Group Antigens Research Articles

New Possibilities of Antibiotic Therapy for Blepharoconjunctivitis in Children

The problem of drug therapy for bacterial eye infections in children has remained relevant for many years. The greatest interest of ophthalmologists in recent years is associated with the use of fluoroquinolones in the treatment of inflammatory eye diseases of the bacterial etiology. At the same time, new ophthalmic dosage forms of fluoroquinolones that have appeared in recent years naturally require additional research on their effectiveness.Objective: to study the clinical efficacy of the antibacterial drug Oftocypro (0.3 % cyprofloxacin in ophthalmic ointment) in the treatment of chronic blepharoconjunctivitis in children.Materials. The study involved 38 children aged 3 to 18 years (mean age 10.3 ± 2.7 years) with clinical manifestations of blepharoconjunctivitis. All patients were divided into 2 groups of equal size: 18 children (36 eyes) — with bacterial blepharoconjunctivitis and 20 (40) — with chlamydial blepharoconjunctivitis. The diagnosis was verified based on the clinical picture of blepharoconjunctivitis and laboratory data: detection of pathogenic microflora in the conjunctival cavity of patients of the first group and chlamydia antigen — in epithelial cells in scraping material from the conjunctiva by immunohistochemical analysis.Results. The analysis of the data obtained during the examination and treatment of children with blepharoconjunctivitis of bacterial etiology (group I), a reliable dynamics of controlled clinical and laboratory parameters was established. There was a significant positive dynamics of all controlled parameters of the clinical course of chronic bacterial blepharoconjunctivitis against the background of the drug Oftocipro ophthalmic ointment 0.3 % use. All children with chronic chlamydial blepharoconjunctivitis with the background of treatment with Oftocypro, ophthalmic ointment 0.3 %, showed a steady tendency towards relief of the estimated clinical signs of the disease. According to the results of laboratory studies, it was found that on the 28th day of treatment with Oftocypro chlamydia in the cells of the epithelium of the conjunctiva was re-detected in 4 out of 20 patients (20 %).Conclusion. The high efficacy of the drug Oftocypro ophthalmic ointment 0.3 %, in combination with the absence of pronounced side effects, makes it possible to recommend this drug for wider practical use.

Correlation of serum interleukin 17 and macrophage migration inhibitory factor levels with clinical response to intralesional Candida antigen and their potential use as predictors of clinical outcome in patients with multiple common warts.

Candida antigen injection is one of the most widely used intralesional immunotherapy in the treatment of warts. It acts through the induction of systemic immune response. The pattern of cytokines production may play an integral role in its mechanism of action. To investigate the possible relation between serum levels of IL17 and MIF, and the clinical response to intralesional Candida antigen in multiple common warts. A total of 90 patients with multiple common warts were divided into 2groups. Sixty patients received intralesional Candida antigen injection into the largest wart, controlled against thirty patients who had intralesional saline, as placebo. The injection was done at a 2-week interval for 5 doses. Blood samples were obtained from both groups, and serum levels of IL17A and MIF were estimated at baseline and 2weeks after the last session using ELISA kits. Complete clearance of warts was statistically higher in the Candida antigen group (40% of the patients) compared to the saline group (p<0.05). The serum levels of IL17had significantly declined from baseline, while the level of MIF had risen after intralesional Candida antigen injection, but not in the saline group. At a cutoff level of 316pg/ml, IL17had a sensitivity of 83.3% to predict therapeutic response. IL17A and MIF may have possible roles in the mechanism of action of Candida antigen in the treatment of common warts. At a certain level, serum IL17A may be a potential predictor of response to treatment.

The HLA-G Immune Checkpoint Plays a Pivotal Role in the Regulation of Immune Response in Autoimmune Diseases.

The human G-leukocyte antigen (HLA-G) molecule is a non-classical major histocompatibility complex (MHC) class I molecule. The pertinence of HLA-G has been investigated in numerous studies which have sought to elucidate the relevance of HLA-G in pathologic conditions, such as autoimmune diseases, cancers, and hematologic malignancies. One of the main goals of the current research on HLA-G is to use this molecule in clinical practice, either in diagnostics or as a therapeutic target. Since HLA-G antigens are currently considered as immunomodulatory molecules that are involved in reducing inflammatory and immune responses, in this review, we decided to focus on this group of antigens as potential determinants of progression in autoimmune diseases. This article highlights what we consider as recent pivotal findings on the immunomodulatory function of HLA-G, not only to establish the role of HLA-G in the human body, but also to explain how these proteins mediate the immune response.

