Background: Genetic alterations play a pivotal role in multiple myeloma (MM) development and therapeutic resistance. Traditionally, the genetic profiling of MM requires invasive bone marrow (BM) procedures; however, these procedures are associated with patient discomfort and cannot fully capture the spatial and temporal heterogeneity of the disease.Therefore, we investigated the clinical implications of liquid biopsy using targeted deep sequencing. Methods: We analyzed the genetic profiles of circulating tumor DNA (ctDNA) by targeted deep sequencing from 102 patients, including those with monoclonal gammopathy of undetermined significance (MGUS, N = 7), smoldering MM (N = 6), and symptomatic MM (N = 89). Results: The number of ctDNA mutations increased with disease progression from MGUS to MM, with averages of 1.0 mutations in MGUS, 1.8 mutations in smoldering MM, and 1.9 mutations in MM, respectively. Shared mutations between BM and ctDNA were more prevalent in MM (68.9%) than in MGUS (25.0%). RAS/RAF and TP53 mutations were significantly enriched in MM ctDNA. Specific mutations were associated with clinical features in patients with MM: hypercalcemia and TET2 (P = 0.006), renal insufficiency and NRAS (P = 0.012), paramedullary myeloma and TP53(P = 0.02), and extramedullary myeloma and NRAS (P = 0.007). TET2 mutations significantly affected 2-yr progression-free survival (hazard ratio = 7.11, P = 0.003). Serial ctDNA profiling accurately predicted treatment response in patients with MM. Conclusions Our findings highlight the potential of liquid biopsy for understanding MM progression and prognosis utilizing a minimally invasive approach, paving the way for its integration into personalized treatment strategies and real-time disease monitoring.

Objective: Biportal endoscopic transforaminal lumbar interbody fusion (BE-TLIF) is an emerging, minimally invasive technique performed under biportal endoscopic guidance. However, concerns regarding cage subsidence and sufficient fusion during BE-TLIF necessitate careful selection of an appropriate interbody cage to improve surgical outcomes. This study compared the fusion rate, subsidence, and other radiographic parameters according to the material and size of the cages used in BE-TLIF. Methods: In this retrospective cohort study, patients who underwent single-segment BE-TLIF between April 2019 and February 2023 were divided into 3 groups: group A, regular-sized three-dimensionally (3D)-printed titanium cages; group B, regular-sized polyetheretherketone cages; and group C, large-sized 3D-printed titanium cages. Radiographic parameters, including lumbar lordosis, segmental lordosis, anterior and posterior disc heights, disc angle, and foraminal height, were measured before and after surgery. The fusion rate and severity of cage subsidence were compared between the groups. Results: No significant differences were noted in the demographic data or radiographic parameters between the groups. The fusion rate on 1-year postoperative computed tomography was comparable between the groups. The cage subsidence rate was significantly lower in group C than in group A (41.9% vs. 16.7%, p=0.044). The severity of cage subsidence was significantly lower in group C (0.93±0.83) than in groups A (2.20±1.84, p=0.004) and B (1.79±1.47, p=0.048). Conclusion Cage materials did not affect the 1-year postoperative outcomes of BE-TLIF; however, subsidence was markedly reduced in large cages. Larger cages may provide more stable postoperative segments.

Objective: Biportal endoscopic transforaminal lumbar interbody fusion (BE-TLIF) is an emerging, minimally invasive technique performed under biportal endoscopic guidance. However, concerns regarding cage subsidence and sufficient fusion during BE-TLIF necessitate careful selection of an appropriate interbody cage to improve surgical outcomes. This study compared the fusion rate, subsidence, and other radiographic parameters according to the material and size of the cages used in BE-TLIF. Methods: In this retrospective cohort study, patients who underwent single-segment BE-TLIF between April 2019 and February 2023 were divided into 3 groups: group A, regular-sized three-dimensionally (3D)-printed titanium cages; group B, regular-sized polyetheretherketone cages; and group C, large-sized 3D-printed titanium cages. Radiographic parameters, including lumbar lordosis, segmental lordosis, anterior and posterior disc heights, disc angle, and foraminal height, were measured before and after surgery. The fusion rate and severity of cage subsidence were compared between the groups. Results: No significant differences were noted in the demographic data or radiographic parameters between the groups. The fusion rate on 1-year postoperative computed tomography was comparable between the groups. The cage subsidence rate was significantly lower in group C than in group A (41.9% vs. 16.7%, p=0.044). The severity of cage subsidence was significantly lower in group C (0.93±0.83) than in groups A (2.20±1.84, p=0.004) and B (1.79±1.47, p=0.048). Conclusion Cage materials did not affect the 1-year postoperative outcomes of BE-TLIF; however, subsidence was markedly reduced in large cages. Larger cages may provide more stable postoperative segments.

