High attenuation mucus in bronchi with allergic bronchopulmonary mycosis.

BACKGROUND: High-attenuation mucus (HAM) is a specific manifestation of allergic bronchopulmonary mycosis (ABPM) on chest computed tomography (CT). OBJECTIVES: To compare the diagnostic accuracy of the two definitions of HAM and to clarify the clinical and radiographic characteristics of HAM-positive and HAM-negative ABPM. METHODS: CT images at the diagnosis of ABPM using Asano's criteria were retrospectively analysed. In Study #1, radiographic data obtained using the same CT apparatus in a single institute were analysed to determine the agreement between the two definitions of HAM: a mucus plug that is visually denser than the paraspinal muscles or that with a radiodensity ≥70 Hounsfield units. In Study #2, HAM was diagnosed by comparison with the paraspinal muscles in patients with ABPM reporting to 14 medical institutes in Japan. RESULTS: In Study #1, 93 mucus plugs from 26 patients were analysed. A substantial agreement for HAM diagnosis was observed between the two methods, with a κ coefficient of 0.72. In Study #2, 60 cases of ABPM were analysed; mucus plugs were present in all cases and HAM was diagnosed in 45 (75%) cases. The median A. fumigatus-specific IgE titre was significantly lower in HAM-positive patients than in HAM-negative patients (2.5 vs. 24.3 UA /mL, p = .004). Nodular shadows were observed more frequently in the airways distal to HAM than in those distal to non-HAM mucus plugs (59% vs. 32%, p < .001). CONCLUSION: In conclusion, agreement between the two methods to diagnose HAM was substantial. HAM was associated with some immunological and radiographic characteristics, including lower levels of sensitization to A. fumigatus and the presence of distal airway lesions.

Clinical characteristics of allergic bronchopulmonary mycosis caused by Schizophyllum commune.

BACKGROUND: Allergic bronchopulmonary mycosis (ABPM) is an allergic disease caused by type I and type III hypersensitivity to environmental fungi. Schizophyllum commune, a basidiomycete fungus, is one of the most common fungi that causes non-Aspergillus ABPM. OBJECTIVE: Herein, we attempted to clarify the clinical characteristics of ABPM caused by S. commune (ABPM-Sc) compared with those of allergic bronchopulmonary aspergillosis (ABPA). METHODS: Patients with ABPM-Sc or ABPA were recruited from a nationwide survey in Japan, a multicenter cohort, and a fungal database at the Medical Mycology Research Center of Chiba University. The definition of culture-positive ABPM-Sc/ABPA is as follows: (1) fulfills five or more of the 10 diagnostic criteria for ABPM proposed by Asano et al., and (2) positive culture of S. commune/Aspergillus spp. in sputum, bronchial lavage fluid, or mucus plugs in the bronchi. RESULTS: Thirty patients with ABPM-Sc and 46 with ABPA were recruited. Patients with ABPM-Sc exhibited less severe asthma and presented with better pulmonary function than those with ABPA (p = 0.008-0.03). Central bronchiectasis was more common in ABPM-Sc than that in ABPA, whereas peripheral lung lesions, including infiltrates/ground-glass opacities or fibrotic/cystic changes, were less frequent in ABPM-Sc. Aspergillus fumigatus-specific immunoglobulin (Ig)E was negative in 10 patients (34%) with ABPM-Sc, who demonstrated a lower prevalence of asthma and levels of total serum IgE than those with ABPM-Sc positive for A. fumigatus-specific IgE or ABPA. CONCLUSIONS: Clinical characteristics of ABPM-Sc, especially those negative for A. fumigatus-specific IgE, differed from those of ABPA.

Chronic Pulmonary Aspergillosis Caused by Aspergillus tubingensis Diagnosed by a Bronchoscopic Biopsy.

We herein report a case of chronic pulmonary aspergillosis (CPA) caused by Aspergillus tubingensis diagnosed by a bronchoscopic biopsy with negative serological and sputum culture findings. A 66-year-old man was referred for the assessment of a pulmonary cavity. Computed tomography showed a thick-walled cavity in the upper right pulmonary lobe. Serum ß-D glucan, Aspergillus galactomannan, and Aspergillus antibody tests were negative. Aspergillus species were not detected in the sputum. Culture and pathological specimens were obtained from the mass by bronchoscopy. Microscopic examination findings were consistent with Aspergillus niger complex morphologically and identified as Aspergillus tubingensis through DNA sequencing. The patient was diagnosed with chronic pulmonary aspergillosis.

