Effectiveness of Carboplatin-Prescreening Intradermal Skin Tests to Reduce Unanticipated Immediate Hypersensitivity Reactions: A Comparative Study.

BACKGROUND: Carboplatin administration poses a risk of immediate hypersensitivity reactions (IHRs) that tend to increase with repeated administration and are mostly IgE-mediated. OBJECTIVE: This study evaluated the usefulness of carboplatin-prescreening intradermal skin tests (IDTs). METHODS: Carboplatin-prescreening IDTs were routinely conducted in patients with a history of receiving six or more carboplatin cycles beginning in January 2021. The primary objective was to assess disparities in the incidence of unanticipated IHRs to carboplatin administration. We compared patients in the intervention group (from 2021 to 2022) and those who did not undergo prescreening IDTs under the same conditions (preintervention group, from 2019 to 2020). Secondary objectives included evaluating the sensitivity and specificity of the prescreening IDT and the incidence of carboplatin IHR according to the number of infusion cycles. RESULTS: The intervention group was composed of 67 patients who were administered 347 carboplatin cycles whereas the preintervention group included 96 patients who were administered 464 carboplatin cycles. The risk of unanticipated carboplatin IHRs decreased by 83.2% in the intervention group compared with results in the preintervention group (preintervention group, 3.45%, n = 16 vs intervention group, 0.58%, n = 2; P = .005). The prescreening IDT showed a sensitivity and specificity of 77.78% and 99.41%, respectively. The risk of newly developed IHRs based on the number of carboplatin cycles was less than 1% (cycles 1-5), 2.11% (cycle 6), 3.90% (cycles 7-12), 2.90% (cycles 13-18), and 0.74% (cycles 19 and greater), respectively. CONCLUSIONS: Initiating carboplatin-prescreening IDTs from the seventh cycle on significantly reduced the risk of unanticipated IHRs.

Effect of omalizumab as add-on therapy to Quality of Life Questionnaire for Korean Asthmatics (KAQLQ) in Korean patients with severe persistent allergic asthma.

BACKGROUND/AIMS: Omalizumab is the first biologic known to be effective in patients with severe allergic asthma. METHODS: This study was conducted as a multicenter, single-group, open trial to evaluate the improvement in the quality of life with the additional administration of omalizumab for 24 weeks in Korean patients with severe persistent allergic asthma. RESULTS: Of the 44 patients, 31.8% were men and the mean age was 49.8 ± 11.8 years. A score improvement of 0.5 points or more in the Quality of Life Questionnaire for Korean Asthmatics (KAQLQ) was noted in 50.0% (22/44) of the patinets. In the improved group, the baseline total immunoglobulin E (IgE) level and the amount of omalizumab used were higher, and the day and night asthma symptoms were more severe, compared to those in the non-improved group. According to the Global Evaluation of Treatment Effectiveness, favorable outcomes were found in 78.6% of patients. The Korean asthma control test (p < 0.005) and forced expiratory volume in 1 second % predicted (FEV1%; p < 0.01) improved significantly in patients who received omalizumab treatment, compared to that at week 0, and the total dose of rescue systemic corticosteroids significantly decreased (p < 0.05). The improved group on KAQLQ showed a significant improvement in FEV1% (p < 0.001). CONCLUSION: Omalizumab can be considered a biological treatment for Korean patients with severe allergic asthma. It is recommended to consider omalizumab as add-on therapy in patients with high baseline total IgE levels and severe asthma symptoms.

A Fatal Case of Bacteremia Caused by Vibrio cholerae Non-O1/O139.

Vibrio cholerae is a pathogen known to cause the waterborne epidemic disease cholera. Overall, V. cholerae O1 or O139 strains produce the cholera toxin that cause gastroenteritis, resulting in watery diarrhea. Most of the enterocolitis caused by V. cholerae can be easily treated with fluid therapy and conservative care. However, V. cholerae non-O1/O139 strains can cause extraintestinal infections, such as wound infection or sepsis, in immunocompromised patients. The clinical course of these infections is very similar to that of V. vulnificus infection. We report about a 52-year-old man without previous underlying disease who was diagnosed with V. cholerae non-O1/O139 infection and died within 72 hours after admission to the intensive care unit.

