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[Purpose] In the present study, we investigated the effects of regular aerobic training with different intensities and durations on new indices of arterial stiffness measured via an upper-arm oscillometric device. [Participants and Methods] We gathered data from 41 middle-aged and older people (age 65.0 ± 11.7 years). Participants were randomly divided into five groups: (1) 15 minutes of low intensity aerobic training (n=10); (2) 30 minutes of low intensity training (n=7); (3) 15 minutes of moderate-intensity training (n=9); (4) 30 minutes of moderate-intensity training (n=8); and (5) a non-training group (n=7). Training was conducted for 8 weeks, three times per week. Arterial pulse wave index, arterial pressure-volume index, brachial-ankle and heart-brachial pulse wave velocity, cardio-ankle vascular index, brachial and ankle blood pressure, heart rate, and peak oxygen uptake were measured before and after the intervention. [Results] All indicators of arterial stiffness and brachial and ankle blood pressure in the exercise groups were significantly lower after versus before the intervention. Peak oxygen uptake did not differ before versus after the intervention. [Conclusion] The present findings indicate that regular aerobic exercise may be important in reducing arterial stiffness regardless of the intensity or duration of aerobic exercise.

We compared arterial stiffness after glucose intake in active and inactive elderly people with impaired glucose tolerance and clarified whether physical activity was associated with arterial stiffness after ingestion of glucose. Twenty older adults with impaired glucose tolerance were analyzed in a cross-sectional design. Based on the international physical activity questionnaire, participants were divided into the active group (daily step count: 10,175.9 ± 837.8 steps/day, n = 10) or the inactive group (daily step count: 4,125.6 ± 485.9 steps/day, n = 10). Brachial­ankle (systemic) and heart­brachial (aortic) pulse wave velocity and cardio-ankle vascular index (systemic) were increased at 30, 60, and 90 min compared to baseline after a 75-g oral glucose tolerance test in the inactive but not the active group. Heart­brachial pulse wave velocity did not change compared to baseline after a 75-g oral glucose tolerance test in either group. The area under the curve for brachial­ankle pulse wave velocity was associated with daily living activity (r = –0.577, p = 0.008), daily step activity (r = –0.546, p = 0.013), and the daily step count (r = –0.797, p = 0.0001). The present findings indicate that physical activity or inactivity is associated with arterial stiffness following glucose ingestion.

Adult T-cell leukemia (ATL) is a tumor of CD4-positive T cells that accompanies an infection by human T-cell lymphotropic virus (HTLV-I). ATL is classified into four types-acute, lymphomatous, chronic, and smoldering. Opportunistic infections are known to occur in patients with acute or lymphomatous type ATL; however, whether patients with chronic or smoldering ATL also have a high risk of opportunistic infections is not yet known. Herein, we report a case of pneumocystis pneumonia in a patient with smoldering ATL. He was a 64-year-old man with primary complaints of cough and dyspnea on exertion. A chest radiograph showed infiltration shadows in the left lung field. He was prescribed antibiotics for pneumonia; however, his symptoms worsened, and he developed hypoxemia. White-blood cell count was 13000/μL, and 7% of atypical lymphocytes were found in the smears of peripheral blood cells. His serum β-D glucan concentration was increased to 85.9 pg/mL, and his serum tested positive for anti-HTLV-1 antibody. Chest-computed tomography revealed diffuse ground-glass opacities in the bilateral lung fields. Pneumocystis-polymerase chain reaction performed on bronchoalveolar lavage fluid confirmed pneumocystis, but atypical lymphocytes were not detected via transbronchial lung biopsy. Therefore, he was diagnosed with pneumocystis pneumonia associated with smoldering ATL. Sulfamethoxazole-trimethoprim and corticosteroid therapies were administered to treat the pneumocystis pneumonia, and his symptoms and lung shadows improved rapidly. Thus, opportunistic infections, including pneumocystis pneumonia, may be caused by smoldering ATL. In the case of atypical lymphocyte detection in peripheral-blood smears, clinicians should consider the possibility of ATL.

