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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.

We herein report a 67-year-old kidney transplant patient who died of COVID-19. He was treated with hydroxychloroquine and azithromycin and received mechanical ventilation that temporarily improved his respiratory status. Despite our efforts, however, he later developed respiratory failure and died 43 days after the disease onset. The autopsy revealed prominent organization of alveoli and alveolar ducts, with a massive accumulation of macrophages in the lungs. A few severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen-positive cells were detected in the lung, suggesting delayed virus clearance owing to his long-term immunosuppressed state, leading to constant lung damage and ultimately respiratory failure.

A 70-year-old Japanese man contracted severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and required oxygen to maintain oxygen saturation (>90%), 5 weeks after onset of coronavirus disease 2019 (COVID-19) symptoms. Transbronchial lung cryobiopsy revealed pathological features of organizing pneumonia with alveolar epithelial injury, and prednisolone administration led to alleviation of respiratory symptoms and recovery of respiratory function. This case report is the first to demonstrate the use of corticosteroids to successfully treat post-COVID-19 respiratory failure in a patient with biopsy-proven organizing pneumonia. We propose that steroid treatment be considered for patients with persistent respiratory dysfunction as COVID-19 pneumonia sequelae.

BackgroundThis study aimed to investigate the ability of whole-body bone scintigraphy (WB-BS) in the detection of multifocal osteonecrosis (ON) compared to whole-body magnetic resonance imaging (WB-MRI) and to clarify the characteristics of patients with multifocal ON among those with ON of the femoral head (ONFH) using WB-MRI.MethodsForty-six patients who had symptomatic ONFH and underwent surgery in our hospital from April 2019 to October 2020 were included in the study. Data on patient demographics, including age, sex, body mass index (BMI), history of corticosteroid intake, alcohol abuse, smoking, and symptomatic joints, were collected from their medical records. All patients underwent WB-MRI and WB-BS before surgery.ResultsThe agreement in the detection of ON by WB-MRI vs the uptake lesions by WB-BS in the hip joints was moderate (κ = 0.584), while that in other joints was low (κ P = 0.035). The patients with a hematologic disease had multifocal ON at a higher rate (P = 0.015).ConclusionsIt might be difficult for WB-BS to detect the asymptomatic ON detected by WB-MRI compared to symptomatic ON. Considering the cost, examination time, and radiation exposure, WB-MRI might be useful for evaluating multifocal ON. Larger longitudinal studies evaluating the benefits of WB-MRI for detecting the risk factors for multifocal ON are required.

Objective To evaluate the efficacy and safety of direct hemoperfusion using a polymyxin B‐immobilized polystyrene column (PMX‐DHP) in severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)‐positive pneumonia patients. Methods This study was a case series conducted at a designated infectious diseases hospital. Twelve SARS‐CoV‐2‐positive patients with partial pressure of arterial oxygen/percentage of inspired oxygen (P/F) ratio

Understanding of the long-term soil fertility trends is the basis for rational and sustainable management of the soil resources in agricultural fields. In tropical Asia, the Green Revolution initia...

Immune checkpoint inhibitors (ICIs) are reportedly effective against many kinds of neoplasm, but may be responsible for several kinds of immune‐related adverse events (irAEs). Among these irAEs, the incidence of myelosuppression due to ICIs is relatively low. Corticosteroids are needed to control most cases of myelosuppression. Here, we report an 88‐year‐old woman with squamous cell lung cancer who was administered pembrolizumab. After five cycles of pembrolizumab, she developed severe pancytopenia. The pancytopenia improved under observation without steroid administration after cessation of pembrolizumab. During recovery from this irAE, the patient also maintained long‐term antitumor efficacy. Key points Significant findings of the study There are several kinds of immune‐related adverse events. We encountered a case of pembrolizumab‐induced pancytopenia with squamous cell lung cancer. What this study adds Corticosteroids are needed to control most cases of myelosuppression induced by ICIs, but pancytopenia induced by pembrolizumab in our case improved without steroids., An 88‐year‐old woman with squamous cell lung cancer was administered pembrolizumab. After 5 cycles of pembrolizumab, she developed severe pancytopenia. Pancytopenia improved under observation without steroid administration after cessation of pembrolizumab. During recovery from this irAE, the patient also maintained long‐term anti‐tumor efficacy.

Background Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2, has been a significant concern worldwide since its outbreak in December 2019. Various treatments are being researched and developed, and there are reports that dexamethasone has reduced the mortality rate and improved the clinical course of critically ill patients with COVID-19. In this study, we examined the clinical efficacy of corticosteroid therapy for patients with COVID-19 in our hospital during the first wave of infections. Methods We retrospectively reviewed the medical records of patients with COVID-19 who were treated with or without corticosteroid therapy at the National Center for Global Health and Medicine in Japan between February and April 2020. The primary outcome was improvement in the patients’ clinical course using a seven-category ordinal scale. We collected data on patient characteristics, treatment, and clinical course, and compared them between two groups: the steroid-using group and the non-steroid-using group. Results Between February and April 2020, 110 patients were diagnosed with COVID-19. Despite poor conditions during admission into the steroid group, there were no statistical differences in clinical course between both groups, as measured using the scale. There were no statistical differences between the two groups in the number of days to fever resolution or negative polymerase chain reaction results. Conclusions There was no difference in the clinical course between both groups. Because of the difference in background, corticosteroids may potentially make the clinical course of severely ill patients similar to that of mildly ill patients.

