Transplantation of patient-specific bile duct bioengineered with chemically reprogrammed and microtopographically differentiated cells.

Cholangiopathy is a diverse spectrum of chronic progressive bile duct disorders with limited treatment options and dismal outcomes. Scaffold- and stem cell-based tissue engineering technologies hold great promise for reconstructive surgery and tissue repair. Here, we report a combined application of 3D scaffold fabrication and reprogramming of patient-specific human hepatocytes to produce implantable artificial tissues that imitate the mechanical and biological properties of native bile ducts. The human chemically derived hepatic progenitor cells (hCdHs) were generated using two small molecules A83-01 and CHIR99021 and seeded inside the tubular scaffold engineered as a synergistic combination of two layers. The inner electrospun fibrous layer was made of nanoscale-macroscale polycaprolactone fibers acting to promote the hCdHs attachment and differentiation, while the outer microporous foam layer served to increase mechanical stability. The two layers of fiber and foam were fused robustly together thus creating coordinated mechanical flexibility to exclude any possible breaking during surgery. The gene expression profiling and histochemical assessment confirmed that hCdHs acquired the biliary epithelial phenotype and filled the entire surface of the fibrous matrix after 2 weeks of growth in the cholangiocyte differentiation medium in vitro. The fabricated construct replaced the macroscopic part of the common bile duct (CBD) and re-stored the bile flow in a rabbit model of acute CBD injury. Animals that received the acellular scaffolds did not survive after the replacement surgery. Thus, the artificial bile duct constructs populated with patient-specific hepatic progenitor cells could provide a scalable and compatible platform for treating bile duct diseases.

High-flow nasal cannula application in an infant patient with laryngomalacia during general anesthesia: A case report.

RATIONALE: Laryngomalacia is defined as the collapse of supraglottic structures and can cause not only strider but also trigger difficulties with ventilation and endotracheal intubation during anesthesia management. High-flow nasal cannula (HFNC) has been used to manage patients at high risk of hypoxemia in the intensive care unit; however, limited literature information is available for the application of HFNC to infant patients with laryngomalacia during anesthesia practice. PATIENT CONCERNS: A 2-month-old male infant was scheduled to undergo surgery for inguinal hernia and undescended testis with general anesthesia. DIAGNOSIS: The patient had subcostal retraction while breathing and frequent oxygen desaturation events and was diagnosed laryngomalacia. INTERVENTIONS: After the patient was supplied oxygen via HFNC and then given general anesthesia, the initial 2 attempts of endotracheal intubation with a rigid laryngoscope were unsuccessful because the vocal cords were obscured by the epiglottis. A third intubation attempt was performed and successful with a 3.0-sized, uncuffed endotracheal tube within 20 minutes of the initial attempt. OUTCOMES: No airway complications emerged and oxygen saturation remained at greater than 98% during general anesthesia. The patient was discharged 5 days after surgery without any adverse side effects. LESSONS: Continuous oxygenation via HFNC is a good choice to prevent desaturation during difficult tracheal intubations in infant patients with laryngomalacia. This device is expected to be useful for intubation not only in patients with laryngomalacia, but also in infant patients with a predicted high risk of oxygen desaturation events during general anesthesia.

The Protective Effects of Dexmedetomidine Preconditioning on Hepatic Ischemia/Reperfusion Injury in Rats.

BACKGROUND: Ischemia/reperfusion (IR) injury is 1 of the major problems in liver surgery. This study aims to evaluate the histologic and biochemical effects of dexmedetomidine on ischemia/reperfusion injury in the liver of rats. METHODS: Twenty-two Sprague-Dawley male rats were separated into 3 groups: group sham, IR (IR injury), and IR-D (IR with dexmedetomidine). Ischemia was induced for 45 minutes with portal clampage and the reperfusion period was 120 minutes. Group IR-D received 3 µg/kg of dexmedetomidine with loading for 10 minutes and then 3 µg/kg/h of dexmedetomidine was continuously injected intravenously 30 minutes before portal clampage. Biochemical factors (alanine aminotransferase and aspartate aminotransferase), variable cytokines (B cell lymphoma-2 (Bcl-2), Bax, caspase 3, caspase 8, nuclear factor-kappa B, interleukin (IL)-1ß, IL-6, IL-10, mixed lineage kinase domain-like protein, and receptor-interacting protein kinase-3), and histologic findings were investigated. RESULTS: Dexmedetomidine preconditioning significantly suppressed the histologic damage. In the IR-D group, the expression of IL-6 was decreased and the Bcl-2 was increased when compared with the IR group. CONCLUSION: Dexmedetomidine suppresses hepatic IR injury and the protective mechanism appears to involve the decrease of IL-6 and upregulation of Bcl-2 expression, which result in the attenuation of inflammatory response and the inhibition of apoptosis.

