Disseminated Disease Research Articles

Prognostic Significance of Immunohistochemical Expression of Cyclin D1 and β-Catenin in Invasive Ductal Carcinoma (IDC)

Introduction: Invasive ductal carcinoma (IDC) is the most prevalent subtype of breast cancer, distinguished by diverse clinical manifestations and molecular heterogeneity. Prognostic outcomes are influenced by multiple factors, including the patient’s age at diagnosis, tumor size, histological grade, disease stage, lymph node metastasis (LNM), and hormone receptor status (ER, PR, HER2). This research has highlighted the potential of emerging molecular biomarkers such as Cyclin D1 and β-Catenin in enhancing prognostic precision. Methodology: This retrospective, cross-sectional study analyzed the medical records of female patients diagnosed with IDC. Tumor size, grade, and stage were examined alongside lymph node involvement to assess the extent of disease dissemination. Immunohistochemistry (IHC) was employed to determine the expression of ER, PR, and HER2 receptors. Additionally, emerging biomarkers such as Cyclin D1 and β-Catenin were evaluated to explore their prognostic value. A total of 150 tumor samples were collected from multiple cancer treatment facilities across Rawalpindi, Punjab, Pakistan. Findings and Discussion: The mean age at diagnosis was 50.6 years, with the majority of patients (68%) between 36 and 55 years. Tumor analysis revealed that 76.7% of lesions were <30 mm in size, and 46.7% were classified as grade II. LNM was detected in 39.3% of patients, indicating significant metastatic potential. Regarding receptor expression, 45.5% of tumors were ER-positive, 42.9% PR-positive, and 54.8% HER2-positive, aligning with global incidence trends. The investigation of molecular markers showed Cyclin D1 overexpression in 60% of cases, predominantly in ER-positive tumors, suggesting better endocrine therapy responsiveness. β-Catenin was detected in 33.3% of samples and correlated with aggressive tumor phenotypes, emphasizing its potential role in identifying high-risk patients. These molecular markers align with globally research. Conclusion: This study emphasizes the significance of early detection and comprehensive molecular profiling in IDC management. Smaller tumors and receptor-positive cases are generally associated with more favorable outcomes. Additionally, emerging biomarkers such as Cyclin D1 and β-Catenin hold promise for refining prognostic models and optimizing individualized treatment plans. Incorporating these biomarkers into clinical practice can further enhance therapeutic decision-making and patient care.

Semiquantitative 2-[18F]FDG PET/CT-based parameters role in lymphoma

2-deoxy-2-[18F]-fluoro-D-glucose (2-[18F]FDG) positron emission tomography/computed tomography (PET/CT) plays a crucial role in the management of lymphoma in different settings, such as staging disease, assessing response to therapy, predicting prognosis, and planning RT. Beside visual analysis, several semiquantitative parameters were introduced to study lymphoma with promising results. These parameters can represent different disease characteristics, like body composition (such as sarcopenic index), dissemination of disease (Dmax), tumor burden (including metabolic tumor volume) and texture features. All these parameters showed promising results, especially in terms of prognosis (progression free survival and overall survival), but lack of standardization and shared methodology remains a big issue. Advances in PET-based biomarkers are on the horizon, yet their integration into clinical decision-making is currently hindered by methodological limitations that require resolution through confirmatory prospective validation in specific patient groups. This review highlights studies demonstrating the prognostic and predictive value of these semiquantitative parameters in lymphoma, while also discussing their potential applicability in clinical practice.

Personalized decision making of neoadjuvant chemotherapy vs. upfront surgery in pancreatic cancer by a simple blood collection?

