DHCR7 links cholesterol synthesis with neuronal development and axonal integrity.

The DHCR7 enzyme converts 7-DHC into cholesterol. Mutations in DHCR7 can block cholesterol production, leading to abnormal accumulation of 7-DHC and causing Smith-Lemli-Opitz syndrome (SLOS). SLOS is an autosomal recessive disorder characterized by multiple malformations, including microcephaly, intellectual disability, behavior reminiscent of autism, sleep disturbances, and attention-deficit/hyperactivity disorder (ADHD)-like hyperactivity. Although 7-DHC affects neuronal differentiation in ex vivo experiments, the precise mechanism of SLOS remains unclear. We generated Dhcr7 deficient (dhcr7-/-) zebrafish that exhibited key features of SLOS, including microcephaly, decreased neural stem cell pools, and behavioral phenotypes similar to those of ADHD-like hyperactivity. These zebrafish demonstrated compromised myelination, synaptic anomalies, and neurotransmitter imbalances. The axons of the dhcr7-/- zebrafish showed increased lysosomes and attenuated autophagy, suggesting that autophagy-related neuronal homeostasis is disrupted.

Incidence and mortality of community-acquired and nosocomial infections in Japan: a nationwide medical claims database study.

BACKGROUND: It is important to determine the prevalence and prognosis of community-acquired infection (CAI) and nosocomial infection (NI) to develop treatment strategies and appropriate medical policies in aging society. METHODS: Patients hospitalized between January 2010 and December 2019, for whom culture tests were performed and antibiotics were administered, were selected using a national claims-based database. The annual trends in incidence and in-hospital mortality were calculated and evaluated by dividing the patients into four age groups. RESULTS: Of the 73,962,409 inpatients registered in the database, 9.7% and 4.7% had CAI and NI, respectively. These incidences tended to increase across the years in both the groups. Among the patients hospitalized with infectious diseases, there was a significant increase in patients aged ≥ 85 years (CAI: + 1.04%/year and NI: + 0.94%/year, P < 0.001), while there was a significant decrease in hospitalization of patients aged ≤ 64 years (CAI: -1.63%/year and NI: -0.94%/year, P < 0.001). In-hospital mortality was significantly higher in the NI than in the CAI group (CAI: 8.3%; NI: 14.5%, adjusted mean difference 4.7%). The NI group had higher organ support, medical cost per patient, and longer duration of hospital stay. A decreasing trend in mortality was observed in both the groups (CAI: -0.53%/year and NI: -0.72%/year, P < 0.001). CONCLUSION: The present analysis of a large Japanese claims database showed that NI is a significant burden on hospitalized patients in aging societies, emphasizing the need to address particularly on NI.

Factors associated with changes in activities of daily living from admission to discharge among older patients with pneumonia.

INTRODUCTION: It has not been fully elucidated that nutritional parameters affect the change of activities of daily living (ADL) during pneumonia treatment. This study assessed the impact of nutritional status, including erector spinae muscle (ESM) size on ADL changes from admission to discharge among older patients with community-acquired pneumonia (CAP). METHODS: We retrospectively included patients (age: ≥65 years) who were admitted to the hospital for CAP and underwent chest computed tomography (CT) on admission. ADL was evaluated using the Barthel index, and patients were divided into the maintained or improved ADL group and the declined ADL group from admission through discharge. The ESM cross-sectional area was measured on a single-slice CT image. Logistic regression models were applied for assessing factors associated with changes in ADL. RESULTS: A total of 523 patients hospitalized for CAP (median age 86 years) were evaluated. The declined group had significantly higher ADL levels on admission, a greater frequency of smoking history and malignancy, and a lower frequency of cerebrovascular disease and dementia. No significant difference in ESM size was observed between the groups. Multivariate analysis revealed that higher ADL levels on admission (odds ratio 1.034, interquartile range 1.026-1.043) and malignancy (3.002, 1.150-7.836) were associated with a decline in ADL, whereas cerebrovascular disease (0.579, 0.373-0.900) was related to improvement or maintenance of ADL. CONCLUSIONS: Although nutritional status might not affect the change of ADL among older patients hospitalized with pneumonia, a cerebrovascular disease history may be a good predictor for ADL improvement.

Antibody Avidity Maturation Following Recovery From Infection or the Booster Vaccination Grants Breadth of SARS-CoV-2 Neutralizing Capacity.

