Predominant Subtype Research Articles

Atrial functional and ventricular functional mitral regurgitation: definitions, epidemiology, and prognostic implications

Abstract Background Severe functional mitral regurgitation (fMR) can be divided into two subgroups: fMR of atrial (AfMR) and fMR of ventricular origin (VfMR). Studies on AfMR are scarce and inconsistent, lacking a uniform definition of AfMR. Hence, little is known about its epidemiology, morphological features, associated risk profiles, and prognostic implications. Purpose The objective of this study was to develop and test a uniform definition of fMR based on the morphological correlate and to describe demographic characteristics, detail entity-specific morphological features and to investigate the associated prognostic impact. Methods 13052 patients with severe fMR and those at risk of severe fMR (comprising mild and moderate fMR)were included. Based on the ratio of left atrial volume (LA) to left ventricular end-diastolic volume (LVEDV), those with severe fMR (n=1163) were divided into AfMR and VfMR. The median of this ratio was used for allocation. Therefore, a LA/LVEDV ratio ≤ 0.56 indicated predominantly ventricular eccentric remodelling, whereas a ratio > 0.56 indicated predominantly atrial remodelling. Results AfMR was more frequently observed in female patients and peak age was a decade later, compared to VfMR. AfMR was the predominant fMR subtype in patients with heart failure with preserved (76%) and mildly reduced ejection fraction (61%), but a significant proportion could be observed even in patients with heart failure with reduced ejection fraction (32%). Severe fMR was associated with excess mortality for both entities: VfMR HR 1.31 [95% CI: 1.14-1.50], p<0.001, with a more pronounced impact in patients with AfMR HR 1.68 [95% CI: 1.47-1.91], p<0.001; AfMR vs. VfMR: HR 1.27 [95% CI: 1.06-1.54], p=0.011. The association between fMR and excess mortality persisted even after multivariate adjustment. In both entities, ischaemic heart disease was common and resulted in a significant increase of mortality (VfMR: HR 1.67 [95% CI: 1.40-1.98], p for interaction<0.001; AfMR: HR 2.10 [95% CI: 1.75-2.52], p for interaction=0.006). Conclusion Based on the entity-specific morphological correlate, severe fMR can be classified into AfMR and VfMR. AfMR occurs across the entire HF spectrum, is more frequently observed in elderly and female patients, and exhibits a worse prognosis than VfMR. The presence of ischaemic heart disease is associated with a near doubling of mortality in both subgroups of severe fMR.Prevalence of fMRKaplan-Meier analysis

Atrial and ventricular mitral regurgitation in the general population

Abstract Background Functional mitral valve regurgitation (FMR) is the result of two concurrent pathomechanisms: (1) the dilatation of mitral valve annulus (atrial) or (2) remodelling of the left ventricle (ventricular) in the absence of relevant leaflet degeneration¹. Even though FMR has been reported to be the most common cause of relevant MR², there is no general accepted definition of the two subtypes, nor are there population-based data regarding their prevalence, distribution and risk profiles¹. Purpose We aimed to evaluate the prevalence of FMR and to provide an in-depth characterisation of the subtypes aFMR and vFMR in the general population. Methods The study included the first 10,000 participants of the population-based Hamburg City Health Study enrolled between 2016 and 2019. Of these, 8.543 echocardiographic samples were available for analysis. Mitral valve was assessed by two independent investigators. Isolated degenerative MRs as determined by valve mobility (prolapse or restrictive) were excluded. FMR was classified as ventricular when fulfilling one of the following criteria: history of myocardial infarction or coronary artery disease, left ventricular ejection fraction (LVEF) ≤ 40%, restrictive leaflet, tenting area ≥ 150 mm² or coaptation depth ≥ 10 mm. All FMR with LVEF > 55% were classified as atrial. Results After excluding the samples with an insufficient image quality or missing data and re-assessment by the second investigator, 216 of 282 participants with a relevant MR (i.e. moderate or severe) remained (2,6% of the total cohort, see figure 1). In the next step, 153 participants were classified as pure FMR (68.9%), the remaining were mainly functional with minor degenerative features. A total of 31 (14.4%) MRs were classified as vFMR, the remaining 185 participants had an aFMR. Female gender was significantly more common in the aFMR cohort. The remaining demographic variables (age, body mass index) as well as established cardiovascular risk factors (i.e., diabetes, smoking, hypertension) were comparable between the vFMR and aFMR cohort. However, vFMR patients had significantly higher levels of NT-proBNP or NHYA state and presented more frequently with an atrial fibrillation (see figure 2). LVEF and LV stroke volume, TAPSE, left atrial ejection fraction and E/A ratio as a parameter of diastolic dysfunction were lower in the vFMR cohort whereas tenting area and left atrial endsystolic volume was significantly increased. Conclusion In our population-based study, aFMR was found to be the predominant subtype of FMR. The established cardiovascular risk factors were comparable in the vFMR and aFMR cohort. Echocardiographic variables differed significantly and indicate more advanced heart failure and LV remodelling in the vFMR cohort. Further categorization of FMR, in particular regarding the prognostic impact and long-term outcomes, is strongly warranted to allow a clinically relevant definition of aFMR and vFMR.Figure 1:Overview of sample sizeFigure 2:Baseline characteristics

