Lysophospholipid Acyltransferase 9 Promotes Emphysema Formation via Platelet-activating Factor.

Cigarette smoking is known to be the leading cause of chronic obstructive pulmonary disease (COPD). However, the detailed mechanisms have not been elucidated. Platelet-activating factor (PAF), a potent inflammatory mediator, is involved in the pathogenesis of various respiratory diseases, such as bronchial asthma or COPD. We focused on lysophospholipid acyltransferase 9 (LPLAT9), a biosynthetic enzyme of PAF, in the pathogenesis of COPD. LPLAT9 gene expression was observed in excised COPD lungs and single-cell RNA sequencing data of alveolar macrophage (AM). LPLAT9 was predominant and upregulated in AM, particularly monocyte-derived AM, in patients with COPD. To identify the function of LPLAT9/PAF in AM on the pathogenesis of COPD, we exposed cigarette smoke (CS) to systemic LPLAT9 knockout (LPALT9-/-) mice. CS increased the number of AM, especially monocyte-derived fraction, which secreted matrix metalloprotease 12 (MMP12). Also, CS augmented LPLAT9 phosphorylation/activation on macrophage and, subsequently, PAF synthesis in mice lung. LPLAT9-/- mice lung reduced PAF production after CS exposure. Intratracheal PAF administration accumulated AM by increasing monocyte chemoattractant protein-1 (MCP1). After CS exposure, AM accumulation and subsequent pulmonary emphysema, a primary pathologic change of COPD, were reduced in LPALT9-/- mice than in LPLAT9+/+ mice. Notably, these phenotypes got worsened again by LPLAT9+/+ bone marrow transplantation in LPALT9-/- mice. Thus, CS-induced LPLAT9 activation in monocyte-derived AM aggravated pulmonary emphysema via PAF-induced further AM accumulation. These results suggest that PAF synthesized by LPLAT9 has an important role in the pathogenesis of COPD.

Modulation of Intestinal Motility in an Adolescent Rat Model of Irritable Bowel Syndrome.

INTRODUCTION: The pathophysiology of irritable bowel syndrome (IBS) remains unknown. This study aimed to evaluate colonic motility and serotonin system response to restraint stress (RS) among adolescent rats who underwent neonatal maternal separation (NMS) to clarify the features of pathogenesis in adolescents with IBS. METHODS: Male rats were exposed to NMS as chronic stress, and a normally handled (NH) group was used as control. Four groups were created by adding RS as acute stress treatment to the NMS and NH groups. To realize the RS treatment, the subjects were restrained for 1 h at the age of 5 weeks, and hourly fecal pellet discharge was determined. After euthanization and proximal colon intestinal tissue collection, 5-hydroxytryptamine (5-HT) and 5-hydroxytryptamine receptor 3 (5-HT3R) concentrations, enterochromaffin (EC) cell density, and the expression of mRNA-encoding slc6a4 were examined. RESULTS: The amount of fecal pellet discharge during RS increased significantly in the RS and NMS+RS groups compared with that in the NH and NMS groups, respectively. The 5-HT concentration in the intestinal tissue of rats in the RS and NMS groups increased significantly compared with that of rats in the NH group. EC cell density also increased significantly in the NMS and NMS+RS groups compared with that in the NH and RS groups. However, combined stress did not result in any significant differences in the expression of 5-HT3R and mRNA-encoding slc6a4. CONCLUSIONS: The combination of juvenile and acute stress effectively induced increased 5-HT concentration or EC cell density via the 5-HT pathway in the proximal colon of adolescent rats.

Participant Selection from the General Japanese Population for Pulmonary Function Tests Using a Questionnaire on Symptoms and Smoking Habits during Annual Health Checkups: The Yamagata-Takahata Study.

