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Purpose: Females typically present with a higher prevalence of knee osteoarthritis (KOA), and such a higher prevalence may be due to unique knee biomechanics during walking. However, the sex-dependent ambulatory mechanics has been yet to be clarified. To address this critical knowledge gap, this study implemented a series of computational approaches (1) to identify sex-related knee joint biomechanics during ambulation in persons with KOA and (2) to compare these biomechanical measures between individuals with vs. without KOA, stratified by sex., Methods: We searched five electronic databases for studies reporting sex-specific knee biomechanics in persons with and/or without KOA. Summary estimates were computed using random-effects meta-analysis and stratified by sex., Results: The systematic review identified eighteen studies (308 males and 383 females with KOA; 740 males and 995 females without KOA). A series of meta-analyses identified female-specific knee biomechanics in a disease-dependent manner. Females with KOA had lower first peak knee adduction moment and peak knee adduction compared to male counterparts. On the other hand, healthy females had lower peak knee flexion moment than male counterparts. Effect estimate in each meta-analysis display poor quality of evidence according to the GRADE approach., Conclusions: The current study is the first to consider sex as a biological variable into ambulatory mechanics in the development of KOA. We discovered that sex-dependent alterations in knee biomechanics is a function of the presence of KOA, indicating that KOA disease may be a driver of the sex-dependent biomechanical alterations or vice versa. Although no strong conclusion can be drawn because of the low quality of evidence, these findings provide new insight into the sex differences in ambulatory knee biomechanics and progression of KOA., Competing Interests: Conflict of Interest and Funding Source: This work was supported by a Grant-in-Aid for Early-Career Scientists (20K19411), (Copyright © 2024 by the American College of Sports Medicine.)

Purpose: Identification of responders/non-responders to unsupervised therapeutic exercise represents a critical challenge towards establishment of tailored self-management at home. Focusing on visualized varus thrust during gait as a possible effect moderator, this study determined whether and how varus thrust influences the therapeutic effects of home-based quadriceps exercise in individuals at increased risk of, or with, established knee osteoarthritis., Methods: This study is a secondary subgroup analysis of a randomized controlled trial (n = 50). Varus thrust at baseline was assessed via recorded gait movie. Analysis of covariance and subsequent mediation analysis were used to determine whether and how varus thrust influences the therapeutic effect of home-based quadriceps exercise after adjustment for covariates. To address the possible distinct impact of varus thrust on unsupervised and supervised exercise, the results were cross-checked with previous supervised exercise cohort using a meta-analysis., Results: Individuals without varus thrust displayed greater and clinically meaningful pain-relief after exercise after adjustment for covariates. The greater pain-relief in individuals without varus thrust was attributed, at least partly, to an improvement in knee flexion range of motion. Notably, the meta-analysis revealed that unsupervised and supervised exercise programs induce consistent and clinically meaningful pain reduction in individuals without varus thrust., Conclusions: Varus thrust is a robust effect moderator of the pain reducing effect of quadriceps exercise. Further, greater pain reduction may be a function of improvement of knee flexion range of motion. These studies provide evidence that varus thrust assessment represents valuable approach to identify responders/non-responders to quadriceps exercise even for unsupervised protocol at their home environment., Competing Interests: Conflict of Interest and Funding Source: This study was supported in part by (1) a JSPS KAKENHI (Grant Number: 23H03308) from the Japan Society for the Promotion of Science (https://www.jsps.go.jp/) for HI., (Copyright © 2024 by the American College of Sports Medicine.)

Simple hepatic cysts (SHC) are generally asymptomatic and incidentally diagnosed using imaging studies. Asymptomatic SHC does not require treatment, but symptomatic SHC warrants treatment using different modalities, including intravenous antibiotic therapy, ultrasound-guided percutaneous catheter drainage (PCD) with sclerotherapy, and surgery. The dissemination of endoscopic ultrasonography (EUS) intervention techniques has enabled the performance of puncture and drainage via the transgastrointestinal route for intra-abdominal abscesses. Despite the development of an EUS-guided drainage method for treating symptomatic SHC, only a few case reports using this method have been reported. This study retrospectively analyzed the safety and feasibility of EUS-guided drainage of symptomatic SHC as well as its clinical outcomes and compared it with combined therapy using PCD and minocycline sclerotherapy. The records of 10 consecutive patients with 11 symptomatic SHCs treated with either EUS-guided drainage or PCD combined with minocycline sclerotherapy at the Musashino Tokushukai Hospital from August 2019 to January 2024 were retrospectively examined. All cases in both groups achieved technical and clinical success, with no reported adverse events. The median reduction rates of the major cyst diameters in the EUS-guided drainage and PCD with sclerotherapy groups were 100% (interquartile range [IQR]: 94%-100%) and 67% (IQR: 48.5%-85%). The length of hospital stay was 7 and 22.5 days in the EUS-guided and PCD with sclerotherapy groups (P = .01). EUS-guided drainage of symptomatic SHC is a safe and effective therapeutic alternative to percutaneous drainage with sclerotherapy and surgery for treating symptomatic SHC., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Despite the increased use of platelet-rich plasma in the treatment of osteoarthritis, whether and how age of the platelet-rich plasma donor affects therapeutic efficacy is unclear., Design: In vitro, male osteoarthritic human chondrocytes were treated with platelet-rich plasma from young (18-35 yrs) or old (≥65 yrs) donors, and the chondrogenic profile was evaluated using immunofluorescent staining for two markers of chondrogenicity, type II collagen and SOX-9. In vivo, we used a within-subjects design to compare Osteoarthritis Research Society International scores in aged mouse knee joints injected with platelet-rich plasma from young or old individuals., Results: In vitro experiments revealed that platelet-rich plasma from young donors induced a more youthful chondrocyte phenotype, as evidenced by increased type II collagen ( P = 0.033) and SOX-9 expression ( P = 0.022). This benefit, however, was significantly blunted when cells were cultured with platelet-rich plasma from aged donors. Accordingly, in vivo studies revealed that animals treated with platelet-rich plasma from young donors displayed a significantly improved cartilage integrity when compared with knees injected with platelet-rich plasma from aged donors ( P = 0.019)., Conclusions: Injection of platelet-rich plasma from a young individual induced a regenerative effect in aged cells and mice, whereas platelet-rich plasma from aged individuals showed no improvement in chondrocyte health or cartilage integrity., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Study Design: Cross-sectional study., Objective: This study aimed to objectively evaluate spastic gait and reveal its novel characteristics via analysis of gait in patients with cervical myelopathy (CM) using the Timed Up and Go (TUG) test with a laser range sensor., Summary of Background Data: Among patients with CM, spastic gait is a common diagnostic symptom; thus, objective assessments of spastic gait would be useful for the diagnosis of CM and recognition of disease status. Although spastic gait has been objectively evaluated in previous studies, the methods employed in those studies are not suitable for clinical settings., Methods: In total, 37 and 24 participants were recruited for a control group and CM group, respectively. CM was diagnosed by spine surgeons. We developed a laser TUG test, in which the position and velocity of both the legs were captured. The parameter values for both groups were statistically compared, and odds ratios were calculated using logistic regression analyses., Results: The total TUG-test time, time to stand up, time to first step, number of steps, and trajectory error for the CM group were significantly higher than those for the control group, whereas the average velocity and average stride length for the CM group were significantly lower than those for the control group. There was a significant independent association between the total TUG-test time and CM. The optimal cutoff point of the total test time for CM risk was approximately 9 seconds., Conclusion: Through the use of the laser TUG test, we were able to identify characteristics of spastic gait, which leads to difficulty in standing and taking the first step, wobbling while walking, and an increased risk of falling. We found that the risk of CM was higher if the individual took longer than 9 seconds to complete the TUG test.Level of Evidence: 4., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Pancreatic fistula (PF) is one of the most common complications after pancreaticoduodenectomy (PD). The soft pancreatic texture is known to be an important predictive factor for PF after PD. However, its evaluation is dependent on the sense of touch by the operator during operation, thus not objective. The aim of this study was to investigate the relationship between mean elasticity via intraoperative ultrasound elastography and histological pancreatic hardness, as well as predictive factor of PF after PD., Methods: Forty-eight patients who underwent ultrasound elastography during PD and had pancreatic parenchyma histologically evaluated were included., Results: Pancreatic fistula was noted in 20 patients. There were significant differences in the histological pancreatic fibrosis rate between soft pancreas group (8.2%) and hard pancreas group (28.4%, P < 0.05) and in the mean elasticity between soft pancreas group (1.94 m/s) and hard pancreas group (3.17 m/s, P < 0.05). The mean elasticity was significantly correlated with pancreatic fibrosis rate (P < 0.05). A multivariate analysis revealed that the mean elasticity of less than 2.2 m/s was a significant predictor of PF after PD (P = 0.003)., Conclusions: Intraoperative ultrasound elastography could predict pancreatic texture objectively. The mean elasticity of less than 2.2 m/s was a significant predictor of PF after PD.