Atezolizumab is an immune checkpoint inhibitor that is a key drug in non-small-cell lung cancer treatment. However, it can cause immune-related adverse events, including liver injury. Several patterns of liver injury associated with immune checkpoint inhibitor therapy have been reported; however, not much is known about sclerosing cholangitis. We present here a case of lung adenocarcinoma with atezolizumab-induced secondary sclerosing cholangitis diagnosed using needle biopsy of the liver. A 77-year-old woman with lung adenocarcinoma, cT3N2M0, stage IIIA, was treated with concurrent chemoradiotherapy involving carboplatin and paclitaxel, which markedly reduced the tumor diameter. However, 5 months later, the lesion regrew, and she underwent 39 cycles of pemetrexed monotherapy. As pulmonary metastasis progressed, she was treated with atezolizumab. After 13 cycles of atezolizumab therapy, she complained of nausea. Laboratory tests showed elevated levels of the biliary tract and hepatic enzymes. Nevertheless, abdominal computed tomography and ultrasonography revealed no underlying related cause. Ultrasound-guided needle biopsy of the liver was performed, and histopathological analysis of biopsy samples showed features of sclerosing cholangitis. Further examinations were performed, and a diagnosis of atezolizumab-induced secondary sclerosing cholangitis without strictures and dilatations of the large bile ducts was established. Prednisolone was administered orally, after which the biliary tract and hepatic enzyme levels improved immediately. In patients presenting with a hepatic injury during immune checkpoint inhibitor therapy, clinicians should be aware of the possibility of immune checkpoint inhibitor-induced sclerosing cholangitis, even if the large bile ducts have no strictures and dilatations.

We examined the effects of increasing physical activity on arterial stiffness during hyperglycemia. Nineteen glucose-intolerant elderly participated in the study. We randomly assigned 10 participants to increase their daily activity in everyday life, regardless of the time or intensity, for 1 month (PAI group) (age, 74.6 ± 1.3 years; mean ± SE) and nine participants to maintain their level of activity (CON group) (age, 79.2 ± 2.1 years; mean ± SE). The 75-g oral glucose tolerance test was conducted in each participant in both groups before and after the start of the intervention to confirm glucose intolerance. Brachial-ankle pulse wave velocity and cardio-ankle vascular index significantly increased from baseline at 30, 60, and 90 min after the 75-g glucose ingestion after the intervention in the CON group (p

Background: We assessed acute effects of palatinose (isomaltulose) consumption on arterial stiffness. Increased arterial stiffness due to elevated postprandial blood glucose levels increases the risk of cardiovascular disease. Palatinose appears to suppress an increase in BG levels while securing energy, and might decrease acute increases in arterial stiffness during hyperglycemia. However, the acute effects of palatinose consumption on arterial stiffness are unknown. Methods: Ten older adults had two interventions in the following cross-over design: (i) ingestion of 25 g of glucose solution (GSI trial) and (ii) ingestion of 25 g of palatinose solution (PSI trial). Participants fasted for 12 h and then visited the laboratory. We assessed brachialankle (ba) and heartbrachial (hb) pulse wave velocity (PWV), the cardio-ankle vascular index (CAVI), brachial and ankle blood pressure, heart rate, and blood glucose levels at baseline (before ingestion) and 30, 60, and 90 min after ingestion. Results: Changes in baPWV, hbPWV, the CAVI, and ankle systolic blood pressure were significantly increased from baseline at 30, 60, and 90 min after ingestion in the GSI trial (p < 0.05), but not in the PSI trial. The changes in baPWV, hbPWV, and CAVI were significantly lower after ingestion in the PSI trial compared with the GSI trial. Blood glucose levels were significantly lower at 30 and 60 min after ingestion in the PSI trial compared with the GSI trial (p < 0.01). Conclusions: We conclude that arterial stiffness may increase after glucose ingestion, but it is not elevated after palatinose ingestion.

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.

