Purpose: Bruton tyrosine kinase inhibitors (BTKis) are effective and well-tolerated treatments for chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). Here, we describe the clinical characteristics of hepatitis B virus (HBV) reactivation in patients with hematological malignancies treated with BTKis. Methods: Patients were required to have a pathologically confirmed diagnosis of CLL or MCL, receive at least one cycle of ibrutinib or zanubrutinib, and have either positive hepatitis B surface antigen or hepatitis B core antibody at diagnosis. Patients were excluded if they had received rituximab or obinutuzumab within the previous 12 months. Results: We identified five patients with CLL and one with MCL who had resolved HBV infections and received BTKis during the study period. None of the patients received anti-HBV prophylaxis after CLL diagnosis. The patient with MCL who received zanubrutinib was confirmed to have HBV reactivation even after prophylactic entecavir administration followed by tenofovir. All five patients with CLL received ibrutinib as second-line therapy. A 62-year-old man died of hepatorenal syndrome associated with HBV reactivation despite entecavir treatment. Conclusion To the best of our knowledge, this is the first description of HBV-related death in patients receiving BTKis from HBV-endemic areas, and the first case of HBV reactivation associated with zanubrutinib despite previous ente‑ cavir prophylaxis. Further prospective studies are warranted to develop useful guidelines for monitoring HBV DNA and antiviral prophylaxis to prevent HBV reactivation after BTKi therapy.

Purpose: Programmed death-1 blockade with pembrolizumab has shown promising activity in relapsed/refractory (R/R) extranodal natural killer/T-cell lymphoma (NKTCL), but studies are limited, with small patient numbers. Materials and Methods: Thirteen institutes involved with the Consortium for Improving Survival of Lymphoma, a Korean lymphoma study group, collected the clinical data of 59 patients treated with pembrolizumab as salvage therapy between 2016 and 2022. Results: The median age of the patients was 60 years (range, 22 to 87 years), and 76.3% had advanced Ann Abor stage disease. Pembrolizumab was given to 35.6%, 40.7%, and 23.7% of the patients as second-, third-, and fourth- or higher-line chemotherapy, respectively. The overall response rate was 40.7%, with 28.8% having complete response. The estimated 2-year progression-free survival (PFS) and overall survival rates for all patients were 21.5% and 28.7%, respectively; for responders, the rates were 53.0% and 60.7%, respectively. Although not statistically significant, Eastern Cooperative Oncology Group performance status ≥ 2 (hazard ratio [HR], 1.91; 95% confidence interval [95% CI], 0.93 to 3.94; p=0.078) and stage III or IV disease (HR, 2.59; 95% CI, 0.96 to 6.96; p=0.060) were associated with a trend toward shorter PFS in multivariate analysis. Grade 3 or 4 adverse events (AEs) were noted in 12 patients (20.3%); neutropenia (10.2%), fatigue (6.8%), and pneumonitis (5.1%) were most common AEs. Conclusion In conclusion, while pembrolizumab had a modest effect on patients with R/R NKTCL, it may be a useful salvage therapy for patients with localized disease and good performance status.

Background: More comprehensive healthcare services should be provided to patients with complex chronic diseases to better manage their complex care needs. This study examined the effectiveness of comprehensive primary care in patients with complex chronic diseases. Methods: We obtained 2002–2019 data from the National Health Insurance Sample Cohort Database. Participants were individuals aged ≥ 30 years with at least two of the following diseases: hypertension, diabetes mellitus, and hyperlipidemia. Doctors’ offices were classified into specialized, functional, and gray-zone based on patient composition and major diagnostic categories. The Cox proportional hazard model was used to examine the association between office type and hospital admission due to all-causes, severe cardiovascular or cerebrovascular diseases (CVDs), hypertension, diabetes mellitus, or hyperlipidemia. Results: The mean patient age was 60.3 years; 55.8% were females. Among the 24,906 patients, 12.8%, 38.3%, and 49.0% visited specialized, functional, and gray-zone offices, respectively. Patients visiting functional offices had a lower risk of all-cause admission (hazard ratio [HR], 0.935; 95% confidence interval [CI], 0.895–0.976) and CVD-related admission (HR, 0.908; 95% CI, 0.844–0.977) than those visiting specialized offices.However, the admission risks for hypertension, diabetes mellitus, and hyperlipidemia were not significantly different among office types. Conclusion This study provides evidence of the effectiveness of primary care in functional doctors’ offices for patients with complex chronic diseases beyond a single chronic disease and suggests the need for policies to strengthen functional offices providing comprehensive care.

Background/Aims: Transarterial radioembolization (TARE) has shown promising results in treating advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). However, whether TARE can provide superior or comparable outcomes to tyrosine kinase inhibitor (TKI) in patients with HCC and PVTT remains unclear. We compared the outcomes of TARE and TKI therapy in treatment-naïve patients with locally advanced HCC and segmental or lobar PVTT. Methods: This multicenter study included 216 patients initially treated with TARE (n=124) or TKI (sorafenib or lenvatinib; n=92) between 2011 and 2021. Baseline characteristics were balanced using propensity score matching (PSM) or inverse probability of treatment weighting (IPTW). The primary outcome was overall survival (OS). The secondary outcomes included progression-free survival (PFS) and objective response rate (ORR). Results: In the unmatched cohort, the median OS of the TARE and TKI groups were 28.2 and 7.2 months, respectively (p<0.001), and the TARE group experienced significantly and independently longer OS compared to the TKI group (adjusted hazard ratio=0.41, 95% confidence interval=0.28–0.60, p<0.001). Similar results were observed in the study cohorts balanced with IPTW (p=0.003) or PSM (p=0.004). Although PFS was comparable between the two groups, the TARE group showed a trend of prolonged PFS in a subpopulation of patients with Vp1 or Vp2 PVTT (p=0.052). In the matched cohorts, the ORR of the TARE group was 53.0–56.7%, whereas that of the TKI group was 12.3–15.0%. Conclusions For patients with advanced HCC with segmental or lobar PVTT and well-preserved liver function, TARE may provide superior OS compared to sorafenib or lenvatinib.