REVIEW OF DNA VACCINE APPROACHES AGAINST THE PARASITE TOXOPLASMA GONDII.

Toxoplasma gondii is an apicomplexan parasite that affects both humans and livestock. Transmitted to humans through ingestion, it is the second-leading cause of foodborne illness-related death. Currently, there exists no approved vaccine for humans or most livestock against the parasite. DNA vaccines, a type of subunit vaccine which uses segments of the pathogen's DNA to generate immunity, have shown varying degrees of experimental efficacy against infection caused by the parasite. This review compiles DNA vaccine efforts against Toxoplasma gondii, segmenting the analysis by parasite antigen, as well as a review of concomitant adjuvant usage. No single antigenic group was consistently more effective within in vivo trials relative to others.

Conserved Antigenic Structure of Contemporary Wild Poliovirus Type 1 Strains Endemic in Pakistan.

Elimination of poliovirus in Pakistan and Afghanistan is challenged by notions against the role of oral poliovirus vaccine (OPV) in eradicating contemporary wild poliovirus (WPV) strains. A total of 1055 WPV type 1 (WPV1) strains isolated between 2013 and 2018 were categorized into 68 antigenic groups and tested for neutralization by OPV-derived antibodies. Molecular docking was conducted to determine neutralization efficiency of antibodies against WPV. The clinical significance of WPV1 variants was assessed to ascertain their role in patient outcomes. We found that 88% of WPV1 strains isolated from paralytic children belonged to a single antigenic lineage identical to the WPV1 strain detected in 1993. WPV1 antigenic variants were effectively neutralized by OPV-derived antibodies, with geometric mean titers comparable to the neutralization titers found for 3 strains in OPV (OPV1-3, 7.96-9.149 [95% confidence interval, 6.864-10.171]; WPV1 strains, 7.542-8.786 [6.493-9.869]). Docking examination underscored a strong antigen-antibody interaction despite variations within the viral protein 1 epitopes. There was no significant association (P =.78) with clinical prognosis among patients infected with antigenically diverse WPV1 strains and patient outcomes, including death. Our findings substantiate the robustness of OPV for neutralizing the contemporary WPV1 strains endemic in Pakistan and Afghanistan. Vaccination coverage must be augmented to achieve early eradication.

Hypersensitivity pneumonitis: Airway-centered pulmonary fibrosis on chest CT.

To evaluate the chest CT appearance of patients with a clinicopathologic diagnosis of hypersensitivity pneumonia. IRB approval was obtained for a retrospective review of patients with a preoperative CT scan, a surgical pathology report from a transbronchial biopsy or wedge resection consistent with hypersensitivity pneumonitis, and a pulmonary consultation, which also supported the diagnosis. The pathology report was evaluated for granulomas, airway-centered fibrosis, microscopic honeycombing, and fibroblast foci. The medical records were reviewed for any known antigen exposure. Patients were separated into two groups; those with and without a known antigen exposure. The CT scans were assessed for distribution of fibrosis: upper lobe or lower lobe predominance, airway-centered versus peripheral distribution, three-density pattern, and honeycombing. 264 pathology reports included the term chronic hypersensitivity pneumonitis (CHP). Thirty-eight of the patients had a pulmonologist who gave the patient a working diagnosis of CHP. The average age of these patients was 64 years, and 21/38 were women. Seventeen of the 38 patients had at least one antigen exposure described in the medical records. All the patients had fibrosis along the airways on chest CT. Both known antigen exposure and no known antigen patients had upper and lower lung-predominant fibrosis. There were more patients with hiatal hernias in the unknown antigen group. Honeycombing was an uncommon finding. Airway-centered fibrosis was present on chest CT in all 38 patients with CHP (100%), with or without known antigen exposure.

Blood groups and oncological diseases

Introduction. The study of the possible impact of the blood group system ABO and other antigenic systems of red blood cells for cancer patients is currently directed at a number of distinct paths, including the study of changes in the expression of a group of antigens in tumors; the appearance of new antigens on tumor cells; the risk of developing tumors depending on the blood group; the possible infl uence of blood group on the prognosis of the disease, etc.Aim — to examine the current state of the problem of the relationship between blood groups and cancer.Main findings. There is evidence that cancer is less common in people with blood type O than in people with other blood groups of the ABO system. According to other data, this dependence is noted only for some types of cancer. In general, the results of work on this topic can be assessed as insuffi cient and sometimes contradictory.