Twelve-lead electrocardiography-based artificial intelligence predicts the upcoming future of patients with heart failure with mildly reduced ejection fraction

Abstract Background Heart failure with mildly reduced ejection fraction (HFmrEF) has emerged as the predominant subtype of heart failure (HF), but there is a paucity of data for identifying it using artificial intelligence (AI) based electrocardiogram (ECG). Purpose This study aimed to develop artificial intelligence (AI)-ECG to identify and predict the prognosis of patients with HFmrEF. Methods We collected 104,336 12-lead electrocardiography (ECG) datasets from April 2009 to December 2021 in a tertiary center. The AI-ECG encompasses a novel model that combines an automatic labelling preprocessing method with a transformer architecture incorporating a triplet loss for HFmrEF analysis. Results The receiver operating characteristic analyses revealed that the area under the curve of AI-ECG for identifying all types of HF were acceptable (0.87, 95% confidence interval [CI]: 0.86-0.89), but that for identifying those with HFmrEF was relatively lower (0.83, 95% CI: 0.78-0.86) than those with HF with reduced ejection fraction (HFrEF) (0.89, 95% CI: 0.85-0.82) and those with normal ejection fraction (EF) (0.87, 95% CI: 0.85-0.89). The analysis of ECG features showed significant increases in QRS duration (p=0.001), QT interval (p=0.045), and corrected QT interval (p=0.041) with increasing ‘Severity by Euclidean distance’. Following the predictability analysis with another group of 1,134 patients for improvements of follow-up EF in HFmrEF, the patients were grouped into three clusters based on the AI- Euclidean distance; Cluster 1 had the most severe cases and poorer outcomes than Clusters 2 (p<0.001) and 3 (p<0.001). Conclusion AI-ECG presents an innovative approach for the prognostic stratification of cardiac contractility in patients with HFmrEF. By using AI-ECG, patients with HFmrEF will be able to predict upcoming disease progression.

Nailfold capillaroscopic assessment in pediatric patients with autoimmune uveitis: a case-control study.

Uveitis is a major cause of visual impairment. Most uveitis cases have autoimmune etiology. Pediatric autoimmune uveitis may be associated with systemic diseases such as juvenile idiopathic arthritis or may arise as an isolated disorder. It may be accompanied by retinal vasculitis due to retinal microcirculation involvement. Nailfold capillaroscopy, a digital microscope, is a non-invasive tool for systemic microcirculation evaluation. We aimed to evaluate systemic microcirculation abnormalities in pediatric autoimmune uveitis. Twenty-five patients with pediatric autoimmune uveitis and 21 healthy children underwent detailed capillaroscopic evaluation. We assessed capillary density/mm, capillary morphology, capillary dimensions, and the presence or absence of microhemorrhages and avascular areas. The mean age of the study and control groups was 11.24 ± 3.03 and 9.9 ± 4.17years, respectively. Most included patients had isolated uveitis and juvenile idiopathic arthritis (64% and 24%, respectively). The predominant uveitis subtype in the study was anterior uveitis (48%). A significant difference was found between cases and controls regarding mean capillary density (p-value = 0.0003) and the number of subjects having capillary density less than 7 (p-value = 0.002). Other capillaroscopic abnormalities did not show any significant difference between the studied groups. Mean capillary density did not correlate significantly with age, disease duration, or acute phase reactants. Children with autoimmune uveitis, whether isolated or asa part of systemic disease, may have systemic microcirculation involvement. Key Points • Idiopathic autoimmune uveitis is not always an isolated intraocular condition. • Systemic microcirculation involvement may occur in pediatric autoimmune uveitis, even in cases with isolated uveitis. • Nailfold capillaroscopy showed that capillary density in children with autoimmune uveitis is significantly reduced compared to healthy controls.