IntroductionBronchial thermoplasty (BT) is a bronchoscopic procedure that involves the delivery of thermal radiofrequency energy to the bronchial wall for treating severe asthma. It has been suggested that too many radiofrequency activations could induce serious adverse events (SAEs) at an early stage. We aimed to examine the number of radiofrequency activations at each session and early lung function changes from baseline to determine whether these are related to SAEs.MethodsWe retrospectively investigated 13 consecutive patients who underwent three sessions each of BT for severe asthma from February 2015 to January 2016. Lung function tests were performed on the day before and after each BT procedure. Since we compared the number of activations and lung function changes from baseline after each session, a total of 39 sessions were reviewed. The relationship between the number of radiofrequency activations and each lung function change from baseline was also examined by linear regression analysis.ResultsA total of 10 SAEs (4 of pneumonia, 3 of atelectasis, 2 of bronchial asthma exacerbation and 1 of hemoptysis) were observed following the 39 BT sessions. When we compared sessions with and without SAEs, there were no differences in the number of activations (mean ± SD, 71.5 ± 28.6 times in sessions with SAEs; 66.5 ± 25.1 times in sessions without SAEs;p = 0.772) and lung function changes (mean changes in FVC/%FVC/FEV1/%FEV1/%PEF from baseline; − 0.49 l/− 14.2%/− 0.36 l/− 11.7%/− 9.6% in sessions with SAEs; − 0.43 l/− 13.3%/− 0.34 l/− 12.1%/− 9.4% in sessions without SAEs;p > 0.05 for all the above). Increase in the number of activations correlated with decreased FEV1(R2 = 0.17,p = 0.0088) and %FEV1(R2 = 0.11,p = 0.0357).ConclusionsIncrease in the number of radiofrequency activations during BT is related to a decrease in FEV1and %FEV1from baseline. The number of radiofrequency activations, however, is not associated with SAEs after BT.

BACKGROUND: We investigated the measurement of end-tidal partial pressure of carbon dioxide (PETCO2) with a capnometer in patients with respiratory failure, and we determined whether this technique could provide an alternative to measurement of PaCO2 using arterial blood gas analysis in the clinical setting. METHODS: We measured PETCO2 in subjects with hypoxemic and hypercarbic respiratory failure using a capnometer. We simultaneously measured PaCO2, venous partial pressure of carbon dioxide (PvCO2), and transcutaneously measured partial pressure PCO2 (PtcCO2). We analyzed agreements among these parameters with Bland-Altman analysis. We obtained 30 samples from subjects with hypoxemic respiratory failure and 30 samples from subjects with hypercarbic respiratory failure. RESULTS: Thirty subjects with hypoxemic respiratory failure and 18 subjects with hypercarbic respiratory failure participated in this study. Significant relationships were found between PETCO2 and PaCO2, between PtcCO2 and PaCO2, and between PvCO2 and PaCO2. Bland-Altman analysis of PETCO2 and PaCO2 in all subjects revealed a bias of 6.48 mm Hg (95% CI 4.93–8.03, P CONCLUSIONS: PETCO2 can be measured simply using a capnometer, and PETCO2 measurements can estimate PaCO2. However, the limits of agreement were wide. Therefore, care providers must pay attention to the characteristics and errors of these devices. These results suggest that measurement of PETCO2 might be useful for screening for hypercarbic respiratory failure in the clinical setting.

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

Background The current gold standard in coronavirus disease (COVID-19) diagnostics is the real-time reverse transcription–polymerase chain reaction (RT-PCR) assay for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in nasopharyngeal swab (NPS) samples. Alternatively, nasal swab (NS) or saliva swab (SS) specimens are used, although available data on test accuracy are limited. We examined the diagnostic accuracy of NPS/NS/SS samples for this purpose. Methods Ten patients were included after being tested positive for SARS-CoV-2 RT-PCR in NPS samples according to the National Institute of Infectious Disease guidelines. In comparison with this conventional diagnostic method, NPS/NS/SS samples were tested using the cobas 6800 systems RT-PCR device. To investigate the usefulness of the cobas method and the difference among sample types, the agreement and sensitivity were calculated. Five to six samples were collected over a total period of 5–6 d from each patient. Results Fifty-seven sets of NPS/NS/SS samples were collected, of which 40 tested positive for COVID-19 by the conventional method. Overall, the concordance rates using the conventional method were 86.0%/70.2%/54.4% for NPS/NS/SS samples (cobas); however, for samples collected up to and including on Day 9 after disease onset (22 negative and one positive specimens), the corresponding rates were 95.7%/87.0%/65.2%. The overall sensitivity estimates were 100.0%/67.5%/37.5% for NPS/NS/SS samples (cobas). For samples up to 9 d after onset, the corresponding values were 100.0%/86.4%/63.6%. Conclusions NS samples are more reliable than SS samples and can be an alternative to NPS samples. They can be a useful diagnostic method in the future.

