SIRT2 deacetylates and decreases the expression of FOXM1 in colon cancer.

New FOXM1-specific inhibitors with the potential to be used for therapeutic purposes are under extensive research. We hypothesized that deacetylation of FOXM1 would decrease protein expression, thus providing novel therapeutic management of colon cancers. Immunostaining was used to determine FOXM1 and SIRT2 expressions in human colon cancer tissue microarrays (n = 90) from Stage I to Stage IV. SIRT2-FOXM1 interaction was evaluated in colon cancer cells using immunoprecipitation. Deacetylation of FOXM1 via SIRT2 was determined using in vitro deacetylation assays. FOXM1 could be hyper-acetylated when p300 and pCAF histone acetyltransferases were administered alongside deacetylase inhibitors. We detected that SIRT2 and FOXM1 physically interacted, and SIRT2 deacetylated FOXM1 in vitro. SIRT2 overexpression led to a significant decrease while knockdown of SIRT2 increased the FOXM1 expression in HCT116 human colon carcinoma cells. In the analysis of 90 human colorectal cancer samples, high SIRT2 expression was observed in about 49% of colorectal cancer, intermediate in 29%, and low or no staining in 22%. Strong SIRT2 expression was found to be negatively associated with the FOXM1 staining in our clinical cohort. This study reveals a molecular interaction and association between SIRT2 and FOXM1 expression in colon cancer cell lines and human colon cancer samples, and suggests that targeting SIRT2 activity using small molecule modulators may be a promising therapeutic approach for colorectal cancer.

Protective Effects of Crotonis Semen Extract against Sepsis through NF-κB Pathway Inhibition.

Sepsis is an inflammatory condition causing organ failure due to an uncontrolled immune response to infection and remains a significant challenge. Crotonis Semen has displayed various pharmacological effects, yet its potential in protecting against sepsis and the mechanisms involved remains largely unclear. Here, we explored the antiseptic properties of Crotons Semen extract (CSE) in both LPS-stimulated J774 macrophages and mice subjected to sepsis through Cecal ligation and Puncture (CLP) or LPS induction. We found that CSE enhanced survival rates in mouse models with acute sepsis induced by CLP operation and LPS injection. Administering CSE also reduced levels of enzymes indicating organ damage, such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatine kinase (CK), in septic mice. Furthermore, CSE lowered the serum levels of inflammatory mediators and cytokines, such as NO, TNF-α, IL-1ß, and IL-6, in septic mice. In LPS-stimulated J774 macrophages, CSE reduced the expression of pro-inflammatory proteins, including iNOS and COX-2. Moreover, CSE inhibited the phosphorylation of IκBα and IKK, key components of the NF-κB signaling pathway, thereby reducing inflammatory mediators and cytokines. These results demonstrate CSE's protective effects against sepsis through NF-κB pathway disruption, indicating its potential as a therapeutic option for acute inflammatory conditions.

Astragalus Complanatus Ethanol Attenuates Septic Shock by Exerting Anti-Inflammatory Effects on Macrophages.

Sepsis is a systemic inflammatory syndrome that results in multiple-organ failure caused by a dysregulated host immune response to microbial infection. Astragali complanati semen extract (ACSE) exhibits pharmacological activities, including antioxidant, anticancer, antiaging, and anti-diabetes effects. It is widely used in traditional medicine to treat liver and kidney diseases; however, the protective effect of ACSE on sepsis and its mechanisms are unknown. In the present study, we investigated the anti-inflammatory effects and potential mechanisms of the action of ACSE on sepsis. We show that ACSE improved survival rates in mouse models of acute sepsis induced by CLP (cecal ligation and puncture) and LPS stimulation. ACSE administration decreased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in sepsis-induced mice. Furthermore, ACSE reduced the levels of nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) in the serum of septic mice. ACSE treatment inhibited the expression of these proinflammatory genes in LPS-stimulated J774 macrophages. Moreover, ACSE inhibited the phosphorylation of the IκB kinase (IKK) and the nuclear translocation of p65 NF-κB by LPS stimulation in macrophages. These results reveal the mechanism underlying the protective effect of ACSE against sepsis by inhibiting NF-κB activation and suggest that ACSE could be a potential therapeutic candidate to treat acute inflammatory diseases.

Unlocking Prognostic Genes and Multi-Targeted Therapeutic Bioactives from Herbal Medicines to Combat Cancer-Associated Cachexia: A Transcriptomics and Network Pharmacology Approach.

