Positive Antigen Research Articles

Multidisciplinary Discussion for Fibrotic Hypersensitivity Pneumonitis with a Positive Antigen Avoidance.

In the two fibrotic hypersensitivity pneumonitis (fHP) diagnostic guidelines, the multidisciplinary discussion (MDD) is required to be performed in diagnosis of fHP, as in idiopathic pulmonary fibrosis (IPF) diagnostic guideline. Although some patients with fHP can improve disease condition during antigen avoidance, which can facilitate the diagnosis of fHP, it is unclear if MDD is necessary in all patients with suspected fHP who improved an antigen avoidance. To investigate the diagnosis of fHP via MDD with positive antigen avoidance tests (AATs) and the clinical diagnosis with positive AATs. A single-center, retrospective study was conducted. Between 2012 and 2019, patients with fHP were enrolled in the study. Patients in the MDD diagnostic group consisted of patients diagnosed with MDD, including histopathology findings and positive ATTs, and patients in the clinical diagnostic group were diagnosed by two respiratory physicians and had positive ATTs. AAT was performed on 72 of 219 patients, and 58 had positive AATs. The study included 37 patients in the MDD diagnosis group and 21 patients in the clinical diagnosis group. No significant differences in overall survival (OS) were detected between the two groups (HR: 1.99 [95% CI: 0.82‒4.83], p = 0.127). The conducting MDD was not a risk factor for OS; only <79% forced vital capacity was a risk factor in the multivariate Cox hazard regression analysis. No significant difference in annual changes of forced vital capacity, diffusion of the lung for carbon monoxide and Krebs von den Lungen-6 between the MDD diagnostic and the clinical diagnostic groups were observed (p = 0.41, 0.79, and 0.81, respectively). In patients with positive AATs, the disease progression of the MDD diagnostic and the clinical diagnostic groups were similar. Therefore, MDD could not be necessary in all patients with suspected fHP who had positive AATs.

Cryptococcal Meningoencephalitis and Immune Reconstitution Inflammatory Syndrome in a patient on Tocilizumab Therapy: A Case Report (P1-10.005)

<h3>Objective:</h3> To describe a case of cryptococcal meningoencephalitis complicated by immune reconstitution inflammatory syndrome (IRIS), vasculitis, ischemic strokes, and hydrocephalus. <h3>Background:</h3> Cryptococcus neoformans is the most common cause of fungal meningitis worldwide and typically affects individuals with defects in cell-mediated immunity. A 71-year-old female with giant cell arteritis on daily prednisone and monthly Tocilizumab infusions presented with worsening headaches for 2 weeks and new-onset confusion for 3 days. Initial workup revealed hyponatremia (sodium 125 mmol/L) and community acquired pneumonia. She was treated with antibiotics, but her mental status rapidly declined necessitating endotracheal intubation. MRI Brain demonstrated multifocal areas of diffusion restriction in the bilateral cerebral and cerebellar hemispheres, basal ganglia, and brainstem with diffuse leptomeningeal enhancement. Cerebrospinal fluid (CSF) studies revealed an elevated opening pressure of 28 cm H₂O, positive CSF cryptococcal antigen, and CSF fungal cultures grew cryptococcus neoformans. She was started on empiric liposomal amphotericin B and flucytosine before the cryptococcal antigen and cultures resulted. Despite treatment, her neurological status continued to decline with repeat MRI showing new ischemic infarctions, subarachnoid hemorrhages, and leptomeningeal and parenchymal enhancement. Digital subtraction angiography revealed cerebral vasospasm and possible vasculitis. Repeat lumbar puncture demonstrated persistently elevated opening pressure, continued pleocytosis, and increased protein. She was continued on antifungal therapy and received IV methylprednisolone for IRIS. She additionally underwent ventriculoperitoneal (VP) shunt placement. Despite these interventions, her clinical status continued to deteriorate and she was palliatively extubated. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> N/A <h3>Conclusions:</h3> This patient presented with cryptococcal meningoencephalitis in the setting of immune suppression from prednisone and tocilizumab, a monoclonal antibody that targets the IL-6 receptor. Despite early and appropriate treatment, she continued to worsen with multiple complications including IRIS, a dysfunctional inflammatory response to infection precipitated by immune recovery. In patients treated appropriately for cryptococcal meningoencephalitis, a failure to respond should raise concern for complicating conditions. <b>Disclosure:</b> Dr. Navalkar has nothing to disclose. Dr. Sui has nothing to disclose. The institution of Dr. Bashir has received research support from NIH. The institution of Dr. Bashir has received research support from PICORI. The institution of Dr. Bashir has received research support from Sanofi. Dr. Bashir has received research support from GWSP. The institution of Dr. Bashir has received research support from Roche. The institution of Dr. Bashir has received research support from Novartis. The institution of Dr. Bashir has received research support from Hoffmann-La Roche.

