Evaluation of the correlation between multiple organ calcification on CT and disease severity in patients with TAFRO syndrome.

PURPOSE: The purpose of this study was to investigate the incidence of multiple organ calcification and the correlation between multiple organ calcification and clinical severity in patients with thrombocytopenia, anasarca, fever, reticulin fibrosis, renal dysfunction, and organomegaly (TAFRO) syndrome. METHODS: We retrospectively identified 13 patients with TAFRO syndrome who were treated at our hospital between February 2019 and March 2021. Computed tomography (CT) images of TAFRO patients, which were acquired at admission and one month after admission, were evaluated. Additionally, clinical and laboratory data related to organ calcification and severity classification of TAFRO syndrome were investigated. The correlation between the presence of organ calcification on CT and TAFRO syndrome-severity classification was evaluated. RESULTS: One month after admission, calcification of the myocardium, adrenal glands, gallbladder wall, pancreas, kidney, skeletal muscle, and skin were observed in 38%, 46%, 15%, 15%, 15%, 23%, and 15% of the thirteen patients, respectively. The occurrence rate of calcifications in the myocardium, adrenal glands, and skeletal muscle was significantly higher in patients with a grade 4 or higher clinical severity than in those with a level up to grade 3 (p = 0.001, p = 0.005, and p = 0.035, respectively). CONCLUSIONS: Our results suggest that the higher the clinical severity in patients with TAFRO syndrome, the higher is the frequency of calcification in the myocardium, adrenal glands, and skeletal muscle; therefore, the assessment of these organ calcifications on CT images may be useful in predicting the severity of TAFRO syndrome.

Comparative evaluation of temporal subtraction computed tomography and non-echoplanar diffusion-weighted imaging for the mastoid extension of middle ear cholesteatoma.

OBJECTIVE: Preoperative imaging assessment influences the decision to perform mastoidectomy for the mastoid extension of middle ear cholesteatoma. This study compared the performance of temporal subtraction CT (TSCT) and non-echoplanar diffusion-weighted imaging (non-EP DWI) in evaluating such mastoid extensions. METHODS: We retrospectively evaluated 239 consecutive patients with surgically proven middle ear cholesteatoma between April 2016 and April 2021. The diagnostic performance of TSCT, wherein the presence of black color indicated progressive bone erosion, and non-EP DWI, wherein high signal intensity in the mastoid region suggested mastoid extension, was compared using Fisher's exact test. RESULTS: In 34 patients with evaluable TSCT images, black color was significantly more common in patients with mastoid extension than in those without; the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of TSCT were 1.00, 0.95, 0.94, 1.00, and 0.97, respectively. In 90 patients with evaluable non-EP DWI, high signal intensity was significantly more common in patients with mastoid extension than in those without; the sensitivity, specificity, PPV, NPV, and accuracy of non-EP DWI were 0.88, 0.85, 0.91, 0.81, and 0.87, respectively. In 16 patients with both evaluable TSCT and non-EP DWI, the diagnostic performance of the TSCT was slightly superior to that of the non-EP DWI for predicting mastoid extension, although the difference was not significant. CONCLUSIONS: TSCT images generated using consecutively acquired preoperative high-resolution CT images are useful for predicting mastoid extension of middle ear cholesteatoma, and the diagnostic performance of TSCT is non-inferior to that of non-EP DWI.

Preoperative prediction for mastoid extension of middle ear cholesteatoma using temporal subtraction serial HRCT studies.

OBJECTIVES: This study investigated the utility of temporal subtraction computed tomography (TSCT) obtained with temporal bone high-resolution computed tomography (HRCT) for the preoperative prediction of mastoid extension of middle ear cholesteatomas. METHODS: Twenty-eight consecutive patients with surgically proven middle ear cholesteatomas were retrospectively evaluated. The presence of black color in the mastoid region on TSCT suggested progressive changes caused by bone erosion. Enlarged width of the anterior part of mastoid on HRCT was interpreted as suggestive of mastoid extension. Fisher's exact test was used to compare the widths and black color on TSCT for cases with and without mastoid extension. The diagnostic accuracy of TSCT and HRCT for detecting mastoid extension and interobserver agreement during the evaluation of black color on TSCT were calculated. RESULTS: There were 15 cases of surgically proven mastoid extension and 13 cases without mastoid extension. Patients with black color on TSCT were significantly more likely to have a mastoid extension (p < 0.001). The sensitivity and specificity of TSCT were 0.93 and 1.00, respectively. Patients in whom the width of the anterior part of the mastoid was enlarged were significantly more likely to have a mastoid extension (p = 0.007). The sensitivity and specificity of HRCT to detect the width of the anterior part of the mastoid were 0.80 and 0.77, respectively. Interobserver agreement during the evaluation of TSCT findings was good (k = 0.71). CONCLUSIONS: This novel TSCT technique and preoperative evaluations are useful for assessing mastoid extension of middle ear cholesteatomas and making treatment decisions. KEY POINTS: •TSCT shows a clear black color in the mastoid region when the middle ear cholesteatoma is accompanied by mastoid extension. •TSCT obtained with preoperative serial HRCT of the temporal bone is useful for assessing mastoid extension of middle ear cholesteatomas.