Cachexia is a devastating fat tissue and muscle wasting syndrome associated with every major chronic illness, including cancer, chronic obstructive pulmonary disease, kidney disease, AIDS, and heart failure. Despite two decades of intense research, cachexia remains under-recognized by oncologists. While numerous drug candidates have been proposed for cachexia treatment, none have achieved clinical success. Only a few drugs are approved by the FDA for cachexia therapy, but a very low success rate is observed among patients. Currently, the identification of drugs from herbal medicines is a frontier research area for many diseases. In this milieu, network pharmacology, transcriptomics, cheminformatics, and molecular docking approaches were used to identify potential bioactive compounds from herbal medicines for the treatment of cancer-related cachexia. The network pharmacology approach is used to select the 32 unique genes from 238 genes involved in cachexia-related pathways, which are targeted by 34 phytocompounds identified from 12 different herbal medicines used for the treatment of muscle wasting in many countries. Gene expression profiling and functional enrichment analysis are applied to decipher the role of unique genes in cancer-associated cachexia pathways. In addition, the pharmacological properties and molecular interactions of the phytocompounds were analyzed to find the target compounds for cachexia therapy. Altogether, combined omics and network pharmacology approaches were used in the current study to untangle the complex prognostic genes involved in cachexia and phytocompounds with anti-cachectic efficacy. However, further functional and experimental validations are required to confirm the efficacy of these phytocompounds as commercial drug candidates for cancer-associated cachexia.

Reversible acetylation modulates p54nrb/NONO-mediated expression of the interleukin 8 gene.

The non-POU domain-containing octamer-binding protein (NONO, also referred to as p54nrb) is a multifunctional nuclear protein engaging in transcriptional regulation, mRNA splicing, nuclear retention of defective RNA, and DNA repair. Emerging evidence has demonstrated that p54nrb is subjected to various posttranslational modifications, including phosphorylation and methylation, which may be important regulators of its multifunction. However, among these modifications, direct evidence of p54nrb acetylation and its underlying mechanism remains unclear. In this study, we reported that lysine 371 of p54nrb was reversibly acetylated by the acetyltransferase general control non-depressible 5 (GCN5) and deacetylase sirtuin 1 (SIRT1), which was crucial for activity of p54nrb to inhibit interleukin-8 (IL-8) expression. Mechanistically, GCN5-mediated acetylation attenuates the recruitment of p54nrb on its core binding motif within the IL-8 gene promoter, preferentially increasing the expression of the IL-8 gene. In contrast, deacetylation by SIRT1 reverses this process. Altogether, our data suggest that reversible acetylation is an important switch for the multiple nuclear functions of p54nrb/NONO.

A Double-Edged Sword: The Two Faces of PARylation.

Poly ADP-ribosylation (PARylation) is a post-translational modification process. Following the discovery of PARP-1, numerous studies have demonstrated the role of PARylation in the DNA damage and repair responses for cellular stress and DNA damage. Originally, studies on PARylation were confined to PARP-1 activation in the DNA repair pathway. However, the interplay between PARylation and DNA repair suggests that PARylation is important for the efficiency and accuracy of DNA repair. PARylation has contradicting roles; however, recent evidence implicates its importance in inflammation, metabolism, and cell death. These differences might be dependent on specific cellular conditions or experimental models used, and suggest that PARylation may play two opposing roles in cellular homeostasis. Understanding the role of PARylation in cellular function is not only important for identifying novel therapeutic approaches; it is also essential for gaining insight into the mechanisms of unexplored diseases. In this review, we discuss recent reports on the role of PARylation in mediating diverse cellular functions and homeostasis, such as DNA repair, inflammation, metabolism, and cell death.

Clinical Outcomes Following the Early Application of Multimodal Scar Programs for Facial Incisional Wounds.

