Therapeutic efficacy of nivolumab plus sorafenib therapy in patients with unresectable hepatocellular carcinoma.

BACKGROUND: Immune checkpoint inhibitor therapy is the backbone of numerous combination regimens for improving the therapeutic response of patients with hepatocellular carcinoma (HCC). We aimed to investigate the therapeutic efficacy of nivolumab plus sorafenib therapy in patients with unresectable HCC. METHODS: Patients with unresectable HCC who received sorafenib and followed at Taipei Tzu Chi Hospital from January 2016 to May 2022 were selected for this study, and those treated with nivolumab plus sorafenib and those with sorafenib alone were propensity score matched. The primary outcome was overall survival (OS) presented as a hazard ratio calculated using Cox proportional hazards regression models. RESULTS: In the analysis, 36 patients receiving nivolumab plus sorafenib and 36 receiving sorafenib alone were propensity score matched. The median OS for those receiving nivolumab plus sorafenib and sorafenib alone were 3.6 years and 1.2 years, respectively (p = 0.031). The hazard ratio of OS for nivolumab plus sorafenib compared to sorafenib alone was 0.36 (95 %CI, 0.19-0.70; p = 0.003). Furthermore, patients receiving nivolumab plus sorafenib with a baseline α-fetoprotein(AFP) < 10 ng/mL and early reduction in AFP had a 100 % objective response rate and disease control rate. CONCLUSION: In patients with unresectable HCC, nivolumab plus sorafenib resulted in better OS outcomes than sorafenib.

Chorioretinal Atrophy in Punctate Inner Choroidopathy/multifocal Choroiditis: A Five-year Follow-up Study.

PURPOSE: To report the 5-year results of chorioretinal atrophy (CRA) progression in patients with punctate inner choroidopathy (PIC) or multifocal choroiditis (MFC). METHODS: A retrospective study included PIC/MFC patients with secondary CRA formation. The area of CRA was measured and the progression rate was calculated. Multiple regression analysis was performed to investigate risk factors associated with CRA progression. RESULTS: Forty-five eyes of 36 patients were included. The mean CRA size significantly increased after an average of 4.83 years of follow-up with progression rate of 0.69 mm2/year. Moreover, we had identified the axial length and initial PIC lesion number as significant risk factors for CRA progression. CONCLUSION: Significant CRA enlargement is noted in PIC/MFC patients after 5 years of follow-up. The progression rate is associated with axial length and initial PIC numbers. Aggressive treatment is suggested for eyes with more initial lesion numbers and longer axial length to control the faster CRA progression.

Metformin inhibits gastric cancer cell proliferation by regulation of a novel Loc100506691-CHAC1 axis.

Long noncoding RNAs (lncRNAs) are a group of nonprotein coding transcripts that play a critical role in cancer progression. However, the role of lncRNA in metformin-induced inhibition of cell growth and its biological function in gastric cancer remain largely unknown. In this study, we identified an oncogenic lncRNA, Loc100506691, the expression of which was decreased in gastric cancer cells with metformin treatment. Moreover, Loc100506691 was significantly overexpressed in gastric cancer compared with adjacent normal tissues (p < 0.001), and high Loc100506691 expression was significantly correlated with poor survival of patients with gastric cancer. Additionally, Loc100506691 knockdown could significantly suppress gastric cancer cell growth in vitro, and ectopic Loc100506691 expression accelerated tumor growth in an in vivo mouse model. Analysis of the cell cycle revealed that Loc100506691 knockdown induced cell cycle arrest at the G2/M phase by impairing cell entry from the G2/M to G1 phase. Loc100506691 negatively regulated CHAC1 expression by modulating miR-26a-5p/miR-330-5p expression, and CHAC1 knockdown markedly attenuated Loc100506691 knockdown-induced gastric cancer cell growth and motility suppression. We concluded that anti-proliferative effects of metformin in gastric cancer may be partially caused by suppression of the Loc100506691-miR-26a-5p/miR-330-5p-CHAC1 axis.

