[A case of suspected vertebral artery stump syndrome assessed by CT angiography].

A 55-year-old man developed ischemic stroke in the bilateral cerebellar hemispheres and bilateral occipital lobes. He was admitted to our hospital 17 months later with recurrent ischemic stroke in the posterior circulation. The left vertebral artery (VA) was occluded on brain magnetic resonance angiography but was visualized with a delay on continuous three-phase CT angiography (CTA). Conventional angiography confirmed a to-and-fro blood flow pattern at the distal end of the left VA, therefore the patient was diagnosed with VA stump syndrome (VASS). VASS is a recurrent posterior circulation ischemic stroke caused by thrombi in an occluded unilateral VA. VASS should be suspected in patients with unilateral VA occlusion and repeated posterior-circulation ischemic stroke. The diagnostic criteria for VASS include confirmation of VA occlusion and the presence of an antegrade flow component at the distal end. In this case, the presence of collateral circulation in the VA was suspected based on CTA findings, leading to the diagnosis of VASS. It was thus suggested that devising the imaging method of CTA may help diagnose VASS.

Noniatrogenic Meningitis Caused by Streptococcus salivarius Associated with Early Esophageal Cancer and Early Gastric Cancer.

Streptococcus salivarius is part of the normal oral cavity and gastrointestinal tract microflora and an unusual cause of acute bacterial meningitis. We herein report an 81-year-old man with S. salivarius meningitis, which led to a diagnosis of early esophageal cancer and early gastric cancer. S. salivarius infection may occur through the gastrointestinal mucosa when it is disrupted in association with early gastrointestinal cancer. To our knowledge, this is the first report describing S. salivarius meningitis associated with multiple early gastrointestinal cancers in the absence of other sources of infection.

Synthesis and structure of photodegradable 1-(4,5-dimeth-oxy-2,3-di-nitro-phen-yl)-2-methyl-propyl N-butyl-carbamate.

The reaction of 1-(4,5-dimeth-oxy-2,3-di-nitro-phen-yl)-2-methyl-propan-1-ol and butyl-iso-cyanate using di-butyl-tin dilaurate as a catalyst afforded 1-(4,5-dimeth-oxy-2,3-di-nitro-phen-yl)-2-methyl-propyl N-butyl-carbamate, C17H25N3O8, which released butyl-amine upon photoirradiation. Single crystals of the title compound were grown in a 1:1 mixed solution of hexane and ethyl acetate. Two nitro groups and one meth-oxy group are twisted out of the plane of the aromatic ring in the novel photo-protecting group. Inter-molecular hydrogen bonds are observed between N-butyl-carbamate moieties parallel to the a axis.

Change in Serum KL-6 Level during Biologic Treatment for Psoriasis.

BACKGROUND: We previously analyzed data from blood examination screenings, including serum Krebs von den Lungen (KL) -6 level, before starting biologic treatment for psoriasis in a real-world setting. However, we did not follow change in KL-6 level after the initiation of biologics. Furthermore, there has been no follow-up study of certolizumab pegol, risankizumab, or tildrakizumab. This study evaluated change in serum KL-6 levels in patients during treatment with biologics, including certolizumab pegol, risankizumab, and tildrakizumab. METHODS: We analyzed data from 111 patients. Change in KL-6 level was regarded as significant if it increased to greater than 500 U/mL at least once and if the maximum level after treatment with biologics was at least 1.5 times that of the baseline level. RESULTS: KL-6 level significantly changed during treatment with TNF inhibitors, IL-17 inhibitors, and IL-23 inhibitors in 9 (20.9%), 2 (6.3%), and 2 (5.6%) patients, respectively. Mean age, mean baseline KL-6 level, and frequency of TNF inhibitor use were higher in patients with a significant change in KL-6 level than those in patients without a significant change. Ten patients had minor interstitial changes on chest CT scans but no clinical signs suggesting interstitial pneumonia. CONCLUSIONS: Older patients with psoriasis and high baseline KL-6 levels must be carefully monitored during treatment with biologics, especially TNF inhibitors. Monitoring of KL-6 level and chest CT scans is necessary to exclude the possibility of drug-induced interstitial pneumonia.

