BACKGROUND: Bone growth factors, particularly bone morphogenic protein-2 (BMP-2), are required for effective treatment of significant bone loss. Despite the extensive development of bone substitutes, much remains to be desired for wider application in clinical settings. The currently available bone substitutes cannot sustain prolonged BMP-2 release and are inconvenient to use. In this study, we developed a ready-to-use bone substitute by sequential conjugation of BMP to a three-dimensional (3D) poly(L-lactide) (PLLA) scaffold using novel molecular adhesive materials that reduced the operation time and sustained prolonged BMP release. METHODS: A 3D PLLA scaffold was printed and BMP-2 was conjugated with alginate-catechol and collagen. PLLA scaffolds were conjugated with different concentrations of BMP-2 and evaluated for bone regeneration in vitro and in vivo using a mouse calvarial model. The BMP-2 release kinetics were analyzed using ELISA. Histological analysis and microCT image analysis were performed to evaluate new bone formation. RESULTS: The 3D structure of the PLLA scaffold had a pore size of 400 lm and grid thickness of 187–230 lm. BMP-2 was released in an initial burst, followed by a sustained release for 14 days. Released BMP-2 maintained osteoinductivity in vitro and in vivo. Micro-computed tomography and histological findings demonstrate that the PLLA scaffold conjugated with 2 lg/ml of BMP-2 induced optimal bone regeneration. CONCLUSION The 3D-printed PLLA scaffold conjugated with BMP-2 enhanced bone regeneration, demonstrating its potential as a novel bone substitute.

Purpose: An increasing number of older patients now undergo liver transplantation (LT). Although the overall outcomes in older patients are not different from those of younger patients, there is no tool to predict LT prognosis in older patients.We hypothesized that a modified Charlson comorbidity index (mCCI) and 5-factor modified frailty index (mFI-5) can predict outcomes in older patients after LT. Methods: This retrospective study included 155 patients (aged >65 years) who underwent LT at Seoul National University Hospital. The recipients were subcategorized into 2 groups based on the mCCI score and mFI-5: the low (0–1) and high (2–5) mCCI groups, and low (≤0.4) and high (>0.4) mFI-5 groups. The independent effect of each variable on post-LT survival was determined using the mCCI subgroup, age at transplantation, sex, Child-Turcotte-Pugh score, model for end-stage liver disease (MELD) score, and mFI-5 subgroup. Results: The high-mCCI group (41 patients) showed significantly lower 1- and 3-month and 1-, 3-, and 5-year survival than the low-mCCI group. Using the Cox regression model, the mCCI, sex, and MELD score remained significant. The mFI-5 was not a significant factor to predict patients’ survival. Conclusion The mCCI and MELD scores could be used to predict post-LT survival in older patients.

BACKGROUND: Inflammatory bowel disease (IBD) is an incurable disease that negatively influences the quality of life of patients. Current and emerging therapies target proinflammatory cytokines and/or receptors to downregulate proinflammatory responses, but insufficient remission requires other therapeutic agents. Herein, we report that the synthetic antiinflammatory peptide 15 (SAP15) is capable of cell penetration and anti-inflammatory activity in human macrophages. METHODS: SAP15 was labeled with fluorescence and administered to human leukemia monocytic cells (THP-1) cells for cell penetration analysis. Using biolayer interferometry analysis, the binding affinity of SAP15 with histone deacetylase 5 (HDAC5) was measured. SAP15-treated THP-1 cells were analyzed by protein phosphorylation assay, flow cytometry, and enzyme-linked immunosorbent assay (ELISA). In addition, in vivo analysis of the therapeutic effect on IBD was observed in a dextran sulfate sodium (DSS)-induced model. Samples from SAP15-treated mice were analyzed at both the macroscopic and microscopic levels using ELISA, myeloperoxidase (MPO) assays, and histological evaluations. RESULTS: SAP15 was internalized within the cytosol and nucleus of THP-1 cells and bound to the HDAC5 protein. SAP15-treated macrophages were assessed for protein phosphorylation and showed inhibited phosphorylation of HDAC5 and other immune-related proteins, which led to increased M2-like macrophage markers and decreased M1-like macrophage markers and tumor necrosis factor-a and interleukin-6 cytokine levels. The SAP15 treatment on IBD model showed significant recovery of colon length. Further histological analysis of colon demonstrated the therapeutic effect of SAP15 on mucosal layer. Moreover, proinflammatory cytokine levels and MPO activity from the plasma show that SAP15 is effective in reduced proinflammatory responses. CONCLUSION These findings suggest that SAP15 is a novel peptide with a novel cell-penetrating peptide with antiinflammatory property that can be used as a therapeutic agent for IBD and other inflammatory diseases.

