Yeungnam University Medical Center

OBJECTIVE: Physical or mental imbalance caused by harmful stimuli can induce stress to maintain homeostasis. During chronic stress, the sympathetic nervous system is hyperactivated, causing physical, psychological, and behavioral abnormalities. At present, there is no accepted standard for stress evaluation. This review aimed to survey studies providing a rationale for selecting heart rate variability (HRV) as a psychological stress indicator. METHODS: , National Library of Medicine (PubMed), and Google Scholar databases yielded 37 publications meeting our criteria. The inclusion criteria were involvement of human participants, HRV as an objective psychological stress measure, and measured HRV reactivity. RESULTS: In most studies, HRV variables changed in response to stress induced by various methods. The most frequently reported factor associated with variation in HRV variables was low parasympathetic activity, which is characterized by a decrease in the high-frequency band and an increase in the low-frequency band. Neuroimaging studies suggested that HRV may be linked to cortical regions (e.g., the ventromedial prefrontal cortex) that are involved in stressful situation appraisal. CONCLUSION: In conclusion, the current neurobiological evidence suggests that HRV is impacted by stress and supports its use for the objective assessment of psychological health and stress.

BACKGROUND: Patients who have residual invasive carcinoma after the receipt of neoadjuvant chemotherapy for human epidermal growth factor receptor 2 (HER2)-negative breast cancer have poor prognoses. The benefit of adjuvant chemotherapy in these patients remains unclear. METHODS: We randomly assigned 910 patients with HER2-negative residual invasive breast cancer after neoadjuvant chemotherapy (containing anthracycline, taxane, or both) to receive standard postsurgical treatment either with capecitabine or without (control). The primary end point was disease-free survival. Secondary end points included overall survival. RESULTS: The result of the prespecified interim analysis met the primary end point, so this trial was terminated early. The final analysis showed that disease-free survival was longer in the capecitabine group than in the control group (74.1% vs. 67.6% of the patients were alive and free from recurrence or second cancer at 5 years; hazard ratio for recurrence, second cancer, or death, 0.70; 95% confidence interval [CI], 0.53 to 0.92; P=0.01). Overall survival was longer in the capecitabine group than in the control group (89.2% vs. 83.6% of the patients were alive at 5 years; hazard ratio for death, 0.59; 95% CI, 0.39 to 0.90; P=0.01). Among patients with triple-negative disease, the rate of disease-free survival was 69.8% in the capecitabine group versus 56.1% in the control group (hazard ratio for recurrence, second cancer, or death, 0.58; 95% CI, 0.39 to 0.87), and the overall survival rate was 78.8% versus 70.3% (hazard ratio for death, 0.52; 95% CI, 0.30 to 0.90). The hand-foot syndrome, the most common adverse reaction to capecitabine, occurred in 73.4% of the patients in the capecitabine group. CONCLUSIONS: After standard neoadjuvant chemotherapy containing anthracycline, taxane, or both, the addition of adjuvant capecitabine therapy was safe and effective in prolonging disease-free survival and overall survival among patients with HER2-negative breast cancer who had residual invasive disease on pathological testing. (Funded by the Advanced Clinical Research Organization and the Japan Breast Cancer Research Group; CREATE-X UMIN Clinical Trials Registry number, UMIN000000843 .).

BACKGROUND: This study aimed to investigate the prevalence and management of diabetes mellitus, risk-factor control, and comorbidities among Korean adults. METHODS: We conducted a cross-sectional analysis of data from the Korea National Health and Nutrition Examination Survey to assess the prevalence, treatment, risk factors, comorbidities, and self-management behaviors of diabetes mellitus from 2019 to 2020. We also analyzed data from the Korean National Health Insurance Service to evaluate the use of antidiabetic medications in people with diabetes mellitus from 2002 through 2018. RESULTS: Among Korean adults aged 30 years or older, the estimated prevalence of diabetes mellitus was 16.7% in 2020. From 2019 through 2020, 65.8% of adults with diabetes mellitus were aware of the disease and treated with antidiabetic medications. The percentage of adults with diabetes mellitus who achieved glycosylated hemoglobin (HbA1c) <6.5% was 24.5% despite the increased use of new antidiabetic medications. We found that adults with diabetes mellitus who achieved all three goals of HbA1c <6.5%, blood pressure (BP) <140/85 mm Hg, and low-density lipoprotein cholesterol <100 mg/dL were 9.7%. The percentage of self-management behaviors was lower in men than women. Excess energy intake was observed in 16.7% of adults with diabetes mellitus. CONCLUSION: The prevalence of diabetes mellitus among Korean adults remained high. Only 9.7% of adults with diabetes mellitus achieved all glycemic, BP, and lipid controls from 2019 to 2020. Continuous evaluation of national diabetes statistics and a national effort to increase awareness of diabetes mellitus and improve comprehensive diabetes care are needed.

