Metabolic habitat imaging with hemodynamic heterogeneity predicts individual progression-free survival in high-grade glioma.

AIM: We design a feasibility study to obtain a set of metabolic-hemodynamic habitats for tackling tumor spatial metabolic patterns with hemodynamic information. MATERIALS AND METHODS: Preoperative data from 69 high-grade gliomas (HGG) patients with subsequent histologic confirmation of HGG were prospectively collected (January 2016 to March 2020) after concurrent chemoradiotherapy (CCRT). Four vascular habitats were automatically segmented by multiparametric magnetic resonance imaging (MRI). The metabolic information, either at enhancing or edema tumor regions, was obtained by two neuroradiologists. The relative habitat volumes were used for weight estimation procedures for computing the coefficients of a linear regression model using weighted least squares (WLS) for metabolite semiquantifications (i.e. the Cho/NAA ratio and the Cho/Cr ratio) at vascular habitats. Multivariate Cox proportional hazard regression analyses are used to obtain the odds ratio (OR) and develop a nomogram using weighted estimators corresponding to each covariate derived from Cox regression coefficients. RESULTS: There was a strongly correlation between perfusion indexes and the Cho/Cr ratio (rCBV, r=0.71) or Cho/NAA ratio (rCBV, r=0.66) at high-angiogenic enhancing tumor habitats (HAT) habitat. Compared isocitrate dehydrogenase (IDH) mutation to their wild type, the IDH wild type had significantly decreased Cho/Cr ratio (IDH mutation: Cho/Cr ratio = 2.44 ± 0.33, IDH wildtype: Cho/Cr ratio = 2.66 ± 0.36, p=0.02) and Cho/NAA ratio (IDH mutation: Cho/Cr ratio = 4.59 ± 0.61, IDH wildtype: Cho/Cr ratio = 4.99 ± 0.66, p=0.022) at the HAT. The C-index for the median progression-free survival (PFS) prediction was 0.769 for the Cho/NAA nomogram and 0.747 for the Cho/Cr nomogram through 1000 bootstrapping validation. CONCLUSIONS: Our findings suggest that spatial metabolism combined with hemodynamic heterogeneity is associated with individual PFS to HGG patients post-CCRT.

Accumulation of Iron Oxide-Based Contrast Agents in Rabbit Atherosclerotic Plaques in Relation to Plaque Age and Vulnerability Features.

Purpose: In this study, a detailed characterization of a rabbit model of atherosclerosis was performed to assess the optimal time frame for evaluating plaque vulnerability using superparamagnetic iron oxide nanoparticle (SPION)-enhanced magnetic resonance imaging (MRI). Methods: The progression of atherosclerosis induced by ballooning and a high-cholesterol diet was monitored using angiography, and the resulting plaques were characterized using immunohistochemistry and histology. Morphometric analyses were performed to evaluate plaque size and vulnerability features. The accumulation of SPIONs (novel dextran-coated SPIONDex and ferumoxytol) in atherosclerotic plaques was investigated by histology and MRI and correlated with plaque age and vulnerability. Toxicity of SPIONDex was evaluated in rats. Results: Weak positive correlations were detected between plaque age and intima thickness, and total macrophage load. A strong negative correlation was observed between the minimum fibrous cap thickness and plaque age as well as the mean macrophage load. The accumulation of SPION in the atherosclerotic plaques was detected by MRI 24 h after administration and was subsequently confirmed by Prussian blue staining of histological specimens. Positive correlations between Prussian blue signal in atherosclerotic plaques, plaque age, and macrophage load were detected. Very little iron was observed in the histological sections of the heart and kidney, whereas strong staining of SPIONDex and ferumoxytol was detected in the spleen and liver. In contrast to ferumoxytol, SPIONDex administration in rabbits was well tolerated without inducing hypersensitivity. The maximum tolerated dose in rat model was higher than 100 mg Fe/kg. Conclusion: Older atherosclerotic plaques with vulnerable features in rabbits are a useful tool for investigating iron oxide-based contrast agents for MRI. Based on the experimental data, SPIONDex particles constitute a promising candidate for further clinical translation as a safe formulation that offers the possibility of repeated administration free from the risks associated with other types of magnetic contrast agents.

[Analysis of ultrasound images features and diagnostic model establishment of alveolar soft part sarcoma and intramuscular capillary-type hemangiomas].