BACKGROUND: Cross-neutralizing capacity of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants is important in mitigating (re-)exposures. Role of antibody maturation, the process whereby selection of higher affinity antibodies augments host immunity, to determine SARS-CoV-2 neutralizing capacity was investigated. METHODS: Sera from SARS-CoV-2 convalescents at 2, 6, or 10 months postrecovery, and BNT162b2 vaccine recipients at 3 or 25 weeks postvaccination, were analyzed. Anti-spike IgG avidity was measured in urea-treated ELISAs. Neutralizing capacity was assessed by surrogate neutralization assays. Fold change between variant and wild-type neutralization inferred the breadth of neutralizing capacity. RESULTS: Compared with early-convalescent, avidity indices of late-convalescent sera were significantly higher (median, 37.7 [interquartile range 28.4-45.1] vs 64.9 [57.5-71.5], P < .0001). Urea-resistant, high-avidity IgG best predicted neutralizing capacity (Spearman r = 0.49 vs 0.67 [wild-type]; 0.18-0.52 vs 0.48-0.83 [variants]). Higher-avidity convalescent sera better cross-neutralized SARS-CoV-2 variants (P < .001 [Alpha]; P < .01 [Delta and Omicron]). Vaccinees only experienced meaningful avidity maturation following the booster dose, exhibiting rather limited cross-neutralizing capacity at week 25. CONCLUSIONS: Avidity maturation was progressive beyond acute recovery from infection, or became apparent after the booster vaccine dose, granting broader anti-SARS-CoV-2 neutralizing capacity. Understanding the maturation kinetics of the 2 building blocks of anti-SARS-CoV-2 humoral immunity is crucial.

An algorithm for PCT-guided antimicrobial therapy: a consensus statement by Japanese experts.

In Japan, a national antimicrobial resistance (AMR) action plan was adopted in 2016, advocating a 20% reduction in antibiotic consumption by 2020. However, there is still room for improvement to accomplish this goal. Many randomized controlled trials have reported that procalcitonin (PCT)-guided antimicrobial therapy could help to reduce antibiotic consumption without negative health effects, specifically in acute respiratory infections. In September 2018, some experts in Europe and the USA proposed algorithms for PCT-guided antimicrobial therapy in mild to moderate infection cases outside the ICU and severe cases in the ICU (the international experts consensus). Thereafter, a group of Japanese experts, including specialists in intensive care medicine, emergency medicine, respiratory medicine and infectious diseases, created a modified version of a PCT-guided algorithm (Japanese experts consensus). This modified algorithm was adapted to better fit Japanese medical circumstances, since PCT-guided therapy is not widely used in daily clinical practice in Japan. The Japanese algorithm has three specific characteristics. First, the target patients are limited to only hospitalized ICU or non-ICU patients. Second, pneumonia due to Pseudomonas aeruginosa, Staphylococcus aureus and Legionella species are excluded. Finally, a different timing of PCT follow-up measurement was proposed to meet restrictions of the Japanese medical insurance system. The adapted algorithms has high potential to further improve the safe reduction in antibiotic consumption in Japan, while reducing the spread of AMR pathogens.

Prevalence of antimicrobial resistant genes in Bacteroides spp. isolated in Oita Prefecture, Japan.

INTRODUCTION: Bacteroides spp. are the most common anaerobic bacteria isolated from the human gastrointestinal tract. Several resistant genes are present in Bacteroides spp. However, most studies have focused on the prevalence of the cfiA gene in Bacteroides fragilis alone. We assessed the susceptibility to antimicrobial agents and the prevalence of cepA, cfiA, cfxA, ermF, nim, and tetQ genes in Bacteroides strains isolated from clinical specimens in our hospital. METHODS: We isolated 86 B. fragilis and 58 non-fragilis Bacteroides strains from human clinical specimens collected from January 2011 to November 2021. Resistance against piperacillin (PIPC), cefotaxime (CTX), cefepime (CFPM), meropenem (MEPM), clindamycin, and minocycline was determined. RESULTS: The resistant rates of penicillins and cephalosporins in non-fragilis isolates were significantly higher than those in B. fragilis isolates. In B. fragilis isolates, the resistant rates of PIPC, CTX, and CFPM in cfxA-positive isolates were significantly higher than those in cfxA-negative isolates (71% vs. 16%, 77% vs. 19%, and 77% vs. 30%, respectively). Thirteen B. fragilis isolates harbored the cfiA gene, two of which were resistant to MEPM. Six of the 13 cfiA-positive B. fragilis isolates were heterogeneously resistant to MEPM. CONCLUSION: It is important to evaluate the use of MEPM as empirical therapy for Bacteroides spp. infections, considering the emergence of carbapenem resistance during treatment, existence of MEPM-resistant strains, and heterogeneous resistance.

