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Background: Osteoarthritis (OA) is a prevalent joint disease affecting the spine, hands, hips, knees, and feet. However, definitive drugs for OA are lacking, and current treatments are limited owing to inconvenient administration, inadequate functional improvement, and long-term side effects including gastrointestinal and cardiovascular adverse events. Therefore, in this study, we aimed to assess the pharmacokinetics and safety profiles of PK101, a fixed-dose combination (FDC) comprising PG201, a 12-herb extract used in OA treatment in traditional East Asian medicine, and celecoxib, a selective cyclooxygenase-2 inhibitor, by comparing its administration as an FDC and the corresponding individual formulations in healthy subjects., Patients and Methods: A randomized, open-label, single-dose, 2 × 2 crossover design with a cohort of healthy participants. All subjects received a single FDC tablet (405.4 mg PG201 and 100 mg celecoxib) or the individual formulations, with 7-day washout period between administrations. The estimation of maximum plasma concentration and area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration of celecoxib involved determining the geometric mean ratios and 90% confidence intervals of the FDC compared to its individual formulations., Results: Forty-six participants were enrolled; however, only 44 completed the study. The geometric mean ratios (90% confidence intervals) for the area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration and maximum plasma concentration of celecoxib were 1.1124 (1.0601-1.1672) and 1.2788 (1.1708-1.3969), respectively. The time of maximum plasma concentration range was 1.0 to 4.0 hours and 1.0 to 6.0 hours (minimum-maximum) for the FDC and individual formulations, respectively. Seven adverse events occurred in 6 subjects., Conclusion: The systemic exposure and safety profiles of the individual and FDC formulations were similar, supporting their potential as an innovative and effective therapeutic approach for OA treatment. All relevant data are within the paper and its Supporting Information files., Competing Interests: HK and H-YM are employees of the PMG Pharm Co., Ltd. All the other authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Dry eye disease (DED) is a common ocular disorder in which the tear film cannot maintain homeostasis. Acupuncture has been used to treat DED in Korean medicine. Particularly, intradermal acupuncture (IDA) is less painful and enables free movement after treatment. However, it can also provoke allergic reactions to metal. To overcome this, biodegradable microneedle acupuncture (BMA) has been developed. This study compared BMA with traditional IDA in terms of efficacy and safety in patients with DED., Methods: This study was designed as an investigator-initiated, assessor-blinded, single-center, parallel randomized controlled trial. Thirty patients with DED were enrolled and randomized to one of the treatments. One group was treated with BMA on the acupoints, including bilateral BL2, GB14, TE23, EX-HN5, and ST1. The other group was treated with traditional IDA at the same acupoints. Treatments were conducted 3 times a week for 4 weeks. The major endpoint was ocular surface disease index (OSDI). The minor endpoints were subjective symptoms visual analog scale (VAS), quality of life (QoL), and tear production measured by the Schirmer I test., Results: All enrolled participants successfully completed the trial, and all of their data was analyzed. Both treatments remarkably improved the OSDI score, VAS score, QoL score, and tear secretion after 4 weeks (P < .05). Except for tear production in the left eye (P < .05), there were no statistical differences between the 2 treatments on the final visit (P > .05). No adverse events were observed., Conclusion: BMA and IDA had the same therapeutic effect for improving DED and both were safe. BMA can be used in patients with DED as an alternative to traditional IDA., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Regdanvimab is a novel neutralizing antibody agent used for the treatment of coronavirus disease 2019 (COVID-19). However, the effectiveness of regdanvimab in delta-variant patients has rarely been investigated. We examined the clinical outcomes and adverse events in COVID 19 patients treated with regdanvimab in the delta-variant era. Data were collected from laboratory-confirmed COVID-19 hospitalized patients who received regdanvimab in 2021 and categorized into pre-delta and delta variant groups. The primary outcome was the need for oxygen therapy. Rescue therapy, clinical improvement, and adverse events were analyzed. Among 101 patients treated with regdanvimab, 31 (30.7%) were delta patients and 49 (48.5) were pre-delta patients. 64.4% were male, the mean age was 60.3 years, and 70 patients (69%) had at least one underlying disease. The median interval from symptom onset to injection was 4 days. Twenty-three patients (23%) needed oxygen therapy, including 9 (29%) in the delta and 8 (16.3%) in the pre-delta group. (P = .176) The risk of early oxygen supplement was higher in the delta group (adjusted hazard ratio (aHR), 6.75; 95% confidence interval(CI), 1.53-29.8). The in-hospital survival rate was 100%, and no patients were admitted to the intensive care unit. Adverse events occurred in 43% of patients:13 (42%) delta patients and 23 (47%) pre-delta patients had any adverse events (P = .661). Patients treated with regdanvimab 4 days after symptom onset showed a favorable prognosis (aHR, 0.26; 95% CI, 0.26-0.91). We found that the high-risk mild to moderate COVID-19 patients treated with regdanvimab showed similar disease progression in delta-variant patients and pre-delta variants; however, we need to be more closely observed delta-variant patients than those in the pre-delta group despite regdanvimab treatment due to rapid disease aggravation., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: The aim of this study was to audit the 22 items and assessed each item's predictive value on surgical outcomes., Background: The KLASS-02 trial revealed that the oncologic outcomes of laparoscopic distal gastrectomy are not inferior to open distal gastrectomy in patients with advanced gastric cancer. The surgeons participating in this trial were chosen based on the assessment scores from the KLASS-02-QC trial, which used 22 items for standardization of D2 lymphadenectomy and quality control., Methods: We reviewed proficiency scores (PSs) for 22 items for 20 surgeons who participated in KLASS-02. The surgeons were divided into 2 groups according to PS, and the perioperative outcomes of 924 patients enrolled in KLASS-02 were compared between groups. Each item's predictive value for perioperative outcome was then assessed using multivariable regression models., Results: Of the total 924 patients, 529 were operated on by high-score surgeons (high PS) and 395 were operated on by low-score surgeons (low-PS). High-PS group had less intraoperative blood loss, longer operation times, and fewer complications, major complications, reoperations, and shorter first flatus and hospital stay than low-PS group ( P =0.006, P <0.001, P <0.001, P <0.001, P =0.042, P =0.013, and P <0.001, respectively). Some items used in KLASS-02-QC predicted perioperative outcomes, such as intraoperative blood loss, major complications, reoperation, and hospital stay., Conclusions: Although this study only analyzed data associated with qualified surgeons, the 22 items effectively assessed the surgeons based on PS. A high score was associated with longer operation times, but better perioperative outcomes., Competing Interests: W.J.H. reported receiving grants from Medtronic and GC pharma, stocks from Hutom, and personal fees from SK Hynix (Wuxi) outside the submitted work. S.-U.H. reported receiving grants from the National R&D Program for Cancer Control and Ethicon Endo-Surgery, a Johnson & Johnson Company, during the study period. S.-H.K. reported receiving grants from Medtronic and Stryker outside the submitted work. D.J.P. reported receiving grants from Daewoong Pharmaceuticals, JW Pharmaceuticals, and Medtronic outside the submitted work. J.W.K. reported receiving grants from the DN Company Co. Ltd research fund outside the submitted work. The remaining authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Neuroinflammation plays an essential role in the process of acute ischemic stroke (AIS) injury repair. The current study seeks to investigate the relationship between the neutrophil/lymphocyte ratio (NLR) and neutrophil/high-density lipoprotein cholesterol ratio (NHR) and AIS disease severity and short-term prognosis. As such, the primary aim of this study is to improve AIS diagnosis and treatment. A total of 136 patients with AIS at the Nantong Third People's Hospital were retrospectively analyzed. The inclusion criteria comprised patients with ischemic stroke admitted to the hospital <24 hours after symptom onset. Baseline, clinical, and laboratory data were collected from all patients within 24 hours of admission. Univariate, multivariate and receiver operating characteristic curve analysis were performed to determine the relationship between NLR, NHR, AIS severity, and short-term prognosis. NLR (odds ratio [OR] = 1.448, 95% confidence interval [CI] 1.116-1.878, P = .005) and NHR (OR = 1.480, 95% CI 1.158-1.892, P = .002) were identified as independent risk factors for stroke severity. Additionally, the correlation between combined NLR and NHR and AIS severity achieved a sensitivity of 81.4% and specificity of 60.4% with a best cutoff value of 6.989. This outcome was superior to that of the single composite inflammatory index. Moreover, NLR (OR = 1.252, 95% CI 1.008-1.554, P = .042) was an independent risk factor for poor short-term prognosis in patients with AIS. When the optimal cutoff value was 2.605, the sensitivity of NLR correlation with the short-term prognosis of AIS was 82.2%, and the specificity was 59.3%. NLR combined with NHR exhibits a strong correlation with disease severity in AIS. Meanwhile, an elevated NLR in patients with AIS can predict a poor short-term prognosis., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The prevalence of dry eye, which is a common lacrimal disease, is steadily increasing in modern society. However, fundamental treatment for it has not yet been established. This study aims to assess the efficacy and safety of a novel medical device, the biodegradable microneedle acupuncture (BMA), using a traditional intradermal acupuncture needle as the control acupuncture for dry eye., Method: This study will be an investigator-initiated, assessor-blinded, comparative, superiority pilot randomized controlled trial. A total of 30 patients with dry eye will be randomly assigned to the experimental or the control group in equal proportion. For the experimental group, the BMA will be applied to both sides of 5 acupoints including BL2, GB14, TE23, EX-HN5, and ST1. For the control group, conventional intradermal acupuncture will be applied to the same acupoints. The needles will be attached for 4 hours. Over 4 weeks, both the interventions will be performed 12 times in total. The primary outcome would be the ocular surface disease index. The secondary outcomes would be the visual analog scale for subjective symptoms, quality of life, Schirmer I test, and general assessment., Discussion: The findings of this study on the efficacy and safety of the BMA would be helpful for patients with dry eye in clinical practice. Further, these results would provide for the foundation of a large-scale BMA study., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Therapeutic drug monitoring (TDM) is effective in optimizing the efficacy of infliximab in patients with inflammatory bowel disease (IBD). An affordable way of monitoring is in high demand. This study evaluated the analytical and clinical performances of the newly available Remsima monitor kits and compared them with the established enzyme-linked immunosorbent assay kits. The trough level of infliximab in patients with IBD treated with an infliximab originator (Remicade) or biosimilar compounds (Remsima and Remaloce) was measured using a Remsima® Monitor Drug Level (Remsima) kit at the Samsung Medical Center, Seoul, Korea. Twenty-six plasma samples were collected immediately before the infusion of infliximab from 18 patients with IBD (Remicade, n = 8; Remsima, n = 6; and Remaloce, n = 4). The intra-assay intraclass correlation coefficient (ICC) of the RIDA and Remsima kits was 0.951 (95% CI = 0.908-0.976) and 0.990 (95% CI = 0.981-0.995). The inter-assay ICC of infliximab trough level between the RIDA and Remsima kits was very high (R = 0.971; 95% CI = 0.935-0.987), and the mean difference between the kits was 1.458 (95% limits of agreement = -3.302 to 6.219). The intra- and inter-assay reliabilities of all types of infliximab did not show significant differences. Qualitative stratification revealed substantial similarities between the kits (weighted kappa = 0.798). This study indicated that the Remsima kit was reproducible and highly correlated with the RIDA kit., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Hyperhomocysteinemia (HHcy) is considered a risk factor for cardiovascular disease (CVD), including chronic kidney disease (CKD). In this study, we investigated the association between levels of serum homocysteine (Hcy) and mortality, inferred from the presence of CKD. Our study included data of 9895 participants from the 1999 to 2016 National Health and Nutrition Examination Surveys (NHANES). Multivariable-adjusted Cox proportional hazard models using propensity-score, were used to examine dose-response associations between Hcy level and mortality. A total of 9895 participants, 1025 (10.3%) participants were diagnosed with CKD. In a multivariate Cox regression analysis including all participants, Hcy level was significantly associated with all-cause mortality in the nonCKD group, compared to the 1st quartile in the fully adjusted model (2nd quartile: hazard ratio (HR) 1.75, 95% confidence interval (CI) 1.348-2.274, P < .001; 3rd quartile: HR 2.22, 95% CI 1.726-2.855, P < .001; 4th quartile: HR 3.77, 95% CI 2.952-4.830, P < .001). However, this finding was not observed in the CKD group. The observed pattern was similar after propensity score matching. In the nonCKD group, overall mortality increased in proportion to Hcy concentration (2nd quartile: HR 2.19, 95% CI 1.299-3.709, P = .003; 3rd quartile: HR 2.60, 95% CI 1.570-4.332, P < .001; 4th quartile: HR 3.72, 95% CI 2.254-6.139, P < .001). However, the risk of all-cause mortality according to the quartile of Hcy level, did not increase in the CKD group. This study found a correlation between the Hcy level and mortality rate only in the nonCKD group. These altered risk factor patterns may be attributed to protein-energy wasting or chronic inflammation status, that is accompanied by CKD., Competing Interests: The authors have no funding and conflict of interests to declare., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Rationale: Chronic ulcerative colitis is an autoimmune disease in which epithelial injury continuously occurs in the colonic mucosa. While mesalazine (5-aminosalicylic acid) is used to treat ulcerative colitis, it can also cause liver failure, headaches, and abdominal pain; therefore, an alternative treatment is required. The purpose of this study was to evaluate the effectiveness of 80 stellate ganglion blocks in reducing pain and other symptoms in a patient with chronic ulcerative colitis., Patient Concerns: A 54-year-old female patient with a history of ulcerative colitis was concerned with worsening symptoms, such as abdominal discomfort and bloody-mucous stools, over the past 3 years., Diagnoses: Oozing mucosal bleeding and a small amount of exudate were observed on colonoscopy; a diagnosis of ulcerative colitis was made upon histologic examination., Interventions and Outcomes: A total of 80 stellate ganglion blocks were administered, after which the patient's symptom and pain level was decreased from 6 to 4 points on the numeric rating scale (11-point, 0 = no pain, 10 = worst pain imaginable). Improved clinical signs were observed on colonoscopy at a follow-up assessment., Lessons: The stellate ganglion block may be effective for the reduction of pain and other symptoms in patients with chronic ulcerative colitis., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: To investigate changes in subfoveal choroidal thickness (SFCT) and their relationship with best-corrected visual acuity and optical coherence tomography parameters after intravitreal dexamethasone implant injection for diabetic macular edema., Methods: Eighty-one eyes treated with dexamethasone implant injection for diabetic macular edema were evaluated for best-corrected visual acuity, central macular thickness, SFCT, and optical coherence tomography parameters at baseline and Weeks 7 and 14., Results: The mean baseline SFCT significantly decreased at Weeks 7 (P < 0.001) and 14 (P < 0.001). At Week 7, each 1-µm reduction in central macular thickness and five Early Treatment Diabetic Retinopathy Study letters (-0.1 logarithm of the minimal angle of resolution) improvement were associated with SFCT reductions of 0.09 (P = 0.002) and 3.91 (P = 0.044) µm, respectively. At Week 14, each 1-µm reduction in central macular thickness was associated with a 0.14-µm reduction in SFCT (P < 0.001). Eyes with good functional and anatomical responses exhibited significantly greater SFCT reductions. Subretinal fluid resulted in greater SFCT changes (P = 0.039) and better best-corrected visual acuity (P = 0.033) at Week 7. A continuous ellipsoid zone/interdigitation zone layer was associated with a smaller mean SFCT at Week 7 (P = 0.002) and better best-corrected visual acuity at Weeks 7 and 14 (both, P < 0.001)., Conclusion: Changes in SFCT after dexamethasone implant injection therapy for diabetic macular edema may predict anatomical and functional outcomes and correlate with optical coherence tomography features that are known as predictors of treatment response., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.)

