Factors predicting the response to low-dose methotrexate therapy in patients with rheumatoid arthritis: a better response in male patients

Methotrexate (MTX) is the most commonly used disease-modifying antirheumatic drug (DMARD) throughout the world. In Japan, MTX is recommended by the Japanese Ministry of Health, Labour, and Welfare to be given as the second or third DMARD and at a dosage of no more than 8 mg/week. We analyzed the efficacy of MTX in Japanese patients with RA in order to determine whether it is comparable to that in Western countries, where 15–20 mg/week of MTX is used, as well as to elucidate the factors associated with the favorable response to MTX. Around 8 mg/week of MTX was effective in half of the RA patients in the current study, and male sex was the only factor associated with a good response to MTX from a multivariate regression model analysis. Some of the patients who had a poor response to MTX showed an improvement with the addition of bucillamine or prednisolone. For the remaining patients, an increase in the MTX dosage to more than 8 mg/week or the use of biologics such as the anti-tumor necrosis factor (TNF)-α monoclonal antibody may be required.     

Impact of Triggering Events on Outcomes of Acute Heart Failure

Background

The onset of acute heart failure is known to be associated with increased physical activity and other specific behaviors that can trigger hemodynamic deterioration. This analysis aimed to describe the distribution of triggers in patients hospitalized for acute heart failure, and investigate their effects on in-hospital outcomes.

Genotypes at chromosome 22q12-13 are associated with HIV-1-exposed but uninfected status in Italians

OBJECTIVE: Despite multiple and repeated exposures to HIV-1, some individuals possess no detectable HIV genome and show T-cell memory responses to the viral antigens. HIV-1-reactive mucosal IgA detected in such uninfected individuals suggests their possible immune resistance against HIV. We tested if the above HIV-1-exposed but uninfected status was associated with genetic markers other than a homozygous deletion of the CCR5 gene. METHODS: Based on our mapping in chromosome 15 of a gene controlling the production of neutralizing antibodies in a mouse retrovirus infection, we genotyped 42 HIV-1-exposed but uninfected Italians at polymorphic loci in the syntenic segment of human chromosome 22, and compared them with 49 HIV-1-infected and 47 uninfected healthy control individuals by a closed testing procedure. RESULTS: A significant association was found between chromosome 22q12-13 genotypes and a putative dominant locus conferring anti-HIV-1 immune responses in the exposed but uninfected individuals. Distributions of linkage disequilibrium across chromosome 22 also differed between the exposed but uninfected and two other phenotypic groups. CONCLUSIONS: The data indicated the presence of a new genetic factor associated with the HIV-1-exposed but uninfected status.     

Slow receptor acquisition by NK cells regenerated in vivo from transplanted fetal liver or adult bone marrow stem cells

Adult mouse natural killer (NK) cells express two families of MHC class I-specific receptors, namely Ly49 and CD94/NKG2, whereas fetal and neonatal NK cells express only CD94/NKG2. After birth, Ly49(+) NK cells slowly increase and CD94/NKG2(+) NK cells decrease. The aim of this study was to determine whether murine NK cells develop differently from transplants of fetal liver and adult marrow stem cells and whether the adult marrow microenvironment is critical for NK receptor maturation. Enriched populations of stem cells were transplanted into adult mice, and the kinetics of NK receptor acquisition was examined. NK cells from osteopetrotic Csf1(op)/Csf1(op) mice, in which hematopoiesis within the marrow is severely limited, were also analyzed.NK cells regenerated from both fetal and adult stem cells initially resembled neonatal NK cells in their slow acquisition of Ly49 over several weeks, although the adult stem cell-derived NK cells matured approximately 10 days sooner. NK cells from adult Csf1(op)/Csf1(op) mice expressed normal levels of Ly49. Maturation of the NK receptor repertoire is a slow process regardless of their stem cell origin or reduced marrow space caused by osteopetrosis.     

Influences of environmental noise level and respiration rate on the accuracy of acoustic respiration rate monitoring

We tested the hypothesis that the environmental noise generated by a forced-air warming system reduces the monitoring accuracy of acoustic respiration rate (RRa). Noise levels were adjusted to 45–55, 56–65, 66–75, and 76–85 dB. Healthy participants breathed at set respiration rates (RRset) of 6, 12, and 30/min. Under each noise level at each RRset, the respiration rates by manual counting (RRm) and RRa were recorded. Any appearance of the alarm display on the RRa monitor was also recorded. Each RRm of all participants agreed with each RRset at each noise level. At 45–55 dB noise, the RRa of 13, 17, and 17 participants agreed with RRset of 6, 12, and 30/min, respectively. The RRa of 14, 17, and 16 participants at 56–65 dB noise, agreed with RRset of 6, 12, and 30/min, respectively. At 66–75 dB noise, the RRa of 9, 15, and 16 participants agreed with RRset of 6, 12, and 30/min, respectively. The RRa of one, nine, and nine participants at 76–85 dB noise agreed with RRset of 6, 12, and 30/min, respectively, which was significantly less than the other noise levels (P?<?0.05). Overall, 72.9% of alarm displays highlighted incorrect values of RRa. In a noisy situation involving the operation of a forced-air warming system, the acoustic respiration monitoring should be used carefully especially in patients with a low respiration rate.     

A case of cryopyrin-associated periodic fever syndrome during canakinumab administration complicated by inflammatory bowel disease

Clinical Rheumatology - Cryopyrin-associated periodic fever syndrome (CAPS) is a highly debilitating disorder, which is characterized by unregulated interleukin-1β production driven by...