Prevalence of major INSTI and HIV-1 drug resistance mutations in pre- and antiretroviral-treated patients in Indonesia

Indonesia has one of the highest HIV infection rates in Southeast Asia. The use of dolutegravir, an integrase strand transfer inhibitor (INSTI), as a first-line treatment underscores the need for detailed data on INSTI drug resistance mutations (DRMs). Currently, there is a lack of comprehensive data on DRMs INSTI and other HIV drug resistance in Indonesian patients, both pre- and post-treatment. The aim of this study was to identify the subtypes and drug resistance mutations of the protease, reverse transcriptase, and integrase genes in both treatment-naive and ARV-treated patients in Bandung, West Java, Indonesia. A cross-sectional study was conducted involving HIV-positive patients at Hasan Sadikin Hospital, Bandung, Indonesia, from September 2022 to January 2023. The patients were categorized into two groups: ARV-treated and pre-treatment patients. Peripheral blood mononuclear cells (PBMCs) were processed for DNA extraction, followed by amplification and sequencing of the pol gene to detect mutations and subtypes. The study found that the predominant subtype was CRF01_AE, accounting for 85.4% and 69% of pre-treatment and treated patients, respectively, followed by recombinant forms such as A1/CRF01_AE, CRF01_AE/CRF02_AG, subtype B, and other subtypes. Among ARV-treated/INSTI-naive patients, major INSTI DRMs R263K and Y143H were identified, while pre-treatment patients exhibited accessory integrase DRMs. The most common DRMs detected were non-nucleoside reverse transcriptase inhibitor (NNRTI) DRMs, with prevalences of 14.6% and 7% in pre-treatment and ARV-treated patients, respectively. In conclusion, CRF01_AE emerged as the predominant subtype in both pre-treatment and ARV-treated patients in Bandung, underscoring the necessity for ongoing surveillance of integrase DRMs, particularly given the presence of major INSTI DRMs in patients undergoing INSTI treatment.

A vaccine candidate based on baculovirus displaying chikungunya virus E1-E2 envelope confers protection against challenge in mice.

Chikungunya fever is a re-emerging mosquito-borne disease caused by the chikungunya virus (CHIKV) and produces acute arthritis that can progress to chronic disease with arthralgia. The first approved live-attenuated chikungunya vaccine has only recently become available for use in humans in the USA, but the access in endemic regions remains unmet. Here, we exploited the baculovirus display technology to develop a vectored vaccine candidate that exposes the CHIKV membrane proteins E1 and E2 on the baculovirus surface. Using recombinant baculovirus as vector vaccines has both productive and regulatory advantages: they are safe for handling and easy to produce in high titers and are non-pathogenic and non-replicative in mammals but have strong adjuvant properties by inducing humoral and cellular immune responses. CHIKV E1 and E2 envelope proteins with their own signal and transmembrane sequences were expressed on the surface of budded baculovirus virions. Immunization of C57BL/6 mice with non-adjuvanted recombinant baculovirus induced IgG antibodies against E2 with a predominant IgG2c subtype, neutralizing antibodies and a specific IFN-γ CD8+ T-cell response. Immunization with a second dose significantly boosted the antibody response, and mice immunized with two doses of the vaccine candidate were completely protected against challenge with CHIKV showing no detectable viremia or signs of disease. Altogether, baculovirus display of CHIKV envelope proteins served as an efficient vaccine platform against CHIKV.IMPORTANCEThe global spread of chikungunya virus (CHIKV) has disproportionately impacted the Americas that experienced a fourfold increase in 2023 in cases and deaths compared with the same period in 2022. The disease is characterized by acute fever and debilitating joint pain that can become chronic. Despite the socioeconomic burden related to the high morbidity rates of CHIKV infection, a vaccine for CHIKV is currently approved only in the USA. Vaccines are the most effective preventive measure against viral diseases, and advances in the development of different vaccine platforms such as nucleic acids and viral vectors have prompted the rapid deployment of vaccines to contain the COVID-19 pandemic. Here, we report the use of baculovirus display as a strategy for the design of a novel vaccine that provides sterilizing immunity in a mouse model of chikungunya disease. Our results encourage further research regarding the potential of baculovirus as platforms for human vaccine design.