Fistula is a representative devastating complication in Crohn's patients due to refractory to conventional therapy and high recurrence. In our phase I clinical trial, adipose tissue-derived stem cells (ASCs) demonstrated their safety and therapeutic potential for healing fistulae associated with Crohn's disease. This study was carried out to evaluate the efficacy and safety of ASCs in patients with Crohn's fistulae. In this phase II study, forty-three patients were treated with ASCs. The amount of ASCs was proportioned to fistula size and fistula tract was filled with ASCs in combination with fibrin glue after intralesional injection of ASCs. Patients without complete closure of fistula at 8 weeks received a second injection of ASCs containing 1.5 times more cells than the first injection. Fistula healing at week 8 after final dose injection and its sustainability for 1-year were evaluated. Healing was defined as a complete closure of external opening without any sign of drainage and inflammation. A modified per-protocol analysis showed that complete fistula healing was observed in 27/33 patients (82%) by 8 weeks after ASC injection. Of 27 patients with fistula healing, 26 patients completed additional observation study for 1-year and 23 patients (88%) sustained complete closure. There were no adverse events related to ASC administration. ASC treatment for patients with Crohn's fistulae was well tolerated, with a favorable therapeutic outcome. Furthermore, complete closure was well sustained. These results strongly suggest that autologous ASC could be a novel treatment option for the Crohn's fistula with high-risk of recurrence.

Exosomal noncoding RNAs (ncRNAs) have unique expression profiles reflecting the characteristics of a tumor, and their role in tumor progression and metastasis is emerging. However, the significance of circulating exosomal ncRNAs in the prognosis of hepatocellular carcinoma (HCC) remains to be elucidated. We therefore determined the prognostic significance of circulating exosomal ncRNAs (miRNA-21 and lncRNA-ATB) for human HCC. This prospective study enrolled 79 HCC patients between October 2014 and September 2015. Exosomes were extracted from serum samples using the ExoQuick Exosome Precipitation Solution. To validate the isolation of the exosomes from serum, immunoblotting for exosome markers and characterization of nanoparticle using NanoSight were performed. NcRNAs were isolated from exosomes using the miRNeasy serum/plasma micro kit. Both circulating exosomal miRNA-21 and lncRNA-ATB were related to TNM stage and other prognostic factors, including the T stage and portal vein thrombosis. Multivariate analysis using the Cox regression test identified that both higher miRNA-21 and higher lncRNA-ATB were independent predictors of mortality and disease progression, along with larger tumor size and higher C-reactive protein (all p < 0.05). The overall survival and progression-free survival were significantly lower in patients with higher circulating levels of exosomal miRNA-21 (≥0.09) and lncRNA-ATB (≥0.0016) (log-rank test: p < 0.05). In conclusion, our study has provided strong evidence that circulating exosomal ncRNAs (miRNA-21 and lncRNA-ATB) are novel prognostic markers and therapeutic targets for HCC.

