Cardioprotective effects of vaccination in hospitalized patients with COVID-19.

COVID-19 vaccination has been shown to prevent and reduce the severity of COVID-19 disease. The aim of this study was to explore the cardioprotective effect of COVID-19 vaccination in hospitalized COVID-19 patients. In this retrospective, single-center cohort study, we included hospitalized COVID-19 patients with confirmed vaccination status from July 2021 to February 2022. We assessed outcomes such as acute cardiac events and cardiac biomarker levels through clinical and laboratory data. Our analysis covered 167 patients (69% male, mean age 58 years, 42% being fully vaccinated). After adjustment for confounders, vaccinated hospitalized COVID-19 patients displayed a reduced relative risk for acute cardiac events (RR: 0.33, 95% CI [0.07; 0.75]) and showed diminished troponin T levels (Cohen's d: - 0.52, 95% CI [- 1.01; - 0.14]), compared to their non-vaccinated peers. Type 2 diabetes (OR: 2.99, 95% CI [1.22; 7.35]) and existing cardiac diseases (OR: 4.31, 95% CI [1.83; 10.74]) were identified as significant risk factors for the emergence of acute cardiac events. Our findings suggest that COVID-19 vaccination may confer both direct and indirect cardioprotective effects in hospitalized COVID-19 patients.

Slowing gait during turning: how volition of modifying walking speed affects the gait pattern in healthy adults.

Background: Turning during walking and volitionally modulating walking speed introduces complexity to gait and has been minimally explored. Research question: How do the spatiotemporal parameters vary between young adults walking at a normal speed and a slower speed while making 90°, 180°, and 360° turns? Methods: In a laboratory setting, the spatiotemporal parameters of 10 young adults were documented as they made turns at 90°, 180°, and 360°. A generalized linear model was utilized to determine the effect of both walking speed and turning amplitude. Results: Young adults volitionally reducing their walking speed while turning at different turning amplitudes significantly decreased their cadence and spatial parameters while increasing their temporal parameters. In conditions of slower movement, the variability of certain spatial parameters decreased, while the variability of some temporal parameters increased. Significance: This research broadens the understanding of turning biomechanics in relation to volitionally reducing walking speed. Cadence might be a pace gait constant synchronizing the rhythmic integration of several inputs to coordinate an ordered gait pattern output. Volition might up-regulate or down-regulate this pace gait constant (i.e., cadence) which creates the feeling of modulating walking speed.

Vaccination protects against acute respiratory distress syndrome (ARDS) in hospitalized patients with COVID-19.

This study aimed to analyze the effect of COVID-19 vaccination on the occurrence of ARDS in hospitalized COVID-19 patients. The study population of this retrospective, single-center cohort study consisted of hospitalized COVID-19 patients with known vaccination status and chest computed tomography imaging between July 2021 and February 2022. The impact of vaccination on ARDS in COVID-19 patients was assessed through logistic regression adjusting for demographic differences and confounding factors with statistical differences determined using confidence intervals and effect sizes. A total of 167 patients (69% male, average age 58 years, 95% CI [55; 60], 42% fully vaccinated) were included in the data analysis. Vaccinated COVID-19 patients had a reduced relative risk (RR) of developing ARDS (RR: 0.40, 95% CI [0.21; 0.62]). Consequently, non-vaccinated hospitalized patients had a 2.5-fold higher probability of developing ARDS. This risk reduction persisted after adjusting for several confounding variables (RR: 0.64, 95% CI [0.29; 0.94]) in multivariate analysis. The protective effect of COVID-19 vaccination increased with ARDS severity (RR: 0.61, 95% CI [0.37; 0.92]). Particularly, patients under 60 years old were at risk for ARDS onset and seemed to benefit from COVID-19 vaccination (RR: 0.51, 95% CI [0.20; 0.90]). COVID-19 vaccination showed to reduce the risk of ARDS occurrence in hospitalized COVID-19 patients, with a particularly strong effect in patients under 60 years old and those with more severe ARDS.

[Handover protocols in the emergency department]. / Übergabe und Übergabeschemata in der Notaufnahme.

