Disseminating Necrotizing Leukoencephalopathy Associated With Intra-CSF Methotrexate Chemotherapy: A Retrospective Observational Study.

BACKGROUND AND OBJECTIVES: Leptomeningeal metastases (LMs) are neoplasms that proliferate to membranes lining the brain and spinal cord. Intra-CSF methotrexate (MTX) chemotherapy is a prevalent treatment option. However, resultant long-term neurotoxicity can lead to irreversible disseminated necrotizing leukoencephalopathy (DNL). This study aims to determine the incidence, characteristics, risk factors, and outcomes of DNL following intra-CSF MTX chemotherapy for LM. METHODS: We retrospectively reviewed patients with LM who received intra-CSF MTX between 2001 and 2021 at the National Cancer Center of Korea. Patients with a follow-up duration of <3 months and those without follow-up MRI after MTX administration were excluded. The primary outcome was the development of DNL, evaluated based on the clinical and radiologic definitions of DNL. Logistic and Cox proportional regression models were used to assess the risk of DNL in patients with LM receiving intra-CSF MTX chemotherapy. RESULTS: Of the 577 patients included in the DNL investigation, 13 (2.3%) were identified to have irreversible DNL. The MRI features of DNL typically include necrotic changes in the bilateral anterior temporal region, extensive white matter, and/or brainstem lesions. All patients with DNL experienced fatal clinical course despite MTX cessation. Logistic regression analysis revealed that a cumulative dose of MTX significantly affected DNL occurrence. Multivariable analysis showed that the factor of ≥10 MTX rounds was significant for DNL development after adjusting for route of MTX administration and prior brain radiotherapy (odds ratio 7.32, 95% CI 1.42-37.77 at MTX rounds ≥10 vs < 10). In the Cox proportional hazards model considering time to occurrence of DNL, ≥10 rounds of MTX were identified as an independent predictor of DNL (hazard ratio 12.57, 95% CI 1.62-97.28, p = 0.015), even after adjusting for the synergistic effect of brain radiotherapy. DISCUSSION: DNL is a rare but fatal complication of intra-CSF MTX chemotherapy, and its progression cannot be prevented despite early recognition. The cumulative dose of intra-CSF MTX was an independent risk factor for DNL occurrence. Thus, intra-CSF MTX treatment for patients with LM should be administered with caution considering the possibility of the cumulative irreversible neurotoxicity.

Assessment of Radiation Doses to the General Public around Nuclear Power Plants Based on Representative Person Concept.

ABSTRACT: The International Commission on Radiological Protection recommended that the representative person concept should be used in radiation dose assessment of the general public to specify exposed individuals. The objective of this study is to assess radiation doses of the residents around nuclear power plants (NPPs) in relation to the introduction of the representative person concept. Critical group candidates and representative agro-livestock product producing areas were selected around a NPP site by considering radioactive effluents and regional meteorological data, geographical information, etc. A total of five exposure scenarios, including adult (non-fishery, fishery, and commuter), 10-y-old, and 1-y-old groups, were selected for the dose assessment. Generally, radiation doses were higher for 1-y-old, 10-y-old, and adult groups, in that sequence. There was no significant difference among the radiation doses by occupation in adult groups. Radiation dose results calculated by applying the representative person concept and dose assessment method currently used in Korea were compared. Application of the representative person concept results in lower radiation dose by 68.2% due to consideration of actual residential and agro-livestock product producing areas for the radiation dose assessment, by 13.3% due to the application method of habit data for dose calculation, and by 33.3% due to representative value of the dose results. Finally, considering all the factors above, radiation dose calculated by the current dose assessment method was 8.16 × 10 -2 mSv y -1 , while that calculated using the representative person concept was 1.40 × 10 -2 mSv y - 1 (82.8% lower). The results of this study can be used as reference data when introducing the representative person concept to the regulatory systems in Korea.