Co-administration of erythropoietin and iron complex improves late-phase liver regeneration.

Erythropoietin and iron have individually shown beneficial effects on early-phase liver regeneration following partial hepatectomy (PHx); however, there are limited data on the combined effect on late-phase liver regeneration after PHx. Here we examined combined effects of recombinant human erythropoietin (rhEPO, 3,000 IU/kg) and iron isomaltoside (IIM, 40 mg/kg) on late-phase liver regeneration following PHx and investigated the possible underlying mechanism. Rats administrated with rhEPO showed significantly higher liver mass restoration, interleukin-6 (IL-6, a hepatocyte mitogen) levels, and Ki-67-positive hepatocytes on day 7 after PHx than saline-treated controls. These beneficial effects were further enhanced on days 7 and 14 by co-treatment with IIM. This combination also significantly improved liver function indices, such as increased albumin production and decreased bilirubin levels, but did not alter serum levels of toxic parameters, such as aspartate transaminase and alanine transaminase. This study demonstrates that the combination of rhEPO and IIM synergistically improves late-phase liver regeneration and function after PHx, probably by promoting IL-6-mediated hepatocyte proliferation without adverse effects. Thus, this combination treatment can be a potential therapeutic strategy for patients undergoing resection for hepatic malignancies. [BMB Reports 2020; 53(3): 148-153].

Effects of acute normovolemic hemodilution on healing of gastric anastomosis in rats.

PURPOSE: Acute normovolemic hemodilution (ANH) is an autologous transfusion method, using blood collected during surgery, to reduce the need for allogeneic blood transfusion. ANH is controversial because it may lead to various complications. Among the possible complications, anastomotic leakage is one that would have a significant effect on the operation outcome. However, the relationship between ANH and anastomotic site healing requires additional research. Therefore, we conducted this prospective study of ANH, comparing it with standard intraoperative management, undergoing gastric anastomosis in rats. METHODS: Sixteen Sprague-Dawley rats were randomly assigned to three groups: group A, surgery with ANH; group N, surgery with standard intraoperative management; and group C, sham surgery with standard intraoperative management. ANH was performed in group A animals by, removing 5.8-6.6 mL of blood and replacing it with 3 times as much crystalloid. All rats were enthanized on postoperative day 6, and histopathologic analyses were performed. RESULTS: The mean hematocrit values, after hemodilution were 22.0% (range, 18.0%-29.0%), group A; 33.0% (29.0%-35.0%), group N; and 32.5% (29.0%-34.0%), group C. There were significant differences between groups A and N (P = 0.019, P = 0.009, P = 0.004, P = 0.039, and P = 0.027), and between groups N and C (P = 0.006, P = 0.027, P = 0.04, P = 0.008, and P = 0.009) with respect to inflammatory cell numbers, neovascularization, fibroblast numbers, edema and necrosis, respectively; there were no differences between groups A and N. CONCLUSION: In rat model, anastomotic complications did not increase in the ANH group, compared with the standard intraoperative management group.

Amorphous Fluoropolymer Membrane for Gas Separation Applications.

