituitary, adrenal medulla, head/neck, genitourinary tract, and skin; and 110 non-neuroendocrine tumors originated in the pancreas, thymus, lung, thyroid, mesothelium, adrenal cortex, stomach, breast, head/neck, skin, and kidney. ISL1 nuclear staining was observed in normal thymic epithelium, pancreatic islets, adrenal medulla, and pituitary gland cells as well as frequently in tumors of these origins: pancreatic NET (78%), paraganglioma/pheochromocytoma (100%), thymoma (82%), and pituitary NET (50%). ISL1 was also variably expressed in certain non-pancreatic NET such as Merkel cell carcinoma (100%), medullary carcinoma of the thyroid (100%), head/neck NEC (80%), genitourinary NEC (71%), lung small cell carcinoma (46%), lung carcinoids (17%), lower intestinal tract NET (93%) but not in upper gastrointestinal tract NET nor parathyroid adenoma. For other non-NETs, focal ISL1 expression was less frequently detected in gastric adenocarcinoma (40%), mesothelioma (29%), adrenal cortical carcinoma (17%), and squamous carcinoma (24%), but not in others tested. ISL1 is not a pan-NE marker as it is consistently lacking in upper gastrointestinal NET and parathyroid adenoma. It is also differentially expressed in thymoma. ISL1 immunohistochemnistry could help to differentiate PanNET and lower intestinal NET from upper gastrointestinal NET and be used as a marker for thymoma.

Phase I Trial of Autologous RNA-electroporated cMET-directed CAR T Cells Administered Intravenously in Patients with Melanoma and Breast Carcinoma.

Purpose: Treatments are limited for metastatic melanoma and metastatic triple-negative breast cancer (mTNBC). This pilot phase I trial (NCT03060356) examined the safety and feasibility of intravenous RNA-electroporated chimeric antigen receptor (CAR) T cells targeting the cell-surface antigen cMET. Experimental Design: Metastatic melanoma or mTNBC subjects had at least 30% tumor expression of cMET, measurable disease and progression on prior therapy. Patients received up to six infusions (1 × 10e8 T cells/dose) of CAR T cells without lymphodepleting chemotherapy. Forty-eight percent of prescreened subjects met the cMET expression threshold. Seven (3 metastatic melanoma, 4 mTNBC) were treated. Results: Mean age was 50 years (35-64); median Eastern Cooperative Oncology Group 0 (0-1); median prior lines of chemotherapy/immunotherapy were 4/0 for TNBC and 1/3 for melanoma subjects. Six patients experienced grade 1 or 2 toxicity. Toxicities in at least 1 patient included anemia, fatigue, and malaise. One subject had grade 1 cytokine release syndrome. No grade 3 or higher toxicity, neurotoxicity, or treatment discontinuation occurred. Best response was stable disease in 4 and disease progression in 3 subjects. mRNA signals corresponding to CAR T cells were detected by RT-PCR in all patients' blood including in 3 subjects on day +1 (no infusion administered on this day). Five subjects underwent postinfusion biopsy with no CAR T-cell signals seen in tumor. Three subjects had paired tumor tissue; IHC showed increases in CD8 and CD3 and decreases in pS6 and Ki67. Conclusions: Intravenous administration of RNA-electroporated cMET-directed CAR T cells is safe and feasible. Significance: Data evaluating CAR T therapy in patients with solid tumors are limited. This pilot clinical trial demonstrates that intravenous cMET-directed CAR T-cell therapy is safe and feasible in patients with metastatic melanoma and metastatic breast cancer, supporting the continued evaluation of cellular therapy for patients with these malignancies.

Myofibroblastoma in the Liver: A Case Report and Review of Literature.

Myofibroblastoma is a rare benign mesenchymal tumor first described in the breast. It is also known as mammary-type myofibroblastoma outside of the breast, more frequently located along the embryonic milk line. Exceptionally, myofibroblastoma can occur at visceral locations. We present a case of myofibroblastoma detected incidentally in the liver. A well-circumscribed mass, grossly measuring 6.2 cm in the liver parenchyma, was found on imaging studies. Histologically, the lesion is characterized by benign spindle cells in a hyalinized collagenous stroma, with positive staining for SMA and ER, focal positivity for CD34, negative for desmin, and loss of RB1. This rare tumor at such an unusual location makes it diagnostically challenging, especially on core biopsy of the lesion. To our knowledge, this is the second case of myofibroblastoma in the liver reported in the English literature and the first such case with a detailed pathology description.

