Background and Objectives: We compared the efficacy and safety of human bone marrow-derived mesenchymal stem cells (hBMSC), delivered at different doses and via different injection routes in an animal model of chronic kidney disease. Methods: and Results: A total of ninety 12-week-old rats underwent 5/6 nephrectomy and randomized among nine groups: sham, renal artery control (RA-C), tail vein control (TV-C), renal artery low dose (RA-LD) (0.5×10 6 cells), renal artery moderate dose (RA-MD) (1.0×10 6 cells), renal artery high dose (RA-HD) (2.0×10 6 cells), tail vein low dose (TV-LD) (0.5×10 6 cells), tail vein moderate dose (TV-MD) (1.0×10 6 cells), and tail vein high dose (TV-HD) (2.0×10 6 cells). Renal function and mortality of rats were evaluated after hBMSC injection. Serum blood urea nitrogen was significantly lower in the TV-HD group at 2 weeks (p＜0.01), 16 weeks (p＜0.05), and 24 weeks (p＜0.01) than in the TV-C group, as determined by one-way ANOVA. Serum creatinine was significantly lower in the TV-HD group at 24 weeks (p＜0.05). At 8 weeks, creatinine clearance was significantly higher in the TV-MD and TV-HD groups (p＜0.01, p＜0.05) than in the TV-C group. In the safety evaluation, we observed no significant difference among the groups. Conclusions Our findings confirm the efficacy and safety of high dose (2×10 6 cells) injection of hBMSC via the tail vein.

Background and Objectives: We evaluated the effect of adipose-derived stem cell-derived conditioned medium (ADSC-CM) on the renal function of rats with renal ischemia-reperfusion injury (IRI)-induced acute kidney injury. Methods: and Results: Forty male Sprague‐Dawley rats were randomly divided into four groups: sham, nephrectomy control, IRI control, ADSC-CM. The ADSC-CM was prepared using the three-dimensional spheroid culture system and injected into renal parenchyme. The renal function of the rats was evaluated 28 days before and 1, 2, 3, 4, 7, and 14 days after surgical procedures. The rats were sacrificed 14 days after surgical procedures, and kidney tissues were collected for histological examination. The renal parenchymal injection of ADSC-CM significantly reduced the serum blood urea nitrogen and creatinine levels compared with the IRI control group on days 1, 2, 3, and 4 after IRI. The renal parenchymal injection of ADSC-CM significantly increased the level of creatinine clearance compared with the IRI control group 1 day after IRI. Collagen content was significantly lower in the ADSC-CM group than in the IRI control group in the cortex and medulla. Apoptosis was significantly decreased, and proliferation was significantly increased in the ADSC-CM group compared to the IRI control group in the cortex and medulla. The expressions of anti-oxidative makers were higher in the ADSC-CM group than in the IRI control group in the cortex and medulla. Conclusions The renal function was effectively rescued through the renal parenchymal injection of ADSC-CM prepared using a three-dimensional spheroid culture system.

Purpose: Several predictive models have been developed to predict the pathological complete response (pCR) after neoadjuvant chemotherapy (NAC); however, few are broadly applicable owing to radiologic complexity and institution-specific clinical variables, and none have been externally validated. This study aimed to develop and externally validate a machine learning model that predicts pCR after NAC in patients with breast cancer using routinely collected clinical and demographic variables. Methods: The electronic medical records of patients with advanced breast cancer who underwent NAC before surgical resection between January 2017 and December 2020 were reviewed. Patient data from Seoul National University Bundang Hospital were divided into training and internal validation cohorts. Five machine learning techniques, including gradient boosting machine (GBM), support vector machine, random forest, decision tree, and neural network, were used to build predictive models, and the area under the receiver operating characteristic curve (AUC) was compared to select the best model. Finally, the model was validated using an independent cohort from Seoul National University Hospital. Results: A total of 1,003 patients were included in the study: 287, 71, and 645 in the training, internal validation, and external validation cohorts, respectively. Overall, 36.3% of the patients achieved pCR. Among the five machine learning models, the GBM showed the highest AUC for pCR prediction (AUC, 0.903; 95% confidence interval [CI], 0.833–0.972).External validation confirmed an AUC of 0.833 (95% CI, 0.800–0.865). Conclusion Commonly available clinical and demographic variables were used to develop a machine learning model for predicting pCR following NAC. External validation of the model demonstrated good discrimination power, indicating that routinely collected variables were sufficient to build a good prediction model.

