Antigen Titers Research Articles

Epidemiological and clinical features of a large blastomycosis outbreak at a paper mill in Michigan.

Blastomycosis is an environmentally acquired fungal infection that can result in severe pulmonary illness and high hospitalization rates. In 2023, a blastomycosis outbreak was detected among workers at a paper mill in Delta County, Michigan. We included patients with clinical and laboratory evidence of blastomycosis who had spent ≥40 hours in Delta County since September 1, 2022 and had illness onset December 1, 2022-July 1, 2023. We assessed epidemiological and clinical features of patients and evaluated factors associated with hospitalization. We performed whole-genome sequencing to characterize genetic relatedness of clinical isolates from eight patients. In total, 131 patients were identified; all had worked at or visited the mill. Sixteen patients (12%) were hospitalized; one died. Compared with non-hospitalized patients, more hospitalized patients had diabetes (p=0.03) and urine antigen titers above the lower limit of quantification (p<0.001). Hospitalized patients were also more likely to have had ≥1 healthcare visits before receiving a blastomycosis diagnostic test (p=0.02) and to have been treated with antibiotics prior to antifungal prescription (p=0.001). All sequenced isolates were identified as Blastomyces gilchristii and clustered into a distinct outbreak cluster. This was the largest documented blastomycosis outbreak in the United States. Epidemiologic evidence indicated exposures occurred at or near the mill, and genomic findings suggested a common exposure source. Patients with diabetes may have increased risk for hospitalization, and elevated urine antigen titers could indicate greater disease severity. Early suspicion of blastomycosis may prompt earlier diagnosis and treatment, potentially reducing unnecessary antibiotic prescriptions and improving patient outcomes.

The relationship between lung CT features and serum cryptococcal antigen titers in localized pulmonary cryptococcosis patients

BackgroundTo explore the associations of computed tomography (CT) image features with the serum cryptococcal antigen (CrAg) titers measured by the lateral flow assay (LFA) in localized pulmonary cryptococcosis patients.MethodsA retrospective analysis of patients with pathologically confirmed pulmonary cryptococcosis admitted to the First Affiliated Hospital of Xiamen University from January 2016 to December 2022 was performed. Clinical data, CT results, serum CrAg-LFA test results, and follow-up data were collected and analyzed.ResultsA total of 107 patients with localized pulmonary cryptococcosis were included, of which 31 had a single lesion in chest CT and the other 76 had multiple lesions. The positivity rate was (94.74% vs 64.52%) and titers of serum CrAg-LFA (1.77 ± 0.87 vs 0.91 ± 0.98) in the multiple lesion group were higher than those in the single lesion group, respectively. Multivariate linear regression analysis showed that the serum CrAg titers were positively associated with the number of lesions (β, 0.08; 95% CI, 0.05 to 0.12) and the lesion size (β, 0.40; 95% CI, 0.31 to 0.50) after adjusting other covariates. The serum CrAg-LFA titers of 60 pulmonary cryptococcosis patients showed a decreasing trend with the reduction in pulmonary lesion size after effective therapy.ConclusionIn pulmonary cryptococcosis patients, the number and size of lung lesions are positively correlated with the titers of the serum CrAg-LFA test. The CrAg-LFA test could be a useful tool for the diagnosis, severity assessment, and therapeutic monitoring of localized pulmonary cryptococcosis patients.

Effects of Rotavirus NSP4 on the Immune Response and Protection of Rotavirus-Norovirus Recombinant Subunit Vaccines in Different Immune Pathways.

Diarrheal disease continues to be a major cause of global morbidity and mortality among children under 5 years of age. To address the current issues associated with oral attenuated rotavirus vaccines, the study of parenteral rotavirus vaccines has promising prospects. In our previous study, we reported that rotavirus nonstructural protein 4 (NSP4) did not increase the IgG antibody titer of co-immune antigen but did have a protective effect against diarrhea via the intramuscular injection method. Here, we explored whether NSP4 can exert adjuvant effects on mucosal immune pathways. In this study, we immunized mice via muscle and nasal routes, gavaged them with the rotavirus Wa strain or the rotavirus SA11 strain, and then tested the protective effects of immune sera against both viruses. The results revealed that the serum-specific VP8* IgG antibody titers of the mice immunized via the nasal route were much lower than those of the mice immunized by intramuscular injection, and the specific IgA antibodies were almost undetectable in the bronchoalveolar lavage fluid (BALF). NSP4 did not increase the titer of specific VP8* antibodies in either immune pathway. Therefore, in the two vaccines (PP-NSP4-VP8* and PP-VP8*+NSP4) used in this study, NSP4 was unable to perform its potential adjuvant role through the mucosal immune pathway. Instead, NSP4 was used as a co-immunized antigen to stimulate the mice to produce specific binding antibodies that play a protective role against diarrhea.

