Additional local therapy before disease progression for EGFR-mutated advanced lung cancer: a systematic review and meta-analysis.

Background: International guidelines recommend the use of local therapy (LT) to limited progression in patients with epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer (NSCLC). However, the use of LT before disease progression has not been extensively analyzed. This meta-analysis evaluates the efficacy and safety of administering additional LT in conjunction with first-line EGFR-tyrosine kinase inhibitors (TKIs) before disease progression in patients with EGFR-mutated advanced NSCLC. Methods: We systematically searched PubMed, Embase, and the Cochrane Library for studies published up until May 31, 2023. The LT group consisted of patients who received first-line EGFR-TKIs in conjunction with additional LT, while the TKI group comprised participants treated with first-line EGFR-TKIs alone. Studies comparing the survival outcomes of the LT and TKI groups were included in this analysis. The primary outcomes were progression-free survival (PFS) and overall survival (OS). This review was registered on PROSPERO (registration number CRD42023439913). Results: Among the 11 investigated studies covering 1,313 patients, the LT modalities included radiotherapy, surgery, and ablation therapy, which accounted for 91%, 27%, and 27% of the studies, respectively. The pooled hazard ratios of median PFS and OS were 0.34 [95% confidence interval (CI): 0.22-0.53; P<0.001] and 0.42 (95% CI: 0.36-0.48; P<0.001), respectively, which indicated significant benefits for the LT group compared to the TKI group. There was no significant difference between the LT and TKI groups (P=0.473) regarding the incidence of grade 3 or higher adverse events. Conclusions: This study suggests that the strategic use of additional LT before disease progression is a promising approach for the treatment of EGFR-mutated advanced NSCLC.

Erratum: Correction of Tables in the Article "Reference Respiratory Muscle Strength Values and a Prediction Equation Using Physical Functions for Pulmonary Rehabilitation in Korea".

This corrects the article on p. e325 in vol. 38, PMID: 37846788.

Optic Nerve Head Curvature Flattening Is Associated with Central Visual Field Scotoma.

This study aimed to develop a new index, the average curvature ratio (ACR), to represent the optic nerve head (ONH) tilting and investigate its clinical relevance. Myopic eyes were included and divided into two subgroups: flat ONH (ACR < 1.0) and convex ONH (ACR ≥ 1.0). The occurrences of central and peripheral visual field (VF) defects were compared between the two groups. A total of 375 myopic eyes were recruited, and 231 and 144 eyes were included in the flat and convex ONH groups, respectively. Central scotoma occurred more frequently in the flat ONH group. According to the Patella-Anderson criteria, the number of eyes with central scotoma was 103 (44.6%) in the flat and 44 (30.6%) in the convex ONH groups (p = 0.009). According to Kook's criteria, the number of eyes with central scotoma was 122 (52.8%) in the flat and 50 (34.7%) in the convex ONH groups (p < 0.001). Peripheral scotoma was not significantly different between the groups. In the correlation analysis, the ACR was positively correlated with spherical equivalence, but not with axial length or central corneal thickness. The ACR reflects the degree of the ONH tilt and is a good index for estimating central VF damage in myopic eyes.

Development of the Korean Association for Lung Cancer Clinical Practice Guidelines: Recommendations on Radial Probe Endobronchial Ultrasound for Diagnosing Lung Cancer - An Updated Meta-Analysis.

PURPOSE: Radial probe endobronchial ultrasound (RP-EBUS) accurately locates peripheral lung lesions (PLLs) during transbronchial biopsy (TBB). We performed an updated meta-analysis of the diagnostic yield of TBB for PLLs using RP-EBUS to generate recommendations for the development of the Korean Association of Lung Cancer guidelines. MATERIALS AND METHODS: We systematically searched MEDLINE and EMBASE (from January 2013 to December 2022), and performed a meta-analysis using R software. The diagnostic yield was evaluated by dividing the number of successful diagnoses by the total lesion number. Subgroup analysis was performed to identify related factors. RESULTS: Forty-one studies with a total of 13,133 PLLs were included. The pooled diagnostic yield of RP-EBUS was 0.72 (95% confidence interval [CI], 0.70 to 0.75). Significant heterogeneity was observed among studies (χ2=292.38, p < 0.01, I2=86.4%). In a subgroup analysis, there was a significant difference in diagnostic yield based on RP-EBUS findings (within, adjacent to, invisible), with a risk ratio of 1.45 (95% CI, 1.23 to 1.72) between within and adjacent to, 4.20 (95% CI, 1.89 to 9.32) between within and invisible, and 2.59 (95% CI, 1.32 to 5.01) between adjacent to and invisible. There was a significant difference in diagnostic yield based on lesion size, histologic diagnosis, computed tomography (CT) bronchus sign, lesion character, and location from the hilum. The overall complication rate of TBB with RP-EBUS was 6.8% (bleeding, 4.5%; pneumothorax, 1.4%). CONCLUSION: Our study showed that TBB with RP-EBUS is an accurate diagnostic tool for PLLs with good safety profiles, especially for PLLs with within orientation on RP-EBUS or positive CT bronchus sign.