3-year follow-up of half-dose verteporfin photodynamic therapy for central serous chorioretinopathy with OCT-angiography detected choroidal neovascularization.

To assess the 3-year outcome of half-dose verteporfin photodynamic therapy (PDT) in central serous chorioretinopathy (CSC) with optical coherence tomography angiography (OCT-A) detected choroidal neovascularization (CNV), we performed a retrospective, interventional study. Patients were divided into 2 groups according to the fluorescein angiography: point source leakage in group 1 and diffuse oozing in group 2. Data were collected from patients including changes of best-corrected visual acuity (BCVA), size of CNV, central macular thickness (CMT), choroidal thickness (CT), reabsorption of subretinal fluid (SRF), sessions of half-dose PDT, and the number of intravitreal injections (IVI) of anti-vascular endothelial growth factor (anti-VEGF). There was a total of 34 eyes in 32 patients included. The mean sessions of half-dose PDT was 1.50 ± 0.75. The mean number of IVI of anti-VEGF was 1.38 ± 3.34. BCVA improved from 0.38 ± 0.33 to 0.20 ± 0.22 (p < 0.001). Mean CMT was significantly reduced along with reduced CT and increased size of CNV. SRF was totally reabsorbed in 31 eyes. Patients in group 1 had significant less sessions of PDT and better final BCVA. In conclusion, half-dose PDT treatment was effective for CSC with CNV. Patients with diffuse oozing in FA may fare less well with half-dose PDT.

Isolated Central Epiretinal Membrane: A Rare Complication of Fovea-Sparing Internal Limiting Membrane Peeling Technique.

PURPOSE: To report a rare complication presenting as an isolated central epiretinal membrane (ERM) related to fovea-sparing internal limiting membrane (ILM) peeling technique. METHODS: Five patients who received fovea-sparing ILM peeling were enrolled. Postoperatively, an isolated central ERM developed. Optical coherence tomography (OCT) was used to evaluate the serial anatomic change. RESULTS: Among the five included patients, one patient had high myopia with foveoschisis, two patients had vitreomacular traction, and two patients had proliferative diabetic retinopathy with tractional retinal detachment and a fovea cyst. With an average of 5.80 months, OCT showed the gradual development of the isolated central ERM with severe fovea distortion. Four patients received secondary revision surgery, with improvement of the fovea contour and visual acuity. CONCLUSION: The fovea-sparing ILM peeling technique may cause a rare but serious complication as the isolated central ERM, which would cause significant fovea distortion as well as visual deterioration. Timely detection and intervention is recommended to prevent further visual loss. This trial is registered with NCT04445142.

Human amniotic membrane grafts for retinal breaks in diabetic tractional retinal detachment and combined tractional and rhegmatogenous retinal detachment.

To describe the surgical outcomes of using human amniotic membrane (hAM) grafts in the management of retinal breaks in diabetic tractional detachment (TRD) and combined tractional and rhegmatogenous retinal detachment (CTRRD). A retrospective case series of 10 eyes with TRD or CTRRD receiving pars plana vitrectomy with hAM grafts implantation, compared with 13 controls receiving the same surgery without hAM grafts. Best-corrected visual acuity (BCVA) and re-detachment rate were compared between two groups. Postoperatively, all eyes in the hAM group had retina attachment without recurrence, while 9 eyes in the control group had retina re-detachment and required additional surgery (0% vs 69.2%, p = 0.003). The BCVA significantly improved in the hAM group (from 1.96 ± 0.95 to 1.44 ± 0.77 in log MAR, p = 0.03), but not improved in control group (p = 0.20). Postoperative optical coherence tomography of the eyes receiving hAM grafts demonstrated glial tissue regeneration and restoration of ellipsoid zone. In diabetic TRD or CTRRD, hAM grafts could be an effective method, with promising outcome. Compared to standard surgery, it could result in higher retina reattachment rate and significant visual improvement. Moreover, it may offer the adjunctive benefit in tissue regeneration and fasten ellipsoid zone restoration.