Importance of Accurate Identification and Antifungal Susceptibility Testing of Aspergillus Species in Clinical Settings.

Aspergillus species have been identified morphologically in most clinical laboratories without conducting antifungal susceptibility tests (ASTs). This review aimed to evaluate the importance of accurate identification and ASTs of Aspergillus spp. strains for adequate clinical management of Aspergillus infections. The Aspergillus spp. were identified by gene sequencing, and ASTs for itraconazole and voriconazole were conducted. In Aspergillus section Nigri, the rate of detection of cryptic species was high, and Aspergillus tubingensis with lower susceptibility to azoles was frequently identified. Azole-resistant Aspergillus fumigatus was detected at a high rate in patients with chronic pulmonary aspergillosis managed with long-term azole treatment. In conclusion, accurate identification of Aspergillus spp. and ASTs are needed to carry out appropriate treatment. Moreover, we hope that these microbiological tests will be widely used in clinical laboratories to improve clinical practice.

Clinical Impact of Pretransplantation Physical Function on Transplantation after Allogeneic Hematopoietic Cell Transplantation in Older Adults.

Clinical research regarding the impact of pretransplantation physical function on transplantation outcomes in older adults remains limited. We retrospectively reviewed the charts of 150 consecutive patients age >55 years who underwent their first allogeneic hematopoietic cell transplantation (HCT) at our center between 2010 and 2021. We evaluated the clinical impact of pretransplantation physical function, including hand grip strength (HGS), knee extension strength (KES), and distance covered in a 6-minute walk test (6MWT), along with other clinical factors, on transplantation outcomes such as overall survival (OS), nonrelapse mortality (NRM), and cumulative incidence of disease relapse (CIR). There was no difference in OS, NRM, or CIR among the 3 age groups studied (56 to 60 years, 61 to 65 years, and 66 to 70 years). With regard to physical function tests, we divided the study patients into 2 groups based on the median HGS, KES, and 6MWT values: higher physical function and lower physical function groups. Because there were significant differences in HGS and KES between male and female patients, sex-specific threshold values were used. In a univariate analysis, OS tended to be better in the higher physical function group compared with the lower physical function group (4-year OS, 42.0% versus 32.0% in HGS, P = .14; 44.8% versus 37.8% in KES, P = .17; 46.7% versus 30.5% in 6MWT, P = .099). NRM was significantly lower in the higher physical function group (4-year NRM, 25.5% versus 39.9% in HGS, P = .045; 17.7% versus 38.0% in KES, P = .005; 22.5% versus 43.4% in 6MWT, P = .033). There was no significant difference in CIR between the higher and lower physical function groups (4-year CIR, 34.6% versus 28.7% in HGS, P = .38; 38.5% versus 25.8% in KES, P = .20; 33.0% versus 27.0% in 6MWT, P = .42). In multivariate analysis, the higher KES group (hazard ratio [HR], .54; 95% confidence interval [CI], .32 to .90) was significantly associated with better OS, as were female sex (HR, .48; 95% CI, .26 to .89) and low/intermediate Disease Risk Index (HR, 3.59; 95% CI, 2.04 to 6.31). Higher KES (HR, .37; 95% CI, .17 to .83) and female sex (HR .36; 95% CI, .13 to .998) were significantly associated with a reduced risk of NRM. Higher HGS and higher 6MWT tended to be associated with a reduced risk of NRM, but this trend was not statistically significant. Pretransplantation physical function, particularly the strength of the lower extremities, but not chronological age, is associated with NRM and OS after allogeneic HCT in adults age >55 years.

Allergic bronchopulmonary aspergillosis with atopic, nonatopic, and sans asthma-Factor analysis.