BACKGROUND: Even though scars are major issues for patients who undergo facial lacerations, programs for their prevention and early management are not well established. The purpose of this study was to evaluate the clinical outcomes of prophylactic scar assessments and early scar interventions in patients with lacerations. PATIENTS AND METHODS: A total of 116 patients underwent suture line and scar prevention treatment in the emergency room from 2014 to 2015. In the retrospective study, 46 patients who met all the criteria were included in the study. They were assigned to one of the following two scar prevention programs: the standard scar program for prevention, which included taping, silicone sheets, and ointments, and the multimodality scar program for treatment, which included triamcinolone, botulinum toxins, or CO2 fractional lasers. The patterns of early scar program were investigated for the standard scar prevention program and the multimodality scar management program, and we evaluated the scar assessment scores of the patients at 3 and 6 months. RESULTS: Scar scores for the patients who received multimodality scar management showed statistically significant improvements in Patient Scar Assessment (PSA) scales, Stony Brook Scar Evaluation Scales (SBSES), Vancouver Scar Scale (VSS) scores, and Visual Analog Scar (VAS) scales (the p values were 0.008, 0.007, 0.017, and 0.01, respectively). CONCLUSION: The multimodality scar program is more effective for scar prevention than the standard scar program. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Sirt3-mediated deacetylation of evolutionarily conserved lysine 122 regulates MnSOD activity in response to stress.

Genetic deletion of the mitochondrial deacetylase sirtuin-3 (Sirt3) results in increased mitochondrial superoxide, a tumor-permissive environment, and mammary tumor development. MnSOD contains a nutrient- and ionizing radiation (IR)-dependent reversible acetyl-lysine that is hyperacetylated in Sirt3⁻/⁻ livers at 3 months of age. Livers of Sirt3⁻/⁻ mice exhibit decreased MnSOD activity, but not immunoreactive protein, relative to wild-type livers. Reintroduction of wild-type but not deacetylation null Sirt3 into Sirt3⁻/⁻ MEFs deacetylated lysine and restored MnSOD activity. Site-directed mutagenesis of MnSOD lysine 122 to an arginine, mimicking deacetylation (lenti-MnSOD(K122-R)), increased MnSOD activity when expressed in MnSOD⁻/⁻ MEFs, suggesting acetylation directly regulates function. Furthermore, infection of Sirt3⁻/⁻ MEFs with lenti-MnSOD(K122-R) inhibited in vitro immortalization by an oncogene (Ras), inhibited IR-induced genomic instability, and decreased mitochondrial superoxide. Finally, IR was unable to induce MnSOD deacetylation or activity in Sirt3⁻/⁻ livers, and these irradiated livers displayed significant IR-induced cell damage and microvacuolization in their hepatocytes.

Liver Histological Improvement After Administration of High-Dose Vitamin C in Guinea Pig with Nonalcoholic Steatohepatitis.

Background: Vitamin C is a strong antioxidant, and the health effects of vitamin C megadoses have not been validated despite the apparent health benefits. Therefore, the present study sought to confirm the effects of vitamin C megadoses. Materials and Methods : Four groups of six guinea pigs were used. Each group was fed one of the following diets for three weeks: normal diet, methionine choline-deficient diet, methionine choline-deficient diet + vitamin C megadose (MCD + vit C 2.5 g/kg/day), and methionine-choline deficient diet + ursodeoxycholic acid (MCD + UDCA 30 mg/kg/day). The MCD diet was given to induce nonalcoholic steatohepatitis, and UDCA was used to treat nonalcoholic steatohepatitis. Three weeks after initial diet administration, the results of biochemical tests and liver biopsy were compared between the groups. Results: The cytoplasm state was similar in the MCD + vit C and MCD + UDCA groups, exhibiting clearing of the cytoplasm and ballooning degeneration. However, macrovesicular steatosis was not observed in the MCD + vit C group. Aspartate transaminase and alanine transaminase were elevated significantly following vitamin C administration. Conclusions: The present study confirmed that alone vitamin C megadoses are potential remedies for nonalcoholic steatohepatitis, based on the liver biopsy results of guinea pigs that were unable to synthesize vitamin C.

A comparison between DACC with chlorhexidine acetate-soaked paraffin gauze and foam dressing for skin graft donor sites.

