Naoki Tsujimoto

Novel aspects on the pathogenesis of Mycoplasma pneumoniae pneumonia and therapeutic implications

Mycoplasma pneumoniae (Mp) is a leading cause of community acquired pneumonia. Knowledge regarding Mp pneumonia obtained from animal models or human subjects has been discussed in many different reports. Accumulated expertise concerning this critical issue has been hard to apply clinically, and potential problems may remain undiscovered. Therefore, our multidisciplinary team extensively reviewed the literature regarding Mp pneumonia, and compared findings from animal models with those from human subjects. In human beings, the characteristic pathological features of Mp pneumonia have been reported as alveolar infiltration with neutrophils and lymphocytes and lymphocyte/plasma cell infiltrates in the peri-bronchovascular area. Herein, we demonstrated the novel aspects of Mp pneumonia that the severity of the Mp pneumonia seemed to depend on the host innate immunity to the Mp, which might be accelerated by antecedent Mp exposure (re-exposure or latent respiratory infection) through up-regulation of Toll-like receptor 2 expression on bronchial epithelial cells and alveolar macrophages. The macrolides therapy might be beneficial for the patients with macrolide-resistant Mp pneumonia via not bacteriological but immunomodulative effects. This exhaustive review focuses on pathogenesis and extends to some therapeutic implications such as clarithromycin, and discusses the various diverse aspects of Mp pneumonia. It is our hope that this might lead to new insights into this common respiratory disease.

High-resolution CT findings of patients with pulmonary nocardiosis

BACKGROUND Opportunistic pulmonary infection with Nocardia species is rare in humans, and only a few studies have radiologically analyzed patients with pulmonary nocardiosis using high-resolution computed tomography (HRCT). METHODS We retrospectively reviewed the medical records of patients with pulmonary nocardiosis at our hospital between April 2006 and December 2011 to assess HRCT and clinical findings. We also searched the medical literature for pulmonary nocardiosis reported in Japan between 2002 and 2011 for comparison. RESULTS We identified seven patients at our institution and 33 reported infections in Japan. Four of our patients were immunocompetent, whereas the other three had impaired cellular immunity due to type 2 diabetes mellitus or having been inappropriately treated with steroid. Thoracic HRCT revealed no zonal predominance, but tropism for distribution from the middle to the peripheral area, and radiological findings of nodules, cavitation, mass, consolidations, bronchial wall thickening, septal line thickening and ground glass opacity (GGO) were evident. The main HRCT finding in our study comprised nodules (n=5, 71.4%) <30 mm and four patients had multiple nodules as described in other reports. Furthermore, we discovered a crazy paving appearance (CPA) around nodules, cavities, masses or consolidations in five patients (71.4%). CONCLUSIONS Multiple nodules distributed from the middle to the peripheral area on HRCT might reflect pulmonary nocardiosis, and CPA seemed to be a worth paying attention to the diagnosis.

Breakthrough Invasive Candida glabrata in Patients on Micafungin: a Novel FKS Gene Conversion Correlated with Sequential Elevation of MIC

ABSTRACT Candida glabrata strains sequentially isolated from blood developed resistance to micafungin (MICs from <0.015 to 4 μg/ml). A novel mutation identified in micafungin-resistant strains at bp 262 of FKS2 (containing a deletion of F659 [F659del]) was inserted into the homologous region in FKS1.

Mechanic's hands revisited: is this sign still useful for diagnosis in patients with lung involvement of collagen vascular diseases?

