Deep Spinal Infection after Outpatient Epidural Injections for Pain: A Retrospective Sample Cohort Study Using a Claims Database in South Korea.

BACKGROUND: Deep spinal infection is a devastating complication after epidural injection. This study aimed to investigate the incidence of deep spinal infection primarily after outpatient single-shot epidural injection for pain. Secondarily, this study assessed the national trends of the procedure and risk factors for said infection. METHODS: Using South Korea's National Health Insurance Service sample cohort database, the 10-yr national trend of single-shot epidural injections for pain and the incidence rate of deep spinal infection after the procedure with its risk factors were determined. New-onset deep spinal infections were defined as those occurring within 90 days of the most recent outpatient single-shot epidural injection for pain, needing hospitalization for at least 1 night, and receiving at least a 4-week course of antibiotics. RESULTS: The number of outpatient single-shot epidural injections per 1,000 persons in pain practice doubled from 40.8 in 2006 to 84.4 in 2015 in South Korea. Among the 501,509 injections performed between 2007 and 2015, 52 cases of deep spinal infections were detected within 90 days postprocedurally (0.01% per injection). In multivariable analysis, age of 65 yr or more (odds ratio, 2.91; 95% CI, 1.62 to 5.5; P = 0.001), living in a rural area (odds ratio, 2.85; 95% CI, 1.57 to 5.0; P < 0.001), complicated diabetes (odds ratio, 3.18; 95% CI, 1.30 to 6.7; P = 0.005), multiple epidural injections (three times or more) within the previous 90 days (odds ratio, 2.34; 95% CI, 1.22 to 4.2; P = 0.007), and recent use of immunosuppressants (odds ratio, 2.90; 95% CI, 1.00 to 6.7; P = 0.025) were significant risk factors of the infection postprocedurally. CONCLUSIONS: The incidence of deep spinal infection after outpatient single-shot epidural injections for pain is very rare within 90 days of the procedure (0.01%). The data identify high-risk patients and procedure characteristics that may inform healthcare provider decision-making.

Effect of Human Corneal Mesenchymal Stromal Cell-derived Exosomes on Corneal Epithelial Wound Healing.

Purpose: Mesenchymal stromal cells (MSCs) have been used therapeutically to modulate inflammation and promote repair. Extracellular vesicles, including exosomes, have been identified as one of the important mediators. This study investigated the effect of human corneal MSC-derived exosomes on corneal epithelial wound healing. Methods: Corneal MSCs (cMSCs) were isolated from human cadaver corneas. The secretome was collected after 72 hours and exosomes were isolated using differential ultracentrifugation. Morphology and size of exosomes were examined by electron microscopy and dynamic light scattering. Expression of CD9, CD63, and CD81 by cMSC exosomes was evaluated by western blotting. Cellular uptake of exosomes was studied using calcein-stained exosomes. The effect of exosome on wound healing was measured in vitro using a scratch assay and in vivo after 2-mm epithelial debridement wounds in mice. Results: cMSC exosomes were morphologically round and main population ranged between 40 and 100 nm in diameter. They expressed CD9, CD63, and CD81, and did not express GM130, Calnexin, and Cytochrome-C. Stained cMSC exosomes were successfully taken up by human cMSCs, human corneal epithelial cells (HCECs), and human macrophages in vitro and by corneal epithelium in vivo. In scratch assay, after 16 hours, cMSC exosome treated HCECs had 30.1% ± 14% remaining wound area compared to 72.9% ± 8% in control (P < 0.005). In vivo, after 72 hours, cMSC exosome-treated corneas had 77.5% ± 3% corneal wound healing compared to 41.6% ± 7% in the control group (P < 0.05). Conclusions: Human cMSC exosomes can accelerate corneal epithelial wound healing, and thus, may provide a therapeutic approach for ocular surface injuries.

Characteristics of heart rate variability in women with polycystic ovary syndrome: A retrospective cross-sectional study.

We aimed to compare the modulation of the autonomic nervous system (ANS) in women with polycystic ovary syndrome (PCOS) with that in healthy ovulatory women on the basis of heart rate variability (HRV), and to analyze the characteristics of the ANS in PCOS.In a retrospective chart review, HRV, body mass index, and physical examination data in women with PCOS and those with regular menstrual cycles were collected. Approval from the institutional review board (IRB) was obtained (IRB No. 2017-05-007-001) for this study. The mean outcomes were the values of HRV in the time [standard deviation of all normal R-R intervals (SDNN), the square root of the sum of the squares of the differences between the adjacent normal R-R intervals (rMSSD), and the mean heart rate turbulence (mean HRT)] and frequency [total power (TP), very-low-frequency power (VLF), low-frequency power (LF), normalized low-frequency power (LF norm), high-frequency power (HF), normalized high-frequency power (HF norm), and LF/HF ratio] domains. Differences between the 2 groups were analyzed by Mann-Whitney U test, using SPSS for Windows (version 22.0).There was no significant difference in the values of the time domain (SDNN, rMSSD, and mean HRT) between the groups. In the frequency domain, women with PCOS showed significantly higher LF (598.63 ±â€Š94.38 vs 459.13 ±â€Š163.64, P = .028), LF norm (48.64 ±â€Š3.39 vs 36.49 ±â€Š2.82, P = .009), and LF/HF ratio (1.49 ±â€Š0.31 vs 0.73 ±â€Š0.13, P = .009) than the control group. HF norm was significantly lower in the women with PCOS than in the controls (51.38 ±â€Š3.39 vs 63.51 ±â€Š2.82, P = .009). The TP, VLF, and HF showed no significant difference between the groups.The results of the present study indicated that PCOS is related to increased sympathetic modulation in HRV.

