Is cytoreductive surgery and hyperthermic intraperitoneal chemotherapy still beneficial in patients diagnosed with colorectal peritoneal metastasis who underwent palliative chemotherapy?

BACKGROUND: With a 5-year overall survival of less than 5%, colorectal peritoneal metastasis (CPM) patients are often managed with palliative chemotherapy (CTx). In the past few decades, cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has been introduced as a possible curative treatment for highly selective CPM patients. We share our experience of CRS and HIPEC given the unique characteristics of the medical system and the benefit of CRS and HIPEC in palliative setting. METHODS: From April 2017 to October 2021, CPM patients who underwent CRS and HIPEC were analyzed. Patients were allocated into perioperative and palliative CTx arm based on the duration between initial diagnosis of CPM to undergoing CRS and HIPEC of 6 months. Data including perioperative parameters, postoperative outcomes, and survival were analyzed with a median follow-up of 28.5 months. RESULTS: Twenty-six CPM patients underwent CRS and HIPEC. Mean time from diagnosis of CPM to CRS and HIPEC was 5.5 months with 14 patients in the perioperative arm and 12 patients in the palliative arm. Perioperative group showed a longer RFS of 13.5 months compared to 8 months in the palliative group. Median overall survival of palliative group was 41.50 months, and 18 patients among all groups are alive at the time of this report. CONCLUSION: CRS and HIPEC could be a treatment option for a carefully selected CPM patients performed by experienced surgeons. Overall survival of 41.50 months in palliative group compared to 16.8 months from conventional systemic CTx supports CRS and HIPEC even in palliative patients.

Predicting severe proximal left anterior descending coronary artery stenosis using proximal left anterior descending coronary artery tortuosity and the angle between the left main and anterior descending coronary arteries: a retrospective cross-sectional study.

Background: Coronary bifurcation angles influence plaque initiation in the coronary artery, and changes in blood flow caused by tortuosity in the coronary arteries can reduce blood pressure distal to the tortuous portion of the coronary artery, leading to myocardial ischemia. We aimed to describe two factors (coronary artery tortuosity and bifurcation angle) as one descriptor for the evaluation of proximal left anterior descending coronary artery (LAD) disease. Methods: We reviewed the medical records of 133 consecutive patients who underwent computed tomography angiography (CTA) for angina symptoms between November 2019 and January 2020. The patients were divided into two groups according to the presence of significant LAD stenosis on CTA (defined as LAD stenosis >50%). The straight length of the vessel was measured using the central luminal line of the flow path, and, calculated using proprietary algorithms in TeraRecon software. We used three-dimensional volume rendering and two-dimensional axial images to measure the left main coronary artery (LM)-LAD angles. Results: In the univariate analysis, there were significant differences in the linear distance between the endpoints of the 20 mm actual curve of the LAD (d20), cosine value for LM-LAD angle (cosθ) <0.8, age, presence of hypertension or diabetes, and number of pack years [hazard ratio (HR): 2.70, 8.04, 1.05, 3.70, 2.82, and 1.04; P=0.029, P<0.001, P=0.020, P=0.024, P=0.021, and P=0.002, respectively]. However, in the multivariate analysis, the cosθ multiplied by d20 (d20*cosθ) <15.5, presence of hypertension and number of pack years (HR: 11.36, 4.54, and 1.04; P<0.001, P=0.019, and P=0.003, respectively) were predictors of significant proximal LAD stenosis. Conclusions: As the tortuosity and LM-LAD angle increased (d20 and cosθ decreased, respectively), the chance of proximal LAD lesions formation increased. d20*cosθ might be useful as a predictor of proximal LAD stenosis.

The lipoprotein-associated phospholipase A2 inhibitor Darapladib sensitises cancer cells to ferroptosis by remodelling lipid metabolism.

Arachidonic and adrenic acids in the membrane play key roles in ferroptosis. Here, we reveal that lipoprotein-associated phospholipase A2 (Lp-PLA2) controls intracellular phospholipid metabolism and contributes to ferroptosis resistance. A metabolic drug screen reveals that darapladib, an inhibitor of Lp-PLA2, synergistically induces ferroptosis in the presence of GPX4 inhibitors. We show that darapladib is able to enhance ferroptosis under lipoprotein-deficient or serum-free conditions. Furthermore, we find that Lp-PLA2 is located in the membrane and cytoplasm and suppresses ferroptosis, suggesting a critical role for intracellular Lp-PLA2. Lipidomic analyses show that darapladib treatment or deletion of PLA2G7, which encodes Lp-PLA2, generally enriches phosphatidylethanolamine species and reduces lysophosphatidylethanolamine species. Moreover, combination treatment of darapladib with the GPX4 inhibitor PACMA31 efficiently inhibits tumour growth in a xenograft model. Our study suggests that inhibition of Lp-PLA2 is a potential therapeutic strategy to enhance ferroptosis in cancer treatment.

