Long-term risks of cardiovascular death among older patients with major hematological malignancies: a population-based cohort study from SEER database.

BACKGROUND: The objective of this study was to identify the risk of cardiovascular disease (CVD)-related death in older patients with major hematological malignancies (HM). METHODS: This study included 103,102 older patients diagnosed with 7 major types of HM between 1975 and 2018 (median follow-up: 2.7 years) from the Surveillance, Epidemiology, and End Result (SEER) database. The proportion of deaths, Fine-Gray sub-distribution hazards regression model, standardized mortality ratios (SMR) and absolute excess risk (AER) were used to evaluate the risk of CVD-related death. RESULTS: For older patients with HM, CVD-related death ranked as the second leading cause of death, surpassed only by primary malignancy. Compared to the general older population, older patients with HM had higher SMR and AER of CVD-related deaths (SMR: 1.16-1.81; AER: 41.24-308.99), heart disease-related deaths (SMR: 1.19-1.90; AER: 39.23-274.69), and cerebrovascular dis-ease-related deaths (SMR: 0.99-1.66; AER: -0.35 -24.15). The proportion of deaths and cumulative mortality increased with the passage of survival time, especially in Hodgkin lymphoma patients with stage I/II and those aged ≥85 years with chronic lymphocytic leukemia, surpassing primary malignancy. The risk of CVD-related death varied among different HM types. CONCLUSIONS: For older patients with HM, long-term cardiovascular risk management needs to be focused on while addressing the primary malignancy. IMPACT: Our results emphasize the need to manage long-term cardiovascular risk in older patients with HM, especially in those identified as high-risk cases.

Overcoming chemoresistance in non-angiogenic colorectal cancer by metformin via inhibiting endothelial apoptosis and vascular immaturity.

The development of chemoresistance which results in a poor prognosis often renders current treatments for colorectal cancer (CRC). In this study, we identified reduced microvessel density (MVD) and vascular immaturity resulting from endothelial apoptosis as therapeutic targets for overcoming chemoresistance. We focused on the effect of metformin on MVD, vascular maturity, and endothelial apoptosis of CRCs with a non-angiogenic phenotype, and further investigated its effect in overcoming chemoresistance. In situ transplanted cancer models were established to compare MVD, endothelial apoptosis and vascular maturity, and function in tumors from metformin- and vehicle-treated mice. An in vitro co-culture system was used to observe the effects of metformin on tumor cell-induced endothelial apoptosis. Transcriptome sequencing was performed for genetic screening. Non-angiogenic CRC developed independently of angiogenesis and was characterized by vascular leakage, immaturity, reduced MVD, and non-hypoxia. This phenomenon had also been observed in human CRC. Furthermore, non-angiogenic CRCs showed a worse response to chemotherapeutic drugs in vivo than in vitro. By suppressing endothelial apoptosis, metformin sensitized non-angiogenic CRCs to chemo-drugs via elevation of MVD and improvement of vascular maturity. Further results showed that endothelial apoptosis was induced by tumor cells via activation of caspase signaling, which was abrogated by metformin administration. These findings provide pre-clinical evidence for the involvement of endothelial apoptosis and subsequent vascular immaturity in the chemoresistance of non-angiogenic CRC. By suppressing endothelial apoptosis, metformin restores vascular maturity and function and sensitizes CRC to chemotherapeutic drugs via a vascular mechanism.

Metformin enhances T lymphocyte anti-tumor immunity by increasing the infiltration via vessel normalization.

