Defining mesenchymal stem/stromal cell-induced myeloid-derived suppressor cells using single-cell transcriptomics.

Mesenchymal stem/stromal cells (MSCs) modulate the immune response through interactions with innate immune cells. We previously demonstrated that MSCs alleviate ocular autoimmune inflammation by directing bone marrow cell differentiation from pro-inflammatory CD11bhiLy6ChiLy6Glo cells into immunosuppressive CD11bmidLy6CmidLy6Glo cells. Herein, we analyzed MSC-induced CD11bmidLy6Cmid cells using single-cell RNA sequencing and compared them with CD11bhiLy6Chi cells. Our investigation revealed seven distinct immune cell types including myeloid-derived suppressor cells (MDSCs) in the CD11bmidLy6Cmid cells, while CD11bhiLy6Chi cells included mostly monocytes/macrophages with a small cluster of neutrophils. These MSC-induced MDSCs highly expressed Retnlg, Cxcl3, Cxcl2, Mmp8, Cd14, and Csf1r as well as Arg1. Comparative analyses of CSF-1RhiCD11bmidLy6Cmid and CSF-1RloCD11bmidLy6Cmid cells demonstrated that the former had a homogeneous monocyte morphology and produced elevated levels of interleukin-10. Functionally, these CSF-1RhiCD11bmidLy6Cmid cells, compared with the CSF-1RloCD11bmidLy6Cmid cells, inhibited CD4+ T cell proliferation and promoted CD4+CD25+Foxp3+ Treg expansion in culture and in a mouse model of experimental autoimmune uveoretinitis. Resistin-like molecule (RELM)-γ encoded by Retnlg, one of the highly upregulated genes in MSC-induced MDSCs, had no direct effects on T cell proliferation, Treg expansion, or splenocyte activation. Together, our study revealed a distinct transcriptional profile of MSC-induced MDSCs and identified CSF-1R as a key cell-surface marker for detection and therapeutic enrichment of MDSCs.

Laminin-Augmented Decellularized Extracellular Matrix Ameliorating Neural Differentiation and Neuroinflammation in Human Mini-Brains.

Non-neural extracellular matrix (ECM) has limited application in humanized physiological neural modeling due to insufficient brain-specificity and safety concerns. Although brain-derived ECM contains enriched neural components, certain essential components are partially lost during the decellularization process, necessitating augmentation. Here, it is demonstrated that the laminin-augmented porcine brain-decellularized ECM (P-BdECM) is xenogeneic factor-depleted as well as favorable for the regulation of human neurons, astrocytes, and microglia. P-BdECM composition is comparable to human BdECM regarding brain-specificity through the matrisome and gene ontology-biological process analysis. As augmenting strategy, laminin 111 supplement promotes neural function by synergic effect with laminin 521 in P-BdECM. Annexin A1(ANXA1) and Peroxiredoxin(PRDX) in P-BdECM stabilized microglial and astrocytic behavior under normal while promoting active neuroinflammation in response to neuropathological factors. Further, supplementation of the brain-specific molecule to non-neural matrix also ameliorated glial cell inflammation as in P-BdECM. In conclusion, P-BdECM-augmentation strategy can be used to recapitulate humanized pathophysiological cerebral environments for neurological study.

Breast cancer malignancy is governed by regulation of the macroH2A2/TM4SF1 axis, the AKT/NF-κB pathway, and elevated MMP13 expression.