FSP1 confers ferroptosis resistance in KEAP1 mutant non-small cell lung carcinoma in NRF2-dependent and -independent manner.

Ferroptosis, a type of cell death induced by lipid peroxidation, has emerged as a novel anti-cancer strategy. Cancer cells frequently acquire resistance to ferroptosis. However, the underlying mechanisms are poorly understood. To address this issue, we conducted a thorough investigation of the genomic and transcriptomic data derived from hundreds of human cancer cell lines and primary tissue samples, with a particular focus on non-small cell lung carcinoma (NSCLC). It was observed that mutations in Kelch-like ECH-associated protein 1 (KEAP1) and subsequent nuclear factor erythroid 2-related factor 2 (NRF2, also known as NFE2L2) activation are strongly associated with ferroptosis resistance in NSCLC. Additionally, AIFM2 gene, which encodes ferroptosis suppressor protein 1 (FSP1), was identified as the gene most significantly correlated with ferroptosis resistance, followed by multiple NRF2 targets. We found that inhibition of NRF2 alone was not sufficient to reduce FSP1 protein levels and promote ferroptosis, whereas FSP1 inhibition effectively sensitized KEAP1-mutant NSCLC cells to ferroptosis. Furthermore, we found that combined inhibition of FSP1 and NRF2 induced ferroptosis more intensely. Our findings imply that FSP1 is a crucial suppressor of ferroptosis whose expression is partially dependent on NRF2 and that synergistically targeting both FSP1 and NRF2 may be a promising strategy for overcoming ferroptosis resistance in cancer.

An integrated view of lipid metabolism in ferroptosis revisited via lipidomic analysis.

Ferroptosis is a form of regulated cell death characterized by iron-dependent lipid peroxidation. This process contributes to cellular and tissue damage in various human diseases, such as cardiovascular diseases, neurodegeneration, liver disease, and cancer. Although polyunsaturated fatty acids (PUFAs) in membrane phospholipids are preferentially oxidized, saturated/monounsaturated fatty acids (SFAs/MUFAs) also influence lipid peroxidation and ferroptosis. In this review, we first explain how cells differentially synthesize SFA/MUFAs and PUFAs and how they control fatty acid pools via fatty acid uptake and ß-oxidation, impacting ferroptosis. Furthermore, we discuss how fatty acids are stored in different lipids, such as diacyl or ether phospholipids with different head groups; triglycerides; and cholesterols. Moreover, we explain how these fatty acids are released from these molecules. In summary, we provide an integrated view of the diverse and dynamic metabolic processes in the context of ferroptosis by revisiting lipidomic studies. Thus, this review contributes to the development of therapeutic strategies for ferroptosis-related diseases.

Intravitreal Brolucizumab and Aflibercept for Polypoidal Choroidal Vasculopathy.

Purpose: To compare the effectiveness of intravitreal injections of brolucizumab and aflibercept in patients with polypoidal choroidal vasculopathy (PCV). Methods: In total, 62 treatment-naive PCV eyes (62 patients) treated with intravitreal brolucizumab or aflibercept were analyzed retrospectively. All patients received a monthly loading injection of antivascular endothelial growth factor for 3 months, followed by further injections as required. Visual and anatomical outcomes were compared between drugs after 12 months of treatment. Results: The improvement in best-corrected visual acuity after 12 months of treatment was not significantly different between the brolucizumab-treated (22 eyes) and aflibercept-treated groups (40 eyes). However, in the brolucizumab-treated group, there was a significantly greater decrease in central retinal thickness (172 vs. 147 µm; P = 0.031) and subfoveal choroidal thickness after treatment (51 vs. 29 µm; P = 0.025). In addition, the regression rate of polypoidal lesions was significantly higher in the brolucizumab-treated group (77.3%, 17/22 eyes) than that in the aflibercept-treated group (45.0%, 18/40 eyes; P = 0.014). Sterile intraocular inflammation showing mild vitritis was observed in 1 of the 22 eyes (4.5%) of brolucizumab-treated patients. Conclusion: Intravitreal brolucizumab injections for PCV showed visual improvement comparable to that of aflibercept during the 12-month treatment period. However, brolucizumab was more effective than aflibercept for the regression of polypoidal lesions and caused a greater decrease in central retinal thickness and subfoveal choroidal thickness.

