Development and external validation of the DOAT and DOATS scores: simple decision support tools to identify disease progression among nonelderly patients with mild/moderate COVID-19.

BACKGROUND: During the fifth wave of the coronavirus disease 2019 (COVID-19) pandemic in Japan, which took place between June and September 2021, a significant number of COVID-19 cases with deterioration occurred in unvaccinated individuals < 65 years old. However, the risk factors for COVID-19 deterioration in this specific population have not yet been determined. This study developed a prediction method to identify COVID-19 patients < 65 years old who are at a high risk of deterioration. METHODS: This retrospective study analyzed data from 1,675 patients < 65 years old who were admitted to acute care institutions in Fukushima with mild-to-moderate-1 COVID-19 based on the Japanese disease severity criteria prior to the fifth wave. For validation, 324 similar patients were enrolled from 3 hospitals in Yamagata. Logistic regression analyses using cluster-robust variance estimation were used to determine predictors of disease deterioration, followed by creation of risk prediction scores. Disease deterioration was defined as the initiation of medication for COVID-19, oxygen inhalation, or mechanical ventilation starting one day or later after admission. RESULTS: The patients whose condition deteriorated (8.6%) tended to be older, male, have histories of smoking, and have high body temperatures, low oxygen saturation values, and comorbidities, such as diabetes/obesity and hypertension. Stepwise variable selection using logistic regression to predict COVID-19 deterioration retained comorbidities of diabetes/obesity (DO), age (A), body temperature (T), and oxygen saturation (S). Two predictive scores were created based on the optimism-corrected regression coefficients: the DOATS score, including all of the above risk factors, and the DOAT score, which was the DOATS score without oxygen saturation. In the original cohort, the areas under the receiver operating characteristic curve (AUROCs) of the DOATS and DOAT scores were 0.81 (95% confidence interval [CI] 0.77-0.85) and 0.80 (95% CI 0.76-0.84), respectively. In the validation cohort, the AUROCs for each score were both 0.76 (95% CI 0.69-0.83), and the calibration slopes were both 0.80. A decision curve analysis confirmed the clinical practicability of both scores in the validation cohort. CONCLUSIONS: We established two prediction scores that can quickly evaluate the risk of COVID-19 deterioration in mild/moderate patients < 65 years old.

Safety and effectiveness of baricitinib for rheumatoid arthritis in Japanese clinical practice: 24-week results of all-case post-marketing surveillance.

OBJECTIVES: To assess the safety and effectiveness of baricitinib treatment for rheumatoid arthritis (RA) in real-world clinical practice. METHODS: This ongoing all-case post-marketing surveillance study (starting September 2017) includes all patients with RA treated with baricitinib in Japan. Safety and effectiveness (disease activity) were assessed for 24 weeks. RESULTS: Safety analyses to February 2021 included 4731 patients (initial baricitinib dose: 4 mg/day, n = 3058; 2 mg/day, n = 1661; other, n = 12); 1059 (22.38%) were ≥75 years and 3362 (71.06%) previously received biologic therapy. The overall observational period was 1863.14 patient-years; 1174 (24.82%) patients discontinued baricitinib before Week 24, mostly for lack of effectiveness (n = 478; 10.10%). Adverse events occurred in 1271 (26.87%) patients [serious: 203 (4.29%); death: 18 (0.38%)]. The incidence of herpes zoster, hepatic function disorder, and serious infection was 3.09%, 2.77%, and 1.90%, respectively. Malignancy occurred in 17 patients (0.36%) and major adverse cardiovascular events in seven patients (0.15%). Among patients with effectiveness data, at least 26.57% (Boolean) achieved remission at Week 24. CONCLUSIONS: This large nationwide surveillance study evaluated the safety and effectiveness of 24 weeks of baricitinib for RA in real-world clinical practice. Continued surveillance of long-term safety is ongoing.

Real-world clinical outcomes of treatment with casirivimab-imdevimab among patients with mild-to-moderate coronavirus disease 2019 during the Delta variant pandemic.

