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Immunoglobulin G4-related disease (IgG4-RD) can affect various organs, including the cardiovascular system. In this study, we described the case of a 72-year-old man with periaortitis both in the ascending and terminal aorta related to IgG4-RD. He presented with swelling in the left leg. Computed tomography (CT) showed increased wall thickness of the ascending aorta and retroperitoneal fibrosis, which, in turn, caused deep vein thrombosis. Using positron emission tomography-computed tomography, the patient was diagnosed with IgG4-RD in the aorta. Although it was difficult to distinguish intramural hematoma (IMH) from IgG4-related periaortitis, treatment with steroids has dramatically improved his periaortitis. IgG4-related periaortitis should be differentiated from IMH due to their similar morphologies.

Background The impact of the outbreak of COVID-19 on the work of respiratory physicians in Japan has not yet been evaluated. The study investigates the impact of the outbreak on respiratory physicians’ work over time and identifies problems to be addressed in the future. Methods We conducted a web-based survey of respiratory physicians in 848 institutions. The survey comprised 32 questions and four sections: Survey 1 (April 20, 2020), Survey 2 (May 27, 2020), Survey 3 (August 31, 2020), and Survey 4 (December 4, 2020). Results The mean survey response rate was 24.9%, and 502 facilities (59.2%) participated in at least one survey. The proportion of facilities that could perform PCR tests for diagnosis and more than 20 tests per day gradually increased. The percentage capable of managing extracorporeal membrane oxygenation (ECMO) or more than five ventilators did not increase over time. The proportion that reported work overload of 150% or more, stress associated with lack of personal protective equipment (PPE), and harassment or stigma in the surrounding community did not sufficiently improve. Conclusion While there was an improvement in expanding the examination system and medical cooperation in the community, there was no indication of enhancement of the critical care management system. The overwork of respiratory physicians, lack of PPE, and harassment and stigma related to COVID-19 did not sufficiently improve and need to be addressed urgently.

We provide the details of the successful management of a patient with active Cushing’s disease complicated with coronavirus disease 2019 (COVID-19) pneumonia. The patient was a 27-year-old Japanese female healthcare worker who was scheduled to undergo pituitary surgery for Cushing’s disease. She had been in close contact with an undiagnosed patient infected with COVID-19 and then developed COVID-19 pneumonia. Despite a lack of known risk factors associated with severe COVID-19 infection, the patient’s dyspnea worsened and her respiratory condition deteriorated, as indicated by the need for 7 L/min oxygen supply by mask to maintain her oxygen saturation at >90%. Medical treatment was initiated to control hypercortisolism by the ‘block and replace’ regimen using steroidogenesis inhibitors and hydrocortisone. The COVID-19 pneumonia improved with multi-modal treatment including antiviral therapy. One month later, after a negative severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) test result and with appropriate protection against virus transmission to medical staff in the operating room and daily medical care nurses, trans-sphenoidal surgery was performed by our highly experienced pituitary surgeon. One month after the surgery, the patient’s basal ACTH and cortisol levels and urinary free cortisol were all under the detection limit. Surgical remission was expected. Since hypercortisolism due to active Cushing’s disease may worsen a COVID-19 infection, multi-disciplinary management that includes appropriate and prompt treatment strategies is mandatory in such cases.

ObjectiveMycobacterium tuberculosis(Mtb) H37Ra strain has been reported to rapidly enter the viable but non-culturable (VBNC) state following treatment with an NADH oxidase inhibitor (diphenyleneiodonium [DPI]) and to be reactivated by fetal bovine serum (FBS). However, the mechanism underlying FBS-induced reactivation is unclear. We tried to reveal the mechanism of FBS-induced reactivation usingM. tuberculosisH37Rv.MethodsFirst, we evaluated the effect of DPI on culturability, viability and changes of acid-fastness toward H37Rv. Secondly, we measured the reactivation-promoting effects of human serum albumin, egg-white albumin and antioxidative agents in DPI-induced VBNC cells. We also inhibited adenylyl cyclase and protein kinase which is the downstream of adenylyl cyclase to evaluate the influence to reactivation capacity of bovine serum albumin (BSA).ResultsDPI treatment induced VBNC state in H37Rv, resulting in a high proportion of viable cells but a low proportion of culturable cells, loss of acid-fastness and lipid-accumulation. Not only FBS but also BSA alone could reactivate H37Rv. Contrary to our expectation, only human serum albumin had a similar restorative effect to BSA. The inhibition of adenylyl cyclase by SQ22536 did not have a significant effect on reactivation; however, the inhibition of mycobacterial protein kinase by H89 and staurosporine strongly suppressed the BSA-induced reactivation.ConclusionDPI-induced VBNC Mtb cells may be reactivated via the activation of protein kinase-dependent cell division processes through interaction with BSA.

