Comparative analysis of changes in retinal layer thickness following femtosecond laser-assisted cataract surgery and conventional cataract surgery.

BACKGROUND: To investigate the influence of femtosecond laser-assisted cataract surgery (FLACS) on macula by examining changes in retinal layers after FLACS and to compare these changes with those after conventional cataract surgery (CCS). METHODS: This study included 113 unrelated Korean patients with age-related cataract who underwent CCS or FLACS in Severance Hospital between September 2019 and July 2021. Optical coherence tomography was performed before and 1 month after surgery. The total retinal layer (TRL) was separated into the inner retinal layer (IRL) and outer retinal layer (ORL); moreover, the IRL was subdivided into the retinal nerve fiber layer, ganglion cell layer, inner plexiform layer, inner nuclear layer (INL), outer plexiform layer, and outer nuclear layer. We performed between-group comparisons of the postoperative thickness in each retinal layer and the postoperative differences in retinal thickness. The average retinal thickness of the four inner macular ring quadrants was used for comparative analysis. RESULTS: Compared with the CCS group, the FLACS group exhibited a thicker ORL (P = 0.004) and a thinner INL (P = 0.007) after surgery. All retinal layer thickness values showed significant postoperative changes regardless of the type of surgery (P < 0.05). The postoperative increase in TRL and IRL thickness was significantly smaller in the FLACS group than in the CCS group (P = 0.027, P = 0.012). CONCLUSIONS: The 1-month postoperative retinal changes were less pronounced in the FLACS group than in the CCS group.

Clinical efficacy and performance evaluation of a bendable remote robot system for a bone tumour surgery: A pilot animal study.

BACKGROUND: Traditional open surgery for bone tumours sometimes has as a consequence an excessive removal of healthy bone tissue because of the limitations of rigid surgical instruments, increasing infection risk and recovery time. METHODS: We propose a remote robot with a 4.5-mm diameter bendable end-effector, offering four degrees of freedom for accessing the inside of the bone and performing tumour debridement. The preclinical studies evaluated the effectiveness, clinical scenario, and usability across 12 total surgeries-six phantom surgeries and six bovine bone surgeries. Evaluation criteria included skin incision size, bone window size, surgical time, removal rate, and conversion to open surgery. RESULTS: Preclinical studies demonstrated that the robotic approach requires significantly smaller incision size and procedure times than traditional open curettage. CONCLUSION: This study validated the performance of the proposed system by assessing its preclinical effectiveness and optimising surgical methods using human phantom and bovine bone tumour models.

Lateral Distance From the Osteotomy Hinge Point to the Tibial Cortex Is Associated With Lateral Hinge Fracture Type and Fracture Occurrence Time After Medial Open-Wedge High Tibial Osteotomy.

PURPOSE: To verify whether the distance from the hinge point to the tibial cortex affects the occurrence time and characteristics of the lateral hinge fracture (LHF) in medial open-wedge high tibial osteotomy. METHODS: We retrospectively reviewed 171 knees in 171 patients (121 women, 50 men; mean age, 53.9 years; range, 36-67 years) who had undergone medial open-wedge high tibial osteotomy with locking plate fixation between January 2011 and December 2020. Osteotomy hinge point and LHFs were identified on intraoperative fluoroscopy and immediate postoperative radiographs. LHF type was classified as suggested by Takeuchi et al. Acute fracture was defined as a fracture that occurred during surgery, and delayed fracture was defined as a fracture observed after 1 month postoperatively. The nearest distances from osteotomy hinge point to lateral, distal, and proximal cortex were measured on postoperative radiographs. We compared the distance between the different types and between acute and delayed LHFs. RESULTS: There were 55 LHFs (32%) (type I, 40 knees; type II, 14 knees; type III, 1 knee) that occurred acutely in 41 knees and were found as delayed fractures in 14 knees. The patient demographics were not significantly different between non-LHFs and each type of LHFs. Proximal and distal distances were not statistically different among fracture types and between occurrence times. However, lateral distances were significantly shorter in type I LHFs (6.2 ± 1.8 mm) and longer in type II LHFs (9.3 ± 2.3 mm) than in non-LHFs (7.1 ± 2.7 mm) (P = .020 and .004, respectively). The lateral cortical distances were also different between acute LHFs (6.4 ± 1.9 mm) and delayed LHF (9.0 ± 2.7 mm) (P < .001). In the case of fracture type, the frequency of type I decreases with increase in the lateral distance, whereas that of type II increases with increase in the lateral cortical distance. In acute fracture, type I was dominant (85.4%), whereas in delayed fracture, type II was dominant (57.2%). CONCLUSIONS: The lateral cortical distance from the hinge point was significantly associated with LHF occurrence. Shorter distance increased the risk for acute type I LHF, whereas longer distance increased the risk for delayed type II LHFs. LEVEL OF EVIDENCE: Level III, retrospective comparative prognostic trial.