Objective Pulmonary function tests are essential for diagnosing respiratory diseases, such as chronic obstructive pulmonary disease (COPD), but are typically not performed in Japan during annual health checkups, which hinders the early diagnosis of respiratory diseases. Methods Individuals who agreed to participate in the Yamagata-Takahata study during medical checkups in Takahata (Yamagata Prefecture, Japan) in 2011 were examined. We interviewed 669 participants (49.0% men; mean age, 67.7 years old) regarding their respiratory symptoms and smoking habits and performed pulmonary function tests during the study. Results Based on pulmonary function test results, 141 participants had pulmonary dysfunction, and 115 had obstructive pulmonary dysfunction. The risk of respiratory dysfunction, particularly obstructive respiratory dysfunction, was examined by referring to a questionnaire tool for an early COPD diagnosis. The associations between age, the smoking history, respiratory symptoms, and obstructive respiratory dysfunction were evaluated. Obstructive respiratory dysfunction was found in 17.6% of participants ≥50 years old and 19.5% ≥60 years old, 30.3% had a smoking history, and 32.8% had respiratory symptoms. Furthermore, the participants with multiple factors had a higher probability of obstructive respiratory dysfunction. Conclusion Subjects with obstructive pulmonary dysfunction are expected to be efficiently identified by extracting individuals by age and smoking habit and through a respiratory symptom questionnaire, although pulmonary function tests cannot be performed for all individuals during health checkups.

Cardiac tamponade during pregnancy due to primary lung cancer: A case report.

We report a rare case of cardiac tamponade caused by lung cancer in a pregnant woman. A 32-year-old multiparous pregnant woman was admitted to the hospital at 15 weeks of gestation with a persistent cough and dyspnea. Transthoracic echocardiography revealed a pericardial effusion with evidence of tamponade physiology. Computed tomography (CT) revealed a massive pericardial effusion and a left lung tumor. Pericardial tamponade was successfully treated using pericardiocentesis. She was diagnosed with lung adenocarcinoma stage IVB based on bronchoscopic lung biopsy, which showed adenocarcinoma and CT, which showed brain metastasis. Pregnancy was terminated at 18 weeks of gestation, followed by molecular-targeted therapy with alectinib hydrochloride and whole-brain irradiation. 24 months after treatment initiation the patient is alive without disease progression. Although pericardial tamponade caused by a malignant tumor during pregnancy is a rare and serious life-threatening condition, appropriate diagnosis and prompt treatment can improve maternal prognosis.

Differentiation of Active Ulcerative Colitis vs Noninflammatory Bowel Disease Proctitis by Transperineal Superb Microvascular Imaging.

BACKGROUND: Transabdominal ultrasonography and transperineal ultrasonography (TPUS) appear correspond to colonoscopy (CS) for evaluating ulcerative colitis (UC) activity, but their utility in UC diagnosis remains unclear. This research compared the accuracy of TPUS and CS for assessing rectal activity and differentiating noninflammatory bowel disease proctitis from UC in pediatric cases. METHODS: The study is a blinded, prospective, and controlled trial. Prospectively, values of fecal calprotectin (FCP) and findings of the TPUS and CS were compared between child cases of UC and non-IBD proctitis. Findings of rectal wall thickening (RWT), rectal wall flow (RWF) on power Doppler, and microvascular signal at wall circumference (MSWC) on monochrome superb microvascular imaging assessed using TPUS were compared with the CS. RESULTS: Thirty patients with Mayo endoscopic subscore (MES) 0 to 1 UC, 57 with MES 2 to 3 UC, and 44 with proctitis were registered. Fecal calprotectin, RWF, and MSWC indicated significant differences among the groups (P < .05). Rectal wall thickening showed no significant difference between MES 0-1 and proctitis (P = .76). Rectal wall thickening and MSWC were independent predictors of endoscopic activity of UC, resulting in a sensitivity and specificity of 100% for RWT ≥4.5 mm and positive MSWC. Fecal calprotectin and RWF were independent predictors for differentiating MES 0 to 1 and proctitis, and FCP and RWT were independent predictors for differentiating MES 2 to 3 and proctitis. Sensitivity and specificity were 77.2% and 80.9%, respectively, for FCP >242.5 µg/g and RWF negative; and they were both 100% for RWT >4.1 mm and MSWC positive. CONCLUSIONS: Transperineal ultrasonography with mSMI may enable the evaluation of rectal activity and differentiation of UC from non-IBD proctitis with accuracy comparable to endoscopy.

