Photodynamic therapy to control microbial biofilms

Microorganisms thrive in well-organized biofilm ecosystems. Biofilm-associated cells typically show increased resistance to antibiotics and contribute significantly to treatment failure. This has prompted investigations aimed at developing advanced and novel antimicrobial approaches that could effectively overcome the shortcomings associated with conventional antibiotic therapy. Studies are ongoing to develop effective curative strategies ranging from the use of peptides, small molecules, nanoparticles to bacteriophages, sonic waves, and light energy targeting various structural and physiological aspects of biofilms. In photodynamic therapy, a light source of a specific wavelength is used to irradiate non-toxic photosensitizers such as tetrapyrroles, synthetic dyes or, naturally occurring compounds to generate reactive oxygen species that can exert a lethal effect on the microbe especially by disrupting the biofilm. The photosensitizer preferentially binds to and accumulates in the microbial cells without causing any damage to the host tissue. Currently, photodynamic therapy is increasingly being used for the treatment of oral caries and dental plaque, chronic wound infections, infected diabetic foot ulcers, cystic fibrosis, chronic sinusitis, implant device-associated infections, etc. This approach is recognized as safe, as it is non-toxic and minimally invasive, making it a reliable, realistic, and promising therapeutic strategy for reducing the microbial burden and biofilm formation in chronic infections. In this review article, we discuss the current and future potential strategies of utilizing photodynamic therapy to extend our ability to impede and eliminate biofilms in various medical conditions.     

Key benefits of dexamethasone and antibody treatment in COVID-19 hamster models revealed by single-cell transcriptomics

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Clinical Outcomes at 1 Year Following Transcatheter Left Atrial Appendage Occlusion in the United States

ObjectivesThe aim of this study was to report 1-year clinical outcomes following commercial transcatheter left atrial appendage occlusion (LAAO) in the United States.BackgroundThe National Cardiovascular Data Registry LAAO Registry was initiated to meet a condition of Medicare coverage and allow the assessment of clinical outcomes. The 1-year rates of thromboembolic events after transcatheter LAAO in such a large cohort of “real-world” patients have not been previously reported.MethodsPatients entered into the National Cardiovascular Data Registry LAAO Registry for a Watchman procedure between January 1, 2016, and December 31, 2018, were included. The primary endpoint was ischemic stroke. Key secondary endpoints included the rate of ischemic stroke or systemic embolism, mortality, and major bleeding. Major bleeding was defined as any bleeding requiring hospitalization, and/or causing a decrease in hemoglobin level > 2g/dL, and/or requiring blood transfusion that was not hemorrhagic stroke. The Kaplan-Meier method was used for 1-year estimates of cumulative event rates.ResultsThe study population consisted of 36,681 patients. The mean age was 76.0 ± 8.1 years, the mean CHA₂DS₂-VASc score was 4.8 ± 1.5, and the mean HAS-BLED score was 3.0 ± 1.1. Prior stroke was present in 25.5%, clinically relevant bleeding in 69.5%, and intracranial bleeding in 11.9%. Median follow-up was 374 days (IQR: 212-425 days). The Kaplan-Meier–estimated 1-year rate of ischemic stroke was 1.53% (95% CI: 1.39%-1.69%), the rate of ischemic stroke or systemic embolism was 2.19% (95% CI: 2.01%-2.38%), and the rate of mortality was 8.52% (95% CI: 8.19%-8.87%). The 1-year estimated rate of major bleeding was 6.93% (95% CI: 6.65%-7.21%). Most bleeding events occurred between discharge and 45 days following the procedure.ConclusionsThis study characterizes important outcomes in a national cohort of patients undergoing transcatheter LAAO in the United States. Clinicians and patients can integrate these data in shared decision making when considering this therapy.     