Lateral Meniscal Allograft Transplantation Shows a Long-Term Chondroprotective Effect on Quantitative MRI T2 Mapping at 7 Years' Minimum Follow-Up.

PURPOSE: The purpose of this study was to assess the long-term chondroprotective effect of lateral meniscal allograft transplantation (MAT) using quantitative magnetic resonance imaging (MRI) T2 mapping. METHODS: In patients who underwent isolated lateral MAT, quantitative MRI T2 mapping was conducted preoperatively and postoperatively with at minimum follow-up of 7 years to assess the articular cartilage status. On the sagittal section image bisecting the lateral femoral condyle, the weight-bearing portions of the femoral and tibial articular cartilage were divided into 3 segments each-6 segments in total-based on the meniscal coverage area. The regions of interest analysis were performed on the 6 segments to measure the mean T2 value. Then, the whole layer was divided into deep and superficial layers for further zonal analysis. The longitudinal change in T2 values was statistically analyzed using paired t-tests. Clinical outcome was evaluated using the Lysholm score. RESULTS: A total of 31 patients were included in the study, with the MRI follow-up period of a minimum follow-up of 7 years (mean: 8.9 ± 1.3 years; range: 7.0-11.2 years). The mean T2 value of the whole layer showed significant improvement in all segments of the femoral cartilage and the posterior segment of tibial cartilage. In the zonal analysis, the mean T2 value of the tibial cartilage showed significant improvement in the superficial layer of the mid to posterior portion, while the deep layer remained stable. In contrast, the mean T2 value of the femoral cartilage showed significant improvement in the superficial and deep layers in all segments. The mean Lysholm score significantly improved from 62.6 ± 12.8 to 90.9 ± 10.5 (P < .001). CONCLUSION: This study suggests that MAT appears to have a long-term chondroprotective effect on the articular cartilage as judged by quantitative T2 mapping. LEVEL OF EVIDENCE: Level Ⅳ, case series.

Tear patterns and locations are different between lateral and medial compartments in patients with early anatomical failure after meniscal allograft transplantation.

PURPOSE: To investigate the characteristics of anatomically failed grafts within 1 year after meniscal allograft transplantation (MAT) and compare the differences between lateral and medial MATs. METHODS: The records of consecutive patients with anatomically failed grafts within 1 year after primary MAT between 2005 and 2018 were reviewed. Anatomical failure was defined as a tear covering > 50% of the allograft or an unstable peripheral rim. The pattern and location of the graft tears were analyzed using magnetic resonance imaging or arthroscopy. RESULTS: A total of 21 patients were included. All 21 patients had anatomical failure with tears involving > 50% of the allograft, whereas 15 had an unstable peripheral rim of the allograft. The mean failure time was 6.6 ± 3.6 months in all patients (lateral MAT, n = 15; medial MAT, n = 6). In the lateral MAT group, meniscocapsular separation was the most common pattern (n = 10, 66.7%), followed by complex (n = 3, 20.0%), radial (n = 1, 6.7%), and longitudinal (n = 1, 6.7%) tear. In the medial MAT group, a root tear was the most common pattern (n = 5, 83.3%), followed by a complex tear (n = 1, 16.7%). Meanwhile, in the lateral MAT, the midbody was the most frequently affected location (n = 9, 60.0%), followed by the posterior (n = 5, 33.3%) and anterior (n = 1, 6.7%) areas; in the medial MAT group, the posterior (n = 5, 83.3%) was the most frequently affected location, followed by the anterior area (n = 1, 16.7%). Significant differences in the pattern (P = 0.002) and location (P = 0.043) of the graft tears were found between lateral and medial MATs. CONCLUSION: In patients with early failure after MAT, meniscocapsular separation in the midbody of the lateral compartment and root tears in the posterior area of the medial compartment were the most common. Thus, surgeons are encouraged to pay extra attention to these vulnerable areas during the early period after MAT. LEVEL OF EVIDENCE: IV.