Genetic variants of MUC4 are associated with susceptibility to and mortality of colorectal cancer and exhibit synergistic effects with LDL-C levels.

As a disease with high mortality and prevalence rates worldwide, colorectal cancer (CRC) has been thoroughly investigated. Mucins are involved in the induction of CRC and the regulation of intestinal homeostasis but a member of the mucin gene family MUC4 has a controversial role in CRC. MUC4 has been associated with either decreased susceptibility to or a worse prognosis of CRC. In our study, the multifunctional aspects of MUC4 were elucidated by genetic polymorphism analysis in a case-control study of 420 controls and 464 CRC patients. MUC4 rs1104760 A>G polymorphism had a protective effect on CRC risk (AG, AOR = 0.537; GG, AOR = 0.297; dominant model, AOR = 0.493; recessive model, AOR = 0.382) and MUC4 rs2688513 A>G was associated with an increased mortality rate of CRC (5 years, GG, adjusted HR = 6.496; recessive model, adjusted HR = 5.848). In addition, MUC4 rs1104760 A>G showed a high probability of being a potential biomarker for CRC patients with low-density lipoprotein cholesterol (LDL-C) in the risk range while showing a significant synergistic effect with the LDL-C level. This is the first study to indicate a significant association between MUC4 genetic polymorphisms and CRC prevalence, suggesting a functional genetic variant with the LDL-C level, for CRC prevention.

Incidence of early complications requiring treatment plan changes after vitreoretinal surgery: a single-center study in South Korea.

BACKGROUND: Information regarding incidence of treatment plan changes may be useful when discussing postoperative treatment plans for patients. Moreover, it may help establish a standardized postoperative treatment plan. This study aimed to evaluate the incidence of early complications requiring treatment plan changes in patients following vitreoretinal surgery and investigate its risk factors. METHODS: This single-center retrospective study included 465 patients who had undergone vitreoretinal surgery. The reasons, incidence, and timing of treatment plan changes within 14 days of surgery were identified. Potential factors associated with the changes, such as patient demographics, surgeon's experience, diagnoses, and type of surgery were also analyzed. RESULTS: The treatment plan was changed in 76 patients (16.3%) at a mean of 4.0 ± 3.2 days after vitreoretinal surgery. The reasons for the plan changes were increased intraocular pressure (IIOP) in 66(86.8%), intraocular inflammation in 2(2.6%), corneal edema in 3(3.9%), leakage from the sclerotomy wound in 3(3.9%) patients, and combined IIOP and intraocular inflammation in 2(2.6%). The date of discharge was postponed because of treatment plan changes in 17 patients (22.4%). The incidence of plan changes was higher in patients who underwent gas or oil tamponade (P < 0.001) and those who underwent surgery performed by less experienced surgeons (P = 0.034). CONCLUSIONS: Treatment plan was changed in 16.3% of patients after vitreoretinal surgery. The risk of treatment plan changes was associated with the surgeon's experience in vitreoretinal surgery and the type of surgery. These results should be considered when establishing standardized care plans for patients who require vitreoretinal surgery.

Conversion to Veno-arteriovenous Extracorporeal Membrane Oxygenation for Differential Hypoxia.