Radiofrequency ablation versus surgical resection for the treatment of solitary hepatocellular carcinoma 2 cm or smaller: A cohort study in Taiwan.

BACKGROUND/PURPOSE: Radiofrequency ablation (RFA) is increasingly being used instead of surgical resection for the treatment of hepatocellular carcinoma (HCC) tumor measuring ≦2 cm. However, the long-term outcomes of RFA, especially in comparison to surgical resection, are still debated. We compared the outcomes of surgical resection and RFA in patients with a solitary HCC tumor measuring ≦2 cm from a 10-year cohort study. METHODS: From Jan 2006 to Dec 2016, 156 patients with a resectable HCC measuring ≦2 cm who underwent surgical resection (n = 83) or RFA (n = 73) at the Buddhist Tzu Chi Medical Foundation were enrolled. Patient characteristics, overall survival (OS), and recurrence-free survival (RFS) were retrospectively examined, and comparisons were made between the two groups and through subgroup analyses. RESULTS: The 1-year, 3-year, 5-year, and 7-year OS outcomes were comparable between the surgical resection group and the RFA group (P = 0.193), but the surgical resection group had significantly higher 1-year, 3-year, 5-year, 7-year, and 10-year RFS than the RFA group (P = 0.018). Multivariate analysis revealed that patients with lower age, Child-Turcotte-Pugh score, or albumin-bilirubin score before treatment had better OS, and patients with an HCV infection or receiving RFA treatment had higher HCC recurrence rates. CONCLUSION: The liver reserve determined the long-term OS of patients with an HCC tumor ≦ 2 cm, and surgical resection offered better RFS than RFA (ClinicalTrials.gov number, NCT04525833.).

A microbial metabolite synergizes with endogenous serotonin to trigger C. elegans reproductive behavior.

Natural products are a major source of small-molecule therapeutics, including those that target the nervous system. We have used a simple serotonin-dependent behavior of the roundworm Caenorhabditis elegans, egg laying, to perform a behavior-based screen for natural products that affect serotonin signaling. Our screen yielded agonists of G protein-coupled serotonin receptors, protein kinase C agonists, and a microbial metabolite not previously known to interact with serotonin signaling pathways: the disulfide-bridged 2,5-diketopiperazine gliotoxin. Effects of gliotoxin on egg-laying behavior required the G protein-coupled serotonin receptors SER-1 and SER-7, and the Gq ortholog EGL-30. Furthermore, mutants lacking serotonergic neurons and mutants that cannot synthesize serotonin were profoundly resistant to gliotoxin. Exogenous serotonin restored their sensitivity to gliotoxin, indicating that this compound synergizes with endogenous serotonin to elicit behavior. These data show that a microbial metabolite with no structural similarity to known serotonergic agonists potentiates an endogenous serotonin signal to affect behavior. Based on this study, we suggest that microbial metabolites are a rich source of functionally novel neuroactive molecules.

Involvement of the MicroRNA-1-LITAF Axis in Gastric Cancer Cell Growth and Invasion.

BACKGROUND/AIM: Lipopolysaccharide-induced tumor necrosis factor alpha factor (LITAF) has been identified as a tumor suppressor in human cancers. Present study, we assessed biological role of LITAF in human gastric cancer. MATERIALS AND METHODS: The clinical impacts of LITAF expression were assessed in gastric cancer using public databases. The biological role of LITAF was assessed in gastric cancer cells using siLITAF transfection. RESULTS: High LITAF expression was correlated well with worse prognosis, including pathological stage (p=0.034) and pathological T stage (p=0.047), as well as with shorter survival. Herein, we present a novel finding that miR-1-3p could inhibit LITAF expression by directly binding to the 3'-untranslated region of LITAF mRNA. Cell functional assays revealed that LITAF knockdown could significantly suppress gastric cancer growth and motility. CONCLUSION: High LITAF expression resulting from low miR-1-3p expression is a biomarker for poor prognosis or therapeutic targets in gastric cancer.