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) develops in the presence or absence of asthma, either atopic or nonatopic. We have tried to explore the essential components in the pathogenesis of the disease, which are either consistent and variable according to the presence and type of asthma. METHODS: Non-cystic fibrosis ABPA cases satisfying Asano's criteria were extracted from a prospective registry of ABPA and related diseases in Japan between 2013 and 2023. According to the type of preceding asthma, ABPA was classified into three groups: ABPA sans asthma (no preceding asthma), ABPA with atopic asthma, and ABPA with nonatopic asthma. Exploratory and confirmatory factor analyses were performed to identify the components that determined the clinical characteristics of ABPA. RESULTS: Among 106 cases of ABPA, 25 patients (24%) had ABPA sans asthma, whereas 57 (54%) and 24 (23%) had ABPA with atopic and nonatopic asthma, respectively. Factor analysis identified three components: allergic, eosinophilic, and fungal. Patients with atopic asthma showed the highest scores for the allergic component (p < .001), defined by total and allergen-specific IgE titers and lung opacities, and the lowest scores for the fungal component defined by the presence of specific precipitin/IgG or positive culture for A. fumigatus. Eosinophilic components, including peripheral blood eosinophil counts and presence of mucus plugs/high attenuation mucus in the bronchi, were consistent among the three groups. CONCLUSION: The eosinophilic component of ABPA is considered as the cardinal feature of ABPA regardless of the presence of preceding asthma or atopic predisposition.

Positive correlation between voriconazole trough concentrations and C-reactive protein levels in patients with chronic pulmonary aspergillosis: A retrospective cohort study.

BACKGROUND: Voriconazole (VRCZ) is the first-line treatment for chronic pulmonary aspergillosis (CPA). VRCZ trough concentration monitoring is recommended for adequate therapy because VRCZ concentrations vary widely. However, factors associated with variations in VRCZ concentrations, especially in the same patient at different time points, have not been identified. The objective of this study was to identify factors influencing VRCZ trough concentrations. PATIENTS AND METHODS: This single-center retrospective study conducted at our institute between April 2014 and August 2016 included patients with CPA who received VRCZ. Patient trough concentrations were measured more than twice while the patients received the same dose using the same administration route (defined as one series). A step-wise method and multiple regression analysis were used to test the effects of patient characteristics on VRCZ trough concentrations. RESULTS: Sixty-nine series in 49 patients were analyzed. VRCZ was administered orally in 59 series, intravenously in 7 series, and by dry syrup in 3 series. The median VRCZ trough concentration and the median variation in VRCZ concentrations were 1.68 and 0.99 µg/ml, respectively. In the simple regression analysis, creatinine, alkaline phosphatase, C-reactive protein (CRP), and creatinine clearance significantly correlated with VRCZ concentrations. Multiple regression analysis demonstrated a significant positive correlation between CRP and VRCZ concentration (P < 0.0001). CONCLUSION: In patients with CPA, VRCZ concentration correlated with CRP levels in the same patients receiving the same dose of VRCZ at different time points.

[Gallbladder Necrosis after Surgery for Stanford Type A Aortic Dissection in an Elderly Patient:Report of a Case].

An 86-year-old woman who suffered from cardiac tamponade due to acute Stanford type A aortic dissection was admitted to our hospital. An emergency operation was performed uneventfully. She suffered from abdominal pain 13 days after the operation. Computed tomography( CT) scan revealed pericholecystic fluid and unclear gallbladder wall, revealing acalculous necrotizing cholecystitis. We performed open cholecystectomy and abdominal cavity drainage. No gallstones were observed. She underwent intensive treatment. She was discharged without complications 44 days after the cholecystectomy.

Efficacy and safety of isavuconazole against deep-seated mycoses: A phase 3, randomized, open-label study in Japan.

