Real-world incidences and risk factors of immune-related adverse events in patients treated with immune checkpoint inhibitors: A nationwide retrospective cohort study.

Immune-related adverse events (irAEs) caused by immune checkpoint inhibitors (ICIs) are rare but fatal, requiring systemic steroid use. Therefore, to examine the outcomes, incidence, timing, and risk factors of ICI-associated steroid-requiring severe irAEs, we conducted a nationwide, retrospective, cohort study utilizing the Korean Health Insurance and Review Assessment database. We identified 357,010 patients with lung cancer, bladder cancer, or skin melanoma, eligible for ICI reimbursement in Korea between January 2012 to June 2020. Steroid-requiring severe irAEs following ICI treatment or treatment-emergent AEs following cytotoxic chemotherapy were defined as moderate- or high-dose steroid administration for over 2 consecutive days, along with corresponding ICD-10 codes indicating affected organ systems. The ICI-exposed group (N = 10,118) was compared to a matched cohort of 55,436 ICI-unexposed patients treated with cytotoxic chemotherapy. Incidences of acute severe irAEs requiring moderate- and high-dose steroids were higher in the ICI-exposed group (1.95% and 6.42%, respectively). The ICI-exposed group also had a higher risk of developing delayed severe irAEs requiring moderate- and high-dose steroid use (3.89% and 7.39%). Male sex, high comorbidity index, or previously diagnosed autoimmune diseases were associated with an increased risk of severe irAEs. Notably, 27.4-38.8% of the patients experienced recurrent severe irAEs after re-challenge with ICIs following moderate- or high-dose steroid use, with the severity matching the initial episode. Steroid-requiring severe irAEs were significantly more prevalent among patients exposed to ICIs than among those treated with chemotherapy in acute and delayed periods.

Risk of Subsequent Primary Cancers Among Adult-Onset 5-Year Cancer Survivors in South Korea: Retrospective Cohort Study.

BACKGROUND: The number of cancer survivors who develop subsequent primary cancers (SPCs) is expected to increase. OBJECTIVE: We evaluated the overall and cancer type-specific risks of SPCs among adult-onset cancer survivors by first primary cancer (FPC) types considering sex and age. METHODS: We conducted a retrospective cohort study using the Health Insurance Review and Assessment database of South Korea including 5-year cancer survivors diagnosed with an FPC in 2009 to 2010 and followed them until December 31, 2019. We measured the SPC incidence per 10,000 person-years and the standardized incidence ratio (SIR) compared with the incidence expected in the general population. RESULTS: Among 266,241 survivors (mean age at FPC: 55.7 years; 149,352/266,241, 56.1% women), 7348 SPCs occurred during 1,003,008 person-years of follow-up (median 4.3 years), representing a 26% lower risk of developing SPCs (SIR 0.74, 95% CI 0.72-0.76). Overall, men with 14 of the 20 FPC types had a significantly lower risk of developing any SPCs; women with 7 of the 21 FPC types had a significantly lower risk of developing any SPCs. The risk of developing any SPC type differed by age; the risk was 28% higher in young (<40 years) cancer survivors (SIR 1.28, 95% CI 1.16-1.42; incidence: 30 per 10,000 person-years) and 27% lower in middle-aged and older (≥40 years) cancer survivors (SIR 0.73, 95% CI 0.71-0.74; incidence: 80 per 10,000 person-years) compared with the age-corresponding general population. The most common types of FPCs were mainly observed as SPCs in cancer survivors, with lung (21.6%) and prostate (15.2%) cancers in men and breast (18.9%) and lung (12.2%) cancers in women. The risks of brain cancer in colorectal cancer survivors, lung cancer in laryngeal cancer survivors, and both kidney cancer and leukemia in thyroid cancer survivors were significantly higher for both sexes. Other high-risk SPCs varied by FPC type and sex. Strong positive associations among smoking-related cancers, such as laryngeal, head and neck, lung, and esophageal cancers, were observed. Substantial variation existed in the associations between specific types of FPC and specific types of SPC risk, which may be linked to hereditary cancer syndrome: for women, the risks of ovarian cancer for breast cancer survivors and uterus cancers for colorectal cancer survivors, and for men, the risk of pancreas cancer for kidney cancer survivors. CONCLUSIONS: The varying risk for SPCs by age, sex, and FPC types in cancer survivors implies the necessity for tailored prevention and screening programs targeting cancer survivors. Lifestyle modifications, such as smoking cessation, are essential to reduce the risk of SPCs in cancer survivors. In addition, genetic testing, along with proactive cancer screening and prevention strategies, should be implemented for young cancer survivors because of their elevated risk of developing SPCs.