The Effect of General Anesthesia on Aminotransferase Levels in Patients with Elevated Aminotransferase Levels: A Single-Center 5-Year Retrospective Study.

BACKGROUND: The effect of commonly used anesthetics on postoperative aminotransferase levels in patients with preoperatively elevated values is unclear. METHODS: The medical records of 25,567 adult patients undergoing elective general anesthesia were retrospectively reviewed. Patients were classified into normal (≤ 40 IU/L), mild (41-119 IU/L), moderate (120-199 IU/L), and marked elevation (200+ IU/L) groups according to their preoperative alanine aminotransferase levels. Changes in these levels before and after general anesthesia were compared according to the anesthetics used. RESULTS: Among the patients with preoperative mild or moderate elevation, 97.8% (2589/2647) did not show a higher alanine aminotransferase level after surgery. Compared with total IV anesthesia (TIVA), sevoflurane showed adjusted odds ratios (95% confidence interval) of 1.27 (1.10-1.46) for mild, 1.33 (0.86-2.05) for moderate, and 3.35 (1.58-7.04) for marked postoperatively elevated levels of alanine aminotransferase versus normal levels. Similarly, compared with TIVA, desflurane showed adjusted odds ratios (95% confidence interval) of 1.21 (0.96-1.53) for mild, 1.44 (0.70-2.94) for moderate, and 3.18 (1.14-8.89) for marked postoperatively elevated levels of alanine aminotransferase versus normal levels (P = 0.05). CONCLUSIONS: In most cases, postoperative alanine aminotransferase levels did not worsen even in patients with preoperatively elevated levels. Sevoflurane was associated with increased odds for postoperative elevation of these levels after general surgery compared with TIVA.

c-Myb negatively regulates Ras signaling through induction of dual phosphatase MKP-3 in NIH3T3 cells.

Mitogen-activated protein kinase phosphatase-3 (MKP-3) negatively regulates ERK1/2 MAPK in a feedback loop. However, little is known about the molecular mechanism by which Ras signaling induces MKP-3 expression. In the present study, we demonstrate that exogenous expression of constitutively active H-Ras increases the level of MKP-3 mRNA. A transfection study using a series of MKP-3 promoter deletion constructs revealed that the c-Myb binding site is required for Ras-induced transcriptional activation of the MKP-3 gene promoter. Furthermore, we show that c-Myb directly binds to the MKP-3 promoter, as revealed by electrophoretic mobility shift assay and chromatin immunoprecipitation. Knock-down of c-Myb expression using siRNA abrogated Ras-induced MKP-3 promoter activity. These findings propose a novel mechanism through which Ras signaling activates c-Myb-dependent transcriptional activation of the MKP-3 gene.

Constitutively active Ras negatively regulates Erk MAP kinase through induction of MAP kinase phosphatase 3 (MKP3) in NIH3T3 cells.

The Ras/Raf/MEK/Erk signaling pathway is important for regulation of cell growth, proliferation, differentiation, survival, and apoptosis in response to a variety of extracellular stimuli. Lack of Erk MAPK activation is observed in several cancer cells despite active activation of Ras. However, little is known about the modulation of Erk1/2 activity by active Ras. Here, we show that overexpression of active H-Ras (H-RasG12R) in NIH3T3 fibroblasts impaired FGF2-induced Erk1/2 phosphorylation, as compared to wild-type cells. Northern blot analysis revealed that prolonged expression of active Ras increased MAP kinase phosphatase 3 (MKP3) mRNA expression, a negative regulator of Erk MAPK. Inhibition of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway abrogated active Ras-induced up-regulation of MKP3 expression, leading to the rescue of Erk1/2 phosphorylation. Our results demonstrated that the Ras/Raf/MEK/Erk signaling cascade is negatively regulated by the PI3K/Akt dependent transcriptional activation of the MKP3 gene.

Trochleoplasty in lateral patellar luxation in two calves.

Two Holstein Friesian calves were referred to the Animal Medical Center of Chonbuk National University with severe lameness on the hind limb(s), flexed stifle joint and an inability to walk since birth. Based on the clinical history, clinical findings and radiography of the stifle joint, the cases were diagnosed as grade III lateral patellar luxation (LPL). Trochleoplasty along with medial retinacular reinforcement and lateral release were performed in both calves. The calves recovered 3 to 4 weeks after surgery. Trochleoplasty along with medial retinacular reinforcement and lateral release can be an effective technique for the treatment of LPL in calves.

Photoactivation of pheophorbide a induces a mitochondrial-mediated apoptosis in Jurkat leukaemia cells.

The mechanism of cell death by pheophorbide a (Pba) which has been established to be a potential photosensitizer was examined in experimental photodynamic therapy (PDT) on Jurkat cells, a human lymphoid tumor cell line. In 30-60 min after irradiation, Pba treated cells exhibited apoptotic features including membrane blebbing and DNA fragmentation. Pba/PDT caused a rapid release of cytochrome c from mitochondria into the cytosol. Sequentially, activation of caspase-3 and the cleavage of poly ADP-ribose polymerase (PARP) were followed. Meanwhile, no evidence of activation of caspase-8 was indicated in the cells. In experiments with caspase inhibitors, it was found that caspase-3 alone was sufficient initiator for the Pba-induced apoptosis of the cells. Pba specific emission spectra were confirmed in the mitochondrial fraction and the light irradiation caused a rapid change in its membrane potential. Thus, mitochondria were entailed as the crucial targets for Pba as well as a responsible component for the cytochrome c release to initiate apoptotic pathways. Taken together, it was concluded that the mode of Jurkat cell death by Pba/PDT is an apoptosis, which is initiated by mitochondrial cytochrome c release and caspase-3-pathways.