Background: Mutations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may reduce the efficacy of neutralizing monoclonal antibody therapy against coronavirus disease 2019 (COVID-19). We here evaluated the efficacy of casirivimab-imdevimab in patients with mild-to-moderate COVID-19 during the Delta variant surge in Fukushima Prefecture, Japan. Methods: We enrolled 949 patients with mild-to-moderate COVID-19 who were admitted to hospital between July 24, 2021 and September 30, 2021. Clinical deterioration after admission was compared between casirivimab-imdevimab users (n = 314) and non-users (n = 635). Results: The casirivimab-imdevimab users were older (P < 0.0001), had higher body temperature (≥ 38°C) (P < 0.0001) and greater rates of history of cigarette smoking (P = 0.0068), hypertension (P = 0.0004), obesity (P < 0.0001), and dyslipidemia (P < 0.0001) than the non-users. Multivariate logistic regression analysis demonstrated that receiving casirivimab-imdevimab was an independent factor for preventing deterioration (odds ratio 0.448; 95% confidence interval 0.263-0.763; P = 0.0023). Furthermore, in 222 patients who were selected from each group after matching on the propensity score, deterioration was significantly lower among those receiving casirivimab-imdevimab compared to those not receiving casirivimab-imdevimab (7.66% vs 14.0%; p = 0.021). Conclusion: This real-world study demonstrates that casirivimab-imdevimab contributes to the prevention of deterioration in COVID-19 patients after hospitalization during a Delta variant surge.

Baricitinib versus Placebo or Adalimumab in Rheumatoid Arthritis.

BACKGROUND: Baricitinib is an oral, reversible inhibitor of the Janus kinases JAK1 and JAK2 that may have therapeutic value in patients with rheumatoid arthritis. METHODS: We conducted a 52-week, phase 3, double-blind, placebo- and active-controlled trial in which 1307 patients with active rheumatoid arthritis who were receiving background therapy with methotrexate were randomly assigned to one of three regimens in a 3:3:2 ratio: placebo (switched to baricitinib after 24 weeks), 4 mg of baricitinib once daily, or 40 mg of adalimumab (an anti-tumor necrosis factor α monoclonal antibody) every other week. End-point measures evaluated after adjustment for multiplicity included 20% improvement according to the criteria of the American College of Rheumatology (ACR20 response) (the primary end point), the Disease Activity Score for 28 joints (DAS28), the Health Assessment Questionnaire-Disability Index, and the Simplified Disease Activity Index at week 12, as well as radiographic progression of joint damage as measured by the van der Heijde modification of the total Sharp score (mTSS) (range, 0 to 448, with higher scores indicating greater structural joint damage) at week 24. RESULTS: More patients had an ACR20 response at week 12 with baricitinib than with placebo (primary end point, 70% vs. 40%, P<0.001). All major secondary objectives were met, including inhibition of radiographic progression of joint damage, according to the mTSS at week 24 with baricitinib versus placebo (mean change from baseline, 0.41 vs. 0.90; P<0.001) and an increased ACR20 response rate at week 12 with baricitinib versus adalimumab (70% vs. 61%, P=0.014). Adverse events, including infections, were more frequent through week 24 with baricitinib and adalimumab than with placebo. Cancers were reported in five patients (two who received baricitinib and three who received placebo). Baricitinib was associated with reductions in neutrophil counts and increases in levels of creatinine and low-density lipoprotein cholesterol. CONCLUSIONS: In patients with rheumatoid arthritis who had had an inadequate response to methotrexate, baricitinib was associated with significant clinical improvements as compared with placebo and adalimumab. (Funded by Eli Lilly and Incyte; ClinicalTrials.gov number, NCT01710358 .).

Safety profile of baricitinib in Japanese patients with active rheumatoid arthritis with over 1.6 years median time in treatment: An integrated analysis of Phases 2 and 3 trials.