Background: Small-cell lung cancer (SCLC) rarely coexists with pulmonary Mycobacterium avium intracellular complex (MAC) infection. The key drug for SCLC treatment is etoposide, which is metabolized by cytochrome P-450 (CYP) 3A4. Meanwhile, the key drugs for pulmonary MAC infection are clarithromycin (CAM) and rifampicin (RFP), and their metabolism influences CYP3A4. Therefore, treatment of concurrent SCLC and pulmonary MAC infection is difficult, and to the best of our knowledge, no report of treatments for concurrent SCLC and pulmonary MAC infection has been published. Patient Concerns and Diagnoses: A 65-year-old man presented to our hospital with abnormal findings of chest computed tomography: (1) a hilar region nodule in the left lung and mediastinal lymphadenopathy and (2) a thick-walled cavity lesion in the right upper lobe of the lung. After further examinations, the former lesions were diagnosed as SCLC, cT4N3M0, stage IIIC and the latter as pulmonary MAC infection, fibrocavitary disease. Interventions and Outcomes: Concurrent treatment was conducted with discontinuation of CAM and RFP before and after etoposide administration. Specifically, intravenous cisplatin and etoposide were administered on day 1 and days 1–3, respectively, and CAM, RFP, and ethambutol (EB) were administered orally on days 6–22 every 4 weeks. Concurrent radiotherapy was added to the drug administration on days 1–27 of the first cycle. The chemotherapy was continued for 4 cycles, followed by continuation of CAM and RFP administration. EB was discontinued because of optic nerve disorder. The treatments were conducted completely and safely, and both of the SCLC lesions and the MAC lesion were improved. Conclusions: Treatments for concurrent SCLC and pulmonary MAC infection may be successfully conducted with discontinuation of CAM and RFP before and after etoposide administration.

Thymic carcinomas are rare malignant tumors, located in the anterior mediastinum. For the treatment of these carcinomas, several chemotherapy regimens have been suggested, including carboplatin plus paclitaxel. However, because of the rarity of these tumors, the standard chemotherapy regimen has not yet been established. Here, we report a case of thymic carcinoma that responded to first-line carboplatin plus nanoparticle albumin-bound paclitaxel (nab-paclitaxel) therapy with continuation maintenance nab-paclitaxel monotherapy. A 78-year-old male presented to a hospital with the chief complaint of dyspnea. Cardiomegaly was detected on chest X-ray scans, and marked pericardial effusion was observed by echocardiography. Chest computed tomography scans revealed the presence of a mediastinal mass, pericardial thickening, and pericardial effusion. The serum levels of the tumor marker CYFRA 21-1 (cytokeratin-19 fragment) were elevated. Eventually, he was diagnosed with squamous cell carcinoma of the thymus, which was staged as cT4N3M0 or stage IV (according to the tumor-node-metastasis classification). Chemotherapy with carboplatin on day 1 and nab-paclitaxel on days 1, 8, and 15, every 4 weeks was initiated. After the administration of 4 cycles of this regimen, the tumor diameter appeared reduced, and the serum CYFRA 21-1 levels were normalized. After a 1-month interval, the serum CYFRA 21-1 levels increased again; therefore, maintenance nab-paclitaxel monotherapy was initiated. At the end of the treatment, the patient experienced a progression-free survival of 10.3 months. Carboplatin plus nab-paclitaxel may be an appropriate alternative first-line treatment for thymic carcinomas. Additionally, maintenance nab-paclitaxel monotherapy may prolong the progression-free survivals of patients with thymic carcinomas.

Nivolumab is an immune checkpoint inhibitor with demonstrated efficacy against several malignant tumors. Alterations in driver oncogenes such as EGFR and ALK are a poor prognostic factor in nivolumab therapy for non-small cell lung cancer (NSCLC), whereas a smoking history is a well-known, favorable prognostic factor. However, an efficacy of nivolumab therapy for multiple primary malignant tumors (MPMTs) has not been reported, and its efficacy for driver oncogene-positive NSCLC in smokers is unclear. Herein, we report the case of a patient with a history of heavy smoking who developed synchronous ALK-positive NSCLC and gastric cancer that responded to nivolumab therapy. A 76-year-old man who was a heavy smoker presented to our hospital with symptoms of hoarseness and dysphagia. He was ultimately diagnosed with ALK-positive advanced NSCLC. An ALK inhibitor (alectinib) was administered, and the lung cancer lesions showed improvement. The alectinib therapy was continued for 5 months. Thereafter, the lesions in the left lower lobe of the lung showed regrowth. During the same period, the patient experienced epigastric pain. Gastrointestinal endoscopy examination revealed gastric cancer. He was administered nivolumab to treat both the lung cancer and the gastric cancer. Two months later, both the lung lesions and the gastric lesions had diminished in size. Nivolumab therapy might be an effective therapy for synchronous MPMTs and NSCLC in heavy smokers, even if the lung cancer possesses driver oncogene mutations.

