Background: Targeted risk population has been highly vaccinated against pneumococcal diseases in South Korea. Despite this, the pneumococcal serotype distribution is evolving, which impedes efficient roll-out of vaccines. Methods: This prospective cohort study included patients aged ≥ 19 years with communityacquired pneumonia (CAP) from five university hospitals in South Korea between September 2018 and July 2021. The outcomes of interest were the demographic and clinical characteristics of patients with CAP, pneumococcal serotype distribution, and risk factors of 30-day mortality in patients with pneumococcal CAP (pCAP). Considering the high seroprevalence, we analyzed the clinical characteristics of serotype 3 pCAP. Results: A total of 5,009 patients hospitalized with CAP was included (mean age ± standard deviation, 70.3 ± 16.0 years; 3,159 [63.1%] men). Streptococcus pneumoniae was the leading causative agent of CAP (11.8% overall, 17.7% in individuals aged < 65 years with chronic medical conditions). Among the 280 serotyped Streptococcus pneumococcus, serotype 3 was the most common (10.0%), followed by serotypes 19A (8.9%), 34 (8.9%), and 35B (8.9%).Non-vaccine serotypes (serotype 35B [13.9%] and 34 [12.0%]) were the most prevalent in 108 individuals vaccinated with 23-valent pneumococcal polysaccharide vaccine (PPSV23).Serotype 3 was prevalent, irrespective of PPSV23 vaccination status, and more common in individuals with chronic lung disease (P = 0.008). Advanced age (adjusted odds ratio [aOR], 1.040; 95% confidence interval [CI], 1.011–1.071), long-term care facility residence (aOR, 2.161; 95% CI, 1.071–4.357), and bacteremia (aOR, 4.193; 95% CI, 1.604–10.962) were independent risk factors for 30-day mortality in patients with pCAP. PPSV23 vaccination reduced the risk of mortality (aOR, 0.507; 95% CI, 0.267–0.961). Conclusion Serotype 3 and 19A were still the most common serotypes of pCAP in South Korea despite the national immunization program of 13-valent pneumococcal conjugated vaccine in children and PPSV23 in old adults. PPSV23 vaccination might reduce the risk of mortality in patients with pCAP.

Purpose: Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers (ARBs) are frequently employed to counteract the detrimental effects of proteinuria on glomerular diseases. However, the effects of ARBs remain poorly examined in pediatric patients with immunoglobulin A (IgA) nephropathy. Herein, we evaluated the efficacy and safety of losartan, an ARB, in pediatric IgA nephropathy with proteinuria. Methods: This prospective, single-arm, multicenter study included children with IgA nephropathy exhibiting proteinuria. Changes in proteinuria, blood pressure, and kidney function were prospectively evaluated before and 4 and 24 weeks after losartan administration. The primary endpoint was the difference in proteinuria between baseline and 24 weeks. Results: In total, 29 patients were enrolled and received losartan treatment. The full analysis set included 28 patients who received losartan at least once and had pre- and post-urinary protein to creatinine ratio measurements (n=28). The per-protocol analysis group included 22 patients who completed all scheduled visits without any serious violations during the study period. In both groups, the mean log (urine protein to creatinine ratio) value decreased significantly at 6 months. After 24 weeks, the urinary protein to creatinine ratio decreased by more than 50% in approximately 40% of the patients. The glomerular filtration rate was not significantly altered during the observation period. Conclusions Losartan decreased proteinuria without decreasing kidney function in patients with IgA nephropathy over 24 weeks. Losartan could be safely employed to reduce proteinuria in this patient population. ClinicalTrials.gov trial registration (NCT0223277)

Purpose: Granular corneal dystrophy type 2 (GCD2) is a hereditary disease that features granular and lattice stromal deposits in the cornea. There are homozygotes and heterozygotes and the opacities are exacerbated by corneal trauma or surgery, such as laser in situ keratomileusis (LASIK). As there is individual variability in GCD2 phenotypes, we investigated various corneal features of GCD2 patients in their twenties, the main age group for refractive surgery. Methods: From genetically confirmed GCD2 patients who had an R124H mutation of the transforming growth factor β induced (TGFBI) gene at age 20 to 29 years, we chose representative patients: one homozygote; one compound heterozygote; one simple heterozygote with a severe phenotype with many granular deposits; one common heterozygote; and four heterozygotes with normal corneas. The corneas of all patients were subject to slit-lamp examination and photographed. Results: The homozygote had confluent granular deposits covering the cornea. The compound heterozygote had granular and lattice deposits covering the center of the cornea. The patient with a severe phenotype had more than 30 granular deposits in one eye, but was a simple GCD2 heterozygote, verified by full-sequencing of the TGFBI gene. In the four patients with normal corneas, a single small lesion was subsequently detected during follow-up in two, at 3 weeks and 6 months, respectively. Both corneas were judged clear at chance examinations. Conclusions Among Koreans in their twenties, GCD2 patients have various phenotypes, from clear corneas to severe confluent opacities. There are GCD2 heterozygotes with nearly clear corneas, so caution must be taken when choosing patients for refractive surgery.