Objectives: Baricitinib is a selective oral inhibitor of JAK1/JAK2 for patients with moderately-to-severely active rheumatoid arthritis (RA). Baricitinib's safety profile in Japanese patients was evaluated using six studies (five Ph2/Ph3 trials, one long-term extension study through 01 September 2016) from an integrated database (nine RA studies).Methods: Incidence rates (IRs) or exposure-adjusted IRs (EAIRs) of adverse events (AEs) per 100 patient-years (PY) were calculated using data which included RA patients exposed to any baricitinib dose.Results: Five hundred and fourteen Japanese patients received baricitinib for 851.5 total PY of exposure (median 1.7 years, maximum 3.2). The EAIR of treatment-emergent AEs was 57.4/100PY. There were no deaths; 31 patients had serious infections (IR: 3.6/100PY), 55 herpes zoster (6.5), 0 tuberculosis, 10 malignancies (1.1) including two lymphomas, two major cardiovascular AEs (0.3), one gastrointestinal perforation (0.1), and four deep vein thrombosis (0.5). In Japanese patients, herpes zoster was more frequent than that of patients overall in the integrated database, but the events were considered manageable.Conclusion: In this analysis, baricitinib had acceptable safety profile in Japanese RA patients in the context of demonstrated efficacy. Aside from herpes zoster, baricitinib safety was not notably different between Japanese RA patients and those RA patients in the integrated database.Trial registration: NCT01185353, NCT00902486, NCT01469013, NCT01710358, NCT01721044, NCT01721057, NCT01711359, and NCT01885078 at https://clinicaltrials.gov/.

Self-monitoring of urinary salt excretion as a method of salt-reduction education: a parallel, randomized trial involving two groups.

OBJECTIVE: The present study aimed to evaluate salt-reduction education using a self-monitoring urinary salt-excretion device. DESIGN: Parallel, randomized trial involving two groups. The following parameters were checked at baseline and endline of the intervention: salt check sheet, eating behaviour questionnaire, 24 h home urine collection, blood pressure before and after urine collection. SETTING: The intervention group self-monitored urine salt excretion using a self-measuring device for 4 weeks. In the control group, urine salt excretion was measured, but the individuals were not informed of the result. SUBJECTS: Seventy-eight individuals (control group, n 36; intervention group, n 42) collected two 24 h urine samples from a target population of 123 local resident volunteers. The samples were then analysed. RESULTS: There were no differences in clinical background or related parameters between the two groups. The 24 h urinary Na:K ratio showed a significant decrease in the intervention group (-1·1) compared with the control group (-0·0; P=0·033). Blood pressure did not change in either group. The results of the salt check sheet did not change in the control group but were significantly lower in the intervention group. The score of the eating behaviour questionnaire did not change in the control group, but the intervention group showed a significant increase in eating behaviour stage. CONCLUSIONS: Self-monitoring of urinary salt excretion helps to improve 24 h urinary Na:K, salt check sheet scores and stage of eating behaviour. Thus, usage of self-monitoring tools has an educational potential in salt intake reduction.

Efficacy and safety of baricitinib in Japanese patients with active rheumatoid arthritis: A 52-week, randomized, single-blind, extension study.

OBJECTIVES: The objective of this study is to evaluate the efficacy and safety of long-term (64 weeks; 52-week extension of a 12-week study) baricitinib treatment in Japanese patients with active rheumatoid arthritis (RA) despite methotrexate therapy. METHODS: Patients (N = 145) with active RA were randomized to placebo, 1mg, 2mg, 4mg, or 8mg baricitinib for the first 12 weeks. During the 52-week extension period, patients on 4mg or 8mg baricitinib remained on the same dose and all other patients were re-randomized to 4mg or 8mg baricitinib. Most patients on 8mg baricitinib were switched to 4mg by week 64 (protocol amendment); data analysis was based on the treatment group at the beginning of the extension period. RESULTS: Increases in the American College of Rheumatology (ACR) response rates (ACR20, ACR50, and ACR70) observed during the first 12 weeks were maintained during the extension period, accompanied by improvements in ACR core components. At week 64, a large proportion of patients (>40%) had low disease activity. Most treatment-related adverse events were mild or moderate; herpes zoster was the most common reason (11/27 patients) for discontinuation. CONCLUSIONS: The efficacy and safety profile of baricitinib was maintained during long-term treatment of Japanese patients with RA and background methotrexate therapy. Clinicaltrials.gov NCT01469013; Funding: Eli Lilly and Incyte.

Efficacy and safety of baricitinib in Japanese patients with rheumatoid arthritis: Subgroup analyses of four multinational phase 3 randomized trials.