Background: Corticosteroids use in coronavirus disease 2019 (COVID-19) is controversial, especially in mild to severe patients who do not require invasive/noninvasive ventilation. Moreover, many factors remain unclear regarding the appropriate use of corticosteroids for COVID-19. In this context, this multicenter, retrospective, propensity score–matched study was launched to evaluate the efficacy of systemic corticosteroid administration for hospitalized patients with COVID-19 ranging in the degree of severity from mild to critically-ill disease.Methods: This multicenter, retrospective study enrolled consecutive hospitalized COVID-19 patients diagnosed January–April 2020 across 30 institutions in Japan. Clinical outcomes were compared for COVID-19 patients who received or did not receive corticosteroids, after adjusting for propensity scores. The primary endpoint was the odds ratio (OR) for improvement on a 7-point ordinal score on Day 15.Results: Of 1092 COVID-19 patients analyzed, 118 patients were assigned to either the corticosteroid and non-corticosteroid group, after propensity score matching. At baseline, most patients did not require invasive/noninvasive ventilation (85.6% corticosteroid group vs. 89.8% non-corticosteroid group). The odds of improvement in a 7-point ordinal score on Day 15 was significantly lower for the corticosteroid versus non-corticosteroid group (OR, 0.611; 95% confidence interval [CI], 0.388–0.962; p = 0.034). The time to improvement in radiological findings was significantly shorter in the corticosteroid versus non-corticosteroid group (hazard ratio [HR], 1.758; 95% CI, 1.323–2.337; p < 0.001), regardless of baseline clinical status. The duration of invasive mechanical ventilation was shorter in corticosteroid versus non-corticosteroid group (HR, 1.466; 95% CI, 0.841–2.554; p = 0.177). Of the 106 patients who received methylprednisolone, the duration of invasive mechanical ventilation was significantly shorter in the pulse/semi-pulse versus standard dose group (HR, 2.831; 95% CI, 1.347–5.950; p = 0.006).Conclusions: Corticosteroids for hospitalized patients with COVID-19 did not improve clinical status on Day 15, but reduced the time to improvement in radiological findings for all patients regardless of disease severity and also reduced the duration of invasive mechanical ventilation in patients who required intubation.Trial registration: This study was registered in the University hospital Medical Information Network Clinical Trials Registry on April 21, 2020 (ID: UMIN000040211).

Radiation can generate huge amounts of carriers in thin-layer SOI-MOSFETs, which change the device-internal potential distribution, known as an origin for of malfunction of circuits. 2D-numerical device-simulation analysis shows that the radiation-generated electrons initially flow-out from the SOI layer to both source and drain electrodes, which moderates the radiation-effect magnitude on device currents in this beginning stage. Subsequent enhancement of the current flow is due to accumulated holes caused by the potential barrier at source/channel junction. Compact modeling of the carrier movements during the initial radiation stage and of the hole-accumulation dynamics is based on the dynamically generated carrier densities. The developed compact model has been implemented into SPICE and model evaluation has been done by comparison to 2D-numerical device-simulation results. Under the off-state, it is shown that circuits can be easily switched to operation condition. Under the on-state, it is demonstrated that circuits can easily malfunction by operating differently from the designed circuit function. Though the radiation itself happens only for a short time, the radiation-induced effects continue for a rather time long, which causes serious effects in the circuits and is explained by the capacitor features of the SOI-MOSFET

An 83-year-old man was hospitalized for coronavirus disease 2019 (COVID-19) after a 10-day history of a persistent fever. Chest computed tomography showed extensive non-segmental ground glass opacity. Despite the initiation of lopinavir and ritonavir, respiratory failure progressed. Two days of polymyxin B-immobilized fiber column-direct hemoperfusion (PMX-DHP) with adjunctive corticosteroid prevented his respiratory condition from worsening. For rapidly progressive COVID-19 cases, the early use of PMX-DHP may avoid the need for mechanical ventilation by suppressing local inflammation of the lung.

Bronchial thermoplasty (BT) is an interventional endoscopic treatment for severe bronchial asthma. Some studies have shown the clinical efficacy of this intervention, but its cost-effectiveness is unclear. The aim of this study was to evaluate the cost-effectiveness of BT. We collected data from the medical records of 16 Japanese patients who were treated with BT between February 2015 and April 2017, and compared asthma-related medical expenses between the year preceding and the year following BT. Four patients were Global Initiative for Asthma (GINA) treatment step 4, and 12 were step 5. In 8 patients who had a successful response to BT, the annual asthma-related medical expenses decreased because of a reduction in hospitalization and emergency outpatient visits due to asthma attacks, and termination of the use of biologics. Most patients in the non-responder group had increased asthma-related medical costs postoperatively. The main reason for the increase in medical costs was the add-on treatment of biologics. BT was cost-effective in the responder group. If its effects continue for more than 10 years, BT will be a cost-effective treatment. Medical costs will be reduced if those who respond to BT can be identified prior to commencement of treatment.

To the Editor,A recent report in this journal described the severe nature and potentially fatal outcome of coronavirus disease 2019 (COVID-19) [1]. We here report a severe familial cluster case in ...

Highlights • Quarantined inpatients with SARS-CoV-2 have psychiatric burdens. • Some inpatients had discrimination, prejudice, and suspension and dismissal from work. • Implementation of necessary measures is needed to minimize the risk of long-term social isolation and potential risk of suicide.

Due to the significant spread of a new type of coronavirus (SARS-CoV-2) infection (COVID-19) in China, the Chinese government blockaded several cities in Hubei Province. Japanese citizens lost a means of transportation to return back to Japan. The National Center for Global Health and Medicine (NCGM) helped the operation of charter flights for evacuation of Japanese residents from Hubei Province, and this article outlines our experiences. A total of five charter flights were dispatched, and the majority of returnees (793/829 [95.7%]) were handled at NCGM. A large number of personnel from various departments participated in this operation; 107 physicians, 115 nurses, 110 clerical staff, and 45 laboratory technicians in total. Several medical translators were also involved. In this operation, we conducted airborne precautions in addition to contact precautions. Eye shields were also used. The doctors collecting the pharyngeal swab used a coverall to minimize the risk of body surface contamination from secretions and droplets. Enhanced hand hygiene using alcohol hand sanitizer was performed. Forty-eight persons were ultimately hospitalized after the triage at NCGM operation, which was more than the number of persons triaged at the airport (n = 34). Of those hospitalized after NCGM triage, 8.3% (4/48 patients) ultimately tested positive for SARS-CoV-2, significantly higher than the positive rate among subjects not triaged (4/48 [8.3%] vs. 9/745 [1.2%]: p = 0.0057). NCGM participated in a large-scale operation to evacuate Japanese nationals from the COVID-19 epidemic area. We were able to establish a scheme through this experience that can be used in the future.