The histone variant, macroH2A (mH2A) influences gene expression through epigenetic regulation. Tumor suppressive function of mH2A isoforms has been reported in various cancer types, but few studies have investigated the functional role of mH2A2 in breast cancer pathophysiology. This study aimed to determine the significance of mH2A2 in breast cancer development and progression by exploring its downstream regulatory mechanisms. Knockdown of mH2A2 facilitated the migration and invasion of breast cancer cells, whereas its overexpression exhibited the opposite effect. In vivo experiments revealed that augmenting mH2A2 expression reduced tumor growth and lung metastasis. Microarray analysis showed that TM4SF1 emerged as a likely target linked to mH2A2 owing to its significant suppression in breast cancer cell lines where mH2A2 was overexpressed among the genes that exhibited over twofold upregulation upon mH2A2 knockdown. Suppressing TM4SF1 reduced the migration, invasion, tumor growth, and metastasis of breast cancer cells in vitro and in vivo. TM4SF1 depletion reversed the increased aggressiveness triggered by mH2A2 knockdown, suggesting a close interplay between mH2A2 and TM4SF1. Our findings also highlight the role of the mH2A2/TM4SF1 axis in activating the AKT/NF-κB pathway. Consequently, activated NF-κB signaling leads to increased expression and secretion of MMP13, a potent promoter of metastasis. In summary, we propose that the orchestrated regulation of the mH2A2/TM4SF1 axis in conjunction with the AKT/NF-κB pathway and the subsequent elevation in MMP13 expression constitute pivotal factors governing the malignancy of breast cancer.

Mid-treatment MRI-based tumor response assessment for tumor recurrence and patient survival in locally advanced adenocarcinoma of the cervix: A retrospective multicenter study of KROG 23-03.

OBJECTIVE: To evaluate the significance of response assessment with magnetic resonance imaging (MRI) during chemoradiotherapy (CRT) for outcomes of adenocarcinoma of the cervix. METHODS: A retrospective analysis of 102 patients diagnosed with FIGO 1B3-IVa cervical adenocarcinoma was conducted. Patients underwent definitive CRT and brachytherapy. Mid-treatment MRI-assessments were used to evaluate tumor response during radiotherapy, focusing on tumor volume reduction rate (TVRR), which was defined as an optimal reduction rate from initial tumor volume for tumor progression. Locoregional recurrence (LRR), distant metastasis (DM), progression-free survival (PFS) and overall survival (OS) rates according to the tumor response were analyzed. RESULTS: Forty-five (44.1 %) of 102 patients experienced tumor downstaging during CRT, with 72 (70.5 %) demonstrating a complete response on post-treatment MRI three months after radiotherapy. With a median follow-up of 35.5 months, the 3-year PFS and overall OS rates for all patients were 60.0 % and 84.0 %, respectively. LRR and DM rates at 3 years were 25.2 % and 23.3 %, respectively. Patients with TVRR≥81.8 % had significantly longer 3-year PFS (75.4 % vs. 36.2 %, P < 0.001) and OS (93.2 % vs. 69.0 %, P = 0.002) rates than the other patients with TVRR<81.8 %. LRR (10.6 % vs. 45.6 %, P = 0.003) and DM (14.6 % vs. 33.5 %, P = 0.008) rates at 3 years were significantly lower in TVRR≥81.8 % group compared to TVRR<81.8 % group. In the multivariate analysis, positive initial lymph node (hazard ratio [HR], 2.11; confidence interval [CI], 1.25-3.87; P = 0.02] and TVRR (HR, 0.42; CI, 0.19-0.93; P = 0.03) were significantly associated with PFS. CONCLUSION: Mid-treatment MRI assessment is crucial and higher rates of tumor volume reduction during radiotherapy indicates better prognosis for tumor recurrence and patient survival in cervical adenocarcinoma.

New potential diagnostic markers for verrucous hyperplasia and verrucous carcinoma based on RNA-sequencing data.

Verrucous carcinoma (VC) is a rare subtype of squamous cell carcinoma (SCC) characterized by its histological presentation as a low-grade tumor with no potential for metastasis, setting it apart from invasive SCC. However, distinguishing VC from its benign counterpart, verrucous hyperplasia (VH), is challenging due to their clinical and morphological similarities. Despite the importance of accurate diagnosis for determining treatment strategies, diagnosis of VH and VC relied only on lesion recurrence after resection. To address this challenge, we generated RNA profiling data from tissue samples of VH and VC patients to identify novel diagnostic markers. We analyzed differentially expressed (DE) mRNA and long non-coding RNA (lncRNA) in tissue samples from VH and VC patients. Additionally, ChIP-X Enrichment Analysis 3 (ChEA3) was conducted to identify the top five transcription factors potentially regulating the expression of DE mRNAs in VH and VC. Our analysis of mRNA and lncRNA expression profiles in VH and VC provides insights into the underlying molecular characteristics of these diseases and offers potential new diagnostic markers. The identification of specific DE genes and lncRNAs may enable clinicians to more accurately differentiate between VH and VC, leading to better treatment choices.