Reference Respiratory Muscle Strength Values and a Prediction Equation Using Physical Functions for Pulmonary Rehabilitation in Korea.

BACKGROUND: In Korea, tests for evaluating respiratory muscle strength are based on other countries' clinical experience or standards, which can lead to subjective evaluations. When evaluating respiratory function based on the standards of other countries, several variables, such as the race and cultures of different countries, make it difficult to apply these standards. The purpose of this study was to propose objective respiratory muscle strength standards and predicted values for healthy Korean adults based on age, height, weight, and muscle strength, by measuring maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), and peak cough flow (PCF). METHODS: This cross-sectional study analyzed MIP, MEP, and PCF in 360 people, each group comprising 30 adult men and women aged 20-70, diagnosed as healthy after undergoing medical check-ups at a general hospital. Hand grip strength (HGS) and the five times sit-to-stand test (FTSST) results were also recorded. Correlations among respiratory muscle strength, participant demographics, and overall muscle strength were evaluated using Pearson's correlation analysis. The predicted values of respiratory muscle strength were calculated using multiple regression analysis. RESULTS: Respiratory muscle strength differed from the values reported in studies from other countries. In the entire samples, both MIP and MEP had the highest correlations with peak HGS (r = 0.643, r = 0.693; P < 0.05), while PCF had the highest correlation with forced expiratory volume in 1 s (r = 0.753; P < 0.05). Age, body mass index, peak HGS, and FTSST results were independent variables affecting respiratory muscle strength. A predictive equation for respiratory muscle strength was developed using the multiple regression equation developed in this study. CONCLUSION: Respiratory muscle strength index may differ by country. For more accurate diagnoses, standard values for each country are required. This study presents reference values for Korea, and a formula for estimation is proposed when no respiratory muscle strength measurement equipment is available. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0006778.

Risk of Hyponatremia after Tramadol/Acetaminophen Single-Pill Combination Therapy: A Real-World Study Based on the OMOP-CDM Database.

BACKGROUND AND OBJECTIVE: Tramadol has been reported to cause hyponatremia but the evidence is conflicting. The risk of hyponatremia resulting from combination oral tramadol/acetaminophen (TA) therapy is thus unknown. This study examined whether, compared with acetaminophen (AA), TA use is associated with an increased risk of hyponatremia. METHODS: Hospital data compatible with the Observational Medical Outcomes Partnership-Common Data Model (OMOP-CDM; version 5.3) for 30,999 patients taking TA or AA from 2011 through 2020 were analyzed. New-onset hyponatremia was defined as a serum sodium level < 135 mEq/L within 10 days after drug initiation. The incidence rate ratio was calculated based on crude and 1:1 propensity-score-matched models. Subgroup analyses compared patients taking TA extended-release (TA-ER) and TA immediate-release (TA-IR) formulations. RESULTS: Among the 30,999 patients, 12,122 (39.1%) were aged > 65 years and 16,654 (53.7%) were male. Hyponatremia within 10 days developed in 1613 (8.4%) of the 19,149 patients in the TA group; the incidence rate was higher than in the AA group (4.2%; 493 out of 11,850 cases). In the propensity-score-matched model, the incidence rate of hyponatremia in the TA group was 6.8 per 1000 person-days (PD), which was 1.57-fold (1.31, 1.89) higher than that in the AA group (4.3 per 1000 PD). In both the crude and propensity-score-matched models, the incidence rate of hyponatremia was significantly higher in the TA-ER than TA-IR subgroup. CONCLUSION: In this real-world study, hyponatremia was more frequently observed in the TA than AA group, and in the TA-ER than TA-IR subgroup. Therefore, it is imperative to prescribe tramadol cautiously and closely monitor electrolyte levels.