Primary Alveolar Soft-Part Sarcoma (ASPS) of the Prostate: Report of a Deceptive Case.

Alveolar soft-part sarcoma (ASPS) is a rare soft tissue tumor that primarily involves the extremities. We report a case of a 30-year-old never-smoker man who presented with hematuria, dysuria, and constipation at an outside hospital. He was diagnosed with and treated for multiple episodes of urinary tract infection. However, he continued to have voiding symptoms for which a cystoscopy was performed and revealed a bladder neck mass. He underwent transurethral resection of a bladder tumor and was diagnosed with muscle-invasive urothelial carcinoma, nested variant, at an outside hospital. Subsequent to this diagnosis he transferred his care to our center. In-house imaging revealed a large vascular mass involving the prostate and pushing against the bladder base. Prostate needle biopsies were performed and revealed an epithelioid neoplasm with a nested growth pattern composed of cells with a moderate amount of eosinophilic cytoplasm, mildly pleomorphic nuclei, and occasional prominent nucleoli. Since the findings were not classic for urothelial carcinoma or for prostate cancer, we included a wider differential of poorly differentiated carcinoma, sarcoma, and paraganglioma. A wide panel of keratin stains was negative, ETS (erythroblast transformation-specific)-related gene highlighted an extensive vascular network and neuroendocrine stains were all negative. A transcription factor E3 fluorescent in-situ hybridization was positive and subsequently, an ASPSCR1 gene rearrangement was demonstrated. The outside hospital transurethral resection of bladder tumor was obtained for review and the tumor was morphologically similar to that seen on the in-house prostate needle biopsies. Based on the above findings a final diagnosis of primary ASPS of the prostate with involvement of the bladder was made. The patient was later diagnosed with bilateral lung metastases. He was treated with pazopanib, radiation therapy, and cystoprostatectomy and is symptom-free on a 15-month follow-up.

Hepatic Macrophage Types Cluster with Disease Etiology in Chronic Liver Disease and Differ Compared to Normal Liver: Implications for Their Biologic and Diagnostic Role.

Introduction. Macrophages are phenotypically heterogeneous cells that play a vital role in hepatic fibrogenesis. We aimed to compare the macrophage profiles between normal livers and those with various chronic liver diseases in the precirrhotic fibrosis stage. Methods. Immunohistochemistry was performed for three macrophage markers (CD163, CD68, and IBA1) on 48 liver biopsies. Digital image analysis and automated cell count were used to calculate the densities of immunostained cells in two selected regions of interest: the periportal region and the perivenous region. Results. The absolute and relative densities of the macrophage phenotypes in relationship with zones and etiologies showed four distinct patterns by hierarchical cluster analysis: (1) no significant increase in the macrophage densities in either periportal or perivenous regions - nonalcoholic steatohepatitis; (2) significant increase in the selected macrophage densities in both periportal and perivenous regions - Hepatitis C; (3) significant increase in the macrophage densities only in periportal region - alcoholic liver disease, primary sclerosing cholangitis, and primary biliary cholangitis; and (4) significant increase in the densities of all types of macrophages in both periportal and perivenous regions - autoimmune hepatitis. Conclusions. There are distinct macrophage phenotypic and zonal geographic signatures correlating to etiologies of chronic liver disease in the precirrhotic stage.

Molecular identification of an ETV6-RET fusion in a secretory carcinoma associated with a pleomorphic adenoma.

Pleomorphic adenoma (PA) is the most common neoplasm of the salivary glands. Although several carcinomas have been reported to arise from PA, only 1 case of salivary gland secretory carcinoma (SC) ex pleomorphic adenoma has been previously reported. SC is a newly described salivary gland tumor harboring an ETV6-NTRK3 translocation, which is classically observed in secretory carcinoma of the breast, although other translocations have recently been observed. We report the first case of the molecular identification of a rare ETV6-RET translocation in an SC arising from a PA in the submandibular salivary gland (SC ex PA). Our results add to the diversity of tumors that are associated with PA and contribute to the molecular characterization of SC, which will have implications on its diagnosis, prognosis, and treatment.

Case Report: Multilevel Ossification of the Ligamentum Flavum in a Patient With Spinal Osteoblastoma.