Impact of Pseudomonas aeruginosa coverage on the prognosis of elderly patients with community-acquired pneumonia.

BACKGROUND: Although the 2019 American Thoracic Society and Infectious Diseases Society of America guidelines for community-acquired pneumonia (CAP) recommend the use of antibiotics with Pseudomonas aeruginosa coverage for patients with prior sputum isolation of P. aeruginosa, further research is needed to confirm its clinical outcomes. This study aimed to assess the impact of the use of antibiotics with P. aeruginosa coverage on mortality in elderly CAP patients with sputum isolation of P. aeruginosa. METHODS: We retrospectively included consecutive elderly patients who were hospitalized for CAP and P. aeruginosa-positive sputum culture. The association between the use of antibiotics with P. aeruginosa coverage and 28-day mortality was assessed based on propensity score to reduce selection bias. RESULTS: A total of 216 patients were included, and 68 (31%) of them were treated with antibiotics with P. aeruginosa coverage. The number of patients treated with antibiotics with P. aeruginosa coverage was significantly higher among nonsurvivors than among survivors. After adjustment using propensity score, the association between the use of antibiotics with P. aeruginosa coverage and the 28-day mortality was found to be statistically nonsignificant (odds ratio 2.182, 95% confidence interval 0.732-6.508, p = 0.162). CONCLUSIONS: The use of antibiotics with P. aeruginosa coverage in elderly CAP patients with sputum isolation of P. aeruginosa did not improve their prognosis. A randomized control study is required to identify cases that should be treated with antibiotics covering P. aeruginosa.

Factors associated with acid-fast bacillus isolation in patients with noncystic fibrosis bronchiectasis: A cross-sectional study.

INTRODUCTION: Acid-fast bacillus (AFB) is a major pathogen that causes noncystic fibrosis bronchiectasis requiring multidrug chemotherapy. Bronchoscopic bronchial wash is performed to determine the causative pathogens of bronchiectasis; but, predictive factors for AFB isolation have not been fully elucidated. This study aimed to determine the factors associated with AFB isolation from bronchial wash samples. METHODS: This was a single-center, cross-sectional study. Patients undergoing bronchoscopic bronchial wash for bronchiectasis were included, whereas those who did not undergo high-resolution computed tomography (HRCT); had acute pneumonia, interstitial lung disease, and a positive polymerase chain reaction result but a negative culture result for AFB; or in whom a guide sheath was used for suspected lung cancer were excluded. Binomial logistic regression was used to analyze the factors associated with a positive culture for AFB. RESULTS: Of the 96 included cases, AFB isolation was observed in the bronchial wash fluid of 26 patients (27%). No smoking history, a positive result for antiglycopeptidolipid (GPL)-core IgA antibody, and the presence of tree-in-bud appearance, multiple granular and nodular images on HRCT were more commonly observed in patients with AFB isolation than in those without. In the multivariate analysis, the tree-in-bud appearance (odds ratio, 4.223; 95% CI, 1.046-17.052) and anti-GPL core IgA antibody (odds ratio, 9.443; 95% CI, 2.206-40.421) were significantly associated with AFB isolation. CONCLUSIONS: The tree-in-bud appearance on HRCT is likely to predict AFB isolation independent of anti-GPL core IgA antibody results. Bronchoscopic bronchial wash should be recommended for bronchiectasis with multiple granulomas on HRCT.

Association between sputum conversion and in-hospital mortality in elderly patients with pulmonary tuberculosis: a retrospective study.

