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Purpose: Retinopathy of prematurity (ROP) stage is defined by the visual appearance of the vascular-avascular border, which reflects a spectrum of pathologic neurovascular tissue (NVT). Previous work demonstrated that the thickness of the ridge lesion, measured using OCT, corresponds to higher clinical diagnosis of stage. This study evaluates whether the volume of anomalous NVT (ANVTV), defined as abnormal tissue protruding from the regular contour of the retina, can be measured automatically using deep learning to develop quantitative OCT-based biomarkers in ROP. Design: Single-center retrospective case series. Participants: Thirty-three infants with ROP in the Oregon Health & Science University neonatal intensive care unit. Methods: OCT B-scans were collected using an investigational ultrawidefield OCT. The ANVTV was manually segmented. A set of 3347 B-scans and corresponding manual segmentations from 12 volumes from 6 patients were used to train an automated segmentation tool using a U-Net. An additional held-out test data set of 60 B-scans from 6 infants was used to evaluate model performance. The Dice–Sorensen coefficient (DSC) comparing manual and automated segmentation of ANVTV was calculated. Scans from 21 additional infants were used for clinical evaluation of ANVTV using the visit in which they had developed their peak stage of ROP. Each infant had every B-scan in a volume automatically segmented for ANVTV (total number of segmented voxels within the 60° temporal to the optic disc). The ANVTV was compared between infants with stage 1 to 3 ROP using a Kruskal–Wallis test and tracked over time in all infants with stage 3 ROP. Main Outcome Measurements: Cross sectional and longitudinal association between ANVTV and stages 1 to 3 ROP. Results: Comparing automated and manual segmentation of ANVTV achieved a DSC of 0.61 ± 0.13. Using the U-Net, ANVTV was associated with higher disease stage both cross sectionally and longitudinally. Median ANVTV significantly increased as ROP stage worsened from 1 (0, [interquartile range: 0–0] kilovoxels) to 2 (170.1 [interquartile range: 104.2–183.6] kilovoxels) to 3 (421.4 [interquartile range: 312.3–1110.8] kilovoxels; P < 0.001). Conclusions: Automated OCT-based measurement of ANVTV was associated with clinical disease stage in ROP, both cross sectionally and longitudinally. Ultrawidefield-OCT may facilitate more objective screening, diagnosis, and monitoring in the future. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Purpose: The landmark randomized trial on chest irradiation in extensive disease small cell lung cancer (CREST) demonstrated that consolidative thoracic radiation therapy (cTRT) improved overall (OS) and progression-free survival (PFS) after initial chemotherapy (chemo) in extensive-stage small cell lung cancer, with potentially increased benefit in women compared with men. It is unknown whether similar findings would apply after chemoimmunotherapy became the standard first-line treatment. In this analysis, we report national practice patterns and survival outcomes of cTRT according to patient sex. Methods and Materials: We included patients from de-identified electronic health record-derived database diagnosed with stage IV small cell lung cancer (2014-2021) who completed 4 to 6 cycles of first-line systemic therapy (platinum-doublet chemotherapy or chemoimmunotherapy). We evaluated OS and PFS using multivariable Cox proportional hazards regression with receipt of cTRT as an independent variable and stratified by sex. As a sensitivity analysis, we weighted the models by the inverse probability of receiving cTRT. Results: A total of 1227 patients were included (850 chemotherapy, 377 chemoimmunotherapy). There were no statistically significant differences in baseline characteristics between patients who did and did not receive cTRT. Among women, cTRT was associated with superior OS (adjusted hazard ratio [HR], 0.67; 95% CI, 0.52-0.87) and PFS (HR, 0.63; 95% CI, 0.49-0.82) compared with those not receiving cTRT. Conversely, no OS or PFS benefit with cTRT was observed in men (OS HR, 1.03; 95% CI, 0.80-1.31; PFS HR, 1.12; 95% CI, 0.85-1.47). Findings were similar in weighted analyses. Conclusions: The survival efficacy of cTRT may be moderated by sex, with female patients appearing more likely to benefit than male patients. These findings reflect sex-based survival trends with similar effect sizes to those observed in the CREST trial. Although the underpinnings of this association need to be elucidated, stratification by sex should be considered for randomized-controlled trials studying cTRT in extensive-stage small cell lung cancer.

Purpose: Retinopathy of prematurity (ROP) is one of the leading causes of blindness in children. Although the role of oxygen in the pathophysiology of ROP is well established, a precise understanding of the dynamic relationship between oxygen exposure ROP incidence and severity is lacking. The purpose of this study was to evaluate the correlation between time-dependent oxygen variables and the onset of ROP. Design: Retrospective cohort study. Participants: Two hundred thirty infants who were born at a single academic center and met the inclusion criteria were included. Infants are mainly born between January 2011 and October 2022. Methods: Patient data were extracted from electronic health records (EHRs), with sufficient time-dependent oxygen data. Clinical outcomes for ROP were recorded as none/mild or moderate/severe (defined as type II or worse). Mixed-effects linear models were used to compare the 2 groups in terms of dynamic oxygen variables, such as daily average and the coefficient of variation (COV) fraction of inspired oxygen (FiO2). Support vector machine (SVM) and long-short-term memory (LSTM)-based multimodal models were trained with fivefold cross-validation to predict which infants would develop moderate/severe ROP. Gestational age (GA), birth weight, and time-dependent oxygen variables were used to develop predictive models. Main Outcome Measures: Model cross-validation performance was evaluated by computing the mean area under the receiver operating characteristic (AUROC) curve, precision, recall, and F1 score. Results: We found that both daily average and COV of FiO2 were associated with more severe ROP (adjusted P

