Pure Subtype Research Articles

Clinicopathological characteristics of mucinous breast cancer: a retrospective analysis of a 6-years study from national cancer center in Vietnam.

To evaluate clinicopathological features in women with mucinous breast cancer (MBC), distinguishing between pure (PMC) and mixed (MMC) subtype. A retrospective analysis of all 358 women with MBC treated at Vietnam National Cancer hospital from June 2015 to December 2020. PMC was defined by ≥ 90% mucinous components. We identified 358 women with MBC (245 PMC and 113 MMC) representing 2.7% of all 13,254 BC patients. The proportions of stage I, II, III and IV were 34.9%, 50.8%, 10.4% and 3.9% respectively. The rate of HER2 overexpression was 12%, and only 1.4% of patients was treated with anti-HER2. 193 patients (53.9%) had chemotherapy, including 55 patients (15.4%) treated in the neoadjuvant setting. Only 3 patients (5.5%) achieved pCR. PMC patients were older (54.4 ± 13.3 vs 51.1 ± 13.1years), had lower Ki67 expression, lower incidence of nodal metastasis (N +) (p values < 0.05). At a median follow-up of 58months, the 5-year overall survival rate of non-metastatic patients was 86.6%. Multivariate analysis showed N + to be the most significant prognostic factor (HR = 3.3; 95%CI 1.5-7.1), followed by T-stage (HR = 2.9; 95%CI 1.4-6.3), HER2 + (HR = 2.5; 95%CI 1.2-5.3) and MMC subtype (HR = 1.9; 95%CI 1.0-3.9). Poor prognostic factors of MBC include high T-stage, N-positivity, HER2 overexpression and MMC subtype. Given the low response rate to neoadjuvant CT, upfront surgery is appropriate for MBC patients.

Mapping Transmission Dynamics and Drug Resistance Surveillance in the Cyprus HIV-1 Epidemic (2017-2021).

The human immunodeficiency virus type 1 (HIV-1) epidemic has been a major public health threat on a global scale since the early 1980s. Despite the introduction of combination antiretroviral therapy (cART), the incidence of new HIV-1 infections continues to rise in some regions around the world. Thus, with the continuous transmission of HIV-1 and the lack of a cure, it is imperative for molecular epidemiological studies to be performed, to monitor the infection and ultimately be able to control the spread of this virus. This work provides a comprehensive molecular epidemiological analysis of the HIV-1 infection in Cyprus, through examining 305 HIV-1 sequences collected between 9 March 2017 and 14 October 2021. Employing advanced statistical and bioinformatic techniques, the research delved deeply into understanding the transmission dynamics of the HIV-1 epidemic in Cyprus, as well as the monitoring of HIV-1's genetic diversity and the surveillance of transmitted drug resistance. The characterization of Cyprus's HIV-1 epidemic revealed a diverse landscape, comprising 21 HIV-1 group M pure subtypes and circulating recombinant forms (CRFs), alongside numerous uncharacterized recombinant strains. Subtypes A1 and B emerged as the most prevalent strains, followed by CRF02_AG. The findings of this study also revealed high levels of transmitted drug resistance (TDR) patterns, raising concerns for the efficacy of cART. The demographic profiles of individuals involved in HIV-1 transmission underscored the disproportionate burden borne by young to middle-aged Cypriot males, particularly those in the MSM community, who reported contracting the virus in Cyprus. An assessment of the spatiotemporal evolutionary dynamics illustrated the global interconnectedness of HIV-1 transmission networks, implicating five continents in the dissemination of strains within Cyprus: Europe, Africa, Asia, North America, and Oceania. Overall, this study advances the comprehension of the HIV-1 epidemic in Cyprus and highlights the importance of understanding HIV-1's transmission dynamics through continuous surveillance efforts. Furthermore, this work emphasizes the critical role of state-of-the-art bioinformatics analyses in addressing the challenges posed by HIV-1 transmission globally, laying the groundwork for public health interventions aimed at curbing its spread and improving patient outcomes.

Rates of Viral Non-Suppression and Acquired HIV-1 Drug Resistance Emergence among Children during the Sociopolitical Crisis in the Northwest Region of Cameroon: A Call for Improved Monitoring Strategies.

