Prediction of immunochemotherapy response for diffuse large B-cell lymphoma using artificial intelligence digital pathology.

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous and prevalent subtype of aggressive non-Hodgkin lymphoma that poses diagnostic and prognostic challenges, particularly in predicting drug responsiveness. In this study, we used digital pathology and deep learning to predict responses to immunochemotherapy in patients with DLBCL. We retrospectively collected 251 slide images from 216 DLBCL patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), with their immunochemotherapy response labels. The digital pathology images were processed using contrastive learning for feature extraction. A multi-modal prediction model was developed by integrating clinical data and pathology image features. Knowledge distillation was employed to mitigate overfitting on gigapixel histopathology images to create a model that predicts responses based solely on pathology images. Based on the importance derived from the attention mechanism of the model, we extracted histological features that were considered key textures associated with drug responsiveness. The multi-modal prediction model achieved an impressive area under the ROC curve of 0.856, demonstrating significant associations with clinical variables such as Ann Arbor stage, International Prognostic Index, and bulky disease. Survival analyses indicated their effectiveness in predicting relapse-free survival. External validation using TCGA datasets supported the model's ability to predict survival differences. Additionally, pathology-based predictions show promise as independent prognostic indicators. Histopathological analysis identified centroblastic and immunoblastic features to be associated with treatment response, aligning with previous morphological classifications and highlighting the objectivity and reproducibility of artificial intelligence-based diagnosis. This study introduces a novel approach that combines digital pathology and clinical data to predict the response to immunochemotherapy in patients with DLBCL. This model shows great promise as a diagnostic and prognostic tool for clinical management of DLBCL. Further research and genomic data integration hold the potential to enhance its impact on clinical practice, ultimately improving patient outcomes.

Removal of intrahepatic bile duct stone could reduce the risk of cholangiocarcinoma: A single-center retrospective study in South Korea.

BACKGROUND: Intrahepatic duct (IHD) stones are among the most important risk factors for cholangiocarcinoma (CCC). Approximately 10% of patients with IHD stones develop CCC; however, there are limited studies regarding the effect of IHD stone removal on CCC development. AIM: To investigate the association between IHD stone removal and CCC development. METHODS: We retrospectively analyzed 397 patients with IHD stones at a tertiary referral center between January 2011 and December 2020. RESULTS: CCC occurred in 36 of the 397 enrolled patients. In univariate analysis, chronic hepatitis B infection (11.1% vs 3.0%, P = 0.03), carbohydrate antigen 19-9 (CA19-9, 176.00 vs 11.96 II/mL, P = 0.010), stone located in left or both lobes (86.1% vs 70.1%, P = 0.042), focal atrophy (52.8% vs 26.9%, P = 0.001), duct stricture (47.2% vs 24.9%, P = 0.004), and removal status of IHD stone (33.3% vs 63.2%, P < 0.001) were significantly different between IHD stone patients with and without CCC. In the multivariate analysis, CA19-9 > upper normal limit, carcinoembryonic antigen > upper normal limit, stones located in the left or both lobes, focal atrophy, and complete removal of IHD stones without recurrence were independent factors influencing CCC development. However, the type of removal method was not associated with CCC risk. CONCLUSION: Complete removal of IHD stones without recurrence could reduce CCC risk.

Ensemble Deep Learning Model to Predict Lymphovascular Invasion in Gastric Cancer.

Lymphovascular invasion (LVI) is one of the most important prognostic factors in gastric cancer as it indicates a higher likelihood of lymph node metastasis and poorer overall outcome for the patient. Despite its importance, the detection of LVI(+) in histopathology specimens of gastric cancer can be a challenging task for pathologists as invasion can be subtle and difficult to discern. Herein, we propose a deep learning-based LVI(+) detection method using H&E-stained whole-slide images. The ConViT model showed the best performance in terms of both AUROC and AURPC among the classification models (AUROC: 0.9796; AUPRC: 0.9648). The AUROC and AUPRC of YOLOX computed based on the augmented patch-level confidence score were slightly lower (AUROC: -0.0094; AUPRC: -0.0225) than those of the ConViT classification model. With weighted averaging of the patch-level confidence scores, the ensemble model exhibited the best AUROC, AUPRC, and F1 scores of 0.9880, 0.9769, and 0.9280, respectively. The proposed model is expected to contribute to precision medicine by potentially saving examination-related time and labor and reducing disagreements among pathologists.

