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Background Mycobacterium abscessus subspecies massiliense is a non-tuberculous mycobacteriosis and was subdivided from Mycobacterium abscessus in 2006. This article is the first report on nasopharyngitis caused by Mycobacterium abscessus subspecies massiliense. Case presentation A 45-year-old woman had an 18-month history of recurrent nasopharyngitis and presented with pain in the throat. Mycobacterial tissue culture and polymerase chain reaction testing revealed the presence of Mycobacterium abscessus subspecies massiliense in the nasopharyngeal tissue. This patient underwent surgery, followed by multiple rounds of chemotherapy with oral and intravenous antibiotic agents for 16 weeks. She has had no recurrence during the 56 weeks since treatment. Conclusion It is difficult to detect the presence of Mycobacterium abscessus subspecies massiliense in a culture from the swabbing sample. The tissue culture from a biopsy specimen is mandatory for the identification of the species. Currently, no definite treatment policy is available and only empirical treatment is applied. This case is an important for the diagnosis and treatment of this bacterial infection on nasopharynx.

Background and objective A cytokine storm is caused by inflammatory cells, including pro-inflammatory macrophage phenotype (M1), and play a critical role in the pathogenesis of COVID-19, in which diffuse alveolar damage occurs in the lungs due to oxidative stress exposure. Heme oxygenase (HO)-1 is a stress-induced protein produced by the anti-inflammatory / anti-oxidative macrophage phenotype (M2), which also produces soluble CD163 (sCD163). In our study, we investigated and determined that serum HO-1 can be a predictive biomarker for assessing both the severity and the outcome of COVID-19 patients. Method The serum concentrations of HO-1 and sCD163 of COVID-19 patients were measured on admission. The relationship between these biomarkers and other clinical parameters and outcomes were evaluated. Results Sixty-four COVID-19 patients (11 mild, 38 moderate, and 15 severe cases) were assessed. The serum HO-1 tended to increase (11.0 ng/mL vs. 24.3 ng/mL vs. 59.6 ng/mL with severity). Serum HO-1 correlated with serum lactate dehydrogenase (R = 0.422), C-reactive protein (R = 0.463), and the ground glass opacity (GGO) and consolidation score (R = 0.625) of chest computed tomography. The serum HO-1 showed a better area under the curve (AUC) for predicting ICU admission than the serum sCD163 (HO-1; 0.816 and sCD163; 0.743). In addition, composite parameters including serum HO-1 and the GGO and consolidation score showed a higher AUC for predicting ICU admission than the AUC of a single parameter. Conclusion Clinically, serum HO-1, reflecting the activation of M2, could be a very useful marker for evaluating disease severity and predicting prognoses for COVID-19 patients. In addition, controlling activated M2 might be a preventative COVID-19 therapeutic target.

We investigated the clinical course of individuals with 2019 novel coronavirus disease (COVID-19) who were transferred from the Diamond Princess cruise ship to 12 local hospitals. The conditions and clinical courses of patients with pneumonia were compared with those of patients without pneumonia. Among 70 patients (median age: 67 years) analyzed, the major symptoms were fever (64.3%), cough (54.3%), and general fatigue (24.3%). Forty-three patients (61.4%) had pneumonia. Higher body temperature, heart rate, and respiratory rate as well as higher of lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and C-reactive protein (CRP) levels and lower serum albumin level and lymphocyte count were associated with the presence of pneumonia. Ground-glass opacity was found in 97.7% of the patients with pneumonia. Patients were administered neuraminidase inhibitors (20%), lopinavir/ritonavir (32.9%), and ciclesonide inhalation (11.4%). Mechanical ventilation and veno-venous extracorporeal membrane oxygenation was performed on 14 (20%) and 2 (2.9%) patients, respectively; two patients died. The median duration of intubation was 12 days. The patients with COVID-19 transferred to local hospitals during the outbreak had severe conditions and needed close monitoring. The severity of COVID-19 depends on the presence of pneumonia. High serum LDH, AST and CRP levels and low serum albumin level and lymphocyte count were found to be predictors of pneumonia. It was challenging for local hospitals to admit and treat these patients during the outbreak of COVID-19. Assessment of severity was crucial to manage a large number of patients.

