Disseminated Disease Research Articles

Guardian of society: Civil society in Nigeria's response to COVID-19 pandemic.

The rapid breakout and dissemination of the coronavirus disease 2019 (COVID-19) infection from the city of Wuhan, China, to the rest of the countries of the world in December 2019 triggered a situation that led the World Health Organization to report it as a global public health emergency. The pandemic resulted in abrupt and significant loss of lives, disruption of economies, loss of livelihoods, and severe hardship across the nations of the world. Nigeria encountered the COVID-19 reality following the discovery of the first case of the infection in the country on February 27, 2020, prompting the government to swing into action to contain its spread. However, the government's response to the pandemic benefited from the support of nonstate actors from the profit and nonprofit sectors. This study, thus, specifically examined the role of civil society organizations (CSOs) in Nigeria's response to the coronavirus crisis. Using data obtained through secondary sources and analysis of thematic and descriptive-interpretive methods, the study found that CSOs impressively contributed to the government's fight against COVID-19, particularly in view of their roles in creating awareness about the virus and rebutting disinformation regarding the disease, among others. Yet, CSOs encountered some problems while undertaking these roles, prominently the closure of the civic space, noninclusion of CSOs in government's pandemic response architecture, and loss of funding. The study recommends, among other things, that in the case of any future public health emergencies of COVID-19 magnitude, the Nigerian Government should make CSOs an integral part of its response structure, while concluding that the application of these measures would incentivize better contributions from CSOs.

Patient's HLA Genotype Is Associated With the Risk of Central Nervous System Dissemination and Clinical Disease Presentation in Diffuse Large B-cell Lymphoma.

Central nervous system (CNS) involvement in aggressive B-cell lymphoma, either as a primary or secondary event to systemic disease, portends a poor prognosis. This study sought to identify patients at high risk for CNS relapse by analyzing their human leukocyte antigen (HLA) genotypes. We retrospectively examined the HLA genotypes of 164 patients with systemic lymphoma, primary CNS lymphoma, and CNS relapse of systemic lymphoma. Patient records were analyzed, and HLA typing was performed by the Finnish Red Cross Blood Service. After excluding patients who received CNS prophylaxis, 131 patients were included in the final analysis. A strong association was found between the HLA-A*31 genotype and CNS disease (p=0.001). Additionally, various HLA genotypes were linked to lactate dehydrogenase levels, extranodal disease, International Prognostic Index score, and disease stage. The patient's genetic constitution, rather than solely disease-related factors, plays a role in the tropism of lymphoma for the CNS. If confirmed in a larger study, defining the HLA genotype of a lymphoma patient could provide valuable information for predicting CNS relapse.

Immunotherapy and PD-L1 Tumor Expression in Moroccan Non-Small Cell Lung Cancer Patients with Various Metastasis.

The question of whether tumor expression of PD-L1 and the presence of distant metastasis could influence the efficacy of immunotherapy represents a major challenge and needs to be further elucidated. The aim of this study is to evaluate the predictive significance of tumor expression of PD-L1 as well as the number and site of metastasis in non-small cell lung cancer (NSCLC) among Moroccan patients treated with immunotherapy. Between January 2019 and February 2023, we recruited Moroccan patients with metastatic NSCLC. All were treated with immunotherapy, either as monotherapy or in combination with chemotherapy. Immunohistochemistry was used to assess PD-L1 (clone 22C3) and ALK (clone D5F3) status. EGFR status was established by qPCR. Tumor PD-L1 expression was classified into 2 levels: TPS <1% (negative expression) and TPS ≥1% (positive expression). Statistical analysis was performed using SPSS Statistics V.21 software. The median age of patients (N=40) was 67 years (39- 92 years) and the sex ratio was 9. Disease dissemination revealed that 22.5% (N=9) of patients had a metastatic burden ≥ 3 (MB≥3). As for the sites of metastasis, the results showed that 20% (N=8), 10% (N=4), 42.5% (N=17), 22.5% (N=9), 27.5% (N=11), 45% (N=18) and 27.5% (N=11) of patients had developed lymph node, liver, bone, brain, pleural, contralateral lung and adrenal metastasis respectively. Positive PD-L1 expression was significantly associated with shorter overall survival (OS = 17.19 vs. 28.85 months, p=0.01). High metastatic burden (MB ≥ 3) was associated with lower objective response rate (ORR), shorter progression-free survival (PFS), and reduced OS, respectively (ORR = 0 vs. 58.06%, p=0.002; PFS = 10.23 vs. 25.27 months, p=0.001; and OS = 11.60 vs. 27.91 months, p=0.003). Only the presence of osseous metastasis was significantly associated with lower ORR, shorter PFS, and OS compared to other metastatic locations (ORR = 5.88 vs. 73.9%, p=0.000; PFS = 10.72 vs. 31.33 months, p=0.000; and OS = 11.39 vs. 36.17 months, p=0.000). Finally, the presence of hepatic metastasis was significantly associated with shorter PFS (10.75 months) compared to those without hepatic metastasis (22.53 months) (p=0.046). Finally, the results of the multivariate analysis revealed that the presence of bone metastasis was strongly correlated with a significant decrease in progression-free survival (p=0.001) as well as overall survival (p=0.002). Our results suggest that tumor expression of PD-L1 and metastatic burden should play a significant role in predicting the response to immunotherapy. Furthermore, it is important to note that the presence of osseous and hepatic metastasis could negatively influence the clinical outcomes of immunotherapy.