FOLFIRINOX or Gemcitabine-based Chemotherapy for Borderline Resectable and Locally Advanced Pancreatic Cancer: A Multi-institutional, Patient-Level, Meta-analysis and Systematic Review.

BACKGROUND: Pancreatic cancer often presents as locally advanced (LAPC) or borderline resectable (BRPC). Neoadjuvant systemic therapy is recommended as initial treatment. It is currently unclear what chemotherapy should be preferred for patients with BRPC or LAPC. METHODS: We performed a systematic review and multi-institutional meta-analysis of patient-level data regarding the use of initial systemic therapy for BRPC and LAPC. Outcomes were reported separately for tumor entity and by chemotherapy regimen including FOLFIRINOX (FIO) or gemcitabine-based. RESULTS: A total of 23 studies comprising 2930 patients were analyzed for overall survival (OS) calculated from the beginning of systemic treatment. OS for patients with BRPC was 22.0 months with FIO, 16.9 months with gemcitabine/nab-paclitaxel (Gem/nab), 21.6 months with gemcitabine/cisplatin or oxaliplatin or docetaxel or capecitabine (GemX), and 10 months with gemcitabine monotherapy (Gem-mono) (p < 0.0001). In patients with LAPC, OS also was higher with FIO (17.1 months) compared with Gem/nab (12.5 months), GemX (12.3 months), and Gem-mono (9.4 months; p < 0.0001). This difference was driven by the patients who did not undergo surgery, where FIO was superior to other regimens. The resection rates for patients with BRPC were 0.55 for gemcitabine-based chemotherapy and 0.53 with FIO. In patients with LAPC, resection rates were 0.19 with Gemcitabine and 0.28 with FIO. In resected patients, OS for patients with BRPC was 32.9 months with FIO and not different compared to Gem/nab, (28.6 months, p = 0.285), GemX (38.8 months, p = 0.1), or Gem-mono (23.1 months, p = 0.083). A similar trend was observed in resected patients converted from LAPC. CONCLUSIONS: In patients with BRPC or LAPC, primary treatment with FOLFIRINOX compared with Gemcitabine-based chemotherapy appears to provide a survival benefit for patients that are ultimately unresectable. For patients that undergo surgical resection, outcomes are similar between GEM+ and FOLFIRINOX when delivered in the neoadjuvant setting.

The Impact of Omicron Wave on Pediatric Febrile Seizure.

BACKGROUND: The coronavirus disease 2019 (COVID-19) omicron (B.1.1.529) variant reduced the risk of severe disease compared with the original strain and other variants, but it appeared to be highly infectious, which resulted in an exponential increase in confirmed cases in South Korea. As the number of confirmed cases increased, so did the number of pediatric patients' hospitalization. This study aims to evaluate the frequency and clinical features of febrile seizure associated with the COVID-19 omicron variant in children. METHODS: We retrospectively reviewed the medical records of children aged under 18 years with febrile seizure who were tested for COVID-19 from February 2020 to April 2022 at Ajou University Hospital, South Korea. Based on the dominant variants, we divided the period into the pre-omicron (from February 2020 to December 2021) and omicron periods (from January 2022 to April 2022) and compared the clinical characteristics between the two. Also, we compared the clinical characteristics of febrile seizure between COVID-19 positive and negative group during the omicron period. RESULTS: Among the 308 children, 211 patients (9.2 patients/months) and 97 patients (24.3 patients/months) were grouped into pre-omicron and omicron periods, respectively. Compared with the pre-omicron period, patients in the omicron period showed significantly higher mean age (pre-omicron vs. omicron, 22.0 vs. 28.0 months; P = 0.004) and COVID-19 positive results (pre-omicron vs. omicron, 0.5% vs. 62.9%; P < 0.001). As the COVID-19 confirmed cases in the omicron period increased, the number of COVID-19 associated febrile seizure also increased. In the omicron period, 61 children were confirmed to be positive for COVID-19, and COVID-19 positive group showed statistically significant higher mean age (positive vs. negative, 33.0 vs. 23.0 months; P = 0.003) and peak body temperature than the negative group (positive vs. negative, 39.1°C vs. 38.6°C; P = 0.030). Despite the lack of significance, COVID-19 positive group showed longer seizure time, multiple seizure episodes, and higher prevalence of complex febrile seizure. CONCLUSION: The frequency of COVID-19 associated febrile seizure increased in the omicron periods. In addition, in this period, children with febrile seizure diagnosed with COVID-19 had a higher mean age and higher peak body temperature.

