Types of diabetes during pregnancy and risk of depression and anxiety in offspring from childhood to young adulthood.

AIMS: To assess maternal pre-existing type 1 diabetes (T1D), type 2 diabetes (T2D), gestational diabetes mellitus (GDM) during pregnancy and risk of depression and anxiety from childhood to young adulthood in offspring. MATERIALS AND METHODS: This birth cohort included singletons born during 1995-2015, followed using electronic medical records through 2020. Cox regression was used to estimate hazard ratio (HR) of depression or anxiety diagnosis during follow-up associated with in-utero exposure to maternal diabetes. RESULTS: Among 439 590 offspring, 29 891 (6.8%) had depression and 51 918 (11.8%) had anxiety. T1D, followed by T2D and GDM requiring antidiabetes medication were associated with risk of depression and anxiety in offspring. Compared with no diabetes during pregnancy, the adjusted HRs (95% confidence interval) of depression in offspring associated with T1D, T2D or GDM requiring medications were 1.44 (1.09-1.91), 1.30 (1.15-1.47) and 1.18 (1.11-1.26) respectively; conversely, HRs were 0.97 (0.82-1.15) for T2D and 0.99 (0.94-1.04) for GDM without medications. The associations with anxiety followed similar patterns. The significant associations were observed for offspring ages 5-12 and >12-18 years and attenuated for 18-25 years. CONCLUSION: These data suggest that the severity of diabetes (T1D vs. T2D requiring medications vs. GDM requiring medications) during pregnancy may increase the vulnerability of offspring for depression or anxiety.

Epstein-Barr Virus Uveitis Confirmed via Aqueous Humor Polymerase Chain Reaction and Metagenomics-A Case Report.

This is a case report of Epstein-Barr virus (EBV) uveitis confirmed via aqueous humor polymerase chain reaction (PCR) and metagenomics. This 72-year-old male with a history of diabetes and herpes zoster complained of redness and blurred vision in his right eye for eight months. Mild conjunctival injection, anterior chamber cells, mutton-fat keratic precipitates, and vitreous haze were noted. Fluorescein angiography revealed dye leakage from retinal vessels without retinal ischemic changes. Only the serum anti-cytomegalovirus (CMV) IgG was positive while the aqueous humor PCR for VZV (Varicella-zoster virus), HSV (Herpes simplex viruses), CMV, and EBV was initially negative. Inflammation recurred and vitreous haze worsened after discontinuing nine-month topical ganciclovir and oral prednisolone. the aqueous humor PCR was repeated due to persistent low-grade inflammation. The EBV PCR turned out to be positive. Shotgun metagenomics revealed 1459 classified sequences (1.62%) and confirmed the EBV infection. Topical ganciclovir and methylprednisolone treatment was resumed. Conjunctival injection improved while pigmented keratic precipitates lessened. Elderly patients with diabetes or under immunosuppression may be susceptible to chronic uveitis associated with subsequent EBV infection. Repeated aqueous humor PCR and shotgun metagenomics are important tools in the diagnosis of this case of chronic indolent panuveitis.

Associations of Autism Spectrum Disorder with PM2.5 Components: A Comparative Study Using Two Different Exposure Models.

This retrospective cohort study examined associations of autism spectrum disorder (ASD) with prenatal exposure to major fine particulate matter (PM2.5) components estimated using two independent exposure models. The cohort included 318 750 mother-child pairs with singleton deliveries in Kaiser Permanente Southern California hospitals from 2001 to 2014 and followed until age five. ASD cases during follow-up (N = 4559) were identified by ICD codes. Prenatal exposures to PM2.5, elemental (EC) and black carbon (BC), organic matter (OM), nitrate (NO3-), and sulfate (SO42-) were constructed using (i) a source-oriented chemical transport model and (ii) a hybrid model. Exposures were assigned to each maternal address during the entire pregnancy, first, second, and third trimester. In single-pollutant models, ASD was associated with pregnancy-average PM2.5, EC/BC, OM, and SO42- exposures from both exposure models, after adjustment for covariates. The direction of effect estimates was consistent for EC/BC and OM and least consistent for NO3-. EC/BC, OM, and SO42- were generally robust to adjustment for other components and for PM2.5. EC/BC and OM effect estimates were generally larger and more consistent in the first and second trimester and SO42- in the third trimester. Future PM2.5 composition health effect studies might consider using multiple exposure models and a weight of evidence approach when interpreting effect estimates.

Optical Coherence Tomography Biomarkers in Predicting Treatment Outcomes of Diabetic Macular Edema after Ranibizumab Injections.

