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The objective of the present study was to examine the effect of various root surface treatments on the initial attachement of gingival fibroblasts. Cultured fibroblasts were well spread and attached to demineralized dentin with citric acid, superficially curetted cementum, and root surface with periodontal ligament, while those on the planed dentin showed a poorly spread appearance. The first three root surfaces exhibited rough and irregular surface appearances with a well-developed filopodia and the latter root surface exhibited a smooth appearance, suggesting the texture of the root surface is closely associated with cell attachment. Interiorized collagen fibrils and numerous cytoplasmic vesicles were seen along the cell membrane of fibro blasts facing the root surfaces of the planed dentin, demineralized dentin, and superficially curetted cementum. Thus even the artificially exposed tooth surface with citric acid may be subjected to further alteration by fibroblasts. [ABSTRACT FROM PUBLISHER]

We examined whether or not gingival fibroblasts attach to curetted cementum surface in periodontally involved teeth. For experiment, superficial cementum in periodontally involved human teeth was curetted and cut into 3 × 3 mm fragments, put into a plastic plate and mixed with fibroblasts for 1 to 3 days. Numerous fibroblasts attached to the curetted cementum surfaces, while only a few fibroblasts could attach to the diseased cementum. For experiment, experimental periodontitis was induced in monkeys by leaving a resin plate in artificially created marginal bone crest for 3 months. In the flap surgery, only superficial cementum was curetted. Two- and 4-month biopsy specimens disclosed that the regenerated gingival tissues attached well to the curetted cementum surface. Both and results indicated subjacent cementum in periodontally involved teeth could be a suitable surface for fibrous attachment. [ABSTRACT FROM PUBLISHER]

Thoracoscopic pleural biopsy is an efficient procedure in patients with undiagnosed exudative pleurisy. Rigid or flexible forceps have been widely used for this procedure. Recently, the use of cryo-techniques was reported in pleural biopsy during semi-rigid thoracoscopy; however, the feasibility and safety of pleural cryobiopsy in elderly patients have not yet been fully elucidated. We describe two elderly patients who safely underwent semi-rigid thoracoscopic cryobiopsy and were diagnosed with tuberculous pleurisy. Both were >85 years of age, and chest auscultation revealed reduced breath sounds in the right lower zones. Laboratory investigations revealed an elevated level of C-reactive protein without leukocytosis in both patients. Computed tomography scan of the chest revealed right pleural effusion in both patients. Pleural fluid biochemical analysis results were indicative of an exudate. Sputum cultures demonstrated no bacterial growth and smears were negative for the presence of acid-fast bacilli. For definitive diagnosis, pleural biopsy was performed via thoracoscopic cryobiopsy. Specimens obtained from the cryoprobe demonstrated 200-300-μm caseating and non-caseating epitheloid cell granulomas with Langerhans type giant cells. Based on the above results, both patients were diagnosed with TB pleurisy. Anti-tuberculosis treatment resulted in good clinical outcome in both patients. Cryobiopsy is easier and more efficient than biopsy with conventional forceps. Our findings in these patients suggest that semi-rigid thoracoscopic cryobiopsy might be a useful alternative diagnostic method for undiagnosed pleural effusion in elderly patients. [ABSTRACT FROM AUTHOR]

