Long-Term Outcomes of Patients with Stroke Predicted by Clinicians to have no Chance of Meaningful Recovery: A Japanese Cohort Study.

BACKGROUND: Little is known about the natural history of comatose patients with brain injury, as in many countries most of these patients die in the context of withdrawal of life-sustaining therapies (WLSTs). The accuracy of predicting recovery that is used to guide goals-of-care decisions is uncertain. We examined long-term outcomes of patients with ischemic or hemorrhagic stroke predicted by experienced clinicians to have no chance of meaningful recovery in Japan, where WLST in patients with isolated neurological disease is uncommon. METHODS: We retrospectively reviewed the medical records of all patients admitted with acute ischemic stroke, intracerebral hemorrhage, or nontraumatic subarachnoid hemorrhage between January 2018 and December 2020 to a neurocritical care unit at Toda Medical Group Asaka Medical Center in Saitama, Japan. We screened for patients who were predicted by the attending physician on postinjury day 1-4 to have no chance of meaningful recovery. Primary outcome measures were disposition at hospital discharge and the ability to follow commands and functional outcomes measured by the Glasgow Outcome Scale-Extended (GOS-E), which was assessed 6 months after injury. RESULTS: From 860 screened patients, we identified 40 patients (14 with acute ischemic stroke, 19 with intracerebral hemorrhage, and 7 with subarachnoid hemorrhage) who were predicted to have no chance of meaningful recovery. Median age was 77 years (interquartile range 64-85), 53% (n = 21) were women, and 80% (n = 32) had no functional deficits prior to hospitalization. Six months after injury, 17 patients were dead, 14 lived in a long-term care hospital, 3 lived at home, 2 lived in a rehabilitation center, and 2 lived in a nursing home. Three patients reliably followed commands, two were in a vegetative state (GOS-E 2), four fully depended on others and required constant assistance (GOS-E 3), one could be left alone independently for 8 h per day but remained dependent (GOS-E 4), and one was independent and able to return to work-like activities (GOS-E 5). CONCLUSIONS: In the absence of WLST, almost half of the patients predicted shortly after the injury to have no chance of meaningful recovery were dead 6 months after the injury. A small minority of patients had good functional recovery, highlighting the need for more accurate neurological prognostication.

Effect of DNMT3A polymorphisms on CpG island hypermethylation in gastric mucosa.

BACKGROUND: CpG methylation of tumor suppressor genes occurs in the early stage of carcinogenesis. Detecting risk factors for aberrant CpG methylation is clinically important for predicting cancer development. DNA methyltransferase (DNMT) 3a is considered to play critical roles in the DNA methylation process during pathogenesis. In this study, we evaluated the association between DNMT3A polymorphisms (rs6733868 and rs13428812) and CpG methylation status in non-cancerous gastric mucosa. METHODS: We determined the DNMT3A genotype and CpG methylation status of 4 genes (p14ARF, p16INK4a, DAPK, and CDH1) in 510 subjects without gastric cancer. Helicobacter pylori (HP) infection status was determined by the rapid urease test, urea breath test, speculum examination, or serum antibody test. We determined the DNMT3A genotype using polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP). CpG methylation status was determined by methylation-specific polymerase chain reaction (MSP). When the methylated band was stronger than 10 ng/µL according to the DNA marker, we judged CpG island hypermethylation (CIHM) to be present. Associations between genotypes and susceptibilities were assessed by logistic regression analysis. RESULTS: The minor allele frequencies of both polymorphisms (rs6733868 and rs13428812) were lower in the CpG methylated groups of each of the 4 genes (p14ARF, p16INK4a, DAPK, and CDH1). Using a dominant genetic model, rs6733868 was significantly associated with the hypermethylation of each gene, whereas rs13428812 was associated with the methylation of 3 genes (all except p14ARF). When low-CIHM was defined as 1 or 2 CpG islands methylated and high-CIHM was defined as 3 or more CpG islands methylated, carrying the minor allele of rs6733868 was associated with both decreased low- and high-CIHM, and that of rs13428812 also was associated with a decrease. Comparing low-CIHM with high-CIHM, carrying the minor alleles of rs6733868 or rs13428812 was related to decreased susceptibility to high-CIHM. In HP-infected subjects, carrying the minor alleles of rs6733868 or rs13428812 had a significantly greater association with decreased susceptibility to high-CIHM. CONCLUSIONS: Our study indicates that polymorphisms of DNMT3A are associated with the accumulation of gene methylation in gastric mucosa. Carrying the minor alleles of rs6733868 or rs13428812 inhibits aberrant gene methylations, which are typically enhanced by HP infection.

