Association between dietary patterns and obesity: a longitudinal prospective cohort study.

OBJECTIVES: The obesity prevalence in South Korea in 2021 stood at 38.4%. South Korea faces unique challenges in providing essential and emergency guidelines for weight management because of stepping into an aging society. We aimed to determine the daily diet patterns among the general Korean population and to investigate the association between such patterns and different obesity. STUDY DESIGN: Longitudinal prospective cohort study. METHODS: A total of 6539 adult participants (mean age 50.8 years, 52.9% male) with normal-weight adults were included from the Ansan-Ansung cohort of 10,030 Korean adults aged 40 or older and followed for an average of 11 years. Obesity was defined according to the criteria from the Korean Society for The Study of Obesity. Baseline dietary intake was assessed using a validated 103-item food frequency questionnaire. Dietary patterns were derived from k-means cluster analysis. RESULTS: In the multivariate analysis, referring to white rice + baechu kimchi, participants from multigrain rice + baechu kimchi showed lower HR for obesity development (waist circumference defined-obesity; HR: 0.87, 95% CI: 0.79, 0.95; body fat percentage defined-obesity; HR: 0.89, 95% CI: 0.80, 0.98). Further analysis documented that except for body fat percentage defined-obesity, consuming milk or dairy products was linked to a reduced incidence of the other three obesity (body mass index defined-obesity; HR: 0.84, 95% CI: 0.72, 0.99; waist circumference defined-obesity; HR: 0.82, 95% CI: 0.71, 0.94; waist-to-hip ratio defined-obesity; HR: 0.75, 95% CI: 0.61, 0.91). CONCLUSIONS: Following a diet that includes multigrain rice, fermented baechu kimchi, and dairy products is linked to a decreased risk of obesity in Korean adults. Public health programs and policies could incorporate these dietary recommendations, targeting specific population groups such as schoolchildren, adults, and the elderly. Additionally, further research is needed to explore the synergistic effects of various foods and their interactions within dietary patterns on obesity outcomes.

A phase II study of tepotinib in patients with advanced solid cancers harboring MET exon 14 skipping mutations or amplification (KCSG AL19-17).

BACKGROUND: We evaluated the efficacy and safety of tepotinib in patients with various solid cancers harboring MET exon 14 skipping mutation (METex14) or MET gene amplification. PATIENTS AND METHODS: A phase II, multicenter study was conducted in patients with advanced or metastatic solid cancers who progressed after standard treatment, harboring either METex14 or MET amplification detected in tissue-based next-generation sequencing (NGS). The primary endpoint was objective response rate (ORR). For exploratory analyses, we analyzed the gene profiles using plasma NGS test. RESULTS: Thirty-five patients were enrolled. The ORR was 57.6% for all patients, 52.2% for those with METex14, and 70% for those with MET amplification. Median progression-free survival (PFS) was 8 months [95% confidence interval (CI) 4.5-11.5 months] and median overall survival (OS) was 14 months (95% CI 7.8-20.2 months) in all patients. For patients with non-small-cell lung cancer with METex14, the median PFS was 9 months (95% CI 4.7-13.4 months) and the median OS was 17 months [95% CI not applicable (NA)-NA]. For patients with MET amplification, the median PFS was 7 months (95% CI 1.5-12.5 months) and the median OS was 10 months (95% CI 5.8-14.2 months). The ORR of patients with MET dysregulation detected by plasma NGS was 72.2%, whereas the ORR was 30% in those without detection. The most common adverse events were peripheral edema, asthenia, transaminase elevation, and anorexia, mostly grade 1 or 2. CONCLUSIONS: Tepotinib demonstrated consistent antitumor activity in patients with METex14, and promising antitumor activity in various cancers with MET amplification. Detection of MET dysregulation by plasma NGS may predict the response to tepotinib.

Hospital water environment and antibiotic use: key factors in a nosocomial outbreak of carbapenemase-producing Serratia marcescens.

