Efficacy of Fovea-Sparing Internal Limiting Membrane Peeling for Epiretinal Membrane Foveoschisis.

INTRODUCTION: The aim of the study was to investigate the outcomes of vitrectomy with fovea-sparing internal limiting membrane (ILM) peeling (FSIP) for epiretinal membrane (ERM) foveoschisis based on new optical coherence tomography definitions. METHODS: Twenty-three eyes of 22 patients (69.7 ± 9.9 years old) who underwent vitrectomy with FSIP without gas tamponade for ERM foveoschisis were analyzed. All patients underwent follow-up examinations for at least 12 months. In the FSIP technique, the ILM is peeled off in a donut shape, preserving the foveal ILM. The logarithm of the minimal angle of resolution best-corrected visual acuity (BCVA), central macular thickness (CMT), and surgical complications were examined. RESULTS: The BCVA at 12 months improved significantly from baseline (p < 0.001). Baseline ellipsoid zone defects were found in 2 eyes (9%), and all defective eyes had recovered at 12 months. CMT decreased significantly from baseline (p < 0.001). Acute macular edema, full-thickness macular hole, and recurrence of ERM were not observed during follow-up. DISCUSSION/CONCLUSION: FSIP achieved good visual outcome and retinal morphological change. Moreover, FSIP might avoid acute macular edema in ERM foveoschisis surgery.

Changes of 18 F-fluoro-2-deoxyglucose position-emission tomography findings by the eradication of Helicobacter pylori in the stomach.

PURPOSE: Helicobacter pylori (HP) infection is reported to increase 18 F-fluoro-2-deoxyglucose (FDG) accumulation in the stomach. The accumulation of FDG by positron-emission tomography (FDG-PET) in the stomach for the voluntary health examinees of cancer checkup was examined before and after the HP eradication. SUBJECTS AND METHODS: From March 2013 to October 2015, eighty-one subjects were performed FDG-PET to detect cancer at the health checkup. All of them were also surveyed by esophagogastroduodenoscopy. Subjects were classified as the 33 cases of HP positive (group A), 38 cases of originally negative (group B), and the 10 negative cases by HP eradication therapy (group C). Group A was treated by combination of amoxicillin, clarithromycin, and proton pump inhibitor for a week, and all of them eradicated HP. A part of group A (n = 7) was serially performed FDG-PET one to five years after the treatment and compared the maximum standard uptake value of FDG (SUV) around the fundic gland region. RESULTS: SUV of group A (3.55 ± 0.69) was significantly higher than those of both group B (2.96 ± 0.72) and group C (2.89 ± 0.51) (p < 0.01, respectively). Groups B and C are almost comparable and showed no significant difference during the course. In group A, HP eradication significantly decreased the SUV to 3.1 ± 0.43 (P < .01). SUV after the eradication was significantly reduced (P < .01) in the mild to moderate atrophy (C1-C3) group according to Kimura and Takemoto classification of chronic gastritis of group A. Although SUV in the advanced atrophy group (O1-O3) tended to decline after the eradication, the change was not significant. CONCLUSION: HP-infected stomach showed higher FDG uptake in the fundic gland region and HP eradication decreased the uptake in the mild to moderate atrophic gastritis but not in the severe atrophic gastritis.

Pemafibrate prevents retinal neuronal cell death in NMDA-induced excitotoxicity via inhibition of p-c-Jun expression.

Excitotoxicity is involved in the retinal neuronal cell death in diabetic retinopathy. Although fenofibrate has been shown to ameliorate the progression of diabetic retinopathy, the effect of pemafibrate, which is highly selective for peroxisome proliferator-activated receptor α on retinal neuronal cell death has not been documented. Here, we investigated whether pemafibrate exerts a beneficial effect against retinal ganglion cell (RGC) death induced by N-methyl-D-aspartate (NMDA) in rats. Experiments were performed on adult male Wistar rats that received an intravitreal injection of 20 nmol NMDA. Fluoro-Gold labeled RGC morphometry showed that oral intake of pemafibrate once a day for 7 days resulted in significant protection on RGC death induced by NMDA. Phosphorylated c-Jun protein, which is involved in apoptosis, was upregulated after NMDA exposure, and this increase was significantly lessened by the systemic pemafibrate treatment. Phosphorylated c-Jun immunopositive cells were colocalized with Thy-1 immunopositive cells, and the increased these cells were ameliorated by the pemafibrate treatment. An increase in TUNEL-positive cells was significantly suppressed by the pemafibrate treatment. Phosphorylated c-Jun immunopositive cells were colocalized with TUNEL-positive cells, and they were decreased by pemafibrate treatment. These results suggest that the RGC protection achieved with pemafibrate appears to be associated with inhibition of phosphorylated c-Jun and its anti-apoptotic effect.