Background and Objectives: The identification of possible biomarkers that can predict treatment response among DME eyes is important for the individualization of treatment plans. We investigated optical coherence tomography (OCT)-based biomarkers that may predict the one-year real-life outcomes among diabetic macular edema (DME) eyes following treatment by intravitreal ranibizumab (IVR) injections. Materials and Methods: A total of 65 eyes from 35 treatment-naïve patients with DME treated with ranibizumab injection were recruited. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), intraocular pressure (IOP), and OCT scans were retrospectively recorded at baseline before treatment and at 3 months, 6 months, and 12 months after treatment. The OCT scans were evaluated for biomarkers of interest, which included central retinal thickness (CRT), amount and locations of hyperreflective foci (HRF), subretinal fluid (SRF), intraretinal cysts (IRC), large outer nuclear layer cyst (LONLC), ellipsoid zone disruption (EZD), disorganization of retinal inner layers (DRIL), hard exudates (HE), epiretinal membrane (ERM), and vitreomacular interface (VMI). Correlations between these OCT biomarkers and outcome measures (visual and structural) were statistically analyzed. Results: A total of 65 eyes from 35 patients with DME were enrolled. The mean age was 64.2 ± 10.9 years old. Significant improvement in terms of mean BCVA (p < 0.005) and mean CRT was seen at final follow-up compared to baseline. The biomarkers of DRIL, LONLC, and SRF were found to be predictive for at least 50 µm CRT reduction after treatment (with odds ratio of 8.69, 8.5, and 17.58, respectively). The biomarkers of IRC, LONLC, and SRF were predictive for significant improvement in terms of BCVA and CRT after treatment. Finally, the number of HRF was predictive for both BCVA improvement and a CRT reduction of less than 100 µm after treatment. No serious complications were reported during the study. Conclusion: Our study demonstrated the utility of OCT biomarkers as therapeutic predictors of ranibizumab treatment among DME eyes.

Use of Ultra-Widefield Fluorescein Angiography to Guide the Treatment to Idiopathic Retinal Vasculitis, Aneurysms, and Neuroretinitis-Case Report and Literature Review.

PURPOSE: To review the clinical features, diagnosis, and treatment of idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN) and to report a case with the use of ultra-widefield fluorescein angiography (UWFA) for confirming the precise staging of IRVAN and aid in early treatment. The patient improved after being treated with intravitreal aflibercept injection. RESULTS: A 26-year-old female complained of progressive blurred vision OD for one week. Her BCVA was 0.6 OD and 1.0 OS. Fundus examination showed vitritis, retinal hemorrhage, and vasculitis over bilateral eyes. Fluorescein angiography (FA) with a 55 degree of view revealed aneurysmal dilations of the peripapillary arteriole, peripapillary focal leakage, venous leakage, and capillary nonperfusion area. Stage 2 IRVAN was impressed OU. Oral prednisolone was administered. After four months, she experienced decreased visual acuity OS. Optical coherence tomography (OCT) revealed subretinal and intraretinal fluid with hyperreflective material. One posterior subtenon triamcinolone and one intravitreal aflibercept injection were performed OS, and macular edema subsided. A 105-degree ultra-widefield fluorescein angiography (UWFA) showed multiple peripheral background hypofluorescence areas corresponding to capillary nonperfusion. Retinal neovascularization (NV) was found OS, which had not been revealed by the previous 55-degree FA. Stage 3 IRVAN was made OS and panretinal laser photocoagulation (PRP) was performed. Oral prednisone and cyclosporine were prescribed. Her vision improved to 1.0 OU. CONCLUSION: UWFA provides visualization of peripheral retinal pathology and for precise staging. It also had direct implications in the follow-up and treatment strategy.

Short-Term Effects of Brolucizumab in the Treatment of Wet Age-Related Macular Degeneration or Polypoidal Choroidopathy Refractory to Previous Anti-Vascular Endothelial Growth Factor Therapy.

