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1.
Heliyon ; 10(10): e31464, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38803887

ABSTRACT

Candida vulturna is a recently discovered and not widely documented ascomycetous yeast phylogenetically related to the outbreak-causing and multidrug-resistant Candida auris. A middle-aged Japanese man with no discernible immunodeficiency was admitted to hospital with ileal diverticulitis. Following laparoscopic right hemicolectomy against abscess formation on postoperative day (POD) 7, continuous fungemia occurred due to Candida haemulonii, identified using a conventional method by confirming the biochemical phenotype. Micafungin was initiated; however, the fungus was persistently isolated from blood cultures. Eventually, the antifungal agent was changed to a combination of liposomal amphotericin B (L-AMB) and caspofungin (CPFG), which cleared the infection, and no pathogens were detected in the blood cultures on POD 31. Contrast-enhanced computed tomography showed septic emboli in the lungs and spleen; however, no evidence of vasculitis was observed. Moreover, sequential echocardiography did not reveal any signs of infectious endocarditis. Finally, CPFG and L-AMB were administered to the patient for 7 and 9 weeks, respectively, during which the patient's symptoms did not relapse. The strain was later genetically identified as C. vulturna. This case report illustrates a clinical presentation of C. vulturna and provides the diagnostic approach and treatment methods for this pathogen.

2.
Respirology ; 2024 May 20.
Article in English | MEDLINE | ID: mdl-38769707

ABSTRACT

BACKGROUND AND OBJECTIVE: The identification of factors associated with long-term prognosis after community-onset pneumonia in elderly patients should be considered when initiating advance care planning (ACP). We aimed to identify these factors and develop a prediction score model. METHODS: Patients aged 65 years and older, who were hospitalized for pneumonia at nine collaborating institutions, were included. The prognosis of patients 180 days after the completion of antimicrobial treatment for pneumonia was prospectively collected. RESULTS: The total number of analysable cases was 399, excluding 7 outliers and 42 cases with missing data or unknown prognosis. These cases were randomly divided in an 8:2 ratio for score development and testing. The median age was 82 years, and there were 68 (17%) deaths. A multivariate analysis showed that significant factors were performance status (PS) ≥2 (Odds ratio [OR], 11.78), hypoalbuminemia ≤2.5 g/dL (OR, 5.28) and dementia (OR, 3.15), while age and detection of antimicrobial-resistant bacteria were not associated with prognosis. A scoring model was then developed with PS ≥2, Alb ≤2.5, and dementia providing scores of 2, 1 and 1 each, respectively, for a total of 4. The area under the curve was 0.8504, and the sensitivity and specificity were 94.6% and 61.7% at the cutoff of 2, respectively. In the test cases, the sensitivity and specificity were 91.7% and 63.1%, respectively, at a cutoff value of 2. CONCLUSION: Patients meeting this score should be considered near the end of life, and the initiation of ACP practices should be considered.

3.
Microbiol Spectr ; 12(4): e0361423, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38426765

ABSTRACT

Invasive aspergillosis (IA) and mucormycosis are life-threatening diseases, especially among immunocompromised patients. Drug-resistant Aspergillus fumigatus strains have been isolated worldwide, which can pose a serious clinical problem. As IA mainly occurs in patients with compromised immune systems, the ideal therapeutic approach should aim to bolster the immune system. In this study, we focused on Vγ9Vδ2 T cells that exhibit immune effector functions and examined the possibility of harnessing this unconventional T cell subset as a novel therapeutic modality for IA. A potent antifungal effect was observed when A. fumigatus (Af293) hyphae were challenged by Vγ9Vδ2 T cells derived from peripheral blood. In addition, Vγ9Vδ2 T cells exhibited antifungal activity against hyphae of all Aspergillus spp., Cunninghamella bertholletiae, and Rhizopus microsporus but not against their conidia. Furthermore, Vγ9Vδ2 T cells also exhibited antifungal activity against azole-resistant A. fumigatus, indicating that Vγ9Vδ2 T cells could be used for treating drug-resistant A. fumigatus. The antifungal activity of Vγ9Vδ2 T cells depended on cell-to-cell contact with A. fumigatus hyphae, and degranulation characterized by CD107a mobilization seems essential for this activity against A. fumigatus. Vγ9Vδ2 T cells could be developed as a novel modality for treating IA or mucormycosis. IMPORTANCE: Invasive aspergillosis (IA) and mucormycosis are often resistant to treatment with conventional antifungal agents and have a high mortality rate. Additionally, effective antifungal treatment is hindered by drug toxicity, given that both fungal and human cells are eukaryotic, and antifungal agents are also likely to act on human cells, resulting in adverse effects. Therefore, the development of novel therapeutic agents specifically targeting fungi is challenging. This study demonstrated the antifungal activity of Vγ9Vδ2 T cells against various Aspergillus spp. and several Mucorales in vitro and discussed the mechanism underlying their antifungal activity. We indicate that adoptive immunotherapy using Vγ9Vδ2 T cells may offer a new therapeutic approach to IA.


