Background: Brentuximab vedotin (BV), a potent antibody-drug conjugate, targets the CD30 antigen.In Korea, BV has been approved for the treatment of relapsed or refractory Hodgkin lymphoma (HL), anaplastic large-cell lymphoma (ALCL), and cutaneous T-cell lymphomas, including mycosis fungoides (MF). However, there are limited data reflecting real-world experiences with BV treatment for HL, ALCL, and MF. Methods: This was a multicenter, non-interventional registry study of the efficacy and safety of BV in patients with relapsed or refractory CD30-positive lymphoma (CISL1803/BRAVO).Outcomes were determined based on the occurrence of relapse or progression and overall survival after BV treatment. Results: A total of 85 patients were enrolled in this study. The median number of BV cycles was 10 (range, 2‒16) in the patients with HL. The objective response rate (ORR) of patients with HL to BV was 85.4% (41/48), comprising 27 complete responses (CRs) and 14 partial responses (PRs). The ORR of ALCL was 88% (22/25), consisting of 17 CRs and five PRs, whereas the ORR of MF was 92% (11/12). At the median follow-up of 44.6 months after BV treatment, the median post-BV progression-free survival of HL, ALCL, and MF patients was 23.6 months, 29.0 months, and 16.7 months, respectively (P =0.641). The most common side effect of BV was peripheral neuropathy; 22 patients (25.9%, 22/85) experienced peripheral neuropathy (all grades). Conclusion The treatment outcomes of patients with relapsed or refractory CD30-positive lymphoma improved with BV treatment, and the safety profile was manageable.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces excessive pro-inflammatory cytokine release and cell death, leading to organ damage and mortality.High-mobility group box 1 (HMGB1) is one of the damage-associated molecular patterns that can be secreted by pro-inflammatory stimuli, including viral infections, and its excessive secretion levels are related to a variety of inflammatory diseases. Here, the aim of the study was to show that SARS-CoV-2 infection induced HMGB1 secretion via active and passive release. Active HMGB1 secretion was mediated by post-translational modifications, such as acetylation, phosphorylation, and oxidation in HEK293E/ACE2-C-GFP and Calu-3 cells during SARS-CoV-2 infection. Passive release of HMGB1 has been linked to various types of cell death; however, we demonstrated for the first time that PANoptosis, which integrates other cell death pathways, including pyroptosis, apoptosis, and necroptosis, is related to passive HMGB1 release during SARS-CoV-2 infection. In addition, cytoplasmic translocation and extracellular secretion or release of HMGB1 were confirmed via immunohistochemistry and immunofluorescence in the lung tissues of humans and angiotensin-converting enzyme 2-overexpressing mice infected with SARS-CoV-2.

Purpose: Diffuse large B-cell lymphoma (DLBCL) is the most common hematologic malignancy worldwide. Although substantial improvement has been achieved by the frontline rituximab-based chemoimmunotherapy, up to 40%-50% of patients will eventually have relapsed or refractory disease, whose prognosis is extremely dismal. Materials and Methods: We have carried out two prospective cohort studies that include over 1,500 DLBCL patients treated with rituximab plus CHOP (#NCT01202448 and #NCT02474550). In the current report, we describe the outcomes of refractory DLBCL patients. Patients were defined to have refractory DLBCL if they met one of the followings, not achieving at least partial response after 4 or more cycles of R-CHOP; not achieving at least partial response after 2 or more cycles of salvage therapy; progressive disease within 12 months after autologous stem cell transplantation. Results: Among 1,581 patients, a total of 260 patients met the criteria for the refractory disease after a median time to progression of 9.1 months. The objective response rate of salvage treatment was 26.4%, and the complete response rate was 9.6%. The median overall survival (OS) was 7.5 months (95% confidence interval, 6.4 to 8.6), and the 2-year survival rate was 22.1%±2.8%. The median OS for each refractory category was not significantly different (p=0.529). Conclusion In line with the previous studies, the outcomes of refractory DLBCL patients were extremely poor, which necessitates novel approaches for this population.

Purpose: This study aimed to develop a model for predicting pathologic extracapsular extension (ECE) and seminal vesicle invasion (SVI) while integrating magnetic resonance imaging-based T-staging (cTMRI, cT1c-cT3b). Materials and Methods: A total of 1,915 who underwent radical prostatectomy between 2006-2016 met the inclusion/exclusion criteria. We performed a multivariate logistic regression analysis as well as Bayesian network (BN) modeling based on possible confounding factors. The BN model was internally validated using 5-fold validation. Results: According to the multivariate logistic regression analysis, initial prostate-specific antigen (iPSA) (β=0.050, p < 0.001), percentage of positive biopsy cores (PPC) (β=0.033, p < 0.001), both lobe involvement on biopsy (β=0.359, p=0.009), Gleason score (β=0.358, p < 0.001), and cTMRI (β=0.259, p < 0.001) were significant factors for ECE. For SVI, iPSA (β=0.037, p < 0.001), PPC (β=0.024, p < 0.001), Gleason score (β=0.753, p < 0.001), and cTMRI (β=0.507, p < 0.001) showed statistical significance. BN models to predict ECE and SVI were also successfully established. The overall area under the receiver operating characteristic curve (AUC)/accuracy of the BN models were 0.76/73.0% and 0.88/89.6% for ECE and SVI, respectively. According to internal comparison between the BN model and Roach formula, BN model had improved AUC values for predicting ECE (0.76 vs. 0.74, p=0.060) and SVI (0.88 vs. 0.84, p < 0.001). Conclusion Two models to predict pathologic ECE and SVI integrating cTMRI were established and installed on a separate website for public access to guide radiation oncologists.

