Background: Bladder cancer is characterized by frequent mutations, which provide potential therapeutic targets for most patients. The effectiveness of emerging personalized therapies depends on an accurate molecular diagnosis, for which the accurate estimation of the neoplastic cell percentage (NCP) is a crucial initial step. However, the established method for determining the NCP, manual counting by a pathologist, is time-consuming and not easily executable. Methods: To address this, artificial intelligence (AI) models were developed to estimate the NCP using nine convolutional neural networks and the scanned images of 39 cases of urinary tract cancer. The performance of the AI models was compared to that of six pathologists for 119 cases in the validation cohort. The ground truth value was obtained through multiplexed immunofluorescence. The AI model was then applied to 41 cases in the application cohort that underwent next-generation sequencing testing, and its impact on the copy number variation (CNV) was analyzed. Results: Each AI model demonstrated high reliability, with intraclass correlation coefficients (ICCs) ranging from 0.82 to 0.88. These values were comparable or better to those of pathologists, whose ICCs ranged from 0.78 to 0.91 in urothelial carcinoma cases, both with and without divergent differentiation/ subtypes. After applying AI-driven NCP, 190 CNV (24.2%) were reclassified with 66 (8.4%) and 78 (9.9%) moved to amplification and loss, respectively, from neutral/minor CNV. The neutral/minor CNV proportion decreased by 6%. Conclusions These results suggest that AI models could assist human pathologists in repetitive and cumbersome NCP calculations.

Background: Copeptin is secreted in equimolar amounts as arginine vasopressin, main hormone regulating body fluid homeostasis. A recent study reported a copeptin-based classification of osmoregulatory defects in syndromes of inappropriate antidiuresis that may aid in prediction of therapeutic success. We investigated usefulness of copeptin for differentiating etiologies of hyponatremia and predicting efficacy and safety of hypertonic saline treatment in hyponatremic patients. Methods: We performed a multicenter, prospective cohort study of 100 inpatients with symptomatic hyponatremia (corrected serum sodium [sNa] ≤ 125 mmol/L) treated with hypertonic saline. Copeptin levels were measured at baseline and 24 hours after treatment initiation, and patients were classified as being below or above median of copeptin at baseline or at 24 hours, respectively. Correlations between target, under correction, and overcorrection rates of sNa within 24 hours/24–48 hours and copeptin levels at baseline/24 hours were analyzed. Results: Mean sNa and median copeptin levels were 117.9 and 16.9 pmol/L, respectively. Ratio of copeptin-to-urine sodium allowed for an improved differentiation among some (insufficient effective circulatory volume), but not all hyponatremia etiologic subgroups. Patients with below-median copeptin levels at baseline achieved a higher target correction rate in 6/24 hours (odds ratio [OR], 2.97; p = 0.02/OR, 6.21; p = 0.006). Patients with below-median copeptin levels 24 hours after treatment showed a higher overcorrection rate in next 24 hours (OR, 18.00, p = 0.02). Conclusion There is a limited diagnostic utility of copeptin for differential diagnosis of hyponatremia. However, copeptin might be useful for predicting responses to hypertonic saline treatment in hyponatremic patients.

Purpose: We evaluated the association of body composition with long-term oncologic outcomes innon-metastatic rectal cancer patients. Materials and Methods: We included 1,384 patients with stage(y)0-III rectal cancer treated at Asan Medical Centerbetween January 2005 and December 2012. Body composition at diagnosis was measuredusing abdomino-pelvic computed tomography (CT). Sarcopenia, visceral obesity (VO), andsarcopenic obesity (SO) were defined using CT measured parameters such as skeletal muscleindex (total abdominal muscle area, TAMA), visceral fat area (VFA), and VFA/TAMA. Inflammatorystatus was defined as a neutrophil-lymphocyte ratio of ! 3. Obesity was categorizedby body mass index (! 25 kg/m2). Results: Among the 1,384 patients, 944 (68.2%) had sarcopenia and 307 (22.2%) had SO. The5-year overall survival (OS) rate was significantly lower in sarcopenic patients (no sarcopeniavs. sarcopenia; 84% vs. 78%, p=0.003) but the 5-year recurrence-free survival (RFS) ratewas not different (77.3% vs. 77.9% p=0.957). Patients with SO showed lower 5-year OS(79.1% vs. 75.5% p=0.02) but no difference in 5-year RFS (p=0.957). Sarcopenia, SO, VO,and obesity were not associated with RFS. However, obesity, SO, age, sex, inflammatorystatus, and tumor stage were confirmed as independent factors associated with OS on multivariateanalysis. In subgroup analysis, association of SO with OS was more prominent inpatients with (y)p stage 0-2 and no inflammatory status. Conclusion The presence of SO and a low body mass index at diagnosis are negatively associated withOS in non-metastatic rectal cancer patients.

