ABSTRACT
Purpose@#For precision medicine, exploration and monitoring of molecular biomarkers are essential. However, in advanced gastric cancer (GC) with visceral lesions, an invasive procedure cannot be performed repeatedly for the follow-up of molecular biomarkers. @*Materials and Methods@#To verify the clinical implication of serial liquid biopsies targeting circulating tumor DNA (ctDNA) on treatment response, we conducted targeted deep sequencing for serially collected ctDNA of 15 HER2-positive metastatic GC patients treated with anti-PD-1 inhibitor in combination with standard systemic treatment. @*Results@#In the baseline ctDNAs, 14 patients (93%) harbored more than one genetic alteration. A number of mutations in wellknown cancer-related genes, such as KRAS and PIK3CA, were identified. Copy number alterations were identified in eight GCs (53.3%), and amplification of the ERBB2 gene (6/15, 40.0%) was the most recurrent. When we calculated the mean variant allele frequency (VAF) of mutations in each ctDNA as the molecular tumor burden index (mTBI), the mTBI trend was largely consistent with the VAF profiles in both responder and non-responder groups. Notably, in the longitudinal analysis of ctDNA, mTBI provided 2–42 weeks (mean 13.4 weeks) lead time in the detection of disease progression compared to conventional follow-up with CT imaging. @*Conclusion@#Our data indicate that the serial genetic alteration profiling of ctDNA is feasible to predict treatment response in HER2-positive GC patients in a minimally invasive manner. Practically, ctDNA profiles are useful not only for the molecular diagnosis of GC but also for the selection of GC patients with poor prognosis for systemic treatment (ClinicalTrials.gov identifier:NCT02901301).
ABSTRACT
Purpose@#This study aimed to (1) evaluate the outcomes of below-knee prosthetic bypass (BKPB) in the absence of the great saphenous vein, and (2) identify risk factors associated with these outcomes. @*Materials and Methods@#This study included 37 consecutive patients who underwent BKPB with or without distal modification between 2010 and 2022. We further assessed the following treatment outcomes: primary patency (PP), secondary patency (SP), limb salvage (LS), and amputation-free survival (AFS) rates. The risk factors for PP were also examined. @*Results@#Most patients (n=31) were male. In 32 (86.5%) patients, BKPBs were performed for chronic limb-threatening ischemia. At the time of initial admission, two (5.4%) early deaths and three (8.1%) major amputations were noted. At 1 year after BKPB, the overall PP, SP, LS, and AFS rates were 78%, 85%, 85%, and 70%, respectively; at 3 years, they were 58%, 70%, 80%, and 52%, respectively; and at 5 years, they were 35%, 58%, 62%, and 29%, respectively. Notably, PP was significantly lower in limbs with ≤1 patent tibial arteries than in limbs with ≥2 patent artery (hazard ratio [HR], 3.80; 95% confidence interval [CI], 1.14-12.69 for overall; and HR, 12.97; 95% CI, 2.15-78.08 for distal anastomosis to below-knee popliteal artery). However, the PP was unaffected by the distal modification. @*Conclusion@#BKPB is a viable option for LS in patients with extensive femoropopliteal disease. Tibial runoff was significantly correlated with patency; therefore, decision-making for BKPB and follow-up must involve careful evaluation of the outflow arteries.
ABSTRACT
Gout is the most common form of arthritis, with the prevalence increasing worldwide. The present treatment guidelines provide recommendations for the appropriate treatment of acute gout, management during the inter-critical period, and prevention of chronic complications. The guidelines were developed based on evidence-based medicine and draft recommendations finalized after expert consensus. These guidelines are designed to provide clinicians with clinical evidence to enable efficient treatment of gout.