Background Febrile neutropenia (FN) is one of the most frequent and serious complications of hematopoietic stem cell transplantation such as bone marrow transplantation (BMT). Anti-Pseudomonas agents should be initiated in all patients complicated with FN without delay, while anti–methicillin-resistant Staphylococcus aureus (MRSA) agents are exclusively recommended in the case of central venous (CV) line infection. Most BMT patients have the potential risk of catheter-related blood stream infection because of long-lasting catheterization including indwelling CV line. Therefore, the patients may also be received anti-MRSA agents empirically in addition to anti-Pseudomonas agents. So far, there are little reports that verify the effectiveness of the combination therapy under FN condition after BMT. The purpose of this study was to address the effectiveness. Methods BMT was performed at Yokohama City University Medical Center between April 2012 and March 2018, and 44 patients who developed FN after BMT were enrolled. We analyzed patient information retrospectively. We used the duration of fever to evaluate the additive effect of anti-MRSA agents to β-lactam anti-Pseudomonas agents. We classified the patients during FN period into two groups whether anti-MRSA agents were administered (Ad group; 34 patients) or not (non-Ad group; 10 patients). Fever is defined as a single axillary temperature measurement of over 37.5 Celsius degrees. The study design and protocol were approved by the ethics committee at the Review Board of our hospital (ID：D1602011). Results Baseline characteristics were similar between the two groups. Blood cultures were performed onset of FN in all cases, in which five showed positive (11.4%). Bacteria requiring administration of anti-MRSA drugs were detected in the four cases. Nonetheless, duration of fever was not significantly shorten (6.8 ± 4.0 vs. 5.2 ± 2.5, P = 0.171) and there was no difference in the hospitalization period. The renal dysfunction was significantly higher in Ad group and the cost of anti-MRSA agents totaled about $ 36,000. Conclusion Our study indicates that no use of empirical combination therapy of anti-MRSA agents in addition to anti-Pseudomonas agents under FN condition after BMT, even if CV line is inserted. Disclosures All authors: No reported disclosures.

World Trade Center (WTC) exposure caused airflow obstruction years after exposure. Chitinases and IgE are innate and humoral mediators of obstructive airway disease. We investigated if serum expression of chitinases and IgE early after WTC exposure predicts subsequent obstruction.With a nested case-control design, 251 FDNY personnel had chitotriosidase, YKL-40 and IgE measured in serum drawn within months of 9/11/2001. The main outcome was subsequent Forced Expiratory Volume after 1 second/Forced Vital Capacity (FEV1/FVC) less than the lower limit of normal (LLN). Cases (N = 125) had abnormal FEV1/FVC whereas controls had normal FEV1/FVC (N = 126). In a secondary analysis, resistant cases (N = 66) had FEV1 (≥107%) one standard deviation above the mean. Logistic regression adjusted for age, BMI, exposure intensity and post-exposure FEV1/FVC modeled the association between early biomarkers and later lung function.Cases and Controls initially lost lung function. Controls recovered to pre-9/11 FEV1 and FVC while cases continue to decline. Cases expressed lower serum chitotriosidase and higher IgE levels. Increase in IgE increased the odds of airflow obstruction and decreased the odds of above average FEV1. Alternately, increasing chitotriosidase decreased the odds of abnormal FEV1/FVC and increased the odds of FEV1 ≥ 107%. Serum YKL-40 was not associated with FEV1/FVC or FEV1 in this cohort.Increased serum chitotriosidase reduces the odds of developing obstruction after WTC-particulate matter exposure and is associated with recovery of lung function. Alternately, elevated IgE is a risk factor for airflow obstruction and progressive lung function decline.

Background and objective We evaluated the association between activities of daily living and drug-induced liver injury by anti-tuberculosis drugs. Methods This retrospective cohort study included adult inpatients with newly diagnosed smear-positive lung tuberculosis treated with standard regimen in two hospitals. (n = 346; 63.6 ± 20.3 years old; 106 (30.6%) females). Activities of daily living was divided into ‘independent’ (Barthel Index (BI) 80–100, 60.4%) and ‘decreased’ (BI 0–75, 39.6%) categories. Liver injury was defined as the withdrawal or change of treatment regimen on the basis of the following criteria: serum transaminase concentrations were more than three times the upper limit of normal range with jaundice and/or hepatitis symptoms, or more than five times the upper limit of the normal range. Results Compared with ‘independent’ patients, patients with ‘decreased’ activities of daily living had odds ratios for liver injury of 4.2 (P