PURPOSE: This study aimed to assess the three-dimensional (3D) facial changes after orthognathic surgery by evaluating the spherical coordinates of facial lines using 3D computed tomography (CT). MATERIALS AND METHODS: A 19-year-old girl was diagnosed with class III malocclusion and facial asymmetry. Orthognathic surgery was performed after orthodontic treatment. Facial CT scans were taken before and after orthognathic surgery. The patient had a menton deviation of 12.72 mm before surgery and 0.83 mm after surgery. The spherical coordinates of four bilateral facial lines (ramal height, ramal lateral, ramal posterior and mandibular body) were estimated from CT scans before and after surgery on the deviated and opposite side. RESULTS: The spherical coordinates of all facial lines changed after orthognathic surgery. Moreover, the bilateral differences of all facial lines changed after surgery, and no bilateral differences were zero. CONCLUSION: The spherical coordinate system was useful to compare differences between the presurgical and postsurgical changes to facial lines.
Facial Asymmetry ; Female ; Humans ; Malocclusion ; Orthognathic Surgery* ; Tomography, X-Ray Computed ; Young Adult

Wegener's granulomatosis (WG) classically consists of necrotizing granulomatous inflammation of the upper and/or lower respiratory tract, necrotizing glomerulonephritis, and an autoimmune necrotizing systemic vasculitis affecting predominantly small vessels. We report a case of WG with central nervous system (CNS) involvement. WG is being diagnosed through pulmonary nodule biopsy. A small nodular lesion in the left posterior basal ganglia of brain being highly suspicious for granulomatosis was detected by MRI. After IV pulse cyclophosphamide and oral corticosteroid treatment for over 4 months, clinical manifestations and CNS lesions in brain MRI is improved. WG might have multiple granulomatous lesions which could be misdiagnosed due to malignancy. CNS involvement in WG is rare but careful evaluation is necessary when there are suspicious symptoms or lesions in CNS.
Basal Ganglia ; Biopsy ; Brain ; Central Nervous System ; Cyclophosphamide ; Glomerulonephritis ; Inflammation ; Lung ; Lung Neoplasms ; Neoplasm Metastasis ; Respiratory System ; Systemic Vasculitis ; Wegener Granulomatosis

The silkworm extract powder contain 1-deoxynojirimycin (DNJ), a potent alpha-glycosidase inhibitor, has therapeutic potency against diabetes mellitus. Therefore, natural products containing DNJ from mulberry leaves and silkworm are consumed as health functional food. The present study was performed to evaluate the safety of the silkworm extract powder, a health food which containing the DNJ. The repeated toxicity studies and gentic toxicity studies of the silkworm extract powder were performed to obtain the data for new functional food approval in MFDS. The safety was evaluated by a single-dose oral toxicity study and a 90 day repeated-dose oral toxicity study in Sprague-Dawley rats. The silkworm extract powder was also evaluated for its mutagenic potential in a battery of genetic toxicity test: in vitro bacterial reverse mutation assay, in vitro chromosomal aberration test, and in vivo mouse bone marrow micronucleus assay. The results of the genetic toxicology assays were negative in all of the assays. The approximate lethal dose in single oral dose toxicity study was considered to be higher than 5000 mg/kg in rats. In the 90 day study, the dose levels were wet at 0, 500, 1000, 2000 mg/kg/day, and 10 animals/sex/dose were treated with oral gavage. The parameters that were monitored were clinical signs, body weights, food and water consumptions, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy findings, organ weights, and histopathological examination. No adverse effects were observed after the 90 day administration of the silkworm extract powder. The No-Observed-Adverse-Effect-Level (NOAEL) of silkworm extract powder in the 90 day study was 2000 mg/kg/day in both sexes, and no target organ was identified.
1-Deoxynojirimycin ; Animals ; Biochemistry ; Biological Agents ; Body Weight ; Bombyx* ; Bone Marrow ; Chromosome Aberrations ; Diabetes Mellitus ; Functional Food ; Food, Organic ; Hematology ; Mice ; Micronucleus Tests ; Morus ; Mutagenicity Tests ; Organ Size ; Rats ; Rats, Sprague-Dawley ; Toxicology ; Urinalysis ; Drinking

Terlipressin is a vasopressin analogue that is widely used in the treatment of hepatorenal syndrome or variceal bleeding. Because it acts mainly on splanchnic vessels, terlipressin has a lower incidence of severe ischemic complications than does vasopressin. However, it can still lead to serious complications such as myocardial infarction, skin necrosis, or bowel ischemia. Herein we report a case of severe ischemic bowel necrosis in a 46-year-old cirrhotic patient treated with terlipressin. Although the patient received bowel resection, death occurred due to ongoing hypotension and metabolic acidosis. Attention should be paid to patients complaining of abdominal pain during treatment with terlipressin.
Bilirubin/blood ; Creatinine/blood ; Electrocardiography ; Fatal Outcome ; Hepatorenal Syndrome/*drug therapy ; Humans ; Intestinal Mucosa/pathology ; Intestines/surgery ; Liver Cirrhosis/diagnosis/therapy ; Lypressin/adverse effects/*analogs & derivatives/therapeutic use ; Male ; Middle Aged ; Necrosis/*chemically induced/surgery ; Tomography, X-Ray Computed ; Vasoconstrictor Agents/*adverse effects/*therapeutic use