Assessment of T-cell immunity to SARS-CoV-2 in COVID-19 convalescents and vaccinated subjects, using TigraTest&lt;sup&gt;®&lt;/sup&gt; SARS-CoV-2 ELISPOT kit

With the onset of the COVID-19 pandemic, a number of molecular-based tests have been developed to diagnose SARS-CoV-2 infection. However, numerous available serological tests lack sufficient sensitivity or specificity. They do not detect specific antibodies in a significant proportion of patients with PCR-confirmed COVID-19. There is evidence that some convalescents have a relatively short-lived humoral immunity. In contrast, a number of publications have shown that T-cell response to human coronaviruses, including SARS-CoV-1, MERS, and SARS-CoV-2, can be strong and long-term. Assessment of T-cell immunity to SARS-CoV-2 is important not only for stratification of risks and identification of potentially protected populations with immunity acquired as a result of previous infection, but also for determining immunogenicity and potential efficacy of vaccines under development. The existing methods of quantitative or semi-quantitative assessment of specific T-cell response are mainly used in scientific research and are not standardised. The aim of the study was to develop and verify experimentally a test kit to be used in a standardised procedure for in vitro determination of T-cells specific to SARS-CoV-2 antigens, in human peripheral blood. Materials and methods: the TigraTest® SARS-CoV-2 kit developed by GENERIUM, which determines the number of T-cells secreting interferon gamma in vitro, was tested in the study. Samples of venous blood of volunteers from three different groups were analysed in the study: presumably healthy volunteers; COVID-19 convalescents; individuals vaccinated against SARS-CoV-2. Results: the authors developed the TigraTest® SARS-CoV-2 kit for in vitro determination of T-cells specific to SARS-CoV-2 antigens in human peripheral blood, demonstrated its specificity and performed preliminary assessment of its sensitivity. The study analysed the range and magnitude of the T-cell response in convalescent and vaccinated individuals. A pronounced T-cell response was also shown in some individuals with no symptoms or with unconfirmed diagnosis. It was discovered that the mean T-cell response to peptides of the spike protein (S-protein) was higher in the vaccinated individuals than in the convalescent patients. A correlation was determined between the severity of the disease and the level of T-cell response. Specific contributions of various groups of antigens to the T-cell response after COVID-19 infection were also determined. Conclusions: the TigraTest® SARS-CoV-2 kit is a specific and sensitive tool for the assessment of T-cell immunity to the SARS-CoV-2 virus, which can also be used for vaccinated individuals. The kit may be used in clinical practice for comprehensive assessment of immunity to SARS-CoV-2.

Immunomics-guided discovery of serum and urine antibodies for diagnosing urogenital schistosomiasis: a biomarker identification study

SummaryBackgroundSensitive diagnostics are needed for effective management and surveillance of schistosomiasis so that current transmission interruption goals set by WHO can be achieved. We aimed to screen the Schistosoma haematobium secretome to find antibody biomarkers of schistosome infection, validate their diagnostic performance in samples from endemic populations, and evaluate their utility as point of care immunochromatographic tests (POC-ICTs) to diagnose urogenital schistosomiasis in the field.MethodsWe did a biomarker identification study, in which we constructed a proteome array containing 992 validated and predicted proteins from S haematobium and screened it with serum and urine antibodies from endemic populations in Gabon, Tanzania, and Zimbabwe. Arrayed antigens that were IgG-reactive and a select group of antigens from the worm extracellular vesicle proteome, predicted to be diagnostically informative, were then evaluated by ELISA using the same samples used to probe arrays, and samples from individuals residing in a low-endemicity setting (ie, Pemba and Unguja islands, Zanzibar, Tanzania). The two most sensitive and specific antigens were incorporated into POC-ICTs to assess their ability to diagnose S haematobium infection from serum in a field-deployable format.FindingsFrom array probing, in individuals who were infected, 208 antigens were the targets of significantly elevated IgG responses in serum and 45 antigens were the targets of significantly elevated IgG responses in urine. Of the five proteins that were validated by ELISA, Sh-TSP-2 (area under the curve [AUC]serum=0·98 [95% CI 0·95–1·00]; AUCurine=0·96 [0·93–0·99]), and MS3_01370 (AUCserum=0·93 [0·89–0·97]; AUCurine=0·81 [0·72–0·89]) displayed the highest overall diagnostic performance in each biofluid and exceeded that of S haematobium-soluble egg antigen in urine (AUC=0·79 [0·69–0·90]). When incorporated into separate POC-ICTs, Sh-TSP-2 showed absolute specificity and a sensitivity of 75% and MS3_01370 showed absolute specificity and a sensitivity of 89%.InterpretationWe identified numerous biomarkers of urogenital schistosomiasis that could form the basis of novel antibody diagnostics for this disease. Two of these antigens, Sh-TSP-2 and MS3_01370, could be used as sensitive, specific, and field-deployable diagnostics to support schistosomiasis control and elimination initiatives, with particular focus on post-elimination surveillance.FundingAustralian Trade and Investment Commission and Merck Global Health Institute.

