Water detection in organic solvents using a copolymer membrane immobilised with a fluorescent intramolecular charge transfer-type dye: effects of intramolecular hydrogen bonds.

Numerous fluorescent dye-based optical sensors have been developed to detect water in organic solvents. However, only a few such sensors can detect water in polar solvents such as methanol or dimethyl sulfoxide, and their detection range is generally narrow. Therefore, in this study, a copolymer membrane incorporated with a pyridinium betaine dye (denoted PB1), which exhibited intramolecular charge transfer (ICT) characteristics, was developed to realise simple water detection in organic solvents. The pyridinium betaine structure, comprising intramolecular hydrogen bonds between the oxygen in the maleimide moiety and the hydrogen in the pyridinium, was vital for achieving efficient fluorescence emission. The membrane was prepared by copolymerising PB1 with the N,N-dimethyl acrylamide/acrylamide monomer on a glass plate, and the fluorescence in water-mixed organic solvents was investigated (λabs = 490 nm, λfl = 630 nm). The fluorescence intensity of the dye-immobilised membrane decreased with increasing water content of the organic solvents. The detection ranges in tetrahydrofuran, ethanol, methanol, and dimethyl sulfoxide were approximately <40, <40, <40, and <60 vol% water, respectively. In contrast, membranes based on a quaternary pyridinium dye (without intramolecular hydrogen bonds) did not detect water in methanol and dimethyl sulfoxide, although it was more sensitive than PB1 in the narrow region of low water concentration in THF. Theoretical calculations corroborated the importance of the pyridinium betaine structure in detecting water in organic solvents, with the increase in polarity and the formation of intermolecular hydrogen bonds between PB1 and water found to induce molecular rotation and fluorescence quenching.

[Outcomes of an Independent Clinical Study to Compare Branded and Generic Formulations of Sustained-Release Oxycodone].

To evaluate the potential for the adoption of a generic formulation of sustained-release oxycodone(Oxycodone SR Capsules), an independent clinical study was planned to accurately evaluate the efficacy and safety during a 9-day period. After a 3-day pretreatment period, the generic formulation was administered to patients with progressive cancer, who had been treated with a branded formulation(OxyContin®Tablets)of the drug for 5 days at the same dose. This was followed by a 1- day observation period. Drug administration to 3 patients with pulmonary cancer achieved the primary(dose, pain level, and adverse drug reactions)and secondary(rescue dose frequency and quality of life)endpoints, as well as safety goals. The merits of adopting a different dosage form were also noted. Independent data collection using an appropriate evaluation method consequently promoted the understanding of generic opioids in the clinical setting.

Drug-induced lung injury in a patient treated with prior atezolizumab and subsequent sotorasib: A case report.

We report a case of drug-induced lung injury treated with prior atezolizumab and subsequent sotorasib. The patient was a 62-year-old woman with lung adenocarcinoma harbouring a KRAS G12C mutation that was resistant to chemotherapy, including immune checkpoint inhibitors. Cough and dyspnea appeared on day 80 after sotorasib was administered as second-line therapy, and chest computed tomography revealed ground glass opacities in all lung lobes. Bronchoalveolar lavage fluid showed an increased total cell count with lymphocyte predominance. The patient was considered to have lung injury caused by prior atezolizumab or sotorasib administration. Withdrawal of sotorasib did not improve symptoms and shadows in both lungs. We administered moderate-dose prednisolone and the lung disorder quickly resolved. Prednisolone tapering was completed in 2 months, followed by several months without relapse. Definitive identification of the responsible drug for the drug-induced lung injury proved challenging in the setting of exposure to multiple potential inciting agents. There is a need for high levels of clinical suspicion for timely evaluation and management.

Long-term follow-up of unresectable adenoid cystic carcinoma of the trachea and bronchus treated with high-dose proton beam therapy: A report of two cases.