Comparison of the Intrableb Characteristics of Anterior Segment Optical Coherence Tomography Imaging in Trabeculectomy according to Amniotic Membrane Transplantation.

INTRODUCTION: The purpose of this study was to compare the characteristics of filtering bleb with anterior segment optical coherence tomography (AS-OCT) according to amniotic membrane transplantation (AMT). METHODS: One hundred and sixteen eyes of 103 glaucoma patients who underwent trabeculectomy with (AMT group; 85 eyes) or without AMT (control group; 31 eyes) were included. Intrableb parameters were evaluated with AS-OCT. Surgical success was defined as an intraocular pressure (IOP) ≤18 mm Hg and IOP reduction ≥20% without medication at the time of AS-OCT examination. Logistic regression analyses were performed to determine factors associated with IOP control. RESULTS: In the eyes with successful IOP control, the fluid-filled space area, score, and height were greater for the AMT group than the control group (all ps < 0.001), while stripping layer thickness was greater and bleb wall reflectivity was lower for the control group than the AMT group (all ps < 0.001). Surgical success in the AMT group was associated with greater fluid-filled space score, lower bleb wall reflectivity, and microcyst formation (odds ratio [OR] = 8.016, 0.913, and 16.202, respectively, all ps ≤ 0.041). Lower bleb wall reflectivity alone was associated with surgical success in the control group (OR = 0.815, p = 0.019). CONCLUSION: The extent of the fluid-filled space was associated with successful IOP control after trabeculectomy with AMT. Hyporeflective bleb wall was associated with successful IOP control in AMT and control groups.

Bleb analysis using anterior segment optical coherence tomography after trabeculectomy with amniotic membrane transplantation.

INTRODUCTION: Little has been known about the intrableb structures associated with bleb function after trabeculectomy with amniotic membrane transplantation (AMT). The aim of this study is to analyze the characteristics of intrableb structures using anterior segment optical coherence tomography (AS-OCT) after trabeculectomy with AMT. METHODS: A total of 68 eyes of 68 patients with primary open-angle glaucoma who underwent trabeculectomy with AMT were included. Surgical success was defined as intraocular pressure (IOP) ≤ 18 mmHg and IOP reduction of ≥ 20% without medication on AS-OCT examination. Intrableb parameters, including bleb height, bleb wall thickness, striping layer thickness, bleb wall reflectivity, fluid-filled space score, fluid-filled space height, and microcyst formation were evaluated using AS-OCT. Logistic regression analysis was performed to determine factors associated with IOP control. RESULTS: Of the 68 eyes, 56 eyes were assigned to the success group and 12 eyes to the failure group. In the success group, bleb height (P = 0.009), bleb wall thickness (P = 0.001), striping layer thickness (P = 0.001), fluid-filled space score (P = 0.001), and frequency of microcyst formation (P = 0.001) were greater than those in the failure group. Bleb wall reflectivity was higher in the failure group than in the success group (P < 0.001). In the univariate logistic regression analysis, previous cataract surgery was significantly associated with surgical failure (odds ratio = 5.769, P = 0.032). CONCLUSION: A posteriorly extending fluid-filled space, tall bleb with low reflectivity, and thick striping layer were characteristics of successful filtering blebs after trabeculectomy with AMT.

Should We Perform Repeated Re-biopsy for the Detection of T790M Mutation?

PURPOSE: Epidermal growth factor receptor (EGFR) T790M mutations have been detected in the second or third rebiopsy, even if the T790M mutation was not identified in the first rebiopsy. This meta-analysis investigated the EGFR T790M mutation detection rates and its additional advantages with repeated rebiopsies. MATERIALS AND METHODS: We searched through the PubMed and EMBASE databases up to June 2022. Studies reporting rebiopsy to identify the EGFR T790M mutation in case of disease progression among patients with advanced non-small cell lung cancer and multiple rebiopsies were included. The quality of the included studies was checked using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. RESULTS: Eight studies meeting the eligibility criteria, reporting 1,031 EGFR mutation-positive patients were selected. The pooled EGFR T790M mutation detection rate of the first and repeated rebiopsies were 0.442 (95% confidence interval [CI], 0.411 to 0.473; I2=84%; p < 0.01) and 0.465 (95% CI, 0.400 to 0.530; I2=69%; p < 0.01), respectively. Overall, the pooled detection rate of EGFR T790M mutation was 0.545 (95% CI, 0.513 to 0.576), which increased by 10.3% with repeated rebiopsies. CONCLUSION: This meta-analysis identified that repeated rebiopsy increases the detection rate of EGFR T790M mutation by 10.3%, even if EGFR T790M mutation is not detected in the first rebiopsy. Our results indicate that the spatiotemporal T790M heterogeneity can be overcome with repeated rebiopsy.