Thrombin Priming Promotes the Neuroprotective Effects of Human Wharton's Jelly-Derived Mesenchymal Stem Cells Via the HGF/AKT/STAT3 Signaling Pathway.

Mesenchymal stem cells (MSCs) directly differentiate into neurons and endothelial cells after transplantation, and their secretome has considerable potential for treating brain injuries. Previous studies have suggested that the effects of MSCs priming with exposure to hypoxia, cytokines, growth factors, or chemical agents could optimize the paracrine potency and therapeutic potential of MSCs. Studies have suggested that thrombin-primed Wharton's Jelly-derived mesenchymal stem cells (Th.WJ-MSCs) significantly enhance the neuroprotective beneficial effects of naive MSCs in brain injury such as hypoxic-ischemic brain injury (HIE) and intraventricular hemorrhage (IVH). This study aimed to characterize WJ-MSCs in terms of stem cell markers, differentiation, cell proliferation, and paracrine factors by comparing naive and Th.WJ-MSCs. We demonstrated that compared with naive MSCs, Th.MSCs significantly enhanced the neuroprotective effects in vitro. Moreover, we identified differentially expressed proteins in the conditioned media of naive and Th.WJ-MSCs by liquid chromatography-tandem mass spectrometry analysis. Secretome analysis of the conditioned medium of WJ-MSCs revealed that such neuroprotective effects were mediated by paracrine effects with secretomes of Th.WJ-MSCs, and hepatocyte growth factor was identified as a key paracrine mediator. These results can be applied further in the preclinical and clinical development of effective and safe cell therapeutics for brain injuries such as HIE and IVH.

Latent tuberculosis infection in Korean patients with multiple sclerosis and neuromyelitis optica spectrum disorder.

BACKGROUND: Latent tuberculosis infection (LTBI) is defined as an immune response to Mycobacterium tuberculosis infection that does not manifest clinically as active tuberculosis (TB). Since some immunotherapies can alter cellular immunity, LTBI screening has been recommended for patients with multiple sclerosis (pwMS) before initiation of long-term immunotherapies. In this study, we investigated the frequency of LTBI in Korean pwMS and patients with neuromyelitis optica spectrum disorder (pwNMOSD) and reported the long-term observation of untreated LTBI under various immunotherapies. METHODS: We enrolled pwMS or pwNMOSD who visited the Neurology department of the National Cancer Center between 2017 and 2021. LTBI was determined based on positive results of interferon-gamma release assay (IGRA) using QuantiFERON Gold Plus test and no evidence of active TB. Annual chest X-ray and careful monitoring for TB symptoms were performed until April 2023 or the time of follow-up loss. RESULTS: Among 531 patients who underwent the IGRA test, 25 pwMS (10.5%) and 42 pwNMOSD (14.3%) were diagnosed with LTBI. Of the 67 patients with LTBI, 59 patients (24 pwMS and 35 pwNMOSD) declined to receive preventive anti-TB drugs. None of the 59 with untreated LTBI demonstrated TB reactivation during 74.8 person-years in pwMS and 166.1 person-years in pwNMOSD. In addition, eight patients who completed the treatment for LTBI experienced no TB reactivation for a median of 5.5 years. CONCLUSION: The LTBI prevalence in Korean pw MS and pwNMOSD was 10.5% and 14.3%, respectively, which was much higher than that in pwMS from Western countries. Notably, none of the 59 patients with untreated LTBI showed TB reactivation over 240 person-years even under long-term immunotherapies, indicating the need for additional research to stratify the risk of LTBI-reactivation.

Aquaporin-4-IgG positive neuromyelitis optica spectrum disorder in a paraneoplastic context.