Transperineal ultrasonography with superb microvascular imaging can differentiate ulcerative colitis from noninflammatory bowel disease proctitis and is therefore useful in distinguishing whether diarrhea and bloody stool during the treatments of ulcerative colitis are due to recurrence or infection.

Prolonged SARS-CoV-2 infection during obinutuzumab and bendamustine treatment for follicular lymphoma: A case report.

Key Clinical Message: SARS-CoV-2 infection has been associated with a prolonged course and a poor prognosis in patients who receive anti-CD20 antibodies. However, there are no established treatments for such patients. Serial changes in the SARS-CoV-2 antigen titer during the clinical course and treatment strategies for immunosuppressed patients are discussed. Abstract: We report a case of prolonged SARS-CoV-2 infection during obinutuzumab and bendamustine treatment for follicular lymphoma. Four years previously, the patient had been diagnosed with follicular lymphoma (Stage IIIA, Grade 2). She received several chemotherapy regimens, including rituximab and radiation therapy. Although these therapies achieved complete response temporally, they did not continue and recurred at 8 months before. Obinutuzumab and bendamustine therapy was selected, and she received five courses of obinutuzumab and bendamustine. She also received a SARS-CoV-2 mRNA vaccine two times. Although she did not have any symptoms, a routine check-up just before the 6th course of obinutuzumab and bendamustine revealed SARS-CoV-2 infection. Because she was immunosuppressed and was considered to be at high risk for the exacerbation of her disease, molnupiravir was immediately administered, and her SARS-CoV-2 antigen decreased. However, it was not completely cleared and flared-up at 6 weeks, with symptoms of COVID-19 appearing. Despite intensive treatment for SARS-CoV-2 infection, including remdesivir, baricitinib, tocilizumab and intravenous immunoglobulin, her SARS-CoV-2 antigen titer never became negative, and she finally died of respiratory failure caused by prolonged SARS-CoV-2 infection. Serial changes in the SARS-CoV-2 antigen titer during the clinical course and treatment strategies for immunosuppressed patients are discussed.

A retrospective study of the efficacy of combined EGFR­TKI plus VEGF inhibitor/cytotoxic therapy vs. EGFR­TKI monotherapy for PD­L1­positive EGFR­mutant non­small cell lung cancer: North Japan Lung Cancer Study Group 2202.

The present multicenter study was performed to compare the efficacy of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) monotherapy with that of combined EGFR-TKI plus vascular endothelial growth factor receptor (VEGF) inhibitor/cytotoxic therapy in patients with programmed death-ligand 1 (PD-L1)-positive EGFR-mutant non-small cell lung cancer (NSCLC). Data from patients with PD-L1-positive EGFR-mutant NSCLC were collected from 12 institutes. Survival in patients treated with first- and second-generation EGFR-TKIs, osimertinib (third-generation EGFR-TKI), and combined EGFR-TKI plus VEGF inhibitor/cytotoxic therapy was analyzed by multiple regression analysis with adjustments for sex, performance status, EGFR mutation status, PD-L1 expression level, and the presence or absence of brain metastasis using a Cox proportional hazards model. Data from a total of 263 patients were analyzed, including 111 (42.2%) patients who had received monotherapy with a first- or second-generation EGFR-TKI, 132 (50.2%) patients who had received osimertinib monotherapy, and 20 (7.6%) patients who had received combined EGFR-TKI plus VEGF inhibitor/cytotoxic therapy (hereafter referred to as combined therapy). Multiple regression analysis using the Cox proportional hazards model showed that the hazard ratio (95% confidence interval) for progression-free survival was 0.73 (0.54-1.00) in the patients who had received osimertinib monotherapy and 0.47 (0.25-0.90) in patients who had received combined therapy. The hazard ratio for overall survival was 0.98 (0.65-1.48) in the patients who had received osimertinib monotherapy and 0.52 (0.21-1.31) in patients who had received combined therapy. In conclusion, combined therapy was associated with a significant reduction in the risk of progression compared with first- and second-generation EGFR-TKI monotherapy, and therefore, may be promising for the treatment of patients of NSCLC.