Prognostic impact of intracranial arteriosclerosis subtype after endovascular treatment for acute ischaemic stroke.

The influence of intracranial arteriosclerosis (ICAR) on acute ischaemic stroke (AIS) prognosis is unclear. This study explored its impact, focusing on ICAR subtypes categorized by intracranial carotid artery calcification (ICAC) patterns: intimal or atherosclerotic versus internal elastic lamina calcification or non-atherosclerotic. The aim was to determine their effect on AIS prognosis in patients undergoing endovascular treatment (EVT). This prospective cohort study included consecutive AIS patients with anterior circulation large vessel occlusion undergoing EVT. ICAC, the hallmark of ICAR, was assessed using non-contrast computed tomography to quantify volume and establish the predominant ICAR subtype. The primary outcome was long-term functional outcome, measured by the 90-day modified Rankin Scale score. Secondary outcomes included first-pass effect, revascularization degree, symptomatic intracranial haemorrhage and 24-h infarct volume. Multivariate-adjusted linear and logistic regression models were used to assess the association of ICAC volume and subtype with these outcomes. From January 2021 to February 2022, 181 patients were included, of whom 172 (95%) had ICAC. Internal elastic lamina calcification was the predominant subtype in 103 (57%), intimal in 52 (29%) and mixed in 17 (9%). The intimal or atherosclerotic ICAC pattern was linked to poorer functional outcomes (adjusted odds ratio 2.12, 95% confidence interval [CI] 1.10-4.09), decreased first-pass effect probability (adjusted odds ratio 0.42, 95% CI 0.21-0.84) and higher infarct volume (adjusted β value 22.11, 95% CI 0.55-43.67). A predominant intimal ICAC subtype, linked to underlying atherosclerosis, correlated with larger infarct volume and poorer 90-day functional outcomes in EVT-treated AIS patients. Intracranial atherosclerosis appears to be a relevant factor hampering clinical benefits post-EVT.

Emerging innovative treatment strategies for advanced clear cell renal cell carcinoma.

Dramatic advances in biological discoveries, since the 1990s, have continued to reshape the treatment paradigm of metastatic renal cell carcinoma (RCC). Von Hippel Lindau (VHL) gene alterations are associated with pro-angiogenic activity and are central to the pathogenesis of clear cell RCC (ccRCC), the most predominant histologic subtype of RCC. Antiangiogenic strategies revolving around this VHL/HIF/VEGF axis have been shown to improve survival in metastatic ccRCC. The discovery of immune checkpoints and agents that target their inhibition introduced a new treatment paradigm for patients with RCC. While initially approved as monotherapy, studies investigating immune checkpoint inhibitor combinations have led to their approval as the new standard of care, providing durable responses and unprecedented improvements in clinical outcome. Despite these advances, the projected 14390 deaths in 2024 from RCC underscore the need to continue efforts in expanding and optimizing treatment options for patients with metastatic RCC. This article reviews key findings that have transformed the way we understand and treat metastatic RCC, in addition to highlighting novel treatment strategies that are currently under development.

Comparative study on the epidemiological characteristics and hazards of respiratory syncytial virus and influenza virus infections among elderly people

ObjectiveTo investigate the epidemiological characteristics and infections of respiratory syncytial virus (RSV) and influenza viruses in hospitalized elderly patients with respiratory tract infections in Suzhou City, China, and to compare the differences in clinical characteristics and economic burden associated with these two infections.MethodsIn this prospective study, pathogenetic testing and clinical data for hospitalized patients aged 60 years and older with respiratory tract infections were collected in five hospitals through stratified cluster sampling from December 2023 to May 2024. Comparative study on epidemic characteristics, clinical features and costs of cases who infected RSV alone and influenza alone were conducted.ResultsAmong 1,894 cases included, the RSV positivity rate was 5.91% during the 2023–2024 winter-spring season, while the influenza positivity rate was 9.61%. RSV-B was the predominant subtype of RSV, and influenza A (primarily H3N2) was the dominant strain among the influenza-positive cases. Compared with cases infected influenza virus alone, those infected RSV alone had lower occurrence frequency of fever (18.8% vs. 35.7%, P = 0.004), higher occurrence frequency of complications of lower respiratory tract infections (70.8% vs. 54.8%, P = 0.011), higher direct medical costs ($996.2 vs. $841.1, P = 0.017) and total costs ($1019.7 vs. $888.1, P = 0.036). RSV single infection is more common in female cases (P = 0.007) and diabetic cases (P = 0.007) than influenza virus single infection.ConclusionsDuring the winter and spring months, RSV is the second most common pathogen after influenza virus among older adults hospitalized for respiratory infections in Suzhou, China. Patients infected RSV are more likely to develop complications with lower respiratory tract infections and have higher medical costs than the influenza. RSV infection in the elderly should be emphasized, especially in female patients and diabetic patients.