Virological failure (VF) among children remains concerning, with high risks of HIV drug resistance (HIVDR) emergence and increased disease progression. Therefore, monitoring of viral non-suppression and emerging HIVDR is crucial, especially in the frame of sociopolitical unrest. The study sought to determine the prevalence of VF and evaluate the acquired HIVDR and viral genetic diversity among children in the northwest region of Cameroon during the ongoing sociopolitical crisis. A cross-sectional facility-based study was conducted among HIV-infected children aged ≤18 years, receiving antiretroviral therapy (ART) in urban and rural settings of Northwest Cameroon, from November 2017 through May 2018. Viral load (VL) was done using the Abbott m2000RealTime. Unsuppressed VL was defined as viral load ≥1,000 copies/ml. HIVDR testing was performed by sequencing of HIV-1 protease-reverse transcriptase at the Chantal Biya International Reference Center (CIRCB) using an in-house protocol. Drug resistance mutations (DRM) were interpreted using Stanford HIVdbv8.5 and phylogeny using MEGAv.6. Data were compared between urban and rural areas with p<0.05 considered statistically significant. A total of 363 children were recruited, average age of 12 years (urban) and 8 years (rural). VL coverage was 100% in the urban setting and 77% in the rural setting. Overall, VF was 40.5% (39% [130/332] in the urban setting and 41% (13/31) in the rural setting; p=0.45). Overall, viral undetectability (defined as VL<40 copies/ml) was 45.5% (46% (urban) and 45% (rural); p=0.47). Among those experiencing confirmed virological failure and who were successfully sequenced (n=35), the overall rate of HIVDR was 100% (35/35). By drug class, HIVDR rates were 97.1% (34/35) for non-nucleoside reverse transcriptase inhibitors (NNRTIs), 97.1% (34/35) for NRTIs and 17.1% (6/35) for protease inhibitors (22.7% (5/22) in the urban setting and 7.7% [1/13] in the rural setting). CRF02_AG was the most prevalent viral clade (75%), followed by other recombinants (09_cpx, 11_cpx, 13_cpx, 22_01A1, 37_cpx) and pure subtypes (A1, F2, G, H). In this population of children and adolescents living with HIV in a context of socio-political instability in the North-West region of Cameroon, rates of viral non-suppression are high, and accompanied by HIVDR selection. Our suggests the need for a more differentiated care of these CAHIV, especially those in these regions faced with significant socio-economic and health impacts due to the ongoing crisis.

HIV-1 diversity and pre-treatment drug resistance in the era of integrase inhibitor among newly diagnosed ART-naïve adult patients in Luanda, Angola

The surveillance of drug resistance in the HIV-1 naïve population remains critical to optimizing the effectiveness of antiretroviral therapy (ART), mainly in the era of integrase strand transfer inhibitor (INSTI) regimens. Currently, there is no data regarding resistance to INSTI in Angola since Dolutegravir-DTG was included in the first-line ART regimen. Herein, we investigated the HIV-1 genetic diversity and pretreatment drug resistance (PDR) profile against nucleoside/tide reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and INSTIs, using a next-generation sequencing (NGS) approach with MinION, established to track and survey DRMs in Angola. This was a cross-sectional study comprising 48 newly HIV-diagnosed patients from Luanda, Angola, screened between March 2022 and May 2023. PR, RT, and IN fragments were sequenced for drug resistance and molecular transmission cluster analysis. A total of 45 out of the 48 plasma samples were successfully sequenced. Of these, 10/45 (22.2%) presented PDR to PIs/NRTIs/NNRTIs. Major mutations for NRTIs (2.2%), NNRTIs (20%), PIs (2.2%), and accessory mutations against INSTIs (13.3%) were detected. No major mutations against INSTIs were detected. M41L (2%) and I85V (2%) mutations were detected for NRTI and PI, respectively. K103N (7%), Y181C (7%), and K101E (7%) mutations were frequently observed in NNRTI. The L74M (9%) accessory mutation was frequently observed in the INSTI class. HIV-1 pure subtypes C (33%), F1 (17%), G (15%), A1 (10%), H (6%), and D (4%), CRF01_AG (4%) were observed, while about 10% were recombinant strains. About 31% of detected HIV-1C sequences were in clusters, suggesting small-scale local transmission chains. No major mutations against integrase inhibitors were detected, supporting the continued use of INSTI in the country. Further studies assessing the HIV-1 epidemiology in the era of INSTI-based ART regimens are needed in Angola.

Identification of a new HIV-1 circulating recombinant form (CRF159_01103) derived from CRF103_01B and CRF01_AE in Hebei Province, China

Recombinant HIV-1 genomes identified in three or more epidemiological unrelated individuals are defined as circulating recombinant forms (CRFs). CRFs can further recombine with other pure subtypes or recombinants to produce secondary recombinants. In this study, a new HIV-1 intersubtype CRF, designated CRF159_01103, isolated from three men who have sex with men with no epidemiological linkage, was identified in Baoding city, Hebei Province, China. CRF159_01103 was derived from CRF103_01B and CRF01_AE. Bayesian molecular clock analysis was performed on the CRF01-AE and CRF103_01B regions of CRF159_01103. The time of origin of CRF159_01103 was predicted to be 2018–2019, indicating that it is a recent recombinant virus. The emergence of CRF159_01103 has increased the complexity of the HIV-1 epidemic in Hebei Province.

