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Background: Cardiac papillary fibroelastoma is a rare benign tumor, which is often mistaken for a vegetation. Predominantly asymptomatic, it can cause life-threatening complications. Although rare, mobile papillary fibroelastoma movement between affected valves may hamper valve closure and damage the valve, leading to valvular regurgitation. Endothelial damage increases the risk of developing infective endocarditis. We report a rare case of a highly mobile papillary fibroelastoma originating from the atrial septum touching the mitral valve, leading to mitral regurgitation and, eventually, infective endocarditis., Case Presentation: A 26-year-old woman with suspected infective endocarditis was referred to us from a previous hospital after having experienced intermittent fever for a month. Before the fever, she had been experiencing exertional dyspnea. In addition, she had undergone a cesarean section two weeks before this admission. A transthoracic echocardiogram showed a mobile mass originating from the atrial septum touching the mitral valve with severe mitral regurgitation. Computed tomography revealed an occluded right profunda femoris artery with an embolus. Infective endocarditis associated with a mobile vegetation with high embolic risk was diagnosed, and urgent surgery was performed. Following the surgery, examinations revealed papillary fibroelastoma originating from the atrial septum and infective endocarditis of the mitral valve. The histopathological examination confirmed that a mass initially thought to be a mobile vegetation was a papillary fibroelastoma. The postoperative course was uneventful except for pericarditis. There has been no recurrence of infective endocarditis or papillary fibroelastoma., Conclusions: The highly mobile papillary fibroelastoma was thought to have caused both chronic mitral regurgitation and infective endocarditis. Mobile papillary fibroelastomas can cause endothelial damage to nearby valves and predispose patients to infective endocarditis., (© 2024. The Author(s).)

Background: The effect of the surgical sealant AQUABRID on outcomes after acute aortic dissection repair has not been evaluated. The objective of this study was to examine whether the use of AQUABRID affects the volume of intraoperative blood transfusion or operative time in patients undergoing emergency surgery to repair acute aortic dissection., Methods: A multicenter retrospective cohort study from January 2007 to December 2021. A total of 399 patients underwent emergency acute aortic dissection repair. Propensity score matching was used to adjust for the type of surgery and other patient characteristics., Results: A total of 387 of the eligible 399 patients were included in this study and propensity score matching yielded 94 patients for whom characteristics were not significantly different between the two groups. The type of surgery was exactly matched (ascending aorta replacement: 19 [40%]; partial arch replacement: 13 [28%]; total arch replacement: 15 [32%] in each group). Within the matched cohort, there was a statistically significant difference in the volume of intraoperative blood transfusion. (AQUABRID vs. control: 34 [26-38] vs. 50 [38-60] U in Japan, p = .03). Operating time was significantly shorter in the AQUABRID group (total operation: mean ± SD, 343 ± 92 vs. 402 ± 161 min, p = .03; reconstruction for arch vessels: 29 ± 17 vs. 56 ± 22, p < .01). The rate of postoperative complications was comparable in the two groups. Failure to use AQUABRID was a significant predictor of the need for massive transfusion (>40 U) (odds ratio: 7.20; 95% confidence interval: 2.56-20.23; p < .01)., Conclusions: The use of AQUABRID during emergency acute aortic dissection repair significantly decreased the volume of intraoperative blood transfusion and the duration of surgery., (© 2022 Wiley Periodicals LLC.)

Objective: Emergency surgical repair is the standard treatment for acute aortic dissection type A. However, the surgical risk of total arch replacement remains high. The Viabahn Open Revascularization TEChnique has been used for supra-aortic reconstruction during total arch replacement. This Cleveland Clinic technique is called "branched stented anastomosis frozen elephant trunk repair." Our total arch replacement with reconstructed extended branched stented anastomosis frozen elephant trunk repair requires no unnecessary cervical artery exposure. We compared the outcomes of extended branched stented anastomosis frozen elephant trunk repair and conventional total arch replacement in acute aortic dissection type A., Methods: We compared the clinical course of patients undergoing total arch replacement using sutureless direct branch vessel stent grafting with frozen elephant trunk (extended branched stented anastomosis frozen elephant trunk repair) for acute aortic dissection type A with patients undergoing conventional total arch replacement. For the procedure, the aortic arch was transected circumferentially distal to the brachiocephalic artery origin. Frozen elephant trunk was fenestrated by heating with a cautery, and the self-expandable stent graft was delivered into the branch vessels through the fenestration., Results: Of 58 cases, 21 and 37 were classified in the extended branched stented anastomosis frozen elephant trunk repair and conventional total arch replacement groups, respectively. The times (minutes) of selective antegrade cerebral perfusion (75 ± 24, 118 ± 47), total operation (313 ± 83, 470 ± 151), and cardiopulmonary bypass (195 ± 46, 277 ± 96) were significantly better in the extended branched stented anastomosis frozen elephant trunk repair group ( P  < .001). Six surgical deaths occurred: 2 (9%) in the extended branched stented anastomosis frozen elephant trunk repair group and 4 (10%) in the conventional total arch replacement group. In all cases, only 1 patient (2%) in the conventional total arch replacement group had a branch artery-related complication during the postoperative follow-up period. In the extended branched stented anastomosis frozen elephant trunk repair group, blood product use significantly decreased ( P  < .05)., Conclusions: Extended branched stented anastomosis frozen elephant trunk repair has shown comparable safety and efficacy to conventional total arch replacement and can be used for acute aortic dissection type A emergency repair. It optimizes true lumen perfusion and facilitates supra-aortic artery remodeling., (© 2022 The Author(s).)