Objective: The ultrasonography features of alveolar soft part sarcoma (ASPS) and intramuscular capillary-type hemangiomas (ICTH) were analyzed, and the diagnostic model of ASPS was established. Methods: A cross-sectional study was carried out. The clinical data of 52 patients [28 males and 24 females, aged (20.7±15.1) years] with pathologically confirmed ASPS and ICTH admitted to People's Hospital of Henan Province from January 2005 to February 2023 were included in the study. According to pathological types, the patients were divided into ASPS group and ICTH group. Clinical data of patients were retrospectively collected, and meaningful indicators in the univariate analysis were included in the regression analysis for screening. After comprehensive consideration of clinical significance and statistical significance, eligible indicators were selected for inclusion in the regression analysis. Binary logistic regression analysis was used to screen the factors that distinguished the pathological types of ASPS and ICTH, and the diagnostic model was established. The area under receiver operating characteristic (ROC) curve (AUC) was used to evaluate the diagnostic effectiveness of the diagnostic model in distinguishing ASPS from ICTH. Results: There were 20 patients in ASPS group, 10 males and 10 females, aged (26.9±13.5) years, and 32 patients in ICTH group, 18 males and 14 females, aged (16.8±15.0) years. The age difference between the ASPS group and the ICTH group was statistically significant (P<0.05), and there were statistically significant differences in the ultrasound imaging features of "clear boundary" "peripheral lobe" "thin blood vessels inside the lesion are straight and out of shape" "intra-lesion liquification" "peripheral thick blood vessels" and "peripheral muscle fiber disruption" between the two groups (all P<0.001).Variables with clinical and statistical significance were selected as independent variables. Binary logistic regression analysis showed that peripheral muscle fiber interruption (OR=97.358, 95%CI:6.833-1 387.249) and internal thin blood vessels were flat and out of shape (OR=0.052, 95%CI:0.003-0.921) was the correlation factor to distinguish the pathological types of ASPS and ICTH. Two ultrasonic image features of "peripheral muscle fiber interruption" and "internal thin blood vessels are straight and out of shape" were used to establish the diagnostic model. The sensitivity of "peripheral muscle fiber interruption" diagnostic model was 81.3%, and the specificity was 95.0%. The AUC was 0.811(95%CI: 0.761-0.954). The sensitivity, specificity and AUC of the diagnosis model of "internal thin vessels with flat misshape" were 90.0%, 96.9% and 0.934(95%CI: 0.830-0.984). The sensitivity, specificity and AUC of the combined diagnosis model of "peripheral muscle fiber interruption" and "internal thin blood vessel straight out of shape" were 96.9%, 90.0% and 0.974(95%CI:0.877-0.999). Conclusion: Ultrasonography can be used to distinguish ASPS from ICTH, and the combined diagnostic model based on the two ultrasonic imaging features of "peripheral muscle fiber interruption" and "internal thin blood vessel straight out of shape" can further improve the diagnostic efficiency.

Different tumor growth pattern of clinically nonfunctioning pituitary neuroendocrine tumor according to sex and age: a longitudinal study.

PURPOSE: Asymptomatic patients with clinically non-functional pituitary neuroendocrine tumors (CNF-PitNETs) are usually followed up. However, the natural course of CNF-PitNETs according to sex and age remains unclear. Therefore, this study assessed growth patterns of CNF-PitNETs according to sex and age. METHODS: In this longitudinal study, we enrolled 431 consecutive patients with CNF-PitNETs who were treated at Seoul National University Hospital from 1997 to 2021. The patients underwent hormone function testing and visual field testing, and were subsequently followed up with imaging over a median duration of 66 months. RESULTS: The median age of the patients was 53.0 years, and 37.1% (n = 160) were men. Men were older and harbored more macroadenomas than women. The annual tumor volume change was higher in men than in women (0.21 vs. 0.04 cm3/year, P < 0.001). The estimated cutoff value of age for significant tumor growth was 51 years. In men, the annual tumor volume change was similar across all age groups. In women, those aged ≤ 50 years showed significantly lower annual tumor volume change than those aged > 50 years (0.01, 0.11, and 0.17 cm3/year, P = 0.001). When comparing sexes within the same age group, the annual tumor volume changes was significantly lower for women than for men, only in patients aged ≤ 50 years (0.01 vs. 0.15 cm3/year, P < 0.001). CONCLUSIONS: Among patients with CNF-PitNET, tumor growth was slower in women aged ≤ 50 years than in men and women aged > 50. These findings may guide the customization of surveillance strategies for CNF-PitNETs according to sex and age.

