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Cardioprotective effect of prostaglandin-E2 receptor-4 (EP4) stimulation on the ischemic heart has been demonstrated. Its effect on the heart affected by myocarditis, however, remains uncertain. In this study, we investigated therapeutic effect of EP4 stimulant using a mouse model of autoimmune myocarditis (EAM) that progresses to dilated cardiomyopathy (DCM). EP4 was present in the hearts of EAM mice. Treatment with EP4 agonist (ONO-0260164: 20 mg/kg/day) improved an impaired left ventricular (LV) contractility and reduction of blood pressure on day 21, a peak myocardial inflammation. Alternatively, DCM phenotype, characterized by LV dilation, LV systolic dysfunction, and collagen deposition, without inflammatory profiles was observed on day 56, along with activation of matrix metalloproteinase (MMP) 2 critical for myocardial extracellular matrix disruption, indicating an important molecular mechanism underlying adverse ventricular remodeling after myocarditis. Continued treatment with ONO-0260164 alleviated the DCM phenotype, but this effect was counteracted by its combination with a EP4 antagonist. Moreover, ONO-0260164 inhibited in vivo proteolytic activity of MMP2 in association with up-regulation of tissue inhibitor of metalloproteinase (TIMP)-3. EP4 stimulant may be a promising and novel therapeutic agent that rescues cardiac malfunction during myocarditis and prevents adverse ventricular remodeling after myocarditis by promoting the TIMP3/MMP2 axis.

The long-term exercise capacity of coronavirus disease 2019 patients with acute respiratory distress syndrome is not clear. The 6-min walking distance of four patients with coronavirus disease 2019-associated acute respiratory distress syndrome was followed for 6 mos after admission to the hospital. These four patients were admitted to the intensive care unit of our hospital and received mechanical ventilation. Rehabilitation therapy (positioning, postural drainage, and passive range-of-motion exercises) was started after intensive care unit admission. Mobilization therapy, including muscle power training, sitting on the edge of the bed, and endurance training, was performed after the end of sedation. The Medical Research Council sum scores and Barthel Indexes for the patients improved after intensive care unit discharge and completely recovered 6 mos after admission to the hospital. However, the 6-min walking distance of the four patients remained shorter than those of healthy persons of the same age at 6 mos after admission to the hospital. Furthermore, the minimum Spo2 during the 6-min walking test remained less than 96%. It is possible that patients who receive mechanical ventilation due to coronavirus disease 2019-associated acute respiratory distress syndrome have decreased long-term exercise capacity, despite muscle power and activities of daily living recovering completely.

Central pontine myelinolysis (CPM) is a rare demyelinating condition which has been reported to occur in a variety of clinical settings, but most commonly in association with a rapid rise in plasma osmolality during correction of chronic hyponatremia. The clinical consequences can vary from a mild motor weakness that resolves completely over time to the devastating locked-in syndrome. In this presentation, we report a case of hyperosmolar hyperglycemic syndrome (HHS) with ponto-occipital disintegration. A 71-year-old female was transferred to our ER by an ambulance due to consciousness disorder and continuous fever for 10 days. We diagnosed septic shock caused by urinary tract infection (UTI), cerebral multiple infarctions, acute kidney injury (AKI) and HHS without treatment for diabetes. Then, we started therapeutic interventions for them based on the guideline with severe control for blood sugar (BS; primary 1635 mg/dl) under insulin therapy and hypernatremia (primary 153 mEq/l) under crystal infusion control in advanced care unit, apparently on routine lab data. However, the initial serum sodium value of 153 mEq/l was slowly compensated to 148 mEq/l in 60 hours under guideline on routine lab data, the initial compensated sodium value with osmolality was changed from 178 mEq/l to 150 mEq/l in the period. She recovered from her primary diagnosis and unconsciousness. After stabilized sepsis and HHS, we detected CPM on brain MRI due to following up multiple cerebral infarctions with left leg paralysis and verbal disorder. She gradually recovered over several months with intensive rehabilitation and eventually regained near normal functional capacity with stabilized BS. When we consider HHS with hypernatremia, it may be necessary to pay attention to not only to BS control and sodium control according to the guideline but also to osmolality changes to prevent CPM.