Introduction: The STOP-Bang test was used to detect patients at high risk of obstructive sleep apnea (OSA). We evaluated the usefulness of the STOP-Bang test for predicting the severity of OSA in Japanese patients., Methods: We retrospectively evaluated the patients who performed full polysomnography at the Mihara Medical Association Hospital. We evaluated the correlation between the STOP-Bang score and the apnea hypopnea index (AHI) using Spearman's rank correlation analysis. We then used multivariate analyses to examine the independent risk factor for severe OSA (AHI ≥ 30/hr)., Results: One hundred seven patients were diagnosed as no (n = 5), mild (n = 17), moderate (n = 30), and severe (n = 55) OSA. The median age was 67 years old (range: 35-84), and 73 of the 107 patients were males. The correlation coefficient between the STOP-Bang score and AHI was 0.701 (P < 0.001). A STOP-Bang score ≥ 5 had sensitivity of 80.0% and specificity of 76.9% for detecting severe OSA. A STOP-Bang score ≥ 5 and BMI ≥ 30 kg/m 2 were the independent risk factor for severe OSA., Conclusions: The STOP-Bang score correlates with AHI and is useful for predicting OSA severity. Polysomnography should be performed actively for the patients with high STOP-Bang scores., Competing Interests: None, (Copyright © Japan Medical Association.)

A 76-year-old female was followed up for rheumatoid arthritis-associated interstitial lung disease(RA-ILD). Consolidation and ground-glass opacities were observed in the right lung. When the corticosteroid was restarted due to a relapse of RA-ILD, most of the shadows disappeared. However, ground-glass nodules remained in the apex of the right lung. Thoracoscopic segmentectomy was performed, and lung cancer was diagnosed. Patients with rheumatoid arthritis suffer from complications such as RA-ILD, drug-induced pneumonia, pulmonary infections, and malignancies. A careful assessment of treatment response should be made in case of a differential diagnosis.

A 54-year-old man with a history of smoking developed infectious bullae at the apex of his left lung and underwent long-term antimicrobial treatment. The bullae gradually reduced in size along with a slight left pleural thickening. Left back pain relapsed after a year, and CT revealed a rapid increase in pleural thickening. Left upper lobectomy led to the diagnosis of pulmonary polymorphic carcinoma. Chronic inflammation due to infection could contribute to carcinogenesis; therefore, post-inflammatory changes should be carefully followed-up.

Rationale: Pembrolizumab, an immune-checkpoint inhibitor (ICI), has been shown to be effective for treatment-naive patients with non-small cell lung cancer (NSCLC) and high expression of programmed death-ligand 1 (PD-L1). Therefore, treatment regimens containing pembrolizumab have become a standard therapy for these patients. However, the use of pembrolizumab is limited owing to the side effects of ICIs., Patient Concerns and Diagnoses: The patient was a 65-year-old man with a left lung mass surrounded by interstitial shadow. The tumor was diagnosed as adenocarcinoma, cT4N3M0, stage IIIC, and the tumor cells showed high PD-L1 expression. It was unclear whether the interstitial shadow was interstitial lung disease (ILD) or lymphangitis carcinomatosa., Interventions and Outcomes: The patient received carboplatin and nab-paclitaxel, a less risky regimen for ILD, as the first-line therapy. Administration of 2 cycles of this regimen markedly improved both the tumor diameter and interstitial shadow. The interstitial shadow was clinically diagnosed as lymphangitis carcinomatosa and not ILD. Subsequently, the patient was treated with pembrolizumab, and the tumor showed much further shrinkage with no deterioration of the interstitial shadow. To date, the patient is alive with no complaints and no disease progression, and has continued pembrolizumab treatment for a total of 12 months., Lessons: In patients at a high risk of ICI-related side effects, platinum-doublet chemotherapy may be permitted as the first-line therapy for NSCLC with high PD-L1 expression. However, if the risk associated with ICIs is resolved, early switching from chemotherapy to pembrolizumab might be desirable, even if the chemotherapy is effective.

