A fatal case of acute exacerbation of interstitial lung disease in a patient with rheumatoid arthritis during treatment with tocilizumab.

A 68-year-old man, who was a patient with established rheumatoid arthritis (RA) with RA-associated interstitial lung disease (RA-ILD) and pulmonary emphysema, began taking tocilizumab. Subsequently, he developed dyspnea parallel to improvement of RA. At 10 months after the administration of tocilizumab, he was urgently admitted because of exacerbation of ILD. He died despite receiving steroid pulse therapy and antibiotic therapy on a respirator. This is the first case report to describe the exacerbation of ILD during treatment with tocilizumab in the postmarketing surveillance (PMS) period

HbA1c is inversely associated with thyroid cysts in a euthyroid population: A cross-sectional study

Anti-thyroid peroxidase antibody (TPO-Ab) is revealed to be inversely associated with thyroid cysts among euthyroid population. TPO-Ab causes autoimmune thyroiditis by bolstering thyroid inflammation. Therefore, at least partly, absence of thyroid cysts could indicate latent thyroid damage. Since participants with subclinical hypothyroidism are reported to have higher HbA1c than normal healthy controls, HbA1c could be inversely associated with thyroid cysts through a mechanism reflecting latent thyroid damage. To investigate the association between HbA1c and thyroid cysts among a euthyroid population, a cross-sectional study was conducted on 1,724 Japanese individuals who were within the normal range of thyroid function [i.e., normal range of free triiodothyronine (T3) and free thyroxine (T4)] and aged 40–74 years. Among this study population, 564 were diagnosed with thyroid cysts. Independently of thyroid related hormones [thyroid stimulating hormone (TSH), free T3, and free T4] and known cardiovascular risk factors, HbA1c was found to be significantly inversely associated with the presence of thyroid cysts. This association remained significant even after this analysis was limited to participants within a normal range of TSH. The fully adjusted odds ratios (ORs) of thyroid cysts for 1 standard deviation (SD) increment of HbA1c were 0.84 (0.74, 0.95) for total participants and 0.80 (0.70, 0.92) for participants within a normal range of TSH. Among participants with normal thyroid function, HbA1c was inversely associated with the presence of thyroid cysts. The absence of thyroid cysts and higher levels of HbA1c could indicate the latent functional damage of the thyroid

Association between serum sodium level within normal range and handgrip strength in relation to hypertension status: a cross-sectional study

Serum sodium concentration within the normal range could act as an indicator of age-related changes such as decrease in muscle strength and impairment of capillary function. Since endothelial injury stimulates endothelial repair by enhancing CD34-positive cell production, the level of serum sodium may be inversely associated with that of circulating CD34-positive cells, thus indicating the degree of age-related endothelial injury. We conducted a cross-sectional study of 246 elderly Japanese men aged 60–69 years. Subjects were stratified by hypertension status because hypertension should act as a strong confounding factor for the analyses performed in this study. Serum sodium concentration was positively associated with handgrip strength in non-hypertensive subjects [standardized parameter estimate (β) = 0.29; p = 0.003], but not for hypertensive subjects (β = 0.01; p = 0.878), while it was inversely associated with circulating CD34-positive cell levels in non-hypertensive subjects [simple correlation coefficient (r) = − 0.28; p = 0.002] but not for hypertensive subjects (r = − 0.07; p = 0.454). For non-hypertensive elderly subjects, serum sodium concentration within the normal range is positively associated with handgrip strength and inversely associated with CD34-positive cells, thus partly indicating the degree of age-related endothelium injury. These associations could prove to be an efficient tool for clarifying the background mechanism governing the decrease in age-related muscle strength

Association between thyroid cysts and hypertension by atherosclerosis status: a cross-sectional study