Viewpoint of multi-omics potential in tuberculosis research: identifying biomarkers for biomanufacturing of efficient control tools

Tuberculosis (TB), caused by Mycobacterium tuberculosis complex (MTBC), remains a global health burden, claiming millions of lives annually. Despite the availability of a vaccine (the Bacillus Calmette-Guérin; BCG), diagnostics (smear microscopy and DNA-based diagnostics) and drugs for treatment, challenges like drug resistance, lower diagnostic sensitivity such as microscopy, instrumentation and high-level operational expertise requirement and poor vaccine efficacy pose a greater hinderance to TB monitoring and control. The inability of the BCG vaccine to protect against TB other than disseminated disease in neonates call for innovative approaches to provide improved interventions. This review highlights the potential of multi-omics as a powerful emerging tool offering a holistic insight into the intricate interplay between pathogens and the host immune response. It discusses the potential of multi-omics for discovering biomarkers as targets for rational drug design, production of more effective vaccines and as stable targets for production of universally applicable rapid diagnostics for early and accurate TB detection as well as monitoring treatment.

Longitudinal Monitoring of the Effects of Anti-Adenoviral Treatment Regimens in a Permissive In Vivo Model.

Adenovirus infections of immunocompromised patients can cause life-threatening disseminated disease. While there are presently no drugs specifically approved to treat these infections, there are several compounds that showed efficacy against adenovirus in preclinical studies. For any such compound, low toxicity is an essential requirement. As cumulative drug effects can accentuate pathology, especially in patients with other morbidities, it is important to limit antiviral exposure to what is absolutely necessary. This is achievable by monitoring the virus burden of the patients and administering antivirals to suppress virus replication to a non-pathogenic level. We modeled such a system using Syrian hamsters infected with a replication-competent adenovirus vector, in which luciferase expression is coupled to virus replication. We found that virus replication could be followed in vivo in the same animal by repeated measurement of luciferase expression. To test the utility of an interrupted treatment regimen, we used NPP-669 and valganciclovir, two antiviral compounds with high and moderate anti-adenoviral efficacy, respectively. We found that short-term treatment of adenovirus-infected hamsters at times of peak virus replication can prevent virus-associated pathology. Thus, we believe that this animal model can be used to model different treatment regimens for anti-adenoviral compounds.

Whole-genome sequence of Mucor velutinosus NIH1002, a strain associated with disseminated disease.

The draft genome of Mucor velutinosus NIH1002, a 2011 isolate from a case of disseminated disease, was sequenced using PacBio long-read and HiSeq short-read technologies. The genome has 43 contigs, an N50 of 2.65 Mb, and 13,295 protein-coding genes. It is the most complete M. velutinosus genome to date.

PARP Inhibitors in Brain Metastases from Epithelial Ovarian Cancer through a Multimodal Patient Journey: Case Reports and Literature Review.