Comprehensive analysis of stereotactic Radiosurgery outcomes in triple-negative breast cancer patients with brain metastases: The influence of immunotherapy and prognostic factors

IntroductionBreast cancer stands as the second most common solid tumors with a propensity for brain metastasis. Among metastatic breast cancer cases, the brain metastasis incidence ranges from 10 % to 30 %, with triple-negative breast cancer (TNBC) displaying a heightened risk and poorer prognosis. SRS has emerged as an effective local treatment modality for brain metastases; however, data on its outcomes specifically in pure triple-negative subtype remain scarce. MethodWe retrospectively reviewed the electronic medical records of all brain metastasis (BM) TNBC patients treated with SRS. Patient, tumour characteristics and treatment details data were collected. This retrospective cohort study aimed to evaluate local control (LC), distant brain metastasis free survival (DBMFS), and overall survival (OS) outcomes in TNBC patients undergoing SRS for brain metastases while identifying potential prognostic factors. ResultForty-three patients with TNBC and brain metastases treated with SRS between January 2017 and 2023 were included. The study found rates of LC (99 % at 1 year) and DBMFS (76 % at 1 year) after SRS, with brain metastasis count (p = 0,003) and systemic treatment modality (p = 0,001) being significant predictors of DBMFS. The median OS following SRS was 19.5 months, with neurological deficit (p = 0.003) and systemic treatment modality (p = 0.019) identified as significant predictors of OS. ConclusionSRS demonstrates favourable outcomes in terms of local control and distant brain metastasis-free survival in TNBC. Neurological deficit and systemic treatment significantly influence overall survival, emphasizing the importance of personalized treatment approaches and (magnetic resonance imaging) MRI surveillance based on these factors.

Post-Infectious Guillain Barré Syndrome Related to COVID-19: Unusual Case Report

Guillain-Barré Syndrome (GBS) is a rare immune mediated inflammatory disease of the peripheral nervous system that is presumed to be triggered by preceding infections. In the era of pandemic COVID-19 (coronavirus disease), there is an emerging case of para/post infectious GBS associated to COVID-19 that are described worldwide. Here, we report a 55-years-old man who was admitted for fatigue, fever and cough related to covid-19. Later, after disappearing of covid-19 symptoms he began presenting an ascending areflexic tetraparesis. CSF and NCS were in favour of GBS diagnosis, in particular pure motor AIDP subtype. Antigangliosides antibodies were negative. Lumbosacral MRI showed contrast enhancement of cauda equina roots. The outcome was good after receiving intravenous immunoglobulins treatment.

Eligibility and Endpoints for Clinical Trials in Trimodality Therapy for Bladder Cancer.

Trimodality therapy (TMT) is a viable option for muscle-invasive localized bladder cancer, providing an alternative to radical cystectomy in properly selected patients. The approval of novel therapeutics in different stages of bladder cancer treatment has sparked interest in exploring concurrent systemic therapies with radiation in clinical trials to enhance long-term outcomes. Achieving uniformity in trial eligibility criteria and endpoint definitions is imperative in describing clinical significance, comparing trials, and changing standard of care guidelines. To delineate eligibility criteria and appropriate endpoints for TMT clinical trials in an attempt to achieve uniformity in trial eligibility criteria and endpoint definitions which will then help move the field of bladder preservation forward and improve the current standard of care. An expert panel, comprising individuals with extensive experience in bladder cancer clinical trials, clinical practice focused on bladder cancer treatment, and patient advocacy, was assembled. The panel systematically reviewed phase II/III clinical trials previously published and assessing the role of radiation in definitive therapy with the specific goal of preserving native bladder function during bladder cancer treatment. Recommendations were summarized based on review of these trials and past experiences of the investigators. To ensure a holistic perspective, the summary was further subjected to rigorous reevaluation by a patient advocate, who added valuable insights from a patient's standpoint. The resulting consensus statements were summarized in this publication to contribute to the evolving landscape of bladder cancer research and treatment. The eligibility criteria for TMT should be pragmatic to encompass patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, bladder cancer stage T2-T4a N0±N1M0, unilateral tumor-associated hydronephrosis, attempted maximal transurethral resection of bladder tumor (TURBT), both pure urothelial carcinoma and/or mixed histologic subtypes (excluding rare and aggressive small cell variants) and patients who are non- cystectomy candidates. Bladder intact event-free survival (BIEFS) is proposed as a suitable endpoint for registration trials designed to compare two different treatment interventions, defined as the time from randomization to muscle-invasive or locoregional recurrence, systemic recurrence, radical cystectomy from any cause, or death from any cause. Overall survival is deemed an appropriate secondary endpoint or a co-primary end point as recent improvements in systemic therapy can produce significant improvement in long-term outcomes. Primary and secondary endpoints should be supported with patient-reported quality of life assessments, when available. The standardization of clinical trial design, eligibility criteria, and endpoints is essential for expediting progress in the field. Inclusivity, patient-centricity, and clinically meaningful endpoints will facilitate the analysis, comparison, and meta-analysis of different trials, fostering advancements in bladder cancer treatment.