OBJECTIVES: Isavuconazole is a convenient triazole antifungal agent with a broad antifungal spectrum. A randomized, open-label study (ClinicalTrials.gov, NCT03471988) was conducted to evaluate the efficacy and safety of isavuconazole in Japanese patients with deep-seated mycoses. PATIENTS AND METHODS: In Cohort A, patients with aspergillosis (chronic pulmonary aspergillosis and invasive aspergillosis) were randomized in a 2:1 ratio to isavuconazole or voriconazole, and in Cohort B, patients with cryptococcosis and mucormycosis were assigned to isavuconazole for up to 84 days of treatment. The overall outcome was evaluated according to the clinical, radiological, and mycological responses at Days 42 and 84 and at the end of treatment (EOT). RESULTS: A total of 103 participants were enrolled and received the study drug. The overall response rate of patients with chronic pulmonary aspergillosis in the isavuconazole (52 patients) and voriconazole (27 patients) groups was 82.7% and 77.8% at EOT, respectively. The response rate in patients with cryptococcosis (10 patients, isavuconazole group only) was 90.0%. One of three participants with invasive aspergillosis and one of three participants with mucormycosis responded in the isavuconazole group. In the safety evaluation, the incidence of adverse events in participants with chronic pulmonary aspergillosis was similar in both groups. Adverse drug reactions were reported in 32 (61.5%) patients receiving isavuconazole and 23 (85.2%) patients receiving voriconazole. CONCLUSIONS: Isavuconazole showed efficacy and safety in Japanese patients with chronic pulmonary aspergillosis and cryptococcosis, for which the drug is not currently indicated.

Validity of Platelia Aspergillus IgG and Aspergillus Precipitin Test To Distinguish Pulmonary Aspergillosis from Colonization.

When Aspergillus, an ubiquitous, saprophytic fungus, is detected in respiratory tract specimens collected from chronic respiratory disease patients, it is important to determine whether it is a true infection or colonization. We investigated the usefulness of the Bio-Rad Platelia Aspergillus IgG (Platelia Aspergillus IgG) enzyme-linked immunosorbent assay (ELISA) method and the Aspergillus precipitin test to distinguish pulmonary aspergillosis from colonization. Between January 2017 and November 2021, 51 confirmed, untreated pulmonary aspergillosis (33 chronic pulmonary aspergillosis [CPA] and 18 allergic bronchopulmonary aspergillosis [ABPA]) and 77 colonization patients were included in this study. At first, the conventional cutoff value was utilized in assessing the validity of the two antibody tests for distinguishing pulmonary aspergillosis from colonization. The Platelia Aspergillus IgG cutoff value was then reevaluated to fit this situation. Finally, differences in test accuracy dependent on Aspergillus species were assessed for both antibody tests by comparing cases with Aspergillus fumigatus complex and those with non-fumigatus Aspergillus complex. Both antibody tests demonstrated significantly higher positive rates for pulmonary aspergillosis (P < 0.0001) than colonization. The cutoff value should be 15.7 arbitrary units (AU)/mL to best distinguish infection from colonization, which was higher than the conventional value of 10 AU/mL. The diagnostic sensitivity of Platelia Aspergillus IgG for the non-fumigatus Aspergillus complex was inferior to the A. fumigatus complex (P = 0.019). In conclusion, both Aspergillus antibody tests were valid to distinguish infection from colonization, although we should note the higher cutoff value for Platelia Aspergillus IgG and the lower sensitivity in cases of non-fumigatus Aspergillus infection. IMPORTANCE Pulmonary aspergillosis is the most common pulmonary fungal infection. However, Aspergillus is a ubiquitous, saprophytic fungus; it can be detected in respiratory specimens even in the absence of infection. Especially since Aspergillus is detected in respiratory specimens collected from patients with chronic respiratory disease, it is important to determine whether it is true infection or colonization. We investigated the validity of the Platelia Aspergillus IgG ELISA method and the Aspergillus precipitin test to distinguish pulmonary aspergillosis from colonization. Both antibody tests were considered useful in differentiating true infection from colonization in respiratory practice. The appropriate cutoff value for Platelia Aspergillus IgG was higher than the conventional value, and it was also noted that the sensitivity of both antibody tests for non-fumigatus Aspergillus complex was low. This study will be significant in real-world clinical practice of pulmonary aspergillosis using antibody tests in respiratory care.

The Treatment and Prognosis of Older Tuberculosis Patients with a Poor Performance Status Caused by Underlying Diseases.