Epithelial ovarian cancer (EOC) is the deadliest gynecological malignancy worldwide. Brain metastasis (BM) is quite an uncommon presentation. However, the likelihood of central nervous system (CNS) metastasization should be considered in the context of disseminated disease. The therapeutic management of BMs is an unmet clinical need, to date. We identified, across different cancer centers, six cases of both BRCA wild-type and BRCA-mutated EOCs spreading to the CNS. They presented either with a single brain lesion or with multiple lesions and most of them had intracranial-only disease. All cases received Poly-ADP ribose polymerase inhibitor (PARPi) maintenance, as per clinical practice, for a long time within a multimodal treatment approach. We also provide an insight into the available body of work regarding the management of this intriguing disease setting, with a glimpse of future therapeutic challenges. Despite the lack of unanimous guidelines, multimodal care pathways should be encouraged for the optimal disease control of this unfortunate patient subset. Albeit not being directly investigated in BM patients, PARPi maintenance is deemed to have a valuable role in this setting. Prospective research, aimed to implement worthwhile strategies in the multimodal patient journey of BMs from EOC, is eagerly awaited.

A methodological framework to characterize the wildlife-livestock interface: The case of wild boar in mainland Spain

BackgroundThe representation of wildlife-livestock interface (WLI) at an accurate spatial resolution poses several challenges. Furthermore, there is a lack of published material providing detailed descriptions of geospatial techniques for the purpose of producing visual results that are interpretable and contrastable for epidemiological analysis. ObjectivesOur aim is to develop a standardized, applicable, and scalable methodological framework for describing and characterizing the WLI across a large spatial extent. Subsequently, we aim to employ this framework to depict specific WLI based on different epidemiological scenarios determined by the abundance of wild boar (Sus scrofa) and domestic ungulates as an illustrative case, specifically focusing on mainland Spain. MethodsTo establish a methodological framework, we merged data from both wild and domestic sources into a hexagonal grid. We utilized data on wild boar hunting and the locations of pig, cattle, sheep, and goat farms in mainland Spain. New variables were derived from this combined dataset to illustrate the overlapping abundance between wild boar and domestic species. Finally, a cluster analysis of the generated variables was carried out, with the aim of distinguishing and characterizing various scenarios of the wild boar-domestic ungulate interface in mainland Spain. ResultsThe hexagonal grid proved appropriate to represent and evaluate the WLI at fine spatial resolution over such broad extent. Despite the inability to ascribe a dominant livestock type and production system to a specific region, we were able to identify fifteen main areas of interest in terms of overlap. As for extensive livestock, normally at the highest risk of interaction with wild boar, the primary regions in Spain were those with dehesa agroecosystem and the Atlantic areas. Certain scenarios were particularly relevant in terms of risk for interaction and subsequent transmission of disease, namely, the case of extensive pig production in south western Spain (dehesa agroecosystem), which is especially concerned about the potential introduction of African Swine fever (ASF) in the Country. Discussion and conclusionsWe provide a basis for visualizing and understanding of different WLI scenarios, which is extensible to other regions and interfaces, and automatable where precise source of data from wildlife and livestock are available. This spatial statistics framework enables the utilization of high-resolution data, ensuring consistency on uniform grids. This aligns with the needs of high-resolution disease dissemination models based on wildlife behaviour. Such aspects are crucial for developing risk assessment and improving strategies for the prevention, control, and eradication of shared priority emerging diseases at national and international levels, such as ASF.

Clinical Characteristics and Outcomes of Disseminated Strongyloidiasis in the United States-A Multicenter Network Analysis.