BACKGROUND: The healthcare water environment is a potential reservoir of carbapenem-resistant organisms (CROs). AIM: To report the role of the water environment as a reservoir and the infection control measures applied to suppress a prolonged outbreak of Klebsiella pneumoniae carbapenemase-producing Serratia marcescens (KPC-SM) in two intensive care units (ICUs). METHODS: The outbreak occurred in the ICUs of a tertiary hospital from October 2020 to July 2021. Comprehensive patient contact tracing and environmental assessments were conducted, and a case-control study was performed to identify factors associated with the acquisition of KPC-SM. Associations among isolates were assessed via pulsed-field gel electrophoresis (PFGE). Antibiotic usage was analysed. FINDINGS: The outbreak consisted of two waves involving a total of 30 patients with KPC-SM. Multiple environmental cultures identified KPC-SM in a sink, a dirty utility room, and a communal bathroom shared by the ICUs, together with the waste bucket of a continuous renal replacement therapy (CRRT) system. The genetic similarity of the KPC-SM isolates from patients and the environment was confirmed by PFGE. A retrospective review of 30 cases identified that the use of CRRT and antibiotics was associated with acquisition of KPC-SM (P < 0.05). There was a continuous increase in the use of carbapenems; notably, the use of colistin has increased since 2019. CONCLUSION: Our study demonstrates that CRRT systems, along with other hospital water environments, are significant potential sources of resistant micro-organisms, underscoring the necessity of enhancing infection control practices in these areas.

CT-guided pretreatment biopsy diagnosis in patients with thymic epithelial tumours: diagnostic accuracy and risk of seeding.

AIM: To investigate the diagnostic performance of computed tomography (CT)-guided percutaneous transthoracic needle biopsy (PTNB) for thymic epithelial tumours (TETs) and the complication rate after PTNB including seeding after PTNB. MATERIALS AND METHODS: This retrospective study identified PTNBs for anterior mediastinal lesions between May 2007 and September 2021. The diagnostic performance for TETs and complications were investigated. The concordance of the histological grades of TETs between PTNB and surgery was evaluated. The factors associated with pleural seeding after PTNB were determined using Cox regression analysis. RESULTS: Of 387 PTNBs, 235 PTNBs from 225 patients diagnosed as TETs (124 thymomas and 101 thymic carcinomas) and 150 PTNBs from 133 patients diagnosed as other than TETs were included. The sensitivity, specificity, and accuracy for TETs were 89.4% (210/235), 100% (210/210), and 93.5% (360/385), respectively, with an immediate complication rate of 4.4% (17/385). The concordance rate of the histological grades between PTNB and surgery was 73.3% (77/105) after excluding uncategorised types of thymomas. During follow-up after PTNB (median duration, 38.8 months; range, 0.3-164.6 months), no tract seeding was observed. Pleural seeding was observed in 26 patients. Thymic carcinoma (hazard ratio [HR], 5.94; 95% confidence interval [CI], 2.07-17.08; p=0.001) and incomplete resection (HR, 3.29; 95% CI, 1.20-9.02; p=0.02) were associated with pleural seeding, while the biopsy approach type (transpleural versus parasternal) was not associated (p=0.12). CONCLUSIONS: Pretreatment biopsy for TETs was accurate and safe and may be considered for diagnosing TETs, particularly when the diagnosis is challenging and histological diagnosis is mandatory.

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)

Localized conditional induction of brain arteriovenous malformations in a mouse model of hereditary hemorrhagic telangiectasia.

BACKGROUND: Longitudinal mouse models of brain arteriovenous malformations (AVMs) are crucial for developing novel therapeutics and pathobiological mechanism discovery underlying brain AVM progression and rupture. The sustainability of existing mouse models is limited by ubiquitous Cre activation, which is associated with lethal hemorrhages resulting from AVM formation in visceral organs. To overcome this condition, we developed a novel experimental mouse model of hereditary hemorrhagic telangiectasia (HHT) with CreER-mediated specific, localized induction of brain AVMs. METHODS: Hydroxytamoxifen (4-OHT) was stereotactically delivered into the striatum, parietal cortex, or cerebellum of R26CreER; Alk12f/2f (Alk1-iKO) littermates. Mice were evaluated for vascular malformations with latex dye perfusion and 3D time-of-flight magnetic resonance angiography (MRA). Immunofluorescence and Prussian blue staining were performed for vascular lesion characterization. RESULTS: Our model produced two types of brain vascular malformations, including nidal AVMs (88%, 38/43) and arteriovenous fistulas (12%, 5/43), with an overall frequency of 73% (43/59). By performing stereotaxic injection of 4-OHT targeting different brain regions, Alk1-iKO mice developed vascular malformations in the striatum (73%, 22/30), in the parietal cortex (76%, 13/17), and in the cerebellum (67%, 8/12). Identical application of the stereotaxic injection protocol in reporter mice confirmed localized Cre activity near the injection site. The 4-week mortality was 3% (2/61). Seven mice were studied longitudinally for a mean (SD; range) duration of 7.2 (3; 2.3-9.5) months and demonstrated nidal stability on sequential MRA. The brain AVMs displayed microhemorrhages and diffuse immune cell invasion. CONCLUSIONS: We present the first HHT mouse model of brain AVMs that produces localized AVMs in the brain. The mouse lesions closely resemble the human lesions for complex nidal angioarchitecture, arteriovenous shunts, microhemorrhages, and inflammation. The model's longitudinal robustness is a powerful discovery resource to advance our pathomechanistic understanding of brain AVMs and identify novel therapeutic targets.

