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Clinical Infectious Diseases : An... Jun 2024Limited data exist on the antifungal activity of daily liposomal amphotericin B with flucytosine induction regimens for cryptococcal meningitis, which are recommended in...
Comparison of early fungicidal activity and mortality between daily liposomal amphotericin B and daily amphotericin B deoxycholate among patients with HIV-associated cryptococcal meningitis.
BACKGROUND
Limited data exist on the antifungal activity of daily liposomal amphotericin B with flucytosine induction regimens for cryptococcal meningitis, which are recommended in high-income countries. Liposomal amphotericin B monotherapy at 3 mg/kg previously failed to meet non-inferiority criteria compared to amphotericin B deoxycholate in its registrational clinical trial. We aimed to compare the quantitative antifungal activity and mortality between daily amphotericin B deoxycholate and daily liposomal amphotericin among persons with HIV-related cryptococcal meningitis receiving adjunctive flucytosine 100 mg/kg/day.
METHODS
We analyzed data from three clinical studies involving participants with HIV-associated cryptococcal meningitis receiving either daily liposomal amphotericin B at 3 mg/kg/day with flucytosine (N = 94) or amphotericin B deoxycholate at 0.7-1.0 mg/kg/day with flucytosine (N = 404) as induction therapy. We compared participant baseline characteristics, CSF early fungicidal activity (EFA), and 10-week mortality.
RESULTS
We included 498 participants in this analysis, of whom 201 had available EFA data (N = 46 liposomal amphotericin; N = 155 amphotericin deoxycholate). Overall, there is no statistical evidence that the antifungal activity of liposomal amphotericin B (mean EFA = 0.495 log10 CFU/mL/day; 95%CI, 0.355-0.634) differ from amphotericin B deoxycholate (mean EFA = 0.402 log10 CFU/mL; 95%CI, 0.360-0.445) (P = 0.13). Mortality at 10 weeks trended lower for liposomal amphotericin (28.2%) vs amphotericin B deoxycholate (34.6%) but was not statistically different when adjusting for baseline characteristics (adjusted Hazard Ratio = 0.74; 95%CI, 0.44-1.25; P = 0.26).
CONCLUSIONS
Daily liposomal amphotericin B induction demonstrated a similar rate of CSF fungal clearance and 10-week mortality as amphotericin B deoxycholate when combined with flucytosine for the treatment of HIV-associated cryptococcal meningitis.
PubMed: 38943665
DOI: 10.1093/cid/ciae326 -
Cancer Imaging : the Official... Jun 2024This study was based on MRI features and number of tumor-infiltrating CD8 + T cells in post-operative pathology, in predicting meningioma recurrence risk.
OBJECTIVE
This study was based on MRI features and number of tumor-infiltrating CD8 + T cells in post-operative pathology, in predicting meningioma recurrence risk.
METHODS
Clinical, pathological, and imaging data of 102 patients with surgically and pathologically confirmed meningiomas were retrospectively analyzed. Patients were divided into recurrence and non-recurrence groups based on follow-up. Tumor-infiltrating CD8 + T cells in tissue samples were quantitatively assessed with immunohistochemical staining. Apparent diffusion coefficient (ADC) histogram parameters from preoperative MRI were quantified in MaZda. Considering the high correlation between ADC histogram parameters, we only chose ADC histogram parameter that had the best predictive efficacy for COX regression analysis further. A visual nomogram was then constructed and the recurrence probability at 1- and 2-years was determined. Finally, subgroup analysis was performed with the nomogram.
RESULTS
The risk factors for meningioma recurrence were ADCp1 (hazard ratio [HR] = 0.961, 95% confidence interval [95% CI]: 0.937 ~ 0.986, p = 0.002) and CD8 + T cells (HR = 0.026, 95%CI: 0.001 ~ 0.609, p = 0.023). The resultant nomogram had AUC values of 0.779 and 0.784 for 1- and 2-years predicted recurrence rates, respectively. The survival analysis revealed that patients with low CD8 + T cells counts or ADCp1 had higher recurrence rates than those with high CD8 + T cells counts or ADCp1. Subgroup analysis revealed that the AUC of nomogram for predicting 1-year and 2-year recurrence of WHO grade 1 and WHO grade 2 meningiomas was 0.872 (0.652) and 0.828 (0.751), respectively.