Background: Fucus vesiculosus -derived fucoidan, a multifunctional bioactive polysaccharide sourced from marine organisms, exhibits a wide range of therapeutic properties, including its anti-tumor effects. While previous research has reported on its anti-cancer potential, limited studies have explored its synergistic capabilities when combined with other natural bioactive ingredients. In this current study, we present the development of an integrative functional beverage, denoted as VMW-FC, which is composed of a fucoidan complex (FC) along with a blend of various herbal components, including vegetables (V), mulberries and fruits (M), and spelt wheat (W). Objective: Colorectal cancer (CRC) remains a significant cause of mortality, particularly in metastatic cases. Therefore, the urgent need for novel alternative medicines that comprehensively inhibit CRC persists. In this investigation, we assess the impact of VMW-FC on CRC cell proliferation, cell cycle dynamics, metastasis, in vivo tumorigenesis, and potential side effects. Methods: Cell growth was assessed using MTT and colony formation assays, while metastatic potential was evaluated through wound healing and transwell migration assays. The underlying signaling mechanisms were elucidated through qPCR and western blot analysis. In vivo tumor formation and potential side effects were evaluated using a subcutaneous tumor-bearing NOD/SCID mouse model. Results: Our findings demonstrate that VMW-FC significantly impedes CRC proliferation and migration in a dose- and time-dependent manner. Furthermore, it induces sub-G1 cell cycle arrest and an increase in apoptotic cell populations, as confirmed through flow-cytometric analysis. Notably, VMW-FC also suppresses xenograft tumor growth in NOD/SCID mice without causing renal or hepatic toxicity. Conclusion: The integrative herbal concoction VMW-FC presents a promising approach for inhibiting CRC by slowing proliferation and migration, inducing cell cycle arrest and apoptosis, and suppressing markers associated with proliferation (Ki-67, PCNA, and CDKs) and epithelial-mesenchymal transition (EMT) (Vimentin, N-cadherin, and β-catenin).

Background: Infants with respiratory-syncytial virus bronchiolitis hospitalization are more likely to develop wheezing and subsequent asthma. Reportedly, palivizumab prophylaxis effectively prevents respiratory-syncytial virus hospitalization in high-risk children—such as premature infants or infants with bronchopulmonary dysplasia (BPD). Objective: We sought to explore the effect of respiratory-syncytial virus immunoprophylaxis on the risk of asthma development in premature infants with BPD in subtropical areas. Methods: This case-control study included preterm children with BPD born at Mackay Memorial Hospital, Taipei, Taiwan, from 1999 to 2015. Overall, medical records of 616 eligible participants were retrospectively collected from their birth to the time they attained an age of 5 to 20 years. The primary outcome was onset of active asthma. Results: Overall, 576 consecutive cases met the inclusion criteria. Of these, 306 (53.2%) patients had palivizumab exposure and 191 (33.2%) were diagnosed with asthma. Patients with history of respiratory-syncytial virus bronchiolitis hospitalization had a higher risk of developing asthma in the future (adjusted odds ratio, 3.77; 95% CI, 2.30-6.20, P < .001; hazard ratio, 2.56; 95% CI, 1.81-3.62, P < .001). Palivizumab prophylaxis reduced future asthma development through the inhibition of respiratory-syncytial virus bronchiolitis hospitalization (coefficient, −0.021; 95% CI, −0.031 to −0.011, P = .027). Asthmatic children who received palivizumab immunoprophylaxis had a lesser active asthma duration than those who did not (P = .005). Conclusions: Children with BPD with hospitalization for respiratory-syncytial virus bronchiolitis had higher risk of developing asthma compared with those without respiratory-syncytial virus infection. Prophylactic palivizumab might reduce later asthma development through inhibition of respiratory-syncytial virus bronchiolitis hospitalization. For those already developing asthma, palivizumab could reduce active asthma duration.

Background:. Weekend presentation has been associated with adverse outcomes in emergent conditions, including stroke, myocardial infarction, and critical limb ischemia. We examine whether a weekend effect exists in the management of and outcomes after extremity degloving injuries. Methods:. The cohort included adults presenting with open extremity degloving injuries to a tertiary level one trauma center between June 2018 and May 2022. We collected demographics, comorbidities, injury information, interventions, and complications. Propensity score weighting was used to minimize confounding differences between those presenting on weekends (Sat–Sun) versus weekdays (Mon–Fri). Weighted regressions were used to examine differences in interventions by day of presentation. Multivariable weighted regressions accounting for differences in interventions received were used to examine whether weekend presentation was associated with amputation risk, complications, or functional deficits. Results:. Ninety-five patients with 100 open extremity degloving injuries were included. In total, 39% of injuries were weekend-presenting. There was a higher rate of noninsulin-dependent diabetes among patients presenting on weekends (P = 0.03). Weekend-presenting injuries had higher median Injury Severity Scores (P = 0.04). Propensity-weighted regression analysis revealed differences in interventions received on weekends, including lower rates of pedicled and free flaps and bone graft, and increased rates of negative-pressure wound therapy (P ≤ 0.02). Multivariable regression analysis revealed weekend presentation was a significant independent risk factor for amputation of the affected extremity [odds ratio 2.27, 95% CI (1.01–5.33), P = 0.05]. Conclusion:. Weekend presentation may impact interventions received and amputation risk in patients presenting with open extremity degloving injuries.

Summary:. In the realm of oncologic reconstructive surgery, local or distant autologous tissue is frequently used to improve function and appearance. Due to advances in microsurgery and intensive care, reconstructive free flap surgery has become the standard treatment for head and neck cancer. However, the complexity of interdisciplinary intervention and prolonged surgical time inevitably increase the risk of cross-contamination, potentially leading to donor site metastasis. According to the literature, tumor transmission to the donor site of free flaps is extremely rare. We present the case of a 54-year-old man with left tongue squamous cell carcinoma. Three months after tumor ablation and reconstruction with a free anterolateral thigh flap, the patient presented with a mass on the donor site of the left thigh, which was proven to be a metastasis. A systemic workup revealed multiple metastases. Six months after reconstruction, the patient died of COVID-19 pneumonia. The incidence and risk factors of donor site metastasis are not well known. The primary causes are direct implantation or hematogenous spread. Cross-contamination is primarily prevented by the surgeon’s awareness and avoidance. The development of new-onset lesions at the donor site warrants additional testing to detect systemic disease progression during follow-up.