Pure and Mixed Variants of Desmoplastic Melanoma: A Single-Center, Retrospective, Clinicopathologic Review.

Desmoplastic melanoma (DM) is a rare melanoma variant. Prognostic indicators and survival vary widely and are further confounded by the histopathologic distinction between pure DM (pDM) and mixed DM (mDM) subtypes. The utility of current treatment guidelines is limited by the lack of evidence-based recommendations. To compare the clinicopathologic characteristics of pure and mixed subtypes of DMs. All cases of DM were identified from the Washington University in St Louis institutional pathology database between January 2000 and September 2022. Fifty-two cases were identified and subsequently categorized as pure ( n = 26) or mixed ( n = 26). Clinical and histopathologic data were collected and compared. There were no differences in demographics or tumor location between pure and mixed subtypes. Patients with mDM were more likely to have mitoses present ( p = .03). There were no differences in Breslow depth, tumor diameter, level of invasion, ulceration, and lymphovascular or perineural invasion. The utilization of sentinel lymph node biopsy ( p = .17) and sentinel lymph node positivity ( p = .67) were also similar. Despite histopathologic distinction between pDM and mDM, these subtypes were found to have similar clinicopathologic characteristics, including similar rates of sentinel lymph node metastasis.

Spectrum of Mucin-containing Lesions of the Breast: Multimodality Imaging Review with Pathologic Correlation.

Mucin-containing lesions of the breast encompass a wide range of benign and malignant processes. The spectrum of histologic findings includes incidental mucus-filled benign cysts or ducts, mucocele-like lesions (MLLs), mucin-producing ductal carcinoma in situ, and invasive mucinous carcinoma. MLL is characterized by the presence of mucin-containing cysts that are typically associated with extravasated stromal mucin. MLL is often benign but can be associated with epithelial atypia or malignancy. Mucinous carcinoma represents the malignant end of the spectrum of mucinous lesions of the breast. Evidence-based literature supports a conservative approach for benign MLLs without associated atypia or malignancy, reserving excision for those lesions exhibiting such pathologic features. The most common imaging finding for MLL is microcalcifications at mammography. No specific imaging feature is predictive of malignant outcome at surgical excision. Invasive mucinous carcinoma is a heterogeneous breast tumor subtype, as defined according to the World Health Organization criteria. Mucinous carcinomas are categorized into pure (>90% mucinous component) or mixed (10%-90% mucinous component) subtypes. Pure mucinous carcinomas are generally associated with excellent prognosis and survival, with a few exceptions. Mixed mucinous carcinomas do not have the same favorable prognosis and instead behave similarly to invasive breast carcinomas of no special type. Characteristic diagnostic imaging features can be identified for mucinous carcinoma based on its mucinous and nonmucinous contents. ©RSNA, 2023 Online supplemental material is available for this article. Quiz questions for this article are available through the Online Learning Center.

Molecular subtype expression and genomic profiling differ between surgically resected pure and combined small cell lung carcinoma

A new molecular subtype classification method has been proposed for small cell lung carcinoma (SCLC). However, little is known about the differences between the pure (P-SCLC) and combined subtypes (C-SCLC). We aimed to compare the molecular subtype expression and genomic profiling in terms of clinical relevance between the two groups. 154 surgically resected SCLCs were analyzed for protein expression of four subtypes (ASCL1, NEUROD1, POU2F3, and YAP1) and two predictive markers (DLL3 and MYC) by immunohistochemistry (IHC). We also performed whole exome sequencing of 60 samples to examine genomic profiles. A total of 113 patients with P-SCLC and 41 with C-SCLC were included. In P-SCLC and C-SCLC, the expression of these markers was 78.8% and 41.5%, 98.2% and 97.6%, 42.5% and 51.2%, 38.9% and 85.4%, 85.0% and 68.3%, and 24.8% and 34.1%, respectively. ASCL1 and DLL3 were highly expressed in P-SCLC (p=0.000 and p=0.021, respectively), and YAP1 expression was significantly enriched in C-SCLC (p=0.000). NGS results, including 45P-SCLCs and 15C-SCLCs, indicated that EGFR gene mutations were mostly observed in C-SCLCs (p=0.000). C-SCLC showed higher CNA burden and wGII than P-SCLC (p<0.01 and p<0.05); conversely, P-SCLC had higher TMB burden and SDI (p<0.05 and p<0.05). YAP1 expression was associated with poor prognosis in P-SCLC but with favorable prognosis in C-SCLC. P-SCLC and C-SCLC are heterogeneous diseases characterized by different molecular subtype expressions and genomic profiles. Our data provide a basis for adopting histological subtype-based treatments, and further prospective studies are required to confirm our conclusions.