Abnormal tumor vasculature blocks the extravasation of T lymphocytes into the tumor, thereby suppressing anti-tumor immunity. Recently, metformin has been shown to affect tumor vasculature and enhance T lymphocyte anti-tumor immunity. However, whether or how metformin affects T lymphocyte anti-tumor immunity via a vascular mechanism remains poorly understood. Herein, we show that a large number of CD8+ lymphocytes gathered in the peri-tumoral region, while very few infiltrated the tumor. Metformin administration increased the expression of anti-tumor immunity-associated genes and the number of tumor-infiltrating CD8+ lymphocytes. Injection of CD8 but not CD4 neutralization antibody into tumor-bearing mice significantly abrogated the anti-tumor effect of metformin. Critically, CD8+ lymphocytes were found to pass through the wall of perfused vessel. Further results of immunofluorescent staining showed that metformin greatly elevated tumor perfusion, which was accompanied by increased vascular maturity in the intratumoral region (ITR) but not peritumoral region (PTR). These findings provide evidence for the vascular mechanism involved in metformin-induced enhancement of T lymphocyte anti-tumor immunity. By remodeling the abnormal tumor vasculature, also called vessel normalization metformin increases vascular maturity and tumor perfusion, thus allowing more CD8+ lymphocytes to infiltrate the tumor.

Predictors of spinal trauma care and outcomes in a resource-constrained environment: a decision tree analysis of spinal trauma surgery and outcomes in Tanzania.

OBJECTIVE: The burden of spinal trauma in low- and middle-income countries (LMICs) is immense, and its management is made complex in such resource-restricted settings. Algorithmic evidence-based management is cost-prohibitive, especially with respect to spinal implants, while perioperative care is work-intensive, making overall care dependent on multiple constraints. The objective of this study was to identify determinants of decision-making for surgical intervention, improvement in function, and in-hospital mortality among patients experiencing acute spinal trauma in resource-constrained settings. METHODS: This study was a retrospective analysis of prospectively collected data in a cohort of patients with spinal trauma admitted to a tertiary referral hospital center in Dar es Salam, Tanzania. Data on demographic, clinical, and treatment characteristics were collected as part of a quality improvement neurotrauma registry. Outcome measures were surgical intervention, American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade improvement, and in-hospital mortality, based on existing treatment protocols. Univariate analyses of demographic and clinical characteristics were performed for each outcome of interest. Using the variables associated with each outcome, a machine learning algorithm-based regression nonparametric decision tree model utilizing a bootstrapping method was created and the accuracy of the three models was estimated. RESULTS: Two hundred eighty-four consecutively admitted patients with acute spinal trauma were included over a period of 33 months. The median age was 34 (IQR 26-43) years, 83.8% were male, and 50.7% had experienced injury in a motor vehicle accident. The median time to hospital admission after injury was 2 (IQR 1-6) days; surgery was performed after a further median delay of 22 (IQR 13-39) days. Cervical spine injury comprised 38.4% of the injuries. Admission AIS grades were A in 48.9%, B in 16.2%, C in 8.5%, D in 9.5%, and E in 16.6%. Nearly half (45.1%) of the patients underwent surgery, 12% had at least one functional improvement in AIS grade, and 11.6% died in the hospital. Determinants of surgical intervention were age ≤ 30 years, spinal injury level, admission AIS grade, delay in arrival to the referral hospital, undergoing MRI, and type of insurance; admission AIS grade, delay to arrival to the hospital, and injury level for functional improvement; and delay to arrival, injury level, delay to surgery, and admission AIS grade for in-hospital mortality. The best accuracies for the decision tree models were 0.62, 0.34, and 0.93 for surgery, AIS grade improvement, and in-hospital mortality, respectively. CONCLUSIONS: Operative intervention and functional improvement after acute spinal trauma in this tertiary referral hospital in an LMIC environment were low and inconsistent, which suggests that nonclinical factors exist within complex resource-driven decision-making frameworks. These nonclinical factors are highlighted by the authors' results showing clinical outcomes and in-hospital mortality were determined by natural history, as evidenced by the highest accuracy of the model predicting in-hospital mortality.

Active ammonia-oxidizing bacteria and archaea in wastewater treatment systems.