Background: As the treatment effects for childhood and adolescent cancer continue to improve, the survivor group is gradually growing and their age is increasing. This study aimed to determine the perceptions toward childhood and adolescent cancer survivors and assess the current situation regarding their return to school, to undertake policy development to help them grow into healthy members of society. Methods: From December 2019, for about 4 months, a structured questionnaire was used to conduct one-on-one interviews with childhood and adolescent cancer survivors and their parents, as well as with parents of healthy children and adolescents. Results: The participants included 79 survivors of childhood and adolescent cancer, 186 parents of cancer survivors, and 661 general parents; their mean age was 21.8, 13.9, and 12.5 years, respectively. After completing their cancer treatment, 77.2% of the cancer survivors returned to school, with the majority returning to regular schools in the same grade as their peers. Reasons for not returning to school (20.3%) included concerns about health management (43.8%), concerns about psychological and emotional adjustment (12.5%), and poor school attendance (12.5%). Among the parents of cancer survivors, 48.9% stated that they were “satisfied” with their children’s school life; a better health status in children was associated with a higher level of satisfaction (P=0.0071). In addition, they stated that national-level support was needed in the following areas for a successful return to school: a continuous health management system (36.1%) and understanding homeroom teachers who enable flexible participation in classes and school events (29.5%). Conclusion For survivors of childhood and adolescent cancer to successfully return to school and society, nationwide awareness-raising activities should be expanded, in addition to services that are tailored to the survivors’ needs and characteristics such as management of physical and mental health and educating homeroom teachers and peers.

Purpose: Estrogen receptor (ER) expression in breast cancer plays an essential role in carcinogenesis and disease progression. Recently, tumors with low level (1%-10%) of ER expression have been separately defined as ER low positive (ERlow). It is suggested that ERlow tumors might be morphologically and behaviorally different from tumors with high ER expression (ERhigh). Materials and Methods: Retrospective analysis of a prospective cohort database was performed. Patients who underwent curative surgery for early breast cancer and had available medical records were included for analysis. Difference in clinicopathological characteristics, endocrine responsiveness and five-year recurrence-free survival was evaluated between different ER subgroups (ERhigh, ERlow, and ER-negative [ER–]). Results: A total of 2,162 breast cancer patients were included in the analysis, Tis and T1 stage. Among them, 1,654 (76.5%) were ERhigh, 54 (2.5%) were ERlow, and 454 (21.0%) were ER- patients. ERlow cases were associated with smaller size, higher histologic grade, positive human epidermal growth factor receptor 2, negative progesterone receptor, and higher Ki-67 expression. Recurrence rate was highest in ER– tumors and was inversely proportional to ER expression. Recurrence-free survival was not affected by hormonal therapy in the ERlow group (p=0.418). Conclusion ERlow breast cancer showed distinct clinicopathological features. ERlow tumors seemed to have higher recurrence rates compared to ERhigh tumors, and they showed no significant benefit from hormonal therapy. Future large scale prospective studies are necessary to validate the treatment options for ERlow breast cancer.