OBJECTIVE: The association between aquaporin-4-immunoglobulin-G-positive neuromyelitis optica spectrum disorder (AQP4-IgG-NMOSD) and cancer via a plausible immunological response has been reported. Here, we investigated the frequency of cancer in a large cohort of patients with AQP4-IgG-NMOSD. METHODS: Between May 2005 and January 2023, patients with AQP4-IgG-NMOSD and a history of cancer were included by searching for diagnostic codes of both NMOSD and cancer in the electronic medical records and/or reviewing the database of the National Cancer Center registry of inflammatory diseases of the central nervous system. Probable paraneoplastic AQP4-IgG-NMOSD was defined according to the 2021 Criteria for Paraneoplastic Neurological Syndrome. RESULTS: Of 371 patients with AQP4-IgG-NMOSD, 23 (6.2%) had a history of cancer and four (1.1%) experienced NMOSD in a paraneoplastic context. Among the four patients with probable paraneoplastic AQP4-IgG-NMOSD, the types of cancer were lung (1 adenocarcinoma, 1 squamous cell carcinoma) and colorectal (2 adenocarcinomas). In three patients, the first NMOSD symptoms developed after a cancer diagnosis (median, 8 months [range, 4-23]), and one patient's symptoms preceded the cancer diagnosis (6 months). Compared to the 367 non-paraneoplastic patients, those in the paraneoplastic context had an older age at onset (median: 59.5 vs. 37 years, p = 0.012) and a higher proportion of longitudinally extensive transverse myelitis (LETM) as an initial manifestation (4/4[100%] vs. 130/367[35.4%], p = 0.017). CONCLUSIONS: In a large cohort of patients with AQP4-IgG-NMOSD, the frequency of cancer was low. Older age, LETM features at onset, and adenocarcinoma as the histological type were usually observed in patients with AQP4-IgG-NMOSD in a paraneoplastic context.

Corrigendum: Blood neurofilament light chain as a biomarker for monitoring and predicting paclitaxel-induced peripheral neuropathy in patients with gynecological cancers.

[This corrects the article DOI: 10.3389/fonc.2022.942960.].

Enhanced Electrical and Thermal Conductivities of Polymer Composites with a Segregated Network of Graphene Nanoplatelets.

Introducing a segregated network constructed through the selective localization of small amounts of fillers can be a solution to overcome the limitations of the practical use of graphene-based conductive composites due to the high cost of fillers. In this study, polypropylene composites filled with randomly dispersed GNPs and a segregated GNP network were prepared, and their conductive properties were investigated according to the formation of the segregated structure. Due to the GNP clusters induced by the segregated structure, the electrical percolation threshold was 2.9 wt% lower than that of the composite incorporating randomly dispersed GNPs. The fully interconnected GNP cluster network inside the composite contributed to achieving the thermal conductivity of 4.05 W/m∙K at 10 wt% filler content. Therefore, the introduction of a segregated filler network was suitable to simultaneously achieve excellent electrical and thermal conductivities at a low content of GNPs.

Effects of prior antiplatelet and/or nonsteroidal anti-inflammatory drug use on mortality in patients undergoing abdominal surgery for abdominal sepsis.

BACKGROUND: The effects of prior antiplatelet and/or nonsteroidal anti-inflammatory drug (NSAID) use on mortality in critically ill patients remain unclear. We investigated the relationship between antiplatelet and/or NSAID use and mortality in patients who had undergone surgery for sepsis caused by intra-abdominal infection. METHODS: We obtained data from adult patients (aged >18 years) admitted to the intensive care unit after abdominal surgery due to intra-abdominal infection. The patients were categorized into those with and without prior antiplatelet and/or NSAID use. RESULTS: Overall, 241 patients were enrolled, with 76 in the antiplatelet and/or NSAID use group and 165 in the non-use group. The 60-day survival probabilities for the antiplatelet and/or NSAID use and non-use groups were 85.5% and 73.3%, respectively, and this difference was significant (P = .040). In the multivariate analysis of 28-day mortality, higher Acute Physiology and Chronic Health Evaluation II score (P < .001), Simplified Acute Physiology Score III (P < .001), and blood transfusion within 5 days postoperatively (P = .034) were significant mortality risk factors. In the multivariate analysis of 60-day mortality, higher Acute Physiology and Chronic Health Evaluation II score (P = .002), Simplified Acute Physiology Score III (P < .001), and blood transfusion within 5 days postoperatively (P = .006) were also significant mortality risk factors. However, prior drug use (P = .036) was a factor in reducing mortality. CONCLUSION: Patients with a prior history of antiplatelet and/or NSAID use had a higher 60-day survival than those who did not use these drugs. Prior antiplatelet and/or NSAID use was significantly associated with a reduction in 60-day mortality.

