Antigenic Changes Research Articles

Correlation between specific antibody response to wild-type BNT162b2 booster and the risk of breakthrough infection with omicron variants: Impact of household exposure in hospital healthcare workers

BackgroundThe emergence of omicron variants exhibiting antigenic changes has led to an increase in breakthrough infection among individuals with a wild-type SARS-CoV-2 vaccine booster. The correlation between post-booster spike-specific antibodies and omicron infection risk remains unclear. MethodsThis prospective cohort study included SARS-CoV-2-naive healthcare workers with three-dose BNT162b2. Post-booster spike-specific IgG and interferon-γ levels were measured. Breakthrough infection was documented during a 10-month omicron-predominant period. Household and healthcare contacts were followed to identify subsequent infections. The IgG titers were additionally measured at the end of follow-up, and the titers at exposure were estimated from the two-point titers. ResultsOf 333 participants, 89 developed infection, of whom 37 (41.6 %) were household contacts. Kaplan-Meier curves indicated that higher IgG titers were significantly correlated with lower cumulative infection incidence (p = 0.029), whereas the interferon-γ levels were not (p = 0.926). Multivariate Cox analysis showed that increasing IgG titers were associated with a reduced hazard ratio (HR) of 0.26 (95% CI, 0.12–0.55). Household exposure posed a greater infection risk than healthcare exposure (HRs, 11.24 [6.88–18.40] vs. 2.82 [1.37–5.44]). The difference in geometric mean IgG titers of infected and uninfected participants was significant among household contacts (20,244 AU/mL vs. 13,842 AU/mL, p = 0.031). Estimation of IgG titers at exposure showed a significantly higher infection incidence in those exposed with titers of <3,000 AU/mL than in those with higher titers (79.2 % vs. 32.3 %, p < 0.001). ConclusionsSpike-specific antibodies induced by a wild-type SARS-CoV-2 vaccine booster are suggested to be effective in protecting against omicron infection. Household exposure would be a significant source of infection for hospital healthcare workers.

Diagnostic Overview of Foot-And-Mouth Disease Viruse (FMDV)

Foot-and-mouth disease (FMD) is one of the highly contagious diseases of domestic animals. Sensitive, specific, and quick detection of FMD virus antigens and antibodies is an essential corner stone diagnostic tool at each tier of control strategy. Continued development of molecular and genetic technologies combined with novel analytical techniques will benefit many areas of FMD research and understanding. Genome sequencing provides excellent insight into the evolutionary and epidemiological dynamics of such viruses. The advent of next generation sequencing (NGS) technologies enables evolutionary studies of the entire viral swarm. Sequencing technologies have advanced uses of viral genomic data; which helps to understand the global distribution and Trans-boundary movements of Foot-and-mouth virus disease. Also sequencing information can be used to understand antigenic change within virus strains; therefore, the aim of this review is to assess various diagnostic techniques including conventional and advanced techniques both from agent and host response sides. Among the agent side virus isolation, RT-PCR, antigen ELISA and immune-chromatography strips are commonly used diagnostic tests. Whereas from the host side: infrared thermo gram, antibody ELISA and Virus neutralization are some mentions. Owing to current technological advancement: DNA sequencing and microarray, expressing a luciferase reporter and quantitative proteomics were reviewed. Therefore, potential confirmatory diagnostic test should be in combination with each other.

Host immunity and HBV S gene mutation in HBsAg-negative HBV-infected patients.