Background: Rituximab is an induction immunosuppressant essential for ABO-incompatible kidney transplantation (ABOi KT). However, studies on its dosing, which differs among countries and transplant centers, are lacking. Therefore, we retrospectively investigated the effectiveness of the induction dose of rituximab against patient mortality, graft failure, and adverse events., Methods: We included the studies referring to at least 2 of eligible induction doses (200 mg, 200-500 mg, or 500 mg) of rituximab during ABOi KT and relevant outcomes such as patient survival, graft failure, and bacterial and viral infections. We performed direct and indirect network meta-analyses using Bayesian models and ranked different rituximab doses using generation mixed treatment comparison. Publications were retrieved using CENTRAL, MEDLINE, EMBASE, and Science Citation Index Expanded databases from 1970 to February 2020 and analyzed. The GRADE of network meta-analysis approach specified 4 levels of certainty for a given result: high, moderate, low, and very low., Results: Among the 4256 patients from 21 trials, glomerular filtration rate, graft loss, antibody-mediated rejection, T-cell mediated rejection, fungal infection, bacterial infection, and CMV infection did not differ among ABOi groups treated with different rituximab doses. The effect on mortality was significantly higher in rituximab 200 to 500 mg, and rituximab 500 mg groups (odds ratios [OR] 3.5, 95% CrI: 1.3-9.8, and OR 3.0, 95% CrI 1.1-9.8), but not in rituximab 20 mg group (OR 0.45, 95% CrI 0.036-2.5). The incidence of BK virus was significantly lower in the rituximab 200-mg group than in the other groups., Discussion: In ABO-incompatible kidney transplantation, low-dose rituximab is more efficacious than higher doses and reduces serious infection risks. Additional randomized controlled trials might be needed to confirm these findings due to small sample size., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