Purpose: To evaluate the performance of a deep learning (DL) algorithm for retinopathy of prematurity (ROP) screening in Nepal and Mongolia. Design: Retrospective analysis of prospectively collected clinical data. Participants: Clinical information and fundus images were obtained from infants in 2 ROP screening programs in Nepal and Mongolia. Methods: Fundus images were obtained using the Forus 3nethra neo (Forus Health) in Nepal and the RetCam Portable (Natus Medical, Inc.) in Mongolia. The overall severity of ROP was determined from the medical record using the International Classification of ROP (ICROP). The presence of plus disease was determined independently in each image using a reference standard diagnosis. The Imaging and Informatics for ROP (i-ROP) DL algorithm was trained on images from the RetCam to classify plus disease and to assign a vascular severity score (VSS) from 1 through 9. Main Outcome Measures: Area under the receiver operating characteristic curve and area under the precision-recall curve for the presence of plus disease or type 1 ROP and association between VSS and ICROP disease category. Results: The prevalence of type 1 ROP was found to be higher in Mongolia (14.0%) than in Nepal (2.2%; P

Background. ABO type B and O kidney transplant candidates have increased difficulty identifying a compatible donor for living donor kidney transplantation (LDKT) and are harder to match in kidney paired donation registries. A2-incompatible (A2i) LDKT increases access to LDKT for these patients. To better inform living donor selection, we evaluated the association between A2i LDKT and patient and graft survival. Methods. We used weighted Cox regression to compare mortality, death-censored graft failure, and all-cause graft loss in A2i versus ABO-compatible (ABOc) recipients. Results. Using Scientific Registry of Transplant Recipients data 2000–2019, we identified 345 A2i LDKT recipients. Mortality was comparable among A2i and ABOc recipients; weighted 1-/5-/10-y mortality was 0.9%/6.5%/24.2%, respectively, among A2i LDKT recipients versus 1.4%/7.7%/22.2%, respectively, among ABOc LDKT recipients (weighted hazard ratio [wHR], 0.811.041.33; P = 0.8). However, A2i recipients faced higher risk of death-censored graft failure; weighted 1-/5-/10-y graft failure was 5.7%/11.6%/22.4% for A2i versus 1.7%/7.5%/17.2% for ABOc recipients (wHR in year 1 = 2.243.565.66; through year 5 = 1.251.782.53; through year 10 = 1.151.552.07). By comparison, 1-/5-/10-y wHRs for A1-incompatible recipients were 0.631.966.08/0.390.942.27/0.390.831.74. Conclusions. A2i LDKT is generally safe, but A2i donor/recipient pairs should be counseled about the increased risk of graft failure and be monitored as closely as their A1-incompatible counterparts posttransplant.

Type 2 diabetes is a major threat to human health in the 21st century. More than half a billion people may suffer from this pandemic disease in 2030, leading to a huge burden of cardiovascular complications. Recently, 2 novel antidiabetic agents, glucagon-like peptide 1 receptor agonists and sodium-glucose cotransporter 2 inhibitors, reduced cardiovascular complications in a number of randomized control trials. To integrate new information and to achieve a streamlined process for better patient care, a working group was appointed by the Taiwan Society of Cardiology to formulate a stepwise consensus pathway for these therapies to reduce cardiovascular events in patients with type 2 diabetes. This consensus pathway is complementary to clinical guidelines, acting as a reference to improve patient care.

Small bowel obstruction is a blockage in the small intestine, which is usually caused by adhesion scar tissue, hernia, medication, or malignancy. The symptoms of small bowel obstruction include nausea and vomiting of bile, abdominal distention and obstipation. We present a case of a 61-year-old man with ankylosing spondylitis and scoliosis, who suffered from incomplete small bowel obstruction due to unusual direction of duodenum and externally compressed by liver, gallbladder and pancreas. We gave conservative treatment and inserted a nasojejunal tube for enteral feeding, and the duodenum broke free from the grip of liver, gallbladder and pancreas to its normal anatomical direction. Besides common etiology of small bowel obstruction, unusual body shape and smaller abdominal cavity may cause obstruction due to external compression of neighbor organs. Conservative treatments include gastrointestinal decompression, correction of electrolytes abnormality and nutrition support, while surgical intervention is suggested for the patient without improvement on conservative management.

Background: Nasal microbiota is crucial for the pathogenesis of allergic rhinitis (AR), which has been reported to be different from that of healthy individuals. However, no study has investigated the microbiota in nasal extracellular vesicles (EVs). We aimed to compare the microbiome composition and diversity in EVs between AR patients and healthy controls (HCs) and reveal the potential metabolic mechanisms in AR. Methods: Eosinophil counts and serum immunoglobulin E (IgE) levels were measured in patients with AR (n = 20) and HCs (n = 19). Nasal EVs were identified using transmission electron microscopy and flow cytometry. 16S rRNA sequencing was used to profile the microbial communities. Alpha and beta diversities were analyzed to determine microbial diversity. Taxonomic abundance was analyzed based on the linear discriminant analysis effect size (LEfSe). Microbial metabolic pathways were characterized using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUst2) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Results: Eosinophils, total serum IgE, and IgE specific to Dermatophagoides were increased in patients with AR. Alpha diversity in nasal EVs from patients with AR was lower than that in HCs. Beta diversity showed microbiome differences between the AR and HCs groups. The microbial abundance was distinct between AR and HCs at different taxonomic levels. Significantly higher levels of the genera Acetobacter, Mycoplasma, Escherichia, and Halomonas were observed in AR patients than in HCs. Conversely, Zoogloea, Streptococcus, Burkholderia, and Pseudomonas were more abundant in the HCs group than in the AR group. Moreover, 35 microbial metabolic pathways recognized in AR patients and HCs, and 25 pathways were more abundant in the AR group. Conclusion: Patients with AR had distinct microbiota characteristics in nasal EVs compared to that in HCs. The metabolic mechanisms of the microbiota that regulate AR development were also different. These findings show that nasal fluid may reflect the specific pattern of microbiome EVs in patients with AR.