COVID-19 Antigen Results Correlate with the Quantity of Replication-Competent SARS-CoV-2 in a Cross-Sectional Study of Ambulatory Adults during the Delta Wave.

Appropriate interpretation of various diagnostic tests for COVID-19 is critical, yet the association among rapid antigen tests, reverse transcription (RT)-PCR, and viral culture has not been fully defined. To determine whether rapid antigen testing correlates with the presence and quantity of replication-competent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in ambulatory adults, 626 adult participants were enrolled in a cross-sectional diagnostic study. Each participant had two anterior nasal swabs obtained for rapid antigen and RT-PCR testing and SARS-CoV-2 viral culture. The primary outcomes were the presence and quantification of SARS-CoV-2 growth in VeroE6-ACE2-TMPRSS2 cells in asymptomatic and symptomatic ambulatory adults. In this cross-sectional study of 626 adult outpatients, the sensitivity of a single positive antigen test to identify replication-competent SARS-CoV-2 was 63.6% in asymptomatic and 91.0% in symptomatic participants. Viral culture titers were the highest at the onset of symptoms and rapidly declined by 7 days after symptom onset. The positive agreement of the rapid antigen test with RT-PCR at a cycle threshold CT less than 30 was 66.7% in asymptomatic and 90.7% in symptomatic participants. Among symptomatic participants a with a CT less than 30, a single antigen test had a positive agreement of 90.7% (95% confidence interval [CI], 84.8% to 94.8%). There was 100% negative agreement as all 425 RT-PCR-negative participants had a negative antigen test. A positive antigen test in symptomatic adults with COVID-19 has a strong correlation with replication-competent SARS-CoV-2. Rapid antigen test results may be a suitable proxy for infectiousness. IMPORTANCE Do rapid antigen test results correlate with replication-competent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (i.e., infectious) virus? In this cross-sectional diagnostic study of 626 adults, the sensitivity of the antigen test to identify replication-competent SARS-CoV-2 was 63.6% in asymptomatic and 91.0% in symptomatic participants. Viral culture titers were the highest at the onset of symptoms and rapidly declined by 7 days after symptom onset. The positive agreement of the rapid antigen test with reverse transcription (RT)-PCR at a CT of less than 30 was 66.7% in asymptomatic participants and 90.7% in symptomatic participants. A positive antigen test may be an appropriate surrogate for identifying replication-competent virus in symptomatic individuals with COVID-19.

Incremental costs of hospital-acquired infections in COVID-19 patients in an adult intensive care unit of a tertiary hospital from a low-resource setting

BackgroundHospital-acquired infections (HAIs) are a global public health problem and put patients at risk of complications, including death. HAIs increase treatment costs, but their financial impact on Serbia’s healthcare system is unknown. Our goal was to assess incremental costs of HAIs in a tertiary care adult intensive care unit (ICU) that managed COVID-19 patients.MethodsA retrospective study from March 6th to December 31st, 2020 included patients with microbiologically confirmed COVID-19 (positive rapid antigen test or real-time polymerase chain reaction) treated in the ICU of the Teaching Hospital for Infectious and Tropical Diseases, University Clinical Centre of Serbia. Demographic and HAI-specific data acquired in our ICU were collected, including total and stratified medical costs (services, materials, laboratory testing, medicines, occupancy costs). Median total and stratified costs were compared in relation to HAI acquisition. Linear regression modelling was used to assess incremental costs of HAIs, adjusted for age, biological sex, prior hospitalisation, Charlson Comorbidity Index (CCI), and Glasgow Coma Scale (GCS) on admission. Outcome variables were length of stay (LOS) in days and mortality.ResultsDuring the study period, 299 patients were treated for COVID-19, of which 214 were included. HAIs were diagnosed in 56 (26.2%) patients. Acinetobacter spp. was the main pathogen in respiratory (38, 45.8%) and bloodstream infections (35, 42.2%), the two main HAI types. Median total costs were significantly greater in patients with HAIs (€1650.4 vs. €4203.2, p < 0.001). Longer LOS (10.0 vs. 18.5 days, p < 0.001) and higher ICU mortality (51.3% vs. 89.3%, p < 0.001) were seen if HAIs were acquired. Patients with ≥ 2 HAIs had the highest median total costs compared to those without HAIs or with a single HAI (€1650.4 vs. €3343.4 vs. €7336.9, p < 0.001). Incremental costs in patients with 1 and ≥ 2 HAIs were €1837.8 (95% CI 1257.8–2417.7, p < 0.001) and €5142.5 (95% CI 4262.3–6022.7, p < 0.001), respectively.ConclusionsThis is the first economic evaluation of HAIs in Serbia, showing significant additional costs to our healthcare system. HAIs prolong LOS and influence ICU mortality rates. Larger economic assessments are needed to enhance infection control practices.

