Pulmonary cryptococcosis mimicking lung cancer with multiple lung metastases.

The differential diagnosis of a lung mass with multiple pulmonary nodules includes metastases of lung cancer, mycobacterial infections, and pulmonary mycosis. Pulmonary cryptococcosis should be recognized, especially in immunocompromised patients.

Bexarotene-induced hypothyroidism and dyslipidemia; a nation-wide study.

Central hypothyroidism and dyslipidemia are well-known adverse events (AEs) of bexarotene therapy. Although hypothyroidism is known to cause dyslipidemia, no study has examined the association between hypothyroidism and dyslipidemia in patients undergoing bexarotene therapy. The aim of this study is to examine this association. A retrospective observational study was performed among 294 patients who initiated bexarotene therapy in Japan (nation-wide postmarketing complete surveillance). Jonckheere-Terpstra (one sided) test was performed to evaluate the effect of the bexarotene dose on lipid metabolisms, and regression analyses were performed to evaluate associations of bexarotene dose, free thyroxine (FT4), body mass index (BMI), and lipid metabolisms. Most patients developed hypothyroidism. Two-third of patients showed FT4 values below the lower limit at 1 week. Triglycerides (TG) increased in a bexarotene dose-dependent manner, and grade ≥3 AEs on hypertriglyceridemia was observed in 39% of the patients. Additionally, one-third of grade ≥3 AEs on hypertriglyceridemia occurred within 1 week. The delta_FT4 (difference in FT4 from baseline) negatively correlated with TG increase at 1 week (p = 0.012) but not with low density lipoprotein cholesterol (LDL-C) increase at any week. Bexarotene-induced hypothyroidism is almost inevitable and occurred quickly. Bexarotene-induced hypertriglyceridemia showed positive bexarotene dose dependency and negative delta_FT4 dependency. Prophylactic and appropriate thyroid hormone compensation therapy and starting bexarotene at low doses with subsequent titration while managing dyslipidemia may have a beneficial effect for the successful continuation of bexarotene therapy without severe endocrine and metabolic AEs.

Natural history of asymptomatic cervical internal carotid artery stenosis in diabetes mellitus patients.

INTRODUCTION: Diabetes mellitus (DM) is known to be a cause of cervical internal carotid artery stenosis (ICS). In this study, we investigated the natural history of asymptomatic ICS in DM patients without surgical intervention. METHODS: We conducted a retrospective study of 148 DM patients with asymptomatic ICS treated medically at the Kansai Electric Power Hospital from April 2013 to March 2023, inclusive. We examined the incidence of ischemic stroke with ICS and evaluated the patients' clinical characteristics and imaging findings. RESULTS: Ischemic stroke with ICS occurred in 7 patients (4.7 %), and only smoking history was significantly correlated with the incidence of ischemic stroke (p = 0.04). DISCUSSION: The incidence rate of ischemic stroke with ICS in this study (4.7%) was comparable to the previous report. The result that, the correlated factors of the incidence of ischemic stroke in DM patients with ICS was only smoking history, seemed acceptable. However, prospective studies with a larger number of cases may be needed in the future to determine the correlated factors more eligibly.

Prompt Electronic Discrimination of Gas Molecules by Self-Heating Temperature Modulation.

Though considerable progress has been achieved on gas molecule recognition by electronic nose (e-nose) comprised of nonselective (metal oxide) semiconductor chemiresistors, extracting adequate molecular features within short time (<1 s) remains a big obstacle, which hinders the emerging e-nose applications in lethal or explosive gas warning. Herein, by virtue of the ultrafast (∼20 µs) thermal relaxation time of self-heated WO3-based chemiresistors fabricated via oblique angle deposition, instead of external heating, self-heating temperature modulation has been proposed to generate sufficient electrical response features. Accurate discrimination of 12 gases (including 3 xylene isomers with the same function group and molecular weight) has been readily achieved within 0.5-1 s, which is one order faster than the state-of-the-art e-noses. A smart wireless e-nose, capable of instantaneously discriminating target gas in ambient air background, has been developed, paving the way for the practical applications of e-nose in the area of homeland security and public health.

Moyamoya disease presenting with symptomatic ischemic stroke during new-generation tyrosine kinase inhibitor treatment: two illustrative cases.