Rationale: Tracheobronchial fistulas are rare complications in lung cancer patients. These lesions are associated with a high rate of mortality caused by infection and bleeding, and there is no consensus on a definitive optimal therapy., Patient Concerns and Diagnoses: The patient was a 59-year-old man with a right lung mass showing mediastinal invasion and tracheal compression, diagnosed with adenocarcinoma, cT4N0M0, stage IIIA. He was treated with concurrent chemoradiotherapy with carboplatin and paclitaxel, and the lesion markedly shrunk. Eleven months later, the lesion showed regrowth, and he underwent repeated chemotherapy for stabilization of the lesion. Thirty-six months after the first regrowth, the tumor showed regrowth again. The patient was then administered docetaxel and bevacizumab as fifth-line therapy. After 11 cycles of docetaxel and bevacizumab therapy, a tracheo-parenchymal fistula appeared., Interventions and Outcomes: Docetaxel and bevacizumab therapy was stopped, and nivolumab therapy was initiated. Subsequently, the fistula and cavity became stable with slight shrinkage. To date, the patient is alive with no complaints and no disease progression and has continued nivolumab for a total of 28 months., Lessons: Immune-checkpoint inhibitor therapy involving nivolumab therapy might be a useful alternative for the treatment of lung cancer involving a tracheobronchial fistula.

Carcinoma of unknown primary site (CUP) is diagnosed only in 2-9% of all cancer cases. Adenocarcinomas account for approximately 60% of CUP, and some of these are putative lung adenocarcinomas. The frequency of driver oncogene positivity in the putative lung adenocarcinomas is unknown, and the efficacy of targeting therapies for the driver oncogene is also unknown. This is the first case report of C-ros oncogene 1 (ROS1)-rearranged putative lung adenocarcinoma presenting as CUP showing a good response to ROS1 inhibitor therapy. A 55-year-old woman presented with neck lymphadenopathy. Computed tomography and [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) showed swelling of the bilateral supraclavicular, left accessory, mediastinal, and abdominal lymph nodes. The pathological analysis of the lymph node specimen biopsy indicated adenocarcinoma with cytokeratin 7 and thyroid transcription factor-1 positivity. Thus, this case was identified as ROS1- rearranged putative lung adenocarcinoma presenting as CUP. Oral crizotinib, an ROS1 inhibitor, was administered at a dose of 250 mg twice daily. Four weeks later, several swollen nodes showed marked improvement, and eight weeks later, FDG PET showed almost no uptake. In conclusion, putative lung adenocarcinoma presenting as CUP may involve ROS1 rearrangement, and ROS1 inhibitor therapy may be effective., Competing Interests: CONFLICTS OF INTEREST The authors have no conflicts of interest to disclose.

Rationale: Only few cases of myasthenia gravis (MG) associated with small-cell lung cancer (SCLC) have been reported, and cases positive for acetylcholine receptor antibody (AChR-ab) are even rarer. The efficacy of standard MG treatment, such as cholinesterase inhibitor therapy, immunosuppressive therapy using steroids and immunosuppressive drugs, plasma exchange, and intravenous immune globulin (IVIg), for these cases is unclear., Patient Concerns and Diagnoses: A 71-year-old man complained of bilateral eyelid ptosis. He also presented with dysphagia and masticatory muscle fatigue after chewing. The edrophonium test was positive, and the serum AChR-ab level was increased; therefore, the patient was diagnosed with MG. Computed tomography scan showed a nodule on the left upper lobe of the lung and mediastinal lymphadenopathy. Further examination revealed the lesion as SCLC. Finally, he was diagnosed with AChR-ab-positive MG associated with SCLC., Interventions and Outcomes: Oral pyridostigmine and tacrolimus were administered to treat MG; however, his symptoms worsened. Therefore, methylprednisolone and IVIg were administrated, which temporarily improved his symptoms. However, they remained uncontrolled. Meanwhile, chemotherapy with carboplatin and etoposide was administered to treat his SCLC. The lesions shrunk, and the MG symptoms and serum AChR-ab level also improved., Lessons: AChR-ab-positive MG may develop as a comorbidity of SCLC. In such cases, management might require treatment for SCLC in addition to the standard MG treatment to stabilize the MG symptoms.