The actual proficiency levels of surgeons after their qualification by the Endoscopic Surgical Skill Qualification System have not been established. This study aimed to investigate whether technically qualified surgeons could safely perform laparoscopic low anterior resection and to evaluate the proficiency level at the time of certification acquisition. A total of 46 patients (mean age, 63.3 y; male to female ratio, 29:17) who underwent low anterior resection were included. Outcomes of 46 low anterior resections for rectal cancer performed by 3 novice surgeons certified by the Endoscopic Surgical Skill Qualification System from 2013 to 2018 at 2 hospitals were retrospectively assessed. The mean operative time and blood loss were 201 minutes and 12.9 mL, respectively. One patient (2.2%) required conversion to open surgery, and major postoperative complications occurred in 4 patients (8.6%), including anastomotic leakage in 2 patients (4.3%). Histologic R0 resection was achieved in all cases. The operative time moving average for the 3 surgeons gradually decreased from 233 to 158 minutes. In cumulative sum charts, the operative time values continuously decreased after the 12th case compared with the target operative time (180 min). In conclusion, surgeons can safely perform laparoscopic low anterior resection just after their qualification but have the potential to further attain proficiency.

Health related quality of life (HRQOL) in chronic liver disease (CLD) patients has been attracting much attention these days because it is closely associated with clinical outcomes in CLD patients. HRQOL has become established as an important concept and target for research and practice in the fields of medicine. A critique of HRQOL research is the lack of conceptual clarity and a common definition of HRQOL. Using a clear definition of HRQOL may increase the conceptual understanding. In this study, we aimed to elucidate the association between serum zinc (Zn) level and HRQOL as assessed by the Beck Depression Inventory-2nd edition (BDI-II), Pittsburgh Sleep Quality Index Japanese version (PSQI-J) and the 36-Item Short Form Health Survey (SF-36) in CLD patients (n = 322, median age = 65 years, 121 liver cirrhosis (LC) patients (37.6%)). The median serum Zn level for all cases was 73.2 μg/dl. The median BDI-II score and PSQI-J score were 6 and 5, respectively. Patients with higher BDI-II score tended to have lower serum Zn level compared with those with lower BDI-II score. Similar tendencies were observed in patients with higher PSQI-J score. In the SF-36, physical functioning, role physical and physical component summary score significantly correlated with serum Zn level regardless of age, liver disease etiology and the LC status. While mental health and mental component summary score did not significantly correlate with serum Zn level regardless of age, liver disease etiology and the LC status. In conclusion, serum Zn level can be a useful marker for decreased HRQOL in patients with CLDs, especially for physical components.

We aimed to compare the impact on survival among albumin-bilirubin (ALBI) grade, modified ALBI (mALBI) and our proposed combined ALBI grade and Mac-2 binding protein glycosylation isomer (M2BPGi) or FIB4 index grading system in chronic hepatitis C (CHC) related compensated liver cirrhosis (n = 165, 93 men and 72 women, median age = 67 years). Patients with ALBI grade 1, 2, and 3 were allocated a score of 1, 2, and 3 points, respectively. Patients with mALBI grade 1, 2A, and 2B were allocated a score of 1, 2, and 3 points, respectively. Patients with a high or low M2BPGi were allocated a score of 1 and 0 point. Patients with a high or low FIB4 index were allocated a score of 1 and 0 point. Sum of the point of ALBI (1, 2, or 3) and M2BPGi (0 or 1) or FIB4 index (0 or 1) was defined as ALBI-M2BPGi grade or ALBI-FIB4 grade. Prognostic accuracy was compared using the Akaike information criterion (AIC) value and time dependent receiver operating characteristics (ROC) curve analysis. The median follow-up duration was 5.422 years. AIC value for survival by ALBI-M2BPGi grade was the lowest among 4 prognostic models (AIC: 205.731 in ALBI grade, 200.913 in mALBI grade, 189.816 in ALBI-M2BPGi grade, and 204.671 in ALBI-FIB4 grade). All area under the ROC curves of ALBI-M2BPGi grade in each time point were higher than those of ALBI grade, mALBI grade, and ALBI-FIB4 grade. In conclusion, our proposed ALBI-M2BPGi grading system seems to be helpful for estimating prognosis in patients with CHC related compensated LC.