27-gauge trocar-assisted sutureless intraocular lens fixation.

BACKGROUNDS: However there have been numerous investigations of intrascleral intraocular lens (IOL) fixation techniques, there is room for improvement in terms of simplifying complicated techniques and reducing the high levels of skill required. This study aimed to report a novel technique for sutureless intrascleral fixation of the IOL using retinal forceps with a 27-gauge trocar. METHODS: Nineteen eyes of 18 patients underwent intrascleral fixation of the IOL from July 2018 to September 2019 were enrolled in this study. A 27-gauge trocar formed 3-mm scleral tunnels positioned at 4 and 10 o'clock, 2 mm from the corneal limbus. We used a 3-piece IOL haptic grasped by a 27-gauge retinal forceps and pulled from the 27-gauge trocar. The IOL was fixed by making a flange. Main outcome measures were visual acuity, corneal endothelial cell density, IOL tilt, decentration, predicted error of refraction and complications. RESULTS: The 19 eyes were followed up for 1 month. The mean pre- and postoperative logMAR uncorrected visual acuity (UCVA) was 1.06 ± 0.63 and 0.40 ± 0.26, respectively (p < 0.01), while the mean pre- and postoperative logMAR best corrected visual acuity (BCVA) was 0.27 ± 0.51 and 0.06 ± 0.15, respectively (p = 0.09). The mean corneal endothelial cell density was 2406 ± 625 to 2004 ± 759 cells/mm2 at 1 month (p = 0.13). The mean IOL tilt was 3.52 ± 3.00°, and the mean IOL decentration was 0.39 ± 0.39 mm. There was no correlation among IOL tilt, decentration and BCVA (p > 0.05). The mean prediction error of the target refraction was - 0.03 ± 0.93 D. The complications were vitreous hemorrhage (3 eyes), hyphema (1 eye), IOP elevation (1 eye), iris capture of the IOL (1 eye) and hypotony (2 eyes). No IOL dislocation occurred. CONCLUSIONS: IOL intrascleral fixation with a flange achieved good IOL fixation and visual outcome in the scleral tunnels created with the 27-gauge trocar.

Akebia Saponin D prevents axonal loss against TNF-induced optic nerve damage with autophagy modulation.

Akebia Saponin D (ASD), a triterpenoid saponin, was shown to have protective effects in certain neuronal cells. The purpose of the present study was to investigate the possibility of ASD to prevent tumor necrosis factor (TNF)-induced axonal loss and the ASD modulation of the biologic process of autophagy in optic nerves. Rats were given intravitreal administration of TNF, simultaneous administration of 2, 20, or 200 pmol ASD and TNF, or ASD alone. LC3-II and p62 expression, which is a marker of autophagic flux, and phosphorylated p38 (p-p38) expression in optic nerves were examined by immunoblot analysis. Morphometric analysis revealed a significant ameliorated effect of ASD against TNF-induced optic nerve damage. p62 was significantly increased in the optic nerve in TNF-treated eyes, but this increase was totally prevented by ASD. The ASD alone injection showed significant reduction of p62 levels compared with the PBS-treated control eyes. LC3-II was significantly increased by ASD treatment in the TNF-injected eyes. p-p38 was significantly increased in the optic nerve in TNF-treated eyes, but this increase was completely prevented by ASD. The protective effects of ASD may be associated with enhanced autophagy activation and inhibition of p-p38.

Favorable outcome of retreatment by direct-acting antivirals for hepatitis C patients with daclatasvir plus asunaprevir combination therapy failure.