MR Imaging Findings and Texture Analysis of Pure and Mixed Mucinous Breast Carcinoma

Purpose: To evaluate the ability of magnetic resonance imaging (MRI) findings and texture features to differentiate between pure and mixed subtypes of mucinous breast carcinoma.Methods: This retrospective study included 136 patients who were surgically diagnosed with mucinous breast carcinoma and underwent pre-treatment breast MRI between January 2008 and December 2020. All clinicopathological and MRI features were reviewed. For texture analysis, regions of interest of the tumors were drawn manually on T2-weighted images and first-subtraction T1-weighted images. Texture feature extraction and analysis were conducted using open-source 3D slicer software. Univariate and multivariate analyses were used to identify significant MRI findings and texture features to differentiate between the two subtypes. To evaluate the diagnostic performance of the texture features, a receiver operating characteristic curve analysis was conducted.Results: Among the MRI findings, very high signal intensity on T2-weighted images was significantly associated with pure mucinous breast carcinoma (odds ratio=5.23, &lt;i&gt;p&lt;/i&gt;=0.001). The homogeneity and skewness texture features from T2-weighted imaging showed statistically significant differences between pure and mixed subtypes, and the areas under the receiver operating curve were 0.749 and 0.815, respectively.Conclusion: Signal intensity and texture features on T2- weighted images derived from breast MRI can assist in the differential diagnosis of pure and mixed types of mucinous breast carcinoma.

Impact of early testing and analysis of germline genetic mutation patterns in patients with breast cancer: A single institution experience.

10613 Background: Approximately 3% of patients with breast cancer have a pathogenic or likely pathogenic variant (mutation) in a high-risk breast cancer gene, such as BRCA1, BRCA2and PALB2, which increases breast cancer risk more than fourfold. Approximately 3% have a germline mutation in a moderate-penetrance breast cancer gene, such as ATM or CHEK2, which confers a two- to threefold increased risk of breast cancer. Methods: In 2020 we started offering germline genetic testing to all newly diagnosed breast cancer patients at the time of diagnosis irrespective of their family history. Our objectives included the following: Prevalence of mutations in breast cancer patients treated at our institution. Germline mutations in patients with Ductal carcinoma in situ (DCIS). To identify if early universal germline testing affected the surgical modality. Results: A total of 525 patients were seen in the oncology clinic from January 2020 to December 2022 with a breast cancer diagnosis. The median age of diagnosis is 66 (32-91) years. Invasive ductal cancer (IDC 66 %) was the most common subtype, followed by DCIS (18%) (Table 1). Most patients had estrogen-positive cancer (82% vs. 18%), and approximately 13% had HER2-positive disease (61% HER2 low). Mutation in CHEK2 (9 patients) was our cohort's most common pathogenic mutation, followed by BRCA1 (6 patients) and MUYTH (6 patients) genes. Predominant germline mutations were identified in patients with IDC, followed by DCIS. One patient with a pure mucinous subtype had a germline pathogenic mutation (RECQL4 gene). We identified a higher percentage of pathogenic breast cancer-related mutations in patients above 60 years (63% vs. 37%) and all CHEK2 mutations were in patients above 60. Out of 41 patients with pathogenic mutations, 17 underwent a partial mastectomy, 12 had a bilateral mastectomy, and two had a unilateral mastectomy. All patients with BRCA1/2 mutation chose bilateral mastectomy, and all patients with a CHEK2 mutation underwent a partial mastectomy. Several variants of unknown significance (VUS) mutations were identified, and they followed a similar pattern, being more common in patients with IDC. VUS mutations in the ATM gene were the most reported abnormality. Conclusions: Pathogenic mutation in the CHEK2 gene is more prevalent, and we hypothesize that this finding could be related to the demographic population treated in our institution. Also, CHEK2 mutation was only identified in patients older than 60, which argues for more testing in patients in this age group. Approximately 9% of all IDC patients had a germline mutation compared to 4.2 % in patients with DCIS. Our review identifies that patients with BRCA1/2 mutations tend to undergo prophylactic mastectomy, and early testing likely impacted this decision. From our study, we believe that germline genetic testing should be offered to all breast cancer patients.