Major Facilitator Superfamily Domain Containing 5 Inhibition Reduces Lipoprotein(a) Uptake and Calcification in Valvular Heart Disease.

BACKGROUND: High circulating levels of Lp(a) (lipoprotein[a]) increase the risk of atherosclerosis and calcific aortic valve disease, affecting millions of patients worldwide. Although atherosclerosis is commonly treated with low-density lipoprotein-targeting therapies, these do not reduce Lp(a) or risk of calcific aortic valve disease, which has no available drug therapies. Targeting Lp(a) production and catabolism may provide therapeutic benefit, but little is known about Lp(a) cellular uptake. METHODS: Here, unbiased ligand-receptor capture mass spectrometry was used to identify MFSD5 (major facilitator superfamily domain containing 5) as a novel receptor/cofactor involved in Lp(a) uptake. RESULTS: Reducing MFSD5 expression by a computationally identified small molecule or small interfering RNA suppressed Lp(a) uptake and calcification in primary human valvular endothelial and interstitial cells. MFSD5 variants were associated with aortic stenosis (P=0.027 after multiple hypothesis testing) with evidence suggestive of an interaction with plasma Lp(a) levels. CONCLUSIONS: MFSD5 knockdown suppressing human valvular cell Lp(a) uptake and calcification, along with meta-analysis of MFSD5 variants associating with aortic stenosis, supports further preclinical assessment of MFSD5 in cardiovascular diseases, the leading cause of death worldwide.

Multimodel habitats constructed by perfusion and/or diffusion MRI predict isocitrate dehydrogenase mutation status and prognosis in high-grade gliomas.

AIM: To determine whether tumour vascular and cellular heterogeneity of high-grade glioma (HGG) is predictive of isocitrate dehydrogenase (IDH) mutation status and overall survival (OS) by using tumour habitat-based analysis constructed by perfusion and/or diffusion magnetic resonance imaging (MRI). MATERIALS AND METHODS: Seventy-eight HGG patients that met the 2021 World Health Organization WHO Classification of Tumors of the Central Nervous System, 5th edition (WHO CNS5), were enrolled to predict IDH mutation status, of which 32 grade 4 patients with unmethylated O6-methylguanine-DNA methyltransferase (MGMT) promoter were enrolled for prognostic analysis. The deep-learning-based model nnU-Net and K-means clustering algorithm were applied to construct the Traditional Habitat, Vascular Habitat (VH), Cellular Density Habitat (DH), and their Combined Habitat (CH). Quantitative parameters were extracted and compared between IDH-mutant and IDH-wild-type patients, respectively, and the prediction potential was evaluated by receiver operating characteristic (ROC) curve analysis. OS was analysed using Kaplan-Meier survival analysis and the log-rank test. RESULTS: Compared with IDH-mutants, median relative cerebral blood volume (rCBVmedian) values in the whole enhancing tumour (WET), VH1, VH3, CH1-4 habitats were significantly increased in IDH-wild-type HGGs (all p<0.05). Additionally, the accuracy of rCBVmedian values in CH1 outperformed other habitats in identifying IDH mutation status (p<0.001) at a cut-off value of 4.83 with AUC of 0.815. Kaplan-Meier survival analysis highlighted significant differences in OS between the populations dichotomised by the median of rCBVmedian in WET, VH1, CH1-3 habitats (all p<0.05). CONCLUSIONS: The habitat imaging technique may improve the accuracy of predicting IDH mutation status and prognosis, and even provide a new direction for subsequent personalised precision treatment.

Dynamic Fixation versus Static Screw Fixation for Syndesmosis Injuries in Pronation External Rotation Ankle Fractures: A Retrospective Case Control Study.

