Intima-Media Thickness in the Carotid Bifurcation is Related to Silent Brain Infarction: A Cross-Sectional Study.

AIMS: Carotid intima-media thickness (IMT) measurement is used to assess subclinical atherosclerosis. We aimed to examine the association between the maximum IMT by location and the occurrence of silent brain infarction (SBI). METHODS: Overall, 280 Japanese individuals (92 females, 52.6±5 years old) underwent a medical check-up at our hospital in Tokyo in 2015. Carotid IMT was measured at each site on ultrasound images (common carotid artery [CCA], internal carotid artery, or bifurcation). The risk factors for arterial dysfunction were evaluated. SBI was assessed using magnetic resonance imaging (MRI). The cross-sectional relationship between carotid maximum IMT and SBI was evaluated. RESULTS: Of the 280 individuals, 18 (6.4%) were diagnosed with SBI on MRI. The mean age of the SBI(-) and SBI(+) groups was 51.9±10.6 and 63.6±18.6 years, respectively. The correlation coefficients between the carotid maximum IMT at each location were very weak (correlation coefficient range: 0.180-0.253). The percentage of participants with SBI increased significantly with increasing maximum CCA and bIMT values. After adjusting for confounders, SBI was found to be significantly associated with the maximum bIMT (per 0.1-mm increase) (adjusted odds ratio [aOR], 1.10; 95% confidence interval [CI]: 1.03-1.17). When bIMT was categorized according to three groups (＜1.0 mm, 1.0-＜2.0 mm, and ≥ 2.0 mm), a significant SBI risk was also observed with an increase by each category of bIMT (aOR: 3.96, 95% CI: 1.63-9.52, P=0.002). CONCLUSION: The maximum bIMT was found to be the main determinant of SBI. A significant SBI risk was associated with an increase in each category of the maximum bIMT. Therefore, the maximum bIMT might be a useful predictor of future stroke in Japanese stroke-free medical check-up participants.

Diaphragm Dysfunction and ICU-Acquired Weakness in Septic Shock Patients with or without Mechanical Ventilation: A Pilot Prospective Observational Study.

Sepsis is a risk factor for diaphragm dysfunction and ICU-acquired weakness (ICU-AW); however, the impact of mechanical ventilation (MV) on these relationships has not been thoroughly investigated. This study aimed to compare the incidence of diaphragm dysfunction and ICU-AW in patients with septic shock, with and without MV. We conducted a single-center prospective observational study that included consecutive patients diagnosed with septic shock admitted to the ICU between March 2021 and February 2022. Ultrasound measurements of diaphragm thickness and manual measurements of limb muscle strength were repeated after ICU admission. The incidences of diaphragm dysfunction and ICU-AW, as well as their associations with clinical outcomes, were compared between patients with MV and without MV (non-MV). Twenty-four patients (11 in the MV group and 13 in the non-MV group) were analyzed. At the final measurements in the MV group, eight patients (72.7%) had diaphragm dysfunction, and six patients (54.5%) had ICU-AW. In the non-MV group, 10 patients (76.9%) had diaphragm dysfunction, and three (23.1%) had ICU-AW. No association was found between diaphragm dysfunction and clinical outcomes. Patients with ICU-AW in the MV group had longer ICU and hospital stays. Among patients with septic shock, the incidence of diaphragm dysfunction was higher than that of ICU-AW, irrespective of the use of MV. Further studies are warranted to examine the association between diaphragm dysfunction and clinical outcomes.

A differential detailed diffusion-weighted imaging-ASPECTS for cerebral infarct volume measurement and outcome prediction.