Background: Degenerative signs on shoulder radiographs, including spur formation and narrow acromiohumeral intervals (AHIs), have been recognized as indicative of atrophic and fat-infiltrated rotator cuff muscles. Past studies have demonstrated that patients with poor quality muscles are prone to retraction of the supraspinatus tendon and failure to repair. However, the association between radiographic signs and tendon retraction has never been elucidated in previous literature. The present study aimed to investigate the association between the degenerative signs on shoulder radiographs and the severity of supraspinatus retraction. Methods: Images of 67 individuals, who had undergone an arthroscopic rotator cuff repair, were retrospectively reviewed. The greater tuberosity (GT) morphology, subacromial spur, AHI, and acromial thickness were evaluated on the radiographs, whereas the retraction of the supraspinatus tendon was assessed via an MRI in accordance with the Patte classification. Simple regression analyses between the radiographic signs and Patte stages were performed, and factors reaching statistical significance were then included in the multiple ordinal logistic regression. Statistically significant predictors from the multiple regression analysis were constructed into combinations, for which the sensitivity and specificity were calculated. Results: The GT morphology (P = .004), AHI (P = .083), subacromial spur (P = .008), and age (P = .004) were associated with supraspinatus retraction in the simple regression analyses. These four parameters were incorporated into the multiple ordinal logistic regression, where the GT spur (adjusted odds ratio 8.63, 95% confidence interval 2.16-34.53, P = .002) and AHI (AOR 0.79, 95% CI 0.63-0.98, P = .032) were demonstrated to be predictive of the Patte stage of supraspinatus retraction. The acromial spur implied a higher risk of severe retraction although this finding was not statistically significant (AOR 2.89, 95% CI 0.90-9.29, P = .075). The presence of concurrent GT spur and narrow AHI was highly specific (sensitivity 27.3% / specificity 91.1%) for advanced supraspinatus retraction. Conclusion: The presence of a radiographic GT spur, narrow AHI, and subacromial spur indicated advanced retraction of the supraspinatus tendon. When patients with clinical suspicion of rotator cuff tear present with combinations of these radiographic signs, a prompt MRI examination and a referral to a shoulder specialist are recommended.

Abernethy malformation refer to a congenital absence of intrahepatic portal veins leading to a primarily extrahepatic congenital portosystemic shunt. The lack of intrahepatic portal veins leads to a characteristic set of physical exam and imaging findings that may include hyperandrogenism and liver masses such as hepatic adenomas or focal nodular hyperplasia. In this case report, we describe a 20-year-old female who presented with an enlarging hepatic adenoma. A separate hepatic adenoma had previously been biopsied and noted to have undergone malignant degeneration into hepatocellular carcinoma. For each lesion, she was treated with combination transarterial embolization and microwave ablation. On follow-up imaging after therapy, it was then noted that her extrahepatic portal vein drained directly into the inferior vena cava, consistent with congenital portosystemic shunt. Recognition of this vascular anomaly is critical in treatment planning, as early intervention with either medical therapy or surgery can prevent the metabolic sequela of this unique constellation of symptoms.

Purpose: Developing robust artificial intelligence (AI) models for medical image analysis requires large quantities of diverse, well-chosen data that can prove challenging to collect because of privacy concerns, disease rarity, or diagnostic label quality. Collecting image-based datasets for retinopathy of prematurity (ROP), a potentially blinding disease, suffers from these challenges. Progressively growing generative adversarial networks (PGANs) may help, because they can synthesize highly realistic images that may increase both the size and diversity of medical datasets. Design: Diagnostic validation study of convolutional neural networks (CNNs) for plus disease detection, a component of severe ROP, using synthetic data. Participants: Five thousand eight hundred forty-two retinal fundus images (RFIs) collected from 963 preterm infants. Methods: Retinal vessel maps (RVMs) were segmented from RFIs. PGANs were trained to synthesize RVMs with normal, pre-plus, or plus disease vasculature. Convolutional neural networks were trained, using real or synthetic RVMs, to detect plus disease from 2 real RVM test datasets. Main Outcome Measures: Features of real and synthetic RVMs were evaluated using uniform manifold approximation and projection (UMAP). Similarities were evaluated at the dataset and feature level using Fréchet inception distance and Euclidean distance, respectively. CNN performance was assessed via area under the receiver operating characteristic curve (AUC); AUCs were compared via bootstrapping and Delong’s test for correlated receiver operating characteristic curves. Confusion matrices were compared using McNemar’s chi-square test and Cohen’s κ value. Results: The CNN trained on synthetic RVMs showed a significantly higher AUC (0.971; P = 0.006 and P = 0.004) and classified plus disease more similarly to a set of 8 international experts (κ = 0.922) than the CNN trained on real RVMs (AUC = 0.934; κ = 0.701). Real and synthetic RVMs overlapped, by plus disease diagnosis, on the UMAP manifold, showing that synthetic images spanned the disease severity spectrum. Fréchet inception distance and Euclidean distances suggested that real and synthetic RVMs were more dissimilar to one another than real RVMs were to one another, further suggesting that synthetic RVMs were distinct from the training data with respect to privacy considerations. Conclusions: Synthetic datasets may be useful for training robust medical AI models. Furthermore, PGANs may be able to synthesize realistic data for use without protected health information concerns.

Abstract. Rationale:. Pituitary apoplexy occurs in about 8% of those with nonfunctioning pituitary adenoma. Subsequent hormone deficiency, especially corticotropic deficiency, is the most common finding. We describe the unusual manifestations of adrenal insufficiency that are usually overlooked in such cases, with the aim of raising awareness of this disease. Patient concerns:. A 53-year-old male with a history of hyponatremia came to our hospital with intermittent fever and generalized pruritic skin rash. He also reported general weakness, abdominal pain, poor appetite, and severe retroorbital headache. Diagnoses:. Laboratory data revealed hypereosinophilia, hypotonic hyponatremia, and hypopituitarism, including secondary adrenal insufficiency. Sellar magnetic resonance imaging revealed a pituitary macroadenoma, 2 cm in height, with mild displacement of the optic chiasm. Pathologic report and immunohistochemical stains of surgical specimen showed pituitary gonadotropic adenoma with apoplexy. Interventions:. Transsphenoidal removal of the pituitary adenoma was performed. The patient received intravenous hydrocortisone then oral form cortisone acetate regularly. Outcomes:. His symptoms and laboratory data recovered after the operation and medical treatment. Lessons:. This case highlights that eosinophilia, pruritic skin rash and fever can be manifestations of adrenal insufficiency, and that they may initially be regarded as cellulitis.