Clinically, some patients whose HBsAg becomes negative owing to antiviral therapy or spontaneously still show a low level of HBV DNA persistence in serum. T-lymphocyte subsets, cytokine levels and HBV S gene sequences were analyzed in this study. A total of 52 HBsAg-negative and HBV DNA-positive patients(HBsAg-/HBV DNA+ patients), 52 persistently HBsAg-positive patients(HBsAg+/HBV DNA+ patients) and 16 healthy people were evaluated. T-lymphocyte subsets of these patients were detected by flow cytometry, serum cytokines and chemokines were detected by the Luminex technique, and the HBV S region was evaluated by Sanger sequencing. T%, T-lymphocyte, CD8+ and CD4+T lymphocyte were lower in the HBsAg-negative group than in the HC group. Compared with the HBsAg-positive group, the HBsAg-negative group had lower levels in T lymphocyte %, CD8+T lymphocyte %, CD8+T lymphocyte and CD4/CD8. These difference were statistically significant (P<0.05). Serum IFN-γ, IFN-α and FLT-3L levels were significantly higher in the HBsAg-negative group than in the HBsAg-positive group (P<0.05). However, levels of many cytokines related to inflammation (i.e., IL-6, IL-8, IL10, IL-12, IL-17A) were lower in the HBsAg-negative group. Fifty-two HBsAg-negative samples were sequenced, revealing high-frequency amino acid substitution sites in the HBV S protein, including immune escape mutations (i.e., Y100C, S114T, C124Y, P127L, G130R, T131N, M133T, C137S, G145A) and TMD region substitutions (i.e., E2K/R/D, G7D/R, G10D, A17R, F20L/S, L21V, L22V). According to the results of T-lymphocyte subsets and serum cytokines, it can be deduced that the cellular immune function of HBsAg-negative patients is superior to that of HBsAg-positive patients, with attenuation of liver inflammation. HBsAg-negative patients may show a variety of mutations and amino acid replacement sites at high frequency in the HBV S region, and these mutations may lead to undetectable HBsAg, HBsAg antigenic changes or secretion inhibition.

Characterization of A/H7 influenza virus global antigenic diversity and key determinants in the hemagglutinin globular head mediating A/H7N9 antigenic evolution.

A/H7 avian influenza viruses cause outbreaks in poultry globally, resulting in outbreaks with significant socio-economical impact and zoonotic risks. Occasionally, poultry vaccination programs have been implemented to reduce the burden of these viruses, which might result in an increased immune pressure accelerating antigenic evolution. In fact, evidence for antigenic diversification of A/H7 influenza viruses exists, posing challenges to pandemic preparedness and the design of vaccination strategies efficacious against drifted variants. Here, we performed a comprehensive analysis of the global antigenic diversity of A/H7 influenza viruses and identified the main substitutions in the hemagglutinin responsible for antigenic evolution in A/H7N9 viruses isolated between 2013 and 2019. The A/H7 antigenic map and knowledge of the molecular determinants of their antigenic evolution add value to A/H7 influenza virus surveillance programs, the design of vaccines and vaccination strategies, and pandemic preparedness.

Molecular epidemiology of rotavirus among children in Western Canada: Dynamic changes in genotype prevalence in four consecutive seasons.

Rotavirus molecular surveillance remains important in the postvaccine era to monitor the changes in transmission patterns, identify vaccine-induced antigenic changes and discover potentially pathogenic vaccine-related strains. The Canadian province of Alberta introduced rotavirus vaccination into its provincial vaccination schedule in June 2015. To evaluate the impact of this program on stool rotavirus positivity rate, strain diversity, and seasonal trends, we analyzed a prospective cohort of children with acute gastroenteritis recruited between December 2014 and August 2018. We identified dynamic changes in rotavirus positivity and genotype trends during pre- and post-rotavirus vaccine introduction periods. Genotypes G9P[8], G1P[8], G2P[4], and G12P[8] predominated consecutively each season with overall lower rotavirus incidence rates in 2016 and 2017. The demographic and clinical features of rotavirus gastroenteritis were comparable among wild-type rotaviruses; however, children with G12P[8] infections were older (p < 0.001). Continued efforts to monitor changes in the molecular epidemiology of rotavirus using whole genome sequence characterization are needed to further understand the impact of the selection pressure of vaccination on rotavirus evolution.

The correlation between ABO Blood Groups and Oral Cancer susceptibility- An Observational Study

Background: Oral cancer (OC) in Bangladesh accounts for about 40% of all cancers of the body. Since the majority of human cancers are derived from epithelial cell changes in blood group antigens, it is an important aspect of human malignancies. Recently, it has been suggested that the ABO blood group may affect the development of oral cancer. The aim of this study was to evaluate the association between ABO blood group type and OC. Material &amp; Methods: This observational study was conducted in the Labaid Cancer Hospital and Super Speciality Center, Dhaka, Bangladesh during the period from April 2021 to January 2023. Results: In total 110 patients from both male and female patient who were histopathologically diagnosed of oral cancer were included in the study. In our study we found the most common age group affected in OC was 51-60 years and more in males. The most common site affected by OC was buccal mucosa. Blood group A patients were more common in OC. Conclusion: The presence of antigen A on cells may increase the risk of oral cancer according to our study, while blood type O was less common in these patients.