BACKGROUND: Diffusion-weighted imaging-Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECTS) has been used to estimate infarct core volume in acute stroke. However, the same and indiscriminate score deduction for punctate or confluent DWI high-intensity lesion might lead to variation in performance. AIMS: To develop and evaluate a differential detailed DWI-ASPECTS method in comparison with the conventional DWI-ASPECTS in core infarct volume measurement and clinical outcome prediction. METHODS: We retrospectively recruited patients with acute ischemic stroke (AIS) treated with endovascular treatment between April 2013 and October 2019. In differential detailed DWI-ASPECTS, restricted diffusion lesion that was punctate or less than half of a cortical region (M1-M6) would not lead to subtraction of point. A favorable outcome was modified Rankin Scale score ⩽2 at 90 days after stroke onset. RESULTS: Among 298 AIS patients, mean age was 75 years (interquartile range (IQR) 67-82), and 194 patients (65%) were males. Mean infarct core volume was 11 mL (IQR 3-37). Overall, the score by detailed DWI-ASPECTS was significantly higher than conventional DWI-ASPECTS (8 (7-9) vs. 7 (5-9); P < 0.01). The detailed DWI-ASPECTS resulted in a higher correlation coefficient (r) for core infarct volume estimation than the conventional DWI-ASPECTS (r = 0.832 vs. 0.773; P < 0.01). Upon re-classification of those scored ⩽6 in conventional DWI-ASPECTS (n = 134) by detailed DWI-ASPECTS, the rate of favorable outcome in patients with detailed DWI-ASPECTS >6 was significantly higher than those with ⩽6 (29 (48%) vs. 14 (19%); P < 0.01). CONCLUSIONS: Detailed DWI-ASPECTS appeared to provide a more accurate infarct core volume measurement and clinical outcome correlation than conventional DWI-ASPECTS among AIS patients treated with endovascular therapy.

Relationship Between Skeletal Muscle Quality and Hospital-Acquired Disability in Patients With Sepsis Admitted to the ICU: A Pilot Study.

Early risk assessment of functional decline in patients with sepsis is clinically challenging. Recently, there is increasing interest in the nonvolitional evaluation of skeletal muscle quality. OBJECTIVES: The aim of this study was to assess the relationship between skeletal muscle quality and functional decline after intensive care. DESIGN SETTING AND PARTICIPANTS: This pilot study was a single-center prospective observational study conducted from March 2021 to February 2022. We included consecutive patients with sepsis who were admitted to our ICU. MAIN OUTCOMES AND MEASURES: The primary outcome was hospital-acquired disability (HAD), which is defined as a decrease in the Barthel index score of at least 5 points from pre-hospital to hospital discharge. Muscle quality was assessed by: 1) muscle echogenicity with ultrasound and 2) phase angle (PhA) with bioelectrical impedance analysis, both of which were measured on ICU days less than 3, 3-5, 5-7, 7-10, and 10-14. We compared longitudinal changes in muscle echogenicity and PhA between the HAD and non-HAD groups using two-way repeated measures analysis of variance with mixed models. RESULTS: Among the 22 patients, 7 (31.8%) had HAD. Muscle echogenicity was higher in the HAD group than in the non-HAD group (p < 0.001); however, no interaction effects were found between the two groups (p = 0.189). PhA showed a main effect on each evaluation day in patients (p = 0.040) and a significant interaction effect between the groups, including an early decreased pattern in the HAD group (p = 0.036). CONCLUSIONS AND RELEVANCE: Higher muscle echogenicity and a decreased PhA pattern are related to HAD. Noninvasive assessment of muscle quality using ultrasound and bioelectrical impedance analysis may be useful in predicting the functional prognosis of patients with sepsis.

Hair transparency decoding in Asia: From stylists' perception to in vitro measurement.

BACKGROUND: The concept of hair transparency has been claimed widely in the Japan (and now it is spreading to Asian) hair color market. Despite the general use of this concept, to date, there is no clear and objective description to accurately explain what it is. In this work, we have decoded and gave clarity to the concept of hair transparency via a technical model (validated for both Japan and China markets) composed of measurable parameters of hair property using a single device. METHODOLOGY AND RESULTS: A comprehensive study composed of various tests was used, starting with a qualitative identification of key parameters via in-depth workshop discussions with over 40 Japanese stylists and a panel of 12 consumers. These identified parameters (luminosity, color visibility, and Shine) were then translated into technically measurable parameters of the hair fiber (Diffused light intensity, ratio of RGB channel intensities of Diffused light, and luster) via a single instrument-Hair SAMBA (a dual-polarized imaging system). Afterward, 10 carefully selected anchor shades were used as visual stimuli in an online pairwise comparison (PC) study with 100 Japanese stylists to generate quantitative transparency perception data of the swatches. Technical parameters of these swatches were measured by SAMBA and consolidated with the PC output, for the creation and validation of the mathematical model. After, with another PC study (N = 100) in China, with seven shades from Japan study and 6 additional Chinese market shades, the applicability of the model in China market was validated. CONCLUSION: We have clarified and quantified the concept of hair transparency through a consumer centric approach and with objective data. Our findings will enable the development of optimum transparent shades which better suits consumer needs. Lastly, we would like to highlight the beauty of digitalization in the study: The digital evaluation pathways chosen allowed us to collect quantitative consumer data from two countries for the creation of a robust model under the impact of COVID-19 and would definitely be the way to go for our future consumer evaluation studies.