Anti-titin antibodies are associated with myocarditis in patients with myasthenia gravis.

BACKGROUND: Myasthenia gravis (MG) can affect cardiac muscles with variable presentations. Myocarditis is a rare but potentially serious cardiac manifestation of MG. Although thymomas and anti-titin antibodies have been suggested as risk factors for myocarditis in patients with MG, their independent influence on myocarditis has rarely been assessed. METHODS: A retrospective chart review was conducted on 247 patients diagnosed with MG who were tested for anti-titin antibodies. Myocarditis was diagnosed on the basis of the European Society of Cardiology 2013 Task Force criteria for clinically suspected myocarditis. Patients were classified into myocarditis-positive and myocarditis-negative groups. Multivariate analysis was performed to analyze the risk factors for myocarditis. RESULTS: Of the 247 patients, 25 (10.1%) were myocarditis-positive and 222 (89.9%) were myocarditis-negative. Anti-titin antibody positivity was higher in the myocarditis-positive group than in the myocarditis-negative group (68.0% vs. 28.4%, p < 0.001). A history of MG crisis was more frequent in the myocarditis-positive group than in the myocarditis-negative group (64.0% vs. 10.4%, p < 0.001). The presence of anti-titin antibodies (odds ratio [OR] 7.906; confidence interval [CI] 2.460-25.401) and MG crisis (OR 24.807; CI 7.476-82.311) was significantly associated with myocarditis. The Cox regression model showed that the anti-titin antibody levels (hazard ratio [HR] 3.639; 95% CI 1.557-8.505) and MG crisis (HR 6.137; 95% CI 2.639-14.272) were significant risk factors for the development of myocarditis. CONCLUSION: The presence of anti-titin antibody was associated with myocarditis in patients with MG, whereas thymoma was not. Although rare, early suspicion of myocarditis could be required, especially in patients with MG having anti-titin antibodies.

Severe neuromuscular immune-related adverse events of immune checkpoint inhibitors at national cancer center in Korea.

PURPOSE: Neuromuscular immune-related adverse events (irAEs) associated with immune checkpoint inhibitors (ICIs) have been increasingly recognized as a consequence of expanding use of ICIs in advanced cancers. We aimed to evaluate the frequency, phenotypes, rescue treatment, and clinical outcomes of severe neuromuscular irAEs of ICIs at National Cancer Center (NCC), Korea. MATERIALS AND METHODS: Consecutive patients with newly developed severe neuromuscular irAEs (common terminology criteria for adverse events grade 3 or greater) after ICI treatment at NCC in Korea between December 2018 and April 2022 were included by searching neuromuscular diagnostic codes in electronic medical records and/or reviewing neurological consultation documentations. RESULTS: Of the 1,503 ICI-treated patients, nine (0.6%) experienced severe neuromuscular irAEs; five with pembrolizumab and four with atezolizumab. The patients included five women and four men; their median age at onset was 59 years. The irAEs included Guillain-Barre syndrome (n = 5) and myasthenia gravis (MG) crisis with myositis (n = 4), and developed after a median of one (range 1-5) ICI cycle. The median modified Rankin score (mRS) was 4 (range 3-5) at the nadir. ICIs were discontinued in all patients, and rescue immunotherapy included corticosteroids (n = 9), intravenous immunoglobulin (n = 7), and plasmapheresis (n = 2). Eight patients showed improvements, with a median mRS of 3 (range 1-4); however, one patient (who had MG crisis with myocarditis) died. CONCLUSIONS: In this real-world monocentric study, ICI-induced neuromuscular irAEs were rare but potentially devastating; thus, physicians should remain vigilant to enable prompt recognition and management of irAEs.