AIM: In patients with hepatitis C virus, treatment failure of daclatasvir plus asunaprevir combination therapy (DCV + ASV) seems to become intractable due to the induction of resistance-associated substitutions. This study aimed to investigate the outcomes of retreatment with direct-acting antivirals (DAAs) in patients with DCV + ASV therapy failure, as well as changes in drug resistance mutations. METHODS: We retrospectively analyzed 44 patients re-treated with DAAs after DCV + ASV failure between December 2015 and April 2018. All patients were analyzed for amino acid substitutions, and additional treatment regimens were selected based on the results and current treatment guidelines. RESULTS: The sustained virological response rate with second-line treatment was 81.8% (36/44), and relapse occurred in five of 16 patients who received sofosbuvir/ledipasvir and three of seven patients who received DCV/ASV/beclabuvir. Third- and fourth-line treatments were also tried in relapsed cases, and the overall sustained virological response rates were 90.9% (40/44) and 93.2% (41/44), respectively. A high rate of viral clearance was eventually observed. Before second-line treatment, the prevalence of mutations in the NS5A and NS3/4A regions was 100% (44/44) and 86.4% (38/44), respectively. There was no significant increase in the number of amino acid substitutions in patients for whom second-line treatment failed. CONCLUSIONS: Amino acid substitutions were frequently observed in patients with DCV + ASV failure, but most patients achieved a sustained virological response after retreatment with DAAs. Although the spread of drug-resistant viruses due to unsuccessful DAA treatment was a matter of concern, most cases of DCV + ASV failure were overcome with additional treatment.

Axonal Protection by Tacrolimus with Inhibition of NFATc1 in TNF-Induced Optic Nerve Degeneration.

Tacrolimus, a calcineurin (CaN) inhibitor, has been used for treatment of refractory allergic ocular disease, although its role in optic nerve degeneration remains to be elucidated. In this study, we investigated whether tacrolimus modulates tumor necrosis factor (TNF)-mediated axonal degeneration and whether it alters nuclear factor of activated T cells (NFATc), a downstream effector of CaN signaling. Immunoblot analysis showed no significant difference in CaNAα protein levels in optic nerve on day 3, 7, or 14 after TNF injection compared with PBS injection. However, a significant increase in NFATc1 protein level was observed in optic nerve 7 days after TNF injection. This increase was negated by simultaneous administration of tacrolimus. Administration of tacrolimus alone did not change the NFATc1 protein level in comparison to that observed after PBS injection. A significant increase in TNF protein level was observed in optic nerve 14 days after TNF injection and this increase was prevented by tacrolimus. Immunohistochemical analysis showed the immunoreactivity of NFATc1 to be increased in optic nerve after TNF injection. This increased immunoreactivity was colocalized with glial fibrillary acidic protein and was suppressed by tacrolimus. Treatment of tacrolimus significantly ameliorated the TNF-mediated axonal loss. These results suggest that tacrolimus is neuroprotective against axon loss in TNF-induced optic neuropathy and that the effect arises from suppression of the CaN/NFATc1 pathway.

HEMI-TEMPORAL INTERNAL LIMITING MEMBRANE PEELING IS AS EFFECTIVE AND SAFE AS CONVENTIONAL FULL PEELING FOR MACULAR HOLE SURGERY.

PURPOSE: To investigate the efficacy of hemi-temporal internal limiting membrane (ILM) peeling for idiopathic macular hole. METHODS: The medical records of patients with macular holes who had undergone vitrectomy with ILM peeling were studied. Forty-two eyes with macular hole were divided into 2 groups based on surgical procedure (hemi-temporal ILM peeling [hemi group]: 15 eyes; 360° ILM peeling [360° group]: 27 eyes). The closure rates and distances between the optic disc and the intersection of two retinal vessels most closely located nasally or temporally to the macular hole were compared. RESULTS: The primary closure rates were not significantly different between the two groups (hemi group: 93.3%; 360° group: 92.5%, P = 0.92). The temporal retinal vessels in the hemi group were displaced 120.5 ± 102.0 µm toward the optic disc at 1 week postoperatively, which did not differ significantly from the 360° group (136.1 ± 106.1 µm) (P = 0.107). However, the nasal retinal vessels in the hemi group were displaced by 42.4 ± 42.9 µm at 1 week postoperatively, which was significantly less than the 90.1 ± 77.3 µm displacement seen in the 360° group (P = 0.040). CONCLUSION: Hemi-temporal ILM peeling may be preferable to 360° ILM peeling because of less displacement of the retina and greater safety.

Efficacy and safety of rifaximin in Japanese patients with hepatic encephalopathy: A phase II/III, multicenter, randomized, evaluator-blinded, active-controlled trial and a phase III, multicenter, open trial.