Objective: Biportal endoscopic transforaminal lumbar interbody fusion (BE-TLIF) is an emerging, minimally invasive technique performed under biportal endoscopic guidance. However, concerns regarding cage subsidence and sufficient fusion during BE-TLIF necessitate careful selection of an appropriate interbody cage to improve surgical outcomes. This study compared the fusion rate, subsidence, and other radiographic parameters according to the material and size of the cages used in BE-TLIF. Methods: In this retrospective cohort study, patients who underwent single-segment BE-TLIF between April 2019 and February 2023 were divided into 3 groups: group A, regular-sized three-dimensionally (3D)-printed titanium cages; group B, regular-sized polyetheretherketone cages; and group C, large-sized 3D-printed titanium cages. Radiographic parameters, including lumbar lordosis, segmental lordosis, anterior and posterior disc heights, disc angle, and foraminal height, were measured before and after surgery. The fusion rate and severity of cage subsidence were compared between the groups. Results: No significant differences were noted in the demographic data or radiographic parameters between the groups. The fusion rate on 1-year postoperative computed tomography was comparable between the groups. The cage subsidence rate was significantly lower in group C than in group A (41.9% vs. 16.7%, p=0.044). The severity of cage subsidence was significantly lower in group C (0.93±0.83) than in groups A (2.20±1.84, p=0.004) and B (1.79±1.47, p=0.048). Conclusion Cage materials did not affect the 1-year postoperative outcomes of BE-TLIF; however, subsidence was markedly reduced in large cages. Larger cages may provide more stable postoperative segments.

Objective: Biportal endoscopic transforaminal lumbar interbody fusion (BE-TLIF) is an emerging, minimally invasive technique performed under biportal endoscopic guidance. However, concerns regarding cage subsidence and sufficient fusion during BE-TLIF necessitate careful selection of an appropriate interbody cage to improve surgical outcomes. This study compared the fusion rate, subsidence, and other radiographic parameters according to the material and size of the cages used in BE-TLIF. Methods: In this retrospective cohort study, patients who underwent single-segment BE-TLIF between April 2019 and February 2023 were divided into 3 groups: group A, regular-sized three-dimensionally (3D)-printed titanium cages; group B, regular-sized polyetheretherketone cages; and group C, large-sized 3D-printed titanium cages. Radiographic parameters, including lumbar lordosis, segmental lordosis, anterior and posterior disc heights, disc angle, and foraminal height, were measured before and after surgery. The fusion rate and severity of cage subsidence were compared between the groups. Results: No significant differences were noted in the demographic data or radiographic parameters between the groups. The fusion rate on 1-year postoperative computed tomography was comparable between the groups. The cage subsidence rate was significantly lower in group C than in group A (41.9% vs. 16.7%, p=0.044). The severity of cage subsidence was significantly lower in group C (0.93±0.83) than in groups A (2.20±1.84, p=0.004) and B (1.79±1.47, p=0.048). Conclusion Cage materials did not affect the 1-year postoperative outcomes of BE-TLIF; however, subsidence was markedly reduced in large cages. Larger cages may provide more stable postoperative segments.