Glomerulonephritis following COVID-19 infection or vaccination: a multicenter study in South Korea.

BACKGROUND: Despite the widespread impact of the severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019, COVID-19) and vaccination in South Korea, our understanding of kidney diseases following these events remains limited. We aimed to address this gap by investigating the characteristics of glomerular diseases following the COVID-19 infection and vaccination in South Korea. METHODS: Data from multiple centers were used to identify de novo glomerulonephritis (GN) cases with suspected onset following COVID-19 infection or vaccination. Retrospective surveys were used to determine the COVID-19-related histories of patients who were initially not implicated. Bayesian structural time series and autoregressive integrated moving average models were used to determine causality. RESULTS: Glomerular diseases occurred shortly after the infection or vaccination. The most prevalent postinfection GN was podocytopathy (42.9%), comprising primary focal segmental glomerulosclerosis and minimal change disease, whereas postvaccination GN mainly included immunoglobulin A nephropathy (IgAN; 57.9%) and Henoch-Schönlein purpura nephritis (HSP; 15.8%). No patient progressed to end-stage kidney disease. Among the patients who were initially not implicated, nine patients with IgAN/HSP were recently vaccinated against COVID-19. The proportion of glomerular diseases changed during the pandemic in South Korea, with an increase in acute interstitial nephritis and a decrease in pauci-immune crescentic GN. CONCLUSION: This study showed the characteristics of GNs following COVID-19 infection or vaccination in South Korea. Understanding these associations is crucial for developing effective patient management and vaccination strategies. Further investigation is required to fully comprehend COVID-19's impact on GN.

Harmful effect of repetitive intravenous iodinated contrast media administration on the long-term renal function of patients with early gastric cancer.

This retrospective study investigated whether repetitive exposure to intravenous iodinated contrast media (ICM) affects long-term renal function in patients who undergo curative surgery for early gastric cancer (EGC) collected from the Korean Health Insurance and Review Assessment (HIRA) database. Patients diagnosed with gastric cancer between January 2010 and December 2013 underwent regular computed tomography (CT) scans to monitor for extragastric recurrence. Patients who already had chronic kidney disease (CKD) before cancer diagnosis or had undergone chemotherapy or repeated surgery were excluded. A nested case-control study design was chosen to analyze the effect of repetitive ICM exposure to long-term renal function by comparing patients who developed CKD 2 years after cancer diagnosis and patients who did not. Among 59,971 patients collected according to inclusion and exclusion criteria, 1021 were diagnosed with CKD 2 years after cancer diagnosis. Using 1:5 matching after adjusting for age, sex and date of cancer diagnosis, 5097 control patients were matched to 1021 CKD patients. Conditional logistic regression showed that the number of CTs taken using ICM slightly increased the odds of CKD (odds ratio, 1.080; 95% confidence interval (CI): 1.059, 1.100; P < 0.0001). Thus, the administration of ICM might contribute to chronic renal function impairment.

Risk of depression and anxiety disorders according to long-term glycemic variability.