We prospectively compared the efficacy of PCR detection of SARS-CoV-2 between paired nasopharyngeal and saliva samples in nine COVID-19 patients. SARS-CoV-2 was detected in saliva in 8 of 9 (89%) patients and in all 11 samples taken within 2 weeks after disease onset. Viral load was equivalent at earlier time points but declined in saliva than nasopharyngeal samples. PCR negativity was also concordant in all 27 saliva samples from 24 patients between nasopharyngeal and saliva samples. These results suggest that saliva is a reliable noninvasive alternative to nasopharyngeal swabs and facilitate widespread PCR testing in the face of shortages of swabs and protective equipment without posing a risk to healthcare workers.

Infectious diseases caused by nontuberculous mycobacteria (NTM) are increasingly becoming a major global problem. Additionally, Mycobacteroides abscessus subsp. abscessus (MAB) infections are refractory to macrolides. This study was conducted to investigate the epidemiology of rapidly growing mycobacteria (RGM) species isolated from clinical specimens in Japan and assess differences in the regional distribution of lower respiratory specimens (LRS)- and non-lower respiratory specimens (NLRS)-derived species. 532 strains (427 LRS, 92 NLRS and 15 unknown specimens) were isolated in nine areas of Japan. We collected 418 specimens from Bio Medical Laboratories (BML), Inc., and 114 specimens from 45 hospitals in Japan. Their epidemiological differences were examined according to the specimen type, region, and climate. Fifteen species were identified. The proportion of M. abscessus group (MAG) strains was significantly lower in NLRS than in LRS (35.9% vs. 68.4%). The proportion of MAG strains was higher in northern Japan than in other regions (83.7% vs. 60.5%). Variations in strain abundance among RGM species was evident in regions with a mean annual temperature below 15 °C. We conclude that the proportions of MAG strains differed between NLRS and LRS in Japan. In addition, the mean annual temperature likely influenced the distribution of RGM species.

Background Mycolicibacterium fortuitum is a species of the rapidly growing mycobacteria that can cause pulmonary infection. It is susceptible to multiple antibiotics both in vitro and in clinical practice, so that any combination of susceptible drugs is effective. However, we encountered a case of infection due to fluoroquinolone-resistant M. fortuitum. In this study, we report the case and describe the mechanism of resistance. Case presentation A 65-year-old man with a history of total gastrectomy and immunosuppressant treatment for rheumatoid arthritis developed a recurrence of pulmonary infection caused by M. fortuitum. He was treated with clarithromycin and levofloxacin as a first-line treatment, based on the favorable susceptibility at that time. After recurrence, a high minimum inhibitory concentration to fluoroquinolones was detected. DNA sequencing of the pathogen showed the substitution of serine for tryptophan at residue 83 in the gyrA gene. He was successfully treated with a combination of other antibiotics. Conclusion This is the first report on the treatment of fluoroquinolone-resistant M. fortuitum and investigation of the mechanism of resistance. We suggest that the susceptibility test remains effective for determining the next line of treatment after a pathogen has acquired resistance, and resistance to fluoroquinolones in M. fortuitum can be attributed to a single change of amino acid.

Background Gemella bergeri is one of the nine species of the genus Gemella and is relatively difficult to identify. We herein describe the first case of septic shock due to a Gemella bergeri coinfection with Eikenella corrodens. Case presentation A 44-year-old Asian man with a medical history of IgG4-related ophthalmic disease who was prescribed corticosteroids (prednisolone) presented to our hospital with dyspnea. On arrival, he was in shock, and a purpuric eruption was noted on both legs. Contrast enhanced computed tomography showed fluid retention at the right maxillary sinus, left lung ground glass opacity, and bilateral lung irregular opacities without cavitation. Owing to suspected septic shock, fluid resuscitation and a high dose of vasopressors were started. In addition, meropenem, clindamycin, and vancomycin were administered. Repeat computed tomography confirmed left internal jugular and vertebral vein thrombosis. Following this, the patient was diagnosed with Lemierre’s syndrome. Furthermore, he went into shock again on day 6 of hospitalization. Additional soft tissue infections were suspected; therefore, bilateral below the knee amputations were performed for source control. Cultures of the exudates from skin lesions and histopathological samples did not identify any pathogens, and histopathological findings showed arterial thrombosis; therefore it was concluded that the second time shock was associated with purpura fulminans. Following this, his general status improved. He was transferred to another hospital for rehabilitation. The blood culture isolates were identified as Gemella bergeri and Eikenella corrodens. Gemella bergeri was identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry and confirmed by 16S rRNA gene sequencing later. The primary focus of the infection was thought to be in the right maxillary sinus, because the resolution of the fluid retention was confirmed by repeat computed tomography. Conclusions Gemella bergeri can be the causative pathogen of septic shock. If this pathogen cannot be identified manually or through commercial phenotypic methods, 16S rRNA gene sequencing should be considered.

Background The third wave of the COVID-19 epidemic in the island of Hokkaido, the second largest island in Japan, began abruptly in October 2020. Methods We conducted a phylodynamic analysis of the SARS-CoV-2 genome sequences obtained from tertiary medical centers in the Greater Tokyo Area and Sapporo, the largest city in the island of Hokkaido, and genome sequences published by GISAID, an international SARS-CoV-2 genome database. We also analyzed the statistics on the person-nights of travelers in the island of Hokkaido from the Greater Tokyo Area in 2019 versus 2020. Results At least eight sub-lineages belonging to the B.1.1.214 lineage were introduced to the island of Hokkaido from the island of Honshu, the mainland of Japan from late July to November 2020, during the governmental travel promotion program. Five of the eight sub-lineages originated from the Greater Tokyo Area. Comparison of the monthly ratios of the person-nights of travelers in the island of Hokkaido from the Greater Tokyo Area in 2019 and 2020 revealed that the highest value occurred in October 2020. Conclusion We contend that the Japanese governmental travel promotion program contributed to the introduction of the B.1.1.214 sub-lineages from the main island of Honshu to the island of Hokkaido, and drove the third wave in Hokkaido, even if we are unable to establish the causality.

Highlights • nCoV-DK halves SARS-CoV-2 detection time by eliminating RNA extraction and purification. • nCoV-DK detects SARS-CoV-2 as effectively as the direct PCR. • Saliva is a reliable tool to detect SARS-CoV-2 by nCoV-DK., Rapid detection of SARS-CoV-2 is critical for the diagnosis of coronavirus disease 2019 (COVID-19) and preventing the spread of the virus. A novel “2019 Novel Coronavirus Detection Kit (nCoV-DK)” halves detection time by eliminating the steps of RNA extraction and purification. We evaluated concordance between the nCoV-DK and direct PCR. The virus was detected in 53/71 (74.6%) and 55/71 (77.5%) by the direct PCR and nCoV-DK, respectively, with overall concordance rate of 94.4%: 95.2% in nasopharyngeal swab, 95.5% in saliva, and 85.7% in sputum. The nCoV-DK effectively detects SARS-CoV-2 in all types of the samples including saliva, while reducing time required for detection, labor, and risk of human error.

A 51-year-old man with severe comorbidities required redo revascularization due to left chronic limb-threatening ischemia caused by a previous vein graft occlusion. The saphenous veins were not available due to previous surgeries. Femoro-posterior tibial artery bypass surgery was successfully performed using the basilic-cephalic loop vein under peripheral nerve blockades. This anesthesia allowed a series of surgical revascularizations without general anesthesia, and the postoperative courses were uneventful. The patient survived for 4 years with ambulatory status. In conclusion, loop graft can be an alternative single vein material for distal bypass when no saphenous veins are available.