The incidence of histoplasmosis and cryptococcal antigenemia among patients attending a large HIV clinic in Trinidad

Our aim was to determine the incidence disseminated histoplasmosis and cryptococcal antigenemia among 280 patients with a CD4<350 cells/mm3 attending a large HIV clinic in Trinidad over the period November 2021-June 2022. Sera were screened for cryptococcal antigen (CrAg) using the Immy CrAg Immunoassay (EIA) and the Immy CrAg lateral flow assay (LFA). Urine was screened for Histoplasma antigen using the Immy EIA and the Optimum Imaging Diagnostics (OIDx) LFA. For the purposes of analysis, it was assumed, that all patients with positive urine Histoplasma antigen tests by both EIA and LFA and those with a single positive urine Histoplasma antigen test and clinical features of disseminated histoplasmosis were true positives. The incidence of probable disseminated histoplasmosis and cryptococcal antigenemia were 6.4% (18/280) and 2.5% (7/280) respectively. The sensitivity and specificity of the Immy Histoplasma EIA were 100% (95% CI, 81.5%-100%) and 98.5% (95% CI, 96.1% - 99.6%) respectively as compared to the OIDx Histoplasma LFA of 88.9% (95% CI, 65.3% - 98.6%) and 93.9% (95% CI, 90.3% - 96.5%) respectively, with substantial agreement between the 2 test kits (Kappa value = 0.763; 95% CI 0.685, 0.841). Testing for disseminated histoplasmosis in HIV patients is important in endemic areas.

SARS-CoV-2-Related Pediatric Encephalopathy with Biphasic Convulsions and Cortical Blindness: A Case Report

AbstractAcute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is an encephalopathy syndrome that develops during the febrile phase of infection and is characterized by biphasic seizures and bright tree appearance (BTA) on imaging. In this study, we examined a 1-year-old child who was diagnosed with AESD caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. He had a fever for 2 days and was diagnosed with coronavirus disease 2019 on the day of consultation based on a positive antigen test for SARS-CoV-2. The seizures had stopped on arrival to hospital; however, symptoms of encephalopathy persisted. Despite being treated for acute encephalopathy with steroid pulse therapy, vitamins, and remdesivir, he had poor expressive language, and electroencephalography showed generalized slow waves. A repeat head magnetic resonance imaging showed BTA in the parietal and occipital lobes, and seizures recurred during hospital stay. He was also found to have cortical blindness. At the 4-month follow-up, the vision gradually improved and the hand movements recovered. SARS-CoV-2 infection can cause febrile convulsions, which can lead to the development of AESD. Furthermore, a subtype of AESD has occipital lobe predominant lesions that can cause visual impairment.

La relación entre los parámetros inmunohistoquímicos, la fibrosis de la médula ósea y la captación de 18F-FDG en la médula ósea en pacientes con mieloma múltiple sometidos a examen PET/TC

AimThe aim of this study was to determine the power of the SUVmax value obtained from 18F-FDG PET/CT in multiple myeloma patients to be able to predict immunophenotype characteristics (CD20, CD44, CD56, CD117, and CD138 antigen expressions), bone marrow fibrosis, cyclin D1 oncogene, and M-protein subtypes which play a role in diagnosis-treatment and prognosis of the disease. Material and methodThe study included 54 patients with multiple myeloma who underwent PET/CT for initial staging and bone marrow biopsy. The relationship was examined in these patients between the SUVmax value measured from the iliac bone region and the immunohistochemical and bone marrow fibrosis data of the biopsy taken from the iliac bone. The Mann–Whitney U-test was used in the comparisons of dependent paired groups, and the Kruskal–Wallis H test in the comparisons of three or more groups. ResultsThe median SUVmax value was 4.5 (1.9-15.6) in patients with CD117 antigen positivity, which was statistically significantly higher than the value in the patients with CD117 negativity (P=0.031). When patient grouping was made according to the reticulin level: We found that the median SUVmax value was 4.9 (3.0-14.8) in the group with increased fibrosis and 3.6 (1.6-15.6) in the group with low fibrosis. The median SUVmax was statistically significantly higher in the group with increased fibrosis compared to the group with low fibrosis (P=0.004). No statistically significant difference was determined in the comparisons of the SUVmax values when the patients were grouped according to the immunoglobulin heavy chain and light chain, CD20, CD44, CD56, and cyclin D1 characteristics (P>0.05). ConclusionIn multiple myeloma patients who underwent PET/CT for initial staging, significant relationships were determined between FDG uptake in the bone marrow (SUVmax) and CD117 antigen and bone marrow fibrosis, which is an important prognostic factor. Higher SUVmax values were determined in the bone marrow of patients with increased fibrosis and CD117 positivity.

