New and old lessons from a devastating case of neonatal E coli meningitis.

BACKGROUND: Neonatal Escherichia coli (E coli) meningitis results in significant morbidity and mortality. We present a case of a premature infant with extensive central nervous system (CNS) injury from recurrent E coli infection and the non-traditional methods necessary to identify and clear the infection. CASE PRESENTATION: The infant was transferred to our institution's pediatric intensive care unit (PICU) after recurrence of E coli CNS infection requiring neurosurgical intervention. He had been treated for early onset sepsis (EOS) with ampicillin and gentamicin for 10 days followed by rapid development of ampicillin-resistant E coli septic shock and meningitis after discontinuation of antibiotics. Sterility of the CNS was not confirmed at the end of 21 days of cefepime therapy and was subsequently followed by recurrent ampicillin-resistant E coli septic shock and CNS infection. Despite 6 weeks of appropriate therapy with sterility of CSF by traditional methods, he suffered from intractable seizures with worsening hydrocephalus. Transferred to our institution, he underwent endoscopic 3rd ventriculostomy with cyst fenestration revealing purulent fluid and significant pleocytosis. An additional 3 weeks of systemic and intraventricular antibiotics with cefepime and tobramycin were given but a significant CNS neutrophil-predominant pleocytosis persisted (average of ∼ 21,000 cells/mm3). Repeated gram stains, cultures, polymerase chain reaction (PCR) testing, and metagenomic next generation sequencing (NGS) testing of CSF were negative for pathogens but acridine orange stain (AO) revealed numerous intact rod-shaped bacteria. After the addition of ciprofloxacin, sterility and resolution of CSF pleocytosis was finally achieved. CONCLUSION: Neonatal E coli meningitis is a well-known entity but unlike other bacterial infections, it has not proven amenable to shorter, more narrow-spectrum antibiotic courses or limiting invasive procedures such as lumbar punctures. Further, microbiologic techniques to determine CSF sterility suffer from poorly understood limitations leading to premature discontinuation of antibiotics risking further neurologic damage in vulnerable hosts.

Variants in the MS4A cluster interact with soluble TREM2 expression on biomarkers of neuropathology.

Recent evidence suggests that Alzheimer's disease (AD) genetic risk variants (rs1582763 and rs6591561) of the MS4A locus are genome-wide significant regulators of soluble TREM2 levels such that the minor allele of the protective variant (rs1582763) is associated with higher sTREM2 and lower AD risk while the minor allele of (rs6591561) relates to lower sTREM2 and higher AD risk. Our group previously found that higher sTREM2 relates to higher Aß40, worse blood-brain barrier (BBB) integrity (measured with the CSF/plasma albumin ratio), and higher CSF tau, suggesting strong associations with amyloid abundance and both BBB and neurodegeneration complicate interpretation. We expand on this work by leveraging these common variants as genetic tools to tune the interpretation of high CSF sTREM2, and by exploring the potential modifying role of these variants on the well-established associations between CSF sTREM2 as well as TREM2 transcript levels in the brain with AD neuropathology. Biomarker analyses leveraged data from the Vanderbilt Memory & Aging Project (n = 127, age = 72 ± 6.43) and were replicated in the Alzheimer's Disease Neuroimaging Initiative (n = 399, age = 73 ± 7.39). Autopsy analyses were performed leveraging data from the Religious Orders Study and Rush Memory and Aging Project (n = 577, age = 89 ± 6.46). We found that the protective variant rs1582763 attenuated the association between CSF sTREM2 and Aß40 (ß = -0.44, p-value = 0.017) and replicated this interaction in ADNI (ß = -0.27, p = 0.017). We did not observe this same interaction effect between TREM2 mRNA levels and Aß peptides in brain (Aß total ß = -0.14, p = 0.629; Aß1-38, ß = 0.11, p = 0.200). In contrast to the effects on Aß, the minor allele of this same variant seemed to enhance the association with blood-brain barrier dysfunction (ß = 7.0e-4, p = 0.009), suggesting that elevated sTREM2 may carry a much different interpretation in carriers vs. non-carriers of this allele. When evaluating the risk variant (rs6591561) across datasets, we did not observe a statistically significant interaction against any outcome in VMAP and observed opposing directions of associations in ADNI and ROS/MAP on Aß levels. Together, our results suggest that the protective effect of rs1582763 may act by decoupling the associations between sTREM2 and amyloid abundance, providing important mechanistic insight into sTREM2 changes and highlighting the need to incorporate genetic context into the analysis of sTREM2 levels, particularly if leveraged as a clinical biomarker of disease in the future.