Objective: Biportal endoscopic transforaminal lumbar interbody fusion (BE-TLIF) is an emerging, minimally invasive technique performed under biportal endoscopic guidance. However, concerns regarding cage subsidence and sufficient fusion during BE-TLIF necessitate careful selection of an appropriate interbody cage to improve surgical outcomes. This study compared the fusion rate, subsidence, and other radiographic parameters according to the material and size of the cages used in BE-TLIF. Methods: In this retrospective cohort study, patients who underwent single-segment BE-TLIF between April 2019 and February 2023 were divided into 3 groups: group A, regular-sized three-dimensionally (3D)-printed titanium cages; group B, regular-sized polyetheretherketone cages; and group C, large-sized 3D-printed titanium cages. Radiographic parameters, including lumbar lordosis, segmental lordosis, anterior and posterior disc heights, disc angle, and foraminal height, were measured before and after surgery. The fusion rate and severity of cage subsidence were compared between the groups. Results: No significant differences were noted in the demographic data or radiographic parameters between the groups. The fusion rate on 1-year postoperative computed tomography was comparable between the groups. The cage subsidence rate was significantly lower in group C than in group A (41.9% vs. 16.7%, p=0.044). The severity of cage subsidence was significantly lower in group C (0.93±0.83) than in groups A (2.20±1.84, p=0.004) and B (1.79±1.47, p=0.048). Conclusion Cage materials did not affect the 1-year postoperative outcomes of BE-TLIF; however, subsidence was markedly reduced in large cages. Larger cages may provide more stable postoperative segments.

Purpose: Interleukin-37 (IL-37) is an anti-inflammatory cytokine that inhibits a broad spectrum of inflammatory responses in various human cells, including neutrophils, macrophages, and endothelial cells. The aim of this study was to identify the role of IL-37 in toll-like receptor 9 (TLR9) signaling in human macrophages. Materials and Methods: Human macrophage U937 cells treated with CpG-oligonucleotides (CpG-ODN), recombinant IL-37, or dexamethasone were used in an in vitro study. IL-37 small interfering RNA (siRNA) and TLR9 siRNA were used to silence endogenous IL-37 and TLR9, respectively. Expression levels of phosphorylated nuclear factor-κB (NF-κB), IκBα, IL-37, IL-1β, tumor necrosis factor-α (TNF-α), and IL-6 protein were assessed by real-time quantitative polymerase chain reaction and Western blotting. CpG-ODN-mediated IL-37 expression stimulated by dexamethasone was detected using immunofluorescent analysis. Results: U937 cells treated with CpG-ODN induced activation of the NF-κB pathway and increased the expression of the pro-inflammatory cytokines IL-1β, TNF-α, and IL-6, but reduced that of IL-37. Recombinant IL-37 attenuated phosphorylation of NF-κB and IκBα and the expression of IL-1β, TNF-α, and IL-6 stimulated by CpG-ODN. Human macrophages transfected with IL-37 siRNA augmented the expression of IL-1β, TNF-α, and IL-6 mRNA and protein in cells treated with CpG-ODN. Dexamethasone markedly inhibited expression of pro-inflammatory cytokines in U937 cells, whereas IL-37 expression was increased with the addition of dexamethasone. Inflammatory responses elicited by CpG-ODN were dependent on an MyD88-TRAF6 pathway. IL-37 inhibited CpG-ODN-induced ubiquitination of TRAF6 in U937 macrophages. Conclusion IL-37 inhibits CpG-ODN-mediated inflammatory responses through regulation of a TRAF6- NF-κB pathway in human macrophages.

Background/Aims: To investigate if BK virus (BKV)-specific T cell immunity measured by an interferon-γ enzyme-linked immunospot (ELISPOT) assay can predict the outcome of BK virus infection in kidney transplant recipients (KTRs). Methods: We included 68 KTRs with different viremia status (no viremia [n = 17], BK viremia [n = 27], and cleared viremia [n = 24]) and 44 healthy controls (HCs). The BK viremia group was divided into controller (< 3 months) and noncontroller (> 3 months) according to sustained duration of BKV infection. We compared BKV-ELISPOT results against five BKV peptides (large tumor antigen [LT], St, VP1-3). Results: BKV-ELISPOT results were higher in three KTRs groups with different BKV infection status than the HCs group (p < 0.05). In KTR groups, they were higher in cleared viremia group than no viremia or BK viremia group. Within the BK viremia group, controller group had higher LT-ELISPOT results compared to noncontroller group (p = 0.032). Also, KTRs without BK virus-associated nephropathy (BKVN) had higher LT, St, VP1, and VP2-ELISPOT results than those with BKVN (p < 0.05). Conclusions BKV-ELISPOT assay may be effective in predicting clinical outcomes of BKV infection in terms of clearance of BK virus and development of BKVN.

