Effect of Intratracheal Administration of Adipose-derived Stromal Cells on Bleomycin-induced Lung Injury in a Rat Model.

BACKGROUND: Mesenchymal stromal cells (MSCs) have been intensively investigated in regenerative medicine. Among the different types of MSCs, adipose tissue-derived stromal cells (ASCs) can be obtained with relatively less invasive techniques. Since ASC administration is a candidate strategy for the treatment of refractory diseases including pulmonary fibrosis, we investigated whether intratracheal injection of ASCs had therapeutic potential against bleomycin (BLM)-induced lung injury in rats. METHODS: BLM was intratracheally administered to rats, and 1 week later ASCs were harvested. Two weeks after BLM treatment, ASCs or phosphate-buffered saline (PBS) were injected autologously into the rats via the trachea A semi-quantitative histological evaluation was conducted to assess the injured lungs, followed by cell tracing at 3 or 6 weeks after BLM instillation. RESULTS: ASC administration did not affect the severity of lung damage on the third week after BLM exposure, but prevented further aggravation of the lung injury, as apparent on the sixth week. A fluorescent cell tracer revealed that the majority of ASCs did not appear to have penetrated inside the lung region injured by BLM on the third week after BLM instillation, but some of these cells sprouted deep into the thick distorted architecture of the injured lung on the sixth week after the BLM instillation. CONCLUSIONS: The results of the present study suggest that ASCs may play a role in the prevention of ongoing aggravation of lung injury in the long term.

COVID-19 vaccination benefits in preventing severe disease in mild-to-moderate cases: An analysis in the first specialized hospital for COVID-19 in Japan.

BACKGROUND: In Japan, the fourth round of coronavirus disease (COVID-19) vaccination is ongoing and is targeted at medical staff and nursing home workers, individuals aged ≥60 years, and those with comorbidities or other high-risk factors, including body mass index (BMI) ≥30 kg/m2. The incidence of severe COVID-19 decreased markedly after widespread COVID-19 vaccination drives, and our hospital experienced a similar trend. We, therefore, examined the characteristics of our patients to clarify who benefited the most from vaccination. METHODS: We retrospectively investigated all patients hospitalized for COVID-19 in Osaka City Juso Hospital between March 1, 2021, and June 30, 2022. Using multivariable logistic analysis, we calculated the adjusted odds ratios (aORs) for severe disease after vaccination in the whole dataset and in subsets stratified by age, sex, BMI, smoking history, pre-hospitalization location, and comorbidities. RESULTS: The analysis included 1041 patients. Multivariable logistic analysis showed that vaccination was associated with a low risk of severe disease, with an aOR of 0.21 (95% confidence interval: 0.12-0.36, p < 0.001). On stratifying the analysis according to background characteristics, lower aORs for severe COVID-19 were found for patients aged ≥60 years and for those with diabetes or hypertension. Notably, patients with BMI >30 kg/m2 and those with BMI ≥18 kg/m2 and ≤30 kg/m2 benefited from vaccination. CONCLUSIONS: Individuals with diabetes or hypertension and those of age ≥60 years benefited more from vaccination than did their counterparts. We recommend extending the fourth round of vaccinations to individuals with a BMI of 18-30 kg/m2.

A cross-sectional, multicenter survey of the prevalence and risk factors for Long COVID.

Long-term sequelae of the coronavirus disease (COVID-19) constitute Long COVID. Although Long COVID has been reported globally, its risk factors and effects on quality of life (QOL) remain unclear. We conducted a cross-sectional study using questionnaires and electronic medical records of COVID-19 patients who were diagnosed or hospitalized at five facilities in Japan. Responses were obtained from 285 out of 1,150 patients. More than half of the participants reported Long COVID symptoms of varying severity 1 year after COVID-19. Common sequelae included fatigue, dyspnea, alopecia, concentration problems, memory problems, sleeplessness, and joint pain, which often significantly reduced their QOL. COVID-19 severity was strongly associated with sputum production, chest pain, dyspnea, sore throat, and diarrhea, but not with fatigue, dysgeusia, anosmia, alopecia, and sleeplessness. Fatigue, dysgeusia, anosmia, alopecia, and sleeplessness affected the QOL among participants with asymptomatic or mild COVID-19 during the acute phase. Moreover, these sequelae persisted for prolonged periods.

Use of adipose tissue-derived stromal cells for prevention of esophageal stricture after circumferential EMR in a canine model.