Tyrosine kinase inhibitors (TKIs) have been widely used to treat chronic myeloid leukemia. Nilotinib and ponatinib, which are second- and third-generation TKIs, have been reported to cause cerebrovascular arterial complications. Here, we present two cases of moyamoya disease presenting with symptomatic ischemic stroke during new-generation TKI treatment. We judged that new-generation TKI treatment was a factor in symptomatic ischemic stroke of unknown moyamoya disease in both cases. Noninvasive examinations using magnetic resonance imaging or carotid ultrasonography should be performed before and during new-generation TKI treatment in order to prevent symptomatic ischemic stroke.

Angiomatous meningioma associated with rapidly aggravated peritumoral leptomeningitis: A case report.

Background: A special type of meningioma is known to have infiltrated inflammatory cells within the tumor, associated with peritumoral inflammation. However, there have been no reports of meningioma with inflammatory response only around the tumor, without inflammatory cells within the tumor itself. Case Description: A 70-year-old woman presented with transient right hemiparesis due to an extra-axial tumor on the left frontal convexity. The tumor appeared hypointense on T1-weighted magnetic resonance images and hyperintense on T2-weighted images without peritumoral edema, and was homogenously enhanced associated with the peritumoral leptomeningeal enhancement. Cerebrospinal fluid examination showed an increase in the number of inflammatory cells with a predominance of mononuclear cells. During the following 1 month, the tumor size was unchanged, but the peritumoral leptomeningeal enhancement was remarkably enlarged with uncontrolled focal seizures. The tumor was subtotally removed and semisolid substances in the subarachnoid space were biopsied. Pathological examination with immunostaining revealed angiomatous meningioma: the tumor had no inflammatory cell infiltration within it, but was associated with the infiltration of immunoglobulin G4-negative lymphocytes into the border zone between the tumor and the dura mater, as well as numerous neutrophils and fibrinous exudates in the peritumoral subarachnoid space. The tumor removal rapidly improved the leptomeningeal enhancement and inflammatory reactions. Conclusion: The authors reported the first case of angiomatous meningioma associated with massive peritumoral inflammation without inflammatory infiltrates within the tumor itself.

Plasma SPARC Elevation in Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage.

Matricellular proteins have been implicated in pathologies after subarachnoid hemorrhage (SAH). To find a new therapeutic molecular target, the present study aimed to clarify the relationships between serially measured plasma levels of a matricellular protein, secreted protein acidic and rich in cysteine (SPARC), and delayed cerebral ischemia (DCI) in 117 consecutive aneurysmal SAH patients with admission World Federation of Neurological Surgeons (WFNS) grades I-III. DCI developed in 25 patients with higher incidences of past history of hypertension and dyslipidemia, preoperative WFNS grade III, modified Fisher grade 4, spinal drainage, and angiographic vasospasm. Plasma SPARC levels were increased after SAH, and significantly higher in patients with than without DCI at days 7-9, and in patients with VASOGRADE-Yellow compared with VASOGRADE-Green at days 1-3 and 7-9. However, there were no relationships between plasma SPARC levels and angiographic vasospasm. Receiver-operating characteristic curves differentiating DCI from no DCI determined the cut-off value of plasma SPARC ≥ 82.1 ng/ml at days 7 - 9 (sensitivity, 0.800; specificity, 0.533; and area under the curve, 0.708), which was found to be an independent determinant of DCI development in multivariate analyses. This is the first study to show that SPARC is upregulated in peripheral blood after SAH, and that SPARC may be involved in the development of DCI without angiographic vasospasm in a clinical setting.

Denileukin diftitox-induced systemic capillary leak syndrome with acute kidney injury.

Systemic capillary leak syndrome is a rare and life-threatening disorder, characterized by recurrent episodes of unexplained hypotension, hemoconcentration, and hypoalbuminemia. This condition is caused by leakage of plasma and proteins into the extravascular space and can be classified as either idiopathic or secondary. Secondary systemic capillary leak syndrome can result from cancer, infections, medications, or surgery. Systemic capillary leak syndrome frequently develops as a side effect of denileukin diftitox treatment of refractory cutaneous T-cell lymphoma. However, the pathophysiology of this disease is not well understood. Herein, we report a case of denileukin diftitox-induced systemic capillary leak syndrome.

Echocardiography image quality of global longitudinal strain in cardio-oncology: a prospective real-world investigation.