Prescription Patterns of Topical Medications in Patients with Atopic Dermatitis: An Investigative Review Using Big Data from the National Health Insurance Corporation.

BACKGROUND: Topical medications play a crucial role in the treatment of atopic dermatitis (AD). Topical corticosteroids (TCSs) remain the main treatment of choice and topical antibiotics have also been used. However, with the new topical calcineurin inhibitors (TCIs), the prescription patterns of topical agents have changed over time. OBJECTIVE: To characterize the prescription patterns of topical medications in Korean patients with AD. METHODS: We investigated topical medications prescribed to Korean patients with AD using the National Health Insurance Sharing System (NHISS) database over a 14-year period (2002~2015). Additionally, the potency of prescribed TCSs was compared with AD and psoriasis patients. RESULTS: The annual prescription of TCSs showed a slightly decreasing trend without significant change. In particular, in terms of steroid class, prescription of moderate-to-low potency TCSs were increased and the use of high potency TCSs were decreased. TCSs were the most commonly prescribed topical medications for AD. Tertiary hospitals had a higher prescription rate for TCIs than secondary or primary hospitals (16.2%, 3.1%, and 1.9%, respectively). Additionally, dermatologists prescribed TCIs more frequently than pediatricians and internists (4.3%, 1.2%, and 0.6%, respectively). Among TCSs, Class 5 was prescribed the most (40.6%) followed by Class 7, 6, 4, 3, 1, and 2. When we compared the potency of TCSs prescribed for AD with psoriasis patients, moderate-to-low-potency TCSs were more commonly prescribed in AD. CONCLUSION: Prescription patterns of topical medications had changed from 2002 to 2015 and differed according to the type of institution and specialty of the physician.

Apoptotic Factors, CaNma111 and CaYbh3, Function in Candida albicans Filamentation by Regulating the Hyphal Suppressors, Nrg1 and Tup1.

The morphological switch from the yeast to hyphal form is a key virulence attribute of the opportunistic fungal pathogen, Candida albicans. Our recent report showed that deletion of the newly identified apoptotic factor, CaNma111 or CaYbh3, leads to hyperfilamentation and increased virulence in a mouse infection model. CaNma111 and CaYbh3 are homologs of the pro-apoptotic protease, HtrA2/Omi, and BH3-only protein, respectively. In this study, we examined the effects of CaNMA111 and CaYBH3 deletion mutations on the expression levels of the hypha-specific transcription factors, Cph1 (a hyphal activator), Nrg1 (a hyphal repressor), and Tup1 (a hyphal repressor). The protein levels of Nrg1 were decreased in Caybh3/Caybh3 cells while those of Tup1 were decreased in both Canma111/Canma111 and Caybh3/Caybh3 cells. These effects on Nrg1 and Tup1 proteins were retained during serum-induced filamentation and appear to explain the hyperfilamentation phenotypes of the CaNMA111 and CaYBH3 deletion mutants. Treatment with the apoptosis-inducing dose of farnesol decreased the Nrg1 protein levels in the wild-type strain and more evidently in Canma111/Canma111 and Caybh3/Caybh3 mutant strains. Together, our results suggest that CaNma111 and CaYbh3 are key regulators of Nrg1 and Tup1 protein levels in C. albicans.

Changing trends in the incidence and spectrum of cancers between 1990 and 2021 among HIV-infected patients in Busan, Korea.

