A Case of Inadvertent Anterior Chamber and Corneal Stromal Injection with Antibiotics during Cataract Operation

Purpose: To report a case of inadvertent anterior chamber and cornea stromal injection with high dose antibiotics and steroids during cataract operation. Methods: During cataract operation on a 78 year-old female patient, high dose gentamicin (20 mg/0.5 ml) and dexamethasone (2 mg/0.5 ml) were inadvertently injected into the anterior chamber and cornea stroma when making cornea edema for sealing of the incision sites. Anterior chamber irrigation with balanced salt solution (BSS) was immediately administered. On postoperative day one, extensive cornea edema was noted, and best-corrected visual acuity was 0.2. Descemet's membrane folds were observed around the corneal incision sites. Topical 5% NaCl and 1% prednisolone were started. Results: Four weeks postoperatively, corneal edema began to reduce significantly. At four months postoperatively, corneal edema fully resolved, and best-corrected visual acuity was 0.8. However, some Descemet's membrane folds still remained, and a decrease in the number of endothelial cells was noted by specular microscope. Conclusions: In this case involving anterior chamber and cornea stromal injection with high dose antibiotics and steroids, immediate anterior chamber irrigation with balanced salt solution seemed an appropriate management, and the patient's long-term visual acuity appears good. To prevent such mistakes, precise labeling of all solutions and use of different syringe needles should be considered.ope

Assessment of the Efficacy of Reducing Peginterferon Alfa-2a and Ribavirin Dose on Virologic Response in Koreans with Chronic Hepatitis C

BACKGROUND/AIMS: The virologic response of Koreans to combination therapy for chronic hepatitis C is similar to westerns; however, dose modification occurs more frequently in Koreans. We evaluated the rates of peginterferon alpha-2a and ribavirin dose modifications and their effect on the virologic response in Koreans. METHODS: Patients with detectable HCV RNA and enrolled from multicenters were treated with peginterferon alpha-2a (180 microgram/week) and ribavirin (800 mg/day) for 24 weeks (genotype non-1, n=37) or peginterferon alpha-2a (180 microgram/week) and ribavirin (1,000-1,200 mg/day) for 48 weeks (genotype 1, n=55). RESULTS: Early virologic response (EVR) and sustained virologic response (SVR) were 77.2% (genotype 1, 75%; non-1, 81%) and 66.3% (genotype 1, 56%; non-1, 81%), respectively. The frequency of dose modification was 32.6% within the first 12 weeks and 52.2% during the entire treatment period. No difference was found in SVR regardless of dose modification. However, the SVR for patients using > or =80% of the peginterferon dose was significantly higher than for those using <80% (81.3 vs. 50.0%, p=0.007), despite varying ribavirin doses. No difference was found in SVR regardless of whether the ribavirin dose was <80% or not. These results did not change based on genotype. CONCLUSIONS: We suggest that using at least 80% of the peginterferon alpha-2a dose in Koreans not only maintains SVR but also reduces drug side effects during the entire treatment period. A lower dose of ribavirin may be as efficacious as a standard doseope

Anti-inflammatory and Immune-regulatory Effects of Subcutaneous Perillae Fructus Extract Injections on OVA-induced Asthma in Mice

Perillae fructus (perilla seed) is a traditional medicinal herb used to treat bronchial asthma in Oriental medical clinics. ST36 is one of the most widely used acupuncture points, particularly for immune system regulation. Injection of an herbal extract into an acupuncture point (herbal acupuncture) is a therapeutic technique combining both acupuncture and herbal treatment. Perillae fructus extract was injected subcutaneously (Perillae fructus herbal acupuncture; PF-HA) at acupoint ST36 of OVA-induced asthmatic mice. The lung weight, bronchoalveolar fluid (BALF) cell count, the number of CCR3+, CD11b+, CD4+ and CD3e+/CD69+ cells in the lung, and the level of IgE, IL-4, IL-5 and IL-13 in BALF and serum were then measured. RT-PCR was used to measure the mRNA expression of IL-4, IL-5, IL-13 and TNF-α in the lung. Lung sections were analyzed histologically. PF-HA significantly reduced lung weight, the number of inflammatory cells in the lung and BALF, the levels of IgE and Th2 cytokines in BALF and serum, mRNA expression of Th2 cytokines in the lung, and pathological changes in lung tissue. Our results suggest that PF-HA may have an anti-inflammatory and immune-regulatory effect on bronchial allergic asthma by restoring the Th1/Th2 imbalance in the immune system and suppressing eosinophilic inflammation in airways