Amorphous fluoropolymers have been studied in the past few decades and received extensive attention due to their unique and useful properties. One of the remarkable properties of amorphous fluoropolymers is high fractional free volume (FFV), and they tend to retain large amounts of solvent inside their polymer chains. In this study, amorphous flouoropolymer membranes were employed to examine the influences of the residual solvent and drying condition on the thermal properties, gas permeation behavior, and structure change by the polymer chains. Thermal properties of the produced membranes were characterized by differential scanning calorimetry (DSC) and a thermogravimetric analysis (TGA) to verify the effects of residual solvent. The residual solvent content and the glass transition temperature (Tg) of amorphous fluoropolymer membranes prepared with both solvents decrease with increasing drying temperature. The effect of the thermal treatment method on the d-spacing between the polymer chains of the prepared membranes was investigated using X-ray diffraction (XRD). The d-spacing decreased with drying below the Tg whereas it drastically increased near the Tg because of chain relaxation. From these phenomena, the helium permeability of the membranes treated at 120 °C radically increased. However, the oxygen and nitrogen permeability decreased with decreasing residual solvent content. The glass transition range shifted to higher temperature, from 75 °C to 133 °C, depending on the reduced amount of residual solvent.

Effects of nefopam with fentanyl in intravenous patient-controlled analgesia after arthroscopic orthopedic surgery: a prospective double-blind randomized trial

Background/aim: We performed this prospective randomized double-blind study to compare the effects of nefopam versus ketorolac in intravenous fentanyl-based patient-controlled analgesia (PCA) after shoulder arthroscopic orthopedic surgery. Materials and methods: Ninety-two patients were randomly divided into two groups to receive intravenous PCA. Patients were assigned to either the nefopam group (nefopam 120 mg and fentanyl 20 µg/kg) or the ketorolac group (ketorolac 2 mg/kg and fentanyl 20 µg/kg). Pain was assessed on a visual analogue scale (VAS) and a numeric rating scale (NRS). Additionally, patient satisfaction, adverse events, and vital signs were monitored. Results: There were no significant differences in VAS score (P = 0.48) or NRS score (P = 0.15) between the two groups. Similarly, patient satisfaction did not differ between the two groups [8.5(0.8) vs. 8.2(1.0), P = 0.14]. There were no statistically significant differences in the incidence of nausea (P = 0.72), vomiting (P = 0.46), urinary retention (P = 0.82), sweating (P = 0.49), or dizziness (P = 0.45) between the two groups. Likewise, there were no differences in heart rate [78.2(7.7) vs. 75.2(6.5), P = 0.18] or SpO2 [98.4(1.8) vs. 98.5(1.9), P = 0.83]. Conclusion: Nefopam is an appropriate alternative for co-administration with fentanyl-based PCA in patients who have difficulty using nonsteroidal antiinflammatory drugs.

Efficacy of Pentax airway scope versus Macintosh laryngoscope when used by novice personnel: A prospective randomized controlled study.

Objective To determine whether intubation education using the Pentax Airway Scope (AWS) in normal airways is more useful than direct laryngoscopy (Macintosh laryngoscope) in novice personnel. Methods Eleven intern doctors without intubation experience performed 60 sequential intubations with each device on a manikin and 10 sequential intubations in adult patients. The time required for successful intubation, percentage of glottic opening (POGO) score, number of intubation attempts, and number of dental injuries were analyzed for each intubation technique. Results The mean (standard deviation) time required for successful intubation decreased as the number of intubations increased and was significantly shorter with the Pentax AWS than direct laryngoscope [22.6 (7.3) vs. 29.6 (10.0) and 33.0 (8.0) vs. 44.7 (5.6) s, respectively] in both the manikin and clinical studies. The Pentax AWS was also associated with higher POGO scores than the direct laryngoscope [81.7 (8.9) vs. 55.1 (13.2) and 80.9 (9.7) vs. 49.6 (16.5), respectively] and fewer intubation attempts. Fewer dental injuries occurred with the Pentax AWS in the manikin study. Conclusions Novices performed intubation more rapidly and easily with an improved laryngeal view using the Pentax AWS. We suggest that intubation education with video laryngoscopy should be mandatory along with direct laryngoscope training.

Comparative Study on Osseointegration of Implants After Flap and Flapless Surgery in the Mandible of Dogs.