Despite the significant development of antibiotics, sepsis is still associated with high morbidity and mortality rates. The identification of pathologic organisms at an early stage of sepsis is critical to improve the outcome, but this is difficult to achieve with the conventional method of blood culture (BC). It has been demonstrated that the genes of pathogenic organisms surviving in neutrophils were detectable with in situ hybridization (ISH) and this method was useful for the accurate and rapid diagnosis of sepsis. In this study, we applied ISH to blood smears 60 patients with suspected sepsis. BC was also carried out using the same blood samples to investigate the diagnostic value of ISH. The number of positive results obtained by ISH was approximately four times higher than that obtained by BC (ISH, 25 [41.7%]; BC, 7 [11.7%]). The positive rate in the 21 patients given antibiotics was 61.9% by ISH (13 patients) and 4.7% by BC (1 patient). The antibiotic treatments targeting the organisms detected by either procedure showed a beneficial clinical outcome. Positive results by ISH were obtained earlier than those with BC (ISH, within 1 day; BC, several days). We conclude that ISH is a useful method for the rapid diagnosis of sepsis.

Background: Serum biomarkers of metabolic syndrome predict abnormal lung function in World Trade Center particulate matter (WTC-PM)-exposed Fire Department of New York (FDNY) rescue workers. In animal models, exposure to ambient PM induces non-alcoholic fatty liver disease (NAFLD), a well-known comorbidity of metabolic syndrome. YKL-40 is an inflammatory biomarker for both liver and lung disease. We tested if YKL-40 is a biomarker for NAFLD in this dust-exposed cohort. Methods: Using a nested case-control design, we studied 131 FDNY personnel who had Computer Tomography performed within 5 years post 9/11. NAFLD was defined by a liver/spleen attenuation ratio of ≤1. Serum biomarkers, lipid panel and liver function were measured in serum that had been drawn within 6 months of September 11, 2001. YKL-40 and chitotriosidase were assayed by ELISA. We tested biomarker and NAFLD association using logistic regression adjusted for age, BMI, and post-911 lung function. Results: NAFLD was present in 29/131 (22%) of the cohort. In a multivariable model increasing YKL-40 was protective while increasing triglyceride and alkaline phosphatase were risk factors for NAFLD. Conclusions: Increased YKL-40 is a protective biomarker in non-alcoholic fatty liver disease. Further studies may reveal a link between PM-induced lung and liver diseases.

Rationale: Metabolic syndrome, inflammatory and vascular injury markers measured in serum after World Trade Center (WTC) exposures predict abnormal FEV1. We hypothesized that elevated LPA levels predict FEV1

Introduction Non-typhi Salmonella species cause severe extra-intestinal focal infection after occult bacteremia. Although the number of cases of non-typhi salmonellosis is increasing worldwide among patients with immunocompromising conditions such as human immunodeficiency virus infection, infection is uncommon in immunocompetent subjects. We report a case of septic arthritis and bone abscess due to a rare non-typhi Salmonella organism that developed after a prolonged asymptomatic period. Case presentation A 44-year-old Japanese immunocompetent man presented with acute-onset left knee pain and swelling. He had no history of food poisoning, and his most recent travel to an endemic area was 19 years ago. Salmonella enterica serovar Ohio was identified from samples of bone abscess and joint tissue. Arthrotomy and necrotic tissue debridement followed by intravenous ceftriaxone was successful. Conclusions Non-typhi Salmonella species only rarely cause extra-intestinal focal infections in immunocompetent patients. Our case suggests that non-typhi Salmonella species can cause severe focal infections many years after the occult bacteremia associated with food poisoning.