Descriptive Analysis of Common Fusion Mutations in Papillary Thyroid Carcinoma in Hungary

Thyroid cancer is the most common type of endocrine malignancy. Papillary thyroid carcinoma (PTC) is its predominant subtype, which is responsible for the vast majority of cases. It is true that PTC is a malignant tumor with a very good prognosis due to effective primary therapeutic approaches such as thyroidectomy and radioiodine (RAI) therapy. However, we are often required to indicate second-line treatments to eradicate the tumor properly. In these scenarios, molecular therapies are promising alternatives, especially if specifically targetable mutations are present. Many of these targetable gene alterations originate from gene fusions, which can be found using molecular diagnostics like next-generation sequencing (NGS). Nonetheless, molecular profiling is far from being a routine procedure in the initial phase of PTC diagnostics. As a result, the mutation status, except for BRAF V600E mutation, is not included in risk classification algorithms either. This study aims to provide a comprehensive analysis of fusion mutations in PTC and their associations with clinicopathological variables in order to underscore certain clinical settings when molecular diagnostics should be considered earlier, and to demonstrate yet unknown molecular–clinicopathological connections. We conducted a retrospective fusion mutation screening in formalin-fixed paraffin-embedded (FFPE) PTC tissue samples of 100 patients. After quality evaluation by an expert pathologist, RNA isolation was performed, and then NGS was applied to detect 23 relevant gene fusions in the tumor samples. Clinicopathological data were collected from medical and histological records. To obtain the most associations from the multivariate dataset, we used the d-correlation method for our principal component analysis (PCA). Further statistical analyses, including Chi-square tests and logistic regressions, were performed to identify additional significant correlations within certain subsets of the data. Fusion mutations were identified in 27% of the PTC samples, involving nine distinct genes: RET, NTRK3, CCDC6, ETV6, MET, ALK, NCOA4, EML4, and SQSTM1. RET and CCDC6 fusions were associated with type of thyroidectomy, RAI therapy, smaller tumor size, and history of Hashimoto’s disease. NCOA4 fusion correlated with sex, multifocality, microcarcinoma character, history of goiter, and obstructive pulmonary disease. EML4 fusion was also linked with surgical procedure type and smaller tumor size, as well as the history of hypothyroidism. SQSTM1 fusion was associated with multifocality and a medical history of thyroid/parathyroid adenoma. NTRK3 and ETV6 fusions showed significant associations with Hashimoto’s disease, and ETV6, also with endometriosis. Moreover, fusion mutations were linked to younger age at the time of diagnosis, particularly the fusion of ETV6. The frequent occurrence of fusion mutations and their associations with certain clinicopathological metrics highlight the importance of integrating molecular profiling into routine PTC management. Early detection of fusion mutations can inform surgical decisions and therapeutic strategies, potentially improving clinical outcomes.

Integrase strand transfer inhibitors resistance-associated mutations in HIV-infected pregnant women.

To date, no data exist regarding the prevalence of integrase inhibitor (INSTI) resistance-associated mutations (HIVDRM) in HIV-infected pregnant women (HPW) in Latin America. We describe the prevalence and transmissibility of integrase HIVDRM in a historical cohort of INSTI-naïve HPW from Argentina (n=56) with Next Generation Sequencing (NGS). Bioinformatics analysis was performed by HyDRA software for 20%, 10%, 5%, 2%, and 1% sensitivity thresholds. We calculated the mutational viral load for each INSTI-HIVDRM, considering those with >1000 c/mL as of high risk of transmissibility. The predominant HIV subtype was BF (78.5%). Major HIVDRM were not detected with the population sequencing 20% filter. With a 1% threshold, the prevalence increased to 8.9%; Y143C/S, E92G, E138K, and T66I mutations were found. The median (range) mutational load (expressed in c/mL) was: 355 (50.2-11705); with only 1 case >1000 c/mL Accessory mutations (G163R/K, T97A) were detected mostly with a 20% sensitivity threshold with an overall prevalence of 23.2%; the median (IQR) mutational load was: 23929 (4009-63158) c/mL; all of them above 1000 c/mL. Our results show evidence of the presence of major INSTI-HIVDRM as aleatory mutations and a high frequency of accessory mutations with potential transmissibility in HPW.