Disseminated Tuberculosis with Poncet’s Disease Masquerading as Systemic Lupus Erythematosus – A Case Report

Tuberculosis (TB) rheumatism (Poncet’s disease) is defined as a polyarthritis associated with extrapulmonary TB in which there is no evidence of bacteriological involvement of the joints. We report a case of 21-year-old female whose initial clinical and laboratory investigations were suggestive of inflammatory arthropathy. The case was complicated by weak anti-nuclear antibody positivity of anti-proliferating cell nuclear antigen (+) antibodies, suggestive of systemic lupus erythematosus. However, after clinical examination and investigations, the patient was diagnosed as a case of disseminated TB with Poncet’s disease. The patient was started on anti-tubercular treatment and showed improvement at the end of 1st month of treatment. The case highlights that Poncet’s disease should be considered as one of the differentials while dealing with cases of unexplained or prolonged arthralgia.

High prevalence of malaria in pregnancy among women attending antenatal care at a large referral hospital in northwestern Uganda: A cross-sectional study.

Malaria in pregnancy contributes to substantial morbidity and mortality among women in Uganda. However, there is limited information on the prevalence and factors associated with malaria in pregnancy among women in Arua district, northwestern Uganda. We, therefore, assessed the prevalence and factors associated with malaria in pregnancy among women attending routine antenatal care (ANC) clinics at Arua regional referral hospital in north-western Uganda. We conducted an analytic cross-sectional study between October and December 2021. We used a paper-based structured questionnaire to collect data on maternal socio-demographic and obstetric factors and malaria preventive measures. Malaria in pregnancy was defined as a positive rapid malarial antigen test during ANC visits. We performed a modified Poisson regression analysis with robust standard errors to determine factors independently associated with malaria in pregnancy, reported as adjusted prevalence ratios (aPR) and 95% confidence intervals (CI). We studied 238 pregnant women with a mean age of 25.32±5.79 years that attended the ANC clinic, all without symptomatic malaria. Of the participants, 173 (72.7%) were in their second or third trimester, 117 (49.2%) were first or second-time pregnant women, and 212 (89.1%) reported sleeping under insecticide-treated bednets (ITNs) every day. The prevalence of malaria in pregnancy was 26.1% (62/238) by rapid diagnostic testing (RDT), with the independently associated factors being daily use of insecticide-treated bednets (aPR 0.41, 95% CI 0.28, 0.62), first ANC visit after 12 weeks of gestation (aPR1.78, 95% CI 1.05, 3.03), and being in the second or third trimester (aPR 0.45, 95% CI 0.26, 0.76). The prevalence of malaria in pregnancy among women attending ANC in this setting is high. We recommend the provision of insecticide-treated bednets to all pregnant women and early ANC attendance to enable access to malaria preventive therapy and related interventions.

Potential diagnostic application of the baculovirus-expressed recombinant truncated nucleocapsid protein of peste des petits ruminants virus in ELISA

The study describes the expression of recombinant truncated nucleocapsid protein (NP) of peste des petits ruminants (PPR) virus in the baculovirus system (PPRV-rBNP) and its potential application as a diagnostic antigen in ELISA for diagnosis of PPR in sheep and goats. The PPRV N-terminal immunogenic region (1–266 aa) of the NP coding sequence was amplified and cloned into the pFastBac HT A vector. The PPRV-rBNP with a molecular weight of ∼30 kDa was expressed in an insect cell system using generated recombinant baculovirus through Bac-to-Bac® Baculovirus Expression System. The crude PPRV-rBNP or Ni-NTA affinity-purified NP was characterized by SDS-PAGE and immunoblot using standard PPRV-specific sera. The PPRV-rBNP reacted well with PPRV anti-N specific monoclonal and polyclonal antibodies and PPRV-specific antiserum, suggesting that the expressed PPRV-rBNP is in its native form. The crude PPRV-rBNP as a diagnostic antigen was evaluated either as a coating antigen or standard positive control antigen in the Avidin-Biotin ELISA using the known standard panel reagents. The results showed that the expressed PPRV-rBNP can be an alternative diagnostic antigen to E. coli expressed recombinant PPRV-NPN and the utility of PPRV-rBNP avoids the need to use live PPRV antigen in the diagnostic ELISA. Hence, this allows scope in the future for large-scale field application of the recombinant antigen-based assays for diagnosis/surveillance and monitoring of PPR at the eradication as well as post-eradication phases in endemic countries or PPR non-endemic countries.