Adenoid cystic carcinoma (ACC) of the trachea is a rare disease that is slow growing and has a risk of distant metastasis. The standard treatment for ACC of the trachea is surgery, but this tumor is often unresectable. In definitive radiotherapy using photons for unresectable ACC of the trachea, it is sometimes difficult to deliver a sufficient dose to the target without exceeding the tolerable dose to the surrounding normal tissues. Here, we report two cases of ACC of the trachea that received a high dose (74 Gy [relative biological effectiveness]) of proton beam therapy and achieved long-term survival.

A case of massive hemoptysis caused by lung cancer saved by V-V ECMO and hemostasis achieved by radiotherapy.

Massive hemoptysis is one of the fatal complications of lung cancer. There is no established standard treatment method for it, and it often causes sudden suffocation, and some cases may be difficult to save. A 63-year-old man was admitted to the hospital with dyspnea, and developed massive hemoptysis from lung cancer shortly after admission. The tumor had obstructed the right main bronchus and had invaded the right pulmonary artery. Surgery and interventional radiology were judged impossible. The patient was successfully saved by the introduction of Veno-Venous Extra Corporeal Membrane Oxygenation (V-V ECMO), and hemostasis was obtained by radiotherapy. Two months after completion of radiotherapy, he was weaned off the ventilator and discharged on his own. He died of increased peritoneal dissemination and other complications 1 year and 1 month later, but no recurrence of hemoptysis was noted until his death. We experienced a case of massive hemoptysis in which V-V ECMO and radiation therapy succeeded in saving life and stopping bleeding. The use of V-V ECMO by emergency care teams and multimodality therapy, including radiotherapy, were effective for massive hemoptysis from lung cancer.

HTLV-1 bZIP factor induces T-cell lymphoma and systemic inflammation in vivo.

Human T-cell leukemia virus type 1 (HTLV-1) is the causal agent of a neoplastic disease of CD4+ T cells, adult T-cell leukemia (ATL), and inflammatory diseases including HTLV-1 associated myelopathy/tropical spastic paraparesis, dermatitis, and inflammatory lung diseases. ATL cells, which constitutively express CD25, resemble CD25+CD4+ regulatory T cells (T(reg)). Approximately 60% of ATL cases indeed harbor leukemic cells that express FoxP3, a key transcription factor for T(reg) cells. HTLV-1 encodes an antisense transcript, HTLV-1 bZIP factor (HBZ), which is expressed in all ATL cases. In this study, we show that transgenic expression of HBZ in CD4+ T cells induced T-cell lymphomas and systemic inflammation in mice, resembling diseases observed in HTLV-1 infected individuals. In HBZ-transgenic mice, CD4+Foxp3+ T(reg) cells and effector/memory CD4+ T cells increased in vivo. As a mechanism of increased T(reg) cells, HBZ expression directly induced Foxp3 gene transcription in T cells. The increased CD4+Foxp3+ T(reg) cells in HBZ transgenic mice were functionally impaired while their proliferation was enhanced. HBZ could physically interact with Foxp3 and NFAT, thereby impairing the suppressive function of T(reg) cells. Thus, the expression of HBZ in CD4+ T cells is a key mechanism of HTLV-1-induced neoplastic and inflammatory diseases.

D2-40-positive lymphatic vessel invasion is not a poor prognostic factor in stage I lung adenocarcinoma.

The present study investigates whether lymphatic vessel invasion (LVI) detected by D2-40 staining is a prognostic factor for stage I adenocarcinoma of the lung. We retrospectively reviewed 124 patients who underwent complete resection for stage I adenocarcinoma of the lung from January 1983 to June 2003. LVI was microscopically evaluated using D2-40 immunostaining. The median follow-up was 71 months. The LVI positive rate was 37%. The 5-year cancer-specific survival rates of the D2-40 positive LVI and negative groups were 88.8% and 84.3%, respectively (P = 0.630). The stage I lung adenocarcinoma patients who were determined to be LVI positive based on D2-40 immunostaining did not have a significantly poorer prognosis than the LVI negative cases. Thus, lymphatic microinvasion may not be a prognostic indicator in early lung cancer, although advanced LVI does appear to correlate with survival. It is therefore unnecessary to use D2-40 immunostaining to diagnose LVI in practical settings, and Hematoxylin-Eosin and Elastica van Gieson staining should continue to be used to predict the prognosis of patients with stage I lung adenocarcinoma.

