Purpose: To report the trends in etiology of patients with anterior uveitis (AU) in Singapore over 6 years.
Methods: A retrospective review of the clinical records of all new patients who presented ...with anterior uveitis to the uveitis subspecialty clinic from 2005 to 2010 at Tan Tock Seng Hospital, Singapore.
Results: There were 552 new cases of AU. This comprised 59.5% of a total of 928 new patients diagnosed with uveitis from 2005 to 2010. The mean age was 48.0 ± 17.2 years. There was a male predominance (62.5%), with a male:female ratio of 1.7:1. The majority were of Chinese ethnicity (69%), followed by Malays (13.2%). Most cases were unilateral (79.5%) and idiopathic (50.4%). Common etiological causes included Fuchs heterochromic iridocyclitis (FHI) (5.6%), ankylosing spondylitis (AS)-related AU (5.1%), herpes simplex virus (HSV) (4.7%), and herpes zoster virus (HZV) (4.5%). There were increasing trends in AS-related AU from 3.2% in 2008 to 6.5% in 2010, and psoriasis-associated AU from 1.7% in 2005 to 4.0% in 2008. There were decreasing trends in the incidence of FHI from 10.6% in 2006 to 4.7% in 2009. No change in incidence of viral etiologies was noted, but cytomegalovirus-related immune-recovery uveitis (IRU) comprised 7.4%. IRU showed an increasing trend from 1.7% in 2005 to 11.9% in 2007, then decreased to 3.3% in 2010. Using the Pearson chi-square test, there was no statistically significant association between ethnicities (Chinese, Malay, Indian) comparing infectious and noninfectious cases (p = 0.788), idiopathic and nonidiopathic cases (p = 0.170), or between the various etiologies of uveitis (p = 0.168).
Conclusions: AU was the predominant form of uveitis seen at our centers. Infectious etiologies (18.5%) are the most common among nonidiopathic cases, with herpes viruses (9.2%) being most prevalent. Despite increased use of polymerase chain reaction (PCR) in the detection of microbial and viral DNA, there was no overall increase in detection of infectious causes for uveitis. The changes in CMV-related immune recovery uveitis from 2005 to 2010 could reflect a change in HIV management in Singapore.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Purpose: The study aims to analyze the trends of posterior uveitis and panuveitis patients seen by a tertiary eye center in Singapore between 2004 and 2012.
Methods: We conducted a retrospective ...analysis of 363 consecutive new cases of posterior uveitis and panuveitis. The cases were segregated into idiopathic, infectious, or noninfectious.
Results: We found statistically significant differences between etiologies and ethnicity (p = 0.014). We noticed a statistically significant downward trend (Spearman's rho (ρ) = −0.812, p = 0.008) for dengue uveitis, and an upward trend for the idiopathic category (Spearman's rho (ρ) = 0.753, p = 0.019).
Conclusions: We observed differences between etiologies and ethnicity, pointing toward potential susceptibility variations. There was an upward trend of idiopathic causes, possibly due to better control of systemic and infectious etiologies. The dengue uveitis incidence correlates well with our national statistics. The downward trend of dengue uveitis could be due to the introduction of Singapore's dengue surveillance in 2005, emphasizing the importance of controlling the disease.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
► Electron microscopy shows variety of horizontal cell gap junctions in the rabbit retina. ► Heterotypic gap junctions or hemichannels contribute to A-type horizontal cell network. ► Invaginated ...forms of Cx57 gap junctions exist in B-type horizontal axon terminal network.
In the rabbit retina, there are two types of horizontal cell (HC). The axonless A-type HCs form a coupled network via connexin 50 (Cx50) gap junctions in the outer plexiform layer (OPL). The axon-bearing B-type HCs form two independently coupled networks; the dendritic network via gap junctions consisted of unknown Cx and the axon terminal network via Cx57. The present study was conducted to examine the localization and morphological features of Cx50 and Cx57 gap junctions in rabbit HCs at cellular and subcellular levels. The results showed that each gap junction composed of Cx50 or Cx57 showed distinct features. The larger Cx50 gap junctions were located more proximally than the smaller Cx50 gap junctions. Both Cx50 plaques formed symmetrical homotypic gap junctions, but some small ones had an asymmetrical appearance, suggesting the presence of heterotypic gap junctions or hemichannels. In contrast, Cx57 gap junctions were found in the more distal part of the OPL but never on the axon terminal endings entering the rod spherules, and they were exclusively homotypic. Interestingly, about half of the Cx57 gap junctions appeared to be invaginated. These distinct features of Cx50 and Cx57 gap junctions show the variety of HC gap junctions and may provide insights into the function of different types of HCs.