Background Small-cell lung cancer (SCLC) is known to be closely associated with smoking; therefore, never-smokers with SCLC are very rare. We conducted a retrospective study to investigate the clinicopathological features of SCLC in never-smokers. Methods We reviewed the medical charts of SCLC patients treated at our institution from December 2000 to May 2016, and identified SCLCs in never-smokers. We collected the clinicopathological data, treatment regimen, and efficacy and survival data. In addition, we compared these data with those of SCLCs in smokers. The EGFR mutations were examined in available samples of SCLCs in never-smokers. Results A total of 196 SCLC patients were reviewed, and 8 never-smokers were identified (4.1%). All of them had de novo SCLC. The median age was 71 years (range: 66–84 years), and 6 patients were female (75%). Seven patients (88%) had been exposed to environmental tobacco smoke (ETS), and the other patient was an atomic bomb survivor. Only 1 patient had an EGFR mutation (13%). The overall response rate (ORR) to anticancer treatments was 88%. The median progression-free survival (PFS) was 6.1 months (95% confidence interval: 2.6-infinity), and the median overall survival (OS) was 74.6 months (95% confidence interval: 4.8-infinity). No marked differences were found in the ORR or PFS between never-smokers and smokers. However, the OS of never-smokers was statistically longer than that of smokers (median: 17.3 months, p =0.0371). Conclusion The prognosis of SCLC in never-smokers was relatively favorable. Never-smoker SCLC with EGFR mutations was relatively rare in our population.

We present the case of a 79-year-old man who showed multiple pulmonary nodules on chest computed tomography (CT) after being treated for 6 months with ruxolitinib, an inhibitor of Janus kinase (JAK) 1 and 2, to treat primary myelofibrosis. We examined the lesions by bronchoscopy, and the biopsy specimen revealed fungus bodies of Cryptococcus with granulomatous inflammation. As a result, the patient was diagnosed with pulmonary cryptococcosis. The patient was treated with fluconazole (200 mg daily for 2 weeks) with concomitant ruxolitinib administration, but the pulmonary lesions progressed. Subsequently, the patient was treated with voriconazole (300 mg daily for 3 weeks), but the lesions worsened further. The administration of ruxolitinib was therefore discontinued, and the dosage of voriconazole was increased to 400 mg daily. Three months later, the pulmonary lesions diminished in size. The present case of pulmonary cryptococcosis occurred in a patient treated with ruxolitinib. Treatment of pulmonary cryptococcosis with concomitant JAK inhibitor administration may result in poor treatment efficacy. It might be better to stop administration of JAK inhibitors, if possible, in patients being treated for pulmonary cryptococcosis.

Background: Post-prandial hyperglycemia is associated with higher cardiovascular risk, which causes arterial stiffening and impaired function. Although post-prandial increases in blood glucose are proportional to the level of intake, the acute effects of different glucose intakes on arterial stiffness have not been fully characterized. The present study aimed to determine the acute effects of differences in glucose intake on arterial stiffness. Methods: Six healthy middle-aged and elderly individuals (mean age, 60.0 ± 12.1 years) were orally administered 15, 20, and 25 g of glucose on separate days in a randomized, controlled, cross-over fashion. Brachial-ankle pulse wave velocity, heart-brachial pulse wave velocity, cardio-ankle vascular index, brachial and ankle blood pressure, heart rate, and blood glucose and serum insulin concentrations before and 30, 60, and 90 min after glucose ingestion were measured. Results: Compared to baseline, brachial-ankle pulse wave velocity was higher at 30, 60 and 90 min after ingestion of 25 g glucose, and higher at 90 min after ingestion of 20 g glucose, but at no time points after ingestion of 15 g. Cardio-ankle vascular index was higher at 60 min than at baseline after ingestion of 25 g glucose, but not after ingestion of 15 or 20 g. Conclusions: These results suggest that brachial-ankle pulse wave velocity and cardio-ankle vascular index is affected by the quantity of glucose ingested. Proposed presently is that glucose intake should be reduced at each meal to avoid increases in brachial-ankle pulse wave velocity and cardio-ankle vascular index during acute hyperglycemia.