Subject(s)
Aspergillosis , Mucormycosis , Humans , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Aspergillus fumigatus , Mucormycosis/drug therapy , Aspergillosis/drug therapy , Aspergillosis/microbiology , Fungi , Aspergillus
4.
Respir Investig ; 62(3): 322-327, 2024 May.
Article in English | MEDLINE | ID: mdl-38401245

ABSTRACT

BACKGROUND: Evidence regarding the association of the usage of biologic agents (Etanercept, Tocilizumab, adalimumab and so on), such as anti-tumor necrosis factor α, with the incidence and risk factors of non-tuberculous Mycobacteria (NTM) infection is limited. Therefore, this study aimed to investigate the incidence and risk factors of NTM and their associations with biologic agents' usage, and also investigated the potential of Mycobacterium avium complex (MAC) antibodies as a predictor of NTM infection development. METHODS: This retrospective study included 672 patients with autoimmune diseases from four hospitals in Nagasaki, Japan, from January 1, 2011, to June 30, 2019, who fulfilled the inclusion criteria. RESULTS: Of the 672 patients, 9 (1.3%) developed complicated NTM infection, including two with disseminated infection, after the introduction of biologic agents. Of the nine patients, two died due to NTM infection but none tested positive for MAC antibodies prior to initiation of biologic agents. The mortality rate was higher in patients complicated with NTM than without NTM (22.2% vs 2.6%, P = 0.024). The corticosteroids dosage at the time of initiating the biologic agents was significantly higher in the NTM group than in the non-NTM group (median, 17 mg vs 3 mg, P = 0.0038). CONCLUSION: In the patients undergoing therapy with biologic agents, although NTM complication was rare, it could be fatal. In particular, for patients on a relatively high dose corticosteroids, careful observation is essential for identifying NTM complication, even if the MAC antibody test is negative.


Subject(s)
Arthritis, Rheumatoid , Biological Products , Mycobacterium Infections, Nontuberculous , Mycobacterium avium-intracellulare Infection , Humans , Mycobacterium Infections, Nontuberculous/drug therapy , Mycobacterium Infections, Nontuberculous/epidemiology , Mycobacterium Infections, Nontuberculous/complications , Retrospective Studies , Mycobacterium avium Complex , Nontuberculous Mycobacteria , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/drug therapy , Mycobacterium avium-intracellulare Infection/epidemiology , Biological Factors/therapeutic use , Risk Factors , Adrenal Cortex Hormones/therapeutic use , Biological Products/adverse effects
5.
J Infect Chemother ; 30(7): 597-602, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38190963

ABSTRACT

BACKGROUND: Nursing- and healthcare-associated pneumonia (NHCAP) constitutes most of the pneumonia in elderly patients including aspiration pneumonia in Japan. Lascufloxacin (LSFX) possesses broad antibacterial activity against respiratory pathogens, such as Streptococcus spp. And anaerobes inside the oral cavity. However, the efficacy and safety of LSFX in NHCAP treatment remains unknown. We aimed to evaluate the efficacy and safety of LSFX tablets in the treatment of patients with NHCAP. METHODS: In this single-arm, open-label, uncontrolled study, LSFX was administered to patients with NHCAP at 24 facilities. The study participants were orally administered 75 mg LSFX once daily for 7 days. The primary endpoint was the clinical efficacy at the time of test of cure (TOC). The secondary endpoints included clinical efficacy at the time of end of treatment (EOT), early clinical efficacy, microbiological efficacy, and safety analysis. RESULT: During the study period, 75 patients provided written informed consent to participate and were included. Finally, 56 and 71 patients were eligible for clinical efficacy and safety analyses, respectively. The median age of the patients was significantly high at 86 years. All patients were classified as having moderate disease severity using the A-DROP scoring system. LSFX tablets demonstrated high efficacy rates of 78.6 % at TOC and 89.3 % at EOT. The risk factors for resistant bacteria or aspiration pneumonia did not affect clinical efficacy. No severe adverse events associated with the study drugs were observed. CONCLUSION: Oral LSFX is an acceptable treatment option for moderate NHCAP in elderly patients who can take oral medications.