AIM: The efficacy and safety of rifaximin in the treatment of hepatic encephalopathy (HE) are widely known, but they have not been confirmed in Japanese patients with HE. Thus, two prospective, randomized studies (a phase II/III study and a phase III study) were carried out. METHODS: Subjects with grade I or II HE and hyperammonemia were enrolled. The phase II/III study, which was a randomized, evaluator-blinded, active-comparator, parallel-group study, was undertaken at 37 institutions in Japan. Treatment periods were 14 days. Eligible patients were randomized to the rifaximin group (1200 mg/day) or the lactitol group (18-36 g/day). The phase III study was carried out in the same patients previously enrolled in the phase II/III study, and they were all treated with rifaximin (1200 mg/day) for 10 weeks. RESULTS: In the phase II/III study, 172 patients were enrolled. Blood ammonia (B-NH3 ) concentration was significantly improved in the rifaximin group, but the difference between the two groups was not significant. The portal systemic encephalopathy index (PSE index), including HE grade, was significantly improved in both groups. In the phase III study, 87.3% of enrolled patients completed the treatment. The improved B-NH3 concentration and PSE index were well maintained from the phase II/III study during the treatment period of the phase III study. Adverse drug reactions (ADRs) were seen in 13.4% of patients who received rifaximin, but there were no severe ADRs leading to death. CONCLUSION: The efficacy of rifaximin is sufficient and treatment is well tolerated in Japanese patients with HE and hyperammonemia.

Clinical and virological features of acute hepatitis E in Gunma prefecture, Japan between 2004 and 2015.

AIM: To evaluate the clinical and virological features of acute hepatitis E (AH-E) in Gunma prefecture and focus on the hepatitis E virus (HEV) infection in immunocompromised patients. METHODS: A total of 30 patients with AH-E diagnosed at our Gunma University Hospital, and located in 3-39-15 Showa-machi, Maebashi, Gunma 371-8511 Japan, and its affiliated hospitals from 2004 to 2015, were studied. We evaluated the detailed medical histories, laboratory examinations and virological features of these participants. RESULTS: Of the 30 patients, 21 patients were men, with a median age of 61 years. Three of these patients had a history of recent oversea travel. A total of 14 patients had eaten raw or undercooked meat/viscera from animals, and two patients had contracted transfusion-transmitted AH-E. Eight patients were immunocompromised, including those with hematological disease, cancer receiving systemic chemotherapy and kidney transplant or connective tissue disease undergoing immunosuppressive medications. The alanine aminotransferase and total bilirubin levels were more significantly reduced in these immunocompromised patients than in the non-immunocompromised patients. Severe thrombocytopenia, an extra-hepatic manifestation of AH-E, occurred in one case. Among the 22 HEV strains whose subgenotype was determined, two were imported strains (1a and 1f), and 11 strains formed four distinct phylogenetic clusters within subgenotype 3b. The remaining nine strains differed from each other by 9.8-22.4%, and were classified into four subgenotypes (3a, 3b, 3e and 3f). CONCLUSION: Markedly divergent HEV strains (3a, 3b, 3e and 3f) were found to circulate in Gunma. Although immunosuppression appears to play a crucial role in establishing chronic sequels, AH-E in eight immunocompromised patients, including transfusion-transmitted HEV infection in two patients, did not become chronic.

Association between Skeletal Muscle Depletion and Sorafenib Treatment in Male Patients with Hepatocellular Carcinoma: A Retrospective Cohort Study.

The effect of skeletal muscle mass (SMM) on the outcomes of sorafenib treatment for hepatocellular carcinoma (HCC) has not been established. We measured the SMM in HCC patients treated with sorafenib, evaluated the patients' survival, and evaluated the association between skeletal muscle depletion and sorafenib treatment. Of the 97 HCC patients treated with sorafenib at our institution in the period from July 2009 to February 2015, our study included 69 patients (51 males, 18 females) who had received sorafenib for ≥ 8 weeks and whose follow-up data were available. SMM was calculated from computed tomography images at the mid-L3 level (cm2) and normalized to height (m2) to yield the L3 skeletal muscle index (L3-SMI, cm2/m2). The median L3-SMI value was higher in the males (43 cm2/m2) compared to the females (36 cm2/m2). In the males only, the multivariate Cox regression identified an L3-SMI <43 cm2/m2 as independently associated with higher mortality compared to an L3-SMI ≥43 cm2/m2 (hazard ratio 2.315, 95% confidence interval: 1.125-4.765, p=0.023). Skeletal muscle depletion is a factor predicting poor prognosis for male patients with advanced HCC treated with sorafenib.

