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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.

BackgroundThe durability and cross-neutralizability of protective antibodies against evolving SARS-CoV-2 variants are primary concerns in mitigating (re-)exposures. The role of antibody maturation, the process whereby selection of higher avidity antibodies augments host immunity, to determine SARS-CoV-2 neutralizability was investigated.MethodsSera collected from SARS-CoV-2 convalescent individuals at 2- or 10-months after recovery, and BNT162b2 vaccine recipients at 3 or 25 weeks post-vaccination, were analyzed. Anti-spike IgG avidity was measured on a urea-treated ELISA platform. Neutralizing ability of antibodies was assessed by surrogate virus neutralization. Fold change between variant and wild-type antigen neutralizability was calculated to infer breadth of neutralizability.ResultsCompared with early-convalescence, the avidity index of late-convalescent sera was significantly higher (median 37.7 (interquartile range 28.4–45.1) vs. 64.9 (57.5–71.5), p < 0.0001), indicative of progressive antibody maturation extending months beyond acute-phase illness. The urea-resistant, high-avidity fraction of IgG was best predictive of neutralizability (Spearman’s r = 0.49 vs. 0.67 for wild-type; 0.18–0.52 vs. 0.48–0.83 for variants). Higher-avidity convalescent sera showed greater cross-neutralizability against SARS-CoV-2 variants (p < 0.001 for Alpha; p < 0.01 for Delta and Omicron). Vaccinees experienced delayed maturation kinetics, translating to limited breadth of neutralizability at week-25 post-vaccination which was only comparable to that of early-convalescence.ConclusionsAvidity maturation grants broader neutralizability that is resilient against emerging SARS-CoV-2 variants. With immunopotentiation through repeat vaccinations becoming a pivotal strategy to accomplish herd immunity, understanding the variable longitudinal evolutions of the two building blocks of ‘hybrid immunity’ is crucial.

We herein report a case of presumed septic shock due to Actinotignum schaalii bacteremia with urinary tract infection. A 65-year-old Japanese man suffering from a fever was diagnosed with septic shock due to urinary tract infection. A urine sample was additionally incubated under 5% CO2 and anaerobic conditions after A. schaalii was identified in a blood culture, but A. schaalii was not detected in the urine culture. If Gram-positive rods are observed on Gram staining of a urine sample in symptomatic patients with a predisposing urogenital condition, 5% CO2 and an anaerobic culture of a urine sample should be performed immediately.

Objective Skeletal muscle size is considered a predictor of prognosis in patients with respiratory diseases including Mycobacterium avium complex lung disease. However, no research focused on its impact on prognosis in patients with pulmonary tuberculosis (TB). Thus, this study aimed to assess the association between erector spinae muscle (ESM) size and in-hospital mortality among patients with pulmonary TB. Results We retrospectively included 258 consecutive patients aged over 65 years old, who were admitted to the hospital for bacteriologically confirmed pulmonary TB, and all underwent chest computed tomography (CT) scan upon admission. The cross-sectional area of the ESM (ESMcsa) was measured at the lower margin of the 12th thoracic vertebra on a single-slice CT scan image and was adjusted according to body surface area (BSA). In total, 71 (28%) patients died during hospitalization. The non-survivor group had a high incidence of respiratory failure and comorbidities and lower hemoglobin and albumin levels, performance status score, and ESMcsa/BSA. Multivariate analysis revealed that low performance status score and hemoglobin and albumin levels, but not ESMcsa/BSA and body mass index, could independently predict in-hospital mortality after adjusting for age and comorbidities. Therefore, ESM size was not associated with in-hospital mortality in patients with pulmonary TB.