BACKGROUND AND PURPOSE: The aim of this study was to determine if automated MRI analysis software (RAPID) can be used to identify patients with stroke in whom reperfusion is associated with an increased chance of good outcome. METHODS: Baseline diffusion- and perfusion-weighted MRI scans from the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution study (DEFUSE; n=74) and the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET; n=100) were reprocessed with RAPID. Based on RAPID-generated diffusion-weighted imaging and perfusion-weighted imaging lesion volumes, patients were categorized according to 3 prespecified MRI profiles that were hypothesized to predict benefit (Target Mismatch), harm (Malignant), and no effect (No Mismatch) from reperfusion. Favorable clinical response was defined as a National Institutes of Health Stroke Scale score of 0 to 1 or a ≥ 8-point improvement on the National Institutes of Health Stroke Scale score at Day 90. RESULTS: In Target Mismatch patients, reperfusion was strongly associated with a favorable clinical response (OR, 5.6; 95% CI, 2.1 to 15.3) and attenuation of infarct growth (10 ± 23 mL with reperfusion versus 40 ± 44 mL without reperfusion; P<0.001). In Malignant profile patients, reperfusion was not associated with a favorable clinical response (OR, 0.74; 95% CI, 0.1 to 5.8) or attenuation of infarct growth (85 ± 74 mL with reperfusion versus 95 ± 79 mL without reperfusion; P=0.7). Reperfusion was also not associated with a favorable clinical response (OR, 1.05; 95% CI, 0.1 to 9.4) or attenuation of lesion growth (10 ± 15 mL with reperfusion versus 17 ± 30 mL without reperfusion; P=0.9) in No Mismatch patients. CONCLUSIONS: MRI profiles that are associated with a differential response to reperfusion can be identified with RAPID. This supports the use of automated image analysis software such as RAPID for patient selection in acute stroke trials.

Characteristics of stroke cases, acute stroke care, and outcomes after stroke differ according to geographical and cultural background. To provide epidemiological and clinical data on stroke care in South Korea, we analyzed a prospective multicenter clinical stroke registry, the Clinical Research Center for Stroke-Fifth Division (CRCS-5). Patients were 58% male with a mean age of 67.2±12.9 years and median National Institutes of Health Stroke Scale score of 3 [1-8] points. Over the 6 years of operation, temporal trends were documented including increasing utilization of recanalization treatment with shorter onset-to-arrival delay and decremental length of stay. Acute recanalization treatment was performed in 12.7% of cases with endovascular treatment utilized in 36%, but the proportion of endovascular recanalization varied across centers. Door-to-IV alteplase delay had a median of 45 [33-68] min. The rate of symptomatic hemorrhagic transformation (HT) was 7%, and that of any HT was 27% among recanalization-treated cases. Early neurological deterioration occurred in 15% of cases and were associated with longer length of stay and poorer 3-month outcomes. The proportion of mRS scores of 0-1 was 42% on discharge, 50% at 3 months, and 55% at 1 year after the index stroke. Recurrent stroke up to 1 year occurred in 4.5% of patients; the rate was higher among older individuals and those with neurologically severe deficits. The above findings will be compared with other Asian and US registry data in this article.

BACKGROUND AND METHODS: To assess the precise mechanisms of stroke in cancer patients, we analyzed the data for cancer patients with acute ischemic stroke registered from 6 centers in South Korea. Clinical features, risk factors, diffusion-weighted imaging lesion patterns, and laboratory findings including D-dimer levels were compared between patients with conventional stroke mechanisms (CSMs) and cryptogenic group. RESULTS: A total of 161 patients were included in this study: 97 (60.2%) patients in the CSM group and 64 (39.8%) in the cryptogenic group. Patients in the CSM group were older and vascular risk factors were more prevalent than in the cryptogenic group. Diffusion-weighted imaging patterns of multiple lesions involving multiple arterial territories were observed more frequently in the cryptogenic group than in the CSM group. In addition, levels of the D-dimer were higher in the cryptogenic group than in the CSM group (11.5+/-14.6 versus 3.6+/-10.3 microg/dL). In multivariate analysis, the diffusion-weighted imaging lesion pattern of multiple vascular territories (odds ratio, 11.2; 95% CI, 3.74 to 33.3), and D-dimer levels of >1.11 microg/dL (odds ratio, 10.6; 95% CI, 3.29 to 33.8) were associated independently with the cryptogenic group. CONCLUSIONS: Stroke outside of CSM occurred in a large number in cancer patients. In stroke patients with cancer, d-dimer levels and diffusion-weighted imaging lesion patterns may be helpful in early identification of non-CSMs (especially coagulopathy associated with cancer) and possibly in guiding preventive strategies for stroke.

