Recent Advances in Diagnosing Chronic Pulmonary Aspergillosis

Purpose: The diagnosis of chronic pulmonary aspergillosis (CPA) is occasionally complicated due to poor sensitivity of mycological culture and colonization of Aspergillus species in the airway. Several diagnostic methods have been developed for the diagnosis of invasive pulmonary aspergillosis; however, their interpretation and significance are different in CPA. This study aimed to review the recent advances in diagnostic methods and their characteristics in the diagnosis of CPA.Recent findings: Radiological findings of lung, histopathology, and culture are the gold standard of CPA diagnosis. Serodiagnosis methods involving the use of galactomannan and β-D-glucan have low sensitivity and specificity. An Aspergillus-specific IgG antibody assay showed good performance and had better sensitivity and reproducibility than conventional precipitant antibody assays. Currently, it is the most reliable method for diagnosing CPA caused by Aspergillus fumigatus, but evidence on its effectiveness in diagnosing CPA caused by non-fumigatus Aspergillus is lacking. Newly developed lateral flow device Aspergillus and detection of volatile organic compounds in breath have potential, but evidence on its effectiveness in diagnosing CPA is lacking. The increasing prevalence of azole-resistant A. fumigatus strains has become a threat to public health. Some of the azole-resistant-related genes can be detected directly from clinical samples using a commercially available kit. However, its clinical efficacy for routine use remains unclear, since resistance-related genes greatly differ among regions and countries.Conclusion: Several issues surrounding the diagnosis of CPA remain unclear. Hence, further investigations and clinical studies are needed to improve the accuracy and efficiency of CPA diagnosis

<CLINICAL>Atraumatic restoration in amelogenesis imperfecta using flowable composite resin

Amelogenesis imperfecta causes defects in the tooth enamel. These defects can appear as small pits or dents in the tooth or can be so widespread as to make the entire tooth small in size and/or mis-shaped. This may result in tooth sensitivity, an unsightly appearance and/or increased susceptibility to dental caries. Here, we report a case of a patient exhibiting amelogenesis imperfecta, the treatment employed to treat the defects, and the result obtained. The affected teeth (all upper teeth) appeared white and the patient requested esthetic improvement of the appearance. We applied flowable composite resin to the hypomineralized defect. The result was dramatic improvement in tooth color of the upper incisors and first premolars. We conclude that atraumatic flowable composite resin restorations are useful in the treatment of amelogenesis imperfecta defects

A rediscovery of Limnotrachelobdella okae (Hirudinida: Piscicolidae) from flathead grey mullet Mugil cephalus in Japan

2007年7月に三重県の鍋田川河口部に近い汽水域で採集したボラMugil cephalus幼魚の鰓腔壁，2013年3月に岡山県沿岸の瀬戸内海に続く汽水路で採集したボラ未成魚の体表にヒダビルLimnotrachelobdella okae（Moore, 1924）の寄生を認めた。ヒダビルのボラへの寄生は1914年に記録されていたが，それはこれまで見落とされてきた。本報告は，ボラからのヒダビルの100年ぶりの記録である。One and seven specimens of the fish leech Limnotrachelobdella okae (Moore, 1924) were collected, respectively, from the branchial cavity of a young flathead grey mullet (Mugil cephalus) (Mugiliformes: Mugilidae) in the brackish-water estuary near the mouth of the Nabeta River, Mie Prefecture, central Japan, in June 2007, and from the body surface of five immature flathead grey mullet in a brackish waterway connected to the Seto Inland Sea on the coast of Okayama Prefecture, western Japan, in March 2013. Although the leech was reported from M. cephalus as early as in 1914 in Japan, its record has been overlooked for 100 years. The present collections represent a rediscovery of L. okae from M. cephalus

A global perspective of the changing epidemiology of invasive fungal disease and real-world experience with the use of isavuconazole.

Global epidemiological data show that the incidence of invasive fungal disease (IFD) has increased in recent decades, with the rising frequency of infections caused by Aspergillus and Mucorales order species. The number and variety of patients at risk of IFD has also expanded, owing in part to advances in the treatment of hematologic malignancies and other serious diseases, including hematopoietic stem cell transplantation (HCT) and other therapies causing immune suppression. Isavuconazonium sulfate (active moiety: isavuconazole) is an advanced-generation triazole antifungal approved for the treatment of invasive aspergillosis and mucormycosis that has demonstrated activity against a variety of yeasts, moulds, and dimorphic fungi. While real-world clinical experience with isavuconazole is sparse in some geographic regions, it has been shown to be effective and well tolerated in diverse patient populations, including those with multiple comorbidities who may have failed to respond to prior triazole antifungal therapy. Isavuconazole may be suitable for patients with IFD receiving concurrent QTc-prolonging therapy, as well as those on venetoclax or ruxolitinib. Data from clinical trials are not available to support the use of isavuconazole prophylactically for the prevention of IFD or for the treatment of endemic IFD, such as those caused by Histoplasma spp., but real-world evidence from case studies suggests that it has clinical utility in these settings. Isavuconazole is an option for patients at risk of IFD, particularly when the use of alternative antifungal therapies is not possible because of toxicities, pharmacokinetics, or drug interactions

Impact of Plasma 5 Hydroxyindoleacetic Acid, a Serotonin Metabolite, on Clinical Severity in Acute Respiratory Distress Syndrome