Study Design: Cross-sectional study using radiological measurements and longitudinal data analysis., Objective: We aim to explore hip/pelvic geometry on anteroposterior radiographs and examine if such parameters are associated with clinical symptoms., Summary of Background Data: Pregnancy-related sacroiliac joint pain is a common disease and is responsible to the disability of daily activities. The etiology is likely to be correlated with the biomechanical factors which are determined by trunk load and hip/pelvic geometry. Previous studies have already found the association between symptoms and weight increase during pregnancy. However, the relationship between bony anatomy and pregnancy-related sacroiliac joint pain remains unknown., Methods: In total, 72 women were included in the final analysis. In pregnant women with self-reported sacroiliac joint pain, pain scores at 12, 24, 30, and 36 weeks of pregnancy were recorded and included in a mixed-effect linear regression model as dependent variables. The radiological measurements were included as independent variables. Furthermore, to investigate the relationship between hip/pelvic geometry and the activity-specific nociceptive phenomenon, the radiological measurements between patients with and without activity-induced pain were compared using a binominal logistic regression model., Results: The relative bilateral is chial tuberosity distance (betta coefficient: 0.078; P = 0.015) and the relative bilateral femoral head length (betta coefficient: 0.011; P = 0.028) showed significant interactions with the slope of pain scores. Moreover, women whose pain exacerbate during prolonged walking had a higher odds in hip/pelvic geometry of the bilateral ischial tuberosity distance (odds ratio [OR]: 1.12; P = 0.050) and the bilateral femoral head length (OR: 1.16; P = 0.076) with approximately significant P-value., Conclusion: These data indicate hip/pelvic anatomical variations are associated with the degree of pain increasing and the activity-specific pain during pregnancy, which may help to have further understanding on the biomechanical factor in developing pregnancy-related sacroiliac joint pain., Level of Evidence: 3.

Rationale: Although esophageal compression due to cardiomegaly may be a risk factor of drug-induced esophageal injuries (DIEIs), the causal relationship between the two conditions has not been fully demonstrated., Patient Concerns: We present a case of a drug-induced esophageal ulcer caused by left atrial enlargement in a 44-year-old woman with end-stage hypertrophic cardiomyopathy. Upper gastrointestinal endoscopy showed a deep, circumferential ulcer in the middle thoracic esophagus. CT revealed that the esophagus was compressed between the enlarged left atrium (LA) and the vertebral body. In the upper gastrointestinal series, retention of contrast media was observed in the esophagus near the LA., Diagnosis: The ulcer was a result of potassium chloride retention in the esophagus, which was compressed by the enlarged LA., Intervention: After cessation of potassium chloride administration for 2 months, the ulcer healed and a stricture developed. Two years after the ulcer development, the patient underwent heart transplantation, and subsequent endoscopic balloon dilation was performed for the esophageal stricture., Outcomes: The patient's oral intake recovered completely without any ulcer recurrence., Lessons: The case demonstrated that esophageal compression by the enlarged LA caused a drug-induced esophageal ulcer. Preventive care and treatment measures for DIEIs, including an anatomical approach, should be considered for patients with LA enlargement.

Objective: We retrospectively assessed the efficacy of our mentor tutoring system for teaching laparoscopic colorectal surgical skills in a general hospital., Materials and Methods: A series of 55 laparoscopic colectomies performed by 1 trainee were evaluated. Next, the learning curves for high anterior resection performed by the trainee (n=20) were compared with those of a self-trained surgeon (n=19)., Results: Cumulative sum analysis and multivariate regression analyses showed that 38 completed cases were needed to reduce the operative time. In high anterior resection, the mean operative times were significantly shorter after the seventh average for the tutored surgeon compared with that for the self-trained surgeon. In cumulative sum charting, the curve reached a plateau by the seventh case for the tutored surgeon, but continued to increase for the self-trained surgeon., Conclusions: Mentor tutoring effectively teaches laparoscopic colorectal surgical skills in a general hospital setting.

We aimed to elucidate the relationship between serum liver fibrosis markers (Mac-2 binding protein glycosylation isomer (M2BPGi), FIB-4 index, aspartate aminotransferase to platelet ratio index and hyaluronic acid), and skeletal muscle mass and to investigate factors linked to skeletal muscle mass loss (SMML) in patients with chronic hepatitis C (CHC, n = 277, median age = 64 years). We defined patients with psoas muscle index [PMI, sum of bilateral psoas muscle mass calculated by manual trace method at the lumber 3 level on the computed tomography images divided by height squared (cm/m)] less than 6.36 cm/m for male and 3.92 cm/m for female as those with SMML based on the recommendations in current guidelines. Receiver operating curve (ROC) analysis was performed for predicting SMML in 4 liver fibrosis markers and parameters linked to SMML were also investigated in the univariate and multivariate analyses. In terms of liver fibrosis stages, F4 was observed in 115 patients, F3 in 67, F2 in 38, F1 in 53, and F0 in 4. The median (range) PMI for male and female were 6.198 (2.999-13.698) and 4.100 (1.691-7.052) cm/m, respectively. There were 72 male patients with SMML (55.4%) and 58 female patients with SMML (39.5%) (P = .0112). In both male and female, a significant inverse correlation between PMI and levels of liver fibrosis markers was observed in all liver fibrosis markers. ROC analyses for predicting SMML revealed that FIB-4 index had the highest area under the ROC (AUC = 0.712), followed by M2BPGi (AUC = 0.692). In the multivariate analysis of factors linked to SMML, gender (P = .0003), body mass index (P < .0001), FIB-4 index (P = .0039), and M2BPGi (P = .0121) were found to be significant predictors. In conclusion, liver fibrosis markers, especially FIB-4 index, can be helpful for predicting SMML in CHC patients.