BackgroundThe presence of “mechanic’s hands” is one of the clinical clues for collagen vascular diseases. However, the exact relevance of “mechanic’s hands” in collagen vascular diseases has not been well documented. The aim of this study was to clarify the relevance of “mechanic’s hands” to collagen vascular diseases including various skin lesions and interstitial pneumonia.MethodsA retrospective review of the medical records of patients with “mechanic’s hands” at our hospital between April 2011 and December 2012 was conducted. A PubMed search was also conducted using the term “mechanic’s hands”.ResultsFour patients in our institution and 40 patients obtained from PubMed who had “mechanic’s hands” were identified. The most frequent diseases were DM/amyopathic DM (n = 24, 54.5%) and anti-ARS syndrome (n = 17, 38.6%). In these patients, the major skin lesions associated with “mechanic’s hands” were periungual erythema (n = 23, 52.3%), Gottron’s sign (n = 17, 38.6%), heliotrope rash (n = 10, 22.7%), Raynaud’s phenomenon (n = 9, 20.5%), and anti-ARS syndrome (n = 17, 38.6%). Six cases (2 DM, 4 anti-ARS syndrome) had only “mechanic’s hands”. Antibodies to anti-ARS (n = 24) were Jo-1 (n = 19), PL-7 (n = 3), OJ (n = 1), and PL-12 (n = 1).ConclusionThe presence of “mechanic’s hands” together with diverse skin lesions could be a clinical clue to the diagnosis of lung involvement associated with collagen vascular diseases, especially in anti-ARS syndrome or DM/amyopathic DM.

A Simple Method for Differentiating Complicated Parapneumonic Effusion/Empyema from Parapneumonic Effusion Using the Split Pleura Sign and the Amount of Pleural Effusion on Thoracic CT.

Background Pleural separation, the “split pleura” sign, has been reported in patients with empyema. However, the diagnostic yield of the split pleura sign for complicated parapneumonic effusion (CPPE)/empyema and its utility for differentiating CPPE/empyema from parapneumonic effusion (PPE) remains unclear. This differentiation is important because CPPE/empyema patients need thoracic drainage. In this regard, the aim of this study was to develop a simple method to distinguish CPPE/empyema from PPE using computed tomography (CT) focusing on the split pleura sign, fluid attenuation values (HU: Hounsfield units), and amount of fluid collection measured on thoracic CT prior to diagnostic thoracentesis. Methods A total of 83 consecutive patients who underwent chest CT and were diagnosed with CPPE (n=18)/empyema (n=18) or PPE (n=47) based on the diagnostic thoracentesis were retrospectively analyzed. Results On univariate analysis, the split pleura sign (odds ratio (OR), 12.1; p<0.001), total amount of pleural effusion (≥30 mm) (OR, 6.13; p<0.001), HU value≥10 (OR, 5.94; p=0.001), and the presence of septum (OR, 6.43; p=0.018), atelectasis (OR, 6.83; p=0.002), or air (OR, 9.90; p=0.002) in pleural fluid were significantly higher in the CPPE/empyema group than in the PPE group. On multivariate analysis, only the split pleura sign (hazard ratio (HR), 6.70; 95% confidence interval (CI), 1.91-23.5; p=0.003) and total amount of pleural effusion (≥30 mm) on thoracic CT (HR, 7.48; 95%CI, 1.76-31.8; p=0.006) were risk factors for empyema. Sensitivity, specificity, positive predictive value, and negative predictive value of the presence of both split pleura sign and total amount of pleural effusion (≥30 mm) on thoracic CT for CPPE/empyema were 79.4%, 80.9%, 75%, and 84.4%, respectively, with an area under the curve of 0.801 on receiver operating characteristic curve analysis. Conclusion This study showed a high diagnostic yield of the split pleura sign and total amount of pleural fluid (≥30 mm) on thoracic CT that is useful and simple for discriminating between CPPE/empyema and PPE prior to diagnostic thoracentesis.

Guillain-Barré syndrome in two patients with respiratory failure and a review of the Japanese literature

We described two patients with Guillain-Barré syndrome and respiratory failure with or without mechanical ventilation. Case 1 was a 44-year-old man who treated as pneumonia under mechanical ventilation for a month and transferred to our hospital with unsuccessful weaning trials because of phrenic nerve palsy. Case 2 was a 74-year-old man who presented with aspiration pneumonia because of bulbar palsy. The present two cases with review of the Japanese literature showed that antecedent infection with initial symptoms within the most recent 5 to 46 days is a clinical clue to the diagnosis even in patients with Guillain-Barré syndrome accompanied by respiratory failure.

