Effect of Functional Inhibition of BACE1 on Sensitization to γ-Irradiation in Cancer Cells.

Developing strategies for the radiosensitization of cancer cells by the inhibition of genes, which harbor low toxicity to normal cells, will be useful for improving cancer radiotherapy. Here, we focused on a ß-site of amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1; ß-secretase, memapsin-2). By functional inhibition of this peptidase by siRNA, it has also recently been shown that the DNA strand break marker, γH2AX foci, increased, suggesting its involvement in DNA damage response. To investigate this possibility, we knocked down BACE1 with siRNA in cancer cell lines, and sensitization to γ-irradiation was examined by a colony formation assay, γH2AX foci and level analysis, and flow cytometry. BACE1 knockdown resulted in the sensitization of HeLa, MDA-MB-231, U2OS, and SAOS cells to γ-irradiation in a diverse range. BACE1 knockdown showed a weak radiosensitization effect in osteosarcoma U2OS cells, which has a normal p53 function. HeLa and SAOS cells, which harbor p53 dysfunction, exhibited a greater level of radiosensitization. These results suggest that BACE1 may be a potential target for the radiosensitization in particular cancer cells.

Gamification of robotic simulation to train general surgery residents.

BACKGROUND: Gamification applies game design elements to non-game contexts in order to engage participation and increase learner motivation. Robotic surgery is gaining popularity in general surgery but requires specialized technical skills. We sought to determine whether gamification of robotic simulation training could increase robotic simulator utilization among general surgery residents. METHODS: General surgery residents were recruited and sent weekly progress on simulator performance including leaderboards for 4 weeks during the intervention periods. There were also two control periods setup in an ABAB study design. Usage time and mean scores were compared between the control periods and intervention periods. A post-study qualitative assessment interview using semi-structured interviews determined barriers and motivational components of simulator usage. RESULTS: Fifteen general surgery residents enrolled in the study (n = 15). Intervention increased total simulator usage time 9.7-fold from 153 to 1485 min. Total simulator days increased threefold from 9 to 27 days. Resident participation increased from 33 to 53%. Median average scores were higher during the intervention periods (58.8 and 81.9 vs 44.0). During the first intervention period, median individual-level simulator usage time increased 17 min (P = 0.03). However, there was no individual-level increase in median usage minutes or days during the second intervention period. Qualitative assessment determined barriers to be limited time due to clinical duties, and simulator availability while motivational factors included competitive factors such as leaderboards and gaming aspects. Potential improvements were increasing attending visibility of scores to increase recognition of progress by the residents and creating dedicated time for training. CONCLUSION: Gamification of robotic simulation training increased general surgery resident participation, usage time and scores. Impact was not durable. Instituting dedicated practice time and more attending engagement may increase trainee motivation and performance.

Distractions in the operating room: a survey of the healthcare team.

BACKGROUND: Distractions during surgical procedures are associated with team inefficiency and medical error. Little is published about the healthcare provider's perception of distraction and its adverse impact in the operating room. We aim to explore the perception of the operating room team on multiple distractions during surgical procedures. METHODS: A 26-question survey was administered to surgeons, anesthesia team members, nurses, and scrub technicians at our institution. Respondents were asked to identify and rank multiple distractions and indicate how each distraction might affect the flow of surgery. RESULTS: There was 160 responders for a response rate of 19.18% (160/834), of which 71 (44.1%) male and 82 (50.9%) female, 48 (29.8%) surgeons, 59 (36.6%) anesthesiologists, Certified Registered Nurse Anesthetists (CRNA), and 53 (32.9%) OR nurses and scrub technicians. Responders were classified into a junior group (< 10 years of experience) and a senior group (≥ 10 years). Auditory distraction followed by equipment were the most distracting factors in the operating room. All potential auditory distractions in this survey were associated with higher percentage of certain level of negative impact on the flow of surgery except for music. The top 5 distractors belonged to equipment and environment categories. Phone calls/ pagers/ beepers and case relevant communications were consistently among the top 5 most common distractors. Case relevant communications, music, teaching, and consultation were the top 4 most perceived positive impact on the flow of surgery. Distractors with higher levels of "bothersome" rating appeared to associate with a higher level of perceived negative impact on the flow of surgery. Vision was the least distracting factor and appeared to cause minimal positive impact on the flow of surgery. CONCLUSIONS: To our knowledge, this is the first survey studying perception of surgery, anesthesia, and OR staff on various distractions in the operating room. Fewer unnecessary distractions might improve the flow of surgery, improve OR teamwork, and potentially improve patient outcomes.