PURPOSE: As a result of various independently proposed nomenclatures and classifications, there is confusion in the diagnosis and prediction of biological behavior of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). A comprehensive nationwide study is needed in order to understand the biological characteristics of GEP-NETs in Korea. MATERIALS AND METHODS: We collected 4,951 pathology reports from 29 hospitals in Korea between 2000 and 2009. Kaplan-Meier survival analysis was used to determine the prognostic significance of clinicopathological parameters. RESULTS: Although the GEP-NET is a relatively rare tumor in Korea, its incidence has increased during the last decade, with the most significant increase found in the rectum. The 10-year survival rate for well-differentiated endocrine tumor was 92.89%, in contrast to 85.74% in well differentiated neuroendocrine carcinoma and 34.59% in poorly differentiated neuroendocrine carcinoma. Disease related death was most common in the biliary tract (62.2%) and very rare in the rectum (5.2%). In Kaplan-Meier survival analysis, tumor location, histological classification, extent, size, mitosis, Ki-67 labeling index, synaptophysin expression, lymphovascular invasion, perineural invasion, and lymph node metastasis showed prognostic significance (p<0.05), however, chromogranin expression did not (p=0.148). The 2000 and 2010 World Health Organization (WHO) classification proposals were useful for prediction of the prognosis of GEP-NET. CONCLUSION: The incidence of GEP-NET in Korea has shown a remarkable increase during the last decade, however, the distribution of tumors in the digestive system differs from that of western reports. Assessment of pathological parameters, including immunostaining, is crucial in understanding biological behavior of the tumor as well as predicting prognosis of patients with GEP-NET.

BACKGROUND: The Korea Acute Myocardial Infarction Registry (KAMIR)-National Institutes of Health (NIH) registry has the aim of evaluating the clinical characteristics, management, and long-term outcomes of patients with acute myocardial infarction (AMI) in Korea. METHODS AND RESULTS: Patients hospitalized for AMI in 20 tertiary university hospitals in Korea have been enrolled since November 2011. The study is expected to complete the scheduled enrollment of approximately 13,000 patients in October 2015, and follow-up duration is up to 5 years for each patient. As of October 2015, an interim analysis of 13,623 subjects was performed to understand the baseline clinical profiles of the study population. The mean age was 64.1 years; 73.5% were male; and 48.2% were diagnosed with ST-segment elevation AMI. Hypertension is a leading cause of AMI in Korea (51.2%), followed by smoking (38.5%) and diabetes mellitus (28.6%). Percutaneous coronary intervention was performed in 87.4% and its success rate was very high (99.4%). In-hospital, 1-year, and 2-year mortality rates were 3.9%, 4.3%, and 8.6%, respectively. The rates of major adverse cardiac events at 1 and 2 years were 9.6% and 18.8%, respectively. CONCLUSIONS: This analysis demonstrated the clinical characteristics of Korean AMI patients in comparison with those of other countries. It is necessary to develop guidelines for Asian populations to further improve their prognosis. (Circ J 2016; 80: 1427-1436).

BACKGROUND AND PURPOSE: To refine the definition of the malignant magnetic resonance imaging profile in acute stroke patients using baseline diffusion-weighted magnetic resonance imaging (DWI) and perfusion-weighted magnetic resonance imaging (PWI) findings from the pooled DEFUSE/EPITHET database. METHODS: Patients presenting with acute stroke within 3 to 6 hours from symptom onset were treated with tissue plasminogen activator or placebo. Baseline and follow-up DWI and PWI images from both studies were reprocessed using the same software program. A receiver operating characteristic curve analysis was used to identify Tmax and DWI volumes that optimally predicted poor outcomes (modified Rankin Scale 5-6) at 90 days in patients who achieved reperfusion. RESULTS: Sixty-five patients achieved reperfusion and 46 did not reperfuse. Receiver operating characteristic analysis identified a PWI (Tmax>8 s) volume of >85 mL as the optimal definition of the malignant profile. Eighty-nine percent of malignant profile patients had poor outcome with reperfusion versus 39% of patients without reperfusion (P=0.02). Parenchymal hematomas occurred more frequently in malignant profile patients who experienced reperfusion versus no reperfusion (67% versus 11%, P<0.01). DWI analysis identified a volume of 80 mL as the best DWI threshold, but this definition was less sensitive than were PWI-based definitions. CONCLUSIONS: Stroke patients likely to suffer parenchymal hemorrhages and poor outcomes following reperfusion can be identified from baseline magnetic resonance imaging findings. The current analysis demonstrates that a PWI threshold (Tmax>8 s) of approximately 100 mL is appropriate for identifying these patients. Exclusion of malignant profile patients from reperfusion therapies may substantially improve the efficacy and safety of reperfusion therapies. Clinical Trial Registration Information- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00238537.

