Enhancing Omicron Sublineage Neutralization: Insights From Bivalent and Monovalent COVID-19 Booster Vaccines and Recent SARS-CoV-2 Omicron Variant Infections.

BACKGROUND: Omicron variants have rapidly diversified into sublineages with mutations that enhance immune evasion, posing challenges for vaccination and antibody responses. This study aimed to compare serum cross-neutralizing antibody responses against various SARS-CoV-2 Omicron sublineages (BA.1, BA.5, XBB.1.17.1, FK.1.1, and JN.1) in recipients of monovalent COVID-19 boosters, bivalent booster recipients, and individuals who had recovered from Omicron BA.5 infections. METHODS: We conducted a micro-neutralization assay on serum samples from monovalent BNT162b2 booster recipients (N = 54), bivalent BNT162b2 booster recipients (N = 24), and SARS-CoV-2 Omicron BA.5-recovered individuals (N = 13). The history of SARS-CoV-2 Omicron infection was assessed using ELISA against the SARS-CoV-2 NP protein. RESULTS: Bivalent booster recipients exhibited significantly enhanced neutralization efficacy against Omicron sublineages compared to those who had received monovalent booster vaccinations. Omicron BA.5-recovered individuals displayed similar neutralizing antibodies (NAbs) to the bivalent booster recipients. Despite the improved neutralization in bivalent recipients and BA.5-recovered individuals, there were limitations in neutralization against the recently emerged Omicron subvariants: XBB.1.17.1 FK.1.1, and JN.1. In both monovalent and bivalent booster recipients, a history of Omicron breakthrough infection was associated with relatively higher geometric mean titers of NAbs against Omicron BA.1, BA.5, and XBB.1.17.1 variants. CONCLUSION: This study underscores the intricate interplay between vaccination strategies, immune imprinting, and the dynamic landscape of SARS-CoV-2 variants. Although bivalent boosters enhance neutralization, addressing the challenge of emerging sublineages like XBB.1.17.1, FK.1.1, and JN.1 may necessitate the development of tailored vaccines, underscoring the need for ongoing adaptation to effectively combat this highly mutable virus.

Prognostic significance of histologic phenotype in periampullary adenocarcinomas.

Background: Periampullary adenocarcinomas typically exhibit either intestinal or pancreatobiliary (PB) differentiation, and the type of differentiation may be prognostically more important than the anatomic site of origin. This study aimed to evaluate prognostic significance of histological type of periampullary carcinomas. Methods: Microscopic slides from 110 consecutive pancreatoduodenectomies performed between 2010 and 2020 were reviewed and classified as intestinal or PB type. Clinicopathological factors were compared between PB-(n=93) and intestinal-type (n=17) differentiation. Results: The intestinal type included significantly more patients with well-differentiated histology (35.3% vs. 11.8%, p=0.001) and fewer patients with perineural invasion (41.2% vs. 76.4%, p=0.029), advanced T stage (> T3; 41.2% vs.74.2%, p=0.007), and systemic recurrence (71.4% vs. 92.9%, p=0.005) than PB type. The 5-year-overall survival rate of intestinal-type was significantly higher than that of PB-type (58.8% vs. 20.4%, p=0.003). When pancreatic cancer was separately analyzed, the intestinal type showed the best 5-year-overall survival rate, with no significant difference between the PB types excluding PDAC and PDAC (39.4% vs. 19.2%, p=0.148). In multivariate analysis, curative resection (hazard ratio, 0.417; 95% CI, 0.219-0.792, p=0.008) was the only significant prognostic factor. Conclusion: Although intestinal histologic phenotype was not an independent prognostic factor on multivariate analysis, it showed pathologic features associated with better survival, while the PB type showed more aggressive tumor biology and consequently worse survival. Further studies are needed to demonstrate the prognostic significance of histologic phenotype.

Coexisting cytomegalovirus colitis in an immunocompetent patient with Clostridioides difficile colitis: A case report.