OBJECTIVES: To evaluate efficacy/safety of baricitinib for rheumatoid arthritis (RA) in Japanese subpopulations from four phase 3 studies, and assess whether results in these subpopulations are consistent with the overall study populations. METHODS: Subgroup analyses (394 patients) of four phase 3 randomized controlled trials: RA-BEGIN [no or limited treatment with disease-modifying antirheumatic drugs (DMARDs)], RA-BEAM [inadequate response (IR) to methotrexate], RA-BUILD [IR to conventional synthetic DMARDs (csDMARDs)], and RA-BEACON (IR to tumor necrosis factor inhibitors receiving csDMARDs). RESULTS: For American College of Rheumatology 20% improvement (ACR20) response rate, Japanese patients receiving baricitinib 4-mg showed similar improvement compared to methotrexate at Week 24 (72 versus 69%; RA-BEGIN), and greater improvement compared with placebo at Week 12 (67 versus 34%; RA-BEAM). Japanese patients receiving baricitinib 4-mg also showed greater improvement compared with placebo at Week 12 in RA-BUILD and RA-BEACON. Across all studies, baricitinib was well-tolerated, with no deaths and one malignancy. In RA-BEGIN and RA-BEAM, herpes zoster rates were higher for Japanese patients than for overall populations; all events were mild/moderate. CONCLUSION: Data for baricitinib, with/without methotrexate, in Japanese subpopulations across all stages of the RA treatment continuum accord with the efficacy/safety profile in overall study populations. Baricitinib appears to be similarly effective in Japanese patients.

Interferon-α acts on the S/G2/M phases to induce apoptosis in the G1 phase of an IFNAR2-expressing hepatocellular carcinoma cell line.

Interferon-α (IFN-α) is used clinically to treat hepatocellular carcinoma (HCC), although the detailed therapeutic mechanisms remain elusive. In particular, IFN-α has long been implicated in control of the cell cycle, but its actual point of action has not been clarified. Here, using time lapse imaging analyses of the human HCC cell line HuH7 carrying a fluorescence ubiquitination-based cell cycle indicator (Fucci), we found that IFN-α induced cell cycle arrest in the G0/G1 phases, leading to apoptosis through an IFN-α type-2 receptor (IFNAR2)-dependent signaling pathway. Detailed analyses by time lapse imaging and biochemical assays demonstrated that the IFN-α/IFNAR2 axis sensitizes cells to apoptosis in the S/G2/M phases in preparation for cell death in the G0/G1 phases. In summary, this study is the first to demonstrate the detailed mechanism of IFN-α as an anticancer drug, using Fucci-based time lapse imaging, which will be informative for treating HCC with IFN-α in clinical practice.

Association of asthma education with asthma control evaluated by asthma control test, FEV1, and fractional exhaled nitric oxide.

BACKGROUND: Asthma education is an important adjunct for asthma control although the way asthma education affects asthma outcomes is poorly understood. The asthma control test (ACT), forced expiratory volume in 1 s (FEV(1)), and fractional exhaled nitric oxide (FeNO) have all been used as markers of asthma control. However, the use of FeNO as a surrogate marker remains controversial. OBJECTIVES: (i) To examine whether asthma education is associated with asthma control; (ii) to compare absolute levels and changes of ACT, FEV(1), and FeNO over a year; and (iii) to evaluate whether FeNO can be used as an additional marker of asthma control. METHODS: Fifty asthmatics with poor adherence (12 mild, 21 moderate, and 17 severe) received asthma education at study entry. Medications were unchanged for the first 3 months, and ACT, FEV(1), and FeNO measurements were recorded at entry, 3, 6, and 12 months. Asthma control was assessed at each visit and patients were categorized as either "stable" or "unstable" asthmatics according to the global initiative for asthma (GINA) guidelines. RESULTS: A significant decrease in FeNO and increase in ACT score were noted in the stable asthmatic group at 3 months (p < .001), and this persisted over 12 months. Significant correlations were seen between changes (Δ) in FeNO, ACT, and FEV(1) over time. However, significant correlations between the absolute levels were not maintained over 12 months. A decrease of ≥18.6% in FeNO and a ≥3-point increase in ACT score (sensitivity: 80% and 73.3% and specificity: 83.3% and 87.5%, respectively) were associated with stable asthma control although the absolute levels were not. CONCLUSIONS: Asthma education may be useful to achieve stable control. In addition, changes rather than absolute levels of FeNO and ACT may be better markers of asthma control.