Enhanced and cross-reactive in vitro memory B cell response against Epstein-Barr virus nuclear antigen 1 in multiple sclerosis.

Multiple sclerosis (MS) is a prototypical autoimmune disease of the central nervous system (CNS). In addition to CD4+ T cells, memory B cells are now recognized as a critical cell type in the disease. This is underlined by the fact that the best-characterized environmental risk factor for MS is the Epstein-Barr virus (EBV), which can infect and persist in memory B cells throughout life. Several studies have identified changes in anti-EBV immunity in patients with MS. Examples include elevated titers of anti-EBV nuclear antigen 1 (EBNA1) antibodies, interactions of these with the MS-associated HLA-DR15 haplotype, and molecular mimicry with MS autoantigens like myelin basic protein (MBP), anoctamin-2 (ANO2), glial cell adhesion molecule (GlialCAM), and alpha-crystallin B (CRYAB). In this study, we employ a simple in vitro assay to examine the memory B cell antibody repertoire in MS patients and healthy controls. We replicate previous serological data from MS patients demonstrating an increased secretion of anti-EBNA1380-641 IgG in cell culture supernatants, as well as a positive correlation of these levels with autoantibodies against GlialCAM262-416 and ANO21-275. For EBNA1380-641 and ANO21-275, we provide additional evidence suggesting antibody cross-reactivity between the two targets. Further, we show that two efficacious MS treatments - natalizumab (NAT) and autologous hematopoietic stem cell transplantation (aHSCT) - are associated with distinct changes in the EBNA1-directed B cell response and that these alterations can be attributed to the unique mechanisms of action of these therapies. Using an in vitro system, our study confirms MS-associated changes in the anti-EBNA1 memory B cell response, EBNA1380-641 antibody cross-reactivity with ANO21-275, and reveals treatment-associated changes in the immunoglobulin repertoire in MS.

Evaluating the Status of Hepatitis B Vaccination in Healthcare Workers at a Central Laboratory in a Tertiary Care Hospital and Research Centre.

Introduction Hepatitis B virusis a significant occupational hazard for healthcare workers worldwide. Long-term protection against hepatitis B infection is conferred by the vaccineand the protective immune response is indicated by anti-hepatitis B surface antigen (HBsAg) titre. It is crucial to monitor anti-HBsAg titres as their levels decrease over time. The study aims to evaluate thestatus of hepatitis B vaccination among personnel working in the Central Laboratory of Shri B.M. Patil Medical College Hospital and Research Centre. The focus is on understanding the immunization practices and protection levels against HBV within this high-risk group. Materials and methods A cross-sectional analysis was conducted, including collecting demographic data, determining HBsAgstatus, evaluating anti-HBsAg titre value, and getting vaccination details of the laboratory personnel. The study participants included doctors, lab technicians, and attendants who were assessed for both vaccination coverage and immunity levels. After obtaining their written consent, 4 ml of blood was collected in sterile blood collection tubes. All the samples were tested for HBsAg. The negative samples were tested for anti-hepatitis B surface antigen antibody (HBsAg-Ab (IgG)) titre. The enzyme-linked immunosorbent assay (ELISA) method was used to evaluate the obtained samples for HBsAg and anti-HBsAg titre. Results A total of 99 healthcare workerswere included in the study. Most of the laboratory healthcare workers were in the age range of 20-30 years.In 84.8% of the subjects, protective antibody levels (>10 IU/ml) were found. The highest protection was seen among doctors (94.5%), followed by lab technicians (82.9%) and attendants (66.6%). However, 15.2% exhibited inadequate immunity, predominantly among the attendants (33.3%). The highest vaccination coverage was among doctors (91.8%), followed by lab technicians (78.7%) and attendants (53.3%). Most doctors had completed the full vaccination schedule (70.2%) or received a booster dose (24.3%) compared to lab technicians (57.4%)and attendants (46.6%). Conclusion The study highlights effective preventive measures against HBV among laboratory healthcare workers, as indicated by the absence of active infections. But it also emphasizes the necessity of focused initiatives to raise vaccination rates, particularly among attendants, in order to guarantee complete protection against HBV for all levels of laboratory workers.

Antigen titers in cryptococcal meningitis: what determines how fast they fall?