Objective To evaluate the association between iron metabolism indicators and disease severity in hospitalized patients with coronavirus disease 2019 (COVID-19). Design Two-center observational study Setting A university hospital and a core hospital in Yokohama, Japan Patients Adults with COVID-19 whose serum iron levels were measured within the first 5 days of hospitalization were included. Patients who refused mechanical ventilation were excluded from the study. Measurements and Main Results One hundred thirty-six patients were included in this study. We analyzed the association between COVID-19 severity and serum iron, total iron binding capacity (TIBC), and transferrin saturation (TSAT) levels. Disease severity was defined as the worst respiratory status during hospitalization. Serum iron levels were significantly lower in patients with mild respiratory failure (RF) (n=55, median serum iron level: 24 [interquartile range: 19–42] mg/dL) than in the non-RF group (n=44, 40 [24–80] mg/dL) and the severe RF group (n=37, 60 [23.5–87] mg/dL); however, there were no significant differences in iron levels between the non-RF and severe RF groups (non-RF vs. mild RF: p=0.019, non-RF vs. severe RF: p>0.999, and mild RF vs. severe RF: p=0.009). That is, there was a U-shaped association between serum iron levels and disease severity. TIBC levels decreased significantly with increasing severity; consequently, TSAT was significantly higher in patients with severe RF than in other patients. Multivariate analysis including only patients with RF adjusted for age and sex demonstrated that higher serum iron or TSAT levels were independently associated with development of severe RF. Conclusions A U-shaped association between serum iron level and RF severity in hospitalized COVID-19 patients was observed. Higher serum iron levels in COVID-19 patients with RF are associated with the development of severe RF, indicating that inadequate response to lower serum iron might be an exacerbating factor for COVID-19.

A 74-year-old man presented for surgical treatment to alleviate chronic post-herniorrhaphy inguinal pain. Physical and imaging examinations suggested that his pain was due to his ilioinguinal nerve being entrapped by a meshoma composed of bilayer mesh and plug mesh. The patient strongly desired mesh removal, although it appeared challenging because of adhesion of the meshes from the previous herniorrhaphies. Anticipating technical difficulty, we performed laparoscopic totally extraperitoneal repair followed by open mesh removal. Thus, the risk of damaging the peritoneum and visceral organs during open mesh removal was eliminated because the peritoneum had already been separated from the pathogenic mesh during the laparoscopic repair. The patient's chronic pain was drastically relieved. Combination surgery may therefore be a safe and useful technique in select patients with chronic postoperative inguinal pain. This approach could also prevent hernia recurrence.

BackgroundTherapeutic effects of steroids on acute respiratory distress syndrome (ARDS) requiring mechanical ventilation (MV) have been reported. However, predictive indicators of early weaning from MV post-treatment have not yet been defined, making treating established ARDS challenging. Interleukin (IL)-6 has been associated with the pathogenesis of ARDS.ObjectiveOur aim was to clarify clinical utility of IL-6 level in ventilated patients with established ARDS.MethodsClinical, treatment, and outcome data were evaluated in 119 invasively ventilated patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-mediated ARDS. Plasma levels of IL-6 and C-reactive protein (CRP) were measured on days 1, 4, and 7 after intubation.ResultsFifty-two patients were treated with dexamethasone (steroid group), while the remaining 67 patients were not (non-steroid group). Duration of MV use was significantly shorter in the steroid group compared to non-steroid group (11.5±0.6 vs. 16.1±1.0 days, P = 0.0005, respectively) along with significantly decreased levels of IL-6 and CRP. Even when restricted to the steroid group, among variables post-MV, IL-6 level on day 7 was most closely correlated with duration of MV use (Spearman’s rank correlation coefficient [ρ] = 0.73, P < 0.0001), followed by CRP level on day 7 and the percentage change in IL-6 or CRP levels between day 1 and day 7. Moreover, among these variables, IL-6 levels on day 7 showed the highest accuracy for withdrawal from MV within 11 days (AUC: 0.88), with optimal cutoff value of 20.6 pg/mL. Consistently, the rate of MV weaning increased significantly earlier in patients with low IL-6 (≤ 20.6 pg/mL) than in those with high IL-6 (> 20.6 pg/mL) (log-rank test P < 0.0001).ConclusionsIn invasively ventilated patients with established ARDS due to SARS-CoV-2, plasma IL-6 levels served as a predictor of early withdrawal from MV after dexamethasone administration.