BACKGROUND: Long-term follow-up data on cancer incidence and spectrum among human immunodeficiency virus (HIV)-infected individuals in Korea have been scarce. MATERIAL AND METHODS: This retrospective cohort study included HIV-infected individuals visiting a tertiary care hospital in Busan, South Korea between 1990 and 2021. The observation was divided into 4 periods. The incidence rate was calculated using direct standardization on age and sex, stratified by calendar period. RESULTS: Of the 1,297 patients, 92 patients (7.1%) were diagnosed with 97 cancers. Excluding 37 patients with prevalent cancer, 1,260 patients were followed for a total of 8,803.7 person-years (PYs), and 55 patients developed 60 incident cancers including 5 second primary incident cancers. In men, the AIDS-defining cancer (ADC) incidence decreased from 294.7 per 100,000 PYs in 1990-1997 to 124.8 per 100,000 PYs in 2014-2021, while the non-AIDS-defining cancer (NADC) incidence increased from 0 per 100,000 PYs to 316.5 per 100,000 PYs during the same period. The proportion of virus-unrelated NADCs (VU-NADCs) increased from 33.3% in 1998-2005 to 49% in 2014-2021. The proportion of human papillomavirus-associated cancers (HPVACs) has recently increased in both ADCs and NADCs. The median time from HIV diagnosis to their first cancer was 1.48 years for ADCs, 6.11 years for VR-NADCs, 8.3 years for VU-NADCs, and 11.5 years for HPVACs. CONCLUSION: The incidence of NADCs is increasing with the aging of HIV-infected patients, and thus, it is necessary to promote cancer screening and prevention programs.

Ultrathin Bronchoscopy for the Diagnosis of Peripheral Pulmonary Lesions: A Meta-Analysis.

BACKGROUND: Ultrathin bronchoscopy (external diameter, ≤3.5 mm) is useful for the diagnosis of peripheral pulmonary lesions because of its good accessibility. OBJECTIVES: We performed a meta-analysis to investigate the diagnostic yield of ultrathin bronchoscopy for peripheral pulmonary lesions. METHODS: We performed a systematic search of MEDLINE and EMBASE (from inception to May 2021), and meta-analysis was performed using R software. The diagnostic yield was evaluated by dividing the number of successful diagnoses by the total number of lesions, and subgroup analysis was performed to identify related factors. RESULTS: Nineteen studies with a total of 1,977 peripheral pulmonary lesions were included. The pooled diagnostic yield of ultrathin bronchoscopy was 0.65 (95% confidence interval, 0.60-0.70). Significant heterogeneity was observed among studies (χ2, 87.75; p < 0.01; I2, 79.5%). In a subgroup analysis, ultrathin bronchoscopy with 1.2 mm channel size showed a diagnostic yield of 0.61 (95% confidence interval, 0.53-0.68), whereas ultrathin bronchoscopy with 1.7 mm channel size showed 0.70 (95% confidence interval, 0.66-0.74) (χ2, 5.35; p = 0.02). In addition, there was a significant difference in diagnostic yield based on lesion size, histologic diagnosis (malignant vs. benign), bronchus sign, and lesion location from the hilum, whereas no significant difference was found based on lobar location. The overall complication rate of ultrathin bronchoscopy was 2.7% (pneumothorax, 1.1%). CONCLUSIONS: Ultrathin bronchoscopy is an excellent tool for peripheral pulmonary lesion diagnosis with a low complication rate. The diagnostic yield of ultrathin bronchoscopy was significantly higher with larger channel size, which might be attributed to the availability of radial endobronchial ultrasound.

Cardiac and Pulmonary Management Status of Duchenne Muscular Dystrophy in South Korea Based on Data From the National Health Insurance Database.

BACKGROUND AND PURPOSE: The purpose of this study was to determine the cardiac and pulmonary management status of patients with Duchenne muscular dystrophy (DMD) in South Korea based on the Korean National Health Insurance database. METHODS: This study used data of patients with code G71.0 in the National Health Information database, and also those with the special case of code V012. Cardiac function was assessed based on whether echocardiography and 24-h electrocardiography were performed, as well as the frequency of these investigations. Furthermore, information on the use of angiotensin-converting enzyme inhibitors (ACEi), angiotensin II receptor blockers (ARB), and beta blockers (BB) in the drug benefit list was checked. Medical charge records were also checked regarding the prescription of respiratory functional assessments and treatments. RESULTS: The diagnostic criteria were met by 479 patients, with 41% of these patients receiving a cardiac evaluation, 29.8% being prescribed ACEi at 14.4±3.7 years of age, 59.5% undergoing pulmonary function tests, and 42.1% received pulmonary rehabilitation. The age at receiving ventilator support was 19.4±2.7 years. The frequency of cardiac and respiratory function tests increased with age, but the interval between tests was longer than the recent DMD care recommendations. The trend of taking ACEi, ARB, and BB for cardiac management in South Korea did not change during the study analysis period. CONCLUSIONS: The findings of this study will contribute to recognizing the current status and the importance of applying an anticipatory approach to cardiopulmonary function in DMD patients.