BACKGROUND: Non-conversion of sputum culture or smear within 2 months after the start of treatment is a known poor prognostic factor of pulmonary tuberculosis. In elderly patients, sputum conversion may be delayed because of the age-related decline in immune competence. This study aimed to assess how a long interval to sputum conversion predicts in-hospital mortality in elderly patients with pulmonary tuberculosis. METHODS: Consecutive elderly patients (age > 65 years) who were admitted to our institution for bacteriologically confirmed pulmonary tuberculosis were included. The association between sputum conversion within 30, 60, 90, or 120 days from the start of treatment and in-hospital mortality were analyzed by Cox proportional-hazards regression after adjustment for other potential variables. RESULTS: This study included 262 patients, and 74 patients (28%) died during hospitalization. Multivariate analyses showed that sputum non-conversion within 90 days (adjusted hazard ratio 0.424, 95% CI 0.252-0.712, p = 0.001) or 120 days (0.333, 0.195-0.570, p < 0.001) was independently associated with in-hospital mortality, whereas that within 60 days was not (p = 0.890). CONCLUSIONS: In elderly patients with tuberculosis, 2 months may be insufficient when evaluating sputum conversion as a prognostic factor. Sputum non-conversion within 90 days or longer may predict in-hospital mortality more accurately.

Methicillin-resistant Staphylococcus aureus among elderly patients with community-acquired pneumonia.

INTRODUCTION: The 2019 American Thoracic Society/Infectious Diseases Society of America guidelines for community-acquired pneumonia (CAP) recommend methicillin-resistant Staphylococcus aureus (MRSA) coverage for patients with prior sputum isolation of MRSA. This study aimed to determine the impact of MRSA coverage on in-hospital mortality in elderly patients with CAP among whom MRSA was isolated. METHODS: Consecutive elderly patients who were admitted for CAP and had positive sputum culture for MRSA were retrospectively included, and the association between MRSA coverage and in-hospital mortality was analyzed. RESULTS: Twenty (18%) of 111 patients received MRSA coverage. Although patients who received MRSA coverage tended to have more frequent prior isolation of MRSA compared to those who did not, no significant difference in in-hospital mortality was observed between both groups (2/20, 10% vs. 8/91, 9%). MRSA coverage was not associated with in-hospital mortality (odds ratio: 1.15; 95% CI: 0.23-5.89, p = 0.864); however, advanced age, hemoglobin level, a high A-DROP score, and C-reactive protein levels were associated with in-hospital mortality. MRSA coverage may not improve the prognosis of elderly patients with CAP who had positive sputum culture for MRSA. CONCLUSIONS: A randomized control study is required to determine the efficacy of MRSA coverage on the management of CAP in elderly patients.

National survey of physicians in Japan regarding their use of diagnostic tests for legionellosis.

INTRODUCTION: Bacterial culture remains the gold standard for the diagnosis of legionellosis. However, past reports indicate that most physicians use the urinary antigen test (UAT) alone. Combining it with other tests is important, especially in patients with negative UAT results. The aim of this study was to investigate the current situation of legionellosis diagnostics and clarify the issues that need to be addressed. METHODS: Between March 1, 2021 and April 30, 2021, a questionnaire survey was conducted in an anonymous manner among physicians working in Japan. Questionnaires were generated on a website and asked questions in a multiple-choice format. RESULTS: Valid responses were received from 309 physicians during the study period. Most (92.9%) physicians reported using UAT as the initial test for patients suspected of having legionellosis, and <10% reported using other tests (e.g., culture, nucleic acid amplification test [NAAT], Gimenez staining, and serum antibody titer measurement [ATM]). When the initial test result was negative, 63% of physicians reported not conducting additional tests. Even when they chose to run additional tests, at most 27.8%, 23.6%, 12.3%, and 10.4% of all physicians used NAAT, culture, Gimenez staining, and serum ATM, respectively. The major reasons for not using tests other than UAT were "unavailability in the medical facility," "long turn-around time," and "difficult to collect sputum." CONCLUSIONS: The present survey revealed that most physicians in Japan used UAT alone for diagnosing legionellosis. Eliminating barriers to creating a reasonable environment and edification of physicians are needed to improve the current situation.

Efficacy of extracorporeal membrane oxygenation for acute respiratory failure with interstitial lung disease: a case control nationwide dataset study in Japan.