Background and objectives: To report the initial response to a single intravitreal brolucizumab (IVI-B) injection in wet age-related macular degeneration (wAMD) or polypoidal choroidopathy (PCV) complicated with either persistent subretinal fluid (SRF) or pigment epithelial detachment refractory to previous anti-vascular endothelial growth factor (anti-VEGF) therapy. Material and methods: In this retrospective study, all eyes received a single IVI-B (6 mg/0.05 mL) for wAMD or PCV with treatment-resistant SRF or PED. Outcome measures included assessment in central retinal thickness (CRT), visual acuity, and evaluation for changes in the SRF or PED on OCT. Follow-up was prior to the first brolucizumab injection, then at 1 week and 5 weeks afterwards. Results: In total, 10 eyes of 10 patients (6 women [60%]) were enrolled. Five patients had wAMD and five patients had PCV. Average age of participants was 67.6 years. All patients received one IVI-B. All patients were not treatment-naïve to anti-VEGF agents. At the first week and fifth week following the first IVI-B, seven out of seven patients (100%) had resolved SRF. However, seven out of nine patients (78%) had no improvement of their PED at 5 weeks follow-up. Mean PED height and width before the first IVI-B was 339.77 µm and 2233.44 µm, respectively. Mean PED height and width at the fifthweek following the first IVI-B was 328.125 µm and 2129.5 µm, respectively. Overall mean visual acuity before the first IVI-B was 0.224; and 5 weeks following the first IVI-B was 0.38. Conclusions: Treatment with brolucizumab resulted in anatomical improvement for all patients with persistent SRF. Limited efficacy was seen for persistent PED. Brolucizumab appears to be a safe and effective option for treatment-resistant SRF. Future multicenter collaborative studies are warranted.

Comparison of Choroidal Thickness, Foveal Avascular Zone, and Macular Capillary Density in Macular Edema Secondary to Branch Retinal Vein Occlusion Treated with Ranibizumab or Aflibercept-A Prospective Study.

This prospective comparative case series aims to compare best-corrected visual acuity (BCVA), retinal microvasculature, and retinal structural changes in patients treated with either ranibizumab or aflibercept for macular edema (ME) secondary to treatment-naïve branch retinal vein occlusion (BRVO) by optical coherence tomography angiography (OCTA). Ten patients were enrolled with macular capillary density of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) and foveal avascular zone (FAZ) measured in both eyes before and after treatment. Final central retinal thickness and BCVA improved significantly (p < 0.05), and densities of SCP and DCP of BRVO sectors were significantly lower at baseline than fellow eye counterparts and remained persistently lower during treatment, particularly in the aflibercept group (p < 0.05). SCP density, DCP density of both BRVO sectors (p = 0.0001, p < 0.0001), and non-BRVO sectors (p < 0.0001, p < 0.0001) were significantly correlated with final BCVA for diseased eyes. Using multivariate general linear model analysis, and including OCTA parameters only, but not all of the available clinical data, DCP density of BRVO sectors in both eyes was the most predictive factor for final visual outcome (probability p < 0.0001). OCTA offered further qualitative and quantitative evaluation of treatment-naïve BRVO. Judging by OCTA parameters, not only in the diseased eye but also in the fellow eye, DCP density of BRVO sectors was the most predictive factor of final visual outcome.

Changes of Estimated Glomerular Filtration Rate and Glycated Hemoglobin A1c in Diabetic Macular Edema Patients Treated by Ranibizumab and Aflibercept in the Tertiary Referral Hospital.

Background and Objectives: Intravitreal injections (IVI) of vascular endothelial growth factor (VEGF) inhibitors are guideline-indicated treatments for diabetic macular edema (DME). However, some recent data have suggested that IVI VEGF inhibitors might, through systemic absorption, lead to a reduction in renal function. Our study aims to compare changes in glycated hemoglobin A1c (HbA1c) and estimated glomerular filtration rate (eGFR) between patients who received IVI ranibizumab and aflibercept treatment and patients who have not received IVI treatments. Materials and Methods: There were 17,165 DME patients with documented ophthalmology visits in the China Medical University Hospital-Clinical Research Data Repository. Those with a history of ESRD or bevacizumab treatment history, and those with missing information on HbA1c or eGFR, were excluded. After matching by age (±2 years), gender, and the year of clinical visit, 154 patients with medical treatment (including ranibizumab and aflibercept) and 154 patients without medical treatment were included in the study. The difference between HbA1c and eGFR at baseline and 3 and 12 months after the index date between the two groups was assessed. Results: Mean HbA1c and eGFR decreased between baseline and 12 months after the index date in both groups (p < 0.05). Compared with the non-treatment group, the treatment group had significantly lower HbA1c 3 and 12 months after the index date. There was no significant difference in eGFR between the two groups. In the generalized estimating equations (GEE) model, HbA1c in the treatment group was lower than the non-treatment group (−0.44%, 95% CI = −0.75, −0.14), but eGFR was similar after adjusting for age, gender, and index-year. HbA1c and eGFR decreased with the time in the adjusted GEE model (p < 0.0001) in both groups. Conclusions: This study showed that eGFR decreased with age and time and was not related to IVI anti-VEGF treatments in our tertiary referral hospital. IVI anti-VEGF therapy was also associated with better HbA1c control. It is suggested that DME patients can receive intravitreal VEGF inhibitors without inducing more renal impairment.