Effectiveness of neutralizing antibody cocktail in hemodialysis patients: a case series of 20 patients treated with or without REGN-COV2.

The number of patients with SARS-CoV-2 infection continues to increase, and it has become a global pandemic. Although there is an urgent need to establish an effective treatment, the medication available for dialysis patients has been limited. An antibody cocktail containing two SARS-CoV-2-neutrarizing antibodies, REGN-COV2 has been granted special approval for COVID-19 in Japan, since July 2021, and this intravenous preparation can be used for dialysis patients. At our hospital, we had 22 hemodialysis patients with COVID-19, and five of them were treated with REGN-COV2. On admission, four of the five patients had moderate disease (pneumonia but O2 inhalation) and one patient had mild disease (not having pneumonia). The mean duration of hospitalization treated with REGN-COV2 was 10.2 ± 2.86 days (mean ± SD), which was less than half, compared to patients untreated of similar severity on admission (22.12 ± 15.5). The time to fever resolution was average 7 days, and no cases progressed to severe illness or death. Among these patients, no obvious adverse reactions were shown. Although more studies with a larger number of patients could be needed for a rigorous evaluation of the effect, our result suggests that REGN-COV2 may be safe and having the possibilities in preventing severe disease in hemodialysis patients. Given the difficulty in securing inpatient beds tend to be in short supply, the strategy combined with neutralizing antibody could be beneficial for end-stage kidney disease (ESKD) patients with hemodialysis who are at high risk of severe disease.

Clinical risk factors related to treatment failure in Mycobacterium abscessus lung disease.

The clinical importance of Mycobacterium abscessus subsp. abscessus (M. abscessus) lung disease has been increasing, but few studies have assessed the clinical characteristics associated with the treatment outcome. We retrospectively analyzed 75 consecutive patients with M. abscessus lung disease diagnosed at a tertiary hospital from January 2004 to April 2018. Among 52 patients with sufficient clinical data, 19 patients (42.2%) achieved treatment success. Compared with 26 (57.8%) patients in the treatment failure group, body mass index (BMI) (19.8 vs 17.5 kg/m2, P = 0.022), previous nontuberculous mycobacterial (NTM) lung disease (26.3% vs 61.5%, P = 0.034), the presence of cavitary lesions (31.6% vs 69.2%, P = 0.017), and the bronchiectasis score (3.0 vs 5.0, P = 0.003) were significantly different in the treatment success group. Multivariate analysis showed that age (adjusted hazard ratio (aHR), 0.94; 95% confidence interval (CI), 0.90 to 0.99; P = 0.010), the presence of cavitary lesions (aHR, 0.34; 95% CI, 0.12 to 0.94; P = 0.039), and previous NTM lung disease (aHR, 0.28; 95% CI, 0.09 to 0.86; P = 0.026) were negatively associated with treatment success. This is the first study to show that previous NTM lung disease might be a clinically important factor related to unfavorable treatment outcomes in M. abscessus lung disease patients. To increase our understanding the characteristics of M. abscessus lung disease, this factor should be independently analyzed in future research.

Effects of Norepinephrine Infusion on Cutaneous Surface Temperatures of the Distal Extremities.