Efficacy of Portal Vein Embolization with a Procedure of Sheath Injection and Balloon Occlusion with Gelatin Sponge.

INTRODUCTION: To evaluate the efficacy, safety, and associated complications of a novel and simple approach to portal vein embolization that utilizes sheath injection and balloon occlusion (PVE-SIBO) with gelatin sponge (GS) for the purpose of increasing future liver remnant (FLR) volume. METHODS: Between 1 January, 2006, and 31 August, 2020, 20 patients (15 men, 5 women, aged 64.6 ± 10.2 years) diagnosed with hepatobiliary malignancy underwent presurgical PVE-SIBO at our institution via a percutaneous transhepatic approach to the right portal vein and embolization of the portal vein with GS. We evaluated the increased ratio of FLR volume, operation duration, recanalization rate, and complications following this procedure. RESULTS: All procedures were successful and without complications such as subcapsular hematoma, intra-abdominal bleeding, and bile leakage. The increased ratio of FLR volume was 34.7 ± 23.7% after a mean of 14.3 ± 2.57 days, and there was a significant difference in the FLR volume before and after PVE (P < 0.01). Procedure time was 52.7 ± 11.4 minutes. CONCLUSION: PVE-SIBO with GS is a simple, effective, and safe procedure to increase the ratio of FLR volume prior to hepatic surgeries.

Hemorrhagic Complication in Surgical Resection for Massive Plexiform Neurofibroma in Body Trunk: The Flow-Void Sign as a Predictor and Preoperative Embolization as Prevention.

BACKGROUND: Plexiform neurofibromas (PNs) are highly vascularized and potentially malignant tumors. Surgical resection of a PN can be complicated by perioperative hemorrhagic events (PHE), including excessive intraoperative blood loss and postoperative hematoma at the surgical site. This study aimed to evaluate the predictive factors of PHE and the usefulness of preoperative embolization for PN. MATERIALS AND METHODS: Consecutive surgical resections of 24 massive PNs in the body trunk with a maximum diameter > 5 cm in 22 patients between January 2015 and December 2020 were reviewed. Patient demographics, laboratory analyses, MRI findings, preoperative transcatheter arterial embolization (TAE), and pathological findings were evaluated between PNs with and without PHE, which consists of intraoperative blood loss over 15% of their estimated total blood volume and/or postoperative hematoma requiring surgical intervention or blood transfusion. RESULTS: PHE was observed in 7 out of 24 PNs (29.2%), with 5 events of excessive intraoperative bleeding and 2 postoperative hematomas. The PHE group (n = 7) showed a significantly higher flow-void effect inside the tumor on preoperative MRI than the non-PHE group (n = 17) (P = 0.0186). Preoperative TAE was not associated with PHE occurrence for the 24 PNs; however, it significantly reduced the PHE risk by 12 PNs with a flow-void sign (P = 0.00126). Other characteristics showed no significant differences between groups. CONCLUSION: The flow-void sign on MRI can be the only predictive factor of PHE in surgical resection for massive PNs in the body trunk. Preoperative TAE can reduce the PHE risk for PNs with a flow-void sign.

Quantitative Histogram Analysis of T2-Weighted and Diffusion-Weighted Magnetic Resonance Images for Prediction of Malignant Thymic Epithelial Tumors.

PURPOSE: To assess the value of histogram analysis for differentiating a high-risk thymic epithelial tumor (TET) from a low-risk TET using T2-weighted images and the apparent diffusion coefficient (ADC). METHODS: Forty-nine patients with histopathologically proven TET after thymectomy were enrolled in this study and retrospectively classified as having low-risk TET (low-risk thymoma) or high-risk TET (high-risk thymoma or thymic carcinoma). Twelve parameters were obtained from the quantitative histogram analysis. The histogram parameters were compared using the Mann-Whitney U test. Diagnostic efficacy was estimated by receiver-operating characteristic curve analysis. RESULTS: Twenty-five patients were classified as having low-risk TET and 24 as having high-risk TET. The mean ADC value showed diagnostic efficacy for differentiating high-risk TET from low-risk TET, with an area under the curve of 0.7, and was better than when using conventional methods alone. CONCLUSION: The ADC-based histogram analysis could help to differentiate between high-risk and low-risk TETs.

