Serological Markers Research Articles

Host and Viral Factors Influencing Chronic Hepatitis B Infection Across Three Generations in a Family.

Chronic hepatitis B (CHB) infection is influenced by both virological and host factors. A total of 5,920 CHB patients were classified into four groups based on HBV seromarkers: three-generation families (CHB grandmother, mother, and child), two-generation families (CHB mother/child pairs), individuals recovered from HBV infection, and a control group. Serological markers, viral load, liver function tests (LFT), HBV mutations, HLA-DQ variations, cytokine polymorphisms, and liver stiffness measurements (LSM) were analyzed using FibroScan. Point mutations in genes such as core/pre-core (G1896A/G1899A), polymerase (H248N, H267Q, N263D), S (G145R, S143L), and X (C1500T, T1464C) were observed in 30% of three-generation pairs and 20% of two-generation pairs. The three-generation group exhibited the highest mean liver stiffness measurement (LSM) (4.94 ± 1.24kPa), which is considered a predictor for the development of hepatocellular carcinoma (HCC). Subsequent HLA allele analysis identified HLA-DQB105:01 (OR = 0.27) as a risk factor for treatment resistance, while HLA-DQB105 (OR = 0.98), HLA-DQB103 (OR = 0.80), and HLA-DQB104:01 (OR = 0.70) were associated with HBV persistence in both three- and two-generation groups. Higher frequencies of specific polymorphisms, including G/G (TNF-α: 75%; IL-18: 74%), A/A (IL-10: 74.28%), and C/C (IL-1ß: 80%), were significantly linked to persistent infection. Analysis of viral sequences, HLA-DQB1 variations, cytokine polymorphisms, and genetic relationships within the phylogenetic tree revealed that 40% of CHB patients from three-generation families were infected by a shared source of transmission, as indicated by the presence of the same HBV genotype. This study underscores the complex interplay of host and viral factors that influence hepatitis B infection outcomes and suggests potential familial transmission pathways.

Collagen triple helix repeat-containing 1 protein: an emerging biomarker and its influence on the clinical and sonographic disease severity in Egyptian medicated female rheumatoid arthritis patients

BackgroundRheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease of synovial joints, with a multifactorial etiology. Collagen triple helix repeat-containing 1 protein (CTHRC1) is a biomarker produced by fibroblast-like synoviocytes, which was shown to be highly expressed in RA patients. The study aimed to measure serum CTHRC1 level in female RA patients currently on medical treatment and its influence on the clinical and sonographic severity of the disease.ResultsThe patients’ mean age was 43.39 ± 8.55 years and median RA disease duration of 5.5 (0.33–20) years. RA patients showed significantly higher serum CTHRC1 level [89.71 ng/ml (53.95–353.45)] in comparison to controls [87.38 ng/ml (44.47–110.3)] (U = 430, P = 0.014). Furthermore, higher serum CTHRC1 levels were recorded in seropositive versus seronegative patients (U = 76, P = 0.022) and in RA patients with severe disease activity compared to those with lower disease activity (H = 9.79, P = 0.007). Furthermore, serum CTHRC1 levels were lower in RA patients receiving biological therapy compared to those receiving conventional therapy; however, this difference did not reach statistical significance.Significant positive correlations were found between CTHRC1 and disease activity, acute-phase reactants, serological markers, functional assessment, fatigue, and erosions detected by ultrasound, while a significant negative correlation was recorded between CTHRC1 and duration of biologic intake (rs = − 0.45, P = 0.036). Furthermore, on multivariate linear regression analysis, serum CTHRC1 was the only significant predictor for higher disease activity (P = 0.028, B = 0.009, 95% CI 0.001 to 0.017).ConclusionRA patients showed higher CTHRC1 serum levels compared to healthy controls, especially those with seropositivity and highly active disease. Furthermore, it was positively associated with poor patient functional outcome, fatigability, and erosive findings by ultrasound, thus suggesting that serum CTHRC1 can be a good predictor for high RA disease activity and possibly severity. Moreover, biological therapy could influence serum CTHRC1 levels in these patients.

Undifferentiated embryonal sarcoma of the liver masquerading as a cystadenoma in a young adult: a case report