Anti-titin antibody is associated with more frequent hospitalization to manage thymoma-associated myasthenia gravis.

Background and purpose: Anti-titin antibodies are antistriational antibodies associated with thymoma-associated myasthenia gravis (MG). We evaluated whether the patients with anti-titin antibody are more frequently hospitalized to manage thymoma-associated MG than those patients without anti-titin antibody. Methods: Patients with thymoma-associated MG who conducted the serological test for anti-titin antibody were retrospectively included. Disease severity, treatments, MG-related annual hospitalization rate, and MG-related emergency room (ER) visit rate were compared between the patients with anti-titin antibody and those patients without anti-titin antibody. Multivariate analysis was conducted to analyze the association between anti-titin antibody serostatus and multiple admissions (hospitalization or ER visit of ≥2 times). Results: Of the 64 included patients, 31 (48.4%) patients were positive for anti-titin antibody (titin+ group) and 33 (51.6%) patients were negative for anti-titin antibody (titin- group). Both the annual rate of MG-related hospitalization and ER visit were significantly higher in the titin+ group [0.2 (0.1-0.6) and 0.1 (0-0.2) per year, respectively] than those in the titin- group [0 (0-0.2) and 0 (0-0) per year, p = 0.004 and p = 0.006, respectively]. In multivariate analysis, positive anti-titin antibody was still significantly associated with multiple admissions [odds ratio (OR) 4.11, 95% CI 1.05-16.03] compared to the titin- group as a reference after adjusting for sex, follow-up duration, age at onset, systemic chemotherapy, and the Masaoka staging. Conclusion: The presence of anti-titin antibody is associated with more frequent hospital utilization. Personalized explanation and careful monitoring strategy could be required in patients with thymoma-associated MG with anti-titin antibody for the timely detection of relapses.

Cerebrospinal fluid neurofilament light chain as a potential prognostic biomarker for leptomeningeal metastasis.

The present study aimed to evaluate whether the cerebrospinal fluid (CSF) neurofilament light chain (NfL) is a potential prognostic marker for patients with leptomeningeal metastasis (LM). NfL levels were measured in CSF using a single-molecule array assay. A total of 42 patients with LM who were treated with ventriculo-lumbar perfusion (VLP) chemotherapy and had available stored CSF samples from the lumbar subarachnoid space before VLP chemotherapy were included in the present study, in order to investigate the prognostic value of CSF NfL. The median CSF NfL level in patients with LM was 8.15 ng/ml; 30% of patients who had died at the time of analysis had CSF NfL levels higher than the calculated overall prognostic cut-off value (11 ng/ml). The median overall survival after initiation of VLP chemotherapy was significantly longer in patients with LM and low CSF NfL levels compared with in patients with LM and high CSF NfL levels (P<0.001). The statistical significance remained after adjusting for other known prognostic factors and in a subgroup analysis according to age. In conclusion, CSF NfL could be considered a putative prognostic marker in patients with LM treated with VLP chemotherapy.

Blood neurofilament light chain as a biomarker for monitoring and predicting paclitaxel-induced peripheral neuropathy in patients with gynecological cancers.

