Safety and Feasibility of Intradiscal Administration of Matrilin-3-Primed Adipose-Derived Mesenchymal Stromal Cell Spheroids for Chronic Discogenic Low Back Pain: Phase 1 Clinical Trial.

Functionally enhanced mesenchymal stromal cells participate in the repair of intervertebral disc. This study aimed to assess the safety and tolerability of intradiscal administration of matrilin-3-primed adipose-derived stromal cell (ASC) spheroids with hyaluronic acid (HA) in patients with chronic discogenic low back pain (LBP). In this single-arm, open-label phase I clinical trial, eight patients with chronic discogenic LBP were observed over 6 months. Each patient underwent a one-time intradiscal injection of 1 mL of 6.0 × 106 cells/disc combined with HA under real-time fluoroscopic guidance. Safety and feasibility were gauged using Visual Analogue Scale (VAS) pain and Oswestry Disability Index (ODI) scores and magnetic resonance imaging. All participants remained in the trial, with no reported adverse events linked to the procedure or stem cells. A successful outcome-marked by a minimum 2-point improvement in the VAS pain score and a 10-point improvement in ODI score from the start were observed in six participants. Although the modified Pfirrmann grade remained consistent across all participants, radiological improvements were evident in four patients. Specifically, two patients exhibited reduced high-intensity zones while another two demonstrated decreased disc protrusion. In conclusion, the intradiscal application of matrilin-3-primed ASC spheroids with HA is a safe and feasible treatment option for chronic discogenic LBP.

Enhanced Intervertebral Disc Repair via Genetically Engineered Mesenchymal Stem Cells with Tetracycline Regulatory System.

The therapeutic potential of Mesenchymal stem cells (MSCs) for the treatment of Intervertebral disc (IVD) degeneration can be enhanced by amplifying specific cytokines and proteins. This study aimed to investigate the therapeutic potential of tetracycline-off system-engineered tonsil-derived mesenchymal stem cells (ToMSC-Tetoff-TGFß1-IGF1-BMP7) for treating intervertebral disc (IVD) degeneration. ToMSCs were isolated from a tonsillectomy patient and genetically modified with four distinct plasmids via CRISPR/Cas9-mediated knock-in gene editing. Transgene expression was confirmed through immunofluorescence, western blots, and an enzyme-linked immunosorbent assay for transforming growth factor beta 1 (TGFß1) protein secretion, and the effect of MSC-TetOff-TGFß1-IGF1-BMP7 on disc injury was assessed in a rat model. The ToMSC-Tetoff-TGFß1-IGF1-BMP7 treatment exhibited superior therapeutic effects compared to ToMSC-TGFß1, and ToMSC-SDF1α implantation groups, stimulating the regeneration of nucleus pulposus (NP) cells crucial for IVD. The treatment showed potential to restore the structural integrity of the extracellular matrix (ECM) by upregulating key molecules such as aggrecan and type II collagen. It also exhibited anti-inflammatory properties and reduced pain-inducing neuropeptides. ToMSC-Tetoff-TGFß1-IGF1-BMP7 holds promise as a novel treatment for IVD degeneration. It appears to promote NP cell regeneration, restore ECM structure, suppress inflammation, and reduce pain. However, more research and clinical trials are required to confirm its therapeutic potential.

Application of critical pathway of integrative medical service for lumbar herniated nucleus pulposus: A protocol for single-centered prospective observational study.

BACKGROUND: Lumbar herniated nucleus pulposus (L-HNP) is a condition in which fibroblasts escape due to degenerative changes or external forces in the intervertebral disc, causing neurological symptoms by compressing the dura mater or nerve root. OBJECTIVES: The purpose of this study is to analyze and compare the effectiveness, economic feasibility, and safety of using an integrated medical service critical pathway (CP) in L-HNP patients. METHODS: This single-center prospective observational study will be performed at Kyung Hee University Medicine Hospital and Kyung Hee University Korean Medicine Hospital. The inclusion criteria are a diagnosis of L-HNP on magnetic resonance imaging or computed tomography scans, age under 80 years, a visual analog scale score of 7 or higher for either lower back pain or lower extremity pain. The included 102 participants will be classified into 6 groups (n = 17 in each group): CP application with conservative treatment; CP application with open discectomy; CP application with intrabody fusion; conservative treatment without CP application; open discectomy without CP application; and interbody fusion without CP application. We will collect data on the visual analog scale, ODI, SF-36, and EQ-5D-3L scores; number of admission days; medical staff satisfaction; patients health service satisfaction; waiting time for consultations; use of pain relievers; and CP application and completion rates. CONCLUSION: In future, this study is expected to serve as a basis for follow-up studies on the development and application of CPs in integrated medical services for various diseases, including lumbar herniated nucleus pulposus.