This study examined the relationships between stress, depression, body mass index, and food addiction in South Korean nursing students. Data from 323 nursing students in Seoul, Gangwon-do, Jeollanam-do, Gyeongsangnam-do, and Jeju-do were collected via self-report questionnaires and analyzed using chi-square tests, Mann-Whitney U tests, logistic regression analyses, and the receiver operating characteristic curve using SPSS 21.0. Overall, 7.1% of students were classified as having a food addiction. Stress and depression affected food addiction, and food addiction influenced obesity. Depression and stress combined were predictors of food addiction. These findings suggest that effective stress management and interventions for depression prevention may be beneficial to prevent food addiction in nursing students.

Background: The rates of cardiovascular mortality and morbidity are increased in advanced chronic kidney disease (CKD). Mild to moderate CKD is associated with an increase in cardiovascular events. This study aims to investigate the effects of statins on patient mortality and cardiac events., Study Appraisal and Synthesis Methods: Studies on statins (atorvastatin, rosuvastatin, fluvastatin, lovastatin, pravastatin, simvastatin, and simvastatin + ezetimibe) in Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and Science Citation Index Expanded databases from 1970 to February 2019 were analyzed. Inclusion criteria were randomized control trials and adult patients (>18 years old). Reviews, observational studies, and clinical trials that did not clearly define outcomes or that did not have thrombosis as an outcome were excluded. We performed direct and indirect network meta-analysis using Bayesian models and ranked different statins using generation mixed treatment comparison (GeMTC) and Stata version 13. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) of network meta-analysis approach specified 4 levels of certainty for a given result: high, moderate, low, and very low. The outcomes were cardiac events, cardiac mortality, and all-cause mortality., Results: Nineteen studies (45,863 patients) were included. Compared with placebos, pravastatin 40 mg group showed a significantly lower patient mortality (odds ratio 0.66 [95% credible interval, 0.46-0.91]).Atorvastatin 80 mg, fluvastatin 40 mg, lovastatin 20 mg, pravastatin 40 mg, and simvastatin 40 mg showed significant results in reducing cardiac events.In rank probability, pravastatin showed the best effect at all-cause mortality rate. Lovastatin, fluvastatin, and pravastatin showed good effects in the 1st, 2nd, and 3rd ranks in cardiac events., Conclusions and Implications of Key Findings: Pravastatin 40 mg demonstrated the best effect on all-cause mortality, and was observed to be effective with high ranking in cardiac events. We anticipate that the data of this study will assist physicians in making informed decisions when selecting statins, such as pravastatin, as a treatment option for CKD patients.

Stereotactic radiosurgery (SRS) is considered the initial treatment for lung cancer patients with small-sized and limited number of brain metastases. The objective of this study was to assess clinical outcomes of SRS treatment using CyberKnife (CK) for recursive partitioning analysis (RPA) class II/III patients with 1 to 3 brain metastases from lung cancer and identify which patients in the high RPA class could benefit from SRS.A total of 48 lung cancer patients who received CK-based SRS for their metastatic brain lesions from 2010 to 2017 were retrospectively analyzed. Radiographic response was evaluated during follow-up period. Overall survival (OS) and intracranial progression-free survival (IPFS) were calculated and prognostic variables associated with OS and IPFS were evaluated.Median follow-up time was 6.6 months. Local control rates at 6 months and 1-year following SRS were 98% and 92%, respectively. The median OS of all patients was 8 months. One-year and 2-year OS rates were 40.8% and 20.9%, respectively. In multivariate analysis, uncontrolled primary disease (P = .01) and Eastern Cooperative Oncology Group performance status of 2 or 3 (P = .001) were independent prognostic factors for inferior OS. These 2 factors were also significantly associated with inferior IPFS. In subgroup analysis according to RPA class, primary disease status was the only prognostic factor, showing statistically significant OS differences in both RPA class II and III (controlled vs uncontrolled: 41.1 vs 12.3 months in RPA class II, P = .03; 26.9 vs 4.1 months in RPA class III, P = .01).Our results indicated that SRS could be an effective treatment option for RPA class II/III patients with brain metastases from lung cancer in the modern treatment era. SRS might be particularly considered for patients with controlled primary disease.

Medication use during pregnancy is gradually increasing; however, the safety of this practice remains largely unknown.We investigated medications with the most adverse drug reactions (ADRs) among pregnant women and the clinical features of those medications.Reports of ADRs among pregnant women were extracted from the Korea Adverse Events Reporting System (January 2012-December 2015). We analyzed the data of drugs frequently reported to cause ADRs and their clinical features among 3 age groups.A total of 5642 ADRs among 3428 patients were analyzed. The number of ADR reports increased annually. The most common drug categories causing ADRs were analgesics, followed by gynecologic, uterotocolytic, anti-infective, antidiabetic, analgesic, and antihypertensive drugs. Analgesics comprised 6 opioids (morphine, fentanyl, hydromorphone, oxycodone, tramadol, pethidine) and an anti-pyretics (nefopam and ketorolac). As an individual drug, ritodrine (24.4%) was the most frequently reported, followed by morphine, 5-HT3 serotonin antagonist, nefopam, fentanyl, magnesium sulfate, insulin lispro, cefazedone, sodium chloride, hydromorphone, oxycodone, cefotetan, nifedipine, human insulin, tramadol, ketorolac, pethidine, methylergometrine, metoclopramide, and misoprostol (in that order). ADRs most frequently occurred in women aged 25 to 34 years, and the trend of ADR with the 20 most commonly reported medications significantly differed among the age groups (P = .011). In addition, the kind of common causative drugs was different among the age groups.Knowledge of medications and clinical conditions resulting in the highest ADR rates among pregnant women is necessary for medical practitioners to administer proper care.

Objective: To determine the toxicity and oncologic outcome of neoadjuvant chemoradiotherapy (CRT) followed by curative total mesorectal excision (TME) in the elderly (≥70 yrs) and younger (<70 yrs) rectal cancer patients., Background: Sufficient data for elderly rectal cancer patients who received definitive trimodality have not been accumulated yet., Patients and Methods: A total of 1232 rectal cancer patients who received neoadjuvant CRT and TME were enrolled in this study. After propensity-score matching, 310 younger patients and 310 elderly patients were matched with 1:1 manner. Treatment response, toxicity, surgical outcome, recurrence, and survival were assessed and compared between the 2 groups of patients., Results: The median age was 58 years for the younger patient group and 74 years for the elderly group. Pathologic complete response rates were not significantly different between the 2 groups (younger and elderly: 17.1% vs 14.8%, P = 0.443). The 5-year recurrence-free survival (younger and elderly: 67.7% vs 65.5%, P = 0.483) and overall survival (younger and elderly: 82.9% vs. 79.5%, P = 0.271) rates were not significantly different between the 2 groups either. Adjuvant chemotherapy after surgery was less frequently delivered to the elderly than that to younger patients (83.9% vs 69.0%). Grade 3 or higher acute hematologic toxicity was observed more frequently in the elderly than that in the younger group (9.0% vs 16.1%, P = 0.008). Late complication rate was higher in the elderly group compared with that in the younger group without statistical significance (2.6% vs 4.5%, P = 0.193)., Conclusions: Although acute hematologic toxicity was observed more frequently in the elderly patients than that in the younger patients, elderly rectal cancer patients with good performance status who received preoperative CRT and TME showed favorable tumor response and recurrence-free survival similar to younger patients.