Microsomal prostaglandin E synthase-1 (mPGES-1)/prostaglandin E2 (PGE2) induces angiogenesis through the prostaglandin E2 receptor (EP1-4). Among immune cells, regulatory T cells (Tregs), which inhibit immune responses, have been implicated in angiogenesis, and PGE2 is known to modulate function and differentiation of Tregs. We hypothesized that mPGES-1/PGE2-EP signaling could contribute to recovery from ischemic conditions by promoting the accumulation of Tregs.Wild-type (WT), mPGES-1-deficient (mPges-1-/-), and EP4 receptor-deficient (Ep4-/-) male mice 6-8 weeks old were used. Hindlimb ischemia was induced by femoral artery ligation. Recovery from ischemia was suppressed in mPges-1-/- mice and compared with WT mice. The number of accumulated forkhead box protein P3 (FoxP3)+ cells in ischemic muscle tissue was decreased in mPges-1-/- mice compared with that in WT mice. Expression levels of transforming growth factor-β (TGF-β) and stromal cell derived factor-1 (SDF-1) in ischemic tissue were also suppressed in mPges-1-/- mice. The number of accumulated FoxP3+ cells and blood flow recovery were suppressed when Tregs were depleted by injecting antibody against folate receptor 4 (FR4) in WT mice but not in mPges-1-/- mice. Recovery from ischemia was significantly suppressed in Ep4-/- mice compared with WT mice. Furthermore, mRNA levels of Foxp3 and Tgf-β were suppressed in Ep4-/- mice. Moreover, the numbers of accumulated FoxP3+ cells in ischemic tissue were diminished in Ep4-/- mice compared with Ep4+/+ mice.These findings suggested that mPGES-1/PGE2 induced neovascularization from ischemia via EP4 by promoting accumulation of Tregs. Highly selective EP4 agonists could be useful for treatment of peripheral artery disease (PAD).Although surgical treatment for PAD in patients improved, some patients with advanced disease have no other option for treatments other than amputation. In the present study, we revealed that endogenous mPGES-1/PGE2-EP4 signaling induced recovery from ischemia by promoting Tregs accumulation at the ischemic site. In addition, we showed that selective EP4 agonist, or transplantation of Tregs, induced recovery from ischemic conditions. These results indicate that the use of selective EP4 agonist, or cell therapy of Tregs, may be a potential treatment option for severe critical limb ischemia patients.

Background Prostaglandin E2 receptor 4 (EP4) plays a crucial role in inflammatory diseases. Inflammatory cardiomyopathy often leads to refractory heart failure. Purpose We aimed to evaluate the role of EP4 in the development of inflammatory cardiomyopathy. Methods Experimental autoimmune myocarditis (EAM) was induced by immunization with cardiac myosin in balb/c mice. EP4 selective antagonist (CJ-42794, Cayman Chemical: 30 mg/kg/day), EP4 selective agonist (20 mg/kg/day), both, or vehicle alone was daily administrated after the immunization. Cardiac function and dimensions were assessed by echocardiography. Blood pressure and heart rate were assessed with tail-cuff method. Cardiac inflammation and fibrosis were immunohistologically examined. Molecular examination was performed by RT-PCR and immunoblotting. Results Cardiac dysfunction and dilatation were worsened on day 21 in EP4 antagonist-treated group compared with in the vehicle-treated group, accompanied by an increase in cellular infiltration area (21.7±1.9 vs. 11.0±2.7%, P=0.0367, respectively). Conversely, cardiac dysfunction and dilatation were improved in EP4 agonist-treated group compared with in the vehicle-treated group (Left ventricular fractional shortening: 69±3% vs. 40±4%, P Conclusions EP4 activation negatively regulated the induction of cardiac autoimmunity, which alleviated cardiac dysfunction, dilatation, and fibrosis. EP4 may be a therapeutic target for preventing the development of inflammatory cardiomyopathy. Funding Acknowledgement Type of funding sources: None.