Multi-Epitope-Based Vaccines for Colon Cancer Treatment and Prevention.

BackgroundOverexpression of nonmutated proteins involved in oncogenesis is a mechanism by which such proteins become immunogenic. We questioned whether overexpressed colorectal cancer associated proteins found at higher incidence and associated with poor prognosis could be effective vaccine antigens. We explored whether vaccines targeting these proteins could inhibit the development of intestinal tumors in the azoxymethane (AOM)-induced colon model and APC Min mice.MethodsHumoral immunity was evaluated by ELISA. Web-based algorithms identified putative Class II binding epitopes of the antigens. Peptide and protein specific T-cells were identified from human peripheral blood mononuclear cells using IFN-gamma ELISPOT. Peptides highly homologous between mouse and man were formulated into vaccines and tested for immunogenicity in mice and in vivo tumor challenge. Mice treated with AOM and APC Min transgenic mice were vaccinated and monitored for tumors.ResultsSerum IgG for CDC25B, COX2, RCAS1, and FASCIN1 was significantly elevated in colorectal cancer patient sera compared to volunteers (CDC25B p=0.002, COX-2 p=0.001, FASCIN1 and RCAS1 p<0.0001). Epitopes predicted to bind to human class II MHC were identified for each protein and T-cells specific for both the peptides and corresponding recombinant protein were generated from human lymphocytes validating these proteins as human antigens. Some peptides were highly homologous between mouse and humans and after immunization, mice developed both peptide and protein specific IFN-γ-secreting cell responses to CDC25B, COX2 and RCAS1, but not FASCIN1. FVB/nJ mice immunized with CDC25B or COX2 peptides showed significant inhibition of growth of the syngeneic MC38 tumor compared to control (p<0.0001). RCAS1 peptide vaccination showed no anti-tumor effect. In the prophylactic setting, after immunization with CDC25B or COX2 peptides mice treated with AOM developed significantly fewer tumors as compared to controls (p<0.0002) with 50% of mice remaining tumor free in each antigen group. APC Min mice immunized with CDC25B or COX2 peptides developed fewer small bowel tumors as compared to controls (p=0.01 and p=0.02 respectively).ConclusionsImmunization with CDC25B and COX2 epitopes consistently suppressed tumor development in each model evaluated. These data lay the foundation for the development of multi-antigen vaccines for the treatment and prevention of colorectal cancer.

Comparative efficacy of intralesional Candida antigen, intralesional bivalent human papilloma virus vaccine, and cryotherapy in the treatment of common warts

Comparative efficacy of intralesional Candida antigen, intralesional bivalent human papilloma virus vaccine, and cryotherapy in the treatment of common warts

Intralesional Candida antigen versus intralesional vitamin D3 in the treatment of recalcitrant multiple common warts

There are various therapies available for recalcitrant common warts; however no specific therapy has been established as entirely effective. To assess the efficacy and safety of intralesional Candida antigen injection of vs. intralesional vitamin D3 injection in the treatment of multiple recalcitrant common warts. A total of 80 adult patients with multiple common warts were randomly assigned to one of three groups in this study. Thirty patients were assigned to Group I, who received a 0.3ml intralesional injection of Candida antigen. Thirty patients were assigned to Group II, who received a 0.6-ml (60000IU) intralesional injection of vitamin D3. Twenty patients were in Group-III, who received 0.3ml of normal saline as a control. Each agent was injected at the base of largest wart every 3weeks until full clearance has been obtained, or for a maximum of four sessions. In the Candida antigen, vitamin D3, and saline groups, complete wart clearance was observed in 76.7 percent, 20%, and 0.0 percent, respectively. The side effects were negligible and transient, and there was no recurrence of the lesions. Intralesional injection of Candida antigen is as a safe, simple, cost-effective treatment modality for multiple recalcitrant common warts and it outperforms intralesional vitamin D3.