Influence of MIF polymorphisms on CpG island hyper-methylation of CDKN2A in the patients with ulcerative colitis.

BACKGROUND: CDKN2A hypermethylation is among the major events associated with carcinogenesis and is also observed in non-neoplastic colonic mucosa in patients with ulcerative colitis (UC). Macrophage migration inhibitory factor (MIF) plays a crucial role in promoting gastrointestinal inflammation characteristic of UC. The aim of this study is to explore associations between CDKN2A methylation status and MIF polymorphisms (rs755622 and rs5844572). METHODS: One hundred and fifty-nine patients diagnosed with UC were enrolled in this study. The methylation status of p14ARF and p16INK4a was determined by MSP; MIF genotypes were identified by PCR-SSCP. RESULTS: We found no differences with respect to mean age, gender, clinical type (chronic continuous or relapse/remitting), or extent of disease among the patients with methylated and unmethylated p14ARF or p16INK4a. Carrying the rs755622 C allele indicated a significantly higher risk for p14ARF methylation (odds ratio (OR), 2.16; 95% confidence interval (CI), 1.08-4.32; p = 0.030); similarly, carrying the rs5844572 7-repeat allele indicated a significantly higher risk for p16INK4a methylation (OR, 2.57; 95% CI, 1.26-5.24; p = 0.0094) after an adjusted regression analysis. The carriers of the rs755662 C allele or the rs5844572 7-repeat allele were both at a significantly higher risk for methylation of both p14ARF and p16INK4a when compared to the cohort in which neither of the genes were methylated (OR, 2.70; 95% CI, 1.22-6.01; p = 0.015 and OR, 2.87; 95% CI, 1.25-6.62; p = 0.013, respectively). Additionally, carrying rs755622 C allele was significantly associated with CIHM in chronic continuous of clinical type and total colitis (OR, 25.9; 95% CI, 2.55-262.6; p = 0.0059 and OR, 4.38; 95% CI, 1.12-17.2; p = 0.034, respectively), and carrying 7-repeat allele of rs5844572 was significantly associated in chronic continuous type (OR, 14.5; 95%CI, 1.46-144.3; p = 0.022). CONCLUSIONS: Taken together, our findings suggest that MIF genotypes associated with inflammation may also be involved in promoting carcinogenesis via CDKN2A hypermethylation in patients diagnosed with UC.

Characterization of newly developed pepper cultivars (Capsicum chinense) 'Dieta0011-0301', 'Dieta0011-0602', 'Dieta0041-0401', and 'Dieta0041-0601' containing high capsinoid concentrations and a strong fruity aroma.

Capsaicinoids are responsible for the pungent flavor of peppers (Capsicum sp.). The cultivar CH-19 Sweet is a non-pungent pepper mutant that biosynthesizes the low-pungent capsaicinoid analogs, capsinoids. Capsinoids possess important pharmaceutical properties. However, capsinoid concentrations are very low in CH-19 Sweet, and Capsicum cultivars with high content capsinoids are desirable for industrial applications of capsinoids. Habanero, Bhut Jolokia, and Infinity are species of Capsicum chinense, and have strong pungency and intense fruity flavors. In the present study, we report new cultivars with high concentrations of capsinoids (more than ten-fold higher than in CH-19 Sweet), and showed that these cultivars (Dieta0011-0301 and Dieta0011-0602 from Bhut Jolokia, Dieta0041-0401 and Dieta0041-0601 from Infinity) are of nutritional and medicinal value and have fruity aromas. We also obtained a vanilla bean flavor, vanillyl alcohol, and vanillyl ethyl ether from capsinoids in the fruit of these cultivars following the addition of ethanol at room temperature. ABBREVIATIONS: p-AMT: putative aminotransferase; C. annuum: Capsicum annuum; C. chinense: Capsicum chinense; dCAPS: derived Cleaved Amplified Polymorphic Sequences.