1,2-Diphenyl-o-carborane and Its Chromium Derivatives: Synthesis, Characterization, X-ray Structural Studies, and Biological Evaluations.

The objective of this study is to design and synthesize substituted η6-chromium(0) tricarbonyl metal complexes carrying o-carborane units as potential boron neutron capture therapy (BNCT) agents. In this study, 1,2-diphenyl-o-carborane (1) units were used as starting materials to generate biologically active species. We investigated how the structural changes of 1 substituted with chromium(0) tricarbonyl affect the biological properties, and 1-(Phenyl-η6-chromium(0) tricarbonyl)-2-phenyl-o-carborane (2) and 1,2-bis(phenyl-η6-chromium(0) tricarbonyl)-o-carborane (3) species were produced in moderate yields. The molecular structures of compounds 1-3 were identified and established by infrared (IR); 1H, 11B, and 13C nuclear magnetic resonance (NMR) and X-ray crystallography analyses. Crystal structures of 1,2-diphenyl-o-carborane and the corresponding chromium complexes 1, 2, and 3 were obtained. In an in vitro study using B16 and CT26 cancer cells containing the triphenyl-o-carboranyl chromium(0) complexes Ph3C2BCr2 and Ph3C2BCr3, which we reported previously, compounds 2 and 3 accumulated at higher levels than compounds Ph3C2BCr2 and Ph3C2BCr3. However, the phenylated o-carboranyl chromium complexes have been found to be more cytotoxic than p-boronophenylalanine (BPA).

Plasma Exosome Analysis for Protein Mutation Identification Using a Combination of Raman Spectroscopy and Deep Learning.

Protein mutation detection using liquid biopsy can be simply performed periodically, making it easy to detect the occurrence of newly emerging mutations rapidly. However, it has low diagnostic accuracy since there are more normal proteins than mutated proteins in body fluids. To increase the diagnostic accuracy, we analyzed plasma exosomes using nanoplasmonic spectra and deep learning. Exosomes, a promising biomarker, are abundant in plasma and stably carry intact proteins originating from mother cells. However, the mutated exosomal proteins cannot be detected sensitively because of the subtle changes in their structure. Therefore, we obtained Raman spectra that provide molecular information about structural changes in mutated proteins. To extract the unique features of the protein from complex Raman spectra, we developed a deep-learning classification algorithm with two deep-learning models. Consequently, controls with wild-type proteins and patients with mutated proteins were classified with high accuracy. As a proof of concept, we discriminated the lung cancer patients with mutations in the epidermal growth factor receptor (EGFR), L858R, E19del, L858R + T790M, and E19del + T790M, from controls with an accuracy of 0.93. Moreover, the protein mutation status of the patients with primary (E19del, L858R) and secondary (+T790M) mutations was clearly monitored. Overall, our technique is expected to be applied as a novel method for companion diagnostic and treatment monitoring.

Contributions of cancer treatment, comorbidities, and obesity to aging-related disease risks among non-Hodgkin lymphoma survivors.