Patient handovers are a vital juncture in the flow of medical information, and regardless of the mode of handover-oral, written, or combined-it often poses a risk of information loss. This could potentially jeopardize patient safety and influences subsequent treatment. The exchange of information in emergency care settings between paramedics and emergency personnel is particularly prone to errors due to situational specifics such as high ambient noise, the involvement of multiple disciplines, and the need for urgent decision-making in life-threatening situations. As handover training is not yet universally incorporated into education and ongoing training programs, there is a high degree of variability in how it is carried out in practice. However, strategies aimed at enhancing the handover process carry substantial potential for improving staff satisfaction, process quality, and possibly even having a positive prognostic impact.

Factors influencing the occurrence of ambulatory care sensitive conditions in the emergency department - a single-center cross-sectional study.

Background and importance: The differentiation between patients who require urgent care and those who could receive adequate care through ambulatory services remains a challenge in managing patient volumes in emergency departments (ED). Different approaches were pursued to characterize patients that could safely divert to ambulatory care. However, this characterization remains challenging as the urgency upon presentation is assessed based on immediately available characteristics of the patients rather than on subsequent diagnoses. This work employs a core set of Ambulatory Care Sensitive Conditions (core-ACSCs) in an ED to describe conditions that do not require inpatient care if treated adequately in the ambulatory care sector. It subsequently analyzes the corresponding triage levels and admission status to determine whether core-ACSCs relevantly contribute to patient volumes in an ED. Settings and participants: Single center cross-sectional analysis of routine data of a tertiary ED in 2019. Outcome measures and analysis: The proportion of core-ACSCs among all presentations was assessed. Triage levels were binarily classified as "urgent" and "non-urgent," and the distribution of core-ACSCs in both categories was studied. Additionally, the patients presenting with core-ACSCs requiring inpatient care were assessed based on adjusted residuals and logistic regression. The proportion being discharged home underwent further investigation. Main results: This study analyzed 43,382 cases of which 10.79% (n = 4,683) fell under the definition of core-ACSC categories. 65.2% of all core-ACSCs were urgent and received inpatient care in 62.8% of the urgent cases. 34.8% of the core-ACSCs were categorized as non-urgent, 92.4% of wich were discharged home. Age, triage level and sex significantly affected the odds of requiring hospital admission after presenting with core-ACSCs. The two core-ACSCs that mainly contributed to non-urgent cases discharged home after the presentation were "back pain" and "soft tissue disorders." Discussion: Core-ACSCs contribute relevantly to overall ED patient volume but cannot be considered the primary drivers of crowding. However, once patients presented to the ED with what was later confirmed as a core-ACSC, they required urgent care in 65.2%. This finding highlights the importance of effective ambulatory care to avoid emergency presentations. Additionally, the core-ACSC categories "back pain" and "soft tissue disorders" were often found to be non-urgent and discharged home. Although further research is required, these core-ACSCs could be considered potentially avoidable ED presentations. Clinical trial registration: The study was registered in the German trials register (DRKS-ID: DRKS00029751) on 2022-07-22.

Effects of Prolonged Serum Calcium Suppression during Extracorporeal Cardiopulmonary Resuscitation in Pigs.

Controlled reperfusion by monitoring the blood pressure, blood flow, and specific blood parameters during extracorporeal reperfusion after cardiac arrest has the potential to limit ischemia-reperfusion injury. The intracellular calcium overload as part of the ischemia-reperfusion injury provides the possibility for the injury to be counteracted by the early suppression of serum calcium with the aim of improving survival and the neurological outcome. We investigated the effects of prolonged serum calcium suppression via sodium citrate during extracorporeal resuscitation using the CARL protocol (CARL-controlled automated reperfusion of the whole body) compared to a single-dose approach in a porcine model after prolonged cardiac arrest. A control group (N = 10) was resuscitated after a 20 min cardiac arrest, initially lowering the intravascular calcium with the help of a single dose of sodium citrate as part of the priming solution. Animals in the intervention group (N = 13) received additional sodium citrate for the first 15 min of reperfusion. In the control group, 9/10 (90.0%) animals survived until day 7 and 7/13 (53.8%) survived in the intervention group (p = 0.09). A favorable neurological outcome on day 7 after the cardiac arrest was observed in all the surviving animals using a species-specific neurological deficit score. The coronary perfusion pressure was significantly lower with a tendency towards more cardiac arrhythmias in the intervention group. In conclusion, a prolonged reduction in serum calcium levels over the first 15 min of reperfusion after prolonged cardiac arrest tended to be unfavorable regarding survival and hemodynamic variables compared to a single-dose approach in this animal model.

