Long-term efficacy and safety of sirolimus for retinal astrocytic hamartoma associated with tuberous sclerosis complex.

Mammalian target of rapamycin (mTOR) inhibitors (sirolimus or everolimus) have been demonstrated effective in reducing the size of tuberous sclerosis complex (TSC)-associated retinal astrocytic hamartoma (RAH) in short term. To investigate the long-term efficacy and safety of sirolimus on TSC-associated RAH, 13 TSC-associated RAH patients (59 RAH lesions) who received sirolimus therapy for at least 2 years were retrospectively enrolled in this study. Changes in the maximal thickness (MT) of RAH on optical coherence tomography and the longest base diameter (LBD) of RAH on color fundus photography were assessed. The results showed that for a mean follow-up of 39 months, sirolimus was associated with a mean reduction of 14.6% in MT and 6.8% in LBD of RAHs. The main impacts of sirolimus occurred within the first 6-12 months, with 14.8% reduction in MT and 4.7% reduction in LBD. Mouth ulceration (10 [76.9%]) and acne (9 [69.2%]) were the most common adverse events. These follow-up data support the long-term use of sirolimus in TSC-associated RAH patients, and persistent use of sirolimus possibly prevents tumor regrowth.

Individual mortality risk predictive system of patients with acute-on-chronic liver failure based on a random survival forest model.

BACKGROUND: The basis of individualized treatment should be individualized mortality risk predictive information. The present study aimed to develop an online individual mortality risk predictive tool for acute-on-chronic liver failure (ACLF) patients based on a random survival forest (RSF) algorithm. METHODS: The current study retrospectively enrolled ACLF patients from the Department of Infectious Diseases of The First People's Hospital of Foshan, Shunde Hospital of Southern Medical University, and Jiangmen Central Hospital. Two hundred seventy-six consecutive ACLF patients were included in the present study as a model cohort (n = 276). Then the current study constructed a validation cohort by drawing patients from the model dataset based on the resampling method (n = 276). The RSF algorithm was used to develop an individual prognostic model for ACLF patients. The Brier score was used to evaluate the diagnostic accuracy of prognostic models. The weighted mean rank estimation method was used to compare the differences between the areas under the time-dependent ROC curves (AUROCs) of prognostic models. RESULTS: Multivariate Cox regression identified hepatic encephalopathy (HE), age, serum sodium level, acute kidney injury (AKI), red cell distribution width (RDW), and international normalization index (INR) as independent risk factors for ACLF patients. A simplified RSF model was developed based on these previous risk factors. The AUROCs for predicting 3-, 6-, and 12-month mortality were 0.916, 0.916, and 0.905 for the RSF model and 0.872, 0.866, and 0.848 for the Cox model in the model cohort, respectively. The Brier scores were 0.119, 0.119, and 0.128 for the RSF model and 0.138, 0.146, and 0.156 for the Cox model, respectively. The nonparametric comparison suggested that the RSF model was superior to the Cox model for predicting the prognosis of ACLF patients. CONCLUSIONS: The current study developed a novel online individual mortality risk predictive tool that could predict individual mortality risk predictive curves for individual patients. Additionally, the current online individual mortality risk predictive tool could further provide predicted mortality percentages and 95% confidence intervals at user-defined time points.

Increased expression of Ki-67 is a poor prognostic marker for colorectal cancer patients: a meta analysis.

BACKGROUND: The prognostic value of Ki-67 expression in colorectal cancer patients was controversial. Therefore, this meta analysis was conducted to ascertain the prognostic value of Ki-67 expression in colorectal cancer patients. METHODS: The electronic databases, including EMBASE, PubMed, Cochrane Library and Web of Knowledge database, were searched from January 1970 to July 2017. The pooled hazard ratios and 95% confidence intervals were calculated to evaluate the prognostic value of Ki-67 expression for colorectal cancer patients. RESULTS: Totally 34 eligible studies and 6180 colorectal cancer patients were included in the present meta analysis. The pooled hazard ratios were 1.54(95% CI 1.17-2.02, P = 0.005) for overall survival and 1.43(1.12-1.83, P = 0.008) for disease free survival in univariate analysis. After adjustment of other prognostic factors, the pooled HR was 1.50(95% CI 1.02-2.22, P = 0.03) for overall survival in multivariate analysis. CONCLUSION: The present meta analysis demonstrated that high Ki-67 expression is significantly correlated with poor overall survival and disease free survival, indicating that high Ki-67 expression may serve as a valuable predictive method for poor prognosis of colorectal cancer patients.