PURPOSE: It is unknown whether cancer treatment contributes more to long-term disease risk than lifestyle factors and comorbidities among B-cell non-Hodgkin lymphoma (B-NHL) survivors. METHODS: B-NHL survivors were identified in the Utah Cancer Registry from 1997 to 2015. Population attributable fractions (PAF) were calculated to assess the role of clinical and lifestyle factors for six cardiovascular, pulmonary, and renal diseases. RESULTS: Cancer treatment contributed to 11% of heart and pulmonary conditions and 14.1% of chronic kidney disease. Charlson Comorbidity Index (CCI) at baseline contributed to all six diseases with a range of 9.9% of heart disease to 26.5% of chronic kidney disease. High BMI at baseline contributed to 18.4% of congestive heart failure and 7.9% of pneumonia, while smoking contributed to 4.8% of COPD risk. CONCLUSION: Cancer treatment contributed more to heart disease, COPD, and chronic kidney disease than lifestyle factors and comorbidities among B-NHL survivors. High BMI at baseline contributed more to congestive heart failure and pneumonia than cancer treatment, whereas smoking at baseline was not a major contributor in this B-NHL survivor cohort. Baseline comorbidities consistently demonstrated high attributable risks for these diseases, demonstrating a strong association between preexisting comorbidities and aging-related disease risks.

Lateral Meniscal Allograft Transplantation Provides a Chondroprotective Effect on Articular Cartilage: Quantitative 3-T Magnetic Resonance Imaging T2 Mapping.

PURPOSE: This study aimed to assess the cartilage status in patients who underwent isolated lateral meniscus allograft transplantation (MAT) using preoperative and postoperative quantitative 3-T magnetic resonance imaging T2 mapping at midterm follow-up period. METHODS: Patients who underwent lateral MAT without cartilage treatment procedures between 2010 and 2019 were assessed by quantitative magnetic resonance imaging preoperatively and postoperatively. On the sagittal section image following the center of the lateral femoral condyle, the weight-bearing area of the articular cartilage was divided into 6 segments based on the meniscal coverage area from anterior to posterior direction. The mean T2 values of each of the 6 segments were measured for 3 regions of interest: overall, deep, and superficial layers. The change in T2 values was statistically analyzed by paired t-tests. The Lysholm score was used to evaluate clinical function. RESULTS: A total of 105 patients were included in the study. The mean follow-up period was 3.2 years (range 2.0-5.4 years). Among the 6 segments, the mean T2 value showed significant improvement in the overall layer of F2 (the middle weight-bearing area of femoral condyle) and TP3 (the posterior weight-bearing area of tibia condyle) segments (P = .013 and .021, respectively) and the superficial layer of the F3 (the posterior weight-bearing area of femoral condyle) segments (P = .028). The mean T2 value of all the other segments did not show a statistically significant change. The mean Lysholm score significantly improved from 66.5 ± 15.8 to 89.3 ± 10.0 (P < .001). Overall, 73.3% and 96.2% of the patients met the minimal clinically important difference and patient acceptable symptomatic state, respectively. CONCLUSIONS: The mean T2 value of the articular cartilage of the weight-bearing area was either maintained or showed statistically significant improvement depending on the location following isolated lateral MAT. Thus, the transplanted meniscus seems to have a chondroprotective effect on the weight-bearing cartilage. LEVEL OF EVIDENCE: Level IV, retrospective therapeutic case series.

Effect of ICRS Lesion Grade on Graft Survival After Medial Meniscal Allograft Transplantation: MRI-Based Objective Evaluation.

