Immunogenicity and safety of a tetanus-diphtheria vaccine and a 13-valent pneumococcal conjugate vaccine after concomitant vaccination in ≥ 50-year-old adults.

BACKGROUND: When two or more vaccines are administered concurrently, there is concern about safety and immunogenicity from vaccine interaction. METHODS: Subjects aged ≥50 years were randomized 1:1:1 to receive tetanus-diphtheria (Td) + 13-valent pneumococcal conjugate vaccine (PCV13; Group 1), PCV13 alone (Group 2), or Td alone (Group 3). After single or concomitant vaccination, enzyme-linked immunosorbent assay and opsonophagocytic assay (OPA) were performed to compare immunogenicity for Td and PCV13, respectively. RESULTS: A total of 448 subjects were available for the assessment. After concomitant administration, the non-inferiority criteria of geometric mean titer (GMT) ratios were met for tetanus, diphtheria, and all four pneumococcal serotypes (1, 5, 18C, and 19A). However, subjects in Group 3 (Td alone) were more likely to have a high IgG anti-tetanus antibody titer (≥ 0.5 U/mL) than those in Group 1 (Td + PCV13) (p <  0.01). As for the pneumococcal serotype 1, the OPA GMT was significantly higher in Group 1 (PCV13 + Td) compared to Group 2 (PCV13 alone) (p = 0.02). No serious adverse event occurred. CONCLUSIONS: Concomitant Td and PCV13 administration induced sufficient immunity without significant interference and showed good safety profiles. TRIALS REGISTRATION: NCT03552445 registered at http://www.clinicaltrials.gov on June 11, 2018 (retrospectively registered).

Perception and Attitudes of Korean Obstetricians about Maternal Influenza Vaccination.

Pregnant women are prioritized to receive influenza vaccination. However, the maternal influenza vaccination rate has been low in Korea. To identify potential barriers for the vaccination of pregnant women against influenza, a survey using a questionnaire on the perceptions and attitudes about maternal influenza vaccination was applied to Korean obstetricians between May and August of 2014. A total of 473 respondents participated in the survey. Most respondents (94.8%, 442/466) recognized that influenza vaccination was required for pregnant women. In addition, 92.8% (410/442) respondents knew that the incidence of adverse events following influenza vaccination is not different between pregnant and non-pregnant women. However, 26.5% (124/468) obstetricians strongly recommended influenza vaccination to pregnant women. The concern about adverse events following influenza vaccination was considered as a major barrier for the promotion of maternal influenza vaccination by healthcare providers. Providing professional information and education about maternal influenza vaccination will enhance the perception of obstetricians about influenza vaccination to pregnant women and will be helpful to improve maternal influenza vaccination coverage in Korea.

A Phase II trial of weekly bortezomib and dexamethasone in veterans with newly diagnosed multiple myeloma not eligible for or who deferred autologous stem cell transplantation.

Once-weekly administration of bortezomib has reduced bortezomib-induced peripheral neuropathy without affecting response rates, but this has only been demonstrated prospectively in three- and four- drug combinations. We report a phase II trial of alternate dosing and schedule of bortezomib and dexamethasone in newly diagnosed multiple myeloma patients who are not eligible for or refused autologous stem cell transplantation. Bortezomib 1·6 mg/m(2) intravenously was given once-weekly for six cycles, together with dexamethasone 40 mg on the day of and day after bortezomib. Fifty patients were enrolled; 58% did not require any dose modification. The majority of patients had multiple co-morbidities, including cardiovascular (76%) and renal insufficiency (54%), and the median number of medications prior to enrollment was 13. Of all evaluable patients, the overall response rate was 79% and at least 45% had at least a very good partial response. The median time to first response was 1·3 months (range, 0·25-2·4 months). The progression-free and overall survivals were 8 months and 46·5 months, respectively. Twenty-four percent developed worsening neuropathy. We conclude that alternate dosing and scheduling of bortezomib and dexamethasone is both safe and effective for management of newly diagnosed multiple myeloma in frail patients. (ClinicalTrials.gov number, NCT01090921).

Randomized, single-blind, active-controlled phase I clinical trial to evaluate the immunogenicity and safety of GC3114 (high-dose, quadrivalent influenza vaccine) in healthy adults.

