Macular dual retinitis with Herpes simplex and Cytomegalovirus following periocular corticosteroid in a patient of Pemphigus Vulgaris

Background Cytomegalovirus (CMV) retinitis may occur in non-HIV individuals following systemic immunosuppressive treatment or periocular corticosteroid administration. However, simultaneous multiple viral retinitis is rare in HIV-negative individuals. We report a case of dual viral retinitis in a non-HIV female on systemic immunosuppressive for pemphigus vulgaris who was administered a periocular corticosteroid injection. Method A 32-year-old female on double immunosuppressive therapy (prednisolone and cyclophosphamide) for pemphigus vulgaris, presented with gradual painless diminution of vision in the right eye for one month. She was initially diagnosed to have possible autoimmune neuroretinitis by the referring ophthalmologist and received a single injection of posterior subtenon triamcinolone acetonide for the same. Her vision however deteriorated further and she received an intravitreal ganciclovir injection with a revised diagnosis of CMV retinitis. Due to suboptimal response she was referred to us. Aqueous Polymerase chain reaction (PCR) revealed dual positivity for CMV and Herpes simplex virus. She was successfully managed with intravitreal ganciclovir injections, systemic acyclovir and tapering of systemic immunosuppressive drugs. Result The retinitis lesions resolved gradually leaving behind a pale optic disc and foveal atrophy at 12 weeks follow-up. Conclusion Infective etiology must be ruled out in immunosuppressed patients before considering periocular corticosteroids. Dual viral involvement, although rare, may cause fulminant retinitis in predisposed individuals. High index of suspicion and PCR from ocular fluids should be performed at the earliest in patients with atypical or poorly responding retinitis lesions.

Serum Cartilage Oligomeric Matrix Protein and Golgi Protein-73: New Diagnostic and Predictive Tools for Liver Fibrosis and Hepatocellular Cancer?

The cartilage oligomeric matrix protein (COMP) and Golgi-protein-73 (GP73) have been proposed as markers of liver fibrosis and hepatocellular carcinoma (HCC). Our aim was to assess the performance of the combination of these markers in diagnosing cirrhosis and predicting HCC development. Sera from 288 consecutive patients with chronic liver diseases were investigated by using COMP and GP73-ELISAs. Dual positivity for COMP (>15 U/L) and GP73 (>20 units) was observed in 24 (8.3%) patients, while 30 (10.4%) were GP73(+)/COMP(−), 37/288 (12.8%) GP73(−)/COMP(+), and 197 (68.5%) GP73(−)/COMP(−). Positivity for both markers was associated with cirrhosis [23/24 (95.8%) for GP73(+)/COMP(+) vs. 22/30 (73.3%) for GP73(+)/COMP(−) vs. 25/37 (67.6%) for GP73(−)/COMP(+) vs. 46/197 (23.4%) for GP73(−)/COMP(−); P < 0.001]. The combination of GP73, COMP, the aspartate aminotransferase/platelets ratio index, and the Fibrosis-4 score had even higher diagnostic accuracy to detect the presence of cirrhosis [AUC (95% CI): 0.916 (0.878–0.946)] or significant liver fibrosis (METAVIR ≥ F2) [AUC (95% CI): 0.832 (0.768–0.883)] than each marker alone. Kaplan-Meier analysis showed that positivity for both GP73 and COMP was associated with higher rates of HCC development (P < 0.001) and liver-related deaths (P < 0.001) during follow-up. In conclusion, the combination of GP73 and COMP seems efficient to detect cirrhosis and predict worse outcomes and the development of HCC in patients with chronic liver diseases.

Herpes Simplex Virus Types 1 and 2 Immunoglobulin G Positivity among Adultsand Associated Factors in Lagos and Osun, Nigeria

Background: Herpes simplex viruses (HSVs) are important, not only because they can cause blindness, encephalitis, genital herpes and neonatal herpes with high morbidity, but because active or reactivated herpes breaks vaginal mucosa exposing CD4+ CCR5+ T cells in sub-mucosa to HIV-1 during unprotected sexual intercourse. This cross-sectional study was therefore designed to assess the level of past exposure of apparently healthy adults to HSVs in selected hospitals in Lagos and Osun States, Nigeria Methodology: This hospital-based cross-sectional study was designed to estimate proportions of consecutively selected adults in Lagos and Osun States, Nigeria, having HSV-1 and -2 IgG antibodies. A total of 270 sera were tested for HSV-1 and 2 IgG using ELISA kits. The results were analyzed with SPSS 16.0. Results: Participants were aged 18-80 years (average: 33.9 years). Age 31-50 years, male gender, and ≤ secondary education were associated (p values: 0.001 – 0.05) with self-reports of STD, lip, and genital blisters. Overall, HSV-1 and -2 IgG positivity rates were respectively 98.9% and 56.3%. Groupspecific prevalence rates for HSV-1 IgG were about 100.0%; predictors of HSV-2 IgG were age 31-50 yrs (p = 0.05, odds ratio [OR]: 2.3); histories of having genital blister (p = 0.001 [OR: 16.4]) and STD (p = 0.001 [OR: 20.4]). With only one dual negativity, the dual positivity rate was slightly higher among males (56.3%) than females (55.1%); highest and lowest respectively among 31-50 yr old (62.8%) and 51-80 yr old (38.7%). Conclusion: The near 100.0% and > 50.0% seroprevalence rates of HSV-1 and -2 IgG, respectively, indicated a high infection burden in Lagos and Osun. Age, histories of genital blister and STD significantly predicted HSV-2 IgG positivity.