Human strongyloidiasis is a potentially life-threatening parasitic disease among immunocompromised hosts. We aim to determine the factors and mortality associated with disseminated strongyloidiasis. We conducted a U.S.-based multicenter retrospective cohort study to determine 90-day clinical outcomes for people diagnosed with Strongyloides infection in the TriNetX patient database. We identified adult patients with the International Classification of Diseases (10th revision, clinical modification) code for Strongyloides infection (B78) or a positive Strongyloides IgG antibody test and captured outcomes at 90 days. We identified 5,434 patients with strongyloidiasis, of whom 48 had disseminated strongyloidiasis for 0.9% prevalence of disseminated disease. Systemic connective tissue disorders, pulmonary eosinophilia, liver cirrhosis, blood disorders (monoclonal gammopathy, aplastic anemia, and lymphoid malignancy), malnutrition, alcohol use disorder, and transplantation status were frequent in patients with disseminated disease. Mortality was significantly higher in people with disseminated disease at 30 days (21%). The 90-day risk of hospitalization, bacteremia, and acute respiratory distress syndrome (ARDS) was higher in those with disseminated infection. People with disseminated strongyloidiasis had a heightened risk of hospitalization, bacteremia, acute respiratory distress syndrome, and mortality. The population at risk for severe strongyloidiasis infection is evolving, reflecting conditions in which glucocorticoids or additional immunosuppressive medications are commonly used for treatment.

Combating Disparities in a Pandemic: Increasing Dissemination of Coronavirus Disease 2019 Resources in Spanish.

Disparities exist in access to coronavirus disease 2019 (COVID-19)-related health information. We aimed to close a gap in online traffic between English and Spanish COVID-19-related health information on our institution's publicly-facing website by 50% within ten months. We used A3 improvement methodology. Outcome measures were the mean monthly difference between English and Spanish COVID-19 online traffic vis-a-vis (1) total webpage views and (2) unique webpage visits. Process measures were stratification of outcome measures by language. Plan-Do-Study-Act cycles included: Recurring advertisements on a local Spanish television station disseminating up-to-date COVID-19 information, including our institution's Spanish COVID-19 online resources, incorporation of QR codes into clinic discharge paperwork linking to institutional Spanish COVID-19 resources, and leveraging social media to expand reach. Control charts assessed impact over time. There were 1,226,196 total webpage views (369,983 Spanish; 856,213 English) and 1,065,536 unique webpage visits (350,518 Spanish; 715,018 English). Both outcome measures displayed sustained, special cause improvement from a mean monthly difference of 25,397 to 11,321 webpage views (55.4% reduction, June 2021) and 25,066 to 7080 unique webpage visits (71.8% reduction, February 2021) corresponding to special cause improvements in process measures. Improvements were not temporally associated with an intervention but coincided with emergency use approval of the COVID-19 vaccine for children aged 12-15 years (May 2021). Although our interventions did not directly show improvements in our measures, we noted increased page views of Spanish COVID-19-related health information on our institution's publicly-facing website in times of high demand for linguistically appropriate services, including pediatric vaccine roll-out.

An injectable subunit vaccine containing Elongation Factor Tu and Heat Shock Protein 70 partially protects American bison from Mycoplasma bovis infection.

Mycoplasma bovis (M. bovis) is the etiologic agent of high mortality epizootics of chronic respiratory disease in American bison (Bison bison). Despite the severity of the disease, no efficacious commercial vaccines have been licensed for the prevention of M. bovis infection in bison. Elongation factor thermal unstable (EFTu) and Heat Shock Protein 70 (Hsp70, DnaK) are highly conserved, constitutively expressed proteins that have previously been shown to provide protection against M. bovis infection in cattle. To assess the suitability of EFTu and Hsp70 as vaccine antigens in bison, the immune response to and protection conferred by an injectable, adjuvanted subunit vaccine comprised of recombinantly expressed EFTu and Hsp70 was evaluated. Vaccinates developed robust antibody and cellular immune responses against both EFTu and Hsp70 antigens. To assess vaccine efficacy, unvaccinated control and vaccinated bison were experimentally challenged with bovine herpes virus-1 (BHV-1) 4 days prior to intranasal infection with M. bovis. Vaccinated bison displayed reductions in joint infection, lung bacterial loads, and lung lesions compared to unvaccinated controls. Together, these results showed that this subunit vaccine reduced clinical disease and bacterial dissemination from the lungs in M. bovis challenged bison and support the further development of protein subunit vaccines against M. bovis for use in bison.