Change in Antinuclear Antibody Titers during Biologic Treatment for Psoriasis.

BACKGROUND: We previously evaluated blood screening data, including antinuclear antibodies (ANA), before initiating biologic treatment for patients with psoriasis in a real-world setting. However, we did not analyze change in ANA titers after the start of biologics. No previous study has comprehensively investigated change in ANA titers over time in individual patients or the effectiveness of certolizumab pegol or tildrakizumab. OBJECTIVES: This study evaluated change in ANA titers in individual patients during treatment with biologics, including certolizumab pegol and tildrakizumab. METHODS: 111 patients were included in this study. Change in ANA was regarded as significant when the ANA titer was ×80 or more in patients with a previously undetectable ANA titer or when it increased by fourfold or more in those with a detectable ANA titer before treatment. RESULTS: The ratios of patients with a significant change in ANA titer who were treated with a tumor necrosis factor (TNF) inhibitor, interleukin (IL) -17 inhibitor, or IL-23 inhibitor were 34.9% (15/43), 0.0% (0/32), and 0.0% (0/36), respectively. There were 4 patterns of significant change in ANA titer: (i) an increase (n=8), (ii) a decrease after an increase (n=4), (iii) a decrease after an increase with a drug change (n=2), and (iv) an increase after a decrease after an increase (n=1). No symptom suggesting lupus syndrome was noted. CONCLUSIONS: ANA titers must be carefully monitored throughout treatment with biologics, especially TNF inhibitors, and the possibility of lupus-like syndrome should be excluded.

Active Tuberculosis in a Patient Receiving Adalimumab for Psoriatic Arthritis and Chemoprophylaxis for Latent Tuberculosis Infection.

Tumor necrosis factor (TNF) inhibitors, including adalimumab, are widely used to treat refractory psoriatic arthritis (PsA). Although isoniazid chemoprophylaxis is generally effective in preventing reactivation of latent tuberculosis infection (LTBI), prophylactic measures do not fully protect against development of active tuberculosis. We report a rare case of active tuberculosis despite chemoprophylaxis for LTBI in a patient receiving adalimumab for PsA. A 60-year-old Japanese woman who had received a diagnosis of psoriasis at age 35 years presented with arthralgia of the right hand, which she first noticed 2 months previously. Physical examination showed scattered erythematous papules and plaques with scales on her trunk, extremities, and scalp. Her right metacarpophalangeal and proximal interphalangeal joints were swollen and painful, and her right wrist and elbow were painful. PsA was diagnosed and adalimumab was initiated. Because an interferon-γ release assay (IGRA) showed a borderline result at screening, isoniazid was administered as chemoprophylaxis for LTBI. At 22 months after initiation of adalimumab, IGRA was positive and chest CT disclosed centrilobular nodules in both lungs and swelling of multiple lymph nodes. Culture of sputum at 24 months demonstrated Mycobacterium tuberculosis. Active tuberculosis was diagnosed, and treatment with a combination of isoniazid, rifampicin, ethambutol hydrochloride, and pyrazinamide was started. To ensure timely diagnosis and treatment of active tuberculosis, a tuberculosis expert should be consulted at an early stage, with regular screening and monitoring.

Erythema and Induration of Bacillus Calmette-Guérin Scar Associated With Multisystem Inflammatory Syndrome in Children in Japan: A Case Report.

Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare febrile disorder with multisystem organ involvement temporally associated with coronavirus 2019 infection (COVID-19) and frequently exhibits features mimicking Kawasaki disease (KD), another febrile disorder in children. The pathogenesis and the full clinical spectrum of MIS-C is poorly understood: It is still unclear whether MIS-C and KD are different syndromes or represent a common spectrum. The erythema and induration of Bacillus Calmette-Guérin (BCG) scar is one of the characteristic findings of KD, and is useful for the diagnosis in countries where BCG vaccination is mandated in infancy. Furthermore, such findings in BCG scar were also reported after SARS-CoV-2 vaccination, which may be related to molecular mimicry. However, there are no reports of changes at the BCG scar in MIS-C cases. Here, we report a case of MIS-C in a 3-year-old Hispanic boy in Japan, with erythema and induration at the BCG scar. The patient received BCG vaccination at 16 months of age in Japan. Four weeks before the onset, he had positive polymerase chain reaction (PCR) results for SARS-CoV-2 following household outbreak, although he was asymptomatic. He presented with fever and gastrointestinal symptoms, followed by the appearance of all six principal findings of complete KD. He exhibited congestive heart failure, following intravenous immunoglobulin (IVIG) therapy. He was diagnosed with MIS-C based on characteristic mucocutaneous and gastrointestinal symptoms, decreased cardiac function, and coagulopathy, in addition to laboratory data consistent with MIS-C. The BCG finding was present from the early stage of the disease. The patient was refractory to two doses of IVIGs, and the third IVIG plus prednisolone resulted in defervescence and improvement in heart failure. No coronary involvement was observed. This is the first case of erythema and induration at the BCG scar associated with MIS-C accompanied by KD features, which may give clinical and mechanistic insights in the understanding of the disease. Since the full spectrum of MIS-C is still evolving and both of them are syndromes with overlapped clinical features, further studies are warranted for deep phenotyping of MIS-C with KD features relative to KD in countries with mandatory BCG programs in infancy.

Real-world blood examination screening data before initiation of biologics for psoriasis patients.

Psoriasis is a chronic immune-mediated inflammatory skin disease characterized by hyperproliferation of epidermal keratinocytes. Biologics have been available for the treatment of patients with refractory psoriasis since 2010 in Japan, and as of December 2021, 10 biologics were available. The Biologics Review Committee of the Japanese Dermatological Association for Psoriasis recommends blood examination tests for antinuclear antibodies (ANA), Krebs von den Lugen (KL)-6, hepatitis B surface antigen (HBsAg), hepatitis B surface antibodies (HBsAb), hepatitis B core antibodies (HBcAb), hepatitis C virus (HCV) antibodies, HIV antibodies, human T-cell leukemia virus (HTLV)-1 antibodies, ß-D-glucan, and the T-cell spot (T-SPOT) test before initiation of biologics at screening. In this study, we evaluated the use of biologics for 127 psoriasis patients and the blood examination screening data before initiation of biologics in the real-world setting. Tumor necrosis factor inhibitors, interleukin (IL)-17 inhibitors and IL-23 inhibitors were initiated for 54 (42.5%), 36 (28.3%), and 37 (29.1%) patients, respectively. The numbers of patients positive for ANA, HBsAg, HBsAb, HBcAb, HCV antibody, HIV antibody, HTLV-1 antibody, and T-SPOT were 27 (21.3%), 0 (0%), 22 (17.3%), 20 (15.7%), three (2.4%), zero (0%), one (0.8%), and 4 (3.1%), respectively. The numbers of patients whose KL-6 and ß-D-glucan levels were higher than the reference values were seven (5.5%) and seven (5.5%), respectively. In the real-world setting, it is sometimes unavoidable to use biologics for those patients with abnormal data although careful monitoring is necessary.

Association of Transition of Laboratory Markers with Transition of Disease Activity in Psoriasis Patients Treated with Biologics.