Does Carboplatin Rapid Desensitization Change Its Adverse Drug Reactions Other than Hypersensitivity and Efficacy in Patients With Ovarian Cancer?

PURPOSE: Rapid drug desensitization is known to be a good strategy in patients with drug hypersensitivity to chemotherapy. However, changes in maximal drug concentration and exposure time in blood through desensitization may alter other adverse reactions and efficacy of the drug. We investigated rapid desensitization for carboplatin in terms of severe adverse drug reactions (ADRs) and efficacy compared with the standard infusion. METHODS: A retrospective cohort study was conducted on patients with recurrent ovarian cancer who received carboplatin chemotherapy from 2017 to 2019. We compared serious adverse events (SAEs), ADRs according to organ classes, time to progression (TTP), and overall survival (OS). RESULTS: Of 108 desensitization procedures performed in 21 patients, 104 were successfully accomplished (96.3%). There were compared with 271 procedures in 41 patients who received the standard infusion method. There were 8 (7.7%) SAEs in the rapid desensitization group and 34 (12.5%) in the control group. One drug-related death occurred in the rapid desensitization group. In the rapid desensitized group, except for neutropenia, there was no statistically significant increase in SAEs and over grade 3 of ADRs according to organ classes compared with the control group. In the efficacy analysis, TTP and OS were similar in the 2 groups. CONCLUSIONS: Rapid desensitization of carboplatin can lower the risk of immediate hypersensitivity reactions without changing the inherent effect and severe ADRs.

Does oral doxycycline treatment affect eradication of urine vancomycin-resistant Enterococcus? A tertiary hospital study.

BACKGROUND: Vancomycin-resistant Enterococcus (VRE) has become more common in nosocomial infections, especially in urine samples. However, until now, no treatment regimen has been proven to effectively eradicate urine VRE colonization. Therefore, to evaluate the efficacy of doxycycline in eradicating urine VRE and shortening VRE isolation period, we compared VRE colony detection period between doxycycline-treated and untreated patients. METHODS: A retrospective cohort study of 83 patients with VRE colonization in urine cultures was conducted at a tertiary academic hospital from January 2011 to February 2018. Kaplan-Meier survival analysis was used to evaluate eradication rates in the treatment and non-treatment groups. Factors affecting urine VRE colonization persistence were analyzed by multiple logistic regression analysis. RESULTS: The overall rate of VRE eradication during the entire hospital stay was higher in the doxycycline treatment group (90.5%) than in the non-treatment group (58.1%, p=0.014). Survival analysis showed that the 5-, 10-, and 20-day cumulative eradication rates were 78.3%, 100%, and 100% in the doxycycline treatment group, and 18.5%, 45.7%, and 67.8% in the non-treatment group, respectively, thereby indicating that eradication rates were higher in the doxycycline treatment group than in the non-treatment group (p<0.001). Only doxycycline treatment was shown to affect urine VRE colonization persistence in multivariate logistic regression analysis. CONCLUSION: Doxycycline treatment enhanced the eradication rate of urine VRE colonization and appeared to be useful in shortening VRE isolation period.

Efficacy of the HLA-B∗58:01 Screening Test in Preventing Allopurinol-Induced Severe Cutaneous Adverse Reactions in Patients with Chronic Renal Insufficiency-A Prospective Study.

BACKGROUND: Thus far, human leukocyte antigen (HLA)-B∗58:01 has been recognized as the most important risk factor for allopurinol induced severe cutaneous adverse reactions (SCARs). OBJECTIVE: To determine the usefulness of prospective screening for the HLA-B∗58:01 allele to identify Korean individuals at risk for SCARs induced by allopurinol treatment. METHODS: We prospectively enrolled 542 patients with chronic renal insufficiency (CRI) from 10 hospitals nationwide and performed DNA genotyping to determine whether they carried the HLA-B∗58:01 allele. Of these, 503 HLA-B∗58:01-negative patients (92.8% of total) were treated with allopurinol, and 39 HLA-B∗58:01-positive patients (7.2%) were treated with febuxostat, an alternative drug. The patients then were followed up biweekly for 90 days using a telephone survey to monitor symptoms of adverse drug reactions, including SCARs. As a control, we used the historical incidence rate of allopurinol-induced SCARs in 4002 patients with CRI from the same hospitals who were enrolled retrospectively. RESULTS: Nineteen patients in the prospective cohort developed mild and transient adverse reactions but none showed allopurinol-induced SCARs. By contrast, we identified 38 patients with allopurinol-induced SCARs (0.95%) in the historical control. The difference in the incidence of allopurinol-induced SCARs between the prospective cohort and historical control was statistically significant (0% vs 0.95%, respectively; P = .029). CONCLUSIONS: The present study demonstrated the clinical usefulness of the HLA-B∗58:01 screening test before allopurinol administration to prevent allopurinol-induced SCARs in patients with CRI.