Lymphoproliferative disease (LPD) is one of the complications of methotrexate (MTX) therapy. In MTX‐associated LPD (MTX‐LPD), LPD lesions limited to the lungs are rare and show various types of opacity. A 75‐year‐old woman with rheumatoid arthritis (RA) presented with myalgia. She had been taking MTX for 11 years. Chest computed tomography (CT) scans showed a nodule in the left lower lobe that had grown significantly and a new nodule in the right lower lobe. 18F‐fluorodeoxyglucose (FDG)/positron emission tomography (PET)/CT revealed significant FDG uptake in these nodules. Transbronchial biopsy specimen showed diffusely distributed CD20‐positive lymphoid cells, and we made a diagnosis of MTX‐LPD. All lung lesions disappeared within months after the immediate discontinuation of MTX. We also had two other patients with MTX‐LPD lung lesions that had high FDG uptake. FDG PET/CT might be a useful diagnostic tool as it may reflect disease progression and help identify separate lesions., Methotrexate (MTX) is one of the key drugs for treating rheumatoid arthritis (RA) and other autoimmune arthritis. Lymphoproliferative disease (LPD) is a complication of low‐dose MTX therapy. We describe three cases of MTX‐LPD where we conducted chest computed tomography (CT) and 18F‐fluorodeoxyglucose (FDG)/positron emission tomography (PET)/CT. This report focuses on the radiological findings of MTX‐LPD, including FDG PET/CT, based on these cases. FDG PET/CT might be a useful diagnostic tool as it may reflect disease progression and help identify separate lesions.

Rationale: Tumor-induced osteomalacia (TIO) is curable by tumor resection, but detection of the tumor can be challenging. Overproduction of fibroblast growth factor 23 (FGF23) by the tumor causes hypophosphatemia and consequently induces inappropriate bone turnover. Conventionally oral phosphate supplementation was the only treatment for TIO, but had risks of hypercalciuria and nephrocalcinosis. Burosumab, a human monoclonal anti-FGF23 antibody, was recently post-marketed in Japan against for FGF23-related hypophosphatemia. Herein, we present a case of TIO with undetectable tumor that was successfully treated with burosumab. Patient concerns: A 47-year-old woman was forced to use a wheelchair because of pain in both feet. Diagnosis: Laboratory findings showed hypophosphatemia, elevated bone markers, and high serum FGF23 without renal tubular defects. Imaging studies revealed bone atrophy in the feet, decreased bone density, and multiple pseudofractures in the talar, sacral, and L5 vertebral regions. After excluding drug-induced and hereditary osteomalacia, we diagnosed her as TIO. Interventions: Comprehensive imaging studies and stepwise venous sampling failed to localize the tumor, and we started to administer subcutaneous burosumab. Outcomes: After administration of burosumab, her serum phosphate was normalized without phosphate supplementation within 2 months. Improvement of pseudofractures, relief of pain evaluated by a visual analog scale, and normalization of bone biomarkers were observed. The patient was able to stand by herself after 6 months administration of burosumab. Lessons: This is the first report in clinical practice to demonstrate favorable effects of burosumab, including not only normalization of serum phosphate but also improvements of pseudofractures and subjective pain, in a patient with TIO and undetectable tumor.

Bronchoscopy is a procedure for diagnosis and treatment decision-making in patients with lung disease, especially those with acute respiratory failure. However, the optimal bronchoscopic method for patients with acute respiratory failure is not known. Therefore, in the real world, we sometimes hesitate to perform bronchoscopy in such patients because of safety and have experienced treating patients without bronchoscopy. To address this problem, we evaluated the usefulness and safety of Jackson mask ventilation, a novel noninvasive method of bronchoscopy performed under mask ventilation using the Jackson Rees circuit, in patients with acute respiratory failure.We retrospectively reviewed patients with acute respiratory failure who underwent bronchoscopy at our institution between January 2015 and May 2018. We compared patients who received Jackson mask ventilation (Jackson group) and those who received conventional oxygen administration (conventional group). Mean percutaneous oxygen saturation (SpO2) and mean oxygen flow rate were compared between the groups by the Wilcoxon signed-rank test. We excluded patients who were intubated and those without acute respiratory failure who received Jackson mask ventilation preventively.Of 1262 patients who underwent bronchoscopy, 12 were classified into the Jackson group and 13 into the conventional group. Proper oxygenation was maintained in the Jackson group, with SpO2 increasing after Jackson mask ventilation (89.4% to 96.8%, P = .03). Mean SpO2 was significantly higher in the Jackson group than in the conventional group (96.8% vs 95.2%, P = .03). Mean oxygen flow rate was significantly lower in the Jackson group (4.0 L/min vs 7.9 L/min, P

BackgroundTo perform medial open-wedge high tibial osteotomy (OWHTO), surgeons expose the medial-proximal tibia by releasing or cutting the superficial layer of the medial collateral ligament (sMCL). Biomechanically, the sMCL provides primary restraint against valgus forces. Therefore, any release of the sMCL can cause valgus instability of the knee joint. The purpose of this study was to assess valgus laxity after release of the medial structure of the knee during OWHTO.MethodsBetween 2009 and 2015, 84 consecutive patients (93 knees) who underwent OWHTO using a locking plate were enrolled in this study. All patients underwent radiological examinations before surgery, during surgery, 1 year after surgery, and after plate removal to objectively assess valgus laxity. The medial joint space (MJS) and the joint line convergence angle (JLCA) of the knee were evaluated using quantitative valgus stress radiography. Clinical evaluation was performed 2 years after surgery.ResultsThe mean functional knee score improved significantly, from 65.5 to 91.1 points (p p ConclusionValgus laxity was significantly greater after release of the sMCL. However, no significant differences were noted in valgus laxity in preoperative, 1-year postoperative periods and after plate removal. Complete release of the sMCL did not cause postoperative valgus laxity after OWHTO surgery.Trial registrationTrial registration number: No.012–0360.