Influenza is a major medically attended respiratory illness. The impact of influenza on morbidity and mortality is particularly high in the elderly. Immunosenescence attenuates the immune response of influenza vaccine in the elderly. High-dose influenza vaccine contains 60 µg of hemagglutinin per strain, four times more compared with standard-dose (SD) influenza vaccine. This study is a phase I clinical trial investigating the immunogenicity and safety of the GC3114, high-dose, quadrivalent inactivated influenza vaccine (HD-QIV) in healthy adults aged 19-64 years during the 2017-2018 season. Seroprotection rates of HD-QIV were 100.0% for A/H1N1, 96.67% for A/H3N2, 83.33% for B/Yamagata, and 96.67% for B/Victoria. Seroconversion rate for A/H1N1, A/H3N2, B/Yamagata, and B/Victoria strains were 86.67%, 90.0%, 53.33%, and 53.33%, respectively, in the HD-QIV group. The post-/pre-vaccination geometric mean titer ratio (GMTR) was 15.28 for A/H1N1, 8.19 for A/H3N2, 3.56 for B/Yamagata, and 3.03 for B/Victoria in the HD-QIV group. Seroconversion rate and post-/pre-vaccination GMTR for A/H3N2 were significantly higher in the HD-QIV group than in the SD-QIV group (control). No serious adverse events were reported. In conclusion, GC3114 was safe, well-tolerated, and immunogenic in healthy adults. Clinical Trials Identifier: NCT03357263.

Spread of ceftriaxone non-susceptible pneumococci in South Korea: Long-term care facilities as a potential reservoir.

Despite the availability of a pneumococcal National Immunization Program, which provides free PPSV23 vaccination for older adults aged ≥65 years in South Korea, pneumococcal pneumonia remains one of the most common respiratory infections, with increasing antimicrobial resistance. From January to December in 2015, all pneumococcal isolates were collected from a 1,050-bed teaching hospital in South Korea. All isolates were analyzed for serotype, genotype, and antimicrobial susceptibility. Demographic, clinical and microbiological data were compared between ceftriaxone susceptible and non-susceptible cases. Among 92 microbiologically identified pneumococcal isolates, ceftriaxone non-susceptible pneumococci (CNSP) accounted for 32 cases (34.8%). Some of these cases also showed levofloxacin resistance (25%, 8/32 isolates) and all CNSP cases were multidrug resistant. Compared to patients with ceftriaxone susceptible pneumococci (CSP), long-term care facility residents (odds ratio [OR] 7.0, 95% confidence interval [CI] 0.8-62.1) and patients with chronic lung (OR 4.1, 95% CI 1.1-15.0) and renal diseases (OR 9.1, 95% CI 1.2-70.5) were more common among those with CNSP on multivariate analysis. PPSV23-unique serotypes not included in PCV13 were more common in CNSP than in CSP (34.4% versus 13.3%, p = 0.02). Regarding genotypes, ST320 (10 cases), ST166 (7 cases) and ST8279 (3 cases) were dominant in CNSP, and ST8279 was only detected in previous long-term care facility residents. Clonal expansion and spread of CNSP strains should be monitored among patients with chronic lung/renal diseases and residents of long-term care facilities.

Effects of influenza immunization on pneumonia in the elderly.

Influenza virus is a common pathogen implicated in respiratory tract infections, annually affecting up to 20% of the general population, and pneumonia is a leading cause of death after influenza infection. Post-influenza pneumonia is especially common in the elderly and chronically ill patients. The risk of post-influenza pneumonia is significantly increased according to the number of concurrent comorbidities. Vaccination is the primary measure used to abate influenza epidemics and associated complications. In meta-analyses, influenza vaccine significantly reduces pneumonia- and influenza-related hospitalizations, with a vaccine effectiveness of 25-53%. However, considering the poor effectiveness of conventional influenza vaccines in the elderly, several highly immunogenic influenza vaccines have been developed. Further evaluations of the comparative effectiveness of diverse vaccine formulations are warranted to assess their utility for preventing influenza infection, post-influenza pneumonia, and related hospitalization/mortality. Based on cost-effectiveness and budget impact analysis, influenza vaccination strategies should be tailored in the elderly.