Background: Nivolumab is an immune checkpoint inhibitor (ICI) that has shown efficacy for treating non-small cell lung cancer and has become a standard therapy for previously treated non-small cell lung cancer. Moreover, immune-related adverse events of ICI therapy are well-known. Malignant pericardial effusions occasionally arise in patients with lung cancer. There have been a few reports of pericardial effusion in non-small cell lung cancer after nivolumab administration. However, the cause of this condition is controversial; the possibilities include serositis as an immune-related adverse event or pseudo-progression. Case Presentation: This report presents two cases of pericardial effusion with tamponade in lung cancer during treatment with nivolumab. Both patients experienced temporal increases in pericardial effusions followed by effusion regression. In one case, nivolumab administration was continued after performance of pericardiocentesis, without an increase in pericardial effusion. In the other case, temporal simultaneous increases in both the pericardial effusion and the primary tumor were detected, followed by simultaneous regression in both the effusion and the tumor. These findings support the fact that the pericardial effusions were caused by pseudo-progression. Conclusions: Pericardial effusion with tamponade can occur in lung cancer patients being treated with nivolumab; moreover, some of these effusions might be caused by pseudo-progression. In the case of putative pseudo-progression, continuation of nivolumab administration might be allowable with strict follow up.

Arterial velocity pulse index (AVI) and arterial pressure‐volume index (API), new indicators of arterial stiffness, are risk factors for the development of cardiovascular disease. Regular aerobic exercise decreases arterial stiffness. In fact, pulse wave velocity (PWV), index of arterial stiffness, is lower in endurance‐trained than in untrained young adults. However, the effect of regular aerobic exercise on AVI and API remains unknown. This study investigates the effect of regular aerobic exercise on AVI and API, new indicators of arterial stiffness. We gathered data from 18 recreationally active females (active group, age: 18 ± 1 years, 2 ± 2 h/week, 3 ± 2 times/week, ≥2 years of aerobic endurance training) and 18 recreationally inactive females (inactive group, age: 18 ± 1 years, ≥2 years without such training) in a cross‐sectional study. Height, body weight, body mass index, AVI, API, brachial blood pressure, heart rate, and 20‐m multistage shuttle run test were measured in a quiet room at a temperature between 24°C and 25°C. AVI and API were lower in the active group than in the inactive group (P

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

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 an

背景. PPaciitaxel (以下TAX) の過敏反応は適切な前投薬を行うにもかかわらず起こることがある. 症例. 症例1は75歳女性. 肺腺癌stage IIIBと診断し, carboplatin (以下CBDCA) +TAX毎週投与法を開始した. 1コース目の投与初日, TAXの投与開始3分後に呼吸困難と喘鳴を生じた. TAXの投与を中止しmethyiprednisoioneを投与した結果, 速やかに症状は軽快した. 症例2は52歳男性. 肺腺癌stager IVと診断し, CBDCA+TAX毎週投与法の治療を開始した. TAXの投与2回目にあたる2コース目の初日, TAXの投与7分後より呼吸困難を生じ, TAX中止の上methyiprednisoioneとepinephrineを投与するも数分後に心肺停止となった. 蘇生術を行ったが, 蘇生後脳症をきたした. 2例とも前投薬を施行したにもかかわらず過敏反応を生じ, また2例ともTAX投与前に末梢血好酸球数が増加していた. 結論. TAXの過敏反応の予防にヒスタミン受容体拮抗剤と副腎皮質ホルモン剤を投与する方法は広く行われているが完全ではない. 重篤な転帰をたどる症例が存在することを認識しておくべきである.

A 19-year-old man was admitted due to acute respiratory failure. He had started cigarette smoking (CS) about three weeks prior to onset. Multiple nodular shadows and patchy infiltrations were found on chest computed tomography. His respiratory state improved promptly by intravenous methylprednisolone. He resumed CS soon after discharge without any symptoms. We suspected CS-induced acute eosinophilic pneumonia and performed broncho-alveolar lavage (BAL) about one month after onset. The proportion of eosinophils in BAL fluid was 72%. A second BAL was performed about 18 months after onset and BAL fluid included no eosinophils, despite the fact that he had continued CS.

An 80-year-old man was admitted because of dyspnea on effort. We suspected an acute exacerbation of chronic heart failure and idiopathic interstitial pneumonia caused by right-sided pneumonia. A nodular shadow in right upper lobe spread and consolidated into the airspace, and it failed to improve despite administration of meropenem trihydrate, vancomycin hydrochloride and clindamycin. A definitive diagnosis of Legionella micdadei pneumonia was made on the basis of this organism being isolated in culture from bronchial lavage fluid and subsequent identification of Legionella micdadei using DNA-DNA hybridization. The airspace consolidation gradually improved following treatment with intravenous erythromycin and minocycline hydrochloride.