BackgroundUndifferentiated embryonal sarcoma of the liver is an infrequent hepatic malignancy, primarily observed in the pediatric population. This neoplasm is exceedingly rare among adults. Despite its scarcity in adult cases, it remains imperative to accurately discern undifferentiated embryonal sarcoma of the liver utilizing diverse imaging modalities to prevent misdiagnosis with more prevalent benign and malignant hepatic masses. In this case, a comprehensive imaging examination was conducted, encompassing ultrasound, computed tomography, magnetic resonance imaging, and positron emission tomography–computed tomography scans. Notably, the positron emission tomography–computed tomography scan revealed 18F-fluorodeoxyglucose uptake characteristics indicative of malignancy, providing a pivotal clue for prompt diagnosis of undifferentiated embryonal sarcoma of the liver.Case presentationThis report presents the diagnostic procedure employed for a 37-year-old female patient of Han ethnicity in China diagnosed with undifferentiated embryonal sarcoma of the liver. The patient was admitted with a 2-day history of mid-upper quadrant abdominal pain. The patient’s temperature and inflammatory markers, such as white blood cell count and hypersensitive reactive protein, were slightly elevated. Ultrasound showed a cystic–solid nodule in the liver. The computed tomography revealed a cystic mass in the right lobe of the liver, characterized by a low-density shadow and a lack of significant enhancement during contrast-enhanced scanning, initially suggesting cystadenoma. Enhanced magnetic resonance imaging revealed a block-like abnormal signal shadow in the right hepatic lobe, suggestive of various etiologies, including benign lesions, cystadenoma with hemorrhage, or hemangioma with hemorrhage. However, the positron emission tomography–computed tomography showed increased 18F-fluorodeoxyglucose consumption within both the cystic wall and lesion, raising suspicion of malignancy. Surgical resection of the posterior hepatic lobe was performed under general anesthesia after comprehensive preoperative preparations. During the procedure, a space-occupying lesion was identified in the right posterior hepatic lobe, adhering to the diaphragm. Surface liver parenchyma overlying the tumor exhibited rupture, with several blood clots visible. The tumor was successfully and completely excised. Pathological examination revealed a fusiform cell tumor, necrosis, hemorrhage, cystic changes, cellular atypia, mitotic images, and eosinophilic globules suggestive of undifferentiated embryonal sarcoma of the liver. Immunohistochemical staining indicated CK (+), vimentin (Vim; +), Desmin (+), actin (−), α1-AT (+), GPC-3 (+), PDGFRa (+), MDM2 (+), P16 (+), Ki-67 (+) 30–35%, and PAS (+). The patient underwent five cycles of combination chemotherapy with ifosfamide and epirubicin, administered at 21-day intervals at our hospital. Following 3 years of postoperative surveillance, the patient remained stable, with no evidence of hepatic tumor recurrence.ConclusionOn the basis of this case and a comprehensive literature review, we recommend that clinicians consider the possibility of undifferentiated embryonal sarcoma of the liver in patients presenting with non-specific clinical and serological markers, particularly when there is inconsistency between ultrasound and computed tomography imaging findings, along with elevated 18F-fluorodeoxyglucose uptake observed in both the cystic wall and lesion on positron emission tomography–computed tomography examination. Given the rarity and high-grade malignancy of undifferentiated embryonal sarcoma of the liver, heightened clinical awareness and recognition are crucial for early diagnosis and successful therapy.

Serological Markers of Clinical Improvement in MuSK Myasthenia Gravis.

In this retrospective longitudinal study, we aimed at exploring the role of (a) MuSK-immunoglobulin G (IgG) levels, (b) predominant MuSK-IgG subclasses, and (c) antibody affinity as candidate biomarkers of severity and outcomes in MuSK-MG, using and comparing different antibody testing techniques. Total MuSK-IgGs were quantified with radioimmunoassay (RIA), ELISA, flow cytometry, and cell-based assay (CBA) serial dilutions using HEK293 cells transfected with MuSK-eGFP. MuSK-IgG subclasses were measured by flow cytometry. SAffCon assay was used for determining MuSK-IgG affinity. Forty-three serum samples were obtained at different time points from 20 patients with MuSK-MG (median age at onset: 48 years, interquartile range = 27.5-72.5; women, 16/20), with 9 of 20 (45%) treated with rituximab. A strong correlation between MuSK-IgG levels measured by flow cytometry and RIA titers was found (rs = 0.74, 95% CI 0.41-0.89, p = 0.0003), as well as a moderate correlation between CBA end-point titers and RIA titers (rs = 0.47, 95% CI 0.01-0.77, p = 0.0414). A significant correlation was found between MuSK-IgG flow cytometry levels and disease severity (rs = 0.39, 95% CI 0.06-0.64, p = 0.0175; mixed-effects model estimate: 2.296e-06, std. error: 1.024e-06, t = 2.243, p = 0.032). In individual patients, clinical improvement was associated with decrease in MuSK-IgG levels, as measured by either flow cytometry or CBA end-point titration. In all samples, MuSK-IgG4 was the most frequent isotype (mean ± SD: 90.95% ± 13.89). A significant reduction of MuSK-IgG4 and, to a lesser extent, of MuSK-IgG2, was seen in patients with favorable clinical outcomes. A similar trend was confirmed in the subgroup of rituximab-treated patients. In a single patient, MuSK-IgG affinity increased during symptom exacerbation (KD values: 62 nM vs 0.6 nM) while total MuSK-IgG and IgG4 levels remained stable, suggesting that affinity maturation may be a driver of clinical worsening. Our data support the quantification of MuSK antibodies by flow cytometry. Through a multimodal investigational approach, we showed that total MuSK-IgG levels, MuSK-IgG4 and MuSK-IgG2 levels, and MuSK-IgG affinity may represent promising biomarkers of disease outcomes in MuSK-MG.