Background: Patients who require initial venoarterial extracorporeal membrane oxygenation (VA ECMO) support may need to undergo veno-arteriovenous ECMO (VAV ECMO) conversion. However, there are no definitive criteria for conversion to VAV ECMO. We report 9 cases of VAV ECMO at Gyeongsang National University Changwon Hospital, Gyeongsang National University College of Medicine. Methods: Of 158 patients who received ECMO support between January 2017 and June 2019, 82 were supported by initial VA ECMO. We retrospectively reviewed the medical records of 9 patients (7 men and 2 women; age, 53.1±19.4 years) who had differential hypoxia and required VAV ECMO support. Percutaneous transaortic catheter venting was used to detect the differential hypoxia. Results: Among the 82 patients who received VA ECMO support, 9 (10.9%) had differential hypoxia and required conversion to VAV ECMO support. The mean time from VA ECMO support to VAV ECMO support and the mean duration of the VAV support were 2.1±2.2 days and 1.9±1.5 days, respectively. The average peak inspiratory pressure before and after VAV ECMO application was 23.89±3.95 cmH2O and 20.67±5.72 cmH2O, respectively, decreasing by an average of 3.2±3.5 cmH2O (p=0.040). The PaO2/FiO2 ratio was kept below 100 mm Hg in survivors and non-survivors for 116±65.4 and 250±124.9 minutes, respectively (p=0.016). Six patients underwent extracorporeal cardiopulmonary resuscitation, of whom 4 survived (67%). The overall survival rate of patients who underwent conversion from VA ECMO to VAV ECMO was approximately 56%. Conclusion: Rapid detection of differential hypoxia is required when VA ECMO is applied, and efficient conversion to VAV ECMO may be critical for patient survival.

Prediction of anti-vascular endothelial growth factor agent-specific treatment outcomes in neovascular age-related macular degeneration using a generative adversarial network.

To develop an artificial intelligence (AI) model that predicts anti-vascular endothelial growth factor (VEGF) agent-specific anatomical treatment outcomes in neovascular age-related macular degeneration (AMD), thereby assisting clinicians in selecting the most suitable anti-VEGF agent for each patient. This retrospective study included patients diagnosed with neovascular AMD who received three loading injections of either ranibizumab or aflibercept. Training was performed using optical coherence tomography (OCT) images with an attention generative adversarial network (GAN) model. To test the performance of the AI model, the sensitivity and specificity to predict the presence of retinal fluid after treatment were calculated for the AI model, an experienced (Examiner 1), and a less experienced (Examiner 2) human examiners. A total of 1684 OCT images from 842 patients (419 treated with ranibizumab and 423 treated with aflibercept) were used as the training set. Testing was performed using images from 98 patients. In patients treated with ranibizumab, the sensitivity and specificity, respectively, were 0.615 and 0.667 for the AI model, 0.385 and 0.861 for Examiner 1, and 0.231 and 0.806 for Examiner 2. In patients treated with aflibercept, the sensitivity and specificity, respectively, were 0.857 and 0.881 for the AI model, 0.429 and 0.976 for Examiner 1, and 0.429 and 0.857 for Examiner 2. In 18.5% of cases, the fluid status of synthetic posttreatment images differed between ranibizumab and aflibercept. The AI model using GAN might predict anti-VEGF agent-specific short-term treatment outcomes with relatively higher sensitivity than human examiners. Additionally, there was a difference in the efficacy in fluid resolution between the anti-VEGF agents. These results suggest the potential of AI in personalized medicine for patients with neovascular AMD.

Percutaneous cholecystoduodenal stent as a definite treatment for acute cholecystitis in elderly or comorbid patients: a bicentric retrospective study

PURPOSE: To investigate the safety and efficacy of percutaneous cholecystoduodenal stent (CDS) placement to prevent recurrence of acute cholecystitis in patients who were unfit for cholecystectomy. METHODS: Between April 2016 and January 2022, 46 patients [median age (range) = 81 (37-99) years; men = 15] with acute cholecystitis who were unfit for surgery underwent percutaneous cholecystostomy followed by a CDS placement in two institutions. Plastic stents of three different materials were used [polyethylene, polyurethane (PU), and polycarbonate (PCB)-based PU]. Clinical outcomes, including technical and clinical success rates and early (<30 days) and delayed adverse events, were retrospectively assessed by stent type. RESULTS: CDS placement was technically successful in 39 patients. Clinical success, defined as cholecystostomy catheter removal, was achieved in 35 of 39 patients. Immediate complications, such as acute pancreatitis and peritonitis, occurred in two patients. Two patients experienced recurrent cholecystitis during a 113-day follow-up (range, 3-1,723). Three-stent groups had significantly different delayed complications on Fisher's exact test (P = 0.021). The Bonferroni post-hoc analysis showed the PCB-PU group tended to have fewer complications than the PU group (P = 0.060). CONCLUSION: CDS placement is applicable in treating acute cholecystitis patients who were initially unfit for surgery, but further investigation is needed. Although it was not statistically significant, a PCB-PU stent can be suitable for this use because it tends to have fewer delayed complications and is equipped with a drawstring and side holes.