Introduction: The current standard treatment for ankle syndesmosis injury is static screw fixation. Dynamic fixation was developed to restore the dynamic function of the syndesmosis. The purpose of this study was to determine that which of static screw fixation and dynamic fixation is better for treatment of ankle syndesmosis injury in pronation-external rotation fractures. Materials and methods: Thirty patients were treated with dynamic fixation (DF group) and 28 patients with static screw fixation (SF group). The primary outcome was Olerud-Molander Ankle Outcome Score. The secondary outcome were Visual Analogue Scale score and American Orthopedic Foot and Ankle Society score, radiographic outcomes, complications and cost effectiveness. To evaluate the radiographic outcome, the tibiofibular clear space, tibiofibular overlap, and medial clear space were compared using the pre-operative and last follow-up plain radiographs. To evaluate the cost effectiveness, the total hospital cost was compared between the two groups. Results: There was no significant difference in primary outcome. Moreover, there were no significant difference in secondary outcome including Visual Analogue Scale score and American Orthopedic Foot and Ankle Society score and radiographic outcome. Two cases of reduction loss and four cases of screw breakage were observed in the SF group. No complication in the DF group was observed. Dynamic fixation was more cost effective than static screw fixation with respect to the total hospital cost. Conclusion: Although dynamic fixation provided similar clinical and radiologic outcome, dynamic fixation is more cost effective with fewer complications than static screw fixation in ankle syndesmosis injury of pronation-external rotation fractures.

[Follow-up analysis of sex hormone levels and prognosis in women after hematopoietic stem cell transplantation].

Objective: To investigate the levels of sex hormone and fertility in female patients after hematopoietic stem cell transplantation (HSCT), as well as their correlation with conditioning regimens, and analyse the effect of hormone replacement therapy (HRT) in young women after HSCT. Methods: Retrospective case series study. The clinical data of 147 women who underwent HSCT in the First Affiliated Hospital of Soochow University from January 2010 to January 2021 were retrospectively analyzed. The sex hormone levels were measured and followed-up, and the survival, menstrual fertility and the use of HRT of the patients were also followed-up. The sex hormone levels were measured after transplantation, and the ovarian function was evaluated. Independent sample t test and χ2 test were used for comparison between the two groups. Results: The median age of the 147 patients was 26 (range, 10-45) years. Of them, 135 patients received allogeneic HSCT and 12 patients received autologous HSCT. Furthermore, 129 patients received myeloablative conditioning, and 18 patients received reduced conditioning dose. The median follow-up time was 50 months (range, 18-134 months). Five patients died of disease recurrence during follow-up. Of the 54 patients with subcutaneous injection of zoladex, three recovered menstruation spontaneously after transplantation, and all of them were myeloablative conditioning patients, one patient gave birth to twins through assisted reproductive technology. Ninety-three patients did not use zoladex before conditioning, two patients with aplastic anemia with non-myeloablative transplantation resumed menstruation spontaneously, and conceived naturally. The level of follicle stimulating hormone after transplantation in patients receiving myeloablative conditioning regimen was significantly higher than that in patients receiving reduced-dose conditioning regimen [(95.28±3.94) U/L vs. (71.85±10.72) U/L, P=0.039]. Among 147 patients, 122 patients developed premature ovarian failure, 83 patients received sex hormone replacement therapy after transplantation, and 76 patients recovered menstruation and improved endocrine function. Conclusions: The incidence of premature ovarian failure is high in female patients after HSCT, and patients have a chance at natural conception. Reducing the dose of conditioning regimen and the application of zoladex before transplantation can reduce ovarian of conditioning drugs. HRT after transplantation can partially improve the endocrine function of patients.

Metformin activates AMPK and mTOR to Inhibit RANKL-stimulated osteoclast formation.

OBJECTIVE: Metformin is a medication used to treat type 2 diabetes by inhibiting hepatic glucose production through adenosine monophosphate-activated protein kinase (AMPK) activation. Autophagy is closely related to the homeostasis and stress mechanisms of the body. In recent years, much research has arisen on therapeutic methods utilizing autophagy mechanisms to treat diagnoses such as metabolic diseases, tumors, and Alzheimer's disease. This study thus aimed to investigate the effects of metformin treatment on the differentiation of osteoclasts and changes in AMPK mechanisms, which play an important role in regulating energy homeostasis, and mTOR, a highly conserved kinase that regulates autophagy. MATERIALS AND METHODS: Experimentation, including 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, tartrate-resistant acid phosphate (TRAP) staining, pit formation assay, immunofluorescence, western blotting, and real-time polymerase chain reaction (PCR) was performed to investigate the effects of metformin on osteoclast differentiation. Additionally, to investigate its association with AMPK and pathways, the AMPK inhibitor compound C and mammalian targets of rapamycin (mTOR) activator leucine were used to examine the expression of osteoclast- or autophagy-related proteins, genes, and TRAP-positive cells. RESULTS: Metformin showed no cytotoxic effects on mouse osteoblastic cell lines (MC3T3-E1) and murine macrophage cell lines (RAW264.7) but did inhibit osteoclast differentiation. Furthermore, metformin was found to inhibit osteoclast differentiation through AMPK activation and mTOR inhibition. In turn, AMPK inhibition using compound C promoted osteoclast differentiation, and mTOR activation using leucine inhibited autophagy and osteoclast differentiation. CONCLUSIONS: Metformin activates the AMPK pathway while functioning as an activator of mTOR, thereby leading to the inhibition of autophagy and osteoclast differentiation.