BACKGROUND: Data are lacking regarding the survival rate after medial meniscal allograft transplantation (MAT) alone. Furthermore, little information is available about prognostic factors for graft survival that affect the outcomes of medial MAT. PURPOSE: To investigate the prognostic factors and survival rate of allograft after medial MAT. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: The records of 78 consecutive patients who underwent primary medial MAT between 1996 and 2018 were reviewed. Kaplan-Meier survival analysis was performed to analyze the anatomic and clinical survival rates. Anatomic failure was defined as a tear covering >50% of the allograft or unstable peripheral rim. Clinical failure was considered Lysholm score <65 or need for additional surgery such as meniscal repair, revision MAT, realignment osteotomy, and meniscectomy for >50% of the allograft. Patient factors affecting anatomic and clinical failure were analyzed. RESULTS: The mean follow-up period was 6.9 ± 5.3 years (range, 2-21 years). Anatomic failure was noted in 19 patients (24.4%), and none of these patients had a persistent poor Lysholm score of <65; of these, 2 patients who underwent meniscal repair also had clinical failure. Clinical failure was noted in 7 patients (9.0%); 4 patients had Lysholm score <65, 2 patients underwent meniscal repair, and 1 patient underwent realignment osteotomy. The estimated 10-year anatomic and clinical survival rates were 73.89% and 87.90%, respectively. Anatomic survival was significantly associated with only high-grade International Cartilage Regeneration & Joint Preservation (ICRS) lesion (ICRS grade 3 or 4) (hazard ratio, 3.171; 95% CI, 1.124-8.944; P = .029). However, the clinical survival rate was not significantly associated with any factors. Patients with low-grade ICRS lesion (ICRS grade 0, 1, or 2) showed a higher estimated 10-year anatomic survival rate compared with patients with high-grade ICRS lesions (87.6% vs 63.3%, respectively; P = .022). CONCLUSION: Low-grade ICRS lesion was associated with higher anatomic survival rate after medial MAT. In patients with high-grade ICRS lesions, the clinical outcome might be good; however, the status of an allograft might be poor. The surgeon should be aware of this and explain to the patient that close observation is necessary.

Mental health disorders are more common in patients with Hodgkin lymphoma and may negatively impact overall survival.

BACKGROUND: Long-term mental health outcomes were characterized in patients who were diagnosed with Hodgkin lymphoma (HL), and risk factors for the development of mental health disorders were identified. METHODS: Patients who were diagnosed with HL between 1997 and 2014 were identified in the Utah Cancer Registry. Each patient was matched with up to five individuals from a general population cohort identified within the Utah Population Database, a unique source of linked records that includes patient and demographic data. RESULTS: In total, 795 patients who had HL were matched with 3575 individuals from the general population. Compared with the general population, patients who had HL had a higher risk of any mental health diagnosis (hazard ratio, 1.77; 95% confidence interval, 1.57-2.00). Patients with HL had higher risks of anxiety, depression, substance-related disorders, and suicide and intentional self-inflicted injuries compared with the general population. The main risk factor associated with an increased risk of being diagnosed with mental health disorders was undergoing hematopoietic stem cell transplantation, with a hazard ratio of 2.06 (95% confidence interval, 1.53-2.76). The diagnosis of any mental health disorder among patients with HL was associated with a detrimental impact on overall survival; the 10-year overall survival rate was 70% in patients who had a mental health diagnosis compared with 86% in those patients without a mental health diagnosis (p < .0001). CONCLUSIONS: Patients who had HL had an increased risk of various mental health disorders compared with a matched general population. The current data illustrate the importance of attention to mental health in HL survivorship, particularly for patients who undergo therapy with hematopoietic stem cell transplantation.

A Developer's Perspective on Clinical Evidence and Benefits for Rituximab Biosimilar Uptake, with a Focus on CT-P10.

To date, four rituximab biosimilars have received regulatory approval from the European Medicines Agency and/or US Food and Drug Administration. CT-P10 was the first rituximab biosimilar to be approved by each agency, in 2017 and 2018, respectively. Regulatory approval of CT-P10 followed demonstration of pharmacokinetic equivalence to the reference product in a phase I study in patients with rheumatoid arthritis. Phase III pivotal studies of CT-P10 subsequently demonstrated equivalence or non-inferiority of pharmacokinetics and efficacy between CT-P10 and reference rituximab in patients with rheumatoid arthritis, advanced-stage follicular lymphoma, and low-tumour-burden follicular lymphoma. Almost 5 years after its initial regulatory approval, significant real-world experience has accumulated with CT-P10 use, particularly in diffuse large B-cell lymphoma, one of the indications approved by extrapolation. This article summarises the pivotal data underlying regulatory approval for the four licensed rituximab biosimilars, before focusing on real-world data gathered with CT-P10. These data provide further support for the safety and effectiveness of CT-P10 and should boost healthcare professional and patient confidence in its use. Pharmacoeconomic analyses support the potential healthcare system cost savings offered by rituximab biosimilar uptake, which could lead to improved patient access to biologic treatments. Opportunities arising from biosimilar uptake extend further, potentially enabling innovative investigator-led research and therapeutic advances.