Squamous Cell Carcinoma of Unknown Primary that Metastasized to an Inguinal Lymph Node: A Case Report.

Carcinoma of unknown primary (CUP) is a malignant tumor with histological characteristics indicating metastasis in a patient with an unidentified primary lesion after whole-body evaluation at the time of examination. CUP incidence is similar in men and women, and average age at diagnosis is 60 years. Reports of overall incidence vary but CUP is believed to account for 1-5% of all cancers. We encountered a case of apparently metastatic squamous cell carcinoma of the inguinal region in a patient without a detectable primary lesion. We report this case and review the literature on CUP, to increase awareness of this rare lesion.

The Effect of Aging and Small-Vessel Disease Burden on Hematoma Location in Patients with Acute Intracerebral Hemorrhage.

INTRODUCTION: Intracerebral hemorrhage (ICH) is a devastating hemorrhagic event and is associated with high mortality or severe neurological sequelae. Age-associated differences in hematoma location for nonlobar ICH are not well known. The aims of the present study were to elucidate the relationship between age and hematoma location and to assess the differences in small-vessel disease (SVD) burden as a potential surrogate marker for longstanding hypertension among various hematoma locations. METHODS: From September 2014 through July 2019, consecutive patients with acute, spontaneous ICH were retrospectively enrolled from a prospective registry. Magnetic resonance imaging was performed during admission, and the total SVD burden score (including microbleeds, lacunes, enlarged perivascular spaces, and white matter hyperintensities) was calculated. The relationships of hematoma location with aging and SVD burden were assessed by using multivariate logistic regression analyses. RESULTS: A total of 444 patients (156 women [35%]; median age 69 [interquartile range 59-79] years; National Institutes of Health Stroke Scale score 9 [17][3-17]) were enrolled in the present study. Multivariate logistic regression analyses showed that advanced age was independently associated with thalamic (odds ratio [OR]: 1.48, 95% confidence interval [CI]: 1.19-1.84, p < 0.001 for 10-year increment) and lobar hemorrhage (OR: 1.58, 95% CI: 1.19-2.09, p = 0.002) and was independently and negatively related to putaminal hemorrhage (OR: 0.55, 95% CI: 0.44-0.68, p < 0.001). The total SVD burden score was independently and positively associated with thalamic hemorrhage (OR: 1.27, 95% CI: 1.01-1.59, p = 0.045) and negatively with lobar hemorrhage (OR: 0.74, 95% CI: 0.55-0.99, p = 0.042), even after adjusting by age, but not with putaminal hemorrhage (OR: 0.91, 95% CI: 0.73-1.14, p = 0.395). CONCLUSION: Putaminal, thalamic, and lobar hemorrhages are prone to occur in specific ages and SVD states: putaminal in young patients, thalamic in old and high SVD burden patients, and lobar hemorrhages in old and low SVD burden patients. Susceptibility to bleeding with aging or severe SVD accumulation seems to differ considerably among brain locations.

Direct Delivery of Apatite Nanoparticle-Encapsulated siRNA Targeting TIMP-1 for Intractable Abnormal Scars.