The Role of Vital Signs in Predicting Cardiac Tamponade in Asymptomatic Patients with Malignancy: Associated Pericardial Effusion

Background: Cardiac tamponade is a potentially life-threatening complication in patients with advanced lung cancer or other metastatic malignant diseases. However, few reports described how to assess the risk for developing cardiac tamponade in asymptomatic patients with pericardial effusion. Methods: The medical records of all patients with malignancy-associated cardiac tamponade diagnosed between April 2006 and June 2012 at Kyorin Hospital were retrospectively reviewed. This study mainly focused on the correlation between the duration between the first recognition of pericardial effusion on computed tomography and cardiac tamponade diagnosis and the vital signs at each point. Results: We identified 17 patients with malignancy-associated cardiac tamponade, mainly due to lung cancer (n=11, adenocarcinoma; n=1, non-small cell carcinoma; n=1, large cell neuroendocrine carcinoma; n=1, small cell carcinoma; and n=1, squamous cell carcinoma) followed by malignant mesothelioma (n=1), and an unknown cause (n=1). Among 17 patients with cardiac tamponade, the systolic blood pressure at the time of malignancy diagnosis was significantly higher than that at the onset of cardiac tamponade (average±SD, 115±13 vs 95±25 mm Hg; p=0.014), whereas heart rate (HR) and cardiothoracic ratio (CTR) determined on chest radiography were significantly higher at the onset of cardiac tamponade (HR, 84±15 bpm vs 111±30; p<0.001) (CTR, 49±7% vs 71±4.9; p=0.001). The correlation coefficient between the days from the first recognition of pericardial effusion on thoracic computed tomography to cardiac tamponade diagnosis and the gap of vital signs at each point such as ΔHR (r=−0.422, p=0.345) and ΔCTR (r=−0.212, p=0.647) was not statistically significant. Conclusion: This preliminary study demonstrated that increased HR and CTR are essential signs for predicting malignancy-associated cardiac tamponade.

Evidence of Unilateral Metastatic Pulmonary Calcification with a Prolonged Fever and Arthralgia Caused by Acute Lymphoblastic Leukemia in a Chronic Dialysis Patient

A 55-year-old man was transferred to our hospital with unilateral lung lesions, a persistent fever and vague chest pain with arthralgia lasting for three months. He had been treated for end-stage renal disease with hemodialysis for 15 years and had a medical history of recurrent subcutaneous calciphylaxis due to secondary hyperparathyroidism. Transbronchial biopsied specimens demonstrated metastatic pulmonary calcification, and a bone marrow biopsy showed Philadelphia chromosome-positive acute lymphoblastic leukemia. Although metastatic calcification often lacks specific symptoms, the lungs is a primary site for deposition. This is the first report of unilateral metastatic pulmonary calcification associated with secondary hyperparathyroidism.

Renal Salt Wasting Syndrome due to Carboplatin in a Patient with Lung Cancer

A 40-year-old woman with lung cancer had multiple episodes of hyponatremia when- ever she had chemotherapy with cisplatin plus etoposide and/or carboplatin plus etoposide over the last year. Although she had been diagnosed as having Syndrome of Inappropriate Secre- tion of Antidiuretic Hormone (SIADH), based on a multidisciplinary assessment, a diagnosis of Renal Salt Wasting Syndrome (RSWS) possibly due to carboplatin was made, and after completion of intravenous treatment with isotonic saline, hyponatremia resolved, and she was discharged uneventfully. Cisplatin is well known for causing renal toxicity via proximal tubu- lar damage, some cases of which present as RSWS. However, RSWS is extremely rare with carboplatin. The differential diagnosis between RSWS and SIADH for hyponatremic patients is sometimes difficult because of similarities in their clinical features, but careful consideration is needed to make the correct diagnosis because their treatments are diametrically opposed.

Three stripes sign: muscle involvement with internal fibrosis in a patient with sarcoidosis

A 62-year-old previously healthy woman was referred to the orthopaedic department because of bilateral thigh pain accompanied by palpable subcutaneous nodules in both thighs. The extremity coronal MRI with fat-suppressed T2-weighted images showed an inner stripe of decreased signal intensity with outer stripes of increased signal intensity, the so-called three stripes sign, both in the left vastus lateralis (figure 1A, arrow) and bilateral vastus medialis muscles (figure 1A, arrowheads), while, on axial image, decreased signal intensity, a ‘dark star’ sign was seen both in the left vastus lateralis (figure 1B, arrow) and bilateral vastus medialis muscles (figure 1B, …