Decreased swallowing function in the sarcopenic elderly without clinical dysphagia: a cross-sectional study.

BACKGROUND: Sarcopenia and dysphagia are prevalent health issues as the elderly population continues to grow. However, whether sarcopenia, defined by either reduced handgrip strength or gait speed, would lead to pathological effects on swallowing function is still a matter of debate. Studies focusing on subclinical changes in the swallowing function in the sarcopenic elderly are lacking. This study evaluates the swallowing function in the sarcopenic elderly without dysphagia. METHODS: A cross-sectional study was conducted including subjects recruited from the community. Ninety-four individuals aged 65 and older without dysphagia were divided into two groups: sarcopenia and nonsarcopenia. The swallowing assessment included tongue pressure measurement, hyoid displacement (HD), hyoid velocity (HV) measurement with submental ultrasonography, 100-ml water-swallowing test, and the 10-item Eating Assessment Tool (EAT-10). RESULTS: The average tongue pressure was 47.0 ± 13.7 and 48.6 ± 11.5 kPa in the sarcopenia and nonsarcopenia groups, respectively (p = 0.55), whereas the average HD during swallowing was 15.3 ± 4.4 and 13.0 ± 4.2 mm in the sarcopenia and nonsarcopenia groups, respectively (p < 0.05). The median of HV during swallowing was 19.5 (6.41-45.86) and 15.9 (3.7-39.7) mm/s in the sarcopenia and nonsarcopenia group (p < 0.05). The median of time needed for consuming 100 ml water was 12.43 (3.56-49.34) and 5.66 (2.07-19.13) seconds in the sarcopenia and nonsarcopenia groups, respectively (p < 0.05). The median of the EAT-10 score was 0 (0-2) and 0 (0-1) in the sarcopenia and nonsarcopenia groups, respectively (p < 0.05). CONCLUSIONS: In elderly individuals, swallowing function was significantly impaired with sarcopenia before clinical symptoms become clear. However, tongue muscles exhibited resistance to sarcopenia. We observed compensative strategies in patients with sarcopenia, such as reduced swallowing speed and increased hyoid bone movement.

Three-year follow-up of choroidal neovascularisation in eyes of chronic central serous chorioretinopathy.

AIMS: This study aimed to report the 3-year follow-up results of the clinical course and structural changes of choroidal neovascularisation (CNV) by optical coherence tomography angiography (OCT-A) in eyes with a history of chronic central serous chorioretinopathy (CSC). METHODS: This is a retrospective study of patients with chronic CSC complicated with CNV. Patients were recorded of best-corrected visual acuity (BCVA) and treatment modalities. OCT was used to evaluate the presence of subretinal fluid (SRF), type of CNV, changes in central retinal thickness (CRT) and subfoveal choroidal thickness (SFCT). Changes in the size, vessel density (VD) and morphology of CNV were evaluated by OCT-A. Comparison between baseline and final parameters was made. RESULTS: A total of 30 eyes in 26 patients, most of whom had previous treatment for chronic CSC, were included with a mean follow-up period of 40.37±4.11 months. No changes in BCVA were noted (p=0.562). During the 3-year follow-up period with OCT-A, five eyes had SRF noted. The other 25 eyes remained SRF free throughout the course. Regarding the morphological changes, the size of CNV enlarged significantly (p<0.01); VD of CNV decreased significantly (p=0.01); and the number of CNV with visible core vessel significantly increased (p<0.01). A significant reduced SFCT was noted (p=0.02), while the CRT remained unchanged (p=0.855). CONCLUSION: For most eyes infected with chronic CSC receiving previous treatment for the activity of chronic CSC, with CNV subsequently found on OCT-A, a midterm stable clinical course up to 3 years was noted, despite significant structural changes of CNV evaluated by OCT-A.

