Association between disease severity according to "MN criteria" and 30-day mortality in patients with Clostridioides difficile infection.

INTRODUCTION: A rapid membrane enzyme immunoassays (EIA) are frequently used to diagnose Clostridioides difficile infection (CDI). If EIA does not provide a definitive CDI diagnosis, whether treatment with anti-CD agents is to be performed depends on the pathogenesis and severity of the disease. In Japan, "MN criteria" have been proposed for the classification of disease severity. In this study, we investigated the association between disease severity and CDI prognosis when MN criteria are used. METHODS: This study included 102 patients diagnosed with CDI between April 2015 and March 2020. The disease serverity classification accorditng to MN criteria was divided into two groups: non-severely ill (mild to moderate) and severely ill (severe to critical) group. RESULTS: Mortality was significantly higher in severely ill patients than non-severely ill patients (46.7% vs. 13.8%, p = 0.0025). Multivariable analysis showed that the mortality of patients with CDI was significantly associated with advanced age (odds ratio [OR] = 1.1; 95% confidence interval [CI] = 1.0-1.2; p = 0.019) and disease severity (OR = 4.2; 95% CI = 1.2-14.8; p = 0.023). DISCUSSION: The classification of disease severity according to the MN criteria would be particularly useful in predicting the patients' prognoses.

Evaluation of Remdesivir for Mildly to Moderately Ill Patients with COVID-19: A Single-Arm, Single-Center, Retrospective Study.

Background and Objectives: Remdesivir (RDV) is the first antiviral agent approved in Japan for the treatment of coronavirus disease 2019 (COVID-19). The aim of our study was to assess the efficacy and safety of RDV treatment in mildly to moderately ill patients with COVID-19. Materials and Methods: A single-center, retrospective study was performed in Fukuoka University Chikushi Hospital. Patients admitted to our hospital from June to October 2021 for RDV treatment against COVID-19 were enrolled. The primary end point was clinical status on days 10 and 14, using a 6-point ordinal scale ranging from death (category 6) to discharge (category 1). Adverse events were assessed and graded using the Japanese version of Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Results: In total, 47 COVID-19 patients receiving RDV treatment were assessed during the study period. Thirty-four (72.3%) out of 47 patients required oxygen therapy. Out of these 34 patients, 30 (88.2%) showed a 2-point clinical improvement on day 14 after RDV was initiated. Serum alanine aminotransferase levels were elevated in three patients (6.4%) (CTCAE Grade 3) and neutropenia was detected in one patient (2.1%) out of the 47 patients. Conclusions: RDV may be highly effective, with good safety profiles, in patients with COVID-19 requiring oxygen therapy.

A proposed prognostic prediction score for pleuroparenchymal fibroelastosis.

BACKGROUND: Clinical course of pleuroparenchymal fibroelastosis (PPFE) shows considerable variation among patients, but there is no established prognostic prediction model for PPFE. METHODS: The prediction model was developed using retrospective data from two cohorts: our single-center cohort and a nationwide multicenter cohort involving 21 institutions. Cox regression analyses were used to identify prognostic factors. The total score was defined as the weighted sum of values for the selected variables. The performance of the prediction models was evaluated by Harrell's concordance index (C-index). We also examined the usefulness of the gender-age-physiology (GAP) model for predicting the prognosis of PPFE patients. RESULTS: We examined 104 patients with PPFE (52 cases from each cohort). In a multivariate Cox analysis, a lower forced vital capacity (FVC [defined as FVC < 65%]; hazard ratio [HR], 2.23), a history of pneumothorax (HR, 3.27), the presence of a lower lobe interstitial lung disease (ILD) (HR, 2.31), and higher serum Krebs von den Lungen-6 (KL-6) levels (> 550 U/mL, HR, 2.56) were significantly associated with a poor prognosis. The total score was calculated as 1 × (FVC, < 65%) + 1 × (history of pneumothorax) + 1 × (presence of lower lobe ILD) + 1 × (KL-6, > 550 U/mL). PPFE patients were divided into three groups based on the prognostic score: stage I (0-1 points), stage II (2 points), and stage III (3-4 points). The survival rates were significantly different in each stage. The GAP stage was significantly associated with the prognosis of PPFE, but no difference was found between moderate (stage II) and severe (stage III) disease. Our new model for PPFE patients (PPFE Prognosis Score) showed better performance in the prediction of mortality in comparison to the GAP model (C-index of 0.713 vs. 0.649). CONCLUSIONS: Our new model for PPFE patients could be useful for predicting their prognosis.