Routine indexes for cirrhosis and significant fibrosis detection in patients with compensated chronic hepatitis B.

BACKGROUND AND AIM: Fibrosis index based on the four factors (FIB-4) and aspartate aminotransferase to platelet ratio index (APRI) were not well validated in patients with chronic hepatitis B (CHB). The aim of this study was to validate the performances of these indexes and construct novel indexes for liver fibrosis assessment. METHODS: A total of 1438 consecutive antivirus treatment-naïve patients with CHB were analysed, and two novel indexes (named HeBCI and HeBFI) were derived for cirrhosis and significant fibrosis detection. RESULTS: For cirrhosis, the area under receiver operating characteristic curves (AUROCs) were 0.841 for HeBCI, 0.708 for FIB-4 and 0.623 for APRI in the model set, and 0.779, 0.690, 0.595 in the validation set. For significant fibrosis, the AUROCs were 0.781 for HeBFI, 0.693 for APRI and 0.641 for FIB-4 in the model set, and 0.776, 0.729, 0.641 in the validation set. HeBCI determined 750 (52.2%) patients as having cirrhosis or non-cirrhosis with an accuracy of 86%. HeBFI detected 673 (46.8%) patients with or without significant fibrosis with an accuracy of 76.6%. CONCLUSIONS: As economical and convenient indexes, HeBCI and HeBFI are suitable to serve as outpatient tools for detecting significant fibrosis and cirrhosis to reduce the need of liver biopsy significantly in resource-limited settings.

Nomogram for hepatic steatosis: A simple and economical diagnostic tool for massive screening.

AIM: To establish a simple economical diagnostic tool for prediction of hepatic steatosis in patients with hepatitis B virus (HBV) infection. METHODS: From January 2006 to January 2015,a total of 1325 consecutive subjects who underwent liver biopsy were enrolled. According to the results of multivariate logistic regression analysis, a new nomogram was conducted. Then discrimination and calibration were conducted to assess the clinical diagnostic value of nomogram. RESULTS: The nomogram consisted of age, triglyceride (TG), low-density lipoprotein (LDL), uric acid (UA), haemoglobin (HGB). For prediction of hepatic steatosis, the AUROC of nomogram was 0.792 (95%CI: 0.758-0.826). With cut off value of 0.11, 699 (52.8%) of 1325 patients could be free from liver biopsy with a correct rate of 95.3% for diagnosis of hepatic steatosis. CONCLUSION: The nomogram for hepatic steatosis has a better clinical diagnostic value for prediction of hepatic steatosis in patients with HBV infection. From the perspective of cost-effectiveness and clinical practice, it is worth considering the use of the nomogram as a mass screening tool before further liver biopsy or imaging examinations.

Spectral domain optical coherence tomography of Vogt-Koyanagi-Harada disease: novel findings and new insights into the pathogenesis.

OBJECTIVE: To provide novel spectral domain optical coherence tomography (SD OCT) findings of Vogt-Koyanagi-Harada (VKH) disease as well as new insights into the pathogenesis of this disease. METHODS: Detailed SD OCT and fluorescein angiography (FA) findings of 18 consecutive VKH patients (11 women and 7 men) from December 2007 to April 2009 who were in acute uveitic stage at presentation were reviewed. All the patients had been followed up for at least 6 months with reevaluation(s) of SD OCT performed in 10 patients. RESULTS: Intraretinal cysts were found to be located in various layers of the outer retina. In addition to the photoreceptor layer, they could also be found between the outer plexiform layer and the outer nuclear layer, or spanning the external limiting membrane. On FA, intraretinal cysts could be hypofluorescent, normofluorescent, or hyperfluorescent. Some intraretinal cysts had a characteristic FA pattern, in which a small round hypofluorescent area was surrounded by a ring of hyperfluorescence (donut-shaped dye pooling). Subretinal fibrinoid deposit appeared in acute uveitic stage in two severe VKH patients and seemed to develop from subretinal exudates and evolved into typical subretinal fibrosis. Gradual transfiguration/migration and progressive proliferation/pigmentation of the subretinal fibrinoid deposit/subretinal fibrosis was observed in one patient. CONCLUSIONS: Intraretinal cysts could form in various layers of the outer retina and may result from extension of choroidal inflammation. Subretinal fibrosis may develop from subretinal exudates in VKH patients and may cause substantial visual impairment.