Objective: We aimed to evaluate the potential of serum neurofilament light chain (sNfL) and serum brain-derived neurotrophic factor (sBDNF) as reliable biomarkers for paclitaxel-induced peripheral neuropathy (PIPN). Methods: Forty-eight patients with gynecologic cancer scheduled to undergo six cycles of paclitaxel-based chemotherapy at the National Cancer Center of Korea between September 2020 and January 2022 were prospectively assessed during and after chemotherapy. Results: At the end of the chemotherapy, 12 (25%) patients were classified as having grade 3 PIPN according to the National Cancer Institute-Common Toxicity Criteria. The sNfL levels increased during paclitaxel treatment in all patients. After two, four, and six cycles, patients with grade 3 PIPN exhibited higher mean sNfL levels than those in the 0-2 grade range (p = 0.004, p = 001, and p < 0.001, respectively). For sNfL levels ≥ 124 pg/mL, after two cycles of chemotherapy, the sensitivity and specificity for predicting grade 3 PIPN at the end of treatment were 80% and 79%, respectively. Over the course of paclitaxel-based treatment, sBDNF levels continued to decrease regardless of the severity of PIPN. At the end of treatment and six months after chemotherapy, patients with grade 3 PIPN had lower sBDNF levels than those within the 0-2 grade range (p =0.037 and 0.02, respectively), and the patients in the latter group had better clinical symptoms six months after the end of treatment. Conclusions: The sNfL levels during paclitaxel-based chemotherapy reflect ongoing neuroaxonal injury and serve as reliable biomarkers of PIPN severity. The sNfL levels during early treatment with paclitaxel might be prognostic indicators for PIPN progression. Low sBDNF levels 6 months after chemotherapy might adversely affect PIPN recovery.

Intussusception in Adults: A Retrospective Review from a Single Institution.

PURPOSE: Intussusception is uncommon in adults and often manifests as nonspecific symptoms. Owing to its low incidence and the lack of knowledge on the symptoms, causes, and treatment of adult intussusception (AI), many surgeons may have limited experience in the diagnosis and treatment of intussusception. This study aimed to describe the experience of AI and discuss its clinical presentation, etiology, and management. MATERIAL AND METHODS: I retrospectively reviewed patients aged 19 years and older who were diagnosed with intussusception at a single institution between March 2010 and December 2019. RESULTS: Among 28 patients who were finally analyzed, abdominal pain was the most commonly observed symptom. Ileocolic and ileoileal intussusceptions were the most common locations, and a lead point was observed in 19 cases (68%), of which malignancy was observed in six (21%). Bowel resection was performed in 27 cases. According to the pathological findings of the tissue from the resected section, nine and three cases of small bowel intussusception (SBI) were benign and malignant, respectively, whereas 13 and three cases of colonic intussusception (CI) were benign and malignant, respectively. On comparing SBI and CI, it was observed that most variables did not significantly differ, except for the duration of symptoms. CONCLUSION: SBI had a higher lead point than CI. The rate of malignancy in CI cases in this study was lower than that reported in other studies. En-bloc resection can be considered the first option for the treatment of AI.

Current status of initial antibiotic therapy and analysis of infections in patients with solitary abdominal trauma: a multicenter trial in Korea.

PURPOSE: Proper use of antibiotics during emergency abdominal surgery is essential in reducing the incidence of surgical site infection. However, no studies have investigated the type of antibiotics and duration of therapy in individuals with abdominal trauma in Korea. We aimed to investigate the status of initial antibiotic therapy in patients with solitary abdominal trauma. METHODS: From January 2015 to December 2015, we retrospectively analyzed the medical records of patients with solitary abdominal trauma from 17 institutions including regional trauma centers in South Korea. Both blunt and penetrating abdominal injuries were included. Time from arrival to initial antibiotic therapy, rate of antibiotic use upon injury mechanism, injured organ, type, and duration of antibiotic use, and postoperative infection were investigated. RESULTS: Data of the 311 patients were collected. The use of antibiotic was initiated in 96.4% of patients with penetrating injury and 79.7% with blunt injury. Initial antibiotics therapy was provided to 78.2% of patients with solid organ injury and 97.5% with hollow viscus injury. The mean day of using antibiotics was 6 days in solid organ injuries, 6.2 days in hollow viscus. Infection within 2 weeks of admission occurred in 36 cases. Infection was related to injury severity (Abbreviated Injury Scale of >3), hollow viscus injury, operation, open abdomen, colon perforation, and RBC transfusion. There was no infection in cases with laparoscopic operation. Duration of antibiotics did not affect the infection rate. CONCLUSION: Antibiotics are used extensively (84.2%) and for long duration (6.2 days) in patients with abdominal injury in Korea.