PURPOSE: The objective of this study was to compare the implant stability and osseointegration of implants using a flap or flapless technique. MATERIAL AND METHODS: Mandibular premolars and molars were extracted from both sides in 6 dogs. After 8 weeks, 4 fixtures were implanted using either a flap or flapless technique. Implant stability quotient was measured on insertion and at 2, 4, and 8 weeks later. The animals were killed while the tissues were histologically analyzed. RESULTS: Implant stability increased for 8 weeks, and no statistically significant differences were observed between the surgical protocols. Bone-implant contact showed 60.27% ± 30.99% for flapless surgery and 59.73% ± 17.12% for flap surgery. And the results of new bone formation area from total area showed 56.07% ± 27.78% for flapless surgery and 57.00% ± 14.66% for flap surgery. There were no statistically significant differences. CONCLUSION: This study showed no significant difference in implant stability as well as osseointegration regardless of flap or flapless technique.

Licochalcone-E induces caspase-dependent death of human pharyngeal squamous carcinoma cells through the extrinsic and intrinsic apoptotic signaling pathways.

The aim of the present study was to investigate licochalcone-E (Lico-E)-induced apoptosis and the associated apoptotic signaling pathway in FaDu cells, a human pharyngeal squamous carcinoma cell line. Treatment with Lico-E exhibited significant cytotoxicity on FaDu cells in a concentration-dependent manner. The IC50 value of Lico-E in FaDu cells was ~50 µM. Treatment with Lico-E increased the number of dead FaDu cells. Furthermore, chromatin condensation, which is associated with apoptotic cell death, was observed in FaDu cells treated with Lico-E for 24 h. By contrast, Lico-E did not produce cytotoxicity or increase the number of dead cells when applied to human normal oral keratinocytes (hNOKs). Furthermore, chromatin condensation was not observed in hNOKs treated with Lico-E. Treatment with Lico-E increased the expression of Fas ligand and the cleaved form of caspase-8 in FaDu cells. Furthermore, treatment with Lico-E increased the expression of pro-apoptotic factors, including apoptosis regulator BAX, Bcl-2-associated agonist of cell death, apoptotic protease-activating factor 1, caspase-9 and tumor suppressor p53, while decreasing the expression of anti-apoptotic factors, including apoptosis regulator Bcl-2 and Bcl-2-like protein 1 in FaDu cells. The expression of cleaved caspases-3 and poly (ADP-ribose) polymerase was significantly upregulated following treatment with Lico-E in FaDu cells, while Lico-E-induced apoptotic FaDu cell death was partially suppressed by treatment with Z-VAD-FMK, a pan caspase inhibitor. Therefore, Lico-E-induced oral cancer (OC) cell-specific apoptosis is mediated by the death receptor-dependent extrinsic and mitochondrial-dependent intrinsic apoptotic signaling pathways. In conclusion, these data suggested that Lico-E exhibits potential chemopreventive effects and warrants further developed as a chemotherapeutic agent against OC.

Design and Fabrication of a Thin-Walled Free-Form Scaffold on the Basis of Medical Image Data and a 3D Printed Template: Its Potential Use in Bile Duct Regeneration.

Three-dimensional (3D) printing, combined with medical imaging technologies, such as computed tomography and magnetic resonance imaging (MRI), has shown a great potential in patient-specific tissue regeneration. Here, we successfully fabricated an ultrathin tubular free-form structure with a wall thickness of several tens of micrometers that is capable of providing sufficient mechanical flexibility. Such a thin geometry cannot easily be achieved by 3D printing alone; therefore, it was realized through a serial combination of processes, including the 3D printing of a sacrificial template, the dip coating of the biomaterial, and the removal of the inner template. We demonstrated the feasibility of this novel tissue engineering construct by conducting bile duct surgery on rabbits. Moving from a rational design based on MRI data to a successful surgical procedure for reconstruction, we confirmed that the presented method of fabricating scaffolds has the potential for use in customized bile duct regeneration. In addition to the specific application presented here, the developed process and scaffold are expected to have universal applicability in other soft-tissue engineering fields, particularly those involving vascular, airway, and abdominal tubular tissues.

Successful transfusion-free pancreatectomy in Jehovah's Witness patients.