The robotic surgical system has been applied in liver surgery. However, controversies concerns exist regarding a variety of factors including the safety, feasibility, efficacy, and cost-effectiveness of robotic surgery. To promote the development of robotic hepatectomy, this study aimed to evaluate the current status of robotic hepatectomy and provide sixty experts' consensus and recommendations to promote its development. Based on the World Health Organization Handbook for Guideline Development, a Consensus Steering Group and a Consensus Development Group were established to determine the topics, prepare evidence-based documents, and generate recommendations. The GRADE Grid method and Delphi vote were used to formulate the recommendations. A total of 22 topics were prepared analyzed and widely discussed during the 4 meetings. Based on the published articles and expert panel opinion, 7 recommendations were generated by the GRADE method using an evidence-based method, which focused on the safety, feasibility, indication, techniques and cost-effectiveness of hepatectomy. Given that the current evidences were low to very low as evaluated by the GRADE method, further randomized-controlled trials are needed in the future to validate these recommendations.

Various types of tumors can affect the subungual space, including benign solid tumors (glomus tumor, subungual exostosis, soft-tissue chondroma, keratoacanthoma, hemangioma, lobular capillary hemangioma), benign cystic lesions (epidermal and mucoid cysts), and malignant tumors (squamous cell carcinoma, malignant melanoma). Imaging plays an important role in the detection and differentiation of subungual tumors because of their small size, nonspecific clinical manifestations, and functional significance. Ultrasonography (US)-in particular, high-resolution US with color Doppler studies-provides useful information regarding tumor size, location, shape, and internal characteristics (cystic, solid, or mixed), but it is limited in the further characterization of tissue. Magnetic resonance (MR) imaging has an important role in categorizing tumors according to their anatomic location, pathologic origin, and signal characteristics. There is some overlap between the US and MR imaging features of subungual tumors; however, certain features can allow accurate diagnosis and expedite management when correlated with clinical and pathologic findings.

Systemic inflammation, as evidenced by elevated inflammatory cytokines, is a feature of advanced renal failure and predicts worse survival. Dialysate IL-6 concentrations associate with variability in peritoneal small solute transport rate (PSTR), which has also been linked to patient survival. Here, we determined the link between systemic and intraperitoneal inflammation with regards to peritoneal membrane function and patient survival as part of the Global Fluid Study, a multinational, multicenter, prospective, combined incident and prevalent cohort study (n=959 patients) with up to 8 years of follow-up. Data collected included patient demographic characteristics, comorbidity, modality, dialysis prescription, and peritoneal membrane function. Dialysate and plasma cytokines were measured by electrochemiluminescence. A total of 426 survival endpoints occurred in 559 incident and 358 prevalent patients from 10 centers in Korea, Canada, and the United Kingdom. On patient entry to the study, systemic and intraperitoneal cytokine networks were dissociated, with evidence of local cytokine production within the peritoneum. After adjustment for multiple covariates, systemic inflammation was associated with age and comorbidity and independently predicted patient survival in both incident and prevalent cohorts. In contrast, intraperitoneal inflammation was the most important determinant of PSTR but did not affect survival. In prevalent patients, the relationship between local inflammation and membrane function persisted but did not account for an increased mortality associated with faster PSTR. These data suggest that systemic and local intraperitoneal inflammation reflect distinct processes and consequences in patients treated with peritoneal dialysis, so their prevention may require different therapeutic approaches; the significance of intraperitoneal inflammation requires further elucidation.