Background: Hemoptysis can cause a life-threatening condition and often needs to be treated urgently. Recently, interventional devices and techniques such as CT angiography were made dramatically an improvement, therefore, we could have performed super selective BAE (ssBAE) which was thinner peripheral artery embolization. Objectives: We conducted a prospective observational study under the hypothesis that elective ssBAE may lead to attributing to the improvement of the hemostasis effect compared to the emergency BAE. [Methods] From June 2016, mild to moderate hemoptysis patients were eligible for this study. Super selective catheterization of abnormal arteries using microcatheters was performed using gelatin sponge. This study was approved by the Committee on Clinical Investigation for National Center for Global Health and Medicine (NCGM-G-002309-00). Results: The cases that we were able to observe the condition of hemoptysis after 1 year were 29 patients (14 males) and they were performed 32 sessions of BAE procedures. The overall efficacy of BAE for control of hemoptysis was 87.5% (n = 32) after one month, 87.1% (n = 31) after three months, and 86.2% (n = 29) after one years. Three cases were unfortunately recurrent hemosputum or hemoptysis within 28 days. Conclusions: The elective ssBAE approach was highly effective to avoid recurrent mild to moderate hemoptysis but especially, chronic inflammatory condition like pulmonary aspergillosis or refractory chronic lower respiratory tract infection with bronchiectasis was too difficult to control only BAE.

Pleuroscopy under local anesthesia is performed by physicians in case with unexplained pleural effusion. There are limits to the bending angle and image resolution of conventional fiberscopes. Olympus Corporation and 4 Japanese institutions, including our hospital, developed a new pleuroscope for use under local anesthesia. Compared to the conventional pleuroscope (LTF-260; Olympus, Japan), the new pleuroscope (LTF-Y0032; Olympus, Japan) comes with an improved bending angle from 160 degrees to 180 degrees, and the internal diameter from 2.8mm to 3.0mm. The quality of images has also been improved. We evaluated the new pleuroscope clinically. The study population comprised 30 patients with pleural effusion of unknown etiology at our hospital, who underwent pleuroscopy using the new pleuroscope from December 2016 to January 2019. The patients included 21 men and 9 women (median age, 76 years) with 18 right and 12 left pleural effusions. In the final diagnosis, there were 17 cases of malignant disease (10 cases of pleural metastasis of lung cancer, 4 cases of malignant pleural mesothelioma, 3 cases of malignant lymphoma), and 13 cases of benign disease (4 cases of pyothorax, 4 cases of nonspecific pleurisy, 2 cases of tuberculous pleurisy, 2 cases of asbestos-related pleurisy and 1 case of IgG4-related disease). In one case of mesothelioma, the lesion was confined to a part of the pleura that cannot be observed with conventional pleuroscope, but it could be visualized by bending the new pleuroscope by 180 degrees. The new pleuroscope has an improved bending angle, image quality and channel inner diameter. The improved bending angle is likely to minimize the blind spot, improving the diagnostic rate.

Objective Rapidly progressive interstitial lung disease (RPILD) is a major cause of death in patients with DM. Although clinically amyopathic DM (CADM) represents risk for RPILD, the incidence rate of RPILD in patients with CADM varies widely. Whole-body (WB) MRI can reveal involvement of systemic muscle and myofascia. The objective of this study was to explore the risk factors for RPILD in patients with DM using WB-MRI. Methods This retrospective study comprised 41 patients with DM who underwent WB-MRI before the initiation of treatment in our hospital. Muscular and myofascial signals were scored on 42 muscular groups. The myofascia/muscle ratio was calculated and used to define the relevance of myofascia-dominant involvement. RPILD was defined as worsening of dyspnoea, hypoxaemia and radiographic ILD/fibrosis within 3 months from the onset of respiratory symptoms. Results Among the 41 patients, 17 had CADM and 30 had ILD, including 10 patients with RPILD. All patients including those with CADM showed abnormal signal intensity in both muscle and myofascia (median score: 15 and 23, respectively). Muscle signal scores positively correlated with the serum creatine kinase level (r = 0.714; P Conclusion Myofascia-dominant involvement was defined and appreciated in patients with DM using WB-MRI. This may be one of the risk factors for RPILD.

A combination of CR-39 track detectors and a stepwise energy filter is a simple method to measure the energy spectrum of laser-accelerated protons. The number of etch pits in each area of the CR-39 detector is expected to represent the energy spectrum because the different thicknesses of the filters result in different areas into which the energy reaches in CR-39. However, the higher energy regions may overlap depending on the sensitivity of CR-39. To avoid overlapping, i.e., overestimation of the number of etch pits for each energy region, a correction method for the energy spectrum from the number of etch pits was developed. Based on the calculation results of the reaching energy values and incident energy ranges for CR-39, etch pits are selected that should be counted in each area. CR-39 with stepwise energy filters provides a corrected energy spectrum of laser-accelerated protons by applying the developed method.