Objective The incidence of tuberculosis in Japan has been decreasing in the overall population but is increasing in older patients ≥90 years old. A poor performance status due to underlying diseases makes it difficult for patients with tuberculosis to receive standard oral treatment. However, there is no consensus concerning alternative treatments. This study examined the treatments and outcomes of older patients with tuberculosis and a poor performance status and determined the limitations of tuberculosis treatment for them. Methods We retrospectively enrolled 121 older patients with tuberculosis and a performance status of 3 or 4 due to underlying diseases during their hospitalization between April 2015 and March 2017 at National Hospital Organization Tokyo National Hospital. We classified them according to the drug administration route (oral, enteral, and injection routes) on admission and compared the characteristics and prognoses among the three groups. Results There were 79 patients in the oral route group, 28 (35.4%) of whom died during hospitalization. Among the 15 patients in the enteral route group, 6 (40.0%) died. Among the 27 patients in the injection route group who received non-oral agents, 22 (81.5%) died. The prognosis of the injection route group was poor, with a median survival time of 21 days. Conclusion Treatment success cannot be expected with injection treatment in patients with a poor general condition because of complications. Although injection treatment may be a viable alternative treatment, its establishment as the standard treatment cannot be currently endorsed.

[Internal Hernia Accompanying Intestinal Necrosis after Aortic Arch Replacement:Report of a Case].

A 76-year-old man with thoracic aortic aneurysm was admitted to our hospital. Aortic arch replacement was performed uneventfully. He suffered from abdominal pain 17 days after the operation. Computed tomography (CT) scan revealed a strangulated bowel obstruction, and we performed emergent open abdominal surgery. During the operation, we found an adhesion between the greater omentum and the retroperitoneum. The small intestine was intussuscepted into this site, and strangulated with necrosis of a 35-cm length. We performed a partial resection of the small intestine. We encountered rare strangulated bowel obstruction after open heart surgery due to adhesion of the great omentum in a patient without a history of abdominal surgery.

Impact of lung cancer surgery on comorbid Mycobacterium avium complex lung disease-A case series.

The number of cases with Mycobacterium avium and Mycobacterium intracellulare lung diseases (Mycobacterium avium complex lung disease [MACLD]) are increasing globally. Lung cancer can sometimes present as a comorbidity with MACLD; however, the clinical presentation and outcomes of comorbid MACLD following lung cancer resection remain unclear. Therefore, we retrospectively assessed 17 patients with MACLD undergoing lung cancer resection to determine the impact of lung cancer surgery on comorbid MACLD. Of the 17 patients, Mycobacterium avium and Mycobacterium intracellulare were present in 15 and 2 patients, respectively; 14 patients had stage I lung cancer and underwent lobectomy. Ten patients were postoperatively observed for MACLD without any further intervention, five patients underwent additional resection for conspicuous MACLD lesions, and the remaining two patients underwent complete resection for MACLD and lung cancer within the same lobe followed by rifampicin, ethambutol, and clarithromycin (RECAM) therapy. Seven patients exhibited postoperative MACLD exacerbation, six of whom developed exacerbation in the operated ipsilateral residual lobes. Six of these seven patients received RECAM, three of whom (43%) subsequently exhibited improvement. Attention should be paid to MACLD exacerbation during postoperative follow-up, especially in ipsilateral lobes. Although RECAM therapy may be beneficial in alleviating MACLD exacerbation, further investigation is warranted to validate these results.

Serum total IgE may be a biomarker among chronic pulmonary aspergillosis patients with elevated serum total IgE levels: A cohort study with pathological evaluations.

High serum total immunoglobulin E (IgE) levels have been reported in chronic pulmonary aspergillosis (CPA). However, researchers have not verified if they reflect the disease activity. We aimed to compare the serum total IgE levels in CPA cases with high serum IgE during an exacerbation or when stable and examined the IgE expression patterns in the lesions via immunofluorescence staining. From April 2016 to September 2019, we extracted CPA cases with elevated serum total IgE levels based on the criteria of the Infectious Diseases Society of America. We retrospectively analyzed serum total IgE levels and other parameters and eventually extracted 32 cases. The patients' serum total IgE levels were significantly higher in the exacerbation period than in the stable period (P < .0001). The median rate of change was 1.76 times (quartile 1.41-3.25). In addition, we used surgical specimens of CPA cases with high serum total IgE levels, normal serum total IgE CPA cases, and control surgical specimens and performed immunofluorescence staining with IgE, mast cell tryptase, CD138, and 4,6-diamidino-2-phenylindole. We observed multiple mast cells and plasma cells in the CPA cases regardless of the serum total IgE level. In contrast, multiple IgE-positive cells co-stained with tryptase were observed in CPA cases with high serum total IgE levels. This finding suggested that serum total IgE could serve as a biomarker for evaluating disease severity. Immunofluorescence staining suggested that IgE may play a role in pathogenesis through activation of mast cells by cross-linking in cases of CPA with high serum total IgE levels. LAY SUMMARY: High serum total IgE levels are common in chronic pulmonary aspergillosis. This novel study indicated that serum total IgE is a possible biomarker of the disease activity in the aforementioned condition. Immunofluorescence staining indicated a possible role of IgE in disease pathogenesis.