[Intestinal amebiasis in the ileac blind end of an ileocolonic anastomosis leading to liver abscess].

A 65-year-old man was admitted complaining of high fever and pain in the right lower abdomen. An ileocolonic side-to-end anastomosis had been performed 38 years previously for an abscess in a colonic diverticulum. On the current admission, findings on contrast-enhanced computed tomography suggested an amebic liver abscess and intestinal amebiasis. Colonoscopy revealed an irregularly shaped ulcer and false membrane in the ileal blind end of the ileocolonic anastomosis. Amebic trophozoites were seen by rapid microscopy. Amebiasis in the blind end of the ileum has rarely been reported. This case is of particular interest because the intestinal amebiasis also led to a liver abscess.

Renal Replacement Therapy in Idiopathic Systemic Capillary Leak Syndrome: A Case Report.

Idiopathic systemic capillary leak syndrome (ISCLS) is a rare disease characterized by hypotensive shock, anasarca, hemoconcentration, and hypoalbuminemia. Despite the life-threatening course of the disease, no treatment strategy has been established. A 68-year-old man presented with hypotensive shock following a prodrome. Based on the characteristic blood test findings, ISCLS was suspected. The patient was resuscitated by administering massive amounts of fluids and inotropic and vasopressor agents. After his blood pressure had stabilized, renal replacement therapy (RRT) was promptly initiated to facilitate the removal of excess fluid, despite the presence of urine output. Typically, ISCLS has three phases: prodromal, leak, and post-leak. Diuresis should be promptly induced during the transition from the leak phase to the post-leak phase to avoid fatal complications such as pulmonary edema. We propose that in patients with ISCLS, early introduction of RRT is recommended if indicated.

Association between fluorescein leakage and optical coherence tomographic characteristics of microaneurysms in diabetic retinopathy.

PURPOSE: To evaluate the characteristics of microaneurysms seen on color fundus photography, fluorescein angiography, and spectral-domain optical coherence tomography in diabetic retinopathy. METHODS: One hundred and thirty-two consecutive eyes of 92 patients with diabetic retinopathy were reviewed retrospectively. The characteristics of microaneurysms, including capsular structure (ring sign), hyperreflective spots in the lumen, the retinal layers in which they are located, and adjacent cystoid spaces, were documented on spectral-domain optical coherence tomography as sectional images. Their appearance on fundus photographs and focal fluorescein leakage were recorded. The association among these characteristics was evaluated. RESULTS: Eighty-eight of 118 microaneurysms (74.6%) with no capsular structure had focal fluorescein leakage, whereas 7 of 34 microaneurysms (20.6%) with complete capsular structure had leakage (P < 0.001). Focal leakage from the microaneurysms correlated positively with hyperreflective spots in the lumen and nearby cystoid spaces (P = 0.013 and P < 0.001, respectively) but not in the layers in which they were located. Multicolored microaneurysms contained hyperreflective spots in the lumens more frequently than whitish or reddish spots (P = 0.038), compared with no significant associations between the appearance and the other optical coherence tomography characteristics. CONCLUSION: Focal fluorescein leakage from microaneurysms was associated positively with the absence of a capsular structure, hyperreflective spots, and nearby cystoid spaces.

Retinal sensitivity after resolution of the macular edema associated with retinal vein occlusion.