Delayed cardiac tamponade (DCT) can be a fatal complication after cardiac surgery, but its early diagnosis and/or prediction is sometimes difficult. This study aimed to confirm the efficacy of postoperative computed tomography (CT) as routine examination compared with transthoracic echocardiography (TTE) for predicting DCT after cardiac surgery. This study was a retrospective single-center analysis of 485 consecutive patients undergoing cardiac surgery from January 2016 to July 2018 in our department. Among them, 237 patients were enrolled in this analysis after application of the exclusion criteria: minimally invasive surgery via small thoracotomy, death in the acute phase, and no CT 7 ± 3 days after surgery. Pericardial effusion (PE) was measured at the thickest part using CT and TTE. DCT was found in nine enrolled patients (3.8%). The mean PE on CT was 7.7 ± 5.5 mm in the no event group and 23.4 ± 5.7 mm in the DCT group (p = 0.026), whereas the mean PE on TTE was 6.2 ± 4.5 mm in the no event group and 10.8 ± 4.4 mm in the DCT group (p = 0.170). On multivariate analysis, PE greater than 20 mm on CT (Odds ratio, 13.93; 95% confidence interval 2.57–75.46; p = 0.002) was a significant predictor of DCT. The present study suggested that postoperative CT examination is superior to TTE for predicting DCT. If PE is less than 20 mm on CT, it could be treated conservatively; otherwise, preventive/therapeutic intervention should be considered.

Mycobacterium abscessus is one of the most pathogenic and chemotherapy-resistant rapidly growing mycobacteria. This Mycobacterium should always be considered as a possible cause of chronic otitis media in children, and treatment might be challenging because of its resistance to multiple antibiotics. There are no reports describing the therapeutic use of tigecycline for the treatment of chronic otitis media caused by M. abscessus. A 10-year-old boy was referred to Tokyo Metropolitan Children’s Medical Center with a 7-year history of recurrent otitis media despite treatment with antibiotics and ventilation tubes. Cultures of the otorrhea yielded Mycobacterium abscessus spp. massiliense, and it showed multiple and high-level resistance. The boy required surgery and underwent initial treatment with clarithromycin, amikacin, and tigecycline for 4 weeks. He experienced emesis as a side-effect of tigecycline, which was well controlled with ondansetron. He was treated successfully with 3 months of subsequent oral clarithromycin and linezolid. This is the first pediatric case of chronic otitis media caused by M. abscessus treated with a tigecycline-containing regimen. Although the therapeutic use of tigecycline remains controversial, especially in the pediatric population, it can be an acceptable option in the treatment of chronic otitis media caused by M. abscessus. Keywords: Mycobacterium abscessus, Chronic otitis media, Tigecycline

The first case of late thoracic wall bleeding after minimally invasive mitral valve repair treated by endovascular therapy is reported. A 55-year-old woman underwent mitral valve repair and tricuspid annuloplasty through a mini-thoracotomy approach. Her postoperative course was uneventful until she had anemia one week after the surgery. Contrast-enhanced computed tomography showed right hemothorax due to bleeding from a branch of the right lateral thoracic artery. Endovascular coil embolization and gelatin sponge injection were performed. The patient was discharged without any complications on postoperative day 20.

Candida auris is a multidrug-resistant and emergent pathogen that has caused healthcare-associated infection outbreaks. Recently, C. auris has spread worldwide; nevertheless, it was unexpectedly rare before 2009. Based on the molecular epidemiological analysis, C. auris may independently emerge at specific areas at first and recently may be transmitted to other continents. As C. auris cannot be detected using conventional methods, internally transcribed spacers, D1/D2 regions of the 26S rDNA sequencing, and/or matrix-assisted laser desorption ionization time-of-flight mass spectrometry method can be selected as comparatively accessible choices. Thus, detection of C. auris using the conventional method might be underestimated. In Japan, all C. auris strains were isolated from ear specimen and not from invasive mycoses. Japan strains were classified as an East Asian clade under a single clone. Although colonization, virulence, and infection pattern are almost the same as with other Candida species, its antifungal resistance is different. Fluconazole resistance is notably common, but resistance to all three classes of antifungals (azole, polyene, and echinocandin) rarely exists. Once C. auris is detected, screening, emphasis on hand hygiene adherence, use of single-patient room isolation, contact precaution, surveillance, and eradication from the environment and patients are appropriately required for infection control.