BACKGROUND AND PURPOSE: In order to improve inter-rater reliability and minimize diagnosis of undetermined etiology for stroke subtype classification, using a stroke registry, we developed and implemented a magnetic resonance imaging (MRI)-based algorithm for acute ischemic stroke subtype classification (MAGIC). METHODS: We enrolled patients who experienced an acute ischemic stroke, were hospitalized in the 14 participating centers within 7 days of onset, and had relevant lesions on MR-diffusion weighted imaging (DWI). MAGIC was designed to reflect recent advances in stroke imaging and thrombolytic therapy. The inter-rater reliability was compared with and without MAGIC to classify the Trial of Org 10172 in Acute Stroke Treatment (TOAST) of each stroke patient. MAGIC was then applied to all stroke patients hospitalized since July 2011, and information about stroke subtypes, other clinical characteristics, and stroke recurrence was collected via a web-based registry database. RESULTS: The overall intra-class correlation coefficient (ICC) value was 0.43 (95% CI, 0.31-0.57) for MAGIC and 0.28 (95% CI, 0.18-0.42) for TOAST. Large artery atherosclerosis (LAA) was the most common cause of acute ischemic stroke (38.3%), followed by cardioembolism (CE, 22.8%), undetermined cause (UD, 22.2%), and small-vessel occlusion (SVO, 14.6%). One-year stroke recurrence rates were the highest for two or more UDs (11.80%), followed by LAA (7.30%), CE (5.60%), and SVO (2.50%). CONCLUSIONS: Despite several limitations, this study shows that the MAGIC system is feasible and may be helpful to classify stroke subtype in the clinic.

PURPOSE: Cisplatin plus 5-fluorouracil has been globally accepted as a standard regimen for the treatment for advanced gastric cancer. However, cisplatin has several disadvantages, including renal toxicity and the need for admission. S-1 plus cisplatin has become a standard treatment for advanced gastric cancer in East Asia. This phase III study was designed to evaluate the potential benefits of adding docetaxel to S-1 without a platinum compound in patients with advanced gastric cancer. METHODS: Patients were randomly assigned to receive docetaxel plus S-1 or S-1 alone. The docetaxel plus S-1 group received docetaxel on day 1 and oral S-1 on days 1-14 of a 21-day cycle. The S-1 alone group received oral S-1 on days 1-28 of a 42-day cycle. The primary end point was overall survival. RESULTS: Of the 639 patients enrolled, 635 were eligible for analysis. The median overall survival was 12.5 months in the docetaxel plus S-1 group and 10.8 months in the S-1 alone group (p = 0.032). The median progression-free survival was 5.3 months in the docetaxel plus S-1 group and 4.2 months in the S-1 alone group (p = 0.001). As for adverse events, neutropenia was more frequent in the docetaxel plus S-1 group, but remained manageable. CONCLUSION: As first-line treatment for advanced gastric cancer, docetaxel plus S-1 significantly improves median overall and progression-free survival as compared with S-1 alone. (ClinicalTrials.gov number: NCT00287768).

Age-related macular degeneration (AMD) is a major cause of blindness, but presents differently in Europeans and Asians. Here, we perform a genome-wide and exome-wide association study on 2,119 patients with exudative AMD and 5,691 controls, with independent replication in 4,226 patients and 10,289 controls, all of East Asian descent, as part of The Genetics of AMD in Asians (GAMA) Consortium. We find a strong association between CETP Asp442Gly (rs2303790), an East Asian-specific mutation, and increased risk of AMD (odds ratio (OR)=1.70, P=5.60 × 10(-22)). The AMD risk allele (442Gly), known to protect from coronary heart disease, increases HDL cholesterol levels by 0.17 mmol l(-1) (P=5.82 × 10(-21)) in East Asians (n=7,102). We also identify three novel AMD loci: C6orf223 Ala231Ala (OR=0.78, P=6.19 × 10(-18)), SLC44A4 Asp47Val (OR=1.27, P=1.08 × 10(-11)) and FGD6 Gln257Arg (OR=0.87, P=2.85 × 10(-8)). Our findings suggest that some of the genetic loci conferring AMD susceptibility in East Asians are shared with Europeans, yet AMD in East Asians may also have a distinct genetic signature.

Abstract A previous phase II clinical trial of adipose-derived stem cell (ASC) therapy for fistulae associated with Crohn's disease, a devastating condition with a high recurrence rate, demonstrated safety and therapeutic potential with a 1-year sustained response. In the present study, 41 of the 43 phase II trial patients were followed for an additional year, regardless of response in the initial year. At 24 months, complete healing was observed in 21 of 26 patients (80.8%) in modified per protocol analysis and 27 of 36 patients (75.0%) in modified intention-to-treat analysis. No adverse events related to ASC administration were observed. Furthermore, complete closure after initial treatment was well-sustained. These results strongly suggest that autologous ASCs may be a novel treatment option for Crohn's fistulae. Significance Long-term follow-up of patients with Crohn's fistula found that one or two doses of autologous adipose-derived stem cell therapy achieved complete closure in 80% of the patients at 12 months. After 24 months, 75% of those patients sustained complete closure, showing sustainable safety and efficacy of the treatment.