Deep learning generates custom-made logistic regression models for explaining how breast cancer subtypes are classified.

Differentiating the intrinsic subtypes of breast cancer is crucial for deciding the best treatment strategy. Deep learning can predict the subtypes from genetic information more accurately than conventional statistical methods, but to date, deep learning has not been directly utilized to examine which genes are associated with which subtypes. To clarify the mechanisms embedded in the intrinsic subtypes, we developed an explainable deep learning model called a point-wise linear (PWL) model that generates a custom-made logistic regression for each patient. Logistic regression, which is familiar to both physicians and medical informatics researchers, allows us to analyze the importance of the feature variables, and the PWL model harnesses these practical abilities of logistic regression. In this study, we show that analyzing breast cancer subtypes is clinically beneficial for patients and one of the best ways to validate the capability of the PWL model. First, we trained the PWL model with RNA-seq data to predict PAM50 intrinsic subtypes and applied it to the 41/50 genes of PAM50 through the subtype prediction task. Second, we developed a deep enrichment analysis method to reveal the relationships between the PAM50 subtypes and the copy numbers of breast cancer. Our findings showed that the PWL model utilized genes relevant to the cell cycle-related pathways. These preliminary successes in breast cancer subtype analysis demonstrate the potential of our analysis strategy to clarify the mechanisms underlying breast cancer and improve overall clinical outcomes.

The effect of lifestyle on the mortality associated with respiratory diseases in the general population.

Lifestyle factors, including smoking habit, diet, and physical activity, affect the prognosis of various diseases. We elucidated the effect of lifestyle factors and health status on deaths from respiratory diseases in the general Japanese population using data from a community health examination database. Data of the nationwide screening program of the Specific Health Check-up and Guidance System (Tokutei-Kenshin), targeting the general population in Japan, from 2008 to 2010 were analyzed. The underlying causes of death were coded according to the International Classification of Diseases (ICD)-10. The hazard ratios of the incidence of mortality associated with respiratory disease were estimated using the Cox regression model. This study included 664,926 participants aged 40-74 years, who were followed up for 7 years. There were 8051 deaths, including 1263 (15.69%) deaths from respiratory diseases. The independent risk factors of mortality associated with respiratory diseases were male sex, older age, low body mass index, no exercise habit, slow walking speed, no drinking habit, smoking history, history of cerebrovascular diseases, high hemoglobin A1c and uric acid levels, low low-density lipoprotein cholesterol level, and proteinuria. Aging and decline of physical activity are significant risk factors for mortality associated with respiratory diseases, regardless of the smoking status.

Eosinophilic enteritis requiring differentiation from chronic enteropathy associated with SLCO2A1 gene: A case report.

BACKGROUND: Eosinophilic gastrointestinal disease (EGID) is a disorder characterized by infiltration of eosinophils causing mucosal damage and dysfunction of the gastrointestinal tract. The endoscopic findings of eosinophilic enteritis (EoN), an EGID variant, are nonspecific and occasionally difficult to diagnose. In contrast, chronic enteropathy associated with SLCO2A1 (CEAS) is a chronic persistent small intestinal disorder characterized by endoscopic findings such as multiple oblique and circular ulcers. CASE SUMMARY: We report the case of a 10-year-old boy who had suffered abdominal pain and fatigue for the preceding 6 mo. He was referred to our institute for investigation of suspected gastrointestinal bleeding because of severe anemia with hypoproteinemia and positive fecal human hemoglobin. The upper and lower gastrointestinal endoscopic findings were normal; however, double-balloon small bowel endoscopy showed multiple oblique and circular ulcers with discrete margins and mild constriction of the intestinal lumen in the ileum. The findings were highly consistent with CEAS, but urine prostaglandin metabolites were within normal limits, and no previously reported mutations in the SLCO2A1 gene were identified. Histological evaluation demonstrated moderate to severe eosinophilic infiltration localized to the small intestine suggesting a diagnosis of EoN. Clinical remission was maintained with montelukast and a partial elemental diet, but emergent surgery for bowel obstruction due to small intestinal stenosis was performed two years after the initial treatment. CONCLUSION: EoN should be considered in the differential diagnosis of CEAS-like small intestinal ulcerative lesions and normal urinary prostaglandin metabolite levels.