经鼻高流量氧气湿化治疗老年慢性阻塞性肺疾病急性加重合并呼吸衰竭的可行性研究

ObjectiveTo investigate the feasibility of transnasal heated humidified high flow nasal cannula oxygen therapy (HFNC) in the treatment of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) with respiratory failure in elderly patients. MethodsA total of 176 elderly patients with AECOPD complicated with respiratory failure who were hospitalized at Peking University Shougang Hospital from December 2016 to January 2022 were enrolled, including 82 patients in an HFNC group and 94 patients in an NPPV group. After treatment, pulse oxygen saturation (SPO₂), arterial partial pressure of carbon dioxide (PaCO₂), oxygenation index (OI), respiratory rate (RR), heart rate (HR), mean arterial pressure (MAP), comfort score, discharge rate, rate of endotracheal intubation, rate of transfer to intensive care unit (ICU), and mortality were compared between the two groups. The independent sample t-test was used for comparison between the two groups. Statistical data are expressed in percentage or number of cases and the χ² test was used for their comparisons. ResultsThe SPO₂ values at 30 min, 1 h, and 6 h were significantly higher in the HFNC group than in the NPPV group (t=-2.049,-2.618, and -3.314, P=0.043, 0.010, and 0.001, respectively). SPO₂ before discharge was significantly lower than that of the NPPV group (t=2.162, P=0.033), but OI at each time point and before discharge had no statistical significance (P＞0.05). MAP at 6 h was significantly higher in the HFNC group than in the NPPV group (t=-2.209, P=0.029), but within the normal range. HRs at 2 h and 3 h in the HFNC group were significantly higher than those of the NPPV group (t=-2.199 and -2.336, P=0.030 and 0.021, respectively). There were no significant differences in RR, HR, or MAP between the two groups at other time points and before discharge (P＞0.05). There was no significant difference in PaCO2 between the two groups (P＞0.05). Comfort score in the HFNC group was significantly higher than that of the NPPV group (t=-46.807, P＜0.001). There were no significant differences in discharge rate, ICU transfer rate, endotracheal intubation rate, and mortality between the two groups (P＞0.05). ConclusionHFNC is as effective as NPPV in treating elderly patients with AECOPD complicated with type Ⅰ or mild type Ⅱ respiratory failure, and HFNC is more comfortable than NPPV.     

Effect of a multi-disciplinary program on anthropometric and biochemical parameters in obese and overweight elementary school girls: A randomized clinical trial

Background and aimsObesity and overweight in children are associated with an increased risk of several health issues. The present study aimed to assess the effects of a multi-disciplinary program (including nutrition education using a smartphone game, physical activity, and cognitive behavioral therapy [CBT]) on the management of obesity and overweight in elementary school girls.Methods and resultsSixty-two school girls above the 85th percentile of body mass index (BMI) for age were randomly assigned to two groups. During 10 weeks of study, the intervention group received a multi-disciplinary intervention, including nutrition education using a smartphone game, aerobic exercise, and CBT. The control group received usual traditional nutritional education. Biochemical and metabolic factors were assessed, including fasting blood sugar (FBS), lipid profile, serum leptin, and anthropometric measurements. The Dutch Eating Behavior Questionnaire (DEBQ) and metabolic equivalent test (MET) were also conducted. The intervention group showed more promising results in weight loss, waist circumference (WC), hip circumference (HC), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and FBS compared to the control group (P < 0.05). In addition, MET and DEBQ scores in all three sections of emotions, stimuli, and restriction were better in the intervention group than in the control group (P < 0.05). However, there was no significant difference between groups regarding the results of serum leptin and waist-to-hip ratio (WHR; p > 0.05).ConclusionsThe results indicated that education through smartphone games could possibly affect performance in real life. In addition, the multi-disciplinary approach to childhood obesity might have better performance in most areas than the single-intervention approach in obesity management.     

Care of Seniors with Breast Cancer – Treatment Received and Refining Decision Making

AimsTreatment decisions for older patients with breast cancer are complex and evidence is largely extrapolated from younger populations. Frailty and comorbidity need to be considered. We studied the baseline characteristics and treatment decisions in older patients in Christchurch with breast cancer and assessed survival outcomes and prognostic/discriminatory performance of several tools.Materials and methodsWe searched the Canterbury Breast Cancer Registry and identified patients aged 70 years or older at diagnosis with invasive, non-metastatic breast cancer between 1 June 2009 and 30 June 2015. We retrieved demographics, treatment and outcome information. Overall survival and breast cancer-specific survival were estimated. Tools analysing performance status and comorbidity were assessed for their prognostic and discriminatory power.ResultsIn total, 440 patients were identified. Primary surgery was carried out for 362 patients (82.3%): breast-conserving surgery in 114 (of whom 88.6% received radiation therapy); mastectomy in 248 (of whom 24.6% received radiation). Hormone therapy was given for 265 (71.1%) patients with oestrogen receptor-positive cancers. Two hundred and seventy-four (62.3%) patients received full standard treatment, which was associated with significantly improved 5-year survival and 5-year breast cancer-specific survival. The median estimated overall survival was 8.2 years (95% confidence interval 7.3–9.1 years). Of those who died, 71.3% of deaths were due to causes other than breast cancer or unknown causes. The comorbidity-adjusted life expectancy (CALE) showed partial prognostic accuracy. CALE, Charlson and Eastern Cooperative Oncology Group tools all showed discriminatory value.ConclusionIn this population-based series of older patients with breast cancer, showing high levels of primary and adjuvant treatment, patients were more likely to die of causes other than breast cancer. Performance status and comorbidity tools showed prognostic and discriminatory potential in this population supporting their use in treatment decision making. CALE showed the most potential to improve treatment decisions but requires validation in this population to improve prognostic accuracy.     

