Biomarker role of thyroid irAE and PD-L1 positivity in predicting PD-1 blockade efficacy in patients with non-small cell lung cancer.

Thyroid immune-related adverse events (irAEs) are associated with programmed cell death protein 1 (PD-1) blockade efficacy in non-small cell lung cancer (NSCLC). However, their independence from PD-L1 expression and quantitative impact on predicting PD-1 blockade efficacy remain unexplored. This multicenter, retrospective, longitudinal study from Korea included 71 metastatic NSCLC patients who underwent PD-L1 expression and thyroid function testing during PD-1 blockade. Disease progression by the Response Evaluation Criteria for Solid Tumors was the main outcome. Three-stage analyses were performed: (1) multivariate Cox regression models adjusted for PD-L1 expression according to thyroid irAEs; (2) subgroup analyses; (3) regrouping and comparing predictivity of current and alternative staging. Patients with thyroid irAE + exhibited a longer progression-free survival [7/20 vs. 34/51, adjusted HR 0.19 (0.07-0.47); P < 0.001] than those with thyroid irAE-, independent of PD-L1 expression; the results remained across most subgroups without interaction. The three groups showed different adjusted HR for disease progression (Group 1: PD L1 + and thyroid irAE + ; Group 2: PD-L1 + or thyroid irAE + : 5.08 [1.48-17.34]; Group 3: PD-L1- and thyroid irAE- : 30.49 [6.60-140.78]). Alternative staging (Group 1 in stage IVB → stage IVA; Group 3 in stage IVA → stage IVB) improved the prognostic value (PVE: 21.7% vs. 6.44%; C-index: 0.706 vs. 0.617) compared with the 8th Tumor-Node-Metastasis staging. Our study suggests thyroid irAEs and PD-L1 expression are independent biomarkers that improve predicting PD-1 blockade efficacy in NSCLC. Thyroid irAEs would be helpful to identify NSCLC patients who benefit from PD-1 blockade in early course of treatment.

Effects of MAFLD defined by fatty liver index or ultrasonography on kidney function decline in the general population.

This study aimed to investigate whether metabolic dysfunction-associated fatty liver disease (MAFLD) defined by the fatty liver index (FLI) affects the decline in kidney function and whether this relationship is still observed in MAFLD defined by ultrasonography (USG). A retrospective cohort study was conducted using de-identified data from participants who received health checkups at Samsung Changwon Hospital between 2002 and 2018. The primary and secondary exposures were the presence of FLI- and USG-defined MAFLD, respectively. The primary outcome was 5-years slope of eGFR. The secondary outcome was a rapid decline in kidney function, defined as a 5-years slope of estimated glomerular filtration rate (eGFR) of less than - 3 mL/min/1.73 m2 per year. A total of 37,500 participants were included in the analysis. Participants with FLI-defined MAFLD had a larger decline in 5-year eGFR slope than those without FLI-defined MAFLD (beta coefficients - 0.11; 95% CI - 0.14 to - 0.08). Participants with FLI-defined MAFLD had a higher risk of rapid kidney function decline than those without FLI-defined MAFLD (odds ratio 1.33; 95% confidence intervals (CIs) 1.05-1.69). However, USG-defined MAFLD was less related to kidney function decline. In conclusion, the presence of FLI-defined MAFLD was associated with larger and faster kidney function decline.

Association of Lipoprotein(a) with Progression of Coronary Artery Calcification: Retrospective Longitudinal Study.

Background: Atherosclerotic cardiovascular disease (ASCVD) is a major health concern, and lipoprotein(a) (Lp(a)) is an independent risk factor. However, there is limited evidence regarding Lp(a) and the risk of ASCVD in Asian populations. This study aimed to assess the predictive value of changes in coronary artery calcification (CAC) for ASCVD risk associated with Lp(a) level. Methods: Participants (n=2,750) were grouped according to their Lp(a) levels, and the association between Lp(a) and CAC progression was examined. CAC progression was defined as the occurrence of incident CAC or a difference ≥2.5 between the square root (√) of baseline and follow-up coronary artery calcium scores (CACSs) (Δ√transformed CACS). To adjust for differences in follow-up periods, Δ√transformed CACS was divided by the follow- up period (in years). Results: Over an average follow-up of 3.07 years, 18.98% of participants experienced CAC progression. Those with disease progression had notably higher Lp(a) levels. Higher Lp(a) tertiles correlated with increased baseline and follow-up CACS, CAC progression (%), and Δ√transformed CACS. Even after adjustment, higher Lp(a) levels were associated with CAC progression. However, annualized Δ√transformed CACS analysis yielded no significant results. Conclusion: This study demonstrated an association between elevated Lp(a) levels and CAC progression in a general population without ASCVD. However, longer-term follow-up studies are needed to obtain meaningful results regarding CAC progression. Further research is necessary to utilize Lp(a) level as a predictor of cardiovascular disease and to establish clinically relevant thresholds specific to the Korean population.