Accuracy of Transperineal Ultrasonography for Assessing Rectal Lesions in Paediatric Ulcerative Colitis: A Prospective Study.

BACKGROUND AND AIMS: Transabdominal ultrasonography [TAUS] appears comparable to colonoscopy for evaluating ulcerative colitis [UC] activity, but it has low accuracy in rectal evaluation. In this study, the accuracy of transperineal ultrasonography [TPUS] for evaluating rectal activity was compared to that of colonoscopy in paediatric UC cases. METHODS: Faecal calprotectin [FCP] values and TPUS and colonoscopic findings were compared prospectively in paediatric UC cases. Rectal wall thickening [RWT] and rectal wall flow [RWF] on power Doppler evaluated by TPUS were compared with the colonoscopy findings and were also measured on TAUS and assessed for the concordance rate of each finding. RESULTS: Thirty Mayo endoscopic sub-score [MES] 0-1 UC cases and 57 MES 2-3 UC cases were enrolled. FCP, RWT and RWF showed significant differences between the two groups [p < 0.05]. RWT and RWF were independent predictors of UC endoscopic activity, showing sensitivity of 95.8% and specificity of 100% with RWT ≥ 4.5 mm and positive RWF. The concordance rates between TPUS and TAUS findings in MES 2-3 were moderate to fair, whereas those in MES 0-1 were fair to poor. The concordance rates between ultrasonic examiners were good for both TAUS and TPUS. CONCLUSIONS: TPUS may evaluate rectal activity of UC with accuracy comparable to endoscopy. If accurate ultrasonic screening for the total colon can be performed by TPUS and TAUS, repeated evaluation of short-term treatment response may be possible.

Secretoglobin 3A2 protects lung from developing cigarette smoke-induced pulmonary emphysema.

Secretoglobin (SCGB) 3A2 is a bioactive molecule exhibiting various functions such as improving allergic airway inflammation and pulmonary fibrosis and promoting bronchial branching and proliferation during lung development. To determine if and how SCGB3A2 is involved in chronic obstructive pulmonary disease (COPD), a multifactorial disease with both airway and emphysematous lesions, a COPD mouse model was created by exposing Scgb3a2-deficient (KO), Scgb3a2-lung-specific overexpressing (TG), and wild type (WT) mice to cigarette smoke (CS) for 6 months. The KO mice showed loss of lung structure under control condition, and CS exposure resulted in more expansion of airspace and destruction of alveolar wall than WT mouse lungs. In contrast, TG mouse lungs showed no significant changes after CS exposure. SCGB3A2 increased the expression and phosphorylation of signal transducers and activators of transcription (STAT)1 and STAT3, and the expression of α1-antitrypsin (A1AT) in mouse lung fibroblast-derived MLg cells and mouse lung epithelial-derived MLE-15 cells. In MLg cells, A1AT expression was decreased in Stat3-knockdown cells, and increased upon Stat3 overexpression. STAT3 formed a homodimer when cells were stimulated with SCGB3A2. Chromatin immunoprecipitation and reporter assays demonstrated that STAT3 binds to specific binding sites on the Serpina1a gene encoding A1AT and upregulates its transcription in lung tissues of mice. Furthermore, nuclear localization of phosphorylated STAT3 upon SCGB3A2 stimulation was detected by immunocytochemistry. These findings demonstrate that SCGB3A2 protects the lungs from the development of CS-induced emphysema by regulating A1AT expression through STAT3 signaling.