The Effect of Therapeutic Adherence on the Effectiveness of a Digital Therapeutic Exercise Program: A Propensity Score Matching Analysis.

Nonspecific back pain (NSBP) contributes greatly to the overall burden of disease from musculoskeletal conditions. Digital therapeutics (DTx) aims to address the excess demand for movement and exercise therapy resulting from this spectrum of conditions. This study aims to investigate the differential therapeutic response of NSBP to different use profiles of a digital home exercise program. METHODS: This study used a PSM model to comparatively assess the achievement of a clinically relevant pain improvement among patients who exhibit a high use (HU), intermediate use (IU), low use (LU), or sub-LU use profile. Sensitivity analyses with commonly accepted thresholds for clinically relevant improvements were conducted. RESULTS: Higher use profiles show a higher probability of achieving a clinically relevant improvement of self-reported pain intensities. Additionally, the achievement of any higher use level is associated with a significant increase in the probability of achieving a clinically relevant improvement. CONCLUSION: To enable the optimal effectiveness of DTx home exercise programs, an HU use profile should be pursued. This finding is in line with earlier guidance for the achievement of optimal therapeutic benefit from conventional movement and exercise therapy and underscores the importance of a cross-disciplinary effort from patients, healthcare professionals and system stakeholders alike to maximize the therapeutic effect from DTx.

Postmarketing Follow-Up of a Digital Home Exercise Program for Back, Hip, and Knee Pain: Retrospective Observational Study With a Time-Series and Matched-Pair Analysis.

BACKGROUND: Musculoskeletal conditions are the main drivers of global disease burden and cause significant direct and indirect health care costs. Digital health applications improve the availability of and access to adequate care. The German health care system established a pathway for the approval of "Digitale Gesundheitsanwendungen" (DiGAs; Digital Health Applications) as collectively funded medical services through the "Digitale-Versorgung-Gesetz" (Digital Health Care Act) in 2019. OBJECTIVE: This article presents real-world prescription data collected through the smartphone-based home exercise program "Vivira," a fully approved DiGA, regarding its effect on self-reported pain intensity and physical inability in patients with unspecific and degenerative pain in the back, hip, and knee. METHODS: This study included 3629 patients (71.8% [2607/3629] female; mean age 47 years, SD 14.2 years). The primary outcome was the self-reported pain score, which was assessed with a verbal numerical rating scale. The secondary outcomes were self-reported function scores. To analyze the primary outcome, we used a 2-sided Skillings-Mack test. For function scores, a time analysis was not feasible; therefore, we calculated matched pairs using the Wilcoxon signed-rank test. RESULTS: Our results showed significant reductions in self-reported pain intensity after 2, 4, 8, and 12 weeks in the Skillings-Mack test (T3628=5308; P<.001). The changes were within the range of a clinically relevant improvement. Function scores showed a generally positive yet more variable response across the pain areas (back, hip, and knee). CONCLUSIONS: This study presents postmarketing observational data from one of the first DiGAs for unspecific and degenerative musculoskeletal pain. We noted significant improvements in self-reported pain intensity throughout the observation period of 12 weeks, which reached clinical relevance. Additionally, we identified a complex response pattern of the function scores assessed. Lastly, we highlighted the challenges of relevant attrition at follow-up and the potential opportunities for evaluating digital health applications. Although our findings do not have confirmatory power, they illustrate the potential benefits of digital health applications to improve the availability of and access to medical care. TRIAL REGISTRATION: German Clinical Trials Register DRKS00024051; https://drks.de/search/en/trial/DRKS00024051.

Correction: The Effect of an App-Based Home Exercise Program on Self-reported Pain Intensity in Unspecific and Degenerative Back Pain: Pragmatic Open-label Randomized Controlled Trial.

[This corrects the article DOI: 10.2196/41899.].

Preliminary Use and Outcome Data of a Digital Home Exercise Program for Back, Hip, and Knee Pain: Retrospective Observational Study With a Time Series and Matched Analysis.