Follow-up of previously healthy patients surviving cryptococcal meningitis found that cryptococcal antigen could be detected for more than one year in serum from 38 of 44 (86%) patients and in CSF from 20 of 31 patients (67%), far beyond the time of culture conversion. The speed of titer decline, measured as the number of days for a two fold drop in titer to occur, was slower in serum than in CSF. Speed of decline of antigen titers was much slower in serum and CSF for patients infected with C. gattii than C. neoformans. The speed of decline in CSF and serum titers was also much slower in patients who had received a ventriculoperitoneal shunt for increased intracranial pressure. The variable and extraordinarily slow rate of clearance in our patients did not appear to reflect differences in disease control but rather differences in species and shunting for increased intracranial pressure.

Potential therapeutic biomolecules of hymenopteran venom against SARS-CoV-2 from Egyptian patients

The therapeutic potential of insect-derived bioactive molecules as anti-SARS-CoV-2 agents has shown promising results. Hymenopteran venoms, notably from Apis mellifera (honeybee) and Vespa orientalis (oriental wasp), were examined for the first time in an in vitro setting for their potential anti-COVID-19 activity. This assessment utilized an immunodiagnostic system to detect the SARS-CoV-2 nucleocapsid antigen titer reduction. Further analyses, including cytotoxicity assays, plaque reduction assays, and in silico docking-based screening, were performed to evaluate the efficacy of the most potent venom. Results indicated that bee and wasp venoms contain bioactive molecules with potential therapeutic effects against SARS-CoV-2.Nevertheless, the wasp venom exhibited superior efficacy compared to bee venom, achieving a 90% maximal (EC90) concentration effect of antigen depletion at 0.184 mg/mL, in contrast to 2.23 mg/mL for bee venom. The cytotoxicity of the wasp venom was assessed on Vero E6 cells 48 h post-treatment using the MTT assay. The CC 50 of the cell growth was 0.16617 mg/mL for Vero E6 cells. The plaque reduction assay of wasp venom revealed 50% inhibition (IC50) at a 0.208 mg/mL concentration. The viral count at 50% inhibition was 2.5 × 104 PFU/mL compared to the initial viral count of 5 × 104 PFU/mL. In silico data for the wasp venom revealed a strong attraction to binding sites on the ACE2 protein, indicating ideal interactions. This substantiates the potential of wasp venom as a promising viral inhibitor against SARS-CoV-2, suggesting its consideration as a prospective natural preventive and curative antiviral drug. In conclusion, hymenopteran venoms, particularly wasp venom, hold promise as a source of potential therapeutic biomolecules against SARS-CoV-2. More research and clinical trials are needed to evaluate these results and investigate their potential for translation into innovative antiviral therapies.

#1173 The duration of SARS-CoV-2 persistence in dialysis patients was inversely correlated with serum albumin levels

Abstract Background and Aims Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who are undergoing dialysis are known to experience delayed viral clearance. However, the clinical characteristics that contribute to viral persistence in these patients have not been well documented. This study reviewed a case series of dialysis patients infected with SARS-CoV-2 at Yokohama General Hospital to investigate factors affecting the duration of viral persistence. The association between clinical features and the duration of SARS-CoV-2 persistence, as assessed by serial viral antigen (Ag) titers, was examined. Method This was a retrospective observational study of 22 dialysis patients infected with SARS-CoV-2 between February 2022 and September 2023 at Yokohama General Hospital. Patients who tested positive for SARS-CoV-2 RNA in nasopharyngeal swabs or saliva were diagnosed with coronavirus disease 2019 (COVID-19). Those with confirmed COVID-19 were serially tested for SARS-CoV-2 Ag on nasopharyngeal swabs. The duration of viral persistence was defined as the interval between the day of diagnosis and the first day that Ag titers fell below 10 pg/mL. Clinical parameters were collected and their association with the duration of Ag positivity was examined. Parameters analyzed included age, body mass index (BMI), dialysis vintage, serum albumin and C-reactive protein (CRP), COVID-19 severity at diagnosis, fever duration, and comorbidities including cardiovascular disease, diabetes, hypertension, and dyslipidemia. COVID-19 severity was classified as mild, moderate I, moderate II, or severe, following the Japanese Ministry of Health, Labour and Welfare guideline. The groups were compared using the Kruskal-Wallis test. Spearman's rank correlation coefficient was used to analyze the correlation. Statistical analyses were performed using JMP version 17. Results Out of the 22 dialysis patients who were infected with SARS-CoV-2, two were excluded from the study due to a lack of serial results for SARS-CoV-2 Ag. Five of the patients were outpatients, while the remaining were infected in hospital clusters. The patients had a mean age of 76.6 years (SD=7.1), and 17 of them were male. Ten of the patients had diabetes mellitus, 11 had hypertension, and 10 had dyslipidemia. Cardiovascular disease was excluded from the analysis because all patients, except for two, had it. The median BMI was 19.45. The median dialysis vintage was 57.5 months. Serum albumin levels ranged from 1.4 g/dl to 4.0 g/dl, with a median of 3.1 g/dl, and CRP levels ranged from 0.38 mg/dl to 8.70 mg/dl, with a median of 2.57 mg/dl. At the time of diagnosis, 15 and 5 patients were classified as having mild and moderate I disease, respectively. Seventeen patients had fever, which lasted from 1 to 11 days, with a median of 3 days. The duration of antigen positivity ranged from 10 to 26 days with a median of 18 days. The duration of Ag positivity showed an inverse correlation with serum albumin levels, which was the only parameter associated with viral clearance (Table 1 and Fig. 1). Conclusion Serum albumin levels were associated with prolonged viral clearance in a small series of dialysis patients infected with SARS-CoV-2 in our study. Serum albumin levels may have prognostic value for the viral clearance in dialysis patients.