Evaluation of the usefulness of cystic duct three-dimensional computed tomography with non-contrast for before laparoscopic cholecystectomy and endoscopic transpapillary gallbladder drainage in comparison to magnetic resonance cholangiopancreatography.

INTRODUCTION: The purpose of this study is to evaluate whether anatomical variations of the cystic duct and accessory bile duct can be grasped by cystic duct three-dimensional (3D)-computed tomography (CT) using non-contrast CT and to examine the possibility of omitting magnetic resonance cholangiopancreatography (MRCP). METHODS: Of patients who underwent non-contrast abdominal CT between May and October 2019, those who underwent MRCP within 1 month before and afterwards were targeted. Seven assessors visually evaluated the cystic duct 3D-CT images on a 5-point scale. Average scores of ≥3 and <3 points were assigned as the good and poor groups, respectively. Regions of interest (ROIs) were placed inside the cystic duct and four places around it, and the CT values in those ROIs were measured. The CT value difference was calculated by subtracting the surrounding CT values from the CT value in the cystic duct and converting the result to an absolute value. The CT value difference was classified into good and poor groups, and statistical analysis was performed. Seven assessors evaluated anatomical variations of the cystic duct and the presence of the accessory bile duct. The results were compared with the MRCP interpretation results to calculate sensitivity, specificity, positive predictive value, and negative predictive value. RESULTS: The average visual evaluation score was 3.8. The good and poor groups were comprised by 53 (85.5%) and 9 (14.5%) patients, respectively. The CT difference value averages were 54.7 and 15.9 for the good and poor groups, respectively, and the value was significantly higher in the good group (p = 0.001). The comparison results with MRCP were sensitivity=83.3%, specificity=78.0%, positive predictive value=47.6%, and negative predictive value=95.1%. CONCLUSION: Cystic duct 3D-CT using non-contrast CT is a useful technique for understanding anatomical variations of the cystic duct and accessory bile duct. Our method may reduce the number of MRCP sessions performed.

Fosravuconazole to treat severe onychomycosis in the elderly.

Fosravuconazole is a novel oral antifungal drug developed in Japan and used to treat tinea unguium since 2018. Its excellent oral absorbability and systemic bioavailability has enabled short-duration therapy of 3 months. Furthermore, no concomitant drugs are contraindicated due to the presence of the mild inhibitor of cytochrome P450 enzyme which is responsible for polypharmacy adverse effects. Therefore, it can be safely administrated to elderly patients. Elderly patients (≥65 years old) with severe onychomycosis (≥50% nail involvement) were treated with oral fosravuconazole 100 mg once daily for 12 weeks. The rate of involvement improved from 86.6% to 28.1% (P < 0.01). The efficacy (i.e. percentage of those rated as "improved" and better) and cure rate was 83.8% (31/37) and 29.7% (11/37), respectively. Furthermore, when focusing on the thin nail group (<3 mm), the efficacy and cure rate was 88.2% (15/17) and 58.8% (10/17), respectively. Although the serum γ-glutamyltransferase levels increased in 21.6% (8/37), all patients recovered without any specific treatments.

Granulomatous polyarthritis caused by Talaromyces georgiensis in a dog.

A 6-y-old, 3.5-kg, spayed female Toy Poodle was presented with left forelimb lameness of 2-d duration. Two months before the initial presentation, radiography showed osteolysis of the medial epicondyle of the left humerus, and the left forelimb was amputated. Grossly, the articular villi of the elbow joint were markedly thickened, and the articular cartilage surfaces of the distal humerus and proximal radius had partial erosion. Histologically, granulomatous arthritis and osteomyelitis characterized by the presence of abundant macrophages containing numerous fungi were observed. ITS and ß-tubulin sequences amplified from the isolate from the specimen were 100% and 99% identical to type strain UTHSC D16-145T of Talaromyces georgiensis, respectively. Canine osteoarthritis caused by T. georgiensis has not been reported previously, to our knowledge.

Systemic Inonotus sp. Infection in a dog.

A 3-years-old male golden retriever was presented for decreased activity (lethargy), anorexia, and titubation. Superficial lymph nodes were enlarged, and arrhythmia and tachycardia were auscultated. Fungal hyphae-like structures were detected in the biopsy samples from an enlarged lymph node and spleen. Nucleotide sequence of the internal transcribed spacer region of the fungi amplified by PCR was highly homologous to that of Inonotus pachyphloeus. The dog was treated with antifungal agents such as itraconazole, fluconazole, and voriconazole. Clinical signs resolved for 325 days but the dog died suddenly, possibly because of arrhythmia. Postmortem examination revealed the presence of a disseminated fungal infection. This report describes the case of canine systemic Inonotus sp. infection treated by an antifungal agent.