ABSTRACT
Background@#The costoclavicular brachial plexus block (CCB) is a recently established technique that uses the infraclavicular approach and is performed just below the clavicle. This meta-analysis aimed to determine whether CCB can reduce the incidence of hemidiaphragmatic paralysis (HDP), which is a major adverse event related to brachial plexus block (BPB), while yielding comparable block performance as other BPB techniques. @*Methods@#We searched electronic databases to identify relevant studies that compared the incidence of HDP between CCB and other BPB techniques. The primary outcome was the incidence of HDP following CCB and other BPB techniques. The secondary outcomes were pulmonary function test results, other adverse events, and block performance parameters such as onset and performance time. @*Results@#We included six randomized controlled trials that included 414 patients. Compared with the other BPB group, the CCB group had a significantly lower incidence of HDP (relative ratio: 0.21, 95% CI [0.12, 0.36], P < 0.001) and higher peak expiratory flow rate (mean difference: 0.68 L/s, 95% CI [0.13, 1.23], P = 0.015). There were no significant between-group differences with respect to other adverse events and block performance parameters. @*Conclusions@#Compared with other BPB techniques, CCB involves a lower incidence of HDP with comparable onset and performance time.
ABSTRACT
Background and Objectives@#The prognostic or safety implication of renin-angiotensinaldosterone system inhibitors (RASi) in hypertrophic cardiomyopathy (HCM) are not well established, mainly due to concerns regarding left ventricular outflow tract (LVOT) obstruction aggravation. We investigated the implications of RASi in a sizable number of HCM patients. @*Methods@#We enrolled 2,104 consecutive patients diagnosed with HCM in 2 tertiary university hospitals and followed up for five years. RASi use was defined as the administration of RASi after diagnostic confirmation of HCM. The primary and secondary outcomes were all-cause mortality and hospitalization for heart failure (HHF). @*Results@#RASi were prescribed to 762 patients (36.2%). During a median follow-up of 48.1months, 112 patients (5.3%) died, and 94 patients (4.5%) experienced HHF. Patients using RASi had less favorable baseline characteristics than those not using RASi, such as older age, more frequent history of comorbidities, and lower ejection fraction. Nonetheless, there was no difference in clinical outcomes between patients with and without RASi use (log-rank p=0.368 for all-cause mortality and log-rank p=0.443 for HHF). In multivariable analysis, patients taking RASi showed a comparable risk of all-cause mortality (hazard ratio [HR], 0.70, 95% confidence interval [CI], 0.43–1.14, p=0.150) and HHF (HR, 1.03, 95% CI, 0.63–1.70, p=0.900). In the subgroup analysis, there was no significant interaction of RASi use between subgroups stratified by LVOT obstruction, left ventricular (LV) ejection fraction, or maximal LV wall thickness. @*Conclusions@#RASi use was not associated with worse clinical outcomes. It might be safely administered in patients with HCM if clinically indicated.
ABSTRACT
Background and Objectives@#Tricuspid valve (TV) repair techniques other than annuloplasty remain challenging and frequently end in tricuspid valve replacement (TVR) in complicated cases. However, the results of TVR are suboptimal compared with TV repair. This study aimed to evaluate the clinical effectiveness of TV edge-to-edge repair (E2E) compared to TVR for severe tricuspid regurgitation (TR). @*Methods@#We retrospectively reviewed 230 patients with severe TR who underwent E2E (n=139) or TVR (n=91) from 2001 to 2020. Clinical and echocardiographic results were analyzed using inverse probability of treatment weighting analysis and propensity score matching. @*Results@#The two groups showed no significant differences in early mortality and morbidities. During the mean follow-up of 106.2±68.8 months, late severe TR and TV reoperation rates were not significantly different between groups. E2E group, however, showed better outcomes in overall survival (p=0.023), freedom from significant tricuspid stenosis (TS) (trans-tricuspid pressure gradient ≥5 mmHg, p=0.021), and freedom from TVrelated events (p<0.001). Matched analysis showed consistent results. @*Conclusions@#E2E for severe TR presented more favorable clinical outcomes than TVR. Our study supports that E2E might be a valuable option in severe TR surgery, avoiding TVR.