Association between cotinine-verified smoking status and moderately increased albuminuria in the middle-aged and older population in Korea: A nationwide population-based study.

OBJECTIVES: Although several self-reported questionnaire-based studies have found an association between smoking and moderately increased albuminuria, this result remains controversial. We investigated whether moderately increased albuminuria was associated with smoking status, verified by urinary cotinine (an objective biomarker of tobacco exposure), using population-based, nationally representative data. METHODS: This study included 2059 participants aged ≥ 50 years from the 2014 Korean National Health and Nutrition Examination Survey. Individuals with a urinary cotinine level ≥ 50 ng/mL were identified as cotinine-verified smokers. Moderately increased albuminuria was defined as a urine albumin-to-creatinine ratio ranging between ≥ 30 mg/g and < 300 mg/g. Multivariable logistic regression was used to evaluate the association between cotinine-verified smoking status and moderately increased albuminuria. RESULTS: Among the study participants, 16.9% were cotinine-verified smokers, 84.8% of whom were men. After adjustment for multiple covariates, cotinine-verified smokers showed a significant positive association with moderately increased albuminuria (adjusted odds ratio: 4.37, 95% confidence interval: 1.63-11.71) compared with cotinine-verified non-smokers. The association between urinary cotinine and moderately increased albuminuria did not differ with age, sex, obesity, or comorbidities (P-value for interaction > 0.05 in all cases). CONCLUSION: This large-scale observational study showed that cotinine-verified smoking is associated with moderately increased albuminuria in the Korean middle-aged and older general population, suggesting that smoking must be strictly controlled to reduce the risk of moderately increased albuminuria.

Nanoparticles from Equine Fetal Bone Marrow-Derived Cells Enhance the Survival of Injured Chondrocytes.

Recent studies have shown that mesenchymal stem cells (MSCs) can play a restorative role against degenerative joint diseases in horses. The purpose of this study was to investigate whether fetal bone marrow-derived cells (BMC)-derived nanoparticles (BMC-NPs) can stimulate the survival of equine chondrocytes. Equine fetal BMCs were isolated and characterized, and the role of BMC-NPs s in equine chondrocytes undergoing inflammatory cell death was examined. BMCs have several characteristics, such as the potential to differentiate into chondrocytes and osteocytes. Additionally, BMCs expressed immunoregulatory genes in response to treatment with tumor necrosis factor-alpha (TNF-α) and Interleukin 1 beta (IL-1ß). We found that BMC-NPs were taken up by equine chondrocytes. Functionally, BMC-NPs promoted the growth of chondrocytes, and reduced apoptosis induced by inflammatory cytokines. Furthermore, we observed that BMC-NPs upregulated the phosphorylation of protein kinase B (Akt) in the presence of IL-1ß, and reduced the phosphorylation of TNF-α-induced activation of extracellular signal-regulated kinase 1/2 (ERK1/2) in the chondrocytes. Cumulatively, our study demonstrated that equine fetal BMC-NPs have the potential to stimulate the survival of chondrocytes damaged by inflammatory cytokines. Thus, BMC-NPs may become an alternative cell-free allogenic therapeutic for degenerative joint diseases in horses.

Blunt Isolated Small Bowel Perforation Intervention: Does a Delay in Management Matter?

