1,25-dihydroxy Vitamin D3 and Interleukin-6 Blockade Synergistically Regulate Rheumatoid Arthritis by Suppressing Interleukin-17 Production and Osteoclastogenesis

BACKGROUND: Immune cells express the vitamin (vit) D receptor, and vit D is a potent immune-modulator. A negative correlation between serum vit D levels and rheumatoid arthritis (RA) disease activity has been reported. Therefore, we aimed to investigate if the sufficient serum vit D level is helpful to control disease activity in RA patients treated with interleukin (IL)-6 receptor antibody tocilizumab.METHODS: RA patients taking tocilizumab were enrolled, and data were collected retrospectively. Disease activity scores (DAS) 28, serum vit D levels, modified Sharp scores of hand X-ray at the time of tocilizumab initiation, and follow-up data were analysed. Peripheral blood mononuclear cells were differentiated into T-helper (Th) 17 or osteoclasts in the presence of various concentrations of tocilizumab and/or 1,25(OH)₂D. Th17 proportions were analysed by fluorescence-activated cell sorting. Supernatant cytokine levels were determined by enzyme-linked immunosorbent assay.RESULTS: Among 98 RA patients taking tocilizumab, 34 (34.7%) had sufficient serum 25(OH)D levels (≥ 30 ng/mL) when tocilizumab was initiated. At 24 weeks, vit D sufficient patients had greater DAS28 reduction (64.6% ± 15.5% vs. 52.7% ± 20.7%, P = 0.004), and lower disease activity (91.2% vs. 70.3%, P = 0.018) or remission (82.4% vs. 57.8%, P = 0.014). These differences in DAS28 reduction and the proportion of patients with remission persisted at 48 weeks. However, there was no significant difference in hand and wrist erosion progression. In vitro, tocilizumab and 1,25(OH)₂D treatment synergistically suppressed IL-17 production and osteoclastogenesis.CONCLUSION: RA patients treated with IL-6 antibody show a better response when they have sufficient serum vit D. Tocilizumab and 1,25(OH)₂D synergistically suppress IL-17 production and osteoclast differentiation in RA patients.

1,25-dihydroxy Vitamin D3 and Interleukin-6 Blockade Synergistically Regulate Rheumatoid Arthritis by Suppressing Interleukin-17 Production and Osteoclastogenesis

BACKGROUND@#Immune cells express the vitamin (vit) D receptor, and vit D is a potent immune-modulator. A negative correlation between serum vit D levels and rheumatoid arthritis (RA) disease activity has been reported. Therefore, we aimed to investigate if the sufficient serum vit D level is helpful to control disease activity in RA patients treated with interleukin (IL)-6 receptor antibody tocilizumab.@*METHODS@#RA patients taking tocilizumab were enrolled, and data were collected retrospectively. Disease activity scores (DAS) 28, serum vit D levels, modified Sharp scores of hand X-ray at the time of tocilizumab initiation, and follow-up data were analysed. Peripheral blood mononuclear cells were differentiated into T-helper (Th) 17 or osteoclasts in the presence of various concentrations of tocilizumab and/or 1,25(OH)₂D. Th17 proportions were analysed by fluorescence-activated cell sorting. Supernatant cytokine levels were determined by enzyme-linked immunosorbent assay.@*RESULTS@#Among 98 RA patients taking tocilizumab, 34 (34.7%) had sufficient serum 25(OH)D levels (≥ 30 ng/mL) when tocilizumab was initiated. At 24 weeks, vit D sufficient patients had greater DAS28 reduction (64.6% ± 15.5% vs. 52.7% ± 20.7%, P = 0.004), and lower disease activity (91.2% vs. 70.3%, P = 0.018) or remission (82.4% vs. 57.8%, P = 0.014). These differences in DAS28 reduction and the proportion of patients with remission persisted at 48 weeks. However, there was no significant difference in hand and wrist erosion progression. In vitro, tocilizumab and 1,25(OH)₂D treatment synergistically suppressed IL-17 production and osteoclastogenesis.@*CONCLUSION@#RA patients treated with IL-6 antibody show a better response when they have sufficient serum vit D. Tocilizumab and 1,25(OH)₂D synergistically suppress IL-17 production and osteoclast differentiation in RA patients.