Purpose: To investigate factors associated with visual improvement and retreatment 12 months after a combination therapy of intravitreal injection of ranibizumab or aflibercept followed by photodynamic therapy for polypoidal choroidal vasculopathy., Methods: Changes in the best-corrected visual acuity and the subfoveal thickness of the retina and choroid were studied in 56 consecutive eyes with polypoidal choroidal vasculopathy treated initially with a combination therapy of either intravitreal ranibizumab injection (n = 23) or intravitreal aflibercept injection (n = 33) followed by photodynamic therapy. Factors associated with visual improvement and retreatment were investigated., Results: Best-corrected visual acuity significantly improved with significant reduction in central macular thickness and subfoveal choroidal thickness at all points irrespective of treatment modalities (P < 0.001). Better best-corrected visual acuity and improvement of best-corrected visual acuity at 12 months were associated with baseline greater subfoveal choroidal thickness (P = 0.028 and P = 0.028) and baseline smaller greatest linear dimension (P = 0.0077 and P = 0.0077). Retreatment during 12-month follow-up was associated with baseline lesser subfoveal choroidal thickness (P = 0.036)., Conclusion: Irrespective of treatment modalities, the visual outcome at 12 months is favorable in eyes with polypoidal choroidal vasculopathy treated by photodynamic therapy combined with intravitreal ranibizumab or aflibercept. Baseline greater subfoveal choroidal thickness was associated with a better visual outcome and with reduction in the need for retreatment.

To the best of our knowledge, no available data with regard to changes in skeletal muscle mass for liver cirrhosis (LC) patients with esophageal varices (EVs) undergoing endoscopic therapy as a primary prophylaxis could exist. As endoscopic therapies, such as endoscopic injection sclerotherapy or endoscopic band ligation for EVs, accompany invasive procedure and patients with EVs receiving endoscopic therapies mostly rest in bed during hospitalization, clarifying these issues are clinically of importance. The purposes of this study were therefore to examine changes in skeletal muscle mass for LC patients with EVs undergoing endoscopic therapy as a primary prophylaxis and to identify pretreatment predictors which are associated with the amelioration in skeletal muscle mass. This is a subgroup analysis in our previous randomized controlled trial. A total of 51 LC patients with EVs were analyzed. Skeletal muscle mass was assessed using bioimpedance analysis (BIA). Skeletal muscle index (SMI) was defined as sum of skeletal muscle mass in body trunk and upper and lower extremities divided by height squared (cm/m) using data for BIA. We compared the changes in SMI at baseline and SMI at Day 50 after endoscopic treatment for EVs. Our study cohort included 33 males and 18 females with median (range) age of 62 (29-81) years. There were 31 patients with Child-Pugh A and 20 with Child-Pugh B. The median SMI for the entire cohort at baseline was 8.96 cm/m (range, 5.87-13.11 cm/m), while the median SMI for the entire cohort at Day 50 was 8.83 cm/m (range, 5.59-12.29 cm/m) (P = .9995). In baseline characteristics, prealbumin (P = .0477), branched-chain amino acid to tyrosine ratio (BTR) (P = .0056), and retinol-binding protein (P = .0296) in the increased SMI group (n = 15) were significantly higher than those in the nonincreased SMI group (n = 36). Multivariate analysis for the above 3 significant factors showed that only BTR was a significant prognostic pretreatment factor linked to the presence of increased SMI (P = .0235). In conclusion, pretreatment BTR level can be helpful for predicting increased SMI after endoscopic therapy as a primary prophylaxis for LC patients with EVs.

We aimed to investigate the impact of decrease of muscle mass on survival after eradication of esophageal varices (EVs) treated by endoscopic therapies as a primary prophylaxis in patients with liver cirrhosis (LC). In all, 177 LC individuals with EVs undergoing endoscopic therapies were analyzed. We retrospectively examined the impact of muscle mass decrease as determined by psoas muscle mass (PMM) at the third lumber on computed tomography (depletion of PMM [DPMM]) on survival as compared with serum sodium combined Model for End-stage Liver Disease (MELD-Na). In comparison of the effects of these parameters, we used time-dependent receiver-operating characteristics (ROC) analysis. We also investigated parameters related to overall survival in the univariate and multivariate analyses. This study included 116 males and 61 females with a median age of 66 years. The median follow-up periods were 2.7 years (range 0.1-9.6 years). In all, 110 patients (62.1%) had DPMM. The median MELD-Na score was 7.200 (range -3.451 to 30.558). The MELD-Na score in patients with DPMM (median 7.685) was significantly higher than that in patients without DPMM (median 6.235) (P = .0212). In the multivariate analysis, presence of hepatocellular carcinoma (P < .0001), presence of DPMM (P < .0001), and MELD-Na ≥7.2 (P = .0438) were revealed to be significant predictors related to overall survival. In time-dependent ROC analyses, all area under the ROCs for DPMM in each time point were higher than those for MELD-Na in the entire cohort and in patients without hepatocellular carcinoma at baseline (n = 133). In conclusion, for LC patients treated by endoscopic therapies for EVs, DPMM had stronger prognostic impact than MELD-Na.

The aim of this study was to examine the effect of nonprotein respiratory quotient (npRQ), as assessed using indirect calorimetry, on clinical outcomes in patients with liver cirrhosis (LC). A total of 244 LC patients were evaluated in this study. For the univariate analysis, for each continuous variable, the optimal cutoff value that maximized the sum of sensitivity and specificity was selected using receiver operating curve (ROC) analysis for survival. There were 137 men and 107 women with the median (range) age of 67 (25-90) years. Indirect calorimetry indicated that 54 patients (22.1%) had hepatocellular carcinoma (HCC) on radiological findings and 59 patients (24.2%) had protein energy malnutrition, as defined by npRQ <0.85 and serum albumin level <3.5 g/dL. In ROC analysis of npRQ for survival, the optimal cutoff point of npRQ was 0.849 for all cases (area under the ROC = 0.61272; sensitivity, 66.22%; and specificity, 57.06%). The median follow-up periods after indirect calorimetry were 4.35 years (range, 1.01-9.66 years) in patients with npRQ ≥0.85 (n = 122) and 3.71 years (range, 0.19-9.51 years) in patients with npRQ <0.85 (n = 122). The 1-, 3-, and 5-year cumulative OS rates in patients with npRQ ≥0.85 were 100%, 87.79%, and 77.24%, respectively, whereas those in patients with npRQ <0.85 were 94.26%, 73.65% and 57.78%, respectively (P = 0.0004). In the multivariate analysis, presence of HCC (P = 0.0045), body mass index (P < 0.0001), serum albumin (P = 0.0441), prothrombin time (P = 0.0463), npRQ (P = 0.0024), estimated glomerular filtration rate (P = 0.0086), and des-γ-carboxy prothrombin (P = 0.0268) were found to be significant predictors associated with OS. For all cases, risk stratification for survival was well performed using these significant variables. In conclusion, npRQ value, as assessed by indirect calorimetry, can be helpful for predicting clinical outcomes for LC patients., Competing Interests: The authors have no conflicts of interest to disclose.