BACKGROUND: Whether acute respiratory failure in patients with interstitial lung disease is reversible remains uncertain. Consequently, indications for extracorporeal membrane oxygenation in these patients are still controversial, except as a bridge to lung transplantation. The objective of this study was to clarify in-hospital mortality and prognostic factors in interstitial lung disease patients undergoing extracorporeal membrane oxygenation. METHODS: In this case-control study using the Japanese Diagnosis Procedure Combination database, hospitalized interstitial lung disease patients receiving invasive mechanical ventilation and extracorporeal membrane oxygenation from 2010 to 2017 were reviewed. Patients' characteristics and treatment regimens were compared between survivors and non-survivors to identify prognostic factors. To avoid selection biases, patients treated with extracorporeal membrane oxygenation as a bridge to lung transplantation were excluded. RESULTS: A total of 164 interstitial lung disease patients receiving extracorporeal membrane oxygenation were included. Their in-hospital mortality was 74.4% (122/164). Compared with survivors, non-survivors were older and received high-dose cyclophosphamide, protease inhibitors, and antifungal drugs more frequently, but macrolides and anti-influenza drugs less frequently. On multivariate analysis, the following factors were associated with in-hospital mortality: advanced age (odds ratio [OR] 1.043; 95% confidence interval [CI] 1.009-1.078), non-use of macrolides (OR 0.305; 95% CI 0.134-0.698), and use of antifungal drugs (OR 2.416; 95% CI 1.025-5.696). CONCLUSIONS: Approximately three-quarters of interstitial lung disease patients undergoing extracorporeal membrane oxygenation died in hospital. Moreover, advanced age, non-use of macrolides, and use of antifungal drugs were found to correlate with a poor prognosis.

Re-expansion pulmonary edema following a pneumothorax drainage in a patient with COVID-19.

BACKGROUND: Re-expansion pulmonary edema is an uncommon complication following drainage of a pneumothorax or pleural effusion. While pneumothorax is noted to complicate COVID-19 patients, no case of COVID-19 developing re-expansion pulmonary edema has been reported. CASE REPRESENTATION: A man in his early 40 s without a smoking history and underlying pulmonary diseases suddenly complained of left chest pain with dyspnea 1 day after being diagnosed with COVID-19. Chest X-ray revealed pneumothorax in the left lung field, and a chest tube was inserted into the intrathoracic space without negative pressure 9 h after the onset of chest pain, resulting in the disappearance of respiratory symptoms; however, 2 h thereafter, dyspnea recurred with lower oxygenation status. Chest X-ray revealed improvement of collapse but extensive infiltration in the expanded lung. Therefore, the patient was diagnosed with re-expansion pulmonary edema, and his dyspnea and oxygenation status gradually improved without any intervention, such as steroid administration. Abnormal lung images also gradually improved within several days. CONCLUSIONS: This case highlights the rare presentation of re-expansion pulmonary edema following pneumothorax drainage in a patient with COVID-19, which recovered without requiring treatment for viral pneumonia. Differentiating re-expansion pulmonary edema from viral pneumonia is crucial to prevent unnecessary medication for COVID-19 pneumonia and pneumothorax.

A solitary pulmonary nodule caused by Mycobacterium tuberculosis var. BCG after intravesical BCG treatment: a case report.

BACKGROUND: Intravesical instillation of bacillus Calmette-Guérin (BCG) as a treatment for superficial bladder cancer rarely causes pulmonary complications. While published cases have been pathologically characterized by multiple granulomatous lesions due to disseminated infection, no case presenting as a solitary pulmonary nodule has been reported. CASE PRESENTATION: A man in his 70 s was treated with intravesical BCG for early-stage bladder cancer. After 1 year, he complained of productive cough with a solitary pulmonary nodule at the left lower lobe of his lung being detected upon chest radiography. His sputum culture result came back positive, with conventional polymerase chain reaction (PCR) identifying Mycobacterium tuberculosis complex. However, tuberculosis antigen-specific interferon-gamma release assay came back negative. Considering a history of intravesical BCG treatment, multiplex PCR was conducted, revealing the strain to be Mycobacterium tuberculosis var. BCG. The patient was then treated with isoniazid, ethambutol, levofloxacin, and para-aminosalicylic acid following an antibiotic susceptibility test showing pyrazinamide resistance, after which the size of nodule gradually decreased. CONCLUSION: This case highlights the rare albeit potential radiographic presentation of Mycobacterium tuberculosis var. BCG, showing a solitary pulmonary nodule but not multiple granulomatous lesions, after intravesical BCG treatment. Differentiating Mycobacterium tuberculosis var. BCG from Mycobacterium tuberculosis var. tuberculosis is crucial to determine whether intravesical BCG treatment could be continued for patients with bladder cancer.