Purpose: Contrast sensitivity, the ability to distinguish the relative difference in luminance of an object from its surrounding or adjacent objects, is a useful measure of visual function. In granular corneal dystrophy type 2 (GCD2), opacity of the corneal stroma causes deterioration in visual function. We compared the contrast sensitivity of GCD2 patients before and after phototherapeutic keratectomy (PTK) to evaluate the perioperative visual function in these patients. Methods: This study included 22 eyes of heterozygote GCD2 patients. The visual acuity and contrast sensitivity were measured before and after PTK. The contrast sensitivity was measured in mesopic and photopic background luminances, with glare (G) levels of 0-2 (G0, G1, and G2, respectively) and spatial frequencies at 1.5, 3, 6, 12, and 18 cycles per degree (cpd). Results: The contrast sensitivity increased after PTK at 1.5 and 3 cpd in mesopic and photopic conditions with G0-2 glare (p < 0.05). At 6 cpd, the contrast sensitivity increased in the mesopic condition with G1 glare, and in the photopic condition with G0-2 glare (p < 0.05). However, there was no change in contrast sensitivity at any glare level at 12 and 18 cpd after PTK. Conclusions In GCD2 patients, the contrast sensitivity increased significantly after PTK. The vision of GCD2 patients, which is decreased due to corneal opacity, is improved after PTK.

Background: Postoperative thyroid stimulating hormone (TSH) suppression therapy is recommended for patients with intermediate- and high-risk differentiated thyroid cancer to prevent the recurrence of thyroid cancer. With the recent increase in small thyroid cancer cases, the extent of resection during surgery has generally decreased. Therefore, questions have been raised about the efficacy and long-term side effects of TSH suppression therapy in patients who have undergone a lobectomy. Methods: This is a multicenter, prospective, randomized, controlled clinical trial in which 2,986 patients with papillary thyroid cancer are randomized into a high-TSH group (intervention) and a low-TSH group (control) after having undergone a lobectomy. The principle of treatment includes a TSH-lowering regimen aimed at TSH levels between 0.3 and 1.99 μIU/mL in the low-TSH group. The high-TSH group targets TSH levels between 2.0 and 7.99 μIU/mL. The dose of levothyroxine will be adjusted at each visit to maintain the target TSH level. The primary outcome is recurrence-free survival, as assessed by neck ultrasound every 6 to 12 months. Secondary endpoints include disease-free survival, overall survival, success rate in reaching the TSH target range, the proportion of patients with major cardiovascular diseases or bone metabolic disease, the quality of life, and medical costs. The follow-up period is 5 years. Conclusion The results of this trial will contribute to establishing the optimal indication for TSH suppression therapy in low-risk papillary thyroid cancer patients by evaluating the benefit and harm of lowering TSH levels in terms of recurrence, metabolic complications, costs, and quality of life.

Background: Postoperative thyroid stimulating hormone (TSH) suppression therapy is recommended for patients with intermediate- and high-risk differentiated thyroid cancer to prevent the recurrence of thyroid cancer. With the recent increase in small thyroid cancer cases, the extent of resection during surgery has generally decreased. Therefore, questions have been raised about the efficacy and long-term side effects of TSH suppression therapy in patients who have undergone a lobectomy. Methods: This is a multicenter, prospective, randomized, controlled clinical trial in which 2,986 patients with papillary thyroid cancer are randomized into a high-TSH group (intervention) and a low-TSH group (control) after having undergone a lobectomy. The principle of treatment includes a TSH-lowering regimen aimed at TSH levels between 0.3 and 1.99 μIU/mL in the low-TSH group. The high-TSH group targets TSH levels between 2.0 and 7.99 μIU/mL. The dose of levothyroxine will be adjusted at each visit to maintain the target TSH level. The primary outcome is recurrence-free survival, as assessed by neck ultrasound every 6 to 12 months. Secondary endpoints include disease-free survival, overall survival, success rate in reaching the TSH target range, the proportion of patients with major cardiovascular diseases or bone metabolic disease, the quality of life, and medical costs. The follow-up period is 5 years. Conclusion The results of this trial will contribute to establishing the optimal indication for TSH suppression therapy in low-risk papillary thyroid cancer patients by evaluating the benefit and harm of lowering TSH levels in terms of recurrence, metabolic complications, costs, and quality of life.