Elevation of the Neutrophil-to-Lymphocyte Ratio Is a Significant Postoperative Poor Prognostic Factor in Patients With Clinical T3-4 Centrally Located Primary Lung Cancer.

In centrally located non-small cell lung cancer (CLNSCLC) surgery, large tumors and extension to neighboring structures prevent the attainment of adequate surgical fields and make operations more difficult, and some patients have extremely poor outcomes. This study aimed to identify novel postoperative prognostic factors in patients with advanced CLNSCLC. CLNSCLC was defined as a tumor requiring pneumonectomy or sleeve lobectomy for complete removal. We retrospectively investigated the clinical courses of 35 patients with cT3-4 CLNSCLC. This study included 21 patients with cT3 and 14 with cT4 lung cancer. Nine patients underwent pneumonectomy and 26 underwent sleeve lobectomy. Univariate analysis revealed that a high neutrophil-to-lymphocyte ratio (NLR, p=0.005) and carcinoembryonic antigen (CEA) positivity (p=0.028) were significant poor prognostic factors. Only high NLR (p=0.020) was a significant independent predictor in multivariate analysis. Nine of 16 patients with high NLR (56%) experienced disease recurrence, whereas 6 of 19 patients without high NLR (32%) had recurrent disease. High NLR and CEA positivity were significant poor prognostic factors in patients with cT3-4 CLNSCLC, and only high NLR was an independent predictor. Our findings may be helpful in selecting optimal treatments for advanced CLNSCLC.

Laparoscopic Graham Patch for Anterior Duodenal Perforation in a 6-Year-Old.

Peptic ulcer disease causing perforation is extremely rare in children and primarily affects teenagers. We present a case of a perforated peptic ulcer in a 6-year-old with abdominal pain and emesis with CT findings of moderate pneumoperitoneum and pelvic free fluid without a distinct cause. He was emergently transferred, found to be peritonitic, and taken to the operating room for diagnostic laparoscopy revealing an anterior duodenal ulcer, and underwent laparoscopic Graham patch repair. Postoperatively, the child had positive fecal antigen for H. pylori. He was treated with triple therapy and underwent subsequent testing to confirm eradication. Perforated peptic ulcer is an uncommon pediatric surgical problem, and imaging may not be diagnostic as in the case presented here. Thus, clinicians need to maintain a high index of suspicion when evaluating children with free air and a surgical abdomen in the setting of long-standing abdominal pain.

The relationship between immunohistochemical parameters, bone marrow fibrosis and bone marrow 18F-FDG uptake in multiple myeloma patients undergoing PET/CT examination

PurposeThe aim of this study was to determine the power of the SUVmax value obtained from 18F-FDG PET/CT in multiple myeloma (MM) patients to be able to predict immunophenotype characteristics (CD20, CD44, CD56, CD117, CD138 antigen expressions), bone marrow fibrosis, cyclin D1 oncogene, and M-protein subtypes which play a role in diagnosis-treatment and prognosis of the disease. Material and methodThe study included 54 patients with multiple myeloma who underwent PET/CT for initial staging and bone marrow biopsy. The relationship was examined in these patients between the SUVmax value measured from the iliac bone region and the immunohistochemical and bone marrow fibrosis data of the biopsy taken from the iliac bone. The Mann Whitney U test was used in the comparisons of dependent paired groups, and the Kruskal Wallis H test in the comparisons of three or more groups. ResultsThe median SUVmax value was 4.5 (1.9−15.6) in patients with CD117 antigen positivity, which was statistically significantly higher than the value in the patients with CD117 negativity (p = 0.031). When patient grouping was made according to the reticulin level; we found that the median SUVmax value was 4.9 (3.0−14.8) in the group with increased fibrosis and 3.6 (1.6−15.6) in the group with low fibrosis. The median SUVmax was statistically significantly higher in the group with increased fibrosis compared to the group with low fibrosis (p = 0.004). No statistically significant difference was determined in the comparisons of the SUVmax values when the patients were grouped according to the immunoglobulin heavy chain and light chain, CD20, CD44, CD56, and cyclin D1 characteristics (p > 0.05). ConclusionIn MM patients who underwent PET/CT for initial staging, significant relationships were determined between FDG uptake in the bone marrow (SUVmax) and CD117 antigen and bone marrow fibrosis, which is an important prognostic factor. Higher SUVmax values were determined in the bone marrow of patients with increased fibrosis and CD117 positivity.

COPD, diabetes, lymphopenia, and increased LDH cause higher mortality in hospitalized COVID-19 patients.

COPD, diabetes, lymphopenia, and increased LDH cause higher mortality in hospitalized COVID-19 patients.