BACKGROUND: Clostridioides difficile (C. difficile) colitis is one of the most common infections in hospitalized patients, characterized by fever and diarrhea. It usually improves after appropriate antibiotic treatment; if not, comorbidities should be considered. Cytomegalovirus (CMV) colitis is a possible co-existing diagnosis in patients with C. difficile infection with poor treatment response. However, compared with immunocompromised patients, CMV colitis in immunocompetent patients is not well studied. CASE SUMMARY: We present an unusual case of co-existing CMV colitis in an immunocompetent patient with C. difficile infection. An 80-year-old female patient was referred to the infectious disease department due to diarrhea, abdominal discomfort, and fever for 1 wk during her hospitalization for surgery. C. difficile toxin B polymerase chain reaction on stool samples was positive. After C. difficile infection was diagnosed, oral vancomycin treatment was administered. Her symptoms including diarrhea, fever and abdominal discomfort improved for ten days. Unfortunately, the symptoms worsened again with bloody diarrhea and fever. Therefore, a sigmoidoscopy was performed for evaluation, showing a longitudinal ulcer on the sigmoid colon. Endoscopic biopsy confirmed CMV colitis, and the clinical symptoms improved after using ganciclovir. CONCLUSION: Co-existing CMV colitis should be considered in patients with aggravated C. difficile infection on appropriate treatment, even in immunocompetent hosts.

Evaluation of the regenerative capacity of stem cells combined with bone graft material and collagen matrix using a rabbit calvarial defect model.

PURPOSE: The purpose of this study was to evaluate the regenerative capacity of stem cells combined with bone graft material and a collagen matrix in rabbit calvarial defect models according to the type and form of the scaffolds, which included type I collagen matrix and synthetic bone. METHODS: Mesenchymal stem cells (MSCs) were obtained from the periosteum of participants. Four symmetrical 6-mm-diameter circular defects were made in New Zealand white rabbits using a trephine drill. The defects were grafted with (1) group 1: synthetic bone (ß-tricalcium phosphate/hydroxyapatite [ß-TCP/HA]) and 1×105 MSCs; (2) group 2: collagen matrix and 1×105 MSCs; (3) group 3: ß-TCP/HA, collagen matrix covering ß-TCP/HA, and 1×105 MSCs; or (4) group 4: ß-TCP/HA, chipped collagen matrix mixed with ß-TCP/HA, and 1×105 MSCs. Cellular viability and cell migration rates were analyzed. RESULTS: Uneventful healing was achieved in all areas where the defects were made at 4 weeks, and no signs of infection were identified during the healing period or at the time of retrieval. New bone formation was more evident in groups 3 and 4 than in the other groups. A densitometric analysis of the calvarium at 8 weeks post-surgery showed the highest values in group 3. CONCLUSIONS: This study showed that the highest regeneration was found when the stem cells were applied to synthetic bone along with a collagen matrix.

Disseminated nontuberculous mycobacteria infection in an immunocompetent host: A case report.

RATIONALE: Disseminated nontuberculous mycobacterial (NTM) infections are rare and occur primarily in immunocompromised hosts. Mycobacterium abscessus complex (MABC), including M abscessus subsp. massiliense (hereafter M massiliense) is a complex of rapidly growing mycobacterial (RGM) species of NTM. Here, we present a rare case of disseminated NTM infection with RGM bacteremia caused by M massiliense in an immunocompetent host. PATIENT CONCERNS: A 64-year-old woman with a recent history of spine fracture and septic pneumonia was transferred to our emergency room for dyspnea and fever. A peripherally inserted central catheter (PICC) had been placed over 6 months prior. DIAGNOSES: Chest computed tomography (CT) showed multifocal patchy consolidations and ground-glass opacity in both lungs. NTM suspected of RGM was isolated from the blood cultures. During hospitalization, multiple erythematous and hemorrhagic crusted nodules developed on the patient's upper and lower extremities, which were confirmed as disseminated NTM infection on skin biopsy. INTERVENTIONS: After NTM suspected of RGM was isolated from the blood cultures, the patient was empirically treated with antibiotics used for NTM infection, and the PICC was removed. Thereafter, the subspecies of NTM was reported as M massiliense and she was treated according to the antibiotic susceptibility testing results. OUTCOME: Although skin lesions and inflammatory markers improved gradually during antibiotic treatment over 10 weeks, NTM could still be isolated from the blood culture. LESSONS: Disseminated NTM infections with RGM bacteremia in an immunocompetent host have rarely been reported. In this case, PICC placement for more than 6 months was suspected to be an important risk factor for RGM bacteremia in an immunocompetent patient. To date, there are only insufficient case reports, moreover no clear guidelines regarding the optimal choice of antibiotics or length of treatment for disseminated NTM infection. Therefore, it is necessary to establish treatment guidelines for patients with disseminated NTM infection and bacteremia.