Association of HBeAg decline rate from mid-pregnancy to delivery with HBeAg seroconversion after delivery in hepatitis B virus-infected mothers.

There is still controversy about whether to continue antiviral therapy (AVT) after delivery, especially for pregnant women in the immune tolerance (IT) phase. In this study, a retrospective cohort study was conducted to explore the relationship between hepatitis B e antigen (HBeAg) decline rate (%) from mid-pregnancy to delivery and HBeAg seroconversion postpartum among patients using nucleos(t)ide analogs (NAs) to prevent mother-to-child transmission (MTCT), with the goal of identifying the ideal candidates for postpartum AVT continuation. This retrospective cohort study included 151 postpartum women. Univariate and multivariable logistic regression analyses were conducted to assess the association between the HBeAg decline rate (%) from mid-pregnancy to delivery and HBeAg seroconversion postpartum. Receiver operating characteristic (ROC) analysis was utilized to evaluate the predictive capacity of the HBeAg decline rate (%) and determine the optimal cut-off point. The univariate analysis revealed a significant association between the HBeAg decline rate (%) and HBeAg seroconversion postpartum (OR 1.068, 95% CI: 1.034-1.103, p < .001). In the multivariate regression analysis, adjusting for age, hepatitis B surface antigen (HBsAg) titre (log10 IU/mL) at mid-pregnancy, HBeAg titre (log10 S/CO) at mid-pregnancy, and hepatitis B virus (HBV) DNA load decline rate (%) from mid-pregnancy to delivery, the HBeAg decline rate(%) remained significantly associated with HBeAg seroconversion postpartum (OR 1.050, 95% CI: 1.015-1.093, p = .009). Then HBeAg decline rate (%) was treated as a categorical variable (tertiles) for sensitivity analysis. In the three distinct models, taking Tertile1 as a reference, women in Tertile3 still had a 4.201-fold (OR 4.201, 95% CI: 1.382-12.773, p = .011) higher risk of developing HBeAg seroconversion (p for trend <.05) after adjusting above covariates. The area under the curve (AUC) was 0.723 (95% CI: 0.627-0.819). The optimal cut-off value was 5.43%, with a sensitivity of 0.561, specificity of 0.791, and Youden's index of 0.352.A higher HBeAg decline rate (%) from mid-pregnancy to delivery independently correlated with an increased risk of HBeAg seroconversion postpartum. This decline rate can serve as a valuable clinical indicator for predicting HBeAg seroconversion.

A laboratory-based cross-sectional study about helicobacter pylori infection and diabetes.

Despite the numerous articles discussing the relationship between diabetes mellitus type 2 (DMT2) and chronic Helicobacter pylori (H. pylori) infection the results have been inconsistent, necessitating further research. This study investigated the coexistence of Helicobacter pylori infection and DMT2. We conducted a study in selected laboratories in Tehran, measuring the H.Pylori stool antigen (HpSA) in individuals referred by physicians for a glycosylated hemoglobin A1c (HbA1c) test. Out of the 2500 patients who were referred to randomly selected laboratories, a total of 2025 (81%) patients had serum HbA1c levels above 6.5%. of 2025 patients with HbA1c levels above 6.5%, 1321 (52.84%) had HpSA in their stool. No significant gender difference was observed, with a mean age ± SD, 48.65 ± 7.55. HpSA was positive in 52.84% of the DM group, while in the non-DM group, HpSA was positive in 37.36% of cases. Fecal antigen titers are not related to gender (P = 0.274) but are related to age (r = 0.213, P=0.034). Long-term infection with Helicobacter pylori may be significantly associated with elevated HgA1c.Testing for H. pylori infection, regular monitoring of blood sugar and HbA1c levels in high-risk people can prevent DMT2.