Phylogenetic identification of feline leukemia virus A and B in cats with progressive infection developing into lymphoma and leukemia

To date, only a few studies have examined the impacts of feline leukemia virus (FeLV) subgroups on disease development in spontaneously infected cats. The present study identified FeLV-A and FeLV-B subgroups in cats with lymphoma and leukemia and explored the phylogenetic relationships of env sequences. Twenty-six cats with lymphoma (n=16) or leukemia (n=10) were selected. FeLV p27 antigen positivity was determined using ELISA, and proviral DNA in blood samples was detected using nested PCR. Positive animals in both tests were classified as cases of FeLV progressive infection and subjected to a second nested PCR for env amplification and subgroup determination. Six samples of FeLV-A and five samples of FeLV-B were sequenced using the Sanger method, and the results were used to build a phylogenetic tree and estimate evolutionary divergence. Among cats with lymphoma, 68.8% carried FeLV-AB and 31.2% FeLV-A. Among cats with leukemia, 70% carried FeLV-AB and 30% FeLV-A. Regarding cat characteristics, 50% were young, 30.8% young adults, and 19.2% adults; 88.5% were mixed-breed and 11.5% pure breed; and 42.3% were males and 57.7% were females. Among lymphomas, 62.5% were mediastinal, 31.3% multicentric, and 6.3% extranodal. Regarding histological classification, lymphoblastic and small non-cleaved-cell lymphomas were the most frequently detected. Among leukemia cases, 30% were acute lymphoid, 30% chronic myeloid, and 40% acute myeloid. Phylogenetic analysis showed that FeLV-A SC sequences were closely related to the Arena, Glasgow-1, and FeLV-FAIDS variants. Meanwhile, FeLV-B SC sequences were divergent from one another but similar to the endogenous FELV env gene (enFeLV). In conclusion, FeLV-AB is prevalent in cats with lymphoma and leukemia, highlighting the genetic diversity involved in the pathogenesis of these neoplasms in Brazil.

Factors Affecting Survival on Biologic Treatments in Patients with Rheumatoid Arthritis: A Single-Center Study From Turkey

Objective: In our study, we aimed to determine the factors affecting survival on biologic treatment in adult rheumatoid arthritis (RA) patients using biolog- ical drugs. Materials and Methods: In our study, the data of 245 patients who were followed up with the diagnosis of RA in the Rheumatology Clinic of Trakya University Medical Faculty Hospital between 2013 and 2016 were analyzed retrospectively. 37 patients were excluded due to missing data. The data of the remaining 208 patients were evaluated. Results: In our study, we found that drug survival was reduced by 0.48 times (95% CI 0.23-0.97) in elderly patients and 3 times (95% CI 1.09-10.3) in females. According to the results of our study, drug survival is shortened 8 times (95% CI 2.12-32.5) in patients with hyperlipidemia and 1.03 times (95% CI 1.01-1.04) in patients with high pretreatment erythrocyte sedimentation rate (ESR). In addition, we found that shorter drug survival 9.2 times (95% CI 2.4-35.3) in patients with Hepatitis B surface antigen (HBsAg) positivity, 2.9 times (95% CI 1.3-6.4) in patients with antibody positivity against citrullinated protein (ACPA), in patients using glucocorticoids 0.36 times (95% CI 0.17-0.76). Despite that; in patients with chronic kidney disease, drug survival was prolonged by 0.18 times (95% CI 0.06-0.57). Conclusion: When starting biologic drugs in RA patients, some parameters may help to predict drug survival. According to the order of effect; while HBsAg positivity, presence of hyperlipidemia, female gender, ACPA positivity, high ESR, advanced age and glucocorticoid use were negative markers for drug survival; chronic kidney damage can be a positive marker.

Will Preoperative Synovial Fluid Antigen Testing Change Our Clinical Practice?