ABSTRACT
Objective@#Venom-induced coagulopathy (VIC) is a common snakebite complication that can cause life-threatening hemorrhage. Previous studies have shown that snake venom can cause a decrease in the erythrocyte sedimentation rate (ESR), but this has not been investigated in actual clinical practice. This study evaluated the clinical utility of erythrocyte sedimentation rate as a predictive factor for VIC in patients with a poisonous snakebite. @*Methods@#From January 2012 to December 2021, this study performed a retrospective study of patients with venomous snakebites presenting to a tertiary emergency department. The demographic and laboratory data were collected through a chart review. The patients were divided into two groups, VIC and NoVIC groups. Logistic regression analysis was performed to identify the factors that predicted the presence of VIC, and the receiver operating characteristic (ROC) curve was drawn. @*Results@#One hundred and fifty-three patients were enrolled, and 31 patients (20.3%) developed VIC. The VIC group had significantly lower ESR than the NoVIC group (5.1±5.6 vs. 14.8±13.8; P<0.001). Logistic regression analysis showed that the decreased ESR was associated with the occurrence of coagulopathy (odds ratio, 0.957; 95% confidence interval, 0.917-0.999; P=0.045). The area under the curve was 0.701 in the ROC curve, and the cutoff value was set to 4.5 mm/hr. @*Conclusion@#ESR measured upon arrival at the emergency department was available to predict venom-induced coagulopathy in snakebite patients.
ABSTRACT
Objective@#The extent of regional variations in cardiovascular risk and associated risk factors in patients with gout in South Korea remains unclear. Therefore, we aimed to investigate the risk of major cardiovascular events in gout patients in different regions. @*Methods@#This was a nationwide cohort study based on the claims database of the Korean National Health Insurance and the National Health Screening Program. Patients aged 20 to 90 years newly diagnosed with gout after January 2012 were included. After cardiovascular risk profiles before gout diagnosis were adjusted, the relative risks of incident cardiovascular events (myocardial infarction, cerebral infarction, and cerebral hemorrhage) in gout patients in different regions were assessed. @*Results@#In total, 231,668 patients with gout were studied. Regional differences in cardiovascular risk profiles before the diagnosis were observed. Multivariable analysis showed that patients with gout in Jeolla/Gwangju had a significantly high risk of myocardial infarction (adjusted hazard ratio [aHR], 1.27; 95% confidence interval [CI], 1.02~1.56; p=0.03). In addition, patients with gout in Gangwon (aHR, 1.38; 95% CI, 1.09~1.74; p<0.01), Jeolla/Gwangju (aHR, 1.41; 95% CI, 1.19~1.67; p<0.01), and Gyeongsang/ Busan/Daegu/Ulsan (aHR, 1.37; 95% CI, 1.19~1.59; p<0.01) had a significantly high risk of cerebral infarction. @*Conclusion@#We found there were regional differences in cardiovascular risk and associated risk factors in gout patients. Physicians should screen gout patients for cardiovascular risk profiles in order to facilitate prompt diagnosis and treatment.
ABSTRACT
Gout is the most common form of arthritis, with the prevalence increasing worldwide. The present treatment guidelines provide recommendations for the appropriate treatment of acute gout, management during the inter-critical period, and prevention of chronic complications. The guidelines were developed based on evidence-based medicine and draft recommendations finalized after expert consensus. These guidelines are designed to provide clinicians with clinical evidence to enable efficient treatment of gout.
ABSTRACT
The cytological diagnosis of lymph node lesions is extremely challenging because of the diverse diseases that cause lymph node enlargement, including both benign and malignant or metastatic lymphoid lesions. Furthermore, the cytological findings of different lesions often resemble one another. A stepwise diagnostic approach is essential for a comprehensive diagnosis that combines: clinical findings, including age, sex, site, multiplicity, and ultrasonography findings; low-power reactive, metastatic, and lymphoma patterns; high-power population patterns, including two populations of continuous range, small monotonous pattern and large monotonous pattern; and disease-specific diagnostic clues including granulomas and lymphoglandular granules. It is also important to remember the histological features of each diagnostic category that are common in lymph node cytology and to compare them with cytological findings. It is also essential to identify a few categories of diagnostic pitfalls that often resemble lymphomas and easily lead to misdiagnosis, particularly in malignant small round cell tumors, poorly differentiated squamous cell carcinomas, and nasopharyngeal undifferentiated carcinoma. Herein, we review a stepwise approach for fine needle aspiration cytology of lymphoid diseases and suggest a diagnostic algorithm that uses this approach and the Sydney classification system.