Autoimmune thyroiditis: an update on treatment possibilities.

Autoimmune thyroiditis (AIT) is due to an autoimmune process that destroys thyrocytes, leading to hormonal disorders. AIT is more common in women, and the aetiology is multifactorial. The destruction of thyroid cells may release free thyroid hormones into the bloodstream, causing hyperthyroid symptoms. With further destruction of thyroid cells, patients develop euthyroidism and eventually chronic hypothyroidism. The diagnosis of AIT is based on clinical symptoms, positive anti-thyroid antibodies, ultrasound, and histological features. The main goal of treatment is correcting hormonal disorders and achieving euthyroidism. Treatment of AIT involves replacing thyroid hormone deficiency with the use of synthetic hormones. Prophylactic levothyroxine (L-T4) treatment of euthyroid patients with AIT may reduce both serological and cellular markers of autoimmunisation. Attention should be paid to the starting dose of L-T4, potential drug interactions, and drug formulation. A follow-up should be planned to determine the optimal dose. The authors highlighted that a healthy lifestyle and supplementing selected vitamins and microelements appropriately are essential. In selected clinical conditions, thyroidectomy should be considered. There are also alternative therapeutic strategies, such as herbal medicine and acupuncture, but their effectiveness has yet to be conclusively confirmed in research studies. Monitoring the thyroid gland enlargement and the possibility of developing nodular goitre is integral to patient care over AIT patients. In conclusion, treating AIT is complex, involving thyroid hormone replacement therapy, taking care of a healthy diet and lifestyle, and proper supplementation. It requires an individual approach. Regular follow-up is necessary to control the disease and minimise its effects.

The impact of maternal serum biomarkers on maternal and neonatal outcomes in twin pregnancies: a retrospective cohort study conducted at a tertiary hospital.

Prior prediction models used for screening preeclampsia (PE) in twin pregnancies were found to be inadequate. In singleton pregnancies, various maternal biomarkers have been shown to be correlated with negative pregnancy outcomes. However, the impact of these biomarkers in twin pregnancies remained uncertain. A retrospective cohort study was carried out on 736 twin pregnancies at a tertiary hospital in Hangzhou, China. Multivariable logistic models were employed to examine the association between levels of serological markers and the likelihood of adverse pregnancy outcomes. The final logistic model was formulated as a user-friendly nomogram. The primary outcome assessed was the occurrence of PE. Results were presented as odds ratios (ORs) with corresponding 95% confidence intervals (CIs). The prevalence of PE in the study was 10.3%. When comparing women diagnosed with PE to those without, it was evident that the former group experienced a significantly higher risk of unfavorable maternal and neonatal outcomes. A multivariable logistic regression analysis revealed notable associations between various factors including maternal age, parity, gestational weight gain, a family history of hypertension, as well as levels of cholesterol, albumin, and creatinine and the risk of developing PE, with a significance level of P < 0.05. The concordance index for the constructed nomogram was determined to be 0.792 (95% CI: [0.739-0.844]). Furthermore, an increment of 1 * 1012/L in red blood cell (RBC) count was associated with more than a two-fold increase in the odds of experiencing adverse maternal outcomes (OR 2.247, 95% CI: [1.229-4.107]). However, no significant correlations were identified between any of the examined variables and neonatal outcomes. In this study, we developed a user-friendly predictive model that achieves notable detection rates by incorporating maternal serum biomarker levels alongside maternal characteristics and medical history. Our findings indicate that the probability of adverse maternal outcomes increases with elevated levels of RBCs. Obstetricians should consider intensifying surveillance for these women in clinical practice.

Proteomic and serological markers for diagnosing cardia gastric cancer and precursor lesions in a Chinese population