BACKGROUND: Three categories of biologics-tumor necrosis factor (TNF) inhibitors, interleukin (IL) -17 inhibitors, and IL-23 inhibitors-are available for treatment of refractory psoriasis. Recent studies have shown that laboratory biomarkers such as peripheral blood neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR), and serum C-reactive protein (CRP) levels are associated with psoriasis or its severity. This study evaluated associations of transition of NLR, PLR, MLR, and CRP with transition of disease activity in psoriasis patients treated with the three categories of biologics. METHODS: Data from 67 patients were analyzed. Associations of transition of psoriasis area and severity index (PASI) score with the abovementioned laboratory markers were evaluated by using a mixed effects model with PASI as the response variable, laboratory markers as fixed effects collectively, and patients as random effects. RESULTS: In an analysis of all the patients, serum CRP and NLR were associated with PASI score (P=0.006 and P=0.001, respectively). In patients treated with TNF inhibitors, CRP and NLR were associated with PASI score (P=0.043 and P=0.002, respectively). In patients treated with IL-17 inhibitors, NLR was associated with PASI score (P=0.001). CONCLUSIONS: NLR appears to be the most reliable biomarker of the effect of treatment with biologics, especially IL-17 inhibitors.

Association study of transition of laboratory marker levels and transition of disease activity of atopic dermatitis patients treated with dupilumab.

BACKGROUND: Dupilumab, a fully human monoclonal antibody that blocks signalling pathways of interleukin (IL)-4 and IL-13, is effective in treating patients with atopic dermatitis (AD). We previously showed that transitions of serum thymus and activation-regulated chemokine (TARC) levels and eosinophil numbers were strongly associated with that of AD activity and that the transitions of serum lactate dehydrogenase (LDH) and immunoglobulin E (IgE) levels were weakly and not associated with that of AD activity, respectively, in patients treated without dupilumab. OBJECTIVES: The purpose of this study was to elucidate whether the association of the transition of laboratory marker levels and transition of disease activity in dupilumab-treated AD patients (present study) was different from that in patients who are not treated with dupilumab (previous study). METHODS: Sixty AD outpatients treated with dupilumab were included in this study. Associations between the transition of the eczema area and severity index (EASI) score and those of above-mentioned laboratory marker levels were evaluated using a mixed effects model of EASI as the response variable, laboratory markers as fixed effects and patients as random effects. RESULTS: The transitions of serum TARC and LDH levels were associated strongly with that of AD activity, but the transitions of serum IgE level and eosinophil numbers were associated with that of AD activity intermediately and weakly, respectively. CONCLUSIONS: Laboratory markers are useful for evaluating the effects of treatments for AD, but the meaning of each laboratory marker depends on the drugs used for treatment.

Association of carotid ultrasonography with perioperative stroke after thoracic aortic aneurysm treatment: a retrospective study.

PURPOSE: The purpose of this study was to verify whether carotid ultrasonography (CUS) findings could be associated with the occurrence of perioperative stroke after thoracic aortic aneurysm (TAA) treatment. METHODS: Patients with TAAs who were treated by either total arch replacement or thoracic endovascular aortic repair (TEVAR) were retrospectively enrolled. Left subclavian artery (LSA) embolization and bypass surgery of the left common carotid artery (CCA) to the LSA before TEVAR were additionally performed for some patients. CUS was performed before TAA treatment to evaluate carotid atherosclerosis and flow velocities of bilateral cervical arteries. After dividing patients into those with and without perioperative stroke, their background, atherosclerotic risk factors, history of stroke, TAA location and size, treatment procedures, and CUS parameters were compared between the two groups. RESULTS: Of the 60 patients (18 women, 42 men; mean age 73.5 ± 10.2 years) with TAA, four (7.5%) developed perioperative stroke. There were no significant differences in the patients' characteristics and their TAAs between those with and without perioperative stroke. For the CUS parameters, end-diastolic velocity (EDV) of bilateral CCAs was significantly decreased in perioperative stroke patients (with vs without stroke; right: 9.2 ± 1.8 vs. 14.5 ± 4.6 cm/s, P = 0.025, left: 9.1 ± 0.3 vs. 15.0 ± 4.5 cm/s, P = 0.012), whereas the resistance index (RI) of bilateral CCAs was significantly elevated (right: 0.76 vs. 0.87, P = 0.008, left: 0.76 vs. 0.87, P < 0.001). CONCLUSIONS: Lower EDV and higher RI of bilateral CCAs were significantly associated with perioperative stroke after TAA treatment. Thus, CUS findings may help predict the occurrence of perioperative stroke.