Real-World Data on the Incidence and Risk of Guillain-Barre Syndrome Following SARS-CoV-2 Vaccination; A Prospective Surveillance Study (P2-5.026)

<h3>Objective:</h3> To report the crude incidence rate of GBS following SARS-CoV-2 vaccination; evaluate how vaccine dose, mechanism, age, and sex may affect the risk of GBS following SARS-CoV-2 vaccination; and clinically compare head-to-head GBS cases following two major mechanisms of vaccines. <h3>Background:</h3> Increasing evidence suggests an association between SARS-CoV-2 vaccines and Guillain-Barré syndrome (GBS). Nevertheless, little is understood about the contributing risk factors and clinical characteristics of GBS post SARS-CoV-2 vaccination. <h3>Design/Methods:</h3> In this prospective surveillance study of 38,828,692 SARS-CoV-2 vaccine doses administered from February 2021 to March 2022 in the Gyeonggi Province, South Korea, 55 cases of GBS were reported post vaccination. We estimated the incidence rate of GBS per million doses and the incidence rate ratio for the vaccine dose, mechanism, age, and sex. Additionally, we compared the clinical characteristics of GBS following mRNA-based and viral vector-based vaccinations. <h3>Results:</h3> The overall incidence of GBS following SARS-CoV-2 vaccination was 1.42 per million doses. Viral vector-based vaccines were associated with a higher risk of GBS. Men were more likely to develop GBS than women. The third dose of vaccine was associated with a lower risk of developing GBS. Classic sensorimotor and pure motor subtypes were the predominant clinical subtypes, and demyelinating type was the predominant electrodiagnostic subtype. The initial dose of viral-vector based vaccine and later doses of mRNA-based vaccine were associated with GBS, respectively. <h3>Conclusions:</h3> GBS following SARS-CoV-2 vaccination may not be clinically distinct. However, physicians should pay close attention to the classic presentation of GBS in men receiving an initial dose of viral vector-based SARS-CoV-2 vaccines. <b>Disclosure:</b> Dr. Ha has nothing to disclose. Dr. Kang has nothing to disclose. Dr. KYUNG has nothing to disclose. Mr. Kim has nothing to disclose. Dr. Kim has nothing to disclose. Dr. KIM has nothing to disclose. Dr. Bae has nothing to disclose. Dr. Song has nothing to disclose. Dr. Lee has nothing to disclose. Dr. Lee has nothing to disclose. Ms. Park has nothing to disclose. Dr. Hwang has nothing to disclose. Dr. Park has nothing to disclose. Jin Myoung Seok has nothing to disclose. Prof. Youn has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Medtronic. Prof. Youn has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Boston Scientific. Prof. Youn has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Boston Scientific. Prof. Youn has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Myung-In Pharm. Prof. Youn has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Boston Scientific. Prof. Youn has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Eisai Co. Ltd. Prof. Youn has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for SK Chem.

Real-world data on the incidence and risk of Guillain–Barré syndrome following SARS-CoV-2 vaccination: a prospective surveillance study

Increasing evidence suggests an association between SARS-CoV-2 vaccines and Guillain–Barré syndrome (GBS). Nevertheless, little is understood about the contributing risk factors and clinical characteristics of GBS post SARS-CoV-2 vaccination. In this prospective surveillance study of 38,828,691 SARS-CoV-2 vaccine doses administered from February 2021 to March 2022 in the Gyeonggi Province, South Korea, 55 cases of GBS were reported post vaccination. We estimated the incidence rate of GBS per million doses and the incidence rate ratio for the vaccine dose, mechanism, age, and sex. Additionally, we compared the clinical characteristics of GBS following mRNA-based and viral vector-based vaccinations. The overall incidence of GBS following SARS-CoV-2 vaccination was 1.42 per million doses. Viral vector-based vaccines were associated with a higher risk of GBS. Men were more likely to develop GBS than women. The third dose of vaccine was associated with a lower risk of developing GBS. Classic sensorimotor and pure motor subtypes were the predominant clinical subtypes, and demyelinating type was the predominant electrodiagnostic subtype. The initial dose of viral-vector based vaccine and later doses of mRNA-based vaccine were associated with GBS, respectively. GBS following SARS-CoV-2 vaccination may not be clinically distinct. However, physicians should pay close attention to the classic presentation of GBS in men receiving an initial dose of viral vector-based SARS-CoV-2 vaccines.