Emergence of Fungal-Like Organisms: Prototheca.

The genus Prototheca consists of achlorophyllic algae that are ubiquitous in the environment and animal intestines. However, this organism has forfeited its photosynthetic ability and switched to parasitism. In 1894, Krüger described two microorganisms isolated in Germany from mucous flux of Tilia and Ulmus spp., namely Prototheca moriformis and P. zopfii. Based on their yeast-like colony morphology, Krüger classified these organisms as fungi. The genus is now included within the class Trebouxiophyceae, order Chlorellales, and family Chlorellaceae. Historically, protothecosis and infections caused by green algae have been studied in the field of medical mycology. Prototheca spp. have been found to colonize human skin, fingernails, the respiratory tract, and digestive system. Although human infection by Prototheca is considered rare, an increase in infections has been noted among immunosuppressed patients, those on corticosteroid treatment, or both. Moreover, the first human outbreak of protothecal algaemia and sepsis was recently reported in a tertiary care chemotherapy oncology unit in 2018. Prototheca is also a causative pathogen of bovine disease. Prototheca zopfii and P. blaschkeae are associated with bovine mastitis, which causes a reduction in milk production and secretion of thin, watery milk containing white flakes. Economic losses are incurred either directly via reduced milk production and premature culling of affected animals or indirectly as a result of treatment and veterinary care expenses. Thus, knowledge of this fungal-like pathogen is essential in human and veterinary medicine. In this mini-review, I briefly introduce human and animal protothecoses.

Isolation of Aspergillus caninus (Synonym: Phialosimplex caninus) from a Canine Iliac Lymph node.

Aspergillus caninus (synonym: Phialosimplex caninus) is an anamorphic fungus species associated with systemic infections in dogs that has been transferred from the genus Phialosimplex to Aspergillus. Here, we report the first case of canine A. caninus infection in Japan. A castrated Japanese Shiba Inu (6 years old; weight, 12.5 kg) was referred to the Yamaguchi University Animal Medical Center, Yamaguchi, Japan, in June 2017 showing vitality loss and depression. Computed tomography revealed iliac and splenic hilum lymphopathies, and histologic examination of an iliac lymph node by biopsy revealed granulomatous lesions with numerous oval to round yeast-like fungal cells. Aspergillus caninus was isolated from the biopsy samples, and in vitro susceptibility tests of the isolate to the antifungal drugs amphotericin B (AMB), fluconazole (FLZ), itraconazole (ITZ), voriconazole (VRZ), and micafungin (MCF) were performed by the E-test method. The isolate from this dog exhibited a minimal inhibitory concentration of < 0.002 µg/ml to AMB, > 256 µg/ml to FLZ, < 0.002 µg/ml to ITZ, < 0.002 µg/ml to VRZ, and < 0.002 µg/ml to MCF, indicating that the isolate was not susceptible to FLZ and susceptible to AMB, ITZ, VRZ, and MCF. Since the response of the patient dog to ITZ and VRZ treatments was poor, more aggressive management using combination therapies of ITZ with other antifungals may be necessary for treating canine A. caninus infection in dogs.

A Giant Dermatophyte Abscess Caused by Trichophyton rubrum in an Immunocompromised Patient.

A 73-year-old male who had been receiving immunosuppressive drugs for 15 years developed a nodule on the left buttock region. The nodule slowly grew into a 15-cm fluctuant multilocular subcutaneous cyst. Serum beta-D-glucan levels were high, and the yellow purulent fluid obtained from the cyst was positive for Trichophyton rubrum. Granuloma formation in the cyst wall and large abscesses in the central cystic area were found, and septated hyphae were observed in both tissues. The cyst was surgically removed, and followed by itraconazole treatment. Notably, the clinical manifestations closely resembled those of a huge atheroma.

Mating Type Gene (MAT) and Itraconazole Susceptibility of Trichophyton tonsurans Strains Isolated in Japan.