We created a model to predict the development of liver carcinogenesis in patients with chronic hepatitis B (CHB) undergoing entecavir (ETV) therapy and to validate the accuracy using an independent dataset.A total of 328 CHB subjects were analyzed. Subjects were randomly assigned into 2 groups: the training group (n = 164) and the validation group (n = 164). Using data from the training group, we built a predictive model for liver carcinogenesis by performing univariate and multivariate analyses using variables associated with liver carcinogenesis. We subsequently assessed the applicability of the constructed model in the validation group.The median (range) follow-up periods in the training and the validation groups were 5.03 years (1.03-9.98) and 4.84 years (1.10-9.97), respectively. The proportion of hepatitis B virus-DNA at 24 weeks <1.9 log IU/mL in the training group was 70.7% (116/164), while that in the validation group was 71.3% (117/164). For the entire cohort (n = 328), the median alpha-fetoprotein (AFP) value at 24 weeks (3.45 ng/mL; range, 0.9-102.7 ng/mL) significantly decreased compared to the baseline values (5.55 ng/mL; range, 0.9-1039.5 ng/mL), while the median alanine aminotransferase (ALT) value at 24 weeks (24 IU/mL; range, 6-251 IU/mL) also significantly decreased compared to baseline values (57 IU/mL; range, 7-1450 IU/mL). During the observation period, hepatocellular carcinoma (HCC) developed in 15 (9.1%) patients in the training group and in 17 (10.4%) patients in the validation group. The 3- and 5-year cumulative HCC incidence rates in the entire cohort were 4.48% and 9.52%, respectively. In the multivariate analysis of the training group, age ≥54 years (P = 0.0273), ALT level at 24 weeks (P = 0.0456), and AFP at 24 weeks (P = 0.0485) were found to be significant predictors linked to HCC. Using these independent predictors, the risk for HCC development was well stratified in the validation group (overall significance, P < 0.0001). Similar results were observed in subgroup analyses of patients with or without cirrhosis and HBe antigen positivity.In conclusion, our predictive model was well verified; hence, it may be a promising model for the prediction of the development of liver carcinogenesis in CHB patients undergoing ETV therapy., Competing Interests: The authors have no funding and conflicts of interest to disclose.

Purpose: To investigate genetic factors associated with choroidal vascular hyperpermeability (CVH) and subfoveal choroidal thickness in eyes with treatment-naive polypoidal choroidal vasculopathy., Methods: We studied 149 consecutive patients with polypoidal choroidal vasculopathy. The presence of CVH was evaluated using indocyanine green angiography. Subfoveal choroidal thickness and axial length were measured by spectral domain optical coherence tomography and optical biometry, respectively. Genotyping of three single nubleotide polymorphisms (SNPs), including age-related maculopathy susceptibility 2 (ARMS2) A69S (rs10490924), complement factor H (CFH) I62V (rs800292), and CFH (rs1329428), which are reportedly associated with central serous chorioretinopathy, was conducted using TaqMan technology., Results: Thicker subfoveal choroidal thickness was associated with younger age, shorter axial length, G-allele frequency in ARMS2 A69S (rs10490924), and T-allele frequency in CFH (rs1329428) (P = 0.001, P < 0.001, P = 0.004, and P = 0.002, respectively; multiple regression analysis). Among 149 eyes with polypoidal choroidal vasculopathy, 35 eyes (23.5%) exhibited CVH on indocyanine green angiography. Patients with CVH had a significantly higher frequency of the G allele of ARMS2 A69S (rs10490924) and the T allele of CFH (rs1329428), which are reported to be risk alleles for central serous chorioretinopathy (P = 0.006 and P = 0.032, respectively; multivariate regression analysis)., Conclusion: Subfoveal choroidal thickness and CVH in eyes with treatment-naive polypoidal choroidal vasculopathy were associated with ARMS2 A69S (rs10490924) and CFH (rs1329428).

We created a predictive model using serum-based biomarkers for advanced fibrosis (F3 or more) in patients with chronic hepatitis B (CHB) and to confirm the accuracy in an independent cohort.A total of 249 CHB patients were analyzed. To achieve our study aim, a training group (n = 125) and a validation group (n = 124) were formed. In the training group, parameters related to the presence of advanced fibrosis in univariate and multivariate analyses were examined, and a formula for advanced fibrosis was created. Next, we verified the applicability of the predictive model in the validation group.Multivariate analysis identified that gamma-glutamyl transpeptidase (GGT, P = 0.0343) and platelet count (P = 0.0034) were significant predictors of the presence of advanced fibrosis, while Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA-M2BP, P = 0.0741) and hyaluronic acid (P = 0.0916) tended to be significant factors. Using these 4 parameters, we created the following formula: GMPH score = -0.755 - (0.015 × GGT) - (0.268 × WFA-M2BP) + (0.167 × platelet count) + (0.003 × hyaluronic acid). In 8 analyzed variables (WFA-M2BP, aspartate aminotransferase-to-platelet ratio index, FIB-4 index, prothrombin time, platelet count, hyaluronic acid, Forns index, and GMPH score), GMPH score had the highest area under the receiver operating characteristic (AUROC) curve for advanced fibrosis with a value of 0.8064 in the training group and in the validation group, GMPH score also had the highest AUROC (0.7782). In all subgroup analyses of the hepatitis B virus (HBV) status (HB surface antigen quantification, HBV-DNA quantification, and HBe antigen seropositivity), GMPH score in F3 or F4 was significantly lower than that in F0 to F2. In the above mentioned 8 variables, differences between the liver fibrosis stages (F0 to F1 vs F2, F2 vs F3, F3 vs F4, F0 to F1 vs F3, F0 to F1 vs F4, and F2 vs F4) for the entire cohort (n = 249) were all significant only in GMPH score.In conclusion, the GMPH scoring system may be helpful for detecting advanced liver fibrosis in patients with CHB., Competing Interests: The authors have no conflicts of interest to disclose.