Bioinformatics and Structural Analysis of Antigenic Variation in the Hemagglutinin Gene of the Influenza A(H1N1)pdm09 Virus Circulating in Shiraz (2013 to 2015).

Circulating influenza A virus provided an excellent opportunity to study the adaptation of the influenza A(H1N1)pdm09 virus to the human host. Particularly, due to the availability of sequences taken from isolates, we could monitor amino acid changes and the stability of mutations that occurred in hemagglutinin (HA). HA is crucial to viral infection because it binds to ciliated cell receptors and mediates the fusion of cells and viral membranes; because antibodies that bind to HA may block virus entry to the cell, this protein is subjected to high selective pressure. In this study, the locations of mutations in the structures of mutant HA were analyzed and the three-dimensional (3D) structures of these mutations were modeled in I-TASSER. Also, the location of these mutations was visualized and studied using Swiss PDB Viewer software and the PyMOL Molecular Graphics System. The crystal structure of the HA from A/California/07/2009 (3LZG) was used for further analysis. The new noncovalent bond formations in mutant luciferases were analyzed via WHAT IF and PIC, and protein stability was evaluated in the iStable server. We identified 33 and 23 mutations in A/Shiraz/106/2015 and A/California/07/2009 isolates, respectively; some mutations are located on the antigenic sites of Sa, Sb, Ca1, Ca2, and Cb HA1 and the fusion peptide of HA2. The results show that with the mutation some interactions are lost and new interactions are formed with other amino acids. The results of the free-energy analysis suggested that these new interactions have a destabilizing effect, which needs confirmation experimentally. IMPORTANCE Due to the fact that the mutations that occurred in the influenza virus HA cause the instability of the protein produced by the virus and antigenic changes and the escape of the virus from the immune system, the mutations that occurred in A/Shiraz/1/2013 were investigated in terms of energy level and stability. The mutations located in a globular portion of the HA are S188T, Q191H, S270P, K285Q, and P299L. On the other hand, the E374K, E46K-B, S124N-B, and I321V mutations are located in the stem portion of the HA (HA2). The change V252L mutation eliminates interactions with Ala181, Phe147, Leu151, and Trp153 and forms new interactions with Gly195, Asn264, Phe161, Met244, Tyr246, Leu165, and Trp167 which can change the stability of the HA structure. The K166Q mutation, which is located within the antigenic site Sa, causes the virus to escape from the immune response.

Comparison of DNA vaccines with AddaS03 as an adjuvant and an mRNA vaccine against SARS-CoV-2

Emerging variants of SARS-CoV-2 call for frequent changes in vaccine antigens. Nucleic acid-based vaccination strategies are superior as the coding sequences can be easily altered with little impact on downstream production. mRNA vaccines, including variant-specific boosters, are approved for SARS-CoV-2. Here, we tested the efficacy of DNA vaccines against the SARS-CoV-2 Spike aided by the AS03 adjuvant using electroporation and compared their immunogenicity with an approved mRNA vaccine (mRNA-1273). DNA vaccination elicited robust humoral and cellular immune responses in C57BL/6 mice with Spike-specific antibody neutralization and T cells produced from 20 μg DNA vaccines similar to that from 0.5 μg mRNA-1273. Furthermore, a Nanoplasmid-based vector further increased the immunogenicity. Our results indicate that adjuvants are critical to the efficacy of DNA vaccines in stimulating robust immune responses against Spike, highlighting the feasibility of plasmid DNA as a rapid nucleic acid-based vaccine approach against SARS-CoV-2 and other emerging infectious diseases.