Background: This study aimed to examine risk factors associated with critical coronavirus disease 19 (COVID-19) and to establish a risk predictive model for Japanese patients., Methods: We retrospectively assessed adult Japanese patients diagnosed with COVID-19 at the Japanese Red Cross Medical Center, Tokyo, Japan between February 1, 2020 and March 10, 2021. The patients were divided into critical and non-critical groups based on their condition during the clinical courses. Univariate and multivariate logistic regression analyses were performed to investigate the relationship between clinical characteristics and critical illness. Based on the results, we established a predictive model for the development of critical COVID-19., Results: In total, 300 patients were enrolled in this study. Among them, 86 were included in the critical group. Analyses revealed that age ≥65 y, hemodialysis, need for O 2 supplementation upon diagnosis, and an initial serum C-reactive protein level of ≥6.5 mg/dL were independently associated with the development of critical COVID-19. Next, a predictive model for the development of critical COVID-19 was created, and this included the following variables: age ≥65 y, male sex, diabetes, hemodialysis, need for O 2 supplementation upon diagnosis, and an initial serum C-reactive protein level of ≥6.5 mg/dL. The area under the receiver operating characteristic curve of the model was 0.86 (95% confidence interval, 0.81-0.90). Using a cutoff score of 12, the positive and negative predictive values of 74.0% and 80.4% were obtained, respectively., Conclusions: Upon diagnosis, the predictive model can be used to identify adult Japanese patients with COVID-19 who will require intensive treatment., Competing Interests: Conflict of Interest The authors declare no conflicts of interest., (Copyright © 2021 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Background: Coronavirus disease 2019 (COVID-19) has spread worldwide and is also an important disease in Japan. Thus, the optimal treatment strategy for severe COVID-19 should be established urgently. The effects of combination treatment with baricitinib-a Janus kinase inhibitor, remdesivir, and dexamethasone (BRD) are unknown., Methods: Patients who received combination therapy with BRD at the Japanese Red Cross Medical Center were enrolled in the study. All patients received baricitinib (≤14 d), remdesivir (≤10 d), and dexamethasone (≤10 d). The efficacy and adverse events were evaluated., Results: In total, 44 patients with severe COVID-19 were enrolled in this study. The 28-d mortality rate was low at 2.3% (1/44 patients). The need for invasive mechanical ventilation was avoided in most patients (90%, 17/19 patients). Patients who received BRD therapy had a median hospitalization duration of 11 d, time to recovery of 9 d, duration of intensive care unit stay of 6 d, duration of invasive mechanical ventilation of 5 d, and duration of supplemental oxygen therapy of 5 d. Adverse events occurred in 15 patients (34%). Liver dysfunction, thrombosis, iliopsoas hematoma, renal dysfunction, ventilator-associated pneumonia, infective endocarditis, and herpes zoster occurred in 11%, 11%, 2%, 2%, 2%, 2%, and 2% of patients, respectively., Conclusions: Combination therapy with BRD was effective in treating severe COVID-19, and the incidence rate of adverse events was low. The results of the present study are encouraging; however, further randomized clinical studies are needed., Competing Interests: Conflict of Interest The authors have no conflict of interest to declare in relation to this work., (Copyright © 2021 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Aims: Emergency medical service (EMS) may detect seizure-like activity in addition to agonal breathing in out-of-hospital cardiac arrest (OHCA). This study investigates the incidence and predictors of seizure-like activity in nontraumatic, EMS-witnessed OHCA and their association with clinical outcomes., Methods: This prospective study explored EMS-recorded concomitant signs/symptoms that lead to the requirement of advanced life support in patients with nontraumatic, EMS-witnessed OHCA. Seizure-like activity includes abnormal/tonic movements and eyeball deviation. Sudden OHCA was defined by the absence of signs/symptoms of impending cardiac arrest at EMS contact or progressive circulatory/respiratory depressions after the EMS contact. Neurologically favorable outcomes were defined as the cerebral performance category score of 1 or 2 at discharge., Results: From April 2012 to March 2020, 465 patients were studied. The incidence of seizure-like activity at cardiac arrest onset was 12.7% (59/465) in all patients with nontraumatic, EMS-witnessed OHCA. Seizure-like activity was common during shockable initial rhythm; in patients with "sudden" OHCA; and in patients who were younger, male, or had a presumed cardiac etiology. In a boosting tree, shockable initial rhythm, "sudden" OHCA, and presumed cardiac etiology were major factors that predicted the incidence of seizure-like activity. Multivariate logistic regression models including and excluding OHCA characteristics revealed that both seizure-like activity and agonal breathing recorded during EMS-witnessed OHCA were associated with favorable outcomes., Conclusions: Seizure-like activity is a major sign/symptom of the onset of "sudden" cardiac arrest of presumed cardiac etiology, particularly in patients with shockable initial rhythms. Such activity were significantly associated with neurologically favorable outcomes., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)