[Ocular features of multiple endocrine neoplasia type 2b].

OBJECTIVE: To analyze the ocular features of multiple endocrine neoplasia type 2b (MEN 2b). METHODS: Three cases with MEN 2b were reviewed and their ocular features analyzed. RESULTS: All patients had medullary thyroid carcinoma and thickened corneal nerve fibers. Adrenal pheochromocytoma, oral mucosal neuroma, marfanoid body habitus, eyelid nodule and conjunctival nodule were found in two patients. And iris nodule was found in one patient. CONCLUSIONS: The most common ocular manifestations of MEN 2b is thickened corneal nerve fibers.

[Relationship between central visual acuity and retinal volume of macular fovea accessed by spectral domain optical coherence tomography in Stargardt disease].

OBJECTIVE: To assess the relationship between central visual acuity and retinal volume of macular fovea in patients with Stargardt disease by spectral-domain optical coherence tomography (SD OCT). METHODS: It was a retrospective case series study. Twenty eyes of 10 patients with Stargardt disease were investigated by three-dimensional spectral-domain optical coherence tomography. SD OCT images were obtained and retrospectively analyzed. The retinal volumes of macular fovea were measured by SD OCT, whose diameters were set as 3 mm and 1 mm separately (volume 3 and volume 1). The retinal thickness of macular fovea (macular thickness) and the width of IS/OS conjunction loss of macular fovea (IS/OS loss) were also measured by SD OCT. We correlated the logMAR BCVA with IS/OS loss, macular thickness, volume 3 and volume 1 by linear regression analysis. RESULTS: LogMAR BCVA was from 0.3 to 1.22. IS/OS loss was from 847 µm to 5306 µm. Macular thickness was from 20 µm to 126 µm. Volume 3 and volume 1 was from 1.06 to 1.76 mm(3) and 0.06 to 0.13 mm(3). LogMAR BCVA correlated with the IS/OS loss (r = 0.695, P < 0.05), macular thickness (r = -0.601, P < 0.05), and volume 3(r = -0.725, P < 0.05). LogMAR BCVA did not correlate with volume 1(r = -0.364, P > 0.05). CONCLUSIONS: SD OCT could demonstrate the retinal structure of Stargardt disease clearly. The retinal volume of macular fovea accessed by SD OCT correlated with the visual acuity of Stargardt disease.

[Recovery of photoreceptor inner/outer segment junction in spectral domain optical coherence tomography after surgery in idiopathic macular hole].

OBJECTIVE: To evaluate the findings of spectral domain optical coherence tomography (SD-OCT) in patients with idiopathic macular hole (IMH). METHODS: It was a retrospective case series study. Pre- and post-operative data from patients with IMH during 14 months were analyzed retrospectively. The main outcome data included logarithm of the minimal angle of resolution (logMAR) and SD-OCT findings, including the size of the IMH and the disruption of the boundary line between inner segments (IS) and outer segments (OS) of the photoreceptors. The data were analyzed using the statistical software SPSS14.0. The correlation among various data was analyzed by Bivariate correlation. The pre-and post-operative data were compared by paired-samples t-tests. RESULTS: Thirty two eyes of 32 patients were studied. The mean logMAR was 1.16 ± 0.46 (ranged from 0.40 to 2.00), the mean diameter of macular hole was (859.7 ± 292.0) µm (ranged from 332 to 1568 µm). The mean diameter of IS/OS disruption was (1965.1 ± 584.1) µm (ranged from 867 to 3444 µm). In eyes after surgery, the mean logMAR was 0.89 ± 0.46 (ranged from 0.30 to 2.00), the mean diameter of the IS/OS disruption was (1350.4 ± 642.6) µm (ranged from 153 to 2546 µm), both were decreased significantly as compare with the preoperative data (t = 3.384, 6.360; P < 0.05). Preoperative diameter of macular hole (r = 0.583) and IS/OS disruption (r = 0.416) were correlated significantly with postoperative logMAR (P < 0.05). CONCLUSIONS: Preoperative diameter of macular hole and IS/OS disruption play the main role in vision prognosis. The IS/OS disruption is decreased significantly after the operation.

[Features of vitreomacular traction syndrome assessed with three-dimensional spectral-domain optical coherence tomography].