Continued evolution of H6 avian influenza viruses isolated from farms in China between 2014 and 2018.

H6 avian influenza virus (AIV) is one of the most prevalent AIV subtypes in the world. Our previous studies have demonstrated that H6 AIVs isolated from live poultry markets pose a potential threat to human health. In recent years, increasing number of H6 AIVs has been constantly isolated from poultry farms. In order to understand the biological characteristics of H6 AIVs in the context of farms, here, we analyzed the phylogenetic relationships, antigenicity, replication in mice and receptor binding properties of H6 AIVs isolated from farms in China between 2014 and 2018. Phylogenetic analysis showed that 19 different genotypes were formed among 20 representative H6 viruses. Notably, the internal genes of these H6 viruses exhibited complicated relationships with different subtypes of AIVs worldwide, indicating that these viruses are the products of complex and frequent reassortment events. Antigenic analysis revealed that 13 viruses tested were divided into three antigenic groups. 10 viruses examined could all replicate in the respiratory organs of infected mice without prior adaptation. Receptor binding analysis demonstrated that some of the H6 AIVs bound to both α-2, 3-linked glycans (avian-type receptor) and α-2, 6-linked glycans (human-type receptor), thereby posing a potential threat to human health. Together, these findings revealed the prevalence, complicated genetic evolution, diverse antigenicity, and dual receptor binding specificity of H6 AIVs in the settings of poultry farms, which emphasize the importance to continuously monitor the evolution and biological properties of H6 AIVs in nature.

Red cell alloimmunization in haemato‐oncology patients transfused with packed red blood cells extended phenotype matched for Rh and Kell antigens versus the standard crossmatched units

Background and ObjectivesThere is limited evidence regarding the advantage of transfusing extended phenotype‐matched (EPM) packed red blood cells (PRBCs) to prevent alloimmunization in haemato‐oncology patients. This randomized control trial aimed to determine the alloimmunization in haemato‐oncology patients transfused with PRBCs which are EPM for Rh (C, E, c, e) and Kell (K) antigens (group I) versus those receiving standard compatible PRBCs (group II).Materials and MethodsPatients having a negative antibody screen (ABS), direct antiglobulin test (DAT) and autologous control (AC) were randomly allocated to either group I or II (n = 50 each). A follow‐up (FU) testing post‐transfusion was conducted for haemoglobin (Hb), ABS and DAT at 1 week, 1 month and 3 months. ABS was conducted using fully automated immunohaematology analyser, while DAT, compatibility testing and extended phenotyping were conducted manually using column agglutination technique.ResultsThere was no significant difference between the two groups with respect to mean (±SD) Hb at initial enrolment (group I, 5·06 ± 1·29 g/dl and group II, 5·41 ± 1·37 g/dl; P = 0·179), age (40 ± 17·3 years v/s 42·2 ± 17·2 years; P = 0·523), gender (P = 0·835) and diagnosis (P = 0·06). All patients in group I and II had negative ABS, DAT and AC at all three FUs. Group II patients were transfused more PRBCs (372 v/s 187, P = 0·000), while the mean Hb increment between successive FU was significant in both the groups (P = 0·003).ConclusionIt appears that there is no added benefit of providing EPM PRBCs in haemato‐oncology patients, as none developed RBC alloantibodies.

Genotyping versus phenotyping of non-ABO erythrocyte antigens in patients with the Mediterranean hemopathic syndromes: Effect of transfusion therapy.

