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Antibodies targeting the receptor programmed death 1 on T cells have been approved for the treatment of lung cancer. Immune checkpoint inhibitors (ICIs) induce various immune-related adverse events. Life-threatening hematotoxicity can be provoked by ICI therapy. Although ICI-related endocrinopathy and interstitial lung disease have been well documented, hematotoxicity requiring intensive treatment is relatively rare. We describe a case of nivolumab induced thrombocytopenia after transient mild fever. A 77-year-old man with non-small cell lung cancer was administered nivolumab (240 mg/body, every 2 weeks) as second line therapy. On the day 2 after the first nivolumab infusion, he had a fever and his C-reactive protein level was elevated. Thoracic computed tomography revealed no interstitial lung disease or pneumonia. The fever resolved on day 9 and was not seen thereafter. On day 15 after the first nivolumab infusion, severe thrombocytopenia suddenly emerged. A bone marrow examination revealed no dysplasia or invasion. Based on the presence of high platelet-associated IgG titer, normal bone marrow plasticity and a lack of effectiveness of platelet infusion, we diagnosed nivolumab-induced immune thrombocytopenia. Daily administration of 60 mg of prednisolone restored the patient's platelet count and platelet-associated IgG. We also found that there was significant shrinkage of the primary lesion and that stable disease was achieved. One must be aware of this relatively rare side effect and the unusual clinical findings that could be associated with immunoreaction. Keywords: Immune checkpoint inhibitors, Nivolumab, Thrombocytopenia, Lung cancer, Immune-related adverse events, Platelet-associated IgG

Background Endobronchial ultrasonography (EBUS) facilitates a lung cancer diagnosis. However, qualitative tissue characterization of lung tumors is difficult using EBUS. Integrated backscatter (IBS) is an ultrasound technique that calculates the power of the ultrasound signal to characterize tissue components in coronary arteries. We hypothesized that qualitative diagnosis of lung tumors is possible using the IBS technique. The aim of the present study was to elucidate whether the IBS technique can be used in lung tissue diagnoses. Methods Thirty-five consecutive patients who underwent surgery for lung cancer were prospectively enrolled. Surgical specimens of the lung and the tumor tissue were obtained, and the IBS values were measured within 48 h after surgery. Histologic images of lung and tumor tissues were compared with IBS values, and the relative interstitial area according to results of Masson’s trichrome staining were determined by using an imaging processor. Results The IBS values in tumor tissue were significantly lower than those in normal lung tissue (–50.9 ± 2.6 dB and –47.6 ± 2.6 dB, respectively; P P r = 0.53 and r = 0.67; P Conclusions Qualitative diagnosis of lung tumors was possible, with a sensitivity of 84% and a specificity of 85%, using the ultrasound IBS technique.

A top-emission organic light-emitting diode (OLED) with a microcavity structure combined with a blue/yellow tandem structure was developed. A high-resolution active-matrix OLED display with the world's lowest level of power consumption using the tandem OLED with red, green, blue, and yellow subpixels was fabricated.

A top-emission organic light-emitting diode (OLED) with a a microcavity structure combined with a blue/yellow tandem structure was developed. A high-resolution active-matrix OLED display with the world's lowest level of power consumption using the tandem OLED with red, green, blue, and yellow subpixels was fabricated.

A 78-year-old man presented with urinary retention and difficulty walking. Both legs showed muscle weakness, and he was experiencing lower body hypoesthesia. T2-weighted magnetic resonance imaging revealed lesions with high signal intensity and enhancement in the spinal cord and cerebrum. A cerebrospinal fluid specimen showed inflammatory changes, but negative cytology findings. Chest computed tomography revealed a tumor measuring 40 mm in diameter, and a lung biopsy revealed the presence of squamous cell carcinoma. We diagnosed the patient with paraneoplastic neurological syndrome related to lung cancer. The patient was treated with steroid pulse therapy and chemotherapy, which relieved the symptoms and enabled the patient to achieve an independent gait.