Distribution of emphysema and fibrosis in idiopathic pulmonary fibrosis with coexisting emphysema.

AIMS: Combined pulmonary fibrosis and emphysema (CPFE) is a syndrome that results from tobacco smoking. Emphysema and fibrosis in CPFE patients have been considered to exist separately, with emphysema in the upper lobes and interstitial pneumonia in the lower lobes. The aim of this study was to examine the intrapulmonary distribution of fibrosis and emphysema in clinically diagnosed patients with idiopathic pulmonary fibrosis (IPF) and coexisting emphysema. METHODS AND RESULTS: Among IPF patients (n = 40) who had been autopsied or pneumonectomised for lung transplantation from 1993 to 2018, we retrospectively selected patients with IPF and coexisting emphysema (n = 19) on the basis of the appearance on chest computed tomography (IPF patients with emphysema). We then histologically determined the intrapulmonary distribution of emphysema and fibrosis in the upper lobes and the lower lobes separately. In 15 of the 19 IPF patients with emphysema (79%), fibrosis and emphysema coexisted in the upper lobes and the lower lobes. No patients showed emphysema exclusively in the upper lobes and fibrosis exclusively in the lower lobes. CONCLUSIONS: In the autopsied and pneumonectomised specimens of IPF patients with emphysema, craniocaudal separation of emphysema and fibrosis (emphysema in the upper lobes and interstitial pneumonia in the lower lobes) was histologically rare; coexistence or collision of fibrosis and emphysema in each lobe was common.

Lower-lobe predominant pleuroparenchymal fibroelastosis.

Upper-lobe predominance of elastofibrosis is agreed upon for the diagnosis of clinical pleuroparenchymal fibroelastosis (PPFE). We herein describe a patient with dermatomyositis-related interstitial pneumonia with a histology of lower-lobe predominant PPFE. A 71-year-old woman who had been diagnosed with dermatomyositis-related interstitial pneumonia died of respiratory failure. The computed tomography patterns of the lower lobes showed reticular and ground-glass opacities with traction bronchiectasis. An autopsy revealed that the bilateral lower lobes were sclerotic with decreased air volume. A microscopic examination of the lower lobes showed pleural fibrosis and subpleural elastofibrosis without the structural destruction, indicative of histological PPFE. PPFE histology was also evident in the upper lobes but relatively modest compared to that of the lower lobes. In addition, because the computed tomography images of the patient were suggestive of non-PPFE-type fibrosis, lower-lobe dominant PPFE might be overlooked in daily practice.