Enhanced antibody responses in fully vaccinated individuals against pan-SARS-CoV-2 variants following Omicron breakthrough infection.

Omicron has become the globally dominant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, creating additional challenges due to its ability to evade neutralization. Here, we report that neutralizing antibodies against Omicron variants are undetected following COVID-19 infection with ancestral or past SARS-CoV-2 variant viruses or after two-dose mRNA vaccination. Compared with two-dose vaccination, a three-dose vaccination course induces broad neutralizing antibody responses with improved durability against different SARS-CoV-2 variants, although neutralizing antibody titers against Omicron remain low. Intriguingly, among individuals with three-dose vaccination, Omicron breakthrough infection substantially augments serum neutralizing activity against a broad spectrum of SARS-CoV-2 variants, including Omicron variants BA.1, BA.2, and BA.5. Additionally, after Omicron breakthrough infection, memory T cells respond to the spike proteins of both ancestral and Omicron SARS-CoV-2 by producing cytokines with polyfunctionality. These results suggest that Omicron breakthrough infection following three-dose mRNA vaccination induces pan-SARS-CoV-2 immunity that may protect against emerging SARS-CoV-2 variants of concern.

Maternal and Neonatal Outcomes in Pregnant Women With Coronavirus Disease 2019 in Korea.

BACKGROUND: This study aimed to describe the maternal, obstetrical, and neonatal outcomes in pregnant women with coronavirus disease 2019 (COVID-19) and identify the predictors associated with the severity of COVID-19. METHODS: This multicenter observational study included consecutive pregnant women admitted because of COVID-19 confirmed using reverse transcriptase-polymerase chain reaction (RT-PCR) test at 15 hospitals in the Republic of Korea between January 2020 and December 2021. RESULTS: A total of 257 women with COVID-19 and 62 newborns were included in this study. Most of the patients developed this disease during the third trimester. Nine patients (7.4%) developed pregnancy-related complications. All pregnant women received inpatient treatment, of whom 9 (3.5%) required intensive care, but none of them died. The gestational age at COVID-19 diagnosis (odds ratio [OR], 1.096, 95% confidence interval [CI], 1.04-1.15) and parity (OR, 1.703, 95% CI, 1.13-2.57) were identified as significant risk factors of severe diseases. Among women who delivered, 78.5% underwent cesarean section. Preterm birth (38.5%), premature rupture of membranes (7.7%), and miscarriage (4.6%) occurred, but there was no stillbirth or neonatal death. The RT-PCR test of newborns' amniotic fluid and umbilical cord blood samples was negative for severe acute respiratory syndrome coronavirus 2. CONCLUSION: At the time of COVID-19 diagnosis, gestational age and parity of pregnant women were the risk factors of disease severity. Vertical transmission of COVID-19 was not observed, and maternal severity did not significantly affect the neonatal prognosis.

Booster Vaccination Strategies for "Living With COVID-19".

Although the primary and secondary vaccination rates in Korea account for over 75% of the total population, confirmed cases of COVID-19 are dramatically increasing due to immune waning and the Omicron variant. Therefore, it is urgent to evaluate the effectiveness of booster vaccination strategies for living with COVID-19. In this work, we have developed an age-specific mathematical model with eight age groups and included age-specific comorbidities to evaluate the effectiveness of age-specific vaccination prioritization strategies to minimize morbidity and mortality. Furthermore, we have investigated the impacts of age-specific vaccination strategies for different vaccine supplies and non-pharmaceutical intervention levels during two periods: (1) when vaccine supply was insufficient and (2) after the emergence of the omicron variant. During the first period, the best option was to vaccinate the 30-49 year age group and the group with comorbidities to minimize morbidity and mortality, respectively. However, a booster vaccination should prioritize the 30-49 year age group to promote both minimal morbidity and mortality. Critical factors, such as vaccination speed, vaccine efficacy, and non-pharmaceutical interventions (NPIs), should be considered for effective vaccination prioritization as well. Primary, secondary vaccinations, and a booster shot vaccinations require different age prioritization strategies under different vaccination rates, vaccine efficacies, and NPI levels.