The increasing requirement of mechanical ventilation (MV) due to the novel coronavirus disease (COVID-19) is still a global threat. The aim of this study is to identify markers that can easily stratify the impending use of MV in the emergency room (ER). A total of 106 patients with COVID-19 requiring oxygen support were enrolled. Fifty-nine patients were provided MV 0.5 hours (interquartile range: 0.3 to 1.4) post-admission. Clinical and laboratory data before intubation were collected. Using a multivariate logistic regression model, we identified four markers associated with the impending use of MV, including the ratio of peripheral blood oxygen saturation to fraction of inspired oxygen (SpO2/FiO2 ratio), alanine aminotransferase, blood glucose (BG), and lymphocyte counts. Among these markers, the combination of SpO2/FiO2 ratio and BG, which can be measured easily and immediately, showed higher accuracy in its prediction (AUC: 0.88) compared to SpO2/FiO2 ratio alone (AUC: 0.84). Moreover, even in patients without severe respiratory failure (SpO2/FiO2 ratio > 300), BG (> 138 mg/dL) was predictive of MV use. Measuring BG and SpO2/FiO2 ratio may be a simple and versatile new strategy to accurately identify ER patients with COVID-19 at high risk for the imminent need of MV.

The prognosis of out-of-hospital cardiac arrest has improved in Japan due to the increasing availability of automated external defibrillators. However, priority should be placed on specificity to not perform unnecessary waveforms rather than sensitivity to perform defibrillation on necessary waveforms. This report describes a case in which the f-wave of bradycardic atrial fibrillation was erroneously analyzed and defibrillated. Health care workers should be aware that the f-wave of bradycardic atrial fibrillation may be erroneously assessed as fine ventricular fibrillation; they should change it to the manual mode and respond as necessary.

Background: Coronavirus disease (COVID-19) pneumonitis associated with severe respiratory failure has a high mortality rate. Based on recent reports, the most severely ill patients present with coagulopathy, and disseminated intravascular coagulation (DIC)-like massive intravascular clot formation is frequently observed. Coagulopathy has emerged as a significant contributor to thrombotic complications. Although recommendations have been made for anticoagulant use for COVID-19, no guidelines have been specified.Case presentation: We describe four cases of critical COVID-19 with thrombosis detected by enhanced CT scan. The CT findings of all cases demonstrated typical findings of COVID-19 and pulmonary embolism or deep venous thrombus without critical exacerbation. Two patients died of respiratory failure due to COVID-19.Discussion: Previous reports have suggested coagulopathy with thrombotic signs as the main pathological feature of COVID-19, but no previous reports have focused on coagulopathy evaluated by whole-body enhanced CT scan. Changes in hemostatic biomarkers, represented by an increase in D-dimer and fibrin/fibrinogen degradation products, indicated that the essence of coagulopathy was massive fibrin formation. Although there were no clinical symptoms related to their prognosis, critical COVID-19-induced systemic thrombus formation was observed. Conclusions: Therapeutic dose anticoagulants should be considered for critical COVID-19 because of induced coagulopathy, and aggressive follow-up by whole body enhanced CT scan for systemic venous thromboembolism (VTE) is necessary.