BACKGROUND: Since type A botulinum toxin was first reported for the treatment of masseter muscle hypertrophy in 1994, there have been few reports about cosmetic indications for contouring procedures of the lower face with injection of botulinum toxin type A, and this procedure remains unpredictable. OBJECTIVES: This study attempted a quantitative prospective analysis of reduction of masseter muscle hypertrophy after Botox injection, using ultrasound and computerized tomography (CT) scans to analyze the possible use of botulinum toxin type A as a contouring procedure for the lower face. METHODS: Forty-five patients consented to the study and received a contouring procedure of the lower face from November 2001 to April 2002. Twenty five to 30 U of Botox per side was injected at five to six points into the prominent portions of the mandibular angle. Serial measurements were made of the thickness of the masseter muscle by ultrasound and CT before the injections and at 1 and 3 months thereafter. A quantitative analysis for the masseter thickness changes was performed on just one patient who underwent all ultrasound and CT scans. Statistical analysis of the masseter thickness change was by two-way and multiple comparison analysis. To evaluate clinical long-term effects, the patient's satisfaction with the procedure and any side effects after injections were monitored during 4 to 10 months of follow-up. RESULTS: Among the total of 45 patients, 15 underwent the three ultrasound measurements, and 14 had the three CT measurements. With regard to quantitative analysis of the thickness change to the masseter on both sides of the face according to time points, this was gradually reduced by both the ultrasound and CT measurements during the first 3 months. By ultrasound, the maximum reduction in masseter thickness was seen 1 month after the injections, with a slight increase being observed at 3 months after injection. A continued reduction of masseteric muscle thickness was seen on the CT up to 3 months after injection. In terms of patient satisfaction for up to 10 months of follow-up, the results were as follows: very satisfied, 1; satisfied, 36; slight improvement, 3; no change or dissatisfied, 5. Main local side effects included masticatory difficulties, muscle aching at injection sites, and speech disturbance. However, these side effects were transitory, usually lasting from 1 to 4 weeks after the injections. CONCLUSIONS: Preliminary results from this study suggest that an injection of Botox resulted in relatively satisfactory clinical effects, although there was only a short-term follow-up. It is suggested that the use of botulinum toxin type A for contouring of the lower face can be established as a simple, predictable, alternative facial contouring procedure without a prolonged recovery time.

BACKGROUND AND PURPOSE: Rathke's cleft cysts often may be difficult to differentiate from other intrasellar or suprasellar masses on radiologic studies. The purpose of this study was to describe the significance of intracystic nodules, a diagnostic characteristic found in Rathke's cleft cysts, on MR images. METHODS: A retrospective review of MR studies was conducted for 13 patients who, after pathologic analysis, were diagnosed as having Rathke's cleft cyst. These patients underwent unenhanced and contrast-enhanced T1- and T2-weighted axial and coronal spin-echo sequential imaging. The signal intensity and incidence of the intracystic nodules on T1- and T2-weighted images were analyzed. The signal intensity of the nodule was compared with that of white matter and surrounding cyst fluid. The signal intensity of cyst fluid was compared with the intraoperative appearance of the cyst fluid. Biochemical and pathologic analyses of the intracystic nodules were conducted in two cases. RESULTS: An intracystic nodule having high signal intensity on T1-weighted images and low signal intensity on T2-weighted images was observed in 10 (77%) of the cases. At surgery, intracystic nodules were yellow, waxy, solid masses. Pathologic analysis showed this nodule to be a mucin clump. Biochemical analysis of the intracystic nodules showed cholesterol and proteins as the main constituents. In the Rathke's cleft cyst with intracystic nodules, cyst fluid revealed low signal intensity to isointensity relative to the intensity of the nodules on T1-weighted images, and isointensity to high signal intensity on T2-weighted images. Intracystic nodules were clearly visible on T2-weighted images. CONCLUSION: Because cyst fluid of Rathke's cleft cysts shows variable intensities on MR images, the specific diagnosis is often difficult when based on MR signal intensity values alone. The presence of an intracystic nodule with characteristic signal intensities on MR images may be indicative of the diagnosis of Rathke's cleft cyst.