Cerebral Cavernous Malformation Bleeding Following Cerebrospinal Fluid Diversion Surgery: A Case Report and Literature Review.

Cavernous malformations (CM) are rare intracerebral vascular lesions occurring in the brain, or less commonly in the spine, with an annual bleeding risk of up to 1.1%. These lesions can be occult or present to signs and symptoms based on location or, more frequently, are a result of hemorrhagic events. The most challenging aspect of managing these cases is weighing the risks and benefits of surgical treatment and intervening before the onset of a devastating hemorrhagic event. Here, we present the second case of CM haemorrhage following the cerebrospinal fluid (CSF) diversion procedure with a literature review of theories explaining this phenomenon. We present a 37-year-old female who has a known case of brainstem cavernoma and underwent left sub-temporal resection with stable residual since 2011, then was managed conservatively due to patient preference till she had a deterioration in December 2021 manifested as confusion, diplopia, dysarthria, and significant left sided weakness leaving her wheelchair bound. CT showed supratentorial hydrocephalus with extensive periventricular transependymal edema and no clear haemorrhage. A ventriculoperitoneal (VP) shunt was inserted, with no intraoperative complications. A few hours post-VP shunt insertion, she experienced a worsening in her mental status, hemiparesis, and dysarthria. Subsequent imaging found evidence of acute haemorrhage in the location of the previously noted residual. She was managed by supportive care. Causative factors of CM haemorrhage are poorly understood, and current data only suggest that prior haemorrhage and CM location could increase bleeding risk. Only one case of CM bleeding post-shunt insertion was reported; however, studies on other types of intracranial vascular lesions suggest that alterations in transmural pressure (including cerebrospinal fluid diversion procedures) can increase the risk of haemorrhage by changing the hemodynamic flow in these abnormally formed and weak vascular structures.

Effectiveness and safety of granulocyte colony-stimulating factor priming regimen for acute myeloid leukemia: A systematic review and meta-analysis of the Clinical Practice Guideline for the use of G-CSF 2022 from the Japan Society of Clinical Oncology.

BACKGROUND: The outcomes of relapsed or refractory acute myeloid leukemia (AML) remain poor. Although the concomitant use of granulocyte colony-stimulating factor (G-CSF) and anti-chemotherapeutic agents has been investigated to improve the antileukemic effect on AML, its usefulness remains controversial. This study aimed to investigate the effects of G-CSF priming as a remission induction therapy or salvage chemotherapy. METHODS: We performed a thorough literature search for studies related to the priming effect of G-CSF using PubMed, Ichushi-Web, and the Cochrane Library. A qualitative analysis of the pooled data was performed, and risk ratios (RRs) with confidence intervals (CIs) were calculated and summarized. RESULTS: Two reviewers independently extracted and accessed the 278 records identified during the initial screening, and 62 full-text articles were assessed for eligibility in second screening. Eleven studies were included in the qualitative analysis and 10 in the meta-analysis. A systematic review revealed that priming with G-CSF did not correlate with an improvement in response rate and overall survival (OS). The result of the meta-analysis revealed the tendency for lower relapse rate in the G-CSF priming groups without inter-study heterogeneity [RR, 0.91 (95% CI 0.82-1.01), p = 0.08; I2 = 4%, p = 0.35]. In specific populations, including patients with intermediate cytogenetic risk and those receiving high-dose cytarabine, the G-CSF priming regimen prolonged OS. CONCLUSIONS: G-CSF priming in combination with intensive remission induction treatment is not universally effective in patients with AML. Further studies are required to identify the patient cohort for which G-CSF priming is recommended.

Detection of tumor-derived cell-free DNA in cerebrospinal fluid using a clinically validated targeted sequencing panel for pediatric brain tumors.