Effect of hyperhomocysteinemia on a murine model of smoke-induced pulmonary emphysema.

Hyperhomocysteinemia was reported to enhance endoplasmic reticulum (ER) stress and subsequent apoptosis in several cells. However, the precise mechanisms of smoking susceptibility associated with hyperhomocysteinemia has not been fully elucidated. This study included 7- to 9-week-old C57BL6 male mice induced with hyperhomocysteinemia and were exposed to cigarette smoke (CS). A549 cells (human alveolar epithelial cell line) were cultured with homocysteine and were exposed to cigarette smoke extract (CSE) to observe cell viability and expression of proteins related to the ER stress. After 6 months of CS exposure, pulmonary emphysema was more severely induced in the group under the condition of hyperhomocysteinemia compared to that in the control group. The apoptotic A549 cells increased as homocysteine concentration increased and that was enhanced by CSE. Protein expression levels of ER stress markers were significantly increased after simultaneous stimulation. Notably, vitamin B12 and folate supplementation improved ER stress after simultaneous stimulation of A549 cells. In this study, we showed that hyperhomocysteinemia exacerbates CS exposure-induced emphysema in mice, suggesting that hyperhomocysteinemia and CS stimulation enhance ER stress and subsequent induced apoptosis in alveolar epithelial cells. It was suggested that there is a synergistic effect between homocysteine and CS.

Role of CC Chemokine Ligand 17 in Mouse Models of Chronic Obstructive Pulmonary Disease.

Lung function deterioration is significantly associated with poor prognosis in patients with chronic obstructive pulmonary disease (COPD). We previously reported that CC chemokine ligand 17/thymus and activation-regulated chemokine (CCL17/TARC) could be a predictive factor of lung function decline in patients with COPD. However, the role of CCL17 in the pathogenesis of COPD is unclear. Here we examined the role of CCL17 in lung inflammation using mouse COPD models. Exposure to cigarette smoking induced CCL17 production in bronchial epithelial cells and accumulation of alveolar macrophages in the lungs. Intranasal administration of recombinant CCL17 further enhanced cigarette smoke-induced macrophage accumulation and also aggravated elastase-induced pulmonary emphysema. We confirmed that cigarette smoke (CS) extract as well as hydrogen peroxide upregulated CCL17 in BAES-2B cells. Of note, macrophages of both M1 and M2 surface markers were accumulated by cigarette smoke. Both alveolar macrophage accumulation via exposure to cigarette smoking and emphysematous changes induced by elastase administration were significantly reduced in CCL17-deficient mice. We further demonstrated that CCL17 strongly induced the expression of CC chemokine ligand 2 (CCL2), a chemoattractant for macrophages, in RAW264.7 cells, and its production was inhibited by knockdown of CCR4, the receptor of CCL17. Collectively, the present results demonstrate that CCL17 is produced by lung epithelial cells upon CS exposure. Furthermore, CCL17 is involved in CS-induced accumulation of alveolar macrophages and development of elastase-induced pulmonary emphysema, possibly through CCL17-induced production of CCL2 by macrophages. Our findings may provide a new insight into the pathogenesis of COPD.

Expression of Oncogenic Molecules in Pediatric Ulcerative Colitis.