BACKGROUND: Left-ventricular (LV) global longitudinal strain (GLS) has been reported to be a robust and sensitive marker of chemotherapy-induced cardiac damage. Image quality is paramount for accurate GLS measurements. In real-world cardio-oncology settings, the incidence of suboptimal echocardiography quality and its significance in clinical decision-making have not been well investigated. This prospective study examined the incidence and impact of suboptimal echocardiographic image quality on detecting subtle myocardial damage by chemotherapy. METHODS: Seventy-seven consecutive patients with breast cancer (age, 52 ± 12 years, 76 women, 33 with left-sided breast cancer) were included in this study. Echocardiography was performed at 3-month intervals 1 year before and after chemotherapy initiation. We classified the image quality of each echocardiographic acquisition into three groups: optimal, suboptimal, or inadequate for speckle tracking. RESULTS: Among the 376 examinations obtained during the cardiac monitoring, the image quality in 194 (52%) was optimal, suboptimal in 159 (42%), and inadequate in 23 (6%). The interobserver reproducibility was 0.91 in the optimal and 0.21 in the suboptimal group. In contrast, the optimal group showed progressive impairment in both GLS (p = 0.001) and LV ejection fraction (LVEF) (p < 0.001) during follow-up, and the suboptimal group showed a progressive decrease in LVEF (p = 0.006), but not in GLS (p = 0.13). Left-sided mammotomy and/or reconstruction surgery and high body mass index were significant determinants of suboptimal image quality. CONCLUSIONS: Even in cases of minor image quality impairment, the physician should assess GLS carefully to avoid errors in crucial clinical decision-making.

Safety and efficacy of bexarotene for Japanese patients with cutaneous T-cell lymphoma: Real-world experience from post-marketing surveillance.

To establish real-world evidence about the safety and efficacy of bexarotene for Japanese patients with cutaneous T-cell lymphoma, we conducted a nationwide cohort study using data from post-marketing surveillance for bexarotene treatment. In total, 294 patients with cutaneous T-cell lymphoma were identified between June 2016 and June 2018. Of these, 267 patients were included as the safety analysis set. Of the 267 patients, 175 were included in the efficacy analysis set. Of these, 139 patients had mycosis fungoides, including 46 with early stage disease and 93 with advanced stage disease. Among the 139 patients with mycosis fungoides, the objective response rate was 46.8%. A significant difference in objective response rate was detected between patients who started with bexarotene at 300 mg/m2 (61.6%) and patients who started with bexarotene at less than 300 mg/m2 (22.6%, p < 0.001). Of the 139 patients with mycosis fungoides, 92 were treated with a combination of bexarotene plus photo(chemo)therapy. A significant difference in objective response rate was seen between bexarotene with a combination of photo(chemo)therapy (57.6%) and bexarotene without a combination of photo(chemo)therapy (25.5%, p < 0.001). Starting bexarotene at 300 mg/m2 and combination with photo(chemo)therapy were detected as independent factors influencing response. Common treatment-related adverse events included hypothyroidism (85.8%), hypertriglyceridemia (68.5%), hypercholesterolemia (43.8%), and neutropenia (21.3%). Hypertriglyceridemia, hypercholesterolemia, and neutropenia occurred more frequently in patients who started with bexarotene at 300 mg/m2 than patients who started with bexarotene at less than 300 mg/m2 (hypertriglyceridemia, 76.4% vs. 57.0%, p = 0.001; hypercholesterolemia, 49.0% vs. 36.4%, p = 0.045; neutropenia, 28.0% vs. 12.1%, p = 0.002; respectively). The present study indicates that starting bexarotene at 300 mg/m2 and combination of photo(chemo)therapy offer a promising efficacy for the treatment of patients with mycosis fungoides. Efficacy of low-dose bexarotene plus photo(chemo)therapy should be evaluated in future.

Pralatrexate for refractory mycosis fungoides in two Japanese patients.

Pralatrexate has been approved for the treatment of relapsed/refractory peripheral T cell lymphomas. Studies in the U.S. also support the clinical efficacy of pralatrexate to treat advanced-stage cutaneous T-cell lymphomas, but outcomes in Japanese patients have not yet been reported. We herein describe two Japanese patients with heavily-pretreated relapsed/refractory mycosis fungoides that were successfully controlled by pralatrexate.

Anti-LGI1 Encephalitis Developing Immunoglobulin Responsive Orthostatic Hypotension after Remission.