PURPOSE: Clinical sequencing of tumor DNA is necessary to render an integrated diagnosis and select therapy for children with primary central nervous system (CNS) tumors, but neurosurgical biopsy is not without risk. In this study, we describe cell-free DNA (cfDNA) in blood and cerebrospinal fluid (CSF) as sources for "liquid biopsy" in pediatric brain tumors. METHODS: CSF samples were collected by lumbar puncture, ventriculostomy, or surgery from pediatric patients with CNS tumors. Following extraction, CSF-derived cfDNA was sequenced using UW-OncoPlex™, a clinically validated next-generation sequencing platform. CSF-derived cfDNA results and paired plasma and tumor samples concordance was also evaluated. RESULTS: Seventeen CSF samples were obtained from 15 pediatric patients with primary CNS tumors. Tumor types included medulloblastoma (n = 7), atypical teratoid/rhabdoid tumor (n = 2), diffuse midline glioma with H3 K27 alteration (n = 4), pilocytic astrocytoma (n = 1), and pleomorphic xanthoastrocytoma (n = 1). CSF-derived cfDNA was detected in 9/17 (53%) of samples, and sufficient for sequencing in 8/10 (80%) of extracted samples. All somatic mutations and copy-number variants were also detected in matched tumor tissue, and tumor-derived cfDNA was absent in plasma samples and controls. Tumor-derived cfDNA alterations were detected in the absence of cytological evidence of malignant cells in as little as 200 µl of CSF. Several clinically relevant alterations, including a KIAA1549::BRAF fusion were detected. CONCLUSIONS: Clinically relevant genomic alterations are detectable using CSF-derived cfDNA across a range of pediatric brain tumors. Next-generation sequencing platforms are capable of producing a high yield of DNA alterations with 100% concordance rate with tissue analysis.

Parent perception of telemetric intracranial pressure monitoring in children - A qualitative case study.

Introduction: Telemetric monitoring of intracranial pressure (ICP) in children with a complex cerebrospinal disorder might help parents distinguish acute and potential life-threatening symptoms of hydrocephalus from other illnesses. Research question: What is patient and parent perceptions of system utility of telemetric ICP monitoring, and how does a long-term telemetric implant influence daily life of both patients and their families? Material and methods: A qualitative case study design with a focus group interview including parents of children with a complex cerebrospinal fluid disorder and an implanted telemetric ICP sensor. Results: Three parents participated. Based on thematic analysis, three themes were created: 'Daily living with telemetric ICP monitoring', 'Parenting a child with a CSF disorder', and 'The healthy sibling'. The ICP sensor provided the parents with security and made them trust their intuition, while the possibility of home monitoring ensured stability for the entire family and had a calming effect on healthy siblings. Home monitoring was seen as the system's greatest advantages, whereas size, weight, and functionality of the external monitoring equipment were highlighted as disadvantages. Discussion and conclusion: All parents supported the telemetric ICP sensor as a valued tool in treatment guidance of their child and stated that advantages exceeded disadvantages. It was stated that the possibility of conducting ICP measurements at home reduced the need for acute hospital admissions, which consequently led to a more stable daily life for the entire family. Suggestions regarding technical improvements with focus on more compatible external monitoring equipment were raised by all parents included.

Abnormal EEG microstates in Alzheimer's disease: predictors of ß-amyloid deposition degree and disease classification.

Electroencephalography (EEG) microstates are used to study cognitive processes and brain disease-related changes. However, dysfunctional patterns of microstate dynamics in Alzheimer's disease (AD) remain uncertain. To investigate microstate changes in AD using EEG and assess their association with cognitive function and pathological changes in cerebrospinal fluid (CSF). We enrolled 56 patients with AD and 38 age- and sex-matched healthy controls (HC). All participants underwent various neuropsychological assessments and resting-state EEG recordings. Patients with AD also underwent CSF examinations to assess biomarkers related to the disease. Stepwise regression was used to analyze the relationship between changes in microstate patterns and CSF biomarkers. Receiver operating characteristics analysis was used to assess the potential of these microstate patterns as diagnostic predictors for AD. Compared with HC, patients with AD exhibited longer durations of microstates C and D, along with a decreased occurrence of microstate B. These microstate pattern changes were associated with Stroop Color Word Test and Activities of Daily Living scale scores (all P < 0.05). Mean duration, occurrences of microstate B, and mean occurrence were correlated with CSF Aß 1-42 levels, while duration of microstate C was correlated with CSF Aß 1-40 levels in AD (all P < 0.05). EEG microstates are used to predict AD classification with moderate accuracy. Changes in EEG microstate patterns in patients with AD correlate with cognition and disease severity, relate to Aß deposition, and may be useful predictors for disease classification.