SUBRETINAL FLUID ASSOCIATED WITH DRUSENOID PIGMENT EPITHELIAL DETACHMENT.

PURPOSE: To analyze the clinical characteristics of drusenoid pigment epithelial detachment (PED) with subretinal fluid (SRF) and to evaluate the impact of SRF on the long-term visual and anatomical outcomes. METHODS: Forty-seven eyes with drusenoid PED (47 patients) who completed >24 months of follow-up were retrospectively analyzed. Intergroup comparisons of the visual and anatomical outcomes with and without SRF were made. RESULTS: The mean duration of follow-up was 32.9 ± 18.7 months. The group with drusenoid PED with SRF (14 eyes) showed significantly higher PED height (468 ± 130 µ m vs. 313 ± 88 µ m, P < 0.001), larger PED diameter (2,328 ± 953 µ m vs. 1,227 ± 882 µ m, P < 0.001), and larger PED volume (1.88 ± 1.73 mm 3 vs. 1.12 ± 1.35 mm 3 , P = 0.021) than that in the group with drusenoid PED without SRF (33 eyes) at baseline. No significant intergroup difference was found regarding the best-corrected visual acuity at the final visit. In addition, the incidence of complete retinal pigment epithelial and outer retinal atrophy (cRORA; 21.4%) and the development of macular neovascularization (MNV; 7.1%) for the group with drusenoid PED with SRF showed no difference compared with those (39.4% for cRORA development and 9.1% for MNV development) with drusenoid PED without SRF. CONCLUSION: The size, height, and volume of drusenoid PED were associated with the development of SRF. The SRF in drusenoid PED did not affect the visual prognosis or the development of macular atrophy during long-term follow-up.

INCIDENCE AND TIMING OF PIGMENT EPITHELIAL DETACHMENT AND SUBRETINAL FLUID DEVELOPMENT IN TYPE 3 MACULAR NEOVASCULARIZATION ASSOCIATED WITH AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To evaluate the incidence and timing of pigment epithelial detachment (PED) and subretinal fluid (SRF) development in type 3 macular neovascularization. METHODS: This retrospective study included 84 patients who were diagnosed with treatment-naïve type 3 macular neovascularization who did not show SRF at diagnosis. All patients were initially treated with three loading injections of ranibizumab or aflibercept. After the initial loading injections, as-needed regimen was performed for retreatment. The development of either PED or SRF was identified. The incidence and timing of PED development in patients without PED at diagnosis and that of SRF development in patients with PED at diagnosis were evaluated. RESULTS: The mean follow-up period was 41.3 ± 20.7 months after diagnosis. Among the 32 patients without serous PED at diagnosis, PED developed in 20 (62.5%) at a mean of 10.9 ± 5.1 months after diagnosis. PED development was noted within 12 months in 15 patients (46.8%; 75.0% among the PED development cases). In 52 patients with serous PED and without SRF at diagnosis, 15 developed SRF (28.8%) at a mean of 11.2 ± 6.4 months after diagnosis. SRF development was noted within 12 months in nine patients (17.3%; 66.6% among the SRF development cases). CONCLUSION: PED and SRF developed in a substantial proportion of patients with type 3 macular neovascularization. The average period of development of these pathologic findings was within 12 months of diagnosis, suggesting the need for active treatment during the early treatment period to improve treatment outcomes.

Difference in characteristics and lesion reactivation between type 3 macular neovascularization with and without subretinal fluid at baseline.