Anti-GM-CSF autoantibodies predict outcome of cryptococcal meningitis in patients not infected with HIV: A cohort study

ObjectivesTo explore the seroprevalence of anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies in non-HIV cryptococcal meningitis (CM) and assess its predictive value for survival. MethodsThis is a retrospective study of 12 years of non-HIV CM. We detected serum anti-GM-CSF autoantibodies, and evaluated the clinical features and outcomes, together with the exploration of prognostic factors for 2-week and 1-year survival. ResultsA total of 584 non-HIV CM cases were included. 301 of 584 patients (51.5%) were phenotypically healthy. 264 Cryptococcus isolates were obtained from cerebrospinal fluid (CSF) culture, of which 251 were identified as C. neoformans species complex and 13 as C. gattii species complex. Thirty-seven of 455 patients (8.1%) tested positive for serum anti-GM-CSF autoantibodies. Patients with anti-GM-CSF autoantibodies were more susceptible to C. gattii species complex infection (66.7% vs. 6.3%; p < 0.001) and more likely to develop pulmonary mass lesions with a diameter >3 centimetres (42.9% vs. 6.5%; p 0.001). Of 584 patients 16 (2.7%) died within 2 weeks, 77 of 563 patients (13.7%) died at 1 year, and 93 of 486 patients (19.1%) lived with disabilities at 1 year. Univariant Cox regression analysis found that anti-GM-CSF autoantibodies were associated with lower 1-year survival (HR, 2.66; 95% CI, 1.34–5.27; p 0.005). Multivariable Cox proportional hazards modelling revealed that CSF cryptococcal antigen titres ≥1:1280 were associated with both, reduced 2-week and 1-year survival rates (HR, 5.44; 95% CI, 1.23–24.10; p 0.026 and HR, 5.09; 95% CI, 1.95–13.26; p 0.001). DiscussionPresence of serum anti-GM-CSF autoantibodies is predictive of poor outcomes, regardless of host immune status and the causative Cryptococcus species complex.

The Correlations between the Intensity of Histopathological Ubiquitin-Specific Protease 11 Staining and Progression of Prostate Cancer.

Ubiquitin-specific protease 11 (USP11), one of the principal phosphatase and tensin homolog (PTEN) deubiquitinases, can reserve PTEN polyubiquitination to maintain PTEN protein integrity and inhibit PI3K/AKT pathway activation. The aim of the current study was to investigate the associations between immunohistochemical USP11 staining intensities and prognostic indicators in individuals with prostate cancer. Tissue microarrays (TMAs) were performed for human prostate cancer and normal tissue (control) samples. Data on patient's age, Gleason score, plasma prostate-specific antigen (PSA) titer, disease stage, and presence of seminal vesicles, lymph nodes, and surgical margin involvement were collected. A pathologist who was blinded to the clinical outcome data scored the TMA for USP11 staining intensity as either positive or negative. Cancerous tissues exhibited lower USP11 staining intensity, whereas the neighboring benign peri-tumoral tissues showed higher USP11 staining intensity. The degree of USP11 staining intensity was lower in patients with a higher PSA titer, higher Gleason score, or more advanced disease stage. Patients who showed positive USP11 staining were more likely to have more optimal clinical and biochemical recurrence-free survival statistics. USP11 staining intensity in patients with prostate cancer is negatively associated with several prognostic factors such as an elevated PSA titer and a high Gleason score. It also reflects both biochemical and clinical recurrence-free survival in such patients. Thus, USP11 staining is a valuable prognostic factor in patients with prostate cancer.

Hepatocellular Carcinoma and Hepatitis: Advanced Diagnosis and Management with a Focus on the Prevention of Hepatitis B-Related Hepatocellular Carcinoma.