Human Papillomavirus Vaccination Knowledge, Barriers, and Recommendations Among Healthcare Provider Groups in the Western United States.

This study compared human papillomavirus (HPV) vaccination occurrences on the same day as provider recommendations at clinics in the Western United States stratified by healthcare provider groups. In addition, the relationships between provider groups' perceived challenges associated with HPV vaccination, HPV vaccination knowledge, HPV recommendation practices, and same-day HPV vaccinations and recommendations are described. Eligible participants included pediatric healthcare providers and staff with influence on patient/parental-level decisions regarding HPV vaccination. Participants filled out a 40-question survey. Results for study participants (N = 99) showed providers reported a higher number of challenges limiting HPV vaccination, higher HPV vaccination knowledge, and more favorable HPV vaccination recommendation practices compared to other healthcare team members (OTM) suggesting providers may have a better overall understanding of the HPV vaccination climate than OTMs. Clinics should examine OTMs' training, expectations, and opportunities to increase the frequency and strength of HPV vaccination recommendations to adolescent patients and parents.

Age-Related Disease Risks in Younger versus Older B-Cell Non-Hodgkin's Lymphoma Survivors.

BACKGROUND: Younger cancer survivors may develop age-related diseases due to the cancer treatment that they undergo. The aim of this population-based study is to estimate incidence of age-related diseases besides cardiovascular disease among younger versus older B-cell non-Hodgkin's lymphoma (B-NHL) survivors compared with their respective general population cohorts. METHODS: Survivors of B-NHL were diagnosed between 1997 and 2015 from the Utah Cancer Registry. Using the Utah Population Database, up to 5 cancer-free individuals from the general population were matched with a B-NHL survivor on sex, birth year, and state of birth. Hazard ratios (HR) for age-related disease outcomes, which were identified from medical records and statewide health care facility data, were estimated using Cox Proportional Hazards models for B-NHL survivors diagnosed at <65 years versus ≥65 years at least 5 years since B-NHL diagnosis. RESULTS: Comparing 2,129 B-NHL survivors with 8,969 individuals from the general population, younger B-NHL survivors had higher relative risks of acute renal failure [HR, 2.24; 99% confidence interval (CI), 1.48-3.39; P heterogeneity = 0.017), pneumonia (HR, 2.42; 99% CI, 1.68-3.49; P heterogeneity = 0.055), and nutritional deficiencies (HR, 2.08; 99% CI, 1.48-2.92; P heterogeneity = 0.051) ≥5 years after cancer diagnosis. CONCLUSION: Younger B-NHL survivors had higher relative risks of acute renal failure, pneumonia, and nutritional deficiencies than older B-NHL survivors compared with their respective general population cohorts, ≥5 years after cancer diagnosis.

Ethyl carbamate in retail market condiments and risk assessment of its dietary exposure for the Korean population.

Ethyl carbamate (EC), a potential human dietary carcinogen, is found in fermented foods including the fermented soybean-based condiments, the major part of the Korean diet. Therefore, it is expected that their EC contents might pose health risks. Herein, we collected 111 condiments and estimated their EC contents via gas chromatography-mass spectrometry. Further, dietary intake of EC was evaluated, and the risk levels were assessed via the margin of exposure (MOE) approach and excess cancer risk assessment. EC contents of the condiments ranged from not detectable to 39.47 µg/kg, and the daily EC exposure ranged from 1.4 to 2.0 ng/kg BW per day, depending on gender and age groups in Korea. Of the condiments, soy sauce was the largest contributor to EC exposure. MOE and excess cancer risks for the average consumer were 166,300 and 9.0 × 10-8, respectively, and those for the consumers in the 95th percentiles (P95) were 53,504 and 2.8 × 10-7, respectively, indicating that the risk of exposure to EC is of lower concern in average consumers than heavy consumers. However, the EC exposure from condiments was higher than that in other Asian countries.Abbreviations: EC: ethyl carbamate; GC-MS: gas chromatography-mass spectrometry; MOE: margin of exposure; MRL: maximum residue level; IDL: instrumental detection level; IQL: instrumental quantification level; MDL: method detection level; MQL: method quantification level; EDI: estimated daily intakes; BMDL10: benchmark dose lower confidence limit.

