Pneumocystis jiroveci pneumonia (PCP) is frequently reported in lymphoma patients treated with rituximab-contained regimens. There is a trend toward a difference in PCP risk between bi- and tri-weekly regimens. The aims of this systemic review and meta-analysis were to estimate the risk for PCP in these patients, compare the impact of different regimens on the risk, and evaluate the efficacy of prophylaxis. The cohort studies with incept up to January 2014 were retrieved from the Cochrane Library, Medline, Embase, and Web of Science databases. Studies that compared the incidence of PCP in patients with and without rituximab treatment were conducted. Studies that reported the results of prophylaxis were concentrated to evaluate the efficacy of prophylaxis. Fixed effect Mantel-Haenszel model was chosen as the main analysis method. Funnel plots were examined to estimate the potential selection bias. Egger’s test and Begg’s test were used for the determination of possible small study bias. Eleven cohort studies that met the inclusion criteria were finally included. Results indicated that rituximab was associated with a significantly increased risk for PCP (28/942 vs 5/977; risk ratio: 3.65; 95% confidence interval 1.65 to 8.07; P=0.001), and no heterogeneity existed between different studies (I2=0%). Little significant difference in PCP risk was found between bi-weekly and tri-weekly regimens (risk ratio: 3.11; 95% confidence interval 0.92 to 10.52, P=0.068). PCP risk was inversely associated with prophylaxis in patients treated with rituximab (0/222 vs 26/986; risk ratio: 0.28; 95% confidence interval 0.09 to 0.94; P=0.039). In conclusion, PCP risk was increased significantly in lymphoma patients subjected to rituximab-contained chemotherapies. Difference in PCP risk between bi-weekly and tri-weekly regimens was not significant. Additionally, prophylaxis was dramatically effective in preventing PCP in rituximab-received lymphoma patients, suggesting that rituximab should be recommended for these patients.

Toll-like receptors (TLRs) are innate pattern recognition receptors that play a critical role in allergic inflammation, yet their contribution to autophagy in asthma remains poorly defined. Here, we investigate the role of Toll-like receptor 2 (TLR2) in phosphoinositide 3-kinases/protein kinase B (PI3K/Akt) pathway-mediated autophagy in ovalbumin-induced airway inflammation in mice. Wild-type (WT) and TLR2-knockout (TLR2) C57BL/6 mice were ovalbumin-sensitized and ovalbumin-challenged. In ovalbumin-challenged WT mice, enhanced expression of TLR2 in lung tissue, remarkable inflammatory cell infiltrates, goblet cell hyperplasia, and increased mucus production were observed. The number of inflammatory cells and interleukin-13 (IL-13) levels increased, while interferon-gamma (IFN-γ) levels decreased in bronchoalveolar lavage fluid. Expression of PI3K, phospho-Akt, Beclin-1 and LC3-II was enhanced significantly. These changes were mitigated dose-dependently in 3-methyl adenine-treated mice. In contrast, similar but weaker changes were found in ovalbumin-challenged TLR2 mice, and the changes were not significantly attenuated by 3-methyl adenine treatment. These results indicate that TLR2 confers a pivotal role in allergic airway inflammation via regulating the PI3K/Akt signaling pathway-related autophagy in mice.

Increased D-dimer levels suggested a shorter survival time in SCLC patients. Pre-treatment D-dimer level is useful in estimating the prognosis of patients with SCLC.

Chronic obstructive pulmonary disease (COPD) is one of the common chronic airway obstructive diseases, characterized by persistent respiratory symptoms and airflow limitation. Chronic respiratory diseases was recognised as the third leading cause of death in 2017 and COPD was the most common cause of chronic respiratory disease-attributable deaths. 1 It is estimated that COPD will become the fourth largest cause of death in the world and potentially the direct cause of 4.4 million deaths. 2 This will place a significant burden on economic and healthcare systems throughout the world. Although the inflammation in the early stage of COPD only involves the trachea and lung, hypoxia and further acute inflammation are systemic. In acute exacerbation stage,

Background COVID-19 has spread worldwide and become a pandemic. We report the epidemiological and clinical characteristics of cluster infections. Methods Data of clustered cases were retrieved from the public health emergency monitoring information system of China. We analyzed the incubation period, generation gap, secondary attack rate, and viral load in various grouped cases. Results A total of 60 COVID-19 infection clusters including 226 patients and 19 asymptomatic cases involving four generations were analyzed. With the increase of transmission generations, secondary attack rate decreased ( P ＜0.001) and severity alleviated ( P = 0.008). The median incubation period and intergenerational interval were 9 and 6 days, respectively. The secondary attack rate was 7.1% in the index cases, 5.0% in the first generation, 1.0% in the second generation, and 4.7% overall. Severe cases were seen more in the index (13, 65%) and first generation (7, 35%) ones, who had a significantly higher viral load than the mild and moderate ones. Conclusions With the increase of transmission generation, secondary infection rate and severity decreased. Severe patients had a higher virus load. Patients in the incubation period and asymptomatic carriers were potential infection sources who might play an important role in transmission.

No abstract

Itaconate has emerged as a novel anti-inflammatory and antioxidative endogenous metabolite, yet its role in allergic airway inflammation (AAI) and the underlying mechanism remains elusive. Here, the itaconate level in the lung was assessed by High Performance Liquid Chromatography (HPLC), and the effects of the Irg1/itaconate pathway on AAI and alveolar macrophage (AM) immune responses were evaluated using an ovalbumin (OVA)-induced AAI model established by wild type (WT) and Irg1−/− mice, while the mechanism of this process was investigated by metabolomics analysis, mitochondrial/cytosolic protein fractionation and transmission electron microscopy in the lung tissues. The results demonstrated that the Irg1 mRNA/protein expression and itaconate production in the lung were significantly induced by OVA. Itaconate ameliorated while Irg1 deficiency augmented AAI, and this may be attributed to the fact that itaconate suppressed mitochondrial events such as NLRP3 inflammasome activation, oxidative stress and metabolic dysfunction. Furthermore, we identified that the Irg1/itaconate pathway impacted the NLRP3 inflammasome activation and oxidative stress in AMs. Collectively, our findings provide evidence for the first time, supporting the conclusion that in the allergic lung, the itaconate level is markedly increased, which directly regulates AMs’ immune responses. We therefore propose that the Irg1/itaconate pathway in AMs is a potential anti-inflammatory and anti-oxidative therapeutic target for AAI.

PurposesTo evaluate the diagnostic efficiency of metagenomics next generation sequencing (mNGS) assay in severe leptospirosis and its role on prognosis. Methods We retrospectively reviewed the medical records of patients with confirmed leptospirosis from Jan. 1, 2019 to Dec. 31, 2021 from three hospitals. Detailed data including socio-demographic data, clinical manifestations, laboratory examination results, CT images etc. were collected and analyzed. Results Six severe cases were included in this study. All were diagnosed by positive mNGS results. Three of the patients were also polymerase chain reaction examined and presented negative results. Five patients were diagnosed by mNGS assay within two or three days and antibiotics were down-graded to ceftriaxone in them. All of them were cured finally. One case, who was diagnosed by mNGS late on day 5, died. Conclusions mNGS is highly efficient in diagnosing leptospirosis and could possibly reduce the mortality rate if used at an early stage.