Incidence and case fatality rates of community-acquired pneumonia and pneumococcal diseases among Korean adults: Catchment population-based analysis.

BACKGROUND: Pneumonia is a leading infectious cause of morbidity and mortality among adults. Pneumococcal pneumonia (PP) is the most common vaccine-preventable bacterial etiology of pneumonia. In this study, we estimated the incidence of community-acquired pneumonia (CAP) and pneumococcal diseases among Korean adults. METHODS: Clinical and microbiological databases from three hospitals were retrospectively reviewed to determine the incidence and case fatality rates of CAP and pneumococcal diseases in Korean adults aged ≥19 years from 2011 to 2014. Incidence and case fatality rates of CAP, PP and invasive pneumococcal diseases (IPD) were evaluated based on the catchment population. Catchment population was calculated using national health insurance data, estimating the proportion of patients with pneumonia that were medically attended at each hospital. RESULTS: Among 5,783 patients with medically attended CAP, 833 (14.4%) had PP. For IPD, a total of 91 culture-confirmed cases were identified. The overall incidence of CAP was 307.7 cases per 100,000 persons per year with an in-hospital mortality rate of 6.2%. The estimated annual incidence of pneumococcal pneumonia was 42.2-49.4 cases per 100,000 persons per year, increasing with age to >280 per 100,000 persons per year in older patients over 70 years. The annual incidence of IPD had a range of 4.1-6.5 cases per 100,000 persons per year. The overall case fatality rate for invasive pneumococcal diseases was 30.8% with the highest rate of 66.7% in patients over 80 years. CONCLUSION: Over the study period, incidences of CAP, PP and IPD were consistently high, particularly in older people. These results provide baseline data to establish healthcare strategies and estimate their impact among Korean adults.

Quantitative optical coherence tomography angiography of macular vascular structure and foveal avascular zone in glaucoma.

OBJECTIVE: The study aimed to evaluate the quantitative characteristics of the macular vessel density (VD) and foveal avascular zone (FAZ) in glaucoma using optical coherence tomography angiography (OCT-A). DESIGN: Cross-sectional, age- and sex-matched case-control study. METHODS: Fifty-two eyes of 52 patients with primary open angle glaucoma and 52 eyes from 52 healthy participants were recruited retrospectively. OCT-A was performed on a 3 x 3-mm macular region centered on the fovea. OCT-A scans were manually graded to define the FAZ. Parafoveal VD in superficial and deep retina were analyzed in the circular- and quadrant-segmented zone. The FAZ parameters included size, perimeter, and circularity index. The regression analysis among VD and FAZ-related parameters and ocular parameters was performed, and the diagnostic ability was calculated with refractive error adjusted. RESULTS: For both groups, the mean age and the sex ratio was not different between groups. With refractive error adjusted, the average macular VD was lower in glaucoma than in the control group for superficial (P = 0.013), deep (P<0.001), and the whole retina (P = 0.002). There were increased FAZ perimeter and decreased FAZ circularity index in glaucoma when compared with controls (P<0.001). In the multivariate regression models, FAZ circularity index were significantly associated with decreased peripapillary RNFL thickness (P = 0.007) and macular GCIPL thickness (P = 0.009) measured by OCT. The refractive-error adjusted area under receiver operating characteristics was highest for FAZ circularity index (0.905; 95% CI, 0.844-0.966), followed by temporal deep retinal VD (0.870; 95% CI, 0.803-0.937) and FAZ perimeter (0.858; 95% CI, 0.784-0.932). CONCLUSIONS: Decreased macular VD, increased FAZ perimeter, and decreased FAZ circularity index were observed in eyes with glaucoma using OCT-A. With refractive error adjusted, these parameters showed considerable diagnostic value for glaucoma. FAZ circularity index may be a novel biomarker representing disruption of the parafoveal capillary network in glaucoma, as supported by its association with structural parameters.

Causes and Surgical Outcomes of Lower Eyelid Retraction.