[Refractory methicillin-resistant Staphylococcus aureus empyema invasion from a cervical abscess: report of a case].

The patient was a 68-year-old male. At the previous hospital, continuous hemodiafiltration (CHDF)was performed through internal jugular vein for diabetic nephropathy. Long term catheterisation caused the abscess of the sternoclavicular joint, which induced methicillin-resistant Staphylococcus aureus( MRSA) empyema. Endoscopic thoracic debridement was performed for the empyema, however inadequate drainage for the abscess. Thereafter, the patient transferred to our hospital. We performed adequate drainage for the abscess under general anesthesia at 5 days after hospitalization, and then open decortication for empyema at 26 days. The patient recovered well after operation and was discharged from the hospital at 46 days. This was a successful case of surgical treatment for refractory MRSA empyema, which controls all focus of infection.

Capillary Leak Syndrome With Pulmonary Edema Preceded by Organizing Pneumonia Caused by Combination Therapy With Nivolumab and Ipilimumab: A Case Report.

Treatment with drugs can cause lung disorders. Immune checkpoint inhibitors are often associated with organizing pneumonia. Capillary leak syndrome is a clinical form of drug-induced lung injury, a rare condition characterized by hemoconcentration, hypoalbuminemia, and hypovolemic shock. There have been no reports of multiple lung injury with immune checkpoint inhibitors, and although capillary leak syndrome alone has been reported in the past, there have been no reports of pulmonary edema as a complication. We report a 68-year-old woman who died of respiratory and circulatory failure owing to pulmonary edema caused by capillary leak syndrome, preceded by organizing pneumonia induced by combination therapy with nivolumab and ipilimumab for postoperative recurrence of lung adenocarcinoma. Residual inflammation and immune abnormalities from previous immune-related pulmonary adverse events may have increased pulmonary capillary permeability, leading to marked pulmonary edema.

[Traumatic rupture of diaphragm with splenic injury].

A 56-year-old woman admitted to our hospital because of injury by a road accident. A chest X-ray film and computed tomography (CT) scan showed multiple left rib fractures, hemothorax in the left pleural cavity, and obscurity of the left diaphragm. The stomach and injured spleen were also shown to shift to the left thoracic cavity. The patient was diagnosed as having diaphragmatic rupture with hemothorax in the left pleural cavity due to splenic injury. Emergent surgery was performed and massive bleeding was observed in the thoracic and abdominal cavities. After performing splenectomy and replacing the stomach in the abdominal cavity, the diaphragm was repaired. The patient was discharged 66 days after the surgery. Since traumatic diaphragm rupture can lead to hemorrhagic shock associated with injuries to adjacent organs, it is important to establish an accurate diagnosis and to performed appropriate surgical treatment without delay.

Lymphatic vessel invasion is a significant prognostic indicator in stage IA lung adenocarcinoma.