High effectiveness of peginterferon alfa-2a plus ribavirin therapy in Korean patients with chronic hepatitis C in clinical practice

Background/AimsIdentifying the impact of a patient's ethnicity on treatment responses in clinical practice may assist in providing individualized treatment regimens for chronic hepatitis C (CHC). The effectiveness of standard peginterferon plus ribavirin therapy and the need for triple combination therapy with protease inhibitors in Koreans remain matters of debate. These issues were investigated in the present study.MethodsThe clinical data of 272 treatment-naïve Korean CHC patients who were treated in a community-based clinical trial (Clinical Trial group; n=51) and in clinical practice (Cohort group; n=221), were analyzed and compared. All were treated with standard protocols of peginterferon alfa-2a plus ribavirin therapy.ResultsFor patients with hepatitis C virus (HCV) genotype 1, the sustained virological response (SVR) rates in the Clinical Trial and Cohort groups were 81% (21/26) and 55% (58/106), respectively, by intention-to-treat (ITT) analysis (P=0.02), and 100% (13/13) and 80% (32/40), respectively, in treatment-adherent patients (P=0.18). For patients with HCV genotype 2, the SVR rates in these two groups were 96% (24/25) and 88% (101/115), respectively, by ITT analysis (P=0.31). Adherence and treatment duration were independent predictors of SVR for genotypes 1 and 2, respectively (P<0.01 for each). Korean patients with CHC achieved high SVR rates with peginterferon alfa-2a plus ribavirin in both the clinical trial and clinical practice settings.ConclusionsMeasures to raise adherence to standard therapy in clinical practice may improve the SVR rates in these patients as effectively as adding protease inhibitors, thus obviating the need for the latter

Clinical Features of Probable Cluster Headache: A Prospective, Cross-Sectional Multicenter Study

Background: Epidemiological data of probable cluster headaches (CH) are scarce in the relevant literature. Here, we sought to assess the prevalence and clinical characteristics of probable CH in comparison with definite CH.Methods: Data used in this study were obtained from the Korean Cluster Headache Registry (KCHR), a prospective, cross-sectional, multicenter headache registry that collected data from consecutive patients diagnosed with CH.Results: In total, 159 patients were enrolled in this study; 20 (12.6%) were diagnosed with probable CH. The most common unfulfilled criterion in patients with probable CH was the duration of attack, which was found in 40% of patients with probable CH. Among clinical characteristics, the number of autonomic symptoms tended to be lower in probable CH than in definite CH (1.7 ± 1.2 vs. 2.4 ± 1.5, p = 0.051) and conjunctival injection and lacrimation showed an increased odds ratio (OR) [OR = 3.03; 95% confidence interval (CI): 1.03–8.33] in definite CH. The groups did not differ with regard to baseline demographic characteristics, disability, impact on life, or treatment response.Conclusions: Probable CH is relatively common among CH disorders, with a clinical impact similar to that of definite CH

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Prevention and Therapy of Hepatocellular Carcinoma by Vaccination with TM4SF5 Epitope-CpG-DNA-Liposome Complex without Carriers

Although peptide vaccines have been actively studied in various animal models, their efficacy in treatment is limited. To improve the efficacy of peptide vaccines, we previously formulated an efficacious peptide vaccine without carriers using the natural phosphodiester bond CpG-DNA and a special liposome complex (Lipoplex(O)). Here, we show that immunization of mice with a complex consisting of peptide and Lipoplex(O) without carriers significantly induces peptide-specific IgG2a production in a CD4+ cells- and Th1 differentiation-dependent manner. The transmembrane 4 superfamily member 5 protein (TM4SF5) has gained attention as a target for hepatocellular carcinoma (HCC) therapy because it induces uncontrolled growth of human HCC cells via the loss of contact inhibition. Monoclonal antibodies specific to an epitope of human TM4SF5 (hTM4SF5R2-3) can recognize native mouse TM4SF5 and induce functional effects on mouse cancer cells. Pre-immunization with a complex of the hTM4SF5R2-3 epitope and Lipoplex(O) had prophylactic effects against tumor formation by HCC cells implanted in an mouse tumor model. Furthermore, therapeutic effects were revealed regarding the growth of HCC when the vaccine was injected into mice after tumor formation. These results suggest that our improved peptide vaccine technology provides a novel prophylaxis measure as well as therapy for HCC patients with TM4SF5-positive tumors

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication