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.

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.

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.

Markedly increased risk of malignancies in women with endometriosis.

OBJECTIVE: To assess the cancer risk in a cohort of women with newly diagnosed endometriosis. METHODS: This retrospective, nationwide, population-based cohort study utilized data from the 10-year claims database of the Korean National Health Insurance from January 2008 to December 2018. Patients diagnosed with endometriosis between 2010 and 2013 were included; those who underwent appendectomy but were not diagnosed with endometriosis during the study period served as controls. No participant was diagnosed with cancer before enrollment. Cancer diagnoses according to the International Classification of Diseases, 10th revision, were compared between the two groups. Cancer occurrence in both groups was identified according to the diagnostic codes for different organ sites. RESULTS: Altogether, 179,865 patients with endometriosis and 87,408 controls were analyzed, and the incidence rates of cancer were 644.3 and 543.8 per 100,000 person-years, respectively. Patients with endometriosis had a significantly increased overall cancer risk (hazard ratio [HR], 1.34; 95% confidence interval [CI], 1.28-1.40; p < 0.001) than controls after adjusting for age, insurance type, and comorbidities. They had significantly increased uterine (HR, 4.59; 95% CI, 3.56-5.91; p < 0.001), ovarian (HR, 2.51; 95% CI, 1.99-3.16; p < 0.001), cervical (HR, 1.84; 95% CI, 1.49-2.28; p < 0.001), breast (HR, 1.44; 95% CI, 1.31-1.58; p < 0.001), and thyroid cancer (HR, 1.34; 95% CI, 1.24-1.45; p < 0.001) risk. Median age at diagnosis was <50 years for all cancer types. CONCLUSIONS: Endometriosis was associated with an increased cancer risk, specifically uterine, ovarian, cervical, breast, and thyroid cancers, suggesting that effective cancer screening for early detection of malignancies in women should be implemented in those with endometriosis.

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.

Invasive dental procedures as risk factors for postoperative spinal infection and the effect of antibiotic prophylaxis.

AIM: To identify invasive dental procedures as a risk factor for postoperative spinal infection (PSI) and evaluate the effectiveness of antibiotic prophylaxis. MATERIALS AND METHODS: We analysed 229,335 patients who underwent spinal surgery with instrumentation from 2010 to 2017, using the nationwide database. The incidence of spinal infection 2 years after surgery was determined. Invasive dental procedures as a risk factor for PSI and the effects of antibiotic prophylaxis during this period were also analysed. RESULTS: A total of 15,346 patients (6.69%) were diagnosed with PSI. It was found that advanced age, male sex, and a high Charlson Comorbidity Index were risk factors for PSI. The risk of PSI did not increase following dental procedures (adjusted hazard ratio [HR] 0.850; 95% confidence interval [CI], 0.793-0.912) and was not affected by antibiotics (adjusted HR 1.097; 95% CI, 0.987-1.218). Patients who received dental treatment as early as 3 months after spinal surgery had the lowest risk of postoperative infection (adjusted HR 0.869; 95% CI, 0.795-0.950). CONCLUSIONS: Invasive dental procedure does not increase the risk of PSI, and antibiotic prophylaxis before dental procedure was not effective in preventing spinal infection.

Revised Korean Antiviral Guideline Reduces the Hepatitis B-related Hepatocellular Carcinoma Risk in Cirrhotic Patients.

BACKGROUND: Since September 2015, the initiation of antiviral therapy (AVT) for patients with chronic hepatitis B (CHB)-related cirrhosis has been reimbursed according to the revised Korean Association for the Study of Liver (KASL) guideline, if the patient had hepatitis B virus DNA level ≥ 2,000 IU/L, regardless of aminotransferase or alanine aminotransferase levels. This study investigated whether the KASL guideline implementation reduced the risk of CHB-related hepatocellular carcinoma (HCC) in patients with cirrhosis in South Korea. METHODS: A total of 429 patients with CHB-related cirrhosis who initiated AVT between 2014 and 2016 were recruited. The risk of HCC development was compared between patients who initiated AVT before and after September 2015 (pre-guideline [n = 196, 45.7%] vs. post-guideline implementation [n = 233, 54.3%]). RESULTS: Univariate analysis showed that AVT initiation before guideline implementation, older age, male gender, and diabetes significantly predicted increased risk of HCC development (all P < 0.05). Subsequent multivariate analysis showed that AVT initiation before guideline implementation (HR = 1.941), older age (HR = 5.762), male gender (HR = 2.555), and diabetes (HR = 1.568) independently predicted increased risk of HCC development (all P < 0.05). Additionally, multivariate analysis showed that AVT initiation before guideline implementation (HR = 2.309), male gender (HR = 3.058), and lower platelet count (HR = 0.989) independently predicted mortality (P < 0.05). The cumulative incidences of HCC and mortality were significantly higher in patients who initiated AVT before guideline implementation than in those who initiated AVT after guideline implementation (all P < 0.05, log-rank test). CONCLUSION: The prognosis of patients with CHB-related cirrhosis who initiated AVT improved after guideline implementation according to the revised KASL guideline.