Risk factors for repeated dexamethasone intravitreal implant therapy for macular edema due to treatment-naïve branch retinal vein occlusion.

BACKGROUND: This study evaluated the effects of dexamethasone intravitreal implant on treatment-naïve branch retinal vein occlusion (BRVO)-induced macular edema (ME), and the risk factors for earlier repeated treatment. METHODS: Patients treated from 2013 to 2016 were enrolled. The patients' demographics, medical history, best-corrected visual acuity (BCVA), and central retinal thickness (CRT) were recorded. Risk factors for repeated treatment were identified using a Cox proportional hazard model and logistic regression. RESULTS: 29 patients (mean age: 58.64 ± 13.3 years) were included; 44.8% received only one injection, while 55.2% received two or more. The mean initial CRT was 457.8 ± 167.1 µm; the peak CRT and final CRT improved significantly to 248.9 ± 57.9 µm and 329.2 ± 115.1 µm, respectively. The peak BCVA improvement and final improvement were 29.5 ± 23.5 approximate ETDRS letters and 19.8 ± 24.4 letters, respectively, with 62.1% of patients improving by more than 15 letters. Older age, higher initial CRT, and diabetes were the risk factors for multiple injections. CONCLUSION: Dexamethasone intravitreal implant results in significant peak CRT and BCVA improvements, while older age, higher initial CRT, and diabetes are risk factors for repeated injections. The optimal retreatment schedule for these patients should be further explored.

Low Rate of Cancer Detection by Colonoscopy in Asymptomatic, Average-Risk Subjects with Negative Results From Fecal Immunochemical Tests.

BACKGROUND & AIMS: Screening colonoscopies are of uncertain benefit for persons with negative results from a fecal immunochemical test (FIT). We investigated detection of CRC by colonoscopy in asymptomatic, average-risk, FIT-negative subjects. METHODS: We conducted a retrospective, population-based cohort study of 96,804 subjects with an initial negative result from a FIT at ages 50-75 years, from 2008 through 2014, who then underwent colonoscopy, using the Kaiser Permanente California databases. We identified participants diagnosed with CRC from January 1, 2008 through December 31, 2015 from a cancer registry. Subjects were followed until initial colonoscopy, health plan disenrollment, death, or December 31, 2015. We reviewed records from 400 randomly selected persons without CRC (controls) for risk features to estimate the proportion who underwent screening colonoscopy. We performed logistic regression to identify variables associated with CRC detection. RESULTS: Of 257 subjects with a diagnosis of CRC, 102 did not have a record of CRC risk factors; 86 of these patients (84.3%) had non-advanced-stage CRC (no regional node spread/distant metastases). Of the 400 controls, 299 (74.75%; 95% CI, 70.49%-79.01%) lacked CRC risk features, enabling estimation that 72,263 (mean age, 57.5 ± 7.0 y; 54.5% female) had undergone screening colonoscopy. CRC was detected in 1.4 per 1000 persons after 1 FIT, without association with increasing FITs (P = .97). CRC was detected in 1.3 per 1000 persons in 2 y or less after the last FIT and in 4.4 per 1000 persons more than 2 y after the last FIT (P < .001). When the last FIT was 2 y earlier or less, CRC increased from 0.7 per 1000 persons age 50-59 y to 3.1 per 1000 persons older than 70 y. Age and time from the last FIT were associated with CRC, with adjusted odds ratios of 1.08 (95% CI, 1.05-1.11) and 2.76 (95% CI, 1.28-5.95), respectively. CONCLUSIONS: In asymptomatic, average-risk persons with a negative result from a FIT, CRC is infrequent within 2 y after the last FIT (especially for persons younger than 60 y), usually non-advanced, and unrelated to the number of FITs performed.

Maternal Gestational Diabetes and Type 2 Diabetes During Pregnancy and Risk of Childhood Asthma in Offspring.