Background: The coronavirus disease (COVID-19) has afflicted large populations worldwide. Although vaccines aroused great expectations, their side effects on Japanese people and the antibody titer transition after vaccination are unclear., Methods: The side effects of the BNT162b2 mRNA COVID-19 vaccine in participants who received vaccination at our center were investigated. Some participants were also surveyed for the antibody titer transition., Results: In this study, 983 and 798 Japanese participants responded to the first and second doses, respectively. Side effects occurred in 757 (77.0%) and 715 participants (90.0%) after the first and second doses, respectively. No Grade 4 side effects occurred. The second dose had significantly more side effects than the first dose (p < 0.001). Side effects occurred after the second dose in 571 female (92.1%) and 178 male participants (80.1%). Female participants had a higher incidence of side effects than the male participants (p < 0.001). A comparison among the age groups showed significant differences (p = 0.018), and the frequency of side effects decreased with age. Twenty-three individuals participated in the survey of antibody titer transition. After the second vaccine dose, the median antibody titers for IgG and IgM were 3.76 and 0.07 AU/mL, respectively. Both IgG and IgM titers showed a significant increase over the study period (p < 0.001)., Conclusions: The BNT162b2 mRNA COVID-19 vaccine might be safe for Japanese people, and the antibody titer increased with two doses of vaccination. Larger nationwide studies are warranted to verify these findings., Competing Interests: Conflict of Interest The authors have no conflicts of interest to declare regarding this study., (Copyright © 2021 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Patients with refractory ascites that develops >3 months after allogenic stem cell transplantation typically have a poor prognosis. We present the case of a 61-year-old man who developed refractory massive ascites approximately 3 months after cord blood transplantation (CBT) and showed complete and spontaneous remission from ascites after 18 months. The patient complained of severe bloating and needed weekly paracentesis to manage the fluid levels. Laboratory tests indicated that the ascites was caused by liver fibrosis. After the patient underwent Keisuke-Matsusaki cell-free and concentrated ascites reinfusion therapy (KM-CART), we were able to decrease the frequency of paracentesis treatments. We planned a transjugular liver biopsy, but the patient contracted pneumocystis pneumonia before the procedure could be performed. Although the pneumonia improved, the ascites worsened again. However, weekly paracentesis spontaneously stopped the progression of ascites and eventually resolved it completely, resulting in the patient's survival.