Comparison of endoscopic retrograde cholangiopancreatography outcomes between cap-fitted forward and side viewing endoscopes in patients with Billroth II anastomosis.

BACKGROUND: There have been no previous studies that directly compared outcomes between cap-fitted forward-viewing and side viewing endoscopes (SE). This study aimed to compare the technical success rate and occurrence of adverse events between the side viewing and cap-fitted forward-viewing endoscope (CE) groups among patients with Billroth II anatomy who underwent ERCP. METHODS: The medical records of patients with a previous history of subtotal gastrectomy using Billroth II reconstruction who underwent ERCP at Yeungnam University Hospital between January 2004 and December 2020 were reviewed retrospectively. The patients were divided into CE and SE group. Propensity score matching analysis was performed to minimize selection bias. RESULTS: Propensity score matching resulted in 55 matched pairs for further analysis. Patients' characteristics were comparable in the matched cohorts. Final success rate of selective bile duct cannulation was not significantly different between the SE and CE groups (98.2% vs. 94.5%, p = 0.308). The complete CBD stone removal rate in CBD stone and successful biliary drainage rate in malignant biliary obstruction were not significantly different between the two groups. The rate of total ERCP-related adverse events was higher in the CE group than in the SE group, but the difference was not statistically significant (10.9% vs. 7.3%, p = 0.507). Among adverse events, the rate of post-ERCP pancreatitis showed higher tendency in the CE group than in the SE group (10.9% vs. 5.5%, p = 0.297). CONCLUSION: In conclusion, CE seems to be equally effective as SE for ERCP in patients with Billroth II anatomy. However, attention should be paid to development of post ERCP complications, especially pancreatitis, when performed by CE.

An Injectable Engineered Cartilage Gel Improves Intervertebral Disc Repair in a Rat Nucleotomy Model.

Lower back pain is a major problem caused by intervertebral disc degeneration. A common surgical procedure is lumbar partial discectomy (excision of the herniated disc causing nerve root compression), which results in further disc degeneration, severe lower back pain, and disability after discectomy. Thus, the development of disc regenerative therapies for patients who require lumbar partial discectomy is crucial. Here, we investigated the effectiveness of an engineered cartilage gel utilizing human fetal cartilage-derived progenitor cells (hFCPCs) on intervertebral disc repair in a rat tail nucleotomy model. Eight-week-old female Sprague-Dawley rats were randomized into three groups to undergo intradiscal injection of (1) cartilage gel, (2) hFCPCs, or (3) decellularized extracellular matrix (ECM) (n = 10/each group). The treatment materials were injected immediately after nucleotomy of the coccygeal discs. The coccygeal discs were removed six weeks after implantation for radiologic and histological analysis. Implantation of the cartilage gel promoted degenerative disc repair compared to hFCPCs or hFCPC-derived ECM by increasing the cellularity and matrix integrity, promoting reconstruction of nucleus pulposus, restoring disc hydration, and downregulating inflammatory cytokines and pain. Our results demonstrate that cartilage gel has higher therapeutic potential than its cellular or ECM component alone, and support further translation to large animal models and human subjects.

How does COVID-19 differ from previous crises? A comparative study of health-related crisis research in the tourism and hospitality context.

The importance of the risk to tourism and hospitality operations from pandemic-related crises has increased. Therefore, the current study offers a literature review targeting tourism and hospitality stakeholders' perceptions of past diseases and has three objectives: (1) Explore major topics from previous research on infectious diseases using topic modeling; (2) compare non-COVID-19 and COVID-19 crises; (3) investigate research topics in the tourism and hospitality industries. To meet our research objectives, we reviewed published pandemic-related articles in the tourism and hospitality literature since the year 2000. Based on the results, we first identified nine key topics related to infectious diseases (i.e., policy, human resources, branding, resilience, technology, global or community change, risk perception, disease impact, and lifestyle). Second, we suggest the application of different topic weights in non-COVID-19 and COVID-19 research. Third, we found that it is appropriate to apply different topic weights in tourism and hospitality research.

Comparison of Inflammatory Markers Changes in Patients Who Used Postoperative Prophylactic Antibiotics within 24 Hours after Spine Surgery and 5 Days after Spine Surgery.