A robust model training strategy using hard negative mining in a weakly labeled dataset for lymphatic invasion in gastric cancer.

Gastric cancer is a significant public health concern, emphasizing the need for accurate evaluation of lymphatic invasion (LI) for determining prognosis and treatment options. However, this task is time-consuming, labor-intensive, and prone to intra- and interobserver variability. Furthermore, the scarcity of annotated data presents a challenge, particularly in the field of digital pathology. Therefore, there is a demand for an accurate and objective method to detect LI using a small dataset, benefiting pathologists. In this study, we trained convolutional neural networks to classify LI using a four-step training process: (1) weak model training, (2) identification of false positives, (3) hard negative mining in a weakly labeled dataset, and (4) strong model training. To overcome the lack of annotated datasets, we applied a hard negative mining approach in a weakly labeled dataset, which contained only final diagnostic information, resembling the typical data found in hospital databases, and improved classification performance. Ablation studies were performed to simulate the lack of datasets and severely unbalanced datasets, further confirming the effectiveness of our proposed approach. Notably, our results demonstrated that, despite the small number of annotated datasets, efficient training was achievable, with the potential to extend to other image classification approaches used in medicine.

Metastatic pancreatic solitary fibrous tumor: A case report.

BACKGROUND: Solitary fibrous tumor (SFT) is a rare mesenchymal tumor that is most commonly found in the pleura but can also originate from non-pleural sites. Among the non-pleural localizations, the pancreas is extremely rare. In particular, metastasis to the pancreas from the central nervous system (CNS) is extremely rare, with only two cases reported so far. We report a case of recurrence in the pancreas 14 years after the initial complete surgical removal of a tumor in the CNS. CASE SUMMARY: A 68-year-old man with a past medical history of recurrent meningeal hemangiopericytoma, currently referred to as SFT, presented to the hospital with jaundice. The patient was first diagnosed with an 8cm-sized meningeal hemangiopericytoma fourteen years ago and underwent osteoplastic craniotomy. After 16 mo, imaging showed recurrence and he underwent gamma knife radiosurgery (GKRS). 2 years later, imaging showed recurrence again leading to a second GKRS. 5 years later, recurrence was again suspected leading to a second craniotomy. Since then 3 years had passed, and imaging showed a 3.5cm-sized mass lesion on the pancreatic head with obstruction of the pancreatic and bile ducts. Endosonography with fine-needle aspiration biopsy was done preoperatively and aided in the diagnosis of SFT. The patient underwent pylorus-preserving pancreaticoduodenectomy. Pathologic findings of the resected pancreatic specimen, consistent with the previously resected brain specimen, confirmed the diagnosis of SFT. CONCLUSION: The rarity and lack of knowledge about SFTs make suspecting and diagnosing this disease challenging. We believe that a report of metastatic pancreatic SFT from the CNS will contribute to a better understanding of this rare disease.

Diagnostic performance of the fibrosis-4 index and the NAFLD fibrosis score for screening at-risk individuals in a health check-up setting.

BACKGROUND: The fibrosis-4 index (FIB-4) and the NAFLD fibrosis score (NFS) have been used as noninvasive screening methods for advanced fibrosis in patients with NAFLD. However, their diagnostic performance has not been evaluated in at-risk individuals regardless of hepatic steatosis. This study evaluated the performance of the FIB-4 and NFS in at-risk groups of health check-up examinees at mass screening centers. METHODS: This retrospective, cross-sectional study included 8545 participants who underwent voluntary magnetic resonance elastography at a discounted fee during their regular health check-ups at 13 mass screening centers nationwide. The at-risk group was defined as those with any of the following conditions: NAFLD, 2 or more metabolic abnormalities, diabetes mellitus, or abnormal aminotransferase levels. A magnetic resonance elastography cutoff of ≥3.6 kPa was used to define conventional advanced fibrosis. RESULTS: According to the proposed criteria, the proportion of at-risk individuals was 67.4%-80.2% in the health check-up cohort without viral or alcohol-associated liver disease. The prevalence of individuals with advanced hepatic fibrosis in each at-risk group was ~2.3%-2.8% according to various criteria. It was higher in patients without NAFLD than in those with NAFLD. A total of 28.2%-39.6% of those in each at-risk group did not show hepatic steatosis on ultrasonography. The performance of FIB-4 for advanced fibrosis in the at-risk group was comparable with that in the NAFLD group. FIB-4 showed a better area under the receiver operating characteristic curve and sensitivity than NFS in the at-risk group. CONCLUSIONS: FIB-4 demonstrated superior performance compared with the NFS, and its performance in at-risk individuals was similar to that observed for patients with NAFLD.