Staphylococcus argenteus is a novel species separated from a strain of coagulase-positive, non-pigmented S. aureus. Although S. argenteus has been reported to occur globally, multilocus sequence type (ST) 2250 is mainly found in Northeastern Thailand. Because conventional biochemical testing misidentifies this pathogen as S. aureus, multilocus sequence typing (MLST) or nucA sequencing is recommended to distinguish between S. argenteus and S. auereus. The patient was a previously healthy 12-year-old boy who was admitted because of right inguinal lymphadenitis and cellulitis. Although intravenous cefazolin was administered, his lymphadenitis worsened and formed an abscess on day 6 of hospitalization. Incision and drainage were performed on day 7 of hospitalization. Cefazolin was changed to oral cefaclor, and the patient was successfully treated over a period of 5 weeks. No recurrence was observed throughout 12-months of follow-up. He had a history of right axillary lymph node abscess 2 months before this admission, which was successfully treated with incision, drainage, and antibiotic therapy. He has lived in Japan since birth and never traveled abroad. He had no opportunity to interact with foreigners. His immune function, especially neutrophil function, was tested and we did not find any dysfunction. First, methicillin-sensitive S. aureus was misidentified from the abscess culture. Subsequently, the causative agent was re-identified as S. argenteus ST2250 based on MLST. To our knowledge, this is the first case of S. argenteus ST2250 infection in Japan. This pathogen should be taken into consideration in the diagnosis if the patient has atypical non-pigmented S. aureus.

We report a case of clinically diagnosed secondary organizing pneumonia (SOP) associated with coronavirus disease 2019 (COVID-19). A 70-year-old woman who had been diagnosed with COVID-19 was admitted to Hokkaido University Hospital. Although her fever, cough, dyspnea, and serum C-reactive protein levels improved, she developed rapidly progressive respiratory failure and computed tomography revealed the development of bilateral lung consolidation. Her dyspnea was relieved, and her oxygenation levels and radiological findings improved after commencing corticosteroid treatment. Blood biomarkers for interstitial lung disease, Krebs von den Lungen-6 (KL-6) and surfactant protein D (SP-D), showed different responses during the clinical course of her disease. Evaluation of serial changes in levels of KL-6 and SP-D may help diagnose and monitor COVID-19-associated organizing pneumonia (OP). Clinicians should be aware that SOP can develop in response to COVID-19 and that these patients may benefit from the use of steroids.

Background Candida auris has not been detected since firstt report in Japan, despite worldwide reports. We recently reported a second isolate of C. auris (TWCC 58191) from ear discharge in Japan. We re-analyzed unidentified yeast strains. Methods Over 2,000 clinical yeast samples were available. Among these, 16 yeast strains isolated from the ear discharge were not identified using conventional method. C. auris was identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and internal transcribed spacer and D1/D2 region sequencing. To determine the minimum inhibitory concentration (MIC), the Clinical and Laboratory Standards Institute broth microdilution method was used. Whole genome sequencing, assembly and error correction was performed (Japanese strains). Average nucleotide identity (ANI) among two Japanese strains and four other strains (India, Pakistan, South Africa) was determined. Our 6 strains and previously reported strains (n = 126) were mapped to JCM15448 and single nucleotide variants (SNVs) were detected. An SNV-based phylogenetic tree was constructed. Results Five were identified as C. auris. Our strains exhibited relatively low MICs (Table 1). Japanese strains had susceptibility to nearly all agents. Because all strains were obtained from chronic otitis media, the susceptibility may be explained by a lack of exposure to antifungal agents. JCM15448 was assembled based on 11 contigs. All ANIs were over 99%; therefore, all of these strains are C. auris. A total of 168,810 SNVs were detected in 133 strains. The SNV-based phylogenetic tree is shown Figure 1. Since independent clusters were observed from strains from each area, it is possible that C. auris emerged independently in different regions worldwide. The SNV-based phylogenetic tree was more effective for the identification of Japanese strains (Figure 2). Table 1. Characteristics of our C. auris Strains Figure 1. Phylogenic tree based on SNVs Figure 2. Phylogenic tree of SNVs (only Japanese strains) Conclusion Despite a general lack of reports, C. auris exists in Japan. Clinicians must consider the potential for C. auris detection from otorrhea samples. A phylogenic analysis separates native strains from each area. During an outbreak, an SNV-based phylogenic tree is suitable for analysis owing to its good identification ability. Disclosures All authors: No reported disclosures.