BACKGROUND/OBJECTIVES: Isoflavones (ISFs) are effective in preventing bone loss, but not effective enough to prevent osteoporosis. Mixtures of soy ISF and lecithin (LCT) were prepared and characterized in an attempt to improve the bone loss.MATERIALS/METHODS: The daidzein (DZ) and genistein (GN) solubility in soy ISF were measured using liquid chromatography-mass spectrometry. The change in the crystalline characteristics of soy ISF in LCT was evaluated using X-ray diffraction analysis.Pharmacokinetic studies were conducted to evaluate and compare ISF bioavailability. Animal studies with ovariectomized (OVX) mice were carried out to estimate the effects on bone loss. The Student's t-test was used to evaluate statistical significance. RESULTS: The solubility of DZ and GN in LCT was 125.6 and 9.7 mg/L, respectively, which were approximately 25 and 7 times higher, respectively, than those in water. The bioavailability determined by the area under the curve of DZ for the oral administration (400 mg/kg) of soy ISF alone and the soy ISF-LCT mixture was 13.19 and 16.09 µg·h/mL, respectively. The bone mineral density of OVX mice given soy ISF-LCT mixtures at ISF doses of 60 and 100 mg/kg daily was 0.189 ± 0.020 and 0.194 ± 0.010 g/mm3 , respectively, whereas that of mice given 100 mg/kg soy ISF was 0.172 ± 0.028 g/mm3 . The number of osteoclasts per bone perimeter was reduced by the simultaneous administration of soy ISF and LCT. CONCLUSIONS The effect of preventing bone loss and osteoclast formation by ingesting soy ISF and LCT at the same time was superior to soy ISF alone as the bioavailability of ISF may have been improved by the emulsification and solvation of LCT. These results suggest the possibility of using the combination of soy ISF and LCT to prevent osteoporosis.

BACKGROUND/OBJECTIVES: Isoflavones (ISFs) are effective in preventing bone loss, but not effective enough to prevent osteoporosis. Mixtures of soy ISF and lecithin (LCT) were prepared and characterized in an attempt to improve the bone loss.MATERIALS/METHODS: The daidzein (DZ) and genistein (GN) solubility in soy ISF were measured using liquid chromatography-mass spectrometry. The change in the crystalline characteristics of soy ISF in LCT was evaluated using X-ray diffraction analysis.Pharmacokinetic studies were conducted to evaluate and compare ISF bioavailability. Animal studies with ovariectomized (OVX) mice were carried out to estimate the effects on bone loss. The Student's t-test was used to evaluate statistical significance. RESULTS: The solubility of DZ and GN in LCT was 125.6 and 9.7 mg/L, respectively, which were approximately 25 and 7 times higher, respectively, than those in water. The bioavailability determined by the area under the curve of DZ for the oral administration (400 mg/kg) of soy ISF alone and the soy ISF-LCT mixture was 13.19 and 16.09 µg·h/mL, respectively. The bone mineral density of OVX mice given soy ISF-LCT mixtures at ISF doses of 60 and 100 mg/kg daily was 0.189 ± 0.020 and 0.194 ± 0.010 g/mm3 , respectively, whereas that of mice given 100 mg/kg soy ISF was 0.172 ± 0.028 g/mm3 . The number of osteoclasts per bone perimeter was reduced by the simultaneous administration of soy ISF and LCT. CONCLUSIONS The effect of preventing bone loss and osteoclast formation by ingesting soy ISF and LCT at the same time was superior to soy ISF alone as the bioavailability of ISF may have been improved by the emulsification and solvation of LCT. These results suggest the possibility of using the combination of soy ISF and LCT to prevent osteoporosis.

BACKGROUND: Intrathecal opioid has been known to enhance the quality and prolong the duration of spinal anesthesia, as well as to reduce postoperative pain. The purpose of this study was to evaluate postoperative analgesic characteristics of intrathecal fentanyl for the first 48 hours after anorectal surgery under saddle anesthesia. METHODS: Eighty patients were recruited in our study. Forty patients were randomly allocated to group B that received 0.5% bupivacaine 5 mg with 0.3 ml normal saline. The other 40 patients were assigned to group BF which was given 0.5% bupivacaine 5 mg with fentanyl 15 μg. The primary outcome variable was a numeric rating scale (NRS) at six hours postoperatively. Secondary outcomes included changes in the NRS score between one and 48 hours postoperatively, consumption of rescue analgesics, and the frequency of rebound pain. RESULTS: Group BF exhibited a lower mean NRS score at postoperative six hours compared to group B (P < 0.001). However, the mean NRS score was not different after postoperative six hours between the two groups. The median consumption of rescue analgesics in group BF was less than that of group B (P = 0.028) and the frequency of rebound pain decreased in group BF when compared to group B (P = 0.021). The levels of sensory block were S1 dermatome and motor block scores were 0 for both groups. There was no significant difference in adverse effects between the groups. CONCLUSIONS: Intrathecal fentanyl 15 μg for anorectal surgery under saddle anesthesia led to an improved pain score for the first six hours after surgery and decreased postoperative analgesic use. Rebound pain diminished with intrathecal fentanyl and adverse effects did not increase.
Analgesics ; Anesthesia* ; Anesthesia, Spinal ; Bupivacaine ; Fentanyl* ; Humans ; Pain, Postoperative*