SummaryPancreatic cancer still has dismal survival rates and high rates of early recurrence despite improvements of multimodal treatment options and more and more aggressive surgical approaches in recent years. Thus, precise and personalized management strategies to improve patient outcomes are needed. Circulating tumor DNA (ctDNA), a component of cell-free DNA (cfDNA) in body fluids, harbors genetic and epigenetic signatures of tumors and can be detected noninvasively for example through simple blood collections or peritoneal fluid during staging laparoscopy (liquid biopsies). This biomarker provides real-time insights into systemic tumor burden, heterogeneity, and genetic profile and has been proven to be of significant prognostic relevance for several gastrointestinal malignancies. Furthermore, the testing of ctDNA has emerged as a pivotal prognostic biomarker to indicate patients with high biological risk for recurrence and worse overall survival. Especially in pancreatic cancer, it has been shown that preoperative ctDNA detectability in peripheral blood is associated with systemic tumor burden (even volumetric). This indicates potential micrometastatic or subclinical disseminated disease, suggesting a benefit from neoadjuvant chemotherapy to address the systemic component of the disease prior to surgery. Furthermore, dynamic changes in ctDNA during systemic treatment can predict therapeutic response and guide adjustments in treatment regimens. Postoperatively, ctDNA presence could assist in detecting minimal residual disease which also predicts early relapse, facilitating timely intervention (or immediate adjuvant chemotherapy as already shown in colorectal cancer, e.g., Dynamic trial). Therefore, perioperative ctDNA detection has the potential to refine the management of pancreatic cancer, enhancing decision-making processes and optimizing personalized treatment approaches in serving as an additional highly sensitive biomarker for guiding treatment decisions between upfront surgery and neoadjuvant chemotherapy in patients with resectable pancreatic cancer. The first ever personalized change of treatment decision from upfront surgery (by current gold standard staging) to neoadjuvant chemotherapy based on additional liquid biopsy results was documented in March 2024 (Linz, Austria).

Primary Cutaneous Anaplastic Large Cell Lymphoma With Rare Extracutaneous Disseminated Disease: A Case Report.

Primary cutaneous anaplastic large cell lymphoma (pcALCL) is a CD30+ lymphoproliferative disorder with generally favorable outcomes and infrequent extracutaneous spread, usually limited to local lymph nodes. However, there may be extensive histologic overlap with more aggressive CD30+ lymphomas, such as large cell transformation of mycosis fungoides or secondary skin involvement by anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma. Definitive diagnosis relies on clinicopathologic correlation. We report on a 26-year-old woman who presented to our institution with progressive lower extremity wounds for several months, previously treated with antibiotics and vacuum-assisted closure dressings. Consultation with dermatology and 2 separate biopsies eventually led to the diagnosis of pcALCL. Subsequent imaging revealed stage IV disease with innumerable intensely fluorodeoxyglucose (FDG)-avid subcutaneous, intramuscular, and visceral foci, but paucity of lymph node involvement. The patient's condition deteriorated, and she died during her hospitalization. This case reviews the clinicopathologic findings of pcALCL, emphasizes the importance of clinicopathologic correlation in differentiating between CD30+ lymphoproliferative disorders, highlights the extremely rare phenomenon of systemic intramuscular and visceral disseminated disease occurring in pcALCL, and discusses implications for prognosis.

Epidemiological Studies on Various Weather Parameters for Development of Brown Spot Disease in Sugarcane

Availability of susceptible host and prevalence of favorable weather condition play important role in the process of disease development, dissemination of diseases and favour epidemics. Epidemiological studies on brown spot disease of sugarcane will gave an idea about the time of occurrence, development, survival of the pathogen in nature and intensity of particular disease on specific location based on various weather parameters which may help us to formulate the management strategy. A field trial on epidemiological studies was conducted during Suru-2023 at Central Sugarcane Research Station, Padegaon farm, Tal. Phaltan Dist. Satara on highly susceptible cv. CoM 0265 in natural condition. Different weather parameters were explored by correlation and regression analysis to find out their contribution to infection and development of the brown spot disease of sugarcane. Epidemiological studies under field conditions revealed that, the first appearance of brown spot disease of sugarcane on susceptible cultivar CoM 0265 was recorded during third week of July. During 2023, correlation matrix showed that, maximum temperature, relative humidity (morning), and bright sunshine were the three significant factors that showed a significantly positive correlation. Rainfall also showed a positive correlation. However, minimum temperature, relative humidity (evening) and wind speed showed significantly negative correlation with correlation coefficient.