Subject(s)
Anti-Bacterial Agents , Fluoroquinolones , Healthcare-Associated Pneumonia , Humans , Male , Female , Aged, 80 and over , Aged , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/administration & dosage , Fluoroquinolones/therapeutic use , Fluoroquinolones/adverse effects , Fluoroquinolones/administration & dosage , Japan , Healthcare-Associated Pneumonia/drug therapy , Healthcare-Associated Pneumonia/microbiology , Treatment Outcome , Administration, Oral , Middle Aged
6.
Perfusion ; 39(3): 593-602, 2024 Apr.
Article in English | MEDLINE | ID: mdl-36757374

ABSTRACT

INTRODUCTION: Glycemic control is essential for improving the prognosis of cardiac surgery, although precise recommendations have not yet been established. Under a constant blood glucose level, the insulin infusion rate correlates with insulin resistance during glycemic control using an artificial pancreas (AP). We conducted this retrospective study to elucidate changes in intraoperative insulin sensitivity as a first step to creating glycemic control guidelines. METHODS: Fifty-five cardiac surgery patients at our hospital who underwent intraoperative glycemic control using an AP were enrolled. Twenty-three patients undergoing surgical procedures requiring cardiac arrest under hypothermic cardiopulmonary bypass (CPB) with minimum rectal temperatures lower than 32°C, 13 patients undergoing surgical procedures requiring cardiac arrest under hypothermic CPB with minimum rectal temperatures of 32°C, eight patients undergoing on-pump beating coronary artery bypass grafting and 11 patients undergoing off-pump coronary artery bypass were assigned to groups A, B, C and D, respectively. We analyzed the time course of changes in the data derived from glycemic control using the AP. RESULTS: Significant time course changes were observed in groups A and B, but not in groups C and D. Insulin resistance was induced after the start of hypothermic CPB in groups A and B, and the induced change was not resolved by the rewarming procedure, remaining sustained until the end of surgery. CONCLUSIONS: Hypothermia is the predominant factor of the induced insulin resistance during cardiac surgery. Thus, careful glycemic management during hypothermic CPB is important. Prospective clinical studies are required to confirm the findings of this study.


Subject(s)
Coronary Artery Bypass, Off-Pump , Heart Arrest , Hypothermia, Induced , Insulin Resistance , Pancreas, Artificial , Humans , Retrospective Studies , Prospective Studies , Cardiopulmonary Bypass/methods
7.
Intern Med ; 63(4): 583-586, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-37344431

ABSTRACT

Tuberculous meningitis is an infectious disease with high mortality. Literature describing intrathecal therapy for tuberculous meningitis is scarce. We herein report a case of refractory tuberculous meningitis in a 52-year-old woman with underlying neuropsychiatric systemic lupus erythematosus. Despite systemic treatment with anti-tuberculosis drugs and dexamethasone, her meningeal irritation deteriorated. Intrathecal isoniazid and prednisolone administration was therefore initiated, and the symptoms of severe meningeal irritation improved along with head magnetic resonance imaging and cerebrospinal fluid findings. This case report highlights the efficacy of intrathecal isoniazid and steroid injections for refractory tuberculous meningitis, particularly in patients with severe meningeal irritation.


Subject(s)
Lupus Vasculitis, Central Nervous System , Tuberculosis, Meningeal , Female , Humans , Middle Aged , Isoniazid/therapeutic use , Tuberculosis, Meningeal/drug therapy , Tuberculosis, Meningeal/diagnosis , Antitubercular Agents/therapeutic use , Prednisolone/therapeutic use
8.
Mycoses ; 67(1): e13658, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37807638

