Pneumocystis jirovecii with high probability detected in bronchoalveolar lavage fluid of chemotherapy-related interstitial pneumonia in patients with lymphoma using metagenomic next-generation sequencing technology.

BACKGROUND: Previous studies achieved low microbial detection rates in lymphoma patients with interstitial pneumonia (IP) after chemotherapy. However, the metagenomic next-generation sequencing (mNGS) is a comprehensive approach that is expected to improve the pathogen identification rate. Thus far, reports on the use of mNGS in lymphoma patients with chemotherapy-related IP remain scarce. In this study, we summarized the microbial detection outcomes of lymphoma patients with chemotherapy-related IP through mNGS testing of bronchoalveolar lavage fluid (BALF). METHODS: Fifteen lymphoma patients with chemotherapy-related IP were tested for traditional laboratory microbiology, along with the mNGS of BALF. Then, the results of mNGS and traditional laboratory microbiology were compared. RESULTS: Of the 15 enrolled patients, 11 received rituximab and 8 were administered doxorubicin hydrochloride liposome. The overall microbial yield was 93.3% (14/15) for mNGS versus 13.3% (2/15) for traditional culture methods (P ≤ 0.05). The most frequently detected pathogens were Pneumocystis jirovecii (12/15, 80%), Cytomegalovirus (4/15, 26.7%), and Epstein-Barr virus (3/15, 20%). Mixed infections were detected in 10 cases. Five patients recovered after the treatment with antibiotics alone without glucocorticoids. CONCLUSION: Our findings obtained through mNGS testing of BALF suggested a high microbial detection rate in lymphoma patients with IP after chemotherapy. Notably, there was an especially high detection rate of Pneumocystis jirovecii. The application of mNGS in patients with chemotherapy-related IP was more sensitive.

CTA Imaging Features Related to Preoperative Coagulopathy in Patients with Stanford Type A Acute Aortic Dissection.

BACKGROUND: Stanford type A acute aortic dissection (TAAAD) is often accompanied by preoperative disorders of coagulation. The study aimed to evaluate the relationship between computed tomography angiography imaging features and preoperative coagulopathy in TAAAD patients. METHODS: This was a single-center retrospective review of adult patients undergoing TAAAD surgery from January 2015 to January 2019 in the Beijing Anzhen Hospital (Beijing, China). Images were obtained using preoperative enhanced computed tomography in 174 patients with TAAAD. Preoperative coagulopathy was defined as the disseminated intravascular coagulation score greater than 5. The patients were divided into coagulopathy and non-coagulopathy groups. Circumferential arc lengths of the false lumen (Fx) and true lumen (Tx) were measured at four planes (ascending aorta, thoracic-descending aorta, descending aorta and abdominal aorta). We define the value of Fx/(Tx+Fx) × 100% as tear index (TI) and take the four planes' averages to weighed the false lumen's size. By analyzing the two groups of clinical data and computed tomography angiography imaging data, potentially related factors were detected by univariate analysis and multivariate binary logistic regression analysis. RESULTS: The incidence of preoperative coagulopathy for TAAAD patients was 12.07%. In adjusted multivariate binary logistic regression analysis, white blood cell count (odds ratio [OR]: 1.204, 95% confidence interval [CI]: 1.035-1.400, P = 0.016); longitude length of aortic dissection (OR: 1.076, 95% CI: 1.016-1.139, P = 0.012); and Tear index (OR = 1.177, 95% CI: 1.075-1.289, P < 0.001) were significant factors related to the occurrence of preoperative coagulopathy for TAAAD. CONCLUSIONS: The incidence of preoperative coagulopathy in TAAAD patients was 12.07%. The longitude length of AD, TI and white blood cell count were significant factors related to preoperative coagulopathy in patients with TAAAD. The significance of imaging and anatomic changes related to coagulopathy are worth further study in TAAAD patients.