Distribution of extrapulmonary tuberculosis in CBNAAT samples received in a tertiary care hospital – A record-based study

ABSTRACT Background: Pulmonary tuberculosis (PTB) accounts for 85% of all reported tuberculosis cases globally. Extrapulmonary involvement can occur in isolation or along with a pulmonary focus as in the case of patients with disseminated tuberculosis (TB). EPTB can occur through hematogenous, lymphatic, or localized bacillary dissemination from a primary source, such as PTB and affects the brain, eye, mouth, tongue, lymph nodes of neck, spine, bones, muscles, skin, pleura, pericardium, gastrointestinal, peritoneum and the genitourinary system as primary and/or disseminated disease. Although pulmonary TB is the most common presentation, EPTB is also an important problem clinically. Cartridge-based nucleic acid amplification (CBNAAT) test has a well-documented role in diagnosing pulmonary tuberculosis. Aim: To determine the distribution of EPTB in various samples received for CBNAAT testing in our Institution. Methods: In this retrospective cross-sectional study, data of suspected EPTB patients were retrieved and analyzed from January 2020 to December 2022. Statistical Analysis: All the statistical analyses were carried out using the Excel spreadsheet and Open-epi version 3.01 platform. Results: A total number of 1118(n) extrapulmonary samples were processed using GeneXpert MTB/RIF assay. Out of the 1118 received samples, (22%) were positive. Among the 249 positive samples, 55% samples were received from the female patients and 45% samples received from the male patients. We found that most MTB positive samples were from this age group (i.e. 21-30). Most common sample received for processing was Lymph node aspirate accounting to 37% followed by pleural fluid (30%), pus (8%) and gastric lavage amounting for 4% along with other miscellaneous samples making up the others to 21%. Out of 249 MTB detected samples, 47% were from lymph node aspirate, 13% from pleural fluid, 12% from pus, 3% from gastric lavage and 25% from other samples. We noted that the majority of the positive cases were rifampicin sensitive (97.68%). Conclusion: Results of our study suggest that younger age (third decade of life) and female gender may be independent risk factors for EPTB. In developing countries, the prevalence of EPTB is relatively lower than PTB but still it is an important cause of morbidity and mortality. Thus, early diagnosis and initiation of appropriate treatment are important for reducing the case load. Women especially should be investigated thoroughly for EPTB and BCG vaccination should be encouraged.

Predictive factors for long-term patency in duodenal stenting for malignant gastric outlet obstruction

Background: Malignant gastric outlet obstruction (GOO) occurs often late during disseminated disease needing palliation. Placement of duodenal self-expandable metal stents (SEMS) is a common method relieving malignant GOO but recurrent obstruction is common warranting reintervention. The aim of the present study was to identify predictive factors for stent patency at three months and survival. Also, stent patency rate and adverse events after duodenal stenting were analyzed. Methods: Retrospective observational single-center study including all patients with malignant GOO receiving duodenal SEMS for palliation (2008-2021). Logistic regression for stent patency (3 months) and Cox regression for survival were undertaken. Results: Overall, 198 patients were included. The most common malignancy was pancreatic adenocarcinoma (40%), gastric adenocarcinoma (18%) and cholangiocarcinoma (13%). Uncovered SEMS were used in 88%, and the reintervention rate was 44%. The stent patency rate was 63% in 188 patients with clinical success. Predictors for stent patency 3 months were jaundice, semi- or fully covered stents, and chemotherapy prior to stenting. Median survival was 81 days (IQR 40-241) after stenting. In Cox regression, predictors for overall survival at 6 months were absence of jaundice and stent patency at 3 months. Stent dysfunction was the most common cause of reintervention and was managed by repeated stent (76%) or dilation (11%). Discussion: Treatment of malignant GOO by duodenal SEMS is effective but the reintervention rate is high. Predictors for stent patency were jaundice, semi- or fully covered SEMS, and chemotherapy. Survival was impaired by jaundice and stent dysfunction.