CONCLUSIONS
Preoperative ADC histogram parameters and tumor-infiltrating CD8 + T cells may be potential biomarkers in predicting meningioma recurrence risk.
CLINICAL RELEVANCE STATEMENT
The findings will improve prognostic accuracy for patients with meningioma and potentially allow for targeted treatment of individuals who have the recurrent form.
Topics: Humans; Meningioma; Nomograms; Male; Female; Neoplasm Recurrence, Local; Middle Aged; CD8-Positive T-Lymphocytes; Retrospective Studies; Meningeal Neoplasms; Lymphocytes, Tumor-Infiltrating; Aged; Adult; Magnetic Resonance Imaging; Risk Factors; Prognosis
PubMed: 38943200
DOI: 10.1186/s40644-024-00731-6 -
BMC Neurology Jun 2024Diagnosis and monitoring of leptomeningeal malignancy remain challenging, and are usually based on neurological, radiological, cerebrospinal fluid (CSF) and pathological... (Comparative Study)
Comparative Study
Comparison of the diagnostic significance of cerebrospinal fluid metagenomic next-generation sequencing copy number variation analysis and cytology in leptomeningeal malignancy.
BACKGROUND
Diagnosis and monitoring of leptomeningeal malignancy remain challenging, and are usually based on neurological, radiological, cerebrospinal fluid (CSF) and pathological findings. This study aimed to investigate the diagnostic performance of CSF metagenomic next-generation sequencing (mNGS) and chromosome copy number variations (CNVs) analysis in the detection of leptomeningeal malignancy.
METHODS
Of the 51 patients included in the study, 34 patients were diagnosed with leptomeningeal malignancies, and 17 patients were diagnosed with central nervous system (CNS) inflammatory diseases. The Sayk's spontaneous cell sedimentation technique was employed for CSF cytology. And a well-designed approach utilizing the CSF mNGS-CNVs technique was explored for early diagnosis of leptomeningeal malignancy.
RESULTS
In the tumor group, 28 patients were positive for CSF cytology, and 24 patients were positive for CSF mNGS-CNVs. Sensitivity and specificity of CSF cytology were 82.35% (95% CI: 66.83-92.61%) and 94.12% (95% CI: 69.24-99.69%). In comparison, sensitivity and specificity of CSF mNGS-CNV were 70.59% (95% CI: 52.33-84.29%) and 100% (95% CI: 77.08-100%). There was no significant difference in diagnostic consistency between CSF cytology and mNGS-CNVs (p = 0.18, kappa = 0.650).
CONCLUSIONS
CSF mNGS-CNVs tend to have higher specificity compared with traditional cytology and can be used as a complementary diagnostic method for patients with leptomeningeal malignancies.
Topics: Humans; Male; Female; Meningeal Neoplasms; High-Throughput Nucleotide Sequencing; Middle Aged; DNA Copy Number Variations; Adult; Metagenomics; Aged; Young Adult; Sensitivity and Specificity; Adolescent; Cytology
PubMed: 38943096
DOI: 10.1186/s12883-024-03655-7 -
European Journal of Trauma and... Jun 2024Depressed skull fractures occur when a portion of the skull is displaced inward towards the brain, leading to complications such as intracranial hematoma, brain...
INTRODUCTION
Depressed skull fractures occur when a portion of the skull is displaced inward towards the brain, leading to complications such as intracranial hematoma, brain contusion, and intracranial infection. Managing these fractures necessitates a multidisciplinary approach, with postoperative management and rehabilitation playing crucial roles in optimizing patient outcomes. This study aimed to assess the predictive factors and outcomes of patients who underwent surgical treatment for depressed skull fractures.