Mycobacterium abscessus subsp. abscessus empyema complicated with subcutaneous abscess.

There have been no case reports of thoracic subcutaneous abscess after surgery for Mycobacterium abscessus complex associated empyema. We herein report a case of Mycobacterium abscessus subsp. abscessus (M. abscessus subsp. abscessus) induced subcutaneous abscesses following surgical treatment for concurrent M. abscessus subsp. abscessus -associated empyema and pneumothorax. A 75-year-old woman had M. abscessus subsp. abscessus -associated empyema and pneumothorax. She underwent surgical treatment of decortication and fistulectomy and suffered from M. abscessus subsp. abscessus -associated subcutaneous abscesses after thoracentesis/drainage. A multidisciplinary approach combined with surgical care, thermal therapy, and multidrug chemotherapy contributed to a successful result. An early multidisciplinary approach is believed to be important in cases of M. abscessus subsp. abscessus -associated empyema and subcutaneous abscess.

The impact of performance status on tuberculosis-related death among elderly patients with lung tuberculosis: A competing risk regression analysis.

While advanced age is a main prognostic factor in patients with tuberculosis, the factors that specifically affect tuberculosis-related death are unclear because elderly people are at a risk for other age-related lethal diseases. We aimed to assess the impact of performance status on tuberculosis-related death among elderly patients with lung tuberculosis. Elderly patients (≥65 years of age) admitted to our hospital for bacteriologically-diagnosed lung tuberculosis were included, and analyzed the influence of performance status on tuberculosis-related in-hospital death, with non-tuberculosis-related death as a competing risk. Forty and 19 of the 275 patients died from tuberculosis-related causes and non-tuberculosis-related causes, respectively. The tuberculosis-related death group had a greater number of patients with a poor performance status (defined as category 3 and 4 [HR 21.022; 95%CI 2.881-153.414; p = 0.003]), a lower serum albumin level (HR 0.179; 95%CI 0.090-0.359; p < 0.001) and a higher C-reactive protein level (HR1.076; 95%CI 1.026-1.127; p = 0.002). A multivariate competing risk regression analysis showed that a poor performance status (HR 7.311; 95%CI 1.005-53.181; p = 0.049) and low albumin level (HR 0.228; 95%CI 0.099-0.524); p = 0.001) significantly predicted tuberculosis-related death. Performance status can be a useful scale for predicting tuberculosis-related death among elderly patients with pulmonary tuberculosis.

Diffuse Large B-Cell Lymphoma Arising from the Lesion of Chronic Lobar Atelectasis.

Pulmonary lymphoma is rare, accounting for < 1% of primary lung cancers. Most primary pulmonary lymphomas (PPL) are low-grade mucosa-associated lymphoid tissue (MALT)-type, and among PPL, diffuse large B-cell lymphoma (DLBCL) is extremely rare. In contrast, there has been an increase in the incidence of DLBCL among patients with autoimmune disorders and recurrent or chronic bacterial infection. A subset of DLBCL has been reported to develop through transformation of preexisting or concurrent MALT. The respiratory symptoms are non-specific, and the chest X-ray findings demonstrate the presence of interstitial and mixed alveolar infiltrates, nodular lesions, and localized homogeneous consolidations; the diagnosis of pulmonary DLBCL is thus challenging and often leads to a misdiagnosis or delayed diagnosis. We herein report a case of DLBCL which was assumed to have arisen from the lesion of chronic atelectasis that was successfully diagnosed by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). A 74-year-old woman with diffuse bronchiectasis and chronic atelectasis of the left lower lobe suffered from productive cough and high fever. Increased airway filling with mucoid secretion was repeatedly observed within the area of atelectasis with bronchiectasis, and left lower lobe atelectasis developed. Subsequently, the hilar and mediastinal lymph nodes gradually became enlarged, and DLBCL was pathologically confirmed. In the present case, DLBCL was considered to have arisen in the lesion of chronic atelectasis. Physicians should recognize that DLBCL may develop at the site of chronic atelectasis during disease course of diffuse bronchiectasis, and thus DLBCL may be misdiagnosed as superimposed infection of chronic atelectasis.

Hierarchical control of interleukin 13 (IL-13) signals in lung fibroblasts by STAT6 and SOX11.