Cardia gastric cancer (CGC) is prevalent in East Asia, and noninvasive, cost-effective screening methods are needed. This study investigated the diagnostic value of serum pepsinogen (PG), gastrin-17 (G-17), Helicobacter pylori (H. pylori) antibodies, and proteomic profiling for CGC and precancerous lesions. We conducted a case-control study involving biopsy-confirmed patients with CGC (n = 60), low-grade intraepithelial neoplasia (CLGD, n = 60), high-grade intraepithelial neoplasia (CHGD, n = 64), and healthy controls (n = 120) matched for age and sex from high-incidence areas in China. Serological markers including PGI, PGII, G-17, and H. pylori were measured using ELISA and Western blot, while plasma protein markers were assessed using Olink® technology. The VSOLassoBag algorithm and nine machine learning (ML) algorithms were employed to identify crucial features and construct predictive models. Various evaluation metrics, including the area under the receiver-operating-characteristic curve (AUC), were utilized to compare predictive performance. Elevated PGII levels, decreased PGR, and H. pylori infection were significantly associated with an increased risk of CGC and precancerous lesions (P for trend < 0.05). The eXtreme Gradient Boosting (XGBoost) model performed best in discriminative ability among the 9 ML models. Following feature reduction based on predictive performance, a final explainable XGBoost model was developed, incorporating five protein biomarkers (CDHR2, ICAM4, PTPRM, CDC27, and FLT1). This model exhibited excellent performance in distinguishing individuals with CGC and precancerous lesions from healthy controls (AUC = 0.931 for CGC, 0.867 for CHGD, and 0.763 for CLGD), surpassing the traditional serological marker-based model. This study underscores the diagnostic potential of serological markers and proteomic profiling in the detection of CGC. Further validation and exploration of combined biomarker approaches are warranted to enhance early diagnosis and improve outcomes in high-risk populations.

Copaiba Oleoresin Improves Weight Gain and IL-10 Concentration, with No Impact on Hepatic Histology, in Liver Cirrhosis

Copaifera sp. is a native tree in the Amazon region. Copaiba oleoresin has components such as sesquiterpenes, which have anti-inflammatory and antioxidant potential. Liver cirrhosis is the end stage of liver disease with limited therapeutic options. We aimed to evaluate the effect of copaiba oleoresin supplementation on the liver of animals with thioacetamide (TAA)-induced cirrhosis. For the induction of liver cirrhosis, 100 mg/kg of TAA was administered intraperitoneally twice a week for 8 weeks. A total of 200 mg/kg/day of copaiba oleoresin was administered via gavage for the same period. Copaiba oleoresin supplementation improved cirrhosis-associated cachexia by increasing weight gain and body fat. In addition, copaiba oleoresin attenuated systemic inflammation, as shown by the decrease in the circulating C-reactive protein. In the liver, the copaiba oleoresin decreased carbonyl proteins and increased IL-10 compared with TAA-treated rats. TAA groups demonstrated increased SOD, catalase, GST, and GSH activity in the liver. In conclusion, the supplementation of copaiba oleoresin demonstrated a beneficial systemic effect in alleviating cirrhotic cachexia and antioxidant and anti-inflammatory action in the liver. However, it failed to improve the serological and histological markers of liver damage, which could be associated with the advanced stage of the disease.

Hepatitis A, B, and C in Brazilian Afro-Descendant Communities from Northeast Brazil: A Seroepidemiological Survey

Background: Viral hepatitis is a disease that is more prevalent among individuals residing in remote regions and in contexts of social vulnerability. The objective of this study was to ascertain the seroprevalence of hepatitis A (HAV), B (HBV), and C (HCV) in vulnerable communities in the rural area of São João do Piauí (SJP), northern Brazil. Methods: Immunoenzymatic assays were employed to detect the presence of anti-HAV (total and IgM), HBsAg, anti-HBc, anti-HBs, and anti-HCV serological markers in serum samples. Samples that yielded positive results were subjected to further analysis using real-time polymerase chain reaction (PCR). Results: A total of 492 individuals, ranging in age from 3 to 101 years, were consecutively recruited from eight rural communities. The majority of individuals were female (51.2%), over 30 years of age (57.1%), self-identified as Black/Brown (92.2%), and resided in Afro-Brazilian communities, designated as “quilombos” (68.1%). The seroprevalence of anti-HAV was 69.5% (95% CI: 65.4–73.6%), while that of anti-HBc was 4.7% (95% CI: 2.8–6.6%), and that of anti-HBs was 35.2% (95% CI: 30.1–39.4%), and 0.2% (95% CI:0.0–0.6%) for anti-HCV. Conclusions: The seroprevalence rates observed were higher than the national average, and a significant proportion of individuals in the target age groups were susceptible to HBV, despite the availability of vaccination. These findings highlight potential shortcomings in the management of vaccine-preventable diseases, which could have implications for public health.