OBJECTIVE: To examine maternal preexisting type 2 diabetes (T2D) and gestational diabetes mellitus (GDM) on risk of childhood asthma. STUDY DESIGN: This retrospective birth cohort study included 97 554 singletons born in 2007-2011 within hospitals from a single integrated healthcare system. Children were prospectively followed from age 5 until December 31, 2017, using electronic medical records. Relative risks of childhood asthma associated with maternal diabetes in utero were estimated by hazard ratios using Cox regression adjusting for potential confounders. RESULTS: There were 3119 children (3.2%) who were exposed to preexisting T2D and 9836 (10.1%) to GDM. Among mothers with GDM, 3380 (34.4%) were dispensed antidiabetic medication during pregnancy. During a median of 7.6 years (IQR, 6.3-9.0 years) after birth, 15 125 children (15.5%) were diagnosed with asthma after age 5. Maternal diabetes interacted with maternal asthma history to affect child's asthma risk (P = .05). Among children without maternal asthma (n = 89 487), the adjusted hazard ratios for childhood asthma were 1.21 (95% CI, 1.08-1.36; P < .001) for exposure to T2D, 1.12 (95% CI, 1.01-1.25; P = .04) for GDM requiring antidiabetic medications, and 1.01 (95% CI, 0.93-1.10; P = .82) for GDM not requiring medications compared with no diabetes during pregnancy. The corresponding hazard ratios were 1.53 (95% CI, 1.19-1.96; P < .001), 1.11 (95% CI, 0.65-1.46; P = .44), and 0.84 (95% CI, 0.66-1.08; P = .17) among children without maternal asthma (n = 8067). Gestational age at GDM diagnosis was not associated with childhood asthma (P = .27). CONCLUSIONS: The risk of childhood asthma was predominately observed for exposure to preexisting T2D, small for GDM requiring medication, and not increased for GDM not requiring medication during pregnancy, compared with no diabetes during pregnancy.

Adjuvant Chemotherapy Does Not Improve Recurrence-Free Survival in Patients With Stage 2 or Stage 3 Rectal Cancer After Neoadjuvant Chemoradiotherapy and Total Mesorectal Excision.