Commentary In their article, Toler et al. evaluated the diagnostic performance of a recently launched synovial fluid antigen test for the preoperative diagnosis of periprosthetic joint infection (PJI). The test is of great interest because identifying the causative microorganism prior to the surgical procedure is important in guiding surgical decision-making and starting targeted antimicrobial treatment as soon as possible. Toler et al. demonstrated a high concordance between synovial fluid culture and the antigen test. Moreover, in culture-negative synovial fluids, the test identified a microorganism in 49% of cases. However, from a clinical point of view, there are important limitations that should be taken into consideration. With regard to how the test will guide antibiotic treatment, the following shortcomings should be taken into account. A limited number of species (i.e., Staphylococcus, Enterococcus, and Candida species) are included in the test, as noted in the article, and it is important to keep in mind that the reference test used to calculate the diagnostic accuracy was a positive synovial fluid culture for the included species. A comparison with intraoperative tissue cultures was not performed, and, because the sensitivity of synovial culture is poor, an infection cannot be ruled out in the case of a negative antigen test. Therefore, empirical antibiotic treatment should still be administered in the case of a negative antigen test when a PJI is suspected. In the case of a positive test, it is important to realize that, in addition to the inclusion of a limited number of species that can be detected, the test only identifies species on a genus level. Because the antibiotic treatments for methicillin-sensitive staphylococci compared with methicillin-resistant staphylococci and for Enterococcus faecalis compared with Enterococcus faecium are different, their identification on a genus level cannot fully target antibiotic treatment. Other tests that overcome this limitation are available, such as the recently launched multiplex polymerase chain reaction (PCR) for bone and joint infections1. The BioFire Joint Infection PCR Panel provides a rapid diagnosis (i.e., within 1 hour), includes more genera and identifies pathogens on a species level, and detects resistance genes, which may better guide antimicrobial treatment1. Also, other microorganisms not detected by the PCR test may be involved. According to the literature, around 30% to 40% of PJIs are polymicrobial in nature, with an even higher incidence observed in early postoperative and chronic infections with a sinus tract2,3. Consequently, empirical antibiotic treatment cannot be easily narrowed in the case of a positive antigen test either. With regard to how the test will help us in surgical decision-making, some experts in the field have advocated a 2-stage exchange instead of 1-stage exchange for PJI caused by difficult-to-treat microorganisms such as enterococci and Candida4,5. Therefore, isolating these species prior to the surgical procedure may guide surgical decision-making. However, in the total cohort in the study by Toler et al., Candida species already grew on synovial fluid culture in 338 cases and Enterococcus species grew on culture in 465 cases. More rapid identification that the antigen provides is not needed in chronic infections, as one has time to wait for the final culture results. In the remaining preoperative samples with negative synovial fluid cultures, the antigen test detected Candida in an additional 142 cases and enterococci in an additional 188 cases. If these extra cases were to be considered to represent real infections, rather than false-positives as stated by Toler et al., only 0.3% of candidal infections and 0.4% of enterococcal infections from the total cohort of patients will have been missed when solely relying on preoperative cultures of synovial fluid. This low percentage of missed infections makes one wonder whether the number needed to test is really justified. Last but not least, Toler et al. analyze their results according to whether the preoperative diagnosis, according to the 2018 International Consensus Meeting, was positive or negative, but the inconclusive cases (7.5% of the total cohort) are not included in the final analysis, although these are the cases that are most clinically challenging. Based on the above-mentioned limitations and the way that the results are analyzed, it seems that the evaluated antigen test will not change our daily clinical practice in a large number of cases. Additional analyses, particularly comparisons with the final postoperative diagnosis and intraoperative culture results, are needed to define the role of this test in the diagnostic workup.

Treatment of Prostate Cancer with CD46-targeted 225Ac Alpha Particle Radioimmunotherapy.

Radiopharmaceutical therapy is changing the standard of care in prostate cancer and other malignancies. We previously reported high CD46 expression in prostate cancer and developed an antibody-drug conjugate and immunoPET agent based on the YS5 antibody, which targets a tumor-selective CD46 epitope. Here, we present the preparation, preclinical efficacy, and toxicity evaluation of [225Ac]DOTA-YS5, a radioimmunotherapy agent based on the YS5 antibody. [225Ac]DOTA-YS5 was developed, and its therapeutic efficiency was tested on cell-derived (22Rv1, DU145), and patient-derived (LTL-545, LTL484) prostate cancer xenograft models. Biodistribution studies were carried out on 22Rv1 tumor xenograft models to confirm the targeting efficacy. Toxicity analysis of the [225Ac]DOTA-YS5 was carried out on nu/nu mice to study short-term (acute) and long-term (chronic) toxicity. Biodistribution study shows that [225Ac]DOTA-YS5 agent delivers high levels of radiation to the tumor tissue (11.64% ± 1.37%ID/g, 28.58% ± 10.88%ID/g, 29.35% ± 7.76%ID/g, and 31.78% ± 5.89%ID/g at 24, 96, 168, and 408 hours, respectively), compared with the healthy organs. [225Ac]DOTA-YS5 suppressed tumor size and prolonged survival in cell line-derived and patient-derived xenograft models. Toxicity analysis revealed that the 0.5 μCi activity levels showed toxicity to the kidneys, likely due to redistribution of daughter isotope 213Bi. [225Ac]DOTA-YS5 suppressed the growth of cell-derived and patient-derived xenografts, including prostate-specific membrane antigen-positive and prostate-specific membrane antigen-deficient models. Overall, this preclinical study confirms that [225Ac]DOTA-YS5 is a highly effective treatment and suggests feasibility for clinical translation of CD46-targeted radioligand therapy in prostate cancer.