BACKGROUND: EMR is an accepted treatment for early esophageal carcinoma. However, resection of a large mucosal area often causes postoperative esophageal stricture. OBJECTIVE: To investigate the efficacy of autologous adipose tissue-derived stromal cells (ADSCs) for prevention of stricture formation after EMR in dogs. DESIGN: Animal study. SETTING: University research center. INTERVENTION: Ten beagle dogs were randomized into a control group and an ADSCs-injected (ADSC) group. The ADSCs were isolated from autologous adipose tissue. Immediately after circumferential esophageal EMR, about 5 × 10(6) ADSCs suspended in 8 mL of phosphate-buffered saline solution were injected endoscopically into the residual submucosa of the ADSC group, whereas the control group received only 8 mL of phosphate-buffered saline solution. MAIN OUTCOME MEASUREMENTS: Dysphagia score, weight loss, rate of mucosal constriction, and histologic assessments. RESULTS: In the control and ADSC groups, the median dysphagia scores were 4 and 1 (P < .043), the mean degrees of mucosal constriction were 75.7% and 45.3% (P < .008), and the numbers of nascent microvessels in the submucosal layer were 7.4 and 16.2 per unit area (P = .007), respectively. Atrophy and fibrosis of the muscularis propria layer were observed in the control group. LIMITATIONS: Animal study, small sample size. CONCLUSION: Injection therapy with autologous ADSCs suppresses constriction of the esophageal mucosa and improves clinical symptoms after circumferential EMR in this canine model.

Neural effects of acute stress on appetite: A magnetoencephalography study.

Stress is prevalent in modern society and can affect human health through its effects on appetite. Therefore, in the present study, we aimed to clarify the neural mechanisms by which acute stress affects appetite in healthy, non-obese males during fasting. In total, 22 volunteers participated in two experiments (stress and control conditions) on different days. The participants performed a stress-inducing speech-and-mental-arithmetic task under both conditions, and then viewed images of food, during which, their neural activity was recorded using magnetoencephalography (MEG). In the stress condition, the participants were told to perform the speech-and-mental-arithmetic task again subsequently to viewing the food images; however, another speech-and-mental-arithmetic task was not performed actually. Subjective levels of stress and appetite were then assessed using a visual analog scale. Electrocardiography was performed to assess the index of heart rate variability reflecting sympathetic nerve activity. The findings showed that subjective levels of stress and sympathetic nerve activity were increased in the MEG session in the stress condition, whereas appetite gradually increased in the MEG session only in the control condition. The decrease in alpha band power in the frontal pole caused by viewing the food images was greater in the stress condition than in the control condition. These findings suggest that acute stress can suppress the increase of appetite, and this suppression is associated with the frontal pole. The results of the present study may provide valuable clues to gain a further understanding of the neural mechanisms by which acute stress affects appetite. However, since the stress examined in the present study was related to the expectation of forthcoming stressful event, our present findings may not be generalized to the stress unrelated to the expectation of forthcoming stressful event.

Decreased alpha-band oscillatory brain activity prior to movement initiated by perception of fatigue sensation.

Fatigue is a health problem prevalent in modern societies. Fatigue sensation plays an important role as a biological alarm urging rest to maintain homeostasis, and clarifying the neural mechanisms related to fatigue sensations by which we decide to engage in rest is therefore essential. This study enrolled healthy male volunteers and showed that the decrease in alpha-band power as assessed by magnetoencephalography of the left Brodmann's area (BA) 6 before perception of fatigue when a button-press based on the level of fatigue was required was smaller than that before perception of the intention to move when a voluntary button-press was required. In addition, the decrease of alpha-band power in the left BA 6 before the perception of fatigue was not altered compared with that in the right BA 6 when a button-press based on the level of fatigue was required. These results suggest that the button-press based on the perception of fatigue is not prepared before the perception of fatigue. These findings will advance the understanding of the neural mechanisms related to subjective feelings such as fatigue sensation.

Neural effects of hand-grip-activity induced fatigue sensation on appetite: a magnetoencephalography study.