INTRODUCTION: Long-term disease duration of ulcerative colitis (UC) is known to increase the risk of developing colorectal cancer in adults; however, this association has not been genetically analyzed in children with UC. Herein, we examined the expression of cancer-related genes in the colonic mucosa of pediatric UC patients and their risk of developing colorectal cancer. METHODS: Microarray analysis of cancer-related gene expression was conducted on rectal mucosa biopsy specimens randomly selected from pediatric cases, including 4 active-phase UC cases, 3 remission-phase UC cases, and 3 irritable bowel syndrome control cases. The subject pool was then expanded to 10 active-phase cases, 10 remission-phase cases, and 10 controls, which were analyzed by real-time polymerase chain reaction (PCR) and immunohistochemical staining. RESULTS: The microarray results indicated significantly higher expression levels of cancer-related genes PIM2 and SPI1 in the active group than in the remission and control groups (p < 0.05). Real-time PCR confirmed that PIM2 and SPI1 expression levels were significantly higher, whereas TP53 and APC expression levels were significantly lower, in the active-phase group than in the remission and control groups (p < 0.05). Immunohistochemical staining for PIM2, SPI1, TP53, and APC proteins supported the real-time PCR results. CONCLUSIONS: Expression levels of previously unreported cancer-related genes in adult UC patients were significantly higher in pediatric UC patients than in controls. Inflammation of the gastrointestinal mucosa increased the expression levels of cancer-related genes even in childhood-onset UC cases, suggesting that chronic inflammation from childhood may increase the risk of colorectal cancer development.

Guillain-Barré syndrome after SARS-CoV-2 infection.

We herein report a case of Guillain-Barré syndrome (GBS) after SARS-CoV-2 infection. The patient was a close contact with a SARS-CoV-2 patient. Initially, she did not have any symptoms and quarantined at a hotel. Dysgeusia and olfactory abnormality appeared at day 6 after testing positive for infection and disappeared by day 9. Subsequently, the patient developed numbness of the arms and legs, difficulty walking, and dyspnea and was referred to our hospital. Her clinical examination showed generalized weakness and hyporeflexia. A cerebrospinal fluid analysis showed albuminocytological dissociation. Her nerve conduction studies were consistent with demyelinating polyneuropathy. Intravenous immunoglobulin was administered based on a diagnosis of GBS.

Novel pediatric granulomatosis with polyangiitis with a marked bloody pericardial effusion and bloody stool: a case report.

BACKGROUND: Granulomatosis with polyangiitis (GPA) is a syndrome of refractory vasculitis involving the upper respiratory tract, lungs, kidneys, and systemic small and medium-sized arteries that affects all age groups. No pediatric case with a bloody pericardial effusion resulting in cardiac tamponade and co-existing hematochezia has been reported. CASE PRESENTATION: A 14-year-old boy was referred for evaluation of prolonged fever, chest pain, and intermittent hematochezia. Diagnostic imaging showed a prominent pericardial effusion. Immediately after admission, his systolic blood pressure decreased. Emergent pericardiocentesis resulted in aspiration of a massive amount of bloody pericardial fluid. This was diagnosed as cardiac tamponade because his blood pressure recovered immediately after the drainage. The patient had an elevated serine proteinase 3-anti-neutrophil cytoplasmic antibody (PR3-ANCA) level on serological examination. Head MRI showed thickening of nasal and sinusoidal mucosa and a cystic mass in the left sphenoid sinus. After ruling out malignancy based on the cytology of the effusion, chest MRI, and gallium scintigraphy, total colonoscopy showed multiple irregular-shaped aphthae from the right transverse colon to the cecum on the contralateral side of the mesenteric attachments. Biopsy specimens of aphthous lesions confirmed necrotizing granulomatous inflammation. A diagnosis of GPA was made based on these findings, and oral prednisolone (PSL) and azathioprine were started. The hematochezia disappeared rapidly, and no recurrence of pericardial effusion was seen after PSL tapering was completed. The PR3-ANCA level decreased into the normal range immediately after the initial therapy. CONCLUSIONS: Pericarditis is a common cardiac complication of GPA, but there have been no reports of resultant cardiac tamponade. This is the first case of pediatric GPA with cardiac and gastrointestinal complications preceding the common symptoms such as respiratory or renal symptoms. A case of pediatric GPA with hematochezia is also extremely rare. In conclusion, serial measurement of ANCA levels is important in patients with persistent fever and bloody stool, such as in inflammatory bowel disease, to make the diagnosis of a vasculitic syndrome.

A case of pulmonary tuberculosis with hemoptysis from a peripheral pulmonary aneurysm.