From Pseudotumor Cerebri to Neurobrucellosis: A Journey With Several Lessons.

We present a case admitted for evaluation of suspected idiopathic intracranial hypertension (IIH) with an unusual but important departure from the expected algorithm. A 31-year-old lady came with a two-week duration of a mild headache and one-week duration of double vision with no previously documented fever or any comorbidities. Clinically, she had papilledema and bilateral abducens palsy with no signs of meningeal irritation. MRI brain radiology was consistent with IIH. Her CSF study showed pleocytosis with elevated protein levels and normal glucose. Serology was positive for Brucella melitensis at low titers but CSF culture grew Brucella melitensis, confirming the diagnosis of neurobrucellosis. Her headache and abducens palsy improved over the first two weeks, and the papilledema resolved over two months with antibiotics. This clinical mimic is important for physicians (including neurophysicians) and Infectious Disease specialists. The radiological mimic comes from chinked (small) ventricles, unlike most meningeal diseases which can present with papilledema and abducens palsy including tuberculosis, cryptococcosis, and leptomeningeal carcinomatosis. A CSF study is mandatory in the workup of IIH despite massive improvements in imaging.

The Effectiveness and Optimal Timing of PEG-rhG-CSF After Autologous Peripheral Blood Stem Cell Transplantation: A Multicenter Experience.

No consensus has been made on the use of PEG-modification recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF) in patients receiving autologous peripheral blood stem cell transplantation (PBSCT). To evaluate the efficacy and safety of PEG-rhG-CSF in provision of neutrophil support for lymphoma patients receiving autologous PBSCT. This retrospective study included lymphoma patients receiving either PEG-rhG-CSF or rhG-CSF after autologous PBSCT from 2018 to 2021 in two clinics. Hematologic recovery time, incidence of infectious complications and toxicity were compared between these two rhG-CSFs and among different initiation time of PEG-rhG-CSF. Of the 139 subjects included, 93 received PEG-rhG-CSF and 46 received rhG-CSF after transplantation. Compared with rhG-CSF, PEG-rhG-CSF marginally but significantly accelerated the neutrophil engraftment by 1 day (10 vs. 9 days, respectively) with no increasing on the risk of infectious complication and toxicity. In the PEG-rhG-CSF group, 50 patients received the growth factor on day 1, 19 received on day 3 and 24 received on day 5. The neutrophil engraftment was significantly shorter in day 1 and day 3 subgroup (9, 9, and 10 days, respectively), with a lower incidence of febrile neutropenia (82%, 100%, 100%) and documented infections (76%, 100%, 100%) in day 1 subgroup. PEG-rhG-CSF might be an alternative to rhG-CSF for lymphoma patients received autologous PBSCT. Administrating PEG-rhG-CSF on day 1 can achieve both faster hematologic recovery and lower infectious complications. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-023-01704-8.

Ventriculoperitoneal shunt for giant porencephaly: a case report and literature review.

Porencephaly (POR) is an exceedingly rare neurological disorder characterized by the presence of solitary or multiple regressive cerebrospinal fluid (CSF) cavities within the brain parenchyma. Currently, there is a limited understanding of the pathogenesis and treatment options for this condition, and clinical presentations can vary significantly. However, imaging plays a crucial role in diagnosis and determining the optimal treatment strategy, necessitating individualized comprehensive treatment upon detection. We reported a 25-year-old male case with persistent head pain that did not resolve with rest. Magnetic resonance imaging (MRI) confirmed the giant POR, and we finally performed a ventriculoperitoneal shunt, and the symptoms of intracranial hypertension were relieved after surgery.

Characterization of HIV variants from paired Cerebrospinal fluid and Plasma samples in primary microglia and CD4+ T-cells.