OBJECTIVES: The etiology of vasopressor-induced digital necrosis is poorly understood, but the skin changes resemble those of frostbite, and it is known from experience that patients taking vasopressors have decreased digital temperatures. We aimed to examine the effects of norepinephrine use on surface temperatures of the distal extremities because there have been no studies examining this relation. METHODS: Surface temperatures of all digits, palms, and soles were measured using an infrared thermometer in patients receiving different rates of norepinephrine infusion in the intensive care unit and compared with those not receiving any vasopressors. RESULTS: A total of 101 measurements from 41 unique individuals were obtained. Temperature gradients between the core and the fingertips were consistently more pronounced in those receiving norepinephrine compared with those not receiving norepinephrine and increased with increasing rates of norepinephrine infusion, except with high-dose norepinephrine. Temperature gradients were more pronounced in the toes. CONCLUSIONS: Norepinephrine use was associated with greater core-to-fingertip temperature gradients and were more pronounced in the toes compared with the fingers.

Pseudomonas aeruginosa-derived flagellin stimulates IL-6 and IL-8 production in human bronchial epithelial cells: A potential mechanism for progression and exacerbation of COPD.

Background and purpose of the study:Pseudomonas aeruginosa commonly colonizes the airway of patients with chronic obstructive pulmonary disease (COPD) and exacerbates their symptoms. P. aeruginosa carries flagellin that stimulates toll-like receptor (TLR)-5; however, the role of flagellin in the pathogenesis of COPD remains unclear. The aim of the study was to evaluate the mechanisms of the flagellin-induced innate immune response in bronchial epithelial cells, and to assess the effects of anti-inflammatory agents for treatment. Materials and methods: We stimulated BEAS-2B cells with P. aeruginosa-derived flagellin, and assessed mRNA expression and protein secretion of interleukin (IL)-6 and IL-8. We also used mitogen-activated protein kinases (MAPK) inhibitors to assess the signaling pathways involved in flagellin stimulation, and investigated the effect of clinically available anti-inflammatory agents against flagellin-induced inflammation. Results: Flagellin promoted protein and mRNA expression of IL-6 and IL-8 in BEAS-2B cells and induced phosphorylation of p38, ERK, and JNK; p38 phosphorylation-induced IL-6 production, while IL-8 production resulted from p38 and ERK phosphorylation. Fluticasone propionate (FP) and dexamethasone (DEX) suppressed IL-6 and IL-8 production in BEAS-2B cells, but clarithromycin (CAM) failed to do so. Conclusions:P. aeruginosa-derived flagellin-induced IL-6 and IL-8 production in bronchial epithelial cells, which partially explains the mechanisms of progression and exacerbation of COPD. Corticosteroids are the most effective treatment for the suppression of flagellin-induced IL-6 and IL-8 production in the bronchial epithelial cells.

Next-generation sequencing-based miRNA expression analysis in Parp1-deficient embryonic stem cell-derived exosomes.

Poly (ADP-ribose) polymerase family, member 1 (Parp1) has pleiotropic and disparate functions in multiple cellular signaling pathways through post-translational protein modification. It contributes to the regulation of various cellular processes, including DNA damage repair, cell death, and cell differentiation, genetically or epigenetically. Meanwhile, the functions of Parp1 in intercellular signaling remain to be established. To examine the functions of Parp1 in intercellular signaling, we examined microRNA (miRNA) regulation in exosomes derived from Parp1-deficient (Parp1-/-) embryonic stem (ES) cells. The percentages of miRNAs among total RNAs, including small RNAs such as miRNAs, snRNAs, snoRNAs, tRNAs, exonic RNAs, and intronic RNAs, in Parp1+/+ and Parp1-/- ES cell-derived exosomes were 8.2% and 3.5%, respectively. Overall, 329 distinct miRNAs exhibited ≥2-fold changes (118 upregulated; 211 downregulated). The upregulated miRNAs targeted 810 candidate genes, and the downregulated miRNAs targeted 716 candidate genes. Pathway analyses revealed that the upregulated miRNAs were significantly associated with five pathways including MAPK signaling cascades (p < 0.05), indicating that the target genes in these pathways were suppressed in Parp1-/- ES cells. In quantitative analyses of miRNA expression, miR365-3p, let-7a-5p, miR196b-5p, miR203-3p, miR98-5p, and miR146a-5p were increased by ≥ 2-fold in Parp1-/- ES cell-derived exosomes. Gene ontology enrichment analyses revealed that the upregulated miRNAs were significantly annotated for growth and stress-related cell signaling and cell communication (p < 0.05). Parp1 deficiency in ES cells led to inhibition of cell-cell communication, possibly by intercellular signal transduction, suggesting that Parp1 functions extracellularly by regulating exosomal miRNAs.