Introduction: Spinal osteoblastomas are primary benign bone tumors most commonly presenting as diffuse back pain in young adults. Rarely, spinal osteoblastoma is associated with ossification of the ligamentum flavum (OLF), a form of ectopic bone formation, which can present with myelopathy. This report highlights a unique case of a patient with spinal osteoblastoma, associated OLF, and thoracic myelopathy. Case Description: The patient presented with subtle myelopathy consisting of mid-thoracic back pain, paresthesias, and gait instability. Imaging findings were suggestive of spinal osteoblastoma with multifocal OLF. The patient was consented for thoracic decompression and stabilization at the T6-10 levels. Histopathology confirmed osteoblastoma with associated OLF. At follow up, the patient's neurological symptoms had completely resolved. Conclusion: This case describes management for a rare presentation of osteoblastoma with associated OLF and myelopathy. Surgeons should be wary of disproportionate neurological compromise when spinal osteoblastoma is associated with OLF. Further study is required to elucidate the pathogenesis of this condition.

Prediction of lung malignancy progression and survival with machine learning based on pre-treatment FDG-PET/CT.

BACKGROUND: Pre-treatment FDG-PET/CT scans were analyzed with machine learning to predict progression of lung malignancies and overall survival (OS). METHODS: A retrospective review across three institutions identified patients with a pre-procedure FDG-PET/CT and an associated malignancy diagnosis. Lesions were manually and automatically segmented, and convolutional neural networks (CNNs) were trained using FDG-PET/CT inputs to predict malignancy progression. Performance was evaluated using area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. Image features were extracted from CNNs and by radiomics feature extraction, and random survival forests (RSF) were constructed to predict OS. Concordance index (C-index) and integrated brier score (IBS) were used to evaluate OS prediction. FINDINGS: 1168 nodules (n=965 patients) were identified. 792 nodules had progression and 376 were progression-free. The most common malignancies were adenocarcinoma (n=740) and squamous cell carcinoma (n=179). For progression risk, the PET+CT ensemble model with manual segmentation (accuracy=0.790, AUC=0.876) performed similarly to the CT only (accuracy=0.723, AUC=0.888) and better compared to the PET only (accuracy=0.664, AUC=0.669) models. For OS prediction with deep learning features, the PET+CT+clinical RSF ensemble model (C-index=0.737) performed similarly to the CT only (C-index=0.730) and better than the PET only (C-index=0.595), and clinical only (C-index=0.595) models. RSF models constructed with radiomics features had comparable performance to those with CNN features. INTERPRETATION: CNNs trained using pre-treatment FDG-PET/CT and extracted performed well in predicting lung malignancy progression and OS. OS prediction performance with CNN features was comparable to a radiomics approach. The prognostic models could inform treatment options and improve patient care. FUNDING: NIH NHLBI training grant (5T35HL094308-12, John Sollee).

COVID-19 mortality prediction in the intensive care unit with deep learning based on longitudinal chest X-rays and clinical data.

OBJECTIVES: We aimed to develop deep learning models using longitudinal chest X-rays (CXRs) and clinical data to predict in-hospital mortality of COVID-19 patients in the intensive care unit (ICU). METHODS: Six hundred fifty-four patients (212 deceased, 442 alive, 5645 total CXRs) were identified across two institutions. Imaging and clinical data from one institution were used to train five longitudinal transformer-based networks applying five-fold cross-validation. The models were tested on data from the other institution, and pairwise comparisons were used to determine the best-performing models. RESULTS: A higher proportion of deceased patients had elevated white blood cell count, decreased absolute lymphocyte count, elevated creatine concentration, and incidence of cardiovascular and chronic kidney disease. A model based on pre-ICU CXRs achieved an AUC of 0.632 and an accuracy of 0.593, and a model based on ICU CXRs achieved an AUC of 0.697 and an accuracy of 0.657. A model based on all longitudinal CXRs (both pre-ICU and ICU) achieved an AUC of 0.702 and an accuracy of 0.694. A model based on clinical data alone achieved an AUC of 0.653 and an accuracy of 0.657. The addition of longitudinal imaging to clinical data in a combined model significantly improved performance, reaching an AUC of 0.727 (p = 0.039) and an accuracy of 0.732. CONCLUSIONS: The addition of longitudinal CXRs to clinical data significantly improves mortality prediction with deep learning for COVID-19 patients in the ICU. KEY POINTS: • Deep learning was used to predict mortality in COVID-19 ICU patients. • Serial radiographs and clinical data were used. • The models could inform clinical decision-making and resource allocation.