Background Many health care workers around the world tackled with COVID-19, however sadly, the infection of many medical care workers were reported. To reduce the risk of infection, we launched selected team (Team COVID) of non-specialists and brought in active telemedicine method and computed tomography (CT)-first protocol. We describe our actual practice and the health status of medical doctors dealing with COVID-19 patients. Methods Between April 17, 2020 and May 24, 2020, 10 doctors worked with COVID-19 patients as part of Team COVID. The Team COVID doctors used a CT-first triage protocol for outpatients and telemedicine for inpatients and outpatients. We evaluated paired serum-specific antibodies for SARS-CoV-2 at the initial and end of the study duration and PCR results for SARS-CoV-2 at the end of the study duration. Furthermore, 36-item short-form of the Medical Outcome Study Questionnaire (SF-36) at the beginning and end of the study period were evaluated. Results Ten doctors worked as Team COVID: seven internal medicine doctors and three surgeons. During the study period, Team COVID treated 165 individuals in the outpatient clinic and isolated hospitalized patients for 315 person-days. There were no positive results of serum-specific antibody testing and PCR testing for SARS-CoV-2 in Team COVID doctors. Furthermore, the SF-36 showed no deterioration in physical and mental QOL status. No in-hospital infection occurred during the study period. Conclusions The Team COVID fulfilled the treatment using the active telemedicine and CT-first triage protocol without in hospital infection and excess stress. The combination strategy seems acceptable for both the protection and stress relief among the medical staff.

Background: Coronavirus disease 2019 (COVID-19) continues to spread worldwide. Because of the absence of reliable rapid diagnostic systems, patients with COVID-19 symptoms are suspected of disease. Computed tomography (CT) in patients with suspected COVID-19 may be reasonable for triaging, and CT-first triage strategies have been proposed. However, clinical evaluation of a CT-first triage protocol is lacking. The aim of this study is to investigate the real-world efficacy and limitations of a CT-first triage strategy in patients with suspected COVID-19.Methods: This was a single-center cohort study evaluating outpatients with suspected COVID-19 who underwent a medical examination at Yokohama City University Hospital and who were prospectively registered between 9 February and 5 May 2020. We treated patients according to the CT-first triage protocol. CT findings were classified into five categories according to the COVID-19 Reporting and Data System (CO-RADS). With the CT-first triage protocol, patients with a suspicious clinical history, symptoms, or suspicious findings on chest CT were allocated to the COVID-19 suspected group. The primary outcome was efficacy of the CT-first triage protocol for outpatients with suspected COVID-19. We conducted additional analyses of the isolation time of outpatients with suspected COVID-19 and reached final diagnoses.Results: In total, 108 outpatients with suspected COVID-19 were examined at our hospital. Forty-eight patients (44.9%) were categorized as CO-RADS 1, 26 patients (24.3%) as CO-RADS 2, 14 patients (13.1%) as CO-RADS 3, 6 patients (5.6%) as CO-RADS 4, and 13 patients (12.1%) as CO-RADS 5. One patient was excluded because of pregnancy. Using the CT-first triage protocol, 48 (44.9%) patients were suspected of having COVID-19. Nine patients (18.8%) in this group were positive for severe acute respiratory syndrome coronavirus 2 using polymerase chain reaction; no patients in the group not suspected of having COVID-19 were diagnosed with COVID-19 during follow up. The protocol significantly shortened the duration of isolation for the not-suspected versus the suspected group (70.5 vs. 1037.0 minutes, P < .001). Conclusions: Our CT-first triage protocol was acceptable for triaging outpatients with suspected COVID-19. This protocol will be helpful for appropriate triage, especially in areas where polymerase chain reaction is limited.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It was first identified in December 2019 in Wuhan, China, and has resulted in global pandemic. There is currently no effective therapeutic strategy for the management of mechanical ventilation or antiviral drugs for the treatment of this disease. As such, the development of a therapeutic strategy is urgently needed and should be established as soon as possible. In this case series, a therapeutic strategy was initially developed based on previous treatment methods used for the treatment of SARS and MERS in the absence of treatment options for COVID-19 due to a lack of information. During the search for a potential treatment, clinical findings were obtained from patients with severe COVID-19, and one therapeutic strategy was established. This therapeutic strategy was then applied to severe COVID-19 patients. In addition, we can require some interesting clinical features and characteristics of COVID-19 from blood analysis and physical findings. Here, we reported on the clinical features and characteristics of a therapeutic strategy for the treatment of severe COVID-19 pneumonia at our institution.