Quantitative evaluation of the molecular marker using droplet digital PCR

Transposable elements (TEs) constitute approximately half of Bovine genome. They can be a powerful species-specific marker without regression mutations by the structure variation (SV) at the time of genomic evolution. In a previous study, we identified the Hanwoo-specific SV that was generated by a TE–association deletion event using traditional PCR method and Sanger sequencing validation. It could be used as a molecular marker to distinguish different cattle breeds (i.e., Hanwoo vs. Holstein). However, PCR is defective with various final copy quantifications from every sample. Thus, we applied to the droplet digital PCR (ddPCR) platform for accurate quantitative detection of the Hanwoo-specific SV. Although samples have low allele frequency variation within Hanwoo population, ddPCR could perform high sensitive detection with absolute quantification. We aimed to use ddPCR for more accurate quantification than PCR. We suggest that the ddPCR platform is applicable for the quantitative evaluation of molecular markers.

1,25-dihydroxy Vitamin D3 and Interleukin-6 Blockade Synergistically Regulate Rheumatoid Arthritis by Suppressing Interleukin-17 Production and Osteoclastogenesis

BACKGROUND@#Immune cells express the vitamin (vit) D receptor, and vit D is a potent immune-modulator. A negative correlation between serum vit D levels and rheumatoid arthritis (RA) disease activity has been reported. Therefore, we aimed to investigate if the sufficient serum vit D level is helpful to control disease activity in RA patients treated with interleukin (IL)-6 receptor antibody tocilizumab.@*METHODS@#RA patients taking tocilizumab were enrolled, and data were collected retrospectively. Disease activity scores (DAS) 28, serum vit D levels, modified Sharp scores of hand X-ray at the time of tocilizumab initiation, and follow-up data were analysed. Peripheral blood mononuclear cells were differentiated into T-helper (Th) 17 or osteoclasts in the presence of various concentrations of tocilizumab and/or 1,25(OH)₂D. Th17 proportions were analysed by fluorescence-activated cell sorting. Supernatant cytokine levels were determined by enzyme-linked immunosorbent assay.@*RESULTS@#Among 98 RA patients taking tocilizumab, 34 (34.7%) had sufficient serum 25(OH)D levels (≥ 30 ng/mL) when tocilizumab was initiated. At 24 weeks, vit D sufficient patients had greater DAS28 reduction (64.6% ± 15.5% vs. 52.7% ± 20.7%, P = 0.004), and lower disease activity (91.2% vs. 70.3%, P = 0.018) or remission (82.4% vs. 57.8%, P = 0.014). These differences in DAS28 reduction and the proportion of patients with remission persisted at 48 weeks. However, there was no significant difference in hand and wrist erosion progression. In vitro, tocilizumab and 1,25(OH)₂D treatment synergistically suppressed IL-17 production and osteoclastogenesis.@*CONCLUSION@#RA patients treated with IL-6 antibody show a better response when they have sufficient serum vit D. Tocilizumab and 1,25(OH)₂D synergistically suppress IL-17 production and osteoclast differentiation in RA patients.

Quantitative evaluation of the molecular marker using droplet digital PCR

Transposable elements (TEs) constitute approximately half of Bovine genome. They can be a powerful species-specific marker without regression mutations by the structure variation (SV) at the time of genomic evolution. In a previous study, we identified the Hanwoo-specific SV that was generated by a TE–association deletion event using traditional PCR method and Sanger sequencing validation. It could be used as a molecular marker to distinguish different cattle breeds (i.e., Hanwoo vs. Holstein). However, PCR is defective with various final copy quantifications from every sample. Thus, we applied to the droplet digital PCR (ddPCR) platform for accurate quantitative detection of the Hanwoo-specific SV. Although samples have low allele frequency variation within Hanwoo population, ddPCR could perform high sensitive detection with absolute quantification. We aimed to use ddPCR for more accurate quantification than PCR. We suggest that the ddPCR platform is applicable for the quantitative evaluation of molecular markers.