Acute respiratory distress syndrome (ARDS) is characterized by dysregulated vascular permeability. The clinical outcomes remain poor, and the disease burden is widespread. We demonstrated that plasma 5-hydroxyindoleacetic acid (5-HIAA), a serotonin metabolite, is a pivotal severity indicator of ARDS. Serotonin is an effector of cellular contraction and a modulator of vascular permeability. Plasma 5-HIAA levels were significantly elevated in severe ARDS cases with shock status (p = 0.047) and positively correlated with SOFA (p < 0.0001) and APACHE-II score (p < 0.0001). In the longitudinal analysis, plasma 5-HIAA levels were also a strong independent predictor of mortality rate (p = 0.005). This study indicates that plasma 5-HIAA is a biomarker of ARDS severity and highlights the importance of evaluating vascular leakage levels for ARDS treatment

Severe pulmonary tuberculosis complicating Ileocecal intussusception due to intestinal tuberculosis: a case report

Adult intussusception is a rare clinical entity that is most often caused by a tumor, such as a lipoma, adenoma, or malignant tumor. A case of adult intussusception due to intestinal tuberculosis of the ileocecal region is reported. There are few cases of intussusception due to intestinal tuberculosis

Immunomodulatory Effect of Linezolid on Methicillin-Resistant Staphylococcus aureus Supernatant-Induced MUC5AC Overexpression in Human Airway Epithelial Cells

Linezolid is the first member of the oxazolidinones and is active against drug-resistant Gram-positive pathogens, such as methi-cillin- resistant Staphylococcus aureus (MRSA). Additionally, linezolid shows an immunomodulatory effect, such as inhibition of inflammatory cytokine production. In this study, we examined the effect of linezolid on MRSA-induced MUC5AC overexpression in airway epithelial cells. In this study, an MRSA supernatant was used to avoid the direct effect of linezolid on MRSA. MUC5AC protein production was significantly increased with a 40-fold dilution of MRSA supernatant. At the mRNA level, MUC5AC gene expression was significantly increased 6 and 9 h after stimulation. In an inhibition study, linezolid significantly reduced MRSA-induced MUC5AC protein and mRNA overexpression at concentrations of 5 and 20 μg/ml, which were the same as the trough and peak concentrations in human epithelial lining fluid. In an analysis of cell signaling, among the mitogen-activated protein kinase inhibitors, only the extracellular signal-regulated protein kinase 1/2 (ERK1/2) inhibitor reduced the MUC5AC protein production to the same level as that of the control; on Western blot analysis, only ERK1/2 was phosphorylated by the MRSA supernatant. In addition, the ERK1/2 phosphorylation was inhibited by linezolid. MUC5AC and MUC5B are the major barrier that traps inhaled microbial organisms, particulates, and foreign irritants. However, in patients with chronic respiratory diseases, pathogen-induced MUC5AC overexpression causes many problems, and control of the overexpression is important. Thus, this study revealed that linezolid showed a direct immunomodulatory effect in airway epithelial cells

Paradoxical response to disseminated non-tuberculosis mycobacteriosis treatment in a patient receiving tumor necrosis factor-α inhibitor: a case report

Background: Biological agents such as tumor necrosis factor-α inhibitors are known to cause mycobacterium infections. Here, we report a disseminated non-tuberculosis case caused by TNF-α inhibitor therapy and a probable paradoxical response to antimycobacterial therapy.Case presentation: A 68-year-old man with relapsing polychondritis was refractory to glucocorticoid therapy; adalimumab was therefore administered in combination with oral glucocorticoids. Treatment with 40 mg of adalimumab led to rapid improvement of his clinical manifestations. The administration of tacrolimus (1 mg) was started as the dosage of oral glucocorticoids was tapered. However, the patient developed an intermittent high fever and productive cough 15 months after starting adalimumab treatment. A chest computed tomography scan revealed new granular shadows and multiple nodules in both lung fields with mediastinal lymphadenopathy, and Mycobacterium intracellulare was isolated from 2 sputum samples; based on these findings, the patient was diagnosed with non-tuberculosis mycobacteriosis. Tacrolimus treatment was discontinued and oral clarithromycin (800 mg/day), rifampicin (450 mg/day), and ethambutol (750 mg/day) treatment was initiated. However, his condition continued to deteriorate despite 4 months of treatment; moreover, paravertebral and subcutaneous abscesses developed and increased the size of the mediastinal lymphadenopathy. Biopsy of the mediastinal lymphadenopathy and a subcutaneous abscess of the right posterior thigh indicated the presence of Mycobacterium avium complex (MAC), and the diagnosis of disseminated non-tuberculosis mycobacteriosis was confirmed. Despite 9 months of antimycobacterial therapy, the mediastinal lymphadenopathy and paravertebral and subcutaneous abscesses had enlarged and additional subcutaneous abscesses had developed, although microscopic examinations and cultures of sputum and subcutaneous abscess samples yielded negative results. We considered this a paradoxical reaction similar to other reports in tuberculosis patients who had discontinued biological agent treatments, and increased the dose of oral glucocorticoids. The patient\u27s symptoms gradually improved with this increased dose and his lymph nodes and abscesses began to decrease in size.Conclusions: Clinicians should consider the possibility of a paradoxical response when the clinical manifestations of non-tuberculosis mycobacteriosis worsen in spite of antimycobacterial therapy or after discontinuation of tumor necrosis factor-α inhibitors. However, additional evidence is needed to verify our findings and to determine the optimal management strategies for such cases