Background Although some predictors of COVID-19 pneumonia severity and mortality have been identified, much of the pathophysiology of this emerging infectious disease remains unclear. We hypothesized that a patient’s cholinesterase level on admission could predict COVID-19 pneumonia severity and mortality. Methods We retrospectively collected data of 26 COVID-19 pneumonia patients from February–May 2020. Outcomes were aggravation of symptoms and in-hospital mortality. We compared receiver operating curves of cholinesterase, C-reactive protein, lymphocytes, albumin, D-dimer, and PaO2/FiO2 ratio and examined prediction accuracy. Regarding the interaction between cholinesterase and other variables, each independent variable was divided into two groups using cutoff values, and interaction terms were created. Results Cholinesterase levels on admission were significantly lower in the severe group than in the mild-to-moderate group (326 vs. 218 IU/L, p = 0.006; area under the curve: 0.81; 95% confidence interval 0.61–0.94). When comparing the area under the curve, cholinesterase was comparable to C-reactive protein, albumin, lymphocytes, and PaO2/FiO2 ratio other than D-dimer in the prediction accuracy of severe cases and mortality. Cholinesterase levels on admission were significantly lower in the death group than in the survival group (274 vs. 187.5 IU/L, p = 0.028; area under the curve: 0.79; 95% interval 0.58–0.93). Regarding the interaction between cholinesterase and established predictors, the prediction accuracy of both severity and death was higher when cholinesterase was combined with each predictor than when cholinesterase was used alone. Conclusions Cholinesterase may reflect the disease state of COVID-19 pneumonia, suggesting that a patient’s cholinesterase level on admission may be useful as a predictor of severity and prognosis.

A 65-year-old man visited a primary care hospital with a continued fever of 38°C for 3 days. As his fever did not improve until 8 days after, he was admitted into another acute care hospital, where his respiratory condition rapidly worsened. Therefore, the patient was transferred to our hospital. On the day of transfer (day 1) he was started on mechanical ventilation. COVID-19 was diagnosed using a polymerase chain reaction assay 6 days after admission (day 6). The rehabilitation therapy was begun on day 6. The initial rehabilitation programs focused on positioning and postural drainage. The patient was extubated on day 19 and he began standing and stepping on the same day. Gait exercises began on day 22, and endurance training was initiated on day 28. The patient was discharged from our hospital on day 34 as he met the physical function milestones. One month after discharge, the Medical Research Council sum score and Barthel Index had each improved; therefore, muscle strength and daily activities had returned to normal. It was assumed that mobilization should be performed as soon as possible after the end of sedation during the acute phase of severe COVID-19 infection in patients receiving mechanical ventilation.