Purpose: To compare the efficacy and efficiency of training neural networks for medical image classification using comparison labels indicating relative disease severity versus diagnostic class labels from a retinopathy of prematurity (ROP) image dataset. Design: Evaluation of diagnostic test or technology. Participants: Deep learning neural networks trained on expert-labeled wide-angle retinal images obtained from patients undergoing diagnostic ROP examinations obtained as part of the Imaging and Informatics in ROP (i-ROP) cohort study. Methods: Neural networks were trained with either class or comparison labels indicating plus disease severity in ROP retinal fundus images from 2 datasets. After training and validation, all networks underwent evaluation using a separate test dataset in 1 of 2 binary classification tasks: normal versus abnormal or plus versus nonplus. Main Outcome Measures: Area under the receiver operating characteristic curve (AUC) values were measured to assess network performance. Results: Given the same number of labels, neural networks learned more efficiently by comparison, generating significantly higher AUCs in both classification tasks across both datasets. Similarly, given the same number of images, comparison learning developed networks with significantly higher AUCs across both classification tasks in 1 of 2 datasets. The difference in efficiency and accuracy between models trained on either label type decreased as the size of the training set increased. Conclusions: Comparison labels individually are more informative and more abundant per sample than class labels. These findings indicate a potential means of overcoming the common obstacle of data variability and scarcity when training neural networks for medical image classification tasks.

Purpose: To determine whether handheld widefield OCT can be used to document retinopathy of prematurity (ROP) stage while using scleral depression to improve peripheral views. Design: Prospective, observational study. Participants: Consecutive neonates admitted to the neonatal intensive care unit in a single academic medical center who also met criteria for ROP screening and whose parents or guardians consented for them to undergo research imaging. Methods: Scleral depression was combined with widefield OCT using an investigational 400-kHz, 55° field of view, handheld OCT during routine ROP screening from October 28, 2020, through March 3, 2021. Main Outcome Measures: Acquisition of en face and B-scan imaging of the peripheral retina to assess early vitreoretinal pathologic features objectively, including the demarcation between vascularized and anterior avascular retina, the presence of early ridge formation, and small neovascular tufts. Results: Various stages of ROP were detected using a rapid-acquisition OCT system. In 1 neonate, serial OCT imaging over a 5-week period demonstrated accumulation of neovascular tufts with progression to stage 3 ROP with extraretinal fibrovascular proliferation along the ridge. Videography of this technique is included in this report for instructional purposes. Conclusions: Serial examinations using widefield OCT and scleral depression are feasible and may improve detection and documentation of ROP disease progression. Earlier detection of ROP-related proliferation may prevent vitreoretinal traction, retinal detachment, and blindness.

Background. Few reports have focused on newer coronavirus disease 2019 (COVID-19) therapies (remdesivir, dexamethasone, and convalescent plasma) in solid organ transplant recipients; concerns had been raised regarding possible adverse impact on allograft function or secondary infections. Methods. We studied 77 solid organ transplant inpatients with COVID-19 during 2 therapeutic eras (Era 1: March–May 2020, 21 patients; and Era 2: June–November 2020, 56 patients) and 52 solid organ transplant outpatients. Results. In Era 1, no patients received remdesivir or dexamethasone, and 4 of 21 (19.4%) received convalescent plasma, whereas in Era 2, remdesivir (24/56, 42.9%), dexamethasone (24/56, 42.9%), and convalescent plasma (40/56, 71.4%) were commonly used. Mortality was low across both eras, 4 of 77 (5.6%), and rejection occurred in only 2 of 77 (2.8%) inpatients; infections were similar in hypoxemic patients with or without dexamethasone. Preexisting graft dysfunction was associated with greater need for hospitalization, higher severity score, and lower survival. Acute kidney injury was present in 37.3% of inpatients; renal function improved more rapidly in patients who received remdesivir and convalescent plasma. Post–COVID-19 renal and liver function were comparable between eras, out to 90 d. Conclusions. Newer COVID-19 therapies did not appear to have a deleterious effect on allograft function, and infectious complications were comparable.

Purpose: Generative adversarial networks (GANs) are deep learning (DL) models that can create and modify realistic-appearing synthetic images, or deepfakes, from real images. The purpose of our study was to evaluate the ability of experts to discern synthesized retinal fundus images from real fundus images and to review the current uses and limitations of GANs in ophthalmology. Design: Development and expert evaluation of a GAN and an informal review of the literature. Participants: A total of 4282 image pairs of fundus images and retinal vessel maps acquired from a multicenter ROP screening program. Methods: Pix2Pix HD, a high-resolution GAN, was first trained and validated on fundus and vessel map image pairs and subsequently used to generate 880 images from a held-out test set. Fifty synthetic images from this test set and 50 different real images were presented to 4 expert ROP ophthalmologists using a custom online system for evaluation of whether the images were real or synthetic. Literature was reviewed on PubMed and Google Scholars using combinations of the terms ophthalmology, GANs, generative adversarial networks, ophthalmology, images, deepfakes, and synthetic. Ancestor search was performed to broaden results. Main Outcome Measures: Expert ability to discern real versus synthetic images was evaluated using percent accuracy. Statistical significance was evaluated using a Fisher exact test, with P values ≤ 0.05 thresholded for significance. Results: The expert majority correctly identified 59% of images as being real or synthetic (P = 0.1). Experts 1 to 4 correctly identified 54%, 58%, 49%, and 61% of images (P = 0.505, 0.158, 1.000, and 0.043, respectively). These results suggest that the majority of experts could not discern between real and synthetic images. Additionally, we identified 20 implementations of GANs in the ophthalmology literature, with applications in a variety of imaging modalities and ophthalmic diseases. Conclusions: Generative adversarial networks can create synthetic fundus images that are indiscernible from real fundus images by expert ROP ophthalmologists. Synthetic images may improve dataset augmentation for DL, may be used in trainee education, and may have implications for patient privacy.