We herein report the rare case of co-occurring dermatomyositis (DM), interstitial pneumonia (IP), and lung cancer in a 59-year-old man. Computed tomography (CT) and positron emission tomography-CT showed the presence of a left lung tumor with IP, which was diagnosed as lung adenocarcinoma by a CT-guided tumor biopsy. We diagnosed DM based on the presence of myalgia, Gottron's papules, and anti-aminoacyl-tRNA synthetase antibody positivity in the patient. Co-occurrence of the above-mentioned three diseases is rare, and acute exacerbation of IP is a major cause of death in such cases. These patients can be treated with immunosuppressive therapy followed by chemotherapy.

Rationale: Only a few cases of putative lung adenocarcinoma presenting as carcinoma of unknown primary site (CUP) with epidermal growth factor receptor (EGFR) mutation have been reported, and the efficacy of EGFR-tyrosine kinase inhibitors (TKIs) for these cases is unclear., Patient Concerns and Diagnoses: A 67-year-old man complained of paresis of the right lower extremity, dysarthria, and memory disturbance. Computed tomography and magnetic resonance imaging showed multiple brain tumors with brain edema and swelling of the left supraclavicular, mediastinal, and upper abdominal lymph nodes. Moreover, a metastatic duodenal tumor was detected via upper gastrointestinal endoscopy examination. The biopsy specimen of the lesion was examined and was diagnosed as adenocarcinoma with CK7 and TTF-1 positivity. Finally, the case was diagnosed as EGFR mutation-positive putative lung adenocarcinoma presenting as CUP., Interventions and Outcomes: Oral erlotinib, an EGFR-TKI, was administered at 150 mg daily. Five weeks later, the brain lesions and several swollen lymph nodes showed marked improvement, and the symptoms of the patient also improved. Three months later, the duodenal lesion was undetected on upper gastrointestinal endoscopy. After an 8-month follow-up, the patient was well with no disease progression., Lessons: Putative lung adenocarcinoma presenting as CUP may have EGFR mutation, and EGFR-TKI therapy may be effective for such malignancy.

Purpose: To evaluate the effects of signals through adrenergic receptors on the changes in the aqueous flare and intraocular pressure (IOP) induced by topical prostaglandin E2 (PGE2) in pigmented rabbits., Methods: Adrenergic agents were applied topically to pigmented Dutch rabbits, and PGE2 was then applied to induce an increase in the aqueous flare and IOP. The degree of aqueous flare was measured with a laser flare meter, and the IOP was measured with a rebound tonometer. Measurements were made every 30 min after the PGE2 had been applied for 2 h and at 4.0 and 4.5 h. Repeated measure analysis of variance and Dunnett's post hoc tests were used for the statistical analyses., Results: The topical application of PGE-2 increased the aqueous flare for more than 4.5 h. The topical instillation of 1.0 % apraclonidine significantly inhibited the increase in the PGE2-induced aqueous flare by 75.1 %, of 0.1 % brimonidine by 57.2 %, of 0.04 % dipivefrin by 57.4 %, and a combination of 0.1 % brimonidine and 5 % phenylephrine by 78.9 %. Topical 5.0 % phenylephrine and 0.05 % isoproterenol had little effect on the aqueous flare elevation induced by PGE2. The IOP increased 0.5 h after the topical application of PGE-2. Topical 1.0 % apraclonidine, 0.1 % brimonidine, 0.1 % dipivefrin, and the combination of 0.1 % brimonidine and 5.0 % phenylephrine significantly inhibited the PGE2-induced IOP elevation. However, topical 5.0 % phenylephrine and 0.05 % isoproterenol did not significantly inhibit the IOP elevation caused by PGE2., Conclusions: Signaling by the α2 receptor inhibits both the PGE2-induced flare and IOP elevation caused by topical PGE2 application.

Cancer cells are surrounded by the extracellular fluid, matrix, and stroma cells. Little is known about how extracellular components such as growth factor ligands affect the biology of lung cancer cells. The objective of this study was to determine whether extracellular fibroblast growth factors (FGFs) can affect the biology of lung cancer cells and to understand how extracellular FGFs affect the biology of lung cancer cells, including non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) cells. Out of the 23 reported FGFs, we focused on FGF2, FGF9 and FGF10. We examined the effect of FGFs on proliferation, treatment sensitivity, and apoptosis of NSCLC (PC9) and SCLC (H69, H82 and H146) cells in vitro. To determine which FGF was the most clinically relevant, we also examined FGF2 and FGF9 concentrations in the serum of patients with lung cancer. We found that extracellular FGFs can affect proliferation, treatment sensitivity, and apoptosis of lung cancer cells in a cell-specific manner. Our results indicate that extracellular FGFs affect the biology of lung cancer cells through multiple functions.