Though the world-wide hepatitis B virus (HBV) vaccination program has been well completed for almost thirty years in many nations, almost HBV-related hepatocellular carcinoma (HCC) occurs in unvaccinated middle-aged and elderly adults. Apparently, treating 80% of qualified subjects could decrease HBV-related mortality by 65% in a short period. Nevertheless, globally, only 2.2% of CHB patients undergo antiviral therapy. The HBV markers related to HCC occurrence and prevention are as follows: the HCC risk is the highest at a baseline of HBV DNA of 6-7 log copies/mL, and it is the lowest at a baseline of an HBV DNA level of >8 log copies/mL and ≤4 log copies/mL (parabolic, and not linear pattern). The titer of an HBV core-related antigen (HBcrAg) reflecting the amount of HBV covalently closed circular DNA (ccc DNA) in the liver is related to HCC occurrence. The seroclearance of HBs antigen (HBsAg) is more crucial than HBV DNA negativity for the prevention of HCC. In terms of the secondary prevention of hepatitis B-related HCC involving antiviral therapies with nucleos(t)ide analogues (NAs), unsolved issues include the definition of the immune-tolerant phase; the optimal time for starting antiviral therapies with NAs; the limits of increased aminotransferase (ALT) levels as criteria for therapy in CHB patients; the normalization of ALT levels with NAs and the relation to the risk of HCC; and the relation between serum HBV levels and the risk of HCC. Moreover, the first-line therapy with NAs including entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF) remains to be clarified. Discussed here, therefore, are the recent findings of HBV markers related to HCC occurrence and prevention, unsolved issues, and the current secondary antiviral therapy for the prevention of HBV-related HCC.

Quantitative Dynamic Contrast-Enhanced Magnetic Resonance Parameters Could Predict International Society of Urological Pathology Risk Groups of Prostate Cancers on Radical Prostatectomy.

The International Society of Urological Pathology (ISUP) grade and positive surgical margins (PSMs) after radical prostatectomy (RP) may reflect the prognosis of prostate cancer (PCa) patients. This study aimed to investigate whether DCE-MRI parameters (i.e., Ktrans, kep, and IAUC) could predict ISUP grade and PSMs after RP. Forty-five PCa patients underwent preoperative DCE-MRI. The clinical characteristics and DCE-MRI parameters of the 45 patients were compared between the low- and high-risk (i.e., ISUP grades III-V) groups and between patients with or without PSMs after RP. Multivariate logistic regression analysis was used to identify the significant predictors of placement in the high-risk group and PSMs. The DCE parameter Ktrans-max was significantly higher in the high-risk group than in the low-risk group (p = 0.028) and was also a significant predictor of placement in the high-risk group (odds ratio [OR] = 1.032, 95% confidence interval [CI] = 1.005-1.060, p = 0.021). Patients with PSMs had significantly higher prostate-specific antigen (PSA) titers, positive biopsy core percentages, Ktrans-max, kep-median, and kep-max than others (all p < 0.05). Of these, positive biopsy core percentage (OR = 1.035, 95% CI = 1.003-1.068, p = 0.032) and kep-max (OR = 1.078, 95% CI = 1.012-1.148, p = 0.020) were significant predictors of PSMs. Preoperative DCE-MRI parameters, specifically Ktrans-max and kep-max, could potentially serve as preoperative imaging biomarkers for postoperative PCa prognosis based on their predictability of PCa risk group and PSM on RP, respectively.

Hepatitis C virus/Hepatitis B virus coinfection: Current prospectives.

In endemic areas, hepatitis C virus (HCV)/hepatitis B virus (HBV) coinfection is common, and patients with coinfection have a higher risk of developing liver disease such as hepatocellular carcinoma, liver fibrosis and cirrhosis. In such cases, HCV predominates, and HBV replication is suppressed by HCV. HCV core proteins and interferons that are activated by HCV are responsible for the suppression of HBV. Immunosuppression is also seen in patients with HCV and HBV coinfections. A decrease in HCV-neutralizing antibody response and circulation of Th1-like Tfh cells is observed in patients with HCV and HBV coinfection. Both viruses interacted in the liver, and treatment of HCV/HBV coinfection is genotype-based and complex due to the interaction of both viruses. In HCV-dominant cases, direct-acting antiviral drugs and peg interferon plus ribavirin are used for the treatment, with continuous monitoring of AST and ALT. HBV-dominant cases are less common and are treated with peg interferon and nucleoside nucleotide analogues with monitoring of AST and ALT. The SVR rate in HCV-HBV coinfection is higher than that in monoinfection when treated with direct-acting antiviral drugs. But there is a risk of reactivation of HBV during and after therapy. The rate of reactivation is lower in patients treated with direct-acting antiviral drugs as compared to those treated with peg interferon plus ribavirin. Biomarkers of HBV such as HBcrAg, HBV DNA and HBVpg RNA are not effective in the prediction of HBV reactivation; only the hepatitis B surface antigen titre can be used as a biomarker for HBV reactivation. HCV can also be reactive, but this is found in very rare cases in which HBV is present and is treated first.

