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Open Forum Infectious Diseases Jun 2024Several recent randomized trials have been conducted in resource-limited settings for cryptococcal meningitis that have rapidly innovated international guidelines. The...
BACKGROUND
Several recent randomized trials have been conducted in resource-limited settings for cryptococcal meningitis that have rapidly innovated international guidelines. The 2010 Infectious Diseases Society of America (IDSA) cryptococcal meningitis guideline has not been updated with recent trials. The 2022 AMBITION-cm trial found that a single 10-mg/kg dose of liposomal amphotericin B plus daily flucytosine and fluconazole for 2 weeks was noninferior to 1 week of amphotericin B deoxycholate with flucytosine. It is unknown whether physicians in high-resource settings are using this regimen or more traditional regimens.
METHODS
We developed an electronic survey in June 2023 to better understand whether physician members of the IDSA Emerging Infections Network (EIN) and Mycoses Study Group Education and Research Consortium (MSG-ERC) had used the AMBITION-cm induction regimen, would use the regimen in hypothetical clinical scenarios, and what perceived barriers to use existed.
RESULTS
A total of 242 of 561 (43%) physicians responded to the survey, of whom 205 provided care for persons with cryptococcal meningitis in the last year. Overall, 29 (14%) had used the AMBITION-cm regimen, and 176 (86%) had not. In various hypothetical clinical scenarios, only ∼10% of 209 respondents selected the AMBITION-cm regimen as preferred. Perceived barriers to uptake included the applicability of trials performed in low-resource settings to high-resource settings, that the regimen is not recommended in the 2010 IDSA guidelines, and the applicability to persons without HIV.
CONCLUSIONS
Most respondents had not used the single-dose liposomal amphotericin B regimen, but the regimen is being used. Further study of this regimen in other patient populations and settings is necessary.
PubMed: 38887490
DOI: 10.1093/ofid/ofae120 -
Open Forum Infectious Diseases Jun 2024Clinical and epidemiological features of 7 human immunodeficiency virus-negative Peruvian patients coinfected with human T-lymphotropic virus type 1 (HTLV-1) and...
Clinical and epidemiological features of 7 human immunodeficiency virus-negative Peruvian patients coinfected with human T-lymphotropic virus type 1 (HTLV-1) and cryptococcosis (2006-2017) were studied. Most cases had meningeal involvement, were male, and originated from Peru's jungle. Patients with cryptococcosis should be tested for HTLV-1 in endemic areas of this retrovirus.
PubMed: 38887485
DOI: 10.1093/ofid/ofae022 -
Cureus May 2024Lyme disease is a multisystem infectious disease. It is caused by the dissemination of after a tick bite. It has various manifestations across different age groups....
Lyme disease is a multisystem infectious disease. It is caused by the dissemination of after a tick bite. It has various manifestations across different age groups. Commonly involved organs are the skin, joints, and nervous system. Nervous system Lyme disease has a wide spectrum of manifestations. While facial nerve palsy and subacute meningitis are commonly observed in the pediatric population, our case report reveals an uncommon manifestation of the nervous system Lyme disease. A four-year-old patient exhibited mood changes, behavioral issues, and generalized tonic-clonic seizures. Extensive diagnostic workup initially yielded no clear cause until positive IgM and IgG serology for suggested Lyme neuroborreliosis. This differs from the usual symptoms seen in pediatric cases. The patient responded positively to antibiotic treatment, but persistent post-treatment behavioral issues raised questions about potential long-term effects. This case underscores the importance of considering Lyme disease in atypical presentations, even in non-endemic areas, necessitating an adaptable diagnostic approach for improved outcomes, especially in pediatric patients. Continued research into the comprehensive understanding of Lyme disease in pediatric patients is crucial.
PubMed: 38887358
DOI: 10.7759/cureus.60535 -
Neural Regeneration Research Mar 2025Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not...
Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain metabolites but also contribute to antigen delivery and immune cell activation. The advent of novel genomic technologies has enabled rapid progress in the characterization of myeloid and lymphoid cells and their interactions with meningeal lymphatic vessels within the central nervous system. In this review, we provide an overview of the multifaceted roles of meningeal lymphatic vessels within the context of the central nervous system immune network, highlighting recent discoveries on the immunological niche provided by meningeal lymphatic vessels. Furthermore, we delve into the mechanisms of crosstalk between meningeal lymphatic vessels and immune cells in the central nervous system under both homeostatic conditions and neurodegenerative diseases, discussing how these interactions shape the pathological outcomes. Regulation of meningeal lymphatic vessel function and structure can influence lymphatic drainage, cerebrospinal fluid-borne immune modulators, and immune cell populations in aging and neurodegenerative disorders, thereby playing a key role in shaping meningeal and brain parenchyma immunity.
PubMed: 38886941
DOI: 10.4103/NRR.NRR-D-23-01595 -
PLOS Global Public Health 2024Tuberculosis (TB) mortality in Zambia remains high at 86 per 100,000 populations, translating to approximately 15,000 TB-related deaths annually. We conducted a...