Analysis of Klebsiella as a Prognostic Factor of Ocular Outcomes in Endogenous Endophthalmitis with Decision Tree Analysis.

BACKGROUND: Endogenous endophthalmitis (EE) is a fulminant ocular disease. This study was conducted to explore frequent pathogens and significant prognostic factors associated with poor ocular outcomes. MATERIALS AND METHODS: A retrospective analysis was performed in a tertiary hospital in Korea. Thirty-nine patients, treated between January 2000 and June 2017, were eligible for the analysis. Ocular outcomes were classified as follows: 1) no light perception (NLP), 2) light perception (LP), 3) hand motion (HM), 4) counting fingers (CF), and 5) 20/200 or better. Logistic regression and decision tree analyses were used to identify risk factors that were associated with poor outcomes. RESULTS: Pathogens were identified in 23 (58.9%) samples from blood, liver aspirate, and/or vitreous humor. Klebsiella pneumoniae was the most frequent organism (12/39, 30.8%), followed by Candida species (3/39, 8.3%). The most common combined infection was liver abscess (16/39, 41.0%). Acute pyelonephritis occurred in 30.8% of cases (12/39). Final ocular outcomes were as follows: 35.9% (14/39) NLP, 15.4% (6/39) LP, 15.4% (6/39) HM, 7.7% (3/39) CF, and 25.6% (10/39) 20/200 or better. K. pneumoniae was a poor prognostic factor in univariate (odds ratio [OR], 13.3; 95% confidence interval [CI], 2.1-130.9) and multivariate (OR, 17.5; 95% CI, 2.1-398.8) regression analyses (NLP and LP vs. HM, CF, and 20/200 or better). Other factors did not reach statistical difference. Decision tree analysis identified K. pneumoniae as a node that divided ocular outcomes (P = 0.017). CONCLUSIONS: In conclusion, K. pneumoniae is the most frequent causative pathogen of EE. Considering the poor prognosis and rapid progression of K. pneumoniae EE, physicians should test for K. pneumoniae EE in patients who experience acute systemic infections with ocular signs and symptoms.

Effectiveness, Safety, and Tolerability of a Switch to Dual Therapy with Dolutegravir Plus Cobicistat-Boosted Darunavir in Treatment-Experienced Patients with Human Immunodeficiency Virus.

BACKGROUND: Dual regimen with dolutegravir plus cobicistat-boosted darunavir (DTG/DRV/c) is reasonable alternative option for patients with existing resistance and/or intolerance to nucleoside reverse transcriptase inhibitors (NRTIs). MATERIAL AND METHODS: All patients who switched to DTG/DRV/c among treatment-experienced patients with human immunodeficiency virus (HIV) in a tertiary university hospital were selected. We analyzed the effectiveness, safety, and tolerability based on serial laboratory data and clinical findings. The primary endpoint was defined as the proportion of patients with plasma HIV RNA below 50 copies/mL at week 48 after switch. Secondary endpoints included evaluation of safety and tolerability. RESULTS: Thirty-one patients were retrospectively analyzed. The main reasons for the change to DTG/DRV/c were treatment failure in 13 patients (41.9%), simplification in 12 patients (38.7%), and adverse drug reaction in 6 patients (19.4%). Among the 13 patients who switched owing to treatment failure, the proportion of patients in whom the viral loads were suppressed to less than 50 copies/mL increased from 0% at baseline to 45% at 4 weeks, 50% at 12 weeks, 50% at 24 weeks, and 66.7% at 48 weeks. HIV virus levels decreased and CD4⁺ T cell counts increased during the follow-up period. In non-treatment failure patients (18 patients), the levels of viral suppression and CD4⁺ T cells were maintained. There were no significant differences in renal function, liver function, glucose levels, and lipid profile before and after regimen changes. The tolerability was very good: 30 patients (96.8%) tolerated the drugs well and only 1 patient discontinued owing to no improvement in renal insufficiency. Two patients (6.4%) in treatment failure group failed to reach viral suppression. CONCLUSION: The use of DTG/DRV/c in HIV treatment-experienced patients appears to be a very good regimen for switch therapy that is effective and well tolerated, without significant adverse drug reaction.