Unusual presentation of cat scratch disease: case report

Cat scratch disease (CSD) is an infection caused by Bartonella henselae, presents with non-specific symptoms like lymphadenopathy, fever, and fatigue. It can progress to disseminated disease, leading to complications such as liver and splenic micro abscesses, osteomyelitis, encephalitis, and uveitis. Diagnosis is challenging due to varied presentations and limited tests. Treatment involves supportive care, with severe cases requiring antimicrobial therapy. In this report, we present a case of Cat scratch disease characterized by an atypical clinical manifestation, hepatosplenic and paravertebral involvement.

Percutaneous radiofrequency ablation of ovarian cancer metastasis in the spleen: a therapeutic option to consider.

Splenic metastasis are rare clinical entities developing in less than 1% of all metastatic cancers and usually in the setting of disseminated disease. To date, splenectomy is traditionally the first line therapy in patient with splenic metastasis, however non-surgical therapies have been reported. Here we described the case of a 57-year-old patient with splenic metastasis from ovarian cancer successfully treated by percutaneous radiofrequency ablation. Furthermore, we performed a literature systematic review of the cases of splenic metastases treated by thermal ablation.

MDB-05. PERSONALIZED, RISK ADAPTED THERAPY FOR PEDIATRIC PATIENTS WITH MEDULLOBLASTOMA – A SINGLE CENTER 8-YEAR RETROSPECTIVE REVIEW

Abstract BACKGROUND Clinically relevant risk stratification and optimal therapies for pediatric medulloblastoma molecular subgroups are still being investigated. METHODS We reviewed host/disease characteristics, patient/tumor specific risk adapted therapy and outcomes of patients treated for medulloblastoma at UC Davis since 2016. RESULTS Fifteen patients (age 1-19 years, 12 male, 3 with Li Fraumeni Syndrome (LFS), 2 with spinal cord disease) were included in our review. Tumor histologies included: Classic (n=8), Desmoplastic-Nodular (n=6), Anaplastic (n=1). Tumor genomic profiles were SHHP53WT(n=5), SHHP53 mutated (n=4), Group4 (n=3), NWNSHH (n=2), WNT (n=1). Gross total resection was achieved in 9 patients. Patients with post resection residual tumor, high risk genomic features or disseminated disease were stratified as high risk. We treated all radiation eligible patients (n=13) per COG ACNS0332 maintenance chemotherapy regardless of risk group with 12/13 receiving radiosensitization (Vincristine/Carboplatin) and either 23.4 Gy/36 Gy CSI (two patients treated per Headstart3D2 and ACNS0334 respectively). 2 patients with spinal cord disease were treated with intrathecal topotecan and liposomal cytarabine respectively. During ACNS0332 maintenance bacteremia, weight loss and hypomagnesemia were frequent complications. 5 patients required chemotherapy dose reductions (4 Vincristine/1 Cisplatin). Two patients with LFS developed glioblastoma/undifferentiated pleomorphic sarcoma following ACNS0332 therapy. Two patients (with WNT and NWNSHH subgroup tumors) experienced medulloblastoma relapse. These patients were treated using LITT/Intrathecal chemotherapy and ACNS0821 chemotherapy. Both are alive and one patient is NED off therapy. All patients who have not developed secondary malignancies (n=13) are alive. (follow up 7-72 months). All attend school with support, 10 have hearing impairment and 5 receive endocrine supplements. CONCLUSIONS Utilizing patient specific risk adapted therapy we have achieved favorable clinical outcomes in our patient cohort. Therapy deintensification for patients with WNT medulloblastomas should be approached with caution. Patients with LFS might require radiation sparing therapeutic protocols for longer term benefit.