PURPOSE: To compare the characteristics and incidence rates of lesion reactivation after anti-vascular endothelial growth factor (VEGF) treatment in type 3 macular neovascularization (MNV) with and without subretinal fluid (SRF) at baseline. METHODS: This retrospective study included 95 patients diagnosed with type 3 MNV. After the initial loading injections, re-treatment was performed when lesion reactivation occurred defined as the re-accumulation of subretinal or intraretinal fluid or the new development of a retinal/subretinal hemorrhage. The differences in the baseline characteristics and the incidence rates of lesion reactivation were compared between patients with SRF (SRF group, n = 42) and those without SRF (non-SRF group, n = 53). RESULTS: At diagnosis, the mean visual acuity was worse (0.68 ± 0.41 vs 0.50 ± 0.36; P = 0.032), mean central retinal thickness was greater (515.4 ± 145.9 µm vs 383.8 ± 105.5 µm; P < 0.001), and the incidence of focal retinal hemorrhages was higher (90.5% vs 66.0%; P = 0.005) in the SRF group than in the non-SRF group. In the SRF group, the first lesion reactivation was noted in 89.7% at a mean of 5.8 ± 4.4 months after the third injection. In the non-SRF group, the first lesion reactivation was noted in 70.6% at a mean of 6.1 ± 3.8 months. There was a significant difference in lesion reactivation between the two groups (P = 0.019). CONCLUSIONS: The difference in the baseline characteristics and incidence of lesion reactivation between type 3 MNV with and without SRF suggests that the presence of SRF may be indicative of more advanced disease with a high risk of visual deterioration. This result also suggests the need for more active treatment to preserve vision in patients with SRF.

Difference in Lesion Reactivation between Pure Type 2 and Mixed Type 1 and 2 Macular Neovascularization and its Influence on Long-Term Treatment Outcomes.

PURPOSE: To compare lesion reactivation and treatment outcomes between pure type 2 and mixed type 1 and 2 macular neovascularization (MNV) treated with anti-vascular endothelial growth factor (VEGF). METHODS: This retrospective study included 155 patients diagnosed with type 2 MNV. After the initial loading injections, as-needed retreatment was provided. The difference in first lesion reactivation after the initial treatment was evaluated between pure type 2 MNV (pure type 2 group, n = 37) and mixed type 1 and 2 MNV (mixed group, n = 118). The degree of change in the best-corrected visual acuity (BCVA) was also compared between the two groups. RESULTS: The mean follow-up period was 32.7 ± 13.7 months. Lesion reactivation differed significantly between the type 2 (60.0%) and mixed (84.5%) (P = .004) groups. The degree of visual change during the follow-up period also differed significantly between the pure type 2 (mean 2.8 lines of improvement) and mixed (mean 0.2 lines of deterioration) (P = .008) groups. In multivariate analysis, lesion type (P = .012) and baseline visual acuity (P = .002) were significantly associated with ≥2 lines of visual improvement. CONCLUSIONS: Lesion reactivation and treatment outcomes differed between pure type 2 and mixed type 1 and 2 MNV. These results suggested the need for different treatment strategies for these two MNV subtypes.

Comparison of 24-month treatment outcomes between as-needed treatment and switching to treat-and-extend in type 3 macular neovascularization.

This study aimed to compare 24-month treatment outcomes between patients with type 3 macular neovascularization (MNV) treated using an as-needed regimen and those who switched to treat-and-extend (TAE). This retrospective study included 32 patients who were initially treated with an as-needed regimen but switched to TAE (TAE group) and 74 patients who were treated with an as-needed regimen throughout the follow-up period (as-needed group). The number of anti-vascular endothelial growth factor (VEGF) injections and degree of change in best-corrected visual acuity (BCVA) over 24 months were compared between the two groups. The incidence of fibrotic scarring, tears of the retinal pigment epithelium (RPE), and subretinal hemorrhage was also evaluated. The number of anti-VEGF injections was higher in the TAE group (mean: 11.7) than in the as-needed group (mean: 6.9; P < 0.001). The BCVA outcome (measured using the mean logarithm of the minimal angle of resolution [logMAR]) was significantly better in the TAE group (mean improvement of logMAR 0.15) than in the as-needed group (mean deterioration of logMAR 0.15). The incidence of fibrotic scarring (6.3% vs. 18.9%), RPE tears (3.1% vs. 6.8%), and subretinal hemorrhage (0% vs. 9.5%) was relatively lower in the TAE group. Treatment outcomes of the TAE group were better than those of the as-needed group, suggesting that switching to the TAE regimen would be a useful approach for patients with type 3 MNV requiring efficient treatment.

Potential Therapeutic Implication of Herbal Medicine in Mitochondria-Mediated Oxidative Stress-Related Liver Diseases.

