Effect of Rifampin and Rifabutin on Serum Itraconazole Levels in Patients with Chronic Pulmonary Aspergillosis and Coexisting Nontuberculous Mycobacterial Infection

We investigated the effects of rifampin and rifabutin on serum itraconazole levels in patients with chronic pulmonary aspergillosis. Serum itraconazole concentrations were significantly lower in patients who received itraconazole with rifampin (median, 0.1 μg/ml; P < 0.001) or rifabutin (median, 0.34 μg/ml; P < 0.001) than those receiving itraconazole alone (median, 5.92 μg/ml). Concomitant use of rifampin or rifabutin and itraconazole should be avoided in patients with chronic pulmonary aspergillosis and coexisting mycobacterial infections.     

Serial blood concentration of polyethoxylated tallow amine and clinical presentations in acute herbicide poisoning

<正>1Department of Emergency Medicine, Chungnam National University Hospital, Daejeon 35015, South Korea2Department of Emergency Medicine, College of Medicine, Chungnam National University, Daejeon 35015, South Korea3Forensic Toxicology Division, National Forensic Service, Daejeon 34054, South Korea4Department of Emergency Medicine, Chungbuk National University Hospital, Cheongju 28644, South Korea Corresponding Author:Wonjoon Jeong, Email:gardenjun@hanmail.net     

Prognostic factors and causes of death in Korean patients with idiopathic pulmonary fibrosis

The purpose of this study was to investigate the prognostic factors at initial presentation and the causes of death in Korean patients with idiopathic pulmonary fibrosis (IPF), which might be different report wise, in comparison to the western countries. A retrospective review of 88 patients (mean 60.3 years, 69 male) was carried out and they were diagnosed as IPF positive. After diagnosis, the survival rate was 57% and 41% for third and fifth year, respectively (mean follow-up 39.1 months). Mortality was closely correlated with severe dyspnea at presentation (Hazard Ratio [HR], 2.6 per grade; p=0.015), lower initial forced vital capacity (HR, 1.7 per 10% predicted; p=0.004) and lower initial diffusing capacity of the lung (HR, 1.5 per 10% predicted; p=0.033). Treatment with specific drugs was ineffective against the survival when compared with symptomatic supportive care. Thirty-four patients (68%) died of worsened respiratory failure, seven (14%) died of infection and only one patient showed cardiovascular death. In conclusion, our study suggests that the severity of dyspnea and lung function tests at the time of diagnosis are the predictive factors for the survival of patients with IPF. In comparison to the reports from western countries, we observed that respiratory failure and pulmonary infection were more frequent causes of death, while cardiovascular death was rare in Korean patients with IPF.     

Short-Term Effectiveness of Oral Nirmatrelvir/Ritonavir Against the SARS-CoV-2 Omicron Variant and Culture-Positive Viral Shedding

BackgroundInformation on the effectiveness of nirmatrelvir/ritonavir against the omicron is limited. The clinical response and viral kinetics to therapy in the real world need to be evaluated.MethodsMild to moderate coronavirus disease 2019 (COVID-19) patients with risk factors for severe illness were prospectively enrolled as a treatment group with nirmatrelvir/ritonavir therapy versus a control group with supportive care. Serial viral load and culture from the upper respiratory tract were evaluated for seven days, and clinical responses and adverse reactions were evaluated for 28 days.ResultsA total of 51 patients were analyzed including 40 in the treatment group and 11 in the control group. Faster symptom resolution during hospitalization (P = 0.048) was observed in the treatment group. Only minor adverse reactions were reported in 27.5% of patients. The viral load on Day 7 was lower in the treatment group (P = 0.002). The viral culture showed a positivity of 67.6% (25/37) vs. 100% (6/6) on Day 1, 0% (0/37) vs. 16.7 (1/6) on Day 5, and 0% (0/16) vs. 50.0% (2/4) on Day 7 in the treatment and control groups, respectively.ConclusionsNirmatrelvir/ritonavir against the omicron was safe and resulted in negative viral culture conversion after Day 5 of treatment with better symptomatic resolution.     

CD8alpha+ dendritic cells enhance the antigen-specific CD4+ T-cell response and accelerate development of collagen-induced arthritis

To investigate the role of CD8alpha(+) DCs in the development of collagen-induced arthritis (CIA). The immunogenic properties of CD8alpha(+) and CD8alpha(-) DC subsets were investigated by mixed-lymphocyte reaction and cytokine enzyme-linked immunoassay. CII-pulsed CD8alpha(+) DCs or CD8alpha(-) DCs with CD4(+) T cells from CIA mice were adoptively transferred onto the hind footpad of DBA mice. The onset of arthritis and the arthritis index were examined for 14 weeks after adoptive transfer. Expression of MHC-II and CD80 but not CD86 and CD40 was higher in CD8alpha(+) DCs than in CD8alpha(-) DCs from the spleens of CIA mice. Culturing CD8alpha(+) DCs with CD4(+) T cells significantly increased the proliferative response of CD4(+) T cells in the presence of CII. The production of interleukin (IL)-12p70, IL-17, interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha was slightly increased in CD8alpha(+) DCs than in CD8alpha(-) DCs. DBA/1 mice that were adoptively transferred with CII-pulsed CD8alpha(+) DCs and CD4(+) T cells into the footpads showed accelerated onset of CIA compared to control group. By contrast, CD8alpha(-) DCs showed a partial inhibitory effect on CIA. These findings show that CD8alpha(+) DCs accelerated the onset of CIA when aoptively transferred with CD4(+) T cells and that CD8alpha(+) DCs provoke the development of CIA probably by stimulating the immune responses of CII-reactive CD4(+) T cells and by increasing the production of inflammatory cytokines.     