MDB-69. RADIOLOGICAL PATTERNS OF RECURRENCE IN MEDULLOBLASTOMA SUBGROUPS AND CORRELATION WITH SURVIVAL

Abstract BACKGROUND Medulloblastomas can recur in up to one-third of the patients despite optimal therapy. The knowledge of the molecular group can provide clues to the possible pattern of relapse and the course of disease, with therapeutic implications. In the present study, we have identified anatomical locations and radiological patterns of relapse. METHODS AND MATERIALS Patients with a histopathological diagnosis and available subgroups of medulloblastoma with first relapse, treated in a single tertiary care center during 2005-2021 with available magnetic resonance imaging of brain and spine were included in the retrospective study. Statistical analysis was done using Pearson chi-square test and Fisher’s exact test. RESULTS 127 patients were included in the final analysis. Median age at diagnosis was 12 years and time to first recurrence was 21 months. Tumor bed relapse was seen in 49% cases, maximum in SHH subgroup, p&amp;lt;0.01. Involvement of the ventricular system (including cisterns and ventricles) was seen in 37% of cases, and was significantly associated (p:&amp;lt;0.01) with non-WNT, non-SHH tumours. Leptomeningeal metastasis was seen in 36% of cases, with significant association (p&amp;lt;0.01) in group 3 (75% of all group 3 cases) and group 4 tumors (50% of all group 4 cases). Disease in spine was most common in group 3 (65%) and group 4 tumours (71%), p&amp;lt;0.01. Hippocampus was involved in 19 cases (15%), mostly in non-WNT, non-SHH (14 cases). Significant difference in survival after recurrence was seen with ventricular, extraventricular metastases with one year survival 83% and 73% respectively, p=0.02. Hippocampal involvement showed significantly decreased survival, one year survival of 37%, p&amp;lt;0.01. CONCLUSIONS Leptomeningeal dissemination and diffuse disease were mostly seen in group 3 tumours, indicating their aggressive nature. The lower rates of ventricular relapse and around hippocampus in SHH medulloblastoma provide the opportunity to explore hippocampal avoidance-craniospinal irradiation.

Coccidioidomycosis in Immunocompromised at a Non-Endemic Referral Center in Mexico.

The incidence and distribution of coccidioidomycosis are increasing. Information scarcity is evident in Mexico, particularly in non-endemic zones and specific populations. We compared the treatment and outcomes for patients with isolated pulmonary infections and those with disseminated coccidioidomycosis, including mortality rates within six weeks of diagnosis. Of 31 CM cases, 71% were male and 55% were disseminated. For 42% of patients, there was no evidence of having lived in or visited an endemic region. All patients had at least one comorbidity, and 58% had pharmacologic immunosuppressants. The general mortality rate was 30%; without differences between disseminated and localized disease. In our research, we describe a CM with a high frequency of disseminated disease without specific risk factors and non-significant mortality. Exposure to endemic regions was not found in a considerable number of subjects. We consider diverse reasons for why this may be, such as climate change or migration.

GCT-10. OUTCOME OF CHILDREN AND ADOLESCENTS DIAGNOSED WITH GERMINOMA WITH HCGΒ VALUES BETWEEN 100-200 MUI/ML TREATED ACCORDING TO THE BRAZILIAN CNS GCT PROTOCOL

Abstract BACKGROUND Primary central nervous system (CNS) germ cell tumors (GCT) are rare tumors, classified according to histological components and tumor markers (TM) as Germinomas and Non-Germinomatous Germ Cell Tumors (NGGCT). The aim of this study is to assess the outcome of patients with Germinoma and HCGβ levels between 100-200mIU/ml treated according to the Brazilian CNS GCT Consortium Protocol. METHODS From 2013 to 2021, forty-three patients presented with histological and/or TM (serum and CSF) consistent with the diagnosis of germinoma, five of them with HCGβ levels between 100-200mIU/ml. The treatment plan performed was four cycles of carboplatin/etoposide followed by whole ventricular field irradiation (WVFI) of 18Gy with a boost to primary site(s) up to 30Gy and 24Gy craniospinal irradiation (CSI) for disseminated disease. RESULTS Average age 13.7 years (6.3-20.3 years), four males and one female. Diagnosis was made by TM (n=2), and biopsy +TM (n=3). The primary tumor location was pineal (n=2), suprasellar (n=1), and bifocal (n=2) with 1 case presenting ventricular spread at diagnosis. Three patients achieved complete response (CR) after two cycles of chemotherapy and one after four cycles. One patient showed partial radiological response (PR) with negative TM after four cycles and was submitted to a second-look surgery, with pathological report of residual scar tissue. Radiotherapy was performed as described in all patients with four patients receiving WVFI (18Gy+30Gy) and one CSI (24Gy+30Gy). In a mean follow-up of 64 months, overall and event-free survival was 100%. CONCLUSION Despite the small sample, the present study shows effectivity with excellent results and a possibility of increasing the cutoff and therefore reducing treatment for patients with HCGβ at levels up to 200mlU/ml currently treated in some protocols as NGGCT cases.