PURPOSE: To investigate the causes of lower eyelid retraction and evaluate the outcomes of various surgical procedures. METHODS: We conducted a retrospective medical record review of patients who underwent lower eyelid retraction surgery performed by a single surgeon at Kim's Eye Hospital between 2006 and 2013. We investigated the causes of lower eyelid retraction, clinical history, characteristics, treatment, and surgical outcomes. Preoperative and postoperative margin reflex distance 2 and inferior scleral show were measured for each eyelid. Success was defined as a positive eyelid elevation and a decrease in inferior scleral show. RESULTS: A total of 19 lower eyelids were treated in 14 patients with lower eyelid retraction. For cosmetic reasons, surgical correction for congenital lower eyelid retraction was performed on seven eyelids (36.8%). Ten eyelids (52.6%) exhibited secondary lower eyelid retraction after surgery. One eyelid (5.3%) was affected by facial palsy and one eyelid (5.3%) exhibited exophthalmos of an unknown origin. We adopted a selective approach based on lower eyelid retraction severity. Spacer grafting via a subconjunctival approach was the most commonly performed surgical technique (13 eyelids, 68.4%). The lateral tarsal strip procedure was used to horizontally tighten three eyelids (15.8%). At the time of the procedure, one of these eyelids (5.3%) also received an adjuvant suborbicularis oculi fat lift. Autogenous dermis fat grafting was performed on two lower eyelids (10.5%), whose retraction was caused by fat and soft tissue loss. Cosmetic outcomes were satisfactory in all cases. CONCLUSIONS: To achieve satisfactory surgical outcomes, surgeons should adopt an approach based on the severity of lower eyelid retraction. Mild lower eyelid retraction can be corrected without grafts. When retraction is severe and exceeds 2 mm, spacer grafts that push the lower eyelid margin upwards and support it from below are required.

Campylobacter jejuni Bacteremia in a Liver Cirrhosis Patient and Review of Literature: A Case Study.

Campylobacter infection causes gastrointestinal symptoms such as abdominal pain or diarrhea. Occasionally, Campylobacter bacteremia affects immunocompromised patients; however, serious outcomes are known to be rare. Here, we present a case of a patient with Campylobacter bacteremia who had underlying liver cirrhosis. The patient had fever and diarrhea. These symptoms subsided after treatment with cefotaxime. Campylobacter jejuni was isolated in the blood culture after 10 days. In addition, previously reported cases of Campylobacter bacteremia in Asian countries were reviewed with respect to antimicrobial sensitivities.

Disease burden of hospitalized community-acquired pneumonia in South Korea: Analysis based on age and underlying medical conditions.

Pneumonia is a leading cause of hospitalization and mortality worldwide. Despite recognition of the importance of community-acquired pneumonia (CAP) in adults, limited epidemiologic information is available in South Korea. This study aimed to evaluate the disease burden of hospitalized CAP in adults aged ≥19 years and its epidemiologic trend using Health Insurance and Review Assessment (HIRA) data.This is a retrospective study using the HIRA database from year 2009 to 2013. We estimated the incidence rate and direct medical cost of hospitalized CAP in adults aged ≥19 years in South Korea. These were further analyzed with respect to age and underlying medical conditions.During 2009 to 2013, 1216,916 hospitalizations were recorded. On average, the annual age-adjusted incidence rate of hospitalized CAP was 626 per 100,000 persons, with the rate increasing with age. When stratified by age- and risk groups, elderly people ≥75 years showed the highest incidence rate of hospitalized CAP over 5-year study periods. With respect to the risk groups based on underlying medical conditions, incidence rate ratios were 2.04 to 5.86 for the high-risk group versus the low-risk group and 1.28 to 5.49 for the moderate-risk group versus the low-risk group. Overall, mean direct medical cost for hospitalized CAP was 1851 USD per capita during the 5-year period: 1263 USD in the low-risk group, 2353 USD in the moderate-risk group, and 2841 USD in the high-risk group.This study shows that the incidence and medical cost of hospitalized CAP were consistently high over the 5-year study period. In particular, elderly people and adults with underlying medical conditions were at increased risk for hospitalized CAP.

Predictors of Silicone Tube Intubation Success in Patients with Lacrimal Drainage System Stenosis.