Mechanisms of Control and Media Protagonism in Management

Objective: The objective of this study is to investigate the mechanisms of control and media protagonism in the management of epidemics in order to demonstrate the influence that the media in association with the State and large private corporations exert on human behavior. Theoretical Framework: In this topic, the main concepts and theories that underlie the research are presented. The issue of fear arising from contagion in a scenario of disease outbreaks, aspects of collective behavior and the use of institutional and media control methods are highlighted, providing a solid basis for understanding the context of the investigation. Method: The methodology adopted for this research comprises the survey and selection of journalistic texts containing national and international coverage of outbreaks of contagious diseases to organize the corpus of comparative analysis of the influence on the process of legitimization of prophylaxis, surveillance and control measures. Results and Discussion: The results obtained revealed that the media is established with other possibilities besides surveillance, in which control is something even more present, and its role will be that of control through discourse. In the discussion section, these results are contextualized in the light of the theoretical framework, highlighting the implications and relationships identified. Possible discrepancies and limitations of the study are also considered in this section. Research Implications: The practical and theoretical implications of this research are discussed, providing insights into how the results can be applied or influence practices in the fields of communication and health, in relation to the construction of the media narrative about public health with possible developments in relation to the vaccination campaigns that followed the epidemic and the pandemic that are the objects of this study. Originality/Value: This study contributes to the literature by demonstrating, in different scenarios separated from each other by a decade, but characterized by the worldwide dissemination of contagious diseases, the performance of the same logic of control and media protagonism. The relevance and value of this research are evidenced by the demonstration of the need for the journalist to perceive in his professional practice the asphyxiating implications arising from the control by the discourse imposed by the media on society.

Parenteral aciclovir for suspected herpes simplex virus infection in children: 0–18 years

Abstract Background Variations in neonatal aciclovir prescribing for suspected herpes simplex virus (HSV) disease are well-known, but there are limited data describing aciclovir prescribing in older children. Methods Medical records of neonates (≤28 days) and children (29 days to 18 years) prescribed intravenous aciclovir for suspected HSV disease (1 January 2019–12 December 2019) in eight Australian and New Zealand hospitals were reviewed. Prescribing indication, HSV testing, aciclovir prescription details, adverse events and discharge diagnosis were recorded. Results 1426 received empirical aciclovir. For neonates (n = 425), the median duration was 1 day (IQR 1–3), 411/425 underwent HSV investigations and 13/425 had HSV disease (two with disseminated encephalitis, four with encephalitis and seven with skin, eye, mouth disease). Of the 1001 children, 906 were immunocompetent. 136/906 suspected of mucocutaneous disease received aciclovir for a median of 2 days (1–2), 121/136 underwent HSV testing, and 69/136 had proven disease. 770/906 received aciclovir for suspected disseminated disease or encephalitis for a median of 1 day (1–2), 556/770 underwent HSV testing, and 5/770 had disseminated disease or encephalitis. Among 95 immunocompromised children, 53/58 with suspected mucocutaneous disease had HSV testing and this was confirmed in 22. Disseminated disease or encephalitis was suspected in 37/95, HSV testing conducted in 23/37 and detected in one. The median aciclovir duration was 3 (2–7) days for immunocompromised children. Nephrotoxicity occurred in 7/1426 and 24/1426 had an extravasation injury. Conclusion Frequent and often unnecessary intravenous aciclovir prescribing for suspected HSV encephalitis or disseminated disease occurred in children, as evidenced by incomplete HSV investigations and only 5/770 older children having the diagnosis confirmed.