Efficacy and safety of baricitinib in Japanese patients with autoinflammatory type I interferonopathies (NNS/CANDLE, SAVI, And AGS).

BACKGROUND: This study evaluated the efficacy and safety of baricitinib (Janus kinase-1/2 inhibitor), in adult and pediatric Japanese patients with Nakajo-Nishimura syndrome/chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (NNS/CANDLE), stimulator of interferon genes-associated vasculopathy with onset during infancy (SAVI), or Aicardi-Goutières syndrome (AGS). METHODS: A Phase 2/3, multicenter, open-label study (NCT04517253) was conducted across 52 weeks. Primary efficacy endpoint assessed the change in mean daily diary score (DDS) from baseline to the end of primary treatment period. Other efficacy endpoints included change in mean DDS to the end of maintenance period, daily corticosteroid use, Physician's Global Assessment of Disease Activity (PGA) scores, and daily symptom-specific score (DSSS) from baseline to primary and maintenance treatment periods. All treatment-emergent adverse events (TEAEs) that occurred postdosing were recorded. RESULTS: Overall, 9 patients (5 with NNS, 3 with SAVI, and 1 with AGS) were enrolled; 55.6% were females, mean age was 26 years, and mean corticosteroid use/weight was 0.2 mg/kg. At the end of primary treatment period, mean DDS decreased from baseline in patients with NNS/CANDLE (0.22) and SAVI (0.21) and increased in the patient with AGS (0.07). At the end of maintenance treatment period, mean DDS decreased from baseline in patients with NNS/CANDLE (0.18) and SAVI (0.27) and increased in the patient with AGS (0.04). Mean percent corticosteroid use decreased by 18.4% in 3 out of 5 patients with NNS/CANDLE and 62.9% in 1 out of 3 patients with SAVI. Mean PGA score decreased from baseline in patients with NNS/CANDLE (1.60), SAVI (1.33), and AGS (1.0), and mean DSSS improved from baseline. All patients reported ≥ 1 TEAE. Frequently reported AEs included BK polyomavirus detection (3; 33.3%), increased blood creatine phosphokinase (2; 22.2%), anemia (2; 22.2%), and upper respiratory tract infection (2; 22.2%). Three (33.3%) patients reported serious adverse events, 1 of which was related to study drug. One patient with SAVI died due to intracranial hemorrhage, which was not related to study drug. CONCLUSION: Baricitinib may offer a potential therapeutic option for patients with NNS/CANDLE, SAVI, and AGS, with a positive benefit/risk profile in a vulnerable patient population with multiple comorbidities. TRIAL REGISTRATION: NLM clinicaltrials.gov, NCT04517253 . Registered 18 August 2020.

Validation Study of Algorithms to Identify Malignant Tumors and Serious Infections in a Japanese Administrative Healthcare Database.

BACKGROUND: This retrospective observational study validated case-finding algorithms for malignant tumors and serious infections in a Japanese administrative healthcare database. METHODS: Random samples of possible cases of each disease (January 2015-January 2018) from two hospitals participating in the Medical Data Vision Co., Ltd. (MDV) database were identified using combinations of ICD-10 diagnostic codes and other procedural/billing codes. For each disease, two physicians identified true cases among the random samples of possible cases by medical record review; a third physician made the final decision in cases where the two physicians disagreed. The accuracy of case-finding algorithms was assessed using positive predictive value (PPV) and sensitivity. RESULTS: There were 2,940 possible cases of malignant tumor; 180 were randomly selected and 108 were identified as true cases after medical record review. One case-finding algorithm gave a high PPV (64.1%) without substantial loss in sensitivity (90.7%) and included ICD-10 codes for malignancy and photographing/imaging. There were 3,559 possible cases of serious infection; 200 were randomly selected and 167 were identified as true cases after medical record review. Two case-finding algorithms gave a high PPV (85.6%) with no loss in sensitivity (100%). Both case-finding algorithms included the relevant diagnostic code and immunological infection test/other related test and, of these, one also included pathological diagnosis within 1 month of hospitalization. CONCLUSIONS: The case-finding algorithms in this study showed good PPV and sensitivity for identification of cases of malignant tumors and serious infections from an administrative healthcare database in Japan.

Intravital two-photon imaging: a versatile tool for dissecting the immune system.