Integrative Korean Medicine Treatments for Traumatic Facial Palsy Following Mandibular Fracture: A Case Report and Literature Review.

Prior studies exploring the effectiveness of traditional Korean medicine (TKM) treatment for facial palsy have mainly focused on Bell's palsy, and there are few studies on the effectiveness of TKM treatments for traumatic facial palsy following mandibular fracture. The patient was a 24-year-old Korean man with left-sided facial paralysis following a left mandibular fracture. Surgery was performed for the fracture and the facial palsy was treated using conventional medicine (CM) treatments for approximately 3 months, but there was no improvement observed in the patient's condition. Subsequently, the patient underwent an integrative Korean medicine treatment regimen consisting of acupuncture, pharmacopuncture, cupping, moxibustion, and herbal medication for a duration of 2 months. After 2 months of treatments, the House-Brackmann facial grading scale changed from Ⅴ to II and Yanagihara's unweighted grading score increased from 9 to 34. This case presentation and previous studies of traumatic facial palsy using TKM treatment show that TKM treatment may be considered a complementary or alternative treatment method to CM treatment in patients with traumatic facial palsy. PROSPERO registration number: CRD42023445051.

Diagnostic Performance of the Fibrosis-4 Index and Nonalcoholic Fatty Liver Disease Fibrosis Score in Lean Adults With Nonalcoholic Fatty Liver Disease.

IMPORTANCE: The diagnostic performance of the fibrosis-4 index (FIB-4) and nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS) for advanced fibrosis in lean patients with NAFLD is limited. OBJECTIVE: To evaluate the diagnostic performance of the FIB-4 and NFS in lean individuals with NAFLD. DESIGN, SETTING, AND PARTICIPANTS: This diagnostic study included adults with biopsy-proven NAFLD from 6 referral centers in Asia from 1995 to 2019. Cohorts were matched by age and sex between the lean and nonlean groups. All statistical analyses were executed from October 2022 to March 2023. MAIN OUTCOMES AND MEASURES: The diagnostic performance of the FIB-4 and NFS at the current cutoff for advanced hepatic fibrosis in lean (body mass index [BMI] below 23 [calculated as weight in kilograms divided by height in meters squared]) and nonlean (BMI above 23) patients were evaluated. RESULTS: A total of 1501 patients were included in analysis (mean [SD] age, 46.1 [16.4] years); 788 male (52.5%), 115 lean (7.7%), 472 (30.2%) Korean, 821 (48.7%) Japanese, and 341 (21.3%) Taiwanese. Among the age- and sex-matched cohort, the mean (SD) age was 52.3 (15.1) years and 41.2% (47 of 114) were male. The diagnostic performance and areas under the operating characteristic curve of the FIB-4 (lean, 0.807 vs nonlean, 0.743; P = .28) and NFS (lean, 0.790 vs nonlean, 0.755; P = .54) between the 2 groups were comparable in the age- and sex-matched cohort. The sensitivity and specificity of the NFS showed increasing and decreasing tendency according to the BMI quartiles (P for trend < .001), while those of the FIB-4 did not (P for trend = .05 and P = .20, respectively). Additionally, although the areas under the operating characteristic curve of the FIB-4 and NFS were not significantly different in the lean group (0.807 vs 0.790; P = .09), the sensitivity of the current NFS cutoff values was lower in the lean group than in that of FIB-4 (54.4% vs 81.8%; P = .03). CONCLUSIONS AND RELEVANCE: In this cohort study, the performance of the FIB-4 and NFS in diagnosing advanced fibrosis did not differ significantly between the 2 groups overall. However, in lean NAFLD, while the sensitivity for diagnosing advanced hepatic fibrosis remained reasonable at the current cutoff level, the sensitivity of NFS at the current cutoff was too low to be an adequate screening tool.