New Advances and Perspectives of Influenza Prevention: Current State of the Art

The modern world, swaddled in the benefits of civilization, has fostered the development of science and the introduction of products of technological progress. This has allowed serious individual health problems, including those associated with viral diseases, to become targets for prophylaxis, treatment, and even cure. Human immunodeficiency viruses, hepatitis viruses, coronaviruses, and influenza viruses are among the most disturbing infectious agents in the human experience. Influenza appears to be one of the oldest viruses known to man; these viruses were among the first to cause major epidemics and pandemics in human history, collectively causing up to 0.5 million deaths worldwide each year. The main problem in the fight against influenza viruses is that they mutate constantly, which leads to molecular changes in antigens, including outer membrane glycoproteins, which play a critical role in the creation of modern vaccines. Due to the constant microevolution of the virus, influenza vaccine formulas have to be reviewed and improved every year. Today, flu vaccines represent an eternal molecular race between a person and a virus, which neither entity seems likely to win.

Treatment outcomes of radium-223 in patients with metastatic castration-resistant prostate cancer: An experience before National Health Insurance reimbursement in Taiwan.

Radium-223 (Ra-223), an α-particle-emitting isotope, inhibits bony metastases and prevents patients from skeletal-related events in metastatic castration-resistant prostate cancer (mCRPC). We retrospectively reviewed the treatment response, predictive factors, and adverse events (AEs) of Ra-223 before the National Health Insurance reimbursement in a Taiwanese tertiary institute. Patients treated with Ra-223 before January 2019 were enrolled and categorized into progressive disease (PD) and clinical benefits (CB) groups. Laboratory data before and after the treatment were collected, and spider plots concerning percentage changes of alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and prostate-specific antigen (PSA) were prepared and calculated statistically. CB/PD, baseline ALP, LDH, and PSA levels were also adopted as stratification factors for overall survival (OS). Among 19 patients included, 5 (26.3%) and 14 (73.4%) belonged to the PD and CB groups, respectively, with no significant difference observed in the baseline laboratory data. The percentage changes in ALP, LDH, and PSA levels after Ra-223 treatment were statistically significant among the two groups (ALP: CB 54.3 ± 21.4% vs PD 77.6 ± 11.8%, p = 0.044; LDH: CB 88.2 ± 22.8% vs PD 138.3 ± 49.0%, p = 0.046; PSA: CB 97.8 ± 61.7% vs PD 277.0 ± 101.1%, p = 0.002). The trends of LDH between the two groups in spider plot were separated significantly. There were no differences in the AEs between the two groups. CB had a longer median OS than the PD group (20.50 months vs 9.43 months, p = 0.009). Patients with LDH <250 U/L at baseline tended to have longer OS but without significance. The CB rate of Ra-223 was 73.7%. No predictive factor for treatment response was obtained from pretreatment data. The mean percentage changes in ALP, LDH, and PSA levels compared with baseline significantly differed between the CB and PD groups, especially the LDH levels. The CB and PD groups showed different OS, with LDH levels exhibiting the potential to predict OS.

Predicting the antigenic evolution of SARS-COV-2 with deep learning

The relentless evolution of SARS-CoV-2 poses a significant threat to public health, as it adapts to immune pressure from vaccines and natural infections. Gaining insights into potential antigenic changes is critical but challenging due to the vast sequence space. Here, we introduce the Machine Learning-guided Antigenic Evolution Prediction (MLAEP), which combines structure modeling, multi-task learning, and genetic algorithms to predict the viral fitness landscape and explore antigenic evolution via in silico directed evolution. By analyzing existing SARS-CoV-2 variants, MLAEP accurately infers variant order along antigenic evolutionary trajectories, correlating with corresponding sampling time. Our approach identified novel mutations in immunocompromised COVID-19 patients and emerging variants like XBB1.5. Additionally, MLAEP predictions were validated through in vitro neutralizing antibody binding assays, demonstrating that the predicted variants exhibited enhanced immune evasion. By profiling existing variants and predicting potential antigenic changes, MLAEP aids in vaccine development and enhances preparedness against future SARS-CoV-2 variants.

RWD55 Predicting Metastatic Disease Progression in Prostate Cancer Patients Using Machine Learning of PSA Kinetics

Although only 5% of patients with prostate cancer (PCA) have metastases at diagnosis, approximately 20% of those with early stage disease have recurrence with metastases, often years later. Changes in prostate specific antigen (PSA) levels can predict recurrence. A machine learning approach to serum PSA lab kinetics, after diagnosis of localized PCA, was used to forecast progression with metastases.