Background: The WTC collapse exposed over 300,000 people to high concentrations of WTC-PM; particulates up to ,50 mm were recovered from rescue workers’ lungs. Elevated MDC and GM-CSF independently predicted subsequent lung injury in WTC-PM-exposed workers. Our hypotheses are that components of WTC dust strongly induce GM-CSF and MDC in AM; and that these two risk factors are in separate inflammatory pathways. Methodology/Principal Findings: Normal adherent AM from 15 subjects without WTC-exposure were incubated in media alone, LPS 40 ng/mL, or suspensions of WTC-PM10–53 or WTC-PM2.5 at concentrations of 10, 50 or 100 mg/mL for 24 hours; supernatants assayed for 39 chemokines/cytokines. In addition, sera from WTC-exposed subjects who developed lung injury were assayed for the same cytokines. In the in vitro studies, cytokines formed two clusters with GM-CSF and MDC as a result of PM10–53 and PM2.5. GM-CSF clustered with IL-6 and IL-12(p70) at baseline, after exposure to WTC-PM10–53 and in sera of WTC dust-exposed subjects (n=70) with WTC lung injury. Similarly, MDC clustered with GRO and MCP-1. WTC-PM10–53 consistently induced more cytokine release than WTC-PM2.5 at 100 mg/mL. Individual baseline expression correlated with WTC-PM-induced GM-CSF and MDC. Conclusions: WTC-PM10–53 induced a stronger inflammatory response by human AM than WTC-PM2.5. This large particle exposure may have contributed to the high incidence of lung injury in those exposed to particles at the WTC site. GM-CSF and MDC consistently cluster separately, suggesting a role for differential cytokine release in WTC-PM injury. Subject-specific response to WTC-PM may underlie individual susceptibility to lung injury after irritant dust exposure.

We encountered a rare case of lymphocytic interstitial pneumonia (LIP) complicated with primary Sjögren's syndrome (SjS), followed by chest CT scanning for a long period of time. A 54-year-old man with hemoptysis was admitted to our hospital in December, 2001. A diagnosis of SjS was made based on elevation of anti-SS-B/La antibody titer in serum in combination with diagnosis of keratoconjunctivitis sicca and xerostomia on a Schirmer test and a lip biopsy, respectively. Subsequent histopathological diagnosis by open lung biopsy showed LIP. Chest CT in September, 1995 at previous hospital revealed ground-glassed opacity (GGO), small nodules, thickened bronchovascular bundles and cyst formation in lungs. Chest CT was performed every year until 2008, when remarkable progression from thickened bronchovascular bundles accompanied by nodular opacities to an air-space consolidation in the right lower lobe was observed. Also, appearance of cyst formation in the right middle lobe, nodular lesions and GGO in the left lower lobe were noticed. Although the nodular opacities and GGO improved after an administration of corticosteroid (PSL 0.5 mg/kg/day), little improvement in the consolidations and cyst formation was demonstrated. In conclusion, it was suggested that differences among CT findings of LIP may be important for evaluating of efficacy of treatment by steroid agents for LIP associated with SjS.

We analyzed the efficacy of both the Streptococcus pneumoniae urine antigen test as a quick diagnostic tool and the administration of high-dose penicillin in response to a positive S. pneumoniae urine antigen test. We conducted a retrospective analysis of 48 cases of pneumococcal pneumonia, in which the patients were treated with high-dose penicillin. All the cases were diagnosed by a positive urine antigen test. Treatment with high-dose penicillin was effective in 43 of the 48 patients. This treatment was also effective in 12 of 16 culture-confirmed cases with low susceptibility to penicillin. Eleven patients who were positive for the S. pneumoniae urine antigen test but culture-negative showed clinical improvement with high-dose penicillin. Pneumonia caused by S. pneumoniae appeared to be treated safely and effectively with high-dose penicillin based on positive results of the urine antigen test, as penicillin resistance was unlikely to be a problem.

Brain metastasis is a critical complication of small-cell lung cancer (SCLC), resulting in rare long-time survival. We report a case of a 72-year-old man who displayed a very unique clinical appearance, with a large metastatic brain tumor that grew much faster than primary SCLC. The brain tumor expressed high levels of vascular endothelial growth factor (VEGF) that was negative in primary lung tumor. The patient, who underwent brain surgery and chemotherapy against SCLC, has survived for > 2 years with a good performance status since initial brain symptoms occurred. Weak expression of VEGF in primary tumor might be associated with good prognosis. However, VEGF upregulation could occur after metastasis, resulting in aggressive tumor growth.