Efficient polymer nanoparticle-mediated delivery of gene editing reagents into human hematopoietic stem and progenitor cells

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Outcomes and risk management in type B aortic dissection patients with acute kidney injury: a concise review

PurposeType B aortic dissection is a rare but life-threatening disease. Thoracic endovascular aortic repair (TEVAR) was widely used for Type B aortic dissection patients in the last decade due to the lower mortality and morbidity compared with open chest surgical repair (OCSR). AKI in type B aortic dissection is a well-recognized complication and indicates poor short-term and long-term outcome. The objective of this concise review was to identify the risk factors and the impact of AKI on type B aortic dissection patients.Methods and resultsA literature search was performed using PubMed, Embase, MEDLINE, and Cochrane Library with the search terms ‘type B aortic dissection’ and ‘acute kidney injury’ (AKI), and all English-language literatures published in print or available online from inception through August 2020 were thoroughly reviewed. Studies that reported relative AKI risks and outcomes in type B aortic dissection patient were included. Major mechanisms of AKI in type B aortic dissection included renal hypoperfusion, inflammation response, and the use of contrast medium. Type B aortic dissection patients with AKI significantly had increased hospital stay duration, need of renal replacement therapy, and 30-d and 1-year mortality.ConclusionsAKI in type B aortic dissection is a well-recognized complication and associated with poor short-term and long-term outcome. Early identification of high-risk patients, early diagnosis of AKI, stabilization of the hemodynamic parameters, avoidance of nephrotoxic drugs, and optimization of the use of contrast agents are the major strategies for the reduction of AKI in type B aortic dissection patients.     

Anticoagulation Strategies in Patients With Cancer: JACC Review Topic of the Week

Patients with active cancer are at an increased risk of arterial and venous thromboembolism (VTE) and bleeding events. Historically, in patients with cancer, low molecular weight heparins have been preferred for treatment of VTE, whereas warfarin has been the standard anticoagulant for stroke prevention in patients with atrial fibrillation (AF). More recently, direct oral anticoagulants (DOACs) have been demonstrated to reduce the risk of venous and arterial thromboembolism in large randomized clinical trials of patients with VTE and AF, respectively, thus providing an attractive oral dosing option that does not require routine laboratory monitoring. In this review, we summarize available clinical trial data and guideline recommendations, and outline a practical approach to anticoagulation management of VTE and AF in cancer.     

宝石CT碘-水基图在急性脑梗死介入治疗后的应用

目的探讨宝石CT碘-水基图在急性脑梗死介入治疗后的诊断价值。方法 31例急性脑梗死患者介入治疗后即刻宝石CT平扫QC图发现颅内异常高密度影,采用碘-水基图进行重建分析,同时测定高密度影碘基值、水基值,并与术后24 h普通CT复查诊断结果作比较。结果通过采用碘-水基图,17例诊断为碘对比剂渗出,14例诊断为脑出血转化,与术后24 h普通CT复查诊断结果完全一致(Kappa=1,P0.01);术后即刻碘基图之碘基值:碘对比剂渗出(32.09±5.36) g/L,脑出血转化(6.86±2.26) g/L,二者差异有统计学意义(t=53.291,P0.01);术后即刻水基图之水基值:碘对比剂渗出(1 027.93±8.29) g/L,脑出血转化(1 069.68±7.18) g/L,二者差异有统计学意义(t=-8.897,P0.01)。结论宝石CT碘-水基图可以准确诊断急性脑梗死介入治疗后颅内碘对比剂渗出和脑出血转化,值得向临床介绍推广。