Robust antibody response after a third BNT162b2 vaccine compared to the second among immunocompromised and healthy individuals,a prospective longitudinal cohort study

PurposeAs protection from COVID-19 following two doses of the BNT162b2 vaccine showed a time dependent waning, a third (booster) dose was administrated. This study aims to compare the antibody response following the third dose versus the second and to evaluate post-booster seroconversion.MethodsA prospective observational study conducted in Maccabi Healthcare Services. Serial SARS-CoV-2 Spike IgG tests, 1,2,3 and 6 months following the second vaccine dose and one month following the third were obtained. Neutralizing antibody levels were measured in a subset of participants. Per individual SARS-CoV-2 Spike IgG titer ratios were calculated one month after the booster administration compared to titers one month following the second dose and prior to booster.ResultsAmong 110 participants, 56 (51%) were women. Mean age was 61.7 ± 1.9 years and 66 (60%) were immunocompromised. One month after third dose, IgG titers were induced 7.83 (95 %CI 5.25–11.67) folds and 2.40 (95 %CI 1.90–3.03) folds compared to one month after the second, in the immunocompromised and immunocompetent groups, respectively. Of the 17 immunocompromised participants who were seronegative after the second dose, 4 (24%) became seropositive following the third. Comparing the titers prior to the third dose, an increase of 50.7 (95 %CI 32.5–79.1) fold in the immunocompromised group and 25.7 (95 %CI 19.1–34.7) fold in and immunocompetent group, was observed.ConclusionA third BNT162b2 vaccine elicited robust humoral response, superior to the response observed following the second, among immunocompetent and immunocompromised individuals.     

Dual-Energy Computed Tomography as an Adjunct in the Evaluation of Peripheral Chronic Total Occlusions: A Feasibility Study

This study investigated the role of dual-energy computed tomography (CT) for lesion characterization in patients with peripheral arterial disease manifesting with chronic total occlusions (CTOs). Forty-one symptomatic patients with CTOs underwent dual-energy CT angiography before endovascular treatment. The lesions were subsequently analyzed in a dedicated workstation, and 2 indexes—dual-energy index (DEI) and effective Z (Z_eff)—were calculated, ranging from 0.0027 to 0.321 and from 6.89 to 13.02, respectively. Statistical analysis showed a significant correlation between the DEI and Z_eff values (P < .001). The interobserver intraclass correlation coefficient was 0.91 for the mean Z_eff values and 0.86 for the mean DEI values. This technique could potentially provide useful information regarding the composition of a CTO.     

Systemic immune inflammation index in patients with recurrent aphthous stomatitis

ObjectivesRecurrent Aphthous Stomatitis (RAS) a chronic idiopathic oral mucosal disease. But yet the etiology and pathogenesis of RAS are not exactly known, it is thought that inflammation play an important role in the pathogenesis. The aim of this study is to demonstrate the role of systemic inflammation among the possible etiological factors of RAS and to find the possible diagnostic correlation between Systemic Immune Inflammation Index (SII).MethodsPatients who were consulted the otolaryngology outpatient clinic and diagnosed with RAS between 2019–2021 were retrospectively analyzed. Neutrophil/Lymphocyte Ratio (NLR), Platelet/Lymphocyte Ratio (PLR) and SII values were calculated based on the results of complete blood count. Demographic and hematological parameters between control and RAS groups were compared. The statistical significance level was considered as <0.05.ResultsThere was no statistically significant difference between the control and RAS groups in terms of sex and age distributions (p = 0.566 and p = 0.173, respectively). SII, NLR and PLR values were significantly higher in the RAS group compared to the controls (p < 0.001, p < 0.001 and p = 0.001, respectively). A very strong correlation between SII and NLR, moderately strong correlation between SII and PLR and moderate correlation between NLR and PLR values were detected (respectively ρ: 0.813, 0.719, 0.532; p-values <0.001).ConclusionSII, NLR and PLR has significantly higher levels in the RAS group compared to the control group, that it supports the role of systemic inflammation in the etiopathogenesis of RAS. In addition, the results show that SII is a valuable marker for inflammation.Level of evidence4.     