PURPOSE: To study the correlation of retinal sensitivity with both morphologic changes in the macula and status of retinal capillary perfusion, after resolution of the macular edema associated with retinal vein occlusion (RVO). METHODS: Retinal sensitivity in the macular area was examined with the Micro Perimeter 1 in 24 eyes after resolution of the macular edema associated with RVO. Using spectral-domain optical coherence tomography, 6 mm × 6 mm areas of macula were examined with 256 sequential horizontal scans. Condition of the photoreceptor layer was evaluated depending upon detection of the junctions between inner and outer segments of the photoreceptors (IS/OS). Fluorescein angiography was performed in 19 eyes. RESULTS: Mean retinal sensitivity on the affected side of the retina was significantly decreased (p < 0.001). On the affected side, the mean retinal sensitivity within the area of deteriorated IS/OS was significantly less (3.8 ± 4.8 dB) than that within areas with complete IS/OS (10.1 ± 6.4 dB, p < 0.001). Mean retinal sensitivity within nonperfused areas was extremely low (0.3 ± 1.3 dB), compared with that in perfused retina (10.9 ± 5.9 dB, p < 0.001). In eyes with a broken foveal capillary ring (FCR), the marked decline in retinal sensitivity was seen within the area where the FCR was broken; this was not seen in eyes with an intact FCR. CONCLUSION: Retinal function was decreased markedly in areas with a damaged photoreceptor layer due to RVO, and was lethally decreased within nonperfused areas. Due to the various limitations of the current study, including implementation of fluorescein angiography in limited number of eyes, wide range of follow-up, and heterogeneity of pretreatments, further prospective studies are necessary to confirm the current findings.

Characteristics of optical coherence tomographic hyperreflective foci in retinal vein occlusion.

PURPOSE: To evaluate the hyperreflective foci in branch retinal vein occlusion and central retinal vein occlusion depicted by spectral-domain optical coherence tomography (OCT). METHODS: Consecutive series of 73 eyes of 73 patients with retinal vein occlusion (58 branch retinal vein occlusion and 15 central retinal vein occlusion) who had Spectralis OCT images obtained were retrospectively reviewed, comparing color fundus photographs and fluorescein angiography. RESULTS: Hyperreflective foci were detected in 54 eyes (74.0%) by spectral-domain OCT, and hard exudates were detected in 17 eyes (23.3%) by color fundus photography. Hard exudates on the color photographs corresponded to the confluence of hyperreflective foci mainly around the outer plexiform layer in the unaffected areas on the spectral-domain OCT images, whereas fine hyperreflective foci were scattered in all retinal layers of the affected areas (P < 0.001). Most eyes with hyperreflective foci attached to the inner side of the external limiting membrane also had serous retinal detachment (P < 0.001). Compared with diabetic macular edema, we did not find subfoveal hard exudates in retinal vein occlusion. CONCLUSION: Hyperreflective foci delineated on spectral-domain OCT suggest the pathogenesis regarding the flow of extravasated blood constituents in retinal vein occlusion.

Foveal cystoid spaces are associated with enlarged foveal avascular zone and microaneurysms in diabetic macular edema.

OBJECTIVE: To study the association between pathomorphology at the foveal center delineated by spectral domain optical coherence tomography (SD-OCT) and vascular changes around the fovea in fluorescein angiography (FA) in patients with diabetic macular edema (DME). DESIGN: Retrospective, observational, cross-sectional study. PARTICIPANTS: Consecutive series of 86 eyes from 72 patients with clinically significant macular edema (CSME) on which SD-OCT and FA were performed on the same day. METHODS: Fluorescein angiography using HRA2 (Heidelberg Engineering, Heidelberg, Germany) and SD-OCT images using Spectralis OCT (Heidelberg Engineering) were obtained for all patients. Microaneurysms (MAs) in the perifoveal capillary network (PCN) and foveal avascular zone (FAZ) in the FA images were quantified. The pathomorphology at the foveal center was evaluated in OCT images. We then investigated the association between pathologic perifoveal capillaries in FA and the neuroglial morphology in OCT. MAIN OUTCOME MEASURES: The relationship between pathologic changes in perifoveal capillaries in FA and foveal pathomorphology in OCT. RESULTS: According to the foveal morphology in OCT images, 44 eyes presented foveal cystoid spaces (cystoid macular edema [CME]), 25 eyes had serous retinal detachment (SRD) at the foveal center, and 17 eyes had foveal thickening without cystoid spaces or retinal detachment (retinal swelling). After 3 eyes with ischemic maculopathy were excluded, the relationship was evaluated. The number of MAs in the PCN was significantly greater in eyes with CME (3.20 ± 1.76) than in eyes with SRD (0.40 ± 1.04; P < 0.01) or retinal swelling (0.47 ± 0.72; P < 0.01). In addition, the FAZ in the eyes with CME (0.553 ± 0.323 mm(2)) was significantly larger than that of the eyes with SRD (0.302 ± 0.245 mm(2); P < 0.01) or retinal swelling (0.268 ± 0.142 mm(2); P < 0.01). These associations were found in eyes with thickened posterior hyaloid membranes. CONCLUSIONS: The eyes with cystoid spaces at the foveal center delineated by OCT had more MAs in the PCN and larger FAZ in FA images.