Foveal microvasculature, refractive errors, optical biometry and their correlations in school-aged children with retinopathy of prematurity after intravitreal antivascular endothelial growth factors or laser photocoagulation.

AIMS: To compare the differences and to assess the correlations regarding to foveal microvasculature, refractive errors and optical biometry in children with history of type 1 retinopathy of prematurity (ROP) treated with either laser photocoagulation or intravitreal injection of antivascular endothelial growth factors (anti-VEGF). METHODS: This is a retrospective and comparative case series. Measurements of fovea microvasculature included the retinal thickness and subfoveal choroid thickness, the size of fovea avascular zone (FAZ), the fovea, parafovea and perifoveal vessel density (VD). Measurements of refractive errors and optical biometry included spherical equivalent, astigmatism, cornea curvature, anterior chamber depth (ACD), lens thickness and axial length (AXL). RESULTS: A total 47 eyes in 25 children were studied (22 laser-treated eyes from 12 children and 25 anti-VEGF treated eyes from 13 children). Laser-treated eyes had significantly smaller FAZ (p=0.004), higher fovea VD, lower parafoveal VD (p=0.02 and 0.01 in superficial capillary plexus; p=0.05 and 0.01 in deep capillary plexus), thicker inner retinal thickness (p=0.002). Laser-treated eyes had significantly higher degree of myopia (p=0.01). Regarding to optical biometry, laser-treated eyes had significant steeper cornea curvature, shallower ACD and thicker lens (p=0.01, 0.01 and 0.02, respectively) but no differences in AXL was noted (p=0.58). Significant correlations presented between inner retina thickness and FAZ to anterior segment variables. CONCLUSION: In school-aged children with history of type 1 ROP, despite similar visual acuity outcome, those who underwent anti-VEGF injection had favourable developmental outcomes compared with laser photocoagulation. Significant correlations exist between fovea microvasculature and optical biometric components.

Metabolic Syndrome With Aortic Arterial Stiffness And First Hospitalization Or Mortality In Coronary Artery Disease Patients.

PURPOSE: Metabolic syndrome (MetS) and aortic arterial stiffness (AS) are risk factors for future cardiovascular events. We evaluated their roles in first hospitalization or all-cause mortality prediction in coronary artery disease (CAD) patients. PATIENTS AND METHODS: From January to December 2012, 115 CAD patients were enrolled from a single center and followed up for 5.5 years. The composite endpoint included hospitalization for unstable angina, myocardial infarction, revascularization, or heart failure and all-cause mortality. Patients with carotid-femoral pulse wave velocity > 10 m/s (measured using applanation tonometry) constituted the high AS group. RESULTS: During a median 54-month follow-up, there were 43 (37.4%) and 11 (9.6%) hospitalization and mortality events, respectively. Overall, 41 (35.7%) and 70 (60.9%) patients were diagnosed with AS and MetS, respectively. CAD patients with high AS had higher diabetes and MetS percentages, were older, and had higher waist circumference and systolic blood pressure (SBP) but lower glomerular filtration rate than those with low AS. Multivariate logistic regression analysis revealed old age (P < 0.001), diabetes (P = 0.003), and high waist circumference (P = 0.044) and SBP (P = 0.007) as independent predictors of AS in CAD patients. Kaplan-Meier analysis showed that CAD patients with concurrent MetS and high AS had a higher risk for hospitalization (log rank test, P = 0.005) or developing all-cause mortality (log rank test, P = 0.002). Compared with CAD patients without MetS or AS, composite outcome development risk in those with both the conditions was 10.2-fold higher (P < 0.001); this risk was 6.54-fold higher in those with AS alone (P = 0.007). CONCLUSION: In CAD patients, age, diabetes, and high waist circumference and SBP are the independent predictors of AS. Additionally, CAD patients with AS with and without MetS have a high first hospitalization or all-cause mortality development risk.

Lens capsular flap in the management of posterior retinal hole associated retinal detachment in high myopic eyes with previous internal limiting membrane peeling: 3 case reports.