Orbital apex syndrome in a man with rhino-ocular cerebral mucormycosis: a case report

BackgroundOrbital apex syndrome is a symptom complex of visual loss and ophthalmoplegia resulting from a disease involving the orbital apex. It can be caused by inflammation, infection, and malignancies. Mucormycosis is an infection caused by filamentous saprophytes of the order Mucorales. It is ubiquitous, and the infection can occur from ingesting contaminated food, inhaling spores, or injecting the disrupted skin or wounds. It is mainly a disease of the immunocompromised, affecting patients with poorly controlled diabetes, organ transplant recipients, and patients with hematological malignancies. We present the case of a man with orbital apex syndrome resulting from rapidly spreading rhino-ocular cerebral mucormycosis, who had a poor outcome despite an aggressive combined medical and surgical treatment. This is an unusual cause of orbital apex syndrome.Case presentationA 46-year-old Bangladeshi man presented to the emergency department with a history of toothache and pain in the left eye. On examination, the patient had a left-sided periorbital edema, ptosis, and proptosis. He had complete ophthalmoplegia and absent direct pupillary response in the left eye. Magnetic resonance imaging of the brain and orbit showed bilateral ethmoidal, left frontal, maxillary, and sphenoidal sinusitis with left orbital cellulitis. His left orbit was surgically decompressed and histology confirmed mucormycosis. Despite aggressive treatment, the patient had only a partial improvement in his symptoms.ConclusionsMucormycosis is a rare disease that can easily be misdiagnosed, leading to delayed treatment and disease dissemination. Clinicians must be suspicious of mucormycosis in patients presenting with multiple cranial nerve palsy.

A Case of Disseminated Tuberculosis with Atypical Presentation In An Older Person

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis. It is a significant health concern, with millions of new cases and deaths reported each year. Disseminated tuberculosis (dTB) is a serious condition which can affect various organs and tissues, leading to widespread symptoms and complications. The diagnosis of dTB can be challenging due to its atypical presentations. We present a case of dTB in a robust older person who presented with musculoskeletal pain, weight loss, and loss of appetite. Initially, he was treated for age-related spine disease, and pain management was provided. However, his subsequent visit raised suspicion of TB, prompting further work up. The diagnosis was revised to dTB, and anti-TB treatment was initiated. The near miss or delay in diagnosis and treatment may have played a role in dissemination of disease, increased frailty and reduction of function in this patient. Healthcare workers must maintain a high index of suspicion and remain vigilant for TB as starting early treatment will prevent dissemination in the patient, reduce risk to the public and improve outcomes.

SURG-52. LEPTOMENINGEAL DISSEMINATION AFTER GAMMATILE AND LITT IN HIGH GRADE ASTROCYTOMA PATIENTS

Abstract PURPOSE To present a case series of leptomeningeal dissemination after localized treatment with GammaTile or laser interstitial thermal therapy (LITT) in patients with high grade astrocytoma. BACKGROUND Leptomeningeal dissemination occurs primarily in glioblastoma patients with prolonged survival and those who undergo aggressive treatment courses. Targeted therapies such as GammaTile (which contains cesium-131 radiation-emitting seeds) or LITT may provide localized disease control following recurrence and serve as an immediate treatment modality for patients with recurrent disease in the weeks leading up to radiotherapy or systemic treatment. METHODS We retrospectively reviewed all consecutive patients with high grade astrocytoma treated with GammaTile or LITT who were found to have leptomeningeal dissemination of disease. Histological diagnosis, NGS and immunohistochemistry of tumor tissue were performed at both original diagnosis and at time of GammaTile placement or LITT procedure. Leptomeningeal dissemination was diagnosed through MRI findings on brain and spine. Cases were analyzed for time to development of leptomeningeal dissemination, median overall survival, survival from time of leptomeningeal dissemination diagnosis, time of dissemination to second radiation therapy. Tumor location, MGMT status and other molecular markers were also reviewed. RESULTS Out of 90 high grade astrocytoma patients treated with gamma tile radiation, 4 progressed to exhibit disseminated disease. There were 2 female patients, mean age was 50 years. Location of tumor was in the left temporal lobe in 3 patients and right temporal in 1. They were all IDH wild type. Two were MGMT methylated, two were non methylated. The median time from initial glioma diagnosis to LMD was 221 months (range 11-152) and overall survival after disseminated disease diagnosis was 7.5 weeks (range 3–13). CONCLUSION Leptomeningeal dissemination is a devastating complication of aggressive gliomas. Currently, there is no standard treatment for disseminated disease in high grade astrocytoma patients. Systemic therapy is needed following localized therapies to control disease. Further research into new therapies is needed to allow for better outcomes.