The efficacy of chemically cross-linked antigens for acellular pertussis vaccine was investigated by a murine respiratory infection model. Filamentous hemagglutinin (FHA), pertussis toxin (PT) and pertactin, prepared from a supernatant fluid of Bordetella pertussis culture or the bacterial cells, were chemically cross-linked by the addition of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysulfosuccinimide (NHSS). The biological activities of FHA and PT were inactivated by the cross-linking reaction. The cross-linked antigens induced potent protective immunity against B. pertussis more than the vaccine prepared by formalin treatment (0.2 M). These data suggest a possibility that the vaccine prepared by using EDC and NHSS is more effective than the formalin-treated vaccine.

The ability of tea-leaf catechins to detoxify agents was examined. Filamentous hemagglutinin (FHA) and pertussis toxin (PT) were detoxified by the catechins at an extraordinarily lower concentration compared with that of formalin. The sera from the mice immunized by the catechin-treated antigens recognized, not only catechin-treated, but also untreated antigens. Furthermore, catechin-treated PT induced the antibody to neutralize PT activity in the sera of the immunized mice. Pertussis vaccines were prepared including antigens detoxified by the treatment of catechins and intraperitoneally injected into mice. Protection against Bordetella pertussis infection was shown in mice immunized with the vaccines prepared by treatment with catechins. These data suggest that catechins are effective toxoiding agents for preparing a pertussis vaccine.

Two endothelin (ET)-binding inhibitors, BE-18257A and BE-18257B, which antagonized 125I-ET-1 binding to a porcine aortic smooth muscle membrane, were isolated from the mycelium of a strain of Streptomyces misakiensis. These binding inhibitors were extracted with methanol from mycelium and purified by HPLC.

A new topoisomerase inhibitor, BE-10988, was isolated from the culture broth of a strain of actinomycetes. The producing strain had a close resemblance to Streptomyces fimicarius and Streptomyces xanthocidicus. The active principle was extracted from the whole broth of strain BA10988 with ethyl acetate and purified by silica gel chromatography and by HPLC. BE-10988 increased DNA-topoisomerase complex formation and inhibited the growth of both doxorubicin-resistant and vincristine-resistant P388 murine leukemia cell lines, as well as sensitive P388 cell lines.

Antibiotics 6108 A1, B, C and D, a new series of analogues of rosaramicin, were found together with rosaramicin, juvenimicin A4 and M-4365 A1 from the cultured broth of strain BA06108 which was assigned to be a new species of Micromonospora. 6108 A1 and C showed inhibitory activity against Gram-positive and some Gram-negative bacteria as potent as rosaramicin and exhibited low acute toxicity in mice. However, 6108 B showed less potent antimicrobial activity and 6108 D showed higher toxicity than those two antibiotics.

A novel antibiotic, kazusamycin B (C32H46O7, MW 542), was isolated from the fermentation broth of Streptomyces sp. No. 81-484 and the structure was established mainly on the basis of its physico-chemical properties. Unambiguous 13C NMR spectral analysis of kazusamycin B has been also accomplished. Kazusamycin B possesses potent cytocidal activities against L1210 (IC50 0.0018 micrograms/ml) and P388 (IC100 0.0016 micrograms/ml) leukemia cells in vitro.

Kazusamycin B, a novel antibiotic (MW 542) isolated from fermentation broth of Streptomyces sp. No. 81-484 showed a broad antitumor spectrum both in vitro and in vivo. IC50 against the growth of tumor cells was around 1 ng/ml at 72 hours-exposure in vitro. Intraperitoneal injection of the antibiotic was effective in inhibiting the growth of murine tumors, S180, P388, EL-4, and B16. It was also active against doxorubicin-resistant P388, hepatic metastases of L5178Y-ML, pulmonary metastases of 3LL, and human mammary cancer MX-1 xenografted to nude mice. However, the activity of kazusamycin B toward L1210 or human lung cancer LX-1 was weaker. According to the results of comparative studies on the effect of kazusamycins B and A, an analog of B, there seemed to be no significant difference in their effectiveness. The effective dose range and toxicity were markedly dependent on tumor lines tested and the regimen used. Maximum tolerated dose in mice with subcutaneous tumors was much higher than that in mice bearing ascitic leukemia as P388. Although intermittent administration could greatly reduce the cumulative toxicity of the drug, therapeutic effect was similar with both successive and intermittent administration schedules.