Trends in incidence, treatment modalities and prognosis of esophageal adenocarcinoma in the US population

BackgroundEsophageal adenocarcinoma (EAC) was the predominant subtype of esophageal cancer in the Western population. However, an updated and comprehensive analysis of epidemiologic, clinical, and prognostic characteristics of esophageal adenocarcinoma is lacking. Materials and methodsThis was a population-based cohort study using the Surveillance Epidemiology and End-Results (SEER) Database. Patients diagnosed with EAC between 1988 and 2020 were included. Incidence trends, clinical characteristics, treatment patterns, and relative survival were systematically analyzed. ResultsThe overall age-standardized incidence rate of EAC significantly increased from 1.7 per 100000 persons in 1988 to 3.6 per 100000 persons in 2020. There were no significant changes in the distribution of age group, sex, and primary site of EAC over time. However, the proportion of EAC clinically staged as I or II decreased from 35.1 % to 27.9 %. Over time, palliative chemotherapy in metastatic EAC increased from 26.7 % to 41.3 %, combination therapy was still the main treatment strategy for nonmetastatic EAC. Despite the 5-year survival rate was less than 20 %, 1-year survival has experienced a moderate increase from 46.7 % to 53.7 %. Specifically, 1-year survival rate for nonmetastatic EAC undergoing surgery only experienced a significant increase from 80.2 % in 2004–2006 to 94.7 % in 2019–2020. For metastatic EAC, obvious improvement in 1-year survival rate was observed in those treated with systematic therapy (from 26.6 % in 2004–2006 to 41.2 % in 2019–2020). In the multivariable analysis, older age, male sex, lower household income, living without a partner, advanced TNM stage, and receiving no cancer treatment were significantly associated with poor survival. ConclusionIn summary, this population-based study of EAC patients in the US showed an increase in incidence, a shift in treatment modalities for metastatic EAC, and moderately improved 1-year survival. The search for more effective surveillance and treatment strategies should be continued in the future.

Associated impairments among children with cerebral palsy: findings from a cross-sectional hospital-based study in Vietnam

ObjectiveThis study aims to explore the associated impairments of cerebral palsy (CP) and their correlates among children with CP in Vietnam.DesignDescriptive cross-sectional study using hospital-based surveillance.SettingNational Children’s Hospital, Hanoi, Vietnam...

The Other Site of Rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) is a rare malignant soft tissue sarcoma (STS), accounting for almost 50% of pediatric STSs. Due to its heterogeneity, RMS presents challenges in diagnosis and treatment, with prognosis varying depending on multiple factors. Tumors localized in the other site (OTH)-including the paraspinal, perianal, thoracic, abdominal, pelvic, and perineal regions-are generally classified as unfavorable. This study assesses the clinical features and prognoses of RMS in OTH locations depending on its site of origin. An explorative analysis of RMS cases from the SEER 17 database 2000-2020 was conducted. Patients of all ages with histologically confirmed RMS as primary malignant disease classified under OTH, were included. OTH was categorized in four granular site classifications. Overall survival (OS) and disease-specific survival (DSS) were analyzed using Kaplan-Meier estimators. Factors independently influencing survival, including a site classification model presented in this study, were identified through Cox regression analysis. Out of 4168 patients with RMS, 990 cases of RMS with the OTH site met the inclusion criteria. The median age was 16 years. The predominant histological subtypes were embryonal (33.0%) and alveolar (25.5%). Most tumors were ≥ 5 cm (median 9 cm) and located primarily in the pelvic region (41.5%). The 3-, 5-, and 10-year OS rates were 45.4% ± 3.332 (95% CI), 40.7 ± 3.332, and 38.6% ± 3.332, respectively, while DSS rates were 43.3% ± 3.136 (95% CI), 38.3% ± 3.136, and 35.1% ± 3.332. In the multivariate analysis age, histological type, site in a granular categorization, stage, regional lymph node examination, and regional lymph node involvement (pathologically proven) were independently associated with survival. Through both univariate and multivariate analyses, an OTH favorable group could be established. The OTH favorable group consists of the anal region, gallbladder and biliary tract, and breast. RMS in OTH shows significant differences in prognosis, putting the current categorization as unfavorable into question and making a more detailed classification necessary. Furthermore, pathological regional lymph node assessment is specifically in the OTH localization recommended.