Giant Pilomatricoma Mistaken for a Malignant Tumor.

Pilomatricomas are tumors originating from the matrices of hair follicles. Giant pilomatricomas, defined as pilomatricomas that are 5 cm or larger, are benign but may appear malignant clinically. We present the case of a 69-year-old man with a rapidly growing mass on his scalp. When he visited our department, the tumor measured 10.0×6.0×4.0 cm and showed inflammation and ulceration. Magnetic resonance imaging and 18 F-fluorodeoxyglucose positron emission tomography-computed tomography showed findings resembling lymph node metastasis from a malignant tumor. However, upon an incisional biopsy, the tumor was diagnosed as a pilomatricoma. Therefore, we performed an excisional biopsy instead of radical surgery and lymph node dissection. The tumor was ultimately diagnosed as a giant pilomatricoma based on the excisional biopsy, and the patient received reconstruction only at the site of the defect. A giant pilomatricoma can be mistaken for a malignant tumor due to its characteristics. In such uncertain cases, it can be helpful to first perform an excisional biopsy.

Predictors of Caregiver Satisfaction With Pediatric Laceration Repair in the Pediatric Emergency Department.

OBJECTIVES: The objective of this study was to define the care factors that are important to caregivers' satisfaction with pediatric laceration repair and the overall emergency department (ED) experience. METHODS: This was a cross-sectional observation study performed in an urban tertiary hospital. The caregivers of patients younger than 18 years who presented to the ED for laceration repair completed a survey. Demographic data were analyzed. Univariate and multivariate logistic regressions were used to determine the factors related to satisfaction with the laceration repair and the overall ED experience. RESULTS: Fifty-five caregivers were enrolled. Most of the children had facial lacerations (n = 44, 80%). The median length of ED stay was 181 minutes (interquartile range [IQR], 157-208 minutes). The children's median age was 41.8 months (IQR, 23-91 months); the caregivers' median age was 37 years (IQR, 35-41 years). Most lacerations were repaired by plastic surgeons (81.8%). In the multivariate regression analysis, preparation before the procedure, mid-income family, caring attitude of the nurse, cosmetic outcome, and measures to control the patient's anxiety were significantly related to the caregiver's satisfaction with laceration repair (P < 0.05), whereas preparation before the procedure and ED environment were significantly related to the caregiver's satisfaction with the overall ED experience (P < 0.05). CONCLUSIONS: Preparation before the procedure was significantly related to the caregiver's satisfaction with both pediatric laceration repair and the overall PED experience. The strongest predictors were cosmetic outcome for laceration repair and preparation for the procedure for the overall PED experience. Our findings suggest that improvements in various aspects will increase parent satisfaction.

Suggested use of empirical antibiotics in acute cholecystitis based on bile microbiology and antibiotic susceptibility.

BACKGROUND: Bacterial infection is common in acute cholecystitis (AC). To identify appropriate empirical antibiotics, we investigated AC-associated microorganisms and their susceptibilities to antibiotics. We also compared preoperative clinical findings of patients grouped according to specific microorganisms. METHODS: Patients who underwent laparoscopic cholecystectomy for AC between 2018 and 2019 were enrolled. Bile cultures and antibiotic susceptibility tests were performed, and clinical findings of patients were noted. RESULTS: A total of 282 patients were enrolled (147 culture-positive and 135 culture-negative). The most frequent microorganisms were Escherichia (n = 53, 32.7%), Enterococcus (n = 37, 22.8%), Klebsiella (n = 28, 17.3%), and Enterobacter (n = 18, 11.1%). For Gram-negative microorganisms, second-generation cephalosporin (cefotetan: 96.2%) was more effective than third-generation cephalosporin (cefotaxime: 69.8%). Vancomycin and teicoplanin (83.8%) were the most effective antibiotics for Enterococcus. Patients with Enterococcus had higher rates of CBD stones (51.4%, p = 0.001) and biliary drainage (81.1%, p = 0.002), as well as higher levels of liver enzymes, than patients with other microorganisms. Patients with ESBL-producing bacteria had higher rates of CBD stones (36.0% vs. 6.8%, p = 0.001) and biliary drainage (64.0% vs. 32.4%, p = 0.005) than those without. DISCUSSION: Preoperative clinical findings of AC are related to microorganisms in bile samples. Periodic antibiotic susceptibility tests should be conducted to select appropriate empirical antibiotics.