Despite antiretroviral therapy (ART), HIV persistence in the central nervous system (CNS) continues to cause a range of cognitive impairments in people living with HIV (PLWH). Upon disease progression, transmigrating CCR5-using T-cell tropic viruses are hypothesized to evolve into macrophage-tropic viruses in the CNS that can efficiently infect low CD4-expressing cells, such as microglia. We examined HIV-1 RNA concentration, co-receptor usage, and CSF compartmentalization in paired CSF and blood samples from 19 adults not on treatment. Full-length envelope CSF- and plasma-derived reporter viruses were generated from 3 subjects and phenotypically characterized in human primary CD4+ T-cells and primary microglia. Median HIV RNA levels were higher in plasma than in CSF (5.01 vs. 4.12 log10 cp/mL; p = 0.004), and coreceptor usage was mostly concordant for CCR5 across the paired samples (n = 17). Genetically compartmentalized CSF viral populations were detected in 2 subjects, one with and one without neurological symptoms. All viral clones could replicate in T-cells (R5 T cell-tropic). In addition, 3 CSF and 1 plasma patient-derived viral clones also had the capacity to replicate in microglia/macrophages and, therefore have an intermediate macrophage tropic phenotype. Overall, with this study, we demonstrate that in a subset of PLWH, plasma-derived viruses undergo genetic and phenotypic evolution within the CNS, indicating viral infection and replication in CNS cells. It remains to be studied whether the intermediate macrophage-tropic phenotype observed in primary microglia represents a midpoint in the evolution towards a macrophage-tropic phenotype that can efficiently replicate in microglial cells and propagate viral infection in the CNS.

Case report: Cerebrospinal fluid neutrophilic pleocytosis upon intrathecal triamcinolone injection.

Intrathecal corticosteroids, initially employed in the 1950s, faced declining use due to complications like arachnoiditis and aseptic meningitis. Triamcinolone, which is nowadays used as intrathecally applied glucocorticoid formulation, has been shown to beneficially influence spasticity without demonstrable influence on disease activity or progression. We here present the case of a patient with recurrent episodes of aseptic cerebrospinal fluid (CSF) neutrophilic pleocytosis over a year following intrathecal triamcinolone treatment. CSF analyses revealed a post-injection CSF cytokine profile resembling cytokine release reaction rather than drug hypersensitivity. This case thus highlights a potential side effect of intrathecal triamcinolone injection with yet unclear clinical relevance, underscores the need for further assessment of clinical benefits of intrathecal triamcinolone, and emphasizes potential short and long-term side effects associated with extended intrathecal triamcinolone use.

Dataset of cell viability and analytes released by cancer cell lines exposed to low pH and conditioned medium.

Cancer cells influence their microenvironment by secreting factors that promote tumour growth and survival while evading immune-mediated destruction. We previously determined the expression of secreted factors in breast and oesophageal squamous cell carcinoma cell lines (MCF-7 and WHCO6, respectively) using Luminex assays. These cells were subsequently treated with low pH medium to mimic in vivo acid exposure, and the effects on cell viability, proliferation, and secretion of cytokines, chemokines and growth factors were described [1]. Here, we present the datasets from these experiments in addition to data obtained from treating cell lines with conditioned medium from apoptotic cell cultures.

Magnetic Resonance Imaging/cerebrospinal Fluid-negative Myelitis Following COVID-19 with a Dramatic Response to Early Aggressive Immunosuppressive Therapy.

A 57-year-old man presented with subacute-onset paraparesis, bilateral dysesthesia in his lower extremities, and bladder/bowel disturbance six weeks after being infected with SARS-CoV-2 infection (COVID-19). A neurological examination suggested transverse myelitis at the level of the lower thoracic spinal cord. However, repeated spinal magnetic resonance imaging (MRI) showed no abnormalities in the spinal cord. Laboratory and cerebrospinal fluid (CSF) tests ruled out other etiologies of myelitis, eventually suggesting COVID-19-associated myelitis. Aggressive immunosuppressive therapy, started soon after hospitalization, dramatically improved his symptoms. Early aggressive immunosuppressive therapy should therefore be considered in cases of MRI/CSF-negative myelitis associated with COVID-19.

Chlorin e6 and BLZ945 Based Self-Assembly for Photodynamic Immunotherapy Through Immunogenic Tumor Induction and Tumor-Associated Macrophage Depletion.