Choroidal Neovascularization and Haller Vessel Morphology Associated with Vision and Treatment Number after 1 Year in Age-related Macular Degeneration.

PURPOSE: The present study aimed to quantify various factors of vessel morphology, including vessel diameter, length, and complexity (fractal dimension and lacunarity) of both choroidal neovascularization (CNV) and en face Haller vessels using optical coherence tomography angiography (OCTA) and en face structural optical coherence tomography in typical neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) and to identify factors associated with visual acuity (VA) loss and number of injections within a year after the day of OCTA. METHODS: We retrospectively analyzed 43 eyes of nAMD patients and 33 eyes of PCV patients whose OCTA was performed at least 12 months after an initial anti-vascular endothelial growth factor treatment. Quantitative parameters, including vessel area, vessel diameter, vessel length, fractal dimension, and lacunarity were analyzed from en face images of CNV and Haller vessels. Clinical information, including logarithm of the minimum angle of resolution visual acuity and injection number of anti-vascular endothelial growth factor were acquired after 12 months from OCTA date. Using logistic regression analyses, parameters associated with logarithm of the minimum angle of resolution VA loss of 0.2 or more (VA loss group) and a number of injections of four or more (unstable group) after 12 months were analyzed. RESULTS: In typical nAMD, the VA loss group was associated with a smaller number of intersections of Haller vessels. The unstable group was associated with an increased lacunarity of CNV in typical nAMD. In PCV, both VA loss and unstable groups were associated with a higher maximal diameter of Haller vessels. CONCLUSIONS: VA loss and injection number of nAMD and PCV 12 months after OCTA imaging were associated with different morphological parameters of CNV and Haller vessels. Therefore, quantitative analyses of both CNV and Haller vessels from OCTA and en face optical coherence tomography might provide prognostic information about visual outcome and injection frequency within 12 months after OCTA imaging.

Cardiovascular disease risks in younger versus older adult B-cell non-Hodgkin's lymphoma survivors.

INTRODUCTION: Young cancer survivors may be at increased risk of early-onset chronic health conditions. The aim of this population-based study is to estimate cardiovascular disease (CVD) risk among younger versus older B-cell non-Hodgkin's lymphoma (B-NHL) survivors compared with their respective general population cohorts. METHODS: B-NHL survivors diagnosed from 1997 to 2015 in the Utah Cancer Registry were matched with up to five cancer-free individuals on birth year, sex, and birth state, using the statewide Utah Population Database. Electronic medical records and statewide health care facility data were used to identify disease outcomes ≥5 years after cancer diagnosis. Cox Proportional Hazards models were used to estimate hazard ratios for B-NHL survivors diagnosed at <65 years and ≥65 years old. RESULTS: Younger B-NHL survivors had higher relative risks than older cancer survivors of chronic rheumatic disease of the heart valves (HR = 4.14, 99% CI = 2.17-7.89; P valueheterogeneity = 0.004); peri-, endo-, and myocarditis (HR = 2.43, 99% CI = 1.38-4.28; P valueheterogeneity = 0.016); diseases of the arteries (HR = 1.63, 99% CI = 1.21-2.21; P valueheterogeneity = 0.044); and hypotension (HR = 2.44, 99% CI = 1.58-3.75; P valueheterogeneity = 0.048). B-NHL survivors of both age groups had elevated relative risks of heart disease overall and congestive heart failure. CONCLUSION: Younger B-NHL survivors had higher risks than older B-NHL survivors of specific cardiovascular diseases compared to their respective general population cohorts.