ABSTRACT
Purpose@#Obesity has emerged as a critical global public health concern as it is associated with and increases susceptibility to various diseases. This condition is characterized by the excessive enlargement of adipose tissue, primarily stemming from an inequity between energy intake and expenditure. The purpose of this study was to investigate the potential of sweet pumpkin powder in mitigating obesity and metabolic disorders in leptin-deficient obese (ob/ob) mice and to compare the effects of raw sweet pumpkin powder (HNSP01) and heat-treated sweet pumpkin powder (HNSP02). @*Methods@#Leptin-deficient obese mice were fed a diet containing 10% HNSP01 and another containing 10% HNSP02 for 6 weeks. @*Results@#The supplementation of ob/ob mice with HNSP01 and HNSP02 resulted in decreased body weight gain, reduced adipose tissue weight, and a smaller size of lipid droplets in the adipose tissue and liver. Furthermore, the ob/ob-HNSP01 and ob/ob-HNSP02 supplemented groups exhibited lower levels of triglycerides, total cholesterol, low-density lipoprotein cholesterol, fasting blood glucose, and insulin, as well as a reduced atherogenic index in comparison with the control group. Molecular analysis also demonstrated that the intake of HNSP01 and HNSP02 resulted in a diminished activation of factors associated with fatty acid synthesis, including acetyl-CoA carboxylase and fatty acid synthase, while concurrently enhancing factors associated with lipolysis, including adipose triglyceride lipase and hormone-sensitive lipase, in the adipose tissue. @*Conclusion@#Taken together, these findings collectively demonstrate the potential of sweet pumpkin powder as a functional food ingredient with therapeutic properties against obesity and its associated metabolic disorders, such as insulin resistance and dyslipidemia.
ABSTRACT
Background/Aims@#It remains unclear which maintenance treatment modality is most appropriate for mild gastroesophageal reflux disease (GERD).We aimed to compare on-demand treatment with continuous treatment using a proton pump inhibitor (PPI) in the maintenance treatment for patients with non-erosive GERD or mild erosive esophagitis. @*Methods@#Patients whose GERD symptoms improved after 4 weeks of standard dose PPI treatment were prospectively enrolled at 25 hospitals.Subsequently, the enrolled patients were randomly assigned to either an on-demand or a continuous maintenance treatment group, and followed in an 8-week interval for up to 24 weeks. @*Results@#A total of 304 patients were randomized to maintenance treatment (continuous, n = 151 vs on-demand, n = 153). The primary outcome, the overall proportion of unwillingness to continue the assigned maintenance treatment modality, failed to confirm the noninferiority of on-demand treatment (45.9%) compared to continuous treatment (36.1%). Compared with the on-demand group, the GERD symptom and health-related quality of life scores significantly more improved and the overall satisfaction score was significantly higher in the continuous treatment group, particularly at week 8 and week 16 of maintenance treatment. Work impairment scores were not different in the 2 groups, but the prescription cost was less in the on-demand group. Serum gastrin levels significantly elevated in the continuous treatment group, but not in the on-demand group. @*Conclusions@#Continuous treatment seems to be more appropriate for the initial maintenance treatment of non-erosive GERD or mild erosive esophagitis than on-demand treatment. Stepping down to on-demand treatment needs to be considered after a sufficient period of continuous treatment.