BACKGROUND: Current guidelines for locally advanced stage 2/3 rectal cancer recommend neoadjuvant chemoradiotherapy followed by total mesorectal excision and adjuvant chemotherapy. The oncologic benefit of adjuvant chemotherapy has not been consistently demonstrated. OBJECTIVE: The purpose of this study was to evaluate disease recurrence and survival in patients with rectal cancer who received adjuvant chemotherapy after chemoradiotherapy and total mesorectal excision. DESIGN: This was a retrospective review of patients with stage 2/3 rectal cancer after chemoradiotherapy and surgery, based on receipt of adjuvant chemotherapy. SETTINGS: The study was conducted at the Kaiser Permanente Southern California system of 14 hospitals and associated clinics. PATIENTS: A total of 862 patients with stage 2/3 rectal cancer diagnosed and treated between January 1, 2005, and December 31, 2016, were included in this study. INTERVENTIONS: The study involved neoadjuvant chemoradiotherapy followed by total mesorectal excision with or without adjuvant chemotherapy. MAIN OUTCOME MEASURES: The primary end point was recurrence-free survival. RESULTS: A total of 348 stage 2 and 514 stage 3 patients were included; 660 patients (76.6%) underwent adjuvant chemotherapy. Mean patient follow-up after surgery was 63.0 months (range, 3-160). Multivariable analysis showed that yp stage (HR for yp stage 2 = 4.74; yp stage 3 = 8.83) and en bloc resection (HR = 1.76) were the only variables that significantly predicted disease recurrence. Neither pretreatment tumor stage nor receipt of adjuvant chemotherapy was significantly associated with recurrence-free survival. Log-rank testing failed to demonstrate significant recurrence-free survival improvement after receipt of adjuvant chemotherapy in any patient subgroup. LIMITATIONS: The study was limited by selection bias attributed to the nature of a retrospective study without patient randomization or predefined treatment protocol. CONCLUSIONS: In stage 2/3 rectal cancer treated with chemoradiotherapy and surgery, the addition of adjuvant chemotherapy was not associated with decreased recurrence-free survival in the entire cohort or in any subgroup, whereas tumor response to chemoradiotherapy is closely associated with disease recurrence. These findings have important consequences for treatment and surveillance decisions for patients with rectal cancer. Presurgical efforts that maximize tumor downstaging, such as total neoadjuvant therapy, may produce better oncologic outcomes than traditional adjuvant chemotherapy. See Video Abstract at http://links.lww.com/DCR/B134. LA QUIMIOTERAPIA ADYUVANTE NO MEJORA LA SOBREVIDA LIBRE DE RECURRENCIA EN PACIENTES CON CÁNCER DE RECTO ESTADÍOS II O III DESPUÉS DE RADIO-QUIMIOTERAPIA NEOADYUVANTE Y ESCISIÓN TOTAL DEL MESORRECTO: Las guías actuales para el tratamiento de cáncer rectal en estadio II-III localmente avanzado, recomiendan la radio-quimioterapia neoadyuvante con escisión total del mesorrecto seguidas de quimioterapia adyuvante. El beneficio oncológico de la quimioterapia adyuvante no ha sido demostrado de manera fehaciente.Evaluar la recurrencia y sobrevida a la enfermedad en pacientes con cáncer rectal que recibieron quimioterapia adyuvante después de radio-quimioterapia y escisión total del mesorrecto.Revisión retrospectiva de pacientes con cáncer rectal en estadios II-III después de radio-quimioterapia y cirugía, basada en la recepción de quimioterapia adyuvante.Sistema Permanente de Kaiser Sur-Californiano de 14 hospitales y clínicas asociadas.862 pacientes con cáncer rectal en estadio II-III diagnosticados y tratados entre el 1 de Enero 2005 y el 31 de Diciembre 2016.Radio-quimioterapia neoadyuvante seguida de escisión total del mesorrecto +/- quimioterapia adyuvante.El objetivo primario fue la sobrevida libre de recurrencia.Fueron incluidos 348 pacientes en estadio II y 514 en estadio III. 660 pacientes (76,6%) se sometieron a quimioterapia adyuvante. El seguimiento medio de cada paciente después de la cirugía fué de 63.0 meses (rango, 3-160). El análisis multivariable mostró que la etapa yp (Cociente de riesgo para estadío yp II = 4.74 y estadío yp III = 8.83) y la resección en bloque (Cociente de riesgo = 1.76) fueron las únicas variables que predijeron significativamente la recurrencia de la enfermedad. Ni el estadío tumoral previo al tratamiento ni la recepción de quimioterapia adyuvante se asociaron significativamente con la sobrevida libre de recurrencia. Las pruebas de rango logarítmico no pudieron demostrar una mejoría significativa de la sobrevida libre de recurrencia después de recibir quimioterapia adyuvante en cualquier subgrupo de pacientes.Sesgo de selección, debido al estudio retrospectivo sin aleatorización de los pacientes o protocolo de tratamiento predefinido.En casos de cáncer de recto estadíos II-III tratados con radio-quimioterapia y cirugía, la adición de quimioterapia adyuvante no se asoció con una disminución de la sobrevida libre de recurrencia en toda la cohorte o en ningún subgrupo, mientras que la respuesta tumoral a la radio-quimioterapia está estrechamente asociada con la recurrencia de la enfermedad. Estos hallazgos tienen consecuencias importantes en la decisión del tratamiento y la vigilancia en pacientes con cáncer de recto. Los esfuerzos pre-quirúrgicos que maximizan la reducción del tamaño del tumor, como la terapia neoadyuvante total, pueden producir mejores resultados oncológicos que la quimioterapia adyuvante tradicional. Consulte Video Resumen en http://links.lww.com/DCR/B134.

Positive culture results and longer duration between onset and microincision vitrectomy have adverse effects on post-cataract surgery endophthalmitis outcome.

PURPOSE: To evaluate the efficacy of microincision vitrectomy surgery (MIVS) for the treatment of post-cataract surgery endophthalmitis, and to report the factors which influence the outcome. METHODS: This retrospective case series included eyes with post-cataract surgery endophthalmitis that had received MIVS between June 2014 and May 2017. The anatomical and functional results were analyzed. RESULTS: 24 eyes of 24 patients were included with mean age 72.0 ± 8.6 years old. Best-corrected visual acuity (BCVA) improved in 70.8% of patients with a significant mean logMAR BCVA change of -0.6 ± 0.9. Positive culture rate was 25%. In all study eyes, inflammation became silent after MIVS. In univariate analysis, patients with improved BCVA have shorter duration between cataract surgery and MIVS and less likely to have positive culture results. Using degree of BCVA improvement as a continuous variable, it showed that duration between cataract surgery and MIVS had significantly negative correlation with BCVA improvement. Patients with positive culture results had significantly lower BCVA improvement. Multiple regression models also confirmed the most important outcome-influencing factors. CONCLUSION: MIVS is an efficient management for post-cataract surgery endophthalmitis. BCVA is significantly improved after MIVS. No matter in univariate or multivariate analysis, positive culture results and longer duration between cataract surgery and MIVS have significant negative effects on the outcome of post-cataract surgery endophthalmitis. Multicenter collaboration should be conducted in order to formulate better management protocols of this vision-threatening complication of cataract surgery.