INNV-01. METASTATIC GLIOBLASTOMA TO THE LUNG TREATED WITH LENVATINIB

Abstract Glioblastoma is the most common malignant brain tumor. Despite its invasive nature, extra-cranial glioblastoma metastases are rare. We present a case of a 63 year-old woman with metastatic glioblastoma to the lung. Sarcomatous histology, a reported risk factor for disseminated disease, was found. Genomic alterations of TP53 mutation, TERT mutation, PTEN mutation, and +7/-10 were also uncovered. Early evidence suggests these molecular aberrations are common in metastatic glioblastoma. Treatment with third-line lenvatinib resulted in a mixed response. This case contributes to the growing body of evidence for the role of genomic alterations for predictive risk in metastatic glioblastoma. There remains an unmet need for treatment of metastatic glioblastoma.

Identification and mapping of objects targeted for surveillance and their role as risk factors for brucellosis in livestock farms in Kazakhstan.

Objects for Targeted Surveillance (OTS) are infrastructure entities that can be considered as focal points and conduits for transmitting infectious animal diseases, necessitating ongoing epidemiological surveillance. These entities encompass slaughterhouses, meat processing plants, animal markets, burial sites, veterinary laboratories, etc. Currently, in Kazakhstan, a funded research project is underway to establish a Geographic Information System (GIS) database of OTSs and investigate their role in the emergence and dissemination of infectious livestock diseases. This initial investigation examined the correlation between brucellosis outbreaks in cattle and small ruminant farms in the southeastern region of Kazakhstan and the presence of OTSs categorized as "slaughterhouses," "cattle markets," and "meat processing plants. The study area (namely Qyzylorda, Turkestan, Zhambyl, Almaty, Zhetysu, Abay and East Kazakhstan oblasts), characterized by the highest livestock density in the country, covers 335 slaughterhouses (with varying levels of biosecurity), 45 livestock markets and 15 meat processing plants. Between 2020 and 2023, 338 cases of brucellosis were reported from livestock farms in this region. The findings of the regression model reveal a statistically significant (p<0.05) positive association between the incidence of brucellosis cases and the number of OTSs in the region. Conversely, meat processing plants and livestock markets did not exhibit a significant influence on the prevalence of brucellosis cases. These results corroborate the hypothesis of an elevated risk of brucellosis transmission in regions with slaughterhouses, likely attributable to increased animal movements within and across regions, interactions with vehicles and contact with slaughterhouse staff. These outcomes mark a pivotal advancement in the national agricultural development agenda. The research will be extended to encompass the entire country, compiling a comprehensive OTS database.

E-selectin affinity glycoproteomics reveals neuroendocrine proteins and the secretin receptor as a poor-prognosis signature in colorectal cancer.

Colorectal cancer (CRC) cells express sialylated Lewis antigens (sLe), crucial for metastasis via E-selectin binding. However, these glycoepitopes lack cancer specificity, and E-selectin-targeted glycoproteins remain largely unknown. Here, we established a framework for identifying metastasis-linked glycoproteoforms. More than 70% of CRC tumors exhibited overexpression of sLeA/X, yet without discernible associations with metastasis or survival. However, The Cancer Genome Atlas (TCGA) analysis unveiled differing expression patterns of sLeA/X-related glycogenes correlating with disease severity, indicating context-dependent regulation by distinct glycosyltransferases. Deeper exploration of metastatic tumor sialoglycoproteome identified nearly 600 glycoproteins, greatly expanding our understanding of the metastasis-related glycoproteome. These glycoproteins were linked to cell adhesion, oncogenic pathways, and neuroendocrine functions. Using an in-house algorithm, the secretin receptor (SCTR) emerged as a top-ranked targetable glycoprotein. Tumor screening confirmed SCTR's association with poor prognosis and metastasis, with N-glycosylation adding cancer specificity to this glycoprotein. Prognostic links were reinforced by TCGA-based investigations. In summary, SCTR, a relatively unknown CRC glycoprotein, holds potential as a biomarker of poor prognosis and as an E-selectin ligand, suggesting an unforeseen role in disease dissemination. Future investigations should focus on this glycoprotein's biological implications for clinical applications.