Hypertrophic scars (HSs) and keloids are histologically characterized by excessive extracellular matrix (ECM) deposition. ECM deposition depends on the balance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteases (TIMPs). TIMP-1 has been linked to ECM degradation and is therefore a promising therapeutic strategy. In this study, we generated super carbonate apatite (sCA) nanoparticle-encapsulated TIMP-1 small interfering RNA (siRNA) (siTIMP1) preparations and examined the effect of local injections on mouse HSs and on ex vivo-cultured keloids. The sCA-siTIMP1 injections significantly reduced scar formation, scar cross-sectional areas, collagen densities, and collagen types I and III levels in the lesions. None of the mice died or exhibited abnormal endpoints. Apatite accumulation was not detected in the other organs. In an ex vivo keloid tissue culture system, sCA-siTIMP1 injections reduced the thickness and complexity of collagen bundles. Our results showed that topical sCA-siTIMP1 injections during mechanical stress-induced HS development reduced scar size. When keloids were injected three times with sCA-siTIMP1 during 6 days, keloidal collagen levels decreased substantially. Accordingly, sCA-siRNA delivery may be an effective approach for keloid treatment, and further investigations are needed to enable its practical use.

Cholesterol Crystal in Thrombus Removed by Mechanical Thrombectomy Should be a Strong Marker for Aortogenic Embolic Stroke.

Aortogenic embolic stroke (AES) is an important stroke mechanism. However, as many stroke patients have aortic atheromatous lesions, it is unclear whether these lesions are the cause of these strokes. Cholesterol crystals are the solid, crystalline form of cholesterol that is found in atherosclerosis, but not in cardiac diseases such as atrial fibrillation, valvular diseases, and cardiomyopathy. Therefore, if a cholesterol crystal is found in a thrombus removed by mechanical thrombectomy (MT), this makes it possible to diagnose a patient as having an atheromatous lesion. Here, we report an AES case with a cholesterol crystal found in a thrombus removed by MT. A 67-year-old man was admitted due to consciousness disturbance, aphasia, and right hemiplegia. Diffusion-weighted imaging (DWI) showed a hyperintense area in the left frontal lobe, and magnetic resonance angiography demonstrated a branch occlusion of the left middle cerebral artery (MCA). MT was performed 1.5 h after stroke onset, with the thrombus removed and a left occluded MCA completely recanalized. Carotid duplex ultrasonography did not reveal any plaque in the carotid artery. Echocardiography did not show any abnormal function or findings, including thrombus. Transesophageal echocardiography showed a 4.9 mm atheromatous lesion at the aortic arch. Therefore, we suspected this patient as having an AES due to the embolic source of atheromatous lesion at the aortic arch. Pathological examination of the embolus revealed a cholesterol crystal cleft in the thrombus. Therefore, we diagnosed this patient as having AES caused by an atheromatous lesion at the aortic arch.

Characteristics of Patients with Hereditary Transthyretin Amyloidosis and an Evaluation of the Safety of Tafamidis Meglumine in Japan: An Interim Analysis of an All-case Postmarketing Surveillance.

PURPOSE: An all-case, single-arm, observational, postmarketing surveillance is underway to assess the safety of tafamidis in patients with hereditary transthyretin (ATTRv) amyloidosis with peripheral polyneuropathy, also called transthyretin-type familial amyloid polyneuropathy, in Japan. Results from an interim analysis (data cutoff date, May 15, 2018) are presented in this preliminary report. METHODS: Patients were registered and treated with tafamidis meglumine 20 mg/d in routine clinical practice (observation period, 156 weeks). Data on patient demographic and clinical characteristics and adverse drug reactions (ADRs) were captured using case-report forms. FINDINGS: Of 219 patients included (mean age, 59.7 years; patients with age at disease onset ≥50 years, 61.2%; mean treatment duration, 95.5 weeks), 143 (65.3%) were male, 126 (57.5%) had a family history of ATTRv amyloidosis, and 149 (68.0%) originated from nonendemic areas. The most common ADRs were diarrhea (1.4%) and hematuria (0.9%). Six serious ADRs (pneumonia, bacteremia, malignant melanoma, pancreatic carcinoma, hematuria, and hereditary neuropathic amyloidosis [primary disease exacerbation]) were reported; no ADRs leading to death were recorded. IMPLICATIONS: This interim analysis successfully provided comprehensive, nationwide epidemiologic data from 219 Japanese patients with ATTRv amyloidosis. The safety profile of tafamidis was largely consistent with that obtained from previous research. No new safety concerns were identified to date. Data presented in this interim analysis are subject to change following completion of the study, and we will continue to assess the safety and effectiveness of tafamidis throughout the study. ClinicalTrials.gov identifier: NCT02146378.