Cosmetic outcomes of cesarean section scar; subcuticular suture versus intradermal buried suture

OBJECTIVE: The objective of the study was to compare cosmetic outcomes and overall satisfaction rate of cesarean section scar between conventional subcuticular suture and intradermal buried vertical mattress. METHODS: Patients were enrolled to the study by chart review. A scar assessment was obtained retrospectively through a telephone survey. The patient component of the patient and observer scar assessment scale (POSAS) was utilized along with the overall satisfaction of the patient regarding their cesarean section scar and their willingness to choose the same skin closure technique when anticipating their next cesarean section. RESULTS: A total of 303 cases of cesarean section was recruited, 102 finished telephone surveys were calculated for the analyses. Subcuticular suture was regarded as control group (n=52) and intradermal buried suture as test group (n=50). The PSAS score of the test group (mean, 21.8) was lower than that of the control group (mean, 28), with a statistical significance (P=0.02). Overall satisfaction rate did not differ between the two groups. Two parameters of the PSAS score and the level of overall satisfaction showed significant correlation (Pearson's r, −0.63; P < 0.01). CONCLUSION: We suggested the use of intradermal buried vertical mattress as a cosmetically superior skin closure method for application in cesarean sections over subcuticular stitch.

Sleep Quality Independently Affects Health-related Quality of Life and Cognitive Function in Korean Female Patients with Rheumatoid Arthritis: a Case-control Study

BACKGROUND: This study aimed to address sleep quality in patients with rheumatoid arthritis (RA) and to determine how it affects health-related quality of life (HRQoL) and cognitive function. METHODS: One hundred and twenty-three patients with RA and 76 healthy controls were enrolled in this study. Sleep quality was assessed using the Korean version of the Pittsburgh Sleep Quality Index (PSQI). Cognitive function and HRQoL was evaluated by a Korean-Montreal Cognitive Assessment (MoCA-K) and 36-item Short-Form Health Survey (SF-36), respectively. Other clinical, demographic, and laboratory data were obtained from retrospective medical chart review. RESULTS: More patients in the RA group reported poor sleep quality (PSQI > 5) than in the control group (61% [75/123] vs. 39.5% [30/76]; P = 0.003). Total PSQI was also significantly higher in the RA group (median [interquartile range], 7 [5–11] vs. 5 [3–6.75]; P = 0.001). Total PSQI score negatively correlated with MoCA-K score (Spearman's rho (r) = −0.223; P = 0.003) with a physical component summary (PCS) of SF-36 (r = −0.221; P = 0.003) and a mental component summary (MCS) of SF-36 (r = −0.341; P < 0.001), which means that poor sleep quality was associated with poor cognitive function and low HRQoL. CONCLUSION: The findings of this study suggest that poor sleep quality is an independent risk factor for low HRQoL and cognitive dysfunction. Efforts to improve the sleep quality of RA patients seem to be an important aspect of integrative treatment for RA.

A Case of Disseminated Candidiasis and Subsequent Breakthrough Pulmonary Mucormycosis after Consolidation Chemotherapy for Acute Myeloid Leukemia / 감염과화학요법

Invasive fungal infections (IFIs) are an important cause of morbidity and mortality in patients with acute leukemia who are receiving chemotherapy. Primary prophylaxis with antifungal agents has become the standard of care in this setting; as a result, invasive candidiasis has shown a significant reduction. However, broad use of antifungal prophylaxis has led to an increase in breakthrough candidiasis with reduced susceptibility or resistance to fluconazole. In addition, an increase in breakthrough mucormycosis has been reported in studies of voriconazole prophylaxis. We report on a case of disseminated candidiasis and subsequent breakthrough pulmonary mucormycosis in a patient with acute myeloid leukemia undergoing consolidation chemotherapy. To the best of our knowledge, in Korea, this is the first report of these two independent IFIs occurring in a single patient.