Bifidumbacterin forte in the treatment of acute viral hepatitis

Relevance. In patients with acute viral hepatitis A and B, favorable conditions are created for the development of dysbacteriosis. As a result, the toxic load on the liver increases. For effective treatment of acute viral hepatitis A and B, it is necessary to examine for intestinal dysbiosis before and after treatment and subsequent correction of identified disorders. Aim. To study the clinical course, functional state of the liver, intestinal microflora in patients with acute viral hepatitis A and B and the effectiveness of using bifidumbacterin forte for the correction of intestinal microflora. Materials and methods. The work used clinical and laboratory data from 54 patients with acute viral hepatitis A and B. The main group of patients received bifidumbacterin forte against the background of basic therapy. Patients in the comparison group were on traditional therapy. Clinical, biochemical, bacteriological parameters were observed before the start of therapy and 15 days after its start, serological markers - upon admission. Results. During the therapy, in patients of the main group, the disappearance of intoxication, lethargy, weakness, pain, and normalization of liver size were observed earlier in comparison with the control group. Symptoms of pigment metabolism disorders disappeared significantly earlier: yellowness of the skin, itching of the skin, changes in the color of urine and feces. A dynamic study of liver tests demonstrated a more rapid reverse development of biochemical disorders of the functional state of the liver in patients who received bifidumbacterin forte as part of complex treatment. Conclusion. The use of bifidumbacterin forte in patients with acute viral hepatitis A and B against the background of basic treatment has a positive effect on some clinical manifestations, biochemical parameters, and individual components of the intestinal microflora.

Activating STAT3 mutations in CD8+ T-cells correlate to serological positivity in rheumatoid arthritis.

Large granular lymphocyte (LGL) leukemia is a rare hematologic malignancy characterized by clonal expansion of cytotoxic T-cells frequent somatic activating STAT3 mutations. Based on the disease overlap between LGL leukemia rheumatoid arthritis (RA)a putative role for CD8+ T-cells in RA we hypothesized that STAT3 mutations may be detected in RA patient CD8+ T-cells correlate with clinical characteristics. Blood samples, clinical parameters, and demographics were collected from 98 RA patients and 9 healthy controls (HCs). CD8+ cell DNA was isolated and analyzed via droplet digital (dd)PCR to detect STAT3 mutations common in LGL leukemia: Y640F, D661Y, and the S614 to G618 region. STAT3 data from 99 HCs from a public dataset supplemented our 9 HCs. RA patients had significantly increased presence of STAT3 mutations compared to controls (Y640F p=0.0005, D661Y p=0.0005). The majority of these were low variant allele frequency (VAF) (0.008-0.05%) mutations detected in a higher proportion of the RA population (31/98 Y640F, 17/98 D661Y) vs. HCs (0/108 Y640F, 0/108 D661Y). In addition, 3/98 RA patients had a STAT3 mutation at a VAF >5% compared to 0/108 controls. Serological markers, RF and anti-CCP positivity, were more frequently positive in RA patients with STAT3 mutation relative to those without (88% vs 59% RF, p=0.047; 92% vs 58% anti-CCP, p=0.031, respectively). STAT3 activating mutations were detected in RA patient CD8+ cells and associated with seropositivity. Thus, STAT3 activating mutations may play a role in disease pathogenesis in a subset of RA patients.

Long-term outcome of tacrolimus-based immunosuppressive treatment for patients with paediatric-onset lupus nephritis.

We have previously reported the mid-term efficacy and safety of tacrolimus (Tac)-based immunosuppressive therapy in such patients, and herein, we aimed to determine their long-term outcomes (over 10 years). We retrospectively evaluate the data of 13 consecutive patients with biopsy-proven long-standing LN who underwent a long-term Tac-based treatment regimen. Tac was administered once daily at a dose of 3 mg as reinduction or maintenance treatment. Treatment outcomes were defined using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), urinary protein/creatinine ratio (Up/cr), serum creatinine, estimated glomerular filtration rate (eGFR) and serological lupus markers (complement C3, complement hemolytic activity [CH 50], and anti-dsDNA antibody titre), and the concomitantly administered prednisolone (PDN) dose. Data on clinical parameters and serological lupus activity were collected annually from each patient throughout the study period. The patients' baseline characteristics at the treatment initiation were as follows: mean age, 18 years; Up/cr, 0.63 ± 0.69; serum C3 level, 57.2 ± 22.4 mg/dL (normal range, 79-152 mg/dL); CH50, 27.9 ± 15.7 U/mL (normal range, 23.0-46.0 U/mL); serum anti-dsDNA antibody titre, 111.7 ± 123.4 IU/mL (normal range, <12.0 IU/mL); serum creatinine, 0.60 ± 0.19 mg/dL; eGFR, 115.6 ± 21.3 mL/min and SLEDAI, 13 ± 8.1. Despite the gradual tapering of the concomitantly administered PDN dose from 18.7 ± 13.5 mg/day at baseline to 3.5 ± 2.8 mg/day at 10 years (p = .002), a marked improvement in the outcomes, compared with the baseline values, was observed within a year. Additionally, these favourable changes persisted throughout study period in most patients. Compared with the baseline values, the following measures confirmed sustained outcome improvements after a 10-year treatment: SLEDAI, 1.7 ± 2.0; serum C3 level, 83.8 ± 16.1 mg/dL; CH50, 45.6 ± 10.9 U/mL (all p < .01) and Up/cr, 0.16 ± 0.18 and serum anti-dsDNA antibody titre, 25.8 ± 28.8 IU/mL (both p < .05). Serum creatinine level and eGFR remained within the normal range in all study participants except for one patient who experienced several flare-ups. No serious adverse effects were observed. Our results suggest that long-term Tac-based immunosuppressive treatment as maintenance therapy is beneficial and has low cytotoxicity. Therefore, it represents an attractive option for the treatment of selected patients with paediatric-onset LN in a real-world setting.