Dietary habits in Japanese patients with palmoplantar pustulosis.

Palmoplantar pustulosis (PPP) is a chronic dermatitis characterized by sterile intra-epidermal pustules associated with erythema and scales on the palms and soles. Tumor necrosis factor (TNF)-α/interleukin (IL)-23/IL-17 inflammatory pathway may be involved in the pathogenesis of PPP, and the skin lesions manifest the enhanced expression of IL-8 in keratinocytes and increased levels of antimicrobial peptide cathelicidin, leucine leucine-37 in vesicles/pustules. Some PPP patients are associated with arthro-osteitis, called pustulotic arthro-osteitis (PAO). Dietary habits may modulate the pathogenesis of PPP, however, have not been investigated in PPP patients. We evaluated dietary habits in adult Japanese PPP patients, using a validated, brief-type self-administered diet history questionnaire, and compared their results to those of age- and sex-matched healthy controls. The results in PPP patients with PAO were compared to those in the patients without. Japanese PPP patients showed higher body mass indices (BMIs), higher intakes of pulses and sugar/sweeteners, and lower intake of vitamin A, compared to those of healthy controls. The bivariate and multivariable logistic regression analysis showed that PPP was associated with high BMI, high intake of pulses, and low intake of vitamin A. The sodium intake and BMI were positively correlated with palmoplantar pustulosis area and severity index (PPPASI). The linear multivariate regression analysis revealed that sodium intake and BMI were predictors of PPPASI. The age and sodium intake in the patients with PAO were lower than those in the patients without. The bivariate and multivariable logistic regression analysis showed that PAO was negatively associated with age and sodium intake. This is the first study showing the dietary habits in patients with PPP. Further studies should clarify if the dietary intervention to correct the BMI and sodium intake will alter the progress of PPP.

Association of HLA-DRB1*04:05 allele with drug-induced interstitial lung disease in Japanese population.

Drug-induced interstitial lung disease (DILD) is a life-threatening adverse reaction. The Japanese population is more susceptible to DILD as compared with other populations, suggesting its pathogenesis could vary depending on ethnic genetic background. We conducted case-control studies to elucidate the association between DILD and HLA alleles in the Japanese. The 177 clinically diagnosed DILD patients and 3002 healthy controls for exploration and 55 DILD patients and 201 healthy controls for validation were genotyped for four HLA genes. HLA-DRB1*04:05 was significantly associated with DILD (corrected p = 0.014); this was also validated in the other set of patients/controls. Chemical drugs other than protein therapeutics showed this association (p = 1.7 × 10-4) . The Japanese population showed a higher HLA-DRB1*04:05 frequency than most other populations. In conclusion, HLA-DRB1*04:05 could be associated with DILD susceptibility in Japanese individuals, and its high general frequency may explain the high reported incidence of DILD in Japanese.

Dietary habits in Japanese patients with chronic spontaneous urticaria.