Outcome of primary rhegmatogenous retinal detachment using microincision vitrectomy and sutureless wide-angle viewing systems.

BACKGROUND: To evaluate the efficacy of micro-incision vitrectomy surgery (MIVS) using Lumera and Resight non-contact sutureless wide-angle viewing systems (WAVS) for primary rhegmatogenous retinal detachment (RRD), and to analyze the anatomical and visual outcomes. METHODS: The retrospective, non-comparative, interventional case series reported here was conducted from June 2014 through November 2016. Enrolled patients presented with primary RRD and received MIVS with/without cryopexy by one surgeon using the Lumera and Resight non-contact sutureless WAVS. All patients were followed-up for a minimum of 12 months. Variables collected included patient demographics, best-corrected visual acuity, and macular status. The number and position of retinal break(s), and the use of cryopexy, were also recorded. Outcome measures included operative time, single-operation anatomical success rate, final anatomical success rate, recurrent rate, postoperative best-corrected visual acuity, and surgical complications. The end points were operative time, anatomical outcome, and functional outcome. RESULTS: In total, 110 eyes from 110 patients (68 men and 42 women) were treated. Of these, 103 (93%) eyes were reattached after primary vitrectomy. One hundred ten eyes (100%) reached final anatomical success. The mean operative time was 50.55 min. Multivariate analyses were performed with best model selection principle based on general linear model by Akaike Information Criteria for detecting possible factors related to operation time, and with multivariate logistic regression analysis for revealing probable clinical parameters which might influence the anatomical outcome after first operation and final visual outcome. Intraoperative cryopexy and multiple breaks increased operative time significantly. More favorable BCVA was significantly correlated with shorter operation time and the preoperative macula-on status. Multivariate logistic regression on the group of patients who have received the cataract surgery revealed that the pre-operative BCVA is a significant factor which can predict the visual outcome after MIVS. CONCLUSIONS: The outcome of primary RRD repaired by MIVS using the Lumera and Resight sutureless WAVS was not inferior to any other published method. This instrument combination resulted in a relatively rapid and comfortable procedure without serious postoperative complications. Cryopexy and multiple breaks affected operative time significantly. Shorter operative times and preoperative macula-on status are associated with better final visual outcomes.

Aurora Kinase B, a novel regulator of TERF1 binding and telomeric integrity.

AURKB (Aurora Kinase B) is a serine/threonine kinase better known for its role at the mitotic kinetochore during chromosome segregation. Here, we demonstrate that AURKB localizes to the telomeres in mouse embryonic stem cells, where it interacts with the essential telomere protein TERF1. Loss of AURKB function affects TERF1 telomere binding and results in aberrant telomere structure. In vitro kinase experiments successfully identified Serine 404 on TERF1 as a putative AURKB target site. Importantly, in vivo overexpression of S404-TERF1 mutants results in fragile telomere formation. These findings demonstrate that AURKB is an important regulator of telomere structural integrity.

Loss of Response Gene to Complement 32 (RGC-32) in Diabetic Mouse Retina Is Involved in Retinopathy Development.

Diabetic retinopathy (DR) is a severe and recurrent microvascular complication in diabetes. The multifunctional response gene to complement 32 (RGC-32) is involved in the regulation of cell cycle, proliferation, and apoptosis. To investigate the role of RGC-32 in the development of DR, we used human retinal microvascular endothelial cells under high-glucose conditions and type 2 diabetes (T2D) mice (+Leprdb/ + Leprdb, db/db). The results showed that RGC-32 expression increased moderately in human retinal endothelial cells under hyperglycemic conditions. Histopathology and RGC-32 expression showed no significant changes between T2D and control mice retina at 16 and 24 weeks of age. However, RGC-32 expression was significantly decreased in T2D mouse retina compared to the control group at 32 weeks of age, which develop features of the early clinical stages of DR, namely reduced retinal thickness and increased ganglion cell death. Moreover, immunohistochemistry showed that RGC-32 was predominantly expressed in the photoreceptor inner segments of control mice, while the expression was dramatically lowered in the T2D retinas. Furthermore, we found that the level of anti-apoptotic protein Bcl-2 was decreased (approximately 2-fold) with a concomitant increase in cleaved caspase-3 (approximately 3-fold) in T2D retina compared to control. In summary, RGC-32 may lose its expression in T2D retina with features of DR, suggesting that it plays a critical role in DR pathogenesis.

Galectin-12 enhances inflammation by promoting M1 polarization of macrophages and reduces insulin sensitivity in adipocytes.