The Association of Calcium and Vitamin D Use With Implant Survival of Total Knee Arthroplasty: A Nationwide Population-Based Cohort Study.

BACKGROUND: Calcium and vitamin D have been regarded as beneficial nutrients for bone metabolism that may affect survival of arthroplasties. However, the relationship between their use and revision rate of knee arthroplasty has not been evaluated. Thus, we investigated an association between calcium and vitamin D use and the revision rate after primary total knee arthroplasty. METHODS: A nationwide population-based cohort study was conducted using the Korean National Health Insurance database. We included patients diagnosed with knee osteoarthritis and underwent primary total knee arthroplasty between 2009 and 2018. Risk for arthroplasty revision was estimated using a Cox proportional hazards model with time-dependent covariates. Log-rank test was used to assess survival of knee arthroplasty. RESULTS: Out of 142,147 subjects, 28,403 were calcium and vitamin D users and 113,744 were never users. Calcium and vitamin D significantly reduced the revision risk with a 6-month drug use lag period (adjusted hazard ratio [aHR] 0.56, 95% confidence interval [CI] 0.45-0.70). Calcium and vitamin D combination use for more than 1 year was associated with reduced revision risks in both patients with periprosthetic joint infection (aHR 0.63, 95% CI 0.42-0.95) and patients without infection (aHR 0.70, 95% CI 0.54-0.91). Implant survival was significantly improved in calcium and vitamin D combination users for more than 1 year compared with never users (log-rank P < .001). CONCLUSION: Combination use of calcium and vitamin D with a dose of 800 IU or greater for more than 1 year was associated with the greatest reduction in the risks for revision surgery after total knee arthroplasty.

Validation of the CAMD Score in Patients With Chronic Hepatitis B Virus Infection Receiving Antiviral Therapy.

BACKGROUND & AIMS: Researchers previously developed a scoring system to determine the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus (HBV) infection, based on the presence of cirrhosis, patient age, male sex, and diabetes (called the CAMD scoring system). We validated the CAMD scoring system and compared its performance with that of other risk assessment models in an independent cohort. METHODS: We followed up 3277 patients with chronic HBV infection (mean age, 48.7 y; 62.6% male; 32.4% with cirrhosis) who were treated with entecavir (n = 1725) or tenofovir (n = 1552) as the first-line antiviral agent in 4 academic teaching hospitals in the Republic of Korea. The primary outcome was development of HCC. We evaluated the ability of the CAMD, PAGE-B, and mPAGE-B scoring systems to identify patients who would develop HCC using integrated area under the curve (iAUC) analysis. RESULTS: Over a median follow-up period of 58.2 months, 8.9% of the patients developed HCC. Patients who developed HCC were older, more likely to be male, and had higher proportions of cirrhosis and diabetes than patients who did not develop HCC (all P < .05). CAMD scores identified patients who developed HCC with an iAUC of 0.790, mPAGE-B scores with an iAUC of 0.769, and PAGE-B scores with an iAUC of 0.760. The 5-year cumulative risks of HCC were 1.3% in patients with low CAMD scores (<8), 8.0% in patients with intermediate CAMD scores (8-13), and 24.3% in patients with high CAMD scores (>13) (P < .001 for comparison of low- vs intermediate-score groups and between intermediate- vs high-score groups). The predicted and observed probabilities of HCC had excellent agreement. CONCLUSIONS: We validated the CAMD scoring system in determining the risk of HCC in patients with chronic HBV treatment receiving entecavir or tenofovir treatment. Validation was performed in a cohort of patients in the Republic of Korea, where most patients have genotype C2 HBV infection.

Pre-screening of patient-reported symptoms using the Edmonton Symptom Assessment System in outpatient palliative cancer care.