Impact of an expanded reimbursement policy on utilization of implantable loop recorders in patients with cryptogenic stroke in Korea.

BACKGROUND/AIMS: The reimbursement policy for cryptogenic stroke (CS) was expanded in November 2018 from recurrent strokes to the first stroke episode. No reports have demonstrated whether this policy change has affected trends in implantable loop recorder (ILR) utilization. METHODS: We identified patients who received an ILR implant using the Korea Health Insurance Review and Assessment Service database between July 2016 and October 2021. Patients meeting all the following criteria were considered to have CS indication: 1) prior stroke history, 2) no previous history of atrial fibrillation or flutter (AF/AFL), and 3) no maintenance of oral anticoagulant for ≥4 weeks within a year before ILR implant. AF/AFL diagnosed within 3 years after ILR implant or before ILR removal was considered ILR-driven. RESULTS: Among 3,056 patients, 1,001 (32.8%) had CS indications. The total ILR implant number gradually increased for both CS and non-CS indications and the number of CS indication significantly increased after implementing the expanded reimbursement policy. The detection rate for AF/AFL was 26.3% in CS patients over 3 years, which was significantly higher in patients implanted with an ILR within 2 months after stroke than those implanted later. CONCLUSION: The expanded coverage policy for CS had a significant impact on the number of ILR implantation for CS indication. The diagnostic yield of ILR for AF/AFL detection seems better when ILR is implanted within 2 months than later. Further investigation is needed to demonstrate other clinical benefits and the optimal ILR implantation timing.

Geriatric Nutritional Risk Index as a Possible Predictor of Decline in Kidney Function in Older People.

BACKGROUND: The Geriatric Nutritional Risk Index (GNRI) is associated with morbidity and mortality in older individuals. Our study explored the relationship between GNRI, decline in kidney function, and all-cause mortality in older individuals. METHODS: This retrospective cohort study analyzed data from participants aged ≥60 years who underwent a general health checkup between 2002 and 2018. The primary exposure was the GNRI, divided into quartiles. The primary and secondary outcomes were a decline in kidney function assessed using the 5-year estimated glomerular filtration rate (eGFR) and all-cause mortality, respectively. RESULTS: The analysis included a total of 1,599 participants (median age, 63 years; interquartile range [IQR], 61-67; 54% males). The mean±standard deviation of GNRI was 114±7. Compared with the highest GNRI quartile, the lower GNRI quartiles were associated with steeper 5-year slopes in eGFR, with a fully adjusted beta coefficient and 95% confidence intervals (CIs) of -0.50 (-0.86, -0.14), -0.29 (-0.63, 0.05), and -0.19 (-0.53, 0.14) for the first, second, and third GNRI quartiles, respectively. The median follow-up duration was 7.4 years (IQR, 4.6-12.4). During this period, we identified 108 deaths (7.8 per 1,000 person-years). The first GNRI quartile was associated with all-cause mortality compared to the highest GNRI quartile (hazard ratio of 2.20; 95% CI 1.23, 3.95). CONCLUSION: Nutritional status, as evaluated using the GNRI, was associated with 5-year changes in kidney function and all-cause mortality in older individuals.

Chronic cavitary pulmonary aspergillosis: Serial clinical and CT findings correlated with antifungal treatment and patient response.