OBJECTIVE: C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR), and white blood cell (WBC) count are inflammatory markers used to evaluate postoperative infections. Although these markers are non-specific, understanding their normal kinetics after surgery may be helpful in the early detection of postoperative infections. To compliment the recent trend of reducing the duration of antibiotic use, this retrospective study investigated the inflammatory markers of patients who had received antibiotics within 24 hours after surgery according to the Health Insurance Review & Assessment Service guidelines and compared them with those of patients who had received antibiotics for 5 days, which was proven to be non-infectious. METHODS: We enrolled 74 patients, divided into two groups. Patients underwent posterior lumbar interbody fusion (PLIF) at a single institution between 2019 and 2020. Group A included 37 patients who received antibiotics within 24 hours after the PLIF procedure, and group B comprised 37 patients who had used antibiotics for 5 days. A 1 : 1 nearest-neighbor propensity-matched analysis was used. The clinical variables included age, sex, medical history, body mass index, estimated blood loss, and operation time. Laboratory data included CRP, ESR, and WBC, which were measured preoperatively and on postoperative days (POD) 1, 3, 5, and 7. RESULTS: CRP dynamics tended to decrease after peaking on POD 3, with a similar trend in both groups. The average CRP level in group B was slightly higher than that in group A; however, the difference was not statistically significant. Multiple linear regression analysis revealed operation time, number of fused levels, and estimated blood loss as significant predictors of a greater CRP peak value (r²=0.473, p<0.001) in patients. No trend (a tendency to decrease from the peak value) could be determined for ESR and WBC count on POD 7. CONCLUSION: Although slight differences were observed in numerical values and kinetics, sequential changes in inflammatory markers according to the duration of antibiotic administration showed similar patterns. Knowledge of CRP kinetics allows the assessment of the degree of difference between the clinical and expected values.

Clinical application of the optimized X-ray parameter model through analysis of disease risk and image quality when combining the ion chamber of automatic exposure control of digital radiography.

OBJECTIVE: To present an optimized examination model by analyzing the risk of disease and image quality according to the combination of the ion chamber of automatic exposure control (AEC) with digital radiography (DR). METHODS: The X-ray quality was analyzed by first calculating the percentage average error (PAE) of DR. After that, when using AEC, the combination of the ion chambers was the same as the left and centre and right, right and centre, left and centre, centre, right, and left, for a total of six. Accordingly, the entrance surface dose (ESD), risk of disease, and image quality were evaluated. ESD was obtained by attaching a semiconductor dosimeter to the L4 level of the lumbar spine, and then irradiating X-rays to dosimeter centre through average and standard deviation of radiation dose. The calculated ESD was input into the PCXMC 2.0 programme to evaluate disease risk caused by radiation. Meanwhile, image quality according to chamber combination was quantified as the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) through Image J. RESULTS: X-ray quality of DR used in the experiment was within the normal range of±10. ESD of six ion chamber combinations was 1.363mGy, 0.964mGy, 0.946mGy, 0.866mGy, 0.748mGy, 0.726mGy for lumbar anteroposterior (AP), and the lumbar lateral values were 1.126mGy, 0.209mGy, 0.830mGy, 0.662mGy, 0.111mGy, and 0.250mGy, respectively. Meanwhile, disease risk analyzed through PCXMC 2.0 was bone marrow, colon, liver, lung, stomach, urinary and other tissue cancer, and disease risk showed a tendency to increase in proportion to ESD. SNR and CNR recorded the lowest values when three chambers were combined and did not show proportionality with dose, while showed the highest values when two chambers were combined. CONCLUSION: In this study, combination of three ion chambers showed the highest disease risk and lowest image quality. Using one ion chamber showed the lowest disease risk, but lower image quality than two ion chambers. Therefore, if considering all above factors, combination of two ion chambers can optimally maintain the disease risk and image quality. Thus, it is considered an optimal X-ray examination parameter.

Natural Course of Early Detected Acute Peripancreatic Fluid Collection in Moderately Severe or Severe Acute Pancreatitis.