Safety of Hepatitis B Virus Screening in Blood Donors from the Hospital Foundation of Hematology and Hemotherapy of the State of Amazonas (HEMOAM) in the Brazilian Amazon

Background: Hepatitis B is an infectious disease of worldwide importance and of great interest to transfusion medicine. The Amazon region has areas of high endemicity, outlining a worrying scenario for transfusion and epidemiological safety. Objective: To analyze the profiles of serological and molecular markers for HBV of blood donors from HEMOAM. Methods: Blood donors with different patterns of reactivity in serological and molecular screening for HBV were tested for viral load by the qPCR method at the reference center for liver diseases in the state of Amazonas. Results: A total of 230,591 donors were tested, with 3104 (1.34%) found reactive for HBV and 2790 (89.9%) found reactive for isolated anti-HBc. Viral load was not detected in 100% of donors reactive only to HBsAg, while 100% of donors with positive anti-HBc and positive HBsAg or HBV NAT demonstrated a detectable viral load. We also detected one case of occult hepatitis B (0.03%) only with reactive HBV NAT and five donors (0.2%) with positive anti-HBc and HBV NAT. Conclusions: With this result, the great importance of the anti-HBc test for the unsuitability of blood donors was verified, as well as the fundamental introduction of the HBV NAT test in screening for hepatitis B in Brazilian blood banks, as this was the only way to detect the viral infection burden in asymptomatic donors who previously would not be treated, which contributed to the maintenance of the endemicity of hepatitis B in the Brazilian Amazon.

Hepatitis B surface antigen reverse seroconversion after hematopoietic stem cell transplantation according to the baseline serological marker levels and vaccination status: a single-center database analysis

PurposeHepatitis B is a major prognostic factor after hematopoietic stem cell transplantation (HSCT). Currently, no consensus exists regarding the management of various scenarios that can lead to reverse seroconversion of the hepatitis B surface antigen (HBsAg-RS). This study focused on HBsAg-RS, which serves as an indicator of active hepatitis, and aimed to obtain exploratory information on the associated patient and treatment factors.MethodsThis single-center retrospective study utilized clinical data extracted from the electronic medical records of Seoul St. Mary’s Hospital, Korea. Patients who underwent HSCT between January 2013 and December 2018 and tested negative for hepatitis B surface antigen (HBsAg) before undergoing HSCT were included. The associations between HBsAg-RS and demographic information, baseline hepatitis B serological markers, and vaccination status were statistically analyzed.ResultsThis study included 1,344 patients, of whom 83.3% tested positive for the hepatitis B surface antibody (HBsAb) during HSCT. HBsAg-RS occurred in 2.2% of HBsAb-negative patients and 3.0% of HBsAb-positive patients, indicating no significant difference in reactivation rates according to HBsAb status. However, positivity for hepatitis B core antibody (HBcAb) was significantly associated with hepatitis B reactivation (HBsAg-RS rate: 8.0%). The vaccination rates were highest in patients who were negative for both HBsAb and HBcAb and had a transient protective effect.ConclusionThe sufficient patient population enabled the identification of an association between baseline HBcAb positivity and the development of HBsAg-RS. Further prospective studies are warranted to determine optimal vaccination strategies for preventing HBsAg-RS.

Parvovirus B19 remains an underestimated pathogen among infections during gestation in Argentina: Insights through the study of symptomatic and asymptomatic pregnant patients and newborns from Córdoba

BackgroundParvovirus B19 (B19 V) infection during pregnancy can cause adverse fetal outcomes. Our aim was to characterize both clinical and asymptomatic maternal and neonatal cases by studying virological and serological markers of B19 V infection, and to sequence the complete genome of the circulating virus in Argentina. MethodsSymptomatic patients were included based on maternal and/or fetal-neonatal signs attributable to B19 V infection during gestation. Pregnant patients were analyzed in either the timely diagnosis group (TD, samples obtained when symptoms were present and infection was suspected) or the retrospective diagnosis group (RD, samples collected immediately postpartum), and newborns were analyzed at birth. A sample of asymptomatic individuals was also analyzed. Diagnostic tests (PCR/qPCR/serology) and sequencing were performed on archived serum samples from 2018 to 2023, and clinical data were obtained from medical records. ResultsWe studied 328 symptomatic patients, including 185 pregnant patients (73 TD and 112 RD) and 143 newborns. Among them, we identified 27/328 (8.2 %) positive cases (B19V+): 12/73 (16.4 %) in the TD group, 6/112 (5.4 %) in the RD group, and 9/143 (6.3 %) newborns. Within the 77 mother-newborn pairs included, there were 8 (10.4 %) B19 V infections and 6 cases of vertical transmission. Additionally, B19 V infection was detected in 26/310 (8.4 %) asymptomatic patients. Phylogenetic analysis identified genotype 1a as a circulating strain in Argentina. ConclusionsOur findings highlight the need to raise awareness and enhance diagnostic approaches in Argentina to more effectively identify and manage B19 V infections during pregnancy in our region.