It has been reported that physical activity not only increases energy expenditure, but also affects appetite. However, little remains known about the effects of physical activity-induced fatigue sensation on appetite. In the present study, classical conditioning related to fatigue sensation was used to dissociate fatigue sensation from physical activity. The participants were 20 healthy male volunteers. After overnight fasting, on day 1, the participants performed hand-grip task trials for 10 min with listening to a sound. The next day, they viewed food images with (target task) and without (control task) listening to the sound identical to that used on day 1, and their neural activity during the tasks were recorded using magnetoencephalography. The subjective levels of appetite and fatigue sensation were assessed using a visual analog scale. The subjective level of fatigue increased and that of appetite for fatty foods showed a tendency toward increase in the target task while the subjective level of fatigue and that of appetite for fatty foods were not altered in the control task. In the target task, the decrease of theta (4-8 Hz) band power in the supplementary motor area (SMA), which was observed in the control task, was suppressed, and the suppression was positively correlated with appetite for fatty foods, suggesting hand grip activity-induced fatigue sensation may increase the appetite for fatty food; this increase could be related to neural activity in the SMA. These findings are expected to contribute to the understanding of the neural mechanisms of appetite in relation to fatigue.

[A case of primary Sjögren's syndrome presenting with middle lobe syndrome complicated by nontuberculous mycobacteriosis].

A 52-year-old woman was found to have abnormal shadows in her chest radiograph in a health examination. At the age of 47 middle lobe syndrome had been pointed out and Mycobacterium intracellulare had been cultured from her sputum. Chest computed tomography scans showed a coin lesion and bronchiectasis in the middle lobe. On the other hand she suffered xerostomia and had a high level of serum anti-SS-A antibody. Further examination of her eyes and mouth gave her a diagnosis of primary Sjögren's syndrome (pSS). By video-assisted thoracoscopic surgery we resected the coin lesion which contained an abscess with acid-fast bacilli, identical to Mycobacterium intracellulare. The histopathology showed lymphocytic infiltration, caseous necrosis with Langhans' giant cells, and epithelioid granulomas. We finally made a diagnosis of pSS presenting with middle lobe syndrome (MLS) complicated by nontuberculous mycobacterial disease (NTM). We discuss the mechanism by which pSS could be complicated by NTM and MLS. Clinicians should pay attention to this possible relationship, especially among middle-aged and elderly women.

Neural activity induced by visual food stimuli presented out of awareness: a preliminary magnetoencephalography study.

Obesity is a major public health problem in modern society. Appetitive behavior has been proposed to be partially driven by unconscious decision-making processes and thus, targeting the unconscious cognitive processes related to eating behavior is essential to develop strategies for overweight individuals and obese patients. Here, we presented food pictures below the threshold of awareness to healthy male volunteers and examined neural activity related to appetitive behavior using magnetoencephalography. We found that, among participants who did not recognize food pictures during the experiment, an index of heart rate variability assessed by electrocardiography (low-frequency component power/high-frequency component power ratio, LF/HF) just after picture presentation was increased compared with that just before presentation, and the increase in LF/HF was negatively associated with the score for cognitive restraint of food intake. In addition, increased LF/HF was negatively associated with increased alpha band power in Brodmann area (BA) 47 caused by food pictures presented below the threshold of awareness, and level of cognitive restraint was positively associated with increased alpha band power in BA13. Our findings may provide valuable clues to the development of methods assessing unconscious regulation of appetite and offer avenues for further study of the neural mechanisms related to eating behavior.

[A case of primary Sjögren's syndrome complicated with lung adenocarcinoma].

A 69-year-old woman presented with headache. Her chest radiograph and computed tomographic scans showed a mass shadow causing superior vena cava syndrome. Bronchofiberscopic examination was nonproductive. The serum value of carcinoembryonic antigen was highly elevated, so we made a presumed diagnosis of primary non-small lung cancer. She also complained of dry eyes and mouth. The elevated values of serum antibodies against SS-A and SS-B and further examinations resulted in a definitive diagnosis of primary Sjögren's syndrome. Chemotherapy was not effective and she died 14 months later. Autopsy revealed that the mass shadow was a primary lung adenocarcinoma. At the age of 66 she suffered a refractory pneumothorax and her pulmonary cysts or bullae were surgically resected. Those lesions had bullae, emphysema, and alveolar septae thickened by infiltration of lymphoplasmacytic cells. Because she had complained of xerostomia for the last few decades, we associated the cysts with Sjögren's syndrome. Thoracic CT scans at that time showed a nodule next to a cystic lesion. We raise a possibility that lung cancer might derive from cystic lesions associated with Sjögren's syndrome.

[A case of interstitial pneumonia preceding microscopic polyangiitis].