Serum sST2 levels predict severe exacerbation of asthma.

BACKGROUND: Neutrophilic inflammation is associated with poorly controlled asthma. Serum levels of sST2, a soluble IL-33 receptor, increase in neutrophilic lung diseases. We hypothesized that high serum sST2 levels in stable asthmatics are a predictor for exacerbation within a short duration. METHODS: This prospective observational study evaluated the serum sST2 levels of 104 asthmatic patients who were treated by a lung disease specialist with follow-ups for 3 months. RESULTS: High serum sST2 levels (> 18 ng/ml) predicted severe asthma exacerbation within 3 months. Serum sST2 levels correlated positively with asthma severity (treatment step), airway H2O2 levels, and serum IL-8 levels. High serum sST2 levels and blood neutrophilia (> 6000 /µl) were independent predictors of exacerbation. We defined a post-hoc exacerbation-risk score combining high serum sST2 level and blood neutrophilia, which stratified patients into four groups. The score predicted exacerbation-risk with an area under curve of 0.91 in the receiver operating characteristic curve analysis. Patients with the highest scores had the most severe phenotype, with 85.7% showing exacerbation, airflow limitation, and corticosteroid-insensitivity. CONCLUSIONS: High serum sST2 levels predicted exacerbation within the general asthmatic population and, when combined with blood neutrophil levels, provided an exacerbation-risk score that was an accurate predictor of exacerbation occurring within 3 months.

Bronchial epithelial cells produce CXCL1 in response to LPS and TNFα: A potential role in the pathogenesis of COPD.

RATIONALE: Neutrophilic airway inflammation plays a central role in chronic obstructive pulmonary disease (COPD). CXC chemokine ligand (CXCL)1 is a neutrophil chemokine involved in the pathogenesis of COPD. However, its clinical significance in COPD patients is poorly understood. AIM OF THE STUDY: To assess the production of CXCL1 by bronchial epithelial cells in response to lipopolysaccharide (LPS) and tumor necrosis factor (TNF)α. MATERIALS AND METHODS: We measured sputum CXCL1 and CXCL8 levels in patients with COPD, asthma, and asthma-COPD overlap (ACO), and compared them to those of patients with interstitial pneumonia (IP). Using primary human bronchial epithelial cells and BEAS-2B cells, CXCL1 protein release and mRNA expression were measured after LPS or TNFα stimulation. We evaluated signal transduction mechanisms for CXCL1 production using nuclear factor-κ B (NF-kB) and mitogen-activated protein kinase (MAPK) inhibitors, and examined the effects of anti-inflammatory agents on CXCL1 production in BEAS-2B cells. RESULTS: Sputum CXCL1 levels in COPD and ACO patients were higher than in IP patients, whereas sputum CXCL8 levels were not. Sputum CXCL1 levels were not affected by inhaled corticosteroid usage, whereas sputum CXCL8 levels tended to be affected. LPS and TNFα stimulated CXCL1 production and mRNA expression in bronchial epithelial cells. NF-kB and MAPK p38 were involved in LPS-induced CXCL1 production. Therapeutic anti-inflammatory agents minimally attenuated CXCL1 production and considerably inhibited CXCL8 production in BEAS-2B cells. CONCLUSIONS: Sputum CXCL1 levels is a potentially better diagnostic marker for COPD than sputum CXCL8 levels, which is explained by that CXCL1 production in bronchial epithelial cells is less affected by therapeutic anti-inflammatory agents than CXCL8 production.

IL-17A synergistically stimulates TNF-α-induced IL-8 production in human airway epithelial cells: A potential role in amplifying airway inflammation.