Clinical Value of Hepatitis B Virus RNA Detection in Patients with Chronic Hepatitis B Infection

Objective: To study the clinical value of hepatitis B virus pregenomic RNA (HBV-pgRNA) detection in the treatment of hepatitis B. Methods: 60 patients with hepatitis B were included in the study. Serum HBV-pgRNA and HBV DNA levels in different phases of infection and during treatment were detected, and serum hepatitis B surface antigen (HbsAg) titer was detected by chemiluminescent immunoassay. DNA was extracted from liver biopsy tissue, and covalently closed circular DNA was detected to predict the therapeutic value in patients. Results: At the initial stage of treatment, the level of HBV-pgRNA in phase I, II, III, and IV showed a gradual decrease. Comparing the levels of HBV-pgRNA before and after treatment, we found that the level of HBV-pgRNA was significantly lower after treatment (P &lt; 0.05). Among the indicators for predicting HBsAg seroconversion, the accuracy of HBV-pgRNA level was 85.0% (51/60). Conclusion: The clinical value of HBV-pgRNA detection in the treatment of hepatitis B is high.

Persistent neurological symptoms and elevated intracranial pressures in a previously healthy host with cryptococcal meningitis

Cryptococcal meningoencephalitis can occur in both previously healthy and immunocompromised hosts. Here, we describe a 55 year-old HIV-negative male with no known prior medical problems, who presented with three months of worsening headaches, confusion, and memory changes without fever. Magnetic resonance imaging of the brain demonstrated bilateral enlargement/enhancement of the choroid plexi, with hydrocephalus, temporal and occipital horn entrapments, as well as marked periventricular transependymal cerebrospinal fluid (CSF) seepage. CSF analysis yielded a lymphocytic pleocytosis and cryptococcal antigen titer of 1:160 but sterile fungal cultures. Despite standard antifungal therapy and CSF drainage, the patient had worsening confusion and persistently elevated intracranial pressures. External ventricular drainage led to improved mental status but only with valve settings at negative values. Ventriculoperitoneal shunt placement could thus not be considered due to a requirement for drainage into the positive pressure venous system. Due to this persistent CSF inflammation and cerebral circulation obstruction, the patient required transfer to the National Institute of Health. He was treated for cryptococcal post-infectious inflammatory response syndrome with pulse-taper corticosteroid therapy, with resultant reductions in CSF pressures along with decreased protein and obstructive material, allowing successful shunt placement. After tapering of corticosteroids, the patient recovered without sequelae. This case highlights (1) the necessity to consider cryptococcal meningitis as a rare cause of neurological deterioration in the absence of fever even in apparently immunocompetent individuals and (2) the potential for obstructive phenomena from inflammatory sequelae and the prompt response to corticosteroid therapy.

Current Epidemiology and Clinical Features of Cryptococcus Infection in Patients Without Human Immunodeficiency Virus: A Multicenter Study in 46 Hospitals in Australia and New Zealand.

Patients without human immunodeficiency virus (HIV) are increasingly recognized as being at risk for cryptococcosis. Knowledge of characteristics of cryptococcosis in these patients remains incomplete. We conducted a retrospective study of cryptococcosis in 46 Australian and New Zealand hospitals to compare its frequency in patients with and without HIV and describe its characteristics in patients without HIV. Patients with cryptococcosis between January 2015 and December 2019 were included. Of 475 patients with cryptococcosis, 90% were without HIV (426 of 475) with marked predominance in both Cryptococcus neoformans (88.7%) and Cryptococcus gattii cases (94.3%). Most patients without HIV (60.8%) had a known immunocompromising condition: cancer (n = 91), organ transplantation (n = 81), or other immunocompromising condition (n = 97). Cryptococcosis presented as incidental imaging findings in 16.4% of patients (70 of 426). The serum cryptococcal antigen test was positive in 85.1% of tested patients (319 of 375); high titers independently predicted risk of central nervous system involvement. Lumbar puncture was performed in 167 patients to screen for asymptomatic meningitis, with a positivity rate of 13.2% where meningitis could have been predicted by a high serum cryptococcal antigen titer and/or fungemia in 95% of evaluable cases. One-year all-cause mortality was 20.9% in patients without HIV and 21.7% in patients with HIV (P = .89). Ninety percent of cryptococcosis cases occurred in patients without HIV (89% and 94% for C. neoformans and C. gattii, respectively). Emerging patient risk groups were evident. A high level of awareness is warranted to diagnose cryptococcosis in patients without HIV.