Background: The Coronavirus disease 2019 pandemic continues to spread worldwide. Because of the absence of reliable rapid diagnostic systems, patients with symptoms of Coronavirus disease 2019 are treated as suspected of the disease. Use of computed tomography findings in Coronavirus disease 2019 are expected to be a reasonable method for triaging patients, and computed tomography-first triage strategies have been proposed. However, clinical evaluation of a computed tomography-first triage protocol is lacking.The aim of this study is to investigate the real-world efficacy and limitations of a computed tomography-first triage strategy in patients with suspected Coronavirus disease 2019.Methods: This was a single-center cohort study evaluating outpatients with fever who received medical examination at Yokohama City University Hospital, prospectively registered between 9 February and 5 May 2020. We treated according to the computed tomography-first triage protocol. The primary outcome was efficacy of the computed tomography-first triage protocol for patients with fever in an outpatient clinic. Efficacy of the computed tomography-first triage protocol for outpatients with fever was evaluated using sensitivity, specificity, positive predictive value, and negative predictive value. We conducted additional analyses of the isolation time of feverish outpatients and final diagnoses.Results: In total, 108 consecutive outpatients with fever were examined at our hospital. Using the computed tomography-first triage protocol, 48 (44.9%) patients were classified as suspected Coronavirus disease 2019. Nine patients (18.8%) in this group were positive for severe acute respiratory syndrome coronavirus 2 using polymerase chain reaction; no patients in the group considered less likely to have Coronavirus disease 2019 tested positive for the virus. The sensitivity, specificity, positive predictive value, and negative predictive value of our computed tomography-first triage protocol for Coronavirus disease 2019 were 100%, 60.2%, 18.8%, and 100%, respectively. The protocol significantly shortened the duration of isolation for the not-suspected versus the suspected group (70.5 vs. 1037.0 minutes, P < .001). Conclusions: Our computed tomography-first triage protocol was acceptable for screening patients with suspected Coronavirus disease 2019. This protocol will be helpful for appropriate triage, especially in areas where polymerase chain reaction is inadequate.

Aim In the present, the coronavirus disease 2019 (COVID‐19) pandemic accelerates all over the world, global health care systems have become overwhelmed with potentially infectious patients seeking testing and care. So, we must set up effective and useful zoning for unfamiliar COVID‐19 because it is the most important to prevent spread of infection to and from medical staffs or other patients and patients relies on effective use of standard precaution with personal protective equipment (PPE). Method We set up a special ward changed a general ward we always used as an acute care unit for severe COVID‐19 patients with taking into consideration airflow, the direction of movement of medical staffs, and prevention of infection spread to medical staffs and other patients. And, we checked daily condition and body temperature of all medical staffs for 60 days. Result There were no evidence of COVID‐19 infection in all medical staffs and patients during the period thanks to effective and useful zoning with PPE. Conclusion We should set up the special wards and rooms with some devices for the time to come due to protect medical staffs and other patients, and prevent from the explosion of COVID‐19 anywhere with effective and useful zoning with PPE.

Background Veno‐venous extracorporeal membrane oxygenation (VV‐ECMO) is one of the ultimate treatments for acute respiratory failure. However, the effectiveness of ECMO in patients with novel coronavirus disease (COVID‐19) is unknown. Case Presentation A 72‐year‐old woman who was a passenger of a cruise ship tested positive for the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) while in quarantine on board using throat swab. Three days after admission, her condition deteriorated, and she was subsequently intubated. On day 6, VV‐ECMO was introduced. Lopinavir/ritonavir was given; continuous renal replacement therapy was also introduced. On day 10, her chest radiography and lung compliance improved. She was weaned off ECMO on day 12. Conclusion Treatment of severe pneumonia in COVID‐19 by ECMO should recognize lung plasticity considering time to ECMO introduction and interstitial biomarkers. In Japan, centralization of ECMO patients has not been sufficient. Thus, we suggest nationwide centralization and further research to respond to the crisis caused by COVID‐19., ECMO is one of the treatment options in severe ARDS by SARS‐CoV‐2. It is important to recognize lung plasticity. Centralization of COVID‐19 ECMO patients may be effective in Japan.

Background Aortoenteric fistula (AEF), occasionally reported as a fatal complication after aortic or other vascular procedures, is a communication between the aorta and the digestive tract. AEF as a fatal complication of overlap esophagojejunostomy after esophagogastrectomy has not been reported previously. Herein, we report a case of AEF after laparoscopic proximal gastrectomy and transhiatal lower esophagectomy for cancer of the esophagogastric junction, in which linear staplers were used for overlap esophagojejunostomy. Case presentation A 66-year-old woman with advanced cancer of the esophagogastric junction underwent laparoscopic proximal gastrectomy and transhiatal lower esophagectomy with abdominal and lower mediastinal lymphadenectomy. Double tract reconstruction by the overlap method was performed. The patient was discharged from the hospital 10 days after surgery with a good postoperative course. However, she developed sudden-onset massive hematemesis and melena the day after discharge, resulting in death. Autopsy revealed that the stapled edge of the entry hole of the overlap esophagojejunostomy was in direct contact with the descending aorta. AEF was found at the esophagojejunostomy site. Conclusions To our knowledge, this is the first report of AEF as a fatal complication of overlap esophagojejunostomy after esophagogastrectomy. Although we could not definitively identify the cause of the AEF, it could be attributed to direct contact between the stapled edge and the bare thoracic aorta over a period of 10 days. To avoid direct contact with the aorta in esophagojejunostomy with linear staplers, all stapled edges should be covered by suturing and attention should be paid to the position of these edges.