Tuberculosis (TB) mortality in Zambia remains high at 86 per 100,000 populations, translating to approximately 15,000 TB-related deaths annually. We conducted a nationwide retrospective cohort study to understand predictors, time to death, and probable causes of mortality among persons on TB treatment in Zambia. We reviewed medical records for persons with TB registered in 54 purposively selected hospitals in Zambia between January and December 2019. We fitted a Cox proportional hazards model to identify predictors of mortality. Of the 13,220 records abstracted, 10,987 were analyzed after excluding records of persons who transferred in from other hospitals, those with inconsistent dates and those whose treatment outcome was not evaluated. The majority of persons with TB were men, (61.5%, n = 6,761) with a median age of 36 years (IQR: 27-46 years). Overall, 1,063 (9.7%) died before completing TB treatment (incidence rate = 16.9 deaths per 1,000 person-months). Median age at death was 40 years (IQR: 31-52). The majority of deaths (75.7%, n = 799) occurred in the first two months of TB treatment, with a median time to death of 21 days (IQR: 6-57). Independent risk factors for TB mortality included age >54 years, being treated in Eastern, Southern, Western, Muchinga and Central provinces, receiving treatment from a third-level or mission hospital, methods of diagnosis other than Xpert MTB/RIF, extrapulmonary TB (EPTB), and positive HIV status. Probable causes of death were septic shock (18.8%), TB Immune Reconstitution Inflammatory Syndrome (TB IRIS) (17.8%), end-organ damage (13.4%), pulmonary TB (11.4%), anemia (9.6%) and TB meningitis (7.8%). These results show high mortality among people undergoing TB treatment in Zambia. Interventions targeted at persons most at risk such as the elderly, those with EPTB, and those living with HIV, can help reduce TB-related mortalities in Zambia.
PubMed: 38885238
DOI: 10.1371/journal.pgph.0003329 -
Behavioural Neurology 2024The most common and aggressive tumor is brain malignancy, which has a short life span in the fourth grade of the disease. As a result, the medical plan may be a crucial...
The most common and aggressive tumor is brain malignancy, which has a short life span in the fourth grade of the disease. As a result, the medical plan may be a crucial step toward improving the well-being of a patient. Both diagnosis and therapy are part of the medical plan. Brain tumors are commonly imaged with magnetic resonance imaging (MRI), positron emission tomography (PET), and computed tomography (CT). In this paper, multimodal fused imaging with classification and segmentation for brain tumors was proposed using the deep learning method. The MRI and CT brain tumor images of the same slices (308 slices of meningioma and sarcoma) are combined using three different types of pixel-level fusion methods. The presence/absence of a tumor is classified using the proposed Tumnet technique, and the tumor area is found accordingly. In the other case, Tumnet is also applied for single-modal MRI/CT (561 image slices) for classification. The proposed Tumnet was modeled with 5 convolutional layers, 3 pooling layers with ReLU activation function, and 3 fully connected layers. The first-order statistical fusion metrics for an average method of MRI-CT images are obtained as SSIM tissue at 83%, SSIM bone at 84%, accuracy at 90%, sensitivity at 96%, and specificity at 95%, and the second-order statistical fusion metrics are obtained as the standard deviation of fused images at 79% and entropy at 0.99. The entropy value confirms the presence of additional features in the fused image. The proposed Tumnet yields a sensitivity of 96%, an accuracy of 98%, a specificity of 99%, normalized values of the mean of 0.75, a standard deviation of 0.4, a variance of 0.16, and an entropy of 0.90.
Topics: Humans; Brain Neoplasms; Magnetic Resonance Imaging; Meningioma; Multimodal Imaging; Tomography, X-Ray Computed; Deep Learning; Sarcoma; Image Processing, Computer-Assisted; Brain; Neural Networks, Computer; Meningeal Neoplasms
PubMed: 38882177
DOI: 10.1155/2024/4678554 -
Zhongguo Fei Ai Za Zhi = Chinese... May 2024Leptomeningeal metastasis (LM) is a lethal complication of malignant tumors, with an incidence rate of 3%-5% among patients with non-small cell lung cancer (NSCLC). LM... (Review)
Review
Leptomeningeal metastasis (LM) is a lethal complication of malignant tumors, with an incidence rate of 3%-5% among patients with non-small cell lung cancer (NSCLC). LM poses significant challenges in diagnosis, has poor prognosis, limited treatment options, and lacks standardized criteria for evaluating therapeutic efficacy, making it a difficult aspect of NSCLC management. Circulating tumor DNA (ctDNA), shed from tumor cells and carrying cancer-related information, holds significant value in precision oncology. Cerebrospinal fluid (CSF), present in the subarachnoid space of the brain, the spinal cord, and the central canal, and in direct contact with meningeal tissues, serves as the fluid medium that best reflects the genetic characteristics of LM. In recent years, CSF ctDNA has become a focal point due to its multi-omics features, playing a crucial role in the management of central nervous system (CNS) metastatic tumors. Its applications span the entire continuum of care, including aiding in diagnosis, assessing treatment response, predicting prognosis, and analyzing resistance mechanisms. This article provides a concise overview of CSF ctDNA detection techniques and their clinical applications in patients with NSCLC-LM. .