Survival of Testicular Pure Embryonal Carcinoma vs. Mixed Germ Cell Tumor Patients across All Stages

Background and Objectives: The impact of pure histological subtypes in testicular non-seminoma germ cell tumors on survival, specifically regarding pure embryonal carcinoma, is not well established. Therefore, this study aimed to test for differences between pure embryonal carcinoma and mixed germ cell tumor patients within stages I, II and III in a large population-based database. Materials and Methods: We relied on the Surveillance, Epidemiology and End Results (SEER) database (2004-2019) to identify testicular pure embryonal carcinoma vs. mixed germ cell tumor patients. Cumulative incidence plots depicted cancer-specific mortality that represented the main endpoint of interest. Multivariable competing risks regression models tested for differences between pure embryonal carcinoma and mixed germ cell tumor patients in analyses addressing cancer-specific mortality and adjusted for other-cause mortality. Results: Of 11,223 patients, 2473 (22%) had pure embryonal carcinoma. Pure embryonal carcinoma patients exhibited lower cancer-specific mortality relative to their mixed germ cell tumor counterparts for both stage III (13.9 vs. 19.4%; p < 0.01) and stage II (0.5 vs. 3.4%, p < 0.01), but not in stage I (0.9 vs. 1.6%, p = 0.1). In multivariable competing risks regression models, pure embryonal carcinoma exhibited more favorable cancer-specific mortality than mixed germ cell tumor in stage III (hazard ratio 0.71, p = 0.01) and stage II (hazard ratio 0.11, p < 0.01). Conclusions: Pure embryonal carcinoma exhibits a more favorable cancer-specific mortality profile relative to mixed germ cell tumor in stage II and III testicular cancers. Consequently, the presence of mixed germ cell tumor elements may be interpreted as a risk factor for cancer-specific survival.

Clinicopathological and Treatment Patterns of Combined Small-Cell Lung Carcinoma with Future Insight to Treatment: A Population-Based Study.

Primary lung cancer is the most common cause of cancer-related mortality in the United States (US). Approximately 90% of lung cancers are associated with smoking and the use of other tobacco products. Based on histology, lung cancers are divided into small-cell lung carcinomas (SCLCs) and non-small-cell lung carcinomas (NSCLCs). Most SCLCs are of the pure subtype, while the rare combined SCLCs contain elements of both small-cell and non-small-cell morphologies. This study sought to evaluate the demographics, clinical factors, molecular abnormalities, treatment approaches, and survival outcomes with combined SCLC and NSCLCs. Data on 2126 combined SCLC patients was extracted from the Surveillance Epidemiology and End Result (SEER) database from 2000 to 2018. Data extracted for analyses included age, sex, race, tumor size, tumor location, metastasis status, stage at diagnosis, treatment received, and treatment outcomes. Multivariate analysis was performed using Statistical Product and Service Solutions (SPSS) software. The patients had a median age of 68 years; 43.9% of the patients were female and 56.1% were male; 84.5% were White and 11.7% were African Americans. The majority of patients had a poorly differentiated disease at 29.6%; 17% were undifferentiated, 3.2% were moderately differentiated, and 0.8% were well differentiated. Chemotherapy was the most common treatment modality (45.3%); 17% underwent surgery only, 10.3% underwent surgery followed by adjuvant chemotherapy, and 10% underwent radiation after surgery. Five-year cancer-specific survival was 15.2% with surgery alone, and combined surgery and chemotherapy provided the highest percentages (38.3% and 34.7%, respectively). Females had significantly higher 1- and 5-year cancer-specific survival rates compared to males (59.3% and 29.9% vs. 48.0% and 23.7, respectively; p < 0.001). Well-differentiated tumors had significantly higher survival compared to other gradings (p < 0.001). Survival decreased as tumor staging moved distally from localized to regional to distant (p < 0.001). Metastasis to bone, liver, brain, and lung significantly decreased survival in comparison to patients who did not have any metastasis (p < 0.001). Females had significantly shorter survival compared to their counterparts when metastasis was to the bone, brain, or liver (p < 0.001). Multivariate analysis identified male sex (Hazard Ratio (HR) = 1.2), undifferentiated grade (HR = 1.9), regional extent of disease (HR = 1.7), distant extent of disease (HR = 3.7), and metastasis to liver (HR = 3.5) as variables associated with worse survival. Combined SCLC is overall very rare. However, the frequency of presentation with combined SCLC is on the rise, in part due to improvements in diagnostic techniques. Despite advances in therapies, treating combined SCLC is challenging, and novel therapies are not utilized, owing to low rates of targetable mutations. Combined SCLC has higher survival rates if well differentiated.

Subtypes of relapsing-remitting multiple sclerosis identified by network analysis.