OBJECTIVE: Retrograde infections often occur with excessive or incomplete drainage of exudate, or as a result of adherence of dressings to wounds. Dialkylcarbamoyl chloride (DACC) irreversibly binds to bacterial surfaces and physically removes bacteria when dressings are changed. Chlorhexidine acetate-soaked paraffin gauze provides a moist wound-healing environment. We hypothesise that when DACC is combined with chlorhexidine acetate-soaked paraffin gauze, wound healing times decrease. METHOD: From January 2013 to June 2015, medical records were retrospectively evaluated in 60 patients who underwent split-thickness skin grafts (STSG). Patients were divided into two groups: a 'thick skin group' and a 'thin skin group'. These two groups were further subdivided into a control group, where conventional foam dressings were applied to wounds, and an experimental group, where chlorhexidine acetate-soaked paraffin gauze with DACC was applied (DACC group). We compared the wound healing time between these subgroups. Differences in infected wound healing times were also compared. The Mann-Whitney test was applied to compare wound healing times between groups. RESULTS: Epithelialisation duration was significantly shorter in the DACC group. The control group had longer wound healing times, regardless of wound size. In the thick skin group, the median healing duration was 12 days in the control subgroup, compared with 9.5 days in the DACC subgroup (p=0.049). In the thin skin subgroup, the median healing duration in the control group was 18 days, compared with 10 days in the DACC subgroup (p=0.013). CONCLUSION: Application of DACC and chlorhexidine acetate-soaked paraffin gauze to skin graft donor sites can shorten healing times and is effective in treating infected wounds.

Clinical Impact of Highly Condensed Stromal Vascular Fraction Injection in Surgical Management of Depressed and Contracted Scars.

BACKGROUND: Recent research on stromal vascular fraction (SVF) has demonstrated the presence of numerous growth factors that aid in tissue regeneration and suggest the potential for scar treatment. This study was conducted to clinically show that adding stem cells can improve the surgical outcomes of scar formation. METHODS: Between March 2014 and February 2016, 17 patients underwent injections of fat and highly condensed SVF simultaneously with scar reduction surgeries and 15 patients received scar revision with or without simultaneous application of highly condensed SVF (4.90 × 107 stem cells/ml) at our institution. Clinical photographs were taken before and after surgery, and the scars were graded using the following standard scales: the Observer Scar Assessment Scale (OSAS), Stony Brook Scar Evaluation Scale (SBSES), Vancouver Scar Scale (VSS), and Visual Analog Scale (VAS). RESULTS: All patients showed improvement, registering significant increases in scar tissue scores (P < 0.05 in all four scoring systems). Patients in the SVF group showed more improved outcomes than patients in the non-SVF group for all scar tissue scores except the SBSES (OSAS, P = 0.029; SBSES, P = 0.281; VSS, P = 0.001; VAS, P = 0.021). Subcategories of these scales reflected more favorable outcomes in terms of height and pliability; however, there was no significant change in vascularity. CONCLUSIONS: SVF injections enhance tissue regeneration by contributing stem cells and growth factors to improve outcomes in scar revisions or tissue grafts. Harvesting the SVF through liposuction also provides a cosmetic benefit. Significant SVF-related gains in the scoring of scars indicate the merit of SVF as an aspect of conventional scar management. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Simultaneous Use of Selective Neurectomy With Liposuction for Calf Reduction in Asians.

BACKGROUND: Calf contouring continues to be popular among Northeast Asians. Calf hypertrophy and distorted leg contours are stressful to many women. Several calf reduction techniques such as a selective neurectomy or calf muscle resection have been attempted, but have inconsistent results. OBJECTIVES: This study was designed to demonstrate improved outcomes when combining a selective neurectomy with simultaneous liposuction. METHODS: A total of 780 patients with hypertrophic calves underwent calf reduction from January 2002 to December 2010. Of these, 193 patients were treated by selective neurectomy with simultaneous liposuction. Calf hypertrophy with a circumference below 34 cm was defined as mild, calves with a circumference of 34 to 38 cm were defined as moderate, and a calf circumference above 38 cm was defined as severe. In all groups, patients whose pinch test was above 2 cm underwent a simultaneous liposuction. RESULTS: Twenty-eight cases (14.5%) were defined as mild, 72 (37.3%) were moderate, and 93 (48.2%) were severe. Over an average of 8.7 months of postoperative follow up, the reduction in calf circumference averaged 3.7 cm in the mild group (11.1%), 4.0 cm in the moderate group (10.7 %), and 4.3 cm in the severe group (10.7%). Overall, 97.5% of patients were satisfied with the results. There were no severe complications including functional problem of lower extremity reported. CONCLUSIONS: The shape, type, and fat distribution of the hypertrophic calves were considered in our patient analysis. A selective neurectomy with liposuction was performed on 193 patients. This technique allowed for a successful calf reduction and improved the patient's aesthetic satisfaction without any reported functional complications.

Effectiveness of Hip External Rotator Strengthening Exercise in Korean Postural Bowleg Women.

