Increased neutrophils in inflammatory bowel disease accelerate the accumulation of amyloid plaques in the mouse model of Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is one of the neurodegenerative diseases and characterized by the appearance and accumulation of amyloid-ß (Aß) aggregates and phosphorylated tau with aging. The aggregation of Aß, which is the main component of senile plaques, is closely associated with disease progression. AppNL-G-F mice, a mouse model of AD, have three familial AD mutations in the amyloid-ß precursor gene and exhibit age-dependent AD-like symptoms and pathology. Gut-brain interactions have attracted considerable attention and inflammatory bowel disease (IBD) has been associated with a higher risk of dementia, especially AD, in humans. However, the underlying mechanisms and the effects of intestinal inflammation on the brain in AD remain largely unknown. Therefore, we aimed to investigate the effects of intestinal inflammation on AD pathogenesis. METHODS: Wild-type and AppNL-G-F mice at three months of age were fed with water containing 2% dextran sulfate sodium (DSS) to induce colitis. Immune cells in the brain were analyzed using single-cell RNA sequencing (scRNA-seq) analysis, and the aggregation of Aß protein in the brain was analyzed via immunohistochemistry. RESULTS: An increase in aggregated Aß was observed in the brains of AppNL-G-F mice with acute intestinal inflammation. Detailed scRNA-seq analysis of immune cells in the brain showed that neutrophils in the brain increased after acute enteritis. Eliminating neutrophils by antibodies suppressed the accumulation of Aß, which increased because of intestinal inflammation. CONCLUSION: These results suggest that neutrophils infiltrate the AD brain parenchyma when acute colitis occurs, and this infiltration is significantly related to disease progression. Therefore, we propose that neutrophil-targeted therapies could reduce Aß accumulation observed in early AD and prevent the increased risk of AD due to colitis.

Mycobacterium avium pleuritis with multiple nodules in the pleura.

As opposed to tuberculosis, pleurisy hardly develops in patients with nontuberculous mycobacteria (NTM) infection. In spite of increasing prevalence of NTM infection, little is known about thoracoscopic or pathological findings of the NTM-infected pleura. We now report the first case of NTM pleuritis with multiple granulomatous nodules in the pleura. A 74-year-old woman was admitted to our hospital due to massive effusion of the left thoracic cavity. The analysis of pleural fluid showed lymphocytic exudative effusions with increased levels of adenosine deaminase, although culture of the pleural fluid was negative. The patient accordingly underwent thoracoscopy, which revealed multiple pleural nodules. Biopsy of the nodules demonstrated epithelioid cell granulomas without caseous necrosis. In addition, culture of the biopsy specimens confirmed infection by Mycobacterium avium. As culture of pleural fluid often fails to detect NTM pathogens, demonstration of pleural nodules during thoracoscopy can contribute to prompt diagnosis and treatment of NTM pleuritis.

Splenic volume in pneumococcal pneumonia patients is associated with disease severity and mortality.

Splenectomy is a risk factor for serious pneumococcal disease like overwhelming post-splenectomy infection (OPSI). In healthy individuals with small spleen, fulminant pneumococcal infection similar to OPSI has been reported. Furthermore, it is reported that small spleen was associated with severe pneumococcal infection patients treated in an intensive care unit. However, the association between the small spleen and pneumococcal pneumonia was not investigated enough. We retrospectively analyzed patients with pneumococcal pneumonia who underwent computed tomography examination with measurement of the splenic volume at Harasanshin Hospital between 2004 and 2019. Data on their background characteristics, laboratory findings, and clinical courses were collected. 413 patients were included in the final analysis. The splenic volume was significantly lower in the moderate (P < 0.001), severe (P < 0.00005), and extremely severe (P < 0.001) pneumonia groups compared with the mild pneumonia group. Furthermore, the splenic volume was significantly lower in patients died within 30 days of pneumonia treatment (median of 73.49 versus 110.77 cm3, P < 0.005) or during hospitalization (median of 71.69 versus 111.01 cm3, P < 0.0005). Splenic volume <40 cm3 was significantly associated with mortality within 30 days and total hospital mortality as a risk factor in univariate analysis. Splenic volume <40 cm3 was an independent risk factor for mortality within 30 days (odds ratio: 5.0, 95% confidence interval: 1.2-21.1, P < 0.05) and total hospital mortality (odds ratio: 7.4, 95% confidence interval: 1.8-30.6, P < 0.01) in multivariate logistic regression analysis. These results suggest that small spleen is a risk factor for severity and mortality of pneumococcal pneumonia.

