Although neoadjuvant chemoradiotherapy (nCRT) is frequently used in esophageal cancer patients undergoing treatment with curative intent, it can negatively impact patients’ physical fitness. A decline in physical fitness during chemoradiotherapy may be an indication of vulnerability. The aim of this study was to evaluate whether changes in physical fitness, weight, and fat-free mass index (FFMI) during nCRT can predict the risk of postoperative pneumonia. A retrospective longitudinal observational cohort study was performed in patients who received curative treatment for esophageal cancer between September 2016 and September 2018 in a highvolume center for esophageal cancer surgery. Physical fitness (handgrip strength, leg extension strength, and exercise capacity), weight, and FFMI were measured before and after chemoradiotherapy. To be included in the data analyses, pre- and post-nCRT data had to be available of at least one of the outcome measures. Logistic regression analyses were performed to evaluate the predictive value of changes in physical fitness, weight, and FFMI during nCRT on postoperative pneumonia, as defined by the Uniform Pneumonia Scale. In total, 91 patients were included in the data analyses. Significant associations were found between the changes in handgrip strength (odds ratio [OR] 0.880, 95% confidence interval [CI]: 0.813–0.952) and exercise capacity (OR 0.939, 95%CI: 0.887–0.993) and the occurrence of postoperative pneumonia. All pneumonias occurred in patients with declines in handgrip strength and exercise capacity after nCRT. A decrease of handgrip strength and exercise capacity during nCRT predicts the risk of pneumonia after esophagectomy for cancer.Measuring physical fitness before and after chemoradiotherapy seems an adequate method to identify patients at risk of postoperative pneumonia.
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Background: Ventilation management may differ between COVID–19 ARDS (COVID–ARDS) patients and patients with pre–COVID ARDS (CLASSIC–ARDS); it is uncertain whether associations of ventilation management with outcomes for CLASSIC–ARDS also exist in COVID–ARDS. Methods: Individual patient data analysis of COVID–ARDS and CLASSIC–ARDS patients in six observational studies of ventilation, four in the COVID–19 pandemic and two pre–pandemic. Descriptive statistics were used to compare epidemiology and ventilation characteristics. The primary endpoint were key ventilation parameters; other outcomes included mortality and ventilator–free days and alive (VFD–60) at day 60. Results: This analysis included 6702 COVID–ARDS patients and 1415 CLASSIC–ARDS patients. COVID–ARDS patients received lower median VT (6.6 [6.0 to 7.4] vs 7.3 [6.4 to 8.5] ml/kg PBW; p < 0.001) and higher median PEEP (12.0 [10.0 to 14.0] vs 8.0 [6.0 to 10.0] cm H2O; p < 0.001), at lower median ΔP (13.0 [10.0 to 15.0] vs 16.0 [IQR 12.0 to 20.0] cm H2O; p < 0.001) and higher median Crs (33.5 [26.6 to 42.1] vs 28.1 [21.6 to 38.4] mL/cm H2O; p < 0.001). Following multivariable adjustment, higher ΔP had an independent association with higher 60–day mortality and less VFD–60 in both groups. Higher PEEP had an association with less VFD–60, but only in COVID–ARDS patients. Conclusions: Our findings show important differences in key ventilation parameters and associations thereof with outcomes between COVID–ARDS and CLASSIC–ARDS. Trial registration: Clinicaltrials.gov (identifier NCT05650957), December 14, 2022.
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Respiratory pathogens like Streptococcus pneumoniae can cause severe pneumonia. Nonetheless, mechanically ventilated intensive care patients, who have a high risk of contracting pneumonia, rarely develop pneumococcal pneumonia. Mechanically ventilated patients are at risk of contracting pneumonia. Therefore, these patients often receive prophylactic systemic antimicrobial therapy. Intriguingly however, a previous study showed that antimicrobial activity in bronchoalveolar aspirates (here referred to as “sputa”) from ventilated patients was only partially explained by antibiotic therapy. Here we report that sputa from these patients presented distinct proteome signatures depending on the presence or absence of antimicrobial activity. Moreover, we show that the same distinction applied to antibodies against Streptococcus pneumoniae , which is a major causative agent of pneumonia. Specifically, the investigated sputa that inhibited growth of S. pneumoniae , while containing subinhibitory levels of the antibiotic cefotaxime, presented elevated levels of proteins implicated in innate immune defenses, including complement and apolipoprotein-associated proteins. In contrast, S. pneumoniae -inhibiting sputa with relatively high cefotaxime concentrations or noninhibiting sputa contained higher levels of proteins involved in inflammatory responses, such as neutrophil elastase-associated proteins. In an immunoproteomics analysis, 18 out of 55 S. pneumoniae antigens tested showed significantly increased levels of IgGs in inhibiting sputa. Hence, proteomics and immunoproteomics revealed elevated levels of antimicrobial host proteins or S. pneumoniae antigen-specific IgGs in pneumococcal growth-inhibiting sputa, thus explaining their anti-pneumococcal activity. IMPORTANCE Respiratory pathogens like Streptococcus pneumoniae can cause severe pneumonia. Nonetheless, mechanically ventilated intensive care patients, who have a high risk of contracting pneumonia, rarely develop pneumococcal pneumonia. This suggests the presence of potentially protective antimicrobial agents in their lung environment. Our present study shows for the first time that bronchoalveolar aspirates, “sputa,” of ventilated patients in a Dutch intensive care unit were characterized by three distinct groups of proteome abundance signatures that can explain their anti-pneumococcal activity. Importantly, this anti-pneumococcal sputum activity was related either to elevated levels of antimicrobial host proteins or to antibiotics and S. pneumoniae -specific antibodies. Further, the sputum composition of some patients changed over time. Therefore, we conclude that our study may provide a novel tool to measure changes that are indicative of infection-related conditions in the lungs of mechanically ventilated patients.
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Chemical preservation is an important process that prevents foods, personal care products, woods and household products, such as paints and coatings, from undesirable change or decomposition by microbial growth. To date, many different chemical preservatives are commercially available, but they are also associated with health threats and severe negative environmental impact. The demand for novel, safe, and green chemical preservatives is growing, and this process is further accelerated by the European Green Deal. It is expected that by the year of 2050 (or even as soon as 2035), all preservatives that do not meet the ‘safe-by-design’ and ‘biodegradability’ criteria are banned from production and use. To meet these European goals, there is a large need for the development of green, circular, and bio-degradable antimicrobial compounds that can serve as alternatives for the currently available biocidals/ preservatives. Anthocyanins, derived from fruits and flowers, meet these sustainability goals. Furthermore, preliminary research at the Hanze University of Applied Science has confirmed the antimicrobial efficacy of rose and tulip anthocyanin extracts against an array of microbial species. Therefore, these molecules have the potential to serve as novel, sustainable chemical preservatives. In the current project we develop a strategy consisting of fractionation and state-of-the-art characterization methods of individual anthocyanins and subsequent in vitro screening to identify anthocyanin-molecules with potent antimicrobial efficacy for application in paints, coatings and other products. To our knowledge this is the first attempt that combines in-depth chemical characterization of individual anthocyanins in relation to their antimicrobial efficacy. Once developed, this strategy will allow us to single out anthocyanin molecules with antimicrobial properties and give us insight in structure-activity relations of individual anthocyanins. Our approach is the first step towards the development of anthocyanin molecules as novel, circular and biodegradable non-toxic plant-based preservatives.