Purpose: To evaluate intravitreal bevacizumab (IVB) injection efficacy for the treatment of chronic, atypical, or recurrent central serous chorioretinopathy (CSC)., Methods: Clinical data from 77 eyes of 71 patients with chronic, atypical, or recurrent CSC treated with IVB were retrospectively analyzed. After initial 6-weekly IVB administration until no subretinal fluid remained at the fovea, additional as-needed IVBs were administered, based on optical coherence tomography findings. Best-corrected visual acuity and central retinal thickness (CRT) were analyzed at baseline and 3, 6, 9, and 12 months after initial IVB., Results: The significant improvement of baseline logarithm of minimum angle of resolution best-corrected visual acuity and CRT at 3 months (both P < 0.001) was maintained throughout the 12-month follow-up period. Best-corrected visual acuity improved significantly in patients with chronic and recurrent CSC, at all time points (all P < 0.05), but not in patients with atypical CSC. The CRT reduction was significant in all subgroups during the follow-up period (all P < 0.05). Definite leakage on initial fluorescein angiography correlated with improved reduction in CRT (P = 0.039)., Conclusion: As-needed optical coherence tomography-based IVB was effective for reducing CRT in patients with chronic, atypical, or recurrent CSC, and for vision improvement in chronic and recurrent CSC over the 1-year follow-up period.

Asthma and chronic obstructive pulmonary disease (COPD) are common chronic airway diseases. Overlap in the clinical features of these 2 diseases is observed in many cases, and thus, the concept of asthma-COPD overlap (ACO) has recently been proposed. However, the definition of ACO and the clinical significance remains to be determined.We evaluated the prevalence and risk of acute exacerbation in ACO among Korean COPD patients as defined by modified Spanish criteria and American Thoracic Society (ATS) Roundtable criteria.The prevalence of ACO was 47.7% (660/1383) by modified Spanish criteria and 1.9% (26/1383) by ATS Roundtable criteria. ACO, regardless of criteria, did not significant affect the exacerbation risk during at least 1-year follow-up period.Substantial discrepancies were found in the prevalence and outcome of ACO according to different diagnostic criteria, which would compromise implementation of ACO before the definition is established.

Purpose: To investigate the differences in the progression of diabetic retinopathy (DR) in both eyes of patients with axial anisometropia., Methods: A retrospective review was conducted on diabetic patients who had different axial lengths (difference greater than 1 mm) in each eye. The primary objective of this study was to analyze the differences in the progression of DR in both eyes of patients with axial anisometropia. Fundus images (fluorescein angiography and photographs of the fundus covering the Early Treatment Diabetic Retinopathy Study seven fields) were graded using the Early Treatment Diabetic Retinopathy Study DR grading system. Also, the severity of diabetic retinopathy was analyzed based on the axial length and subfoveal choroidal thickness., Results: Thirty-four of 6,963 patients with DR were included after applying the exclusion and inclusion criteria. The mean age was 53.53 ± 12.20 years and duration of diabetes was 9.63 ± 7.73 years. The mean axial length of the longer and shorter eye was 26.21 ± 2.04 mm and 23.21 ± 1.73 mm, respectively (P < 0.001). In shorter eyes, 61.7% (21 of 34) of the eyes had proliferative diabetic retinopathy. In contrast to the shorter eye, only 8 of the longer eyes (8 of 34, 23.5%) had proliferative diabetic retinopathy (McNemar test, P < 0.001). In eyes with thin subfoveal choroidal thickness (<250 µm), the proliferative diabetic retinopathy ratio was significantly lower (P = 0.007)., Conclusion: In patients with axial anisometropia, the longer eye had a lower degree of DR progression than the shorter eye. This result showed that elongation of the axial length had a protective effect against the progression of DR without individual confounding factors.

The objective is to evaluate the magnetic resonance imaging (MRI) findings in rhabdomyolysis in detail and determine their correlation with the development of peripheral neuropathy.Magnetic resonance images for 23 patients with confirmed rhabdomyolysis with (n = 11) or without (n = 12) peripheral neuropathy were retrospectively reviewed for the signal intensity on T1- and T2-weighted images, intramuscular hemorrhage, enhancement pattern, shape and margin in the longitudinal plane, edema in the deep fascia and overlying subcutaneous layer, multiplicity, and bilateral limb involvement. The collected data were statistically analyzed and the relationship between the imaging findings and the development of peripheral neuropathy was determined.Abnormal signal intensities on T1- or T2-weighted images were observed for all patients except one. Fourteen patients (60.9%) showed intramuscular hemorrhage. Stippled enhancement (11/23; 47.8%) was the most common enhancement pattern. Nineteen patients (86.4%) showed a well-defined rectangular shape with a ragged margin in the longitudinal plane. The affected muscle volume usually increased (17/23; 73.9%), with edema in the deep fascia and the overlying subcutaneous layer (13/23; 56.5%). Multiplicity within a muscle, compartment, and limb was observed in 7 (31.8%), 18 (81.8%), and 16 (72.7%) patients, respectively. Bilateral involvement was observed in 7 patients (30.4%). Only multiplicity within a compartment showed a statistically significant correlation with peripheral neuropathy development.Common MRI findings in rhabdomyolysis include intramuscular hemorrhage, stippled enhancement, a well-defined rectangular shape with a ragged margin in the longitudinal plane, and multiplicity. Multiplicity within a compartment may be a predictor of the development of peripheral neuropathy.

Background: The benefit of access flow surveillance in preventing vascular access thrombosis and failure remains controversial, as many randomized clinical trials (RCTs) have failed to demonstrate consistent results. The aim of this study was to perform a meta-analysis including newly published RCTs with a subgroup analysis for arteriovenous fistulas (AVFs) and arteriovenous grafts (AVGs)., Methods: A systematic review of the available literature was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. An electronic search was conducted using the MEDLINE, EMBASE, and Cochrane Library databases of RCTs conducted from 1970 to 2017 that involved access flow surveillance. As a result, 9 RCTs met our criteria. The control group was defined by indirect and various surveillance methods such as dynamic venous pressure measurement and physical examination. Conversely, the interventional group was defined as a noninvasive duplex ultrasound scan (USS) or ultrasound dilution that directly measured the flow of vascular access., Results: The studies included 990 patients comprising 658 native AVFs and 332 AVGs. The prevalence of diabetes was 29.3%and 30.5% in the interventional and control groups, respectively. The estimated overall pooled risk ratio (RR) of thrombosis was 0.782 [95% confidence interval (95% CI), 0.553-1.107; P = .17], favoring interventional group, although this was not statistically significant. In the subgroup analysis, the pooled RR of thrombosis was .562 (95% CI, 0.346-0.915; P = .02) for AVFs, which significantly favored the interventional group. Conversely, the pooled RR for AVGs was 1.104 (95% CI, 0.672-1.816; P = .70)., Conclusion: The surveillance method to measure access flow through USS showed a significant benefit for reducing thrombosis in AVFs. The result encourages adherence to the current guidelines for AVFs. However, no benefit was found regarding AVGs. Recent guidelines with a "one-size-fits-all" approach may be revised to a "tailored-to-risk" approach.

