Organ‐ and tissue‐level biological functions are intimately linked to microscale cell–cell interactions and to the overarching tissue architecture. Together, biofabrication and organoid technologies offer the unique potential to engineer multi‐scale living constructs, with cellular microenvironments formed by stem cell self‐assembled structures embedded in customizable bioprinted geometries. This study introduces the volumetric bioprinting of complex organoid‐laden constructs, which capture key functions of the human liver. Volumetric bioprinting via optical tomography shapes organoid‐laden gelatin hydrogels into complex centimeter‐scale 3D structures in under 20 s. Optically tuned bioresins enable refractive index matching of specific intracellular structures, countering the disruptive impact of cell‐mediated light scattering on printing resolution. This layerless, nozzle‐free technique poses no harmful mechanical stresses on organoids, resulting in superior viability and morphology preservation post‐printing. Bioprinted organoids undergo hepatocytic differentiation showing albumin synthesis, liver‐specific enzyme activity, and remarkably acquired native‐like polarization. Organoids embedded within low stiffness gelatins (<2 kPa) are bioprinted into mathematically defined lattices with varying degrees of pore network tortuosity, and cultured under perfusion. These structures act as metabolic biofactories in which liver‐specific ammonia detoxification can be enhanced by the architectural profile of the constructs. This technology opens up new possibilities for regenerative medicine and personalized drug testing.
Introduction: Vulnerable or “frail” patients are susceptible to the development of delirium when exposed to triggers such as surgical procedures. Once delirium occurs, interventions have little effect on severity or duration, emphasizing the importance of primary prevention. This review provides an overview of interventions to prevent postoperative delirium in elderly patients undergoing elective surgery. Methods: A literature search was conducted in March 2018. Randomized controlled trials (RCTs) and before-and-after studies on interventions with potential effects on postoperative delirium in elderly surgical patients were included. Acute admission, planned ICU admission, and cardiac patients were excluded. Full texts were reviewed, and quality was assessed by two independent reviewers. Primary outcome was the incidence of delirium. Secondary outcomes were severity and duration of delirium. Pooled risk ratios (RRs) were calculated for incidences of delirium where similar intervention techniques were used. Results: Thirty-one RCTs and four before-and-after studies were included for analysis. In 19 studies, intervention decreased the incidences of postoperative delirium. Severity was reduced in three out of nine studies which reported severity of delirium. Duration was reduced in three out of six studies. Pooled analysis showed a significant reduction in delirium incidence for dexmedetomidine treatment, and bispectral index (BIS)-guided anaesthesia. Based on sensitivity analyses, by leaving out studies with a high risk of bias, multicomponent interventions and antipsychotics can also significantly reduce the incidence of delirium. Conclusion: Multicomponent interventions, the use of antipsychotics, BIS-guidance, and dexmedetomidine treatment can successfully reduce the incidence of postoperative delirium in elderly patients undergoing elective, non-cardiac surgery. However, present studies are heterogeneous, and high-quality studies are scarce. Future studies should add these preventive methods to already existing multimodal and multidisciplinary interventions to tackle as many precipitating factors as possible, starting in the pre-admission period.
Background Delirium is a common and serious complication in elderly patients undergoing major abdominal surgery, with significant adverse outcomes. Successful strategies or therapies to reduce the incidence of delirium are scarce. The objective of this study was to assess the role of prehabilitation in reducing the incidence of delirium in elderly patients. Methods A single-center uncontrolled before-and-after study was conducted, including patients aged 70 years or older who underwent elective abdominal surgery for colorectal carcinoma or an abdominal aortic aneurysm between January 2013 and October 2015 (control group) and between November 2015 and June 2018 (prehabilitation group). The prehabilitation group received interventions to improve patients’ physical health, nutritional status, factors of frailty and preoperative anaemia prior to surgery. The primary outcome was incidence of delirium, diagnosed with the DSM-V criteria or the confusion assessment method. Secondary outcomes were additional complications, length of stay, unplanned ICU admission, length of ICU stay, readmission rate, institutionalization, and in-hospital or 30-day mortality. Result A total of 360 control patients and 267 prehabilitation patients were included in the final analysis. The mean number of prehabilitation days was 39 days. The prehabilitation group had a higher burden of comorbidities and was more physically and visually impaired at baseline. At adjusted logistic regression analysis, delirium incidence was reduced significantly from 11.7 to 8.2% (OR 0.56; 95% CI 0.32–0.98; P = 0.043). No statistically significant effects were seen on secondary outcomes. Conclusion Current prehabilitation program is feasible and safe, and can reduce delirium incidence in elderly patients undergoing elective major abdominal surgery. This program merits further evaluation. Trial registration Dutch Trial Registration, NTR5932 .
Introduction: Revascularization is the cornerstone of the treatment of critical limb ischemia (CLI), but the number of elderly frail patients increase. Revascularization is not always possible in these patients and conservative therapy seems to be an option. The goals of this study are to analyze the 1-year quality of life (QoL) results and mortality rates of elderly patients with CLI and to investigate if conservative treatment could be an acceptable treatment option. Methods: Patients with CLI ≥70 years old were included in a prospective observational cohort study in 2 hospitals in the Netherlands between 2012 and 2016 and were divided over 3 treatment modalities: endovascular therapy, surgical revascularization, and conservative treatment. The World Health Organization Quality of Life (WHOQoL-Bref) instrument, a generic QoL assessment tool that includes components of physical, psychological, social relationships and environment, was used to evaluate QoL at baseline, 6 months, and 1 year. Results: In total, 195 patients (56% male, 33% Rutherford 4, mean age of 80) were included. Physical QoL significantly increased after surgical (10.4 vs 14.9, P < .001), endovascular (10.9 vs 13.7, P < .001), and conservative therapy (11.6 vs 13.2, P = .01) at 1 year. One-year mortality was relatively low after surgery (10%) compared to endovascular (40%) and conservative therapy (37%). Conclusion: The results of this study could not be used to designate the superior treatment used in elderly patients with CLI. Conservative treatment could be an acceptable treatment option in selected patients with CLI unfit for revascularization. Treatment of choice in elderly patients with CLI is based on multiple factors and should be individualized in a shared decision-making process.
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