Background and Objectives: Acute peripancreatic fluid collection (APFC) is an acute local complication of acute pancreatitis (AP) according to the revised Atlanta classification. Sometimes APFC resolves completely, sometimes it changes into a pseudocyst or walled-off necrosis (WON), so called late complications. The aim of this study is to investigate the natural course of APFC detected on early computed tomography (CT) in moderately severe (MSAP) or severe AP (SAP). Materials and Methods: From October 2014 to September 2015, patients with MSAP or SAP were enrolled if there was APFC within 48 h of onset on imaging studies at six medical centers. The status of fluid collection was followed 4-8 weeks after onset. Initial laboratory findings, CT findings and clinical scoring systems were analyzed. Results: A total of 68 patients were enrolled and APFC was completely resolved in 32 (66.7%) patients in the MSAP group and 9 (34.6%) in the SAP group. Patients with a high bedside index for severity in acute pancreatitis (BISAP) score (≥3 points) were common in the SAP group. C-reactive protein (CRP) after 48 h from admission and BUN level were also high in the SAP group. In multivariate analysis, BISAP score (≥3 points), elevation of CRP after 48 h (≥150 mg/L) and nasojejunal feeding after 48 h were risk factors for the development of late complications. Conclusions: Spontaneous resolution of APFC was more common in MSAP group and APFC can be changed to pseudocyst or WON in patients with elevated BISAP score, CRP level after 48 h, and non-improved abdominal pain.

What Topics Do Members of the Eating Disorder Online Community Discuss and Empathize with? An Application of Big Data Analytics.

Given the stigma of eating disorders (EDs), anonymous online communities of individuals with EDs can play a critical role in their treatment. In our study, we aimed to identify prevalent topics related to EDs in one community. To discover latent topics in an online community dedicated to EDs, we applied an automated text-mining approach to topic modeling after collecting data from Reddit created between January 2011 and September 2020. As a result of topic modeling, topics regarding emotional support, informational support, and inquiries about EDs were discovered. In frequently asked questions and advice about EDs in the online community, community members empathized more with topics soliciting emotional support rather than informational support. Despite the importance of online communities, studies on this topic, especially those analyzing online conversations, have remained limited. By demonstrating the role of online communities in supplementary interventions, our findings can support clinicians in caring for patients with EDs.

Veganism during the COVID-19 pandemic: Vegans' and nonvegans' perspectives.

Although the COVID-19 pandemic has triggered growing public interest in veganism, veganism's conceptualization remains ambiguous. Moreover, vegans' and nonvegans' different perspectives have rarely been addressed. Hence, this study involved the opinions of both vegans and nonvegans in the COVID-19 context to understand their attitudes, motivations, and opinions related to veganism. We analyzed online discourses in vegan and antivegan online communities using Word2Vec analysis and qualitative analysis. We identified lists of terms associated with three key veganism dimensions (i.e., lifestyle, animal rights, and food). Moreover, we compared actual online discussions among vegans to those among nonvegans regarding specific veganism attributes. This study preliminarily identifies specific attributes associated with veganism in online discourse among vegans. The issues addressed in this study can be tested in future research. Our findings can also be useful for people in various stages of veganism-such as active vegans, people who are interested in veganism, or even nonvegans who are uninterested in veganism-to comprehend the different perceptions prevailing in each group.

Comparison of the impact of endoscopic retrograde cholangiopancreatography between pre-COVID-19 and current COVID-19 outbreaks in South Korea: Retrospective survey.

BACKGROUND: The coronavirus disease 2019 (COVID-19) outbreak has markedly influenced the endoscopic patterns. Endoscopic retrograde cholangiopancreatography (ERCP) is an essential technique for pancreatobiliary disease but increases the risk of exposure to the virus-containing body fluid; however, the impact of COVID-19 on ERCP is unknown. AIM: To compare the number of endoscopic activities and to analyze the clinical outcomes of ERCPs before and during the COVID-19 outbreak in Daegu, South Kore. METHODS: This retrospective cohort study included patients aged ≥ 18 years who underwent ERCP between February 18 and March 28, 2020, at a tertiary hospital. ERCP indications and endoscopic details were compared with those from the same period in 2018 and 2019 as control groups. RESULTS: Of the 269 ERCP procedures, 113 (42.0%) cases were performed as emergency procedures. The number of ERCP procedures in 2018 and 2019 decreased by 20.2% and 56.6%, respectively, compared with that in 2020 (P < 0.01); among the 113 emergency ERCPs, the observed numbers in 2018 (n = 42) and 2019 (n = 55) dramatically dropped by 61.9% and 70.9%, respectively, compared with that in 2020 (n = 16). Of the 16 cases in 2020, stone removal was performed in five, biliary stenting in five, sphincterotomy in five, and nasobiliary drainage in one. No case of ERCP-related infection in medical workers or other patients has been reported. CONCLUSION: The COVID-19 outbreak significantly reduced the number of ERCPs; however, there is no difference in the indications and endoscopic interventions before and during the COVID-19 outbreak.

A Concomitant Occurrence of the Atlantoaxial Subluxation with Rare Vertebral Formation and Segmentation Defects.