Background: This study was conducted to assess the prognostic value of a simplified mortality score (SMS) using the delta neutrophil index (DNI) and thrombotic microangiopathy (TMA) score, both easily obtained from the complete blood count, to identify critically ill patients at high risk of death., Methods: This was a retrospective study performed in the medical ICU at Yonsei University College of Medicine from June 2015 to February 2016. The primary end point was 28-day all-cause mortality. Participants were divided into two groups: a training (n = 232) and a test (n = 57) set. We used Cox proportional-hazards analysis, Harrell's C index, and Kaplan-Meier survival analysis to derive the SMS and test its internal validity., Results: We enrolled 289 patients. The 28-day mortality rate was 31.1% (n = 90). Nonsurvivors had higher APACHE II, SOFA, and TMA scores, and DNI. The SMS, derived by Cox proportional-hazards analysis, consisted of age, sex, DNI, and TMA score. We assigned a weighted point to each variable in the SMS, as follows: age + 11 if male + (2 × DNI) + (61 [TMA = 1], 76 [TMA = 2], 74 [TMA = 3], 26 [TMA = 4], 99 [TMA = 5]). Nonsurvivors had a higher median SMS than survivors, and the Harrell's C index was 0.660. Analysis of survival by risk group according to SMS (low, intermediate, high risk) showed a significant difference among these three groups (P < 0.001). We then investigated this SMS in the test set to determine internal validity; the results were similar to those of the training set., Conclusions: The SMS is a more rapid, simple prognostic score for predicting 28-day mortality and stratifying risk than the APACHE II or SOFA scores. However, external validation using a larger sample is needed.

Rationale: Sinonasal inverted papilloma (IP) is a locally aggressive tumor found in the schneiderian membrane, lining the nasal cavity and paranasal sinuses., Patient Concerns: We report a case of a 63-year-old woman with undifferentiated carcinoma (UC) arising in an IP in the left maxillary sinus., Diagnoses: The preoperative diagnosis was IP of the maxillary sinus., Interventions: We performed endoscopic medial maxillectomy to remove the remnant mass in the left maxillary sinus., Outcomes: Histological examination of the specimen revealed typical area of IP and sinonasal UC., Lessons: Clinicians should consider sinonasal UC in the differential diagnosis of malignancy arising in the sinonasal IP.

Objective: To assess the impact of targeted interventions on trends in central line-associated bloodstream infection., Design: A before-and-after study between January 2013 and September 2014., Setting: Tertiary hospital in the Republic of Korea., Patients: All patients with central-line catheters in the hospital., Interventions: In September 2013, interventions that targeted central line insertion practices were implemented in 10 ICUs, including compliance monitoring with a central line insertion practices bundle and use of an all-inclusive catheter kit. The impact of targeted interventions on trends in central line-associated bloodstream infection was evaluated by segmented autoregression analysis of an interrupted time series., Measurements and Main Results: The average hospital-wide central line-associated bloodstream infection rates in the baseline and intervention periods were 1.84 and 1.56 per 1,000 catheter-days, respectively. During the baseline period, there was an increase of central line-associated bloodstream infection rate of 0.12 per 1,000 catheter-days per month. In the intervention period, there was a decrease of central line-associated bloodstream infection rate of 0.16 per 1,000 catheter-days per month (change in slope, -0.28; 95% CI, -0.37 to -0.19; p < 0.0001). In ICUs, the average central line-associated bloodstream infection rates in the baseline and intervention periods were 1.92 and 1.64 per 1,000 catheter-days, respectively. During the baseline period, there was an increase of central line-associated bloodstream infection rate of 0.18 per 1,000 catheter-days per month in ICUs. After sequential-targeted interventions, there was a decrease of central line-associated bloodstream infection rate of 0.16 per 1,000 catheter-days per month (change in slope, -0.34; 95% CI, -0.50 to -0.18; p = 0.0007)., Conclusions: Targeted interventions were associated with significant changes in trends in the occurrence rate of central line-associated bloodstream infection in ICUs and the entire hospital.

Consumption of red meat and alcohol are known risk factors for colorectal cancer, but associations for dietary fat remain unclear. We investigated the associations of dietary fat, protein, and energy intake with prevalence of colorectal adenoma.We performed a prospective cross-sectional study on asymptomatic persons who underwent a screening colonoscopy at a single center during a routine health check-up from May to December 2011. Dietary data were obtained via a validated Food Frequency Questionnaire (FFQ), assisted by a registered dietician. We also obtained information on alcohol consumption and smoking status, and measured metabolic syndrome markers including abdominal circumference, blood pressure, fasting glucose, serum triglyceride and high-density lipoprotein cholesterol. We calculated odds ratio (OR) and 95% confidence interval (CI) to evaluate the associations using the polytomous logistic regression models. As a secondary analysis, we also conducted a matched analysis, matched by age and sex (557 cases and 557 non-cases).The study sample included 557 cases (406 males and 151 females) with histopathologically confirmed colorectal adenoma, and 1157 controls (650 males and 507 females). The proportion of advanced adenoma was 28.1% of men and 18.5% of female, respectively. Although vegetable protein intake was inversely associated with the prevalence of colorectal adenoma, further adjustment for potential confounding factors attenuated the association, resulting in no significant associations. There were no significant associations between dietary fat intake and colorectal adenoma in energy-adjusted models. For vegetable protein in women, the OR for the comparison of those in the highest tertile with those in the lowest tertile was 0.47 (95% CI 0.25-0.91, P for trend = 0.07) after adjustment for total energy intake. However, after controlling for metabolic syndrome markers, body mass index, smoking status, alcohol consumption, and family history of colorectal adenoma, which were all significantly high in the colorectal adenoma patients group, the association became attenuated (OR 0.54, 95% CI 0.27-1.11, P for trend = 0.13).In conclusion, we did not observe the significant associations for intakes of total energy, total, animal and vegetable fats, and total, animal and vegetable proteins in relation to colorectal adenoma prevalence., Competing Interests: The authors have no conflicts of interest to disclose.

Objective: To evaluate the association between anesthetic management before and after graft reperfusion and early graft regeneration in living donor liver transplantation (LDLT)., Background: Sufficient graft regeneration is essential for the success of LDLT. Diverse signals start to trigger liver regeneration immediately after graft reperfusion., Methods: Graft volume at 14 ± 2 days after LDLT was measured in 379 consecutive recipients using computed tomography images with 3-dimensional reconstruction. The association between anesthetic variables and the degree of graft regeneration for 2 weeks was analyzed using simple and multiple linear regressions. The anesthetic variables included hemodynamics, laboratory measurements, vasoactive drugs, and blood products transfusion., Results: The degree of graft regeneration for 2 weeks was 52% in median and ranged from 5% to 123%. Platelet transfusion was identified as the sole independent anesthetic factor contributing to graft regeneration. Platelet concentrate transfusion of 1 to 6 units vs none was correlated with a 6.5% increase in graft regeneration (P = 0.012). Platelet concentrate transfusion of more than 6 units vs none was further correlated with an 18.4% increase in regeneration (P < 0.001). In the subgroup of recipients without intraoperative platelet transfusion, mean platelet count measured during the intraoperative reperfusion phase was positively associated with graft regeneration (P = 0.033)., Conclusions: Graft regeneration after LDLT increased in relation to a graded increase in the amount of transfused platelets and higher postreperfusion platelet counts during surgery. These results offer additional evidence regarding the important role of platelets in initiating liver regeneration and, furthermore, the indications for and the benefits vs risks of platelet transfusion during LDLT.

Background: Coccygodynia is a pain in the region of the coccyx that radiates to the sacral, perineal area. The cause of the pain is often unknown. Coccygodynia is diagnosed through the patient's past history, a physical examination, and dynamic radiographic study, but the injection of local anesthetics or a diagnostic nerve blockade are needed to distinguish between somatic, neuropathic, and combined pain. Ganglion impar is a single retroperitoneal structure made of both paravertebral sympathetic ganglions. Although there are no standard guidelines for the treatment of coccygodynia, ganglion impar blockade is one of the effective options for treatment., Methods: Here, we report a 42-year-old female patient presenting with severe pain in the coccygeal area after spinal arachnoid cyst removal., Results: Treatment involved neurolysis with absolute alcohol on the ganglion impar through the transsacrococcygeal junction. Pain was relieved without any complications., Conclusion: Our case report offers the ganglion impar blockade using the transsacrococcygeal approach with absolute alcohol can improve intractable coccydynia., Competing Interests: The authors have no conflicts of interest to disclose.