Purpose: To observe the impact of using scribes on documentation efficiency in ophthalmology clinics. Design: Single-center retrospective cohort study. Participants: A total of 29 997 outpatient visits conducted by 7 attending ophthalmologists between January 1, 2018, and December 31, 2019, were included in the study: 18 483 with a scribe present during the encounter and 11 514 without a scribe present. Methods: Use of a scribe. Main Outcome Measures: Total physician documentation time, physician documentation time during and after the visit, visit length, time to chart closure, note length, and percentage of note text edited by physician. Results: Total physician documentation time was significantly less when working with a scribe (mean ± standard deviation, 4.7 ± 2.9 minutes/note vs. 7.6 ± 3.8 minutes/note; P < 0.001), as was documentation time during the visit (2.8 ± 2.2 minutes/note vs. 5.9 ± 3.1 minutes/note; P < 0.001). Physicians also edited scribed notes less, deleting 1.9 ± 4.4% of scribes’ draft note text and adding 14.8 ± 11.4% of the final note text, compared with deleting 6.0 ± 9.1% (P < 0.001) of draft note text and adding 21.2 ± 15.3% (P < 0.001) of final note text when not working with a scribe. However, physician after-visit documentation time was significantly higher with a scribe for 3 of 7 physicians (P < 0.001). Scribe use was also associated with an office visit length increase of 2.9 minutes (P < 0.001) per patient and time to chart closure of 3.0 hours (P < 0.001), according to mixed-effects linear models. Conclusions: Scribe use was associated with increased documentation efficiency through lower total documentation time and less note editing by physicians. However, the use of a scribe was also associated with longer office visit lengths and time to chart closure. The variability in the impact of scribe use on different measures of documentation efficiency leaves unanswered questions about best practices for the implementation of scribes and warrants further study of effective scribe use.

Purpose: Retinopathy of prematurity (ROP) is a leading cause of childhood blindness related to oxygen exposure in premature infants. Since oxygen monitoring protocols have reduced the incidence of treatment-requiring ROP (TR-ROP), it remains unclear whether oxygen exposure remains a relevant risk factor for incident TR-ROP and aggressive ROP (A-ROP), a severe, rapidly progressing form of ROP. The purpose of this proof-of-concept study was to use electronic health record (EHR) data to evaluate early oxygen exposure as a predictive variable for developing TR-ROP and A-ROP. Design: Retrospective cohort study. Participants: Two hundred forty-four infants screened for ROP at a single academic center. Methods: For each infant, oxygen saturations and fraction of inspired oxygen (FiO2) were extracted manually from the EHR until 31 weeks postmenstrual age (PMA). Cumulative minimum, maximum, and mean oxygen saturation and FiO2 were calculated on a weekly basis. Random forest models were trained with 5-fold cross-validation using gestational age (GA) and cumulative minimum FiO2 at 30 weeks PMA to identify infants who developed TR-ROP. Secondary receiver operating characteristic (ROC) curve analysis of infants with or without A-ROP was performed without cross-validation because of small numbers. Main Outcome Measures: For each model, cross-validation performance for incident TR-ROP was assessed using area under the ROC curve (AUC) and area under the precision-recall curve (AUPRC) scores. For A-ROP, we calculated AUC and evaluated sensitivity and specificity at a high-sensitivity operating point. Results: Of the 244 infants included, 33 developed TR-ROP, of which 5 developed A-ROP. For incident TR-ROP, random forest models trained on GA plus cumulative minimum FiO2 (AUC = 0.93 ± 0.06; AUPRC = 0.76 ± 0.08) were not significantly better than models trained on GA alone (AUC = 0.92 ± 0.06 [P = 0.59]; AUPRC = 0.74 ± 0.12 [P = 0.32]). Models using oxygen alone showed an AUC of 0.80 ± 0.09. ROC analysis for A-ROP found an AUC of 0.92 (95% confidence interval, 0.87–0.96). Conclusions: Oxygen exposure can be extracted from the EHR and quantified as a risk factor for incident TR-ROP and A-ROP. Extracting quantifiable clinical features from the EHR may be useful for building risk models for multiple diseases and evaluating the complex relationships among oxygen exposure, ROP, and other sequelae of prematurity.

Purpose: Stereotactic body radiation therapy (SBRT) treatment planning for renal cell carcinoma requires accurate delineation of tumor from normal tissue due to the radiosensitivity of normal renal cortical tissue. Tc-99m dimercapto succinic acid (DMSA) renal imaging is a functional imaging technique that precisely differentiates normal renal cortical tissue from tumor. There are no prior publications reporting using this imaging modality for SBRT treatment planning. Methods and Materials: A 59-year-old female with stage IV renal cell carcinoma progressed on systemic therapy and was dispositioned to primary cytoreduction with SBRT. She had baseline renal dysfunction and her tumor was 9 cm without clear delineation from normal tissue on conventional imaging. DMSA-single-photon emission computerized tomography (SPECT)/computed tomography (CT) was used for treatment planning. Results: DMSA-SPECT/CT precisely delineated normal renal cortical tissue from tumor. Three months after treatment, labs were stable and DMSA-SPECT/CT was unchanged. The treated lesion had markedly decreased positron emission tomography avidity. Conclusions: DMSA-SPECT or SPECT/CT can be incorporated into radiation therapy planning for renal lesions to improve target delineation and better preserve renal function.

Background. Kidney transplantation (KT) is controversial in patients with pretransplant pulmonary hypertension (PtPH). We aimed to quantify post-KT graft and patient survival as well as survival benefit in recipients with PtPH. Methods. Using UR Renal Data System (2000–2018), we studied 90 819 adult KT recipients. Delayed graft function, death-censored graft failure, and mortality were compared between recipients with and without PtPH using inverse probability weighted logistic and Cox regression. Survival benefit of KT was determined using stochastic matching and stabilized inverse probability treatment Cox regression. Results. Among 90 819 KT recipients, 2641 (2.9%) had PtPH. PtPH was associated with higher risk of delayed graft function (odds ratio, 1.23; 95% CI, 1.10-1.36; P

Background. A widely accepted severe acute respiratory syndrome 2 (SARS-CoV-2) vaccine could protect vulnerable populations, but the willingness of solid organ transplant recipients (SOTRs) to accept a potential vaccine remains unknown. Methods. We conducted a national survey of 1308 SOTRs and 1617 non-SOTRs between November 11 and December 2, 2020 through the network of the National Kidney Foundation. Results. Respondents were largely White (73.2%), female (61.1%), and college graduates (56.2%). Among SOTRs, half (49.5%) were unsure or would be unwilling to receive a SARS-CoV-2 vaccine once available. Major concerns included potential side effects (85.2%), lack of rigor in the testing and development process (69.7%), and fear of incompatibility with organ transplants (75.4%). Even after the announcement of the high efficacy of the mRNA-1273 vaccine (Moderna Inc.) at the time of survey distribution, likeliness to receive a vaccine only slightly increased (53.5% before announcement versus 57.8% after the announcement). However, 86.8% of SOTRs would accept a vaccine if recommended by a transplant provider. Conclusions. SOTRs reported skepticism in receiving a potential SARS-CoV-2 vaccine, even after announcements of high vaccine efficacy. Reassuringly, transplant providers may be the defining influence in vaccine acceptance and will likely have a critical role to play in promoting vaccine adherence.