BACKGROUND: Recent reports have suggested an involvement of neutrophilic inflammation driven by interleukin (IL)-17 from Th17 cells, especially in severe, refractory asthma. It remains unknown about the possible interactions of this cytokine and other proinflammatory cytokines to direct neutrophilic airway inflammation. MATERIALS AND METHODS: We evaluated the effects of IL-17A, IL-17E, and IL-17F in combination with other stimuli such as tumor necrosis factor (TNF) -α on the production and expression of IL-8 in human bronchial epithelial cells. We also studied their effects on other cytokine production. The possible role of mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways was evaluated by specific inhibitors. We examined the effects of anti-asthma drugs, such as steroids or salmeterol. RESULTS: IL-17A alone induced only a minimal effect on IL-8 expression. IL-17A, but not IL-17E or IL-17F, in combination with TNF-α showed a synergistic effect on IL-8 expression. Similar findings were found when combination with IL-1ß and IL-17A were used, but such was not the case with lipopolysaccharide (LPS). In addition, we further found such synergy on GM-CSF production. The synergy with TNF-α and IL-17A was significantly inhibited by MAPKs inhibitors. Corticosteroids such as fluticasone propionate and dexamethasone, but not salmeterol, partially suppressed the IL-17A and TNF-α-induced IL-8 production. CONCLUSIONS: IL-17A in the combination with TNF-α or IL-1ß showed a synergistic augmenting effect on IL-8 and GM-CSF production in human airway epithelial cells.

Clarithromycin ameliorates pulmonary inflammation induced by short term cigarette smoke exposure in mice.

BACKGROUND: Cigarette smoking is considered to be one of major causes of acute worsening of asthma as well as chronic obstructive pulmonary disease (COPD). Macrolide antibiotics have been reported to reduce the risk of exacerbations of COPD, and possibly neutrophilic asthma. However, the effect of clarithromycin (CAM) on pulmonary inflammation caused by short term exposure to cigarette smoke still remains to be investigated. METHODS: C57BL/6J female mice were daily exposed to tobacco smoke using a tobacco smoke exposure system, or clean air for 8 days, while simultaneously treated with either oral CAM or vehicles. Twenty four hours after the last exposure, mice were anaesthetized and sacrificed, and bronchoalveolar lavage (BAL) fluids were collected. Cellular responses in BAL fluids were evaluated. Levels of cytokine mRNA in the lung tissues were measured by quantitative RT-PCR. Paraffin-embedded lung tissues were evaluated to quantitate degree of neutrophil infiltration. RESULTS: The numbers of total cells, macrophages and neutrophils in the BAL fluid of smoke-exposed mice were significantly increased as compared to clean air group. These changes were significantly ameliorated in CAM-treated mice. The lung morphological analysis confirmed decrease of neutrophils by CAM treatment. Studies by quantitative PCR demonstrated CAM treatment significantly reduced lung expression levels of IL-17A, keratinocyte-derived chemokine (KC), granulocyte-macrophage colony stimulating factor (GM-CSF) and MMP-9 induced by cigarette smoke. CONCLUSION: We demonstrate that CAM administration resolves enhanced pulmonary inflammation induced by short term cigarette smoke exposure in mice.

Serial quantification of procalcitonin (PCT) predicts clinical outcome and prognosis in patients with community-acquired pneumonia (CAP).