BACKGROUND: Poor glycemic control has been linked to psychiatric symptoms. However, studies investigating the relationship between glycemic variability (GV) and depression and anxiety disorders are limited. We investigated the association of GV with depression and anxiety disorders. In addition, the relationship between trends in fasting plasma glucose (FPG) levels and these disorders were explored. METHODS: We analyzed the National Health Insurance Service-National Sample Cohort database (2002-2013) with 151,814 participants who had at least three health screenings between 2002 and 2010. Visit-to-visit FPG variability was measured as variability independent of the mean (VIM). Depression and anxiety disorders were diagnosed using ICD-10 codes (F41 for anxiety and F32 or F33 for depression) after index date. We analyzed the association between GV and incidences of these disorders using Kaplan-Meier and Cox proportional hazards methods. Trajectory analysis was conducted to explore the relationship between FPG trends and these disorders. RESULTS: During follow-up, 7166 and 14,149 patients were newly diagnosed with depression and anxiety disorders, respectively. The highest quartile group of FPG-VIM had a greater incidence of depression and anxiety than the lowest quartile group, with adjusted hazard ratios of 1.09 (95 % confidence interval [CI]: 1.02-1.17) and 1.08 (95 % CI: 1.03-1.14). Group with persistent hyperglycemia, identified through trajectory clustering of FPG levels, had a 1.43-fold increased risk of depression compared to those with consistently low FPG levels. LIMITATIONS: Potential selection bias by including participants with at least three health screenings. CONCLUSIONS: High GV and persistent hyperglycemia are associated with increased incidence of depression and anxiety disorders.

Haplotype diversity of Heterodera koreana (Tylenchida: Heteroderidae), affecting bamboo in Korea.

In a survey of plant-parasitic nematodes in agricultural fields, cyst-forming nematodes were found in soil planted bamboo in Korea. The aim of this study was to identify the cyst nematodes based on morphological and molecular characteristics. As the results, the morphology and morphometrics of cysts and second-stage juveniles (J2s) were consistent with those of previous descriptions of Heterodera koreana. In phylogenetic analyses based on DNA sequences, these cyst nematodes were clustered together with clade of H. koreana in internal transcribed spacer (ITS) region, and large subunit D2-D3 segments (LSU D2-D3). These nematodes were clustered together with clade of H. koreana in cytochrome c oxidase subunit I (COI) gene, but a haplotype was different when compared with previous reported haplotypes (haplotype A-C) in Japan. This study showed these cyst nematodes were identified as H. koreana, and a new haplotype of H. koreana is distributed in Korea. We suggest that the new haplotype of H. koreana name as haplotype D.

Outcomes in Patients with Pulmonary Arterial Hypertension Underwent Transcatheter Closure of an Atrial Septal Defect.

Pulmonary arterial hypertension (PAH) related to an atrial septal defect (ASD) poses a challenge to transcatheter closure of an ASD (tcASD). We aimed to determine the predictors for remaining PAH (rPAH) post-tcASD. This retrospective study was conducted at a single tertiary university hospital. Adult patients with an ASD and PAH were divided into three groups according to pulmonary vascular resistance (PVR). Normalization of pulmonary atrial systolic pressure (PASP) was defined as an estimated right ventricular systolic pressure < 40 mmHg and was determined using transthoracic echocardiography. Among 119 patients, 80% showed PAH normalization post-tcASD. Normalization of PAH post-tcASD was observed in 100%, 56.2%, and 28.6% of patients in mild, moderate, and severe PVR groups, respectively. The patients' New York Heart Association functional class improved. Multivariate logistic regression analysis showed that age and high PVR were significant risk factors for rPAH. A receiving operator curve analysis showed a PASP cutoff value > 67.5 mmHg to be predictive of rPAH post-tcASD, with an area under the curve value of 0.944 (sensitivity, 0.922; specificity 0.933). Most patients, including moderate-to-severe PAH patients, improved hemodynamically and clinically with tcASD. Since patients with severe PAH are at a risk of rPAH, tcASD should be performed by selecting the patient carefully based on pre-procedure medication, a vasoreactivity test, and a balloon occlusion test.

Restless leg syndrome and risk of all-cause dementia: a nationwide retrospective cohort study.