Background: We aimed to evaluate the clinicopathological features and biological behaviors of Korean thyroid cancer patients with rare variants of papillary thyroid carcinoma (PTC) to address the ambiguity regarding the prognostic consequences of these variants. Methods: We retrospectively reviewed the medical records of 5,496 patients who underwent thyroid surgery for PTC, between January and December 2012, in nine tertiary hospitals. Rare PTC variants included tall cell (TCV), columnar cell (CCV), diffuse sclerosing (DSV), cribriform-morular (CMV), solid (SV), hobnail, and Warthin-like variants. Recurrence-free survival (RFS) was defined as the time from the date of thyroidectomy until recurrence. Results: Rare variants accounted for 1.1% (n=63) of the PTC patients; with 0.9% TCV, 0.02% CCV, 0.1% DSV, 0.1% CMV, and 0.1% SV. The mean age of patients and primary tumor size were 42.1±13.1 years and 1.3±0.9 cm, respectively. Extrathyroidal extension and cervical lymph node metastasis were observed in 38 (60.3%) and 37 (58.7%) patients, respectively. Ultrasonographic findings revealed typical malignant features in most cases. During a median follow-up of 7 years, 6.3% of patients experienced a locoregional recurrence. The 5-year RFS rates were 71.4% in patients with DSV or SV, 95.9% for TCV, or CCV, and 100% for other variants. DSV emerged an independent risk factor associated with shorter RFS. Conclusion In this multicenter Korean cohort, rare variants accounted for 1.1% of all PTC cases, with TCV being the most frequent subtype. DSV emerged as a significant prognostic factor for RFS.

Background: Postoperative thyroid stimulating hormone (TSH) suppression therapy is recommended for patients with intermediate- and high-risk differentiated thyroid cancer to prevent the recurrence of thyroid cancer. With the recent increase in small thyroid cancer cases, the extent of resection during surgery has generally decreased. Therefore, questions have been raised about the efficacy and long-term side effects of TSH suppression therapy in patients who have undergone a lobectomy. Methods: This is a multicenter, prospective, randomized, controlled clinical trial in which 2,986 patients with papillary thyroid cancer are randomized into a high-TSH group (intervention) and a low-TSH group (control) after having undergone a lobectomy. The principle of treatment includes a TSH-lowering regimen aimed at TSH levels between 0.3 and 1.99 μIU/mL in the low-TSH group. The high-TSH group targets TSH levels between 2.0 and 7.99 μIU/mL. The dose of levothyroxine will be adjusted at each visit to maintain the target TSH level. The primary outcome is recurrence-free survival, as assessed by neck ultrasound every 6 to 12 months. Secondary endpoints include disease-free survival, overall survival, success rate in reaching the TSH target range, the proportion of patients with major cardiovascular diseases or bone metabolic disease, the quality of life, and medical costs. The follow-up period is 5 years. Conclusion The results of this trial will contribute to establishing the optimal indication for TSH suppression therapy in low-risk papillary thyroid cancer patients by evaluating the benefit and harm of lowering TSH levels in terms of recurrence, metabolic complications, costs, and quality of life.

Background: We aimed to evaluate the clinicopathological features and biological behaviors of Korean thyroid cancer patients with rare variants of papillary thyroid carcinoma (PTC) to address the ambiguity regarding the prognostic consequences of these variants. Methods: We retrospectively reviewed the medical records of 5,496 patients who underwent thyroid surgery for PTC, between January and December 2012, in nine tertiary hospitals. Rare PTC variants included tall cell (TCV), columnar cell (CCV), diffuse sclerosing (DSV), cribriform-morular (CMV), solid (SV), hobnail, and Warthin-like variants. Recurrence-free survival (RFS) was defined as the time from the date of thyroidectomy until recurrence. Results: Rare variants accounted for 1.1% (n=63) of the PTC patients; with 0.9% TCV, 0.02% CCV, 0.1% DSV, 0.1% CMV, and 0.1% SV. The mean age of patients and primary tumor size were 42.1±13.1 years and 1.3±0.9 cm, respectively. Extrathyroidal extension and cervical lymph node metastasis were observed in 38 (60.3%) and 37 (58.7%) patients, respectively. Ultrasonographic findings revealed typical malignant features in most cases. During a median follow-up of 7 years, 6.3% of patients experienced a locoregional recurrence. The 5-year RFS rates were 71.4% in patients with DSV or SV, 95.9% for TCV, or CCV, and 100% for other variants. DSV emerged an independent risk factor associated with shorter RFS. Conclusion In this multicenter Korean cohort, rare variants accounted for 1.1% of all PTC cases, with TCV being the most frequent subtype. DSV emerged as a significant prognostic factor for RFS.