Immunotherapeutic effect is restricted by the nonimmunogenic tumor phenotype and immunosuppression behaviors of tumor-associated macrophages (TAMs). In this work, a drug self-assembly (designated as CeBLZ) is fabricated based on chlorin e6 (Ce6) and BLZ945 to activate photodynamic immunotherapy through tumor immunogenic induction and tumor-associated macrophage depletion. It is found that Ce6 tends to assemble with BLZ945 without any drug excipients, which can enhance the cellular uptake, tumor penetration, and blood circulation behaviors. The robust photodynamic therapy effect of CeBLZ efficiently suppresses the primary tumor growth and also triggers immunogenic cell death to reverse the nonimmunogenic tumor phenotype. Moreover, CeBLZ can deplete TAMs in tumor tissues to reverse the immunosuppression microenvironment, activating abscopal effect for distant tumor inhibition. In vitro and in vivo results confirm the superior antitumor effect of CeBLZ with negligible side effect, which might promote the development of sophisticated drug combinations for systematic tumor management.

Circadian Regulation of Bone Remodeling.

Adult bones are continuously remodeled by the balance between bone resorption by osteoclasts and subsequent bone formation by osteoblasts. Many studies have provided molecular evidence that bone remodeling is under the control of circadian rhythms. Circadian fluctuations have been reported in the serum and urine levels of bone turnover markers, such as digested collagen fragments and bone alkaline phosphatase. Additionally, the expressions of over a quarter of all transcripts in bones show circadian rhythmicity, including the genes encoding master transcription factors for osteoblastogenesis and osteoclastogenesis, osteogenic cytokines, and signaling pathway proteins. Serum levels of calcium, phosphate, parathyroid hormone, and calcitonin also display circadian rhythmicity. Finally, osteoblast- and osteoclast-specific knockout mice targeting the core circadian regulator gene Bmal1 show disrupted bone remodeling, although the results have not always been consistent. Despite these studies, however, establishing a direct link between circadian rhythms and bone remodeling in vivo remains a major challenge. It is nearly impossible to repeatedly collect bone materials from human subjects while following circadian changes. In addition, the differences in circadian gene regulation between diurnal humans and nocturnal mice, the main model organism, remain unclear. Filling the knowledge gap in the circadian regulation of bone remodeling could reveal novel regulatory mechanisms underlying many bone disorders including osteoporosis, genetic diseases, and fracture healing. This is also an important question for the basic understanding of how cell differentiation progresses under the influence of cyclically fluctuating environments.

Balancing Benefits and Risks: A Literature Review on Hypersensitivity Reactions to Human G-CSF (Granulocyte Colony-Stimulating Factor).

Human granulocyte colony-stimulating factor (G-CSF) is a granulopoietic growth factor used in the treatment of neutropenia following chemotherapy, myeloablative treatment, or healthy donors preparing for allogeneic transplantation. Few hypersensitivity reactions (HRs) have been reported, and its true prevalence is unknown. We aimed to systematically characterize G-CSF-induced HRs while including a comprehensive list of adverse reactions. We reviewed articles published before January 2024 by searching in the PubMed, Embase, Cochrane Library, and Web of Science databases using a combination of the keywords listed, selected the ones needed, and extracted relevant data. The search resulted in 68 entries, 17 relevant to our study and 7 others found from manually searching bibliographic sources. A total of 40 cases of G-CSF-induced HR were described and classified as immediate (29) or delayed (11). Immediate ones were mostly caused by filgrastim (13 minimum), with at least 9 being grade 5 on the WAO anaphylaxis scale. Delayed reactions were mostly maculopapular exanthemas and allowed for the continuation of G-CSF. Reactions after first exposure frequently appeared and were present in at least 11 of the 40 cases. Only five desensitization protocols have been found concerning the topic at hand in the analyzed data. We believe this study brings to light the research interest in this topic that could benefit from further exploration, and propose regular updating to include the most recently published evidence.

Cytokine profiles associated with disease severity and prognosis of autoimmune pulmonary alveolar proteinosis.

