<scp><i>LTA4H</i></scp> Prevalence and Mortality in Adult Zambians with Tuberculous Meningitis

Siddiqi, Omar K.; Ghebremichael, Musie; Musukuma, Kalo; Dang, Xin; Mubanga, Eugene; Birbeck, Gretchen L.; Love, Shawn; Buback, Clayton; Kosloff, Barry; Ayles, Helen; Atadzhanov, Masharip; Koralnik, Igor J.

doi:10.1002/ana.26240

Cited by 4 publications

(3 citation statements)

References 14 publications

(34 reference statements)

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“…While the global distribution of rs17525495 SNP genotypes is similar across the Vietnamese, Indonesian, Zambian and our study cohorts, important differences exist in the in vivo and in vitro observations 5,10,11 . Zebrafish larvae modelling studies show the LTA4H gene regulates inflammatory milieu by controlling the balance between pro-and anti-inflammatory eicosanoids and Tumor necrosis factor-alpha (TNF-α) production.…”

Section: Discussionmentioning

confidence: 68%

“…CC correlates to hypo-inflammation with low TNF alpha levels and increased bacterial burden while TT with high TNF alpha levels, controlled mycobacterial burden and hyperinflammatory host immune response 5 . TT genotype predicted high pro-inflammatory cytokine milieu in the CSF and the response to corticosteroids among HIV uninfected patients in Vietnam but not in Indonesia and Zambia 5,10,11 . Among HIV-pulmonary TB coinfected patients, TT genotype was associated with severe IRIS phenomena 6 .…”

Section: Discussionmentioning

confidence: 91%

“…# TB lymphadenitis includes intra-abdominal lymphadenopathy. Other sites involved were bone (11), spleen (6), pleura (4), eye (4), psoas abscess (3), epididymis (2), skin (1), pericardium (1), pyometra (1), renal abscess (1), prostatic abscess (1). Patients are counted more than in the presentation of manifestations.…”

Section: Discussionmentioning

confidence: 99%

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Leukotriene A4 hydrolase (LTA4H rs17525495) gene polymorphisms and paradoxical reactions in extrapulmonary tuberculosis

Kumar

Solomon

Gautam

et al. 2023

Sci Rep

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Paradoxical reactions (PRs) are poorly studied complex immunological phenomena, among patients with tuberculosis (TB). When PRs involves critical structures like the central nervous system (CNS), immunomodulatory therapy is often required. Predictors for PRs in TB to pre-empt appropriate treatment strategies in high-risk groups are lacking. TT genotype of Leukotriene A4 hydrolase (LTA4H) promoter region rs17525495 polymorphisms are associated with exaggerated immune responses in Tuberculous meningitis (TBM), the most severe form of extrapulmonary tuberculosis (EPTB). The association of these polymorphisms with PRs is not known. We evaluated this plausibility among 113 patients with EPTB, at high risk of PRs. Majority [81 (71.7%)] had disseminated tuberculosis with prominent CNS [54 (47.8%)] and lymph node involvement [47 (41.6%)]. Human immunodeficiency Virus (HIV) co-infection was seen among 23 (20.3%) patients. PRs were noted in 38.9% patients, at a median duration of 3 months (IQR 2–4). LTA4H rs17525495 single nucleotide polymorphism (SNP) analysis showed 52 (46%) patients had CC, 43 (38.1%) had CT and 18 (15.9%) had TT genotypes. There was no statistically significant difference in occurrence [CC 38.5% vs CT 39.5% vs TT 38.7%] and time of onset [median (IQR)] of PRs across the genotypes [CC 3 (1–4.7), CT 3 (2–5), TT 2 (2–3)]. PRs was shown to be significantly linked with HIV co-infection (RR 0.6, 95% CI 0.29–1.28), culture positivity (RR 0.5, 95% CI 0.28–1.14), TB Lymphadenitis (RR 0.7, 95% CI 0.44–1.19) and CNS involvement RR 2.1, 95% CI 1.27–3.49) in the univariate analysis (p < 0.2). On multivariate analysis, CNS involvement alone was associated with PRs (aRR 3.8 (1.38–10.92); p < 0.01). PRs were associated with CNS involvement but not with LTA4H rs17525495 polymorphisms.