The Effect of Amniotic Membrane Transplantation on Trabeculectomy in Patients with Pseudoexfoliation Glaucoma.

Purpose: The aim is to evaluate the effect of amniotic membrane transplantation (AMT) on trabeculectomy with mitomycin C in patients with pseudoexfoliation glaucoma (PXG). Methods: This retrospective cohort study included 85 eyes of PXG who underwent trabeculectomy with or without AMT (52/33 eyes in the AMT/control group). Surgical success was defined by these criteria: (1) intraocular pressure (IOP) ≤18 mmHg and IOP reduction ≥20% and (2) IOP ≤15 mmHg and IOP reduction ≥25%. Criteria A and B defined complete success rates as patients who met these criteria without medication, respectively. Criteria C and D defined qualified success rates as patients who met these criteria with medication, respectively. Cumulative probabilities of success were compared using the Kaplan-Meier survival analysis. Cox proportional hazard models were used to evaluate the influence of AMT on surgical success accounting for confounding variables. Results: For the AMT group, compared with the control group, the complete success rates at 12 months for criterion A were 86.5% and 63.6%, respectively (P = 0.017) and for criterion B, 86.4% and 63.6% (P = 0.005). The qualified success rates at 12 months for criterion C were 92.1% and 75.1%, respectively (P = 0.047) and for criterion D, 92.1% and 72.1% (P = 0.021). On multivariable Cox regression analyses, AMT was associated with a lower failure rate on criteria A, B, and D (all P ≤ 0.047). Incidence of avascular bleb was higher in the control group than in the AMT group (7 vs 0 eyes; P = 0.004). Conclusions: In patients with PXG, trabeculectomy with AMT was associated with higher success rates and a lower incidence of avascular bleb compared with conventional trabeculectomy. Research Registration. This retrospective cohort study was registered at the Clinical Trial Registry of Korea (https://cris.nih.go.kr/cris/index/index.do, KCT0007228).

Corticosteroid use and bone health management for Duchenne muscular dystrophy in South Korea.

This study aimed to determine the current corticosteroid use and bone health management status of patients with Duchenne muscular dystrophy (DMD) in South Korea. This is a national population-based study utilized information from the databased of Korean National Health Insurance Database. Database regarding bone status, spine radiography findings, bone mineral density, and laboratory test results were obtained, as well as the proportion of patients with spine and lower limb prostheses, occurrence of scoliosis, and age at scoliosis surgery. Deflazacort dose in the ambulant group (aged < 15 years) increased by age and year. The maintenance dose of prednisolone and deflazacort for the 15-19 years group decreased by year. Among the patients, 12.47% underwent spine radiography, 23.11% underwent dual-energy X-ray absorptiometry, and 22.7% underwent vitamin D tests. Moreover, 40.9% of the patients were prescribed vitamin D at a mean age of 14.6 ± 6.1 years, while 10.22% were prescribed bisphosphonate at 17.92 ± 3.4 years. Further, 16.1% of the patients underwent posterior spinal instrumentation and fusion at 14.4 ± 2.3 years and 5.3% underwent anterior spinal instrumentation and fusion at 14.4 ± 2.3 years. Ankle-foot orthosis and spine orthosis prescriptions were noted in 4.91% and 1.84% of patients, respectively. In this our study, the current corticosteroid use and bone health management status of DMD in South Korea has been presented. The dose prescription for corticosteroid and bone health monitoring did not reach to current recommendation.

Fus3 and Tpk2 protein kinases regulate the phosphorylation-dependent functions of RNA helicase Dhh1 in yeast mating and Ste12 protein expression.