The impact of the updated EORTC/MSG criteria on the classification of hematological patients with suspected invasive pulmonary aspergillosis

ObjectivesOur aim was to evaluate the effect of the updated European Organization for Research and Treatment of Cancer (EORTC) and Mycoses Study Group 2019 definitions for invasive pulmonary aspergillosis (IPA) on patient classification and the related all-cause 12-week mortality.MethodsIn this retrospective cohort study from our tertiary care centre, we reclassified patients with haematological malignancy who underwent bronchoalveolar lavage between 2014 and 2019 for suspected IPA using the novel EORTC 2019 criteria. We performed receiver operating characteristic curve analysis to define the optimal cut-off for positive PCR and galactomannan and present survival analyses and their possible association with these diagnostic criteria through post hoc comparisons with log rank and Cox regression.ResultsFrom 323 episodes of suspected IPA in 282 patients, 73 were reclassified: 31 (42.5%) from possible to probable IPA, 5 (6.8%) from EORTC criteria not met to probable IPA, and 37 (50.7%) from EORTC criteria not met to possible IPA. Probable IPA increased therefore 11.1% (64/323, 19.8% to 100/323, 30.9%), mostly due to positive PCR (31/36, 86.1%). There was no difference in mortality between newly defined possible and probable IPA (log rank p = 0.950). Mortality was higher in probable cases with lower cycle thresholds (Ct values) versus higher Ct values (p = 0.004). Receiver operating characteristic curve analysis showed an optimal Ct value cut-off of 36.8 with a sensitivity of 75% (95% CI 64.9%–85.1%) and a specificity of 61.7% (95% CI 53.5–69.9) for 12-week mortality.DiscussionThe new EORTC criteria led to 11.1% more probable IPA diagnoses, mostly due to Aspergillus PCR. Restricting positive PCR to below a certain threshold might improve the discrimination of the new EORTC IPA categories for mortality.     

Recent advances in lipid nanoparticles for delivery of nucleic acid,mRNA, and gene editing-based therapeutics

Lipid nanoparticles (LNPs) are becoming popular as a means of delivering therapeutics, including those based on nucleic acids and mRNA. The mRNA-based coronavirus disease 2019 vaccines are perfect examples to highlight the role played by drug delivery systems in advancing human health. The fundamentals of LNPs for the delivery of nucleic acid- and mRNA-based therapeutics, are well established. Thus, future research on LNPs will focus on addressing the following: expanding the scope of drug delivery to different constituents of the human body, expanding the number of diseases that can be targeted, and studying the change in the pharmacokinetics of LNPs under physiological and pathological conditions. This review article provides an overview of recent advances aimed at expanding the application of LNPs, focusing on the pharmacokinetics and advantages of LNPs. In addition, analytical techniques, library construction and screening, rational design, active targeting, and applicability to gene editing therapy have also been discussed.     

What is the impact of zinc deficiency for pancreatectomies in patients with pancreatic ductal adenocarcinoma?

Backgroundand purpose: Zinc is an essential element for human health and plays an important role in metabolic, immunological and other biological processes. The present study was conducted to investigate the association between zinc deficiency (ZD) and the perioperative clinical course in patients with pancreatic ductal adenocarcinoma (PDAC).MethodsOf 216 patients with PDAC who underwent elective pancreatectomy between 2013 and 2017 at our institution, 206 patients with sufficient clinical data were retrospectively reviewed. The perioperative variables were compared and the risk factors associated with infectious complications were identified.ResultsZD was preoperatively present in 36 (17.5%) of 206 patients with PDAC. In the patients of the ZD group, a higher proportion of males, higher preoperative modified Glasgow prognostic scores, a higher neutrophil-to-lymphocyte ratio, and a higher occurrence of postoperative infectious complications after pancreatectomy were observed, compared to the non-ZD group. By a univariate analysis, three risk factors were significantly associated with infectious complications after pancreatectomy: ZD (vs non-ZD: p = 0.002), serum albumin <3.5 g/dl (vs ≥ 3.5 g/dl: p = 0.005), and the procedure of pancreaticoduodenectomy (vs others: p = 0.013). By multivariate logistic regression analysis, the occurrence of infectious complications was significantly associated with ZD (OR 3.430, 95%CI 1.570 to 7.490, p = 0.002) and the procedure of pancreaticoduodenectomy (OR 2.030, 95%CI 1.090 to 3.770, p = 0.025).ConclusionsThe current study newly demonstrated that ZD could serve as a preoperative predictor of infectious complications after pancreatectomies in the patients with PDAC.     