Postural bowleg is a subclinical entity with both aesthetic and functional outcomes and appears to be common in East Asian countries. Internal rotation of the hip joint is associated with varus alignment at the knee joint of the bowleg. Strengthening exercise for the hip external rotator muscles seems to be effective in improving varus alignment of bowleg, but no standardized exercise program exists. A standardized active resistance strengthening exercise for hip external rotator muscles could improve varus alignment of the lower limb in bowlegged Korean women. In this article, a case series study was conducted to observe changes following a standardized 3-month program using equipment designed for strengthening of the hip external rotator muscles. Photogrammetric and radiographic data were used to compare the gap between knees and tibiofemoral (TF) angles before and after the exercise program. As a result, on average, the knee gap decreased by 1.6 cm. The TF angle decreased by 1.5°. Regression analysis revealed a statistically significant association between changes in knee gap and TF angle. The standardized 3-month active resistance strengthening exercise program of hip external rotator muscles was effective in improving postural deviation and cosmetic outcomes in bowlegged Korean women. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Effect of bilateral upper extremity exercise on trunk performance in patients with stroke.

[Purpose] The aim of this study was to investigate the effect of bilateral upper extremity exercises on trunk performance in patients with stroke. [Subjects and Methods] Twenty in-patients with chronic stroke of at least 6 month's duration participated in this study. Patients in the experimental and control groups received neurological rehabilitation treatment for stroke. In addition to the neurological rehabilitation treatment, patients in the experimental group received 30 minutes of bilateral upper extremity exercises 3 times weekly for 4 weeks. Outcomes were measured using the Trunk Impairment Scale before and after the 4-week training period. [Results] Significant intragroup differences in all items of Trunk Impairment Scale were observed after intervention. In particular, significant intergroup differences were observed for dynamic sitting balance, trunk coordination, and between total scores of the Trunk Impairment Scale. [Conclusion] The results of this study suggest bilateral upper extremity exercises could be used in addition to trunk exercises to improve trunk performance in patients with stroke.

Changes in cardiopulmonary function according to posture during recovery after maximal exercise.

[Purpose] This study was undertaken to measure cardiopulmonary function according to body position during the recovery period after maximal exercise and to identify an effective position after high-intensity exercise. [Subjects and Methods] Fifteen male university students in their twenties participated in the study. The subjects were randomly assigned to the supine position, the sitting position, or the trunk forward leaning position during the recovery period following maximal exercise. Oxygen uptake, minute ventilation volume, respiration rate, and heart rate according to posture were measured in a stable state, at maximal exercise loading, and at 1, 3, and 5 minutes after maximal exercise. [Results] Changes of cardiopulmonary function according to posture during the recovery period after maximal exercise showed that minute ventilation volume was smaller in the trunk forward leaning position than in the sitting or supine positions, and oxygen uptake also declined. [Conclusion] The trunk forward leaning position has a more positive effect on pulmonary ventilation after high-intensity exercise.

Effect of breathing maneuver combined with upper extremity exercise on respiratory capacity in healthy adult men.

[Purpose] This study aimed to determine the effect of the breathing maneuver combined with dynamic motion of the upper limbs on respiratory capacity in healthy adult men. [Subjects and Methods] Twenty-four healthy adult men participated in this study. Subjects were randomly assigned to a control group (n=12) or an experimental group (n=12). The subjects in the control group performed the breathing maneuver without the upper extremity exercise. The subjects in the experimental group performed upper extremity exercise with the breathing maneuver three times a week for 4 weeks. Outcomes were measured using maximum inspiratory and expiratory pressures. [Results] There was a significant difference in maximum inspiratory and expiratory pressures before and after intervention in the experimental group and the control group. In addition, there was a significant difference in maximal expiratory pressure between groups after intervention. [Conclusion] The results of this study suggest the respiration maneuver combined with upper extremity exercise could be used as a program for clinical respiration training.

SIRT2 directs the replication stress response through CDK9 deacetylation.