We encountered a case of interstitial pneumonia preceding microscopic polyangiitis (MPA). A 64-year-old asymptomatic woman was found to have interstitial pneumonia on a chest radiograph taken during a work-up before an operation for cataract. Six months later she presented with non-productive cough, low grade fever and renal dysfunction. Interstitial pneumonia worsened with new lesions. The test for MPO-ANCA was positive, though it had been negative six months previously. The histopathology of the lung by video-assisted lung biopsy showed the usual interstitial pneumonitis pattern and small vessel pulmonary vasculitis. Renal biopsy showed necrotizing glomerulonephritis. She was given a diagnosis of MPA and was immediately treated with methylprednisolone pulse therapy and a combination of prednisolone and cyclophosphamide. She has remained stable for two years. This positive inversion of MPO-ANCA, while interstitial pneumonia advanced, was of interest concerning the etiology of MPA. We discuss the important topic of the mechanism of the development of MPA.

[A human T-cell lymphotropic virus type 1 carrier presenting with Sjögren's syndrome and bronchopneumopathy].

A 77-year-old asymptomatic woman was found to have a coin lesion on a chest radiograph. Chest computed tomography scans showed the coin lesion, bronchiectasis, tree-in-bud appearance, and ground glass opacity. The histopathology of the lung by video-assisted thoracic surgery showed organizing pneumonia, follicular bronchiolitis, and non-specific interstitial pneumonitis patterns, all of which consisted of mainly mature lymphocytes and plasma cells. She suffered from dry eyes and had a high level of serum anti-SS-A antibody. Examination of her eyes and mouth revealed Sjögren's syndrome. The patient herself and her parents were born in Nagasaki prefecture, an area where human T-cell lymphotropic virus type 1 (HTLV-1) is endemic, and her sister suffered from a hematological malignancy. She was found to be an HTLV-1 carrier. We finally made a diagnosis of an HTLV-1 carrier presenting with Sjögren's syndrome and bronchopneumopathy. This combination (HTLV-1, Sjögren's syndrome, and bronchopneumopathy) is rarely reported.

Epidermal growth factor receptor tyrosine kinase inhibitors in previously treated advanced non-small-cell lung cancer with wild-type EGFR.

INTRODUCTION: While epidermal growth factor receptor (EGFR) - tyrosine kinase inhibitors (TKIs) lead to longer progression-free survival (PFS) when compared with conventional chemotherapy in non-small-cell lung cancer (NSCLC) harboring activating EGFR mutations, the role of EGFR-TKI remains unclear in EGFR-wild-type (WT) NSCLC. AREAS COVERED: This article reviews selected data from randomized trials regarding the use of TKIs in EGFR-WT NSCLC. Nine randomized phase III trials have compared EGFR-TKI with chemotherapy in NSCLC patients in a second or later line setting. Two of these trials, TAILOR and DELTA, which were designed to investigate treatment benefits according to EGFR genotype, demonstrated that docetaxel chemotherapy displayed significantly better in progression-free survival (PFS) when compared with the EGFR-TKI erlotinib. Biomarkers to predict clinical benefits of the drug against EGFR WT tumor, and the efficacy of combination regimens using erlotinib or single-use afatinib against tumors are also covered in this article. EXPERT OPINION: Considering the modest benefits of erlotinib for EGFR-WT tumors, future studies are warranted, including the exploration of useful biomarkers and new treatment strategies for EGFT-TKI use, as well as the development of more sensitive EGFR mutation tests.

Microscopic polyangiitis after influenza vaccination.

After influenza vaccination an 83-year-old woman was referred to us because of fever and sore throat with no response to antibiotics. Chest computed tomography showed thickened bronchovascular bundles, multiple nodules with feeding vessels, and consolidation. Laboratory tests showed a high level of serum myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) and soluble interleukin-2 receptor (sIL-2R), as well as abnormal renal function and urinary sediment. Transbronchial lung biopsy revealed organizing pneumonia. We made a diagnosis of microscopic polyangiitis after influenza vaccination. Corticosteroids and cyclophosphamide were effective. Careful attention should be paid to severe adverse effects such as systemic vasculitides after influenza vaccination.

[Case report of limited form of Wegener's granulomatosis detected by a health examination with no subjective symptoms].