Serum hyaluronic acid (HA) is a well-established marker of fibrosis in patients with chronic liver disease (CLD). However, the relationship between serum HA level and protein-energy malnutrition (PEM) in patients with CLD is an unknown. We aimed to examine the relationship between serum HA level and PEM in patients with chronic hepatitis C (CHC) compared with the relationships of other serum markers of fibrosis. A total of 298 CHC subjects were analyzed. We defined patients with serum albumin level of ≤3.5 g/dL and nonprotein respiratory quotient <0.85 using indirect calorimetry as having PEM. We investigated the effect of serum HA level on the presence of PEM. Receiver operating characteristic curve (ROC) analysis was performed for calculating the area under the ROC (AUROC) for serum HA level, platelet count, aspartate aminotransferase (AST) to platelet ratio index, FIB-4 index, AST to alanine aminotransferase ratio, and Forns index for the presence of PEM. The median serum HA level in this study was 148.0 ng/mL (range: 9.0-6340.0 ng/mL). In terms of the degree of liver function (chronic hepatitis, Child-Pugh A, B, and C), the analyzed patients were well stratified according to serum HA level (overall significance, P < 0.0001). The median value (range) of serum HA level in patients with PEM (n = 61) was 389.0 ng/mL (43.6-6340.0 ng/mL) and that in patients without PEM (n = 237) was 103.0 ng/mL (9.0-783.0 ng/mL) (P < 0.0001). Among 6 fibrosis markers, serum HA level yielded the highest AUROC with a level of 0.849 at an optimal cut-off value of 151.0 ng/mL (sensitivity 93.4%; specificity 62.0%; P < 0.0001). In the multivariate analysis, serum HA level was found to be a significant prognostic factor related to the presence of PEM (P = 0.0001).In conclusion, serum HA level can be a useful predictor of PEM in patients with CHC.

Nonalcoholic fatty liver disease has been suggested to be associated with alanine aminotransferase (ALT) elevation in hepatitis B virus (HBV)-infected patients with HBe antigen (HBeAg)-negativity and a low HBV-DNA level. However, few studies have evaluated the association according to histological findings of the liver.Among a total of 198 HBV-infected patients who received a percutaneous liver biopsy, we studied the histological and laboratory findings of HBeAg-negative patients without receiving nucleoside/nucleotide analogues treatment (N = 70) in order to evaluate whether hepatic steatosis and its related metabolic disorders were associated with an elevation in ALT levels in HBeAg-negative patients.In HBeAg-negative patients with a high serum HBV-DNA level (≥2000 IU/mL), the level of HBV-DNA was the only significant factor related to ALT elevation. However, in HBeAg-negative patients with a low HBV-DNA level, the serum ferritin level, and histologically observed hepatic steatosis were significantly associated factors with ALT elevation. When we evaluated 2 metabolic variables (serum ferritin and fasting insulin) that are suggested to be relevant to the presence of progressive disease in Japanese patients, we found that the rate of metabolic disorders was significantly higher among patients with a high ALT level and a low HBV-DNA level than it was among those with other conditions. The triglyceride level and the frequency of moderate or severe hepatic steatosis were significantly higher in patients with a low HBV-DNA level than in those with a high HBV-DNA level.Histologically proven hepatic steatosis and its related metabolic disorders are suggested to be involved in the elevation of aminotransferases of HBeAg-negative patients, particularly those with low HBV-DNA levels., Competing Interests: The authors have no conflicts of interest to disclose.

The aims of the present study were to examine the relationship between serum B-cell activating factor belonging to the tumor necrosis factor family (BAFF) levels and serum interferon-γ-inducible protein-10 (IP-10) levels in patients with autoimmune hepatitis (AIH).A total of 80 corticosteroid therapy naive AIH patients were analyzed in this analysis. First, we examined the relationship between pretreatment serum BAFF and IP-10 levels and liver histological findings. Next, we investigated the relationship of pretreatment serum BAFF and IP-10 levels and aspartate aminotransferase value (AST), alanine aminotransferase value, and serum Immunoglobulin G (IgG) level as serum liver inflammation markers.Our study included 14 men and 66 women with the median (range) age of 64 (21-83) years. The serum BAFF levels ranged from 122.5 to 7696.0 pg/mL (median value, 1417.8 pg/mL), whereas the serum IP-10 levels ranged from 142.0 to 4198.7 pg/mL (median value, 640.1 pg/mL). The serum BAFF levels were significantly stratified in each 2 liver inflammation stage. Similarly, the serum IP-10 levels were significantly stratified in each 2 liver inflammation stage. Among 3 serum inflammation markers, AST value had the highest rs value in terms of the relationship with BAFF level (rs = 0.511, P < 0.001) and IP-10 level (rs = 0.626, P < 0.001). In addition, the serum BAFF level significantly correlated with serum IP-10 level (rs = 0.561, P < 0.001). In patients without advanced fibrosis (F3 or more), the serum BAFF level significantly correlated with serum IP-10 level (rs = 0.658, P < 0.001), whereas in patients with advanced fibrosis, the serum BAFF level significantly correlated with serum IP-10 level (rs = 0.542, P < 0.001).In conclusion, both BAFF and IP-10 are useful for predicting the degree of liver inflammation activity in AIH. BAFF and IP-10 may have the common clinical implication for liver inflammation activity for AIH patients., Competing Interests: The remaining authors declare that they have no conflicts of interest.

We aimed to elucidate the incidence of protein-energy malnutrition (PEM) in patients with chronic liver disease and to identify factors linked to the presence of PEM.A total of 432 patients with chronic liver disease were analyzed in the current analysis. We defined patients with serum albumin level of ≤3.5 g/dL and nonprotein respiratory quotient (npRQ) value using indirect calorimetry less than 0.85 as those with PEM. We compared between patients with PEM and those without PEM in baseline characteristics and examined factors linked to the presence of PEM using univariate and multivariate analyses.There are 216 patients with chronic hepatitis, 123 with Child-Pugh A, 80 with Child-Pugh B, and 13 with Child-Pugh C. Six patients (2.8%) had PEM in patients with chronic hepatitis, 17 (13.8%) in patients with Child-Pugh A, 42 (52.5%) in patients with Child-Pugh B, and 10 (76.9%) in patients with Child-Pugh C (P < 0.001). Multivariate analysis revealed that Child-Pugh classification (P < 0.001), age ≥64 years (P = 0.0428), aspartate aminotransferase (AST) ≥40 IU/L (P = 0.0023), and branched-chain amino acid to tyrosine ratio (BTR) ≤5.2 (P = 0.0328) were independent predictors linked to the presence of PEM. On the basis of numbers of above risk factors (age, AST, and BTR), the proportions of patients with PEM were well stratified especially in patients with early chronic hepatitis or Child-Pugh A (n = 339, P < 0.0001), while the proportions of patients with PEM tended to be well stratified in patients with Child-Pugh B or C (n = 93, P = 0.0673).Age, AST, and BTR can be useful markers for identifying PEM especially in patients with early stage of chronic liver disease.