Trends in diagnosis of de novo metastatic hormone sensitive prostate cancer in US Veterans, 2002-2021.

10527 Background: The incidence of non-localized prostate cancer in the US has been increasing since 2011. While the etiology of this increase is unknown, improved detection of metastatic disease and changes in prostate-specific antigen (PSA) screening may be contributing factors. In this retrospective study, we report the frequency and characteristics of veterans with de novo metastatic prostate cancer to understand changes in the diagnosis over time. Methods: The study population consisted of veterans diagnosed with de novo metastatic Hormone Sensitive Prostate Cancer (mHSPC) with a biopsy between 2002 and 2021 in the Veterans Health Affairs Prostate Cancer Data Core were included. All patients had no prior diagnosis of prostate cancer and were classified as SEER stage ‘distant’. We collected the highest PSA within 3 months of diagnosis, age, race, and calculated the Charlson Comorbidity Index. Year of diagnosis was categorized into 5-year periods and differences over tine were assessed by chi-square linear by linear ANOVA test for linearity as appropriate. Results: 15,485 patients were diagnosed with de novo mHSPC between 2002 and 2021. The mean age was 72.9 years and the median PSA was 88.0 ng/mL. There was a 39% increase of the number of patients diagnosed with mHSPC (from 3,274 between 2002-2006 to 4,560 between 2017-2021). Mean age increased from 71.6 years between 2002-2006 to 74.4 between 2017-2021 (p &lt; 0.001). Median PSA decreased from 96.6 ng/mL in 2002-2006 to 80.3 ng/mL in 2006-2021 (p &lt; 0.001). The percentage of patients who were identified as black decreased from 29.8% between 2002-2006 to 25.4% between 2017 and 2021 (p &lt; 0.001). Mean comorbidity index increased from 3.2 between 2002-2006 to 4.5 between 2017-2021 (p &lt; 0.001). BMI increased from 26.2 between 2002-2006 to 27.2 between 2017-2021 (p &lt; 0.001). Median overall survival improved from 26.7 months in 2002-2006 to 31.7 months in 2016-2021 (p &lt; 0.001). Conclusions: Over a 20-year period, the Veterans diagnosed with prostate cancer were older, with higher comorbidities and with decreased PSA at diagnosis. Additionally, overall survival improved from 26.7 to 31.7 months. The findings of this study are consistent with a reduction in screening and more sensitive imaging modalities to detect metastatic disease combined with changes in the veteran population and improvements in treatment of mHSPC. Further study is warranted to understand these trends over the same time period. [Table: see text]

Molecular predictors and immunomodulatory role of dual checkpoint inhibitor blockade using ipilimumab/nivolumab in patients with extensive stage small cell lung cancer.

8597 Background: Small cell lung cancer (SCLC) is an aggressive neuroendocrine carcinoma with poor prognosis. In extensive stage patients, frontline treatment with chemoimmunotherapy shows modest clinical benefit. However, the biological impact of immunotherapy in SCLC is poorly understood with no clear predictive biomarkers to guide patient selection in this setting. Methods: We collected paired baseline (pre-treatment), on-treatment (week 4), and progression biopsies from patients with relapsed advanced-stage SCLC treated with combination nivolumab (nivo) and ipilimumab (ipi) in a single-arm, phase 2 clinical trial (NCT03670056). Nivo 1 mg/kg and ipi 3 mg/kg were administered every 3 weeks for 4 cycles, followed by nivo maintenance until progressive disease (PD) by RECIST 1.1 or treatment-limiting toxicity. Paired pre/on-treatment samples were available from 16/22 patients, as well as 3 biopsies at progression. The tumor samples were studied using whole exome DNA sequencing (including germline DNA) and RNA-sequencing coupled to Ocean Genomics TxomeAI data analysis pipeline. Results: 6/11 evaluable patients had PD; 5 patients showed clinical activity of treatment (3 with stable disease, 2 with partial response). The frequency of deleterious mutations in TP53 and RB1 was 91% and 64%, respectively. Mutations in HLA-A were more common in baseline samples from patients with PD than those with clinical activity. New TP53 and PLEC mutations were found 4 of 6 patients with PD in week 4 samples vs baseline. The baseline tumor mutational burden was not associated with treatment sensitivity and prominently increased in week 4 biopsies of PD patients. All four molecular SCLC transcriptomic subtypes based on the expression of ASCL1, NEUROD1, and POU2F3 were present in the trial with SCLC-A being the most common (9/16 cases). All patients with clinical activity to ipi/nivo were of SCLC-A subtype. 2/16 of cases showed a different molecular subtype after 4 weeks of treatment: one case with SCLC-N switched to SCLC-A and another case converted from SCLC-A to SCLC-N. Comparison of baseline and on-treatment samples showed upregulation of transcripts associated with T-cell activation and PD-1 signaling. In the 3 biopsies at progression, transcriptomic changes included reduction of neutrophil degranulation, type 1/2 interferon and signatures, as well as down-regulation of β-2 microglobulin, while cell cycle and mitotic prophase pathways were overexpressed. Conclusions: Dual checkpoint blockade using nivo/ipi has a prominent immunomodulatory role in extensive stage SCLC characterized by increased local adaptive immune responses, reduced HLA class-I antigen presentation and change in the molecular subtype in a subset of cases. We identified genomic features associated with treatment sensitivity/resistance. Clinical trial information: NCT03670056 .