Enhanced pregenomic RNA levels and lowered precore mRNA transcription efficiency in a genotype A hepatitis B virus genome with C1766T and T1768A mutations obtained from a fulminant hepatitis patient.

The viral factors associated with the development of fulminant hepatitis B are not fully understood. We recently found four unique mutations [G to A at nucleotide 1742 (G1742A), C1766T, T1768A and T1809C] in the basal core promoter (BCP) region of a genotype A hepatitis B virus (HBV) strain (FH) obtained from a 53-year-old man with fatal fulminant hepatitis. To elucidate the association of the mutations of the FH genome with the disease, we constructed a 1.3-fold FH genome and its five variants by replacing one or two mutated nucleotides with wild-type nucleotide(s) via site-directed mutagenesis, and transfected human hepatoma cells (HepG2/C3A) with the constructs. There were no discernible differences between FH and two variants (FH_A1742G and FH_C1809T) with regard to viral replication and protein expression. However, in comparison to three other variants (FH_T1766C, FH_A1768T and FH_T1766C/A1768T) with wild-type nucleotide(s) at 1766 and/or 1768, the FH genome exhibited a 2.5-5-fold enhancement of viral replication by heightened pregenomic RNA synthesis and a 1.5-2.5-fold reduction in the hepatitis B e antigen (HBeAg) synthesis by the downregulation of the precore mRNA level. An immunofluorescence analysis revealed the increased and predominant cytoplasmic localization of the core protein in the FH genome. The present study demonstrates that the C1766T/T1768A mutations in the BCP region of genotype A HBV enhance viral replication, downregulate HBeAg expression and are responsible for the predominant localization of the core protein in the cytoplasm, which are likely associated with the development of fulminant hepatitis.

Axonal protection by thioredoxin-1 with inhibition of interleukin-1ß in TNF-induced optic nerve degeneration.

Interleukin (IL)-1ß, a proinflammatory cytokine, is a key mediator in several acute and chronic neurological diseases. Thioredoxin-1 (TRX1) acts as an antioxidant and plays a protective role in certain neurons. We examined whether exogenous TRX1 exerts axonal protection and affects IL-1ß levels in tumor necrosis factor (TNF)-induced optic nerve degeneration in rats. Immunoblot analysis showed that IL-1ß was upregulated in the optic nerve after intravitreal injection of TNF. Treatment with recombinant human (rh) TRX1 exerted substantial protective effects against TNF-induced axonal loss. The increase in the IL-1ß level in the optic nerve was abolished by rhTRX1. Treatment with rhTRX1 also significantly inhibited increased glial fibrillary acidic protein (GFAP) levels induced by TNF. Immunohistochemical analysis showed substantial colocalization of IL-1ß and GFAP in the optic nerve after TNF injection. These results suggest that IL-1ß is upregulated in astrocytes in the optic nerve after TNF injection and that exogenous rhTRX1 exerts axonal protection with an inhibitory effect on IL-1ß.

Axonal protection by brimonidine with modulation of p62 expression in TNF-induced optic nerve degeneration.

PURPOSE: The p62, also called sequestosome 1 (SQSTM1), plays a crucial role in tumor necrosis factor (TNF)-induced optic nerve degeneration. Brimonidine has been shown to have protective effects on retinal ganglion cell bodies, although its role in their axons remains to be examined. We determined whether brimonidine modulates axonal loss induced by TNF and affects the expression of p62 in the optic nerve. METHODS: Experiments were performed on adult male Wistar rats that received an intravitreal injection of 10 ng TNF alone or simultaneous injection of TNF and 2, 20, or 200 pmol of brimonidine tartrate. The expression of p62 in the optic nerve was examined by immunoblot analysis. The effects of brimonidine on axons were evaluated by counting axon numbers 2 weeks after intravitreal injection. RESULTS: Intravitreal injection of brimonidine exerted substantial axonal protection against TNF-induced optic nerve degeneration. Immunoblot analysis showed that p62 was upregulated in the optic nerve after intravitreal injection of TNF, and that this increase was completely inhibited by brimonidine. Treatment with brimonidine alone also significantly decreased p62 protein levels in the optic nerve compared with the basal level. CONCLUSIONS: These results suggest that the modulation of p62 levels in the optic nerve by brimonidine may be involved partly in its axonal protection.