Anti-leucine-rich glioma-inactivated 1 (LGI1) antibody is associated with limbic encephalitis. We herein report a patient with anti-LGI1 encephalitis who developed severe orthostatic hypotension (OH) responsive to immunoglobulin therapy five years after developing symptoms of encephalitis. A 71-year-old man presented with amnesia caused by limbic encephalitis. The symptoms of encephalitis improved partially without any immunotherapy. Five years later, he developed severe OH, and anti-LGI1 antibody was positive. The catecholamine dynamics indicated that the central autonomic nervous system was the lesion of his OH. Intravenous immunoglobulin therapy improved the OH. This case suggests that anti-LGI1 antibody can be associated with severe OH.

Cardiology consultation in oncology practice: a 5-year survey.

OBJECTIVE: Onco-cardiology services are expanding rapidly in Japan. To provide a better service, it is important to consider the needs of oncologists. However, little is known regarding specific needs for which oncologists should consult cardiologists to manage cardiovascular problems of their patients. We analysed cardiology consultations sought by oncologists to evaluate the role of cardiologists in cancer treatment. METHOD: We retrospectively investigated consecutive 2064 cardiology consultations of cancer patients in the University of Tsukuba Hospital, Tsukuba, Japan, between January 2014 and December 2018. RESULTS: The most common timing of cardiology consultation was before the commencement of cancer treatment (n = 1355; 65.7%), followed by after the commencement of cancer treatment (n = 686; 33.2%). Among the 361 consultations before the administration of anticancer drugs, 235 (65.1%) were for anthracycline-based regimens. There were 506 (24.5%) consultations for the management of cardiovascular emergencies developing after the commencement of cancer treatment; venous thromboembolism was the most frequent (n = 125; 24.7%), followed by atrial fibrillation (n = 110; 21.7%) and heart failure (n = 74; 14.6%). There were marked differences in the types of cardiovascular emergencies depending on the type of cancer. CONCLUSIONS: This survey revealed the various cardiovascular problems for which oncologists sought interventions by cardiologists. A multidisciplinary approach in an onco-cardiology service is essential to achieve optimal long-term outcomes.

Skin and hair abnormalities of Cantu syndrome: A congenital hypertrichosis due to a genetic alteration mimicking the pharmacological effect of minoxidil.

Cantu syndrome is an autosomal dominant disorder, first described by Cantu in 1982, that is characterized by congenital hypertrichosis, characteristic facial anomalies and cardiomegaly. Recent investigations have revealed that this syndrome is caused by mutations of ABCC9, which encodes a regulatory subunit of SUR2, an adenosine triphosphate-mediated potassium channel opener, expressed not only in smooth muscle but also in hair follicles. However, the abnormalities of skin and hair in patients with Cantu syndrome have not been well explored. We herein report three Japanese patients with Cantu syndrome and describe their specific skin manifestations and alterations in the histopathology of their hair follicles and sebaceous glands. Similar alterations were shared among those three patients and may be related to the function of SUR2, namely the regulation of hair follicle growth, because SUR2 is a known pharmacological target of minoxidil.

Bexarotene Reduces Production of CCL22 From Tumor-Associated Macrophages in Cutaneous T-Cell Lymphoma.

Bexarotene is a third-generation retinoid X receptor-selective retinoid that has been approved for use in the treatment of both early and advanced cutaneous T-cell lymphoma (CTCL). Although bexarotene has been used for decades in the treatment of CTCL, little is known about the mechanisms underlying its anti-tumor effects in CTCL patients. This study therefore focused on the immunomodulatory effects of bexarotene in vivo using an EL4 mouse T-cell lymphoma model, followed by investigation in CTCL patients treated with bexarotene. Intraperitoneal injection of bexarotene significantly decreased expressions of CCL22, CXCL5, CXCL10, and p19 in the tumor microenvironment. Based on those results, we then evaluated serum levels of CCL22, CXCL5, and CXCL10 in 25 patients with CTCL, revealing that CCL22 was significantly increased in advanced CTCL compared with early CTCL. Next, we evaluated serum levels of CCL22, CXCL5, and CXCL10 in CTCL patients treated with bexarotene. Serum levels of CCL22 were significantly decreased in 80% of CTCL patients who responded to bexarotene therapy. In addition, immunofluorescence staining revealed CD163+ M2 macrophages as the main source of CCL22. Moreover, bexarotene decreased the production of CCL22 by M2 macrophages generated from monocytes in vitro. Our findings suggest that the clinical benefits of bexarotene are partially attributable to suppressive effects on the production of CCL22 by M2-polarized tumor-associated macrophages.