Abstract Background Retinal microvascular changes have been shown to reflect systemic inflammation in vivo. We aimed to investigate whether retinal microvascular changes are correlated with, and ...predictive of, CD4 and CD8 cell count changes in patients with HIV/AIDS being treated with highly active antiretroviral therapy (HAART). Methods We did a longitudinal hospital-based study. 50 HIV/AIDS patients being treated with HAART were sequentially recruited from March, 2011, to September, 2011, from the Communicable Disease Center, Singapore, and then followed up at a 9 month visit. Demographic and socioeconomic information and history of HIV infection were collected at baseline. Blood pressure and anthropometric measurements, blood tests for immune status assessment (CD4 and CD8 cell counts), and retinal photography were done at baseline and at 9 months. Retinal vascular parameters (calibre, tortuosity, branching angle, and fractal dimension) were assessed by a semiautomated computer-based programme (Singapore I vessel assessment SIVA, version 3.0, Singapore Eye Research Institute, Singapore). Changes of retinal vascular parameters and CD4 and CD8 cell counts were defined as the difference between baseline and 9 months. Findings The mean age of the 50 participants was 46·36 years (SD 8·67). Participants were ethnically Chinese, Malay, and Indian; most (82%) were Chinese and most male (96%). 35 of 50 patients had CD4 counts of fewer than 200 cells per μL at baseline. Years of HAART ranged from 0 to 11 years. There were significant increments in CD4 cell counts (153·42 vs 227·74 cells per μL; p<0·0001) and CD8 cell counts (819·90 vs 1014·1 cells per μL; p=0·012) between baseline and the 9 month visit, respectively. There were no temporal changes in retinal vascular parameters during this period. After adjustment for age, sex, ethnicity, and years of HAART, each 10 μm reduction in retinal venular calibre at baseline was associated with a 191·08 cells per μL increase in CD8 count (SE 63·54; p=0·004), but not in CD4 cell count, during the 9 month period. Changes of retinal arteriolar calibre and other retinal vascular geometric parameters were not associated with CD4 or CD8 cell count changes. Interpretation Retinal venular narrowing was associated with an increase in CD8 cell counts over time. Our findings suggest that improved retinal venular health was predictive of immune restoration in HIV/AIDS patients who had been on HAART for at least 9 months. Longer follow-up is warranted to monitor the retinal vascular calibre changes in response to HAART treatment. Funding Singapore Medical Research Counsel SIG/11016.
Accurate and reliable criteria to rapidly estimate the probability of infection with the novel coronavirus-2 that causes the severe acute respiratory syndrome (SARS-CoV-2) and associated disease ...(COVID-19) remain an urgent unmet need, especially in emergency care. The objective was to derive and validate a clinical prediction score for SARS-CoV-2 infection that uses simple criteria widely available at the point of care.
Data came from the registry data from the national REgistry of suspected COVID-19 in EmeRgency care (RECOVER network) comprising 116 hospitals from 25 states in the US. Clinical variables and 30-day outcomes were abstracted from medical records of 19,850 emergency department (ED) patients tested for SARS-CoV-2. The criterion standard for diagnosis of SARS-CoV-2 required a positive molecular test from a swabbed sample or positive antibody testing within 30 days. The prediction score was derived from a 50% random sample (n = 9,925) using unadjusted analysis of 107 candidate variables as a screening step, followed by stepwise forward logistic regression on 72 variables.
Multivariable regression yielded a 13-variable score, which was simplified to a 13-point score: +1 point each for age>50 years, measured temperature>37.5°C, oxygen saturation<95%, Black race, Hispanic or Latino ethnicity, household contact with known or suspected COVID-19, patient reported history of dry cough, anosmia/dysgeusia, myalgias or fever; and -1 point each for White race, no direct contact with infected person, or smoking. In the validation sample (n = 9,975), the probability from logistic regression score produced an area under the receiver operating characteristic curve of 0.80 (95% CI: 0.79-0.81), and this level of accuracy was retained across patients enrolled from the early spring to summer of 2020. In the simplified score, a score of zero produced a sensitivity of 95.6% (94.8-96.3%), specificity of 20.0% (19.0-21.0%), negative likelihood ratio of 0.22 (0.19-0.26). Increasing points on the simplified score predicted higher probability of infection (e.g., >75% probability with +5 or more points).