BACKGROUND: Musculoskeletal conditions are among the main contributors to the global burden of disease. International guidelines consider patient education and movement exercises as the preferred therapeutic option for unspecific and degenerative musculoskeletal conditions. Innovative and decentralized therapeutic means are required to provide access to and availability of such care to meet the increasing therapeutic demand for this spectrum of conditions. OBJECTIVE: This retrospective observational study of preliminary use and outcome data explores the clinical outcomes of Vivira (hereafter referred to as "program"), a smartphone-based program for unspecific and degenerative pain in the back, hip, and knee before it received regulatory approval for use in the German statutory health insurance system. METHODS: An incomplete matched block design was employed to assess pain score changes over the intended 12-week duration of the program. Post hoc analyses were performed. In addition, a matched comparison of self-reported functional scores and adherence rates is presented. RESULTS: A total of 2517 participants met the inclusion criteria and provided sufficient data to be included in the analyses. Overall, initial self-reported pain scores decreased significantly from an average of 5.19 out of 10 (SD 1.96) to an average of 3.35 out of 10 (SD 2.38) after 12 weeks. Post hoc analyses indicate a particularly emphasized pain score reduction over the early use phases. Additionally, participants with back pain showed significant improvements in strength and mobility scores, whereas participants with hip or knee pain demonstrated significant improvements in their coordination scores. Across all pain areas and pain durations, a high yet expected attrition rate could be observed. CONCLUSIONS: This observational study provides the first insights into the clinical outcomes of an exercise program for unspecific and degenerative back, hip, and knee pain. Furthermore, it demonstrates a potential secondary benefit of improved functionality (ie, strength, mobility, coordination). However, as this study lacks confirmatory power, further research is required to substantiate the clinical outcomes of the program assessed. TRIAL REGISTRATION: German Clinical Trials Register DRKS00021785; https://drks.de/search/en/trial/DRKS00021785.

Balancing adaptability and standardisation: insights from 27 routinely implemented ICHOM standard sets.

BACKGROUND: Healthcare systems around the world experience increasing pressure to control future growth of healthcare expenditures. Among other initiatives, quality and value-based benchmarking has become an important field to inform clinical evaluation and reimbursement questions. The International Consortium for Health Outcomes Measurement (ICHOM) has become one of the driving forces to translate scientific evidence into standardized assessments that are routinely applicable in day-to-day care settings. These aim to provide a benchmarking tool that allows the comparison and competition of health care delivery on the basis of value-based health care principles. METHODS: This work focuses on the consolidation of the ICHOM methodology and presents insights from 27 routinely implemented Standard Sets. The analysis is based on a literature review of the ICHOM literature repository, a process document review and key informant interviews with ICHOM's outcomes research and development team. RESULTS: Key findings are that the scope of ICHOM Standard Sets shifted from a more static focus on burden of disease and poorly standardized care pathways to a more dynamic approach that also takes into account questions about the setting of care, feasibility of implementing a benchmarking tool and compatibility of different Standard Sets. Although certain overlaps exist with other initiatives in the field of patient reported outcomes (PRO), their scopes differ significantly and they hence rather complement each other. ICHOM pursues a pragmatic approach to enable the benchmarking and the analysis of healthcare delivery following the principles of value-based healthcare. CONCLUSION: The ICHOM Standard Sets complement other initiatives in the field of patient-reported outcomes (PRO) and functional reporting by placing a particular focus on healthcare delivery, while other initiatives primarily focus on evaluation of academic endpoints. Although ICHOM promotes a pragmatic approach towards developing and devising its Standard Sets, the definition of standardized decision making processes emerged as one of the key challenges. Furthermore, the consolidation of core metrics across number of disease areas to enable the parallel implementation of different Standard Sets in the same care setting is an important goal that will enable the widespread implementation of patient-reported outcome measures (PROM).

The Effect of an App-Based Home Exercise Program on Self-reported Pain Intensity in Unspecific and Degenerative Back Pain: Pragmatic Open-label Randomized Controlled Trial.