Risk Factors for Early- and Late-Onset Cholecystitis after Y-Configured Metal Stent Placement in Patients with Malignant Hilar Biliary Obstruction: A Single-Center Study.

This study evaluated the prevalence and risk factors of early- (within 7 days of placement) and late-onset (after 7 days of placement) cholecystitis after Y-configured metal stent placement. Between June 2005 and August 2020, 109 patients who had been treated with Y-configured metal stents for malignant hilar obstruction were enrolled in the study. We retrospectively analyzed the potential risk factors for post-stent cholecystitis. The presence of diabetes (p = 0.042), the length of the common part of the Y-stent (p = 0.017), filling of the gallbladder with contrast medium during the procedure (p = 0.040), and tumor invasion of the cystic duct accompanied by filling the gallbladder with contrast medium during metal stent placement (p = 0.001) were identified as important risk factors. In cases of late-onset cholecystitis, stent obstruction (p = 0.004) and repeated endoscopic procedures due to stent malfunction (p = 0.024) were significant risk factors. In the multivariate logistic regression analysis, significant risk factors were the length of the common part of the Y-stent (p = 0.032) in early-onset cholecystitis and stent obstruction (p = 0.007) in late-onset cholecystitis. This study demonstrated that early-onset cholecystitis may occur in patients according to the length of the common portion of the Y-stent. In contrast, late-onset cholecystitis may occur in patients with stent obstruction.

Diagnostic Performance of Noninvasive Tests for Advanced Hepatic Fibrosis in Young Age Population.

BACKGROUND & AIMS: Most noninvasive tests (NITs) for hepatic fibrosis are designed for middle-aged patients with chronic liver disease. We compared the diagnostic performance of major NITs (aspartate aminotransferase-to-platelet ratio index [APRI], Fibrosis-4 index, and nonalcoholic fatty liver disease fibrosis score) for a community-based cohort. METHODS: This cross-sectional study analyzed 8775 participants who underwent magnetic resonance elastography at community health check-up centers. Advanced hepatic fibrosis (≥F3) was defined by magnetic resonance elastography thresholds of 3.6 kPa. The diagnostic performance of 3 NITs was evaluated according to the etiology of liver disease, sex, metabolic syndrome, obesity, and increased aminotransferase levels in 4 age groups. RESULTS: The APRI generally showed the best area under the receiver operating characteristic curve in patients aged 45 years or younger, and it was statistically significant in patients with chronic viral hepatitis and alcoholic fatty liver disease (P < .043). The best APRI cut-off value for detecting advanced hepatic fibrosis was 0.4, with a sensitivity and specificity of 75.8% and 73.5%, respectively, in the community-based cohort. The APRI showed balanced sensitivity and specificity across all age groups, whereas the other metrics showed low sensitivity in those aged <45 and low specificity in those >65 years. CONCLUSIONS: The APRI showed better sensitivity and negative predictive value than the Fibrosis-4 index and the nonalcoholic fatty liver disease fibrosis score in community-based populations with mixed etiology, and, thus, can be performed as the primary test in young adults (age, ≤45 y).

Long-Term Outcomes of Cementing Highly Cross-Linked Polyethylene Liners Into Well-Fixed Acetabular Shells in Revision Total Hip Arthroplasty.

BACKGROUND: Cementing a new liner into a secure, well-positioned metallic shell can be a less-invasive strategy in revision total hip arthroplasty (THA). This study aimed to report the mean 14-year outcomes of cementing highly cross-linked polyethylene (XLPE) liners into well-fixed acetabular shells in revision THAs. METHODS: This study reviewed a single-surgeon series of cementing XLPE liners into well-fixed acetabular components. Of the 52 hips (51 patients) evaluated, 48 hips (47 patients) that satisfied a minimum follow-up of 10 years were included. The Harris Hip score was used for clinical evaluation. Final hip radiographs were used to determine the extent of acetabular osteolysis and stability of the components. The mean age at index operation was 53 years (range, 32 to 72). The mean follow-up duration was 14 years (range, 10 to 18). RESULTS: The mean Harris Hip score improved from 58 points (range, 23-81) preoperatively to 91 points (range, 45-100) at the final evaluation (P < .001). A total of 3 acetabular rerevisions were performed, all for aseptic loosening of the outer shell. One postoperative dislocation occurred, but it was successfully treated with a closed reduction. Final radiographs showed a significant reduction in acetabular osteolysis (P < .001). Implant survivorship free from any rerevision was 93.3% (95% confidence interval, 85.9-100%) at 14 years. CONCLUSION: Cementing an XLPE liner into a well-fixed acetabular shell in revision THA demonstrated excellent clinical and radiographic outcomes at a mean of 14 years postoperatively. This technique could be a safe and durable option in the absence of XLPE liners compatible with preimplanted shells.