Gene Expression Profile of Isolated Dermal Vascular Endothelial Cells in Keloids.

Wound healing is a complex biological process, and imbalances of various substances in the wound environment may prolong healing and lead to excessive scarring. Keloid is abnormal proliferation of scar tissue beyond the original wound margins with excessive deposition of extracellular matrix (ECM) and chronic inflammation. Despite numerous previous research efforts, the pathogenesis of keloid remains unknown. Vascular endothelial cells (VECs) are a major type of inductive cell in inflammation and fibrosis. Despite several studies on vascular morphology in keloid formation, there has been no functional analysis of the role of VECs. In the present study, we isolated living VECs from keloid tissues and investigated gene expression patterns using microarray analysis. We obtained 5 keloid tissue samples and 6 normal skin samples from patients without keloid. Immediately after excision, tissue samples were gently minced and living cells were isolated. Magnetic-activated cell sorting of VECs was performed by negative selection of fibroblasts and CD45+ cells and by positive selection of CD31+cells. After RNA extraction, gene expression analysis was performed to compare VECs isolated from keloid tissue (KVECs) with VECs from normal skin (NVECs). After cell isolation, the percentage of CD31+ cells as measured by flow cytometry ranged from 81.8%-98.6%. Principal component analysis was used to identify distinct molecular phenotypes in KVECs versus NVECs and these were divided into two subgroups. In total, 15 genes were upregulated, and 3 genes were downregulated in KVECs compared with NVECs using the t-test (< 0.05). Quantitative RT-PCR and immunohistochemistry showed 16-fold and 11-fold overexpression of SERPINA3 and LAMC2, respectively. SERPINA3 encodes the serine protease inhibitor, α1-antichymotripsin. Laminin γ2-Chain (LAMC2) is a subunit of laminin-5 that induces retraction of vascular endothelial cells and enhances vascular permeability. This is the first report of VEC isolation and gene expression analysis in keloid tissue. Our data suggest that SERPINA3 and LAMC2 upregulation in KVECs may contribute to the development of fibrosis and prolonged inflammation in keloid. Further functional investigation of these genes will help clarify the mechanisms of abnormal scar tissue proliferation.

Diagnosis and prediction of prognosis for Bickerstaff's brainstem encephalitis using auditory brainstem response: a case report.

BACKGROUND: It is difficult to diagnose Bickerstaff's brainstem encephalitis (BBE) in the acute phase, and emergency physicians could diagnose BBE as an unknown cause of consciousness disturbance. CASE PRESENTATION: A 75-year-old woman presented with dizziness and weakness in both arms 1 week after an upper respiratory infection. She experienced gradual worsening of consciousness, had dilated pupils and no light reflex. She was suspected of brainstem dysfunction at the upper part of the brainstem; however, there were not significant findings on magnetic resonance imaging, cerebrospinal fluid, or electroencephalography. The auditory brainstem response demonstrated a low voltage, but there was no prolonged latency. At a later date, she was diagnosed with BBE based on serum immunoglobulin G anti-GQ1b antibody. She was discharged home without any neurological sequelae. CONCLUSION: It is necessary to analyze serum immunoglobulin G anti-GQ1b antibodies to diagnose BBE. Auditory brainstem response would be helpful in detecting lesions and predicting functional recovery.

Early Cognitive Assessment Following Acute Stroke: Feasibility and Comparison between Mini-Mental State Examination and Montreal Cognitive Assessment.