Shedding and extensive and prolonged environmental contamination of goat farms of Q fever patients by Coxiella burnetii.

BACKGROUND: A majority (>70%) of Q fever patients in South Korea do not have a history of animal contact. Therefore, unconscious environmental exposure is suspected. The aim of this study was to investigate exposure of Q fever patients to environmental contamination and animal shedding. METHODS: Two goat farmers were enrolled. One was diagnosed with Q fever 3 years ago (Farm 1). Among 20 goats on Farm 1, five were tested randomly and found to be Q fever PCR-positive. Three of the five were Q fever ELISA-positive. Two of five environmental samples taken in 2015 were PCR-positive. In 2018, 17 of 18 environmental samples were PCR-positive. On Farm 2, 54 of the 77 goats were PCR-positive, and 63 were ELISA-positive. Twelve of 14 environmental samples were PCR-positive. Repeat administration of oxytetracycline to goats led to a gradual reduction in PCR-positive tests over a 5-month period. However, PCR-positivity of the farm environment persisted for 5 months. CONCLUSION: The environment on farms owned by Q fever patients was contaminated extensively and persistently, even after antibiotic treatment of goats and environmental decontamination. Undetected environmental contamination can be a major source of sporadic Q fever infection in South Korea.

Differences in seroprevalence between epicenter and non-epicenter areas of the COVID-19 outbreak in South Korea.

To compare the standardized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence of high epicenter region with non-epicenter region, serological studies were performed with a total of 3,268 sera from Daegu City and 3,981 sera from Chungbuk Province. Indirect immunofluorescence assay (IFA) for SARS-CoV-2 IgG results showed a high seroprevalence rate in the Daegu City (epicenter) compared with a non-epicenter area (Chungbuk Province) (1.27% vs. 0.91%, P = 0.0358). It is noteworthy that the highest seroprevalence in Daegu City was found in elderly patients (70's) whereas young adult patients (20's) in Chungbuk Province showed the highest seroprevalence. Neutralizing antibody (NAb) titers were found in three samples from Daegu City (3/3, 268, 0.09%) while none of the samples from Chungbuk Province were NAb positive. These results demonstrated that even following the large outbreak, the seropositive rate of SARS-CoV-2 in the general population remained low in South Korea.

3D Antidrying Antifreezing Artificial Skin Device with Self-Healing and Touch Sensing Capability.

Hydrogels are attractive, active materials for various e-skin devices based on their unique functionalities such as flexibility and biocompatibility. Still, e-skin devices are generally limited to simple structures, and the realization of optimal-shaped 3D e-skin devices for target applications is an intriguing issue of interest. Furthermore, hydrogels intrinsically suffer from drying and freezing issues in operational capability for practical applications. Herein, 3D artificial skin devices are demonstrated with highly improved device stability. The devices are fabricated in a target-oriented 3D structure by extrusion-based 3D printing, spontaneously heal mechanical damage, and enable stable device operation over time and under freezing conditions. Based on the material design to improve drying and freezing resistance, an organohydrogel, prepared by solvent displacement of hydrogel with ethylene glycol for 3 h, exhibits excellent drying resistance over 1000 h and improved freezing resistance by showing no phase transition down to -60 °C while maintaining its self-healing functionality. Based on the improved drying and freezing resistance, artificial skin devices in target-oriented optimal 3D structures are presented, which enable accurate positioning of touchpoints even on a complicated 3D structure stably over time and excellent operation at temperatures below 0 °C without losing their flexibility.

Renin-angiotensin system modulators and other risk factors in COVID-19 patients with hypertension: a Korean perspective.