Fate of Patients With Intraductal Papillary Mucinous Neoplasms of Pancreas After Resection According to the Pathology and Margin Status: Continuously Increasing Risk of Recurrence Even After Curative Resection Suggesting Necessity of Lifetime Surveillance.

OBJECTIVE: This study evaluated the associated factors and prognosis according to pathology and margin after surgical resection of intraductal papillary mucinous neoplasms (IPMN). BACKGROUND: There is limited information on recurrence patterns according to pathology and margin in IPMN. METHODS: Total 577 patients who underwent operation for IPMN at a tertiary center were included. Factors associated with recurrence, survival, and recurrence outcomes according to pathology and margin were analyzed. RESULTS: Among 548 patients analyzed, 353 had low-grade dysplasia (LGD), 78 had high-grade dysplasia (HGD), and 117 had invasive IPMN. Total 50 patients developed recurrences, with 4 resection margins, 10 remnant pancreas, 11 locoregional, and 35 distant recurrences. Invasive IPMN showed worse 5-year cumulative recurrence risk (LGD vs HGD vs invasive: 0.7% vs 4.3% vs 37.6%, P < 0.001) and 5-year survival rate (89.0% vs 84.0% vs 48.4%, P < 0.001). Recurrence risk increased after 5 years, even in LGD and HGD. Malignant margin (HGD and invasive) had worse 5-year cumulative recurrence rate (R0 vs LGD vs malignant: 8.3% vs 5.9% vs 50.6%, P < 0.001) and 5-year survival rate (80.7% vs 83.0% vs 30.8%, P < 0.001). Carbohydrate antigen 19-9 >37 ( P = 0.003), invasive IPMN ( P < 0.001), and malignant margin ( P = 0.036) were associated with recurrence. CONCLUSIONS: Invasive IPMN developed more recurrences and had worse survival than LGD or HGD, indicating the need for more efficient postoperative treatment strategies. Patients with LGD and HGD also need regular follow-up for recurrence after 5 years. Malignant margins need additional resection to achieve negative or at least LGD margin.

Prevalence and detection of Tropheryma whipplei in the stools of Korean patients with diarrhea using real-time PCRs.

BACKGROUND: The prevalence of Tropheryma whipplei varies depending on age, region, and underlying disease. We estimated the prevalence of T. whipplei in the stools of Korean patients with diarrhea using real-time PCR (RT-PCR) and compared three RT-PCR targets, rpoB, hsp65, and Dig15. METHODS: A total of 1404 nucleic acid samples extracted from the stools of Korean patients with diarrhea were tested using an initial RT-PCR targeting T. whipplei-specific regions of 16S-23S rRNA intergenic spacer. Subsequently, the samples positive for the initial RT-PCR were tested using the follow-up RT-PCRs targeting rpoB, hsp65, and Dig15 and analyzed by sequencing to confirm the presence of T. whipplei. We estimated the prevalence of T. whipplei and compared them according to gender and age. We also compared the performance of three targets in the follow-up RT-PCRs. RESULTS: T. whipplei was detected in 1.4% of all samples (20 of 1404), and there were no differences according to gender and age. In pediatric samples (≤ 19 years), T. whipplei was detected higher in children aged 6-19 than in those aged 1-5 (2.7% vs. 0.7%, P = 0.01). Sensitivities of the rpoB, hsp65, and Dig15 RT-PCR were 50.0%, 85.0%, and 95.0%, respectively; specificities were 100.0%, 100.0%, and 84.6%, respectively. CONCLUSIONS: This is the first study that estimated the prevalence of T. whipplei in the stools of Korean patients with diarrhea. This study demonstrated the presence of T. whipplei in stools of Koreans, even though the bacterium was detected low. The RT-PCRs targeting hsp65 and Dig15 showed reliable performance, and a multiplex PCR including these targets is expected to be useful for T. whipplei detection.