Our recent studies indicate that thyroid cysts have clinical implications. Thyroid cysts could have a positive effect on the supply of thyroid hormones. Both hyperthyroidism and hypothyroidism cause hypertension. Hypothyroidism, but not hyperthyroidism, is a risk factor for atherosclerosis. Therefore, thyroid cysts could be associated with hypertension, and atherosclerosis might influence the association between thyroid cysts and hypertension. To evaluate the clinical significance of thyroid cysts, a cross-sectional study was conducted with 1801 Japanese aged 40–74 years. Thyroid cysts were significantly positively associated with hypertension in participants without atherosclerosis. However, there was a significant inverse association in those with atherosclerosis. The potential confounding factor adjusted odd ratios and 95% confidence intervals (95% CIs) were 1.49 (95% CI 1.17–1.90) for participants without atherosclerosis and 0.49 (95% CI 0.24–0.98) for those with atherosclerosis. The present study demonstrates that thyroid cysts have clinical implications because thyroid cysts support thyroid hormone activity. Our findings provide sufficient evidence to develop a risk assessment for hypertension for the general population, even though further research is required

Gamma-glutamyl transpeptidase (γ-GTP) has an ambivalent association with hypertension and atherosclerosis among elderly Japanese men: a cross-sectional study

Background: Even though there is bidirectional association between hypertension and atherosclerosis, atherosclerosis itself is involved in the process of endothelial repair. To clarify the association of endothelial repair with hypertension, a cross-sectional study was conducted. Methods: We conducted a cross-sectional study of 562 elderly Japanese men aged 60-69. As gamma-glutamyl transpeptidase (γ-GTP) could act as a marker of oxidative stress that injures endothelial cell and higher levels of CD34-positive cell indicate a higher activity of endothelial repair, we therefore performed a CD34-positive level specific analysis of γ-GTP on atherosclerosis and hypertension. Results: In the present study population, hypertension was independently and positively associated with atherosclerosis (multivariable odds ratio (OR) = 2.09 (1.30, 3.35)). Among participants with high CD34-positive cells, γ-GTP showed significant and positive association with atherosclerosis (OR of the log-transformed value of γ-GTP (OR) = 2.26 (1.32, 3.86)) but not with hypertension (OR = 0.77 (0.51, 1.17)). Among participants with low CD34-positive cells, even γ-GTP showed no significant association with atherosclerosis (OR = 0.92 (0.51, 1.68)), but was significantly and positively associated with hypertension (OR = 1.99 (1.27, 3.12)). Conclusions: γ-GTP revealed to have ambivalent association with hypertension and atherosclerosis. Active endothelial repair that is associated with atherosclerosis might have beneficial association with hypertension

Height and Active Arterial Wall Thickening in Relation to Thyroid Cysts Status among Elderly Japanese: A Prospective Study

Height is inversely associated with inflammation that stimulates endothelial repair. In our previous study involving elderly men aged 60–69 years, we found that active arterial wall thickening, which is known as the process of endothelial repair, requires CD34-positive cells. As thyroid hormone regulates CD34-positive cell production and as the absence of thyroid cysts might indicate latent damage in the thyroid, the status of thyroid cysts possibly influences the association between height and active arterial wall thickening. We conducted a 2-year follow-up study of Japanese aged 60–69 years. For participants with thyroid cysts, height was significantly inversely associated with active arterial wall thickening (thyroid function and baseline CIMT adjusted odds ratio of active arterial wall thickening for one increment of standard deviation of height (5.7 cm for men and 4.8 cm for women), 0.66 [0.49, 0.89]), while for those without thyroid cysts, a positive tendency between the two parameters was observed (1.19 [0.96, 1.50]). An inverse association between height and active arterial wall thickening was observed only for elderly participants with thyroid cysts possibly because of a supportive role of thyroid hormone, as the absence of thyroid cysts might indicate latent damage in the thyroid

Subclinical hypothyroidism and hypertension in relation to thyroid cysts: A cross-sectional study

Subclinical hypothyroidism is a condition characterized by a normal range of thyroid hormone [triiodothyronine (T 3) and thyroxine (T 4)] but with an elevated level of thyroid stimulating hormone (TSH) . It is also reported to be associated with hypertension. Since thyroid cysts could have a beneficial effect on the activation of thyroid hormone as reported in our previous study, their presence could influence the association between subclinical hypothyroidism and hypertension. To clarify those associations, a cross-sectional study of 1,724 Japanese within normal range of thyroid hormone (i.e., normal range of free T 3 and free T 4), aged 40-74 years, who participated in an annual health checkup in 2014 was conducted. Among the study population, 98 were diagnosed as having sublicnical hypothyroidism. For participants without a thyroid cyst, hypertension had a significant positive association with subclinical hypothyroidism, while for participants with a thyroid cyst, even though the power could not reach a significant value, an inverse tendency between hypertension and subclinical hypothyroidism was observed. The adjusted odd ratios (ORs) and 95% confidence intervals (CIs) were 1.91 (1.08, 3.37) for participants without thyroid cysts and 0.63 (0.26, 1.55) for participants with thyroid cysts, respectively. The status of thyroid cysts could act as a determining factor in the association between subclinical hypothyroidism and hypertension among participants within normal range of thyroid hormone