Dissection and removal of bile duct plastic stents penetrating the duodenal papilla: report of three rare cases.

We encountered three cases with incidental penetration of a straight Amsterdam-type bile duct plastic stent into the duodenal papilla. All patients had undergone insertion of a biliary plastic stent due to common bile duct stones. However, in all three cases, we observed penetration of the biliary plastic stent into the duodenal papilla just before the elective surgery or at the time of plastic stent replacement. We, therefore, performed stent dissection using a bipolar snare and were able to safely remove the plastic stents in all three cases. We believe that this is the first report of plastic stent dissection using a bipolar snare.

MAFK Polymorphisms Located in 3'-UTR are Associated with Severity of Atrophy and CDKN2A Methylation Status in the Gastric Mucosa.

Objective: This study aimed to clarify the association of MAFK polymorphisms (rs4268033, rs3735656, and rs10226620) with the degree of gastric mucosal atrophy and CDKN2A CpG methylation status. Methods: A total of 491 subjects were enrolled in this study. Genotypes and methylation status were determined by polymerase chain reaction (PCR)-single-stranded conformation polymorphism and methylation-specific PCR (Fujita Health University, HM18-094). Methods: A total of 491 subjects were enrolled in this study. Genotypes and methylation status were determined by polymerase chain reaction (PCR)-single-stranded conformation polymorphism and methylation-specific PCR (Fujita Health University, HM18-094). Results: Either rs3735656 or rs10226620, located in the 3'-UTR of MAFK, was significantly associated with the severity of gastric mucosal atrophy using a dominant genetic model (odds ratio [OR], 2.10; p = 0.0012, and OR, 1.98; p = 0.0027, respectively). However, using a recessive genetic model, no significant association was found between three polymorphisms and gastric mucosal atrophy. The serum pepsinogen I/II ratio was significantly lower in subjects with minor alleles of rs3735656 and rs10226620 than in subjects with the wild homozygous allele (p = 0.018 and 0.013, respectively). In a subgroup including 400 of the 491 subjects, the CpG of p14ARF and p16 INK4a were methylated in 132 and 112 subjects, respectively. Fifty subjects had both CpG methylations and 206 subjects had neither methylation. When comparing the groups with both and neither methylations, there were no significant associations between three polymorphisms and CDKN2A methylation using a dominant genetic model. However, all polymorphisms investigated in this study (rs4268033, rs3735656, and rs10226620) were significantly associated with CDKN2A methylation in a recessive genetic model (OR, 3.58; p = 0.0071, OR, 4.49; p = 0.0004, and OR, 3.45; p = 0.0027, respectively). Conclusions: Our results indicate that carrying the minor allele of the MAFK polymorphisms, particularly when they are located in the 3'-UTR, has a high risk for the severity of gastric mucosal atrophy; furthermore, CDKN2A CpG methylation may develop in subjects with homozygous minor allele of these polymorphisms.

Optical coherence tomographic evaluation of foveal hard exudates in patients with diabetic maculopathy accompanying macular detachment.