The accuracy and clinical impact of the morphological identification of Aspergillus species in the age of cryptic species: A single-centre study.

BACKGROUND: Aspergillus spp. is identified morphologically without antifungal susceptibility tests (ASTs) in most clinical laboratories. The aim of this study was to examine the clinical impact of the morphological identification of Aspergillus spp. to ensure the adequate clinical management of Aspergillus infections. PATIENTS/METHODS: Aspergillus isolates (n = 126) from distinct antifungal treatment-naïve patients with aspergillosis were first identified morphologically, followed by species-level identification via DNA sequencing. An AST for itraconazole (ITC) and voriconazole (VRC) was performed on each Aspergillus isolate. RESULTS: Based on the genetic test results, morphology-based identification was accurate for >95% of the isolates at the species sensu lato level although the test concordance of Aspergillus spp. with low detection rates was low. The rates of cryptic species were found to be 1.2% among the isolates of A. fumigatus complex and 96.8% in the A. niger complex. Cryptic species with lower susceptibilities to antifungal drugs than sensu stricto species among the same Aspergillus section were as follows: The A. lentulus (n = 1) isolates had low susceptibilities to azoles among the A. fumigatus complex species (n = 86), and A. tubingensis isolates (n = 18) exhibited lower susceptibility to azoles among the A. niger complex species (n = 31). CONCLUSION: Diagnostic accuracy was high at the A. fumigatus and A. niger complex level. However, in the presence of cryptic species, a solely morphological identification was insufficient. Particularly, ITC and VRC might be inappropriate for aspergillosis treatment when the A. niger complex is identified morphologically because it is possible that the Aspergillus isolate is A. tubingensis.

Non-fumigatus Aspergillus Infection Associated with a Negative Aspergillus Precipitin Test in Patients with Chronic Pulmonary Aspergillosis.

Aspergillus antibody testing is key for the clinical diagnosis of chronic pulmonary aspergillosis (CPA) with high sensitivity. However, false-negative results in patients with CPA might be obtained, depending on the Aspergillus species. The aim of this study was to investigate which factors are associated with false-negative results in Aspergillus precipitin tests and whether the sensitivity of precipitin tests in CPA is influenced by Aspergillus fumigatus and non-fumigatus Aspergillus species. Between February 2012 and December 2020, 116 consecutive antifungal treatment-naive patients with CPA were identified and included in this retrospective chart review. Aspergillus species isolated from the respiratory tract of patients were identified by DNA sequencing. Characteristics of patients with positive and negative results for Aspergillus precipitin tests were compared. The sensitivity of the Aspergillus precipitin tests was compared between patients with A. fumigatus-associated CPA and non-fumigatus Aspergillus-associated CPA. A non-fumigatus Aspergillus species was the only factor significantly associated with negative Aspergillus precipitin test results in patients with CPA in the multivariate analysis (hazard ratio, 8.3; 95% confidence interval, 3.2 to 22.1; P < 0.0001). The positivity of the Aspergillus precipitin test for patients with non-fumigatus Aspergillus-associated CPA was lower than that for patients with A. fumigatus-associated CPA (84.8% versus 37.9%; P < 0.0001). These results revealed that the presence of non-fumigatus Aspergillus-associated CPA should be considered with a negative Aspergillus precipitin test; this finding may prevent diagnostic delay or misdiagnosis for CPA.

Kawasaki Disease Shock Syndrome in Japan and Comparison With Multisystem Inflammatory Syndrome in Children in European countries.