The Mediterranean hemopathic syndromes (MHS) are the most prevalent hemoglobinopathies in the Mediterranean basin. Transfusion therapy is the main therapy for these disorders, particularly for severe forms of the disease. Currently, pre-transfusion serological typing of erythrocyte antigens is the standard tool for reducing complications of transfusion in those patients. This study compared genotyping with phenotyping of non-ABO erythrocyte antigens in patients with MHS and assessed the effect of transfusion therapy on their results. One-hundred ninety-eight MHS patients were recruited, screened, and proven negative for allo-antibodies. They were grouped into two groups: (1) 20 newly diagnosed patients with no transfusion history and (2) 178 previously diagnosed patients undergoing transfusion therapy. Patients were interviewed and clinically examined. Full blood count (FBC) and high performance liquid chromatography (HPLC) were done for group 1 only. Genotyping and phenotyping of non-ABO erythrocyte antigens were performed for group 1, and 25 patients out of group 2 were propensity score-matched (PSM) with group 1. Both groups were gender and age matched; 55% and 74% of groups 1 and 2 had major disease, respectively. Insignificant differences were observed between genotyping and phenotyping of non-ABO erythrocyte antigens in group 1, while significant discrepancies and mixed field results were noted in group 2 patients. Discrepancies were obvious with JKa, JKb, and little c antigens. Conclusively, molecular typing is a powerful tool for pre-transfusion testing in chronically transfused MHS patients. This testing reduces incidence of transfusion reactions. JKa, JKb and little c antigens are the most clinically significant non-ABO erythrocyte antigens.

Serological reactivity against T. cruzi-derived antigens: Evaluation of their suitability for the assessment of response to treatment in chronic Chagas disease.

Chagas disease, caused by the protozoan Trypanosoma cruzi, affects more than 6 million people worldwide. Following a mostly asymptomatic acute phase, the disease progresses to a long-lasting chronic phase throughout which life-threatening disorders to the heart and/or gastrointestinal tract will manifest in about 30% of those chronically infected. During the chronic phase, the parasitemia is low and intermittent, while a high level of anti-T. cruzi antibodies persist for years. These two features hamper post-chemotherapeutic follow-up of patients with the tools available. The lack of biomarkers for timely assessment of therapeutic response discourages a greater use of the two available anti-parasitic drugs, and complicates the evaluation of new drugs in clinical trials. Herein, we investigated in a blinded case-control study the serological reactivity over time of a group of parasite-derived antigens to potentially address follow up of T. cruzi chronically infected subjects after treatment. We tested PFR2, KMP11, HSP70, 3973, F29 and the InfYnity multiplexed antigenic array, by means of serological assays on a multi-national retrospective collection of samples. Some of the antigens exhibited promising results, underscoring the need for further studies to determine their potential role as treatment response biomarkers.

Detrimental effects of microplastic exposure on normal and asthmatic pulmonary physiology

Concerns that airborne microplastics (MP) may be detrimental to human health are rising. However, research on the effects of MP on the respiratory system are limited. We tested the effect of MP exposure on both normal and asthmatic pulmonary physiology in mice. We show that MP exposure caused pulmonary inflammatory cell infiltration, bronchoalveolar macrophage aggregation, increased TNF-α level in bronchoalveolar lavage fluid (BALF), and increased plasma IgG1 production in normal mice. MP exposure also affected asthma symptoms by increasing mucus production and inflammatory cell infiltration with notable macrophage aggregation. Further, we found co-labeling of macrophage markers with MP incorporating fluorescence, which indicates phagocytosis of the MP by macrophages. A comparative transcriptomic analysis showed that MP exposure altered clusters of genes related to immune response, cellular stress response, and programmed cell death. A bioinformatics analysis further uncovered the molecular mechanism whereby MP stimulated production of tumor necrosis factor and immunoglobulins to activate a group of transmembrane B-cell antigens, leading to the modulation of cellular stress and programmed cell death in the asthma model. In summary, we show that MP exposure had detrimental effects on the respiratory system in both healthy and asthmatic mice, which calls for urgent discourse and action to mitigate environmental microplastic pollutants.

Ocular manifestation of rickettsial disease in South Indian population.