Background: Coronavirus disease 2019 (COVID-19) is currently spreading worldwide. This study examined whether serum Krebs von den Lungen-6 (KL-6) level is a useful biomarker for evaluating the severity of COVID-19., Methods: We retrospectively examined patients diagnosed with COVID-19 at the Japanese Red Cross Medical Center between February 1, 2020, and May 15, 2020. Patients were divided into four categories based on clinical and radiological findings: mild, moderate, severe, and critical. Patients who presented with a mild or moderate illness and patients who started with or worsened to a severe or critical illness were classified as the non-severe and severe groups, respectively. The two groups were compared for patient characteristics, including serum KL-6 levels. Receiver operating characteristic curves were used to define the optimum cut-off value of serum KL-6 level to evaluate COVID-19 severity., Results: A total of 54 patients were enrolled, including 33 in the non-severe group and 21 in the severe group, of which four died. Compared with those in the non-severe group, more patients in the severe group were significantly older and had comorbidities. Serum KL-6 levels were significantly higher in the severe group than in the non-severe group both at diagnosis (median, 338 U/mL) and at peak levels within one week after diagnosis (median, 781 U/mL) (both p < 0.001). Serum KL-6 value at peak level (371 U/mL) was used as the optimal cut-off to evaluate disease severity (sensitivity, 85.7%; specificity, 96.6%)., Conclusions: Serum KL-6 levels were significantly elevated in severe COVID-19 and is useful for evaluating its severity., Competing Interests: Conflict of interest The authors declare no conflicts of interest., (Copyright © 2020 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Objective Patients with chronic respiratory failure requiring long-term oxygen therapy (LTOT) are at a risk of CO 2 retention because of excessive oxygen administration. The CapnoEye™ is a novel portable capnometer that can measure end-tidal CO 2 (EtCO 2 ) noninvasively. This retrospective study evaluated the usefulness of this device. Methods EtCO 2 was measured using the CapnoEye™. The EtCO 2 and partial pressure of venous carbon dioxide (PvCO 2 ) were analyzed, and other clinical data were assessed. Patients Sixty-one consecutive patients with chronic respiratory failure receiving LTOT in the outpatient department at the Japanese Red Cross Medical Center between July 2017 and March 2018 were retrospectively reviewed. Results There was a significant correlation between EtCO 2 and PvCO 2 (r=0.63) in the total study population as well as in the COPD group (r=0.65) and ILD group (r=0.67). The PvCO 2 and EtCO 2 gradient was correlated with only the body mass index in a multivariate analysis (p=0.0235). The EtCO 2 levels on the day of admission were significantly higher than those in the same patients when they were in a stable condition (p=0.0049). There was a significant correlation between ΔEtCO 2 and ΔPvCO 2 (r=0.4). A receiver-operating characteristic curve analysis revealed the optimal cut-off EtCO 2 value for identifying hypercapnia to be 34 mmHg (p=0.0005). Conclusion The evaluation of EtCO 2 by the CapnoEye™ was useful for predicting PvCO 2 . The body mass index was identified as a possible predictor of the PvCO 2 and EtCO 2 gradient. An increase in EtCO 2 may indicate deterioration of the respiratory status in patients with chronic respiratory failure receiving LTOT.

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive disease often accompanied by skeletal muscle wasting. We investigated whether skeletal muscle mass and muscle attenuation on computed tomography (CT) are predictors of mortality in IPF patients, using a nationwide cloud-based database and web-based multidisciplinary discussion (MDD) system., Methods: IPF patients diagnosed using MDD from April 2009 to March 2014 were included. We analyzed the cross-sectional area (CSA) of the erector spinae muscle (ESM CSA ) and the pectoralis muscle (PM CSA ), muscle attenuation of the ESM (ESM MA ), and PM (PM MA ) on single-slice axial CT. Survival probability was assessed using the Kaplan-Meier method and compared by the log-rank test. Multivariate Cox proportional hazards models were used to evaluate the relationship among the ESM CSA , PM CSA , ESM MA , PM MA , clinical parameters, and prognosis., Results: A total of 199 IPF patients were enrolled. Seventy-four patients died during the study period and the most frequent cause was acute exacerbation (13.1%). The group with the lowest quartile of ESM CSA had significantly worse survival than other groups (P = 0.009). Survival rates of the groups with the lowest quartile of PM CSA , lower ESM MA , and lower PM MA did not differ from those of other groups. According to multivariate analysis, ESM CSA  < lower quartile was significantly associated with all-cause mortality (hazards ratio, 1.96; P = 0.030), whereas, ESM MA  < median, PM CSA  < lower quartile, and PM MA  < median were not., Conclusions: Low ESM CSA on CT images may be a strong risk factor for all-cause mortality in IPF patients based on MDD diagnosis., Competing Interests: Declaration of Competing Interest T.S. received a lecture fee from Boehringer Ingelheim and AstraZeneca. T.I. received a lecture fee from Boehringer Ingelheim, AstraZeneca, MSD, and Chugai. T.S. received research funds from Novartis, Ono, and AstraZeneca. T.S. received grants from Astellas, Ono, Daiichi Sankyo, Taiho, Takeda, Novartis, Pfizer, Boeringer Ingelheim, and MSD., (Copyright © 2019 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