Immunohistochemistry analyses of LAG-3 expression across different tumor types and co-expression with PD-1.

e15086 Background: Concomitant blockade of LAG-3 and PD-1 has been shown to restore T-cell activation and enhance anti-tumor immunity in preclinical models. Clinical trials evaluating anti-LAG-3/anti-PD-1 mAb combinations or bispecific molecules are ongoing. Establishing the tumor expression profile of LAG-3 and its relationship to PD-1 will aid in patient selection and interpretation of clinical responses to combined inhibition. Methods: LAG-3 Ab clone EPR4392(2) (Abcam) and PD-1 Ab clone NAT105 (Ventana) were developed as individual or combined dual IHC assays on the Ventana Discovery Ultra platform. LAG-3 IHC was performed on panels of commercially available tissues: 33 normal human tissues (2 each) and various tumor types including anal (n = 39), cervical cancer (40), cholangiocarcinoma (11), DLBCL (40), gastric cancer (34), HCC (18), SCCHN (39), HER2-positive breast cancer (48), mesothelioma (40), NSCLC (39), ovarian cancer (47), SCLC (48), and TNBC (40). LAG-3 IHC expression was confirmed by in situ hybridization (ACD RNAScope). Positivity was defined as at least one LAG-3+ve or PD-1+ve tumor-infiltrating lymphocyte (TIL) per 40x magnification hot spot field (HSF); high LAG-3 expression was defined as > 15 LAG-3+ve TILs per HSF. Results: LAG-3-specific staining in normal tissues was limited to mononuclear cells in lymphoid organs and GALT, with no staining observed in normal parenchyma. Across various tumor types, the frequency of LAG-3+ve tumor samples and high expression, respectively (%, %), were as follows: cervical (100; 57.5), anal (97.4; 30.8), DLBCL (95; 75), NSCLC (92.3; 25.6), TNBC (90; 22.5), gastric (88.2; 44.1), SCCHN (87.2; 56.4), HER2-positive breast (85.4; 39.6), HCC (83.3; 22.2), cholangiocarcinoma (81.8; 9.1), ovarian (70.2; 21.3), SCLC (50; 14.6) and mesothelioma (25; 10). In addition to TILs, LAG-3 expression was observed on tumor cells in DLBCL and a fraction of anal, breast, cervical, gastric, hepatocellular, SCCHN, NSCLC and ovarian cancers. LAG-3/PD-1 double IHC staining revealed dual positivity across 92.3% of NSCLC samples, with approximately 60% demonstrating TIL co-expression of PD-1 and LAG-3. Conclusions: LAG-3 expression was detected on TILs across a broad range of solid tumors and DLBCL, with varying level of intensity or association with PD-1 expression. Correlative assessments of LAG-3/PD-1 expression with clinical responses to MGD013, an investigational bispecific DART(R) molecule targeting LAG-3/PD-1 (NCT03219268), will be undertaken.

Immunocytochemical expression of Ki-67/p16 in normal, atypical, and neoplastic cells in urine cytology using BD SurePath™ as preparation method

Objective: The objective of this study was to investigate the expression of Ki-67/p16 in urothelial cells in cytological material. Materials and Methods: There were 142 urines including normal controls, anonymous rest urine, controls after treatment for urothelial carcinoma (UC) and newly diagnosed UC. Immunocytochemistry for ki-67/p16 dual staining kit was performed on all specimens. Results: Eight high-grade UC and six anonymous specimens showed dual positivity. None of the low-grade UC or the control specimens after treated UC showed dual staining. Fifteen of 84 (17.8%) symptomatic cases were negative for both markers, and 59/84 (70.2%) showed positivity for both but not dual staining. Twenty-seven of 84 cases were positive for either Ki-67 (n = 22) or p16 (n = 5). Normal controls and benign specimens were negative for p16. Conclusions: Co-expression of p16/Ki-67 in the same cells was found in 16.6% of the cases. All were high grade, and co-expression seems to have limited practical impact as an additional marker in urine cytology. Any positivity for p16 alone strongly indicates malignancy. Negative p16 accompanied by a positive Ki-67 rate at 5% or more could be considered as an additional marker for further clinical follow-up. Both markers, co-expressed and separate, can give additional information in follow-up patients after treatment for UC.

Anti-Gbm Disease in Children: Outcomes and Association with Systemic Vasculitis

Anti-Glomerular Basement Membrane (anti-GBM) disease is a rare autoimmune disorder affecting the glomerular and alveolar basement membranes. Diagnosis is based on the detection of anti-GBM autoantibodies, along with renal or lung biopsy. Some patients are both anti-GBM and ANCA positive, reflecting an association with systemic vasculitis that has been reported only in some adult cases. Dual positivity of anti-GBM and ANCA is associated with poorer prognosis and higher relapse rates therefore more aggressive and longer treatment is essential. In this case, series we report four cases of children diagnosed with anti-GBM disease that we also screened for signs of systemic vasculitis.