Synthesis of Functionalized Triblock Copolyesters Derived from Lactic Acid and Macrolactones for Bone Tissue Regeneration.

Synthetic and functional grafts are a great alternative to conventional grafts. They can provide a physical support and the precise signaling for cells to heal damaged tissues. In this study, a novel RGD peptide end-functionalized poly(ethylene glycol)-b-poly(lactic acid)-b-poly(globalide)-b-poly(lactic acid)-b-poly(ethylene glycol) (RGD-PEG-PLA-PGl-PLA-PEG-RGD) is synthetized and used to prepare functional scaffolds. The PGl inner block is obtained by enzymatic ring-opening polymerization of globalide. The outer PLA blocks are obtained by ring-opening polymerization of both, l-lactide or a racemic mixture, initiated by the α-ω-telechelic polymacrolactone. The presence of PGl inner block enhances the toughness of PLA-based scaffolds, with an increase of the elongation at break up to 300% when the longer block of PGl is used. PLA-PGl-PLA copolymer is coupled with α-ω-telechelic PEG diacids by esterification reaction. PEGylation provides hydrophilic scaffolds as the contact angle is reduced from 114° to 74.8°. That difference improves the contact between the scaffolds and the culture media. Moreover, the scaffolds are functionalized with RGD peptides at the surface significantly enhancing the adhesion and proliferation of bone marrow-derived primary mesenchymal stem cells and MC3T3-E1 cell lines in vitro. These results place this multifunctional polymer as a great candidate for the preparation of temporary grafts.

Effect of supplementation of cryoprotectant solution with hydroxypropyl cellulose for vitrification of bovine oocytes.

BACKGROUND: Successful cryopreservation of bovine oocytes is very important for research and commercial applications. However, the survival and development rate of vitrified-thawed (VT) oocytes are lower than those of non-vitrified-thawed (non-VT) oocytes. OBJECTIVE: To investigate the effect of adding hydroxypropyl cellulose (HPC) to the vitrification solution for bovine oocytes. MATERIALS AND METHODS: For vitrification, bovine metaphase II oocytes were pretreated with a solution containing 10% ethylene glycol supplemented with 0, 10, 50, or 100 ug/mL HPC for 5 min, exposed to a solution containing 30% ethylene glycol supplemented with 0, 10, 50, or 100 ug/mL HPC for 30 s, and then directly plunged into liquid nitrogen. RESULTS: The survival rate of oocytes was significantly higher in the 50 HPC group than in the 0, 10, and 100 HPC groups. The reactive oxygen species level was lower in the non-VT and 50 HPC groups than in the other groups. The mRNA levels of proapoptotic genes (Bax) were lower in the non-VT, 0, and 50 HPC groups than in the other groups. The mRNA levels of antiapoptotic genes (BCl2) were higher in the non-VT than in the other groups. The development rates of embryos (day 8) obtained via parthenogenetic activation (PA) were determined in the non-VT, 0 HPC, and 50 HPC groups. The cleavage rate was significantly higher in the non-VT group. CONCLUSION: Supplementation of vitrification solution with HPC improves the survival of VT bovine oocytes and the development capacity of embryos derived from these oocytes via PA. doi.org/10.54680/fr23110110212.

BMP10 functions independently from BMP9 for the development of a proper arteriovenous network.