Transforming growth factor-α activates pancreatic stellate cells and may be involved in matrix metalloproteinase-1 upregulation.

The role that transforming growth factor-α (TGF-α) has in chronic pancreatitis and pancreatic cancer has not been fully elucidated. We evaluated the effects of TGF-α on the human pancreatic stellate cell (PSC) line RLT-PSC and primary human PSCs, and the expression levels of TGF-α and metalloproteinase-1 (MMP-1) in human chronic pancreatitis and pancreatic cancer tissues. TGF-α stimulated the proliferation and migration of PSCs. Although the mRNA expression levels of tissue inhibitor of metalloproteinase-1 and α1(I) collagen were unchanged, the mRNA expression levels of MMP-1 increased concomitant with increases in MMP-1 protein levels and collagenase activity. TGF-α-stimulated migration of RLT-PSC cells was partially blocked by tissue inhibitor of metalloproteinase-1 protein and MMP-1 small interfering RNA. MMP-1 was also observed to stimulate the migration of PSCs. TGF-α-induced MMP-1 expression was completely blocked by gefitinib in PSCs. The Ras-ERK and PI3/Akt pathways appear to be involved in the activation of MMP-1 in PSCs. Immunohistochemical analyses showed that MMP-1 expression was significantly increased in the pancreatic interstitial tissues in case of chronic pancreatitis or pancreatic cancer compared with those in case of normal pancreas. In conclusion, TGF-α increased proliferation and migration of PSCs. TGF-α-induced migration of cells may be partly due to upregulation of MMP-1. TGF-α and MMP-1 upregulation may contribute to the pathogenesis of chronic pancreatitis and pancreatic cancer.

Photoreceptor outer segment length: a prognostic factor for idiopathic epiretinal membrane surgery.

PURPOSE: To investigate prognostic factors for visual improvement in patients undergoing vitrectomy for epiretinal membrane (ERM) using spectral domain (SD) optical coherence tomography (OCT). DESIGN: Prospective cohort study. PARTICIPANTS: A total of 41 eyes of 38 patients. METHODS: A total of 41 eyes of 38 patients with idiopathic ERM underwent ERM resection. Ophthalmic evaluations included best-corrected visual acuity (BCVA) and OCT parameters before and 1, 3, and 6 months after surgery. Correlations between OCT parameters and BCVA were assessed at each time point. Correlations between postoperative BCVA and preoperative factors were evaluated, including age, preoperative BCVA, photoreceptor outer segment (PROS) length, central foveal thickness (CFT), outer foveal thickness (OFT), and outer nuclear layer thickness (ONLT). The factors influencing postoperative BCVA were evaluated using multiple regression analysis. MAIN OUTCOME MEASURES: The BCVA at 6 months postoperatively. RESULTS: The PROS length had the most significant correlation with BCVA at each time point (baseline: P = 0.0098, r = -0.409; 1 month: P = 0.0002, r = -0.586; 3 months: P < 0.0001, r = -0.642; 6 months: P = 0.0002, r = -0.577). The PROS length 1 month postoperatively was significantly decreased compared with that preoperatively (P = 0.0325), and the PROS length at 3 months recovered to the baseline length. Preoperative BCVA and PROS length were significantly correlated with postoperative BCVA at 6 months (P = 0.0055, r = 0.439 and P = 0.0089, r = -0.414, respectively). Other parameters, including age, CFT, OFT, and ONLT, were not significantly correlated with postoperative BCVA. Multiple regression analysis showed that preoperative PROS length yielded the highest regression coefficient with postoperative BCVA (P = 0.0363, standard regression coefficient = -0.335, overall R(2) = 0.289). CONCLUSIONS: Imaging of PROS length with SD-OCT was found to be a good indicator of BCVA at each time point after surgery and a predictor of postoperative BCVA in patients with idiopathic ERM. The PROS length changes after surgery may indicate surgical injury and restoration of the macular outer layer.

Effects of indocyanine green staining on the recovery of visual acuity and macular morphology after macular hole surgery.