Background: Immune checkpoint inhibitors (ICIs) have become an increasingly important tool in cancer treatment, revealing durable responses in several different types of tumors, including NSCLCs. Nevertheless, ICIs carry a risk of immune-mediated toxicities. There is a paucity of data for concurrent use of these agents in patients with autoimmune disorders, such as multiple sclerosis (MS). Case Presentation: We report a case of a man with a history of MS and metastatic NSCLC with brain metastases who had cancer progression after receiving chemotherapy, whole-brain radiation therapy, and stereotactic radiosurgery to brain lesions and was treated with the programmed death-ligand 1 inhibitor, atezolizumab. He had dramatic clinical and radiographic benefit but developed a severe MS flare and neurologic decline precluding further treatment. Considerable growth of a previously radiated brain lesion prompted resection, with pathologic findings consistent with radiation necrosis and demyelination without viable tumor cells. Conclusions: Although patients with preexisting autoimmune diseases, including MS, might be at an increased risk of developing immune-related adverse events with ICIs, they may also experience anticancer benefit. Intracranial disease can be challenging to accurately diagnose in a patient with MS who previously underwent radiation, as progressing lesions can be tumor growth, MS flare, or radiation necrosis.

Introduction: Geriatric-orthopaedic co-management models can improve patient outcomes. However, prior reports have been at large academic centers with “closed” systems and an inpatient geriatric service. Here we describe a Geriatric Fracture Program (GFP) in a mixed practice “pluralistic” environment that includes employed academic faculty, private practice physicians, and multiple private hospitalist groups. We hypothesized GFP enrollment would reduce length of stay (LOS), time to surgery (TTS), and total hospital costs compared to non-GFP patients. Materials and Methods: A multidisciplinary team was created around a geriatric Nurse Practitioner (NP) and consulting geriatrician. Standardized geriatric focused training programs and electronic tools were developed based on best practice guidelines. Fracture patients >65 years old were prospectively enrolled from July 2018 – June 2019. A trained biostatistician performed all statistical analyses. A p < 0.05 was considered significant. Results: 564 operative and nonoperative fractures in patients over 65 were prospectively followed with 153 (27%) enrolled in the GFP and 411 (73%) admitted to other hospitalists or their primary care provider (non-GFP). Patients enrolled in the GFP had a significantly shorter median LOS of 4 days, compared to 5 days in non-GFP patients (P < 0.001). There was a strong trend towards a shorter median TTS in the GFP group (21.5 hours v 25 hours, p = 0.066). Mean total costs were significantly lower in the GFP group ($25,323 v $29085, p = 0.022) Discussion: Our data shows that a geriatric-orthopaedic co-management model can be successfully implemented without an inpatient geriatric service, utilizing the pre-existing resources in a complex environment. The program can be expanded to include additional groups to improve care for entire geriatric fracture population with significant anticipated cost savings. Conclusions: With close multidisciplinary team work, a successful geriatric-orthopaedic comanagement model for geriatric fractures can be implemented in even a mixed practice environment without an inpatient geriatrics service.

Atrial fibrillation (AF) is the most common sustained arrhythmia, causing a 2-fold increase in mortality and a 5-fold increase in stroke. The Asian population is rapidly aging, and in 2050, the estimated population with AF will reach 72 million, of whom 2.9 million may suffer from AF-associated stroke. Therefore, stroke prevention in AF is an urgent issue in Asia. Many innovative advances in the management of AF-associated stroke have emerged recently, including new scoring systems for predicting stroke and bleeding risks, the development of non-vitamin K antagonist oral anticoagulants (NOACs), knowledge of their special benefits in Asians, and new techniques. The Asia Pacific Heart Rhythm Society (APHRS) aimed to update the available information, and appointed the Practice Guideline sub-committee to write a consensus statement regarding stroke prevention in AF. The Practice Guidelines sub-committee members comprehensively reviewed updated information on stroke prevention in AF, emphasizing data on NOACs from the Asia Pacific region, and summarized them in this 2017 Consensus of the Asia Pacific Heart Rhythm Society on Stroke Prevention in AF. This consensus includes details of the updated recommendations, along with their background and rationale, focusing on data from the Asia Pacific region. We hope this consensus can be a practical tool for cardiologists, neurologists, geriatricians, and general practitioners in this region. We fully realize that there are gaps, unaddressed questions, and many areas of uncertainty and debate in the current knowledge of AF, and the physician׳s decision remains the most important factor in the management of AF.

The present report describes a case of acute airway obstruction in a newborn caused by an expanding hemorrhagic macrocystic lymphatic malformation (LM), which was successfully treated with emergent decompression and interventional radiology-guided sclerotherapy. The use of sclerotherapy for macrocystic LMs has been well described for various indications. The urgent interventional treatment obviated the need for a tracheostomy. This case describes the rapid diagnosis and use of sclerotherapy in a large expanding macrocystic LM.