A Complex Case of Extrahepatic Biliary Obstruction: Syphilitic abdominal lymphadenitis

Abstract Introduction/Objective Syphilis, a sexually transmitted disease that is caused by spirochete Treponema pallidum, can vary widely in presentation. Infective lymphadenitis due to syphilis have been reported before in cervical and inguinal lymph nodes.Here we present an interesting case of syphilitic lymphadenitis with unusual presentation and location. Methods/Case Report A 30-year-old male with no past medical history presented with epigastric pain, fever, jaundice, weight loss, and night sweats. Computed tomography imaging revealed a 4.1 cm solid mass at the porta hepatis with involvement of perihepatic lymph nodes, raising suspicion of malignancy. All serological tumor markers were negative. The patient underwent ERCP with biliary drainage to relieve obstructive jaundice. Bile duct brushing and liver biopsy at that time were non-diagnostic. Later the patient underwent laparoscopic lymph node excision. Histological examination of the lymph node showed intact follicular architecture with an increase in plasma cells and sinus histiocytes, without evidence of carcinoma or lymphoma cells. Flow cytometry on the lymph node showed polytypic B-cells and antigenically normal T-cells with CD4: CD8 ratio of 0.5 showing relatively excess of CD8 positive cytotoxic cells. Positive staining for Treponema pallidum with appropriate control highlighted micro-organisms suggestive of secondary syphilitic infection. This evidence was later supported by positive rapid plasma reagin (RPR) test. He subsequently tested positive for Human immunodeficiency virus (HIV-1). Results (if a Case Study enter NA) NA Conclusion In summary, appropriate histologic and serological testing lead to timely diagnosis in this case. This case contributes to the limited literature on syphilitic lymphadenitis and reports the first documented case of isolated intra- abdominal lymph node involvement.

Emerging insights into ferroptosis in cholangiocarcinoma (Review).

Cholangiocarcinoma (CCA) is a malignant tumor that arises within the biliary system, which exhibits a progressively increasing incidence and a poor patient prognosis. A thorough understanding of the molecular pathogenesis that drives the progression of CCA is essential for the development of effective molecular target therapeutic approaches. Ferroptosis is driven by excessive iron accumulation and catalysis, lipid peroxidation and the failure of antioxidant defense systems. Key molecular targets of iron metabolism, lipid metabolism and antioxidant defense systems involve molecules such as transferrin receptor, ACSL4 and GPX4, respectively. Inhibitors of ferroptosis include ferrostatin-1, liproxstatin-1, vitamin E and coenzyme Q10. By contrast, compounds such as erastin, RSL3 and FIN56 have been identified as inducers of ferroptosis. Ferroptosis serves a notable role in the onset and progression of CCA. CCA cells exhibit high sensitivity to ferroptosis and aberrant iron metabolism in these cells increases oxidative stress and iron accumulation. The induction of ferroptosis markedly reduces the ability of CCA cells to proliferate and migrate. Certain ferroptosis agonists, such as RSL3 and erastin, cause lipid peroxide build up and GPX4 inhibition to induce ferroptosis in CCA cells. Current serological markers, such as CA-199, have low specificity and cause difficulties in the diagnosis of CCA. However, novel techniques, such as non-invasive liquid biopsy and assays for oxidative stress markers and double-cortin-like kinase 1, could improve diagnostic accuracy. CCA is primarily treated with surgery and chemotherapy. A close association between the progression of CCA with ferroptosis mechanisms and related regulatory pathways has been demonstrated. Therefore, it could be suggested that multi-targeted therapeutic approaches, such as ferroptosis inducers, iron chelating agents and novel modulators such as YL-939, may improve treatment efficacy. Iron death-related genes, such as GPX4, that are highly expressed in CCA and are associated with a poor prognosis for patients may represent potential prognostic markers for CCA. The present review focused on molecular targets such as p53 and ACSL4, the process of targeted medications in combination with PDT in CCA and the pathways of lipid peroxidation, the Xc-system and GSH-GPX4 in ferroptosis. The present review thus offered novel perspectives to improve the current understanding of CCA.