Criteria that are available at the point of care can accurately predict the probability of SARS-CoV-2 infection. These criteria could assist with decisions about isolation and testing at high throughput checkpoints.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Autoimmune thyroid diseases (AITD) are common, affecting 2-5% of the general population. Individuals with positive thyroid peroxidase antibodies (TPOAbs) have an increased risk of autoimmune ...hypothyroidism (Hashimoto's thyroiditis), as well as autoimmune hyperthyroidism (Graves' disease). As the possible causative genes of TPOAbs and AITD remain largely unknown, we performed GWAS meta-analyses in 18,297 individuals for TPOAb-positivity (1769 TPOAb-positives and 16,528 TPOAb-negatives) and in 12,353 individuals for TPOAb serum levels, with replication in 8,990 individuals. Significant associations (P<5×10(-8)) were detected at TPO-rs11675434, ATXN2-rs653178, and BACH2-rs10944479 for TPOAb-positivity, and at TPO-rs11675434, MAGI3-rs1230666, and KALRN-rs2010099 for TPOAb levels. Individual and combined effects (genetic risk scores) of these variants on (subclinical) hypo- and hyperthyroidism, goiter and thyroid cancer were studied. Individuals with a high genetic risk score had, besides an increased risk of TPOAb-positivity (OR: 2.18, 95% CI 1.68-2.81, P = 8.1×10(-8)), a higher risk of increased thyroid-stimulating hormone levels (OR: 1.51, 95% CI 1.26-1.82, P = 2.9×10(-6)), as well as a decreased risk of goiter (OR: 0.77, 95% CI 0.66-0.89, P = 6.5×10(-4)). The MAGI3 and BACH2 variants were associated with an increased risk of hyperthyroidism, which was replicated in an independent cohort of patients with Graves' disease (OR: 1.37, 95% CI 1.22-1.54, P = 1.2×10(-7) and OR: 1.25, 95% CI 1.12-1.39, P = 6.2×10(-5)). The MAGI3 variant was also associated with an increased risk of hypothyroidism (OR: 1.57, 95% CI 1.18-2.10, P = 1.9×10(-3)). This first GWAS meta-analysis for TPOAbs identified five newly associated loci, three of which were also associated with clinical thyroid disease. With these markers we identified a large subgroup in the general population with a substantially increased risk of TPOAbs. The results provide insight into why individuals with thyroid autoimmunity do or do not eventually develop thyroid disease, and these markers may therefore predict which TPOAb-positives are particularly at risk of developing clinical thyroid dysfunction.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Among a comprehensive range of frontline emergency department health care personnel, we assessed symptoms of anxiety and burnout, specific coronavirus disease 2019 (COVID-19) work-related stressors, ...and risk for post-traumatic stress disorder (PTSD). We also determined whether COVID-19 serologic testing of HCP decreased their self-reported anxiety.
In a prospective cohort study from May 13, 2020, to July 8, 2020, we used electronic surveys to capture participant self-reported symptoms before and after serologic testing for anti-SARS-CoV-2 immunoglobulin G antibodies. Participants were physicians, nurses, advanced practice providers, and nonclinical ED personnel at 20 geographically diverse United States EDs. We evaluated these domains: 1) the effects of the COVID-19 pandemic on overall stress and anxiety; 2) COVID-19-related work stressors; 3) burnout; and 4) PTSD risk (measured using the Primary Care-PTSD Screen for DSM-5, a 5-item screening instrument in which a score of ≥3 signifies high risk for PTSD). We also assessed perceptions of whether results of COVID-19 antibody testing decreased participants’ self-reported anxiety.
Of 1,606 participants, 100% and 88% responded to the baseline and follow-up surveys, respectively. At baseline, approximately half (46%) reported symptoms of emotional exhaustion and burnout from their work, and 308 (19.2%, 95% confidence interval CI 17.3% to 21.1%) respondents screened positive for increased PTSD risk. Female respondents were more likely than males to screen positive (odds ratio OR 2.03, 95% CI 1.49 to 2.78). Common concerns included exposing their family and the health of coworkers diagnosed with COVID-19. After receiving antibody test results, 54% (95% CI 51.8 to 56.7) somewhat agreed, agreed, or strongly agreed that knowledge of their immune status had decreased their anxiety. A positive serology result indicating prior SARS-CoV-2 infection was associated with a higher likelihood of reporting decreased anxiety (2.83, 95% CI 1.37 to 5.83).