Background: Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease with a poor prognosis. Fibroblast proliferation amplifies extracellular matrix deposition and increases angiogenesis. Vascular endothelial growth factor (VEGF) is one of the most potent angiogenic factors. VEGF interacts with VEGF receptors (VEGFR1 and VEGFR2). A previous study showed that VEGFR1 tyrosine kinase (TK) signaling induced blood flow recovery mediated by bone marrow (BM)-derived stem cells. We hypothesized that VEGFR1-TK signaling might be related to pulmonary fibrosis. Material and methods: Six-week-old male C57Bl/6 wild-type (WT) mice and VEGFR1 TK knockout mice (TKKO mice) were treated with a single intratracheal injection of bleomycin (BLM; 0.1 μg in 50 μl saline) or vehicle (saline; 50 μl). Lung fibrosis was evaluated by histology, real-time PCR and ELISA for pro-fibrotic factors, and assessment of lung mechanics. Results: The fibrotic area in the lung and the lung elastance were significantly reduced in TKKO mice (P

Compensatory lung growth models have been widely used to investigate alveolization because the remaining lung can be kept intact and volume loss can be controlled. Vascular endothelial growth factor (VEGF) plays an important role in blood formation during lung growth and repair, but the precise mechanisms involved are poorly understood; therefore, the aim of this study was to investigate the role of VEGF signaling in compensatory lung growth. After left pneumonectomy, the right lung weight was higher in VEGF transgenic mice than wild-type (WT) mice. Compensatory lung growth was suppressed significantly in mice injected with a VEGF neutralizing antibody and in VEGF receptor-1 tyrosine kinase-deficient mice (TK(-/-) mice). The mobilization of progenitor cells expressing VEGFR1(+) cells from bone marrow and the recruitment of these cells to lung tissue were also suppressed in the TK(-/-) mice. WT mice transplanted with bone marrow from TK(-/-)transgenic GFP(+) mice had significantly lower numbers of GFP(+)/aquaporin 5(+), GFP(+)/surfactant protein A(+), and GFP(+)/VEGFR1(+) cells than WT mice transplanted with bone marrow from WTGFP(+) mice. The GFP(+)/VEGFR1(+) cells also co-stained for aquaporin 5 and surfactant protein A. Overall, these results suggest that VEGF signaling contributes to compensatory lung growth by mobilizing VEGFR1(+) cells.

We report a rare case of visceral injury after totally extraperitoneal endoscopic inguinal hernia repair. A 48-year-old man underwent needlescopic totally extraperitoneal repair of a direct inguinal hernia. Bleeding from a branch of the inferior epigastric vessels occurred at the beginning of the extraperitoneal dissection with a monopolar electrosurgical device. Hemostasis was prolonged. However, herniorrhaphy and mesh repair were successfully performed, and no peritoneal disruption or pneumoperitoneum was visible. The patient was discharged home on the next day. However, 30 h after this operation, he underwent diagnostic and operative laparoscopy because of acute abdominal pain. Ileal perforation was found and repaired, and pathological examination indicated cautery artifact. Thus, thermal damage to the ileum during the initial operation may have caused the bowel perforation. To the best of our knowledge, no other cases of bowel perforation after totally extraperitoneal repair without peritoneal disruption have been reported.