Summary: Several studies have shown the beneficial effect of renal denervation (RDN) in the treatment of ventricular arrhythmia, especially in the setting of heart failure (HF). However, the underlying mechanism of antiarrhythmic effect of RDN is unknown. Arrhythmogenic cardiac alternans, particularly spatially discordant repolarization alternans, characterized by simultaneous prolongation and shortening of action potential duration (APD) in different myocardial regions, is central to the genesis of ventricular fibrillation in HF. Whether RDN decreases the susceptibility to arrhythmogenic cardiac alternans in HF has never been addressed before. The authors used a rat model of post-myocardial infarction HF and dual voltage-calcium optical mapping to investigate whether RDN could attenuate arrhythmogenic cardiac alternans that predisposes to ventricular arrhythmias, as well as the hemodynamic effect of RDN in HF. The HF rats had increased body weights, dilated hearts, and lower blood pressure. The HF rats also had longer ventricular APDs and a delay in the decay of the calcium transient, typical electrophysiological features of human HF. Susceptibility to calcium transient alternans, APD alternans, and spatially discordant APD alternans was increased in the HF hearts. RDN significantly attenuated a delay in the decay of the calcium transient, calcium transient and APD alternans, and importantly, the discordant APD alternans, and thereby decreased the incidence of induced ventricular arrhythmia in HF. RDN did not further decrease blood pressure in HF rats. In conclusion, RDN improves calcium cycling and prevents spatially discordant APD alternans and ventricular arrhythmia in HF. RDN does not aggravate hemodynamics in HF. Key Words: alternans, arrhythmia mechanism, heart failure, renal denervation

ABSTRACT: Objective: To increase awareness of unusual inflammatory and other responses including severe insulin resistance (IR) associated with the use of targeted immunotherapies such as brentuximab. Methods: We report the case of a man without any previous diagnosis of diabetes who developed diabetic ketoacidosis complicated by severe IR (unresponsive to >600 units of intravenous insulin per hour) after receiving brentuximab for Hodgkin lymphoma. Results: Autoantibodies to the insulin receptor were not detected in the patient's serum, thus excluding a diagnosis of type B IR. Conclusion: We hypothesize that brentuximab administration led to a rare reaction leading to systemic cytokine release with extreme IR in our patient.

Background. A multicenter, randomized, open-label, parallel group, pilot, 52-week study in Asian countries that assessed the renal function, efficacy, and safety of reduced-exposure versus standard-exposure prolonged-release tacrolimus (PR-T) in adult kidney transplant recipients (KTRs). Methods. Posttransplantation, KTRs received PR-T from weeks 0 to 4 (initial dose, 0.2–0.3 mg/kg; target trough level, 6–10 ng/mL). At week 4, KTRs were randomized (1:1) to receive reduced-exposure PR-T (target 4–6 ng/mL, weeks 4–12; 3–5 ng/mL, weeks 12–52) or standard-exposure PR-T (target: 6–10 ng/mL, weeks 4–52). Primary end point: estimated glomerular filtration rate (eGFR) over 52 weeks. Secondary end points (week 52) included creatinine clearance, serum creatinine, graft/patient survival, biopsy-confirmed acute rejection (AR), composite of graft loss/patient death/biopsy-confirmed AR, and steroid-resistant AR. Treatment-emergent adverse events were recorded. Results. Sixty-six KTRs received PR-T (reduced-exposure, n = 32; standard-exposure, n = 34) and were analyzed. After per-protocol dose adjustment, mean ± standard deviation tacrolimus trough level was lower with reduced- versus standard-exposure PR-T (week 52, 4.5 ± 1.1 ng/mL vs 8.0 ± 2.2 ng/mL). In the reduced- versus standard-exposure group, eGFR was similar at weeks 8 to 52 (overall least-square mean difference, –2.82; 95% confidence interval, −7.91 to 2.27; P = 0.272). At week 52, there was no significant difference in creatinine clearance (P = 0.375) or serum creatinine (P = 0.547) between groups. All grafts/patients survived, no steroid-resistant AR was reported, and 4 and 3 patients had AR in reduced- and standard-exposure groups, respectively. Drug-related treatment-emergent adverse events were reported in 34.4% and 38.2% of patients, respectively. Conclusions. Reducing exposure to PR-T resulted in a clinically acceptable short-term safety profile and was generally as effective as standard tacrolimus exposure for Asian patients.

Introduction . Radiation therapy using ionizing radiation is widely used for the treatment of prostate cancer. The intrinsic radiation sensitivity of cancer cells could be enhanced by modulating multiple factors including the capacity to repair DNA damage, especially double-strand breaks (DSBs). We aimed to examine the effect of zerumbone on radiation sensitivity and its protective effects against ionizing radiation–induced DSB in human prostate cancer cells. Materials and Methods . The human prostate cancer PC3 and DU145 cell lines were used. A colony formation assay was performed to analyze the radiation survival of cells. DNA histogram and generation of reactive oxygen species (ROS) were examined using flow cytometry. Western blotting was used to examine the expression of regulatory molecules related to DNA damage repair. Results . Pretreatment with zerumbone enhanced the radiation effect on prostate cancer cells. Zerumbone delayed the abrogation of radiation-induced expression of γ-H2AX, an indicator of DNA DSB. Zerumbone pretreatment markedly reduced ionizing radiation–induced upregulated expression of phosphorylated ATM (ataxia telangiectasia-mutated), which was partially reversed by the ATM agonist methyl methanesulfonate. Ionizing radiation augmented and zerumbone pretreatment reduced the expression of Jak2 and Stat3, which are involved in DNA damage repair signaling. No significant effect on the generation of ROS and expression of ATR was noted after zerumbone treatment. Conclusion : Zerumbone sensitized DU145 and PC3 prostatic cancer cells to ionizing radiation by modulating radiation-induced ATM activation during repair of DNA DSBs.

Relatively few studies have addressed the risk factors of erectile dysfunction (ED) in Taiwanese— most have described ED and medical problems in the general population. In this study, the cardiovascular risk factors of ED among aborigines in Taiwan were investigated. However, alcohol dependence (AD) was prevalent in Taiwan’s aborigine population. So this study also focused on the relationship among AD, the cardiovascular risk factors and ED. A cross-sectional study was conducted, and data was obtained from a baseline survey of 192 aboriginal adults (35-75 years of age). The participants’ demographic data, AD, markers of endothelial function, serum testosterone, and ED status were assessed. Ninety-four (49%) of the 192 participants had a history of alcoholism and 79 (84%) of those with alcoholism had ED. The study reported that AD and hyperlipidemia, metabolic syndrome (MetS), ED, abnormality of testosterone, and high-sensitivity C-reactive protein are highly prevalent among the aborigines. Factors that may affect ED included age, AD, central obesity, diabetes mellitus, hyperlipidemia, hypertension, MetS, and testosterone. ED is highly prevalent among aborigines with the risk factors of AD, MetS, old age, and abnormal testosterone serum level. MetS, atherosclerosis, and ED are risk factors for cardiovascular diseases. Hence, an increased focus on Taiwanese aborigines with ED is necessary.