Hepatocellular carcinoma incidence is decreasing in Korea but increasing in the very elderly.

BACKGROUND/AIMS: A comprehensive analysis of trends in the incidence of hepatocellular carcinoma (HCC) is important for planning public health initiatives. We aimed to analyze the trends in HCC incidence in South Korea over 10 years and to predict the incidence for the year 2028. METHODS: Data from patients with newly diagnosed HCC between 2008 and 2018 were obtained from Korean National Health Insurance Service database. Age-standardized incidence rates (ASRs) were calculated to compare HCC incidence. A poisson regression model was used to predict the future incidence of HCC. RESULTS: The average crude incidence rate (CR) was 22.4 per 100,000 person-years, and the average ASR was 17.6 per 100,000 person-years between 2008 and 2018. The CR (from 23.9 to 21.2 per 100,000 person-years) and ASR (from 21.9 to 14.3 per 100,000 person-years) of HCC incidence decreased during the past ten years in all age groups, except in the elderly. The ASR of patients aged ≥80 years increased significantly (from 70.0 to 160.2/100,000 person-years; average annual percent change, +9.00%; P<0.001). The estimated CR (17.9 per 100,000 person-years) and ASR (9.7 per 100,000 person-years) of HCC incidence in 2028 was declined, but the number of HCC patients aged ≥80 years in 2028 will be quadruple greater than the number of HCC patients in 2008 (from 521 to 2,055), comprising 21.3% of all HCC patients in 2028. CONCLUSION: The ASRs of HCC in Korea have gradually declined over the past 10 years, but the number, CR, and ASR are increasing in patients aged ≥80 years.

Regular Alpha-Fetoprotein Tests Boost Curative Treatment and Survival for Hepatocellular Carcinoma Patients in an Endemic Area.

Guidelines vary on alpha-fetoprotein (AFP) testing for hepatocellular carcinoma (HCC) screening. This study aims to reassess AFP's role in HCC surveillance, utilizing a comprehensive, recent, nationwide cohort. Utilizing the National Health Claims Database from the Korean National Health Insurance Service, this research included data from 185,316 HCC patients registered between 2008 and 2018. Specifically, 81,520 patients diagnosed with HCC from 2008 to 2014 were analyzed. The study focused primarily on mortality and, secondarily, on the status of curative treatments. Multivariate analysis revealed that frequent AFP testing significantly impacts overall survival in HCC patients. Specifically, each additional AFP test correlated with a 6% relative improvement in survival (hazard ratio = 0.94, 95% CI: 0.940-0.947, p < 0.001). Patients who underwent AFP testing three or more times within two years prior to HCC diagnosis showed improved survival rates, with 55.6% receiving liver transplantation or hepatectomy. This trend was particularly pronounced in hepatitis B patients undergoing antiviral treatment. The findings highlight the potential of regular AFP testing to enhance survival in HCC patients, especially those with hepatitis B. Integrating frequent AFP testing with ultrasonography could increase the likelihood of early detection and access to curative treatments.

Deep learning model to predict Epstein-Barr virus associated gastric cancer in histology.

The detection of Epstein-Barr virus (EBV) in gastric cancer patients is crucial for clinical decision making, as it is related with specific treatment responses and prognoses. Despite its importance, the limited medical resources preclude universal EBV testing. Herein, we propose a deep learning-based EBV prediction method from H&E-stained whole-slide images (WSI). Our model was developed using 319 H&E stained WSI (26 EBV positive; TCGA dataset) from the Cancer Genome Atlas, and 108 WSI (8 EBV positive; ISH dataset) from an independent institution. Our deep learning model, EBVNet consists of two sequential components: a tumor classifier and an EBV classifier. We visualized the learned representation by the classifiers using UMAP. We externally validated the model using 60 additional WSI (7 being EBV positive; HGH dataset). We compared the model's performance with those of four pathologists. EBVNet achieved an AUPRC of 0.65, whereas the four pathologists yielded a mean AUPRC of 0.41. Moreover, EBVNet achieved an negative predictive value, sensitivity, specificity, precision, and F1-score of 0.98, 0.86, 0.92, 0.60, and 0.71, respectively. Our proposed model is expected to contribute to prescreen patients for confirmatory testing, potentially to save test-related cost and labor.