Erector spinae muscle (ESM) size has been reported as a predictor of prognosis in patients with some respiratory diseases. This study aimed to assess the association of ESM size on all-cause in-hospital mortality among elderly patients with pneumonia. We retrospectively included patients (age: ≥ 65 years) admitted to hospital from January 2015 to December 2017 for community-acquired pneumonia who underwent chest computed tomography (CT) on admission. The cross-sectional area of the ESM (ESMcsa) was measured on a single-slice CT image at the end of the 12th thoracic vertebra and adjusted by body surface area (BSA). Cox proportional hazards regression models were used to assess the influence of ESMcsa/BSA on in-hospital mortality. Among 736 patients who were admitted for pneumonia, 702 patients (95%) underwent chest CT. Of those, 689 patients (98%) for whom height and weight were measured to calculate BSA were included in this study. Patients in the non-survivor group were significantly older, had a greater frequency of respiratory failure, loss of consciousness, lower body mass index, hemoglobin, albumin, and ESMcsa/BSA. Multivariate analysis showed that a lower ESMcsa/BSA independently predicted in-hospital mortality after adjusting for these variables. In elderly patients with pneumonia, quantification of ESMcsa/BSA may be associated with in-hospital mortality.

BackgroundDiffuse pulmonary ossification is a specific lung condition that is accompanied by underlying diseases. However, idiopathic dendriform pulmonary ossification (IDPO) is extremely rare, and the clinical features remain unclear. In this study, we aimed to report the clinical characteristics of IDPO.MethodsWe conducted a nationwide survey of patients with IDPO from 2017 to 2019 in Japan and evaluated the clinical, radiological, and histopathological findings of patients diagnosed with IDPO.ResultsTwenty-two cases of IDPO were identified. Most subjects (82%) were male, aged 22–56 years (mean (SD), 37.9 (9.1)) at diagnosis. Nearly 80% of the subjects were asymptomatic, and the condition was discovered during a medical check-up. However, 36% of the subjects showed a decline in forced vital capacity (%FVC) predicted )) at diagnosis. Nearly 80% of the subjects were asymptomatic, and the condition was discovered during a medical check-up. However, 36% of the subjects showed a decline in forced vital capacity (%FVC) predicted ConclusionsIDPO develops at a young age with gradually progressive phenotype. Further research and long-term (>20 years) follow-up are required to clarify the pathogenesis and clinical findings in IDPO.

Free itraconazole and hydroxyitraconazole concentrations were markedly elevated despite almost no changes in total concentrations when itraconazole was discontinued due to adverse effects. Elevated free itraconazole concentration may have a causal relationship with the development of adverse effects.

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.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.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.A randomized control study is required to determine the efficacy of MRSA coverage on the management of CAP in elderly patients.

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.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.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, and10% 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."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.

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 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.

To the Editor,A recent review in the present journal summarized the present knowledge on the virulence of Stenotrophomonas maltophilia [1]. The capability of the agent to act as an opportunistic pa...

The quality of life of rheumatoid arthritis (RA) patients has dramatically improved in the approximately two decades since biological agents were first introduced for its treatment [1]. However, whether current treatment strategies for RA have helped improve the prognosis of patients suffering from complications due to RA remains controversial. National data from the USA have shown that the mortality rate of RA-associated interstitial lung disease (ILD), a major complication associated with a poor prognosis in RA patients, seems to be gradually increasing, whereas the mortality rate of patients with any type of RA-associated disease has been decreasing [2]., The rates of death due to RA-LD among deaths from any type of RA-related cause have been increasing in Japan. A large-scale study is required to explain this trend. http://bit.ly/2Ew8fhW

Background: Although interferon-γ release assay (IGRA) is widely used for diagnosis of latent tuberculosis (TB) infection, which factors are related to false negative results are uncertain. The aim of this systematic review was to describe the risk factors associated with false negative IGRA results. Methods: Two authors independently identified studies designed to evaluate risk factors for false negative IGRA results from PubMed, the Cochrane Register of Control Trial database, and EMBASE assessed on October 22, 2018. Meta-analyses were conducted with random-effect models and heterogeneity was calculated with the I2 method. Findings: Of 1,377 titles and abstracts screened, 47 full texts were selected for review, and we finally included 17 studies in this systematic review. The most commonly studied risk factor (14 studies) was advanced age followed by low peripheral lymphocyte counts (7 studies), and these factors were associated with false negative results even under different TB prevalence (pooled odds ratio, 2.06; 95%CI, 1.68-2.52 in advanced age, and 7.93; 95%CI, 1.74-36.09 in low peripheral lymphocyte counts, respectively). However, detailed procedure of these assays were not clearly stated in many studies and the cut-off value of these factors were varied. Interpretation: Advanced age and low peripheral lymphocyte counts may be common risk factors for false negative IGRA results, suggesting people with these factors need careful followed-up even if they have negative IGRA results. Standardization of the assay procedure and assessment of risk factors with common definition and the same cut-off value are needed. Funding Statement: The authors state: "There was no funding source for this study." Declaration of Interests: The authors declare declare no competing interests.