Many studies have found that probiotics or synbiotics can be used in patients with diarrhea or inflammatory bowel disease for the prevention and treatment of some pathologies by improving gastrointestinal barrier function. However, there are few studies availing the use of probiotics in patients with colorectal cancer. To lay the foundation for the study of nutritional support in colorectal cancer patients, a meta-analysis has been carried out to assess the efficacy of probiotics on the intestinal mucosa barrier in patients with colorectal cancer after operation. To estimate the efficacy of probiotics on the intestinal mucosa barrier in patients with colorectal cancer after operation, a meta-analysis of randomized controlled trials has been conducted. Databases including PubMed, Ovid, Embase, the Cochrane Central Register of Controlled Trials, and the China National Knowledge Infrastructure have been searched to identify suitable studies. Stata 12.0 was used for statistical analysis, and sensitivity analysis was also conducted. Six indicators were chosen to evaluate probiotics in protecting the intestinal mucosa barrier in patients with colorectal cancer. Ratios of lactulose to mannitol (L/M) and Bifidobacterium to Escherichia (B/E), occludin, bacterial translocation, and levels of secretory immunoglobulin A (SIgA), interleukin-6 (IL-6), and C-reactive protein (CRP) were chosen to evaluate probiotics in protecting the intestinal mucosa barrier in patients with colorectal cancer. Seventeen studies including 1242 patients were selected for meta-analysis, including 5 English studies and 12 Chinese studies. Significant effects were found in ratios of L/M (standardized mean difference = 3.83, P = 0.001) and B/E (standardized mean difference = 3.91, P = 0.000), occludin (standardized mean difference = 4.74, P = 0.000), bacterial translocation (standardized mean difference = 3.12, P = 0.002), and levels of SIgA (standardized mean difference = 2.91, P = 0.004) and CRP (standardized mean difference = 4.21, P = 0.000), but no significant effects were found for levels of IL-6 (standardized mean difference = 1.33, P = 0.184). Probiotics can effectively protect the intestinal mucosa physical and biological barrier in patients with colorectal cancer after operation. However, to evaluate the protective effect on intestinal mucosal barrier, further studies on the type and concentration of the probiotics, duration of therapy, and the therapeutic route are required.

The purpose of this study is to identify dose-volumetric parameters that predict radiation-induced hepatic toxicity (RIHT) by analyzing the relationship between the biologically effective dose (BED) delivered to the normal liver and RIHT.The clinical and dosimetric data from 123 patients with unresectable hepatocellular carcinoma (HCC) treated with helical tomotherapy were analyzed. The median radiation dose was a 50 Gy in 4.5 Gy fractions (range, 30-60 Gy in 1.8-5.0 Gy fractions) to 95% of the planning target volume. RIHT was defined as a Child-Pugh score increase of at least 2 points within 3 months of helical tomotherapy completion.RIHT developed in 60 patients (48.7%). Multivariate logistic regression analysis showed that VBED20 (percentage of nontarget normal liver volume that received more than a BED of 20 Gy) was a significant parameter (P < 0.001), and the cut-off value was 40.8% with a sensitivity and specificity of 0.833 and 0.698, respectively, according to the receiver operating characteristic curve (P < 0.001).Maintaining a VBED20 below 40.8% will reduce the risk of RIHT, and the proposed normal liver tolerance curve could be a useful guideline when treating unresectable HCC patients with various radiotherapy dose schedules.

Study Design: Retrospective analysis., Objective: The main objectives of this study were to analyze and compare cervical sagittal parameters, including the T1 slope, in a population of 45 patients with degenerative cervical spondylolisthesis (DCS) and to compare these patients with a control group of asymptomatic population., Summary of Background Data: Sagittal balance in the cervical spine is as important as the pelvic incidence and is related to the concept of T1 slope. Compared with degenerative lumbar spondylolisthesis, there are few studies evaluating DCS, and characteristic changes of the cervical sagittal parameters (including T1 slope) in patients with DCS are not well studied., Methods: We identified 45 patients with DCS (5.8%) from a database of 767 patients, using cervical radiograph in a standing position. All had radiograph and computed tomographic scan at the same time. Cervical sagittal parameters were analyzed on computed tomographic scan in a standardized supine position. The following cervical sagittal parameters were measured: T1 slope, neck tilt, thoracic inlet angle, and cervical lordosis (C2-C7 angle). The DCS group was compared with a control group of 45 asymptomatic age- and sex-matched adults to the DCS group, who were studied in a recently published study., Results: Of our initial group of 767 patients, 45 with anterolisthesis (5.8%) were included for this study. The T1 slope was significantly greater for DCS (26.06° ± 7.3°) compared with the control group (22.32° ± 7.0°). No significant difference of the neck tilt, thoracic inlet angle, and C2-C7 angle was seen between the DSC group and the control group. Therefore, the T1 slope of the DSC group was significantly greater than that of the control group (P < 0.005)., Conclusion: The DCS group was characterized by a greater T1 slope than the control group; therefore, we suggest that a high T1 slope may be a predisposing factor in developing DCS., Level of Evidence: 3.

Study Design: Retrospective study., Objective: The purpose of this study was to analyze the relationship of the parameters of cervical sagittal alignment between those obtained from cervical CT and those obtained from radiography, as well as to determine which parameter would help predict physiological lordosis of the cervical spine., Summary of Background Data: Sagittal balance in the cervical spine is as important as the pelvic incidence and is related to the concept of T1 slope. However, many articles including this article based on unclear cervical x-ray radiographs could weakly explain the parameters. To overcome the fundamental limitation of x-ray radiographs, Hallym University Sacred Heart Hospital reported the strong correlation between T1 slope and cervical lordosis on the cervical dimensional CT scans like result by checking by the cervical x-ray radiographs., Methods: A retrospective analysis of data from 50 asymptomatic adults in whom both cervical CT scans and cervical radiograph were obtained at the same time. The T1 slope, Cobb angle C2-C7, neck tilt, and thoracic inlet angle (TIA) obtained from the CT scans and radiographs were assessed., Results: The T1 slope on x-ray was significantly correlated with the T1 slope on CT. The mean of the T1 slope on x-ray was larger than the mean of the T1 slope on CT (3.3° ± 6.1°). More cervical spine lordosis was evident on the cervical radiograph than on the cervical CT scan (5.93° ± 9.0°). No significant difference was seen between the TIA on x-ray and the TIA on CT (TIA on x-ray - TIA on CT, -0.1 ± 7.6, P = 0.959)., Conclusion: This difference may be due to the differing effect of gravity upon the spine between the upright versus the supine position. Accordingly, TIA and T1 slope may be used as a guide for the assessment of sagittal balance of the cervical spine.

Background: The aim of this study was to investigate the feasibility and safety of endoscopic resection of gastric neoplasm in solid-organ transplant (SOT) recipients., Methods: Between January 1994 and December 2011, the results of endoscopic resection of 17 lesions in 15 consecutive patients who had previously undergone SOT at Asan Medical Center were retrospectively evaluated. We compared clinical outcomes of this group with 1:5 matched non-SOT patients treated by endoscopic resection., Results: Of the 6,491 patients who underwent SOT during the study periods, 30 patients (0.46%) with 31 lesions were diagnosed with gastric cancer, and eight patients (0.12%) with nine lesions were diagnosed with gastric adenoma. Among them, 15 patients with 17 lesions were treated by endoscopic resection, and 19 patients with 20 lesions have undergone gastrectomy. In endoscopically resected SOT group, the median duration between transplantation and endoscopic treatment was 41 months (range, 5-196 months). En bloc and complete resection were achieved in 13 (76.5%) and 15 (88.2%) lesions. Four lesions (23.5%) experienced bleeding, which was successfully managed endoscopically. When compared with post-endoscopic resection bleeding rate of non-SOT group (5.9%, [5/85]), there was no significant difference in multivariable analysis (P=0.083)., Conclusions: In endoscopic resection for gastric neoplasm of SOT recipients, only manageable complications were noted in some patients, and graft dysfunctions or perforations did not occur. To avoid surgical resection with its associated perioperative mortality and morbidity, endoscopic resection for gastric neoplasm in SOT recipients is recommended as a feasible treatment with high efficacy and safety.