BACKGROUNDS/AIMS: Although perioperative therapies have improved greatly, pancreatectomies still often need blood transfusions. However, the morbidity from blood transfusions, the poor prognosis of blood transfused patients, high cost, and decreasing supply of blood products is accelerating transfusion-free (TF) surgery in the patients who have pacreatectomies. The aim of this study was to assess the feasibility of TF pancreatectomies for patients who are Jehovah's Witness. METHODS: We investigated the possibility of TF pancreatectomies for the Jehovah's Witness patients undergoing pancreatectomies between January 2007 and Februay 2014. There were 4 cases of Whipple's operation, 4 of pylorus-preserving pancreaticoduodenectomy, 2 of radical antegrade modular pancreatosplenectomy and 1 of laparoscopic distal pancreatectomy. All were performed by one surgeon. RESULTS: Most of the TF pancreatecomies patients received perioperative blood augmentation and intraoperative acute normovolemic hemodilution (ANH). They received no blood transfusions at any time during their hospitalization, and pre- and intra-operative data and outcomes were acceptably favorable. CONCLUSIONS: To the best of our knowledge, this report is the first successful consecutive pancreatectomy program for Jehovah's Witness not involving blood transfusion. TF pancreatectomy can be performed successfully in selected Jehovah's Witness. Postoperative prognosis and outcomes should be confirmed in follow up studies.

Early Bone Formation at a Femur Defect Using CGF and PRF Grafts in Adult Dogs: A Comparative Study.

PURPOSE: The purpose of this study was to compare the predictability of new bone formation using an autologous concentrated growth factor (CGF) graft alone and platelet graft alone. MATERIALS AND METHODS: Four bony defects of 8 mm were formed, and 3.7- × 10-mm implants were placed in the right femur. The platelet-rich fibrin (PRF), CGF, and synthetic bone were grafted to the bone defect area. Enzyme linked immunosorbent assay quantitative analysis and microscopic analysis of the fibrinogen structure were performed. RESULTS: At 4 weeks, the comparisons of each experimental group showed a significant difference between the CGF group and the synthetic bone graft group. When comparing the CGF and allograft material groups, the allograft group showed significantly more new bone formation. In the case of vascular endothelial growth factor, CGF had 1.5 times more than PRF. CGF showed a fibrinogen structure with a constant diameter. CONCLUSION: When applied to a clinical case, CGF is predicted to show better results than PRF.

Tachycardia-bradycardia syndrome in a patient with atrial fibrillation: a case report.

An 83-year-old woman was scheduled for a second transurethral resection of a bladder tumor. The preoperative electrocardiogram evaluation revealed atrial fibrillation with a slow ventricular response (ventricular rate: 59 /min). After intravenous injection of 1% lidocaine 40 mg and propofol 60 mg, the ventricular rate increased to 113 beats/min and then fell rapidly to 27 beats/min. Blood pressure was 70/40 mmHg. Later an atrial fibrillation rhythm, with a ventricular rate of 100-130 beats/min, was observed together with a sinus pause and sinus rhythm with a ventricular rate of 40-50 beats/min. An external pacemaker was applied and set at 60 mA, 40 counts. After the patient regained consciousness, she presented an alert mental state and had no chest symptoms. She was discharged 2 weeks later without complications after insertion of a permanent pacemaker.

Implant Stability Measurements in the Long-Term Follow-up of Dentis Implants: A Retrospective Study With Periotest.

PURPOSE: The purpose of this study was to evaluate retrospectively the stability of Dentis implant with the Periotest. METHODS: In total, 36 patients and 88 implants were investigated. Periotest was used to measure implant stability, and a periapical view was taken immediately after surgery and again immediately after, 3 months after, 6 months and 5 years after prosthesis placement. Bone loss on the periapical view, bone quality according to tactile sensation, and area of implant installation were assessed. RESULTS: The mean Periotest value (PTV) immediately after surgery was -1.02, and the mean bone loss rate (bone loss/fixture length × 100) at 6 months after prosthesis placement was 8.42%. PTV was higher with more bone loss (types III, IV vs types I, II bone). The lowest mean PTV was in the lower molar area (-1.48), followed by the lower anterior (-1.41), upper molar (0.11), and upper anterior area (5). One implant failed and survival rates were 98.9%. CONCLUSION: Implant stability was lower in cases with more bone loss and poor bone quality and in the maxilla versus the mandible.

Comparison of emergence times with different fresh gas flow rates following desflurane anaesthesia.