Mutual information networks reveal evolutionary relationships within the influenza A virus polymerase.

The influenza A virus (IAV) RNA polymerase is an essential driver of IAV evolution. Mutations that the polymerase introduces into viral genome segments during replication are the ultimate source of genetic variation, including within the three subunits of the IAV polymerase (polymerase basic protein 2, polymerase basic protein 1, and polymerase acidic protein). Evolutionary analysis of the IAV polymerase is complicated, because changes in mutation rate, replication speed, and drug resistance involve epistatic interactions among its subunits. In order to study the evolution of the human seasonal H3N2 polymerase since the 1968 pandemic, we identified pairwise evolutionary relationships among ∼7000 H3N2 polymerase sequences using mutual information (MI), which measures the information gained about the identity of one residue when a second residue is known. To account for uneven sampling of viral sequences over time, we developed a weighted MI (wMI) metric and demonstrate that wMI outperforms raw MI through simulations using a well-sampled severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) dataset. We then constructed wMI networks of the H3N2 polymerase to extend the inherently pairwise wMI statistic to encompass relationships among larger groups of residues. We included hemagglutinin (HA) in the wMI network to distinguish between functional wMI relationships within the polymerase and those potentially due to hitch-hiking on antigenic changes in HA. The wMI networks reveal coevolutionary relationships among residues with roles in replication and encapsidation. Inclusion of HA highlighted polymerase-only subgraphs containing residues with roles in the enzymatic functions of the polymerase and host adaptability. This work provides insight into the factors that drive and constrain the rapid evolution of influenza viruses.

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.

Prognostic role of early prostate specific antigen changes after [177 Lu]Lu-PSMA radioligand therapy of metastasized prostate cancer: A meta-analysis.

Approximately 10%-20% of prostate cancers progress to metastatic and castration-resistant forms (mCRPC). Radioligand (RLT) therapy with [177 Lu]Lu-prostate-specific membrane antigen (PSMA) is an emerging treatment for metastasized mCRPC and its efficacy is assessed not only but also by prostate specific antigen (PSA) measurement after 12 weeks or more after treatment. Our aim was to evaluate the role of early PSA measurement after RLT in predicting overall survival (OS) of mCRPC patients. A systematic search on PubMed, Web Of Science and Scopus was performed from January to December 2022. PRISMA guidelines for prognostic studies was adopted. Risk of bias was assessed using quality of prognostic studies (QUIPS). Twelve studies at low-intermediate risk of bias, were included in the meta-analysis (1646 patients, mean age 70 years). About 50% of patients showed a PSA decline after 1-2 of [177 Lu]Lu-PSMA, and more than 30% reported a PSA decline ≥50%. The median OS range for patients with any PSA decline was 13-20 months, while for patients with stable or increased PSA, the median OS fell to 6-12 months. The OS rate for a PSA decline after the one-two [177 Lu]Lu-PSMA cycles was 0.39 (95% CI: 0.31-0.50), while OS for a PSA decline ≥50% was 0.69 (95% CI: 0.57-0.83). A PSA decline is observed in almost 50% of mCRPC patients after 1-2 [177 Lu]Lu-PSMA cycles, with a significantly longer OS compared to stable or increased PSA levels, respectively. Accordingly, any PSA decline after 1-2 cycles of therapy should be regarded as a favourable prognostic factor for OS.