Tetomilast was originally identified as a potent inhibitor of superoxide production in human neutrophils, and is of interest because it may relieve oxidative stress related to chronic obstructive pulmonary disease (COPD). Our objective was to determine whether tetomilast effectively protects against the development of porcine pancreatic elastase (PPE)-induced emphysema in rabbits. Rabbits were divided into three groups (sham n=19, PPE n=19, PPE/Tetomilast n=18). The rabbits were once daily orally administered vehicle solution or tetomilast 5 d/week for 4 weeks before the PPE instillation. We compared pulmonary function, inflammatory cell infiltration, oxidative stress, and the incidences of apoptosis among the three groups. Tetomilast suppressed PPE-induced increases in the incidence of apoptosis and the production of 8-hydroxy-deoxyguanosine (8-OHdG) in lung tissues. PPE-instilled rabbits treated with tetomilast showed significantly less mean linear intercept and significantly better pulmonary function than rabbits administered PPE alone. Tetomilast may inhibit the development of emphysema by attenuating pulmonary inflammation and apoptosis caused by PPE-induced oxidative stress.

We report a case of gefitinib-induced bilateral upper urinary tract bleeding in an 82-year-old woman administered the drug daily for advanced non-small cell adenocarcinoma of the lung (T4N3M0). Hematuria is an uncommon adverse effect of gefitinib, and in most cases, the bleeding site is unknown. On the 44th day of oral gefitinib administration, the patient noted asymptomatic macroscopic bloody urine. Cystoscopy revealed bleeding from the bilateral ureteric orifices without hemorrhagic inflammation of the bladder. One week later, she was admitted complaining of severe abdominal pain, and her condition was found to be complicated by liver damage and renal dysfunction. We stopped gefitinib administration and started hydration and diuresis. Renal function and urine output soon recovered, and at the request of the patient, we restarted gefitinib, administering it every other day, which was sufficient to maintain antitumor activity and stabilize the disease. On the 41 st day after restarting gefitinib, hematuria and proteinuria reappeared. We therefore stopped the gefitinib, and the patient was followed with supportive care. The patient's autopsy findings denied organic urologic diseases. Instead, the reproducibility of the hematuria from the upper urinary system strongly suggests an unexpected gefitinib-related adverse effect.

An improvement of the recording density in a coaxial holographic recording system is described. We employ a new optical setup into our coaxial system, where the numerical aperture (NA) of an objective lens and the data capacity in one page increase up to 0.85 and 135 kbits, respectively. The recording performances are evaluated experimentally and numerically. The obtained results demonstrate that implemented techniques successfully improve the recording density by a factor of 1.5, achieving a raw data density of 270 Gbit/in.2.

Toxicity and efficacy of pemetrexed monotherapy in advanced non-small-cell lung cancer patients with impaired renal function treated between May 2009 and May 2012 at Gifu University Hospital were retrospectively analyzed. A total of 10 and 17 patients had a creatinine clearance rate (Ccr) of45 mL/min and ≥45 mL/min, respectively. The median age was higher in the Ccr45 mL/min group (78.9 years) than in the ≥45 mL/min group (65.2 years). The rate of neutropenia above Grade 3 was 30% in the Ccr45 mL/min group and 6% in the ≥45 mL/min group. Therefore, reducing the dose of pemetrexed should be considered in patients with impaired renal function. Non-hematologic toxicities were not correlated with the renal function. There was no treatment-related death, and most of the toxicities were mild and tolerable. Stable disease was observed in 6 patients (60%) in the Ccr45 mL/min group, and in 12 patients (70%) in the Ccr≥45 mL/min group, although some patients in both groups showed neither complete nor partial responses. The disease control rate and median progression-free survival time were 60% and 2.8 months in the Ccr45 mL/min group, and 70% and 2.9 months in the Ccr≥45 mL/min group, respectively. Thus, in this analysis, treatment with pemetrexed resulted in clinically equivalent efficacy in advanced non-small-cell lung cancer patients regardless of the state of renal function.