Serum Soluble Interleukin-2 Receptor Is a Biomarker for Pneumocystis jirovecii Pneumonia among Patients with Rheumatoid Arthritis under Methotrexate Therapy.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic joint inflammation and may manifest as interstitial pneumonia (IP). Methotrexate (MTX) is one of the main therapeutic drugs used for RA, but MTX could cause severe side effects, including Pneumocystis jirovecii pneumonia (PCP) and IP. Owing to similar symptoms, it is sometimes difficult to discriminate MTX therapy-associated PCP (MTX-PCP) and MTX therapy-associated IP (MTX-IP). Soluble interleukin-2 receptor (sIL-2R) is considered a marker of T-cell activation, and serum sIL-2R levels are elevated in RA and PCP. This led us to hypothesize that serum sIL-2R is a potential biomarker for discriminating MTX-PCP and MTX-IP. Accordingly, we carried out a retrospective analysis of 20 MITX-PCP cases, 30 MTX-IP cases, and as controls, 16 patients with RA-associated IP (RA-IP) and 13 patients with PCP without MTX treatment (PCP group). C-reactive protein and alveolar-arterial oxygen differences were higher in the MTX-PCP group than those in the RA-IP and MTX-IP groups. Importantly, serum levels of sIL-2R in MTX-PCP were significantly higher than those in other three groups. Based on the receiver operating characteristic curve, the cut-off level of sIL-2R resulting in the highest diagnostic accuracy for MTX-PCP was 1,311.5 U/mL, discriminating between MTX-PCP and other groups with 91.7% sensitivity and 78.6% specificity. Thus, patients with MTX-PCP show a higher degree of systemic inflammation, severe hypoxemia, and increased sIL-2R levels compared with those in MTX-IP cases. In conclusion, serum sIL-2R could be a biomarker for PCP diagnosis among patients with RA under MTX therapy.

The similarities and differences between pleuroparenchymal fibroelastosis and idiopathic pulmonary fibrosis.

The idiopathic form of pleuroparenchymal fibroelastosis (PPFE) is categorized as a rare idiopathic interstitial pneumonia in the current classification. The majority of PPFE cases are idiopathic, but many predisposing factors or comorbidities have been reported. Although histological PPFE is predominantly located in the upper lobes, which are less often affected by fibrosis in patients with idiopathic pulmonary fibrosis (IPF), the clinical course of PPFE is seemingly similar to that of IPF. However, upper lobe fibroelastosis has various clinical and physiological characteristics that differ from those of IPF, including a flattened thoracic cage and a marked decrease in the forced vital capacity (FVC) but with a preserved residual volume. Compared with IPF, the decrease in the walking distance is mild despite the markedly decreased FVC in PPFE, and chest radiograph more frequently shows the elevation of bilateral hilar opacities with or without tracheal deviation. The prognosis may be related to the development of fibrosing interstitial pneumonia in the lower lobes with elevated levels of serum Krebs von den Lungen-6; however, there is marked variation in the pathogenesis and clinical features in PPFE. A proposal of the diagnostic criteria for idiopathic PPFE with and without surgical lung biopsy, which has recently been published, may be useful.

Significant increases in the density and number of lymphatic vessels in pleuroparenchymal fibroelastosis.

AIMS: Some investigators have detected fibrinous exudate or immature organisation in the alveolar spaces prior to the development of subpleural elastofibrosis in patients with pleuroparenchymal fibroelastosis (PPFE). We hypothesised that PPFE progress is associated with an impaired lymphatic drainage system, resulting in the failed resolution of intra-alveolar exudate. The aim of this study is to investigate the pulmonary lymphatic vessels in PPFE, histologically. METHODS AND RESULTS: We retrospectively reviewed our medical records from 1995 to 2017, and selected autopsied or surgically biopsied patients with PPFE (n = 18), pulmonary apical cap (n = 18), and IPF (n = 26). We detected lymphatic endothelial cells by using immunostained specimens, calculating the percentage of lymphatic vessel area in the non-aerated area (lymphatic vessel density) and the number of lymphatic vessels per non-aerated area (per mm2 ) (lymphatic vessel number). These parameters in PPFE were compared with those in apical cap, IPF, and normal lung tissue. The lymphatic vessel density in PPFE patients [2.97%; interquartile range (IQR) 2.61-3.86] was significantly higher than that in normal lung (0.91%; IQR 0.84-1.07), pulmonary apical cap (0.67%; IQR 0.58-0.83), and IPF (0.91%; IQR 0.68-1.25) (P < 0.01 in any comparison). The lymphatic vessel number in PPFE was also significantly higher than that in normal lung, pulmonary apical cap, and IPF. Among PPFE patients, the increase in lymphatic vessel density was found to be correlated with the characteristic physiology of PPFE, such as a flattened chest cage on computed tomography and high residual volume/total lung capacity ratio on spirometry. CONCLUSIONS: Significant increase in the density and number of lymphatic vessels is a supportive characteristic that enables the differentiation of PPFE from IPF and apical cap.