Purpose: Interleukin-37 (IL-37) is an anti-inflammatory cytokine that inhibits a broad spectrum of inflammatory responses in various human cells, including neutrophils, macrophages, and endothelial cells. The aim of this study was to identify the role of IL-37 in toll-like receptor 9 (TLR9) signaling in human macrophages. Materials and Methods: Human macrophage U937 cells treated with CpG-oligonucleotides (CpG-ODN), recombinant IL-37, or dexamethasone were used in an in vitro study. IL-37 small interfering RNA (siRNA) and TLR9 siRNA were used to silence endogenous IL-37 and TLR9, respectively. Expression levels of phosphorylated nuclear factor-κB (NF-κB), IκBα, IL-37, IL-1β, tumor necrosis factor-α (TNF-α), and IL-6 protein were assessed by real-time quantitative polymerase chain reaction and Western blotting. CpG-ODN-mediated IL-37 expression stimulated by dexamethasone was detected using immunofluorescent analysis. Results: U937 cells treated with CpG-ODN induced activation of the NF-κB pathway and increased the expression of the pro-inflammatory cytokines IL-1β, TNF-α, and IL-6, but reduced that of IL-37. Recombinant IL-37 attenuated phosphorylation of NF-κB and IκBα and the expression of IL-1β, TNF-α, and IL-6 stimulated by CpG-ODN. Human macrophages transfected with IL-37 siRNA augmented the expression of IL-1β, TNF-α, and IL-6 mRNA and protein in cells treated with CpG-ODN. Dexamethasone markedly inhibited expression of pro-inflammatory cytokines in U937 cells, whereas IL-37 expression was increased with the addition of dexamethasone. Inflammatory responses elicited by CpG-ODN were dependent on an MyD88-TRAF6 pathway. IL-37 inhibited CpG-ODN-induced ubiquitination of TRAF6 in U937 macrophages. Conclusion IL-37 inhibits CpG-ODN-mediated inflammatory responses through regulation of a TRAF6- NF-κB pathway in human macrophages.

Background: To determine the effects of Jerusalem Artichoke extract (JAE) and inulin on blood glucose levels and insulin secretion in streptozotocin (STZ)-induced diabetic mice.
Methods: Thirty four mice were divided into a normal control group and three experimental groups: diabetic control, JAE, and inulin. STZ (50 mg/kg) was injected intraperitoneally to induce diabetes in the three experimental groups. The JAE and inulin groups were fed 10 g/kg JAE or fed 1 g/kg inulin, respectively, for 6 weeks. Fasting glucose was checked weekly. After 6 weeks, the oral glucose tolerance test (OGTT) was performed, and the insulin level was checked.
Results: Four mice from the JAE group (n = 9) died and autopsies revealed inflammation and ulceration of skin lesions on the chest areas. Fasting glucose levels were not decreased in the inulin or JAE group relative to diabetic control group. In the OGTT at 60 minutes and 120 minutes, the serum glucose levels were significantly higher in the inulin group (572.6 ± 52.0 mg/dL and 555.8 ± 72.9 mg/dL, respectively) than in diabetic control group (484.3 ± 81.6 mg/dL and 467.3 ± 111.1 mg/dL, respectively). Insulin levels were not increased in the inulin group relative to the diabetic control group.
Conclusion These results indicate that JAE and inulin might not be useful therapeutic strategies for diabetes mellitus and indiscreet intake of Jerusalem Artichoke could exacerbate to diabetes.