Chronic recurrent multifocal osteomyelitis (CRMO) is an inflammatory bone disorder presenting with sterile osteomyelitis, most often presenting in childhood. Although the etiology is understood incompletely, its association with other auto-inflammatory diseases including inflammatory bowel disease (IBD); psoriasis; Wegener’s disease; arthritis; and synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome suggests that dysregulated innate immunity may play an important role in the pathogenesis. We report a case of a 13-year-old boy with CRMO associated with Crohn’s disease (CD) successfully treated with infliximab after failure of non-steroidal anti-inflammatory drug (NSAID) treatment. He initially was diagnosed with CRMO based on symmetric and aseptic bone lesions with no fever, lack of response to antibiotic treatment, vertebral involvement, and normal blood cell counts. Despite five months of NSAID treatment, his musculoskeletal symptoms were aggravated, and he developed gastrointestinal symptoms. Finally, he was diagnosed with CRMO associated with CD. Due to the severity of symptoms, infliximab was initiated and produced symptom improvement. This case supports infliximab as another choice for treatment of bowel symptoms in addition to the bone and joint symptoms of CRMO when other first-line treatments are ineffective.

Purpose: Febrile neutropenia (FN) can cause suboptimal treatment and treatment-related mortality (TRM) in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP). Materials and methods: We conducted a prospective cohort study to evaluate the effectiveness of pegfilgrastim prophylaxis in DLBCL patients receiving R-CHOP, and we compared them with the PROCESS cohort (n=485). Results: Since January 2015, 986 patients with DLBCL were enrolled. Pegfilgrastim was administered at least once in 930 patients (94.3%), covering 90.3% of all cycles. FN developed in 137 patients (13.9%) in this cohort (23.7% in the PROCESS cohort, p<0.001), and 4.2% of all cycles (10.2% in the PROCESS cohort, p<0.001). Dose delay was less common (≥3 days: 18.1% vs. 23.7%, p=0.015; ≥5 days: 12.0% vs. 18.3%, p=0.023) in this cohort than in the PROCESS cohort. The incidence of TRM (3.2% vs. 5.6%, p=0.047) and infection-related death (1.8% vs. 4.5%, p=0.004) was lower in this cohort than in the PROCESS cohort. The 4-year overall survival (OS) and progression-free survival (PFS) rates of the two cohorts were not different (OS: 73.0% vs. 71.9%, p=0.545; PFS: 69.5% vs. 68.8%, p=0.616). However, in patients aged ≥75 years, the 4-year OS and PFS rates were higher in this cohort than in the PROCESS cohort (OS: 49.6% vs. 33.7%, p=0.032; PFS: 44.2% vs. 30.3% p=0.047). Conclusion Pegfilgrastim prophylaxis is effective in the prevention of FN and infection-related death in DLBCL patients receiving R-CHOP, and it also improves OS in patients aged ≥75 years.

Peroxiredoxins (Prxs) are ubiquitously expressed peroxidases that reduce hydrogen peroxide or alkyl peroxide production in cells. Prxs are released from cells in response to various stress conditions, and they function as damage-associated molecular pattern molecules. However, the secretory mechanism of Prxs and their roles have not been elucidated. Thus, we aimed to determine whether inflammasome activation is a secretory mechanism of Prxs and subsequently identify the effect of the secreted Prxs on activation of the classical complement pathway. Using J774A.1, a murine macrophage cell line, we demonstrated that NLRP3 inflammasome activation induces Prx1, Prx2, Prx5, and Prx6 secretion in a caspase-1 dependent manner. Using HEK293T cells with a transfection system, we revealed that the release of Prx1 and Prx2 relies on gasdermin-D (GSDMD)-mediated secretion. Next, we confirmed the binding of both Prx1 and Prx2 to C1q; however, only Prx2 could induce the C1q-mediated classical complement pathway activation. Collectively, our results suggest that inflammasome activation is a secretory mechanism of Prxs and that GSDMD is a mediator of their secretion. Moreover, secreted Prx1 and Prx2 bind with C1q, but only Prx2 mediates the classical complement pathway activation.