OBJECTIVE: To describe features of vitreomacular traction syndrome (VMT) on three-dimensional (3D) spectral-domain optical coherence tomography (SD OCT). METHODS: Eighteen eyes of 18 patients with VMT were diagnosed by SD OCT. SD OCT images were obtained and retrospectively analyzed. These VMT cases were defined as focal type or broad type by the region of the vitreous attachment to the macula. The relationship between the logMAR best corrected visual acuity (BCVA) and the retinal thickness of macular fovea was evaluated by linear regression analysis. RESULTS: SD OCT provided detailed 3D images of VMT and revealed information about the extent of vitreomacular traction. Focal VMT was seen in 14 eyes. Broad VMT was seen in four eyes. Eight cases had concurrent epiretinal membrane in the areas surrounding the fovea. Two cases had concurrent full thickness macular hole and two cases had concurrent lamellar macular hole. LogMAR BCVA correlated with the retinal thickness of macular fovea (r = 0.616, P = 0.007, linear regression analysis). CONCLUSIONS: SD OCT allows good visualization of the architectural morphology of the vitreous and retina in vitreomacular traction syndrome. It is useful and irreplaceable for the diagnosis and follow-up of VMT.

[Clinical analysis of intraocular pressure elevation following vitreoretinal surgery].

OBJECTIVE: To study the incidence and risk factors of intraocular pressure (IOP) elevation in patients who underwent vitreoretinal surgery. METHODS: Data for 422 patients (446 eyes) who underwent vitreoretinal surgery from June 2005 to June 2007 were retrospectively analyzed. IOP was measured before surgery and on day 1, 2, 3, 7-14 after surgery with Goldmann applanation tonometer. Ocular hypertension was defined as IOP 25 mmHg or more. All factors were analyzed for association with Ocular hypertension. RESULTS: 232 of the 422 patients were female. 190 were male. The IOP was elevated significantly in 185 eyes (41%) after surgery within 2 weeks. Among them the IOP occurred mostly in day 1 (152 eyes, 82%). The rate of IOP elevation with intraocular tamponade of C3F8 or silicone oil was 53% or 55%, the difference being not statistically significant (P>0.05). The incidence of high IOP in C3F8 injection group and silicone oil injection group were statistically higher than simple pars plana vitrectomy group (P<0.01). The risk factors of ocular hypertension include C3F8 injection (chi2=37.82, P<0.01), silicone oil injection (chi2=27.84, P<0.01), lentectomy (chi2=8.98, P<0.01), scatter endolaser (chi2=7.41, P<0.01), diabetes (chi2=12.12, P<0.01) and increasing patient age (chi2=7.07, P<0.01). CONCLUSION: IOP elevation was a common complication of vitreoretinal surgery. The risk factors of ocular hypertension include C3F8 injection, silicone oil injection, lentectomy, scatter endolaser, diabetes and increasing patient age.

[In vitro differentiation of rat mesenchymal stem cells into photoreceptors].

OBJECTIVE: To isolate and culture rat mesenchymal stem cells (MSCs) and induce them to differentiate into photoreceptor cells in vitro. METHODS: It was a experimental study. MSCs were isolated and attached to the wall of culture dishes by their specific adherent ability. Then the cells were characterized by flow cytometry. MSCs were induced by murine EGF for 8-10 days in-vitro. Then we used immunohistochemistry staining and flow cytometry to see whether they could express rhodopsin and differentiated into photoreceptor cells. RESULTS: Many MSCs, which were highly purified, were obtained. After induction by EGF, 15.32% MSCs expressed rhodopsin. CONCLUSION: After induction by EGF, approximately 15.32% MSCs could differentiate into photoreceptor cells.

[Differentiation of rat mesenchymal stem cells in the microenvironment of choroidal neovascularization].

OBJECTIVE: To assay the differentiation of rat mesenchymal stem cells (MSCs) in the microenvironment of choroidal neovascularization (CNV). METHOD: Cultured BN rat MSCs were injected into the subretinal space in 25 Argon laser-induced CNV rat. The differentiation of MSCs was traced by immunofluorescent labeling successively in 5 weeks after the surgery. RESULTS: MSCs distributed on the surface of CNV in the 1st week after injection. From the 2nd week, CD31 positive MSCs were found in CNV until 5 weeks after cell injection, while rhodopsin positive MSCs in the photoreceptor layer were revealed until the 5th week after the injection. CONCLUSION: Injected MSCs in the microenvironment of CNV can differentiate into endothelium and photoreceptor.