Unlabelled: Several studies recently reported the usefulness of plating methods following limb lengthening with external fixators. This study describes modification at the time of plate insertion, selection of a locking plate, and the direction of plating. From April 2006 to July 2009, 12 consecutive patients, mean age 17.8 years, were enrolled in the study. The mean follow-up period was 36.5 months. All lengthening procedures were performed at the tibia. After proximal tibial osteotomy, a monoaxial external fixator was maintained on the lateral side of the tibia. At the end of distraction, a manually bent locking plate was inserted on the anteromedial side of the tibia, and the external fixator was removed. The mean final lengthening amount was 4.23 cm (range, 3.6-5.0 cm). The mean duration of the external fixator was 54.9 days (range, 47-67 days) and the mean external fixator index was 13.0 days/cm (range, 12.3-14.4 days/cm). The mean time to bony consolidation was 195.7 days (range, 150-264 days) and the mean healing index was 46.1 days/cm (range, 38.4-55 days). There were only minor complications in four patients. This case series showed that, especially with tibia lengthening, our method allows for successful early removal of the external fixator as compared with other methods (plating after lengthening), is associated with fewer complications, and is an effective alternative., Level of Evidence: Therapeutic Level IV.

Background: It is known that sirolimus (SRL) aggravates cyclosporine A (CsA)-induced nephrotoxicity and pancreatic injury, but the influence of everolimus (EVR) on CsA-induced organ injury is undetermined., Methods: Rats were treated with CsA (15 mg/kg) and EVR or SRL (0.3 mg/kg) subcutaneously for 4 weeks. The influences of EVR or SRL on CsA-induced nephrotoxicity and pancreatic islet dysfunction were compared, and drug interactions between CsA and EVR or SRL were evaluated at blood and tissue levels., Results: Treatment with EVR or SRL alone did not cause severe pancreatic dysfunction and renal injury, but when combined with CsA they aggravated CsA-induced pancreatic and renal injury. Drug interactions between CsA and EVR or SRL differed at the tissue level. Combined treatment with CsA and SRL significantly increased the CsA or SRL levels in kidney and pancreas compared with CsA or SRL alone. However, combined treatment with CsA and EVR did not increase CsA or EVR levels in kidney and pancreas., Conclusions: Both EVR and SRL aggravate CsA-induced organ injury, but the pharmacologic interaction between EVR and CsA at the tissue level is less than that between CsA and SRL. This finding provides better understanding of the difference between EVR and SRL when combined with CsA treatment.

Background: The aim of this study was to observe the effect of sirolimus (SRL) on calcineurin inhibitor (CNI)-induced nephrotoxicity in the aging process by using renal expression of KLOTHO, an antiaging gene. METHODS.: Mice were treated with vehicle (VH; 1 mL/kg/day of olive oil), cyclosporine A (CsA; 30 mg/kg/day), or tacrolimus (FK; 1 mg/kg/day) with or without SRL (0.3 mg/kg/day) for 2 weeks. KLOTHO expression was evaluated by using reverse-transcriptase polymerase chain reaction, immunoblotting, and immunohistochemistry. Oxidative stress was evaluated by using immunohistochemistry and urinary excretion of 8-hydroxy-2'-deoxyguanosine (8-OHdG). The calcium metabolism was evaluated by using renal ectopic calcification, serum intact parathyroid hormone level, and renal fibroblast factor 23 (FGF23) expression., Results: Treatment with CsA or FK alone significantly decreased KLOTHO expression and increased urinary 8-OHdG excretion compared with VH treatment but SRL treatment did not. Treatment SRL+CsA or SRL+FK further decreased KLOTHO expression and increased urinary 8-OHdG excretion compared with treatment of CsA or FK alone. There was a strong correlation between KLOTHO expression and urinary 8-OHdG excretion (r=-0.893; P<0.001). Treatment of CsA or FK alone increased renal ectopic calcification and serum intact parathyroid hormone level and decreased renal FGF23 expression compared with VH treatment (P<0.05) but SRL treatment did not. Treatment with SRL+CNI aggravated these parameters compared with CNI alone., Conclusions: SRL accelerates the CNI-induced oxidative process by down-regulating the renal antioxidant KLOTHO expression in the kidney.

Background: There is an increasing evidence that the presence of CD20 B cells is associated with poor clinical outcomes in acute cellular rejection (ACR), but clinical significance of CD38 B cells is undetermined. We attempted to examine the clinical significance of the CD38 B cells alone or in combination with CD20 B cells in renal transplant recipients with ACR., Methods: Fifty-four patients with ACR were included. Biopsy specimens were stained for CD20 and CD38. The clinical outcomes of CD20 or CD38 B cells were evaluated with late-onset and repeated ACR, steroid resistance, incomplete recovery after rejection treatment, and allograft survival., Results: Twenty-three patients (42.6%) had CD20 and 25 (46.3%) patients had CD38 B cells. Of these, 15 patients (27.8%) were positive for both CD20 and CD38 (CD20CD38). CD38 patients had higher rates of late-onset or repeated ACR and incomplete recovery compared with CD38 patients (P<0.05). The patients with CD20CD38 had a higher incomplete recovery rate than did patients with only CD20 or CD38 (P<0.05). The 5-year allograft survival was lower in CD20 and CD38 patients than in CD20 or CD38 patients (P<0.05 for each). CD20CD38 patients had lower graft survival than did patients with CD20 or CD38 alone (P<0.05)., Conclusion: Infiltration of CD38 B cells alone or in combination with CD20 B cells is a predictor for poor clinical outcomes of ACR in renal allograft.

Purpose: The purpose of this study was to evaluate the effect of intravitreal injection of bevacizumab on subretinal fluid associated with choroidal osteoma., Methods: In this retrospective noncomparative case series, eyes with serous retinal detachment involving the macula were treated with intravitreal injection of bevacizumab (1.25 mg/0.05 mL) and carefully followed-up with complete ophthalmic examination, including angiography and optical coherence tomography. The changes in best-corrected visual acuity and central foveal thickness were assessed by optical coherence tomography., Results: Six eyes received intravitreal injection of bevacizumab for serous retinal detachment. Only one eye had choroidal neovascularization associated with serous retinal detachment. The mean number of injections for the 6 eyes was 2.0 during the mean follow-up period of 11.3 months. The median logarithm of the minimum angle of resolution best-corrected visual acuity improved from 0.70 (Snellen equivalent, 20/100) at baseline to 0.30 (Snellen equivalent, 20/40; P = 0.043) at the final visit. The optical coherence tomography result also showed a significant reduction in central foveal thickness with a median central foveal thickness of 357.0 microm at baseline and 169.50 microm at the final visit (P = 0.028). The treatment was well tolerated, without ocular or systemic adverse events., Conclusion: Intravitreal injection of bevacizumab for serous retinal detachment secondary to choroidal osteoma resulted in both visual and anatomical improvements.

STUDY DESIGN.: Retrospective study. OBJECTIVE.: To compare the efficacy of anterior cervical discectomy and fusion with cage alone (ACDF-CA) with cage and plate construct (ACDF-CPC) in regards to fusion rate, radiologic and clinical outcomes. SUMMARY OF BACKGROUND DATA.: ACDF-CA has shown good results; however, debate exists regarding the high rate of complications such as pseudarthrosis, subsidence, and local kyphosis. In an attempt to avoid these complications, the authors have performed ACDF with cage and plate construct (ACDF-CPC). METHODS.: A total of 78 consecutive patients who underwent 1- or 2-level ACDF-CA or ACDF-CPC suffering from cervical radiculopathy were divided into 2 groups; Group A (n = 38) underwent ACDF-CA; Group B (n = 40) underwent ACDF-CPC. Fusion rate, segmental kyphosis, disc height, and subsidence rate were assessed by radiographs. Clinical outcomes were assessed using Robinson criteria. RESULTS.: Solid fusion was achieved in 78.9% (30/38) of subjects in group A compared to 97.5% (39/40) of subjects in group B (P = 0.01). Segmental kyphosis was noted in 42.1% (16/38) in group A compared with 10% (4/40) in group B (P < 0.01). There was a significant decrease in disc height in group A compared to group B (P < 0.05). Subsidence occurred in 32.3% (19/59 levels) of group A compared with 9.7% (6/62 levels) of group B (P < 0.01). Clinical outcomes were similar for both treatment groups. The pseudarthrosis rate in group A was higher than that in group B (P = 0.01). Revision surgery was required in 10.5% (4/38) of group A, whereas none of group B required reoperation (P < 0.01). CONCLUSION.: The use of cage and plate construct in 1- or 2-level ACDF results in a more lordotic alignment, an increased disc height, a higher fusion rate, a lower subsidence rate, and a lower complication rate than that of cage alone; however, there is no significant difference in clinical outcome between groups.