Background: Long-acting β2-agonists and leukotriene receptor antagonists are two principal agents that can be added to inhaled corticosteroids (ICS) for patients with asthma that is not adequately controlled by ICS alone. The Gly16Arg genotype of the β2-adrenergic receptor (ADRB2) gene may influence the bronchodilator effects of β2-agonists. We hypothesized that differential responses to long-acting β2-agonists or leukotriene receptor antagonists might be determined partly by the Gly16Arg polymorphism in Japanese asthma patients., Materials and Methods: This randomized, genotype-stratified, two-period crossover study included 80 patients with mild-to-moderate asthma (35 Arg/Arg and 45 Gly/Gly individuals). The primary study outcome was the difference in peak expiratory flow (ΔPEF) (ΔPEF, l/min) by genotype after 16 weeks of treatment with salmeterol (ΔPEFsal) or montelukast (ΔPEFmon). In addition, multivariate analyses were used to identify independent factors that were predictive of responses to each treatment., Results: The mean ΔPEFsal-ΔPEFmon was 19.3±46.6 among Arg/Arg individuals and 16.8±51.5 among Gly/Gly individuals, indicating that the Gly16Arg genotype did not influence the differential bronchodilator effect of the two agents. Multivariate analysis showed that higher peripheral eosinophil counts were associated with better response to salmeterol (P<0.05)., Conclusion: The Gly16Arg genotype did not influence the differential bronchodilator effect of salmeterol or montelukast as an add-on therapy to ICS within 16 weeks of follow-up. Higher peripheral eosinophil counts may be associated with better responses to salmeterol in combination with ICS.

Purpose: To compare the association of systemic risk factors between neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV)., Methods: Seven hundred and three patients (235 with nAMD and 468 with PCV) were included. Associated systemic conditions, including hypertension, cardiovascular disease, stroke, diabetes mellitus, and end-stage renal disease, were investigated through an interview and questionnaire., Results: The prevalence of diabetes mellitus and end-stage renal disease in nAMD was significantly higher than that in PCV (P < 0.001 and P = 0.021, respectively, multivariate logistic regression analysis). Moreover, in diabetic patients with nAMD or PCV, the more severe form of diabetic retinopathy was more prevalent in nAMD cases than in PCV cases (P = 0.006, multivariate logistic regression analysis)., Conclusion: Diabetes mellitus and end-stage renal disease are more prevalent in patients with nAMD than in those with PCV. Specific systemic conditions might be associated with the development of nAMD.

Purpose: To investigate whether there is an association of the LOC387715 A69S genotype with visual prognosis after photodynamic therapy in eyes with polypoidal choroidal vasculopathy (PCV)., Methods: Photodynamic therapy was repeated every 3 months until the disappearance of angiographic signs of active lesions in 71 eyes of 71 patients with PCV who were followed-up for at least 12 months. All patients were genotyped for LOC387715 A69S polymorphism (rs10490924, risk-allele T)., Results: Although there was no statistically significant difference in the mean baseline visual acuity (P = 0.53) among the 3 genotypes, there was a statistically significant difference in the visual acuity both at the 12-month and final visits (P = 0.002 and P < 0.001, respectively) with the poorer acuity in patients with the higher "T-"allele frequency. "T" allele was more frequently observed in those with the recurred PCV lesions (odds ratio: 5.8, 95% confidential interval: 2.3-15.1, T vs. G)., Conclusion: There is a pharmacogenetic association between the LOC387715 A69S variant and the long-term results after photodynamic therapy in eyes with PCV. The LOC387715 A69S genotype is of clinical importance to predict the visual prognosis after photodynamic therapy in eyes with PCV. These results should be confirmed or refuted by replication studies.

Purpose: To investigate whether the LOC387715/ARMS2 variants are associated with an angiographic phenotype, including lesion size and composition, in subfoveal polypoidal choroidal vasculopathy., Methods: Ninety-two subjects with symptomatic subfoveal polypoidal choroidal vasculopathy, whose visual acuity was from 0.1 to 0.5 on the Landolt chart, were genotyped for the LOC387715 polymorphism (rs10490924) using denaturing high-performance chromatography. The angiographic phenotype, including lesion composition and size, was evaluated by evaluators who were masked for the genotype. Lesion size was assessed by the greatest linear dimension based on fluorescein or indocyanine green angiography., Results: Although there was no statistically significant difference in lesion size on indocyanine green angiography (P = 0.36, Kruskal-Wallis test) and in lesion composition (P = 0.59, chi-square test) among the 3 genotypes, there was a statistically significant difference in lesion size on fluorescein angiography (P = 0.0022, Kruskal-Wallis test)., Conclusion: The LOC387715 A69S genotype is not associated with lesion composition or size on indocyanine green angiography but with lesion size on fluorescein angiography in patients with subfoveal polypoidal choroidal vasculopathy. Because fluorescein angiography findings represent secondary exudative changes, including subretinal hemorrhages and retinal pigment epithelial detachment, the results in the present study likely indicate that the T allele at the LOC387715 gene is associated with the exudative activity of polypoidal lesions.

Objective: We conducted a phase I dose escalation study to determine the maximum tolerated dose, recommended dose, and safety profile of a biweekly gemcitabine and carboplatin combination regimen in the treatment of patients with completely resected nonsmall cell lung cancer (NSCLC)., Patients and Methods: Patients with completely resected pathologically documented stage IB, II, or IIIA NSCLC, performance status (ECOG) 0-1, with adequate bone marrow, renal, liver, and cardiac functions, were treated with gemcitabine and carboplatin. The starting dose was gemcitabine 800 mg/m2 on days 1 and 15 and carboplatin area under the time-concentration curve (AUC) 4 mg/mL/min on day 1. Gemcitabine was increased to 1000 mg/m2 (level 3). Carboplatin was increased to AUC 5 (level 2, 3). The regimen was performed every 4 weeks. The dose-limiting toxicity of the regimen was assessed during the first chemotherapy cycle., Results: Nine patients were enrolled in this study. All patients were assessed for safety. Grade 3 leukopenia occurred in 1 patient (11%) and grade 3/4 neutropenia occurred in 3 patients (33%). No other grade 3/4 toxicity was observed. No dose-limiting toxicity was experienced at dose levels 1, 2, and 3 of this schedule., Conclusion: Maximum tolerated dose was not reached in this study. Considering treatment continuation, the recommended dose for a phase II study is gemcitabine 1000 mg/m2 on days 1 and 15 and carboplatin AUC 5 on day 1, every 4 weeks. Biweekly administration of gemcitabine and carboplatin is a feasible and well-tolerated regimen for the treatment of patients with completely resected NSCLC as adjuvant chemotherapy.