Endobronchial ultrasonography (EBUS) facilitates a lung cancer diagnosis. However, qualitative tissue characterization of lung tumors is difficult using EBUS. Integrated backscatter (IBS) is an ultrasound technique that calculates the power of the ultrasound signal to characterize tissue components in coronary arteries. We hypothesized that qualitative diagnosis of lung tumors is possible using the IBS technique. The aim of the present study was to elucidate whether the IBS technique can be used in lung tissue diagnoses.Thirty-five consecutive patients who underwent surgery for lung cancer were prospectively enrolled. Surgical specimens of the lung and the tumor tissue were obtained, and the IBS values were measured within 48 h after surgery. Histologic images of lung and tumor tissues were compared with IBS values, and the relative interstitial area according to results of Masson's trichrome staining were determined by using an imaging processor.The IBS values in tumor tissue were significantly lower than those in normal lung tissue (-50.9 ± 2.6 dB and -47.6 ± 2.6 dB, respectively; P .001). The IBS values of adenocarcinomas associated with a good 5-year survival rate were higher than those of non-adenocarcinomas (-48.1 ± 1.6 dB and -52.6 ± 1.4 dB; P .001). There were significant correlations between the IBS values and the relative interstitial area or micro air area in tumor (r = 0.53 and r = 0.67; P .01). After combining normal lung tissue and adenocarcinomas with a good prognosis, the sensitivity and specificity for establishing the presence of lung tumors were 84% and 85%.Qualitative diagnosis of lung tumors was possible, with a sensitivity of 84% and a specificity of 85%, using the ultrasound IBS technique.

Malnutrition, particularly protein undernutrition, contributes to the occurrence of osteoporotic fracture by lowering bone mass. In this study, the effects of dietary protein on bone mineral density and body weight in protein undernutrition were compared between gelatin and milk casein. When mice were fed for 10 wk with a low protein diet containing 10(%) casein or 6% casein +4% gelatin, there was no significant difference in the final body weight between the 6% casein+4% gelatin group and the 10% casein group. In contrast, bone mineral content and bone mineral density of the femur were significantly higher in the 6% casein+4% gelatin group than in the 10% casein group. Bone mineral content and bone mineral density did not differ significantly in 14% protein groups between 14% casein and 6% casein +80% gelatin. These results suggest that gelatin has differential effects on bone mineral density and body weight in protein undernutrition.

Objective: When treating lung cancer, pneumocystic pneumonia is a life-threatening complication seen during chemotherapy. Polymerase chain reaction is used to detect its cause, Pneumocystis jirovecii, but polymerase chain reaction positives without pneumocystic pneumonia are sometimes seen. The purpose of this study was to assess the frequency of pneumocystic pneumonia during cancer treatment. Methods: Fifty induced sputum specimens and 4 bronchoalveolar lavage specimens collected from 50 patients with acute respiratory symptoms during anticancer therapy were retrospectively studied after classifying the patients into lung cancer (n ¼ 29) and solid tumor (n ¼ 21) groups. All of the patients in both groups had an interstitial shadow suspected of being pneumocystic pneumonia, and all had polymerase chain reaction tests. Results: Eleven of the 54 specimens were polymerase chain reaction positive, and 1 patient was clinically diagnosed with pneumocystic pneumonia. The incidence of polymerase chain reaction positivity in the lung cancer group was significantly higher than in the solid tumor group (31 vs. 5%; P ¼ 0.03), and the incidence of subclinical pneumocystic pneumonia (29 vs. 5%; P ¼ 0.059) also tended to be higher in that group. There were no significant biochemical differences between the two groups, irrespective of the polymerase chain reaction results. Among polymerase chain reaction-positive patients in the lung cancer group, the cumulative dose of corticosteroid administration tended to be higher than among the polymerase chain reaction-negative patients (P ¼ 0.09). Following the polymerase chain reaction tests, nearly all polymerase chain reaction-positive patients without pneumocystic pneumonia received antipneumocystic agents, and none developed pneumocystic pneumonia. Conclusions: Our findings suggest polymerase chain reaction positivity for P. jirovecii will be detected in a fraction of lung cancer patients. Although it is difficult to predict the need for administration of pneumocystic pneumonia treatment to subclinical pneumocystic pneumonia based on polymerase chain reaction and biochemical results, polymerase chain reactionpositive patients should be followed-up with antipneumocystic agents to ensure they are not at an early stage of pneumocystic pneumonia.