Long-Term Outcomes of Revision Total Hip Arthroplasty Using a Tapered and Fluted Modular Stem: A Mean Follow-Up of 16 Years.

BACKGROUND: Tapered modular stems are increasingly used in revision total hip arthroplasty (THA) with deficient femoral bone stock. This study aimed to report the long-term outcomes of revision THA using a tapered and fluted modular stem. METHODS: Between December 1998 and February 2006, 113 revision THAs (110 patients) were performed with a tapered and fluted modular stem at a single institution. Hip radiographs were used to identify stem subsidence, stability, and femoral radiolucency. Final outcomes were assessed in 72 hips (70 patients), with a minimum follow-up of 10 years. RESULTS: The mean follow-up duration was 16 years (range, 10-23). At the final evaluation, the Harris Hip Score improved from a mean of 41 points (range, 10-72) preoperatively to 83 points (range, 56-100) (P < .001). Six femoral re-revisions were performed for the following reasons: 1 aseptic loosening, 2 stem fractures, and 3 infections. One stem fracture occurred at the modular junction after 14 years, and the other at a more distal location after 15 years. Stem subsidence was >5 mm in 6 hips (9.1%), but secondary stability was achieved in all stems. Osseointegration was observed in 63 (95.5%) hips. Stem survivorship was 91.1% with an end point of any re-revision and 94.6% for aseptic re-revision. CONCLUSION: A tapered and fluted modular stem demonstrated excellent implant survivorship with reliable bony fixation at a mean follow-up of 16 years. This type of stem can be a durable option for revision THA in patients who have femoral defects.

Ovarian Masses in Patients With Breast Cancer.

PURPOSE: The aim of the study was to investigate the characteristic findings of computed tomography (CT) or magnetic resonance imaging (MRI) to discriminate metastasis from primary ovarian tumors in patients with a history of breast cancer. METHODS: This retrospective study enrolled consecutive 72 patients with a history of breast cancer who underwent surgical confirmation of an ovarian mass detected on CT or MRI (primary ovarian tumors, n = 66; metastases, n = 6). Two independent readers analyzed the grade of solid portions of the ovarian mass using a 5-point scale on CT or MRI. A predominantly cystic mass was defined as a solid grade of 1 to 2. Cancer antigen 125 (CA 125) and the initial stage of breast cancer were also investigated. RESULTS: The proportions of predominantly cystic masses were significantly different between metastases (0% for both readers) and primary ovarian tumors (59% for reader 1 and 53% for reader 2, P < 0.05). For masses of solid portion grades 3 to 5, CA 125 was significantly higher for malignant epithelial tumors than for the other tumors ( P < 0.001), and the initial stage of breast cancer was significantly higher for metastases than for the other tumors ( P < 0.001), respectively. CONCLUSIONS: In patients with a history of breast cancer, predominantly cystic masses detected on CT or MRI seem to be primary ovarian tumors. For the other masses, knowledge of CA 125 and initial breast cancer stage may help in the differential diagnosis.

Association of Keratin 8 Level in Aqueous Humor With Outcomes of Intravitreal Ranibizumab Treatment for Neovascular Age-Related Macular Degeneration.

Purpose: To investigate keratin 8 (KRT8) level in the aqueous humor (AH) of patients with neovascular age-related macular degeneration (nAMD) and elucidate its association with intravitreal ranibizumab (IVR) treatment outcomes. Methods: This prospective study involved 58 eyes of treatment-naïve nAMD patients treated with three IVR doses monthly and whose AH samples were collected at baseline and two months after the initial treatment. KRT8 level was determined using the enzyme-linked immunosorbent assay and compared with that of the control group, which comprised patients who underwent cataract surgery during the same period. The nAMD-affected eyes were classified into responder (dry) and poor responder (persistent fluid) groups, according to optical coherence tomography (OCT) findings at month three. Additionally, associations between the KRT8 level and IVR treatment outcomes were analyzed. Results: The baseline KRT8 level was significantly higher in the AMD group than in the control group. In the AMD group, responders demonstrated significant differences between the KRT8 level at the baseline and month two, whereas poor responders exhibited no significant change. Regression analysis revealed that a higher KRT8 level at month two was significantly associated with persistent fluid upon OCT at months three and six. Conclusions: Monitoring aqueous KRT8 level may facilitate early determination of the therapeutic effects of IVR in nAMD patients and reflect the conditions of retinal pigment epithelium during the disease course. Translational Relevance: Monitoring aqueous KRT8 may aid early determination of therapeutic effects of IVR in neovascular AMD patients and reflect the health conditions of retinal pigment epithelium.