OBJECTIVES: Although early palliative care is associated with a better quality of life and improved outcomes in end-of-life cancer care, the criteria of palliative care referral are still elusive. METHODS: We collected patient-reported symptoms using the Edmonton Symptom Assessment System (ESAS) at the baseline, first and second follow-up visits. A total of 71 patients were evaluable, with a median age of 65 years, male (62%) and Eastern Cooperative Oncology Group (ECOG) performance status distribution of 1/2/3 (28%/39%/33%) respectively. RESULTS: Twenty (28%) patients had moderate/severe symptom burden with the mean ESAS ≥ 5. Interestingly, most of the patients with moderate/severe symptom burdens (ESAS ≥ 5) had globally elevated symptom expression. While the mean ESAS score was maintained in patients with mild symptom burden (ESAS < 5; 2.7 at the baseline; 3.4 at the first follow-up; 3.0 at the second follow-up; p = .117), there was significant symptom improvement in patients with moderate/severe symptom burden (ESAS ≥ 5; 6.5 at the baseline; 4.5 at the first follow-up; 3.6 at the second follow-up; p < .001). CONCLUSIONS: In conclusion, advanced cancer patients with ESAS ≥ 5 may benefit from outpatient palliative cancer care. Pre-screening of patient-reported symptoms using ESAS can be useful for identifying unmet palliative care needs in advanced cancer patients.

Morphological and molecular characterizations of Heterodera oryzae in Korea.

Rice is one of the most important staple grains in Korea and the largest starch source in addition to its usefulness in the production of beverages. Under different areas and environments of production, various pests and diseases including soil-borne plant pathogens such as plant-parasitic nematodes can compromise rice productivity. In a survey to identify plant parasitic nematodes on rice, cyst nematodes were encountered in rice fields that required characterization and identification. Phylogenetic analysis of the LSU D2-D3 region and ITS region could not separate the studied species from Heterodera elachista. However, phylogenetic analysis of the COI gene of the mitochondrial DNA clearly separated H. elachista from the new species into two different clusters. Combining morphology and molecular diagnostics, the species was identified as Heterodera oryzae belonging to the 'Cyperi' group whose cysts are characterized by vulval cones that are ambifenestrate, underbridge present with bullae. Second-stage juveniles have three incisors in the lateral field with long tails and long hyaline region.

Hepatocellular Carcinoma versus Other Hepatic Malignancy in Cirrhosis: Performance of LI-RADS Version 2018.

Purpose To evaluate the diagnostic accuracy of the Liver Imaging Reporting and Data System (LI-RADS) version 2018 for differentiating between hepatocellular carcinoma (HCC) and other (hepatic) malignancy (OM) in patients with liver cirrhosis. Materials and Methods From 2008 to 2017, 55 patients with untreated OM and liver cirrhosis were eligible for this retrospective case-control study (mean age, 58 years ± 10 [standard deviation] [range, 32-79 years], with 45 men [mean age, 58 years ± 11] and 10 women [mean age, 62 years ± 7]). Control subjects consisted of 165 treatment-naive patients with HCC and liver cirrhosis (mean age, 58 years ± 10 [range, 29-80 years], with 134 men [mean age, 58 years ± 9] and 31 women [mean age, 59 years ± 11]). Two radiologists blinded to the final diagnosis independently determined the presence of LR-M features and major HCC features (non-rim arterial phase hyperenhancement, non-peripheral washout, and enhancing capsule). The diagnostic performances of each feature, the LR-M criteria (probably or definitely malignant, but not specific for HCC), and the LR-5 criteria (definitely HCC) were calculated and compared by using the generalized estimating equation method. Results Individual LR-M features had a sensitivity of 9%-71% and a specificity of 83%-97% for the diagnosis of OM. Major features of HCC had a sensitivity of 62%-83% and a specificity of 69%-89% for the diagnosis of HCC. The LR-M criteria had a sensitivity of 89% (95% confidence interval [CI]: 81%, 97%) for diagnosing OM, with a specificity of 48% (95% CI: 40%, 56%). The LR-5 criteria had a sensitivity of 74% (95% CI: 67%, 81%) for diagnosing HCC, with a specificity of 89% (95% CI: 81%, 97%). The accuracy of the LR-5 criteria was higher than that of the LR-M criteria (78% [95% CI: 72%, 83%] vs 58% [95% CI: 52%, 65%], P <. 001). Conclusion The LR-5 criteria as well as the LR-M criteria can effectively distinguish hepatocellular carcinoma from other hepatic malignancy in patients with liver cirrhosis. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Furlan in this issue.