Exposure to Secondhand Smoke and Risk of Cancer in Never Smokers: A Meta-Analysis of Epidemiologic Studies.

This is first meta-analysis to evaluate cancer risk associated with secondhand smoking across all cancers. A literature search was conducted for articles published before June 2014 on Pubmed, SCOPUS, Cochrane library, and CINAHL, and 40 articles on secondhand smoke and the prevalence of cancer among never smokers were selected for final analysis as per the inclusion criteria. Of the 40 articles, 27 were case-control studies and 13 were prospective cohort studies. With respect to overall cancer risk, odds ratio (OR) involving never smokers with significant exposure to secondhand smoke compared to never smokers without such exposure was 1.163 (95%CI 1.058⁻1.279). Subgroup meta-analyses by study design showed significant positive associations for both case-control studies and prospective cohort studies (OR 1.165, 95%CI 1.029⁻1.320; and OR 1.160, 95%CI 1.002⁻1.343, respectively). The association was stronger in the case of females (OR 1.253, 95%CI 1.142⁻1.374), lung cancer (OR 1.245, 95%CI 1.026⁻1.511), and breast cancer (OR 1.235, 95%CI 1.102⁻1.385). Secondhand smoking may increase the overall risk of cancer for never smokers, particularly lung and breast cancer, and especially in women. Strict implementation of smoking cessation programs should be encouraged, not only to reduce active smoking but also to limit exposure to secondhand smoke.

A New Scoring System for the Differential Diagnosis between Tuberculous Meningitis and Viral Meningitis.

BACKGROUND: Tuberculous meningitis (TBM) is associated with high mortality and morbidity despite administering anti-tuberculous chemotherapy to the patients. Differential diagnosis between TBM and viral meningitis (VM) is difficult in some clinical situations. METHODS: We reviewed and analyzed records of adult patients who were admitted and diagnosed with TBM or VM at a tertiary hospital in Korea, between January 2006 and December 2015. Diagnostic criteria for TBM were categorized into three groups: definite, probable, and possible TBM. The VM group included patients with no evidence of other meningitis who achieved complete recovery with only conservative treatments. Clinical, laboratory and radiological findings, as well as outcomes, were compared between the TBM and VM groups. RESULTS: Ninety-eight patients were enrolled. Among the study patients, 47 had TBM and 51 had VM. Based on univariate analysis and multivariate logistic regression, sodium < 135 mmol/L in serum (hyponatremia), lactate dehydrogenase > 70 (U/L) in cerebrospinal fluid (CSF), protein > 160 (mg/dL) in CSF, voiding difficulty, and symptoms of cranial nerve palsy were significant predictive factors for TBM in the final model. We constructed a weighted scoring system with predictive factors from multiple regression analyses. Receiver operating characteristic curve analyses and decision tree analyses were plotted to reveal an optimum cutoff point as 4 with this scoring system (range: 0-13). CONCLUSION: For differential diagnosis between TBM and VM, we created a new weighted scoring system. This scoring system and decision tree analysis are simple and easy to apply in clinical practice to differentiate TBM from VM.

A Randomized, Multicenter, Double-blind, Phase III Study to Evaluate the Efficacy on Allergic Rhinitis and Safety of a Combination Therapy of Montelukast and Levocetirizine in Patients With Asthma and Allergic Rhinitis.