ABSTRACT

BACKGROUND: Cryptococcal meningitis (CM) is an invasive fungal infection with a poor prognosis that often occurs in both healthy individuals and compromised hosts, such as patients infected with human immunodeficiency virus (HIV). Unlike CM in HIV patients, evidence regarding CM in non-HIV patients is limited to small retrospective studies. OBJECTIVE: To identify the pretreatment prognostic factors for CM in non-HIV patients. METHODS: We conducted a large retrospective analysis of CM in non-HIV patients using data from a nationwide Japanese database. The study included hospitalized patients diagnosed with CM between 1 April 2010 and 31 March 2017. All-cause mortality was compared between patients with CM with and without HIV infection. Poor diagnostic factors were analysed in the non-HIV CM group. RESULTS: Overall, 533 (64 HIV and 469 non-HIV) patients met the criteria. The mortality rate at 90 days was significantly lower in the HIV group (6.3% vs. 25.4% p = .0002). In a logistic regression analysis of the non-HIV group, age ≥ 65 y (odds ratio [OR] 2.37, 95% CI 1.17-4.78), impaired consciousness (Japan Coma Scale ≥1) (OR 2.25, 95% CI 1.29-3.93), haemodialysis (OR 3.53, 95% CI 1.12-11.20) and previous corticosteroid usage (OR 2.40, 95% CI 1.37-4.19) were associated with poor prognosis at 30 days after diagnosis. CONCLUSION: More caution is suggested when treating non-HIV with CM in older patients with impaired consciousness, previous corticosteroid usage and haemodialysis.


Subject(s)
HIV Infections , Meningitis, Cryptococcal , Humans , Aged , Meningitis, Cryptococcal/drug therapy , Meningitis, Cryptococcal/epidemiology , Meningitis, Cryptococcal/complications , HIV Infections/complications , HIV , Retrospective Studies , Prognosis , Adrenal Cortex Hormones
9.
J Obstet Gynaecol Res ; 50(2): 262-265, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37875278

ABSTRACT

Factor XIII deficiency is an extremely rare autosomal recessive genetic disorder, occurring in 1 of 3-5 million people, and is associated with perinatal complications, such as habitual abortion and prolonged bleeding. Although plasma-derived factor XIII (Fibrogamin®) carries a risk of infection and contains very low concentrated forms of factor XIII (FXIII) used for a pregnant woman with congenital coagulation factor XIII deficiency, recombinant factor XIII (rFXIII, Novo Thirteen®; Tretten®, Novo Nordisk, Bagsvaerd, Denmark), which has no risk of infection and is highly concentrated, has emerged as a novel formulation. Herein, we report the first case of a Japanese pregnant woman with congenital coagulation factor XIII deficiency successfully managed by rFXIII. She had a good perinatal course without pregnancy-related complications and transfusion through the perinatal period.


Subject(s)
Abortion, Habitual , Factor XIII Deficiency , Pregnancy , Female , Humans , Factor XIII , Factor XIII Deficiency/complications , Factor XIII Deficiency/drug therapy , Recombinant Proteins , Blood Coagulation
10.
Open Forum Infect Dis ; 10(10): ofad480, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37808895

ABSTRACT

Background: Mucormycosis is a potentially fatal fungal infection, and there is limited information on its precise epidemiology and treatment practices, including the optimal dosage of liposomal amphotericin B. Methods: A retrospective, multicenter, nationwide analysis of 82 proven and probable cases of mucormycosis was performed. Cases between 2015 and 2022 were collected from 51 hospitals in Japan by hematologists and infectious disease specialists. The study included the epidemiology, treatment details, and association between the dose of liposomal amphotericin B and the outcome. Results: The lungs were the most commonly involved organ (70.7% of cases), and 35.4% of patients had disseminated disease. Rhizopus spp., Cunninghamella spp., and Mucor spp. were the most common organisms. Mortality at 4 weeks was 41.5%. The survivors had a shorter duration of neutropenia (P = .006) and less persistent hyperglycemia (P = .023). The site of infection and species of Mucorales had no detectable effect on survival. Survival did not differ between patients receiving liposomal amphotericin B at 5 mg/kg/d relative to those receiving >5 mg/kg/d (P = .625). Using Cox proportional hazards models and adjusting for confounders, the hazard ratio for the influence of >5 mg/kg/d liposomal amphotericin B on 4-week survival was 0.86 (95% CI, 0.28-2.68; P = .796) compared with 5 mg/kg/d. Conclusions: This study provides important insights into the precise epidemiology and treatment practices of mucormycosis. Treatment with liposomal amphotericin B at doses higher than 5 mg/kg/d did not improve outcomes relative to 5 mg/kg/d.