Purpose:The aim of this work was to study the ocular manifestations and its management in spotted fever and typhus group of rickettsial disease.Methods:A retrospective analysis of 50 patients with serologically confirmed Rickettsial disease. In all patients, relevant history, investigations and treatment details were collected and they underwent complete ophthalmic evaluation including measurement of best-corrected visual acuity, anterior segment examination and dilated fundus examination.Results:Mean age was 12.5 ± 8.99 years. Of the 50 patients, 40 patients were ≤18 years of age and 27 (54%) had ocular involvement. Out of 27 patients, bilateral involvement was seen in 10 patients. Most of the patients had no ocular symptoms. Ocular findings included, Retinal vasculitis 6 (22.22%); macular edema 4 (14.81%); vasculitis with macular edema 1 (3.7%); Retinitis 7 (25.92%); Papilloedema 6 (22.22%); Papilloedema with 6th cranial nerve palsy 1 (3.7%); Isolated 6th cranial nerve palsy 1 (3.7%) and optic neuritis 1 (3.7%). Ocular involvement was more common in double antigen group (68%) than spotted fever group (50%) or Scrub typhus group (21%) (P = 0.01). Ocular involvement was seen in 94% of the patients with CNS involvement. Cases with bilateral involvement (P = 0.01), pediatric age group (P = 0.01) and CNS involvement (P = 0.02) had poor visual outcome.Conclusion:Rickettsioses patients can have ocular manifestations with predominant posterior segment involvement during acute phase of illness. Ocular involvement was more common in the double antigen group. For any patient who presents with fever and rash living in endemic area, ophthalmic evaluation should be part of routine checkup during the acute phase of illness associated with less frequent ocular symptoms.

Changing trends in robot-assisted radical prostatectomy: Inverse stage migration-A retrospective analysis.

BackgroundWith increasing availability of data on outcomes of surgery for prostate cancer, the profile of patients undergoing robot-assisted radical prostatectomy (RARP) has changed over the past decade. This impacts the decision-making process for surgeons and patients, particularly in low-incidence regions of Asia. Our institution was among the first in Asia to acquire a da Vinci surgical robot in 2005. We evaluated the changes in the clinical and pathology profile of patients undergoing RARP at our institution over the past 15 years (2005-2019).MethodsA retrospective analysis of patients undergoing RARP between April 2005 and December 2019 was conducted from the hospital database. The patients were divided into two groups; patients undergoing RARP from April 2005 to December 2012 (Group I, first 8 years) and January 2013 to December 2019 (Group II, next 7 years). The perioperative characteristics were compared between these two groups to assess changes in their profile and outcome.ResultsFour hundred forty-seven patients were included in this study; 244 (54.6%) in Group I and 203 (45.4%) in Group II. The median prostate specific antigen in Group II was significantly higher than that in Group I (14.5 vs. 11.7 ng/ml, P = 0.016). Unfavorable pathological characteristics, i.e., Gleason Grade ≥3, perineural invasion, and the margin positivity rate increased substantially from 18.5% to 37.5%, 20.5% to 36.9%, and 15.2% to 26.6%, respectively, in Group II compared with Group I. More patients in Group II received adjuvant therapy than in Group I (P < 0.001).ConclusionThere has been a change in profile of patients undergoing RARP and patients with more unfavorable disease characteristics such as higher prostate specific antigen and tumor grade are undergoing surgery. In line with international trends, the number of patients with low-grade disease undergoing surgery has substantially decreased. Multimodal treatment with adjuvant therapy is increasingly used, particularly in high-risk disease.

Cancer/testis antigens: from serology to mRNA cancer vaccine.

Cancer/testis antigens (CTAs) are a group of tumor antigens expressed in numerous cancer tissues, as well as in the testis and placental tissues. There are over 200 CTAs supported by serology and expression data. The expression patterns of CTAs reflect the similarities between the processes of gametogenesis and tumorigenesis. It is notable that CTAs are highly expressed in three types of cancers (lung cancer, bladder cancer, and skin cancer), all of which have a metal etiology. Here, we review the expression, regulation, and function of CTAs and their translational prospects as cancer biomarkers and treatment targets. Many CTAs are highly immunogenic, tissue-specific, and frequently expressed in cancer tissues but not under physiological conditions, rendering them promising candidates for cancer detection. Some CTAs are associated with clinical outcomes, so they may serve as prognostic biomarkers. A small number of CTAs are membrane-bound, making them ideal targets for chimeric antigen receptor (CAR) T cells. Mounting evidence suggests that CTAs induce humoral or cellular immune responses, providing cancer immunotherapeutic opportunities for T-cell receptors (TCRs), CAR T cell, antibody-based therapy and peptide- or mRNA-based vaccines. Indeed, CTAs are the dominating non-mutated targets in mRNA cancer vaccine development. Clinical trials on CTA TCR and vaccines have shown effectiveness, safety, and tolerance, but these successes are limited to a small number of patients. In-depth studies on CTA expression and function are needed to improve CTA-based immunotherapy.