Hereditary hemorrhagic telangiectasia (HHT) is a genetic vascular disorder characterized by the presence of arteriovenous malformation (AVM) in multiple organs. HHT is caused by mutations in genes encoding major constituents for transforming growth factor-ß (TGF-ß) family signaling: endoglin (ENG), activin receptor-like kinase 1 (ALK1), and SMAD4. The identity of physiological ligands for this ENG-ALK1 signaling pertinent to AVM formation has yet to be clearly determined. To investigate whether bone morphogenetic protein 9 (BMP9), BMP10, or both are physiological ligands of ENG-ALK1 signaling involved in arteriovenous network formation, we generated a novel Bmp10 conditional knockout mouse strain. We examined whether global Bmp10-inducible knockout (iKO) mice develop AVMs at neonatal and adult stages in comparison with control, Bmp9-KO, and Bmp9/10-double KO (dKO) mice. Bmp10-iKO and Bmp9/10-dKO mice showed AVMs in developing retina, postnatal brain, and adult wounded skin, while Bmp9-KO did not display any noticeable vascular defects. Bmp10 deficiency resulted in increased proliferation and size of endothelial cells in AVM vessels. The impaired neurovascular integrity in the brain and retina of Bmp10-iKO and Bmp9/10-dKO mice was detected. Bmp9/10-dKO mice exhibited the lethality and vascular malformation similar to Bmp10-iKO mice, but their phenotypes were more pronounced. Administration of BMP10 protein, but not BMP9 protein, prevented retinal AVM in Bmp9/10-dKO and endothelial-specific Eng-iKO mice. These data indicate that BMP10 is indispensable for the development of a proper arteriovenous network, whereas BMP9 has limited compensatory functions for the loss of BMP10. We suggest that BMP10 is the most relevant physiological ligand of the ENG-ALK1 signaling pathway pertinent to HHT pathogenesis.

Margetuximab with retifanlimab as first-line therapy in HER2+/PD-L1+ unresectable or metastatic gastroesophageal adenocarcinoma: MAHOGANY cohort A.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2)-positive metastatic gastric and gastroesophageal adenocarcinoma (GEA) is globally treated with chemotherapy plus trastuzumab. Novel therapeutic strategies strive to not only optimize efficacy, but also limit toxicities. In MAHOGANY cohort A, margetuximab, an Fc-engineered, anti-HER2 monoclonal antibody (mAb) was combined with retifanlimab, an anti-programmed cell death protein 1 mAb, in the first-line HER2-positive/programmed death-ligand 1 (PD-L1)-positive GEA. PATIENTS AND METHODS: MAHOGANY cohort A part 1 is a single-arm trial to evaluate margetuximab plus retifanlimab in patients with HER2 immunohistochemistry 3+, PD-L1-positive (combined positive score ≥1%), and non-microsatellite instability-high tumors. Primary objectives for cohort A were safety/tolerability and the confirmed objective response rate (ORR). RESULTS: As of 3 August 2021, 43 patients were enrolled and received margetuximab/retifanlimab. Nine grade 3 treatment-related adverse events (TRAEs) were reported in eight (18.6%) patients and eight serious TRAEs in seven (16.3%) patients. There were no grade 4/5 TRAEs. Three patients discontinued margetuximab/retifanlimab because of immune-related adverse events. The ORR by independent assessment was 53% [21/40 (95% confidence interval (CI) 36.1-68.5)], with a median duration of response of 10.3 months (95% CI 4.6-not evaluable); disease control rate was 73% [29/40 (95% CI 56.1-85.4)]. The study sponsor discontinued the study in advance of the planned enrollment when it became apparent that the study design would no longer meet the requirements for drug approval because of recent advances in the treatment of GEA. CONCLUSIONS: The chemotherapy-free regimen of combined margetuximab/retifanlimab as first-line treatment in double biomarker-selected patients demonstrated a favorable toxicity profile compared with historical outcomes using chemotherapy plus trastuzumab. The ORR observed in this study compares favorably versus ORR observed with other chemotherapy-free approaches.

Emerging pathogenic mechanisms in human brain arteriovenous malformations: a contemporary review in the multiomics era.

A variety of pathogenic mechanisms have been described in the formation, maturation, and rupture of brain arteriovenous malformations (bAVMs). While the understanding of bAVMs has largely been formulated based on animal models of rare hereditary diseases in which AVMs form, a new era of "omics" has permitted large-scale examinations of contributory genetic variations in human sporadic bAVMs. New findings regarding the pathogenesis of bAVMs implicate changes to endothelial and mural cells that result in increased angiogenesis, proinflammatory recruitment, and breakdown of vascular barrier properties that may result in hemorrhage; a greater diversity of cell populations that compose the bAVM microenvironment may also be implicated and complicate traditional models. Genomic sequencing of human bAVMs has uncovered inherited, de novo, and somatic activating mutations, such as KRAS, which contribute to the pathogenesis of bAVMs. New droplet-based, single-cell sequencing technologies have generated atlases of cell-specific molecular derangements. Herein, the authors review emerging genomic and transcriptomic findings underlying pathologic cell transformations in bAVMs derived from human tissues. The application of multiple sequencing modalities to bAVM tissues is a natural next step for researchers, although the potential therapeutic benefits or clinical applications remain unknown.