BACKGROUND: Restless leg syndrome (RLS) is associated with poor sleep quality, depression or anxiety, poor dietary patterns, microvasculopathy, and hypoxia, all of which are known risk factors for dementia. However, the relationship between RLS and incident dementia remains unclear. This retrospective cohort study aimed to explore the possibility that RLS could be deemed as a non-cognitive prodromal feature of dementia. METHODS: This was a retrospective cohort study using the Korean National Health Insurance Service-Elderly Cohort (aged ≥ 60). The subjects were observed for 12 years, from 2002 to 2013. Identifying patients with RLS and dementia was based on the 10th revised code of the International Classification of Diseases (ICD-10). We compared the risk of all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VaD) in 2501 subjects with newly diagnosed RLS and 9977 matched controls based on age, sex, and index date. The association between RLS and the risk of dementia was assessed using Cox regression hazard regression models. The effect of dopamine agonists on the risk of dementia among RLS patients was also explored. RESULTS: The baseline mean age was 73.4, and the subjects were predominantly females (63.4%). The incidence of all-cause dementia was higher in the RLS group than that in the control group (10.4% vs 6.2%). A baseline diagnosis of RLS was associated with an increased risk of incident all-cause dementia (adjusted hazard ratio [aHR] 1.46, 95% confidence interval [CI] 1.24-1.72). The risk of developing VaD (aHR 1.81, 95% CI 1.30-2.53) was higher than that of AD (aHR 1.38, 95% CI 1.11-1.72). The use of dopamine agonists was not associated with the risk of subsequent dementia among patients with RLS (aHR 1.00, 95% CI 0.76-1.32). CONCLUSIONS: This retrospective cohort study suggests that RLS is associated with an increased risk of incident all-cause dementia in older adults, providing some evidence that requires confirmation through prospective studies in the future. Awareness of cognitive decline in patients with RLS may have clinical implications for the early detection of dementia.

Risk of cancer, tuberculosis and serious infections in patients with ankylosing spondylitis, psoriatic arthritis and psoriasis treated with IL-17 and TNF-α inhibitors: a nationwide nested case-control analysis.

OBJECTIVES: Targeting interleukin (IL)-17 and tumour necrosis factor (TNF)-α is recommended for the management of severe/refractory ankylosing spondylitis (AS), psoriatic arthritis (PsA), and psoriasis (PsO); however, safety data comparing these agents, especially in a large Asian population are unavailable. METHODS: Patients with AS, PsA and PsO were searched using the Health Insurance Review and Assessment Service database, defined according to the International Classification of Diseases-10 and unique insurance codes for rare diseases. By including patients newly diagnosed with AS, PsA, and PsO between 2010-2020, the outcomes of cancer, tuberculosis (TB) and serious infections following IL-17 and TNF-α inhibitor usage were evaluated. To investigate the association between treatments and outcomes, nested case-control analyses matching patients to controls (maximum of 1:10 ratio) according to index age, sex, index year, and follow-up duration were performed. RESULTS: Among 40322, 4953, and 5347 patients with AS, PsA, and PsO, respectively, three different datasets were generated to evaluate incidence of outcomes. Conditional logistic regression analysis revealed that cyclosporine use (odds ratio [OR] 2.286, p=0.0176) increased cancer, and a higher Charlson Comorbidity Index (CCI) score (OR 1.085, p=0.0406) and IL-17 inhibitor use only (OR 0.126, p=0.0457) showed a positive and negative association with TB, respectively. Serious infections increased in patients with high CCI scores (OR 1.117, p<0.0001), cyclosporine users (OR 1.445, p=0.0098), and medical-aided individuals (OR 1.667, p<0.0001). CONCLUSIONS: In this nationwide cohort of IL-17 and TNF-α inhibitor users, both treatments conferred comparable risk of cancer and serious infections, while IL-17 inhibitors may be advantageous for TB.

Machine-Learning Model for the Prediction of Hypoxaemia during Endoscopic Retrograde Cholangiopancreatography under Monitored Anaesthesia Care.