PURPOSE: The aim of this study was to evaluate the efficacy and safety of a fixed-dose combination of montelukast and levocetirizine in patients with perennial allergic rhinitis with mild to moderate asthma compared with the efficacy and safety of montelukast alone. METHODS: This study was a 4-week, randomized, multicenter, double-blind, Phase III trial. After a 1-week placebo run-in period, the subjects were randomized to receive montelukast (10 mg/day, n = 112) or montelukast (10 mg/day)/levocetirizine (5 mg/day) (n = 116) treatment for 4 weeks. The primary efficacy end point was mean daytime nasal symptom score. Other efficacy end points included mean nighttime nasal symptom score, mean composite symptom score, overall assessment of allergic rhinitis by both subjects and physicians, forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC, asthma control test score, and the frequency of rescue medication used during the treatment period. FINDINGS: Of 333 patients screened for this study, 228 eligible patients were randomized to treatment. The mean (SD) age of patients was 43.32 (15.02) years, and two thirds of subjects were female (66.67%). The demographic characteristics were similar between the treatment groups. Compared with the montelukast group, the montelukast/levocetirizine group reported significant reductions in mean daytime nasal symptom score (least squares mean [SE] of combination vs montelukast, -0.98 [0.06] vs -0.81 [0.06]; P = 0.045). For all other allergic rhinitis efficacy end points, the montelukast/levocetirizine group showed greater improvement than the montelukast group. Similar results were observed in overall assessment scores and in FEV1, FVC, FEV1/FVC, and asthma control test score changes from baseline for the 2 treatment groups. Montelukast/levocetirizine was well tolerated, and the safety profile was similar to that observed in the montelukast group. IMPLICATIONS: The fixed-dose combination of montelukast and levocetirizine was effective and safe in treating perennial allergic rhinitis in patients with asthma compared with montelukast alone. ClinicalTrials.gov identifier: NCT02552667.

Clinical Features of Hereditary Angioedema in Korean Patients: A Nationwide Multicenter Study.

BACKGROUND: Hereditary angioedema (HAE) is a genetically heterogeneous autosomal dominant disorder characterized by recurrent episodes of nonpruritic, nonpitting edema increasing after puberty. It can be fatal due to laryngeal or gastrointestinal (GI) involvement with varied and changing frequency of mortality according to studies published from the Western countries. Epidemiological and clinical data of HAE in Asian countries are sparse. We sought to examine the clinical characteristics of HAE patients in Korea. METHODS: Patients diagnosed with HAE at 15 tertiary hospitals across the country until 2016 were retrospectively reviewed. RESULTS: A total of 65 patients diagnosed with HAE by 2016 were identified. The prevalence of HAE was estimated at 1.3/1,000,000 in Korea. Of the 65 patients, 21 (32.3%) were males. A total of 90.8% patients had type I HAE, while the remaining 9.2% patients had type II HAE. The first symptom developed after 20 years in 73.8% of patients, with a mean age 28.4 ± 14.1 years. The age at diagnosis was 36.5 ± 15.8 years, with a mean time delay of 7.8 ± 10.5 years. While the face (82.3%) and extremities (upper 71.0%, lower 62.9%) were the most frequently involved, the GI tract was affected in 40.5% of Korean HAE patients. Prophylaxis was maintained in 62.5% of patients. There was no reported case of death from HAE so far. CONCLUSIONS: The clinical manifestation and severity of HAE may vary according to ethnicity. HAE is more infrequent and GI involvement is less likely in Korea compared with Western countries.

Awareness and Acceptance of HIV Pre-exposure Prophylaxis among Medical Personnel and Men Who Have Sex with Men in Korea.

BACKGROUND: We aimed to investigate the awareness of human immunodeficiency virus (HIV) infection among high-risk individuals, including men who have sex with men (MSM) and medical personnel (MP) in Korea through a cross-sectional survey, identify possible obstacles hindering their access to pre-exposure prophylaxis (PrEP). METHODS: In 2016, the first questionnaire survey was sent to randomly selected MSM and MP. To compare the changes in attitudes and knowledge of MSM, a second questionnaire survey was conducted in August 2017. RESULTS: More than half of MSM (61.3% in 2016, 88.6% in 2017) were aware of PrEP. However, MP who offered PrEP had less knowledge regarding PrEP (23.4%). The background knowledge and experience with PrEP among MSM and MP in this survey was low (3.4% in 2016 and 5.7% in 2017, 1.9% in MP). The major obstacles that MSM reported were lack of insurance coverage (29% in 2016 and 32% in 2017), concern regarding adverse effects of PrEP (19% and 21%), and risk of exposing HIV-positive status to other people (15% and 18%). Among MP, lack of knowledge regarding the efficacy of PrEP was the most common obstacle (30%), followed by lack of insurance coverage (22%), and concern regarding adverse effects (20%). CONCLUSION: Our study showed that PrEP is required among MSM in Korea; however, most MP were not aware of PrEP. Lack of insurance coverage and knowledge regarding PrEP were major hindrances in the access to PrEP; therefore, further studies on how to make PrEP information more accessible are needed to help prevent HIV infection.