BACKGROUND: A radical resection is considered to be the most effective treatment for resectable non-small cell lung cancer. However, even when resected in early stages (T1aN0, T1bN0) up to 20% of patients will experience recurrence. The aim of this retrospective study was to evaluate the prognostic influence of lymphatic vessel invasion (LVI) in stage IA adenocarcinoma patients. METHODS: From January 1983 to June 2003, a total of 229 consecutive patients with pT1a or T1b N0 M0 lung adenocarcinoma who had undergone radical resection and lymph node dissection were retrospectively reviewed. Sections stained by the hematoxylin-eosin and the Elastica van Gieson method were examined for the presence of LVI. The overall survival was estimated using the Kaplan-Meier method, log-rank test, and the Cox proportional hazards analysis. RESULTS: The median follow-up was 81 months. A total of 143 patients (62%) were able to be diagnosed with regard to the presence of LVI, while information was not provided for 86 patients (38%), who were therefore excluded from the study. LVI was noted in 22 of the evaluable patients (15%) and was not seen in the other 121 patients (85%). The 5-year overall survival rate of the LVI-negative group and the LVI-positive group was 94.5 and 70.9%, respectively (P = .003). A multivariate analysis revealed LVI to be an independent predictive factor (hazard ratio: 0.202; P = .001). CONCLUSION: LVI is an independent poor prognostic factor in patients with pathologic stage IA adenocarcinoma. The T1a and T1b patients with LVI both might benefit from adjuvant chemotherapy.

[Clinical study of forty-two patients who underwent resection for pulmonary adenosquamous carcinoma].

Pulmonary adenosquamous carcinoma is a rare malignant tumor as defined by the Japan Lung Cancer Society Classification. At our institution, of the 1,023 patients who underwent resection for primary lung cancer, 42 (4.0%) had adenosquamous carcinoma. Here, we present the clinical features of this malignant tumor. The male : female ratio was low. Many tumors were located peripherally, and the positive rate for carcinoembryonic antigen (CEA) was 54.8%; these clinical findings were similar to those of adenocarcinoma. On the other hand, many tumors had relatively large diameter, and most of the patients were heavy smokers; these findings were consistent with those of squamous cell carcinoma. Hence, the cases of adenosquamous carcinoma had the characteristics of both adenocarcinoma and squamous cell carcinoma. The prognosis of patients with adenosquamous carcinoma was poorer than those of patients with adenocarcinoma and those with squamous cell carcinoma, irrespective of whether it was stages I or II. Adenosquamous carcinoma is characterized by a highly aggressive biological behavior and a high rate of early metastasis. Therefore, even if the diagnosis is made at an early phase, an aggressive approach, including adjuvant chemotherapy, might be necessary for adenosquamous carcinoma.

A case of COVID-19 with superficial thrombophlebitis caused by an indwelling peripheral venous catheter.

A local hypercoagulable state caused by SARS-CoV-2 and an indwelling peripheral venous catheter can lead to superficial thrombophlebitis. If the venous catheter is no longer needed during treatment for COVID-19 it should be removed promptly.

Posterior mediastinal nodule diagnosed as a tuberculous granuloma infiltrating into the aorta.

Although tuberculous infection rarely results in aortic aneurysm formation or rupture, its precursor lesion has never been identified in cases with tuberculosis. We incidentally encountered a case of a posterior mediastinal nodule with concomitant chest computed tomography (CT) findings of multiple pulmonary micronodular shadows. Since an enlargement of the mediastinal nodule was retrospectively apparent, we considered the lesion as malignant. Enhanced CT showed luminal irregularity in the descending aorta, located adjacent to the nodule, in addition to the disappearance of the fat plane between the lesion and the aorta. We successfully resected the nodule with the aorta under partial cardiopulmonary bypass. Based on the pathological and postoperative bacterial findings, the nodule was diagnosed as a tuberculous granuloma infiltrating into the medial layer of the aorta.

Mantle cell lymphoma shows three morphological evolutions of classical, intermediate, and aggressive forms, which occur in parallel with increased labeling index of cyclin D1 and Ki-67.