Purpose: : To evaluate the concentration of various cytokines in the aqueous humor of patients with naive, recurrent, and regressed choroidal neovascularization (CNV) of age-related macular degeneration after bevacizumab treatment., Methods: : Aqueous humor samples were collected from 36 eyes with age-related macular degeneration and 10 controls during cataract surgery. Of 36 patients with age-related macular degeneration, 5 eyes were naïve to bevacizumab injection, 14 eyes had recurrent CNV after bevacizumab treatment, and 17 eyes had regressed CNV after bevacizumab treatment. Cytokines were measured by an immunoassay using multianalyte biochip array technology (Evidence investigator cytokine and growth factor biochip array, RANDOX laboratories Ltd., Crumlin, UK)., Results: : No significant difference in the cytokine levels was noted between the control group and the naïve CNV group (all P > 0.05). Vascular endothelial growth factor in both naive (66.8 +/- 35.1 pg/mL) and recurrent CNV groups (55.7 +/- 63.0 pg/mL) was significantly higher compared with regressed CNV group (9.8 +/- 12.8 pg/mL, P = 0.025 and P = 0.004, respectively) but was not statistically different from the control group (81.8 +/- 43.7 pg/mL, P = 0.310 and P = 0.212, respectively). The aqueous humor level of tumor necrosis factor-alpha and interleukin (IL)-2 was significantly lower in recurrent CNV group (P = 0.036 and P = 0.019) compared with the control group. In the active CNV patients (recurrent and naïve CNV groups), the aqueous humor levels of IL-6 and IL-8 significantly correlated with the size of CNV (rho = 0.692, P = 0.001 and rho = 0.745, P < 0.001, respectively)., Conclusion: : Levels of Vascular endothelial growth factor measured in the aqueous humor were significantly related to the disease activity of CNV in age-related macular degeneration. Moreover, IL-2, IL-6, IL-8, and tumor necrosis factor-alpha may be related to the activity of CNV.

This study compares the effectiveness of the Pitt bacteremia score, the Charlson weighted index of comorbidity, and the Acute Physiology and Chronic Health Evaluation II (APACHE II) scoring systems for the prediction of mortality in intensive care unit (ICU) patients with sepsis using the retrospective observational method on 134 patients with ICU-acquired sepsis. The statistical analyses show several important findings. First, Pitt bacteremia score is significantly correlated with the APACHE II scoring system (correlation coefficient = 0.738, P < 0.001). Second, the APACHE II scoring system, the Pitt bacteremia score, and the Charlson weighted index of comorbidity are independently correlated with mortality. Third, the Pitt bacteremia score and the APACHE II scores are positively related to mortality in patients with ICU-acquired sepsis. As the result of the analyses, the mortality rate in patients with sepsis in the ICU is better predicted with the Pitt bacteremia score because it provides better estimation of sensitivity and specificity than the APACHE II scoring system and the Charlson weighted index of comorbidity.

Background: Human (H) cytomegalovirus (CMV) infections are a major cause of morbidity and mortality among kidney transplants. We performed a prospective study to evaluate the clinical usefulness of HCMV antigenemia assay for preemptive treatment after kidney transplantation., Methods: A total of 100 patients were followed up by HCMV antigenemia assay at posttransplantation weeks 1, 3, 5, 7, 9, 13, 17, and 21. Asymptomatic patients with positive antigenemia were observed without specific antiviral therapy., Results: Most patients had been given cyclosporine A- and prednisolone-based immunosuppressive therapy (99.0%) and were HCMV seropositive before transplantation (99.0%). A positive antigenemia assay was detected in 41 patients among 97 eligible patients. Symptomatic CMV diseases were observed in 10 of 41 patients. HCMV infections were related to history of acute rejection and use of antithymocyte globulin. HCMV-related symptoms and signs were clearly correlated with the level of antigenemia. All patients who had an HCMV antigenemia titer of higher than 50 per 400,000 leukocytes developed HCMV-related symptoms and signs during the follow-up period. This criterion showed the highest positive predictive value and specificity in the development of symptomatic HCMV infection., Conclusions: Data suggest that HCMV antigenemia titer can be used as a useful guide to preemptive treatment of HCMV infection after kidney transplantation in HCMV-positive donor and recipient.

Differential effects of ATP on tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant (TTX-R) sodium currents in rat dorsal root ganglion neurons were studied using the whole-cell variation of path-clamp technique. Currents were evoked by step depolarizations to 0 mV from a holding potential of -80 mV. ATP suppressed TTX-S sodium currents while it increased TTX-R sodium currents. The effects were concentration-dependent and were reversible upon washout with ATP-free external solution. ATP-gamma-S, a hydrolysis-resistant ATP analog, also affected two types of sodium currents similarly to ATP, excluding the possibility that the effects were caused by the products of ATP hydrolysis, namely adenosine. ATP by modulating sodium currents may exert profound effects on the transmission of sensory information such as nociception.

The relationship between the level of expression of tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant (TTX-R) sodium currents and the occurrence of two kinetically different ATP-induced currents in rat dorsal root ganglion neurons was studied. ATP evoked two distinct types of currents, one with fast activation and desensitization (I-fast) and the other with slow and persistent development (I-slow). In all TTX-S cells which expressed solely TTX-S sodium currents ATP evoked I-fast. The other cells expressed a variable proportion of TTX-S and TTX-R sodium currents. Only 15% of these TTX-R+S cells responded to ATP with I-fast. I-slow was evoked in both cell types but the magnitude of response was much greater in TTX-R+S cells. This result suggests that a different array of ion channels is equipped in different types of sensory neurons.

The differential effects of the anticonvulsants phenytoin and carbamazepine on the sodium channels of rat dorsal root ganglion (DRG) neurons were studied using the patch clamp technique. The action potentials from tetrodotoxin-resistant (TTX-R) cells were less sensitive to phenytoin and carbamazepine than those from tetrodotoxin-sensitive (TTX-S) cells. The steady-state inactivation curve for TTX-S sodium channels was shifted by as much as 20.6 mV and 11.4 mV by phenytoin and carbamazepine at 300 microM, respectively, yet the curve for TTX-R sodium channels was shifted only by 6.0 mV and 6.9 mV, respectively. Thus, the differential action potential block of TTX-S and TTX-R cells by phenytoin and carbamazepine is due to different voltage dependence of and differential drug effects on the inactivation kinetics of two types of sodium channels.

Nitromethylene heterocyclic insecticides are known to act on the nicotinic acetylcholine receptor-channel complex. The effects of the nitromethylene heterocycle imidacloprid on the nicotinic acetylcholine receptor of clonal rat pheochromocytoma (PC 12) cells were studied using the single-channel patch clamp technique. Imidacloprid generated single-channel currents of multiple conductance states in PC12 cells. Both acetylcholine and imidacloprid induced single-channel currents of main conductance and subconductance states with conductances of 33.3 and 9.4 pS by acetylcholine and 30.4 and 9.8 pS by imidacloprid. However, the main conductance currents were generated predominantly by acetylcholine, whereas the subconductance currents were generated predominantly by imidacloprid. Partial block of acetylcholine-induced currents by imidacloprid may be explained on the basis of the single-channel behavior.