11.
Intern Med ; 2023 Oct 27.
Article in English | MEDLINE | ID: mdl-37899245

ABSTRACT

Allergic bronchopulmonary aspergillosis (ABPA) and chronic pulmonary aspergillosis (CPA) are diseases caused by Aspergillus infection, and CPA can develop from ABPA in some cases. We herein report a patient with CPA overlapping with ABPA. Serum cytokine levels were evaluated at 4 time points: the ABPA diagnosis, CPA diagnosis, 6 months after the start of voriconazole (VRCZ), and 12 months after re-administration of VRCZ. Interleukin (IL)-13 levels decreased upon glucocorticoid treatment, whereas IL-25 and IL-33 levels decreased rapidly with the initiation of antifungals. Early antifungal therapy may be important to control disease progression and prevent CPA overlap.

12.
Med Mycol ; 61(10)2023 Oct 05.
Article in English | MEDLINE | ID: mdl-37740432

ABSTRACT

Data on antifungal susceptibility of Cryptococcus neoformans are limited in Japan. A total of 89 C. neoformans strains isolated from 83 non-human immunodeficiency virus-infected patients with cryptococcosis between 1997 and 2021 in Nagasaki, Japan, were investigated. Using the reference method M27-Ed4 by the Clinical and Laboratory Standards Institute, the minimum inhibitory concentration for 90% of isolates of fluconazole, itraconazole, voriconazole, amphotericin B, and flucytosine were 4, 0.125, 0.06, 0.5, and 4 µg/ml, respectively, which were below the reported epidemiological cutoff values, without any detectable non-wild-type strains. Our findings imply no increasing trend of antifungal-resistant C. neoformans in Nagasaki, Japan.


Cryptococcus neoformans strains obtained from non-human immunodeficiency virus-infected patients were observed to maintain good antifungal susceptibility to fluconazole, itraconazole, voriconazole, amphotericin B, and flucytosine over a 25-year-long period in Nagasaki, Japan.

13.
Microorganisms ; 11(9)2023 Aug 24.
Article in English | MEDLINE | ID: mdl-37763989

ABSTRACT

Sarcoidosis is a systemic inflammatory disease characterized by noncaseating epithelioid cell granulomas. However, certain infections can exhibit similar histological findings. We present a case of a 69-year-old man who was initially diagnosed with sarcoidosis and later was confirmed, through 16S rRNA sequencing, to have disseminated Mycobacterium genavense infection. Acid-fast bacteria were detected in the bone marrow biopsy using Ziehl-Neelsen staining, but routine clinical tests did not provide a definitive diagnosis. The patient tested negative for HIV, anti-interferon-gamma antibodies, and genetic immunodeficiency disorders. He was treated with multiple drugs, including aminoglycosides and macrolides, but showed no improvement in fever and pancytopenia. However, these clinical signs responded favorably to steroid therapy. We reviewed 17 Japanese cases of M. genavense infection. All cases were in males; 7/17 (41%) were HIV-negative; and 12/17 (71%) had a decreased CD4 count. Genetic analysis confirmed M. genavense isolation, and macrolides were used universally. Mycobacterium genavense infection is challenging to identify and mimics other systemic inflammatory diseases such as sarcoidosis. There are no standard treatment protocols. Our case report and Japanese case review contribute to understanding this rare disease.

15.
Microorganisms ; 11(8)2023 Jul 27.
Article in English | MEDLINE | ID: mdl-37630465

ABSTRACT

Studies indicated potential harm from empirical broad-spectrum therapy. A recent study of hospitalizations for community-acquired pneumonia suggested that empirical anti-methicillin-resistant Staphylococcus aureus (MRSA) therapy was associated with an increased risk of death and other complications. However, limited evidence supports empirical anti-MRSA therapy for older patients with aspiration pneumonia. In a nationwide Japanese database, patients aged ≥65 years on admission with aspiration pneumonia were analyzed. Patients were divided based on presence of respiratory failure and further sub-categorized based on their condition within 3 days of hospital admission, either receiving a combination of anti-MRSA agents and other antibiotics, or not using MRSA agents. An inverse probability weighting method with estimated propensity scores was used. Out of 81,306 eligible patients, 55,098 had respiratory failure, and 26,208 did not. In the group with and without respiratory failure, 0.93% and 0.42% of the patients, respectively, received anti-MRSA agents. In patients with respiratory failure, in-hospital mortality (31.38% vs. 19.03%, p < 0.001), 30-day mortality, and 90-day mortality were significantly higher, and oxygen administration length was significantly longer in the anti-MRSA agent combination group. Anti-MRSA agent combination use did not improve the outcomes in older patients with aspiration pneumonia and respiratory failure, and should be carefully and comprehensively considered.