Single-port robot plus one port (SP + 1) distal pancreatectomy using the new da Vinci SP system.

PURPOSE: Single-incision laparoscopic distal pancreatectomy has not been widely applied due to technical challenges and increased operative risks. The newly released da Vinci SP system has been introduced to overcome these limitations and offer improvements for established robotic single-site procedures. We report our experience of robotic single port plus one port distal pancreatectomy using the da Vinci SP system. METHODS: We performed robotic distal pancreatectomy in three patients using the da Vinci SP surgical system with one additional port used for applying the energy device and stapling. Technical and clinical feasibility were examined. RESULTS: The mean age and body mass index were 70.7 years and 27.8 kg/m2, respectively. The mean operation time was 215 min. The estimated blood loss was less than 500 mL. All patients underwent combined splenectomy. The postoperative course of all patients was uneventful. CONCLUSION: Robotic distal pancreatectomy using the da Vinci SP system is safe and feasible, with acceptable perioperative outcomes.

Prevention of Intra-Abdominal Adhesions Using the Combination of Mediclore® and a Statin.

PURPOSE: This study investigated the antiadhesive effects of Mediclore®, rosuvastatin, and a combination of Mediclore and rosuvastatin in a rat adhesion model. METHODS: The adhesion models (a total of 58 adult male rats) were divided into 4 groups. The control group (group C) received no special materials except for a saline. The experimental groups were treated with 5 mL of Mediclore (group M), rosuvastatin (group R), or rosuvastatin and Mediclore (group RM), and these materials were intraperitoneally placed under the incision. At postoperative day 14, the rats underwent re-laparotomy and adhesiolysis. Three investigators blinded to group assignment scored the extent of adhesion formation, the numbers of remote adhesions, and the extent of acute/chronic inflammation, fibrosis, edema, and congestion on resected specimens via histologic examination. RESULTS: The macroscopic adhesion score in group RM (7.27 ± 3.51) was significantly lower than those in groups C (13.36 ± 2.24) and R (11.71 ± 1.98); group M (9.13 ± 4.09) had a significantly lower adhesion score than group C. The number of remote adhesions was significantly lower in groups R and RM than in group C. The acute inflammation score, chronic inflammation score, and fibrosis score in group RM; the acute inflammation score in group R; and the fibrosis score in group M were significantly lower than those in group C. CONCLUSION: The intraperitoneal application of Mediclore and a combination of Mediclore and rosuvastatin effectively reduced postoperative adhesions.

Comparison of the Clinical Characteristics of Pediatric Poisoning Patients Who Visited Emergency Department Before and During the COVID-19 Pandemic.

BACKGROUND: We aimed to investigate changes in the clinical characteristics of pediatric poisoning patients who visited the emergency department (ED) before and during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: Poisoning cases below age 18 who visited the ED from January 2018 to December 2021 were retrospectively analysed. The study period was then divided into pre-COVID-19 and COVID-19 pandemic to compare poisoning patterns. RESULTS: During the study period, 86,153 visits to the pediatric ED had been recorded, with 625 patients being included the final analysis. During the COVID-19 period, the proportion of poisoned patients increased from 0.62% to 0.98%. The average age of the patients was higher in the COVID-19 period, with 53.4% of the cases being intentional (pre-COVID-19, 32.5%; P < 0.001). Moreover, 70.4% of poisoning cases during the COVID-19 period were caused by drugs (pre-COVID-19, 60.6%; P = 0.038). More patients underwent decontamination and laboratory investigation during the COVID-19 period than during the previous period (P = 0.007 and P < 0.001, respectively). The length of ED stay and the proportion of hospitalisation were significantly greater during the COVID-19 period. After analysing accidental poisoning cases, we found that antipyretics/nonsteroidal anti-inflammatory drugs and respiratory drugs were more common in the pre-COVID-19 group, whereas iron/vitamins, cardiovascular drugs and hormones were more common in the COVID-19 group. After analysing intentional poisoning cases, we found that 73.6% and 76.4% of the patients in the pre-COVID-19 and COVID-19 group had a history of psychiatric disease, respectively. Although no difference was observed in the frequency of previous first suicide attempts, 19.0% of the patients in the COVID-19 group attempted suicide more than three times. CONCLUSION: During the COVID-19 pandemic, intentional poisoning cases, especially in adolescence, increased and were treated more. Many of the patients with intentional poisoning had a history of mental illness or suicide in the past. Therefore, it seems that policy consideration for mentally vulnerable adolescents during this new pandemic period is necessary.