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Circulating Tumor DNA; Lung Neoplasms; Meningeal Neoplasms
PubMed: 38880925
DOI: 10.3779/j.issn.1009-3419.2024.102.16 -
Journal of Microorganism Control 2024Although recent propagation of carbapenemase-producing Enterobacterales (CPE) has become a problem worldwide, the picture of CPE infection in Japan has not fully been...
Although recent propagation of carbapenemase-producing Enterobacterales (CPE) has become a problem worldwide, the picture of CPE infection in Japan has not fully been elucidated. In this study, we examined clinical and microbiological characteristics of invasive CPE infection occurring at 8 hospitals in Minami Ibaraki Area between July 2001 to June 2017. Of 7294 Enterobacterales strains isolated from independent cases of bacteremia and/or meningitis, 10 (0.14%) were CPE (8 Enterobacter cloacae-complex, 1 Escherichia coli, and 1 Edwardsiella tarda), all of which had the bla gene and susceptible to gentamicin and trimethoprim/sulfamethoxazole. These strains were isolated from 7 adult and 2 infant bacteremia (1 infant patient developed CPE bacteremia twice) after 2007. The most common portal of entry was intravenous catheters. All of the adult patients were recovered, while the infant patients eventually died. Genomic analyses showed that the 8 E. cloacae-complex strains were classified into 5 groups, each of which was exclusively detected in specific facilities at intervals of up to 3 years, suggesting persistent colonization in the facilities. This study showed that invasive CPE infection in the area was rare, caused by IMP-1-type CPE having susceptibility to various antibiotics, and nonfatal among adult patients.
Topics: Humans; Japan; Bacteremia; Enterobacteriaceae Infections; beta-Lactamases; Male; Female; Anti-Bacterial Agents; Bacterial Proteins; Infant; Microbial Sensitivity Tests; Middle Aged; Adult; Aged; Enterobacter cloacae; Gentamicins; Trimethoprim, Sulfamethoxazole Drug Combination; Aged, 80 and over; Carbapenem-Resistant Enterobacteriaceae
PubMed: 38880620
DOI: 10.4265/jmc.29.2_81 -
MBio Jun 2024Mitogen-activated protein kinase (MAPK) pathways are fundamental to the regulation of biological processes in eukaryotic organisms. The basidiomycete , known for causing...
Mitogen-activated protein kinase (MAPK) pathways are fundamental to the regulation of biological processes in eukaryotic organisms. The basidiomycete , known for causing fungal meningitis worldwide, possesses five MAPKs. Among these, Cpk1, Hog1, and Mpk1 have established roles in sexual reproduction, stress responses, and cell wall integrity. However, the roles of Cpk2 and Mpk2 are less understood. Our study elucidates the functional interplay between the Cpk1/Cpk2 and Mpk1/Mpk2 MAPK pathways in . We discovered that overexpression compensates for Δ mating deficiencies via the Mat2 transcription factor, revealing functional redundancy between Cpk1 and Cpk2. We also found that Mpk2 is phosphorylated in response to cell wall stress, a process regulated by the MAPK kinase (MAP2K) Mkk2 and MAP2K kinases (MAP3Ks) Ssk2 and Ste11. Overexpression of partially restores cell wall integrity in Δ by influencing key cell wall components, such as chitin and the polysaccharide capsule. Contrarily, overexpression cannot restore thermotolerance and cell membrane integrity in Δ. These results suggest that Mpk1 and Mpk2 have redundant and opposing roles in the cellular response to cell wall and membrane stresses. Most notably, the dual deletion of and restores wild-type mating efficiency in Δ mutants via upregulation of the mating-regulating transcription factors and , suggesting that the Mpk1 and Mpk2 cooperate to negatively regulate the pheromone-responsive Cpk1 MAPK pathway. Our research collectively underscores a sophisticated regulatory network of cryptococcal MAPK signaling pathways that intricately govern sexual reproduction and cell wall integrity, thereby controlling fungal development and pathogenicity.IMPORTANCEIn the realm of fungal biology, our study on offers pivotal insights into the roles of specific proteins called mitogen-activated protein kinases (MAPKs). Here, we discovered the cryptic functions of Cpk2 and Mpk2, two MAPKs previously overshadowed by their dominant counterparts Cpk1 and Mpk1, respectively. Our findings reveal that these "underdog" proteins are not just backup players; they play crucial roles in vital processes like mating and cell wall maintenance in . Their ability to step in and compensate when their dominant counterparts are absent showcases the adaptability of . This newfound understanding not only enriches our knowledge of fungal MAPK mechanisms but also underscores the intricate balance and interplay of proteins in ensuring the organism's survival and adaptability.
PubMed: 38874410
DOI: 10.1128/mbio.01156-24