OBJECTIVES: Cognitive assessment is not performed routinely in the acute stroke setting. We investigated factors associated with cognitive impairment and the differences between the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores in patients with acute stroke. METHODS: In this prospective study, 881 consecutive patients (median age, 73 years) with acute stroke were enrolled. Clinical characteristics, such as education, vascular risk factors, premorbid cognitive status using the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), and stroke severity, were assessed. Cognitive performance was measured using MMSE and MoCA within 5 days of stroke onset. RESULTS: Both MMSE and MoCA were feasible in 621 (70.5%) patients. Factors independently associated with nonfeasibility were age (odds ratio [OR]: 1.05; 95% confidence interval [CI]: 1.02-1.08), IQCODE score (OR: 1.02; 95%CI: 1.00-1.04), and National Institutes of Health Stroke Scale (NIHSS) score (OR, 1.16; 95%CI, 1.12-1.20). Impaired MoCA (with a cut-off <26/30) performance was observed in 544 of 621 (87.6%) patients. Factors independently associated with cognitive impairment were age (OR: 1.06; 95%CI: 1.03-1.10) and NIHSS score (OR: 1.34; 95%CI: 1.14-1.57). Eighty percent of patients with normal MMSE scores had an impaired MoCA score (MMSE-MoCA mismatch). The differences were highest in the visuospatial (94.8% versus 65.3%; P < .0001), recall (76.6% versus 35.6%; P < .0001), abstraction (82.5% versus 49.8%; P < .0001), and language (72.3% versus 65.9%; P < .0001) domains between the normal MMSE and MoCA group and MMSE-MoCA mismatch group. CONCLUSIONS: The MoCA can be particularly useful in patients with cognitive deficits undetectable on the MMSE in the acute stroke phase.

Effects of a structured group intervention on obesity among breast cancer survivors.

BACKGROUND: Obesity is associated with an increased risk for developing breast cancer and poor cancer-related outcomes. Endocrine therapy is a key part of treatment for breast cancer, but can result in weight gain. This study examined the efficacy of a structured group intervention during adjuvant endocrine therapy for obese patients with breast cancer. The intervention involved a combination of proper nutrition, exercise, and group coaching. METHODS: Participants were patients with breast cancer who were undergoing adjuvant endocrine therapy and exhibited apparent weight gain while undergoing therapy, or had a diagnosis of abnormal lipid metabolism. We conducted a single-arm prospective study with a combined intervention. The intervention comprised 15 min of nutrition education, a 30-min group health coaching program, and three 45-min group aerobic exercise sessions. We evaluated participants' parameters (e.g., body weight, body mass index [BMI], cholesterol, psychological distress) at baseline, and at 1, 3, and 6 months after the intervention. RESULTS: At 1 month after the intervention, there were significant reductions in body weight (p < 0.01), BMI (p < 0.01), triglyceride levels (p < 0.05), total cholesterol levels (p < 0.01), psychological distress (p < 0.05), and cancer-related fatigue (p < 0.01). At 3 and 6 months after the intervention, we observed further reductions in body weight, BMI, and triceps skinfold thickness. CONCLUSION: Our study showed that a short-term structured intervention helped modify dietary and exercise behaviors and promote health among breast cancer survivors, and resulted in favorable changes in participants' body weight.

Photoimmunotherapy targeting biliary-pancreatic cancer with humanized anti-TROP2 antibody.

Photoimmunotherapy (PIT) is a new type of tumor-specific treatment utilizing monoclonal antibody (mAb)-photosensitizer conjugates and near-infrared (NIR) light irradiation. One potential PIT target, the type I transmembrane protein TROP2, is expressed at high levels in many cancers, including pancreatic carcinoma (PC) and cholangiocarcinoma (CC), in which its expression is correlated with poor prognosis and tumor aggressiveness. In this study, we assessed the efficacy of PIT utilizing newly developed humanized anti-TROP2 mAb conjugated to the photosensitizer IR700 (TROP2-IR700) for PC and CC. Immunohistochemistry on PC and CC tissue microarrays confirmed that TROP2 is overexpressed in about half of PC and CC specimens. Using cultured PC and CC cells, TROP2-IR700 localized TROP2-specific and target-specific cell killing was observed after NIR light irradiation. In addition, TROP2-IR700 was localized to mouse xenograft tumors expressing TROP2 after intravenous injection. PC and CC xenograft tumor growth was significantly inhibited by TROP2-targeted PIT relative to controls. The efficacy of TROP2-targeted PIT in vitro and against xenografted tumors in vivo suggests promise as a therapy for human PC and CC, both of which currently have dismal prognoses and limited therapeutic options.