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.

Although Klebsiella pneumoniae pneumonia is an insidious threat among the elderly, the role of radiological features has not been elucidated. We aimed to evaluate thin-section chest computed tomography (CT) features and assess its associations with disease prognosis in elderly patients with acute K. pneumoniae pneumonia. We retrospectively included elderly patients, admitted for acute K. pneumoniae pneumonia, and investigated thin-section CT findings to determine whether bronchopneumonia or lobar pneumonia was present. The association between the radiological pattern of pneumonia and in-hospital mortality was analyzed. Eighty-six patients with acute K. pneumoniae pneumonia were included, and among them, the bronchopneumonia pattern was observed in 70 (81%) patients. Twenty-five (29%) patients died in hospital, and they had a greater incidence of lobar pneumonia pattern (40% in nonsurvivors vs 10% in survivors; P = .008), low albumin level (2.7 g/dL, range, 1.6-3.8 in nonsurvivors vs 3.0 g/dL, range, 1.7-4.2 in survivors; P = .026) and higher levels of aspartate aminotransferase (30 U/L, range, 11-186 in nonsurvivors vs 23 U/L, range, 11-102 in survivors, P = .017) and C-reactive protein (8.0 mg/dL, range, 0.9-26.5 in nonsurvivors vs 4.7 mg/dL, range, 0.0-24.0 in survivors; P = .047) on admission. Multivariate analysis showed that lobar pneumonia pattern was independently associated with increased in-hospital mortality (adjusted hazard ratio, 3.906; 95% CI, 1.513-10.079; P = .005). In elderly patients with acute K. pneumoniae pneumonia, the lobar pneumonia pattern may be less commonly observed, and this pattern could relate to poor prognosis.

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.

Although complication with non-mycobacterial pneumonia among patients with pulmonary tuberculosis (TB) may lead to poor prognosis, discrimination between TB complicated with and without non-mycobacterial pneumonia using radiological imaging has not been fully elucidated. We aimed to clarify the differences in chest computed tomography (CT) features between pulmonary TB patients with culture-positive and culture-negative sputum for non-mycobacteria. We retrospectively included consecutive patients admitted to our hospital from January 2013 to December 2015 for bacteriologically-confirmed pulmonary TB, who were tested by sputum culture for non-mycobacteria, and who underwent chest CT within 2 weeks before or after admission. Chest CT features were compared between pulmonary TB patients who had positive non-mycobacterial cultures and in those who had not. Of 202 patients with pulmonary TB, 186 (92%) were tested by sputum culture for non-mycobacteria and underwent chest CT. Among these, non-mycobacteria were isolated in 118 patients (63%), while 68 patients (37%) had negative cultures. Patients with a positive culture for non-mycobacteria were significantly older and had lower levels of physical activity and albumin, higher levels of C-reactive protein, and a greater number of respiratory failures. By CT, emphysematous lesions, ground-glass opacities, airspace consolidation, air-bronchogram, interlobular septal thickening, bronchiectasis, pleural effusion, pleural thickening, and lymph node enlargement were more frequently in patients with a positive culture for non-mycobacteria. These chest CT features could be helpful for detecting complication with non-mycobacterial pneumonia in patients with pulmonary TB.

The World Health Organization (WHO) has published guidance recommending systemic corticosteroids for the treatment of patients with severe or critical COVID-19 and no corticosteroids for those with nonsevere COVID-19. Although their recommendations for critical cases were based on the results from seven randomized controlled trials (RCTs), those for noncritical cases were based on the results from only one RCT, the Randomized Evaluation of COVID-19 Therapy (RECOVERY) trial. In search of additional evidence of corticosteroids’ effect on COVID-19, we systematically reviewed controlled observational studies, besides RCTs, that assessed the impact of corticosteroid treatment on any type of mortality and/or other outcomes in noncritical patients. Of the 4037 titles and abstracts screened, we ultimately included the RECOVERY trial and five controlled observational studies using propensity score matching, (accessed on September 8, 2020). Two of the controlled observational studies assessed the association between corticosteroid treatment and in-hospital mortality, without finding statistical significance. Four of the controlled observational studies assessed corticosteroids’ effect on other outcomes, demonstrating that they were associated with reduced risk of intubation in patients requiring oxygen and with longer hospitalization and viral shedding in mild or moderate cases. These results support the WHO recommendations not to use corticosteroids for nonsevere COVID-19.