Extrauterine Causes of Severe and Concealed Postpartum Bleeding: Clinical Aspects and Challenges

Abstract Objective To describe the challenges in diagnosing concealed postpartum bleeding, a rare but potentially life-threatening condition, and to highlight key factors in identifying and managing this condition. Methods We reviewed clinical cases and diagnostic approaches where concealed postpartum bleeding was suspected, focusing on the role of imaging, serologic markers, and angiography. We examined instances of hemodynamic instability, the utility of pelvic space analysis via computed tomography, and the limitations of digital angiography, particularly in identifying bleeding sources in the posterior iliac internal artery division. Results Concealed postpartum bleeding often originates from venous damage or, less commonly, arterial injury. Hemodynamic instability was noted to occur periodically, despite negative findings on vaginal examination and ultrasound, leading to diagnostic delays. Digital angiography often yields negative results when the focus is limited to the anterior division of the internal iliac artery. Bleeding typically arises from damage to the vaginal muscular layer or levator ani muscle, both supplied by branches of the internal pudendal artery (posterior iliac division). In some cases, laparotomy also failed to locate the source due to the bleeding being in the subperitoneal spaces. Conclusion Concealed postpartum bleeding presents a diagnostic challenge due to intermittent hemodynamic instability and often negative imaging results. A detailed pelvic space analysis and awareness of posterior iliac internal artery involvement are crucial. Advanced expertise, along with serologic markers of hidden bleeding, is essential for timely diagnosis and management.

The Effect of Lacticaseibacillus paracasei LPC100 and Lactiplantibacillus plantarum LP140 on Bone Mineral Density in Postmenopausal Women: A Multicenter, Randomized, Placebo-Controlled Study

Objectives: modulation of gut microbiota by probiotics has been proposed as a target for intervention to reduce bone mineral density (BMD) loss in the postmenopausal period. This study aims to evaluate the effect of Lacticaseibacillus (L.) paracasei LPC100 and Lactiplantibacillus (L.) plantarum LP140 on BMD in postmenopausal women in a multicenter, randomized, double-blind, placebo-controlled trial. Methods: the primary outcome was the change in T-score of the lumbar spine measured by dual-energy X-ray absorptiometry assessed after twelve-month probiotic supplementation. Secondary outcomes included changes in serological markers of inflammation and calcium–phosphate metabolism, body mass index, gastrointestinal symptoms, and satisfaction with the intervention. Results: a decrease in T-score indicating the progressive bone demineralization reached a statistically significant difference in the placebo group (from mean values of 0.06 ± 1.04 to −0.28 ± 1.12, p = 0.041) but not in the probiotic group (0.19 ± 0.99 and −0.08 ± 1.05, respectively, p = 0.125) with a p-value = 0.089 between the groups. No significant differences were found in secondary outcomes with the exception of vitamin D concentration and a significant reduction in some gastrointestinal symptoms in the probiotic group. A significant decrease in vitamin D level was observed only in the placebo group (p = 0.014). Probiotics were safe and well tolerated. Conclusions: this study suggests that the oral administration of L. paracasei LPC100 and L. plantarum LP140 may be a viable strategy to prevent BMD loss and vitamin D deficiency in postmenopausal women, but further research is necessary to confirm clinical benefits and to know the mechanism of action [ClinicalTrial.gov NCT06375668].

Frequency of hepatitis D virus with different hepatitis B virus serological markers and coinfections in hospital patients from Argentina: synchronous testing of anti-HDV antibodies and HDV RNA.

Hepatitis D virus (HDV) RNA-positive cases with total anti-HDV antibodies nonreactive were documented. Moreover, HDV infection was observed in subjects with occult hepatitis B virus infection. The prevalence of HDV infection in Argentina is low; however, further research in different populations is needed. This study aimed to perform synchronous HDV detection in reactive hepatitis B virus patients treated in a public hospital in the province of Buenos Aires, Argentina, some of whom were coinfected with hepatitis C virus and/or HIV. A total of 189 hepatitis B virus-reactive serum samples with or without hepatitis C virus and/or HIV coinfection were synchronously analyzed for anti-HDV antibodies and HDV RNA. HDV prevalence was 4.2% with HDV RNA found in 61 samples, most of which were nonreactive to anti-HDV antibodies and hepatitis B surface antigen. Genotype 1 was identified in all HDV sequences. Moreover, triple and quadruple infections were observed, showing a high frequency of HDV infection in hospitalized patients not following the recommended diagnostic algorithm. This study is evidence that the synchronous testing of anti-HDV antibodies and HDV RNA is necessary for the diagnosis of HDV infection in Argentina. Finally, further research is necessary to identify high-risk populations and improve prevention and control strategies for triple and quadruple infections and their potential consequences.