ABSTRACT
Background/Aims@#Gastroesophageal reflux disease (GERD) is a common chronic gastrointestinal disorder that typically requires long-term maintenance therapy. However, little is known about patient preferences and satisfaction and real-world prescription patterns regarding maintenance therapy for GERD. @*Methods@#This observational, cross-sectional, multicenter study involved patients from 18 referral hospitals in Korea. We surveyed patients who had been prescribed proton pump inhibitors (PPIs) for GERD for at least 90 days with a minimum follow-up duration of 1 year. The main outcome was overall patient satisfaction with different maintenance therapy modalities. @*Results@#A total of 197 patients were enrolled. Overall patient satisfaction, patient preferences, and GERD health-related quality of life scores did not significantly differ among the maintenance therapy modality groups. However, the on-demand therapy group experienced a significantly longer disease duration than the continuous therapy group. The continuous therapy group demonstrated a lower level of awareness of potential adverse effects associated with PPIs than the on-demand therapy group but received higher doses of PPIs than the on-demand therapy group. The prescribed doses of PPIs also varied based on the phenotype of GERD, with higher doses prescribed for non-erosive reflux disease than erosive reflux disease. @*Conclusion@#Although overall patient satisfaction did not significantly differ among the different PPI maintenance therapy modality groups, awareness of potential adverse effects was significantly different between the on-demand and continuous therapy groups.
ABSTRACT
Background@#Menorrhagia is a common cause of iron deficiency anemia (IDA) in premenopausal women. However, the effects of menorrhagia on IDA in premenopausal women have been underestimated compared to those on other IDA-related disorders (IRDs) such as gastrointestinal malignancies (GIMs). To better understand the relationship between menorrhagia and IDA in premenopausal women, we analyzed the National Health Insurance Service-National Health Information Database (NHIS-NHID). @*Methods@#From 2005 to 2008, data about women between the age of 20 and 59 years were extracted from the NHIS-NHID to create a propensity score-matched case (IDA) and control group. The annual incidence of IDA was calculated per age group. A 10-year follow up of the study population was determined to detect IRDs in case and control groups. We compared the risk of detection (ROD) of IRDs, including GIM and gynecological disorders associated with menorrhagia - leiomyoma of uterus (LM) and adenomyosis (AM), in the case and the control group. @*Results@#From 2005 to 2008, women diagnosed with IDA (n = 535,249) and healthy women as a control group (n = 1,070,498) were identified from the NHIS-NHID. The annual incidence of IDA was 767.4 (2005), 948.7 (2006), 981.6 (2007), and 897.7 (2008) per 100,000 women.The age distribution of IDA was similar each year; IDA was common in women aged 30–39 years (36–37%) and 40–49 years (30–32%), and its incidence was significantly decreased in women aged 50–59 years (< 10%). The ROD of IRDs were significantly higher in the IDA group than in the control group (LM: 20.8% vs. 6.9%, AM: 5.6% vs. 1.6%, and GIM: 2.6% vs.0.7%). The corresponding hazard ratios were 3.89 (95% confidence interval [CI], 3.85–3.93) for LM, 4.99 (95% CI, 4.90–5.09) for AM, and 3.43 (95% CI, 3.32–3.55) for GIM. The ROD of the IRDs varied; the ROD of LM in the IDA group increased with age and decreased in the age group 50–59 years. AM was more frequently detected in women with IDA aged 30–39 years and less in women older than 40 years. The frequency of GIM increased with age. @*Conclusion@#In this study, we found that the gynecologic disease is the main cause of IDA in premenopausal women. Gynecological evaluations should be performed more actively in the clinic to prevent and control IDA and IRDs.
ABSTRACT
Living liver donors (LLDs) are screened for transmissible diseases including cancer. We investigated the actual cancer incidence of LLDs compared with a matched healthy control group from the general Korean population using data from the Korean National Health Insurance Services (NHIS). A total of 12,372 LLDs who donated a liver graft between 2002 and 2018 were registered in the Korean Network for Organ Sharing. They were compared to a matched healthy control group selected from the Korean NHIS. Cancer diagnosis was identified in 175 LLDs (1.4%) and 1,014 controls (0.8%). Compared to the healthy control group, the incidence rate ratio of liver and thyroid cancer in the LLD group were significantly higher at 18.30 and 1.39, respectively. The incidences of 11 other specified cancers were not different between the two groups. The present study suggests that LLD after donor hepatectomy may require medical surveillance, especially for liver cancer.