BACKGROUND: While hypertension is the most common comorbid condition in patients with coronavirus disease 2019 (COVID-19) in Korea, there is a lack of studies investigating risk factors in COVID-19 patients with hypertension in Korea. In this study, we aimed to examine the effects risk factors in hypertensive Korean COVID-19 patients. METHODS: We selected patients from the database of the project #OpenData4Covid19. This information was linked to their 3-year historical healthcare data. The severity of the disease was classified into five levels. We also clustered the levels into two grades. RESULTS: The risk factors associated with COVID-19 severity were old age, diabetes mellitus, cerebrovascular disease, chronic obstructive pulmonary disease (COPD), malignancy, and renal replacement therapy. The use of angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) both before and after a diagnosis of COVID-19 were not associated with COVID-19 severity. A multivariate analysis revealed that old age, male sex, diabetes mellitus, and renal replacement therapy were risk factors for severe COVID-19. CONCLUSION: The results suggest that in hypertensive patients with COVID-19, older age, male sex, a diagnosis of diabetes mellitus, and renal replacement therapy were risk factors for a severe clinical course. In addition, the use of ARBs and ACEIs before or after COVID-19 infection did not affect a patient's risk of contracting COVID-19 nor did it contribute to a worse prognosis for the disease. These results highlighted that precautions should be considered for hypertensive patients with those risk factors and do not support discontinuation of ARBs and ACEIs during COVID-19 pandemic.

Endoscopic salvage treatment of histoacryl after stent application on the anastomotic leak after gastrectomy: A case report.

BACKGROUND: Endoscopic approach could effectively manage postoperative anastomotic leakage. Various endoscopic methods have been developed for the treatment of anastomotic leakage. CASE SUMMARY: A 53-year-old woman developed anastomotic leak after laparoscopic proximal gastrectomy. Endoscopic clip closure failed due to strong wall tension; therefore, a fully covered self-expandable esophageal metal stent (fc-SEMS) was placed to cover the leak after it was filled with a mixture of fibrin glue and histoacryl. However, fluoroscopy with gastrograffin showed dye leaking out of the fc-SEMS. Using the previous fluoroscopic image for guidance, a catheter was inserted at the leakage site. The radiocontrast dye was injected and was seen spreading along the sinus tract. Thereafter, histoacryl was injected. Seven days after the last procedure, upper gastrointestinal contrast studies showed no leaks. The patient was subsequently discharged 9 d after histoacryl injection without any complications. CONCLUSION: To seal an anastomosis leak after stent application, salvage technique using histoacryl injection at the leakage site with fluoroscopy guidance could be considered cautiously.

Exploration of Superspreading Events in 2015 MERS-CoV Outbreak in Korea by Branching Process Models.

South Korea has learned a valuable lesson from the Middle East respiratory syndrome (MERS) coronavirus outbreak in 2015. The 2015 MERS-CoV outbreak in Korea was the largest outbreak outside the Middle Eastern countries and was characterized as a nosocomial infection and a superspreading event. To assess the characteristics of a super spreading event, we specifically analyze the behaviors and epidemiological features of superspreaders. Furthermore, we employ a branching process model to understand a significantly high level of heterogeneity in generating secondary cases. The existing model of the branching process (Lloyd-Smith model) is used to incorporate individual heterogeneity into the model, and the key epidemiological components (the reproduction number and the dispersive parameter) are estimated through the empirical transmission tree of the MERS-CoV data. We also investigate the impact of control intervention strategies on the MERS-CoV dynamics of the Lloyd-Smith model. Our results highlight the roles of superspreaders in a high level of heterogeneity. This indicates that the conditions within hospitals as well as multiple hospital visits were the crucial factors for superspreading events of the 2015 MERS-CoV outbreak.

Viable SARS-CoV-2 in various specimens from COVID-19 patients.

