Two Decades of Advances and Limitations in Organ Recellularization.

The recellularization of tissues after decellularization is a relatively new technology in the field of tissue engineering (TE). Decellularization involves removing cells from a tissue or organ, leaving only the extracellular matrix (ECM). This can then be recellularized with new cells to create functional tissues or organs. The first significant mention of recellularization in decellularized tissues can be traced to research conducted in the early 2000s. One of the landmark studies in this field was published in 2008 by Ott, where researchers demonstrated the recellularization of a decellularized rat heart with cardiac cells, resulting in a functional organ capable of contraction. Since then, other important studies have been published. These studies paved the way for the widespread application of recellularization in TE, demonstrating the potential of decellularized ECM to serve as a scaffold for regenerating functional tissues. Thus, although the concept of recellularization was initially explored in previous decades, these studies from the 2000s marked a major turning point in the development and practical application of the technology for the recellularization of decellularized tissues. The article reviews the historical advances and limitations in organ recellularization in TE over the last two decades.

Adipose-Derived Stem Cells: Angiogenetic Potential and Utility in Tissue Engineering.

Adipose tissue (AT) is a large and important energy storage organ as well as an endocrine organ with a critical role in many processes. Additionally, AT is an enormous and easily accessible source of multipotent cell types used in our day for all types of tissue regeneration. The ability of adipose-derived stem cells (ADSCs) to differentiate into other types of cells, such as endothelial cells (ECs), vascular smooth muscle cells, or cardiomyocytes, is used in tissue engineering in order to promote/stimulate the process of angiogenesis. Being a key for future successful clinical applications, functional vascular networks in engineered tissue are targeted by numerous in vivo and ex vivo studies. The article reviews the angiogenic potential of ADSCs and explores their capacity in the field of tissue engineering (TE).

Preload dependence indices to titrate volume expansion during septic shock: a randomized controlled trial.

INTRODUCTION: In septic shock, pulse pressure or cardiac output variation during passive leg raising are preload dependence indices reliable at predicting fluid responsiveness. Therefore, they may help to identify those patients who need intravascular volume expansion, while avoiding unnecessary fluid administration in the other patients. However, whether their use improves septic shock prognosis remains unknown. The aim of this study was to assess the clinical benefits of using preload dependence indices to titrate intravascular fluids during septic shock. METHODS: In a single-center randomized controlled trial, 60 septic shock patients were allocated to preload dependence indices-guided (preload dependence group) or central venous pressure-guided (control group) intravascular volume expansion with 30 patients in each group. The primary end point was time to shock resolution, defined by vasopressor weaning. RESULTS: There was no significant difference in time to shock resolution between groups (median (interquartile range) 2.0 (1.2 to 3.1) versus 2.3 (1.4 to 5.6) days in control and preload dependence groups, respectively). The daily amount of fluids administered for intravascular volume expansion was higher in the control than in the preload dependence group (917 (639 to 1,511) versus 383 (211 to 604) mL, P = 0.01), and the same held true for red cell transfusions (178 (82 to 304) versus 103 (0 to 183) mL, P = 0.04). Physiologic variable values did not change over time between groups, except for plasma lactate (time over group interaction, P <0.01). Mortality was not significantly different between groups (23% in the preload dependence group versus 47% in the control group, P = 0.10). Intravascular volume expansion was lower in the preload dependence group for patients with lower simplified acute physiology score II (SAPS II), and the opposite was found for patients in the upper two SAPS II quartiles. The amount of intravascular volume expansion did not change across the quartiles of severity in the control group, but steadily increased with severity in the preload dependence group. CONCLUSIONS: In patients with septic shock, titrating intravascular volume expansion with preload dependence indices did not change time to shock resolution, but resulted in less daily fluids intake, including red blood cells, without worsening patient outcome. TRIAL REGISTRATION: Clinicaltrials.gov NCT01972828. Registered 11 October 2013.

What is the optimal remifentanil dosage for providing excellent intubating conditions when coadministered with thiopental? A prospective randomized dose-response study.

BACKGROUND AND OBJECTIVE: The aim of the present study was to determine the dosage of remifentanil that must be added to thiopental 5 mg kg(-1) to provide excellent intubating conditions in 95% of patients. METHODS: Sixty-eight premedicated female American Society of Anesthesiologists class 1 and 2 patients were randomly allocated to four remifentanil dose groups (3, 4, 5 or 6 microg kg(-1)). Induction of anaesthesia was performed with a blinded dose of remifentanil infused over 60 s, simultaneously coadministered with thiopental 5 mg kg(-1) infused over 20 s; and tracheal intubation was attempted 150 s after the beginning of induction. The intubating conditions were assessed with the Copenhagen score, according to jaw relaxation, resistance to laryngoscope, vocal cord position and movements and reaction to cuff inflation. A probit analysis was performed to calculate the intubating efficient doses (IEDs) of remifentanil in 50 and 95% of patients (IED50 and IED95). Haemodynamic tolerance was also analysed. RESULTS: The IED95 of remifentanil was 7.8 microg kg(-1) (95% confidence interval 5.9-10.9). Although the maximum decrease in heart rate and mean arterial pressure was less than 30% during induction of anaesthesia, the haemodynamic tolerance of such a relaxant-free protocol for anaesthesia providing excellent intubating conditions in 95% of patients when using remifentanil and thiopental could not be assessed, as the IED95 of remifentanil was more than 6 microg kg(-1). CONCLUSION: The dosage of remifentanil providing excellent intubating conditions in 95% of patients when coadministered with thiopental 5 mg kg(-1) in healthy premedicated female patients undergoing elective surgery was more than 7 microg kg(-1). Our results question the feasibility of using thiopental for a relaxant-free protocol for anaesthesia.