OBJECTIVE: To study morphologic changes of serous retinal detachment (SRD) and hyperreflective dots, which have been reported to be precursors of hard exudates, detectable in SRD using optical coherence tomography (OCT) to assess whether or not the OCT findings are correlated with the subfoveal deposition of hard exudates in patients with diabetic macular edema (DME) accompanied by SRD. DESIGN: Retrospective chart review. PARTICIPANTS: Twenty-eight eyes of 19 patients with DME accompanied by SRD. METHODS: We imaged SRD and the hyperreflective dots in SRD using spectral domain OCT (SD-OCT). The number and distribution of the hyperreflective dots in SRD were evaluated before the initial treatment at our hospital for DME accompanied by SRD. Based on a difference in the SD-OCT findings, the study eyes were divided into 2 groups: eyes with a few dots and those with many dots. We studied the clinical course of these 2 groups to assess whether or not the findings of SRD and hyperreflective dots on the SD-OCT images were correlated with deposition of hard exudates in the subfoveal space during follow-up. MAIN OUTCOME MEASURES: Correlation of the SD-OCT findings of SRD and hyperreflective dots with deposition of hard exudates in the subfovea of patients with DME accompanied by SRD. RESULTS: Subfoveal deposition of hard exudates was seen in 11 of the 28 eyes at the final examination. Before initial treatment at our hospital, 14 eyes had a few hyperreflective dots SRD and 14 eyes had many hyperreflective dots. Whereas no deposition of hard exudates in the subfoveal space was seen in the former eyes, it was seen in 11 of the latter 14 eyes (P < 0.0001). In addition, using SD-OCT, we found discontinuity of the outer border of detached neurosensory retina in 9 of the 28 eyes. Of these 9 eyes, 1 was in the group with few hyperreflective dots and eight were in the group with many hyperreflective dots (P = .0046). CONCLUSIONS: In patients with DME accompanied by SRD, SD-OCT revealed that hyperreflective dots may be associated with the subfoveal deposition of hard exudates during follow-up.

Durvalumab-induced Immune-related Hepatitis in a Patient with Non-small Cell Lung Cancer.

We herein report the case of a 79-year-old patient with unresectable stage III non-small cell lung cancer who developed immune-related hepatitis caused by durvalumab administration. Durvalumab was administered at 10 mg/kg every two weeks after the treatment with carboplatin (AUC2), paclitaxel (35 mg/m2), and 60 Gy radiation. At the day 208 in which the 14th durvalumab administration was scheduled, the patient was urgently hospitalized due to CTCAE Grade 4 hepatic dysfunction detected during the an outpatient blood sampling test. He was diagnosed with immune-related hepatitis and started on methylprednisolone 60 mg/day. After 51 days, his liver dysfunction improved and he was discharged.

Retinal structural changes associated with retinal arterial macroaneurysm examined with optical coherence tomography.

PURPOSE: To study the retinal structural changes associated with a retinal arterial macroaneurysm and their association with visual prognosis. METHODS: We studied retrospectively the medical records of 44 eyes of 44 patients with a retinal arterial macroaneurysm; all eyes showed hemorrhagic and/or exudative changes of the fovea with a visual disturbance. The retinal structural changes were examined by optical coherence tomography (OCT). RESULTS: At the initial visit, 30 eyes (68%) showed severe hemorrhagic complications. In eyes with subretinal hemorrhage beneath the fovea, retinal structure was relatively preserved at the initial visit. At the final visit, however, foveal structure was often degenerated, especially in its outer aspect, with limited visual recovery. The 14 eyes (32%) with minimal hemorrhagic complications showed an extensive exudative change caused by the aneurysm. In 13 of these eyes, OCT examination revealed extensive retinal edema, predominantly in the outer retina. Retinal edema beneath the fovea caused a focal serous retinal detachment in 12 eyes. Eight eyes with extensive exudative change showed an accumulation of hard exudates in the macular area, and visual recovery of these eyes was often limited. CONCLUSION: Subretinal hemorrhage or extensive exudative change from a retinal arterial macroaneurysm can cause destruction of the foveal outer photoreceptor layer, resulting in a poor visual outcome.