During the past decade, multi-photon or 'two-photon' excitation microscopy has launched a new era in the field of biological imaging. The near-infrared excitation laser for two-photon microscopy can penetrate thicker specimens, enabling the visualisation of living cell behaviour deep within tissues and organs without thin sectioning. The minimised photobleaching and toxicity enables the visualisation of live and intact specimens for extended periods. In this brief review, recent findings in intravital two-photon imaging for the physiology and pathology of the immune system are discussed. The immune system configures highly dynamic networks, where many cell types actively travel throughout the body and interact with each other in specific areas. Hence, real-time intravital imaging may be a powerful tool for dissecting the mechanisms of this dynamic system. The most unique characteristic of the immune system is its highly dynamic nature. A variety of cell types, such as lymphocytes, macrophages and dendritic cells (DCs), are continuously circulating throughout the body, migrating through the peripheral tissues and interacting with each other in their respective niches. Conventional methodologies in immunology, such as flow cytometry, cell or tissue culture, biochemistry and histology, have brought tremendous achievement within this field, although the dynamics of immune cells in an entire animal remain less clear. Technological progress of fluorescence microscopy has enabled us to visualise the intact biological phenomenon that has been uninvestigated. Among the advancements, the recent emergence and prevalence of two-photon, excitation-based, laser microscopy has revolutionised the research field, such that the dynamic behaviour of cells deep inside living organs can be visualised and analysed.

Validation study of asthma screening criteria based on subjective symptoms and fractional exhaled nitric oxide.

BACKGROUND: In the latest Global Initiative for Asthma guideline, neither sputum eosinophilia nor fractional exhaled nitric oxide (FeNO) have been evaluated prospectively as an aid in asthma diagnosis, but these measurements are being evaluated for potential use in determining optimal treatment. OBJECTIVE: To report criteria for screening asthma using subjective symptoms and FeNO levels and results of a prospective validation study using these criteria. METHODS: Sixty-one outpatients with recurrent cough, wheezing, or dyspnea underwent measurements of FeNO levels, pulmonary function, methacholine airway responsiveness, and inflammatory cells in induced sputum. The sensitivity, specificity, and concordance achieved using the FeNO-based criteria (at least 1 of the following subjective symptoms: recurrent cough, wheezing, or dyspnea and/or FeNO level ≥ 40 ppb) were analyzed and compared with the values obtained using conventional asthma diagnostic criteria, which includes subjective symptoms with any 2 of the following conditions: airway hyperresponsiveness, reversible airflow limitation, and eosinophilia in induced sputum. RESULTS: Of the 61 patients, 41 were diagnosed as having asthma by the conventional criteria, and 33 were diagnosed as having asthma by the FeNO-based criteria, which showed a sensitivity of 78.6%, a specificity of 89.5%, and a concordance rate of 0.62. Nine of 42 patients were misdiagnosed as not having asthma by FeNO-based criteria (mean [SD] FeNO level, 23.9 [8.0] ppb). Seven of 9 patients were diagnosed as having nonatopic asthma according to IgE levels. CONCLUSIONS: Asthma may be accurately diagnosed in daily practice on the basis of subjective symptoms and FeNO levels, particularly in atopic patients.

Spontaneous perirenal hematoma due to Wegener's granulomatosis after initiation of immunosuppressant.

Spontaneous perirenal hematoma (SPH) is a rare, life-threatening condition. We present a patient with Wegener's granulomatosis (WG) who developed SPH soon after the initiation of immunosuppressant therapy. Few cases of SPH as a complication of WG have been reported, though a rupture of an aneurysm in patients with polyarteritis nodosa can lead to SPH. Though immunosuppressant therapy is considered to be the first-line therapy for SPH with vasculitis, SPH could still occur after the initiation of an adequate treatment regimen.

Tocilizumab, a humanized anti-interleukin-6 receptor antibody, ameliorated clinical symptoms and MRI findings of a patient with ankylosing spondylitis.

Ankylosing spondylitis (AS) is a chronic inflammatory osteoarticular disease. Although the etiology remains unknown, proinflammatory cytokines, such as tumor necrosis factor α and interleukin-6, have been implicated in the development of AS. Here, we report that a patient with AS, whose disease had been refractory to conventional treatment regimens and who needed to receive continuous corticosteroid, responded well to tocilizumab. While further clinical evaluation is required, tocilizumab may be an optional treatment for AS.