Auditory cortex hyperconnectivity before rTMS is correlated with tinnitus improvement.

INTRODUCTION: Repetitive transcranial magnetic stimulation (rTMS) has been used as a potential treatment for tinnitus; however, its effectiveness is variable and unpredictable. We hypothesized that resting-state functional connectivity before rTMS may be correlated with rTMS treatment effectiveness. METHODS: We applied 1-Hz rTMS to the left primary auditory (A1) and dorsolateral prefrontal cortices (DLPFC) of 10 individuals with tinnitus and 10 age-matched controls. Resting-state functional magnetic resonance imaging (fMRI) studies were performed approximately one week before rTMS. Seed-based connectivity analyses were conducted for each individual, with seed regions as rTMS target areas. RESULTS: Compared to controls, the left superior temporal areas showed significantly increased positive connectivity with the left A1 and negative connectivity with the left DLPFC in the tinnitus group. The left frontoparietal and right cerebellar areas showed significantly increased negative connectivity with the left A1 and positive connectivity with the left DLPFC. Seed-based hyperconnectivity was correlated with tinnitus improvement (pre-rTMS vs. 2-week post-rTMS Tinnitus Handicap Inventory scores). Tinnitus improvement was significantly correlated with left A1 hyperconnectivity; however, no correlation was observed with left DLPFC connectivity. Positive rTMS outcomes were associated with significantly increased positive connectivity in bilateral superior temporal areas and significantly increased negative connectivity in bilateral frontal areas. CONCLUSIONS: Our results suggest that oversynchronisation of left A1 connectivity before rTMS of the left A1 and DLPFC is associated with treatment effectiveness.

Auditory cortex hyperconnectivity before rTMS is correlated with tinnitus improvement / Correlación entre hiperconectividad de la corteza auditiva antes del tratamiento con estimulación magnética transcraneal repetitiva y mejoría de los acúfenos

Introduction: Repetitive transcranial magnetic stimulation (rTMS) has been used as a potential treatment for tinnitus; however, its effectiveness is variable and unpredictable. We hypothesized that resting-state functional connectivity before rTMS may be correlated with rTMS treatment effectiveness. Methods: We applied 1-Hz rTMS to the left primary auditory (A1) and dorsolateral prefrontal cortices (DLPFC) of 10 individuals with tinnitus and 10 age-matched controls. Resting-state functional magnetic resonance imaging (fMRI) studies were performed approximately one week before rTMS. Seed-based connectivity analyses were conducted for each individual, with seed regions as rTMS target areas. Results: Compared to controls, the left superior temporal areas showed significantly increased positive connectivity with the left A1 and negative connectivity with the left DLPFC in the tinnitus group. The left frontoparietal and right cerebellar areas showed significantly increased negative connectivity with the left A1 and positive connectivity with the left DLPFC. Seed-based hyperconnectivity was correlated with tinnitus improvement (pre-rTMS vs. 2-week post-rTMS Tinnitus Handicap Inventory scores). Tinnitus improvement was significantly correlated with left A1 hyperconnectivity; however, no correlation was observed with left DLPFC connectivity. Positive rTMS outcomes were associated with significantly increased positive connectivity in bilateral superior temporal areas and significantly increased negative connectivity in bilateral frontal areas. Conclusions: Our results suggest that oversynchronisation of left A1 connectivity before rTMS of the left A1 and DLPFC is associated with treatment effectiveness.(AU)