An 88-year-old woman visited our hospital for hemoptysis due to ruptured peripheral pulmonary aneurysm diagnosed by contrast computed tomography (CT) and angiography. Her bleeding was stopped by interventional radiology vascular embolization. She was diagnosed with pulmonary tuberculosis due to a positive acid-fast bacillus (AFB) smear test following admission and the positive polymerase chain reaction for tuberculosis, despite no obvious cavity lesions or scatter shadows on CT. The causes of hemoptysis due to pulmonary tuberculosis are known to be Rasmussen aneurysm, in which the blood vessel wall adjacent to the lung cavity is thinned to form an aneurysm, or bleeding from the bronchial artery. In this case, it was considered that the inflammation caused by pulmonary tuberculosis spread directly to the pulmonary artery and formed a pulmonary aneurysm without forming a cavity. Similar cases have been rarely reported. Clinicians need to consider pulmonary tuberculosis as the cause of pulmonary aneurysm, even without cavity lesions in the lungs. It is important to perform AFB examination to diagnose pulmonary tuberculosis.

The Incidence and Risk Analysis of Lung Cancer Development in Patients with Chronic Obstructive Pulmonary Disease: Possible Effectiveness of Annual CT-Screening.

PURPOSE: Lung cancer is a serious complication in patients with chronic obstructive pulmonary disease (COPD) and accounts for approximately 15% of deaths in patients with COPD. However, with the exception of emphysema, few reports to date have been published on the factors that predict lung cancer development in COPD patients. It has been reported that patients with COPD develop lung cancer at a rate of 0.8% - 1.7%/year, but the incidence may be higher in the Japanese population. Therefore, we investigated the incidence of lung cancer and the lung cancer mortality rate in Japanese COPD patients, as well as factors that are associated with the development of lung cancer in COPD patients. PATIENTS AND METHODS: We followed up 224 patients with stable COPD and performed CT examinations at least once per year. The incidence of lung cancer was recorded and data at enrollment were compared with data of the group that did not develop lung cancer. RESULTS: Over a median follow-up period of 4.58 years, lung cancer was newly diagnosed in 19 patients; the incidence of lung cancer in this population was 1.85%/year. Patients who developed lung cancer had more severe emphysema assessed by CT and GOLD classification and were more likely to be current smokers than those who did not develop lung cancer. No other significant differences were observed between these two groups. Mortality was significantly increased in patients who developed lung cancer compared with those who did not. CONCLUSION: In COPD patients, the incidence of lung cancer is higher and the development of lung cancer worsens the prognosis; however, lung cancer development is unpredictable and attention should be paid to all patients. Annual CT screening is important for early detection of lung cancer.

Association between low mean corpuscular hemoglobin and prognosis in patients with exacerbation of chronic obstructive pulmonary disease.

BACKGROUND: Several studies have demonstrated the association between mean corpuscular hemoglobin concentration (MCHC), a hematological index used for the assessment of anemia, and the prognosis of patients with heart disease. While the red cell distribution width (RDW) is known to be related to the prognosis of patients with chronic obstructive pulmonary disease (COPD), few studies have focused on the association between the MCHC and COPD. Therefore, we examined the association between the MCHC and prognosis in patients with exacerbation of COPD. METHODS: We examined the association between the 30-day mortality and clinical findings in patients with COPD exacerbation who were hospitalized between October 2008 and December 2018. RESULTS: We enrolled 195 patients with COPD exacerbation (average age: 76.4 years; 181 men, 14 women). The MCHC was significantly lower, while the RDW was significantly higher in the 27 patients (13.8%) who died during the 30-day observation period compared to those in the patients who survived. Multivariate logistic regression analysis revealed that the MCHC was independently associated with 30-day mortality. The area under the curve calculated from the MCHC obtained from peripheral blood was 0.688 and the cutoff value was 31.6 g/dL, with a sensitivity of 0.593 and specificity of 0.810 (p = 0.0001). CONCLUSION: The MCHC might be a valuable biomarker for evaluating the prognosis of patients with COPD exacerbation.