Splenic preservation is associated with a reduction in perioperative infectious complications,1,2 postoperative pancreatic fistulas,3,4 and cancer occurrence.5,6 Therefore, in patients with benign or low-grade malignant tumors in the body and/or tail of the pancreas, spleen-preserving distal pancreatectomy is preferred over combined splenectomy. Furthermore, improvement in procedural feasibility and safety improvement have made laparoscopic spleen-preserving distal pancreatectomy (LSPDP) more common.3,7–12 To preserve the spleen, 2 surgical techniques can be used: (1) dissecting out the splenic artery and vein with division of the arterial and venous branches between the pancreas and the splenic artery and vein or (2) resection of the splenic artery and vein along with the pancreas but with careful preservation of the vascular collaterals in the splenic hilum, which allows the spleen to survive on the short gastric vessels (Warshaw technique).13 A recent study compared short-term outcomes between the preservation and the division of the splenic vessels during LSPDP, showing that the former was associated with an improved rate of spleen conservation.12 This procedure may become the strategy of choice in selected patients with benign or low-grade malignant tumors in the body/tail of the pancreas. In contrast, LSPDP with preservation of the splenic vessels is technically demanding. Splenic vessel injuries or difficulties during the dissection occasionally require a conversion to the Warshaw technique.12 Hence, the approach to the splenic vessels is an important step. The present study describes the standard operating procedure for splenic vessel-preserving LSPDP (SVP-LSPDP) in our institute, and 2 types of approaches to the splenic artery are highlighted.

To evaluate the scoring of whole-body magnetic resonance imaging (WBMRI) for efficacy assessment in rheumatoid arthritis (RA) patients receiving biological disease-modifying anti-rheumatic drugs (bDMARDs).Thirty consecutive RA patients receiving bDMARDs were included in this retrospective study. Contrast WBMRI was performed before and 1 year after bDMARDs initiation.At baseline, mean age was 57.1 years and mean disease duration was 3.0 years. Median disease activity score in 28 joints improved from 5.1 to 2.1. Treatment with bDMARDs improved mean whole-body synovitis score from 31.2 to 23.2 and median whole-body bone-edema score from 11 to 3. Whole-body bone-erosion score improved in seven patients and deteriorated in 17 patients. Logistic regression analysis identified whole-body synovitis score as a poor prognostic factor for whole-body bone-erosion progression. Bone-edema score in individual bones was identified as a poor prognostic factor for the progression of bone-erosion. Changes in hand synovitis score correlated with those of other joints, but neither changes in bone-edema nor erosion score of hands correlated with those of other joints in WBMRI.WBMRI scoring may be a novel useful tool to evaluate the efficacy of anti-rheumatic drugs, as well as a potential predictor of joint prognosis, in patients with RA.

The purpose of this study was to determine the relationship between serum zinc (Zn) level and clinicopathological profiles in patients with hepatocellular carcinoma (HCC). Furthermore, we investigate the influence of serum Zn level on the long-term prognosis after hepatectomy. A retrospective analysis was conducted of 310 patients who underwent initial hepatectomy for HCC. The correlation between serum Zn level and preoperative liver functional indicator, pathological features, including the degree of hepatic fibrosis, and perioperative outcome were evaluated. The patients were divided into two groups (serum Zn ≤ 65 mg/dL; n = 71 and Zn > 65 mg/dL; n = 239), and their long-term prognosis were compared. There were strong correlations between preoperative serum Zn level and serum albumin (r = 0.47, P

Aim Hepatectomy is feasible for patients with hepatocellular carcinoma (HCC) with good hepatic function who meet the Milan criteria. Several studies have indicated that tumor markers of HCC, α-fetoprotein (AFP), Lens culinaris agglutinin-reactive fraction of AFP percentage and protein induced by vitamin K absence/antagonist-II were good predictors of malignant potential. It is important to identify highly malignant cases of HCC, and the aim of this study was to clarify the impact of triple positive tumor markers as the prognostic factors for early stage HCC within the Milan criteria. Methods This study investigated 199 patients who underwent hepatectomy for HCC within the Milan criteria between January 2001 and May 2009. Cumulative recurrence-free survival (RFS), overall survival (OS) and clinicopathological parameters were analyzed according to the number of positive tumor markers. Results In patients with triple positive tumor markers, 5-year RFS and OS was poor (17.1 and 61.4%, respectively). Multivariate analyses revealed independent risk factors for recurrence to be hepatitis C virus antibody positivity, non-initial treatment for HCC and triple positive tumor markers, and the independent risk factors for OS were high indocyanine green retention rate at 15 min value, maximum tumor size and triple positive tumor markers. Pathologically invasive growth, microvascular invasion and moderate to poor differentiation were significantly related to the number of the three tumor markers. Conclusion Triple positive tumor markers for early stage HCC within the Milan criteria showed poor prognosis and malignant characteristics. These markers could be a useful predictor for the degree of malignant potential in early stage HCC.

Patients with unresectable pancreatic and biliary cancers sometimes need decompression due to obstruction of the gastrointestinal tract and/or biliary tract. The aim of this study was to determine the prognostic factors associated with an indication for palliative bypass surgery in patients with unresectable pancreatic and biliary cancers. Between April 2005 and September 2011, 37 patients with unresectable pancreatic and biliary cancers underwent palliative bypass surgery. Prognostic factors were searched for among clinical characteristics, operation-related factors, and tumor-related factors using a prospective database. The median survival time (MST) of these patients was 4.6 months, with a 6-month survival rate of 40.5 %. A multivariate Cox proportional hazards regression analysis revealed that mGPS >2 was the only independent prognostic factor for bypass surgery. Patients with an mGPS of 2 had an MST of 1.7 months, and they had a significantly worse prognosis than mGPS 0–1 patients with an MST of 6.3 months. The mGPS is useful for predicting survival after surgical decompression due to gastrointestinal obstruction in patients with unresectable pancreatic and biliary cancers. Patients with a poor mGPS may not be indicated for palliative bypass surgery.