Infection by Trichophyton tonsurans is an emerging fungal epidemic in Japan. Itraconazole (ITZ) and terbinafine have been used for the treatment of this infection for 15 years. However, patients with T. tonsurans infections have been shown to remain uncured or to become reinfected, suggesting that subclinical infection or polyphyletic strains and/or antifungal drug-resistant strains might be occurring in Japan. In this study, PCR analysis was performed to confirm the presence of the mating type locus MAT in genomic DNA from 60 Japanese clinical isolates of T. tonsurans, and to assess the previously postulated clonal origin of clinical isolates of this species. Antifungal susceptibility testing on isolates also was performed to confirm the absence of strains resistant to ITZ. PCR analysis proved that all 60 strains contained the MAT1-1 allele, while none contained the MAT1-2 allele. As determined by E-test, the mean MIC of ITZ in the 60 strains was 0.023 mg/L (range 0.002-0.125 mg/L). All strains of T. tonsurans isolated in Japan were clonal and were not resistant to ITZ. Therefore, dermatophytosis due to T. tonsurans is expected to respond to ITZ, since clinical isolates of T. tonsurans tested to date have been susceptible to this antifungal. This infection is proliferating as a subclinical infection in Japan.

Suppurative granulomatous sinorhinitis associated with Nocardia spp. infection in a cat.

A 9-year-old spayed female cat was examined for cheek skin drainage. The skin lesion did not respond to medical therapy; thereafter, facial deformity developed. A computed tomography revealed an intranasal mass and maxillary osteolysis. The mass was histopathologically diagnosed as suppurative granulomatous inflammation caused by filamentous bacteria. The lesion responded well to radiation therapy. Although actinomycosis was suspected histopathologically, no actinomycetes were detected in the nasal lesion by a bacterial culture conducted at a commercial laboratory. The submandibular lymph node and subcutaneous tissue exhibited swelling. Microbiological examination and genetic analysis based on 16S rDNA gene sequence revealed that Nocardia spp. were isolated from both lesions.

Two cases of feline orbital aspergillosis due to Aspergillus udagawae and A. viridinutans.

Aspergillus udagawae and A. viridinutans are members of the section Fumigati; both cause invasive aspergillosis in humans. These two Aspergillus species are discriminated from A. fumigatus by molecular methods. Herein, we report two cases of feline orbital aspergillosis, one caused by A. udagawae and the other by A. viridinutans. To our knowledge, Case 1 represents the first reported case of treatment of A. udagawae with a high dosage of itraconazole, and Case 2 represents the first reported case of A. viridinutans infection associated with sarcoma. Identification of the etiologic agents of these cases was confirmed by comparative analyses of the sequences of ß-tubulin-encoding genes. With the spread of non-fumigatus aspergillosis, increasing emphasis should be placed on molecular identification of the infecting Aspergillus species and the use of in vitro drug susceptibility tests to ensure the selection of appropriate antibiotics.

Disseminated mycosis in a killer whale (Orcinus orca).

Hematological findings in a female killer whale (Orcinus orca) undergoing rehabilitation after sudden severe anorexia revealed continuing increases in serum lactate dehydrogenase and aspartate aminotransferase activities as well as fibrinogen concentration. Serologic evidence of herpesvirus infection and skin vesicles were detected 2 weeks into the treatment regimen of antibiotics and corticosteroids. The whale showed signs of improvement after treatment with anti-herpesvirus drugs, but sudden severe anorexia reappeared, along with marked elevation of fibrinogen concentration that continued until the death. Postmortem examination revealed multiple light tan foci of necrosis in the skeletal and cardiac muscles, and lung consolidation. Microscopic findings indicated disseminated fungal granulomas in the skeletal and cardiac muscles, as well as myocarditis, mycotic embolic thromboarteritis of cardiac blood vessels, and bronchopneumonia with numerous typical Aspergillus-like fungi. Mucor-like structures in granulomas in the heart and skeletal muscle and Aspergillus-like fungi in the lungs were identified using periodic acid-Schiff, Gomori methenamine silver stain, and immunohistochemistry. The present case involves dual infection with Mucor and Aspergillus species in a killer whale with concurrent herpesvirus.

Therapeutic efficacy of ABT-737, a Bcl-2 inhibitor, in a canine melanoma cell line.

The small molecule inhibitor, ABT-737, inhibits Bcl-2 that is overexpressed in many tumor cell lines and, in combination with an anticancer drug, can strongly enhance proapoptotic activity. In the present study, we evaluated the inhibitory activity of ABT-737 on the survival of a canine melanoma cell line (MCM-N1). MCM-N1 cell viability was decreased following 24- and 48-hr culture with ABT-737, depending on ABT-737 concentration, while cell viability was unchanged in controls. ABT-737 synergized with carboplatin to promote cell death. Notably, approximately 50% of MCM-N1 cells survived following culture with 2-4 µg/ml of carboplatin; whereas, less than 20% of MCM-N1 cells survived following culture with ABT-737 (1 mM) plus carboplatin (2-10 µg/ml).