Introducción: La estimulación magnética transcraneal repetitiva (EMTr) se ha utilizado como posible tratamiento para los acúfenos, aunque su efectividad es variable e impredecible. Planteamos la hipótesis de que existe una correlación entre la conectividad funcional en estado de reposo antes de aplicar EMTr y la efectividad de dicho tratamiento. Métodos: Aplicamos EMTr a 1 Hz sobre la corteza auditiva primaria (A1) y la corteza prefrontal dorsolateral (CPFDL) izquierdas de 10 pacientes con acúfenos y 10 controles del mismo rango de edad. Se realizaron estudios de resonancia magnética funcional (RMF) en estado de reposo de todos los pacientes aproximadamente una semana antes de la EMTr. En cada caso, se construyó un mapa de conectividad basado en las ROIs, en el que las ROIs eran las áreas que se tratarían con la EMTr. Resultados: La región temporal superior izquierda mostró una conectividad positiva significativamente mayor con el área A1 izquierda y mayor conectividad negativa con la CPFDL izquierda en los pacientes con acúfenos que en los controles. Además, las áreas frontoparietal izquierda y cerebelar derecha mostraron una conectividad negativa significativamente superior con el área A1 izquierda y mayor conectividad positiva con la CPFDL izquierda. La hiperconectividad de las ROIs se correlacionó con mejoría de los acúfenos según las puntuaciones pre-EMTr y 2 semanas post-EMTr en la escala Tinnitus Handicap Inventory. La mejoría de los acúfenos se correlacionó de manera significativa con la hiperconectividad del área A1 izquierda; sin embargo, no se encontró correlación con la conectividad de la CPFDL izquierda. El resultado favorable del tratamiento con EMTr se asocia con una mayor conectividad positiva en áreas temporales superiores de ambos hemisferios y con mayor conectividad negativa en áreas frontales bilaterales...(AU)

[Recompensation of complications in patients with hepatitis B virus-related decompensated cirrhosis treated with entecavir antiviral therapy].

Objective: To analyze the occurrence of recompensation conditions in patients with chronic hepatitis B virus-related decompensated cirrhosis after entecavir antiviral therapy. Methods: Patients with hepatitis B virus-related decompensated cirrhosis with ascites as the initial manifestation were prospectively enrolled. Patients who received entecavir treatment for 120 weeks and were followed up every 24 weeks (including clinical endpoint events, hematological and imaging indicators, and others) were calculated for recompensation rates according to the Baveno VII criteria. Measurement data were compared using the Student t-test or Mann-Whitney U test between groups. Categorical data were compared by the χ (2) test or Fisher's exact probability method between groups. Results: 283 of the 320 enrolled cases completed the 120-week follow-up, and 92.2% (261/283) achieved a virological response (HBV DNA 20 IU/ml). Child-Pugh and MELD scores were significantly improved after treatment (8.33 ± 1.90 vs. 5.77 ± 1.37, t = 12.70, P < 0.001; 13.37 ± 4.44 vs. 10.45 ± 4.58, t = 5.963, P < 0.001). During the 120-week follow-up period, 14 cases died, two received liver transplants, 19 developed hepatocellular cancer, 11 developed gastroesophageal variceal bleeding, and four developed hepatic encephalopathy. 60.4% (171/283) (no decompensation events occurred for 12 months) and 56.2% (159/283) (no decompensation events occurred for 12 months and improved liver function) of the patients had achieved clinical recompensation within 120 weeks. Patients with baseline MELD scores > 15 after active antiviral therapy achieved higher recompensation than patients with baseline MELD scores ≤15 [50/74 (67.6%) vs. 109/209 (52.2%), χ (2) = 5.275, P = 0.029]. Conclusion: Antiviral therapy can significantly improve the prognosis of patients with hepatitis B virus-related decompensated cirrhosis. The majority of patients (56.2%) had achieved recompensation. Patients with severe disease did not have a lower probability of recompensation at baseline than other patients.

[Efficacy and safefy of Polymyxin B treatment for neutropenic patients suffering from refractory Gram-negative bacterial bloodstream infection].