POST-TREATMENT PREDICTION OF OPTICAL COHERENCE TOMOGRAPHY USING A CONDITIONAL GENERATIVE ADVERSARIAL NETWORK IN AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To develop a deep learning model to generate posttreatment optical coherence tomography (OCT) images of neovascular age-related macular degeneration. METHODS: Two hundred ninety-eight patients with neovascular age-related macular degeneration were included. The conditional generative adversarial network was trained using 15,183 augmented paired OCT B-scan images obtained from 723 scans of 241 patients at baseline and 1 month after 3 loading doses of an anti-vascular endothelial growth factor treatment. The network was also trained using baseline fluorescein angiography (FA) or indocyanine green angiography (ICGA) images together with baseline OCT images. A test set of 150 images of 50 eyes was used to evaluate its ability to predict the presence of intraretinal fluid, subretinal fluid, PED, and subretinal hyperreflective material. Posttreatment OCT images were compared with images generated from baseline OCT with or without FA and indocyanine green angiography images. RESULTS: The predicted images inferred from baseline OCT images achieved an acceptable accuracy, specificity, and negative predictive value for four lesions (range: 77.0-91.9, 94.1-95.1, and 54.7-96.5%, respectively). The addition of both FA and indocyanine green angiography images improved the accuracy, specificity, and negative predictive value (range: 80.7-96.3, 97.3-99.0, and 59.0-98.3%, respectively). CONCLUSION: A conditional generative adversarial network is able to generate posttreatment OCT images from baseline OCT, FA, and indocyanine green angiography images.

FBXW7-mediated stability regulation of signal transducer and activator of transcription 2 in melanoma formation.

In this study, we provide critical evidence that STAT2 stability regulation plays an essential role in melanoma cell proliferation and colony growth. We found that the interaction of FBXW7 and STAT2 induced STAT2 destabilization via a ubiquitination-mediated proteasomal degradation pathway. Notably, GSK3ß-mediated STAT2 phosphorylation facilitated STAT2-FBXW7 interactions via the DNA binding domain of STAT2 and domains 1, 2, 6, and 7 of FBXW7 WD40. Importantly, the inverse correlation between protein levels of STAT2 and FBXW7 were observed not only in human melanoma cells but also in a human skin cancer tissue array. The relationship between protein levels of STAT2 and FBXW7, cell proliferation, and colony growth were similarly observed in the melanoma cell lines SK-MEL-2, -5, and -28. Moreover, STAT2 knockdown in melanoma cells suppressed melanoma cell proliferation and colony formation. These data demonstrated that FBXW7-mediated STAT2 stability regulation plays an essential role in melanoma cell proliferation and cancer growth.

Long-term diabetes risk among endometrial cancer survivors in a population-based cohort study.

OBJECTIVE: The majority of endometrial cancer patients are overweight or obese at cancer diagnosis. Obesity is a shared risk factor for both endometrial cancer and diabetes, but it is unknown whether endometrial cancer patients have increased diabetes risks. The aim of our study was to investigate diabetes risk among endometrial cancer patients. METHODS: Endometrial cancer patients diagnosed between 1997 and 2012 in Utah (n = 2,314) were identified. Women from the general population (n = 8,583) were matched to the cancer patients on birth year and birth state. Diabetes diagnoses were identified from electronic medical records and statewide healthcare facility databases. Cox proportional hazards models were used to estimate hazard ratios for diabetes after cancer diagnosis. RESULTS: Endometrial cancer survivors had a significantly higher risk of type II diabetes when compared to women from the general population in the first year after cancer diagnosis (HR = 5.22, 95% CI = 4.05, 6.71), >1-5 years after cancer diagnosis (HR = 1.67, 95% CI = 1.31, 2.12), and >5 years after cancer diagnosis (HR = 1.65, 95% CI = 1.29, 2.11). Endometrial cancer patients who were obese at cancer diagnosis had a three-fold increase in type II diabetes risk (HR = 2.99, 95%CI = 2.59, 3.45). Although endometrial cancer patients diagnosed at distant stage had a higher risk of diabetes, cancer treatment did not appear to contribute to any diabetes risks. CONCLUSIONS: In conclusion, endometrial cancer survivors had a higher risk of diabetes than women in the general population. These results suggest that long term monitoring for diabetes is indicated for endometrial cancer survivors.