We used network analysis to identify subtypes of relapsing-remitting multiple sclerosis subjects based on their cumulative signs and symptoms. The electronic medical records of 113 subjects with relapsing-remitting multiple sclerosis were reviewed, signs and symptoms were mapped to classes in a neuro-ontology, and classes were collapsed into sixteen superclasses by subsumption. After normalization and vectorization of the data, bipartite (subject-feature) and unipartite (subject-subject) network graphs were created using NetworkX and visualized in Gephi. Degree and weighted degree were calculated for each node. Graphs were partitioned into communities using the modularity score. Feature maps visualized differences in features by community. Network analysis of the unipartite graph yielded a higher modularity score (0.49) than the bipartite graph (0.25). The bipartite network was partitioned into five communities which were named fatigue, behavioral, hypertonia/weakness, abnormal gait/sphincter, and sensory, based on feature characteristics. The unipartite network was partitioned into five communities which were named fatigue, pain, cognitive, sensory, and gait/weakness/hypertonia based on features. Although we did not identify pure subtypes (e.g., pure motor, pure sensory, etc.) in this cohort of multiple sclerosis subjects, we demonstrated that network analysis could partition these subjects into different subtype communities. Larger datasets and additional partitioning algorithms are needed to confirm these findings and elucidate their significance. This study contributes to the literature investigating subtypes of multiple sclerosis by combining feature reduction by subsumption with network analysis.

Hyperglycaemia induces metabolic reprogramming into a glycolytic phenotype and promotes epithelial-mesenchymal transitions via YAP/TAZ-Hedgehog signalling axis in pancreatic cancer.

Hyperglycaemia is a well-known initial symptom in patients with pancreatic ductal adenocarcinoma (PDAC). Metabolic reprogramming in cancer, described as the Warburg effect, can induce epithelial-mesenchymal transition (EMT). The biological impact of hyperglycaemia on malignant behaviour in PDAC was examined by in vitro and in vivo experiments. Hyperglycaemia promoted EMT by inducing metabolic reprogramming into a glycolytic phenotype via yes-associated protein (YAP)/PDZ-binding motif (TAZ) overexpression, accompanied by GLUT1 overexpression and enhanced phosphorylation Akt in PDAC. In addition, hyperglycaemia enhanced chemoresistance by upregulating ABCB1 expression and triggered PDAC switch into pure basal-like subtype with activated Hedgehog pathway (GLI1 high, GATA6 low expression) through YAP/TAZ overexpression. PDAC is characterised by abundant stroma that harbours tumour-promoting properties and chemoresistance. Hyperglycaemia promotes the production of collagen fibre-related proteins (fibronectin, fibroblast activation protein, COL1A1 and COL11A1) by stimulating YAP/TAZ expression in cancer-associated fibroblasts (CAFs). Knockdown of YAP and/or TAZ or treatment with YAP/TAZ inhibitor (K975) abolished EMT, chemoresistance and a favourable tumour microenvironment even under hyperglycemic conditions in vitro and in vivo. Hyperglycaemia induces metabolic reprogramming into glycolytic phenotype and promotes EMT via YAP/TAZ-Hedgehog signalling axis, and YAP/TAZ could be a novel therapeutic target in PDAC.

Genetic diversity of the human immunodeficiency virus (HIV-1) in the Kaliningrad region

As is currently known, the epidemic process in the Kaliningrad Region was mainly associated with the spread of the recombinant form of HIV-1 (CRF03_AB); however, regular HIV importations from other countries and continents has created favorable conditions for emergence and spread of various recombinant forms of the virus.The most complete information on the diversity of recombinant forms in the region is also necessary to understand the structure of drug resistance (DR). The aim of the study was to explore the HIV-1 genetic diversity in the Kaliningrad Region. We studied 162 blood plasma samples obtained from patients from the Kaliningrad Region, both with confirmed virological failure of antiretroviral therapy (ART) and with newly diagnosed HIV infection. For reverse transcription and amplification of HIV genome fragments, diagnostic «AmpliSense HIVResist-Seq». The various recombinants between subtypes A and B (74%) were predominant in study group: recombinant was between CRF03_AB and subtype A (33.95%) and CRF03_AB-like (13.58%) were the most common. Among the "pure" subtypes of the virus, subtype A6 (16.67%). The circulation of subtypes B (3.70%) and G (1.23%) was also noted.Ninety-six patients (59.26%) were identified with at least one mutation associated with antiretroviral (ARV) drug resistance. The observed diversity of subtypes and recombinant forms of the virus implies that the new recombinants are actively emerging in the studied region, both between existing recombinant forms and "pure" subtypes, as well as between "pure" subtypes.