We conducted a phase I study to determine the maximum tolerated dose, the recommended dose and the safety profile of S-1 and carboplatin combination regimen in the treatment of patients with advanced non-small-cell lung cancer. Chemotherapy-naive patients with advanced non-small-cell lung cancer were treated with S-1 and carboplatin. S-1 was administered orally twice daily for 14 days and carboplatin on day 1 of each cycle, and this was repeated every 4 weeks. Doses of each drug were planned as follows: level 1, 5/65; level 2, 5/80; level 3, 6/80 [carboplatin (area under the curve, mg/ml/min)/S-1 (mg/m/day)]. The dose-limiting toxicity of the regimen was assessed during the first chemotherapy cycle. Twelve patients were enrolled in this study. The main grade 3 or grade 4 toxicities observed during the first cycle were neutropenia (41%), thrombocytopenia (41%) and transaminase elevation. Two of three patients in level 2 had dose-limiting toxicity and this level was considered the maximum tolerated dose. Level 1 was selected as the recommended dose. Objective responses were seen in four patients (response rate 33%). The combination of S-1 plus carboplatin is a feasible and well-tolerated regimen for the treatment of patients with advanced non-small-cell lung cancer.

Purpose: To study the efficacy of additional intravitreal gas injection for unclosed macular holes within 2 weeks after surgery with internal limiting membrane peeling., Methods: We reviewed the results for five consecutive eyes receiving additional intravitreal gas injection for unclosed macular holes within 2 weeks after initial macular hole surgery with internal limiting membrane peeling. The initial surgery consisted of standard pars plana vitrectomy with phacoemulsification and intraocular lens implantation, indocyanine green-assisted peeling of the retinal internal limiting membrane, and fluid-gas exchange with 20% sulfur hexafluoride. The patients were instructed to assume face down positioning for > or =7 days after surgery. If an unclosed macular hole was found after the residual gas volume decreased to <30% of the eyeball volume, fluid-gas exchange was performed using 15% octafluoropropane., Results: All five eyes receiving additional intravitreal gas 7 to 14 days after vitrectomy had complete macular hole closure with macular flattening, as shown by optical coherence tomography 1 month after the additional gas injection. Visual acuity improved (range, 20/100 to 20/30). A minimum of 9 months of follow-up revealed no reopening or serious complications., Conclusion: Additional gas injection during the early postoperative period is recommended for eyes with unclosed macular holes that have undergone vitrectomy with internal limiting membrane peeling.

Recent studies have shown that the homeobox gene Hex plays an important role in inducing differentiation of vascular endothelial cells. In this study, we examined the expression of Hex in vascular smooth muscle cells (VSMCs) in vitro and in vivo. Immunohistochemistry showed a marked induction of Hex protein in neointimal VSMCs after balloon injury in rat aorta. Western and reverse transcriptase-polymerase chain reaction analyses demonstrated that Hex was abundantly expressed in cultured VSMCs, whereas it was undetectable in other cell types or in normal aorta. The expression pattern of Hex was similar to that of SMemb/NMHC-B, a nonmuscle isoform of myosin heavy chain that we have previously reported to be a molecular marker of dedifferentiated VSMCs. We next examined the role of Hex in SMemb gene transcription. Promoter analysis demonstrated that the sequence identical to consensus cAMP-responsive element (CRE) located at -481 of the SMemb promoter was critical for Hex responsiveness. Mutant Hex expression vector, which lacks the homeodomain, failed to stimulate SMemb gene transcription, suggesting the requirement of the homeodomain for its transactivation. Elecrophoretic mobility shift assay showed that Hex binds to a consensus binding sequence for homeobox proteins, but not to CRE. Cotransfection of protein kinase A expression vector increased the ability of Hex to stimulate SMemb promoter activity in a CRE-dependent manner. Overexpression of CRE binding protein (CREB), but not Mut-CREB which contains mutation at Ser133, strongly activated Hex-induced SMemb promoter activity. These results suggest that Hex mediates transcriptional induction of the SMemb/NMHC-B gene via its homeodomain, and Hex can function as a transcriptional modulator of CRE-dependent transcription in VSMCs.

Purpose: To study the effects of retinal pigment epithelial (RPE) deprivation on retinal sensitivity with serial automated static perimetry in cases of RPE tear involving the foveal area., Methods: Two eyes with a tear of the RPE were diagnosed as such on biomicroscopic and fluorescein angiographic examination. Static perimetry was performed in the follow-up study with the Humphrey field analyzer central 10-2 program., Results: The first patient showed a dense scotoma corresponding to a defect in the RPE, which showed mild deterioration throughout the follow-up period from 2-11 weeks after the development of RPE tear. In contrast, the second patient showed preserved visual acuity and an absence of central visual field defects, despite an apparently denuded Bruch membrane involving the fovea during 8-month follow-up., Conclusion: Apparent RPE defect in eyes with RPE tears may or may not be associated with severe visual field defects. The pathophysiology of the disease should be studied, considering these perimetric findings.

Purpose: To document the clinical course of Nd:YAG laser photodisruption for eyes with preretinal hemorrhage following rupture of a retinal macroaneurysm., Methods: We reviewed six eyes of five patients with preretinal hemorrhage due to retinal macroaneurysm that received Nd:YAG laser photodisruption. Nd:YAG laser created a focal opening in the anterior surface of the preretinal hemorrhage, permitting the blood to enter the vitreous cavity where it would be absorbed more rapidly., Results: Three eyes showed both subhyaloid hemorrhage, which was resorbed without treatment within 2 months, and hemorrhagic detachment of the internal limiting membrane (ILM), which required Nd:YAG laser photodisruption. All eyes showed disappearance of the preretinal hemorrhage and improvement of vision within 1 week of Nd:YAG laser photodisruption. Visual recovery was less prominent in eyes associated with subretinal macular hemorrhage., Conclusion: Preretinal hemorrhage due to a ruptured retinal macroaneurysm could be dispersed into the vitreous cavity with Nd:YAG laser photodisruption. It should be considered in the decision of Nd:YAG laser photodisruption that the visual increment may be limited in eyes that also have subretinal hemorrhage in the macula and that the hemorrhage beneath the ILM tends to remain longer than the subhyaloid hemorrhage.