Multisystem inflammatory syndrome in children (MIS-C) is a severe Kawasaki-like illness that was first linked to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in European countries in the spring of 2020 and has been suggested to have overlap with Kawasaki disease shock syndrome (KDSS). There are few reports of MIS-C from Asia. This observational study aimed to identify the clinical features in children presenting with KDSS in Japan over a 5-year period and to summarize similarities and differences between KDSS and MIS-C. We retrospectively collected data on patient characteristics, clinical signs and symptoms, treatment, and prognosis including coronary artery abnormalities (CAAs), which were compared with data of patients with KDSS worldwide and patients with MIS-C from a review. KDSS was identified in 6 (1.1%) of 552 patients with Kawasaki disease (KD) treated at a single institution in Japan between 2015 and 2020 (1 in 2020). In patients with KDSS in Japan or worldwide vs. patients with MIS-C, KDSS was more likely to have a diagnosis of complete KD (100, 70 vs. 6.3%), a higher incidence of CAAs (50, 65 vs. 11%), and a greater requirement for vasoactive agonists (67, 67 vs. 43%) because of circulatory shock (100, 50 vs. 26%). Both KDSS and MIS-C had good prognosis (mortality 0, 6.7 vs. 1.7%). Although KDSS in Japan and MIS-C show some overlap in clinical symptoms, they are unlikely to be the same disease entity. KDSS is more likely to have a cardiovascular phenotype with CAAs and requires treatment with cardiovascular agents.

[Clinical Application of Gemcitabine plus Cisplatin plus Bevacizumab Combination Chemotherapy for Ovarian Clear Cell Carcinoma].

Ovarian clear cell carcinoma(OCCC)shows a poor response to standard chemotherapy, and it is often difficult to choose a regimen for patients with recurrent OCCC. Several reports have suggested a synergistic effect between gemcitabine and cisplatin; another report suggested that gemcitabine, platinum, and bevacizumab are efficacious against recurrent ovarian cancer. We treated patients with OCCC using a combination chemotherapy regimen consisting of gemcitabine(1,000 mg/ m2)and cisplatin(40 mg/m2)on days 1 and 15, and bevacizumab(15 mg/kg)on day 1, with the cycle repeated every 4 weeks. Six patients received this therapy after informed consent, and 2 evaluable patients showed a partial response. Adverse events were mild, with Grade 3 anemia, leukopenia, and neutropenia occurring in 67%, 33%, and 17% of cases, respectively. No Grade 4 events were observed, including hematological or non-hematological toxicities. This suggests that a regimen of combined gemcitabine, platinum, and bevacizumab can be efficacious and feasible for the treatment of OCCC.

Prognostic factors of chronic pulmonary aspergillosis: A retrospective cohort of 264 patients from Japan.

BACKGROUND: Chronic pulmonary aspergillosis (CPA) develops in various underlying pulmonary conditions. There is scarce data evaluating interstitial lung disease (ILD)/abnormalities (ILA) as such conditions, and it has not been explored much whether non-tuberculous mycobacterial pulmonary disease (NTM-PD) is a prognostic factor for mortality in CPA patients. Few reports had investigated prognostic factors of CPA including underlying pulmonary conditions. OBJECTIVES: To explore prognostic factors of CPA including pulmonary conditions. METHODS: We conducted a retrospective cohort study of 264 CPA patients from a center for pulmonary aspergillosis in Japan. RESULTS: Survival rates were 78.7%, 61.0%, and 47.4% at 1, 3, and 5 years, respectively. Of 264 patients, 53 (20.1%) and 87 (33.1%) were complicated with ILA and NTM-PD. Several independent prognostic factors were identified by multivariate Cox proportional analysis: ILA (HR 1.76, 95%CI 1.06-2.92, p = 0.029), age (1.05, 1.02-1.08, p<0.001), male sex (2.48, 1.34-4.59, p = 0.004), body mass index of <18.5 kg/m2 (1,87, 1.20-2.90, p = 0.005), presence of aspergilloma (1.59, 1.04-2.45, p = 0.033), and lower serum albumin (0.56, 0.38-0.83, p = 0.004). NTM-PD was not associated with higher mortality (0.85, 0.52-1.38, p = 0.51). CONCLUSIONS: The poor prognosis of CPA and several prognostic factors were revealed. Early diagnosis and intervention is required with reference to such factors.