早孕期监测子宫动脉多普勒参数在预测低危人群不良妊娠结局的价值

目的 建立妊娠11~13+6周子宫动脉多普勒参数在低危人群中的正常参考值，同时评估其对不良妊娠结局的预测价值。方法 收集2019年6月至2021年6月于我院行产前超声检查的妊娠11~13+6周孕妇，根据妊娠结局分组。收集两侧子宫动脉多普勒指标，包括搏动指数（PI）、阻力指数（RI）、舒张早期是否有切迹，以及孕妇基本临床资料和胎儿出生信息，将以上相关参数进行统计学分析。结果 最终纳入800例孕妇，包括正常妊娠结局组740例和不良妊娠结局组60例。两组孕妇体质量指数（BMI）、分娩孕周和胎儿出生体质量比较，差异均有统计学意义（均P＜0.05）。随着孕周的增加，子宫动脉两侧平均搏动指数（mPI）、平均阻力指数（mRI）和两侧舒张早期切迹检出率均呈逐渐下降的趋势。ROC曲线分析显示，mPI、mRI及两侧舒张早期切迹预测妊娠结局的曲线下面积（AUC）分别为0.542、0.574、0.521，三者联合预测妊娠结局的AUC为0.648；孕妇BMI、年龄mPI、mRI及两侧舒张早期切迹预测妊娠结局的AUC为0.751。结论 建立了低危人群在妊娠11~13+6周子宫动脉多普勒参数的正常参考值范围。在妊娠11~13+6周单纯应用子宫动脉多普勒参数预测妊娠结局的价值有限，将子宫动脉参数与临床相关指标结合可提高对不良妊娠结局的预测价值。     

DNA损伤应答缺陷作为乳腺癌治疗靶点的研究进展

DNA损伤应答（DNA damage response,DDR）缺陷是近年来乳腺癌治疗研究的热门靶点之一。DDR通路负责DNA损伤后的识别、信号转导和修复,其功能异常可导致细胞的凋亡或基因组不稳定性的增加。目前进入临床研究阶段的乳腺癌DDR靶向药物主要包括多聚腺苷二磷酸核糖聚合酶[poly (ADP-ribose) polymerase,PARP]抑制剂、ATM抑制剂、CHEK1抑制剂、ATR抑制剂及WEE1抑制剂等。主要从DDR缺陷的概念、以DDR作为靶点的基本原理、DDR各类靶向药物的临床研究现状及其在临床应用中的难点与挑战等方面展开综述。     

Adherence to a Mediterranean Lifestyle and Changes in Frequency,Severity, and Localization of Pain in Older Adults

ObjectiveTo assess the association between adherence to a Mediterranean lifestyle and changes in pain, and its characteristics over time in older adults.Patients and MethodsWe analyzed data from 864 and 862 community-dwelling individuals aged 65+ years from the Study on Cardiovascular Health, Nutrition and Frailty in Older Adults in Spain (Seniors-ENRICA) Seniors-ENRICA-1 (2008–2010 to 2012) and Seniors-ENRICA-2 (2015–2017 to 2019) cohorts, with a median follow-up of 2.8 and 2.4 years, respectively. Adherence to a Mediterranean lifestyle was assessed at baseline with the 27-item Mediterranean lifestyle (MEDLIFE) index. Pain changes over time were calculated with a pain scale that assessed the frequency, severity, and the number of pain locations both at baseline and follow-up. Multivariable-adjusted relative risk ratios (RRRs) were obtained using multinomial logistic regression.ResultsIn the pooled cohorts, after a median follow-up of 2.6 years, pain worsened for 697 participants, improved for 734, and did not change for 295. Compared with the lowest category of MEDLIFE adherence, those in the highest category showed an RRR of improvement vs worsening of overall pain of 1.85 (95% CI, 1.28 to 2.67; P-trend<.001). MEDLIFE adherence was also linked to improvement in pain frequency (RRR, 1.98; 95% CI, 1.31 to 3.01; P-trend=.001), pain severity (RRR, 2.00; 95% CI, 1.33 to 3.00; P-trend=.001), and a reduction in the number of pain locations (RRR, 1.68; 95% CI, 1.13 to 2.50; P-trend=.004). Limitations of this study are the use of self-reported lifestyle data.ConclusionA Mediterranean lifestyle was associated with improvement of pain characteristics in older adults. Experimental studies should assess the efficacy of an integral lifestyle approach for the management of pain in older adults.