Pleuroparenchymal fibroelastosis (PPFE) is a newly described entity of interstitial lung disease,which has been recently recognized as a rare complication of bone marrow transplantation. We report a case of 30-year-old man who developed a unique combination of pleuroparenchymal fibroelastosis with cellular and fibrotic non-specific interstitial pneumonia (NSIP) and bronchiolitis obliterans (BO) sixteen years after hematopoietic stem cell transplantation. Histological examination revealed almost exclusive infiltration of CD3-positive T lymphocytes associated with lymphoepithelial lesions and multi-focal denudation of covering epithelial cells in all components. This case suggests PPFE, NSIP, and BO might be conditions of the same spectrum, pathogenetically related to chronic graft-versus-host disease. Immunostaining for CD3 and CD20 in transbronchial lung biopsies may be helpful for identifying graft-versus-host-driven interstitial lung disease., Respiratory Medicine Case Reports, 26, pp.244-247; 2019

Tosufloxacin, which is not used to treat Mycobacterium tuberculosis, is a fluoroquinolone recommended for pneumonia when the possibility of tuberculosis infection cannot be excluded. In the present case, symptoms and chest infiltrative shadow initially improved by tosufloxacin. Therefore, we regarded this patient as having general pneumonia and did not perform follow-up chest X-ray until the infiltrates had completely disappeared. However, a few weeks later, the symptoms and the infiltrates had worsened, so M. tuberculosis was isolated from the patient's sputum. This case suggests that patients suspected of having pulmonary tuberculosis should be monitored carefully, even if antibiotics without antituberculous activity are initially effective.

To the editor,A recent report in the present journal focussed on rate and risk factors of recurrent tuberculosis (TB) in Yemen, a country where TB is a major public health concern [1]. The authors ...

BackgroundAlthough combination therapy using clarithromycin, rifampicin, and ethambutol is recommended for patients with pulmonary Mycobacterium avium complex (MAC) disease, some patients do not tolerate it because of adverse effects or underlying diseases. The efficacy and safety of fluoroquinolone-containing combination regimens as an alternative remain uncertain. This study aimed to compare the efficacy and safety of fluoroquinolone-containing regimens with those of the standard regimens for treating pulmonary MAC disease.MethodsWe retrospectively included consecutive MAC patients who were treated in our hospital between January 2011 and May 2019. Patients treated with fluoroquinolone-containing regimens who had relapsed after treatment with standard regimens were excluded. A propensity score analysis was conducted to reduce selection bias, and the proportions of clinical improvement, defined by chest imaging findings and sputum conversion, were compared between the fluoroquinolone-containing regimen and standard regimen groups.ResultsWe analyzed 28 patients who received fluoroquinolone-containing regimens and 46 who received the standard regimen. Fluoroquinolone-containing regimens were more likely selected for patients with cavitary lesions, diabetes mellitus, culture negativity, a low daily physical activity level, a decreased lymphocyte count and an increased CRP level. The propensity score was calculated using these variables (C-statistic of the area under the receiver operating characteristic curve of the propensity score: 0.807, p < 0.0001). The fluoroquinolone-containing regimens were significantly inferior to the standard regimen in clinical improvements (p = 0.002, Log-rank test) in the univariate analysis, but the significance was lost after adjusting for the propensity score (HR 0.553, 95% CI 0.285-1.074, p = 0.080). Six (21%) patients in the fluoroquinolone-containing regimen group and ten (22%) patients in the standard regimen group experienced low-grade adverse effects.ConclusionsThere was no significant difference in clinical improvement between these regimens after propensity score adjustment. A large-scale prospective study is required to validate these results.

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.