ABSTRACT
Background@#Interscalene brachial plexus block (ISB) is a common regional technique to manage acute postoperative pain for arthroscopic rotator cuff tear repair. However, rebound pain may compromise its overall benefit. Our aim was to investigate the primary hypothesis that perineural and intravenous dexamethasone have different effects on rebound pain after resolution of ISB for arthroscopic rotator cuff tear repair. @*Methods@#Patients aged ≥ 20 years scheduled for elective arthroscopic rotator cuff tear repair under general anesthesia with preoperative ISB were included. The participants were randomized to receive dexamethasone either perineurally (perineural group) or intravenously (intravenous group). In the perineural group, patients received ISB with 12 mL of 0.5% ropivacaine containing 5 mg of dexamethasone; simultaneously, 1 mL of 0.9% normal saline was administered intravenously. In the intravenous group, patients received ISB with 12 mL of 0.5% ropivacaine; simultaneously, 1 mL of dexamethasone 5 mg was administered intravenously. The primary outcome was the difference in the pain score (0–10 on numeric rating scale) between before and after ISB resolution. The secondary outcomes were the incidence of rebound pain; onset, duration, and intensity of rebound pain; time to the first analgesic request; and pain-related sleep disturbance. @*Results@#A total of 71 patients were randomized to either perineural group (n = 36) or intravenous group (n = 35). After block resolution, pain scores increased significantly more in the perineural group (mean ± standard deviation, 4.9 ± 2.1) compared to the intravenous group (4.0 ± 1.7, P = 0.043). The duration of ISB was more prolonged in the perineural group (median [interquartile range], 19.9 [17.2–23.1] hours) than the intravenous group (15.1 [13.7–15.9] hours, P < 0.001). The incidence of rebound pain and pain-related sleep disturbance during the first postoperative week was significantly higher in the perineural group than in the intravenous group (rebound pain: 44.4% vs. 20.0%, P = 0.028; sleep disturbance: 55.6% vs. 25.7%, P = 0.011). The duration and intensity of rebound pain were similar between the two groups. @*Conclusion@#Although perineural dexamethasone provided longer postoperative analgesia, intravenous dexamethasone was more beneficial in reducing pain increase after ISB resolution, incidence of rebound pain, and pain-related sleep disturbance.
ABSTRACT
Purpose@#Gastric cancer (GC) is among the most prevalent and fatal cancers worldwide.National cancer screening programs in countries with high incidences of this disease provide medical aid beneficiaries with free-of-charge screening involving upper endoscopy to detect early-stage GC. However, the coronavirus disease 2019 (COVID-19) pandemic has caused major disruptions to routine healthcare access. Thus, this study aimed to assess the impact of COVID-19 on the diagnosis, overall incidence, and stage distribution of GC. @*Materials and Methods@#We identified patients in our hospital cancer registry who were diagnosed with GC between January 2018 and December 2021 and compared the cancer stage at diagnosis before and during the COVID-19 pandemic. Subgroup analyses were conducted according to age and sex. The years 2018 and 2019 were defined as the “before COVID” period, and the years 2020 and 2021 as the “during COVID” period. @*Results@#Overall, 10,875 patients were evaluated; 6,535 and 4,340 patients were diagnosed before and during the COVID-19 period, respectively. The number of diagnoses was lower during the COVID-19 pandemic (189 patients/month vs. 264 patients/month) than before it.Notably, the proportion of patients with stages 3 or 4 GC in 2021 was higher among men and patients aged ≥40 years. @*Conclusions@#During the COVID-19 pandemic, the overall number of GC diagnoses decreased significantly in a single institute. Moreover, GCs were in more advanced stages at the time of diagnosis. Further studies are required to elucidate the relationship between the COVID-19 pandemic and the delay in the detection of GC worldwide.