PURPOSE: Blunt small bowel injury is rare, and its timely diagnosis may be difficult. The effects of a delayed intervention on prognosis are unclear. We aimed to determine whether the time to surgical intervention affects outcomes in patients with blunt small bowel perforation. METHODS: The study was performed between March 2010 and December 2018 in adults (age >18 years) who initially underwent computed tomography and small bowel surgery only and survived more than one day postoperatively. They were categorized into three groups based on injury-to-surgery time intervals: ≤8, 8-24, and >24 h; similarly, they were also categorized into two groups of ≤24 and >24 h. RESULTS: Bowel resection, length of stay (LOS), intensive care unit (ICU) LOS, morbidity, and mortality were analyzed as outcomes in 52 patients. The number of patients in the three groups (≤8, 8-24, and >24 h) based on the time-to-surgery was 33, 13, and 6, respectively. On comparing the three groups, there were no significant differences in LOS (24 [18-35], 21 [10-40], and 28 [20-98] days, respectively; p=0.321), ICU LOS (2 [1-12], 4 [2-26], and 11 [7-14] days; respectively, p=0.153), mortality (3% (n = 1), 15% (n = 2), and 0%, respectively; p=0.291), and morbidity (46% (n = 15), 39% (n = 5), and 50% (n = 3), respectively; p=0.871). However, there was a significant difference between the groups in bowel resection (67% (n = 22), 31% (n = 4), and 83% (n = 5), respectively; p=0.037). Additionally, there was no significant difference in outcomes between the two groups (≤24 and >24 h) with small bowel perforation. CONCLUSIONS: Delay in surgical intervention following blunt abdominal trauma may not affect the outcomes of patients with small bowel injuries, such as LOS, ICU LOS, morbidity, and mortality, except bowel resection.

Therapeutic potential of stem cell-derived extracellular vesicles in osteoarthritis: preclinical study findings.

Extracellular vesicles (EVs) are nano-sized particles secreted by almost all cell types, and they mediate various biological processes via cell-to-cell communication. Compared with parental cells for therapeutic purposes, stem cell-derived EVs have several advantages such as reduced risk of rejection, less oncogenic potential, ease of long-term storage, lower chance of thromboembolism, and readiness for immediate use. Recent studies have demonstrated that EVs from stem cells, mostly from mesenchymal stem cells (MSCs) from various tissues, have anti-inflammatory, anti-oxidative, anti-apoptotic, and proliferative role in injured organs including osteoarthritic lesions. Herein, we provide a review about the up-to-date studies in preclinical application of stem cell-derived EVs in osteoarthritis animal arthritis models.

Pediatric Adenocarcinoma in Korea: A Multicenter Study.

PURPOSE: Adenocarcinoma is an extremely rare malignancy in the pediatric population. Research regarding pediatric adenocarcinoma is very rare in Korea. This study aimed to investigate the clinical features of pediatric adenocarcinomas of various primary organ sites in Korea. MATERIALS AND METHODS: Pediatric patients under 18 years, diagnosed with adenocarcinoma of various sites between January 1995 and December 2016, were included. We retrospectively reviewed patient and tumor characteristics and calculated survival estimates, reported as 5-year survival rate and 95% confidence interval. RESULTS: Of 80 patients (median age, 15 years; range, 10 to 17 years), 37 (46.3%) were men, and 24 (30%) had a family history of cancer or underlying disease relevant to malignancy. The cancer locations were the colon and rectum (n=32), ovaries (n=18), stomach (n=15), lung (n=4), small bowel (n=1), and other sites (n=10). Totally, 54.8% patients (42/77) had stage 3 or 4 disease. The median follow-up period was 2.0 years (range, 0 to 20.4). The 5-year overall survival estimate for all patients, and for those with stomach, colorectal, ovarian, and other cancer sites were 57.9%±11.5%, 58.2%±25.7%, 41.5%±18.2%, 87.5%±16.2%, and 64.0%±34.4%, respectively. The 5-year survival rate differed significantly between categories of adenocarcinomas into gastrointestinal (GI) (44.7%) and non-GI adenocarcinomas (78.8%) (p=0.007). The 5-year survival rate also differed significantly according to carcinoembryonic antigen level (69.3% in < 3 ng/mL, 23.8% in > 3 ng/mL; p < 0.001). CONCLUSION: In pediatric patients, adenocarcinomas arise from various organs and are often diagnosed at advanced stages. Large, prospective studies for their accurate clinical characteristics and prognostic factors are needed.