OBJECTIVE: To investigate emergence times with different fresh gas flow rates, following desflurane anaesthesia. METHODS: Patients undergoing surgery with desflurane anaesthesia were randomly assigned to receive fresh gas flow rates of 100% oxygen during emergence of 2 l/min (group D2), 4 l/min (group D4) or 6 l/min (group D6). Time to eye opening, spontaneous movement and extubation (emergence time) were assessed after desflurane discontinuation. The end-tidal concentration of desflurane and bispectral index were recorded at each of these timepoints. RESULTS: A total of 105 patients were included in the study, with 35 in each of the three groups. Mean times to extubation were 17.6 min, 9.9 min and 9.1 min in groups D2, D4 and D6, respectively. Times to eye opening, spontaneous movement and extubation in group D2 were significantly longer than in groups D4 and D6. CONCLUSIONS: These results suggest that there is the potential to predict emergence time based on fresh gas flow rate following desflurane anaesthesia. It should therefore be possible to use a low-flow technique during the emergence period, in addition to the maintenance period, without delaying recovery if the inhaled anaesthetic is stopped at the predicted time before the end of surgery.

Osteogenic ability according to the decalcified modality of auto-tooth bone grafts in peri-implant defects in dogs.

PURPOSE: The purpose of this study was to evaluate the bone generation capacity of the autotransplantation material with clinical and histological analyses after controlled acid treatment conditions. MATERIAL AND METHODS: Bony defects were formed in the femur. Then, autotransplantation material was grafted after hydroxyapatite-coated implant placement. Experimental groups were classified according to the acid treatment method: 2% H2SO4 (group 1), 2% HCl (group 2), 2% HNO3 (group 3), or 2% ethylenediaminetetraacetic acid (EDTA) (group 4). RESULTS: The new bone formation area and bone-implant contact (BIC) of the autotransplantation materials were measured after 8 weeks. The new bone formation area in experimental groups 2, 3, and 4 were greater than that in the control group (no graft) and in experimental group 1 at 8 weeks, and the BIC of experimental group 4 was greater than that in the control group and in experimental group 1; these differences showed statistical significance (P < 0.05). CONCLUSION: Auto-tooth bone treated with EDTA resulted in more effective bone formation in dogs' femurs than bone treated with other solutions.

Displaced implants into maxillary sinus: report of cases.

Although the number of implant placement in the edentulous maxillary region is increasing, there are often some cases in which implants accidentally get displaced into maxillary sinus because of low bone quality, insufficient bone height, bone resorption after surgery, and improper treatment plan. Implants displaced into the maxillary sinus can cause some complications, including mucosal thickening and sinusitis; however, there are also many cases causing no symptoms at all. Treatment procedures for implants displaced into maxillary sinus are observation, removal of implants through intraoral approach, and removal through nasal cavity using endoscope. But treatment may vary according to the presence of sinusitis, ostium obstruction, and oroantral fistula. In this study, 4 patients with present illness of implants displaced into maxillary sinus were selected, and appropriate evaluation and treatment for these cases were studied.

Autogenous teeth used for bone grafting: a comparison with traditional grafting materials.

OBJECTIVES: This study evaluated the surface structures and physicochemical characteristics of a novel autogenous tooth bone graft material currently in clinical use. STUDY DESIGN: The material's surface structure was compared with a variety of other bone graft materials via scanning electron microscope (SEM). The crystalline structure of the autogenous tooth bone graft material from the crown (AutoBT crown) and root (AutoBT root), xenograft (BioOss), alloplastic material (MBCP), allograft (ICB), and autogenous mandibular cortical bone were compared using x-ray diffraction (XRD) analysis. The solubility of each material was measured with the Ca/P dissolution test. RESULTS: The results of the SEM analysis showed that the pattern associated with AutoBT was similar to that from autogenous cortical bones. In the XRD analysis, AutoBT root and allograft showed a low crystalline structure similar to that of autogenous cortical bones. In the CaP dissolution test, the amount of calcium and phosphorus dissolution in AutoBT was significant from the beginning, while displaying a pattern similar to that of autogenous cortical bones. CONCLUSIONS: In conclusion, autogenous tooth bone graft materials can be considered to have physicochemical characteristics similar to those of autogenous bones.