Sphingosine-1-Phosphate Facilitates Skin Wound Healing by Increasing Angiogenesis and Inflammatory Cell Recruitment with Less Scar Formation.

Wound healing starts with the recruitment of inflammatory cells that secrete wound-related factors. This step is followed by fibroblast activation and tissue construction. Sphingosine-1-phosphate (S1P) is a lipid mediator that promotes angiogenesis, cell proliferation, and attracts immune cells. We investigated the roles of S1P in skin wound healing by altering the expression of its biogenic enzyme, sphingosine kinase-1 (SphK1). The murine excisional wound splinting model was used. Sphingosine kinase-1 (SphK1) was highly expressed in murine wounds and that SphK1-/- mice exhibit delayed wound closure along with less angiogenesis and inflammatory cell recruitment. Nanoparticle-mediated topical SphK1 overexpression accelerated wound closure, which associated with increased angiogenesis, inflammatory cell recruitment, and various wound-related factors. The SphK1 overexpression also led to less scarring, and the interaction between transforming growth factor (TGF)-ß1 and S1P receptor-2 (S1PR2) signaling is likely to play a key role. In summary, SphK1 play important roles to strengthen immunity, and contributes early wound healing with suppressed scarring. S1P can be a novel therapeutic molecule with anti-scarring effect in surgical, trauma, and chronic wound management.

The Interplay of Mechanical Stress, Strain, and Stiffness at the Keloid Periphery Correlates with Increased Caveolin-1/ROCK Signaling and Scar Progression.

BACKGROUND: Fibroproliferative disorders result in excessive scar formation, are associated with high morbidity, and cost billions of dollars every year. Of these, keloid disease presents a particularly challenging clinical problem because the cutaneous scars progress beyond the original site of injury. Altered mechanotransduction has been implicated in keloid development, but the mechanisms governing scar progression into the surrounding tissue remain unknown. The role of mechanotransduction in keloids is further complicated by the differential mechanical properties of keloids and the surrounding skin. METHODS: The authors used human mechanical testing, finite element modeling, and immunohistologic analyses of human specimens to clarify the complex interplay of mechanical stress, strain, and stiffness in keloid scar progression. RESULTS: Changes in human position (i.e., standing, sitting, and supine) are correlated to dynamic changes in local stress/strain distribution, particularly in regions with a predilection for keloids. Keloids are composed of stiff tissue, which displays a fibrotic phenotype with relatively low proliferation. In contrast, the soft skin surrounding keloids is exposed to high mechanical strain that correlates with increased expression of the caveolin-1/rho signaling via rho kinase mechanotransduction pathway and elevated inflammation and proliferation, which may lead to keloid progression. CONCLUSIONS: The authors conclude that changes in human position are strongly correlated with mechanical loading of the predilection sites, which leads to increased mechanical strain in the peripheral tissue surrounding keloids. Furthermore, increased mechanical strain in the peripheral tissue, which is the site of keloid progression, was correlated with aberrant expression of caveolin-1/ROCK signaling pathway. These findings suggest a novel mechanism for keloid progression.

Accurate etiology diagnosis in patients with stroke and atrial fibrillation: A role for brain natriuretic peptide.