PURPOSE: Hypoxaemia is a significant adverse event during endoscopic retrograde cholangiopancreatography (ERCP) under monitored anaesthesia care (MAC); however, no model has been developed to predict hypoxaemia. We aimed to develop and compare logistic regression (LR) and machine learning (ML) models to predict hypoxaemia during ERCP under MAC. MATERIALS AND METHODS: We collected patient data from our institutional ERCP database. The study population was randomly divided into training and test sets (7:3). Models were fit to training data and evaluated on unseen test data. The training set was further split into k-fold (k=5) for tuning hyperparameters, such as feature selection and early stopping. Models were trained over k loops; the i-th fold was set aside as a validation set in the i-th loop. Model performance was measured using area under the curve (AUC). RESULTS: We identified 6114 cases of ERCP under MAC, with a total hypoxaemia rate of 5.9%. The LR model was established by combining eight variables and had a test AUC of 0.693. The ML and LR models were evaluated on 30 independent data splits. The average test AUC for LR was 0.7230, which improved to 0.7336 by adding eight more variables with an l1 regularisation-based selection technique and ensembling the LRs and gradient boosting algorithm (GBM). The high-risk group was discriminated using the GBM ensemble model, with a sensitivity and specificity of 63.6% and 72.2%, respectively. CONCLUSION: We established GBM ensemble model and LR model for risk prediction, which demonstrated good potential for preventing hypoxaemia during ERCP under MAC.

Pharmacokinetic and Pharmacodynamic Modeling and Simulation Analysis of Prasugrel in Healthy Male Volunteers.

This study evaluated the pharmacokinetics and pharmacodynamics of the antiplatelet agent prasugrel, and explored its optimal dose regimens via modeling and simulation using NONMEM. We measured platelet aggregation and the serial plasma concentrations of the inactive (R-95913) and active metabolites (R-138727) of prasugrel after a single oral dose of 10-60 mg in 20 healthy adult male volunteers. A pharmacokinetic model for R-95913 and R-138727, and a pharmacodynamic model between the concentration of R-138727 and maximal platelet aggregation measured by light transmittance were constructed. The predictability of the model for platelet aggregation was evaluated by comparing the model prediction values with the observed ones not used in the construction of the model. Pharmacokinetic data were best described by a 3-compartment models for R-95913, a 1-compartment model for R-138727 with transit compartment model for absorption delay, and first-pass metabolic conversion of R-95913 into R-138727 during absorption. The association-dissociation model between R-138727 and its receptor in platelets was applied for the inhibitory effect of prasugrel on platelet aggregation. Prasugrel rapidly inhibited platelet aggregation after oral administration, with a prolonged duration of action; however, the concentration of the active metabolite decreased rapidly, which may have been due to the slow dissociation rate of R-138727 from its target receptor in platelets. The external validation suggests that our model could be used to individualize prasugrel treatment in various clinical situations. Simulation showed rapid onset of inhibitory effect with great magnitude and consistent inhibition after therapeutic dose of prasugrel.

Risk of Dental Discoloration and Enamel Dysplasia in Children Exposed to Tetracycline and Its Derivatives.

PURPOSE: To examine the risk of dental abnormalities after exposure to tetracycline and its derivatives (TCs) in Korean children. MATERIALS AND METHODS: Children aged 0-17 years with a claim for prescriptions of TCs between 2002 and 2015 were identified from the Sample Research Database 2.0 of the National Health Insurance Service. Children not exposed to TCs were selected as the control group by matching sex and age (1:4). Cumulative incidence rate and relative risk of dental abnormalities after TCs exposure were investigated. RESULTS: The 10-year cumulative incidence rate in the 0-12 years group was 3.1% [95% confidence interval (CI), 2.3-3.9]. The 10-year cumulative incidence rates were 7.0%, 1.9%, and 1.6% in the 0-7, 8-12, and 13-17 years age groups (95% CI: 4.7-9.3, 1.2-2.6, and 1.3-1.9, respectively). There was no significant difference in the risk of dental abnormalities according to TC exposure among the age groups of 0-7 years [adjusted hazard ratio (aHR)=1.0], 8-12 years (aHR=1.1), and 13-17 years (aHR=1.2). CONCLUSION: Short-term exposure to TCs does not appear to increase the risk of dental abnormalities in children aged 0-7 and 0-12 years. Restrictions on the use of TCs in children aged 8-12 years, in some countries, may warrant consideration.

Periodontal disease and cancer risk: A nationwide population-based cohort study.