This retrospective study evaluated the outcomes of patients treated with combination of bendamustine and rituximab (BR) for recurrent indolent B-cell lymphoma from January 2011 to February 2018 in our department. The cohort included 36 males and 27 females, and majority of the patients (59%) were between 51 and 70 years of age. The disease types were follicular lymphoma (FL) and mantle-cell lymphoma in 42 (67%) and 15 (24%) patients, respectively. Median progression-free survival (PFS) was not reached in patients with FL who completed BR therapy. The analysis of patients who received BR therapy revealed that the number of CD4-positive lymphocytes remained around 200/µl even five years after the end of treatment. BR therapy was a useful treatment option for recurrent indolent B-cell lymphoma, especially in patients with FL, and completion of BR therapy appeared to be important for improved PFS. Furthermore, attention should be paid for potential infections for at least five years after BR therapy because cell-mediated immunodeficiency may become apparent after treatment.

Monocyte-derived fibrocytes recently garnered attention because the novel pathogenesis of myelofibrosis (MF), and suppression of fibrocyte differentiation by serum amyloid P remarkably improved MF. We previously revealed that human fibrocytes highly expressed signaling lymphocytic activation molecule F7 (SLAMF7) compared with macrophages and that SLAMF7 high monocytes in the peripheral blood (PB) of MF patients were significantly elevated relative to those in healthy controls (HCs). In this study, we evaluated SLAMF7 high monocyte percentage in the PB of HCs, myeloproliferative neoplasm (MPN) patients with MF, and MPN patients without MF by using a cross-sectional approach. We found that MPN patients with MF who harbored JAK2 V617F had a significantly elevated SLAMF7 high monocyte percentage, which correlated positively with the JAK2 V617F allele burden. In addition, the serum concentration of interleukin-1ra (IL-1ra) was significantly correlated with the SLAMF7 high monocyte percentage and JAK2 V617F allele burden. These findings suggest that both SLAMF7 high monocytes and IL-1ra could be useful noninvasive markers of MF onset. Furthermore, the JAK2 V617F allele burden of SLAMF7 high monocytes was significantly higher than that of SLAMF7 low monocytes and could be a potential target of elotuzumab (Elo), an anti-SLAMF7 antibody used for treating multiple myeloma. Elo independently inhibited differentiation of fibrocytes derived not only from HCs but also from MF patients in vitro. Elo also ameliorated MF and splenomegaly induced by romiplostim administration in humanized NOG mice. In conclusion, an increase of SLAMF7 high monocytes with higher JAK2 V617F allele burden was associated with the onset of MF in MPN patients harboring JAK2 V617F, and Elo could be a therapeutic agent for MPN patients with MF who harbor JAK2 V617F., (© 2019 by The American Society of Hematology.)

A 69-year-old woman presented to National Defense Medical College hospital for suspected nephrotic syndrome due to weight gain of 30 kg in 3 weeks and bilateral lower leg edema. However, her urinalysis showed microproteinuria, which excluded nephrotic syndrome. Computed tomography revealed severe systemic edema, pleural effusion, ascites, and enlarged cervical and axillary lymph nodes. Histological examination of axillary lymph node specimen showed a typical architecture of angioimmunoblastic T-cell lymphoma. One course of CHOP chemotherapy regimen was administered which improved the lymph nodes and systemic edema. The patient achieved complete remission after 6 courses of CHOP. Because serum vascular endothelial growth factor (VEGF) level was elevated before the treatment and normalized after the treatment, increased vascular permeability mediated by VEGF was hypothesized to have caused the systemic edema. In addition, VEGF secretion from Epstein-Barr virus (EBV)-infected cells was likely associated with the patient's clinical condition because B lymphocytes stained with CD20 were positive for Epstein-Barr virus-encoded small RNAs (EBERs) and VEGF.