The limited impact of psychiatric disease and psychotropic medication on the outcome of hospitalization for pneumonia.

Psychotropic medicine has been suggested to be a risk factor for the onset of pneumonia, especially aspiration pneumonia. However, the impact of coexisting psychiatric disease and psychotropic medication on the outcomes of pneumonia patients in the respiratory care unit setting is less well-known. We conducted a single-centre retrospective study of 209 consecutive patients who were hospitalized due to pneumonia. Using the patients' records, coexisting psychiatric diseases and the use of psychotropic medicines were reviewed to examine their association with the clinical course of inpatients with pneumonia. Psychotropic medicines, including agents for insomnia, were used in 73 (34.9%) patients, and there were 35 (16.9%) patients who had psychiatric disease. Among the 12 (5.7%) fatal cases, 4 patients were treated with psychotropic medicines, all of which were agents for insomnia. However, the rate of psychotropic medicine usage in the fatal cases (33.3%) was equivalent to that of the survivors (35%, p = 0.905), and the coexistence of psychiatric disease did not affect survival. The median duration of hospitalization was 15 days. The duration of hospitalization of the patients who received psychotropic medicines (median: 17 [range: 7-89] days) was also equivalent to that of the other patients (14 [2-55] days, p = 0.081). While the present study was a single-centre study and had a small population, coexisting psychiatric disease and psychotropic medicine use did not have a strong impact on the outcomes of pneumonia patients who were hospitalized in the respiratory unit of a university hospital. Further prospective studies targeting a larger cohort are needed.

Proliferation of elastic fibres in idiopathic pulmonary fibrosis: a whole-slide image analysis and comparison with pleuroparenchymal fibroelastosis.

AIMS: We occasionally encounter patients with idiopathic pulmonary fibrosis (IPF) who have similar imaging patterns to those of pleuroparenchymal fibroelastosis (PPFE) in the upper lung fields but are not diagnosed as having PPFE clinically. The aim of this study is to identify the clinicopathological features and intrapulmonary distribution of elastic fibres and collagen fibres in these patients. METHODS AND RESULTS: We retrospectively reviewed the medical records of patients with a clinical diagnosis of IPF, and selected consecutive patients who underwent autopsy or pneumonectomy for lung transplantation. Patients with histologically confirmed PPFE were also reviewed for comparison. We quantified the collagen fibres and elastic fibres in each lobe as a percentage of the non-aerated lung area (collagen fibre score and elastic fibre score, respectively) in histological specimens by using whole-slide image analysis, and compared these scores between IPF and PPFE patients. In a total of 55 patients (IPF, 48; PPFE, 7), there were no significant differences in the collagen fibre scores between IPF and PPFE patients. The elastic fibre scores in the upper lobe in PPFE patients were significantly higher than those in IPF patients (23.5 versus 10.3, P = 0.005). However, it is of note that, in 12 of 48 IPF patients, the elastic fibre scores of the upper lobes were above the first quartile of those in PPFE patients. CONCLUSIONS: IPF occasionally shows intense elastosis in the upper lobes, and such cases are histologically indistinguishable from PPFE. There seem to be histologically borderline cases between PPFE and IPF.

Disseminated tuberculosis with acute respiratory distress syndrome lacking granuloma formation in the lung.

A 66-year-old woman, who had been treated with systemic corticosteroids for four months for vasculitis of unknown etiology, was referred to our department due to a fever, dyspnea and patchy ground-glass opacities on chest computed tomography. As transbronchial biopsy specimens were suggestive of interstitial pneumonia, the prescribed dose of corticosteroids was increased. However, the patient developed pyrexia and presented diffuse ground-glass attenuation in the lungs bilaterally. Antituberculous drugs were administered because a previous blood interferon-gamma release assay was positive, however, the patient died of severe respiratory failure within several days, and cultures of her blood, urine and bone marrow posthumously revealed Mycobacterium tuberculosis. An autopsy revealed multiple foci of air-space pneumonia containing numerous acid-fast bacilli without granuloma formation, accompanied by diffuse alveolar damage. An immunosuppressive condition might inhibit air-space pneumonia to become granulomatous inflammation as an initial stage of pulmonary tuberculosis.