We report a rare case of sarcoidosis-lymphoma syndrome with vertebral bone destruction. A 63-year-old woman was previously diagnosed as sarcoidosis by supraclavicular lymph node biopsy, and came to our hospital complaining of back pain. Both serum angiotensin-converting enzyme and lysozyme level had been continuously elevated. Magnetic resonance imaging revealed lumbar vertebral bone destruction. Histopathologic examination of lumbar vertebral tumor obtained by CT-guided biopsy revealed non-caseating epithelioid granuloma with CD 68 (+), AE1/AE3 (-), and no malignant cells. She was admitted to our hospital again for dyspnea and pancytopenia. We diagnosed active sarcoidosis and administered oral 30mg prednisolone daily. One month later, prednisolone became ineffective. Flow cytometry of tumor cells obtained from the gastric ulcer floor showed CD 5 (+), CD 20 (+), K chain monoclonality and we diagnosed B-cell non Hodgkin's lymphoma. She was treated by eight cycles of CHOP plus rituximab chemotherapy and achieved complete response. FDG uptake of the entire body decreased, whereas MRI revealed residual mass in the vertebrae. Sarcoidosis had been diagnosed for two and half years before lymphoma developed. Bone destruction is very rare and sarcoidosis is rarely the cause. This is quite an unusual case presenting histologically proved epithelioid granuloma and vertebral destruction in sarcoidosis-lymphoma syndrome.

Background: Bronchial artery (BA) embolization (BAE) is recommended as a minimally invasive therapy for hemoptysis, though some patients recover after only conservative treatment. Objectives: The purpose of our study was to assess the characteristics of BAs using multidetector row computed tomography (MDCT) and identify BAs requiring BAE without BA angiography (BAG). Methods: We retrospectively studied 41 patients and classified the visualized BAs into groups based on their BAE and bleeding statuses. Patients presenting with massive hemoptysis requiring emergency BAE were excluded. Patients presenting with persistent hemoptysis that was resistant to conservative treatment received BAE. Radiologists measured BA diameters at the ostium, bronchial bifurcation and pulmonary hilum, and also evaluated the degree of vascularization. Results: MDCT enabled visualization of 102 ostia and 96 traceable BAs. Among the participating patients, 13 had at least one ectopic origin. We obtained a good correlation between BAG and MDCT diameters (r = 0.709, p < 0.001). The diameters of BAs responsible for bleeding and receiving BAE were apparently larger in each measured segment than those that were not (p < 0.05). Moreover, the diameters of arteries receiving BAE remained largely unchanged from the origin to the hilum and through the mediastinum. BAs with low MDCT scores were significantly less likely to required BAE than those with high scores (p = 0.004), and in multiple logistic regression analysis, ostium diameter and bleeding status were independent predictive factors for BAE. Conclusions: Evaluation of BAs on MDCT could be useful for identifying the anatomical characteristics of bleeding-related BAs and determining whether BAE is indicated or whether conservative treatment is sufficient.

We have developed a coaxial-type holographic disk system with a small drive. We achieved stable operation without use of a vibration-isolating table, with a 91-Mbps data-transfer rate for recording and retrieving using LDPC code.

We have shown that the signal loss induced by the media temperature change in the coaxial holographic recording can be compensated by tuning the magnification and the wavelength of the reading reference beam appropriately. This technique offers a significant improvement in the temperature tolerance of the coaxial holographic data storage.

We have experimentally evaluated the coherent addition technique, and revealed that the coherent addition can enhance detected data intensity and realize clear three-level data retrieving. Moreover, we have achieved great improvements in the multiplexed performance, which are the SNR gain of +3.5 dB and the data density increase with the factor of 2. We consider that this technique will strongly contribute to future holographic technologies.

We have applied LDPC codes into our coaxial recording system, and revealed its fundamental characteristics. In addition, by applying the E(16, 3, 8) code and optimizing optical conditions, we have successfully improved the recording density, achieving the raw data density of 415 Gbit/in.2.