BACKGROUND: The recommended first-line treatment for unspecific and degenerative back pain consists of movement exercises and patient education. OBJECTIVE: Using a pragmatic, randomized controlled trial, we evaluated the effectiveness of a digital home exercise program on self-reported pain intensity compared with the standard of care for physiotherapy. METHODS: Participant recruitment was based on newspaper advertisements and a consecutive on-site assessment for eligibility and enrollment. Participants with unspecific and degenerative back pain aged ≥18 years were randomly assigned in a 1:1 ratio to receive a 12-week stand-alone digital home exercise program or physiotherapy. The digital home exercise program included 4 exercises daily, while physiotherapy included 6 to 12 sessions, depending on the severity of symptoms. The primary outcome was pain, which was assessed using a verbal numerical rating scale. The clinical relevance of pain reduction was assessed using the following thresholds: improvement of at least 1.4 points on the verbal numerical rating scale and a pain reduction of at least 30%. RESULTS: During the study period, 108 participants were assigned to the intervention group and 105 participants to the control group. The mean difference in pain scores between the 2 groups at 12 weeks was -2.44 (95% CI -2.92 to -1.95; P<.01) in favor of the intervention group. The group receiving the digital therapeutic achieved a clinically relevant reduction in pain over the course of the study (baseline vs 12 weeks), with a mean change of -3.35 (SD 2.05) score points or -53.1% (SD 29.5). By contrast, this change did not reach clinical relevance in the control group (mean -0.91, SD 1.5; -14.6%, SD 25.3). Retention rates of 89.9% in the intervention group and 97.3% in the control group were maintained throughout the study. CONCLUSIONS: The use of the app-based home exercise program led to a significant and clinically relevant reduction in pain intensity throughout the 12-week duration of the program. The intervention studied showed superior improvement in self-reported pain intensity when compared with the standard of care. Given the great demand for standard physiotherapy for unspecific and degenerative back pain, digital therapeutics are evolving into a suitable therapeutic option that can overcome the limitations of access and availability of conventional modes of health care delivery into this spectrum of indications. However, further independent evaluations are required to support the growing body of evidence on the effectiveness of digital therapeutics in real-world care settings. TRIAL REGISTRATION: German Clinical Trials Register DRKS00022781; https://tinyurl.com/hpdraa89.

Advances in and the Applicability of Machine Learning-Based Screening and Early Detection Approaches for Cancer: A Primer.

Despite the efforts of the past decades, cancer is still among the key drivers of global mortality. To increase the detection rates, screening programs and other efforts to improve early detection were initiated to cover the populations at a particular risk for developing a specific malignant condition. These diagnostic approaches have, so far, mostly relied on conventional diagnostic methods and have made little use of the vast amounts of clinical and diagnostic data that are routinely being collected along the diagnostic pathway. Practitioners have lacked the tools to handle this ever-increasing flood of data. Only recently, the clinical field has opened up more for the opportunities that come with the systematic utilisation of high-dimensional computational data analysis. We aim to introduce the reader to the theoretical background of machine learning (ML) and elaborate on the established and potential use cases of ML algorithms in screening and early detection. Furthermore, we assess and comment on the relevant challenges and misconceptions of the applicability of ML-based diagnostic approaches. Lastly, we emphasise the need for a clear regulatory framework to responsibly introduce ML-based diagnostics in clinical practice and routine care.

Automated spheroid generation, drug application and efficacy screening using a deep learning classification: a feasibility study.

The last two decades saw the establishment of three-dimensional (3D) cell cultures as an acknowledged tool to investigate cell behaviour in a tissue-like environment. Cells growing in spheroids differentiate and develop different characteristics in comparison to their two-dimensionally grown counterparts and are hence seen to exhibit a more in vivo-like phenotype. However, generating, treating and analysing spheroids in high quantities remains labour intensive and therefore limits its applicability in drugs and compound research. Here we present a fully automated pipetting robot that is able to (a) seed hanging drops from single cell suspensions, (b) treat the spheroids formed in these hanging drops with drugs and (c) analyse the viability of the spheroids by an image-based deep learning based convolutional neuronal network (CNN). The model is trained to classify between 'unaffected', 'mildly affected' and 'affected' spheroids after drug exposure. All corresponding spheroids are initially analysed by viability flow cytometry analysis to build a labelled training set for the CNN to subsequently reduce the number of misclassifications. Hence, this approach allows to efficiently examine the efficacy of drug combinatorics or new compounds in 3D cell culture. Additionally, it may provide a valuable instrument to screen for new and individualized systemic therapeutic strategies in second and third line treatment of solid malignancies using patient derived primary cells.

Assessment of hydrogels for bioprinting of endothelial cells.