Decapping of mRNA is a key regulatory step for mRNA decay and translation. The RNA helicase, Dhh1, is known as a decapping activator and translation repressor in yeast Saccharomyces cerevisiae. Dhh1 also functions as a gene-specific positive regulator in the expression of Ste12, a mating-specific transcription factor. A previous study showed that the N-erminal phosphorylation of Dhh1 regulates its association with the mRNA-binding protein, Puf6, to affect the protein translation of Ste12. Here, we investigated the roles of the phosphorylated residues of Dhh1 in yeast mating process and Ste12 expression. The phospho-deficient mutation, DHH1-T10A, was associated with decreased diploid formation during mating and decreased level of the Ste12 protein in response to α-mating pheromone. A kinase overexpression analysis revealed that Ste12 protein expression was affected by overexpression of Fus3 MAP kinase or Tpk2 kinase. Tpk2 was shown to be responsible for phosphorylation of Dhh1 at Thr10. Our study shows that overexpression of Fus3 or Tpk2 alters the Dhh1-Puf6 protein interaction and thereby affects Ste12 protein expression.

Nationwide population-based incidence of cancer among patients with HIV/AIDS in South Korea.

Cancers are the leading cause of death among people living with HIV/AIDS (PLWHA); however, nationwide studies on cancer incidence are limited. We aimed to determine the trends in the incidence rates of AIDS-defining cancers (ADCs) and non-AIDS-defining cancers (NADCs) among Korean PLWHA. Data from the National Health Insurance Sharing Service from 2004 to 2017 were collected. Age- and sex-adjusted standardized incidence ratios (SIRs) for various cancer types relative to the general population were calculated. Of the 11,737 PLWHA followed-up for 65,052 person-years (PYs), 445 (ADCs, 130 and NADCs, 298) developed cancer. The incidence rate of ADCs decreased, whereas that of NADCs remained unchanged. PLWHA were at an increased risk of ADCs (SIR: 12.6, 95% CI: 10.6-15.0), including Kaposi's sarcoma, non-Hodgkin's lymphoma, and cervical cancer, and some NADCs, including anal cancer, lung cancer, liver cancer, and oropharyngeal cancer. Of the 396 patients who received antiretroviral therapy (ART), 215 with optimal adherence had lower incidence rates for ADCs and NADCs than those with non-optimal adherence. The 5-year survival rate of PLWHA with NADCs was 57.8%. Close surveillance and routine screening of cancers and improvement in ART adherence are required to improve the clinical outcomes of PLWHA.

Heart Failure and Stroke Risks in Users of Liothyronine With or Without Levothyroxine Compared with Levothyroxine Alone: A Propensity Score-Matched Analysis.

Background: Combination therapy with liothyronine (LT3) and levothyroxine (LT4) is used in patients with persistent symptoms, despite being administered an adequate dose of LT4. LT3 may also be used in some thyroid cancer patients preparing for radioactive iodine therapy. However, there is a controversy regarding the safety of LT3 use, and there has been no definite evidence of long-term safety of LT3 therapy in Asian populations. The aim of this study was to examine the long-term safety of LT3 therapy using the Common Data Model (CDM). Methods: We conducted a retrospective multicenter study across four hospital databases encoded in the Observational Medical Outcomes Partnership (OMOP) CDM. LT3 users were defined as those who received an LT3 prescription for at least 90 days (with or without LT4), and their safety outcomes were compared with those in LT4-only users after 1:4 propensity score matching. Safety outcomes included the incidences of osteoporosis, cardiovascular disease, cancer, anxiety disorder, and mood disorder. Results: We identified 1434 LT3 users and 3908 LT4-only users. There was a statistically significant difference in the incidence rate of safety outcomes between LT3 users and LT4-only users. The risks of heart failure (incidence rate ratio [IRR] = 1.664, 95% confidence interval [95% CI] 1.002-2.764, p = 0.049) and stroke (IRR = 1.757, CI 1.073-2.877, p = 0.025) were higher in LT3 users than in LT4-only users. When subgroup analysis was performed according to the presence/absence of thyroid cancer history and duration of thyroid hormone replacement, the risk of heart failure was higher in LT3 users with a history of thyroid cancer and those who underwent ≥52 weeks of LT3 therapy. In addition, the risk of stroke was higher in LT3 users without thyroid cancer history and those who underwent ≥52 weeks of LT3 therapy. Conclusions: The use of LT3 was associated with increased incidence of heart failure and stroke in patients with a longer duration of LT3 use and history of thyroid cancer. Therefore, clinicians should consider the risk of heart failure and stroke in thyroid cancer patients with long-term use of LT3. These findings require confirmation in other populations.