16.
Jpn J Radiol ; 41(12): 1373-1388, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37498483

ABSTRACT

PURPOSE: Deep learning reconstruction (DLR) has been introduced by major vendors, tested for CT examinations of a variety of organs, and compared with other reconstruction methods. The purpose of this study was to compare the capabilities of DLR for image quality improvement and lung texture evaluation with those of hybrid-type iterative reconstruction (IR) for standard-, reduced- and ultra-low-dose CTs (SDCT, RDCT and ULDCT) obtained with high-definition CT (HDCT) and reconstructed at 0.25-mm, 0.5-mm and 1-mm section thicknesses with 512 × 512 or 1024 × 1024 matrixes for patients with various pulmonary diseases. MATERIALS AND METHODS: Forty age-, gender- and body mass index-matched patients with various pulmonary diseases underwent SDCT (CT dose index volume : mean ± standard deviation, 9.0 ± 1.8 mGy), RDCT (CTDIvol: 1.7 ± 0.2 mGy) and ULDCT (CTDIvol: 0.8 ± 0.1 mGy) at a HDCT. All CT data set were then reconstructed with 512 × 512 or 1024 × 1024 matrixes by means of hybrid-type IR and DLR. SNR of lung parenchyma and probabilities of all lung textures were assessed for each CT data set. SNR and detection performance of each lung texture reconstructed with DLR and hybrid-type IR were then compared by means of paired t tests and ROC analyses for all CT data at each section thickness. RESULTS: Data for each radiation dose showed DLR attained significantly higher SNR than hybrid-type IR for each of the CT data (p < 0.0001). On assessments of all findings except consolidation and nodules or masses, areas under the curve (AUCs) for ULDCT with hybrid-type IR for each section thickness (0.91 ≤ AUC ≤ 0.97) were significantly smaller than those with DLR (0.97 ≤ AUC ≤ 1, p < 0.05) and the standard protocol (0.98 ≤ AUC ≤ 1, p < 0.05). CONCLUSION: DLR is potentially more effective for image quality improvement and lung texture evaluation than hybrid-type IR on all radiation dose CTs obtained at HDCT and reconstructed with each section thickness with both matrixes for patients with a variety of pulmonary diseases.


Subject(s)
Deep Learning , Lung Diseases , Humans , Radiation Dosage , Tomography, X-Ray Computed/methods , Lung/diagnostic imaging , Lung Diseases/diagnostic imaging , Radiographic Image Interpretation, Computer-Assisted/methods , Algorithms
17.
Eur J Radiol ; 166: 110969, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37454556

ABSTRACT

PURPOSE: To compare the capability of CTs obtained with a silver or copper x-ray beam spectral modulation filter (Ag filter and Cu filter) and reconstructed with FBP, hybrid-type IR and deep learning reconstruction (DLR) for radiation dose reduction for lung nodule detection using a chest phantom study. MATERIALS AND METHODS: A chest CT phantom was scanned with a 320-detector row CT with Ag filter at 0.6, 1.6 and 2.5 mGy and Cu filters at 0.6, 1.6, 2.5 and 9.6 mGy, and reconstructed with the aforementioned methods. To compare image quality of all the CT data, SNRs and CNRs for any nodule were calculated for all protocols. To compare nodule detection capability among all protocols, the probability of detection of any nodule was assessed with a 5-point visual scoring system. Then, ROC analyses were performed to compare nodule detection capability of Ag and Cu filters for each radiation dose data with the same method and of the three methods for any radiation dose data and obtained with either filter. RESULTS: At any of the doses, SNR, CNR and area under the curve for the Ag filter were significantly higher or larger than those for the Cu filter (p < 0.05). Moreover, with DLR, those values were significantly higher or larger than all the others for CTs obtained with any of the radiation doses and either filter (p < 0.05). CONCLUSION: The Ag filter and DLR can significantly improve image quality and nodule detection capability compared with the Cu filter and other reconstruction methods at each of radiation doses used.