Pulmonary Necrotizing Granulomas in a patient with familial mediterranean fever.

We herein report a case of familial Mediterranean fever (FMF) presenting with granulomatous lung lesions with neuronal apoptosis inhibitory protein (NAIP), MHC class II transcription activator (CIITA), incompatibility locus protein from Podospora anserina (HET-E), and telomerase-associated protein (TP1) (NACHT) leucine-rich-repeat 1-positive inflammatory cell infiltrates. FMF is an autoinflammatory disorder characterized by recurrent and self-limited attacks of pyrexia, arthritis and erysipelas-like skin lesions. Lung disorders associated with FMF are extremely rare. This is the first report of an immunologically-confirmed case of pulmonary manifestations of this disease.

Autopsy analyses in acute exacerbation of idiopathic pulmonary fibrosis.

BACKGROUND: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is associated with high mortality. However, few studies have so far reviewed analyses of autopsy findings in patients with AE-IPF. METHODS: We retrospectively reviewed 52 consecutive patients with AE-IPF who underwent autopsies at five university hospitals and one municipal hospital between 1999 and 2013. The following variables were abstracted from the medical records: demographic and clinical data, autopsy findings and complications during the clinical course until death. RESULTS: The median age at autopsy was 71 years (range 47-86 years), and the subjects included 38 (73.1%) males. High-dose corticosteroid therapy was initiated in 45 (86.5%) patients after AE-IPF. The underling fibrotic lesion was classified as having the usual interstitial pneumonia (UIP) pattern in all cases. Furthermore, 41 (78.8%) patients had diffuse alveolar damage (DAD), 15 (28.8%) exhibited pulmonary hemorrhage, nine (17.3%) developed pulmonary thromboembolism and six (11.5%) were diagnosed with lung carcinoma. In addition, six (11.5%) patients developed pneumothorax prior to death and 26 (53.1%) developed diabetes that required insulin treatment after the administration of high-dose corticosteroid therapy. In addition, 15 (28.8%) patients presented with bronchopneumonia during their clinical course and/or until death, including fungal (seven, 13.5%), cytomegalovirus (six, 11.5%) and bacterial (five, 9.6%) infections. CONCLUSIONS: The pathological findings in patients with AE-IPF represent not only DAD, but also a variety of pathological conditions. Therefore, making a diagnosis of AE-IPF is often difficult, and the use of cautious diagnostic approaches is required for appropriate treatment.

Sunitinib-related interstitial pneumonia after treatment with temsirolimus: a case of possible recall phenomenon.

A 55-year-old Japanese man was admitted to Oita University Hospital (Oita, Japan) for pyrexia, malaise and dyspnea, and abnormal shadows on chest radiographs. He had started receiving sunitinib (37.5 mg a day for 3 weeks, followed by a 3-week break before beginning the next dosing cycle) for metastatic renal cell carcinoma after the improvement of temsirolimus-induced interstitial pneumonia. Sunitinib is a multiple tyrosine kinase receptor inhibitor approved for the treatment of metastatic renal cell carcinoma, and the most common clinical adverse effects of sunitinib are diarrhea, mucositis, stomatitis, hypertension, rashes and altered taste. We herein report a rare case of sunitinib-related interstitial pneumonia after treatment with temsirolimus for metastatic renal cell carcinoma. This case suggests the possibility of recall phenomenon of drug-induced pneumonia during the administration of additional chemotherapy.

Pseudomonas fluorescens pneumonia.