Purpose: The association of the initial serum ammonia level with in-hospital mortality in patients with acute glufosinate-ammonium herbicide poisoning was studied. Methods: This retrospective cohort study was conducted between March 2012 and August 2019 in the emergency department after glufosinate-ammonium herbicide poisoning. Survivors and non-survivors were analyzed using a Mann-Whitney U test and Fisher’s exact test. Multivariate logistic regression analysis was performed to determine the independent risk factors for mortality. Results: One hundred and six patients were enrolled; 11 died, yielding a mortality of 10.4%. The serum bicarbonate level was significantly lower in the non-survival group than the survival group. Age, serum ammonia, blood urea nitrogen, creatinine levels, SOFA score, and APACHE II score were significantly higher in the non-survival group than the survival group. Age, serum ammonia, and creatinine level were independent risk factors for mortality in multivariate logistic regression analysis. Conclusion The initial serum ammonia level is associated with mortality in patients with acute glufosinate herbicide poisoning.

Purpose: The association of the initial serum ammonia level with in-hospital mortality in patients with acute glufosinate-ammonium herbicide poisoning was studied. Methods: This retrospective cohort study was conducted between March 2012 and August 2019 in the emergency department after glufosinate-ammonium herbicide poisoning. Survivors and non-survivors were analyzed using a Mann-Whitney U test and Fisher’s exact test. Multivariate logistic regression analysis was performed to determine the independent risk factors for mortality. Results: One hundred and six patients were enrolled; 11 died, yielding a mortality of 10.4%. The serum bicarbonate level was significantly lower in the non-survival group than the survival group. Age, serum ammonia, blood urea nitrogen, creatinine levels, SOFA score, and APACHE II score were significantly higher in the non-survival group than the survival group. Age, serum ammonia, and creatinine level were independent risk factors for mortality in multivariate logistic regression analysis. Conclusion The initial serum ammonia level is associated with mortality in patients with acute glufosinate herbicide poisoning.

PURPOSE: Data are lacking on the association between the allergic rhinitis (AR) phenotype and sensitization to specific allergens or bronchial hyperresponsiveness (BHR) in children. We here investigated risk factors and comorbidities, including sensitization to specific allergens and BHR, for the AR phenotype by AR and its Impact on Asthma (ARIA) classification in a general population-based birth cohort study. METHODS: We enrolled 606 children aged 7 years from the Panel Study of Korean Children. The AR phenotype was assigned in accordance with the ARIA classification in children. Skin prick tests and Provocholine provocation test were performed. Risk factors and comorbidities for AR phenotypes were then analyzed. RESULTS: The prevalence of mild and moderate to severe AR in our study cohort was 37.2% and 8.8%, respectively. Recent use of analgesics or antipyretics and current cat ownership were associated with the risk of mild persistent AR. Sensitizations to Dermatophagoides Pteronyssinus (Der p), Japanese hop and cat were associated with moderate to severe persistent AR. Children with moderate to severe AR had a higher risk of current asthma and BHR compared to mild AR cases (adjusted odds ratio [aOR], 5.26; 95% confidence interval [CI], 1.77–15.62). Moderate to severe AR with allergic sensitization was associated with the highest risk of BHR (aOR, 11.77; 95% CI, 3.40–40.74). CONCLUSIONS: Moderate to severe-persistent AR is more closely related to respiratory comorbidities and sensitizations than mild AR. Stratifying the AR phenotype by ARIA classification may assist in disease management.
Allergens ; Analgesics ; Animals ; Antipyretics ; Asian Continental Ancestry Group ; Asthma ; Bronchial Hyperreactivity ; Cats ; Child ; Classification ; Cohort Studies ; Comorbidity ; Dermatophagoides pteronyssinus ; Disease Management ; Humans ; Methacholine Chloride ; Odds Ratio ; Ownership ; Parturition ; Phenotype ; Prevalence ; Rhinitis, Allergic ; Risk Factors ; Skin

Purpose: Targeted next-generation sequencing (NGS) panels for solid tumors have been useful in clinical framework for accurate tumor diagnosis and identifying essential molecular aberrations. However, most cancer panels have been designed to address a wide spectrum of pan-cancer models, lacking integral prognostic markers that are highly specific to gliomas. Materials and Methods: To address such challenges, we have developed a glioma-specific NGS panel, termed “GliomaSCAN,” that is capable of capturing single nucleotide variations and insertion/deletion, copy number variation, and selected promoter mutations and structural variations that cover a subset of intron regions in 232 essential glioma-associated genes. We confirmed clinical concordance rate using pairwise comparison of the identified variants from whole exome sequencing (WES), immunohistochemical analysis, and fluorescence in situ hybridization. Results: Our panel demonstrated high sensitivity in detecting potential genomic variants that were present in the standard materials. To ensure the accuracy of our targeted sequencing panel, we compared our targeted panel to WES. The comparison results demonstrated a high correlation. Furthermore, we evaluated clinical utility of our panel in 46 glioma patients to assess the detection capacity of potential actionable mutations. Thirty-two patients harbored at least one recurrent somatic mutation in clinically actionable gene. Conclusion We have established a glioma-specific cancer panel. GliomaSCAN highly excelled in capturing somatic variations in terms of both sensitivity and specificity and provided potential clinical implication in facilitating genome-based clinical trials. Our results could provide conceptual advance towards improving the response of genomically guided molecularly targeted therapy in glioma patients.