BACKGROUND: Atrial fibrillation (AF) is the leading cause of cardioembolic stroke (CES), and patients with stroke and AF are frequently assumed to have CES. However, strokes presumably due to atherosclerotic pathophysiologies in large or small vessels can also occur in patients with AF. The aims of the present study were to clarify the prevalence of and factors related to a non-cardioembolic etiology in acute stroke patients with AF. METHODS: From March 2011 through May 2017, consecutive acute ischemic stroke patients with AF were retrospectively recruited. The concomitant presence of non-cardioembolic features (small vessel occlusion [SVO] or large artery atherosclerosis [LAA]) on imaging was evaluated. The frequency of and factors associated with co-existing SVO/LAA features were assessed. RESULTS: A total of 560 consecutive patients with AF and acute stroke (237 women; median age 78 [IQR 71-85] years; NIHSS score 9 [3-20]) were enrolled. Of these, 42 (7.5%) had co-existing SVO/LAA features. Multivariable logistic regression analysis showed that the brain natriuretic peptide level (BNP, OR 0.78, p = .030 per 100 pg/mL increase) was independently and negatively associated with co-existing SVO/LAA features and receiver operating characteristic curve analysis revealed the practical cut-off BNP value was 130 pg/mL (sensitivity 54% and specificity 68%). CONCLUSION: SVO/LAA features were found in 7.5% of acute stroke patients with AF. A relatively low BNP level on admission was independently associated with co-existing SVO/LAA features. Thorough examination for a more appropriate etiology may be particularly necessary in acute stroke patients with AF and a relatively low BNP level.

Ischemic stroke during anticoagulant interruption by healthcare professionals in stroke patients with atrial fibrillation.

BACKGROUND: Anticoagulant therapy often requires temporary interruption. Nevertheless, the frequency and clinical characteristics of stroke patients who develop stroke during anticoagulant interruption are not fully known. METHODS: From March 2011 through May 2017, consecutive acute ischemic stroke patients with AF who were admitted to our stroke unit were retrospectively recruited. Patients who developed ischemic stroke during anticoagulant interruption were defined as those who developed ischemic stroke within 30 days from anticoagulant interruption. The frequency and clinical characteristics of patients during anticoagulant interruption were analyzed. RESULTS: A total of 561 patients with AF and acute ischemic stroke (237 women; median age 78 [IQR 71-85] years) were admitted during the study period. Of these, 21 (3.7%, 12 patients discontinued vitamin K antagonist [VKA] and 9 discontinued direct oral anticoagulants [DOACs]) patients were admitted during the period of anticoagulant interruption. Severity and functional outcomes in stroke patients during anticoagulant interruption were not different from those without anticoagulant treatment. The number of days between anticoagulant interruption and stroke onset was shorter in patients who discontinued DOACs (3 [3-5] days) than in those who discontinuedVKAs (10 [7-20] days, p = .004). The major reason for interruption was planning of invasive procedures (52%). Guideline deviations were suspected in 82% of such cases. CONCLUSION: Patients developing stroke during anticoagulant interruption accounted for 3.7% of stroke patients with AF. Strokes occurred relatively early after interruption, especially in patients who discontinued DOACs. Guideline deviations was frequent.

Sarcopenia in adults with congenital heart disease: Nutritional status, dietary intake, and resistance training.

BACKGROUND: This study aimed (1) to assess the nutritional status and dietary intake, (2) compare the body composition and nutritional intake between sarcopenia and non-sarcopenia, and (3) evaluate the effects of resistance training and amino acid intake in adults with congenital heart disease (CHD). METHODS: Study 1 In total, 172 adults with CHD were prospectively enrolled. The Food Frequency Questionnaire was used, and body composition analysis was conducted. Study 2: Thirty of 172 adult patients with CHD were divided into two groups: amino acid intake plus resistance training (group A) and amino acid intake only (group B) for 2 months. RESULTS: Study 1: Skeletal muscle mass index was lower in adults with CHD compared to healthy Japanese. Calorie, protein, and fat intake in adults with CHD was higher than those in the National Nutritive Intake Investigation; however, the difference in carbohydrate or salt intake was non-significant. Study 2: In adults with CHD in group A, body fat percentage, edema index, and N-terminal prohormone of brain natriuretic peptide improved, and body weight, skeletal muscle mass index, and basic metabolism increased after the intervention. There was no improvement after intervention for group B. CONCLUSIONS: According to this study, adults with CHD have higher calorie, protein, and fat intake than those in a national survey despite decreased skeletal muscle mass. Amino acid intake plus resistance training positively improved body fat percentage, skeletal muscle mass, and edema in adults with CHD. Appropriate nutritional education and resistance training guidelines should be provided.