P4.07E.06 Distinct Genomic and Immune Microenvironment Features of Solid or Micropapillary Predominant Subtype in Stage I Lung Adenocarcinomas

P4.07E.06 Distinct Genomic and Immune Microenvironment Features of Solid or Micropapillary Predominant Subtype in Stage I Lung Adenocarcinomas

MRNA expression profile and prognostic values of the CDHR family genes in lung adenocarcinoma

Lung adenocarcinoma (LUAD), the predominant subtype of lung cancer, has a high incidence and annual mortality worldwide. Members of the cadherin-related (CDHR) family are associated with many malignant tumor types. However, their role and clinical significance in LUAD have not been clarified. We analyzed the association of CDHRs mRNA expression profiles with prognostic significance, immune infiltration, and potential biological functional signatures in several public databases. We constructed a co-expressed mRNA network, and performed an intrinsic molecular structure and function enrichment analysis. Our results showed that CDHR2 mRNA expression was upregulated in LUAD, whereas CDHR1, CDHR3, CDHR4, and CDHR5 mRNAs were downregulated. Upregulation of CDHR2 mRNA is associated with a poor prognosis in patients with LUAD. Next, the correlation between CDHR family members and immune infiltration was observed. A receiver operating characteristic curve showed that the CDHR family is valuable for diagnosing LUAD. In this study, we found that CDHR2 mRNA expression was upregulated in LUAD. Upregulation of CDHR2 mRNA was associated with a poor prognosis in patients with LUAD.

Diversity, Geographical Distribution and Predictive Factors of Hepatitis C Virus Genotypes and Subtypes in Rwanda

Existing data on the prevalence of hepatitis C virus (HCV) genotypes and subtypes in Rwanda need to be strengthened. The aim of this study was to identify HCV genotypes and subtypes among HCV-infected patients, as well as their geographical distribution in Rwanda, and to identify the social and economic factors that could influence HCV epidemiology which would make it possible to target national preventive and management actions for infected patients. This study included 560 patients with confirmed chronic HCV infection. Patients were recruited from various health facilities in the four provinces of Rwanda as well as in the City of Kigali and had never received treatment with direct-acting antiviral (DAAs). HCV viral loads were measured using Cobas® AmpliPrep/Cobas® TaqMan® HCV Quantitative Test, version 2.0. HCV genotyping was performed using an in-house sequencing protocol targeting the NS5B central region. Genotypic HCV prevalence was correlated with patient geographic location, sociodemographic, behavioral, lifestyle, and clinical factors. HCV genotype 4 was detected in 99.3% of the patients, while genotype 3 was identified in 0.7%. A total of eight (8) HCV subtypes were detected, with 4k being the predominant subtype nationwide (49.5%), followed by subtypes 4r (21.2%), 4q (16.2%), 4v (7.9%), 4b (2.0%), 4l (1.8%), 4c and 3h represent 0.7% each. Our findings reveal subtype distribution variations among provinces. Subtype 4k was prevalent across regions, particularly in Kigali (64.0%) and the Eastern Province (61.6%). Subtype 4q was more common in the northern province (40.7%), 4r in the southern (43.9%) and western provinces (37.1%), and 4v in the eastern province (17.8%). Farmers exhibit a distinct infection profile compared to other occupations, showing a lower prevalence of subtype 4k but a higher prevalence of subtype 4r. Our study revealed that HCV infection is unevenly distributed in Rwanda, dominated by HCV genotype 4, with considerable heterogeneity in the repartition of the different subtypes. We found potential associations between rural/urban lifestyles and HCV subtype profiles. Determined HCV distribution and diversity can serve as basis not only for HCV infection awareness and prevention campaigns, but also success and guidance for personalized treatment.