Mitochondria are double-membrane organelles that play a role in ATP synthesis, calcium homeostasis, oxidation-reduction status, apoptosis, and inflammation. Several human disorders have been linked to mitochondrial dysfunction. It has been found that traditional therapeutic herbs are effective on alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) which are leading causes of liver cirrhosis and hepatocellular carcinoma. The generation of reactive oxygen species (ROS) in response to oxidative stress is caused by mitochondrial dysfunction and is considered critical for treatment. The role of oxidative stress, lipid toxicity, and inflammation in NAFLD are well known. NAFLD is a chronic liver disease that commonly progresses to cirrhosis and chronic liver disease, and people with obesity, insulin resistance, diabetes, hyperlipidemia, and hypertension are at a higher risk of developing NAFLD. NAFLD is associated with a number of pathological factors, including insulin resistance, lipid metabolic dysfunction, oxidative stress, inflammation, apoptosis, and fibrosis. As a result, the improvement in steatosis and inflammation is enough to entice researchers to look into liver disease treatment. However, antioxidant treatment has not been very effective for liver disease. Additionally, it has been suggested that the beneficial effects of herbal medicines on immunity and inflammation are governed by various mechanisms for lipid metabolism and inflammation control. This review provided a summary of research on herbal medicines for the therapeutic implementation of mitochondria-mediated ROS production in liver disease as well as clinical applications through herbal medicine. In addition, the pathophysiology of common liver disorders such as ALD and NAFLD would be investigated in the role that mitochondria play in the process to open new therapeutic avenues in the management of patients with liver disease.

Comparison of treatment methods for submacular hemorrhage in neovascular age-related macular degeneration: conservative versus active surgical strategy.

The optimal treatment of submacular hemorrhage (SMH) following neovascular age-related macular degeneration (nAMD) is controversial. This study aimed to compare visual outcomes of conservative versus active surgical treatment. Two hundred thirty-six eyes of 236 patients with SMH (≥ 1 disc diameter) were stratified into four groups: observation (n = 21); anti-vascular endothelial growth factor (VEGF) monotherapy (n = 161); non-surgical gas tamponade (n = 31); and subretinal surgery (n = 23). The primary outcome was best-corrected visual acuity (BCVA) at 12 months. The baseline BCVAs of the observation, anti-VEGF monotherapy, non-surgical gas tamponade, and subretinal surgery groups were 1.50 ± 0.70, 1.09 ± 0.70, 1.31 ± 0.83, and 1.62 ± 0.77 logarithm of minimal angle resolution (LogMAR), respectively. The mean BCVAs at 12 months were 1.39 ± 0.84, 0.90 ± 0.83, 1.35 ± 0.88, and 1.44 ± 0.91 LogMAR, respectively. After adjusting for age, baseline BCVA, SMH size, and the number of intravitreal anti-VEGF injections before SMH, the mean BCVA showed no significant difference among treatments at 12 months (P = 0.204). The anti-VEGF monotherapy group showed better mean BCVA significantly at 3 months (P < 0.001). Only baseline BCVA was associated with VA gain at 12 months (Odds ratio = 3.53, P < 0.001). This study demonstrated that there was no difference in 12 month visual outcomes among treatments and a better early visual outcome can be expected with anti-VEGF monotherapy.

Neovascular age-related macular degeneration without exudative recurrence over 24 months after initial remission.

We investigated the characteristics of neovascular age-related macular degeneration (AMD), which rarely recurs after initial remission. This study retrospectively analyzed 392 neovascular AMD patients treated with anti-vascular endothelial growth factor (VEGF). All patients received three monthly loading doses of anti-VEGF injections, followed by a pro re nata (as needed) regimen for 24 months. The baseline characteristics associated with the odds of having no recurrence within 24 months were evaluated using multivariate modeling. After the initial three loading injections over 24 months, 58 (14.8%) eyes showed no exudative recurrence and did not require additional anti-VEGF injections. These patients without exudative recurrence had significantly better best-corrected visual acuity (P = 0.003) and lower central subfoveal thickness (P = 0.035) at 24 months than those with exudative recurrence. Additionally, the incidence of macular atrophy was significantly lower in the former than in the latter (8.6% vs. 21.9%; P = 0.020). Multivariate analysis revealed that younger age (odds ratio [OR], 0.901; P = 0.033), smaller lesion size (OR, 0.589; P = 0.016), and absence of fibrovascular pigment epithelial detachment (PED) (OR, 1.349; P = 0.028) were associated with higher odds of no recurrence during follow-up. Approximately 15% of the neovascular AMD patients showed no exudative recurrence after initial remission during the 24-month follow-up. The infrequent recurrence after initial remission correlated with younger age, smaller lesion size, and absence of fibrovascular PED.