Analysis of Caputo Fractional-Order Co-Infection COVID-19 and Influenza SEIR Epidemiology by Laplace Adomian Decomposition Method

Around the world, the people are simultaneously susceptible to or infected with several infections. This work aims at the analysis of the dynamics of transmission of two deadly viruses, COVID-19 and Influenza, using a co-infection epidemiological model by applying the Caputo fractional derivative. Fractional differential equations are currently used worldwide to model physical and biological phenomena. Our comprehension of complicated phenomena is improved when fractional-order derivatives are used to model systems with memory effects and long-range interactions. Mathematical depictions of infectious disease dynamics and dissemination across communities are provided by epidemiological models, which are essential resources for understanding and controlling infectious diseases. These models support informed decision making to prevent outbreaks, evaluate intervention measures, and help researchers and policymakers understand how diseases spread. A subclass of epidemiological models called co-infection models focuses on studying the dynamics of several infectious illnesses that occur in the same population at the same time. They are especially useful in situations where people are simultaneously susceptible to or infected with several infections. Co-infection models provide information on the development of effective control techniques, the progression of disease, and the interactions between several pathogens. The qualitative study via stability analysis is discussed at equilibrium, the reproduction number is computed, and the results are simulated using the Laplace Adomian Decomposition Method (LADM) for Fractional Differential Equations. We employ MATLAB R2023a for graphical presentations and numerical simulations.

When does a melanoma metastasize? Implications for management.

Selecting which patients with clinically-localized melanoma require treatment other than wide excision of the primary tumor is based on the risk or presence of metastatic disease. This in turn is linked to survival. Knowing if and when a melanoma is likely to metastasize is therefore of great importance. Several studies employing a range of different methodologies have suggested that many melanomas metastasize long before the primary lesion is diagnosed. Therefore, waiting for dissemination of metastatic disease to become evident before making systemic therapy available to these patients may be less effective than giving them post-operative adjuvant therapy initially if the metastatic risk is high. The identification of these high-risk patients will assist in selecting those to whom adjuvant systemic therapy can most appropriately be offered. Further studies are required to better identify high-risk patients whose primary melanoma is likely to have already metastasized.

Diagnosis of Coccidioidomycosis with the Second-Generation Miravista IgG and IgM Enzyme Immunoassay and the Role of Adding Miravista Coccidioides Antigen Detection to Immunodiagnostic Assays.

In the present study, we validate and compare the second-generation Miravista Coccidioides IgG and IgM enzyme immunoassays (EIA) (MiraVista Diagnostics [MVD] Ab EIA) to Meridian Diagnostics Coccidioides IgG and IgM EIA (Meridian Ab EIA), immunodiffusion (ID) and complement fixation (CF). We also evaluated whether the addition of Coccidioides antigen testing to anti-Coccidioides antibody testing increased the sensitivity for the diagnosis of currently active coccidioidomycosis. We retrospectively studied 555 patients evaluated at Valleywise Health Medical Center between January 2013 and May 2017 for whom coccidioidomycosis was suspected and samples were submitted to MVD for testing. Specimens were tested for antigen in the MVD antigen enzyme immunoassay (MVD Ag EIA) and for IgG and IgM antibodies with MVD and Meridian Diagnostics EIAs. ID and CF were obtained from medical records. Sensitivity and specificity were 83.0% and 91.1% or MVD Ab EIA, 69.3% and 99.7% for Meridian Ab EIA, 85.4% and 100% for ID and 65.5% and 100% for CF. Combined MVD antigen and antibody detection by EIA and ID resulted in increased sensitivity in disseminated and pulmonary disease (MVD Ag/MVD Ab: 100%, 88.3%; MVD Ag/Meridian Ab: 98.2%, 78.6%; and MVD Ag/ID: 100%, 91.7%). The detection of antibodies by MVD EIA was more sensitive than Meridian EIA or CF but similar to ID. This study supports the use of antigen testing in immunocompromised patients and those with suspected disseminated disease. Furthermore, the addition of antigen detection by EIA to antibody detection resulted in higher sensitivity of all serological tests.