Brillouin light scattering in niobium doped lead zirconate single crystal.

Brillouin light scattering experiments were performed for lead zirconate single crystals doped with niobium. Special attention was paid to the elastic mode softening near phase transition temperatures. The results are compared with data obtained by Raman light scattering experiments. We observed that the interaction between acoustic and optic modes is responsible for symmetry breaking far above TC, leading to polar regions' appearance. No changes in the acoustic mode frequency and its damping are observed at TC, where ε(T) exhibits a maximum value. The absence of these changes and the central peak observed in Raman experiments suggest that the phase transition at TC is mainly of the order-disorder type. The origin of other phase transitions is discussed as well.

Suppression of BMP signaling by PHD2 deficiency in Pulmonary Arterial hypertension.

BMP signaling deficiency is evident in the lungs of patients with pulmonary arterial hypertension. We demonstrated that PHD2 deficiency suppresses BMP signaling in the lung endothelial cells, suggesting the novel mechanisms of dysregulated BMP signaling in the development of pulmonary arterial hypertension.

Usefulness of Wave-CAIPI for Postcontrast 3D T1-SPACE in the Evaluation of Brain Metastases.

BACKGROUND AND PURPOSE: High-resolution postcontrast 3D T1WI is a widely used sequence for evaluating brain metastasis, despite the long scan time. This study aimed to compare highly accelerated postcontrast 3D T1-weighted sampling perfection with application-optimized contrasts by using different flip angle evolution by using wave-controlled aliasing in parallel imaging (wave-T1-SPACE) with the commonly used standard high-resolution postcontrast 3D T1-SPACE for the evaluation of brain metastases. MATERIALS AND METHODS: Among the 387 patients who underwent postcontrast wave-T1-SPACE and standard SPACE, 56 patients with suspected brain metastases were retrospectively included. Two neuroradiologists assessed the number of enhancing lesions according to lesion size, contrast-to-noise ratiolesion/parenchyma, contrast-to-noise ratiowhite matter/gray matter, contrast ratiolesion/parenchyma, and overall image quality for the 2 different sequences. RESULTS: Although there was no significant difference in the evaluation of larger enhancing lesions (>5 mm) between the 2 different sequences (P = .66 for observer 1, P = .26 for observer 2), wave-T1-SPACE showed a significantly lower number of smaller enhancing lesions (<5 mm) than standard SPACE (1.61 [SD, 0.29] versus 2.84 [SD, 0.47] for observer 1; 1.41 [SD, 0.19] versus 2.68 [SD, 0.43] for observer 2). Furthermore, mean contrast-to-noise ratiolesion/parenchyma and overall image quality of wave-T1-SPACE were significantly lower than those in standard SPACE. CONCLUSIONS: Postcontrast wave-T1-SPACE showed comparable diagnostic performance for larger enhancing lesions (>5 mm) and marked scan time reduction compared with standard SPACE. However, postcontrast wave-T1-SPACE showed underestimation of smaller enhancing lesions (<5 mm) and lower image quality than standard SPACE. Therefore, postcontrast wave-T1-SPACE should be interpreted carefully in the evaluation of brain metastasis.

Genetics and Emerging Therapies for Brain Arteriovenous Malformations.

Brain arteriovenous malformations (AVMs) are characterized by a high-pressure, low-resistance vascular nidus created by direct shunting of blood from feeding arteries into arterialized veins, bypassing intervening capillaries. AVMs pose a risk of spontaneous rupture because the vessel walls are continuously exposed to increased shear stress and abnormal flow phenomena, which lead to vessel wall inflammation and distinct morphologic changes. The annual rupture rate is estimated at 2%, and once an AVM ruptures, the risk of rerupture increases 5-fold. The ability of AVMs to grow, regress, recur, and undergo remodeling shows their dynamic nature. Identifying the underlying cellular and molecular pathways of AVMs not only helps us understand their natural physiology but also allows us to directly block vital pathways, thus preventing AVM development and progression. Management of AVMs is challenging and often necessitates a multidisciplinary approach, including neurosurgical, endovascular, and radiosurgical expertise. Because many of these procedures are invasive, carry a risk of inciting hemorrhage, or are controversial, the demand for pharmacologic treatment options is increasing. In this review, we introduce novel findings of cellular and molecular AVM physiology and highlight key signaling mediators that are potential targets for AVM treatment. Furthermore, we give an overview of syndromes associated with hereditary and nonhereditary AVM formation and discuss causative genetic alterations.