Sirtuin 2 (SIRT2) is a sirtuin family deacetylase that directs acetylome signaling, protects genome integrity, and is a murine tumor suppressor. We show that SIRT2 directs replication stress responses by regulating the activity of cyclin-dependent kinase 9 (CDK9), a protein required for recovery from replication arrest. SIRT2 deficiency results in replication stress sensitivity, impairment in recovery from replication arrest, spontaneous accumulation of replication protein A to foci and chromatin, and a G2/M checkpoint deficit. SIRT2 interacts with and deacetylates CDK9 at lysine 48 in response to replication stress in a manner that is partially dependent on ataxia telangiectasia and Rad3 related (ATR) but not cyclin T or K, thereby stimulating CDK9 kinase activity and promoting recovery from replication arrest. Moreover, wild-type, but not acetylated CDK9, alleviates the replication stress response impairment of SIRT2 deficiency. Collectively, our results define a function for SIRT2 in regulating checkpoint pathways that respond to replication stress through deacetylation of CDK9, providing insight into how SIRT2 maintains genome integrity and a unique mechanism by which SIRT2 may function, at least in part, as a tumor suppressor protein.

Osteonevus of Nanta Presenting as Flesh-Colored Papule of Cheek Following Laser Ablation.

Osteonevus of Nanta is a melanocytic nevus displaying secondary ossification and carrying a potential for malignancy. A solitary occurrence is reported herein, presenting as a flesh-colored papule following laser ablation.A 56-year-old woman sought treatment for a minor papular growth of the cheek. This lesion had developed at the site of prior CO2 laser ablation done elsewhere to eradicate a pigmented nevus. The patient's medical records and histopathology report were obtained after surgical excision.Histologically, a completely excised osteonevus of Nanta was evident, marked by an intradermal nevus with subjacent osseous metaplasia. Clinical presentations of these lesions may vary, but the potential for malignancy remains.

Early Intervention with Highly Condensed Adipose-Derived Stem Cells for Complicated Wounds Following Filler Injections.

BACKGROUND: A rise in cosmetic procedures has seen the use of fillers become more prevalent. Complications resulting from use of fillers have prompted introduction of various medical and surgical interventions. Recently, stem cell therapies have become more widely used as a new treatment option for tissue repair and regeneration. METHODS: We utilized adipose-derived stem cells (ASCs) for tissue regeneration in patients with filler-related complications such as necrosis. All 12 patients were treated with ASCs and some patients had additional treatment. After relief of symptoms, wound surface area was compared in terms of pixel numbers and scar condition was evaluated using the Vancouver Scar Scale (VSS). RESULTS: In general, we achieved satisfactory resolution of filler-related complications in a short period of time without serious side effects. The average number of days from stem cell treatment to symptom relief was 7.3 days. The proportion of wound surface area from photographic record was 4.39 % before treatment, decreasing considerably to 1.01 % following treatment. Last, the VSS showed almost all patients scored below 3, with two patients receiving scores of 7 and 8; the average score was 2.78 (range from 0 to 8). CONCLUSIONS: ASCs are a new treatment option for post-filler injection wounds such as necrosis. Using stem cells, we were able to obtain satisfactory results in a short period of time without complications requiring surgical procedures. We suggest stem cell injections could be used as the first option for treatment of complications from filler injections. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Association of Intraplaque Hemorrhage and Acute Infarction in Patients With Basilar Artery Plaque.

BACKGROUND AND PURPOSE: High-resolution magnetic resonance imaging (HRMRI) is ideal for serial examination of diseased arterial walls because it is noninvasive and has superior capability of discriminating tissue characteristics. The aim of this study is to evaluate the prevalence and clinical relevance of intraplaque hemorrhage (IPH) in patients with basilar artery (BA) atherosclerosis using HRMRI. METHODS: We analyzed HRMRI and clinical data from 74 patients (45 symptomatic and 29 asymptomatic), all of whom had >50% BA stenosis. High-signal intensity within a BA plaque on magnetization-prepared rapid acquisition with gradient-echo was defined as an area with an intensity that was >150% of the signal from the adjacent muscle. The relationship between IPH within a BA plaque region and clinical presentation was analyzed. RESULTS: Thirty patients were positive for IPH on HRMRI (42.3%, 24 symptomatic and 6 asymptomatic). Symptomatic lesions in the MR-positive IPH group were significantly more prevalent than in the MR-negative group (80.0% versus 48.8%; P<0.01). Also, MR-predicted IPH was significantly more prevalent in the high-grade stenosis group (P<0.001) than in the low-grade group. The relative risk of an acute focal stroke event among patients who were magnetization-prepared rapid acquisition with gradient-echo-positive for IPH compared with patients who were magnetization-prepared rapid acquisition with gradient-echo-negative was 1.64. CONCLUSIONS: IPH within a BA plaque region on HRMRI is highly prevalent and is associated with acute stroke.