Pseudomonas fluorescens (P. fluorescens) is not generally considered a bacterial pathogen in humans; however, multiple culture-based and culture-independent studies have identified it in the indigenous microbiota of multiple body sites. We herein report a rare case of pneumonia caused by P. fluorescens. A man in his 80 s with chronic obstructive pulmonary disease and diabetes mellitus was diagnosed with stage II rectal cancer. He underwent laparoscopic surgery, and on the 6th postoperative day, he developed a high fever. Chest computed tomography revealed infiltration in the left lower lung. Gram staining of the sputum showed Gram-negative rods phagocytosed by neutrophils, suggesting postoperative nosocomial pneumonia. The patient was started on tazobactam/piperacillin, and his pneumonia quickly improved. Later, only P. fluorescens was detected in a sputum culture. It was susceptible to common antipseudomonal agents. Gram staining of P. fluorescens appears to show a slightly thicker and larger morphology in comparison to Pseudomonas aeruginosa. Although there have been reports of opportunistic infections caused by P. fluorescens in immunosuppressed patients, including those with advanced cancer, most have been bloodstream infections, with very few reports of pneumonia alone. Clinicians should be aware that patients, who are not necessarily immunosuppressed, may develop pneumonia caused by P. fluorescens.

Target sign of the lung.

A target sign of the lung consists of a ring-like opacity and a central nodular opacity and has been limited to reports associated with SARS-CoV-2 infection or organizing pneumonia. This is the first report of a target sign that was potentially associated with drug-induced lung injury.

An 88-Year-Old Woman With Pneumothorax and Black Pleural Effusion.

CASE PRESENTATION: An 88-year-old woman was admitted to our hospital with the sudden onset of dyspnea after eating. The patient had undergone nephrectomy for a left renal tumor 24 years previously. The patient had been prescribed ferrous citrate for iron-deficiency anemia. She complained of appetite loss a few days before admission but had no abdominal pain. CT scan showed no abnormalities in the lungs but a mass in the liver.

Desquamative Interstitial Pneumonia with Progressive Pulmonary Fibrosis.

A 70-year-old man who smoked was referred to our hospital because of progressive cough and dyspnea. Radiologic images showed ground-glass attenuation predominantly in the lower lung lobes. A surgical lung biopsy was performed, and a diagnosis of desquamative interstitial pneumonia (DIP) was made. The patient's symptoms improved with smoking cessation and steroid treatment, but the ground-glass attenuation did not completely resolve. At 10 years after the diagnosis, the fibrotic lesions deteriorated and treatment with nintedanib was subsequently initiated. Careful observation is needed in patients with DIP whose lung involvement does not completely improve with initial treatment.

Platythorax increases residual volume/total lung capacity in idiopathic pleuroparenchymal fibroelastosis.

Platythorax significantly contributes to the increase in residual volume/total lung capacity ratio in patients with idiopathic pleuroparenchymal fibroelastosis https://bit.ly/3uZ0rmP.

Impact of Nucleic Acid Amplification Test on Clinical Outcomes in Patients with Clostridioides difficile Infection.

A nucleic acid amplification test (NAAT) is recommended to determine whether or not patients have a Clostridioides difficile infection (CDI) when the glutamate dehydrogenase activity assay is positive and the rapid membrane enzyme immunoassays for toxins is negative. In our hospital, a NAAT was introduced to diagnose CDI precisely in April 2020. This study aimed to investigate the impact of a NAAT on the clinical outcomes in patients with CDI at our hospital. Seventy-one patients diagnosed with CDI between April 2017 and March 2022 were included in our study. Patients with CDI were divided into two groups: before (pre-NAAT) and after (post-NAAT) the introduction of NAAT. The clinical outcome was compared between the two groups. Of the 71 patients with CDI, 41 were sorted into the pre-NAAT group and 30 into the post-NAAT group. The clinical cure rate was significantly higher in the post-NAAT group compared to the pre-NAAT group (76.7% vs. 48.8%, p = 0.018). In the multivariable analysis, the clinical cure was significantly associated with the introduction of NAAT (p = 0.022). Our findings suggest that the introduction of NAAT can improve the clinical outcomes in CDI patients.