Retinal sensitivity after intravitreal injection of bevacizumab for the treatment of macular edema secondary to retinal vein occlusion.

PURPOSE: To evaluate the change in macular function after intravitreal injection of bevacizumab for the treatment of macular edema associated with retinal vein occlusion. METHODS: For this interventional case series, 20 eyes of 20 patients with macular edema associated with retinal vein occlusion were treated with an intravitreal injection of bevacizumab. Microperimetry in the macular area was performed with a Micro Perimeter 1 before and at 1, 3, and 6 months after treatment. RESULTS: Improvement in macular function was detected immediately after treatment and lasted for at least 6 months. As measured by the Micro Perimeter 1, mean retinal sensitivities within the central 10 degrees field (4.9 +/- 2.7 dB at baseline) improved to 7.2 +/- 3.1 dB at 1 month, to 7.6 +/- 3.4 dB at 3 months, and to 7.7 +/- 3.9 dB at 6 months (P < 0.001). Of the 20 eyes, a recurrence of macular edema was observed in 14 (70%), but with the use of optical coherence tomography, integrity of the outer aspect of the foveal photoreceptors was detected at 3 months to 6 months in 15 (75%) eyes. CONCLUSION: In eyes with macular edema associated with retinal vein occlusion, improvement in macular function was detected immediately after intravitreal injection of bevacizumab and lasted for at least 6 months.

Evaluation of potential visual acuity in eyes with macular oedema secondary to retinal vein occlusion.

PURPOSE: To evaluate the potential visual acuity (VA) of eyes with macular oedema (MO) associated with retinal vein occlusion (RVO). METHODS: Thirty-one eyes of 31 patients with MO associated with RVO were examined and then treated with an intravitreal injection of bevacizumab. Of these 31 eyes, 22 showed complete resolution of the MO at 1 month after treatment, at which time potential VA was determined; 12 eyes had good function and 10 had poor function at this time. Optical coherence tomography was used to detect the junctions between inner and outer segments of the photoreceptors (IS/OS) as a hallmark of integrity of the outer photoreceptor layer. RESULTS: In the poor function group, pretreatment VA was significantly worse (P = 0.0106) and pretreatment central macular thickness was significantly greater (P = 0.0121). Preservation of the foveal photoreceptor layer before treatment was associated closely with good visual function after resolution of MO, and IS/OS line beneath the fovea was detected more frequently before treatment in eyes with good function (P = 0.0053). CONCLUSIONS: In eyes with MO associated with RVO, when the IS/OS line was detected beneath the fovea, they would be expected to have good vision after resolution of the MO.

Association of genetic polymorphisms in DNMT3A with the progression of gastric mucosal atrophy and susceptibility to gastric cancer in Japan.

The aim of the present study was to investigate whether single nucleotide polymorphisms in the DNMT3A gene are associated with susceptibility to gastric cancer in the Japanese population. The present case-control study examined the associations between single nucleotide polymorphisms (rs6733868 and rs13428812) in DNMT3A and cancer susceptibility in 343 patients with gastric cancer and 708 subjects without gastric malignancies on upper gastro-duodenal endoscopy. Of 708 controls, 409 were classified into two groups histologically: 99 cases with and 310 cases without gastric mucosal atrophy. Overall, homozygosity for the DNMT3A rs6733868 minor allele was significantly associated with a reduced risk of gastric cancer (odds ratio [OR], 0.621; 95% confidence interval [CI], 0.402-0.958; P=0.031), especially of the intestinal type (OR, 0.494; 95% CI, 0.274-0.890; P=0.019). In subjects >60 years, rs6733868 minor allele homozygosity was significantly associated with gastric cancer susceptibility. Carriers of the rs6733868 minor allele had a reduced risk of severe gastric mucosal atrophy (OR, 0.495; 95% CI, 0.299-0.826; P=0.0069). In addition, the number of minor alleles of both rs6733868 and rs13428812 was significantly correlated with the risk of Helicobacter pylori (HP) infection (P=0.0070 and P=0.0050, respectively). However, rs13428812 was not associated with severe gastric mucosal atrophy or gastric carcinogenesis. The present results suggest that DNMT3A polymorphisms serve roles in the progression from HP infection to gastric mucosal atrophy and gastric carcinogenesis in terms of degree and manner.