We encountered a very rare case of cT0N2M0 small cell lung cancer (SCLC) with Lambert-Eaton myasthenic syndrome (LEMS). A 69-year-old man with a complaint of muscle weakness was admitted to our hospital. Although his chest radiograph on admission showed no abnormal findings, CT scanning detected a mediastinal lymphadenopathy. Also, 2-[18F]-2-fluorodeoxy-D-glucose position emission tomography (FDG-PET) revealed increased accumulation in the same portion in the mediastinum. A diagnosis of LEMS was made from the distinctive electromyogram (EMG) findings (waning and waxing phenomenon in response to low-and high-frequency repetitive stimulation, respectively) in combination with the increased serum level of a P/Q-type anti-voltage-gated calcium channel (VGCC) antibody. Subsequent histopathological diagnosis by mediastinoscopic resection of a paraaortic lymph node was small cell carcinoma. No distant metastasis was detected by MRI of the brain, abdominal CT scan or an FDG-PET. Eight courses of chemotherapy (carboplatin + etoposide) with radiotherapy of the mediastinum (for a total dose of 45 Gy) was performed. A decreased serum level of P/Q-type anti-VGCC antibody titers followed by marked improvement of neurological dysfunction (muscle weakness, gait disturbance and scanning speech) and of an EMG finding (a loss of waning phenomenon) was observed. A close relationship between reduction of the antibody titers and improvement of neurological symptoms after the therapy was noticed. It was suggested that monitoring the level of a P/Q-type anti-VGCC antibody titer in the serum is important for evaluating the efficacy of chemotherapy for LEMS associated with SCLC.

Calcitonin gene-related peptide (CGRP) is one of the major neuropeptides released from sensory nerve endings and neuroendocrine cells of the lung. Two CGRP isoforms, alpha-and beta-CGRP, have been identified in rats and humans, but no studies have attempted to reveal direct evidence of differences in action or location of these isoforms in allergic inflammation (AI). We investigated mRNA expressions of alpha-and beta-CGRP in lungs, nodose ganglia (NG), and dorsal root ganglia (DRG) of an animal model for AI of the airways, utilizing a model created by sensitizing Brown Norway (BN) rats with ovalbumin (OVA). By semiquantitative RT-PCR analysis, long-lasting enhanced expression of the beta-CGRP mRNA was shown in the lungs of the AI rats (14.5-fold enhancement at 6 hr, 8.1-fold at 24 hr, and 3.7-fold at 120 hr after OVA-challenge compared to the level in the lungs of phosphate-buffered saline (PBS)-challenged control rats). In contrast, the mRNA expression of the alpha-CGRP in AI lungs showed only a transient increase after OVA-challenge (2.7-fold at 6 hr) followed by a lower level of expression (0.5-fold at 48 hr and 0.6-fold at 120 hr). The mRNA expressions of both isoforms in NG, but not in DRG, were transiently up-regulated at 6 hr after antigen challenge. In situ RT-PCR in combination with immunohistochemical analysis revealed that beta-CGRP was expressed in neuroendocrine cells in clusters (termed neuroepithelial bodies [NEBs]) in AI lungs. These results indicate that the long-term induction of beta-CGRP in NEBs may play an important role in pulmonary AI such as bronchial asthma.

Summary Background Firefighters exposed to World Trade Center (WTC) dust have developed chronic rhinosinusitis (CRS) and abnormal forced expiratory volume in 1 s (FEV 1 ). Overlapping but distinct immune responses may be responsible for the clinical manifestations of upper and lower airway injury. We investigated whether a panel of inflammatory cytokines, either associated or not associated with WTC-LI, can predict future chronic rhinosinusitis disease and its severity. Methods Serum obtained within six months of 9/11/2001 from 179 WTC exposed firefighters presenting for subspecialty evaluation prior to 3/2008 was assayed for 39 cytokines. The main outcomes were medically managed CRS ( N = 62) and more severe CRS cases requiring sinus surgery ( N = 14). We tested biomarker-CRS severity association using ordinal logistic regression analysis. Results Increasing serum IL-6, IL-8, GRO and neutrophil concentration reduced the risk of CRS progression. Conversely, increasing TNF-α increased the risk of progression. In a multivariable model adjusted for exposure intensity, increasing IL-6, TNF-α and neutrophil concentration remained significant predictors of progression. Elevated IL-6 levels and neutrophil counts also reduced the risk of abnormal FEV 1 but in contrast to CRS, increased TNF-α did not increase the risk of abnormal FEV 1 . Conclusions Our study demonstrates both independent and overlapping biomarker associations with upper and lower respiratory injury, and suggests that the innate immune response may play a protective role against CRS and abnormal lung function in those with WTC exposure.