In tissue engineering applications, vascularization can be accomplished by coimplantation of tissue forming cells and endothelial cells (ECs), whereby the latter are able to form functional blood vessels. The use of three-dimensional (3D) bioprinting technologies has the potential to improve the classical tissue engineering approach because these will allow the generation of scaffolds with high spatial control of endothelial cell allocation. This study focuses on a side by side comparison of popular commercially available bioprinting hydrogels (Matrigel, fibrin, collagen, gelatin, agarose, Pluronic F-127, alginate, and alginate/gelatin) in the context of their physicochemical parameters, their swelling/degradation characteristics, their biological effects on vasculogenesis-related EC parameters and their printability. The aim of this study was to identify the most suitable hydrogel or hydrogel combination for inkjet printing of ECs to build prevascularized tissue constructs. Most tested hydrogels displayed physicochemical characteristics suitable for inkjet printing. However, Pluronic F-127 and the alginate/gelatin blend were rapidly degraded when incubated in cell culture medium. Agarose, Pluronic F-127, alginate and alginate/gelatin hydrogels turned out to be unsuitable for bioprinting of ECs because of their non-adherent properties and/or their incapability to support EC proliferation. Gelatin was able to support EC proliferation and viability but was unable to support endothelial cell sprouting. Our experiments revealed fibrin and collagen to be most suitable for bioprinting of ECs, because these hydrogels showed acceptable swelling/degradation characteristics, supported vasculogenesis-related EC parameters and showed good printability. Moreover, ECs in constructs of preformed spheroids survived the printing process and formed capillary-like cords. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 935-947, 2018.

Cytocompatibility testing of hydrogels toward bioprinting of mesenchymal stem cells.

Mesenchymal stem cells (MSCs) represent a very attractive cell source for tissue engineering applications aiming at the generation of artificial bone substitutes. The use of three-dimensional bioprinting technologies has the potential to improve the classical tissue engineering approach because bioprinting will allow the generation of hydrogel scaffolds with high spatial control of MSC allocation within the bioprinted construct. In this study, we have performed direct comparisons between commercially available hydrogels in the context of their cytocompatibility toward MSCs and their physicochemical parameters with the aim to identify the most suitable hydrogel for drop-on-demand (DoD) printing of MSCs. In this context, we examined matrigel, fibrin, collagen, gelatin, and gelatin/alginate at various hydrogel concentrations. Matrigel, fibrin, collagen, and gelatin were able to support cell viability, but the latter showed a limited potential to promote MSC proliferation. We concentrated our study on fibrin and collagen hydrogels and investigated the effect of hydroxyapatite (HA) inclusion. The inclusion of HA enhanced proliferation and osteogenic differentiation of MSCs and prevented degradation of fibrin in vitro. According to viscosity and storage moduli measurements, HA-blends displayed physicochemical characteristics suitable for DoD printing. In bioprinting experiments, we confirmed that fibrin and collagen and their respective HA-blends represent excellent hydrogels for DoD-based printing as evidenced by high survival rates of printed MSCs. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3231-3241, 2017.

Large scale production and controlled deposition of single HUVEC spheroids for bioprinting applications.

We present (1) a fast and automated method for large scale production of HUVEC spheroids based on the hanging drop method and (2) a novel method for well-controlled lateral deposition of single spheroids by drop-on-demand printing. Large scale spheroid production is achieved via printing 1536 droplets of HUVEC cell suspension having a volume of 1 µl each within 3 min at a pitch of 2.3 mm within an array of 48 × 32 droplets onto a flat substrate. Printing efficiencies between 97.9% and 100% and plating efficiencies between 87.3% and 100% were achieved. Harvested spheroids (consisting of approx. 250 HUVECs each) appear uniform in size and shape. After incubation and harvesting, the spheroids are deposited individually in user-defined patterns onto hydrogels using an automated drop-on-demand dispenser setup. Controlled by an image detection algorithm focusing the dispenser nozzle, droplets containing exactly one spheroid are printed onto a substrate, while all other droplets are discarded. Using this approach an array of 6 × 3 HUVEC spheroids with intermediate distances of 500 µm embedded in fibrin was generated. Successful progress of spheroid sprouting and merging of neighboring sprouts was observed during the first 72 h of incubation indicating a good viability of the deposited spheroids.