LKB1 and STRADα Promote Epithelial Ovarian Cancer Spheroid Cell Invasion.

Late-stage epithelial ovarian cancer (EOC) involves the widespread dissemination of malignant disease throughout the peritoneal cavity, often accompanied by ascites. EOC metastasis relies on the formation of multicellular aggregates, called spheroids. Given that Liver Kinase B1 (LKB1) is required for EOC spheroid viability and LKB1 loss in EOC cells decreases tumor burden in mice, we investigated whether the LKB1 complex controls the invasive properties of human EOC spheroids. LKB1 signalling was antagonized through the CRISPR/Cas9 genetic knockout of LKB1 and/or the RNAi-dependent targeting of STE20-related kinase adaptor protein (STRAD, an LKB1 activator). EOC spheroids expressing nuclear GFP (green) or mKate2 (red) constructs were embedded in Matrigel for real-time live-cell invasion monitoring. Migration and invasion were also assessed in spheroid culture using Transwell chambers, spheroid reattachment, and mesothelial clearance assays. The loss of LKB1 and STRAD signalling decreased cell invasion through Matrigel and Transwell membranes, as well as mesothelial cell clearance. In the absence of LKB1, zymographic assays identified a loss of matrix metalloproteinase (MMP) activity, whereas spheroid reattachment assays found that coating plates with fibronectin restored their invasive potential. A three-dimensional EOC organoid model demonstrated that organoid area was greatly reduced by LKB1 loss. Overall, our data indicated that LKB1 and STRAD facilitated EOC metastasis by promoting MMP activity and fibronectin expression. Given that LKB1 and STRAD are crucial for EOC metastasis, targeting LKB1 and/or STRAD could disrupt the dissemination of EOC, making inhibitors of the LKB1 pathway an alternative therapeutic strategy for EOC patients.

Clinical Presentation of Cat Scratch Disease in Pediatric Patients-A Single-Center Study.

Cat scratch disease (CSD) is the infectious disease caused by Bartonella henselae. Its typical presentation is regional lymphadenopathy. Also it may present with symptoms related to involved organs or disseminated disease with fever of unknown origin (FUO). Here children with CSD are evaluated to increase awareness about disease. A total of 29 children diagnosed with CSD between 2019 and 2022 were involved in the study. Patients' demographic characteristics, clinical, laboratory and radiological findings, treatments, and outcomes were analyzed. Seventeen of the patients were male, 12 were female, and their mean age was 116.5 ± 51 months. About 69.6% of them had a history of cat contact. Twenty-seven patient (93.1%) had lymphadenopathy, mostly axillary involved (61.5%). Other manifestations were disseminated disease presented with FUO, neuroretinitis, and encephalopathy. Twenty-seven patients (93.1%) had received antibiotics before admission without any improvement. Ultrasound showed that the affected lymph nodes were conglomerated, lobulated contoured, and cortical thickened, with one-third having cystic suppurative components. Serologic tests were positive in 24 of 27 patients. Twenty-one patients gave response to 5 days azithromycin treatment, in 8 patients this treatment extended to 10-14 days, rifampicin with/without doxycycline was given to 6 patients, and steroids were given to 3 patients. In case of regional lymphadenopathy, especially axillary, not responding to nonspecific antibiotics CSD should be suspected. Cat contact history and serological and ultrasonographic findings are useful for diagnosis. Even if CSD responds well to azithromycin, sometimes prolongation of azithromycin and addition of other antibiotic or steroid may be required.