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Section: Discussionmentioning

confidence: 68%

Section: Discussionmentioning

confidence: 91%

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Leukotriene A4 hydrolase (LTA4H rs17525495) gene polymorphisms and paradoxical reactions in extrapulmonary tuberculosis

Kumar

Solomon

Gautam

et al. 2023

Sci Rep

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Do you see what I see? Diffusion imaging protocol heterogeneity biases ischemic core volume, location, and clinical associations in acute stroke

Rafael-Patiño,

Fischi-Gomez,

Madrona

et al. 2024

Preprint

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PurposeDiffusion-weighted magnetic resonance imaging (DWI) is essential for diagnosing ischemic stroke and identifying targets for emergency revascularization. Apparent diffusion coefficient (ADC) maps derived from DWI are commonly used to locate the infarct core, but they are not strictly quantitative and can vary across platforms and sites due to technical factors. This retrospective study was conducted to examine how differences in ADC map generation, resulting from varied protocols across platforms and sites, affect the determination of infarct core size, location, and related clinical outcomes in acute stroke.MethodsIn this retrospective study, 726 acute anterior circulation stroke patients admitted to the Lausanne University Hospital between May 2018 and January 2021 were selected. DWI data were used to generate ADC maps as they would appear from different protocols: two simulated with low and medium angular resolution (4 and 12 diffusion gradient directions) and one with high angular resolution (20 directions). Using a DEFUSE like criteria and image post-processing, ischemic cores were localized; core volume, location, and associations to National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) scores were compared between the two imaging sequences.ResultsSignificant differences were observed in the ADC distribution within white matter, particularly in the kurtosis and skewness, with the segmented infarct core volume being higher in protocols with reduced angular resolution compared to the 20-directions data (7.63 ml vs. 3.78 ml). The volumetric differences persisted after correcting for age, sex, and type of intervention. Infarcted voxels locations varied significantly between the two protocols. This variability affected associations between infarct core volume and clinical scores, with lower associations observed for 4-directions data compared to 20-directions data for NIHSS at admission and after 24 hours, and mRS after 3 months, further confirmed by multivariate regression.ConclusionsImaging protocol heterogeneity leads to significant changes in the ADC distribution, ischemic core location, size, and association with clinical scores. Work is needed in standardizing imaging protocols to improve the reliability of ADC as an imaging biomarker in stroke management.protocols to improve the reliability of ADC as an imaging biomarker in stroke management.Key ResultsOrientation changes in diffusion imaging significantly impact ADC distribution and threshold-based infarct core volume determination, affecting multi-centric studies.Lower number of directions in DWI acquisitions weakens associations between infarct volume measurements and clinical scores.Findings emphasize the impact of DWI acquisition protocol heterogeneity and image processing on acute stroke workups.

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Susceptibility vessel sign, a predictor of long-term outcome in patients with stroke treated with mechanical thrombectomy

Beyeler,

Rea,

Weber

et al. 2023

J NeuroIntervent Surg

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BackgroundThe absence of the susceptibility vessel sign (SVS) in patients treated with mechanical thrombectomy (MT) is associated with poor radiological and clinical outcomes after 3 months. Underlying conditions, such as cancer, are assumed to influence SVS status and could potentially impact the long-term outcome. We aimed to assess SVS status as an independent predictor of long-term outcomes in MT-treated patients.MethodsSVS status was retrospectively determined in consecutive MT-treated patients at a comprehensive stroke center between 2010 and 2018. Predictors of long-term mortality and poor functional outcome (modified Rankin Scale (mRS) ≥3) up to 8 years were identified using multivariable Cox and logistic regression, respectively.ResultsOf the 558 patients included, SVS was absent in 13% (n=71) and present in 87% (n=487) on baseline imaging. Patients without SVS were more likely to have active cancer (P=0.003) and diabetes mellitus (P<0.001) at the time of stroke. The median long-term follow-up time was 1058 days (IQR 533–1671 days). After adjustment for active cancer and diabetes mellitus, among others, the absence of SVS was associated with long-term mortality (adjusted HR (aHR) 2.11, 95% CI 1.35 to 3.29) and poor functional outcome in the long term (adjusted OR (aOR) 2.90, 95% CI 1.29 to 6.55).ConclusionMT-treated patients without SVS have higher long-term mortality rates and poorer long-term functional outcome. It appears that this association cannot be explained by comorbidities alone, and further studies are warranted.

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LTA4H Prevalence and Mortality in Adult Zambians with Tuberculous Meningitis

Cited by 4 publications

References 14 publications

Leukotriene A4 hydrolase (LTA4H rs17525495) gene polymorphisms and paradoxical reactions in extrapulmonary tuberculosis

Leukotriene A4 hydrolase (LTA4H rs17525495) gene polymorphisms and paradoxical reactions in extrapulmonary tuberculosis

Do you see what I see? Diffusion imaging protocol heterogeneity biases ischemic core volume, location, and clinical associations in acute stroke

Susceptibility vessel sign, a predictor of long-term outcome in patients with stroke treated with mechanical thrombectomy

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