Galectin-12 is a member of an animal lectin family with affinity for ß-galactosides and containing consensus amino acid sequences. Here, we found that galectin-12 was expressed in macrophages and thus aimed to determine how galectin-12 affects inflammation and macrophage polarization and activation. The ablation of galectin-12 did not affect bone marrow cells to differentiate into macrophages, but reduced phagocytic activity against Escherichia coli and lowered the secretion of nitric oxide. The ablation of galectin-12 also resulted in the polarization of macrophages into the M2 direction, as indicated by increases in the levels of M2 markers, namely, resistin-like ß (FIZZ1) and chitinase 3-like 3 (Ym1), as well as a reduction in the expression levels of a number of M1 pro-inflammatory cytokines. We found that the diminished expression of pro-inflammatory cytokines in macrophages resulting from galectin-12 deletion was due to reduced activation of IKKα/ß, Akt and ERK, which in turn caused decreased activation of NF-κB and activator protein 1. The activation of STAT3 was much higher in Gal12(-/-) macrophages activated by lipopolysaccharide, which was correlated with higher levels of IL-10. Adipocytes showed higher insulin sensitivity when treated with Gal12(-/-) macrophage-conditioned media than those treated with Gal12(+/+) macrophages. We conclude galectin-12 negatively regulates macrophage polarization into the M2 population, resulting in enhanced inflammatory responses and also in turn causing decreased insulin sensitivity in adipocytes. This has implications in the treatment of a wide spectrum of metabolic disorders.

RELATIONSHIP BETWEEN UVEITIS, DIFFERENT TYPES OF VIRAL HEPATITIS, AND LIVER CIRRHOSIS: A 12-Year Nationwide Population-Based Cohort Study.

PURPOSE: This study investigates whether patients with viral hepatitis and cirrhosis are at risk of uveitis in the years following hepatitis. METHODS: We used data from Taiwan National Health Insurance system. The cases were patients newly diagnosed with viral hepatitis from 2000 to 2011. The end point of interest was a diagnosis of uveitis. A chi-square test was used for the difference of demographic characteristics between viral hepatitis and comparison. The risk of uveitis in hepatitis was stratified using Cox proportional hazard regression. RESULTS: We selected 17,389 patients with viral hepatitis and 34,778 matched comparison. The risk of uveitis in hepatitis cohort was 1.30-fold (95% confidence interval = 1.01-1.69). Patients with hepatitis B virus and hepatitis C virus coinfection had the highest risk (hazard ratio = 2.88; 95% confidence interval = 1.07-7.78), and followed by only hepatitis C virus infection (hazard ratio = 1.75; 95% confidence interval = 1.10-2.79). Patients with cirrhosis had a higher risk in the multivariable model but did not attach statistic difference. CONCLUSION: Patients with hepatitis B virus and hepatitis C virus coinfection had the highest risk of uveitis. In patients with hepatitis C virus and/or hepatitis B virus infection, the symptoms of uveitis should be alerted. Although these epidemiologic studies yielded informative results, the underlying mechanisms and the host's genetic factors remain to be investigated.

Effect of microRNA-155 on the interferon-gamma signaling pathway in biliary atresia.

MicroRNAs (miRNAs) are ~22-nucleotide long RNAs that negatively regulate gene expression and inflammatory responses in eukaryotes. The aim of this work was to evaluate the roles of miRNA (miR)-155 on the interferon-γ (IFN-γ)-induced response in biliary atresia (BA), which is the most common form of pediatric chronic liver disease and a leading indication for pediatric liver transplantation. The expression of miR-155 and the suppressor of cytokine signaling 1 (SOCS1) gene in human and mice liver tissues of BA and healthy controls was evaluated. IFN-γ-induced expression of miR-155, inflammatory cytokines and chemokines was determined in bile duct cells. A miR-155 inhibitor was used to determine the influence in the IFN-γ-induced signaling pathway by western blot analysis. A strong up-regulation of miR-155 expression was observed in BA histologic sections and mouse bile duct cells treated with IFN-γ. miR-155 down-regulated SOCS1 protein expression by targeting its mRNA. Up-regulation of miR-155 expression by IFN-γ in bile duct cells led to the activation of signal transducers and activators of transcription 1 (Stat1) and inflammatory cytokines through the Janus kinase (Jak)/Stat pathway, whereas targeted inhibition of miR-155 expression by anti-miRNA oligonucleotides significantly decreased the mRNA or protein expression levels of these inflammatory cytokines and Stat1. Overall, our results suggest that miR-155 regulates the IFN-γ signaling pathway by targeting SOCS1 expression and may be a potential target in BA therapy.