Although the 2008 World Health Organization classification defines two subtypes of mantle cell lymphoma (MCL), classical and aggressive, we often encounter MCL with both features in the same site. We named this feature "MCL with focal aggressive form (intermediate MCL)". In the present study, we reclassified 237 patients with cyclin D1 (CCND1)-positive MCL on the basis of the concept of intermediate MCL, and analyzed the correlation of this reclassification with immunohistochemical detection of CCND1, Ki-67, p53, p27(Kip1), and p21(WAF/Cip1). The median overall survival was 77, 31, and 18 months for classical, intermediate, and aggressive MCL, respectively, showing a statistically significant difference (P < 0.0001). The expression levels of CCND1, Ki-67, p53, and p21(WAF/Cip1) in aggressive MCL (mean 80.1 +/- 27.8%, 73.7 +/- 28.9%, 31.0 +/- 69.0%, and 10.4 +/- 24.8%, respectively) were higher than those in classical MCL (mean 58.1 +/- 36.7%, 25.2 +/- 25.5%, 6.5 +/- 24.3%, and 2.5 +/- 13.0%, respectively) and intermediate MCL (mean 75.7 +/- 31.4%, 30.8 +/- 33.3%, 21.0 +/- 57.4%, and 4.8 +/- 16.5%, respectively). Significantly different levels of Ki-67 and p21(WAF/Cip1) were only recognized between intermediate and aggressive (P < 0.05 and P < 0.0001, respectively), whereas those of CCND1 and p53 were only between classical and intermediate (P < 0.0001 and P < 0.05, respectively). There were no significant differences in p27(Kip1) among the three groups. The subsequent discriminant analysis with independent prognostic factors clearly demonstrated that the morphological evolution of MCL occurs in parallel with increased labeling index of CCND1 and Ki-67. The diagnosis of intermediate MCL thus proved to be of major significance and should enable the design of more tailored therapies.

Fluorescence navigation with indocyanine green for identification of intersegmental planes using a photodynamic eye camera.

BACKGROUND: Pulmonary segmentectomy is an important surgical option for complete resection in patients with poor lung function. However, correctly recognizing the intersegmental plane for accurate segmentectomy is sometimes difficult. We therefore developed a novel method that allows the detection of intersegmental planes using an indocyanine green (ICG) fluorescence imaging device, photodynamic eye (PDE) camera, PDE-neo. METHODS: As a prospective study, we performed bronchial ICG-guided segmentectomy using PDE-neo. The patients were placed in a lateral position under general anesthesia, and we performed a combined muscle-sparing minithoracotomy with video assistance. The pulmonary artery, pulmonary vein, and segmental bronchi were separated, and ICG mixed with autologous blood was introduced by spraying through the resected segment bronchi to enable visualization of the intersegmental surface with PDE-neo. This study protocol was approved by the Research Ethics Board of Hamamatsu University School of Medicine, Japan. Written informed consent was obtained from all patients. RESULTS: Overall, 10 lung malignancy patients, including 8 males and 2 females, participated in this study from March 2011 to October 2013. The median age was 69 years (range, 29-76 years). Pathologic diagnoses were 7 adenocarcinomas, 1 adenosquamous carcinoma, 1 carcinoid tumor, and 1 lung metastasis from the parotid gland cancer. The intersegmental planes of 8 cases could be identified by this method using a PDE-neo, whereas those of 2 cases did not show clear demarcations. The reason was that because of severe emphysema, air flowed from the resected segment to the surrounding segments, obliterating the demarcation between the two segmental planes. There were no recurrent cases and only two deaths due to other diseases were observed; and the 5-year cause-specific survival rate was 100%. CONCLUSIONS: Intersegmental planes could be more easily identified using ICG fluorescence imaging during segmentectomy. This method is feasible and effective and has a good long-term prognosis.

Coenzyme A and Its Thioester Pools in Obese Zucker and Zucker Diabetic Fatty Rats.

Feeding behavior is closely related to hypothalamic malonyl-CoA level in the brain and diet-induced obesity affects total CoA pools in liver. Herein, we performed a comprehensive analysis of the CoA pools formed in thirteen tissues of Zucker and Zucker diabetic fatty (ZDF) rats. Hypothalamic malonyl-CoA levels in obese rats remained low and were almost the same as those of lean rats, despite obese rats having much higher content of leptin, insulin, and glucose in their sera. Regardless of the fa-genotypes, larger total CoA pools were formed in the livers of ZDF rats and the size of hepatic total CoA pools in Zucker rats showed almost one tenth of the size of ZDF rats. The decreased total CoA pool sizes in Zucker rats was observed in the brown adipose tissues, while ZDF-fatty rats possessed 6% of total CoA pool in the lean rats in response to fa deficiency. This substantially lower CoA content in the obese rats would be disadvantageous to non-shivering thermogenesis. Thus, comparing the intracellular CoA behaviors between Zucker and ZDF rats, as well as the lean and fatty rats of each strain would help to elucidate features of obesity and type 2 diabetes in combination with result (s) of differential gene expression analysis and/or comparative genomics.