ABSTRACT
Background and Objectives@#To analyze mapping changes in dynamic range (DR) and neural response threshold (NRT) as prognostic factors for cochlear implant (CI). To analyze whether postoperative speech perception performance could be predicted using DR change and initial NRT. @*Subjects and Methods@#The speech comprehension data of 33 patients with CI were retrospectively analyzed after 1, 3, 6, and 12 months of device use. All subjects were adult, postlingually hearing-impaired, and Cochlear Nucleus CI users. Speech perception performance was evaluated using aided pure tone audiometry, consonant, vowel, one-word, two-word, and sentence tests. @*Results@#The averages of initial NRT and DR changes were 197.8±25.9 CU (104–236) and 22.2±18.4 CU (-15–79), respectively. The initial DR was 40.8±16.6 CU. The postoperative DR was 50.3±16.4 CU at 3 months, 58±12.3 CU at 6 months, and 62.9±10.4 CU at 12 months. A gradual increase of DR was observed during the first year of CI. Compared with the initial DR, significant increases in DR were observed at 3 (p<0.05), 6 (p<0.001), and 12 (p<0.001) months. Compared with initial speech performance outcomes, a significant gain in all performance outcomes was achieved at 12 months (p<0.001). @*Conclusions@#Patients with low NRT after CI surgery could initially set DR to a wider range and had better final speech perception outcomes. Conversely, patients with high NRT after CI surgery had to set up a gradual increase in DR while adjusting the T-C level, and the final speech perception outcomes were worse. DR and NRT, the main CI mapping variables, can help predict prognosis related to speech perception outcomes after CI surgery. In conclusion, the post-CI speech perception is better with a lower initial NRT, wider final DR, or younger age.
ABSTRACT
Mesenchymal stromal cells (MSCs) have attracted scientific and medical interest due to their self-renewing properties, pluripotency, and paracrine function. However, one of the main limitations to the clinical application of MSCs is their loss of efficacy after transplantation in vivo. Various bioengineering technologies to provide stem cell niche-like conditions have the potential to overcome this limitation. Here, focusing on the stem cell niche microenvironment, studies to maximize the immunomodulatory potential of MSCs by controlling biomechanical stimuli, including shear stress, hydrostatic pressure, stretch, and biophysical cues, such as extracellular matrix mimetic substrates, are discussed. The application of biomechanical forces or biophysical cues to the stem cell microenvironment will be beneficial for enhancing the immunomodulatory function of MSCs during cultivation and overcoming the current limitations of MSC therapy.
ABSTRACT
Background/Aims@#Among several methods used to prevent endoscopic submucosal dissection (ESD) bleeding, the recently developed hemostatic powder (HP) has few technical limitations and is relatively easy-to-use. This study aimed to analyze the hemostatic effects and mechanisms of two HPs using a porcine upper gastrointestinal hemorrhage model. @*Methods@#We evaluated HPs (Endospray and epidermal growth factor [EGF]-endospray) for adhesion, waterproofing ability, permeability, and absorption in vitro. ESD was performed to induce bleeding ulcers in the porcine stomachs. In a total of three pigs, three bleeding ulcers per animal were generated. Hemostasis and rebleeding were evaluated endoscopically. After 72 hours, the animals were sacrificed, and histologically analyzed. @*Results@#The water absorption of HPs was over 20 times the initial value within 30 minutes. The gelated HPs completely blocked water penetration into the applied site within 5 minutes and strongly adhered to the Petri-dish surface for up to 6 hours. The initial hemostasis rates within 5 minutes were 33.3%, 100.0%, and 66.7%, and the rebleeding rates at 6 to 72 hours after HP application were 33.3%, 16.7%, and 33.3% (control, Endospray, and EGF-endospray groups, respectively). Histological analysis revealed the thickness of the regenerated mucosa (522.1, 514.5, and 680.3 µm) and the submucosal layer (1,510.3, 2,848.2, and 3,062.3 µm) and the number of newly formed blood vessels (15.3, 17.9, and 20.5) in the control, Endospray, and EGFendospray groups, respectively. @*Conclusions@#The endoscopic HPs demonstrated the ability to elicit effective initial hemostasis and the histological ulcer-healing effect of EGF in an animal model of hemorrhagic gastric ulcers.