BACKGROUND: Chronic spontaneous urticaria (CSU) is defined as the spontaneously appearing weals and/or angioedema for more than 6 weeks. Dietary habits can modulate the pathogenesis of CSU. However, dietary intakes of nutrients or food in CSU patients, compared with healthy controls, have not been examined in quality and quantity. METHODS: We evaluated dietary habits in adult Japanese patients with chronic spontaneous urticaria using a validated, brief-type self-administered diet history questionnaire and compared the results to those of age- and sex-matched healthy controls. The severity of CSU was evaluated using the Urticaria Control Test. RESULTS: Japanese CSU patients showed higher body mass indices, higher intakes of eggs, vegetables other than green/yellow vegetables/mushrooms/algae, cholesterol, folic acid, dietary fibres, vitamin D, vitamin K, Cu, Fe, Pi, Ca, Mg, Na and salt, and lower intake of alcohol, compared to controls. The logistic regression analysis showed that CSU was associated with high body mass index and high intake of eggs. The intake of beverages was higher in uncontrolled CSU patients (Urticaria Control Test ≦11 points) than in controlled patients. The logistic regression analysis showed that uncontrolled CSU was associated with high intake of beverages. The intake of coffee, caffeine-rich and non-alcohol beverage, in uncontrolled CSU patients was higher than that in controlled patients. CONCLUSIONS: Chronic spontaneous urticaria was associated with high body mass index and high intake of eggs. Uncontrolled CSU was associated with high intake of beverages. Further studies should elucidate the relationships of these results with the development or exacerbation of CSU.

Dietary habits in Japanese patients with psoriasis and psoriatic arthritis: Low intake of meat in psoriasis and high intake of vitamin A in psoriatic arthritis.

Psoriasis is characterized by T-helper 17 cell-dominant abnormal immunity, and hyperproliferation and abnormal differentiation of epidermal keratinocytes. Some patients are associated with arthritis. Dietary habits can modulate the pathogenesis of psoriasis. Previous studies in Western countries showed higher body mass indices, higher intake of fat and lower intake of fish or vegetables in psoriatic patients compared with the reference groups. We evaluated dietary habits in adult Japanese psoriatic patients, using a validated brief-type self-administered dietary history questionnaire, and compared the results to those of age- and sex-matched healthy controls. The results in psoriatic patients with arthritis were compared with those in the patients without. Japanese psoriatic patients showed higher body mass indices, higher intake of fish/shellfish, pulses, sugar/sweeteners, vitamin B12 and vitamin D, and lower intake of meat, compared with those of healthy controls. The logistic regression analysis showed that psoriasis was associated with high body mass index and low intake of meat. The intake of confection in patients with high Psoriasis Area and Severity Index was higher than that in those with low index. The intake of ß-carotene, vitamin A and green/yellow vegetables in psoriatic patients with arthritis were higher than those in the patients without. The dietary habits in Japanese psoriatic patients are rather different from those in Western patients. This is the first study showing the differences in dietary habits between psoriatic patients with arthritis and those without. Further studies should elucidate the relationships of these results with skin and joint lesions in psoriatic patients.

The relationship between acrolein and oxidative stress in COPD: in systemic plasma and in local lung tissue.

Purpose: Cigarette smoke produces a high level of acrolein, which is thought to be pathogenically involved in the development of chronic obstructive pulmonary disease (COPD). The present study investigated the pathological role of acrolein in the development of COPD. Patients and methods: Acrolein concentration was measured in plasmas obtained from 47 patients with COPD and 18 current smokers without COPD, and in supernatants of homogenized lung tissues obtained from 10 never-smokers, 8 current smokers, and 8 patients with COPD by high-performance liquid chromatography. Oxidant status and antioxidant activity were measured using derivatives of reactive oxygen metabolite (d-ROM) and bio-antioxidant power (BAP), respectively, in the Free Radical Elective Evaluation FRAS4 system. In addition, immunohistochemistry was used to evaluate the over-presentation of acrolein in lung tissues of patients with COPD. Results: Plasma concentrations of acrolein were significantly higher in the patients with COPD than the non-COPD smokers (P<0.001), which significantly correlated with the oxidant status in patients with COPD (R=0.69, P<0.05). Similar pathological alterations in acrolein concentrations were found in the lung tissue supernatants of patients with COPD, which significantly correlated with the oxidant status in patients with COPD. Furthermore, acrolein was strongly expressed in the lung tissues of patients with COPD. Conclusion: The increased acrolein concentrations were highly involved in the pathogenesis of COPD through interference in the balance of oxidative stress versus antioxidant potentiality.