METHOD
A comprehensive retrospective review was undertaken on the medical records of all patients who underwent surgery for depressed skull fractures at the University Comprehensive Specialized Hospital from January 1, 2021, to January 1, 2023 G.C. Patients with missile injuries were excluded from this study. The analysis incorporated a total of 163 patients.
RESULTS
A total of 163 patients (mean age 23.9; standard deviation 14.8; range 3-65) were studied, comprising 136 men (83.4%) and 27 women (16.6%). Among them, 153 (93.9%) were under 50 years old. Physical assault accounted for 102 (62.5%) of the injuries, with 62 (38%) involving a stone, 32 (19.6%) a stick, and 8 (5%) other objects (e.g., shovel, beer bottle). Using the Glasgow Coma Scale (GCS), minor head injuries were found in 123 individuals (75%). Fracture sites predominantly included frontal depressions (61 patients, 37.4%) and parietal depressions (53 patients, 32.5%). The associated injuries featured brain contusion (52 cases, 32%), epidural hematoma (26 cases, 16%), subdural hematoma (3 cases, 1.8%), and IVH/SAH (3 cases, 1.8%). Following surgery, full recovery occurred in 148 patients (91%), while sequelae-such as hemiparesis and aphasia-affected 15 patients (9%); unfortunately, three patients (1.8%) died due to critical head injuries prior to admission. Complications included meningitis (4 cases, 2.55%), brain abscesses (2 cases, 1.2%), surgical site infections (10 cases, 6.1%), hypocalcemia in one patient, post-traumatic stress disorder in two patients(1.6%), and osteomyelitis of the skull bone in two patients(1.2%). The multivariable logistic regression revealed that low GCS scores, compound fractures, hemiparesis, and the presence of an epidural hematoma were found to be substantially associated with a poorer outcome.
CONCLUSION
The overall outcome of patients with depressed skull fracture was favorable. Factors associated with worse outcomes include compound fracture, low Glasgow Coma Scale at admission, presence of weakness, and presence of epidural hematoma. Complications associated with depressed skull fractures observed in our patients include wound infection, meningitis, brain abscess, osteomyelitis, PTSD, and hypocalcemia.
PubMed: 38943025
DOI: 10.1007/s00068-024-02590-z -
The rapidly progressing and fatal outcome of rhombencephalitis by listeriosis in a 61-year-old male.Annals of Agricultural and... Jun 2024Listeria monocytogenes is a Gram-positive facultative anaerobic bacterium that is ubiquitous in the environment and can cause severe infections in immunocompromised...
Listeria monocytogenes is a Gram-positive facultative anaerobic bacterium that is ubiquitous in the environment and can cause severe infections in immunocompromised individuals, pregnant women, and newborns. Listeriosis can manifest as meningitis, encephalitis, or sepsis, and its diagnosis requires a high index of suspicion. The case is reported of a rare presentation of rhombencephalitis by listeriosis in a 61-year-old male who initially suffered from subacute gastric disturbances and fever. Neurological consultation showed abnormal functions of cranial nerves and meningeal signs were observed. MRI revealed a poorly demarcated focus of approximately 45 × 16 × 15mm, indicating possible inflammatory processes, necessitating a lumbar puncture. Assessment of the CSF indicated infection with the bacterium- Listeria Monocytogenes, with the final diagnosis of Listeriosis encephalitis. Despite antibiotic therapy of Ceftazidine and Ampicillin, the patient's condition deteriorated, followed by death.
Topics: Humans; Male; Listeriosis; Middle Aged; Fatal Outcome; Listeria monocytogenes; Encephalitis; Anti-Bacterial Agents; Rhombencephalon
PubMed: 38940119
DOI: 10.26444/aaem/178178 -
Case Reports in Pediatrics 2024In infants and children, bacterial meningitis caused by anaerobic bacteria is rare. However, a serious infection with the anaerobe can occur in previously healthy...