BACKGROUND: Rituximab plus cyclophosphamide, vincristine, and prednisone (R-CVP) is one of the effective chemotherapeutic regimens for patients with advanced stage marginal zone lymphoma (MZL). However, prognostic factors that affect the outcome of treatment for MZL are not well understood. METHODS: Between August 2006 and June 2013, patients with newly diagnosed stage III and IV MZL treated with R-CVP as a first-line therapy from 15 institutions were retrospectively analyzed. Patients' clinical and laboratory data at diagnosis were collected by review of medical records. RESULTS: A total of 80 patients were analyzed. Bone marrow involvement was observed in 30% cases. Twelve patients (15%) had nodal MZL, and 41.3% patients exhibited multiple mucosa-associated lymphoma tissue sites. Overall response rate was 91.3%, including 73.8% achieving complete response. Advanced MZL patients treated with R-CVP showed a 3-year progression-free survival (PFS) rate of 69.6%. Prognostic markers significantly affecting PFS in univariate analysis were platelet to lymphocyte ratio (PLR, <95 vs. ≥95, P=0.014), serum albumin (≤3.9 vs. >3.9 g/dL, P=0.008), and the International Prognostic Index (IPI) score (1 vs. 2–4, P=0.032). In multivariate analysis, only PLR (<95 vs. ≥95, HR 0.367, 95% CI, 0.139–0.971, P=0.043) was an independent risk factor for PFS. CONCLUSION: PLR ≥95 at diagnosis is an independent prognostic marker for PFS in advanced stage MZL patients treated with R-CVP. This marker may aid clinicians in predicting the response to R-CVP chemotherapy in stage III and IV MZL patients.
Blood Platelets* ; Bone Marrow ; Cyclophosphamide* ; Diagnosis ; Disease-Free Survival ; Drug Therapy ; Drug Therapy, Combination* ; Humans ; Lymphocytes* ; Lymphoma* ; Medical Records ; Multivariate Analysis ; Prednisone* ; Prognosis ; Retrospective Studies ; Risk Factors ; Rituximab* ; Serum Albumin ; Vincristine*

BACKGROUND: We investigated the clinical features and treatment outcomes of patients with mantle cell lymphoma (MCL) in Korea. METHODS: We retrospectively analyzed the clinical characteristics and prognosis of 131 patients diagnosed with MCL between January 2004 and December 2009 at 15 medical centers in Korea; all patients received at least 1 chemotherapeutic regimen for MCL. RESULTS: The median age for the patients was 63 years (range, 26-78 years), and 77.9% were men. A total of 105 patients (80.1%) had stage III or IV MCL at diagnosis. Fifty-two patients (39.7%) were categorized with high- or high-intermediate risk MCL according to the International Prognostic Index (IPI). Eighteen patients (13.7%) were in the high-risk group according to the simplified MCL-IPI (MIPI). The overall incidence of extranodal involvement was 69.5%. The overall incidence of bone marrow and gastrointestinal involvements at diagnosis was 41.2% and 35.1%, respectively. Cyclophosphamide, doxorubicin, vincristine, prednisolone, and rituximab were used frequently as the first-line treatment (41.2%). With a median follow-up duration of 20.0 months (range, 0.2-77.0 months), the overall survival (OS) at 2 years was 64.7%, while the event-free survival (EFS) was 39.7%. Multivariate analysis showed that the simplified MIPI was significantly associated with OS. However, the use of a rituximab-containing regimen was not associated with OS and EFS. CONCLUSION: Similar to results from Western countries, the current study found that simplified MIPI was an important prognostic factor in Korean patients with MCL.
Bone Marrow ; Cyclophosphamide ; Diagnosis ; Disease-Free Survival ; Doxorubicin ; Drug Therapy ; Epidemiology ; Follow-Up Studies ; Humans ; Incidence ; Korea* ; Lymphoma* ; Lymphoma, Mantle-Cell* ; Male ; Multivariate Analysis ; Prednisolone ; Prognosis ; Retrospective Studies ; Vincristine ; Rituximab

PURPOSE: This study was performed to evaluate the compliance with, and adequacy of, the Korean national guidelines which had been recommended until 2011 for isolation of patients with group 1 nationally notifiable infectious diseases (NNIDs), namely cholera, typhoid fever, paratyphoid fever, shigellosis, and enterohemorrhagic Escherichia coli (EHEC) infection. MATERIALS AND METHODS: We evaluated the clinical and microbiological characteristics of confirmed cases of group 1 NNIDs and compliance with the guidelines in 20 Korean hospitals nationwide in 2000-2010. We also compared the Korean guidelines with international guidelines. RESULTS: Among 528 confirmed cases (8 cases of cholera, 232 of typhoid fever, 81 of paratyphoid fever, 175 of shigellosis, and 32 EHEC infections), strict compliance with the Korean guideline was achieved in only 2.6% to 50.0%, depending on the disease. While the Korean guidelines recommend isolation of all patients with group 1 NNIDs, international guidelines recommend selective patient isolation and screening for fecal shedding, depending on the type of disease and patient status. CONCLUSION: Compliance with the previous national guidelines for group 1 NNIDs in Korea was generally very low. Further studies are needed to evaluate whether compliance was improved after implementation of the new guideline in 2012.
Cholera ; Communicable Disease Control ; Communicable Diseases* ; Compliance* ; Dysentery, Bacillary ; Enterohemorrhagic Escherichia coli ; Guideline Adherence ; Humans ; Korea* ; Mass Screening ; Methods ; Paratyphoid Fever ; Patient Isolation ; Typhoid Fever