OBJECTIVES: The aim was to determine whether various clinical specimens obtained from COVID-19 patients contain the infectious virus. METHODS: To demonstrate whether various clinical specimens contain the viable virus, we collected naso/oropharyngeal swabs and saliva, urine and stool samples from five COVID-19 patients and performed a quantitative polymerase chain reaction (qPCR) to assess viral load. Specimens positive with qPCR were subjected to virus isolation in Vero cells. We also used urine and stool samples to intranasally inoculate ferrets and evaluated the virus titres in nasal washes on 2, 4, 6 and 8 days post infection. RESULTS: SARS-CoV-2 RNA was detected in all naso/oropharyngeal swabs and saliva, urine and stool samples collected between days 8 and 30 of the clinical course. Notably, viral loads in urine, saliva and stool samples were almost equal to or higher than those in naso/oropharyngeal swabs (urine 1.08 ± 0.16-2.09 ± 0.85 log10 copies/mL, saliva 1.07 ± 0.34-1.65 ± 0.46 log10 copies/mL, stool 1.17 ± 0.32 log10 copies/mL, naso/oropharyngeal swabs 1.18 ± 0.12-1.34 ± 0.30 log10 copies/mL). Further, viable SARS-CoV-2 was isolated from naso/oropharyngeal swabs and saliva of COVID-19 patients, as well as nasal washes of ferrets inoculated with patient urine or stool. DISCUSSION: Viable SARS-CoV-2 was demonstrated in saliva, urine and stool samples from COVID-19 patients up to days 11-15 of the clinical course. This result suggests that viable SARS-CoV-2 can be secreted in various clinical samples and respiratory specimens.

Human Granulocytic Anaplasmosis Diagnosed Based on a Peripheral Blood Smear Test in South Korea: a Case Report.

We report a case of human granulocytic anaplasmosis (HGA) in a 76-year-old woman, diagnosed rapidly based on the characteristic peripheral blood smear finding of intragranulocytic morulae. The smear was prepared on the day of hospitalization, which was 1-2 weeks before results of the serology test or polymerase chain reaction (PCR) became available. Owing to the blood smear test, we could start timely and appropriate antimicrobial treatment. The sensitivity of peripheral blood smear is lower compared to that of serology or PCR for the diagnosis of HGA but may increase with the examiner's experience. In our case, the diagnosis of HGA was confirmed based on PCR and serology 7 and 14 days after the positive peripheral blood smear test, respectively. Morulae in neutrophils are a diagnostic indicator of HGA, particularly for febrile patients with a history of tick bites or outdoor activities in rural areas.

Laparoscopic management of gastric remnant ischemia after laparoscopic distal gastrectomy with Billroth-I anastomosis-A case report.

INTRODUCTION: Gastric remnant ischemia after laparoscopic distal gastrectomy (LDG) in gastric cancer patients is a very rare but life-threatening condition, especially when accompanied by a splenic infarction or unplanned splenectomy. PRESENTATION OF CASE: A 72-year-old male with no comorbid diseases was diagnosed with a well-differentiated adenocarcinoma of the lower stomach and underwent LDG with D2 lymph node dissection. However, a splenic artery injury necessitated a splenectomy intra-operatively, and delta anastomosis was performed based on a clinically viable remnant stomach. During the late post-operative period, the patient developed abdominal pain and showed increased levels of inflammatory biomarkers with hemodynamic stability. Esophagogastroduodenoscopy (EGD) showed necrotic patches over the distal part of the remnant stomach with normal anastomosis and duodenal mucosa. Progression of the necrosis was noted on follow up EGD performed 15 days post-surgery. Total laparoscopic subtotal gastrectomy with Roux-en-Y reconstruction was performed and the patient recovered uneventfully. DISCUSSION: Careful dissection of the lymph nodes over the major vessels is essential to avoid complications in gastric cancer patients requiring LDG. Moreover, major complications occurring intra-operatively may necessitate changes in the surgical plan, including re-excision of the remnant stomach or conversion to Roux-en-Y reconstruction. CONCLUSION: Careful evaluation of the clinical findings and close observation with EGD can help detect mucosal demarcation lines and ascertain the perfect timing for intervention in cases with suspected ischemia. Although gastric remnant ischemia requires emergency treatment, laparoscopic management is a feasible option when performed by an expert surgeon.