Three-dimensional imaging of cystoid macular edema in retinal vein occlusion.

OBJECTIVE: To study the pathomorphologic features of cystoid macular edema (CME) associated with retinal vein occlusion by three-dimensional (3D) optical coherence tomography (OCT) and to study the relationship of the ocular findings to visual function. DESIGN: Observational case series. PARTICIPANTS: Twenty eyes of 20 patients with retinal vein occlusion. METHODS: A prototype 3D OCT system based on Fourier-domain OCT technology was fabricated for patient examination in this study. This system uses a superluminescent diode, which has a center wavelength of 830 nm and a bandwidth of 50 nm, as the light source, resulting in 4.3-microm axial resolution in tissue. Data acquisition rates of approximately 18 700 axial scans per second and a sensitivity of 98 dB were achieved. Three-dimensional imaging was performed by volume rendering based on the 3D data set acquired with a raster scan of 256x256 axial scans. MAIN OUTCOME MEASURES: Images of CME pathologic features obtained by 3D OCT and by Stratus OCT (Carl Zeiss, Dublin, CA). RESULTS: The 3D OCT imaging system generates a realistic 3D image of CME with high resolution. In 16 eyes, 3D OCT showed large foveal cystoid spaces, most of which were accompanied by small cystoid spaces in the parafoveal region. Cystoid spaces were seen often in the inner nuclear layer and outer plexiform layer, but were detected to some extent in all retinal layers. The 3D OCT showed clearly a thin back-reflecting line corresponding to the external limiting membrane (ELM) in 18 eyes; of these, cystoid spaces were located on the inside of the ELM in 7 eyes and appeared to be in contact with the ELM in 9 eyes. In 2 eyes, the ELM line could not be seen clearly beneath the large foveal cystoid spaces. Integrity of the ELM in the foveal region had a direct correlation with visual acuity. CONCLUSIONS: Observation of CME using 3D OCT enabled visualization of its spatial extent in each retinal layer and discernment of its relationship to the ELM. The use of 3D OCT thus may improve the monitoring of CME progression and its response to treatment.

Foveal photoreceptor layer in eyes with persistent cystoid macular edema associated with branch retinal vein occlusion.

PURPOSE: To study the correlation of visual acuity and the foveal photoreceptor layer in eyes with persistent cystoid macular edema associated with branch retinal vein occlusion (BRVO). DESIGN: Retrospective chart review. METHODS: We studied retrospectively the medical records of 42 eyes of 42 patients with persistent cystoid macular edema secondary to BRVO, eyes in which the foveal thickness was greater than 250 microm at final examination. On the vertical image obtained by optical coherence tomography at the final examination, we measured thickness of the foveal photoreceptor layer that was beneath the foveal cystoid spaces. We also assessed status of the junction between inner and outer segments of the photoreceptors (IS/OS) in the fovea. RESULTS: The photoreceptor layer beneath the foveal cystoid spaces was detected as a distinct layer with thickness varying between 33 microm and 124 microm (mean, 71.1 +/- 26.8 microm). Final visual acuity showed no correlation with total foveal thickness (r = 0.336, P = .092). However, it did show a close correlation with thickness of the foveal photoreceptor layer (r = -0.571, P < .0001). Of the 42 eyes, 15 showed a continuous IS/OS line in the fovea. Visual acuity in these eyes with a continuous IS/OS line in the fovea was significantly better than that in eyes with a discontinuous or interrupted IS/OS line (P < .0001). CONCLUSIONS: Both the thickness and the integrity of the foveal photoreceptor layer are associated with visual function in eyes with persistent cystoid macular edema associated with BRVO.