A case of ROS1-rearranged lung adenocarcinoma exhibiting pleural effusion caused by crizotinib.

Reports of crizotinib-induced pleural effusion in non-small cell lung cancer (NSCLC) are limited. A 35-year-old Japanese woman was diagnosed with ROS1-rearranged lung adenocarcinoma (primary left lower lobe, cT4N3M1c). Crizotinib was administered as first-line therapy, and the primary and mediastinal hilar lymph node metastases rapidly shrank. On the fourth day of treatment, chest X-ray demonstrated contralateral pleural effusion. On the 41st day of treatment, crizotinib was discontinued because of grade 3 neutropenia. Examination including surgical thoracoscopy did not reveal causative findings, and the continued cessation of drug administration enabled the right pleural effusion to decrease gradually and disappear, suggesting that this event was a side effect of crizotinib. The disease did not progress even though the drug was withdrawn for more than one year. In conclusion, crizotinib was considered to cause pleural effusion as an adverse event in a case of ROS1-rearranged lung adenocarcinoma with a complete response.

Detection of circulating tumor cells in patients with lung cancer using metallic micro-cavity array filter: A pilot study.

We have developed a metallic micro-cavity array filter and an automated detection system for capturing circulating tumor cells (CTCs). In this single institutional pilot study, we assessed the ability of this device to detect CTCs in patients with lung cancer at each stage. Patients diagnosed with lung cancer, undergoing planned surgery for lung cancer, or suspected of having lung cancer were recruited (40 recruited and 2 excluded). Blood samples were obtained from the patients and 3 ml whole blood was applied to the device without any preparation. The captured cells were stained to differentiate the nucleus, and determine cytokeratin and CD45 expression. Subsequently, two operators blinded to clinical information counted the number of CTCs. Sample collection was performed at the time of recruitment, before treatment and ~3 months after initial blood collection. CTC counts at recruitment were 1.4±0.4, 1.8±1.2, 1.3±0.6 and 7.4±5.1 (mean ± SE) in clinical stages I, II, III and IV, respectively. No significant difference was observed among the stages. These data indicated the ability of this device to detect CTCs at early or non-metastatic stages of lung cancer. Further research on a larger scale is needed for a more accurate assessment of the device, and research on the utility of captured cells remains a future challenge.

Clinicopathological Features in Elderly ALK-rearranged Non-small Cell Lung Cancer Patients.

AIM: To clarify the clinicopathological features in elderly anaplastic lymphoma kinase (ALK) rearranged non-small cell lung cancer (NSCLC) patients. PATIENTS AND METHODS: A retrospective study was performed in 129 ALK rearranged NSCLC patients diagnosed between April 2008 and March 2019 in fifteen Institutions of the Ibaraki prefecture, Japan. RESULTS: Median age of patients was 63 years. In 59 patients aged 65 and older, the proportions of patients with advanced stage and those treated with ALK-tyrosine kinase inhibitor (TKI) were lower than those younger than 65 years. There was no difference in overall survival (OS) between the two age groups. Among the elderly patients, no difference was observed in OS between the patients aged 65-69 and those aged 70 and older. In 89 patients treated with TKI, no significant differences were observed in the progression-free survival of TKIs and OS between patients aged 65 and older and those younger than 65, respectively. CONCLUSION: Evaluation of ALK gene status and TKI treatment are desirable even for elderly patients.