Aim Pneumonia in older adults is increasingly recognized as a healthcare issue in countries with an aging population. Long-term macrolide therapy reduces exacerbations of chronic respiratory diseases, but its effects on the prevention of pneumonia have not been determined. Methods We carried out a randomized, controlled trial to test the effect of long-term clarithromycin therapy on the prevention of pneumonia among older adults. People aged ≥65 years who had recovered from pneumonia within the previous 3 months were recruited and randomly allocated to a long-term, low-dose clarithromycin (CAM) therapy group (n = 13) or a control group (n = 15). Results Both groups were followed up until recurrence of pneumonia. The median follow-up period was 251 days (95% CI 171-330) in the CAM group and 132 days (95% CI 67-196) in the control group (P = 0.627). The recurrence rate of pneumonia was two out of 13 (15%) in the CAM group and five out of 15 (33%) in the control group (P = 0.268). The median time to recurrence of pneumonia was 315 days (95% CI 249-382) in the CAM group and 260 days (95% CI 184-335) in the control group (P = 0.260). None of the differences between groups were statistically significant. Conclusions No statistically significant suppressive effects of long-term, low-dose macrolide therapy on the development of pneumonia among older people were found in this small sample. A large-scale, randomized, controlled study is required. Geriatr Gerontol Int 2019; 19: 1006-1009.

The pathogenesis of pleuroparenchymal fibroelastosis (PPFE), a rare interstitial lung disease, remains unclear. Based on previous reports and our experience, we hypothesized that alveolar epithelial denudation (AED) was involved in the pathogenesis of PPFE. This multicenter retrospective study investigated the percentage of AED and the features of the denudated areas in 26 PPFE cases, 30 idiopathic pulmonary fibrosis (IPF) cases, and 29 controls. PPFE patients had lower forced vital capacities and higher residual volume/total lung capacities in pulmonary function tests compared to IPF and control patients. Histopathologically, subpleural fibroelastosis was observed in PPFE, and AED was observed in 12.01% of cases in the subpleural or interlobular septa regardless of fibroelastosis. The percentage of AED in the PPFE group was significantly higher than that in the IPF group (6.84%, p = 0.03) and the normal group (1.19%, p &lt, 0.001). In the IPF group, the percentage of AED and the presence of PPFE-like lesions in the upper lobes were examined radiologically, but no correlation was found. We showed that AED frequently occurred in PPFE. AED was less frequent in IPF, which, in combination with imaging data, suggests that PPFE may have a different pathogenesis from IPF.

Pulmonary alveolar proteinosis (PAP) is characterized by the accumulation of periodic acid-schiff stain-positive lipoproteinaceous materials in the alveolar space due to impaired surfactant clearance by alveolar macrophage. Autoimmune PAP is the most common form of PAP, but rarely accompanies collagen disease or sarcoidosis. We report here a rare case of autoimmune PAP preceded by systemic sclerosis and sarcoidosis. A 64-year-old woman was admitted to our hospital for blurred vision, muscle weakness of extremities, Raynaud's phenomenon, and exertional dyspnea. We diagnosed her as having systemic sclerosis complicated with sarcoidosis. Chest computed tomography (CT) and transbronchial lung biopsy showed the findings of pulmonary fibrosis without PAP. We treated her with corticosteroid and intravenous cyclophosphamide therapy, followed by tacrolimus therapy. Thereafter, her symptoms improved except for exertional dyspnea, and she began to complain of productive cough thirteen months after corticosteroid and immunosuppressant therapy. On the second admission, a chest CT scan detected the emergence of crazy-paving pattern in bilateral upper lobes. Bronchoalveolar lavage (BAL) fluid with milky appearance and a lung biopsy specimen revealed acellular periodic acid-schiff stain-positive bodies. The serum titer of anti-granulocyte macrophage colony stimulating factor (GM-CSF) antibodies was elevated on first admission and remained high on second admission. We thus diagnosed her as having autoimmune PAP. Reducing the dose of immunosuppressive agents and repeating the segmental BAL resulted in the improvement of her symptoms and radiological findings. Immunosuppressant therapy may trigger the onset of autoimmune PAP in a subset of patients with systemic sclerosis and/or sarcoidosis.