Pretreatment Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio as Prognostic Factors and Reference Markers of Treatment Options for Locally Advanced Squamous Cell Carcinoma Located in the Middle and Upper Esophagus.

BACKGROUND: Various inflammatory biomarkers, such as the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), have been well authenticated to predict clinical outcomes in numerous types of cancer. The optimal treatment for patients with locally advanced esophageal squamous cell carcinoma (ESCC) located in the middle or upper region is still inconclusive. The aim of the study was to examine pretreatment NLR and PLR to select from radical surgery or definitive chemoradiotherapy (dCRT) for these patients. The linkage between pretreatment NLR/PLR and prognosis was also analyzed. METHODS: NLR and PLR were calculated in 113 locally advanced ESCC located in the middle or upper esophagus of patients who underwent radical surgery or dCRT between January 2014 and December 2019. A receiver operating characteristic curve was plotted to select the best cut-off value of NLR and PLR for predicting survival. A survival curve was plotted using the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were applied to assess predictors for survival. RESULTS: NLR and PLR were associated with the extent of lymph node metastasis (NLR: P = 0.045; PLR: P = 0.002). Additionally, high PLR and recurrence with distant organ metastasis were closely related (P = 0.014), and NLR was related to the tumor stage (P = 0.043). The results of the multivariate analysis revealed that NLR (>2.07) and PLR (>183.06) were independently associated with poor prognosis. It is noteworthy that surgery was associated with a superior OS compared with dCRT in the low NLR population (P = 0.045). CONCLUSION: Low pretreatment NLR patients are fit to undergo radical surgery with a substantial therapeutic benefit. Pretreatment NLR and PLR are independent predictors for patients with locally advanced ESCC located in the middle and upper esophagus who underwent radical surgery or dCRT.

Impact of autologous platelet rich plasma use on postoperative acute kidney injury in type A acute aortic dissection repair: a retrospective cohort analysis.

BACKGROUND: Perioperative coagulopathy and blood transfusion are common in patients undergoing Stanford type A acute aortic dissection (AAD) repair. The autologous platelet-rich plasmapheresis (aPRP) technique is a blood conservation approach to reduce blood transfusions and morbidity in patients at high risk of bleeding. The purpose of this study was to analyze the effect of aPRP on outcomes, especially in postoperative acute kidney injury (post-AKI), in patients undergoing AAD surgery. METHODS: Six hundred sixty patients were divided into aPRP and non-aPRP groups according to aPRP use. The primary endpoint was the difference in the incidence of post-AKI between two groups. The secondary endpoints were risk factors for post-AKI and to assess clinical outcomes. The risk factors associated with post-AKI were calculated, and all outcomes were adjusted by propensity-score matching analysis. RESULTS: A total of 272 patients (41.2%) received aPRP, whereas 388 were in the non-aPRP group. Compared to non-aPRP group, the occurrence of post-AKI increased by 14.1% (p = 0.002) and 11.1% (p = 0.010) with and without propensity adjustment in the aPRP group, respectively. The aPRP group required fewer intraoperative transfusions (p < 0.05) and shortened the duration of mechanical ventilation (p < 0.05) than those in the non-aPRP group. Multiple regression analyses showed that aPRP (odds ratio: 1.729, 95% confidence interval: 1.225-2.440; p < 0.001) was one of the independent risk factors for post-AKI. CONCLUSIONS: The use of aPRP significantly reduced intraoperative blood transfusions and decreased postoperative mortality-adjusted mechanical ventilation. However, aPRP use was independently associated with an increased hazard of post-AKI after adjusting for confounding factors.

Perioperative risk factors predict one-year mortality in patients with acute type-A aortic dissection.