PURPOSE: To evaluate prognostic factors affecting silicone tube intubation outcomes in Asian patients with lacrimal drainage system stenosis. METHODS: A retrospective review was conducted on the medical records of 822 patients (1,118 eyes) who had undergone silicone tube intubation to treat lacrimal drainage system stenosis between January 2011 and December 2012. Patients were divided into two groups: a success group and a failure group. Success was defined as the disappearance of epiphora symptoms, normalization of tear meniscus height, and the easy passage of fluid without resistance on the postoperative syringing test. Patient and ocular parameters were compared between the success and failure groups. RESULTS: A total of 994 eyes of 727 patients were included in analyses. Patients had a mean follow-up period of 34.11 ± 18.70 weeks. Silicone tube intubation was successful in 67.2% of participants. Significant differences between the success and failure groups were found for age (p < 0.001), history of ipsilateral facial palsy (p = 0.028), follow-up period (p < 0.001), and degree of passage on the preoperative syringing test (p = 0.001). Only age (p < 0.001) and degree of passage on the preoperative syringing test (p = 0.002) remained significantly associated with silicone tube intubation success in multivariate analysis. CONCLUSIONS: Age was negatively associated with silicone tube intubation success in patients with lacrimal drainage system stenosis. The success rate was higher in patients who showed easy passage of fluid without resistance on the preoperative syringing test. These factors should be considered by surgeons planning silicone tube intubation in patients with lacrimal drainage system stenosis.

Preoperative Computed Tomography Findings for Patients with Nasolacrimal Duct Obstruction or Stenosis.

PURPOSE: To identify and analyze the role of preoperative computed tomography (CT) in patients with tearing symptoms with nasolacrimal duct obstruction (NLDO). METHODS: We retrospectively reviewed the medical records and CT results on 218 patients who complained of tearing symptoms with NLDO between January 2014 and December 2014. All patients were recruited from Kim's Eye Hospital's outpatient clinic and assessed by clinical history, examination, and CT to evaluate periocular pathology and nasolacrimal drainage system. Patients with abnormal findings assessed by preoperative CT were further reviewed. RESULTS: CT was performed on 218 patients (average age, 58.2 ± 11.9 years). Of these, 196 (89.9%) had endonasal dacryocystorhinostomy, 14 (6.4%) declined surgery, and 8 (3.7%) were inoperable due to abnormal CT findings. Soft tissue opacity was the most common finding which 243 cases (85.9%) of 283 obstructed nasolacrimal duct and 89 cases (81.7%) of 109 non-obstructed nasolacrimal duct showed it. Thirty-nine (17.8%) of 218 patients showed either maxillary sinusitis or ethmoidal sinusitis and 32 (14.7%) of 218 patients presented with periocular inflammation. Other abnormal CT findings included septal deviations, previous fractures, masses, and structural abnormalities of nasal cavity. CONCLUSIONS: Preoperative CT imaging is useful in the assessment of both nasolacrimal drainage and nearby anatomical structures. This information will be helpful in planning surgical interventions and management of NLDO.

Clinical characteristics of patients with a periorbital mass after autologous fat injection for facial augmentation and short-term outcomes of steroid treatment.

AIM: The aim of this study was to evaluate the clinical features of patients with a periorbital palpable mass or swelling after autologous fat injection for facial augmentation. METHODS: This retrospective case study included 50 patients who developed a periorbital palpable mass or swelling after undergoing autologous fat injection for facial augmentation performed by various plastic surgeons. The patients' medical records were reviewed for clinical history, radiological findings, and treatment outcomes. RESULTS: All patients were female with a mean age of 43.18 ± 12.04 (range, 19-63) years. After fat injection, the average time of symptom onset was 9.09 ± 8.45 (1-36) months, and the mean follow-up duration was 13 ± 1 (4-36) weeks. Majority of patients complained of eyelid swelling or periorbital palpable mass. All patients had received fat injection in the forehead area, except for the following patients: Five patients who were unaware of the site of fat injection and one patient who had received the injection in the upper eyelid area with simultaneous double-fold surgery. In addition, 39 patients had received a second injection of cryopreserved autologous fat tissue. Forty-five patients developed a mass in the upper eyelid area, four were found to have the mass in the lower eyelid area, and one patient developed the mass in both eyelids. Computed tomography and magnetic resonance imaging revealed isolated fat tissue, periorbital inflammation, or a soft tissue mass with fat density. Oral steroids were used to treat 41 (82.0%) patients; 31 (75.6%) showed satisfactory outcomes, nine (22.0%) patients did not return to the clinic after the first oral steroid treatment, and the periorbital mass persisted in one patient (2%) even after the oral steroid treatment. The patient with the periorbital mass underwent surgical removal and tissue biopsy. Asymptomatic patients (eight; 16%) underwent observation without treatment. As a first treatment, one patient (2%) requested an immediate surgical removal of the periorbital mass. Therefore, surgical excision and biopsy were performed in two patients (4%). During surgery, a granulomatous mass was found in the preseptal region, with liquefied necrotic fat flowing out. Histological examination revealed a lipogranuloma with granulomatous inflammation. CONCLUSIONS: Clinicians should confirm a history of autologous fat injection and be aware of the clinical features in patients who present with a periorbital palpable mass or swelling. Oral steroid therapy should be considered before surgery because it may prove to be effective. Further studies with long-term follow-up periods are necessary.