Circulation of unusual and diverse enteric virus strains in adults with acute gastroenteritis: a study from Pune (Maharashtra), Western India.

In India, studies on the epidemiological and genetic characteristics of enteric viruses in adults with acute gastroenteritis (AGE) are lacking. In this study, fecal samples (n = 110) from adults with acute gastroenteritis in Pune, Western India, were tested for six enteric viruses, and the prevalence of these viruses was as follows: rotavirus A (RVA), 38.5%; enterovirus (EV), 23.1%; astrovirus (AstV), 23.1%; adenovirus (AdV), 7.7%; human bocavirus (HBoV), 7.7%; norovirus (NoV), 0%. Circulation of the RVA G1P[8], G3P[8], G9P[4], CVA-10, echovirus E13, EVC-116, AstV-5, AstV-2, HBoV-1, and AdVC-2 types was observed. When compared to the RotaTeq, Rotarix, and RotaVac vaccine strains, antigenic changes were found in the A, B, C, and F regions of the RVA strains. The circulation of genetically diverse, unusual enteric virus strains, reported here for the first time in adults with acute gastroenteritis, warrants multi-center hospital-based surveillance studies across the country.

Constructing and evaluating the effect of micron-scale structures on von Willebrand factor damage

The incidence of clinical complication gastrointestinal bleeding has been proved as consequence of von Willebrand factor (VWF) damage after mechanical circulatory support in clinic. Many studies have been conducted to evaluate VWF damage, of which the most studied influencing factors are mechanical factors such as shear stress. However, in addition to mechanical factors, VWF damage may also be affected by interface factors. To address this issue, a roller pump circulation platform was established to investigate the effect of material surface micron-scale structures distribution on VWF damage in flow state. A composite micro-structure combining microngrating and micronpost was designed and constructed on the surface of Si wafer by lithography and reactive ion etching, and detailed characterization of material surfaces was also performed. Then the changes of VWF antigen, VWF ristocetin cofactor activity, and the degradation of high molecular weight VWF on these surfaces were investigated and compared. The results showed that, with the encryption of surface micro-structures arrangement, the material surface tends to be more hydrophobic, which is beneficial to reduce VWF damage. Therefore, in the design of material surface inside the mechanical circulatory support devices, it can be considered to add some surface micro-structures with a certain distribution density to change the hydrophilicity and hydrophobicity, so as to minimize the VWF damage. These results can provide important references for the evaluation of VWF damage caused by interface factors, and aid in designing material surface inside the mechanical circulatory support devices.

The Efficacy of Cyclooxygenase-2 Inhibitors for the Male Treatment of Lower Urinary Tract Symptoms: A Systematic Review and Meta-Analysis.

To investigate the potential use of cyclooxygenase-2 (COX-2) inhibitors in the treatment of lower urinary tract symptoms (LUTS) in male patients, we conducted a comprehensive meta-analysis. Our study involved the identification and collection of randomized controlled trials (RCTs) from leading databases including PubMed, MEDLINE, EMBASE, and Cochrane Library. The primary objective of this analysis was to evaluate the effectiveness of COX-2 inhibitors for the treatment of LUTS. Our analysis involved six short-term (within 3 months) RCTs involving 707 patients. We found that COX-2 inhibitor treatment significantly improved the International Prostate Symptom Score (IPSS) of patients (mean difference [MD] = -2.99, 95% confidence interval (CI): -3.65 to -2.33, p < .00001), nocturia frequency (MD = -1.90; 95% CI: -3.18 to -0.61, p = .004), and maximum flow rate (Qmax) (MD = 1.02; 95% CI: 0.06 to 1.98, p = .04). However, no significant differences were found between patients in terms of changes in prostate-specific antigen (PSA) (MD = 0.02; 95% CI: -0.39 to 0.43, p = .92) and total prostate volume (TPV) (MD = -2.93; 95% CI: -6.45 to 0.59, p = .10). Therefore COX-2 inhibitors are an effective treatment for LUTS.