Background: Although emerging evidence suggests that periodontitis might increase the risk of cancer, comorbidity and lifestyle behaviors, such as smoking and body mass index (BMI), may have confounded this reported association. This study aimed to investigate whether chronic periodontitis is associated with cancer risk using a large, nationwide database. Methods: We conducted a population-based, retrospective cohort study using data from the Korean National Health Insurance Cohort Database obtained between January 2003 and December 2015. We included 713,201 individuals without a history of cancer who were followed up to 10 years. Confounding factors included demographic factors (age, sex, income, and residential area), lifestyle behaviors (smoking history and BMI), and comorbidities, such as hypertension, diabetes, heart failure, and pulmonary disease, using the Charlson Comorbidity Index. Multivariable Cox regression analysis was applied to estimate the adjusted hazard ratio (aHR) for cancer risk. Results: Of the 713,201 participants, 53,075 had periodontitis and were placed in the periodontitis group; the remaining 660,126 individuals were included as the control group. Overall, the cumulative incidence of cancer in the periodontitis group was 2.2 times higher than that in the control group. The periodontitis group had an increased risk of total cancer compared to the control group after adjusting for age, sex, comorbidities, BMI, and smoking history (aHR, 1.129; 95% confidence interval [CI], 1.089-1.171; P<0.0001). When examining specific cancer types, significant associations were also observed between periodontitis and stomach cancer (aHR, 1.136; 95% CI, 1.042-1.239; P=0.0037), colon cancer (aHR, 1.129; 95% CI, 1.029-1.239; P=0.0105), lung cancer (aHR, 1.127; 95% CI, 1.008-1.260; P=0.0353), bladder cancer (aHR, 1.307; 95% CI, 1.071-1.595; P=0.0085), thyroid cancer (aHR, 1.191; 95% CI, 1.085-1.308; P=0.0002), and leukemia (aHR, 1.394; 95% CI, 1.039-1.872; P=0.0270). There was no significant association between the development of secondary malignancy and periodontitis in cancer survivors who were alive 5 years after they were diagnosed with the primary malignancy. Conclusions: Periodontal disease, including periodontitis, was associated with increased risk of cancer, which persisted after controlling for confounding factors. Further prospective research is warranted to establish a causal relationship.

Crystal-clear days and unclear days in migraine: A population-based study.

OBJECTIVE: To investigate crystal-clear days and unclear days in participants with migraine. BACKGROUND: Migraine affects individuals during the headache-free period. Therefore, headache-free days do not indicate migraine symptom-free days. Crystal-clear days can be characterized by days without headache and having minimal or no migraine symptoms. In contrast, days without headache, but with more than minimal migraine symptoms, can be defined as unclear days. METHODS: We used the baseline respondent data set of the Circannual Change in Headache and Sleep study, a nationwide population survey on headache and sleep. This study was a cross-sectional and case-control analysis of longitudinally collected data. The number of crystal-clear days per 30 days was assessed by asking "How many days have you had crystal-clear days without headache during the previous 30 days?". We defined headache-free, but not crystal-clear days, as unclear days. The number of unclear days per 30 days was calculated as follows: 30 - the number of headache days per 30 days - the number of crystal-clear days per 30 days. RESULTS: Of 170 participants with migraine, 165 (97.1%) had unclear days. The numbers of crystal-clear days (median [interquartile range] 20.0 [15.0-25.0] vs. 25.0 [20.0-29.0], p < 0.001) and unclears days (4.0 [0.0-8.0] vs. 1.0 [0.0-7.0], p < 0.001) per 30 days in participants with migraine were significantly lower and higher, respectively, than in those with non-migraine headache. Headache days (incident rate ratio and 95% confidence interval, 0.94 [0.90-0.97], p < 0.001) and weekly average sleep duration (0.95 [0.91-1.00], p = 0.035) were significant factors for crystal-clear days. CONCLUSIONS: The number of crystal-clear days were different from that of headache-free days. Almost all participants with migraine had unclear days. Our findings will facilitate understanding the symptoms and burden of migraine.