PURPOSE: To evaluate whether indocyanine green (ICG)-assisted internal limiting membrane peeling affects visual outcome and macular morphologic changes in spectral-domain optical coherence tomography images after macular hole (MH) surgery. METHODS: A retrospective analysis was performed of 34 eyes in 34 patients who had undergone surgical treatment for MH. Best-corrected visual acuity (BCVA) and optical coherence tomography parameters including central foveal thickness, length of the external limiting membrane (ELM) defect, and length of the inner segment and outer segment (IS/OS) defect were analyzed pre- and postoperatively. RESULTS: The eyes were divided into 2 groups based on ICG use (ICG+/-). The changes in BCVA did not differ significantly between the 2 groups at 6 months. However, the ICG+ group had poorer changes compared with the ICG- group at 1 and 3 months (p = 0.038, p = 0.012, respectively). Central foveal thickness and ELM defect did not differ between the 2 groups at each period. The IS/OS defect in the ICG+ group was significantly greater at 1 and 3 months than that in the ICG- group (p = 0.026, p = 0.048, respectively). CONCLUSIONS: ICG staining may affect the recovery process of macular morphology and visual acuity in the first several months after MH surgery.

Drug induced hypersensitivity syndrome by triple therapy of peginterferon alpha2b, ribavirin and telaprevir in patient with double positive for HBV and HCV.

Sixty year-old male positive for both HCV-RNA and HBsAg was treated by triple therapy of peginterferon alpha2b, ribavirin and telaprevir. Eight weeks after the beginning of the therapy, the patient developed drug induced hypersensitivity syndrome (DIHS) with general erythema multiforme and 64 times anti-HHV6 antibody elevation. Sixty milligram of prednisolone was administered with gradual dose reduction and the skin lesion was improved. HBV-DNA and transaminase elevated one week after the steroid induction and entecavir improved them. DIHS itself and the aggravation of hepatitis B by corticosteroid should be kept in mind in cases with dual infection of HBV and HCV treated by antivirals including telaprevir.

[A case of so-called carcinosarcoma of the middle portion of the bile duct diagnosed preoperatively].

A 73-year-old man was admitted to a hospital with a complaint of epigastralgia and for evaluation of liver dysfunction. After hospitalization, he experienced disturbance of consciousness with septic shock, and was then transferred to our hospital. Computed tomography revealed dilatation of the intrahepatic bile duct and tumor of the middle bile duct. We diagnosed acute obstructive suppurative cholangitis. As a result, endoscopic nasobiliary drainage was performed, and the patient recovered. Based on pathological examinations of the bile duct biopsy specimen, the tumor was diagnosed as a carcinosarcoma. Consequently, the patient underwent pylorus-preserving pancreatoduodenectomy. However, 4 months after surgery, the patient died due to widespread metastasis of the carcinosarcoma. Preoperative diagnosis of carcinosarcoma of the bile duct is extremely rare. Our study suggests the efficacy of bile duct biopsy in such cases.

The Diagnosis, Pathophysiology, and Treatment of Chronic Hepatitis E Virus Infection-A Condition Affecting Immunocompromised Patients.

Hepatitis E is a zoonosis caused by hepatitis E virus (HEV), which was first discovered 40 years ago. Twenty million HEV infections worldwide are estimated each year. Most hepatitis E cases are self-limiting acute hepatitis, but the virus has been recognized to cause chronic hepatitis. Following the first case report of chronic hepatitis E (CHE) in a transplant recipient, CHE has recently been identified as associated with chronic liver damage induced by HEV genotypes 3, 4, and 7-usually in immunocompromised patients such as transplant recipients. In addition, patients infected with HIV and those receiving chemotherapy for malignancy, along with patients with rheumatic disease and COVID-19, have recently been reported as having CHE. CHE can be easily misdiagnosed by usual diagnostic methods of antibody response, such as anti-HEV IgM or IgA, because of the low antibody response in the immunosuppressive condition. HEV RNA should be evaluated in these patients, and appropriate treatments-such as ribavirin-should be given to prevent progression to liver cirrhosis or liver failure. While still rare, cases of CHE in immunocompetent patients have been reported, and care must be taken not to overlook these instances. Herein, we conduct an overview of hepatitis E, including recent research developments and management of CHE, in order to improve our understanding of such cases. The early diagnosis and treatment of CHE should be performed to decrease instances of hepatitis-virus-related deaths around the world.