Normal Anti-Thyroid Peroxidase Antibody (TPO-Ab) Titers and Active Arterial Wall Thickening among Euthyroid Individuals: A Prospective Study

Among euthyroid individuals, having an anti-thyroid peroxidase antibody (TPO-Ab) titer in the normal range (negative) is positively associated with atherosclerosis as evaluated based on carotid intima-media thickness (CIMT). Atherosclerosis is an established risk factor for cardiovascular disease, but no significant association between yearly progression in CIMT and cardiovascular disease has been reported. Therefore, clarifying the association between having a TPO-Ab titer in the normal range and yearly progression in CIMT (i.e., active arterial wall thickening) among euthyroid individuals could help inform strategies for preventing cardiovascular disease. We conducted a prospective study of 1069 Japanese subjects with free triiodothyronine and free thyroxine levels within the normal range. Having a TPO-Ab titer in the normal range was significantly positively associated with baseline atherosclerosis and significantly inversely associated with active arterial wall thickening. After adjusting for known confounding factors, the adjusted odds ratio (OR) and 95% confidence interval (CI) of log (TPO-Ab titer) for baseline atherosclerosis and active arterial wall thickening was 2.16 (1.07, 4.35) and 0.59 (0.37, 0.93), respectively. Since progression in CIMT is a process of aggressive endothelial repair, deficient endothelial repair inhibits active arterial wall thickening. Therefore, high–normal TPO-Ab titers might induce a deficiency in endothelial repair

Associations among Ratio of Free Triiodothyronine to Free Thyroxine, Chronic Kidney Disease, and Subclinical Hypothyroidism

The ratio of free triiodothyronine (FT3) to free thyroxine (FT4) (FT3/FT4), a maker of peripheral thyroxin deiodination, could indicate activity of thyroid hormone. Since positive association between subclinical hypothyroidism (SCH) and chronic kidney disease (CKD) was reported, clarifying the association among FT3/FT4, SCH, and CKD could be an efficient tool to make a strategy for preventing CKD. A cross-sectional study with 1724 Japanese with normal thyroid hormone was conducted. Significant positive association between SCH and CKD was observed; the adjusted odds ratio (OR) and 95% confidence interval (95% CI) was 2.23 (1.38, 3.59). Even though, FT3/FT4 was found to be inversely associated with CKD whereas positively associated with SCH; the adjusted ORs and 95% CIs for 1 standard deviation (SD) increment of FT3/FT4 were 0.51 (0.35, 0.74) for CKD and 2.40 (1.34, 4.29) for SCH, respectively. FT3/FT4 was also found to be positively associated with SCH without CKD but not those with CKD; 1 SD increment of FT3/FT4 were 3.44 (1.72, 6.91) for SCH without CKD and 1.11 (0.40, 3.06) for SCH with CKD, respectively. Although further investigation is necessary, present study indicates that higher activity of peripheral thyroxin deiodination might have beneficial association on absence of CKD even among SCH which is positively associated with CKD

Two rare cases of adult-onset phalangeal microgeodic syndrome with magnetic resonance imaging-proven bone edema transiently occurring in winter

We report two rare cases of adult-onset phalangeal microgeodic syndrome (PMS), which commonly develops in children. Both cases were Japanese women, with case 1: 60. years old and case 2: 58. years old. They developed swelling and stiffness in their fingers in winter, and their symptoms disappeared without any treatment in summer. Magnetic resonance imaging (MRI) of bilateral hands showed diffuse bone edema of the middle and proximal phalanges in winter, but the abnormal findings also disappeared in summer. The specific abnormalities observed on MRI were very useful for the diagnosis of PMS. Interestingly, they appeared in winter and disappeared in summer in parallel with the symptoms