Pancreatic neuroendocrine tumor (PNET) is relatively rare and has a generally better prognosis than does pancreatic cancer. However, as its prognosis in patients with lymph node metastasis (LNM) is unclear, lymph node dissection for PNET is controversial. Our study aimed to clarify the significance of LNM in PNET. We retrospectively examined 83 PNET patients who underwent pancreatic resections with lymph node dissection at Kumamoto University Hospital, Saiseikai Kumamoto Hospital, and Kumamoto Regional Medical Center from April 2001 to December 2014. Their clinicopathological parameters were analyzed by the absence or presence of LNM, and with regard to the disease-free survival (DFS) and overall survival (OS). A predictive score of LNM was also made using the age, tumor size, primary tumor location, and tumor function. Although the 5-year OS was 74.8% for LNM+ and 94.6% for LNM− (P = 0.002), LNM was not an independent risk factor for the OS in a multivariate analysis. However, tumors larger than 1.8 cm were found to be an independent prognostic factor, and the cut-off value for the predictive score was 1.69. Although LNM was not an independent prognostic factor, lymph node dissection is recommended for patients whose predictive score is larger than 1.69.

RATIONALE: Anti-aminoacyl transfer RNA synthetases (ARS) antibodies are a group of myositis specific autoantibodies. It also is frequently found in patients with complicating interstitial pneumonia. However, the clinical characteristics in these patients with anti-ARS antibody were not yet fully elucidated. METHODS: We retrospectively investigated clinical symptoms, radiological findings, treatments, and its outcome in 30 patients with anti-ARS antibody-positive interstitial pneumonia (ARS-IP) in our institution. The radiological patterns of interstitial pneumonia were evaluated with thin-sliced HRCT by two specialists. Anti-ARS antibodies were evaluated using RNA immunoprecipitation assey and anti-synthetase ELISA kit (BML, Japan). RESULTS: Mean age was 59.4 years (28-82), 60.0% were female. Nine patients were with anti-Jo-1, 7 with anti-EJ, 4 with anti-PL-12, 3 with anti-PL-7, 2 with anti- OJ, and 5 with unknown or anti-KS. Seven cases were diagnosed as having ARS-IP with dermatomyositis (DM), and 7 with polymyositis. There were no differences in the demographic features, laboratory data, HRCT findings, between ARS-IP with myositis and without. ARS-IP with myositis recurs more often than without myositis (p=0.019). Serum creatinine kinase (CK) levels were elevated in 13 patients. Patient achieved good responses to initial corticosteroid and immunosuppressant. Mean observation time was 64.9 months (4 months- 138 months). CONCLUSIONS: Most of the patients with interstitial pneumonia associated with anti-ARS antibodies showed remarkable responses to the therapy and favorable outcome.

Clinically, we often encounter cancer patients who also have cardiovascular disease such as coronary artery disease. We experienced a case of severe coronary artery disease and a large hepatocellular carcinoma in a 69-year-old man. To reduce the risk of a perioperative cardiovascular event during mesohepatectomy, an elective intra-aortic balloon pump (IABP) was used. After an uneventful recovery, the patient was discharged on day 15. While IABP is frequently introduced in cardiac surgery, there have been few reports of its use during liver surgery. Here, we present IABP-assisted major hepatectomy as an option in a patient with both cancer and coronary artery disease.

Major hepatectomy is associated with significant morbidity and mortality rates, particularly in patients aged more than 70 years. This study assessed whether physical indicators, such as sarcopenia and visceral fat amount, could predict morbidity and mortality after major hepatectomy.The study enrolled 144 patients who underwent curative major hepatectomy. Skeletal muscle and visceral fat amount at the third lumbar vertebra (L3) in the inferior direction were quantified using enhanced computed tomography scans. The patients were divided into two subgroups, with and without sarcopenia, based on median skeletal muscle mass in men and women (43.2 cm(2)/m(2) in men; 35.3 cm(2)/m(2) in women).The study included 108 men and 36 women, with median skeletal muscle tissue of 43.2 and 35.3 cm(2)/m(2), respectively. The mortality rate was significantly higher in patients with than without sarcopenia [seven cases (9.7 %), one case (1.4 %), respectively; P = 0.021], whereas liver-related morbidity and mortality rates were similar. In patients aged70 years, the morbidity, liver dysfunction-related morbidity, and mortality rates were significantly higher in patients with than without sarcopenia (P0.05 each). In contrast, surgical outcomes were similar in patients with high and low visceral fat amounts.Sarcopenia was a risk factor for postoperative complications after major hepatectomy, particularly in elderly patients.

333 Background: Ampullay cancer (AC) is relatively good prognosis in the biliary tract cancer. Such as LN metastasis, pancreatic invasion is a prognostic factor in AC. On the other hand, Distal bile duct cancer (DBDC) is somewhat good prognosis in the biliary tract cancer. Such as ductal resection margin positive is a prognostic factor in DBDC. There are few papers considered to both difference. Therefore, we conducted this study to examine the difference of AC and DBDC. Methods: To evaluate Cancer-Specific Survival (CaSS), Recurrence-Free Survival (RFS) and prognostic factors after pancreatoduodenectomy (including pylorus-preserving pancreatoduodenectomy: PPPD, subtotal stomach-preserving pancreatoduodenectomy: SSPPD) based on a series of 80 patients of AC and 36 patients of DBDC from 1996 to 2015. We reviewed and analyzed the clinicopathologic data, recurrence and survival. Results: Five years CaSS and RFS of AC were 72.3% and 72.5%. In univariate analysis, pancreatic invasion, R1or R2 resection, duodenal invasion and lymph node metastasis are significantly poor prognosis. In multivariate analysis, pancreatic invasion and R1or R2 resection are poor prognostic factors (pancreatic invasion, p = 0.0012, hazard ratio (HR) 5.65 [confidence interval (CI) 1.92-19.5 95%], R1or R2 resection, p = 0.0043, HR 6.22 [CI 1.68-40.2 95%]). On the other hand, five years CaSS and RFS of DBDC were 35.8% and 46.8%. In univariate analysis, pancreatic invasion (+) ≥ 5 mm in depth, and duodenal invasion are significantly poor prognosis. In multivariate analysis, duodenal invasion is the only poor prognostic factors (p = 0.0227, HR 2.90 [CI 1.16-7.39 95%]). Conclusions: DBDC is considerable poor prognosis compared with AC. Lymph node metastasis is not prognostic factor depends on D2 LN dissection in AC, than pancreatic invasion. Cancer cells invaded pancreatic parenchyma in AC; pancreatic invasion may be the most important prognostic factor by biology-like pancreatic cancer. Duodenal invasion in DBDC was prognostic factor reflects the degree of development of the cancer beyond pancreatic parenchyma. Further clinicopathological and biological studies are needed to confirm our findings.