Comparison of developing tuberculosis following tumor necrosis factor inhibition and interleukin-6 inhibition in patients with rheumatoid arthritis: a nationwide observational study in South Korea, 2013-2018.

BACKGROUND: Tumor necrosis factor (TNF) inhibitors increase the risk of tuberculosis (TB) in patients with rheumatoid arthritis (RA). This study compared the incidence of TB after treatment with TNF inhibitors and tocilizumab in patients with RA, separately in those who were treated for latent tuberculosis infection (LTBI) and those without evidence of LTBI. METHODS: This study included patients with RA who initiated TNF inhibitors and tocilizumab between December 2013 and August 2018. Patient data were collected from the nationwide database of the Health Insurance Review and Assessment service in South Korea. The incidence of TB was compared among different biologic drugs in patients with or without LTBI treatment. RESULTS: Of 4736 patients, 1168 were treated for LTBI and 48 developed TB (554.9 per 100,000 person-years). When compared based on etanercept, infliximab showed a higher risk of TB (adjusted incidence rate ratio 2.71, 95% confidence interval 1.05-7.01), especially in patients without evidence of LTBI. Other TNF inhibitors and tocilizumab showed a comparable incidence of TB, regardless of treatment for LTBI. There was no significant difference in TB incidence after biologic therapy between patients with and without LTBI treatment (627.9/100,000 vs. 529.5/100,000 person-years). In patients treated for LTBI, no differential risk of TB was observed among biologic drugs. CONCLUSIONS: The incidence of TB was not significantly different among biologic drugs in the current era, except for infliximab in patients who were not treated for LTBI. Treatment of LTBI might alleviate the drug-specific risk of TB in patients with RA.

Osteonecrosis in Korean Paediatric and Young Adults with Acute Lymphoblastic Leukaemia or Lymphoblastic Lymphoma: A Nationwide Epidemiological Study.

Osteonecrosis (ON) is a serious complication of acute lymphocytic leukaemia (ALL) or lymphoblastic lymphoma (LBL) treatment, and there is little information regarding ON in Korean paediatric and young adult patients. This retrospective cohort study assessed the cumulative incidence of and risk factors for ON using national health insurance claims data from 2008 to 2019 in 4861 ALL/LBL patients. The Kaplan-Meier method was used to estimate the cumulative incidence of ON according to age groups; the Cox proportional hazard regression model was used to identify risk factors related to ON development after diagnosing ALL/LBL. A cause-specific hazard model with time-varying covariates was used to assess the effects of risk factors. Overall, 158 (3.25%) patients were diagnosed with ON, among whom 23 underwent orthopaedic surgeries. Older age, radiotherapy (HR = 2.62, 95% confidence interval (CI) 1.87-3.66), HSCT (HR = 2.40, 95% CI 1.74-3.31), steroid use and anthracycline use (HR = 2.76, CI 1.85-4.14) were related to ON in the univariate analysis. In the multivariate analysis, age and steroid and asparaginase use (HR = 1.99, CI 1.30-3.06) were factors associated with ON. These results suggest that Korean patients with ALL/LBL who used steroids and asparaginase should be closely monitored during follow-up, even among young adult patients.

US, Mammography, and Histopathologic Evaluation to Identify Low Nuclear Grade Ductal Carcinoma in Situ.