Retrospective cohort study on the safety and efficacy of docetaxel in Japanese non-small cell lung cancer patients with nondialysis chronic kidney disease stage 3b or higher.

BACKGROUND: It has been reported that 20% of lung cancer patients have renal impairment caused by chronic kidney disease (CKD). Since docetaxel is predominantly excreted by the hepatobiliary system, it is administered to non-small cell lung cancer (NSCLC) patients with renal impairment. However, few clinical data are available on the toxicity and efficacy of docetaxel for patients with nondialysis renal impairment. Furthermore, some cases of tubular nephrotoxicity caused by docetaxel in NSCLC patients have been reported. Therefore, a retrospective cohort study was conducted to assess the influence of nondialysis CKD on the toxicity and efficacy of docetaxel in NSCLC patients. METHODS: NSCLC patients who received docetaxel were assessed for renal function, occurrence of adverse events and treatment efficacy. RESULTS: A total of 34 NSCLC patients who received docetaxel were studied. Eight (23.5%) patients had nondialysis CKD stage 3b or higher, with an estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m2 . Although the differences were not statistically significant, the starting dose of docetaxel (mg/m2 ) was lower (60 mg/m2 ; 37.5% vs. 69.2%) in patients with an eGFR <45 than that in patients with an eGFR ≥45. No significant association was observed between pretreatment eGFR and hematological and nonhematological toxicities. No significant difference was observed in the disease control rate (62.5% vs. 65.4%, P = 1.000) or in the median overall survival (10.7 vs. 11.7, P = 0.735) between patients with an eGFR <45 and those with an eGFR ≥45. CONCLUSION: Docetaxel is a reasonable option for NSCLC patients with nondialysis CKD stage 3b or higher. Dose reduction of docetaxel is also a possibility for NSCLC patients with CKD stage 3b or higher.

Meteorological effects on severe hemoptysis: A hospital-based observational study.

BACKGROUND: Although some meteorological factor are likely to contribute to the onset of hemoptysis, few studies have investigated this issue, with none conducted in the Asia-Pacific region. Therefore, the present study aimed to evaluate the associations of meteorological factors with the occurrence of hemoptysis. Differences in the frequency of hemoptysis among several calendar variables were also assessed. METHODS: A total of 47 hemoptysis patients aged ≥ 20 years undergoing bronchial artery embolization in Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers from January 2012 to December 2017 were included in the study. All hemoptysis events were assembled in a single time series, and the proportion of hemoptysis days was 2.1%. The associations of meteorological variables with hemoptysis days were estimated as odds ratios with 95% confidence intervals by using multivariable-adjusted logistic regression models. The frequency of hemoptysis days was compared among several calendar variables using a chi-square test. RESULTS: Mean relative humidity was negatively associated with hemoptysis (P for trend = 0.02). The inverse association remained significant when only the hemoptysis events with no infectious lung diseases were used (P for trend=0.02). No significant difference was observed in the occurrence of hemoptysis among seasons, months, or other calendar variables (all P ≥ 0.21). CONCLUSIONS: Lower relative humidity was a significant risk factor for the development of hemoptysis. Clinicians should be aware of the potential for increases in hemoptysis events on days with low ambient humidity.

33S nuclear magnetic resonance spectroscopy of biological samples obtained with a laboratory model 33S cryogenic probe.

(33)S nuclear magnetic resonance (NMR) spectroscopy is limited by inherently low NMR sensitivity because of the quadrupolar moment and low gyromagnetic ratio of the (33)S nucleus. We have developed a 10 mm (33)S cryogenic NMR probe, which is operated at 9-26 K with a cold preamplifier and a cold rf switch operated at 60 K. The (33)S NMR sensitivity of the cryogenic probe is as large as 9.8 times that of a conventional 5 mm broadband NMR probe. The (33)S cryogenic probe was applied to biological samples such as human urine, bile, chondroitin sulfate, and scallop tissue. We demonstrated that the system can detect and determine sulfur compounds having SO(4)(2-) anions and -SO(3)(-) groups using the (33)S cryogenic probe, as the (33)S nuclei in these groups are in highly symmetric environments. The NMR signals for other common sulfur compounds such as cysteine are still undetectable by the (33)S cryogenic probe, as the (33)S nuclei in these compounds are in asymmetric environments. If we shorten the rf pulse width or decrease the rf coil diameter, we should be able to detect the NMR signals for these compounds.