A 60-year-old woman with no subjective symptoms was admitted to our hospital because of chest radiograph abnormality detected by a health examination. A computed tomographic scan of the thorax showed multiple nodules in both lungs without cavitation. Other organ lesions were not detected. Specimens from transbronchial lung biopsy revealed non-specific granuloma with necrosis. Antituberculous therapy was not effective, and serum PR 3-ANCA revealed to be positive. So we performed an excisional biopsy of the lung by video-assisted thoracoscopic surgery. The specimens showed necrotizing vasculitides, and granulomata which consisted of mainly lymphocytes, epithelioid cells and Langhans' giant cells. We here report a rare case of a patient with a limited form of Wegener's granulomatosis suffering from no subjective symptoms detected by a health examination.

[Carbamazepine-induced pneumonitis definitively diagnosed by accidental readministration].

An 82-year-old man had been treated by carbamazepine for convulsions. A month later he felt febrile and malaise. Laboratory data revealed liver dysfunction, hypoxemia, and chest radiograph and computed tomography (CT) of the thorax showed ground glass opacity in both lungs and mediastinal lymphadenopathy. Analysis of bronchoalveolar lavage fluid revealed pulmonary lymphocytosis. Drug-induced lymphocyte stimulation test (DLST) for carbamazepine using peripheral blood lymphocytes was negative. We gave him a possible diagnosis of carbamazepine-induced liver damage and pneumonitis. After stopping carbamazepine, we initiated corticosteroid therapy and he recovered well. One year later he again suffered from convulsions and was treated with carbamazepine in another hospital. A week later he became febrile and suffered appetite loss, and came to our hospital. His chest radiograph and CT again showed ground glass opacity and pleural effusion in both lungs. Along with the laboratory data we established a definitive diagnosis of carbamazepine-induced pneumonitis. We discuss the mechanism of carbamazepine-induced pneumonitis in which the DLST results were negative and the challenge test was positive.

[Sucessful treatment by micafungin of pulmonary aspergillosis occurring in an old lung abscess].

A 55-year-old man, who had diabetes from age 46 years old had been treated for a lung abscess in the right upper lobe at age 51. He underwent an operation for stomach cancer at age 52. When he was 55 years old, a cavity lesion appeared in his right upper lobe at the site of the treated lung abscess. Pulmonary aspergillosis was diagnosed by bronchial biopsy. In this case, we controlled his diabetes and used micafungin which has a mechanism unlike other conventional antifungal agents. The shadow decreased and examination of the resected specimen showed that the fungus had disappeard. Pulmonary aspergillosis is an important mycosis profunda and micafungin seems to be an effective antifungal agent against it.

[A case of effective readministration of itraconazole for recurrent allergic bronchopulmonary aspergillosis].

A 67-year-old woman suffered from productive cough but not from bronchial asthma. Her peripheral blood showed eosinophilia, a high serum level of total immunoglobulin E (IgE), and elevated specific IgE and positive precipitating antibody against Aspergillus fumigatus. Her chest radiograph and computed tomography revealed infiltrative shadows but not central bronchiectasis. Fibreoptic bronchoscopy detected some mucous plugs which grew Aspergillus fumigatus on culture. We therefore made a diagnosis of allergic bronchopulmonary aspergillosis (ABPA). We treated her using only itraconazole. Her respiratory symptoms, eosinophilia, serum IgE level, and pulmonary infiltration gradually improved, but withdrawal of itraconazole exacerbated her respiratory symptom and laboratory data. Administration of itraconazole again resulted in improvement of her symptoms and laboratory data. We report a case of ABPA without bronchial asthma or central bronchiectasis and refer to our diagnostic rationale. Furthermore, we discuss the decrease of allergens by the eradication of Aspergillus fumigatus in the airway with itraconazole to reduce the allergic reaction and improve the clinical symptoms.

[Two cases of prostate cancer found primarily from lung metastatic lesions].

We report two cases of prostate cancer found primarily from a metastatic lesion appearing in a chest radiograph. Patient 1 was admitted to our hospital because his chest radiograph and chest CT showed pleural effusion on the left. Thoracocentesis and pleural biopsy were unremarkable, so he was observed as both an outpatient and an inpatient. His general condition worsened, and after the third admission, he died. His autopsy revealed prostate cancer and positive immunohistochemical reactions for PSA and PSAP in both lungs, and prostate specimens demonstrated that prostate cancer had metastasized to the lung. Patient 2 was referred for evaluation of a bilateral multiple nodular shadow in a chest radiograph, and prostate cancer was discovered. Immunohistochemical reactions for PSA and PSAP were positive in both specimens of TBLB and prostate biopsy, confirming that the multiple lung tumors were metastases from prostate cancer.