Background/Aims: The microvascular invasion (MVI) of hepatocellular carcinoma (HCC) involves a wide histological spectrum, and it is unclear whether the degree of MVI correlates with patient prognosis or imaging findings. Here, we evaluate the prognostic value of MVI classification and analyze the radiologic features predictive of MVI. Methods: Using a retrospective cohort of 506 patients with resected solitary HCCs, the histological and imaging features of MVI were reviewed and correlated with clinical data. Results: MVI-positive HCCs invading ≥5 vessels or those with ≥50 invaded tumor cells were significantly associated with decreased overall survival (OS). The 5-year OS, recurrence-free survival (RFS), and beyond Milan criteria RFS rates were significantly poorer in patients with severe MVI compared with those with mild or no MVI. Severe MVI was a significant independent predictive factor for OS (odds ratio [OR], 2.962; p<0.001), RFS (OR, 1.638; p=0.002), and beyond Milan criteria RFS (OR, 2.797; p<0.001) on multivariable analysis. On MRI, non-smooth tumor margins (OR, 2.224; p=0.023) and satellite nodules (OR, 3.264; p<0.001) were independently associated with the severe-MVI group on multivariable analysis. Both non-smooth tumor margins and satellite nodules were associated with worse 5-year OS, RFS, and beyond Milan criteria RFS. Conclusions Histologic risk classification of MVI according to the number of invaded microvessels and invading carcinoma cells was a valuable predictor of prognosis in HCC patients. Non-smooth tumor margin and satellite nodules were significantly associated with severe MVI and poor prognosis.

Coronavirus disease 2019 (COVID-19) vaccination may non-specifically alter the host immune system. This study aimed to evaluate the effect of COVID-19 vaccination on hepatitis B surface Ag (HBsAg) titer and host immunity in chronic hepatitis B (CHB) patients. Consecutive 2,797 CHB patients who had serial HBsAg measurements during antiviral treatment were included in this study. Changes in the HBsAg levels after COVID-19 vaccination were analyzed. The dynamics of NK cells following COVID-19 vaccination were also examined using serial blood samples collected prospectively from 25 healthy volunteers. Vaccinated CHB patients (n=2,329) had significantly lower HBsAg levels 1–30 days post-vaccination compared to baseline (median, −21.4 IU/ml from baseline), but the levels reverted to baseline by 91–180 days (median, −3.8 IU/ml). The velocity of the HBsAg decline was transiently accelerated within 30 days after vaccination (median velocity: −0.06, −0.39, and −0.04 log 10 IU/ml/year in pre-vaccination period, days 1–30, and days 31–90, respectively). In contrast, unvaccinated patients (n=468) had no change in HBsAg levels. Flow cytometric analysis showed that the frequency of NK cells expressing NKG2A, an NK inhibitory receptor, significantly decreased within 7 days after the first dose of COVID-19 vaccine (median, −13.1% from baseline; p<0.001). The decrease in the frequency of NKG2A + NK cells was observed in the CD56dimCD16+ NK cell population regardless of type of COVID-19 vaccine. COVID-19 vaccination leads to a rapid, transient decline in HBsAg titer and a decrease in the frequency of NKG2A + NK cells.

Background/Aims: While switching strategies of P2Y12 receptor inhibitors (RIs) have sometimes been used in acute myocardial infarction (AMI) patients, the current status of in-hospital P2Y12RI switching remains unknown. Methods: Overall, 8,476 AMI patients who underwent successful revascularization from Korea Acute Myocardial Infarction Registry-National Institute of Health (KAMIR-NIH) were divided according to in-hospital P2Y12RI strategies, and net adverse cardiovascular events (NACEs), defined as a composite of cardiac death, non-fatal myocardial infarction (MI), stroke, or thrombolysis in myocardial infarction (TIMI) major bleeding during hospitalization were compared. Results: Patients with in-hospital P2Y12RI switching accounted for 16.5%, of which 867 patients were switched from clopidogrel to potent P2Y12RI (C-P) and 532 patients from potent P2Y12RI to clopidogrel (P-C). There were no differences in NACEs among the unchanged clopidogrel, the unchanged potent P2Y12RIs, and the P2Y12RI switching groups. However, compared to the unchanged clopidogrel group, the C-P group had a higher incidence of non-fatal MI, and the P-C group had a higher incidence of TIMI major bleeding. In clinical events of in-hospital P2Y12RI switching, 90.9% of non-fatal MI occurred during pre-switching clopidogrel administration, 60.7% of TIMI major bleeding was related to pre-switching P2Y12RIs, and 71.4% of TIMI major bleeding was related to potent P2Y12RIs. Only 21.6% of the P2Y12RI switching group switched to P2Y12RIs after a loading dose (LD); however, there were no differences in clinical events between patients with and without LD. Conclusions In-hospital P2Y12RI switching occurred occasionally, but had relatively similar clinical outcomes compared to unchanged P2Y12RIs in Korean AMI patients. Non-fatal MI and bleeding appeared to be mainly related to pre-switching P2Y12RIs.