Procalcitonin (PCT), a calcitonin precursor, is commonly measured in the setting of community-acquired pneumonia (CAP). However, the clinical significance of serial PCT changes has not been established. We conducted a prospective observational study of 122 patients with CAP. Thirty-day mortality was the primary endpoint. Secondary endpoints included: (1) initial treatment failure, (2) 30-day mortality and/or initial treatment failure, and (3) intensive care unit (ICU) admission. In subgroup analysis, we classified patients into pneumococcal pneumonia and non-pneumococcal pneumonia groups. The baseline frequency of 30-day mortality was 10.7%. Increases in serum PCT levels from admission to Day 3 were observed with statistically higher frequency in patients with 30-day mortality (P = 0.002). For secondary endpoints, only the 30-day mortality and/or initial treatment failure group was statistically significant (P = 0.007). Subgroup analysis revealed statistically significant changes in the non-pneumococcal pneumonia group (N = 85) across several endpoints, including 30-day mortality (P = 0.001), initial treatment failure (P = 0.013), and 30-day mortality and/or initial treatment failure (P < 0.001). No significant changes in endpoint measurements were found in the pneumococcal pneumonia group (N = 28). Interestingly, serum PCT levels at the time of diagnosis were higher in patients with pneumococcal pneumonia than those with non-pneumococcal pneumonia (P = 0.006), and this positively correlated with disease severity scores for all patients (PCT vs. PSI: R = 0.380, P < 0.001; PCT vs. A-DROP: R = 0.422, P < 0.001) and for non-pneumococcal pneumonia (PCT vs. PSI: R = 0.468, P < 0.001; PCT vs. A-DROP: R = 0.448, P < 0.001), but not for pneumococcal pneumonia. In conclusion, serial quantification of PCT can predict clinical outcomes for patients with CAP.

Association of IL-33 in modeling type-2 airway inflammation and pulmonary emphysema in mice.

We developed pulmonary emphysema and a type 2 airway inflammation overlap mouse model. The bronchoalveolar lavage (BAL) interleukin 13 (IL-13), IL-4, and IL-5 levels in the overlap model were higher than in the pulmonary emphysema model and lower than in the type 2 airway inflammation model, but IL-33 level in the lung was higher than in other models. IL-33 and interferon-γ (IFNγ) in lungs may control the severity of a type 2 airway inflammation in lung.

Impact of Cough Severity on the Diagnostic Yield of Endobronchial Ultrasonography Transbronchial Biopsy with Guide Sheath: A Retrospective Observational Study.

Bronchoscopy is an invasive procedure, and patient coughing during examination has been reported to cause patient distress. This study aimed to clarify the relationship between cough severity and diagnostic yield of endobronchial ultrasonography with guide sheath transbronchial biopsy (EBUS-GS-TBB). Data of patients who underwent bronchoscopy at Kyorin University Hospital between April 2019 and March 2022 were retrospectively evaluated. Bronchoscopists assessed the cough severity upon completion of the procedure using a four-point cough scale. Cough severity was included as a predictive factor along with those reportedly involved in bronchoscopic diagnosis, and their impact on diagnostic yield was evaluated. Predictors of cough severity were also examined. A total of 275 patients were enrolled in this study. In the multivariate analysis, the diagnostic group (n = 213) had significantly more 'within' radial endobronchial ultrasound findings (odds ratio [OR] 5.900, p < 0.001), a lower cough score (cough score per point; OR 0.455, p < 0.001), and fewer bronchial generations to target lesion(s) (OR 0.686, p < 0.001) than the non-diagnostic group (n = 62). The predictive factors for severe cough include the absence of virtual bronchoscopic navigation (VBN) and prolonged examination time. Decreased cough severity was a positive predictive factor for successful EBUS-GS-TBB, which may be controlled using VBN and awareness of the procedural duration.

Listeria monocytogenes bacteremia developed during treatment of COVID-19.

Listeria monocytogenes is an important pathogen in older patients and immunosuppressed patients, often causing bacteremia. Complications resulting from infections other than COVID-19 must also be considered during COVID-19 treatment.

Barrier Factors of Adherence to Dupilumab Self-Injection for Severe Allergic Disease: A Non-Interventional Open-Label Study.