Interleukin (IL)-13 is a signature cytokine of type 2 inflammation important for the pathogenesis of various diseases, including allergic diseases. Signal transducer and activator of transcription (STAT) 6 is a critical transcriptional factor for the IL-13 signals; however, it remains unknown how expression of the IL-13-induced genes is differentiated by the transcriptional machineries. In this study, we identified IL-13-induced transcriptional factors in lung fibroblasts using DNA microarrays in which SOX11 was included. Knockdown of SOX11 down-regulated expression of periostin and CCL26, both of which are known to be downstream molecules of IL-13, whereas enforced expression of SOX11 together with IL-13 stimulation enhanced expression of periostin. Moreover, we found that in DNA microarrays combining IL-13 induction and SOX11 knockdown there exist both SOX11-dependent and -independent molecules in IL-13-inducible molecules. In the former, many inflammation-related and fibrosis-related molecules, including periostin and CCL26, are involved. These results suggest that SOX11 acts as a trans-acting transcriptional factor downstream of STAT6 and that in lung fibroblasts the IL-13 signals are hierarchically controlled by STAT6 and SOX11.

Impact of additional antibiotics on in-hospital mortality in tuberculosis isolated general bacteria: A propensity score analysis.

Whether or not additional antibiotics with anti-tuberculosis agents are required to treat bacterial co-infection with pulmonary tuberculosis is unclear. We aimed to assess the impact of additional antibiotics on mortality in pulmonary tuberculosis patients whose sputum cultures were positive for general bacteria as a surrogate definition of bacterial pneumonia. This study was a single-center retrospective cohort using a propensity score analysis. We included patients who were admitted for pulmonary tuberculosis and whose sputum cultures were positive for general bacteria. The mortality of patients who received additional antibiotics was analyzed after adjusting for other variables, including the propensity score predicting treatment with additional antibiotics. We assessed 68 and 55 tuberculosis patients treated with and without general antibiotics, respectively. Additional antibiotics tended to be administered to patients with a high level of C-reactive protein and neutrophil count, poor performance status, hypoxemia and hypoalbuminemia (C-statistics of area under receiver operating characteristic curve to the propensity score; 0.884, p < 0.001). In the multivariate analysis, advanced age and not the use of additional antibiotics was associated with in-hospital mortality. Additional antibiotics with anti-tuberculosis agents may not improve the prognosis of pulmonary tuberculosis patients whose sputum cultures were positive for general bacteria. Isolation of general bacteria does not equate to complication with bacterial pneumonia, so physicians should not administer general antibiotics to TB patients based solely on the results of sputum culture for general bacteria. A prospective study is needed to verify these results using a more accurate definition of pulmonary tuberculosis complicated with bacterial pneumonia.

Asthma Exacerbation Coincident with Saddle Pulmonary Embolism and Paradoxical Embolism.

Saddle pulmonary embolism (PE) and paradoxical embolism (PDE) are life-threatening disorders carrying a risk of sudden death, and their prompt diagnosis is extremely important. Saddle PE is a radiologic definition and refers to a thrombus that straddles the bifurcation of the pulmonary artery trunk, carrying a risk of sudden hemodynamic collapse. PDE is defined as a systemic arterial embolus due to the passage of a venous thrombus though a right-to-left shunt, such as patent foramen ovale (PFO). We herein present the rare case of asthma exacerbation coincident with saddle PE and PDE. A 69-year-old woman with asthma was suffering from dyspnea, pulse attenuation of the left radial artery and left upper limb pain. An arterial blood gas analysis revealed hypoxemia, and a pulmonary function test demonstrated an obstructive pattern. Enhanced computed tomography (CT) revealed saddle PE, right popliteal venous thrombosis, and left brachial artery occlusion. After the treatment with edoxaban, an anticoagulant, and aspirin, the PE was significantly alleviated, and the brachial artery occlusion was recanalized. Subsequently, the right-to-left shunt through PFO was confirmed, and PDE was suspected of inducting her brachial artery embolism. In the present case, the pulse attenuation of the radial artery and upper limb pain prompted us to consider peripheral vascular disease or coagulation disorders. Physicians should keep in mind that patients with asthma are at considerable risk of PE, and it is important to be aware of possible PFO in patients presenting with the coexistence of PE and systemic arterial embolism.