A Case Report for Acute Myopericarditis After NVX-CoV2373 (Novavax®) COVID-19 Vaccination.

Post-vaccination myocarditis after administration of the NVX-CoV2373 coronavirus disease 2019 (COVID-19) vaccine has been reported in a limited population. We report the first biopsy-proven case of myopericarditis after administration of second dose of NVX-CoV2373 COVID-19 vaccine (Novavax®) in Korea. A 30-year-old man was referred to emergency department with complaints of chest pain and mild febrile sense for two days. He received the second dose vaccine 17 days ago. Acute myopericarditis by the vaccination was diagnosed by cardiac endomyocardial biopsy. He was treated with corticosteroid 1 mg/kg/day for 5 days and tapered for one week. He successfully recovered and was discharged on the 12th day of hospitalization. The present case suggests acute myopericarditis as a vaccination complication by Novavax® in Korea.

G9a Knockdown Suppresses Cancer Aggressiveness by Facilitating Smad Protein Phosphorylation through Increasing BMP5 Expression in Luminal A Type Breast Cancer.

Epigenetic abnormalities affect tumor progression, as well as gene expression and function. Among the diverse epigenetic modulators, the histone methyltransferase G9a has been focused on due to its role in accelerating tumorigenesis and metastasis. Although epigenetic dysregulation is closely related to tumor progression, reports regarding the relationship between G9a and its possible downstream factors regulating breast tumor growth are scarce. Therefore, we aimed to verify the role of G9a and its presumable downstream regulators during malignant progression of breast cancer. G9a-depleted MCF7 and T47D breast cancer cells exhibited suppressed motility, including migration and invasion, and an improved response to ionizing radiation. To identify the possible key factors underlying these effects, microarray analysis was performed, and a TGF-ß superfamily member, BMP5, was selected as a prominent target gene. It was found that BMP5 expression was markedly increased by G9a knockdown. Moreover, reduction in the migration/invasion ability of MCF7 and T47D breast cancer cells was induced by BMP5. Interestingly, a G9a-depletion-mediated increase in BMP5 expression induced the phosphorylation of Smad proteins, which are the intracellular signaling mediators of BMP5. Accordingly, we concluded that the observed antitumor effects may be based on the G9a-depletion-mediated increase in BMP5 expression and the consequent facilitation of Smad protein phosphorylation.

Preoperative volume assessment using bioelectrical impedance analysis for minimizing blood loss during hepatic resection.

BACKGROUND: Maintaining low central venous pressure (CVP) is an effective strategy to reduce blood loss during hepatic resection. As an alternative to measuring CVP, which requires the placement of a central venous catheter, bioelectrical impedance analysis (BIA) is a noninvasive method recently used for monitoring volume status in critically ill patients. METHODS: We investigated 192 patients who underwent hepatic resection from January 2017 to December 2020. The ratio of extracellular water:total body water (ECW/TBW), as an index of volume status, was measured using InBody S10 (Biospace, Seoul, Korea). The correlation between the ECW/TBW and CVP was determined, and their influences on operative outcomes were analyzed. RESULTS: ECW/TBW and CVP showed a significant correlation; an ECW/TBW <0.378 correlated with a CVP <5 mmHg (R2 = 0.839, P<0.001). Estimated blood loss (EBL) was significantly increased in patients with an ECW/TBW ≥0.378 compared to those with a ratio <0.378 (508 ± 321 vs. 324 ± 193, mL, P<0.001). Identified predictors for an EBL ≥500 mL were operative time (odds ratio [OR], 1.008; 95% confidence interval [CI], 1.001-1.015; P = 0.021) and an ECW/TBW <0.378 (OR, 0.263; 95% CI, 0.121-0.572; P = 0.001). CONCLUSIONS: BIA can be utilized for preoperative volume assessment to minimize blood loss during hepatic resection.