Effects of depth of neuromuscular block on postoperative pain during laparoscopic gastrectomy: A randomised controlled trial.

BACKGROUND: Evidence on whether the use of deep neuromuscular block (NMB) influences postoperative pain after laparoscopic surgery is limited, and existing studies have shown conflicting results. We studied the effect of the depth of NMB during laparoscopic gastrectomy on postoperative pain. OBJECTIVE: The aim of this study was to evaluate the effect of depth of NMB during laparoscopic gastrectomy on postoperative pain by allocating patients randomly to either deep or moderate NMB with a standard-pressure pneumoperitoneum. DESIGN: A randomised, controlled, double-blind study. SETTING: A university-affiliated hospital. PARTICIPANTS: One hundred patients. INTERVENTIONS: Patients were allocated randomly to receive either deep (posttetanic count 1 to 2) or moderate (train-of-four count 1 to 2) levels of NMB. Following surgery, the patients were asked to rate their pain every 10 min using a visual analogue scale (VAS) (0 = no pain, 10 = most severe pain) in the postanaesthesia care unit (PACU). Patients received intravenous oxycodone, 2 mg every 10 min, until the pain intensity (VAS) had decreased to less than 3 at rest and less than 5 on wound compression, at which point the minimum effective analgesia dose (MEAD) of oxycodone was determined. MAIN OUTCOME MEASURES: The primary endpoint was the MEAD of oxycodone. Secondary endpoints included area under the curve of VAS for wound pain, VAS scores for wound and shoulder pain at 6 and 24 h after the end of surgery, rescue analgesics, a five-point surgical rating scale, Rhodes index of nausea vomiting retching at 6 and 24 h after the end of surgery and duration of pneumoperitoneum. RESULTS: The median value for the MEAD of oxycodone was 8 mg in both groups. Area under the curves of VAS over time were similar in both groups. Variables associated with postoperative pain including mean VAS at PACU and frequency of rescue analgesics in the ward did not differ significantly between the two groups. The duration of pneumoperitoneum was a significant variable in determining the MEAD of oxycodone (linear regression, R = 0.07, P = 0.008). The number of patients who reached the acceptable surgical score was not significantly different between the two groups. However, the moderate NMB group did have a significantly higher proportion of cases that required additional muscle relaxants (P < 0.001). CONCLUSION: Deep, compared with moderate, NMB did not significantly reduce the MEAD of oxycodone administered in the PACU. The duration of pneumoperitoneum was positively correlated with the MEAD. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03266419.

Assessment of stem cell viability in the initial healing period in rabbits with a cranial bone defect according to the type and form of scaffold.

PURPOSE: Increased bone regeneration has been achieved through the use of stem cells in combination with graft material. However, the survival of transplanted stem cells remains a major concern. The purpose of this study was to evaluate the viability of transplanted mesenchymal stem cells (MSCs) at an early time point (24 hours) based on the type and form of the scaffold used, including type I collagen membrane and synthetic bone. METHODS: The stem cells were obtained from the periosteum of the otherwise healthy dental patients. Four symmetrical circular defects measuring 6 mm in diameter were made in New Zealand white rabbits using a trephine drill. The defects were grafted with 1) synthetic bone (ß-tricalcium phosphate/hydroxyapatite [ß-TCP/HA]) and 1×105 MSCs, 2) collagen membrane and 1×105 MSCs, 3) ß-TCP/HA+collagen membrane and 1×105 MSCs, or 4) ß-TCP/HA, a chipped collagen membrane and 1×105 MSCs. Cellular viability and the cell migration rate were analyzed. RESULTS: Cells were easily separated from the collagen membrane, but not from synthetic bone. The number of stem cells attached to synthetic bone in groups 1, 3, and 4 seemed to be similar. Cellular viability in group 2 was significantly higher than in the other groups (P<0.05). The cell migration rate was highest in group 2, but this difference was not statistically significant (P>0.05). CONCLUSIONS: This study showed that stem cells can be applied when a membrane is used as a scaffold under no or minimal pressure. When space maintenance is needed, stem cells can be loaded onto synthetic bone with a chipped membrane to enhance the survival rate.