Patterns of Inhalant Allergen Sensitization and Geographical Variation in Korean Adults: A Multicenter Retrospective Study.

PURPOSE: Inhalant allergen sensitization is one of the major factors involved in the pathogenesis of allergic respiratory diseases. However, the sensitization is determined by interactions between genetic and environmental factors. Thus, testing panels of inhalant allergens may differ among geographical areas. Here we aimed to determine 10 common inhalant allergens in Korean adult patients with suspected respiratory allergies and to examine the variation between different geographical locations. METHODS: A total of 28,954 patient records were retrieved for retrospective analysis, from 12 referral allergy clinics located in 9 different areas. Inclusion criteria were Korean adults (≥18 years old) who underwent the inhalant allergen skin prick test for suspected history of respiratory allergy. The primary outcome was inhalant allergen skin prick response. Demographic and clinical information were also collected. Positive skin prick responses to allergens were defined as allergen-to-histamine wheal ratio ≥1. Based on skin test results, the most prevalent aeroallergens were determined. RESULTS: The overall prevalence of allergic sensitization was 45.3%. Dermatophagoides farinae and Dermatophagoides pteronyssinus were the most commonly sensitized allergens. Other common inhalant allergens were cat epithelium (8.1%), birch (7.7%), mugwort (6.9%), alder (6.7%), hazel (6.7%), beech (6.7%), oak (6.6%), and Tyrophagus putres (6.2%), in decreasing order frequency. These 10 inhalant allergens explained 90% of inhalant allergen sensitization in the study participants. However, distinct patterns of the 10 inhalant sensitization were observed in patients living in Chungnam and Jeju. American cockroach, Gernam cockroach, and Trichophyton metagrophytes were unique in Chungnam. Orchard, Japanese cedar, and Velvet were unique in Jeju. CONCLUSIONS: The present analysis suggests a panel of 10 most common inhalant allergens in Korean adult patients with suspected respiratory allergies, which explained 90% of inhalant allergen sensitization. This panel can be utilized as a practical and convenient tool for primary practice and epidemiological surveys of respiratory allergic diseases.

Association between Type A blaZ Gene Polymorphism and Cefazolin Inoculum Effect in Methicillin-Susceptible Staphylococcus aureus.

Some proportion of type A blaZ gene-positive methicillin-susceptible Staphylococcus aureus strains exhibit the cefazolin inoculum effect (CIE). The type A blaZ gene was divided into two groups by single nucleotide polymorphisms (SNPs) at Ser226Pro and Cys229Tyr. The median cefazolin MICs at a high inoculum concentration were 5.69 µg/ml for the Ser-Cys group and 40.32 µg/ml for the Pro-Tyr group (P = 0.01). The SNPs at codons 226 and 229 in the amino acid sequence encoded by the blaZ gene were closely associated with the CIE.

A Case of Pranlukast-Induced Anaphylactic Shock.

Leukotriene receptor antagonists, which are generally considered safe with a few adverse drug reactions, are increasingly used in the treatment of various allergic diseases, including asthma and allergic rhinitis. Although a few anaphylactic reactions to montelukast have been reported worldwide, there is still a lack of reports about severe adverse drug reactions associated with pranlukast. Here, we report a case of severe hypersensitivity reaction associated with pranlukast. A 65-year-old woman developed anaphylactic shock that presented as generalized urticaria, angioedema, collapse, and loss of consciousness after receiving pranlukast. A positive response to oral challenge and skin prick testing with pranlukast was observed in the patient. In this case, it was demonstrated that pranlukast can induce anaphylaxis, possibly mediated by the IgE-dependent pathway.