STAT3 phosphorylation inhibition for treating inflammation and new bone formation in ankylosing spondylitis.

OBJECTIVE: AS is a rheumatic disease characterized by chronic inflammation and bony ankylosis. This study was to evaluate whether a signal transducer and activator of transcription 3 phosphorylation inhibitor (stat3-p Inh) could treat both chronic inflammation and bone formation in AS. METHODS: Primary AS osteoprogenitor cells and spinal entheseal cells were examined for osteogenic differentiation. SF mononuclear cells (SFMCs) and lamina propria mononuclear cells (LPMCs) were obtained from AS patients. Inflammatory cytokine-producing cells were analysed using flow cytometry and ELISA. Female SKG mice were treated with stat3-p Inh, IL-17A blocker or vehicle. Inflammation and new bone formation were evaluated using immunohistochemistry, PET and micro-CT. RESULTS: In the SKG mouse model, stat3-p Inh significantly suppressed arthritis, enthesitis, spondylitis and ileitis. In experiments culturing SFMCs and LPMCs, the frequencies of IFN-γ-, IL-17A- and TNF-α-producing cells were significantly decreased after stat3-p Inh treatment. When comparing current treatments for AS, stat3-p Inh showed a comparable suppression effect on osteogenesis to Janus kinase inhibitor or IL-17A blocker in AS-osteoprogenitor cells. Stat3-p Inh suppressed differentiation and mineralization of AS-osteoprogenitor cells and entheseal cells toward osteoblasts. Micro-CT analysis of hind paws revealed less new bone formation in stat3-p Inh-treated mice than vehicle-treated mice (P = 0.005). Hind paw and spinal new bone formation were similar between stat3-p Inh- and anti-IL-17A-treated SKG mice (P = 0.874 and P = 0.117, respectively). CONCLUSION: Stat-3p inhibition is a promising treatment for both inflammation and new bone formation in AS.

Radiological tumour invasion of splenic artery or vein in patients with pancreatic body or tail adenocarcinoma and effect on recurrence and survival.

BACKGROUND: Major vessel invasion is an important factor for determining the surgical approach and long-term prognosis for patients with pancreatic head cancer. However, clinical implications of vessel invasion have seldom been reported in pancreatic body or tail cancer. This study aimed to evaluate the clinical relevance of splenic vessel invasion with pancreatic body or tail cancer compared with no invasion and investigate prognostic factors. METHODS: This study enrolled patients who underwent upfront distal pancreatectomy from 2005 to 2018. The circular degree of splenic vessel invasion was investigated and categorized into three groups (group 1, no invasion; group 2, 0-180°; group 3, 180° or more). Clinicopathological variables and perioperative and survival outcomes were evaluated, and multivariable Cox proportional analysis was performed to evaluate prognostic factors. RESULTS: Among 249 enrolled patients, tumour size was larger in patients with splenic vessel invasion (3.9 versus 2.9 cm, P = 0.001), but the number of metastatic lymph nodes was comparable to that in patients with no vessel invasion (1.7 versus 1.4, P = 0.241). The 5-year overall survival rates differed significantly between the three groups (group 1, 38.4 per cent; group 2, 16.8 per cent; group 3, 9.7 per cent, P < 0.001). Patients with both splenic artery and vein invasion had lower 5-year overall survival rates than those with one vessel (7.5 versus 20.2 per cent, P = 0.021). Cox proportional analysis revealed adjuvant treatment, R0 resection and splenic artery invasion as independent prognostic factors for adverse outcomes in pancreatic body or tail cancer. CONCLUSION: Splenic vessel invasion was associated with higher recurrence and lower overall survival in pancreatic body or tail cancers suggesting a need for a neoadjuvant approach.