A 30-year-old primigravida with gestational age of 25 weeks and 4 days was admitted for emergency cesarean section. She was diagnosed as pre-eclampsia with fetal distress. We anesthetized the patient through the combined spinal-epidural anesthetic technique, and there was no specific event throughout the surgical procedures and in post anesthetic care unit. Subsequently, she complained of unilateral hearing difficulty in the ward and an otolaryngology consultation was obtained. She was diagnosed with left sudden sensorineural hearing loss in full frequency range after an acoustic examination. She received intravenous and local steroid treatments for 4 weeks. She showed 32 dB on pure tone audiometry after 5 months. However, we could not continue follow-up testing on the patient because she stopped visiting the hospital since the last examination. We reported a case of uncommon unilateral sudden sensorineural hearing loss after a combined spinal-epidural anesthesia for emergency cesarean section.
Acoustics ; Adult ; Anesthesia* ; Audiometry ; Cesarean Section* ; Emergencies* ; Female ; Fetal Distress ; Follow-Up Studies ; Gestational Age ; Hearing ; Hearing Loss ; Hearing Loss, Sensorineural* ; Humans ; Otolaryngology ; Pre-Eclampsia ; Pregnancy

Only a few cases of anterior longitudinal ligament (ALL) injury related with retropharyngeal hematoma without fracture have previously been reported. The treatment of choice for retropharyngeal hematoma is generally considered to be conservative care, but we believe that early surgery of this pathology would be better in certain situations. Here, we describe two cases with life-threatening large retropharyngeal hematomas related with ALL injuries and operated on at an early stage. Two previously healthy patients visited the emergency room with neck pain and dyspnea after falling. Serious neck swelling was observed and lateral neck X-ray showed severe widening of the prevertebral space. Due to dyspnea progression, emergency endotracheal intubation was performed. Although there was no primary cause of the retropharyngeal hematoma on preoperative examination, ALL tearing was intraoperatively confirmed during early surgery. The in-hospital evolutions of the patients were favorable after surgery. We should bear in mind the possibility of ALL injury and perform early surgery where possible given the earlier convalescence and good prognosis.
Airway Obstruction ; Convalescence ; Dyspnea ; Emergencies ; Emergency Service, Hospital ; Hematoma* ; Humans ; Intubation ; Intubation, Intratracheal ; Longitudinal Ligaments ; Neck ; Neck Pain ; Pathology ; Prognosis ; Spine ; Tears

Systemic capillary leak syndrome (SCLS) is very rare and lethal disease and only 150 cases have been reported after the first publication of its report in 1960 by Clarkson. SCLS is characterized by hemoconcentation and hypoalbuminemia caused by reversible plasma extravasation. Its mechanism is unknown, but transient dysfunction of the endothelium is the most suspected cause and trigger of this event may cause immunologic disarrangement. After recovery of endothelial function, fluid injected during the shock period is redistributed and can cause severe pulmonary edema. SCLS should be considered in patients with acute and severe hypotension with hemoconcentration and hypoalbuminemia without obvious cardiac dysfunction. Especially we should take into account the possibility of SCLS if fluid replacement does not work or the shock state is aggravated despite aggressive fluid resuscitation and vasopressor administration. SCLS itself is a very rare disease; furthermore, SCLS that develops during well-controlled surgery is even more rare. So we report this case with review of the literature.
Anesthesia, General* ; Capillary Leak Syndrome* ; Endothelium ; Humans ; Hypoalbuminemia ; Hypotension ; Plasma ; Publications ; Pulmonary Edema ; Rare Diseases ; Resuscitation ; Shock

BACKGROUND AND OBJECTIVES: The effective management of tinnitus should start with an accurate diagnosis, but no concensus has been developed in Korea concerning how to measure the features of tinnitus. This study surveyed otologists in the training hospitals and hospitals specialized in otologic care in Korea to identify the current status in the assessment of patients with tinnitus. SUBJECTS AND METHOD: The questionnaire on the assessment of tinnitus was sent by email to otologists in training and to specialized hospitals specializing in otologics in Korea. The questionnaire included inquiry about various types of tests conducted, such as the audiologic test, tinnitus test, blood test, radiologic test, and the methods of history taking and physical examination for somatic tinnitus. RESULTS: Regarding the audiologic assessment of tinnitus, all the otologist were using pure tone audiometry, 97% speech audiometry, and 87% tinnitus test. For the psychophysical measure of tinnitus, both loudness and pitch matching were conducted by all the otologists. The performance rate of blood test were 38.5%, and the most preferred radiologic test in pulsatile tinnitus was temporal bone computed tomography (59%). Finally, the rate of investigation including the history taking and physical examination of somatic tinnitus was between 74-84%. CONCLUSION: Our results showed that although the tests perfermed by otologists varied, the essential tests for assessing tinnitus were commonly practiced. We analyzed the current status of tinnitus assessment and supplemented guidlines to help measure tinnitus. Further concensus on tinnitus diagnosis is needed, particularly about the standadized and unified principles.
Audiometry ; Audiometry, Speech ; Diagnosis ; Electronic Mail ; Hematologic Tests ; Humans ; Korea ; Physical Examination ; Surveys and Questionnaires ; Temporal Bone ; Tinnitus*