PURPOSE: Patients with work related burns suffer from anxiety, depression, insomnia and suicide ideation etc. Psychiatric symptoms could be reduced by treatment. Almost all patients are referred to psychiatric intervention in our hospital. However, a number of patients show non-adherence. The aim of this study is to figure out the reason of non-adherence and psychiatric symptoms of work related burns patients. METHODS: 123 patients participated in this study. Startle, Physiological arousal, Anger, and Numbness (SPAN), Feeling Suicide, Patient Health Questionnaire-2 (PHQ-2) were administered as screening tool. Questions about psychiatric intervention and reasons to refuse psychiatric intervention were asked. RESULTS: 32% patients were depressed, 34% patients had suicide ideation and 59% had PTSD after work related burns. However, 46% of burn patients had not been treated. Stigma of psychiatric intervention and concerns about dependency were major reasons for non-adherence. CONCLUSION: There are gap between necessity and reality of psychiatric intervention on work related burn patients.
Anger ; Anxiety ; Arousal ; Burns ; Dependency (Psychology) ; Depression ; Humans ; Hypesthesia ; Mass Screening ; Occupational Injuries ; Referral and Consultation ; Sleep Initiation and Maintenance Disorders ; Stress Disorders, Post-Traumatic ; Suicide

OBJECTIVES: This study sought to evaluate the efficacy of collagen graft materials, as compared to other graft materials, for use in healing calvarial defects in rabbits. MATERIALS AND METHODS: Ten mm diameter calvarial defects were made in ten rabbits. The rabbits were then divided into 4 groups: control, autogenous bone graft, SureOss graft, and Teruplug graft. Bone regeneration was evaluated using histological and radiographic methods. RESULTS: Based on visual examination, no distinct healing profile was observed. At 4 weeks after treatment, histological analysis showed there was no bone regeneration in the control group; however, at 8 weeks after treatment, new bone formation was observed around the margin of the defective sites. In the autogenous bone graft group, new bone formation was observed at 4 weeks after treatment and mature bone was detected around the grafted bone after 8 weeks. In the SureOss graft group, at 4 weeks after treatment, acute inflammatory and multinuclear cells were noted around the grafted materials; at 8 weeks after treatment, a decrease in graft materials coupled with new bone formation were observed at the defective sites. In the Teruplug graft group, new bone formation was detected surrounding the bone margin and without signs of inflammation. There were statistically significant differences observed between the graft and control group in terms of bone density as evidenced by radiographic analysis using computed tomography (P<0.05), particularly for the autogenous bone graft group (P<0.001). CONCLUSION: These results suggested that autogenous bone, SureOss and Teruplug have the ability to induce bone regeneration as compared to an untreated control group. The osteogenic potential of Teruplug was observed to be lower than that of autogenous bone, but similar to that of SureOss.
Bone Density ; Bone Regeneration ; Collagen ; Durapatite ; Inflammation ; Osteogenesis ; Porifera ; Rabbits ; Transplantation, Homologous ; Transplants

OBJECTIVES: Autobiographical memory (ABM) is a special type of episodic memory, containing events that have occurred in a personal life. Overgeneral tendency of ABM refers to the retrieval of memory with only general and categorical descriptions rather than specific events. ABM specificity in depression and posttraumatic stress disorder is a robust finding with relation to cognitive vulnerability, affect regulation, problem-solving ability. It is also implicated in bipolar disorder with frequent relapses. In this study, we investigated whether ABM specificity was related to manic or euthymic mood states in patients with bipolar disorder. METHODS: Forty bipolar patients with manic and euthymic episodes and 25 healthy controls participated in this study. Prompted by 5 positively and 5 negatively valenced emotional cue words, each participant was instructed to recall positive or negative memories and describe them in detail. The one-way ANOVA was used to compare ABM scores and post-hoc analyses were done. RESULTS: Comapred to the healthy persons, the bipolar patients reported significantly more general than specific negative memories in both manic and euthymic episodes (p = 0.003). However, there was no significant difference between manic and euthymic patients (p = 0.074). CONCLUSIONS: These results suggest that overgeneral tendency of negative ABM may be a trait abnormality in bipolar disorder. Moreover, this phenomenon might be related to underlying cognitive deficits or affect regulation irrespective of the mood state.
Bipolar Disorder ; Cues ; Depression ; Humans ; Memory ; Memory, Episodic ; Recurrence ; Sensitivity and Specificity ; Stress Disorders, Post-Traumatic