OBJECTIVE: The goal of this study was to analyze perioperative risk factors to predict one- year mortality after operation for acute type A aortic dissection (AAD). METHODS: A total of 121 consecutive patients undergoing Stanford type A AAD surgery in Beijing Anzhen Hospital were enrolled. Preoperative clinical and laboratory data from patients were collected. RESULTS: Multivariable Cox regression analysis showed that significant factors associated with increased one-year mortality were elder age (year) (hazard ratio (HR) 1.0985; 95% confidence interval (CI) 1.0334-1.1677), intraoperative blood transfusion ≥2000 mL (HR 8.8081; 95% CI 2.3319-33.2709), a higher level of serum creatinine (µmol/L) at postoperative one day (HR 1.0122; 95% CI 1.0035-1.0190) and oxygenation index (OI) < 200 (mmHg) at the end of surgery (HR 5.7575; 95% CI 1.1695-28.3458). CONCLUSION: In this study, perioperative risk factors to predict one-year prognosis are age, intraoperative blood transfusion ≥2000 mL, postoperative OI < 200 mmHg and level of postoperative serum creatinine. The results aid in the comprehension of surgical outcomes and assist in the optimization of treatment strategies for those with perioperative risk factors to decrease one-year mortality.

A macrocyclic 1,4-bis(4-pyridylethynyl)benzene showing unique aggregation-induced emission properties.

A box-like macrocycle based on 1,4-bis(4-pyridylethynyl)benzene was derived in high yield. The macrocyclic fluorogen shows unique aggregation-induced emission properties.

Effects of the combination of decitabine and homoharringtonine in SKM-1 and Kg-1a cells.

The methylation inhibitor decitabine (DAC) has great therapeutic value for myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). However, DAC monotherapy is associated with relatively low rates of overall response and complete remission. Previous studies have shown promising results for combination treatment regimens including DAC. Homoharringtonine (HHT), an alkaloid from Chinese natural plants and Cephalotaxus, has demonstrated potential for leukemia treatment. Our studies have suggested that the combination of DAC and HHT has synergistic effects for inhibiting the viability of SKM-1 and Kg-1a cells. This combination leads to enhanced inhibition of colony formation and apoptosis induction compared with DAC alone in SKM-1 but not Kg-1a cells. Only high-dose DAC and HHT significantly up-regulate caspase-3 and caspase-9 and inhibit BCL-XL in the SKM-1 cell line. The combined effects of DAC plus HHT on apoptosis may not only depend on regulation of the apoptosis-related genes we examined but others as well. HHT had no demethylation effects, and HHT in combination with DAC had no enhanced effects on hypomethylation and DNMT1, DNMT3A and DNMT3B mRNA expression in SKM-1 cells. Overall, these results suggest that DAC used in combination with HHT may have clinical potential for MDS treatment.

Discriminatory detection of cysteine and homocysteine based on dialdehyde-functionalized aggregation-induced emission fluorophores.

We demonstrate a concept-proof work of using fluorescence (FL) "turn-on" probes for the discriminatory detection of cysteine (Cys) over homocysteine (Hcy). The fluorogens are provided with aggregation-induced emission (AIE) characteristic and functionalized with two aldehyde-groups (DMTPS-ALD and TPE-ALD). All the detections were carried out in a biocompatible medium (10 mM HEPES buffer and DMSO, pH 7.4). In principle, the formation of thiazinane/thiazolidine through the chemical reaction of aldehydes on the probe molecules and the residue of Cys/Hcy determines the selective recognition of Cys and Hcy over other amino acids and glucose. The FL responses originate from the AIE property of thiazinane/thiazolidine resultants, which have low solubility and precipitate (aggregate) in the detection medium. The discrimination between Cys and Hcy comes from the difference in reaction kinetics of TPE-ALD/DMTPS-ALD with Cys and Hcy, thereby the FL responses show different time courses and intensity enhancement. It is worth noting that TPE-ALD outshined the other two probes in performance with fast response, a high FL enhancement up to 16-fold, high sensitivity, and good specificity and selectivity. Moreover, its FL response threshold at 250 µM is very close to the lower limit of the normal level of Cys in human plasma, which implies that TPE-ALD could be applied as a potential indicator of Cys deficiency.