The purpose of this study was to assess the effect on bone mineral density (BMD) of systemic corticosteroid (SCS) intermittently administered for rescue from asthmatic exacerbation. Through digital image processing and calculation of four other indices, BMD was compared in groups of asthmatic patients receiving inhaled corticosteroid (ICS) alone or ICS plus intermittent SCS. We defined SCS as intermittent administration of the equivalent of 1 mg/day prednisolone in the management of asthma exacerbations during the previous 1 year. Serum NTX, a bone resorption marker, was significantly higher (p = 0.02) in the SCS group than the ICS group. SCS had no effect on BMD, although the frequency of patients at "high-risk" for osteoporosis according to the Female Osteoporosis Self-assessment Tool for Asia (FOSTA) tended to be higher in the SCS group (35%) than in the ICS (28%) or control (10%) group. Because patients in the ICS group already had impaired respiratory function due to repeated asthma exacerbations, it was difficult to determine whether it was asthma itself or SCS that is the risk factor for osteoporosis. In addition, the response of biochemical markers of bone turnover to intermittent SCS remains unclear and likely differs from that elicited by high-dose, short-term, or continuous SCS. That said, relatively low-dose intermittent administration of SCS raised levels of bone resorption markers, which likely reflects altered bone metabolism. Taken together, these findings suggest that, without consideration of its effects on bone, SCS administration should be avoided.

A 65-year-old man was admitted to our hospital complaining of diplopia, dysarthria, difficulty in walking and progressive dysesthesia that developed in his left hand and leg. Brain MRI revealed high signal intensity regions on T2-weighted and FLAIR images of the hippocampus and the corpus amygdaloideum. After admission, the patient's neurological symptoms progressed to delirium and dementia with hallucinations. When he eventually developed severe respiratory failure requiring ventilatory support, brain MRI revealed new high signal intensity regions on T2-weighted images of the medulla oblongata and pons. Chest CT scans showed a mass under the aortic arch, and based on subsequent histopathological examination of a transesophageal endoscopic ultrasonography-guided fine needle aspiration biopsy of the tumor, a diagnosis of small cell lung cancer was made. In addition, anti-Hu antibody was found in the patient's serum, leading to a diagnosis of paraneoplastic encephalomyelitis/sensory neuropathy. One course of chemotherapy (carboplatin + etoposide) was administered; however, the protocol was not completed because the patient developed severe pneumonia. Given that neurological symptoms usually precede a diagnosis of malignancy in paraneoplastic neurological syndromes, it is important that these are considered carefully, as they may contribute to early diagnosis and treatment. Here we report a rare case of severe central hypoventilation in paraneoplastic encephalomyelitis/sensory neuropathy.

Cardiotoxicity is a known adverse reaction of high cumulative doses of anthracycline drugs. We encountered a case successfully treated without myocardial disorder. A 54-year-old man who had been given a diagnosis of small-cell lung cancer (SCLC) (extensive disease) was treated with cisplatin (CDDP) plus irinotecan (CPT-11) as first-line chemotherapy, followed by amrubicin (AMR) (30 mg/m2) for 3 consecutive days against the relapsed SCLC. The cumulative dose reached 1110 mg/m2. This case report suggests that repeated treatment with AMR may be effective for relapsed SCLC.

We successfully produced offspring of old male BDF1 mice using in vitro fertilization. Although 7 old male mice (33 months of age) were infertile and revealed frequent degeneration in the seminiferous epithelia, 4 of them had spermatozoa in the caudae epididymides. The IVF rate of their sperm with eggs from young ICR mice was very high (82.0%). The production rate of offspring was also satisfactory (61.6%). The present study indicates that the IVF method is useful for producing offspring of aged male mice.

大豆種子浸出液による牛精子の特異的な尾部凝集の成因を調べるため,大豆種子浸出液の希釈試験ならびに糖による凝集阻止試験を実施した.希釈試験では4系統の大豆について,ホルスタイン種牛6頭の精子による凝集の有無を調べたが,凝集反応が最も多く出現したのは4倍希釈で,続いて8倍,2倍,16倍,と順次少なくなり,256倍では凝集が全く見られなしった.糖による凝集阻止と試験では,7種の糖についてホルスタイン種牛4頭の精子を用いて調べたが,L-arabinose, D-galactoseおよびN-acetyl-D-galactosamineによって凝集が阻止された.以上の結果より,大豆種子浸出液による牛精子の特異的な尾部凝集は,抗原•抗体反応類似の機構によることが示唆された.