Breast cancer molecular subtype classification according to immunohistochemistry markers and its association with pathological characteristics among women attending tertiary hospitals in Tanzania

BackgroundBreast cancer immunohistochemistry is a biological characteristic of the tumour which has a role to diagnose molecular subtype, prognosticate and guide treatment and is categorised into 4 subtypes. Data in Tanzania was lacking and was based off data extrapolated from studies in Western Africa thus hypothesizing that women of African ancestry predominately develop Triple Negative Breast Cancer (TNBC). MethodsA retrospective cross-sectional study was carried out at two tertiary referral hospitals on participants who were recruited from the cancer registries from 2015 to 2022. Prevalence of each molecular subtype was determined and association between molecular subtype to demographic and pathological characteristics were evaluated. Predictors of molecular subtypes was then determined using logistic regression. ResultsTotal number of participants were 1214, median age was 50 (IQR: 41–61), median tumor size was 5 cm (IQR: 4–7) with lymph node positivity in 73.7 %. Immunohistochemistry studies showed estrogen, progesterone and Human Epidermal Growth Factor Receptor 2 (HER2) receptor positivity in 54.4 %, 34.4 % and 27.8 % of cases respectively. Molecular subtype classification prevalence for Luminal A was 21.17 % (95 % CI: 18.87–23.47), for Luminal B 35.75 % (95 % CI: 33.05–38.45), for HER2 enriched 11.86 % (95 % CI: 10.04–13.68) and for TNBC 31.22 % (95 % CI: 28.61–33.83). Significant association was seen between molecular subtype with age, tumor size, tumor grade and lymph node involvement. Predictors of Luminal tumors were larger tumor size (aOR 1.217, 95 % CI: 1.149–1.291) no lymph node involvement (aOR 0.429, 95 % CI: 0.313–0.589) while an advanced tumor grade reduced likelihood (aOR 0.041, 95 % CI: 0.011–0.019). ConclusionIn Tanzania Luminal B was most predominant subtype presenting at an earlier age and associated with more favorable pathological characteristics.

HBx induces chemoresistance in diffuse large B cell lymphoma by inhibiting intrinsic apoptosis via the NF-κB/XIAP pathway

Diffuse large B-cell lymphoma (DLBCL) is the predominant subtype of malignant lymphoma in adults with high heterogeneity. Hepatitis B virus (HBV) has been shown to infect B lymphocytes and has been associated with a higher risk of developing DLBCL, most clearly in countries where HBV is endemic. Accumulating evidence suggests the standard chemotherapy regimens for DLBCL patients with HBV infection exhibit limited efficacy and unfavorable outcomes. The HBx antigen, encoded by the X gene in the four open reading frames of HBV, maybe a key molecule promoting the heightened malignant biological characteristics of DLBCL, but whether it affects the chemotherapy response and the mechanism in DLBCL remains unclear. Through the implementation of in vitro and vivo experiments, our study demonstrates that HBx antigen triggers excessive activation of the NF-κB pathway, resulting in increased expression of X-linked inhibitor of apoptosis protein (XIAP). This upregulation inhibits caspase 3-mediated intrinsic apoptosis and enhances resistance to first-line chemotherapeutic agents like epirubicin and vincristine in DLBCL. These findings offer insights into the development of innovative combination therapies for DLBCL patients with HBV infection.

Thyroid Cancer Recurrence: Risk Factors and Preventive Strategies

<i>Introduction</i>: Several risk factors influence the recurrence of thyroid cancer, including age, tumor size, lymph node involvement, and other prognostic indicators. The purpose of this study is to evaluate the impact of these risk factors on the recurrence rates of thyroid cancer, with the aim of improving diagnostic and treatment strategies for better patient outcomes. <i>Aim of the study</i>: The aim of the study was to evaluate risk factors for thyroid cancer recurrence and preventive strategies. <i>Methods</i>: This retrospective cohort study conducted at the Department of Otolaryngology-Head & Neck Surgery at Bangabandhu Sheikh Mujib Medical University (BSMMU) included 108 thyroid cancer patients treated between April 2023 and March 2024. Patients were categorized into low-risk and high-risk groups based on prognostic factors. Follow-up for three years assessed recurrence and survival through outpatient visits and telephone interviews. Statistical analyses using SPSS version 22.0 included descriptive statistics, chi-square tests for recurrence rates, and Kaplan-Meier survival analysis. Result: The study identified Differentiated Thyroid Carcinoma (DTC) as the most common type, with Papillary Thyroid Carcinoma being the predominant subtype. Recurrence rates were notably higher in patients aged ≥45 and in males. Significant predictors of recurrence included age, gender, tumor diameter, and lymph node metastasis. High-risk patients mostly received Total Thyroidectomy, Radioiodine ablation, and Thyroxin. Follow-up showed recurrence rates of 8.33% in low-risk and 7.55% in high-risk patients over three years. <i>Conclusion</i>: The study highlights the critical role of age, gender, tumor diameter, and lymph node metastasis in predicting thyroid cancer recurrence, emphasizing the need for personalized treatment and monitoring based on risk levels.