Multisystem inflammatory syndrome in neonates (MIS-N): a systematic review.

Recently, a new pattern of multisystem inflammatory syndrome following an infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has emerged globally. The initial cases were described in the adult population followed by sporadic cases in the pediatric population also. By the end of 2020, similar reports were recognised in the neonatal age group. The purpose of this study was to systematically review clinical characteristics, laboratory parameters, treatment, and outcomes of neonates with multisystem inflammatory syndrome in neonates (MIS-N). A systematic review was conducted after registering with PROSPERO and electronic databases including MEDLINE, EMBASE, PubMed, SCOPUS, Google Scholar, and Web of Science were searched from January 1st 2020 till September 30th 2022. A total of 27 studies describing 104 neonates were analysed. The mean gestation age and birth weight was 35.9 ± 3.3weeks and 2255.7 ± 783.7g respectively. A large proportion (91.3%) of the reported cases belonged to the South-East Asian region. The median age of presentation was 2days (range: 1-28days) with cardiovascular system being the predominant system involved in 83.65% followed by respiratory (64.42%). Fever was noted in only 20.2%. Commonly elevated inflammatory markers were IL-6 in 86.7% and D-dimer in 81.1%. Echocardiographic evaluation suggested ventricular dysfunction in 35.8% and dilated coronary arteries in 28.3%. Evidence of SARS-CoV-2 antibodies (IgG or IgM) was seen in 95.9% neonates and evidence of maternal SARS-CoV-2 infection, either as history of COVID infection or positive antigen or antibody test, was noted in 100% of the cases. Early MIS-N was reported in 58 (55.8%) cases, late MIS-N in 28 (26.9%), and 18 cases (17.3%) did not report the timing of presentation. There was a statistically increased proportion of preterm infants (67.2%, p < 0.001), and a trend towards increased low birth weight infants, in the early MIS-N group when compared to the infants with late MIS-N. Fever (39.3%), central nervous system (50%), and gastrointestinal manifestations (57.1%) were significantly higher in the late MIS-N group (p = 0.03, 0.02, 0.01 respectively). The anti-inflammatory agents used for the treatment of MIS-N included steroids 80.8% which were given for a median of 10 (range 3-35) days and IVIg in 79.2% with a median of 2 (range 1-5) doses. The outcomes were available for 98 cases, of whom 8 (8.2%) died during treatment in hospital and 90 (91.8%) were successfully discharged home. Conclusion: MIS-N has a predilection for late preterm males with predominant cardiovascular involvement. The diagnosis is challenging in neonatal period due to overlap with neonatal morbidities and a high risk of suspicion is warranted, especially in presence of supportive maternal and neonatal clinical history. The major limitation of the review was inclusion of case reports and case series, and highlights need of global registries for MIS-N. What is Known: • A new pattern of multisystem inflammatory syndrome following SARS-CoV-2 infection has emerged in adult population with sporadic cases now being reported in neonates. What is New: • MIS-N isan emerging condition with a heterogeneous spectrum and has a predilection for late preterm male infants.Cardiovascular system is the predominant system involved followed by respiratory, however fever remains an uncommon presentation unlike other age-groups. There are two subtypes based on timing of presentation, with early MIS-N being reported more in preterm and low-birth weight infants.

Development of an indirect ELISA test for the detection of Tilapia lake virus (TiLV) in fish tissue and mucus samples

A serological test for screening of TiLV in Oreochromis niloticus would be useful for the epidemiological investigations. Using polyclonal antisera against TiLV (TiLV-Ab), an indirect enzyme-linked immune sorbent assay (iELISA) was developed for the detection of TiLV antigen in fish tissue and mucus. After a cutoff value was established and antigen and antibody concentrations were optimized, the iELISA's sensitivity and specificity were assessed. We found the ideal dilutions of TiLV-Ab as 1: 4000 and secondary antibody as 1:65,000. High analytical sensitivity and moderate specificity were displayed by the developed iELISA. The Positive and Negative Likelihood Ratio (LR+, LR-) were 1.75 and 0.29, respectively. The estimated Positive and Negative Predictive Values (PPV and NPV) of the test were 76.19% and 65.62%, respectively. The accuracy of the developed iELISA was estimated as 73.28%. An immunological survey was performed using the developed iELISA with samples from the field and 155/195 fishes tested positive, indicating a 79.48% TiLV antigen positives. Among the pooled organs and mucus tested, the highest positive rate of 92.3% (36/39) is observed in mucus compared to other tissues, and least positive rate is found in liver of 46% (18/39). The newly designed iELISA proved sensitive and may be helpful for extensive examinations of TiLV infections and monitoring disease status even from apparently healthy samples using a non-invasive technology by collecting mucus as sample for iELISA.