Ammonia-oxidizing bacteria (AOB) and archaea (AOA) are two microbial groups mediating nitrification, yet little is presently known about their abundances and community structures at the transcriptional level in wastewater treatment systems (WWTSs). This is a significant issue, as the numerical abundance of AOA or AOB at the gene level may not necessarily represent their functional role in ammonia oxidation. Using amoA genes as molecular markers, this study investigated the transcriptional abundance and community structure of active AOA and AOB in 14 WWTSs. Quantitative PCR results indicated that the transcriptional abundances of AOB amoA (averaged: 1.6 × 108 copies g-1 dry sludge) were higher than those of AOA (averaged: 3.4 × 107 copies g-1 dry sludge) in all WWTSs despite several higher abundances of AOA amoA at the gene level. Moreover, phylogenetic analysis demonstrated that Nitrosomonas europaea and unknown clusters accounted for 37.66% and 49.96% of the total AOB amoA transcripts, respectively, suggesting their dominant role in driving ammonia oxidation. Meanwhile, AOA amoA transcripts were only successfully retrieved from 3 samples, and the Nitrosospaera sister cluster dominated, accounting for 83.46%. Finally, the substrate utilization kinetics of different AOA and AOB species might play a fundamental role in shaping their niche differentiation, community composition, and functional activity. This study provides a basis for evaluating the relative contributions of ammonia-oxidizing microorganisms (AOMs) to nitrogen conversions in WWTSs.

Synthesis of silver nanoplates on electrospun fibers via tollens reaction for SERS sensing of pesticide residues.

Silver nanoplates were for the first time synthesized on electrospun chitosan/polyethylene oxide (CS/PEO) fibers via tollens reaction. Ag nanoplates/CS/PEO fibers were used as the SERS-active substrates for quantitative evaluation of 2-naphthylthiol, with an enhancement factor (1.41 ± 0.07) × 106. The SERS-active substrates are flexible, stable, and easy for transportion and preservation, and act as the SERS platform for sensitive detection of the target. Thiram and thiabendazole as the representatives of pesticide residues were identified and detected by the Ag nanoplates/CS/PEO fibers, exhibiting linear response ranges from 10-11 to 10-7 M with a detection limit of 10-11 M. The Ag nanoplates/CS/PEO fibers meet the requirement of thiram detection in practical samples, such as apple, pear, tomato, and cucumber juices. The strategy revealed the feasibility of fabrication of Ag nanoplates on electrospun fibers via tollens reaction and SERS sensing of pesticides in real samples. Ag nanoplates/CS/PEO fibers were fabricated by tollens reaction and electrospinning for SERS sensing of pesticide residues with high sensitivity.

Electrospun polyacrylonitrile fibers with and without magnetic nanoparticles for selective and efficient separation of glycoproteins.

Polyacrylonitrile fibers with and without magnetic nanoparticles (Fe3O4 NPs) were prepared by electrospinning. The pure polyacrylonitrile (PAN) fibers and the composited polyacrylonitrile (PAN/Fe3O4) fibers were studied with respect to their capability for enrichment of glycoproteins. Specifically, the glycoproteins ovalbumin (OB) and transferrin (Trf) were studied and compared to the non-glycoproteins bovine serum albumin and lysozyme. Following adsorption and subsequent protein elution with 0.1 wt% of CTAB solution, the glycoproteins were analyzed by SDS polyacrylamide gel electrophoresis. The strong interaction between PAN or PAN/Fe3O4 fibers and glycoproteins is attributed to the synergistic effects of hydrophilic and hydrogen bond interactions. The PAN/Fe3O4 fibers have an attractive additional feature of allowing magnetic separation. The PAN and PAN/Fe3O4 fibers have a high adsorption capacity toward OB and Trf. The treated PAN/Fe3O4 fibers display good selectivity, fast adsorption kinetics, and were applied to extractions of mixed protein samples. The detection limits of OB and Trf are 0.32 and 0.22 µg·mL-1, respectively. The PAN/Fe3O4 fibers offered an alternative solution for adsorption of glycoproteins from biological samples. Graphical abstract The pure polyacrylonitrile (PAN) fibers and the composited polyacrylonitrile (PAN/Fe3O4) fibers were studied with respect to their capability for enrichment of glycoproteins: glycoproteins ovalbumin (OB) and transferrin (Trf). The treated PAN/Fe3O4 fibers showed fast adsorption kinetics, were applied in a physiological state, mixed and real samples.