Background Low nuclear grade ductal carcinoma in situ (DCIS) identified at biopsy can be upgraded to intermediate to high nuclear grade DCIS at surgery. Methods that confirm low nuclear grade are needed to consider nonsurgical approaches for these patients. Purpose To develop a preoperative model to identify low nuclear grade DCIS and to evaluate factors associated with low nuclear grade DCIS at biopsy that was not upgraded to intermediate to high nuclear grade DCIS at surgery. Materials and Methods In this retrospective study, 470 women (median age, 50 years; interquartile range, 44-58 years) with 477 pure DCIS lesions at surgical histopathologic evaluation were included (January 2010 to December 2015). Patients were divided into the training set (n = 330) or validation set (n = 147) to develop a preoperative model to identify low nuclear grade DCIS. Features at US (mass, nonmass) and at mammography (morphologic characteristics, distribution of microcalcification) were reviewed. The upgrade rate of low nuclear grade DCIS was calculated, and multivariable regression was used to evaluate factors for associations with low nuclear grade DCIS that was not upgraded later. Results A preoperative model that included lesions manifesting as a mass at US without microcalcification and no comedonecrosis at biopsy was used to identify low nuclear grade DCIS, with a high area under the receiver operating characteristic curve of 0.97 (95% CI: 0.94, 1.00) in the validation set. The upgrade rate of low nuclear grade DCIS at biopsy was 38.8% (50 of 129). Ki-67 positivity (odds ratio, 0.04; 95% CI: 0.0003, 0.43; P = .005) was inversely associated with constant low nuclear grade DCIS. Conclusion The upgrade rate of low nuclear grade ductal carcinoma in situ (DCIS) at biopsy to intermediate to high nuclear grade DCIS at surgery occurred in more than a third of patients; low nuclear grade DCIS at final histopathologic evaluation could be identified if the mass was viewed at US without microcalcifications and had no comedonecrosis at histopathologic evaluation of biopsy. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Rahbar in this issue. An earlier incorrect version appeared online. This article was corrected on April 14, 2022.

Coexisting and Second Primary Cancers in Patients with Uveal Melanoma: A 10-Year Nationwide Database Analysis.

Uveal melanoma is the most common intraocular tumor in adults. Metastatic disease occurs in about 30% of patients, for which there is currently no effective treatment. More than half of patients are long-term survivors, and it is well established that cancer survivors are prone to developing second primary cancers. In this study, we analyzed 10 years' worth of data from the nationwide database to determine the rates of coexisting malignancies and second primary cancers associated with uveal melanoma. The mean annual incidence of uveal melanoma was 1.1 per million. Approximately 43% of patients had coexisting cancers. The most common coexisting cancer was lung cancer (10%) followed by liver cancer (6%) and non-Hodgkin lymphoma (6%). In patients whose first cancer in their lifetime was uveal melanoma, the 10-year cumulative incidence of second primary cancers was 22% (95% confidence interval, 9-31%). The age- and sex-adjusted standard incidence rates was 3.61 (95% confidence interval, 2.61-4.86). The most common second primary cancers were lung cancer and hepatocellular carcinoma, followed by prostate, thyroid, pancreatic, and ovarian cancers. Age was the only factor associated with second primary cancer development. Our findings will be helpful in providing counseling for cancer screening in uveal melanoma patients.

A nationwide nested case-control study of new-onset obsessive-compulsive disorder following antipsychotics use in schizophrenia.

OBJECTIVE: A substantial proportion of patients with schizophrenia suffer from comorbid obsessive-compulsive disorder (OCD) possibly associated with antipsychotics. However, little is known about the comparative risks of the antipsychotics. The present study aimed to investigate the risk of new-onset OCD following the initiation of different antipsychotic medications for schizophrenia relative to haloperidol. METHODS: Using the Korean national claims data, patients aged 15-60 years newly diagnosed with schizophrenia between 2010 and 2018 were identified. Of the 47,808 patients with schizophrenia treated with nine commonly prescribed antipsychotics, 775 new-onset OCD patients were matched to 3,100 patients without OCD using nested case-control design with 1:4 case-control matching based on the sex, age of index date, date of schizophrenia diagnosis, observation period, locations of medical institutions, and level of medical facilities. Using multivariable conditional logistic regression analysis, odd ratios (ORs) for new-onset OCD comparing each antipsychotic agent relative to haloperidol were computed. RESULTS: The risk for new-onset OCD during treatment with clozapine was significantly higher than that with haloperidol (adjusted OR 2.86; 95% confidence interval [1.63-5.03]). The risks for new-onset OCD with other antipsychotics were not significantly different from that with haloperidol. In subgroup analysis, the early and intermediate, but not late-onset schizophrenia group showed significant risk for OCD associated with clozapine use. CONCLUSION: The present findings, based on real-world national representative data, provide reliable evidence for the risk of new-onset OCD in patients with schizophrenia receiving clozapine at a population level.