BACKGROUND: Chronic cavitary pulmonary aspergillosis (CCPA) is the most common form of chronic pulmonary aspergillosis. OBJECTIVE: We hypothesise that by observing serial clinical and CT findings of CCPA patients with antifungal therapy, factors helping predict responses to antifungal therapy could be withdrawn. METHODS: A total of 31 patients with CCPA who received antifungal therapy for greater than six months and who had serial CT studies were included. Clinical finding analyses were performed at initial and last follow-up CT acquisition dates. Clinical characteristics and CT features were compared between clinically improving or stable and deteriorating groups. RESULTS: With antifungal therapy, neutrophil-to-lymphocyte ratio (2.66 vs. 5.12, p = .038) and serum albumin (4.40 vs. 3.85 g/dl, p = .013) and CRP (1.10 vs. 42.80 mg/L, p = .007) were different between two groups. With antifungal therapy, meaningful CT change, regardless of clinical response grouping, was decrease in cavity wall thickness (from 13.70 mm to 8.28 mm, p < .001). But baseline (p = .668) and follow-up (p = .278) cavity wall thickness was not different between two groups. In univariate analysis, initial maximum diameter of cavity (p = .028; HR [0.983], 95% CI [0.967-0.998]) and concurrent NTM infection (p = .030; HR [0.20], 95% CI [0.05-0.86]) were related factors for poor clinical response. CONCLUSIONS: With antifungal therapy, cavities demonstrate wall thinning. Of all clinical and radiological findings and their changes, initial large cavity size and concurrent presence of NTM infection are related factors to poor response to antifungal therapy.

Effect of TSH levels during active surveillance of PTMC according to age.

We previously reported that high thyroid-stimulating hormone (TSH) levels are associated with papillary thyroid microcarcinoma (PTMC) progression during active surveillance. However, validation with multicenter, long-term data, and identification of appropriate age or TSH levels are needed. This multicenter retrospective study enrolled PTMC patients under active surveillance with TSH measurements and ultrasonography. The primary outcome was PTMC progression (volume increase ≥50%, size increase ≥3 mm, or new lymph node (LN) metastasis). PTMC progression according to time-weighted average of TSH (TW-TSH) groups was compared using survival analyses in overall patients and each age subgroups (<40, 40-49, 50-59, and ≥60 years). The identification of TW-TSH cutoff point for PTMC progression and trend analysis of PTMC progression rate according to LT4 treatment were also performed. During 1061 person-years of follow-up, 93 of 234 patients (39.7%) showed PTMC progression (90, 17, and 5 patients for volume increase ≥50%, size increase ≥3 mm, and new LN metastasis, respectively). The highest TW-TSH group was the risk factor most strongly associated with PTMC progression (hazard ratio 2.13 (1.24-3.65); P = 0.006), but the impact was significant only in patients aged <40 or 40-49 years (hazard ratio 30.79 (2.90-326.49; P = 0.004), 2.55 (1.00-6.47; P = 0.049)). For patients aged <50 years, TW-TSH cutoff for PTMC progression was 1.74 mU/L, and PTMC progression rates successively increased in the order of effective, no, and ineffective LT4 treatment group (P for trend = 0.034). In young PTMC patients (<50 years), sustained low-normal TSH levels during active surveillance might be helpful to prevent progression.

Comparative Analysis of Stroke Patients with and without Sequelae: A Cross-Sectional Analysis Using the KOREA National Health and Nutrition Examination Survey (2016-2019).

(1) Background: We aimed to evaluate the association between sociodemographic factors and mental health problems and the sequelae of stroke in South Korea by analyzing the annual Korea National Health and Nutrition Examination Surveys (KNHANES) conducted from 2016 to 2019. (2) Methods: Data were obtained from 32,379 participants who participated in the KNHANES (2016-2019). A total of 567 participants diagnosed with stroke were included in this study. Patients were divided into two groups based on the presence of sequelae: (a) stroke patients with sequelae (n = 227, 40.0%) and (b) stroke patients without sequelae (n = 340, 60.0%). (3) Results: Compared to stroke patients without sequelae, those with sequelae were significantly associated with sex (male, 61.2% vs. 47.6%, p = 0.002), household income (lower half, 78.9% vs. 67.4%, p = 0.005), owning a house (60.4% vs. 68.5%, p = 0.048), marital status (unmarried, 7.05% vs. 1.76%, p < 0.001), depression (13.2% vs. 7.35%, p = 0.045), suicidal ideation (6.17% vs. 3.24%, p = 0.010), and suicide attempts (2.64% vs. 0.88%, p = 0.012). (4) Conclusions: Our study showed that poor sociodemographic factors and mental health problems were significantly associated with sequelae from stroke. Clinical physicians should therefore carefully screen for depression and suicidality in stroke patients with sequelae, especially in those with poor sociodemographic factors.