Open lung biopsy in nonresolving ARDS frequently identifies diffuse alveolar damage regardless of the severity stage and may have implications for patient management.

PURPOSE: The aim of the present study was to assess the rate of diffuse alveolar damage (DAD) on open lung biopsy (OLB) performed in the ICU for nonresolving ARDS. METHODS: A single-center retrospective study of patients meeting the Berlin definition criteria for ARDS who had undergone OLB for nonresolving ARDS. Patients were classified into mild, moderate and severe ARDS categories and according to the presence or absence of DAD on the OLB. The ARDS categories were assessed at baseline and at the time of the OLB. The OLBs were reviewed by two pathologists blinded to the ARDS classification. The primary endpoint was the rate of DAD according to the ARDS stage in the patients with nonresolving ARDS who had OLB. The secondary endpoint was the ability of DAD to predict ARDS among all the patients who had OLB. The same clinico-histopathological confrontation was cross validated in another ICU. RESULTS: From January 1998 to August 2013, 113 patients underwent OLB for acute hypoxemic respiratory failure, 83 of whom met the inclusion criteria for ARDS. At the time the OLB was performed, 11 of these patients had mild, 56 moderate, and 16 severe ARDS, respectively. The median (1st-3rd quartiles) time to OLB was 13 (10-18) and 9 (6-14) days from the onset of respiratory symptoms and from ARDS onset, respectively, with no statistical difference between the three ARDS groups. DAD was found in 48 (58 %) patients with ARDS, 4 (36 %) in the mild, 33 (59 %) in the moderate, and 11 (69 %) in the severe stage (P = 0.23). For the 113 patients who underwent OLB, the sensitivity and specificity of DAD to the Berlin definition was 0.58 (0.46-0.69) and 0.73 (0.54-0.88), respectively. Similar results were found in the other ICU. CONCLUSIONS: DAD is present in the majority of patients with nonresolving ARDs and its frequency is no different across the three ARDS stages. On this basis, the systematic use of steroids in nonresolving ARDS is not recommended.

Laryngeal injuries and intubating conditions with or without muscular relaxation: an equivalence study.

PURPOSE: The need for muscular relaxation to improve intubating conditions and to reduce the incidence of laryngeal morbidity is still controversial. The aim of this study was to determine the incidence of symptomatic laryngeal injuries (SLI) and of acceptable intubating conditions (including both good and excellent conditions), both with and without cisatracurium during induction of anesthesia, along with moderate doses of remifentanil and propofol. METHODS: In this prospective, randomized double-blind equivalence trial, the intubating conditions were compared in 130 ASA I or II female patients. All subjects received remifentanil 2 microg x kg(-1) i.v. and propofol 2.5 mg x kg(-1) i.v., with either cisatracurium 0.15 mg x kg(-1) i.v. (group Cisatracturium), or saline (group Placebo). Tracheal intubating conditions were assessed with the Copenhagen Score. A systematic screening for postoperative hoarseness and sore throat was performed 24 and 48 hr after anesthesia, followed by a nasofibroscopic examination when laryngeal symptoms persisted at 48 hr. RESULTS: Twenty-four hr after anesthesia, the incidence of postoperative hoarseness and sore throat in the Cisatracurium and Placebo groups was 26.5% and 21.5%, respectively, and 48 hr after anesthesia, the incidence was 7.8% and 6.1%, respectively (P = 0.32 and P = 0.50 between groups, respectively). In the clinically evaluable population, the incidence of SLI, assessed at 48 hr by nasofibroscopy, was equivalent in both groups, 1.6% vs 1.5% in group Placebo and group Cisatracurium, respectively (P < 0.001 for equivalence test), as was the occurrence of acceptable intubating conditions (95.4% vs 100%, P < 0.05 for equivalence test). However, the occurrence of excellent intubating conditions was more frequent in group Cisatracurium than in group Placebo (P = 0.0003). CONCLUSION: Following induction of anesthesia with propofol and moderate-dose remifentanil, cisatracurium did not confer a higher rate of good-to-excellent conditions for tracheal intubation, nor did muscle relaxation with cisatracurium decrease the rate of SLI after tracheal intubation.