Purpose: The status of dupilumab self-injection at home is not well understood. We therefore aimed to identify the barriers to adherence to dupilumab self-injection. Patients and Methods: This non-interventional open-label study was conducted between March 2021 and July 2021. Patients with atopic dermatitis, bronchial asthma, and chronic rhinosinusitis with nasal polyps receiving dupilumab, from 15 sites, were requested to complete a self-administered questionnaire regarding the frequency and effectiveness of dosing as well as their use and satisfaction with dupilumab. Barriers to adherence were assessed using the Adherence Starts with Knowledge-12. Results: We included 331 patients who used dupilumab for atopic dermatitis (n = 164), chronic rhinosinusitis with nasal polyps (n = 102), and bronchial asthma (n = 65). The median efficacy of dupilumab scored 9.3 on the visual analog scale. Overall, 85.5% of the patients self-injected dupilumab, and 70.7% perfectly complied with the established injection dates. The pre-filled pen was significantly superior to the conventional syringe in terms of usability, operability, ease of pushing the plunger, and patient satisfaction. However, the pre-filled pen caused more pain during self-injection than did the syringe. Multivariate logistic regression analysis showed that adherence decreased with longer dupilumab treatment duration (p = 0.017) and was not associated with age, sex, underlying disease, or device type. There was a difference in responses related to "inconvenience/forgetfulness" between the good and poor adherence groups. Conclusion: The pre-filled dupilumab pen was superior to the syringe in terms of usability, operability, ease of pushing the plunger, and satisfaction. Repetitive instructions are recommended for preventing poor adherence to dupilumab self-injection.

Pulmonary Involvement in Microscopic Polyangiitis: Computed Tomography Findings in 55 Patients With Analysis of Risk Factors for Recurrence.

Background and objective Pulmonary involvement is seen in up to 30% of microscopic polyangiitis (MPA) patients. Pulmonary radiological findings for MPA have been scarcely reported to date. This study was conducted to evaluate computed tomography (CT) and clinical findings at the time of MPA diagnosis as predictors for systemic or lung recurrence. Methods We retrospectively reviewed the medical records and radiological data of 55 MPA patients with pulmonary involvement who were admitted to our hospital between April 2008 and December 2016. Results Aside from pulmonary lesions, lesions were found in the kidneys (52.7%), skin (7.3 %), and peripheral nerves (3.6%). Biopsies were performed for 29.1% of the patients, with an overall diagnostic accuracy of 78.9%. Parenchymal opacities (74.5%, mainly ground-glass opacities and reticular shadowing) were more commonly seen than airway abnormalities were (40.0%, mainly bronchiectasis). Systemic recurrence in the first year after diagnosis was found in 10.9% of the patients, and it mainly involved the kidneys or lungs. A serum WBC count ≥ 10,900/µL was a risk factor for predicting systemic recurrence within the first year after diagnosis according to the Cox regression analysis (HR 11.1, 95%CI: 1.3-95.9, p=0.028). Lung recurrence within five years after the diagnosis was observed in 9.1% of the patients. The incidences of reticular shadowing and honeycombing in thoracic CT at diagnosis were significantly higher in recurrence-positive patients than in recurrence-negative patients, but these differences could not be used to predict lung recurrence. Conclusions Ground glass opacities, reticular shadowing, and bronchiectasis are prominent thoracic CT findings for MPA. There are no radiological patterns capable of predicting recurrence. However, a serum WBC count ≥ 10,900/µL at diagnosis might be a predictive factor for systemic recurrence within the year.

Chronic pulmonary aspergillosis in a patient with hyper-IgE syndrome.

Hyperimmunoglobulin E (IgE) syndrome (HIES) is a rare disease with an unclear prognosis. We report a case of HIES comorbid with chronic pulmonary aspergillosis (CPA). A 19-year-old male was referred to our department with a medical history of bacterial pneumonia and skin infection. Laboratory data showed an elevated eosinophil count and serum IgE level. Chest computed tomography (CT) showed a pneumatocele and bronchiectasis. On the basis of the clinical and laboratory findings and genetic mutation analysis, we diagnosed him as having HIES. Fourteen months later, he complained of blood-tinged sputum and haemoptysis. Chest CT showed pneumatocele wall thickening, fungus ball and consolidation. Serum Aspergillus precipitating antibody and serum galactomannan Aspergillus antigen were positive, and Aspergillus fumigatus was detected in the sputum. We diagnosed CPA and treated him using antifungal agents and bronchial artery embolization. CPA is a complication that requires attention in patients with HIES.