An atlantoaxial subluxation from the unstable Os odontoideum by the failure of proper integrations between the embryological somites might be a commonly reported pathology. However, its suspicious origin or paralleled occurrence with other congenital anomalies of vertebral body might be a relatively rare phenomenon. The authors present two cases, who simply presented with clinical signs of prolonged, intractable cervicalgia without any neurological deficits, revealed this rare feature of C1-2 subluxation from the unstable, orthotropic type of Os odontoideum that coincide with congenitally fused cervical vertebral bodies between C2-3. Surprisingly, in one case, when traced from the lower cervical down to the thoracic-lumbar levels during the preoperative work-up process, was also compromised with multi-level butterfly vertebrae formations. Presented cases highlight the association of various congenital vertebrae anomalies and the rationale to fuse only affected joints.

Changes in endoscopic patterns before and during COVID-19 outbreak: Experience at a single tertiary center in Korean.

BACKGROUND: The surge of coronavirus disease 2019 (COVID-19) patients has markedly influenced the treatment policies of tertiary hospitals because of the need to protect medical staff and contain viral transmission, but the impact COVID-19 had on emergency gastrointestinal endoscopies has not been determined. AIM: To compare endoscopic activities and analyze the clinical outcomes of emergency endoscopies performed before and during the COVID-19 outbreak in Daegu, the worst-hit region in South Korea. METHODS: This retrospective cohort study was conducted on patients aged ≥ 18 years that underwent endoscopy from February 18 to March 28, 2020, at a tertiary hospital in Daegu. Demographics, laboratory findings, types and causes of emergency endoscopies, and endoscopic reports were reviewed and compared with those obtained for the same period in 2018 and 2019. RESULTS: From February 18 to March 28, a total of 366 emergent endoscopic procedures were performed: Upper endoscopy (170, 50.6%), endoscopic retrograde cholangiopancreatography (113, 33.6%), and colonoscopy with sigmoidoscopy (53, 15.8%). The numbers of procedures performed in 2018 and 2019 dropped by 48.8% and 54.8%, respectively, compared with those in 2020. During the COVID-19 outbreak, the main indications for endoscopy were melena (36.7%), hematemesis (30.6%), and hematochezia (10.2%). Of the endoscopic abnormalities detected, gastrointestinal bleeding was the most common: 39 cases in 2018, 51 in 2019, and 35 in 2020. CONCLUSION: The impact of COVID-19 is substantial and caused dramatic reductions in endoscopic procedures and changes in patient behaviors. Long-term follow-up studies are required to determine the effects of COVID-19 induced changes in the endoscopy field.

Difficult Biliary Cannulation from the Perspective of Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis: Identifying the Optimal Timing for the Rescue Cannulation Technique.

Background/Aims: Recently, the European Society of Gastrointestinal Endoscopy (ESGE) proposed criteria for "difficult biliary cannulation" during endoscopic retrograde cholangiopancreatography (ERCP). This study aimed to investigate the clinical relevance of the ESGE criteria from the perspective of post-ERCP pancreatitis (PEP). Methods: An ERCP database was prospectively maintained between November 2014 and December 2015 across six teaching hospitals in South Korea. The ESGE criteria (biliary cannulation time, the number of cannulation attempts, and inadvertent pancreatic duct [PD] manipulation) were recorded in this database as well as other technical factors. Logistic regression analysis was used to identify risk factors for PEP. Then, the PEP prediction model was investigated using decision tree analysis. Results: We analyzed 1,067 consecutive patients with naïve papilla. The overall rate of PEP was 6.6%. Multivariate analysis revealed that female sex (odds ratio [OR], 1.860; 95% confidence interval [CI], 1.124 to 3.078), a selective biliary cannulation duration >5 minutes (OR, 3.282; 95% CI, 1.641 to 6.566), and inadvertent PD manipulation (OR, 2.614; 95% CI, 1.480 to 4.617) were significant factors affecting PEP. Decision tree analysis revealed that biliary cannulation time (χ2=49.857, p<0.001) and inadvertent PD manipulation (χ2=8.556, p=0.010) were decisive factors. PEP occurred in 3.9%, 11.8%, and 16.2% of patients with biliary cannulation duration lasting 3 to 5 minutes, >5 minutes, and >5 minutes with inadvertent PD manipulation, respectively. Conclusions: Biliary cannulation time and inadvertent PD manipulation could be relevant indicators of PEP, and 5 minutes might be used as a cutoff value for the implementation of the rescue cannulation technique.