Successful treatment of acquired hemophilia A, complicated by chronic GVHD, with tocilizumab.

A 65-year-old woman who had suffered from chronic graft-versus-host disease (GVHD) presented with extensive purpura and was diagnosed with acquired hemophilia A. Because she was refractory to corticosteroids and her condition was complicated with diabetes mellitus, glaucoma, and hypoglobulinemia, she was treated with tocilizumab. Tocilizumab treatment increased the activity of factor VIII in a rapid and sustained manner, leading to a reduction of the prednisolone dose. Tocilizumab may thus be an optional treatment modality for acquired hemophilia A.

[Differences of fractional exhaled nitric oxide (FeNO) levels performed using two different analyzers].

The measurement of fractional exhaled nitric oxide (FeNO) is going to become more wide-spread as a noninvasive marker for diagnosing and controlling bronchial asthma. In Japan, both stationary and portable FeNO analyzers are now available. However, the difference between these analyzers has not been fully examined. Therefore, the aim of this study is to determine whether there is a difference between a stationary FeNO analyzer (NA623NP, CHEST inc. Tokyo, Japan) and a portable analyzer (NIOX MINO, Aerocrine, Solna, Sweden). One hundred subjects (17 non-treated asthma cases, 45 asthma cases treated with inhaled corticosteroids, 21 with other respiratory disorders, 17 healthy subjects) were enrolled in the study. All the subjects were non- or ex-smokers. There was a strong positive correlation between FeNO (CHEST) and FeNO (MINO) (r = 0.970, p < 0.001). However, when FeNO levels between FeNO (CHEST) and FeNO (MINO) were compared in all subjects and each subject group, the levels of FeNO (MINO) were significantly lower than those of FeNO (CHEST) (p < 0.05). Finally, the following conversion equation was calculated: FeNO (CHEST) = FeNO (MINO) x 1.278 + 3.065. From these results, the following conclusion was drawn: when FeNO is measured by different analyzers, there might be differences between devices. Therefore, the conversion equation could help clinicians and researchers to compare data obtainable by these two analyzers.

[Transesophageal endoscopic ultrasonography guided-fine needle aspiration for the diagnosis of sarcoidosis].

Sarcoidosis is a multi-organ disorder of unknown etiology characterized by noncaseating epithelioid cell granulomas. The specimen for histopathological diagnosis is usually obtained by transbronchial lung biopsy (TBLB), but the diagnostic accuracy rate of TBLB is not satisfactory, especially for stage I patients. Since hilar and mediastinal lymphadenopathy is a common finding in patients with sarcoidosis, an approach to lymph nodes is expected to have a good diagnosis yield. We present 3 sarcoidosis patients in whom specimens obtained by TBLB, transbronchial needle aspiration (TBNA) and transesophageal endoscopic ultrasonography guided-fine needle aspiration (EUS-FNA). The histopathological appearance of specimens obtained by EUS-FNA for swollen mediastinal lymph nodes showed noncaseating epithelioid granulomas which are characteristic of sarcoidosis in all 3 patients. On the other hand, no specific findings were recognized in the specimens obtained by TBLB and TBNA in 2 out of 3 patients. These results suggest that EUS-FNA is useful to obtain diagnostic specimens in cases of sarcoidosis.

[A case of Lambert-Eaton myasthenic syndrome with small cell lung cancer, treated with 3,4-diaminopyridine].

A 77-year-old man was admitted to our hospital with muscle weakness and shortness of breath. Chest CT showed a mass in the left upper lobe, and electromyography showed waxing phenomenon with high-frequency repetitive stimulation. We diagnosed Lambert-Eaton myasthenic syndrome accompanying small cell lung cancer. He was treated with carboplatin and etoposide, and concurrent thoracic irradiation. Although, the tumor size decreased, his myasthenic symptoms remained. He started taking 3,4-diaminopyridine and his muscle weakness improved dramatically, and he was eventually able to walk finally. In some cases, anti-tumor therapies cannot improve the myasthenic symptoms. In such cases, 3,4-diaminopyridine could improve the quality of life, and should be approved in Japan.