RATIONALE: Managing retinal detachment due to posterior retinal holes is problematic since standard laser retinopexy or scleral buckling may be difficult to apply and may have brought serious complication. Another surgical method in treating posterior hole related retinal detachment is desired. PATIENT CONCERNS: Three high myopia patients with previous vitrectomy and membrane peeling history suffered from blurred vision and retinal detachment due to posterior pole retinal holes was diagnosed. DIAGNOSES: Patient diagnosed retinal detachment due to posterior retinal holes either as paracentral retinal breaks or macular hole from both indirect ophthalmoscope exam and fundus photography INTERVENTIONS:: The patient underwent lens capsular flap insertion into all the retinal holes, along with gas tamponade or silicone oil tamponade. No laser retinopexy was performed around the retinal holes. OUTCOMES: Of 3 included patients, 1 patient had insertion of the lens capsular flap, an incomplete air-fluid exchange, and 24% sulfur hexafluoride gas tamponade. The other 2 patients, after lens capsular flap insertion, had air-fluid exchange and subretinal fluid drainage with extrusion via soft needle through superior drainage retinotomy and silicon oil tamponade. The retinal holes of all eyes were sealed with retina attached postoperatively. LESSONS: Lens capsular flap is effective in sealing posterior retinal holes and treating the associated retinal detachment without the complication resulting from laser retinopexy, especially in eyes without sufficient internal limiting membrane (ILM) tissue due to previous ILM peeling.

Microvascular change in acute macular neuroretinopathy by using optical coherence tomography angiography.

A 27-year-old pregnant female underwent cesarean section due to preeclampsia. Two days after the delivery, she presented with acute onset of blurred vision in the left eye. Optical coherence tomography (OCT) revealed characteristic findings of acute macular neuroretinopathy (AMN) in both eyes. During the follow-up, her vision improved gradually, but outer nuclear layer thinning with disruption of ellipsoid zone was identified from OCT. OCT angiography was arranged and revealed both vascular defect in superficial and deep vascular plexus, which correlated with previous AMN lesions in both eyes. Subsequent microvascular change in AMN was found to involve both superficial and deep vascular plexus, which is different from the current consensus that AMN mainly involved deep vascular plexus. By using the OCT angiography, we can better visualize the detail retinal vascular structure and may identify the real mechanism in this rare retinal disorder.

Internal Limiting Membrane Flap in the Management of Retinal Detachment due to Paracentral Retinal Breaks.

PURPOSE: To describe the technique and outcomes of using either inverted or free internal limiting membrane flap in the management of retinal detachment due to paracentral retinal breaks. METHODS: This retrospective observational case series includes nine patients who received surgery for retinal detachment due to paracentral retinal breaks developed either from primary rhegmatogenous origin, or secondary iatrogenic retinal breaks after prior membrane peeling, or during surgery for tractional retinal detachment. Either inverted or free internal limiting membrane flaps were inserted in the identified breaks, followed by air fluid exchange and gas tamponade. Visual acuity and structural changes were evaluated. RESULTS: Nine eyes were included. One had primary rhegmatogenous retinal detachment, one had highly myopic eye with peripapillary atrophic hole, three had secondary retinal detachment after membrane peeling for foveoschisis or macular pucker, one had recurrent retinal detachment due to proliferative vitreoretinopathy, one had combination of tractional and rhegmatogenous retinal detachment, and two had iatrogenic breaks during surgery. The retinal breaks of all eyes were sealed with retina attached postoperatively. Visual acuity in logarithm of minimal angle of resolution improved from 1.18 ± 0.55 preoperatively to 0.74 ± 0.47 postoperatively (p=0.04). CONCLUSION: Internal limiting membrane flap technique can be a surgical approach selectively for retinal detachment due to paracentral retinal breaks with difficulty for laser application. The retina can be attached successfully and achieve good visual outcome without major complication. This trial is registered with NCT03707015.