Five-year outcomes of sirolimus-eluting versus paclitaxel-eluting stents: A propensity matched study: Clinical evidence of late catch-up?

Background

Siroliums-eluting stents (SES) and paclitaxel-eluting stents (PES) have been widely used for the treatment of coronary artery disease. We investigated 5-year clinical outcomes of patients treated with SES versus PES in a multicenter registry.

Methods

We used a propensity score matching method with 2:1 matching, including 512 patients treated with SES and 256 patients treated with PES from March 2003 to December 2004. The primary endpoint was major adverse cardiac events, which included all-cause death, myocardial infarction (MI), and target vessel revascularization (TVR).

Results

After matching, baseline characteristics were similar between the two groups. At 5 years, cumulative survival free of major adverse cardiac events, MI, and stent thrombosis did not differ between the two groups. Survival free of TVR at 5 years was higher in the SES group (88.4%) than the PES group (84.3%, Log-rank p = 0.016). In contrast to the trend toward more likely target lesion revascularization in the PES group during the first 2 years (hazard ratio 0.62, p = 0.057), target lesion revascularization tended to occur more frequently in the SES group from 2 to 5 years (hazard ratio 2.26, p = 0.099).

Conclusions

Long-term risk of TVR was slightly lower with SES, compared with PES, despite no significant difference in major adverse cardiac events. However, the SES group had more frequent target lesion reintervention 2 to 5 years after stent implantation, whereas reintervention in the PES group occurred mainly within the first 2 years. This may reflect the temporal difference in neointimal growth of the two stent types.     

Pre-B cells and other possible precursor lymphoid cell lines derived from patients with X-linked agammaglobulinemia

A group of unique Epstein-Barr virus-containing cell lines was derived from the bone marrow of three patients with X-linked agammaglobulinemia. Efforts to obtain cell lines from the peripheral blood of these patients were uniformly unsuccessful. Immunofluorescence analyses as well as biosynthetic studies with [(35)S]methionine indicated unusual patterns of Ig synthesis in many of these bone marrow derived lines. Seven of the lines were of particular interest in that two produced no Ig of any type; two others showed no Ig by fluorescence but small amounts by [(35)S]methionine labeling; one expressed only cytoplasmic μ chains without any evidence of light chain synthesis, and two produced primarily μ chains with only slight amounts of light chains. One of the lines without membrane or cytoplasmic Ig studied in detail grew like a typical lymphoid line and was carried in intermittent culture over a period of 2 yr without Ig expression. One line grew quite differently and resembled the round cell type described previously, which has been obtained from a variety of sources. The cell line with cytoplasmic μ chains and no light-chain expression had the characteristic properties of pre-B cells. Three normal type Ig-producing cell lines also were obtained from the patients. The accumulated evidence obtained in the present study indicates that these unusual cell lines represent normal precursor cells of the B-cell lineage; these grew out in these cases because of the virtual absence of mature B cells that ordinarily overgrow the culture system. However, the possibility that in certain instances they reflect abnormal Ig synthesis characteristic of the disease has not been ruled out.     

Effects of a 12-week home-based exercise program on the level of physical activity, insulin, and cytokines in colorectal cancer survivors: a pilot study

Purpose

The purposes of this study are to examine (1) the feasibility and efficacy of two different home-based exercise protocols on the level of physical activity (PA), and (2) the effect of increased PA via home-based exercise program on biomarkers of colorectal cancer.

Methods

Seventeen patients (age 55.18 ± 13.3 years) with stage II–III colorectal cancer completed the 12-week home-based exercise program. Subjects were randomized into either casually intervened home-based exercise group (CIHE) or intensely intervened home-based exercise group (IIHE). The primary outcome was the level of PA. Furthermore, insulin, homeostasis model assessment of insulin resistance, insulin-like growth factor axis, and adipocytokines were measured.

Results

Both CIHE and IIHE program significantly increased the level of PA at 12 weeks compared to its level at baseline (CIHE, 10.00?±?8.49 vs. 46.07?±?45.59; IIHE, 12.08?±?11.04 vs. 35.42?±?27.42 MET hours per week). Since there was no difference in PA change between groups (p?=?0.511), the data was combined in analyzing the effects of increased PA on biomarkers. Increase in PA significantly reduced insulin (6.66?±?4.58 vs. 4.86?±?3.48 μU/ml, p?=?0.006), HOMA-IR (1.66?±?1.23 vs. 1.25?±?1.04, p?=?0.017), and tumor necrosis alpha-α (TNF-α 4.85?±?7.88 vs. 2.95?±?5.38 pg/ml, p?=?0.004), and significantly increased IGF-1 (135.39?±?60.15 vs. 159.53 ng/ml, p?=?0.007), IGF binding protein (IGFBP)-3 (2.67?±?1.48 vs. 3.48?±?1.00 ng/ml, p?=?0.013), and adiponectin (6.73?±?3.07 vs. 7.54?±?3.96 μg/ml, p?=?0.015).

Conclusion

CIHE program was as effective as IIHE program in increasing the level of PA, and the increase in PA resulted in significant change in HOMA-IR, IGF-1 axis, TNF-α, and adiponectin levels in stage II–III colorectal cancer survivors.