Viral Shedding and Environmental Cleaning in Middle East Respiratory Syndrome Coronavirus Infection.

Viral shedding lasted 31 and 19 days from symptom onset in two patients with east respiratory syndrome coronavirus (MERS-CoV) pneumonia, respectively. Environmental real-time RT-PCR was weakly positive for bed guardrail and monitors. Even after cleaning the monitors with 70% alcohol-based disinfectant, RT-PCR was still weakly positive, and converted to negative only after wiping with diluted sodium chlorite. Further studies are required to clarify the appropriate methods to clean environments during and after treatment of patients with MERS-CoV infection.

Complete response to thalidomide and dexamethasone in a patient with necrobiotic xanthogranuloma associated with monoclonal gammopathy: a case report and review of the literature.

Necrobiotic xanthogranuloma (NXG) was first described in 1980 by Kossard and Winkelmann in an article in which they discussed 8 patients with xanthomatous plaques who were noted to have monoclonal gammopathy, predominantly of the Ig(immunoglobulin)G-κ type.(1) Since then more than 50 patients with this disorder have been described, with approximately 80% of them having an associated monoclonal gammopathy. We describe the first case, to our knowledge, of NXG with associated monoclonal gammopathy treated with thalidomide plus dexamethasone, achieving complete resolution of the skin lesions and sustaining response more than 3 years after treatment.

Anticancer activity of a broccoli derivative, sulforaphane, in barrett adenocarcinoma: potential use in chemoprevention and as adjuvant in chemotherapy.

INTRODUCTION: The incidence of Barrett esophageal adenocarcinoma (BEAC) has been increasing at an alarming rate in western countries. In this study, we have evaluated the therapeutic potential of sulforaphane (SFN), an antioxidant derived from broccoli, in BEAC. METHODS: BEAC cells were treated with SFN, alone or in combination with chemotherapeutic, paclitaxel, or telomerase-inhibiting agents (MST-312, GRN163L), and live cell number determined at various time points. The effect on drug resistance/chemosensitivity was evaluated by rhodamine efflux assay. Apoptosis was detected by annexin V labeling and Western blot analysis of poly(ADP-ribose) polymerase cleavage. Effects on genes implicated in cell cycle and apoptosis were determined by Western blot analyses. To evaluate the efficacy in vivo, BEAC cells were injected subcutaneously in severe combined immunodeficient mice, and after the appearance of palpable tumors, mice were treated with SFN. RESULTS: SFN induced both time- and dose-dependent decline in cell survival, cell cycle arrest, and apoptosis. The treatment with SFN also suppressed the expression of multidrug resistance protein, reduced drug efflux, and increased anticancer activity of other antiproliferative agents including paclitaxel. A significant reduction in tumor volume was also observed by SFN in a subcutaneous tumor model of BEAC. Anticancer activity could be attributed to the induction of caspase 8 and p21 and down-regulation of hsp90, a molecular chaperon required for activity of several proliferation-associated proteins. CONCLUSIONS: These data indicate that a natural product with antioxidant properties from broccoli has great potential to be used in chemoprevention and treatment of BEAC.