In infants and children, bacterial meningitis caused by anaerobic bacteria is rare. However, a serious infection with the anaerobe can occur in previously healthy children with a peak incidence in preschool children and in adolescents. As the clinical presentation can be very similar to meningitis caused by aerobic bacteria, one should consider as the causative agent when preceded by or associated with otitis media with purulent otorrhea or mastoiditis, in combination with minimal or no improvement on empiric antibiotic treatment. As this pathogen can be difficult to culture, anaerobic cultures should be obtained. Prompt treatment with a third-generation cephalosporin and metronidazole should be initiated once suspected or confirmed. Surgical source control is often necessary, but even with adequate and prompt treatment, the morbidity and mortality in children with a meningitis remains high. In this report, we describe a case of meningitis in a previously healthy child and review the available literature.
PubMed: 38939326
DOI: 10.1155/2024/6365796 -
Case Reports in Infectious Diseases 2024Coadministering two different classes of antibiotics as empirical therapy can be critical in treating healthcare-associated infections in hospitals. Herein, we report a...
Coadministering two different classes of antibiotics as empirical therapy can be critical in treating healthcare-associated infections in hospitals. Herein, we report a case of acute kidney injury (AKI) caused by coadministration of vancomycin with high-dose meropenem that manifested as a rapid increase in serum creatinine levels and an associated increase in vancomycin trough concentrations. The patient was diagnosed with meningioma at 50 years and was followed up regularly. The patient underwent surgery and antibiotic treatment between 63 and 66 years for suspected meningitis and pneumonia. Coadministration of vancomycin with high-dose meropenem (6.0 g/day) caused AKI; however, no AKI occurred when vancomycin was administered alone or with a low dose of meropenem (1.5 or 3.0 g/day). To our knowledge, this report is the first to show that administering different dosages of meropenem in combination with vancomycin may contribute to the risk of developing AKI. We suggest that coadministered vancomycin and high-dose meropenem (6.0 g/day) may increase the risk of AKI. Our report adds to the limited literature documenting the coadministration of vancomycin with varying doses of meropenem and its impact on the risk of AKI and highlights the importance of investigating AKI risk in response to varying dosages of meropenem when it is coadministered with vancomycin.
PubMed: 38939108
DOI: 10.1155/2024/7956014 -
CHEST Critical Care Jun 2024A 48-year-old man with history of recent travel to central Mexico and immunosuppression sought treatment with a 1-month-long history of progressive headache, fatigue,...
A 48-year-old man with history of recent travel to central Mexico and immunosuppression sought treatment with a 1-month-long history of progressive headache, fatigue, word-finding difficulties, and night sweats. The patient had a history of end-stage renal disease; he had undergone a kidney transplantation 7 years prior with good graft function with immunosuppression with tacrolimus, everolimus, and low-dose prednisone. At an outside hospital, he recently had been treated with empiric antibiotics for meningitis, but these were discontinued given the low suspicion for a bacterial cause. After discharge, he continued to have headaches, limited oral intake, persistent nausea, urinary frequency, and falls, prompting him to seek treatment at the ED. Physical examination findings were benign aside from disorientation. Laboratory workup was significant for hyponatremia of 122 mM, creatinine of 1.4 mg/dL (baseline, 1.4-1.5 mg/dL), WBC count of 7.2 10/L, hemoglobin of 13 g/dL, and platelet count of 349 10/L. Neither tacrolimus nor everolimus levels were supratherapeutic.
PubMed: 38938509
DOI: 10.1016/j.chstcc.2024.100064 -
Zoonoses and Public Health Jun 2024Angiostrongylus cantonensis, commonly known as the rat lungworm, is a metastrongyloid nematode found primarily not only in tropical and subtropical regions but also in...
BACKGROUND
Angiostrongylus cantonensis, commonly known as the rat lungworm, is a metastrongyloid nematode found primarily not only in tropical and subtropical regions but also in temperate areas and considered the leading cause of eosinophilic meningitis in humans. Synanthropic rodents such as Rattus norvegicus and Rattus rattus are the most frequent definitive hosts of this parasite.
METHODS AND RESULTS
The presence of this parasite was detected in the pulmonary arteries of three specimens of R. norvegicus in the city of Buenos Aires representing the species' southernmost known record in natural hosts. Species confirmation was achieved through partial sequences of 18S and COI genes. By comparing the COI gene sequences with those available in GenBank through the construction of a haplotype network, we obtained that the analysed specimen presents high similarity with those reported in Japan and Southeast Asia.
CONCLUSIONS
All infected rats were captured in an area surrounding a port with significant import and export activity, suggesting that A. cantonensis may have been introduced through commercial ships. Specifically, the parasite was detected in a neighbourhood with vulnerable socio-economic conditions and in a nature reserve, which exhibit biotic and abiotic characteristics conducive to sustaining high-density rat populations, scattered waste, areas of spontaneous vegetation, debris accumulation and flooded areas or lagoons offering suitable habitats for intermediate hosts such as snails. Thus, the close proximity of the port to these sites creates a favourable ecological context for the establishment of A. cantonensis. This study shows the need to conduct research to detect A. cantonensis in non-endemic areas but with the characteristics that promote its arrival and development of its life cycle in order to implement control measures to prevent expansion of this parasite and its transmission to humans and other animals.
PubMed: 38937928
DOI: 10.1111/zph.13163 -
Journal of Neuroinflammation Jun 2024Traumatic brain injury (TBI) is a significant risk factor for Alzheimer's disease (AD), and accumulating evidence supports a role for adaptive immune B and T cells in...
Traumatic brain injury alters the effects of class II invariant peptide (CLIP) antagonism on chronic meningeal CLIP + B cells, neuropathology, and neurobehavioral impairment in 5xFAD mice.
BACKGROUND
Traumatic brain injury (TBI) is a significant risk factor for Alzheimer's disease (AD), and accumulating evidence supports a role for adaptive immune B and T cells in both TBI and AD pathogenesis. We previously identified B cell and major histocompatibility complex class II (MHCII)-associated invariant chain peptide (CLIP)-positive B cell expansion after TBI. We also showed that antagonizing CLIP binding to the antigen presenting groove of MHCII after TBI acutely reduced CLIP + splenic B cells and was neuroprotective. The current study investigated the chronic effects of antagonizing CLIP in the 5xFAD Alzheimer's mouse model, with and without TBI.
METHODS
12-week-old male wild type (WT) and 5xFAD mice were administered either CLIP antagonist peptide (CAP) or vehicle, once at 30 min after either sham or a lateral fluid percussion injury (FPI). Analyses included flow cytometric analysis of immune cells in dural meninges and spleen, histopathological analysis of the brain, magnetic resonance diffusion tensor imaging, cerebrovascular analysis, and assessment of motor and neurobehavioral function over the ensuing 6 months.
RESULTS
9-month-old 5xFAD mice had significantly more CLIP + B cells in the meninges compared to age-matched WT mice. A one-time treatment with CAP significantly reduced this population in 5xFAD mice. Importantly, CAP also improved some of the immune, histopathological, and neurobehavioral impairments in 5xFAD mice over the ensuing six months. Although FPI did not further elevate meningeal CLIP + B cells, it did negate the ability of CAP to reduce meningeal CLIP + B cells in the 5xFAD mice. FPI at 3 months of age exacerbated some aspects of AD pathology in 5xFAD mice, including further reducing hippocampal neurogenesis, increasing plaque deposition in CA3, altering microgliosis, and disrupting the cerebrovascular structure. CAP treatment after injury ameliorated some but not all of these FPI effects.
Topics: Animals; Mice; Mice, Transgenic; Male; Brain Injuries, Traumatic; Histocompatibility Antigens Class II; Antigens, Differentiation, B-Lymphocyte; B-Lymphocytes; Meninges; Amyloid beta-Protein Precursor; Alzheimer Disease; Humans; Disease Models, Animal; Presenilin-1; Mice, Inbred C57BL
PubMed: 38937750
DOI: 10.1186/s12974-024-03146-z