Prognostic impact of perioperative change in serum p53 antibody titers in esophageal squamous cell carcinoma.

The clinical effectiveness of tumor markers for estimating prognosis in esophageal squamous cell carcinoma (ESCC) remains unclear. We assessed the clinical impact of changes in perioperative serum p53 antibodies (s-p53-Abs) titers in ESCC. From January 2011 to March 2021, 249 patients were enrolled in this study. Titers of s-p53-Abs were measured before the initial treatment and 3months after esophagectomy. Patients were divided into a s-p53-Abs decreased or unchanged group (Group D, n = 217) and an increased group (Group I, n = 32). Short- and long-term outcomes were compared between the groups. There was no correlation between the changes in squamous cell carcinoma antigen and carcinoembryonic antigen titers and recurrence site, number of recurrent lesions, and prognosis. However, the recurrence rate was significantly higher in Group I than in Group D (53.1% vs. 28.6%, p = 0.008), especially for distant organ recurrence (37.5% vs. 18.4%, p = 0.019). Furthermore, the rate of polyrecurrence was higher in Group I than in Group D (34.4% vs. 14.3%, p = 0.009). Recurrence-free survival (RFS) was significantly worse in Group I than in Group D (median survival time, 21.2months vs. 36.7months, p = 0.015). Multivariate analysis revealed that lymphatic vessel infiltration (hazard ratio [HR], 1.721; 95% CI 1.069-2.772; p = 0.026), blood vessel infiltration (HR, 2.348; 95% CI 1.385-3.982; p = 0.002), advanced pathological stage (≥ III) (HR, 3.937; 95% CI 2.295-6.754; p < 0.001), and increased s-p53-Abs titers (HR, 2.635; 95% CI 1.488-4.667; p = 0.001) were independent predictors of poor RFS. Elevation of s-p53-Abs titers after esophagectomy can predict polyrecurrence in distant organs and poor prognosis.

Successful Treatment with High-Dose Immunoglobulin of a Complicated Patient with Catatonia and Central Nervous System Autoantibodies

Ms. X is a 52-year-old Filipino female with no prior psychiatric or medical history who initially presented to an outside hospital for new onset headache, neck pain, and altered mental status. She was admitted inpatient medicine service and was found to have HIV/AIDs and cryptococcal meningoencephalitis. Ms. X had a good response to appropriate antifungal therapies and was able to discharge home with full resolution of symptoms on high dose fluconozaole. Unfortunately, Ms. X developed transaminitis on high dose fluconazole, the dose was reduced and she presented to our institution with recurrent cryptococcal meningoencephalitis as evidenced by elevated titers of cryptococcal antigen in CSF and MRI studies showing T2 and FLAIR hyperintensities in bilateral basal ganglia, thalamus and medial temporal lobes and evidence of intracranial hypertension. Consequently, Ms. X developed prominent neuropsychiatric symptoms including agitation, cognitive impairment, paranoia, visual hallucinations and symptoms of catatonia. Despite adequate treatment of the cryptococcal infection evidenced by decreasing cryptococcal antigen titers in CSF, and appropriate psychiatric treatment, her neuropsychiatric symptoms persisted and her MRI studies continued to show signs of neuroinflammation in the aforementioned areas. Antibody testing for basal ganglia targets was completed to investigate a possible non-infectious cause of neuroinflammation and neuropsychiatric symptoms. Ms. X was found to have elevated titers of anti-D1, anti-GM1 and anti-tubulin receptor antibodies in her CSF. Due to the severity and treatment resistant nature of her neuropsychiatric symptoms, she was treated with 2 g/kg/day IVIG for 4 days. She showed significant improvement in her neuropsychiatric symptoms after 3 days and full resolution of her neuropsychiatric symptoms 1 week following IVIG. Given remarkable clinical response to IVIG a second round of IVIG was administered 2 weeks later in order to sustain the response. After several months of prolonged hospitalization, Ms X was able to discharge to the care of her family and to date her neuropsychiatric symptoms remain in remission. We propose Ms. X’s persistent, treatment resistant neuropsychiatric symptoms were related to a post-infectious inflammatory encephalopathy that responded robustly to IVIG.