Symptoms of anxiety and burnout were prevalent across the spectrum of ED staff during the COVID-19 pandemic. One-fifth of ED personnel appeared to be at risk for PTSD. Increased provision of serologic testing may help to mitigate anxiety.
Background/Aims: Hepatoblastoma (HB) and hepatocellular carcinoma (HCC) are the two most common primary malignant liver tumours in children. Hepatic progenitor cells have been described and can be ...stained with K19, EpCAM and CD117. We investigated the morphology and staining patterns of primary liver tumours in Asian children.
Methods: Four pathologists studied slides from 39 paediatric patients from Vietnam and Korea aged 8 months to 16 years. We performed immunohistochemical stains for K19, EpCAM and CD117, and polymerase chain reaction for tissue hepatitis B virus (HBV) DNA and hepatitis C virus (HCV) RNA.
Results: There was agreement on the diagnosis of 24 cases of HCC and 10 cases of HB (one recurrent case). The diagnosis was split for six cases (HCC/HB). All 20 cases of HCC tested were HBV DNA+ and HCV RNA−. All nine cases of HB tested were HBV DNA−, while one was HCV RNA+. Of four HCC/HB cases tested, three were HBV DNA+ and all were HCV RNA−. By immunohistochemistry, 8/24 (33%) cases of HCC were K19+ and 18/24 (75%) were EpCAM+, 5/10 (50%) cases of HB were K19+ and 7/10 (70%) were EpCAM+ and 3/6 (50%) cases of HCC/HB were K19+ and 5/6 (83%) were EpCAM+. CD117 was negative in all 38 cases tested. Paediatric HCC has a morphology different from adult HCC, sometimes resembling HB, and a larger proportion of paediatric tumours have progenitor cell features.
Conclusions: HB and HCC in children may represent malignant transformation at an early stage in the cellular lineage and often arise from hepatic progenitor cells.
Screening for cytomegalovirus retinitis (CMVR) is important in patients with acquired immune deficiency syndrome and low CD4(+) counts. However, many human immunodeficiency virus (HIV) patients lack ...access to specialist ophthalmological care. Telemedicine screening is a cost-effective method for screening these patients. We aimed to report the use of composite nine-field digital fundus photography (DFP) images for CMVR screening. We report its sensitivity and specificity in detecting CMVR and the level of agreement with gold-standard binocular indirect ophthalmoscopy.
An audit was performed on our national CMVR screening program that screened all HIV patients referred to the Ophthalmology Department at Tan Tock Seng Hospital, Singapore. All patients underwent retinal screening with DFP. Images were categorized as CMVR-positive, CMVR-negative, suspicious, or unreadable by blinded retinal specialists. Patients subsequently underwent dilated gold-standard indirect ophthalmoscopy by a different retinal specialist. Diagnoses were categorized as CMVR-positive, CMVR-negative, or unreadable. Sensitivity and specificity of retinal findings on DFP and kappa values for level of agreement between the two screening methods were calculated.
Three hundred seventy screenings on 188 patients were performed. Twenty-three eyes diagnosed with CMVR on indirect ophthalmoscopy were also identified on DFP (100% sensitivity). A 99.9% specificity was achieved. The fundus photograph of one eye without CMVR was read as CMVR-positive because of an artifact, accounting for a false-positive. Kappa values ranged from 0.739 to 0.987.
DFP is a sensitive and specific method of screening HIV patients for CMVR and has a high level of agreement with indirect ophthalmoscopy.
Purpose: Identification of optimal enrollment criteria for a CMVR screening program suitable for a resource-limited environment.
Methods: A prospective audit was performed on newly diagnosed HIV ...patients referred for CMVR screening with any of the following four criteria: (1) visual symptoms, (2) low CD4
+
counts (<50 cells/µL), (3) AIDS-defining illnesses (ADI), and/or (4) opportunistic infections (OI). Odds ratios for each of the demographic factors and enrollment criteria were calculated. Sensitivities, specificities, and workload reduction for the various combinations were determined.
Results: A total of 348 screening visits for 176 HIV patients were performed. While individually only ADI was statistically significant for increased CMVR risk, the combination of CD4
+
counts <50 cells/μL with either ADI or visual symptoms or all 3 criteria were also statistically significant. Two enrollment criteria, ADI and ADI with CD4
+
<50 cells/μL, demonstrated good sensitivities, specificities, and workload reduction.
Conclusion: We propose ADI and possibly CD4
+
counts <50 cells/μL as enrollment criteria for CMVR screening.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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