Background: Postoperative thyroid stimulating hormone (TSH) suppression therapy is recommended for patients with intermediate- and high-risk differentiated thyroid cancer to prevent the recurrence of thyroid cancer. With the recent increase in small thyroid cancer cases, the extent of resection during surgery has generally decreased. Therefore, questions have been raised about the efficacy and long-term side effects of TSH suppression therapy in patients who have undergone a lobectomy. Methods: This is a multicenter, prospective, randomized, controlled clinical trial in which 2,986 patients with papillary thyroid cancer are randomized into a high-TSH group (intervention) and a low-TSH group (control) after having undergone a lobectomy. The principle of treatment includes a TSH-lowering regimen aimed at TSH levels between 0.3 and 1.99 μIU/mL in the low-TSH group. The high-TSH group targets TSH levels between 2.0 and 7.99 μIU/mL. The dose of levothyroxine will be adjusted at each visit to maintain the target TSH level. The primary outcome is recurrence-free survival, as assessed by neck ultrasound every 6 to 12 months. Secondary endpoints include disease-free survival, overall survival, success rate in reaching the TSH target range, the proportion of patients with major cardiovascular diseases or bone metabolic disease, the quality of life, and medical costs. The follow-up period is 5 years. Conclusion The results of this trial will contribute to establishing the optimal indication for TSH suppression therapy in low-risk papillary thyroid cancer patients by evaluating the benefit and harm of lowering TSH levels in terms of recurrence, metabolic complications, costs, and quality of life.

PURPOSE: Noninvasive positive pressure ventilation (NIPPV) is one of the ventilation-supporting methods by providing adequate exogenous pressure without intubation or tracheostomy. We aimed to assess the frequency and clinical factors for pneumothorax occurring during NIPPV application in a tertiary children's hospital. METHODS: We selected cases of pneumothorax related to NIPPV by keyword searching in our institution's clinical data warehouse, and their medical records were retrospectively reviewed. RESULTS: During a period of 17 years, 15 cases undergoing NIPPV developed pneumothorax, which was an incidence of 0.64% (15 of 2,343). There were 9 neonates and 6 adolescents. In 9 neonates, pneumothorax was caused by the continuous positive airway pressure (CPAP) ventilator, and occurred on 2 days after birth (median, range 1–3 days). In neonates, pneumothorax developed within 36 hours after CPAP application. One neonate underwent tracheal intubation and 3 neonates underwent chest tube insertion. In the postteenager group, pneumothorax developed 23 months (median, range 5 days to 47 months) after NIPPV application with a mask. All of the 6 patients had underlying neuromuscular disorders and one had superimposed interstitial lung disease. One of the 7 cases underwent surgical treatment and 4 cases were intubated. One case died from the deterioration of underlying interstitial lung disease. CONCLUSION: Although it rarely happens, the NIPPV can result in pneumothorax. In most cases, it can be resolved by supportive cares with oxygen or chest tube with or without tracheostomy. The prognosis is related to the type of underlying disease and its progression.
Adolescent ; Chest Tubes ; Continuous Positive Airway Pressure ; Humans ; Incidence ; Infant, Newborn ; Intubation ; Lung Diseases, Interstitial ; Masks ; Medical Records ; Noninvasive Ventilation ; Oxygen ; Parturition ; Pneumothorax* ; Positive-Pressure Respiration* ; Prognosis ; Respiratory Insufficiency ; Retrospective Studies ; Tracheostomy ; Ventilators, Mechanical