Impact of acute kidney injury on long-term adverse outcomes in obstructive uropathy.

Obstructive uropathy is known to be associated with acute kidney injury (AKI). This study aimed to investigate the etiologies, clinical characteristics, consequences and also assess the impact of AKI on long-term outcomes. This multicenter, retrospective study of 1683 patients with obstructive uropathy who underwent percutaneous nephrostomy (PCN) analyzed clinical characteristics, outcomes including progression to end-stage kidney disease (ESKD), overall mortality, and the impact of AKI on long-term outcomes. Obstructive uropathy in adults was most commonly caused by malignancy, urolithiasis, and other causes. AKI was present in 78% of the patients and was independently associated with preexisting chronic kidney disease (CKD). Short-term recovery was achieved in 56.78% after the relief of obstruction. ESKD progression rate was 4.4% in urolithiasis and 6.8% in other causes and older age, preexisting CKD, and stage 3 AKI were independent factors of progression. The mortality rate (34%) was highly attributed to malignant obstruction (52%) stage 3 AKI was also an independent predictor of mortality in non-malignant obstruction. AKI is a frequent complication of adult obstructive uropathy. AKI negatively affects long-term kidney outcomes and survival in non-malignant obstructions. A better understanding of the epidemiology and prognostic factors is needed for adult obstructive uropathy.

Immobilized DNA aptamers used as potent attractors for vascular endothelial cell: in vitro study of female rat.

Vascular endothelial cells are essential to vascular function and maintenance. Dysfunction of these cells can lead to the development of cardiovascular disease or contribute to tumorigenesis. As such, the therapeutic modulation and monitoring of vascular endothelial cells are of significant clinical interest, and several endothelial-specific ligands have been developed for drug delivery and the monitoring of endothelial function. However, the application of these ligands has been limited by their high cost and tendency to induce immune responses, highlighting a need for alternate methods of targeting vascular endothelial cells. In the present study, we explore the therapeutic potential of DNA aptamers. Using cell-SELEX technology, we identified two aptamers with specific binding affinity for vascular endothelial cells and propose that these molecules show potential for use as new ligands for drug and biomarker research concerning vascular endothelial cells.

HIGHER-ORDER ABERRATIONS IN EYES WITH SILICONE OIL TAMPONADE.

PURPOSE: To investigate the changes in higher-order aberrations (HOAs) after silicone oil removal and to evaluate their associations with visual acuity. METHODS: Fifty-nine eyes of 58 patients who underwent SO removal were included. Total, corneal, and internal optic HOAs, and best-corrected visual acuity were measured before and 1 month after SO removal, and changes were compared between phakic and pseudophakic eyes. RESULTS: Total ocular and internal optic HOAs decreased significantly after SO removal both in pseudophakic (n = 40, all P < 0.001) and phakic eyes (n = 19, P = 0.017, P = 0.004). Preoperative HOAs (P < 0.001) and changes in HOAs (P = 0.006) were greater in pseudophakic eyes than in phakic eyes. Best-corrected visual acuity was significantly improved after SO removal, from 20/105 to 20/78 (P < 0.001) in pseudophakic eyes, whereas there was no difference in phakic eyes (P = 0.714). Preoperative HOAs and the reduction in HOAs after SO removal were greater in best-corrected visual acuity-improved eyes than best-corrected visual acuity-unchanged eyes (P < 0.001). CONCLUSION: Silicone oil tamponade induced an increase in HOAs, and these increases were greater in pseudophakic eyes than in phakic eyes. Silicone oil may cause additional visual impairments because of HOAs, beyond those caused by retinal diseases, particularly in pseudophakic eyes.