Presepsin as a diagnostic marker of sepsis in children and adolescents: a systemic review and meta-analysis.

BACKGROUND: Early diagnosis of sepsis in pediatric patients is vital but remains a major challenge. Previous studies showed that presepsin is potentially a reliable diagnostic biomarker for sepsis in adult and neonates. However, there is no pooled analysis of its efficacy as a diagnostic biomarker for sepsis in children. The aims of the present meta-analysis were to assess the overall diagnostic accuracy of presepsin in pediatric sepsis and compare it to those for C-reactive protein (CRP) and procalcitonin (PCT). METHODS: A systematic literature search was performed in Medline/Pubmed, Embase, the Cochrane Library, and ISI Web of Science to identify relevant studies reporting the diagnostic accuracy of presepsin in patients with pediatric sepsis. Sensitivities and specificities were pooled by bivariate meta-analysis. Heterogeneity was evaluated by χ2 test. RESULTS: We identified 129 studies in total. Most were disqualified on the basis of their titles/abstracts and duplication. Four studies were included in the final analysis. They comprised 308 patients aged between 1 mo and 18 y. The pooled diagnostic sensitivity and specificity of presepsin were 0.94 (95% confidence interval [CI]: 0.74-0.99) and 0.71 (95% CI: 0.35-0.92), respectively. The pooled diagnostic odds ratio, positive likelihood ratio (LR), and negative LR of presepsin were 32.87 (95% CI: 2.12-510.09), 3.24 (95% CI, 1.14-12.38), and 0.08 (95% CI, 0.01-0.74), respectively. Heterogeneity was found in both sensitivity (χ2 = 11.17; P = 0.011) and specificity (χ2 = 65.78; P < 0.001). No threshold effect was identified among the studies (r = - 0.938). The pooled sensitivity of presepsin (0.94) was higher than that of CRP (0.51) and PCT (0.76), whereas the overall specificity of presepsin (0.71) was lower than that of CRP (0.81) and PCT (0.76). The AUC of presepsin (0.925) was higher than that of CRP (0.715) and PCT (0.820). CONCLUSION: Currently available evidence indicates that presepsin has higher sensitivity and diagnostic accuracy, but lower specificity, than PCT or CRP in detecting sepsis in children. However, these results must be carefully interpreted as the number of studies included was small and the studies were statistically heterogeneous.

Effectiveness of the polysaccharide hemostatic powder in non-variceal upper gastrointestinal bleeding: Using propensity score matching.

BACKGROUND AND AIM: Recently, the application of hemostatic powder to the bleeding site has been used to treat active upper gastrointestinal bleeding (UGIB). We aimed to assess the effectiveness of the polysaccharide hemostatic powder (PHP) in patients with non-variceal UGIB. METHODS: We reviewed prospectively collected 40 patients with UGIB treated with PHP therapy between April 2016 and January 2017 (PHP group) and 303 patients with UGIB treated with conventional therapy between April 2012 and October 2014 (conventional therapy group). We compared the rate of successful hemostasis and the rebleeding between the two groups after as well as before propensity score matching using the Glasgow-Blatchford score and Forrest classification. RESULTS: Thirty patients treated with the PHP and 60 patients treated with conventional therapy were included in the matched groups. Baseline patient characteristics including comorbidities, vital signs, and bleeding scores were similar in the matched groups. The rate of immediate hemostasis and 7-day and 30-day rebleeding were also similar in the two groups before and after matching. In the subgroup analysis, no significant differences in immediate hemostasis or rebleeding rate were noted between PHP in monotherapy and PHP combined with a conventional hemostatic method. At 30 days after the therapy, there were no significant PHP-related complications or mortality. CONCLUSIONS: Given its safety, the PHP proved feasible for endoscopic treatment of UGIB, having similar effectiveness as that of conventional therapy. The PHP may become a promising hemostatic method for non-variceal UGIB.

Comment on "Mode conversion of waves in the ion-cyclotron frequency range in magnetospheric plasmas".

A Comment on the Letter by Y. O. Kazakov and T. Fülöp, Phys. Rev. Lett. 111, 125002 (2013). The authors of the Letter offer a Reply.

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.

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.

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.