Overview of Fungi Classified as Risk Group 3 by the Japanese Society for Medical Mycology.

Fungi are categorized into Risk or Hazard Groups, depending on their potential to harm humans, with groupings ranging from 1 (least risky) to 4 (most risky). Similarly, Biosafety or Containment Levels ranging from 1 to 4 denote the level of control over microorganisms in laboratories. This review focuses on fungi categorized as Risk Group 3 by the Biosafety Committee of the Japanese Society for Medical Mycology. One such fungus is Blastomyces dermatitidis, which is primarily found in North America and causes blastomycosis, a condition that can result in a pulmonary or disseminated disease. It is classified as Risk Group 3, as substantiated by 11 laboratory-acquired infections and two fatalities. Cladophialophora bantiana, commonly found in Asia, causes brain abscesses and is also classified as Risk Group 3 due to a high mortality rate of 65.2%. Coccidioides immitis/posadasii, found in the Americas, can cause severe respiratory conditions with the potential for dissemination. Their Risk Group 3 classification is substantiated by a history of laboratory-acquired infections. Histoplasma capsulatum, which is found globally, causes a range of infections, from asymptomatic to fatal. Its classification as Risk Group 3 is substantiated by 81 laboratory-acquired infections and one fatality. Rhinocladiella mackenziei, which primarily affects the nervous system, has a mortality rate of 92.5% and is also classified as Risk Group 3. These fungi necessitate strict containment measures in laboratories owing to their high mortality rates or reported cases of laboratory-acquired infections and fatalities, emphasizing the critical need for heightened awareness and stringent safety protocols.

Modeling foot-and-mouth disease dissemination in Rio Grande do Sul, Brazil and evaluating the effectiveness of control measures.

Foot-and-mouth disease (FMD) affects multiple food-animal species and spreads rapidly among ungulate populations, posing significant challenges for disease control. Understanding the dynamics of FMD transmission and evaluating the effectiveness of control measures are critical for mitigating its impact. This study introduces a multiscale compartmental stochastic model to simulate FMD spread and assess countermeasures. We developed a model that integrates population dynamics, including births, deaths, and species-specific transmission dynamics, at both the between-farm and within-farm levels. Four scenarios were created to evaluate different control strategies: the base scenario included vaccinating 20 farms and depopulating four infected farms, while alternative scenarios increased vaccination and depopulation capacities or omitted vaccination altogether. Our simulations showed that bovines were the most frequently infected species, followed by swine and small ruminants. After 10 days of initial spread, the number of infected farms ranged from 1 to 123, with 90.12% of simulations resulting in fewer than 50 infected farms. Most secondary spread occurred within a 25 km radius. An early response to control actions significantly reduced the time spent managing outbreaks, and increasing daily depopulation and vaccination capacities further enhanced control efforts. Emergency vaccination effectively reduced the magnitude and duration of outbreaks, while increasing depopulation without vaccination also eliminated outbreaks. These findings highlight the importance of rapid response and capacity scaling in controlling FMD outbreaks, providing valuable insights for future decision-making processes in disease management.

Progressive Unilateral Proptosis and [18F]FDG-Avid Lesions Connoting Aggressive Disease in Radioiodine-Refractory Differentiated Thyroid Carcinoma

AbstractRadioiodine-refractory differentiated thyroid carcinoma (RAIR-DTC) have poor prognosis as compared with radioiodine concentrating thyroid carcinoma. We present a case of follicular thyroid carcinoma presenting as a disseminated disease initially, underwent thyroid surgery and radioiodine (RAI) therapy. Following RAI, the patient developed a sudden-onset unilateral proptosis, finally diagnosed as orbital metastasis. [18F]-Fluorodeoxyglucose (FDG)-positron emission tomography-computed tomography identified FDG-avid metastatic lesions more numerous than the RAI-avid lesions. The patient was treated with local and systemic targeted therapy, but despite these treatments, he developed progressive disease indicating aggressive nature of the disease consistent with [18F]FDG-avid RAIR-DTC.