Objective: To assess the efficacy and safety of polymyxin B in neutropenic patients with hematologic disorders who had refractory gram-negative bacterial bloodstream infection. Methods: From August 2021 to July 2022, we retrospectively analyzed neutropenic patients with refractory gram-negative bacterial bloodstream infection who were treated with polymyxin B in the Department of Hematology of the First Affiliated Hospital of the Soochow University between August 2021 to July 2022. The cumulative response rate was then computed. Results: The study included 27 neutropenic patients with refractory gram-negative bacterial bloodstream infections. Polymyxin B therapy was effective in 22 of 27 patients. The median time between the onset of fever and the delivery of polymyxin B was 3 days [interquartile range (IQR) : 2-5]. The median duration of polymyxin B treatment was 7 days (IQR: 5-11). Polymyxin B therapy had a median antipyretic time of 37 h (IQR: 32-70). The incidence of acute renal dysfunction was 14.8% (four out of 27 cases), all classified as "injury" according to RIFLE criteria. The incidence of hyperpigmentation was 59.3%. Conclusion: Polymyxin B is a viable treatment option for granulocytopenia patients with refractory gram-negative bacterial bloodstream infections.

Arterial Spin-Labeling MR Imaging for the Differential Diagnosis of Venous-Predominant AVMs and Developmental Venous Anomalies.

BACKGROUND AND PURPOSE: Venous-predominant AVMs are almost identical in appearance to developmental venous anomalies on conventional MR imaging. Herein, we compared and analyzed arterial spin-labeling findings in patients with developmental venous anomalies or venous-predominant AVMs, using DSA as the criterion standard. MATERIALS AND METHODS: We retrospectively collected patients with either DVAs or venous-predominant AVMs, each available on both DSA and arterial spin-labeling images. Arterial spin-labeling imaging was visually assessed for the presence of hyperintense signal. CBF measured at the most representative section was normalized to the contralateral gray matter. The temporal phase of developmental venous anomalies or venous-predominant AVMs was measured on DSA as a delay between the first appearance of the intracranial artery and the lesion. Correlation between the normalized CBF and the temporal phase was evaluated. RESULTS: Analysis of 15 lesions (13 patients) resulted in categorization into 3 groups: typical venous-predominant AVMs (temporal phase, <2 seconds), intermediate group (temporal phase between 2.5 and 5 seconds), and classic developmental venous anomalies (temporal phase, >10 seconds). Arterial spin-labeling signal was markedly increased in the typical venous-predominant AVM group, while there was no discernible signal in the classic developmental venous anomaly group. In the intermediate group, however, 3 of 6 lesions showed mildly increased arterial spin-labeling signal. The normalized CBF on arterial spin-labeling and the temporal phase on DSA were moderately negatively correlated: r(13) = 0.66, P = .008. CONCLUSIONS: Arterial spin-labeling may predict the presence and amount of arteriovenous shunting in venous-predominant AVMs, and using arterial spin-labeling enables confirmation of typical venous-predominant AVMs without DSA. However, lesions with an intermediate amount of shunting suggest a spectrum of vascular malformations ranging from purely vein-draining developmental venous anomalies to venous-predominant AVMs with overt arteriovenous shunting.

Exploratory Multisite MR Spectroscopic Imaging Shows White Matter Neuroaxonal Loss Associated with Complications of Type 1 Diabetes in Children.

BACKGROUND AND PURPOSE: Type 1 diabetes affects over 200,000 children in the United States and is associated with an increased risk of cognitive dysfunction. Prior single-site, single-voxel MRS case reports and studies have identified associations between reduced NAA/Cr, a marker of neuroaxonal loss, and type 1 diabetes. However, NAA/Cr differences among children with various disease complications or across different brain tissues remain unclear. To better understand this phenomenon and the role of MRS in characterizing it, we conducted a multisite pilot study. MATERIALS AND METHODS: In 25 children, 6-14 years of age, with type 1 diabetes across 3 sites, we acquired T1WI and axial 2D MRSI along with phantom studies to calibrate scanner effects. We quantified tissue-weighted NAA/Cr in WM and deep GM and modeled them against study covariates. RESULTS: We found that MRSI differentiated WM and deep GM by NAA/Cr on the individual level. On the population level, we found significant negative associations of WM NAA/Cr with chronic hyperglycemia quantified by hemoglobin A1c (P < .005) and a history of diabetic ketoacidosis at disease onset (P < .05). We found a statistical interaction (P < .05) between A1c and ketoacidosis, suggesting that neuroaxonal loss from ketoacidosis may outweigh that from poor glucose control. These associations were not present in deep GM. CONCLUSIONS: Our pilot study suggests that MRSI differentiates GM and WM by NAA/Cr in this population, disease complications may lead to neuroaxonal loss in WM in children, and deeper investigation is warranted to further untangle how diabetic ketoacidosis and chronic hyperglycemia affect brain health and cognition in type 1 diabetes.