Background This study was designed to investigate the association between infectious ascites, clinical parameters and treatment outcomes after hepatectomy. Methods Of 891 patients who underwent hepatectomy between 2006 and 2013, 74 who underwent paracentesis for bacterial cultivation of postoperative ascites after hepatectomy were analyzed. Results Of the 74 patients, 42 had positive bacterial cultures (positive group) and 32 patients had negative cultures (negative group). Hospital mortality was significantly higher in the positive group than in the negative group [9/42 (21.4%) vs. 2/32 (6.3%); P = 0.035]. Hospital mortality associated with each bacterial strain was as follows: methicillin-resistant staphylococci (MRS) (5/13, 38.5%), staphylococci (2/11, 18.2%), enterococci (2/12, 16.7%), Enterobacter (0/3, 0%), Klebsiella (0/2, 0%), and others (0/1, 0%). Cox proportional multivariate analysis revealed that MRS infection in ascites was the only risk factor of hospital death (HR = 5.08, P = 0.041) and MRS wound infection was the only risk factor to predict MRS infection in ascites (HR = 5.67, P = 0.015). Conclusion Postoperative MRS infection in postoperative ascites after hepatectomy is a potentially fatal complication; therefore, the prevention of MRS wound infection is critical to decrease postoperative hospital mortality.

To determine whether the preoperative pancreatic apparent diffusion coefficient (ADC) can be used to predict the development of postoperative pancreatic anastomotic failure (PAF).We retrospectively examined the cases of 79 patients who underwent pancreatic head resection between January 2010 and October 2013. The patients underwent 1.5-T MR imaging including diffusion-weighted imaging before surgery. The main pancreatic duct diameter (MPD), the pancreatic parenchymal thickness (PT), and the ADC of the pancreatic remnant parenchyma were measured. Two radiologists blinded to the patients' outcomes performed the measurements. The imaging parameters were compared between the patients who developed PAF and those who did not. The cut-off ADC for the development of PAF was calculated with a receiver operating characteristic analysis.The imaging parameters were highly correlated between the two observers. The MPD and PT did not differ significantly among the patients. The mean pancreatic ADCs were significantly higher in the patients with PAF than in those without PAF. An ADC higher than 1.50 × 10(-3) mm(2)/s (Az = 0.719, observer-1) or 1.35 × 10(-3) mm(2)/s (Az = 0.752, observer-2) was optimal for predicting the development of postoperative PAF.Measuring the preoperative non-tumorous pancreatic ADC may be useful for the prediction of a postoperative PAF.

753 Background: It was reported that early tumor shrinkage (ETS) was associated with better overall survival (OS) in patients (pts) with metastatic colorectal cancer (mCRC) receiving first line chemotherapy. We investigated association of ETS with progression-free survival (PFS) and OS in pts with mCRC treated with first-line bevacizumab (BV)-based chemotherapy (HGCSG0802). Methods: The objective of HGCSG0802 was to evaluate PFS, OS, response rate (RR), safety and so on. The key eligibility criteria were evaluable lesions, older than 20 years old, ECOG PS 0-2. This analysis evaluated the association of ETS at 8 weeks from the start of chemotherapy with pts characteristics, PFS and OS. To identify factors associated with ETS, if there were clinical variables with p < 0.2 in univariate analysis, we planned a multivariate analysis using the logistic regression model. To identify predictive and prognostic factors, a multivariate analysis was performed using Cox proportional hazard model with backward elimination for variables with p < 0.2 in univariate analysis. Results: Of 108 pts (the full analysis set), 99 pts were evaluable for ETS. Sixty-eight pts (68.7%) had ETS ≥20%. The pts characteristics between ETS ≥20% (ETS) and

749 Background: It was reported that early tumor shrinkage (ETS) was associated with better overall survival (OS) in patients (pts) with metastatic colorectal cancer (mCRC) receiving cetuximab. We investigated association of ETS with progression free survival (PFS) in pts with unresectable colorectal liver metastases (CLM) from HGCSG0802 observational cohort study in pts with mCRC treated with first-line bevacizumab (BV)-based chemotherapy. Methods: The objective of HGCSG0802 was to evaluate PFS, OS, time to treatment failure (TTF), response rate (RR), safety and so on. The key eligibility criteria were evaluable lesions, older than 20 years old, ECOG PS 0-2. In this analysis, association of ETS at 8 weeks from the start of chemotherapy with pts characteristics, PFS and TTF was evaluated. Pts characteristics were compared using Student-t test, chi-square test and Fisher’s exact test. PFS and TTF were analyzed with Kaplan-Meier method and compared using log-rank test. Univariate analysis for the association of pts characteristics with PFS and TTF was performed using log-rank test, and multivariate analysis was performed using Cox proportional hazards model. Results: Of 108 pts (the full analysis set), 74 pts with CLM were evaluable for ETS. Forty-nine pts (66.2%) had ETS ≥20%. The pts characteristics between ETS ≥20% and