Subject(s)
Copper , Silver , Humans , X-Rays , Drug Tapering , Radiation Dosage , Tomography, X-Ray Computed/methods , Phantoms, Imaging , Radiographic Image Interpretation, Computer-Assisted/methods , Algorithms
18.
J Fungi (Basel) ; 9(5)2023 Apr 29.
Article in English | MEDLINE | ID: mdl-37233240

ABSTRACT

Outbreaks of invasive infections, with high mortality rates, caused by multidrug-resistant Candida auris have been reported worldwide. Although hotspot mutations in FKS1 are an established cause of echinocandin resistance, the actual contribution of these mutations to echinocandin resistance remains unknown. Here, we sequenced the FKS1 gene of a caspofungin-resistant clinical isolate (clade I) and identified a novel resistance mutation (G4061A inducing R1354H). We applied the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system to generate a recovered strain (H1354R) in which only this single nucleotide mutation was reverted to its wild-type sequence. We also generated mutant strains with only the R1354H mutation introduced into C. auris wild-type strains (clade I and II) and analyzed their antifungal susceptibility. Compared to their parental strains, the R1354H mutants exhibited a 4- to 16-fold increase in caspofungin minimum inhibitory concentration (MIC) while the H1354R reverted strain exhibited a 4-fold decrease in caspofungin MIC. In a mouse model of disseminated candidiasis, the in vivo therapeutic effect of caspofungin was more closely related to the FKS1 R1354H mutation and the virulence of the strain than its in vitro MIC. The CRISPR-Cas9 system could thus aid in elucidating the mechanism underlying drug resistance in C. auris.

19.
PNAS Nexus ; 2(5): pgad153, 2023 May.
Article in English | MEDLINE | ID: mdl-37234205

ABSTRACT

The effectiveness of population-wide compliance to personal precautions (mask-wearing and hand hygiene) in preventing community-acquired pneumonia has been unknown. In Japan, different types of nonpharmaceutical interventions from personal precautions to containment and closure policies (CACPs, e.g. stay-at-home requests) were sequentially introduced from late January to April 2020, allowing for separate analysis of the effects of personal precautions from other more stringent interventions. We quantified the reduction in community-acquired pneumonia hospitalizations and deaths and assessed if it coincided with the timing of increased public awareness of personal precautions before CACPs were implemented. A quasi-experimental interrupted time-series design was applied to non-COVID-19 pneumonia hospitalization and 30-day death data from April 2015 to August 2020 across Japan to identify any trend changes between February and April 2020. We also performed a comparative analysis of pyelonephritis and biliary tract infections to account for possible changes in the baseline medical attendance. These trend changes were then compared with multiple indicators of public awareness and behaviors related to personal precautions, including keyword usage in mass media coverage and sales of masks and hand hygiene products. Hospitalizations and 30-day deaths from non-COVID-19 pneumonia dropped by 24.3% (95% CI 14.8-32.8) and 16.1% (5.5-25.5), respectively, in February 2020, before the implementation of CACPs, whereas pyelonephritis and biliary tract infections did not suggest a detectable change. These changes coincided with increases in indicators related to personal precautions rather than those related to contact behavior changes. Community-acquired pneumonia could be reduced by population-wide compliance to moderate precautionary measures.

20.
Jpn J Infect Dis ; 76(5): 314-318, 2023 Sep 22.
Article in English | MEDLINE | ID: mdl-37258176

ABSTRACT

Following an endobronchial examination, a young mine supervisor was treated with antibiotics for a pulmonary nontuberculous mycobacterial infection for approximately one year. However, a review of the radiological findings revealed a different possibility. Accordingly, pulmonary resection was performed, and histopathological analysis revealed numerous yeast-like fungi. Since the patient had stayed in the southwestern United States for two months in 2009, eight years previously, coccidioidomycosis was strongly suspected. The diagnosis of coccidioidomycosis was subsequently confirmed by serology and polymerase chain reaction testing of the excised specimen. Here, we report an educational case that emphasizes the importance of meticulous medical history-taking and awareness of endemic mycoses in other countries in the context of globalization.


Subject(s)
Coccidioidomycosis , Lung Diseases , Mycobacterium Infections, Nontuberculous , Mycoses , Humans , Coccidioidomycosis/diagnosis , Coccidioidomycosis/drug therapy , Coccidioidomycosis/epidemiology , Lung/diagnostic imaging , Lung/microbiology , Mycobacterium Infections, Nontuberculous/diagnosis , Mycobacterium Infections, Nontuberculous/drug therapy , Lung Diseases/diagnosis
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