BACKGROUND: Pulmonary alveolar proteinosis (PAP) is characterized by an abnormal accumulation of surfactants in the alveoli. Most cases are classified as autoimmune PAP (APAP) because they are associated with autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF). However, GM-CSF autoantibody levels are unlikely to correlate with the disease severity or prognosis of APAP. METHODS: We collected clinical records and measured 38 serum cytokine concentrations for consecutive patients with APAP. After exclusion of 21 cytokines because of undetectable levels, 17 cytokine levels were compared between low and high disease severity scores (DSSs). We also compared whole lung lavage (WLL)-free survival with cut-off values defined by receiver operating characteristic (ROC) curves of cytokine levels and WLL administration at 11 months. RESULTS: Nineteen patients with APAP were enrolled in the study. Five were classified as DSS 1 or 2, while the others were classified as DSS 4 or 5. Comparison between DSS 1-2 and 4-5 revealed that the concentrations of IP-10 and GRO increased in the latter groups (p < 0.05). Fifteen patients underwent WLL. Comparison between those who underwent WLL within 11 months and the others showed that IP-10 and TNF-α were tended to be elevated in the former group (p = 0.082 and 0.057, respectively). The cut-off values of IP-10, 308.8 pg/mL and TNF-α, 19.1 pg/mL, defined by the ROC curves, significantly separated WLL-free survivals with log-rank analyses (p = 0.005). CONCLUSIONS: The concentrations of IP-10 and GRO may reflect the DSSs of APAP. A combination of IP-10 and TNF-α levels could be a biomarker to predict WLL-free survival.

The neutrophil to lymphocyte ratio associates with markers of Alzheimer's disease pathology in cognitively unimpaired elderly people.

BACKGROUND: An elevated neutrophil-lymphocyte ratio (NLR) in blood has been associated with Alzheimer's disease (AD). However, an elevated NLR has also been implicated in many other conditions that are risk factors for AD, prompting investigation into whether the NLR is directly linked with AD pathology or a result of underlying comorbidities. Herein, we explored the relationship between the NLR and AD biomarkers in the cerebrospinal fluid (CSF) of cognitively unimpaired (CU) subjects. Adjusting for sociodemographics, APOE4, and common comorbidities, we investigated these associations in two cohorts: the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the M.J. de Leon CSF repository at NYU. Specifically, we examined associations between the NLR and cross-sectional measures of amyloid-ß42 (Aß42), total tau (t-tau), and phosphorylated tau181 (p-tau), as well as the trajectories of these CSF measures obtained longitudinally. RESULTS: A total of 111 ADNI and 190 NYU participants classified as CU with available NLR, CSF, and covariate data were included. Compared to NYU, ADNI participants were older (73.79 vs. 61.53, p < 0.001), had a higher proportion of males (49.5% vs. 36.8%, p = 0.042), higher BMIs (27.94 vs. 25.79, p < 0.001), higher prevalence of hypertensive history (47.7% vs. 16.3%, p < 0.001), and a greater percentage of Aß-positivity (34.2% vs. 20.0%, p = 0.009). In the ADNI cohort, we found cross-sectional associations between the NLR and CSF Aß42 (ß = -12.193, p = 0.021), but not t-tau or p-tau. In the NYU cohort, we found cross-sectional associations between the NLR and CSF t-tau (ß = 26.812, p = 0.019) and p-tau (ß = 3.441, p = 0.015), but not Aß42. In the NYU cohort alone, subjects classified as Aß + (n = 38) displayed a stronger association between the NLR and t-tau (ß = 100.476, p = 0.037) compared to Aß- subjects or the non-stratified cohort. In both cohorts, the same associations observed in the cross-sectional analyses were observed after incorporating longitudinal CSF data. CONCLUSIONS: We report associations between the NLR and Aß42 in the older ADNI cohort, and between the NLR and t-tau and p-tau in the younger NYU cohort. Associations persisted after adjusting for comorbidities, suggesting a direct link between the NLR and AD. However, changes in associations between the NLR and specific AD biomarkers may occur as part of immunosenescence.

Cerebrospinal Fluid-Venous Fistulas.

Cerebrospinal fluid-venous fistulas (CSFVFs) were first described in 2014 and have since become an increasingly diagnosed cause of spontaneous intracranial hypotension due to increased clinical recognition and advancements in diagnostic modalities. In this review, the authors discuss CSFVF epidemiology, the variety of clinical presentations, the authors' preferred diagnostic approach, recent advancements in diagnostic methods, treatment options, current challenges, and directions of future research.